I am composing this editorial 4 days after the U.S. Capitol was invaded and 10 days before the presidential inauguration. It is impossible to ignore what is happening in our country, but I hesitate to add my thoughts to the overwhelming sea of opinions circulating in standard media, social media, and the dark web. I hope, as do many, that we return to a civil discourse, recognize the voices of all people, respect each other, and return to a belief in science and facts.

SARS-CoV-2 has devastated the world and will continue to cause preventable deaths until we adopt stricter mitigation measures, vaccinate most people, and develop widespread immunity. We are gaining immense knowledge about this virus, and as gastroenterologists, we are on the front lines in many aspects. A recent article in American Journal of Gastroenterology, among others, emphasized that mild GI symptoms may be the only presenting complaint for people with COVID-19. Responses to COVID-19, such as limits on elective procedures and social distancing, have upended our endoscopic processes and even altered the business models of GI practice. We will never go back to pre-COVID models.

The front page of this month’s GI & Hepatology News features important articles for our practice. One article delves into an extensive guideline from the American Gastroenterological Association on medical management of colonic diverticulitis. In another article, they also describe how efforts to encourage our patients with nonalcoholic fatty liver disease to exercise and manage their diet can make a real difference in their health. Finally, another explores how and why your immunocompromised patients (including those with inflammatory bowel disease) should and can be safely vaccinated for COVID-19.

Meanwhile, we need civility, science, and community. Without common purpose, we will experience the William Forster Lloyd’s Tragedy of the Commons. Incivility has economic and emotional costs, according to the Harvard Business Review. “Weathering,” the deterioration of Black women’s health over time that’s related to continued socioeconomic disadvantage, has multigenerational impacts; for example the Department of Health & Human Services reports that infant mortality among African American women is 2.3 times that of non-Hispanic Whites. Late effects of redlining continue to cause economic, health, and emotional harms (Badger E. “How Redlining’s Racist Effects Lasted for Decades” The New York Times. 2017 Aug 24).

“If Men were angels, no government would be necessary,” James Madison wrote. “In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and the next place, oblige it to control itself.”

John I. Allen, MD, MBA, AGAF
Editor in Chief

I am composing this editorial 4 days after the U.S. Capitol was invaded and 10 days before the presidential inauguration. It is impossible to ignore what is happening in our country, but I hesitate to add my thoughts to the overwhelming sea of opinions circulating in standard media, social media, and the dark web. I hope, as do many, that we return to a civil discourse, recognize the voices of all people, respect each other, and return to a belief in science and facts.

SARS-CoV-2 has devastated the world and will continue to cause preventable deaths until we adopt stricter mitigation measures, vaccinate most people, and develop widespread immunity. We are gaining immense knowledge about this virus, and as gastroenterologists, we are on the front lines in many aspects. A recent article in American Journal of Gastroenterology, among others, emphasized that mild GI symptoms may be the only presenting complaint for people with COVID-19. Responses to COVID-19, such as limits on elective procedures and social distancing, have upended our endoscopic processes and even altered the business models of GI practice. We will never go back to pre-COVID models.

The front page of this month’s GI & Hepatology News features important articles for our practice. One article delves into an extensive guideline from the American Gastroenterological Association on medical management of colonic diverticulitis. In another article, they also describe how efforts to encourage our patients with nonalcoholic fatty liver disease to exercise and manage their diet can make a real difference in their health. Finally, another explores how and why your immunocompromised patients (including those with inflammatory bowel disease) should and can be safely vaccinated for COVID-19.

Meanwhile, we need civility, science, and community. Without common purpose, we will experience the William Forster Lloyd’s Tragedy of the Commons. Incivility has economic and emotional costs, according to the Harvard Business Review. “Weathering,” the deterioration of Black women’s health over time that’s related to continued socioeconomic disadvantage, has multigenerational impacts; for example the Department of Health & Human Services reports that infant mortality among African American women is 2.3 times that of non-Hispanic Whites. Late effects of redlining continue to cause economic, health, and emotional harms (Badger E. “How Redlining’s Racist Effects Lasted for Decades” The New York Times. 2017 Aug 24).

“If Men were angels, no government would be necessary,” James Madison wrote. “In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and the next place, oblige it to control itself.”

John I. Allen, MD, MBA, AGAF
Editor in Chief

I am composing this editorial 4 days after the U.S. Capitol was invaded and 10 days before the presidential inauguration. It is impossible to ignore what is happening in our country, but I hesitate to add my thoughts to the overwhelming sea of opinions circulating in standard media, social media, and the dark web. I hope, as do many, that we return to a civil discourse, recognize the voices of all people, respect each other, and return to a belief in science and facts.

SARS-CoV-2 has devastated the world and will continue to cause preventable deaths until we adopt stricter mitigation measures, vaccinate most people, and develop widespread immunity. We are gaining immense knowledge about this virus, and as gastroenterologists, we are on the front lines in many aspects. A recent article in American Journal of Gastroenterology, among others, emphasized that mild GI symptoms may be the only presenting complaint for people with COVID-19. Responses to COVID-19, such as limits on elective procedures and social distancing, have upended our endoscopic processes and even altered the business models of GI practice. We will never go back to pre-COVID models.

The front page of this month’s GI & Hepatology News features important articles for our practice. One article delves into an extensive guideline from the American Gastroenterological Association on medical management of colonic diverticulitis. In another article, they also describe how efforts to encourage our patients with nonalcoholic fatty liver disease to exercise and manage their diet can make a real difference in their health. Finally, another explores how and why your immunocompromised patients (including those with inflammatory bowel disease) should and can be safely vaccinated for COVID-19.

Meanwhile, we need civility, science, and community. Without common purpose, we will experience the William Forster Lloyd’s Tragedy of the Commons. Incivility has economic and emotional costs, according to the Harvard Business Review. “Weathering,” the deterioration of Black women’s health over time that’s related to continued socioeconomic disadvantage, has multigenerational impacts; for example the Department of Health & Human Services reports that infant mortality among African American women is 2.3 times that of non-Hispanic Whites. Late effects of redlining continue to cause economic, health, and emotional harms (Badger E. “How Redlining’s Racist Effects Lasted for Decades” The New York Times. 2017 Aug 24).

“If Men were angels, no government would be necessary,” James Madison wrote. “In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and the next place, oblige it to control itself.”

John I. Allen, MD, MBA, AGAF
Editor in Chief

Introduction

Gastroenterologists are in a unique position to manage individuals with feeding tubes as their training underscores principles in digestion, absorption, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require a basic understanding of intestinal anatomy and physiology. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Indications for tube feeding

When deciding on the appropriate route for artificial nutrition support, the first decision to be made is enteral access versus parenteral nutrition support. Enteral nutrition confers multiple benefits, including preservation of the mucosal lining, reductions in complicated infections, decreased costs, and improved patient compliance. All attempts at adequate enteral access should be made before deciding on the use of parenteral nutrition. Following the clinical decision to pursue artificial means of nutrition support and enteral access, the next common decision is the anticipated duration of nutrition support. Generally, the oral or nasal tubes are used for short durations (i.e., less than 4 weeks) with percutaneous placement into the stomach or small intestine for longer-term feeding (i.e., percutaneous endoscopic gastrostomy [PEG] or percutaneous endoscopic jejunostomy [PEJ]).

The most general indication for nutrition support is an inability to maintain adequate nutritional needs with oral intake alone. General categories of inadequate oral intake include neurologic disorders, malignancy, and gastrointestinal conditions affecting digestion and absorption (Table 1). Absolute and relative contraindications to PEG placement are listed in Table 2. If an endoscopic placement is not possible, alternative means of placement (i.e., surgery or interventional radiology) can be considered to avoid the consequences of prolonged malnutrition. In-hospital mortality following PEG placement has decreased 40% over the last 10 years, which can be attributed to improved patient selection, enhanced discharge practices, and exclusion of patients with the highest comorbidity and mortality rates, like those with advanced dementia or terminal cancer.¹

PEG placement in patients with dementia is controversial, with previous studies not demonstrating improved outcomes and association with high mortality rates,² so the practice is currently not recommended by the American Geriatrics Society in individuals with advanced dementia.³ However, a large Japanese study showed that careful selection of patients with mild dementia to undergo gastrostomy increased independence fourfold; therefore, multidisciplinary involvement is often necessary in the decision to pursue artificial means of nutrition support in this population.⁴

The recent coronavirus disease 2019 (COVID-19) pandemic has placed additional strains on endoscopic placement and has highlighted the effect of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) on GI symptoms. A recent meta-analysis showed an overall incidence of GI symptoms of 17.6% in the following conditions in decreasing order of prevalence: anorexia, diarrhea, nausea, vomiting, and abdominal discomfort.⁵ In addition, the prolonged ventilatory requirements among a subset of individuals with the most severe COVID-19 results in extended periods of nutrition support via enteral tube placements. In individuals with ICU-acquired weakness and discharge to long-term care facilities, the placement of percutaneous endoscopic tubes may be required, although with the additional consideration of the need for an aerosolizing procedure. Delay of placement has been advocated, in addition to appropriate personal protective equipment, in order to ensure safe placement for the endoscopy staff.⁶
 

Types of feeding tubes

After deciding to feed a patient enterally and determining the anticipated duration of enteral support, the next decision is to determine the most appropriate location of feeding delivery: into the stomach or the small bowel. Gastric feeding is advantageous most commonly because of its increased capacity, allowing for larger volumes to be delivered over shorter durations. However, in the setting of postsurgical anatomy, gastroparesis, or obstructing tumors/pancreatic inflammation, distal delivery of tube feeds may be required into the jejunum. Additionally, percutaneous tubes placed into the stomach can have extenders into the small bowel (GJ tubes) to allow for feeding into the small bowel and decompression or delivery of medications into the stomach.

In general, gastric feeding is preferred over small bowel feeding as PEG tubes are more stable and have fewer complications than either PEG-J or direct PEJ tubes. Gastrostomy tubes are generally shorter and larger in diameter making them less likely to clog. PEG-J tubes have separate lumens for gastric and small intestinal access, but the smaller-bore jejunal extension tubes are more likely to clog or become dislodged. While direct PEJ is shown to have higher rates of tube patency and decreased rates of endoscopic re-intervention, compared with PEG-J,⁷ one limitation of a direct PEJ is difficulty in placement and site selection, which can be performed with a pediatric colonoscope or balloon enteroscopy system. Most commonly, this procedure is performed under general anesthesia.

In the case of a critically ill patient in the ICU, it is recommended to start enteral nutrition within 24-48 hours of arrival to avoid complications of prolonged calorie deficits. Nasally inserted feeding tubes (e.g., Cortrak, Avanos Medical Devices, Alpharetta, Ga.) are most commonly used at the bedside and can be placed blindly using electromagnetic image guidance, radiographically, or endoscopy. However, the small caliber of nasoenteric tubes comes with the common complication of clogging, which can be overcome with slightly larger bore gastric feeding tubes. If gastric feeding is not tolerated (e.g., in the case of vomiting, witnessed aspiration), small bowel feeding should be initiated and can be a more durable form of enteral feeding with fewer interruptions as feedings do not need to be held for procedures or symptomatic gastric intolerance. In clinical areas of question, or if there is a concern for intolerance of enteral feeding, a short trial with nasogastric or nasojejunal tube placement should be performed before a more definitive percutaneous placement.

With respect to percutaneous tubes, important characteristics to choose are the size (diameter in French units), type of internal retention device, and external appearance of the tube (standard or low profile). All percutaneous tubes contain an external retention device (i.e., bumper) that fits against the skin and an internal retention device that is either a balloon or plastic dome or funnel that prevents the tube from becoming dislodged. Balloon retention tubes require replacement every 3-6 months, while nonballoon tubes generally require replacement annually in order to prevent the plastic from cracking, which can make removal complicated. Low-profile tubes have an external cap, which, when opened, allows for extension tubing to be securely attached while in use and detached while not in use. Low-profile tubes are often preferred among younger, active patients and those with adequate dexterity to allow for attachment of the external extension tubing. These tubes are most often inserted as a replacement for an initially endoscopically placed tube, although one-step systems for initial placement are available. The size of the low-profile tube is chosen based on the size of the existing PEG tube and by measuring the length of the stoma tract using specialized measuring devices.⁸ Patients and caregivers can also be trained to replace balloon-type tubes on their own to limit complications of displaced or cracked tubes. Low-profile tubes are commercially available for both gastric placement and gastric placement with extension into the small bowel, which often requires fluoroscopy for secure placement.

All percutaneous enteral tubes are being transitioned to the ENfit connector system, which prevents connections from the enteral system to nonenteral systems (namely intravenous lines, chest tubes) and vice versa. Tubing misconnections have been rarely reported, and the EnFIT system is designed to prevent such misadventures that have resulted in serious complications and even mortality.⁹ Adapter devices are available that may be required for patients with feeding tubes who have not been transitioned yet. Most commonly with new tube placements and replacements, patients and providers will have to become familiar with the new syringes and feeding bags required with EnFIT connectors.

Gastrostomy placement can be considered a higher-risk endoscopic procedure. One complicating factor is the increased use of antiplatelet and anticoagulant therapies in individuals with a history of neurologic insults. The American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend that coumadin be held 5 days before the procedure and bridged with heparin if the patient is at high risk of thromboembolic complications. For patients on dual anti-platelet therapy, thienopyridines like clopidogrel are often stopped 5-7 days prior to procedure with continuation of aspirin,¹⁰ but there are more recent data that PEG insertion is safe with continued use of DAPT.¹¹ Direct-acting anticoagulants (DOACs) are often stopped 24-48 hours prior to procedure and then restarted 48 hours after tube placement, but this is dependent on the half-life of the specific DOAC and the patient’s renal function. Patients with decreased creatinine clearance may need to hold the DOAC up to 3-4 days prior to the procedure. In this situation, referring to ASGE guidelines and consultation with a hematologist or managing anti-coagulation clinic is advised.¹⁰
 

Troubleshooting complications

Nasoenteric tubes: One of the most common and irritating complications with nasoenteric feeding tubes is clogging. To prevent clogging, the tube should be flushed frequently.¹² At least 30 mL of free water should be used to flush the tube every 4-8 hours for continuous feedings or before and after bolus feeding. Additionally, 15-30 mL of water should be given with each separate medication administration, and if possible, medication administration via small-bore small bowel feeding tubes should be avoided.¹² Water flushing is especially important with small-caliber tubes and pumps that deliver both feeding and water flushes. It is available for small bowel feeding in order to allow for programmed water delivery.

Warm water flushes can also help unclog the tube,¹² and additional pharmacologic and mechanical devices have been promoted for clogged tubes. One common technique is mixing pancreatic enzymes (Viokase) with a crushed 325-mg tablet of nonenteric coated sodium bicarbonate and 5 mL of water to create a solution that has the alkaline properties allowing for both pancreatic enzyme activation and clog dissolution. Additionally, an endoscopic retrograde cholangiopancreatography (ERCP) catheter can be placed into longer feeding tubes to directly infuse the activated agent to the site of the clog.¹³ If water and enzymes are not successful in unclogging the tube, commercially available brushes can help remove clogs. The TubeClear® system (Actuated Medical, Bellefonte, Penna) has a single-use stem that is connected to AC power to create a jackhammerlike movement to remove clogs in longer nasoenteral and gastrojejunal tubes.
 

PEG tubes (short-term complications): Procedural and immediate postprocedural complications include bleeding, aspiration, pneumoperitoneum, and perforation. Pneumoperitoneum occurs in approximately 50% of cases and is generally clinically insignificant. The risk of pneumoperitoneum can be reduced by using CO2 insufflation.¹⁴ If the patient develops systemic signs of infection or peritoneal signs, CT scan with oral contrast is warranted for further evaluation and to assess for inadvertent perforation of overlying bowel or dislodged tube. Aspiration during or following endoscopy is another common complication of PEG placement and risk factors include over-sedation, supine positioning, advanced age, and neurologic dysfunction. This risk can be mitigated by avoiding over-sedation, immediately aspirating gastric contents when the stomach is reached, and avoiding excessive insufflation.¹⁵ In addition, elevating the head of the bed during the procedure and dedicating an assistant to perform oral suctioning during the entire procedure is recommended.

PEG tubes (long-term complications): More delayed complications of PEG insertion include wound infection, buried bumper syndrome, tumor seeding, peristomal leakage, and tube dislodgement. The prevalence of wound infection is 5%- 25%,¹⁶ and randomized controlled trials have demonstrated the efficacy of a single dose of an IV antibiotic (i.e., cephalosporin) in those not already receiving a broad spectrum antibiotic and administered prophylactically before tube placement.¹⁷ The significance of this reduction is such that antibiotic administration before tube placement should be considered a quality measure for the procedure. A small amount of redness around the tube site (less than 5 mm) is typical, but extension of erythema, warmth, tenderness, purulent drainage, or systemic symptoms is consistent with infection and warrants additional antibiotic administration. Minor infections can be treated with local antiseptics and oral antibiotics, and early intervention is important to prevent need for hospital admission, systemic antibiotics, and even surgical debridement.

Peristomal leakage is reported in approximately 1%-2% of patients.¹⁸ Photographs of the site can be very useful in evaluating and managing peristomal leakage and infections. Interventions include reducing gastric secretions with proton pump inhibitors and management of the skin with barrier creams, such as zinc oxide (Calmoseptine®) ointment. Placement of a larger-diameter tube only enlarges the stoma track and worsens the leakage. In such cases, thorough evaluations for delayed gastric emptying (gastroparesis), distal obstruction, or constipation should be performed and managed accordingly. Opiates are common contributors to constipation and delayed gastric emptying and often require reduction in use or directed antagonist therapy to reduce leaking. Continuous feeding over bolus feedings and delivering nutrition distally into the small bowel (PEG-J placement) can improve leaking from gastrostomy tubes. Additional means of management include stabilizing the tube by replacing a traditional tube with a low-profile tube or using right-angle external bumpers. If all measures fail, removing the tube and allowing for stomal closure can be attempted,¹⁶ although this option often requires parenteral nutrition support to prevent prolonged periods of inadequate nutrition.

Buried bumper syndrome (BBS) occurs in 1.5%-8.8% of PEG placements and is a common late complication of PEG placement, although early reports have been described.¹⁸ The development of BBS occurs when the internal bumper migrates from the gastric lumen through and into the stomach or abdominal wall. It occurs more frequently with solid nonballoon retention tubes and is caused by excessive compression of the external bumper against the skin and abdominal wall. Patients with BBS usually present with an immobile catheter, resistance with feeds (because of a closure of the stomach wall around the internal portion of the gastrostomy tube), abdominal pain, or peristomal leakage. Physicians should be aware of and assess tubes for BBS, in particular when replacing an immobile tube (cannot be pushed into the free stomach lumen) or when there is difficulty in flushing water into the tube. This complication can be easily prevented by allowing a minimum of 0.5-1.0 cm (1 finger breadth) between the external bumper and the abdominal wall. In particular, patients and caregivers should be warned that if the patient gains significant amounts of weight, the outer bumper will need to be loosened. Once BBS is diagnosed, the PEG tube requires removal and replacement as it can cause bleeding, infection, or fasciitis. The general steps to replacement include endoscopic removal of the existing tube and replacement of new PEG in the existing tract as long as the BBS is not severe. In most cases a replacement tube can be pulled into place using the pull-PEG technique at the same gastrostomy site as long as the stoma tract can be cannulated with a wire after the existing tube is removed.

Similar to nasoenteric tubes, PEG tubes can become clogged, although this complication is infrequent. The primary steps for prevention include adequately flushing with water before and after feeds and ensuring that all medications are liquid or well crushed and dissolved before instilling. Timely tube replacement also ensures that the internal portions of the gastrostomy tube remain free of debris. Management is similar to that of unclogging nasoenteral tubes, as discussed above, and specific commercial declogging devices for PEG tubes include the Bionix Declogger® (Bionix Development Corp., Toledo, Ohio) and the Bard® PEG cleaning brush (Bard Peripheral Vascular Inc., Tempe, Ariz.). The Bionix system has a plastic stem with a screw and thread design that will remove clogs in 14-24 French PEG tubes, while the Bard brush has a flexible nylon stem with soft bristles at the end to prevent mucosal injury and can be used for prophylaxis against clogs, as well as removing clogs themselves.¹²

Lastly, a rare but important complication of PEG placement is tumor seeding of the PEG site in patients with active head and neck or upper gastrointestinal cancer.¹⁹ The presumed mechanism is shearing of tumor cells as the PEG is pulled through the upper aerodigestive tract and through the wall of the stomach, as prior studies have demonstrated frequent seeding of tubes and incision sites as shown by brushing the tube for malignant cells after tube placement.²⁰ It is important to recognize this complication and not misdiagnose it as granulation tissue, infection, or bleeding as the spread of the cancer generally portends a poor prognosis. Therefore, it is best to use a PEG insertion technique that does not involve pulling or pushing the PEG through the upper aerodigestive tract in patients with active cancer and instead place tubes via an external approach by colleagues in interventional radiology or via direct surgical placement.
 

Conclusion

Gastroenterologists occupy a unique role in evaluation, diagnosis, and management of patients requiring enteral feeding. In addition, they are best equipped to place, prevent, and manage complications of tube feeding. For this reason, it is imperative that gastroenterologists familiarize themselves with indications for enteral tubes and types of enteral tubes available, as well as the identification and management of common complications. Comprehensive understanding of these concepts will augment the practicing gastroenterologist’s ability to manage patients requiring enteral nutrition support with confidence.

References

1. Stein DJ et al. Dig Dis Sci. 2020 Jun 19. doi: 10.1007/s10620-020-06396-y.

2. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.

3. Dietrich CG, Schoppmeyer K. World J Gastroenterol. 2020;26(20):2464-71.

4. Suzuki Y et al. T Gastroenterology Res.2012 Feb;5(1):10-20.

5. Cheung KS et al. Gastroenterology. 2020 Jul;159(1):81-95.

6. Micic D et al. Am J Gastroenterol. 2020 Sep;115(9):1367-70.

7. Fan AC et al. Gastrointest Endosc. 2002;56(6):890-4.

8. Tang SJ. Video J Encycl GI Endosc. 2014;2(2):70-3.

9. Guenter P, Lyman B. Nutr Clin Pract. 2016;31(6):769-72.

10. Acosta RD et al. Gastrointest Endosc. 2016;83(1):3-16.

11. Richter JA et al. Gastrointest Endosc. 2011;74(1):22-34.

12. Boullata JI et al. JPEN. 2017;41(1):15-103.

13. McClave SA. Tech Gastrointest Endosc. 2021;3(1):62-8.

14. Murphy CJ et al. Endosc Int Open. 2016;4(3):E292. doi: 10.1053/tgie.2001.19915.

15. Lynch CR et al. Pract Gastroenterology. 2004;28:66-77.

16. Hucl T et al. Best Pract Res Clin Gastroenterol. 2016;30(5):769-81. doi: 10.1016/j.bpg.2016.10.002.

17. Jafri NS et al. Aliment Pharmacol & Therapeut. 2007;25(6):647-56. doi: 10.1111/j.1365-2036.2007.03247.x.

18. Blumenstein I et al. World J Gastroenterol. 2014;20(26):8505-24. doi: 10.3748/wjg.v20.i26.8505.

19. Fung E et al. Surgical Endosc. 2017;31(9):3623-7. doi: 10.1007/s00464-016-5394-8.

20. Ellrichmann M et al. Endoscopy. 2013;45(07):526-31. doi: 10.1055/s-0033-1344023.

Dr. Toy is with the department of internal medicine at the University of Utah, Salt Lake City. Dr. Fang is with the division of gastroenterology and hepatology at the University of Utah.

Introduction

Gastroenterologists are in a unique position to manage individuals with feeding tubes as their training underscores principles in digestion, absorption, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require a basic understanding of intestinal anatomy and physiology. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Indications for tube feeding

When deciding on the appropriate route for artificial nutrition support, the first decision to be made is enteral access versus parenteral nutrition support. Enteral nutrition confers multiple benefits, including preservation of the mucosal lining, reductions in complicated infections, decreased costs, and improved patient compliance. All attempts at adequate enteral access should be made before deciding on the use of parenteral nutrition. Following the clinical decision to pursue artificial means of nutrition support and enteral access, the next common decision is the anticipated duration of nutrition support. Generally, the oral or nasal tubes are used for short durations (i.e., less than 4 weeks) with percutaneous placement into the stomach or small intestine for longer-term feeding (i.e., percutaneous endoscopic gastrostomy [PEG] or percutaneous endoscopic jejunostomy [PEJ]).

The most general indication for nutrition support is an inability to maintain adequate nutritional needs with oral intake alone. General categories of inadequate oral intake include neurologic disorders, malignancy, and gastrointestinal conditions affecting digestion and absorption (Table 1). Absolute and relative contraindications to PEG placement are listed in Table 2. If an endoscopic placement is not possible, alternative means of placement (i.e., surgery or interventional radiology) can be considered to avoid the consequences of prolonged malnutrition. In-hospital mortality following PEG placement has decreased 40% over the last 10 years, which can be attributed to improved patient selection, enhanced discharge practices, and exclusion of patients with the highest comorbidity and mortality rates, like those with advanced dementia or terminal cancer.¹

PEG placement in patients with dementia is controversial, with previous studies not demonstrating improved outcomes and association with high mortality rates,² so the practice is currently not recommended by the American Geriatrics Society in individuals with advanced dementia.³ However, a large Japanese study showed that careful selection of patients with mild dementia to undergo gastrostomy increased independence fourfold; therefore, multidisciplinary involvement is often necessary in the decision to pursue artificial means of nutrition support in this population.⁴

The recent coronavirus disease 2019 (COVID-19) pandemic has placed additional strains on endoscopic placement and has highlighted the effect of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) on GI symptoms. A recent meta-analysis showed an overall incidence of GI symptoms of 17.6% in the following conditions in decreasing order of prevalence: anorexia, diarrhea, nausea, vomiting, and abdominal discomfort.⁵ In addition, the prolonged ventilatory requirements among a subset of individuals with the most severe COVID-19 results in extended periods of nutrition support via enteral tube placements. In individuals with ICU-acquired weakness and discharge to long-term care facilities, the placement of percutaneous endoscopic tubes may be required, although with the additional consideration of the need for an aerosolizing procedure. Delay of placement has been advocated, in addition to appropriate personal protective equipment, in order to ensure safe placement for the endoscopy staff.⁶
 

Types of feeding tubes

After deciding to feed a patient enterally and determining the anticipated duration of enteral support, the next decision is to determine the most appropriate location of feeding delivery: into the stomach or the small bowel. Gastric feeding is advantageous most commonly because of its increased capacity, allowing for larger volumes to be delivered over shorter durations. However, in the setting of postsurgical anatomy, gastroparesis, or obstructing tumors/pancreatic inflammation, distal delivery of tube feeds may be required into the jejunum. Additionally, percutaneous tubes placed into the stomach can have extenders into the small bowel (GJ tubes) to allow for feeding into the small bowel and decompression or delivery of medications into the stomach.

In general, gastric feeding is preferred over small bowel feeding as PEG tubes are more stable and have fewer complications than either PEG-J or direct PEJ tubes. Gastrostomy tubes are generally shorter and larger in diameter making them less likely to clog. PEG-J tubes have separate lumens for gastric and small intestinal access, but the smaller-bore jejunal extension tubes are more likely to clog or become dislodged. While direct PEJ is shown to have higher rates of tube patency and decreased rates of endoscopic re-intervention, compared with PEG-J,⁷ one limitation of a direct PEJ is difficulty in placement and site selection, which can be performed with a pediatric colonoscope or balloon enteroscopy system. Most commonly, this procedure is performed under general anesthesia.

In the case of a critically ill patient in the ICU, it is recommended to start enteral nutrition within 24-48 hours of arrival to avoid complications of prolonged calorie deficits. Nasally inserted feeding tubes (e.g., Cortrak, Avanos Medical Devices, Alpharetta, Ga.) are most commonly used at the bedside and can be placed blindly using electromagnetic image guidance, radiographically, or endoscopy. However, the small caliber of nasoenteric tubes comes with the common complication of clogging, which can be overcome with slightly larger bore gastric feeding tubes. If gastric feeding is not tolerated (e.g., in the case of vomiting, witnessed aspiration), small bowel feeding should be initiated and can be a more durable form of enteral feeding with fewer interruptions as feedings do not need to be held for procedures or symptomatic gastric intolerance. In clinical areas of question, or if there is a concern for intolerance of enteral feeding, a short trial with nasogastric or nasojejunal tube placement should be performed before a more definitive percutaneous placement.

With respect to percutaneous tubes, important characteristics to choose are the size (diameter in French units), type of internal retention device, and external appearance of the tube (standard or low profile). All percutaneous tubes contain an external retention device (i.e., bumper) that fits against the skin and an internal retention device that is either a balloon or plastic dome or funnel that prevents the tube from becoming dislodged. Balloon retention tubes require replacement every 3-6 months, while nonballoon tubes generally require replacement annually in order to prevent the plastic from cracking, which can make removal complicated. Low-profile tubes have an external cap, which, when opened, allows for extension tubing to be securely attached while in use and detached while not in use. Low-profile tubes are often preferred among younger, active patients and those with adequate dexterity to allow for attachment of the external extension tubing. These tubes are most often inserted as a replacement for an initially endoscopically placed tube, although one-step systems for initial placement are available. The size of the low-profile tube is chosen based on the size of the existing PEG tube and by measuring the length of the stoma tract using specialized measuring devices.⁸ Patients and caregivers can also be trained to replace balloon-type tubes on their own to limit complications of displaced or cracked tubes. Low-profile tubes are commercially available for both gastric placement and gastric placement with extension into the small bowel, which often requires fluoroscopy for secure placement.

All percutaneous enteral tubes are being transitioned to the ENfit connector system, which prevents connections from the enteral system to nonenteral systems (namely intravenous lines, chest tubes) and vice versa. Tubing misconnections have been rarely reported, and the EnFIT system is designed to prevent such misadventures that have resulted in serious complications and even mortality.⁹ Adapter devices are available that may be required for patients with feeding tubes who have not been transitioned yet. Most commonly with new tube placements and replacements, patients and providers will have to become familiar with the new syringes and feeding bags required with EnFIT connectors.

Gastrostomy placement can be considered a higher-risk endoscopic procedure. One complicating factor is the increased use of antiplatelet and anticoagulant therapies in individuals with a history of neurologic insults. The American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend that coumadin be held 5 days before the procedure and bridged with heparin if the patient is at high risk of thromboembolic complications. For patients on dual anti-platelet therapy, thienopyridines like clopidogrel are often stopped 5-7 days prior to procedure with continuation of aspirin,¹⁰ but there are more recent data that PEG insertion is safe with continued use of DAPT.¹¹ Direct-acting anticoagulants (DOACs) are often stopped 24-48 hours prior to procedure and then restarted 48 hours after tube placement, but this is dependent on the half-life of the specific DOAC and the patient’s renal function. Patients with decreased creatinine clearance may need to hold the DOAC up to 3-4 days prior to the procedure. In this situation, referring to ASGE guidelines and consultation with a hematologist or managing anti-coagulation clinic is advised.¹⁰
 

Troubleshooting complications

Nasoenteric tubes: One of the most common and irritating complications with nasoenteric feeding tubes is clogging. To prevent clogging, the tube should be flushed frequently.¹² At least 30 mL of free water should be used to flush the tube every 4-8 hours for continuous feedings or before and after bolus feeding. Additionally, 15-30 mL of water should be given with each separate medication administration, and if possible, medication administration via small-bore small bowel feeding tubes should be avoided.¹² Water flushing is especially important with small-caliber tubes and pumps that deliver both feeding and water flushes. It is available for small bowel feeding in order to allow for programmed water delivery.

Warm water flushes can also help unclog the tube,¹² and additional pharmacologic and mechanical devices have been promoted for clogged tubes. One common technique is mixing pancreatic enzymes (Viokase) with a crushed 325-mg tablet of nonenteric coated sodium bicarbonate and 5 mL of water to create a solution that has the alkaline properties allowing for both pancreatic enzyme activation and clog dissolution. Additionally, an endoscopic retrograde cholangiopancreatography (ERCP) catheter can be placed into longer feeding tubes to directly infuse the activated agent to the site of the clog.¹³ If water and enzymes are not successful in unclogging the tube, commercially available brushes can help remove clogs. The TubeClear® system (Actuated Medical, Bellefonte, Penna) has a single-use stem that is connected to AC power to create a jackhammerlike movement to remove clogs in longer nasoenteral and gastrojejunal tubes.
 

PEG tubes (short-term complications): Procedural and immediate postprocedural complications include bleeding, aspiration, pneumoperitoneum, and perforation. Pneumoperitoneum occurs in approximately 50% of cases and is generally clinically insignificant. The risk of pneumoperitoneum can be reduced by using CO2 insufflation.¹⁴ If the patient develops systemic signs of infection or peritoneal signs, CT scan with oral contrast is warranted for further evaluation and to assess for inadvertent perforation of overlying bowel or dislodged tube. Aspiration during or following endoscopy is another common complication of PEG placement and risk factors include over-sedation, supine positioning, advanced age, and neurologic dysfunction. This risk can be mitigated by avoiding over-sedation, immediately aspirating gastric contents when the stomach is reached, and avoiding excessive insufflation.¹⁵ In addition, elevating the head of the bed during the procedure and dedicating an assistant to perform oral suctioning during the entire procedure is recommended.

PEG tubes (long-term complications): More delayed complications of PEG insertion include wound infection, buried bumper syndrome, tumor seeding, peristomal leakage, and tube dislodgement. The prevalence of wound infection is 5%- 25%,¹⁶ and randomized controlled trials have demonstrated the efficacy of a single dose of an IV antibiotic (i.e., cephalosporin) in those not already receiving a broad spectrum antibiotic and administered prophylactically before tube placement.¹⁷ The significance of this reduction is such that antibiotic administration before tube placement should be considered a quality measure for the procedure. A small amount of redness around the tube site (less than 5 mm) is typical, but extension of erythema, warmth, tenderness, purulent drainage, or systemic symptoms is consistent with infection and warrants additional antibiotic administration. Minor infections can be treated with local antiseptics and oral antibiotics, and early intervention is important to prevent need for hospital admission, systemic antibiotics, and even surgical debridement.

Peristomal leakage is reported in approximately 1%-2% of patients.¹⁸ Photographs of the site can be very useful in evaluating and managing peristomal leakage and infections. Interventions include reducing gastric secretions with proton pump inhibitors and management of the skin with barrier creams, such as zinc oxide (Calmoseptine®) ointment. Placement of a larger-diameter tube only enlarges the stoma track and worsens the leakage. In such cases, thorough evaluations for delayed gastric emptying (gastroparesis), distal obstruction, or constipation should be performed and managed accordingly. Opiates are common contributors to constipation and delayed gastric emptying and often require reduction in use or directed antagonist therapy to reduce leaking. Continuous feeding over bolus feedings and delivering nutrition distally into the small bowel (PEG-J placement) can improve leaking from gastrostomy tubes. Additional means of management include stabilizing the tube by replacing a traditional tube with a low-profile tube or using right-angle external bumpers. If all measures fail, removing the tube and allowing for stomal closure can be attempted,¹⁶ although this option often requires parenteral nutrition support to prevent prolonged periods of inadequate nutrition.

Buried bumper syndrome (BBS) occurs in 1.5%-8.8% of PEG placements and is a common late complication of PEG placement, although early reports have been described.¹⁸ The development of BBS occurs when the internal bumper migrates from the gastric lumen through and into the stomach or abdominal wall. It occurs more frequently with solid nonballoon retention tubes and is caused by excessive compression of the external bumper against the skin and abdominal wall. Patients with BBS usually present with an immobile catheter, resistance with feeds (because of a closure of the stomach wall around the internal portion of the gastrostomy tube), abdominal pain, or peristomal leakage. Physicians should be aware of and assess tubes for BBS, in particular when replacing an immobile tube (cannot be pushed into the free stomach lumen) or when there is difficulty in flushing water into the tube. This complication can be easily prevented by allowing a minimum of 0.5-1.0 cm (1 finger breadth) between the external bumper and the abdominal wall. In particular, patients and caregivers should be warned that if the patient gains significant amounts of weight, the outer bumper will need to be loosened. Once BBS is diagnosed, the PEG tube requires removal and replacement as it can cause bleeding, infection, or fasciitis. The general steps to replacement include endoscopic removal of the existing tube and replacement of new PEG in the existing tract as long as the BBS is not severe. In most cases a replacement tube can be pulled into place using the pull-PEG technique at the same gastrostomy site as long as the stoma tract can be cannulated with a wire after the existing tube is removed.

Similar to nasoenteric tubes, PEG tubes can become clogged, although this complication is infrequent. The primary steps for prevention include adequately flushing with water before and after feeds and ensuring that all medications are liquid or well crushed and dissolved before instilling. Timely tube replacement also ensures that the internal portions of the gastrostomy tube remain free of debris. Management is similar to that of unclogging nasoenteral tubes, as discussed above, and specific commercial declogging devices for PEG tubes include the Bionix Declogger® (Bionix Development Corp., Toledo, Ohio) and the Bard® PEG cleaning brush (Bard Peripheral Vascular Inc., Tempe, Ariz.). The Bionix system has a plastic stem with a screw and thread design that will remove clogs in 14-24 French PEG tubes, while the Bard brush has a flexible nylon stem with soft bristles at the end to prevent mucosal injury and can be used for prophylaxis against clogs, as well as removing clogs themselves.¹²

Lastly, a rare but important complication of PEG placement is tumor seeding of the PEG site in patients with active head and neck or upper gastrointestinal cancer.¹⁹ The presumed mechanism is shearing of tumor cells as the PEG is pulled through the upper aerodigestive tract and through the wall of the stomach, as prior studies have demonstrated frequent seeding of tubes and incision sites as shown by brushing the tube for malignant cells after tube placement.²⁰ It is important to recognize this complication and not misdiagnose it as granulation tissue, infection, or bleeding as the spread of the cancer generally portends a poor prognosis. Therefore, it is best to use a PEG insertion technique that does not involve pulling or pushing the PEG through the upper aerodigestive tract in patients with active cancer and instead place tubes via an external approach by colleagues in interventional radiology or via direct surgical placement.
 

Conclusion

Gastroenterologists occupy a unique role in evaluation, diagnosis, and management of patients requiring enteral feeding. In addition, they are best equipped to place, prevent, and manage complications of tube feeding. For this reason, it is imperative that gastroenterologists familiarize themselves with indications for enteral tubes and types of enteral tubes available, as well as the identification and management of common complications. Comprehensive understanding of these concepts will augment the practicing gastroenterologist’s ability to manage patients requiring enteral nutrition support with confidence.

References

1. Stein DJ et al. Dig Dis Sci. 2020 Jun 19. doi: 10.1007/s10620-020-06396-y.

2. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.

3. Dietrich CG, Schoppmeyer K. World J Gastroenterol. 2020;26(20):2464-71.

4. Suzuki Y et al. T Gastroenterology Res.2012 Feb;5(1):10-20.

5. Cheung KS et al. Gastroenterology. 2020 Jul;159(1):81-95.

6. Micic D et al. Am J Gastroenterol. 2020 Sep;115(9):1367-70.

7. Fan AC et al. Gastrointest Endosc. 2002;56(6):890-4.

8. Tang SJ. Video J Encycl GI Endosc. 2014;2(2):70-3.

9. Guenter P, Lyman B. Nutr Clin Pract. 2016;31(6):769-72.

10. Acosta RD et al. Gastrointest Endosc. 2016;83(1):3-16.

11. Richter JA et al. Gastrointest Endosc. 2011;74(1):22-34.

12. Boullata JI et al. JPEN. 2017;41(1):15-103.

13. McClave SA. Tech Gastrointest Endosc. 2021;3(1):62-8.

14. Murphy CJ et al. Endosc Int Open. 2016;4(3):E292. doi: 10.1053/tgie.2001.19915.

15. Lynch CR et al. Pract Gastroenterology. 2004;28:66-77.

16. Hucl T et al. Best Pract Res Clin Gastroenterol. 2016;30(5):769-81. doi: 10.1016/j.bpg.2016.10.002.

17. Jafri NS et al. Aliment Pharmacol & Therapeut. 2007;25(6):647-56. doi: 10.1111/j.1365-2036.2007.03247.x.

18. Blumenstein I et al. World J Gastroenterol. 2014;20(26):8505-24. doi: 10.3748/wjg.v20.i26.8505.

19. Fung E et al. Surgical Endosc. 2017;31(9):3623-7. doi: 10.1007/s00464-016-5394-8.

20. Ellrichmann M et al. Endoscopy. 2013;45(07):526-31. doi: 10.1055/s-0033-1344023.

Dr. Toy is with the department of internal medicine at the University of Utah, Salt Lake City. Dr. Fang is with the division of gastroenterology and hepatology at the University of Utah.

Introduction

Gastroenterologists are in a unique position to manage individuals with feeding tubes as their training underscores principles in digestion, absorption, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require a basic understanding of intestinal anatomy and physiology. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Indications for tube feeding

When deciding on the appropriate route for artificial nutrition support, the first decision to be made is enteral access versus parenteral nutrition support. Enteral nutrition confers multiple benefits, including preservation of the mucosal lining, reductions in complicated infections, decreased costs, and improved patient compliance. All attempts at adequate enteral access should be made before deciding on the use of parenteral nutrition. Following the clinical decision to pursue artificial means of nutrition support and enteral access, the next common decision is the anticipated duration of nutrition support. Generally, the oral or nasal tubes are used for short durations (i.e., less than 4 weeks) with percutaneous placement into the stomach or small intestine for longer-term feeding (i.e., percutaneous endoscopic gastrostomy [PEG] or percutaneous endoscopic jejunostomy [PEJ]).

The most general indication for nutrition support is an inability to maintain adequate nutritional needs with oral intake alone. General categories of inadequate oral intake include neurologic disorders, malignancy, and gastrointestinal conditions affecting digestion and absorption (Table 1). Absolute and relative contraindications to PEG placement are listed in Table 2. If an endoscopic placement is not possible, alternative means of placement (i.e., surgery or interventional radiology) can be considered to avoid the consequences of prolonged malnutrition. In-hospital mortality following PEG placement has decreased 40% over the last 10 years, which can be attributed to improved patient selection, enhanced discharge practices, and exclusion of patients with the highest comorbidity and mortality rates, like those with advanced dementia or terminal cancer.¹

PEG placement in patients with dementia is controversial, with previous studies not demonstrating improved outcomes and association with high mortality rates,² so the practice is currently not recommended by the American Geriatrics Society in individuals with advanced dementia.³ However, a large Japanese study showed that careful selection of patients with mild dementia to undergo gastrostomy increased independence fourfold; therefore, multidisciplinary involvement is often necessary in the decision to pursue artificial means of nutrition support in this population.⁴

The recent coronavirus disease 2019 (COVID-19) pandemic has placed additional strains on endoscopic placement and has highlighted the effect of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) on GI symptoms. A recent meta-analysis showed an overall incidence of GI symptoms of 17.6% in the following conditions in decreasing order of prevalence: anorexia, diarrhea, nausea, vomiting, and abdominal discomfort.⁵ In addition, the prolonged ventilatory requirements among a subset of individuals with the most severe COVID-19 results in extended periods of nutrition support via enteral tube placements. In individuals with ICU-acquired weakness and discharge to long-term care facilities, the placement of percutaneous endoscopic tubes may be required, although with the additional consideration of the need for an aerosolizing procedure. Delay of placement has been advocated, in addition to appropriate personal protective equipment, in order to ensure safe placement for the endoscopy staff.⁶
 

Types of feeding tubes

After deciding to feed a patient enterally and determining the anticipated duration of enteral support, the next decision is to determine the most appropriate location of feeding delivery: into the stomach or the small bowel. Gastric feeding is advantageous most commonly because of its increased capacity, allowing for larger volumes to be delivered over shorter durations. However, in the setting of postsurgical anatomy, gastroparesis, or obstructing tumors/pancreatic inflammation, distal delivery of tube feeds may be required into the jejunum. Additionally, percutaneous tubes placed into the stomach can have extenders into the small bowel (GJ tubes) to allow for feeding into the small bowel and decompression or delivery of medications into the stomach.

In general, gastric feeding is preferred over small bowel feeding as PEG tubes are more stable and have fewer complications than either PEG-J or direct PEJ tubes. Gastrostomy tubes are generally shorter and larger in diameter making them less likely to clog. PEG-J tubes have separate lumens for gastric and small intestinal access, but the smaller-bore jejunal extension tubes are more likely to clog or become dislodged. While direct PEJ is shown to have higher rates of tube patency and decreased rates of endoscopic re-intervention, compared with PEG-J,⁷ one limitation of a direct PEJ is difficulty in placement and site selection, which can be performed with a pediatric colonoscope or balloon enteroscopy system. Most commonly, this procedure is performed under general anesthesia.

In the case of a critically ill patient in the ICU, it is recommended to start enteral nutrition within 24-48 hours of arrival to avoid complications of prolonged calorie deficits. Nasally inserted feeding tubes (e.g., Cortrak, Avanos Medical Devices, Alpharetta, Ga.) are most commonly used at the bedside and can be placed blindly using electromagnetic image guidance, radiographically, or endoscopy. However, the small caliber of nasoenteric tubes comes with the common complication of clogging, which can be overcome with slightly larger bore gastric feeding tubes. If gastric feeding is not tolerated (e.g., in the case of vomiting, witnessed aspiration), small bowel feeding should be initiated and can be a more durable form of enteral feeding with fewer interruptions as feedings do not need to be held for procedures or symptomatic gastric intolerance. In clinical areas of question, or if there is a concern for intolerance of enteral feeding, a short trial with nasogastric or nasojejunal tube placement should be performed before a more definitive percutaneous placement.

With respect to percutaneous tubes, important characteristics to choose are the size (diameter in French units), type of internal retention device, and external appearance of the tube (standard or low profile). All percutaneous tubes contain an external retention device (i.e., bumper) that fits against the skin and an internal retention device that is either a balloon or plastic dome or funnel that prevents the tube from becoming dislodged. Balloon retention tubes require replacement every 3-6 months, while nonballoon tubes generally require replacement annually in order to prevent the plastic from cracking, which can make removal complicated. Low-profile tubes have an external cap, which, when opened, allows for extension tubing to be securely attached while in use and detached while not in use. Low-profile tubes are often preferred among younger, active patients and those with adequate dexterity to allow for attachment of the external extension tubing. These tubes are most often inserted as a replacement for an initially endoscopically placed tube, although one-step systems for initial placement are available. The size of the low-profile tube is chosen based on the size of the existing PEG tube and by measuring the length of the stoma tract using specialized measuring devices.⁸ Patients and caregivers can also be trained to replace balloon-type tubes on their own to limit complications of displaced or cracked tubes. Low-profile tubes are commercially available for both gastric placement and gastric placement with extension into the small bowel, which often requires fluoroscopy for secure placement.

All percutaneous enteral tubes are being transitioned to the ENfit connector system, which prevents connections from the enteral system to nonenteral systems (namely intravenous lines, chest tubes) and vice versa. Tubing misconnections have been rarely reported, and the EnFIT system is designed to prevent such misadventures that have resulted in serious complications and even mortality.⁹ Adapter devices are available that may be required for patients with feeding tubes who have not been transitioned yet. Most commonly with new tube placements and replacements, patients and providers will have to become familiar with the new syringes and feeding bags required with EnFIT connectors.

Gastrostomy placement can be considered a higher-risk endoscopic procedure. One complicating factor is the increased use of antiplatelet and anticoagulant therapies in individuals with a history of neurologic insults. The American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend that coumadin be held 5 days before the procedure and bridged with heparin if the patient is at high risk of thromboembolic complications. For patients on dual anti-platelet therapy, thienopyridines like clopidogrel are often stopped 5-7 days prior to procedure with continuation of aspirin,¹⁰ but there are more recent data that PEG insertion is safe with continued use of DAPT.¹¹ Direct-acting anticoagulants (DOACs) are often stopped 24-48 hours prior to procedure and then restarted 48 hours after tube placement, but this is dependent on the half-life of the specific DOAC and the patient’s renal function. Patients with decreased creatinine clearance may need to hold the DOAC up to 3-4 days prior to the procedure. In this situation, referring to ASGE guidelines and consultation with a hematologist or managing anti-coagulation clinic is advised.¹⁰
 

Troubleshooting complications

Nasoenteric tubes: One of the most common and irritating complications with nasoenteric feeding tubes is clogging. To prevent clogging, the tube should be flushed frequently.¹² At least 30 mL of free water should be used to flush the tube every 4-8 hours for continuous feedings or before and after bolus feeding. Additionally, 15-30 mL of water should be given with each separate medication administration, and if possible, medication administration via small-bore small bowel feeding tubes should be avoided.¹² Water flushing is especially important with small-caliber tubes and pumps that deliver both feeding and water flushes. It is available for small bowel feeding in order to allow for programmed water delivery.

Warm water flushes can also help unclog the tube,¹² and additional pharmacologic and mechanical devices have been promoted for clogged tubes. One common technique is mixing pancreatic enzymes (Viokase) with a crushed 325-mg tablet of nonenteric coated sodium bicarbonate and 5 mL of water to create a solution that has the alkaline properties allowing for both pancreatic enzyme activation and clog dissolution. Additionally, an endoscopic retrograde cholangiopancreatography (ERCP) catheter can be placed into longer feeding tubes to directly infuse the activated agent to the site of the clog.¹³ If water and enzymes are not successful in unclogging the tube, commercially available brushes can help remove clogs. The TubeClear® system (Actuated Medical, Bellefonte, Penna) has a single-use stem that is connected to AC power to create a jackhammerlike movement to remove clogs in longer nasoenteral and gastrojejunal tubes.
 

PEG tubes (short-term complications): Procedural and immediate postprocedural complications include bleeding, aspiration, pneumoperitoneum, and perforation. Pneumoperitoneum occurs in approximately 50% of cases and is generally clinically insignificant. The risk of pneumoperitoneum can be reduced by using CO2 insufflation.¹⁴ If the patient develops systemic signs of infection or peritoneal signs, CT scan with oral contrast is warranted for further evaluation and to assess for inadvertent perforation of overlying bowel or dislodged tube. Aspiration during or following endoscopy is another common complication of PEG placement and risk factors include over-sedation, supine positioning, advanced age, and neurologic dysfunction. This risk can be mitigated by avoiding over-sedation, immediately aspirating gastric contents when the stomach is reached, and avoiding excessive insufflation.¹⁵ In addition, elevating the head of the bed during the procedure and dedicating an assistant to perform oral suctioning during the entire procedure is recommended.

PEG tubes (long-term complications): More delayed complications of PEG insertion include wound infection, buried bumper syndrome, tumor seeding, peristomal leakage, and tube dislodgement. The prevalence of wound infection is 5%- 25%,¹⁶ and randomized controlled trials have demonstrated the efficacy of a single dose of an IV antibiotic (i.e., cephalosporin) in those not already receiving a broad spectrum antibiotic and administered prophylactically before tube placement.¹⁷ The significance of this reduction is such that antibiotic administration before tube placement should be considered a quality measure for the procedure. A small amount of redness around the tube site (less than 5 mm) is typical, but extension of erythema, warmth, tenderness, purulent drainage, or systemic symptoms is consistent with infection and warrants additional antibiotic administration. Minor infections can be treated with local antiseptics and oral antibiotics, and early intervention is important to prevent need for hospital admission, systemic antibiotics, and even surgical debridement.

Peristomal leakage is reported in approximately 1%-2% of patients.¹⁸ Photographs of the site can be very useful in evaluating and managing peristomal leakage and infections. Interventions include reducing gastric secretions with proton pump inhibitors and management of the skin with barrier creams, such as zinc oxide (Calmoseptine®) ointment. Placement of a larger-diameter tube only enlarges the stoma track and worsens the leakage. In such cases, thorough evaluations for delayed gastric emptying (gastroparesis), distal obstruction, or constipation should be performed and managed accordingly. Opiates are common contributors to constipation and delayed gastric emptying and often require reduction in use or directed antagonist therapy to reduce leaking. Continuous feeding over bolus feedings and delivering nutrition distally into the small bowel (PEG-J placement) can improve leaking from gastrostomy tubes. Additional means of management include stabilizing the tube by replacing a traditional tube with a low-profile tube or using right-angle external bumpers. If all measures fail, removing the tube and allowing for stomal closure can be attempted,¹⁶ although this option often requires parenteral nutrition support to prevent prolonged periods of inadequate nutrition.

Buried bumper syndrome (BBS) occurs in 1.5%-8.8% of PEG placements and is a common late complication of PEG placement, although early reports have been described.¹⁸ The development of BBS occurs when the internal bumper migrates from the gastric lumen through and into the stomach or abdominal wall. It occurs more frequently with solid nonballoon retention tubes and is caused by excessive compression of the external bumper against the skin and abdominal wall. Patients with BBS usually present with an immobile catheter, resistance with feeds (because of a closure of the stomach wall around the internal portion of the gastrostomy tube), abdominal pain, or peristomal leakage. Physicians should be aware of and assess tubes for BBS, in particular when replacing an immobile tube (cannot be pushed into the free stomach lumen) or when there is difficulty in flushing water into the tube. This complication can be easily prevented by allowing a minimum of 0.5-1.0 cm (1 finger breadth) between the external bumper and the abdominal wall. In particular, patients and caregivers should be warned that if the patient gains significant amounts of weight, the outer bumper will need to be loosened. Once BBS is diagnosed, the PEG tube requires removal and replacement as it can cause bleeding, infection, or fasciitis. The general steps to replacement include endoscopic removal of the existing tube and replacement of new PEG in the existing tract as long as the BBS is not severe. In most cases a replacement tube can be pulled into place using the pull-PEG technique at the same gastrostomy site as long as the stoma tract can be cannulated with a wire after the existing tube is removed.

Similar to nasoenteric tubes, PEG tubes can become clogged, although this complication is infrequent. The primary steps for prevention include adequately flushing with water before and after feeds and ensuring that all medications are liquid or well crushed and dissolved before instilling. Timely tube replacement also ensures that the internal portions of the gastrostomy tube remain free of debris. Management is similar to that of unclogging nasoenteral tubes, as discussed above, and specific commercial declogging devices for PEG tubes include the Bionix Declogger® (Bionix Development Corp., Toledo, Ohio) and the Bard® PEG cleaning brush (Bard Peripheral Vascular Inc., Tempe, Ariz.). The Bionix system has a plastic stem with a screw and thread design that will remove clogs in 14-24 French PEG tubes, while the Bard brush has a flexible nylon stem with soft bristles at the end to prevent mucosal injury and can be used for prophylaxis against clogs, as well as removing clogs themselves.¹²

Lastly, a rare but important complication of PEG placement is tumor seeding of the PEG site in patients with active head and neck or upper gastrointestinal cancer.¹⁹ The presumed mechanism is shearing of tumor cells as the PEG is pulled through the upper aerodigestive tract and through the wall of the stomach, as prior studies have demonstrated frequent seeding of tubes and incision sites as shown by brushing the tube for malignant cells after tube placement.²⁰ It is important to recognize this complication and not misdiagnose it as granulation tissue, infection, or bleeding as the spread of the cancer generally portends a poor prognosis. Therefore, it is best to use a PEG insertion technique that does not involve pulling or pushing the PEG through the upper aerodigestive tract in patients with active cancer and instead place tubes via an external approach by colleagues in interventional radiology or via direct surgical placement.
 

Conclusion

Gastroenterologists occupy a unique role in evaluation, diagnosis, and management of patients requiring enteral feeding. In addition, they are best equipped to place, prevent, and manage complications of tube feeding. For this reason, it is imperative that gastroenterologists familiarize themselves with indications for enteral tubes and types of enteral tubes available, as well as the identification and management of common complications. Comprehensive understanding of these concepts will augment the practicing gastroenterologist’s ability to manage patients requiring enteral nutrition support with confidence.

References

1. Stein DJ et al. Dig Dis Sci. 2020 Jun 19. doi: 10.1007/s10620-020-06396-y.

2. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.

3. Dietrich CG, Schoppmeyer K. World J Gastroenterol. 2020;26(20):2464-71.

4. Suzuki Y et al. T Gastroenterology Res.2012 Feb;5(1):10-20.

5. Cheung KS et al. Gastroenterology. 2020 Jul;159(1):81-95.

6. Micic D et al. Am J Gastroenterol. 2020 Sep;115(9):1367-70.

7. Fan AC et al. Gastrointest Endosc. 2002;56(6):890-4.

8. Tang SJ. Video J Encycl GI Endosc. 2014;2(2):70-3.

9. Guenter P, Lyman B. Nutr Clin Pract. 2016;31(6):769-72.

10. Acosta RD et al. Gastrointest Endosc. 2016;83(1):3-16.

11. Richter JA et al. Gastrointest Endosc. 2011;74(1):22-34.

12. Boullata JI et al. JPEN. 2017;41(1):15-103.

13. McClave SA. Tech Gastrointest Endosc. 2021;3(1):62-8.

14. Murphy CJ et al. Endosc Int Open. 2016;4(3):E292. doi: 10.1053/tgie.2001.19915.

15. Lynch CR et al. Pract Gastroenterology. 2004;28:66-77.

16. Hucl T et al. Best Pract Res Clin Gastroenterol. 2016;30(5):769-81. doi: 10.1016/j.bpg.2016.10.002.

17. Jafri NS et al. Aliment Pharmacol & Therapeut. 2007;25(6):647-56. doi: 10.1111/j.1365-2036.2007.03247.x.

18. Blumenstein I et al. World J Gastroenterol. 2014;20(26):8505-24. doi: 10.3748/wjg.v20.i26.8505.

19. Fung E et al. Surgical Endosc. 2017;31(9):3623-7. doi: 10.1007/s00464-016-5394-8.

20. Ellrichmann M et al. Endoscopy. 2013;45(07):526-31. doi: 10.1055/s-0033-1344023.

Dr. Toy is with the department of internal medicine at the University of Utah, Salt Lake City. Dr. Fang is with the division of gastroenterology and hepatology at the University of Utah.

When starting a career in gastroenterology, physicians tend to work in the hospital, where there is usually high demand for services and productivity goals are easy to meet. This is a little different in private GI groups, where it takes some time to build up your patient base. This might be a significant concern for young physicians considering private practice. But understanding the role that productivity plays in compensation packages can help in choosing the right group to join.

While compensation models may differ from practice to practice, there is usually a base salary provided with a productivity bonus. Some practices may use productivity along with other measures to determine when a physician is eligible to become a partner in the practice. Partnership is often accompanied with the benefits of ancillary services ownership such as ambulatory surgery centers (ASCs) and anesthesia, pathology, and infusion services.

How is productivity measured?

Most practices utilize relative value units (RVUs), a standard used by Medicare to determine the amount to pay physicians according to their productivity. Most public and private payers are utilizing the RVU system first developed for Medicare as a useful, time-saving way to handle physician payments. The RVU defines the volume of work doctors perform for all procedures and services covered under the Medicare Physician Fee Schedule.

The Medicare Physician Payment System has three components:

• The geographic practice cost indices (GPCIs)

• Relative value units (RVUs)

• A conversion factor

It is important to understand the types of RVUs that exist to understand how to calculate them properly – these include the following categories:

• Physician work, which accounts for the time and effort to perform a procedure.

• Practice expense, which is for the costs of nonphysician labor such as rent and supplies.

• Global fees, which includes fees for initial visits, follow-ups, and practice expense, and applies during a predetermined length of time known as the “global periods,” primarily for major surgeries.

• Malpractice expense, such as costs for professional liability insurance.

There is no specific dollar amount attached to an RVU because RVUs are part of a resource-based relative value scale (RBRVS) which uses RVUs to relate medical procedures to each other. Payment for physician work is based on whether the procedure is performed in an ASC or hospital outpatient department or in an office. A separate facility fee payment is made to the ASC or hospital outpatient department for procedures performed there. Other elements include skills and the amount of time needed to perform a procedure. Calculating the reimbursement from an RVU involves several components and a significant amount of complex math.

Meeting goals while building a practice

For many young physicians working in the hospital where patients are plentiful, it might seem daunting to build your practice with productivity goals. Practices should, and many do, design their initial productivity plans to minimum or mean RVUs for young physicians rather than someone 10 years into practice. Younger physicians have fellowship and training, but it takes years to become highly efficient with time and productivity. It’s important for everyone involved to set attainable benchmarks.

The practice should also do its best to support your efforts to grow your patient base. While you should be expected to develop relationships with referring physicians, you’ll benefit from the practice’s marketing efforts. When new patients come in, they usually go to newly hired physicians because more senior physicians are booked weeks or months in advance.

Practice administrators also work hard to time new hires to overlap with expected retirements. Senior partners will always have follow-up colonoscopies and associates will need to take on these cases as their colleagues retire. In some practices, younger physicians are expected to take the hospital on call schedules or respond to emergency department calls, so it shouldn’t be difficult to meet productivity goals.

And once you become a partner and are further along on in your career, your productivity plan will change. Some groups have productivity-based compensation, which allows more senior partners to work when they want to – as long as they are meeting the productivity rates that will cover their portion of the practice expenses.

If a physician is consistently not meeting productivity measures, a practice may exercise the right to terminate the relationship, but this is rare. More often, physicians meet their productivity levels and receive certain bonuses for exceeding their goals. In most practices, the partners you work with will know if you aren’t meeting your goals. In most cases, they will take on a mentorship role to help you succeed.
 

Ask questions, be engaged

Another thing to be aware of is that all practices worth joining make sure productivity plans do not violate the Stark Law, anti-kickback statutes, or other regulations. A huge red flag to look out for is a productivity plan that is based on the number of procedures – it should never be tied to volume.

It’s also best to consider how often the productivity plan is measured. It might be a red flag if it is measured weekly or monthly or if there are heavy consequences for not meeting RVU goals. Most groups look at productivity on a quarterly basis and integrate those discussions into a standard review process.

The successful early-career GIs we interview in our practices are those who are interested in understanding the ins and outs of our practices and what they can achieve through practicing independently. The practices worth joining will likewise be interested in discussing your level of entrepreneurship, the opportunities for you to grow in your career, and what it takes to be on the track to partner.
 

Dr. Baig is a practicing gastroenterologist at Allied Digestive Care in New Jersey and is the chair of communications for the Digestive Health Physicians Association (DHPA); Mr. Harlen is the president of PE Practice Solutions and immediate past chief operating officer of Capital Digestive Care in Maryland. He is the executive director of DHPA.

When starting a career in gastroenterology, physicians tend to work in the hospital, where there is usually high demand for services and productivity goals are easy to meet. This is a little different in private GI groups, where it takes some time to build up your patient base. This might be a significant concern for young physicians considering private practice. But understanding the role that productivity plays in compensation packages can help in choosing the right group to join.

While compensation models may differ from practice to practice, there is usually a base salary provided with a productivity bonus. Some practices may use productivity along with other measures to determine when a physician is eligible to become a partner in the practice. Partnership is often accompanied with the benefits of ancillary services ownership such as ambulatory surgery centers (ASCs) and anesthesia, pathology, and infusion services.

How is productivity measured?

Most practices utilize relative value units (RVUs), a standard used by Medicare to determine the amount to pay physicians according to their productivity. Most public and private payers are utilizing the RVU system first developed for Medicare as a useful, time-saving way to handle physician payments. The RVU defines the volume of work doctors perform for all procedures and services covered under the Medicare Physician Fee Schedule.

The Medicare Physician Payment System has three components:

• The geographic practice cost indices (GPCIs)

• Relative value units (RVUs)

• A conversion factor

It is important to understand the types of RVUs that exist to understand how to calculate them properly – these include the following categories:

• Physician work, which accounts for the time and effort to perform a procedure.

• Practice expense, which is for the costs of nonphysician labor such as rent and supplies.

• Global fees, which includes fees for initial visits, follow-ups, and practice expense, and applies during a predetermined length of time known as the “global periods,” primarily for major surgeries.

• Malpractice expense, such as costs for professional liability insurance.

There is no specific dollar amount attached to an RVU because RVUs are part of a resource-based relative value scale (RBRVS) which uses RVUs to relate medical procedures to each other. Payment for physician work is based on whether the procedure is performed in an ASC or hospital outpatient department or in an office. A separate facility fee payment is made to the ASC or hospital outpatient department for procedures performed there. Other elements include skills and the amount of time needed to perform a procedure. Calculating the reimbursement from an RVU involves several components and a significant amount of complex math.

Meeting goals while building a practice

For many young physicians working in the hospital where patients are plentiful, it might seem daunting to build your practice with productivity goals. Practices should, and many do, design their initial productivity plans to minimum or mean RVUs for young physicians rather than someone 10 years into practice. Younger physicians have fellowship and training, but it takes years to become highly efficient with time and productivity. It’s important for everyone involved to set attainable benchmarks.

The practice should also do its best to support your efforts to grow your patient base. While you should be expected to develop relationships with referring physicians, you’ll benefit from the practice’s marketing efforts. When new patients come in, they usually go to newly hired physicians because more senior physicians are booked weeks or months in advance.

Practice administrators also work hard to time new hires to overlap with expected retirements. Senior partners will always have follow-up colonoscopies and associates will need to take on these cases as their colleagues retire. In some practices, younger physicians are expected to take the hospital on call schedules or respond to emergency department calls, so it shouldn’t be difficult to meet productivity goals.

And once you become a partner and are further along on in your career, your productivity plan will change. Some groups have productivity-based compensation, which allows more senior partners to work when they want to – as long as they are meeting the productivity rates that will cover their portion of the practice expenses.

If a physician is consistently not meeting productivity measures, a practice may exercise the right to terminate the relationship, but this is rare. More often, physicians meet their productivity levels and receive certain bonuses for exceeding their goals. In most practices, the partners you work with will know if you aren’t meeting your goals. In most cases, they will take on a mentorship role to help you succeed.
 

Ask questions, be engaged

Another thing to be aware of is that all practices worth joining make sure productivity plans do not violate the Stark Law, anti-kickback statutes, or other regulations. A huge red flag to look out for is a productivity plan that is based on the number of procedures – it should never be tied to volume.

It’s also best to consider how often the productivity plan is measured. It might be a red flag if it is measured weekly or monthly or if there are heavy consequences for not meeting RVU goals. Most groups look at productivity on a quarterly basis and integrate those discussions into a standard review process.

The successful early-career GIs we interview in our practices are those who are interested in understanding the ins and outs of our practices and what they can achieve through practicing independently. The practices worth joining will likewise be interested in discussing your level of entrepreneurship, the opportunities for you to grow in your career, and what it takes to be on the track to partner.
 

Dr. Baig is a practicing gastroenterologist at Allied Digestive Care in New Jersey and is the chair of communications for the Digestive Health Physicians Association (DHPA); Mr. Harlen is the president of PE Practice Solutions and immediate past chief operating officer of Capital Digestive Care in Maryland. He is the executive director of DHPA.

When starting a career in gastroenterology, physicians tend to work in the hospital, where there is usually high demand for services and productivity goals are easy to meet. This is a little different in private GI groups, where it takes some time to build up your patient base. This might be a significant concern for young physicians considering private practice. But understanding the role that productivity plays in compensation packages can help in choosing the right group to join.

While compensation models may differ from practice to practice, there is usually a base salary provided with a productivity bonus. Some practices may use productivity along with other measures to determine when a physician is eligible to become a partner in the practice. Partnership is often accompanied with the benefits of ancillary services ownership such as ambulatory surgery centers (ASCs) and anesthesia, pathology, and infusion services.

How is productivity measured?

Most practices utilize relative value units (RVUs), a standard used by Medicare to determine the amount to pay physicians according to their productivity. Most public and private payers are utilizing the RVU system first developed for Medicare as a useful, time-saving way to handle physician payments. The RVU defines the volume of work doctors perform for all procedures and services covered under the Medicare Physician Fee Schedule.

The Medicare Physician Payment System has three components:

• The geographic practice cost indices (GPCIs)

• Relative value units (RVUs)

• A conversion factor

It is important to understand the types of RVUs that exist to understand how to calculate them properly – these include the following categories:

• Physician work, which accounts for the time and effort to perform a procedure.

• Practice expense, which is for the costs of nonphysician labor such as rent and supplies.

• Global fees, which includes fees for initial visits, follow-ups, and practice expense, and applies during a predetermined length of time known as the “global periods,” primarily for major surgeries.

• Malpractice expense, such as costs for professional liability insurance.

There is no specific dollar amount attached to an RVU because RVUs are part of a resource-based relative value scale (RBRVS) which uses RVUs to relate medical procedures to each other. Payment for physician work is based on whether the procedure is performed in an ASC or hospital outpatient department or in an office. A separate facility fee payment is made to the ASC or hospital outpatient department for procedures performed there. Other elements include skills and the amount of time needed to perform a procedure. Calculating the reimbursement from an RVU involves several components and a significant amount of complex math.

Meeting goals while building a practice

For many young physicians working in the hospital where patients are plentiful, it might seem daunting to build your practice with productivity goals. Practices should, and many do, design their initial productivity plans to minimum or mean RVUs for young physicians rather than someone 10 years into practice. Younger physicians have fellowship and training, but it takes years to become highly efficient with time and productivity. It’s important for everyone involved to set attainable benchmarks.

The practice should also do its best to support your efforts to grow your patient base. While you should be expected to develop relationships with referring physicians, you’ll benefit from the practice’s marketing efforts. When new patients come in, they usually go to newly hired physicians because more senior physicians are booked weeks or months in advance.

Practice administrators also work hard to time new hires to overlap with expected retirements. Senior partners will always have follow-up colonoscopies and associates will need to take on these cases as their colleagues retire. In some practices, younger physicians are expected to take the hospital on call schedules or respond to emergency department calls, so it shouldn’t be difficult to meet productivity goals.

And once you become a partner and are further along on in your career, your productivity plan will change. Some groups have productivity-based compensation, which allows more senior partners to work when they want to – as long as they are meeting the productivity rates that will cover their portion of the practice expenses.

If a physician is consistently not meeting productivity measures, a practice may exercise the right to terminate the relationship, but this is rare. More often, physicians meet their productivity levels and receive certain bonuses for exceeding their goals. In most practices, the partners you work with will know if you aren’t meeting your goals. In most cases, they will take on a mentorship role to help you succeed.
 

Ask questions, be engaged

Another thing to be aware of is that all practices worth joining make sure productivity plans do not violate the Stark Law, anti-kickback statutes, or other regulations. A huge red flag to look out for is a productivity plan that is based on the number of procedures – it should never be tied to volume.

It’s also best to consider how often the productivity plan is measured. It might be a red flag if it is measured weekly or monthly or if there are heavy consequences for not meeting RVU goals. Most groups look at productivity on a quarterly basis and integrate those discussions into a standard review process.

The successful early-career GIs we interview in our practices are those who are interested in understanding the ins and outs of our practices and what they can achieve through practicing independently. The practices worth joining will likewise be interested in discussing your level of entrepreneurship, the opportunities for you to grow in your career, and what it takes to be on the track to partner.
 

Dr. Baig is a practicing gastroenterologist at Allied Digestive Care in New Jersey and is the chair of communications for the Digestive Health Physicians Association (DHPA); Mr. Harlen is the president of PE Practice Solutions and immediate past chief operating officer of Capital Digestive Care in Maryland. He is the executive director of DHPA.

Ceftolozane-tazobactam (C/T) was found effective for treating pneumonia, intra-abdominal, and urinary tract infections caused by Pseudomonas aeruginosa, according to the results of a retrospective, observational study conducted in critically ill patients.

The multicenter, observational study assessed 95 patients who received C/T for P. aeruginosa serious infections, according to a report published online in the International Journal of Antimicrobial Agents.

C/T is a novel beta-lactam/ beta-lactamase inhibitor combination active against gram-negative bacteria including P. aeruginosa, “This paper presents the largest real-life experience published on C/T therapy for treating serious P. aeruginosa infections according to researchers Barbara Balandin, MD, of the Hospital Universitario Puerta de Hierro, Majadahonda, Spain, and colleagues.

The main infections treated were nosocomial pneumonia (56.2%), intra-abdominal infection (10.5%), tracheobronchitis (8.4%), and urinary tract infection (6.3%). Most infections were complicated with sepsis (49.5%) or septic shock (45.3%), and bacteremia (10.5%).

A total of 46 episodes were treated with high-dose C/T (3 g every 8 hours), and 38 episodes were treated with standard dosage (1.5 g every 8 hours). Almost half (44.2%) of the patients were treated with C/T monotherapy, and the remaining group received combination therapy with other antibiotics, according to the researchers.

The primary outcome of the study was to assess the efficacy and toxicity of C/T therapy. The secondary outcome was to evaluate the risk factors for all-cause 30-day mortality from the first day of therapy.

Favorable results

Most of the infections (93.7%) were severe and included the presence of sepsis (49.5%) or septic shock (45.3%). Bacteremia was observed in 15 (15.7%) patients. Bacteremia was secondary to nosocomial pneumonia in eight cases, catheter infection in five, urinary tract infection in one, and soft tissue infection in one. According to their susceptibility profiles, 46 (48.4%) of the strains were classified as extensively drug-resistant (XDR) P. aeruginosa and 35 (36.5%) were multidrug-resistant (MDR) P. aeruginosa.

Sixty-eight (71.6%) patients presented a favorable clinical response, which was defined as a resolution of presenting symptoms and signs of the infection by the end of therapy. An unfavorable clinical response was considered as persistence or worsening of the presenting symptoms and signs or death occurring during treatment with no other cause identified. Death associated with infection was defined as persistence of signs and symptoms of P. aeruginosa infection during C/T therapy with no other cause identified.

Microbiological eradication was documented in 42.1% (40/95) of the episodes. However, the global ICU mortality was still high, at 36.5%, with mortality mainly related to the severity of the infection.

Mortality was found to be significantly correlated with the Charlson Comorbidity Index (5.7 vs. 4.3; P = .04) and the need for life-supporting therapies such as vasopressors (66.6% vs. 46.9%; P = .03) and renal replacement therapy (46.6% vs. 18.1%; P = .002). In addition, mortality was significantly associated with a higher sequential organ failure assessment (SOFA) score during C/T therapy (SOFA1, SOFA 3, and SOFA 7; P < .001).

No significant differences in outcomes were correlated with demographic features, type and severity of infection, and dose of C/T. Also, there were no differences seen in outcomes between patients treated with C/T monotherapy and combined therapy (30.9% vs. 30.1%; P = .55).

“The lack of a positive effect from combined therapy suggests that C/T monotherapy may be sufficient for treating P. aeruginosa isolates that are susceptible to that agent,” the researchers suggested. “This study shows that C/T appears to be a suitable, effective, and safe drug for treating severe infections due to P. aeruginosa, highlighting nosocomial pneumonia caused by MDR/XDR P. aeruginosa in ICU patients with multiple comorbidities, such as immunosuppression, and needing life-sustaining therapies,” they concluded.

The authors reported that they had no outside funding source and had no conflicts of interest.

[email protected]

Ceftolozane-tazobactam (C/T) was found effective for treating pneumonia, intra-abdominal, and urinary tract infections caused by Pseudomonas aeruginosa, according to the results of a retrospective, observational study conducted in critically ill patients.

The multicenter, observational study assessed 95 patients who received C/T for P. aeruginosa serious infections, according to a report published online in the International Journal of Antimicrobial Agents.

C/T is a novel beta-lactam/ beta-lactamase inhibitor combination active against gram-negative bacteria including P. aeruginosa, “This paper presents the largest real-life experience published on C/T therapy for treating serious P. aeruginosa infections according to researchers Barbara Balandin, MD, of the Hospital Universitario Puerta de Hierro, Majadahonda, Spain, and colleagues.

The main infections treated were nosocomial pneumonia (56.2%), intra-abdominal infection (10.5%), tracheobronchitis (8.4%), and urinary tract infection (6.3%). Most infections were complicated with sepsis (49.5%) or septic shock (45.3%), and bacteremia (10.5%).

A total of 46 episodes were treated with high-dose C/T (3 g every 8 hours), and 38 episodes were treated with standard dosage (1.5 g every 8 hours). Almost half (44.2%) of the patients were treated with C/T monotherapy, and the remaining group received combination therapy with other antibiotics, according to the researchers.

The primary outcome of the study was to assess the efficacy and toxicity of C/T therapy. The secondary outcome was to evaluate the risk factors for all-cause 30-day mortality from the first day of therapy.

Favorable results

Most of the infections (93.7%) were severe and included the presence of sepsis (49.5%) or septic shock (45.3%). Bacteremia was observed in 15 (15.7%) patients. Bacteremia was secondary to nosocomial pneumonia in eight cases, catheter infection in five, urinary tract infection in one, and soft tissue infection in one. According to their susceptibility profiles, 46 (48.4%) of the strains were classified as extensively drug-resistant (XDR) P. aeruginosa and 35 (36.5%) were multidrug-resistant (MDR) P. aeruginosa.

Sixty-eight (71.6%) patients presented a favorable clinical response, which was defined as a resolution of presenting symptoms and signs of the infection by the end of therapy. An unfavorable clinical response was considered as persistence or worsening of the presenting symptoms and signs or death occurring during treatment with no other cause identified. Death associated with infection was defined as persistence of signs and symptoms of P. aeruginosa infection during C/T therapy with no other cause identified.

Microbiological eradication was documented in 42.1% (40/95) of the episodes. However, the global ICU mortality was still high, at 36.5%, with mortality mainly related to the severity of the infection.

Mortality was found to be significantly correlated with the Charlson Comorbidity Index (5.7 vs. 4.3; P = .04) and the need for life-supporting therapies such as vasopressors (66.6% vs. 46.9%; P = .03) and renal replacement therapy (46.6% vs. 18.1%; P = .002). In addition, mortality was significantly associated with a higher sequential organ failure assessment (SOFA) score during C/T therapy (SOFA1, SOFA 3, and SOFA 7; P < .001).

No significant differences in outcomes were correlated with demographic features, type and severity of infection, and dose of C/T. Also, there were no differences seen in outcomes between patients treated with C/T monotherapy and combined therapy (30.9% vs. 30.1%; P = .55).

“The lack of a positive effect from combined therapy suggests that C/T monotherapy may be sufficient for treating P. aeruginosa isolates that are susceptible to that agent,” the researchers suggested. “This study shows that C/T appears to be a suitable, effective, and safe drug for treating severe infections due to P. aeruginosa, highlighting nosocomial pneumonia caused by MDR/XDR P. aeruginosa in ICU patients with multiple comorbidities, such as immunosuppression, and needing life-sustaining therapies,” they concluded.

The authors reported that they had no outside funding source and had no conflicts of interest.

[email protected]

Ceftolozane-tazobactam (C/T) was found effective for treating pneumonia, intra-abdominal, and urinary tract infections caused by Pseudomonas aeruginosa, according to the results of a retrospective, observational study conducted in critically ill patients.

The multicenter, observational study assessed 95 patients who received C/T for P. aeruginosa serious infections, according to a report published online in the International Journal of Antimicrobial Agents.

C/T is a novel beta-lactam/ beta-lactamase inhibitor combination active against gram-negative bacteria including P. aeruginosa, “This paper presents the largest real-life experience published on C/T therapy for treating serious P. aeruginosa infections according to researchers Barbara Balandin, MD, of the Hospital Universitario Puerta de Hierro, Majadahonda, Spain, and colleagues.

The main infections treated were nosocomial pneumonia (56.2%), intra-abdominal infection (10.5%), tracheobronchitis (8.4%), and urinary tract infection (6.3%). Most infections were complicated with sepsis (49.5%) or septic shock (45.3%), and bacteremia (10.5%).

A total of 46 episodes were treated with high-dose C/T (3 g every 8 hours), and 38 episodes were treated with standard dosage (1.5 g every 8 hours). Almost half (44.2%) of the patients were treated with C/T monotherapy, and the remaining group received combination therapy with other antibiotics, according to the researchers.

The primary outcome of the study was to assess the efficacy and toxicity of C/T therapy. The secondary outcome was to evaluate the risk factors for all-cause 30-day mortality from the first day of therapy.

Favorable results

Most of the infections (93.7%) were severe and included the presence of sepsis (49.5%) or septic shock (45.3%). Bacteremia was observed in 15 (15.7%) patients. Bacteremia was secondary to nosocomial pneumonia in eight cases, catheter infection in five, urinary tract infection in one, and soft tissue infection in one. According to their susceptibility profiles, 46 (48.4%) of the strains were classified as extensively drug-resistant (XDR) P. aeruginosa and 35 (36.5%) were multidrug-resistant (MDR) P. aeruginosa.

Sixty-eight (71.6%) patients presented a favorable clinical response, which was defined as a resolution of presenting symptoms and signs of the infection by the end of therapy. An unfavorable clinical response was considered as persistence or worsening of the presenting symptoms and signs or death occurring during treatment with no other cause identified. Death associated with infection was defined as persistence of signs and symptoms of P. aeruginosa infection during C/T therapy with no other cause identified.

Microbiological eradication was documented in 42.1% (40/95) of the episodes. However, the global ICU mortality was still high, at 36.5%, with mortality mainly related to the severity of the infection.

Mortality was found to be significantly correlated with the Charlson Comorbidity Index (5.7 vs. 4.3; P = .04) and the need for life-supporting therapies such as vasopressors (66.6% vs. 46.9%; P = .03) and renal replacement therapy (46.6% vs. 18.1%; P = .002). In addition, mortality was significantly associated with a higher sequential organ failure assessment (SOFA) score during C/T therapy (SOFA1, SOFA 3, and SOFA 7; P < .001).

No significant differences in outcomes were correlated with demographic features, type and severity of infection, and dose of C/T. Also, there were no differences seen in outcomes between patients treated with C/T monotherapy and combined therapy (30.9% vs. 30.1%; P = .55).

“The lack of a positive effect from combined therapy suggests that C/T monotherapy may be sufficient for treating P. aeruginosa isolates that are susceptible to that agent,” the researchers suggested. “This study shows that C/T appears to be a suitable, effective, and safe drug for treating severe infections due to P. aeruginosa, highlighting nosocomial pneumonia caused by MDR/XDR P. aeruginosa in ICU patients with multiple comorbidities, such as immunosuppression, and needing life-sustaining therapies,” they concluded.

The authors reported that they had no outside funding source and had no conflicts of interest.

[email protected]

Even in the most experienced hands, dermoscopy poses a challenge when the usual pigment clues are lacking to help distinguish melanoma from amelanotic melanoma and pigmented basal cell carcinoma (BCC) from nonpigmented BCC.

Copyright Dr. Jennifer A. Stein

“For me, pink lesions are challenging,” Jennifer A. Stein, MD, PhD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference. “How can dermoscopy help us distinguish between Spitz nevus, melanoma, clear cell acanthoma, psoriasis, basal cell carcinoma, and squamous cell carcinoma?”

Dr. Stein, professor of dermatology at New York University, offered four tips. First, look for the shiny white perpendicular lines, otherwise known as the chrysalis or crystalline pattern. “You can only see this feature when you’re looking with polarized light,” she said. “This is why you want a dermatoscope that has polarized light, and better yet, one that you’re able to turn on and off, the hybrid kind, because then you can convince yourself that you’re looking at this feature, because it blinks on and off.”

The differential diagnosis for white shiny perpendicular lines includes dermatofibroma/scars (which is most common), Spitz and atypical genital nevi, BCC, and melanoma. “Dermatofibromas sometimes have white circles or rings in the center,” Dr. Stein said. “In BCC, the lines aren’t always perpendicular. Sometimes it’s more of a blotch or strands.”

A second tip for managing a pink lesion on dermoscopy is to look for any brown color. “When you see that combo together you have to worry,” she said. “When you see pigment network on dermoscopy, you have to put melanoma in your differential. If you see shiny white lines in something that is melanocytic, there’s a 98% specificity for melanoma.”

A third tip she offered for managing pink lesions is to check the blood vessels for clues. “For years, I was just naming the vessels based on making the diagnosis and then deciding, ‘that’s a basal cell carcinoma; those must be branching vessels,’ ” said Dr. Stein, who manages NYU’s medical dermatology faculty group practice.

However, blood vessel patterns differ. For example, branching or arborizing vessels are suggestive of BCC. “These vessels are very crisp-looking on dermoscopy,” she said. “They’re all in the same plane of focus and they look like they were drawn in with a fine point marker. That’s different from other blood vessel patterns.” She also pointed out that superficial basal cells have short, fine telangiectasias. “When you put on the polarized light, the clue is the white, shiny structures,” she said.

Dotted vessels, meanwhile, appear on dermoscopy as small red dots aligned perpendicular to the skin surface. The differential includes inflammatory lesions like psoriasis, stasis, and trauma; clear cell acanthoma (characterized by a “string of pearls” arrangement), nevi, and melanoma. “I find dermoscopy most useful in diagnosing SCC – especially squamous cell in situ,” she said. “Important clinical clues suggestive of SCC or melanoma include a solitary lesion, it’s new, it’s growing, and it’s not going away with a topical steroid.”

An additional pattern to be aware of are hairpin vessels, which are looped and feature a sharp bend at one end. These are often seen in seborrheic keratoses. “You can’t count on the hairpin vessels alone, because you can see this in anything keratotic, such as in keratoacanthoma (at the periphery with a yellow keratotic center), warts, SCC, BCC, as well as in dermal nevi and Spitz nevi,” said Dr. Stein, who recommended dermoscopedia.org as resource.

Comma vessels, meanwhile, appear in dermal or compound nevi. She described these as “slightly curved vessels that are much less in focus than branched vessels, because they come in and out of the plane of focus,” she said. “If you put your dermatoscope on top of the nevus and wobble it around you can appreciate the curve. If you look at it from the side, it looks like a curve. If you look at it straight on it will look more like a line. If you look at from the end it will look like a dot.”

Another vessel type she discussed are linear irregular and polymorphous vessels, which she described as “any combination of different types of vessels. We get most worried when we see dotted and linear irregular vessels together. In that case, you worry about melanoma. These can also be seen in nevi and other tumors, such as BCC.”

Dr. Stein’s fourth tip of the presentation was a reminder to consider dermoscopy as one piece of the clinical exam. “Always think about the lesion in context of the rest of the clinical picture and history,” she said. “Don’t get discouraged if it’s hard; just keep practicing. Look for any brown and use your clinical clues to put together to make the right decision.”

She disclosed that NYU receives compensation from MoleSafe for her telemedicine dermoscopic diagnoses.

[email protected]

Even in the most experienced hands, dermoscopy poses a challenge when the usual pigment clues are lacking to help distinguish melanoma from amelanotic melanoma and pigmented basal cell carcinoma (BCC) from nonpigmented BCC.

Copyright Dr. Jennifer A. Stein

“For me, pink lesions are challenging,” Jennifer A. Stein, MD, PhD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference. “How can dermoscopy help us distinguish between Spitz nevus, melanoma, clear cell acanthoma, psoriasis, basal cell carcinoma, and squamous cell carcinoma?”

Dr. Stein, professor of dermatology at New York University, offered four tips. First, look for the shiny white perpendicular lines, otherwise known as the chrysalis or crystalline pattern. “You can only see this feature when you’re looking with polarized light,” she said. “This is why you want a dermatoscope that has polarized light, and better yet, one that you’re able to turn on and off, the hybrid kind, because then you can convince yourself that you’re looking at this feature, because it blinks on and off.”

The differential diagnosis for white shiny perpendicular lines includes dermatofibroma/scars (which is most common), Spitz and atypical genital nevi, BCC, and melanoma. “Dermatofibromas sometimes have white circles or rings in the center,” Dr. Stein said. “In BCC, the lines aren’t always perpendicular. Sometimes it’s more of a blotch or strands.”

A second tip for managing a pink lesion on dermoscopy is to look for any brown color. “When you see that combo together you have to worry,” she said. “When you see pigment network on dermoscopy, you have to put melanoma in your differential. If you see shiny white lines in something that is melanocytic, there’s a 98% specificity for melanoma.”

A third tip she offered for managing pink lesions is to check the blood vessels for clues. “For years, I was just naming the vessels based on making the diagnosis and then deciding, ‘that’s a basal cell carcinoma; those must be branching vessels,’ ” said Dr. Stein, who manages NYU’s medical dermatology faculty group practice.

However, blood vessel patterns differ. For example, branching or arborizing vessels are suggestive of BCC. “These vessels are very crisp-looking on dermoscopy,” she said. “They’re all in the same plane of focus and they look like they were drawn in with a fine point marker. That’s different from other blood vessel patterns.” She also pointed out that superficial basal cells have short, fine telangiectasias. “When you put on the polarized light, the clue is the white, shiny structures,” she said.

Dotted vessels, meanwhile, appear on dermoscopy as small red dots aligned perpendicular to the skin surface. The differential includes inflammatory lesions like psoriasis, stasis, and trauma; clear cell acanthoma (characterized by a “string of pearls” arrangement), nevi, and melanoma. “I find dermoscopy most useful in diagnosing SCC – especially squamous cell in situ,” she said. “Important clinical clues suggestive of SCC or melanoma include a solitary lesion, it’s new, it’s growing, and it’s not going away with a topical steroid.”

An additional pattern to be aware of are hairpin vessels, which are looped and feature a sharp bend at one end. These are often seen in seborrheic keratoses. “You can’t count on the hairpin vessels alone, because you can see this in anything keratotic, such as in keratoacanthoma (at the periphery with a yellow keratotic center), warts, SCC, BCC, as well as in dermal nevi and Spitz nevi,” said Dr. Stein, who recommended dermoscopedia.org as resource.

Comma vessels, meanwhile, appear in dermal or compound nevi. She described these as “slightly curved vessels that are much less in focus than branched vessels, because they come in and out of the plane of focus,” she said. “If you put your dermatoscope on top of the nevus and wobble it around you can appreciate the curve. If you look at it from the side, it looks like a curve. If you look at it straight on it will look more like a line. If you look at from the end it will look like a dot.”

Another vessel type she discussed are linear irregular and polymorphous vessels, which she described as “any combination of different types of vessels. We get most worried when we see dotted and linear irregular vessels together. In that case, you worry about melanoma. These can also be seen in nevi and other tumors, such as BCC.”

Dr. Stein’s fourth tip of the presentation was a reminder to consider dermoscopy as one piece of the clinical exam. “Always think about the lesion in context of the rest of the clinical picture and history,” she said. “Don’t get discouraged if it’s hard; just keep practicing. Look for any brown and use your clinical clues to put together to make the right decision.”

She disclosed that NYU receives compensation from MoleSafe for her telemedicine dermoscopic diagnoses.

[email protected]

Even in the most experienced hands, dermoscopy poses a challenge when the usual pigment clues are lacking to help distinguish melanoma from amelanotic melanoma and pigmented basal cell carcinoma (BCC) from nonpigmented BCC.

Copyright Dr. Jennifer A. Stein

“For me, pink lesions are challenging,” Jennifer A. Stein, MD, PhD, said during the virtual Orlando Dermatology Aesthetic and Clinical Conference. “How can dermoscopy help us distinguish between Spitz nevus, melanoma, clear cell acanthoma, psoriasis, basal cell carcinoma, and squamous cell carcinoma?”

Dr. Stein, professor of dermatology at New York University, offered four tips. First, look for the shiny white perpendicular lines, otherwise known as the chrysalis or crystalline pattern. “You can only see this feature when you’re looking with polarized light,” she said. “This is why you want a dermatoscope that has polarized light, and better yet, one that you’re able to turn on and off, the hybrid kind, because then you can convince yourself that you’re looking at this feature, because it blinks on and off.”

The differential diagnosis for white shiny perpendicular lines includes dermatofibroma/scars (which is most common), Spitz and atypical genital nevi, BCC, and melanoma. “Dermatofibromas sometimes have white circles or rings in the center,” Dr. Stein said. “In BCC, the lines aren’t always perpendicular. Sometimes it’s more of a blotch or strands.”

A second tip for managing a pink lesion on dermoscopy is to look for any brown color. “When you see that combo together you have to worry,” she said. “When you see pigment network on dermoscopy, you have to put melanoma in your differential. If you see shiny white lines in something that is melanocytic, there’s a 98% specificity for melanoma.”

A third tip she offered for managing pink lesions is to check the blood vessels for clues. “For years, I was just naming the vessels based on making the diagnosis and then deciding, ‘that’s a basal cell carcinoma; those must be branching vessels,’ ” said Dr. Stein, who manages NYU’s medical dermatology faculty group practice.

However, blood vessel patterns differ. For example, branching or arborizing vessels are suggestive of BCC. “These vessels are very crisp-looking on dermoscopy,” she said. “They’re all in the same plane of focus and they look like they were drawn in with a fine point marker. That’s different from other blood vessel patterns.” She also pointed out that superficial basal cells have short, fine telangiectasias. “When you put on the polarized light, the clue is the white, shiny structures,” she said.

Dotted vessels, meanwhile, appear on dermoscopy as small red dots aligned perpendicular to the skin surface. The differential includes inflammatory lesions like psoriasis, stasis, and trauma; clear cell acanthoma (characterized by a “string of pearls” arrangement), nevi, and melanoma. “I find dermoscopy most useful in diagnosing SCC – especially squamous cell in situ,” she said. “Important clinical clues suggestive of SCC or melanoma include a solitary lesion, it’s new, it’s growing, and it’s not going away with a topical steroid.”

An additional pattern to be aware of are hairpin vessels, which are looped and feature a sharp bend at one end. These are often seen in seborrheic keratoses. “You can’t count on the hairpin vessels alone, because you can see this in anything keratotic, such as in keratoacanthoma (at the periphery with a yellow keratotic center), warts, SCC, BCC, as well as in dermal nevi and Spitz nevi,” said Dr. Stein, who recommended dermoscopedia.org as resource.

Comma vessels, meanwhile, appear in dermal or compound nevi. She described these as “slightly curved vessels that are much less in focus than branched vessels, because they come in and out of the plane of focus,” she said. “If you put your dermatoscope on top of the nevus and wobble it around you can appreciate the curve. If you look at it from the side, it looks like a curve. If you look at it straight on it will look more like a line. If you look at from the end it will look like a dot.”

Another vessel type she discussed are linear irregular and polymorphous vessels, which she described as “any combination of different types of vessels. We get most worried when we see dotted and linear irregular vessels together. In that case, you worry about melanoma. These can also be seen in nevi and other tumors, such as BCC.”

Dr. Stein’s fourth tip of the presentation was a reminder to consider dermoscopy as one piece of the clinical exam. “Always think about the lesion in context of the rest of the clinical picture and history,” she said. “Don’t get discouraged if it’s hard; just keep practicing. Look for any brown and use your clinical clues to put together to make the right decision.”

She disclosed that NYU receives compensation from MoleSafe for her telemedicine dermoscopic diagnoses.

[email protected]

Combining transcatheter arterial chemoembolization (TACE) therapy with sorafenib improved progression-free survival (PFS), but not overall survival (OS), when compared with TACE alone in patients with unresectable hepatocellular carcinoma (HCC), final results from the phase 2 TACTICS trial showed.

The lack of a statistically significant difference in OS may have been due to the fact that patients randomized to receive TACE alone had more frequent post-trial therapies compared with patients assigned to TACE plus sorafenib, said study investigator Masatoshi Kudo, MD, PhD, of the Kindai University faculty of medicine in Osaka, Japan.

“These subsequent anticancer procedures and active systemic therapies have potentially diluted OS benefit in TACE plus sorafenib by extending post-progression survival and confounding survival analysis, implying the OS endpoint is not feasible anymore for TACE combination trials in the era of multitargeted agents and immune checkpoint inhibitors,” Dr. Kudo said at the 2021 Gastrointestinal Cancers Symposium (abstract 270).
 

Unresectable HCC

The TACTICS trial was launched in October 2010. Investigators enrolled 156 patients with unresectable HCC, Child-Pugh scores of 7 or less, treatable tumors (10 or fewer nodules of 10 cm or less) and adequate organ function.

Patients were randomized to receive TACE alone or with sorafenib. Sorafenib was delivered at a dose of 400 mg daily starting 2-3 weeks before the first TACE procedure to assess tolerability, followed by 800-mg daily doses. Sorafenib was interrupted for 2 days before and 3 days after each TACE session.

The trial had a gate-keeping design, which specified that OS would be formally analyzed only if PFS results were positive.

As reported in GUT in 2020, the trial met its PFS coprimary endpoint, with a median PFS of 25.2 months for the combination, compared with 13.5 months for TACE alone, at a median follow-up of 122.3 weeks. The hazard ratio (HR) for progression with the combination was 0.59 (P = .006).
 

Updated results

At the symposium, Dr. Kudo presented updated PFS results. At a median follow-up for all randomized patients of 33.4 months, the median PFS with the combination was 22.8 months, compared with 13.5 months for TACE alone (HR, 0.661; P­ = .02).

However, OS did not differ significantly between the groups, with a median of 36.2 months for the combination and 30.8 months for TACE alone (HR, 0.861; P = .40)

In a subgroup analysis of OS, there were small trends in favor of the combination compared with TACE alone in most categories, but the benefit of the combination was statistically significant only for the 12 patients with HCC of hepatitis B virus etiology (HR, 0.72; 95% CI, 0.006-0.808).

There were also trends favoring TACE plus sorafenib for PFS in a subgroup analysis, but none of the differences were statistically significant, except for patients who had received one or two TACE treatments prior to study entry (HR, 0.474; 95% CI, 0.276-0.812).

Treatment-emergent adverse events were consistent with those seen in the primary analysis, with no new safety signals seen at the last follow-up, Dr. Kudo said.

A majority of patients in both arms had subsequent anticancer therapy – 76.3% of the TACE-alone arm and 58.8% of the combination arm.

Patients in the TACE-alone arm were more likely than were those in the combination arm to have ablation (22.4% vs. 14.9%) or additional sorafenib (50% vs. 10.6%). Patients in the TACE-alone arm were also more likely to receive hepatic artery infusion chemotherapy a single time (27.6% vs. 19.1%) but less likely to receive it continuously (10.3% vs. 19.1%).

Dr. Kudo noted that in six trials in which TACE was combined with another agent, the correlation coefficient between PFS and OS was low, and the slope of weighted linear regression was more gentle than that seen in trials of other therapies for advanced HCC, “suggesting that long post-progression survivals strongly affected the OS in TACE combination trials.”

The TACTICS study was funded by the Japan Liver Oncology Group. Dr. Kudo disclosed relationships with Bayer, codeveloper of sorafenib, and multiple other companies.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Combining transcatheter arterial chemoembolization (TACE) therapy with sorafenib improved progression-free survival (PFS), but not overall survival (OS), when compared with TACE alone in patients with unresectable hepatocellular carcinoma (HCC), final results from the phase 2 TACTICS trial showed.

The lack of a statistically significant difference in OS may have been due to the fact that patients randomized to receive TACE alone had more frequent post-trial therapies compared with patients assigned to TACE plus sorafenib, said study investigator Masatoshi Kudo, MD, PhD, of the Kindai University faculty of medicine in Osaka, Japan.

“These subsequent anticancer procedures and active systemic therapies have potentially diluted OS benefit in TACE plus sorafenib by extending post-progression survival and confounding survival analysis, implying the OS endpoint is not feasible anymore for TACE combination trials in the era of multitargeted agents and immune checkpoint inhibitors,” Dr. Kudo said at the 2021 Gastrointestinal Cancers Symposium (abstract 270).
 

Unresectable HCC

The TACTICS trial was launched in October 2010. Investigators enrolled 156 patients with unresectable HCC, Child-Pugh scores of 7 or less, treatable tumors (10 or fewer nodules of 10 cm or less) and adequate organ function.

Patients were randomized to receive TACE alone or with sorafenib. Sorafenib was delivered at a dose of 400 mg daily starting 2-3 weeks before the first TACE procedure to assess tolerability, followed by 800-mg daily doses. Sorafenib was interrupted for 2 days before and 3 days after each TACE session.

The trial had a gate-keeping design, which specified that OS would be formally analyzed only if PFS results were positive.

As reported in GUT in 2020, the trial met its PFS coprimary endpoint, with a median PFS of 25.2 months for the combination, compared with 13.5 months for TACE alone, at a median follow-up of 122.3 weeks. The hazard ratio (HR) for progression with the combination was 0.59 (P = .006).
 

Updated results

At the symposium, Dr. Kudo presented updated PFS results. At a median follow-up for all randomized patients of 33.4 months, the median PFS with the combination was 22.8 months, compared with 13.5 months for TACE alone (HR, 0.661; P­ = .02).

However, OS did not differ significantly between the groups, with a median of 36.2 months for the combination and 30.8 months for TACE alone (HR, 0.861; P = .40)

In a subgroup analysis of OS, there were small trends in favor of the combination compared with TACE alone in most categories, but the benefit of the combination was statistically significant only for the 12 patients with HCC of hepatitis B virus etiology (HR, 0.72; 95% CI, 0.006-0.808).

There were also trends favoring TACE plus sorafenib for PFS in a subgroup analysis, but none of the differences were statistically significant, except for patients who had received one or two TACE treatments prior to study entry (HR, 0.474; 95% CI, 0.276-0.812).

Treatment-emergent adverse events were consistent with those seen in the primary analysis, with no new safety signals seen at the last follow-up, Dr. Kudo said.

A majority of patients in both arms had subsequent anticancer therapy – 76.3% of the TACE-alone arm and 58.8% of the combination arm.

Patients in the TACE-alone arm were more likely than were those in the combination arm to have ablation (22.4% vs. 14.9%) or additional sorafenib (50% vs. 10.6%). Patients in the TACE-alone arm were also more likely to receive hepatic artery infusion chemotherapy a single time (27.6% vs. 19.1%) but less likely to receive it continuously (10.3% vs. 19.1%).

Dr. Kudo noted that in six trials in which TACE was combined with another agent, the correlation coefficient between PFS and OS was low, and the slope of weighted linear regression was more gentle than that seen in trials of other therapies for advanced HCC, “suggesting that long post-progression survivals strongly affected the OS in TACE combination trials.”

The TACTICS study was funded by the Japan Liver Oncology Group. Dr. Kudo disclosed relationships with Bayer, codeveloper of sorafenib, and multiple other companies.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Combining transcatheter arterial chemoembolization (TACE) therapy with sorafenib improved progression-free survival (PFS), but not overall survival (OS), when compared with TACE alone in patients with unresectable hepatocellular carcinoma (HCC), final results from the phase 2 TACTICS trial showed.

The lack of a statistically significant difference in OS may have been due to the fact that patients randomized to receive TACE alone had more frequent post-trial therapies compared with patients assigned to TACE plus sorafenib, said study investigator Masatoshi Kudo, MD, PhD, of the Kindai University faculty of medicine in Osaka, Japan.

“These subsequent anticancer procedures and active systemic therapies have potentially diluted OS benefit in TACE plus sorafenib by extending post-progression survival and confounding survival analysis, implying the OS endpoint is not feasible anymore for TACE combination trials in the era of multitargeted agents and immune checkpoint inhibitors,” Dr. Kudo said at the 2021 Gastrointestinal Cancers Symposium (abstract 270).
 

Unresectable HCC

The TACTICS trial was launched in October 2010. Investigators enrolled 156 patients with unresectable HCC, Child-Pugh scores of 7 or less, treatable tumors (10 or fewer nodules of 10 cm or less) and adequate organ function.

Patients were randomized to receive TACE alone or with sorafenib. Sorafenib was delivered at a dose of 400 mg daily starting 2-3 weeks before the first TACE procedure to assess tolerability, followed by 800-mg daily doses. Sorafenib was interrupted for 2 days before and 3 days after each TACE session.

The trial had a gate-keeping design, which specified that OS would be formally analyzed only if PFS results were positive.

As reported in GUT in 2020, the trial met its PFS coprimary endpoint, with a median PFS of 25.2 months for the combination, compared with 13.5 months for TACE alone, at a median follow-up of 122.3 weeks. The hazard ratio (HR) for progression with the combination was 0.59 (P = .006).
 

Updated results

At the symposium, Dr. Kudo presented updated PFS results. At a median follow-up for all randomized patients of 33.4 months, the median PFS with the combination was 22.8 months, compared with 13.5 months for TACE alone (HR, 0.661; P­ = .02).

However, OS did not differ significantly between the groups, with a median of 36.2 months for the combination and 30.8 months for TACE alone (HR, 0.861; P = .40)

In a subgroup analysis of OS, there were small trends in favor of the combination compared with TACE alone in most categories, but the benefit of the combination was statistically significant only for the 12 patients with HCC of hepatitis B virus etiology (HR, 0.72; 95% CI, 0.006-0.808).

There were also trends favoring TACE plus sorafenib for PFS in a subgroup analysis, but none of the differences were statistically significant, except for patients who had received one or two TACE treatments prior to study entry (HR, 0.474; 95% CI, 0.276-0.812).

Treatment-emergent adverse events were consistent with those seen in the primary analysis, with no new safety signals seen at the last follow-up, Dr. Kudo said.

A majority of patients in both arms had subsequent anticancer therapy – 76.3% of the TACE-alone arm and 58.8% of the combination arm.

Patients in the TACE-alone arm were more likely than were those in the combination arm to have ablation (22.4% vs. 14.9%) or additional sorafenib (50% vs. 10.6%). Patients in the TACE-alone arm were also more likely to receive hepatic artery infusion chemotherapy a single time (27.6% vs. 19.1%) but less likely to receive it continuously (10.3% vs. 19.1%).

Dr. Kudo noted that in six trials in which TACE was combined with another agent, the correlation coefficient between PFS and OS was low, and the slope of weighted linear regression was more gentle than that seen in trials of other therapies for advanced HCC, “suggesting that long post-progression survivals strongly affected the OS in TACE combination trials.”

The TACTICS study was funded by the Japan Liver Oncology Group. Dr. Kudo disclosed relationships with Bayer, codeveloper of sorafenib, and multiple other companies.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.

“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.

This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.

In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.

“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.

Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.

The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).

The findings were presented at the 2021 Gastrointestinal Cancers Symposium.

Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”

These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.

One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
 

Study details

For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.

Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.

Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.

The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.

Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”

Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”

The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”

The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.

“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.

This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.

In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.

“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.

Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.

The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).

The findings were presented at the 2021 Gastrointestinal Cancers Symposium.

Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”

These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.

One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
 

Study details

For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.

Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.

Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.

The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.

Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”

Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”

The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”

The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pancreatic enzyme replacement therapy (PERT) is often an essential component of the treatment regimen for patients with pancreatic cancer, but it can be very pricey.

“Out-of-pocket costs for a 30-day supply of enzymes for Medicare beneficiaries can be as high as $1,000,” commented Arjun Gupta, MD, an oncology fellow at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore.

This can contribute to financial toxicity for patients who already have a high symptom burden and distress. The high cost of this supportive care has been underappreciated, he said.

In addition to its use for patients with pancreatic cancer, PERT is also prescribed to patients with chronic pancreatitis and cystic fibrosis. These enzymes can reduce symptoms of indigestion and improve nutrition for patients with exocrine pancreatic insufficiency, he explained.

“Out-of-pocket costs for two large pancreas enzyme capsules, which are often required for a meal, may be $15. And these need to be taken at every meal and may be more expensive than the meal itself,” he said in an interview.

Dr. Gupta led a new study which showed that, among Medicare beneficiaries, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations. Patients’ costs, including deductibles and coinsurance, ranged from $853 to $1,536.

The out-of-pocket costs were lower after patients met the deductible ($673; range, $527-$1,210) and continued to decrease after reaching catastrophic coverage ($135; range, $105-$242).

The findings were presented at the 2021 Gastrointestinal Cancers Symposium.

Dr. Gupta noted that there has been a lot of publicity about very expensive anticancer drugs, but little has been said about the costs of products used in supportive care. “While it’s true that many patients cannot afford the drugs, there are patient-assistance programs where they can often get them free of charge,” he said. “But supportive care agents, such as those for constipation or the enzymes – all of those can nickel and dime you and end up being very costly.”

These agents add substantially to the drug cost burden. “Some patients also need insulin, which is also insanely expensive,” he said.

One of the reasons for the high cost of PERT is that there are very few options, and all the available products are brand-name agents. Dr. Gupta noted that clinicians often underprescribe pancreatic enzymes in clinical practice. “Because of this, we wanted to look at what are the estimated out-of-pocket costs for patients directly when they’re prescribed an optimal regimen of pancreatic enzymes,” he said.
 

Study details

For their study, Dr. Gupta and colleagues assessed PERT costs using the Medicare Part D formulary and pricing files for the first quarter of 2020. Point-of-sale and out-of-pocket costs for each PERT formulation were calculated among Part D standalone and Medicare Advantage prescription drug plans.

Costs were then assessed using three scenarios: the standard-benefit design, with a $435 deductible and 25% coinsurance after the deductible is met; 25% coinsurance to fill a prescription after the deductible while in the coverage gap until the patient spends $6,350 out of pocket; and 5% coinsurance once catastrophic coverage is reached.

Across 3,974 plans nationwide, four formulations in 17 different doses were covered by Medicare plans during the study period. Doses ranged from 3,000 to 40,000 lipase units, and the per-unit list price ranged from $1.44 to $13.89.

The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840.

Dr. Gupta noted that a “good-sized meal often requires 80,000 units of lipase, or two of the very largest pills. Of note, these pills need to be taken meal after meal every meal throughout a patient’s life.”

Prescribers and dietitians try to find the least expensive options, including patient-assistance programs, but in the end, they are sometimes forced to underprescribe. “Some patients will go and buy over-the-counter pancreatic enzyme supplements, and it seems like a good way to cut costs,” said Dr. Gupta, “but it is not recommended for people with pancreatic cancer.”

The problem with these formulations is that they are not regulated. “The enzyme content in them is also minuscule, in the range of hundreds of units instead of the 50,000 units needed per meal,” he said. “Patients end up spending much more for ineffective therapies.”

The study received no outside funding. Dr. Gupta disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An investigational elastography technique for evaluating thyroid nodules while individuals use their voice could improve the detection of malignant tumors, which are sometimes missed by ultrasound and fine-needle aspiration biopsy, say French researchers. However, it has not yet been tested for cancer detection.

The new approach involves holding a linear ultrasound probe to the throat of the patient, who is then requested to vocalize an “eee” sound at 150 Hz. A loudspeaker plays a 150-Hz sound to guide the patient.

The vocal vibrations generated, called shear waves, are detected by the probe as they pass through the thyroid. Software the researchers developed calculates the velocity of the shear waves, which move faster through stiffer tissue. The software produces a stiffness map that is then superimposed onto a gray-scale (B mode) thyroid image from the ultrasound.

Cancerous tissue is stiffer than healthy tissue and benign nodules, so shear waves pass through it more quickly, the researchers explained. Areas of particular stiffness that are revealed by the test are a concern.

The study was published online Jan. 12 in Applied Physics Letters.

The new approach is a noninvasive method that “would reduce the stress of patients during their medical exams. Having to sing during a medical exam can perhaps help release some of the nervous tension even more,” lead investigator Steve Beuve, PhD, of the Université de Tours (France), said in a press release. The main benefit of this technique is that it is “quick and easy,” he added. Data acquisition takes about a second, and no specialized equipment is required. Imaging can be rendered by any Doppler ultrasound set at an ultrafast frame rate to track the shear waves. The computer program automatically calculates wave velocity through various parts of the thyroid.

The technique, dubbed vocal passive elastography (VPE), has not yet been tested to see how well it distinguishes cancerous from benign thyroid nodules.

“We want to cooperate with physicians to propose protocols to verify [VPE’s] relevance,” Dr. Beuve said.

Because no data are currently available on how accurate VPE is in diagnosing malignant nodules, it is not possible to comment on its potential usefulness, Aya Kamaya, MD, a radiology professor at Stanford (Calif.) University Medical Center, said in an interview.

Ultrasound elastography for diagnosing thyroid disease has been in development for years. More than 100 reports have been published in the medical literature since 2005. Various devices are available commercially, but for now, elastography for thyroid nodules remains investigational, she said.

Another expert who was approached for comment was more critical.

Lisa Orloff, MD, a professor and director of endocrine head and neck surgery and the thyroid tumor program at Stanford University, noted that, in general, “elastography has not gained more traction in thyroid evaluation to date because it does not appear to reduce the need for [fine-needle aspiration] of suspicious nodules based on gray-scale ultrasound alone, without elastography.”

As for the French report, she said that “while the voice might be a convenient shear wave source, I am very skeptical at many levels. I get the impression that [this is] a laboratory-based concept that is fraught with confounding factors in attempting real-world application.

“One concern is that the thyroid gland and nodule stiffness are affected by factors including underlying goiter, autoimmune disease, fluid content of nodules, calcifications, and other variables that can be present in benign or malignant conditions. And there are so many variables that would affect an individual patient’s ability (or not) to phonate at 150 Hz,” Dr. Orloff said.

VPE is an extension of passive elastography, which extracts elasticity data from the natural vibrations caused by the heart, blood pulsatility, and muscle activity, the authors explained. The team turned to vocalization at 150 Hz in part to overcome the physiological background noise in the thyroid from carotid pulsation at about 1-10 Hz.

The group is exploring vocalizations at other frequencies and is working to improve the computer program interface. They are also exploring VPE for other organs, including the brain.

The source of funding for the study and the authors’ relevant financial relationships were not reported.

A version of this article first appeared on Medscape.com.

An investigational elastography technique for evaluating thyroid nodules while individuals use their voice could improve the detection of malignant tumors, which are sometimes missed by ultrasound and fine-needle aspiration biopsy, say French researchers. However, it has not yet been tested for cancer detection.

The new approach involves holding a linear ultrasound probe to the throat of the patient, who is then requested to vocalize an “eee” sound at 150 Hz. A loudspeaker plays a 150-Hz sound to guide the patient.

The vocal vibrations generated, called shear waves, are detected by the probe as they pass through the thyroid. Software the researchers developed calculates the velocity of the shear waves, which move faster through stiffer tissue. The software produces a stiffness map that is then superimposed onto a gray-scale (B mode) thyroid image from the ultrasound.

Cancerous tissue is stiffer than healthy tissue and benign nodules, so shear waves pass through it more quickly, the researchers explained. Areas of particular stiffness that are revealed by the test are a concern.

The study was published online Jan. 12 in Applied Physics Letters.

The new approach is a noninvasive method that “would reduce the stress of patients during their medical exams. Having to sing during a medical exam can perhaps help release some of the nervous tension even more,” lead investigator Steve Beuve, PhD, of the Université de Tours (France), said in a press release. The main benefit of this technique is that it is “quick and easy,” he added. Data acquisition takes about a second, and no specialized equipment is required. Imaging can be rendered by any Doppler ultrasound set at an ultrafast frame rate to track the shear waves. The computer program automatically calculates wave velocity through various parts of the thyroid.

The technique, dubbed vocal passive elastography (VPE), has not yet been tested to see how well it distinguishes cancerous from benign thyroid nodules.

“We want to cooperate with physicians to propose protocols to verify [VPE’s] relevance,” Dr. Beuve said.

Because no data are currently available on how accurate VPE is in diagnosing malignant nodules, it is not possible to comment on its potential usefulness, Aya Kamaya, MD, a radiology professor at Stanford (Calif.) University Medical Center, said in an interview.

Ultrasound elastography for diagnosing thyroid disease has been in development for years. More than 100 reports have been published in the medical literature since 2005. Various devices are available commercially, but for now, elastography for thyroid nodules remains investigational, she said.

Another expert who was approached for comment was more critical.

Lisa Orloff, MD, a professor and director of endocrine head and neck surgery and the thyroid tumor program at Stanford University, noted that, in general, “elastography has not gained more traction in thyroid evaluation to date because it does not appear to reduce the need for [fine-needle aspiration] of suspicious nodules based on gray-scale ultrasound alone, without elastography.”

As for the French report, she said that “while the voice might be a convenient shear wave source, I am very skeptical at many levels. I get the impression that [this is] a laboratory-based concept that is fraught with confounding factors in attempting real-world application.

“One concern is that the thyroid gland and nodule stiffness are affected by factors including underlying goiter, autoimmune disease, fluid content of nodules, calcifications, and other variables that can be present in benign or malignant conditions. And there are so many variables that would affect an individual patient’s ability (or not) to phonate at 150 Hz,” Dr. Orloff said.

VPE is an extension of passive elastography, which extracts elasticity data from the natural vibrations caused by the heart, blood pulsatility, and muscle activity, the authors explained. The team turned to vocalization at 150 Hz in part to overcome the physiological background noise in the thyroid from carotid pulsation at about 1-10 Hz.

The group is exploring vocalizations at other frequencies and is working to improve the computer program interface. They are also exploring VPE for other organs, including the brain.

The source of funding for the study and the authors’ relevant financial relationships were not reported.

A version of this article first appeared on Medscape.com.

An investigational elastography technique for evaluating thyroid nodules while individuals use their voice could improve the detection of malignant tumors, which are sometimes missed by ultrasound and fine-needle aspiration biopsy, say French researchers. However, it has not yet been tested for cancer detection.

The new approach involves holding a linear ultrasound probe to the throat of the patient, who is then requested to vocalize an “eee” sound at 150 Hz. A loudspeaker plays a 150-Hz sound to guide the patient.

The vocal vibrations generated, called shear waves, are detected by the probe as they pass through the thyroid. Software the researchers developed calculates the velocity of the shear waves, which move faster through stiffer tissue. The software produces a stiffness map that is then superimposed onto a gray-scale (B mode) thyroid image from the ultrasound.

Cancerous tissue is stiffer than healthy tissue and benign nodules, so shear waves pass through it more quickly, the researchers explained. Areas of particular stiffness that are revealed by the test are a concern.

The study was published online Jan. 12 in Applied Physics Letters.

The new approach is a noninvasive method that “would reduce the stress of patients during their medical exams. Having to sing during a medical exam can perhaps help release some of the nervous tension even more,” lead investigator Steve Beuve, PhD, of the Université de Tours (France), said in a press release. The main benefit of this technique is that it is “quick and easy,” he added. Data acquisition takes about a second, and no specialized equipment is required. Imaging can be rendered by any Doppler ultrasound set at an ultrafast frame rate to track the shear waves. The computer program automatically calculates wave velocity through various parts of the thyroid.

The technique, dubbed vocal passive elastography (VPE), has not yet been tested to see how well it distinguishes cancerous from benign thyroid nodules.

“We want to cooperate with physicians to propose protocols to verify [VPE’s] relevance,” Dr. Beuve said.

Because no data are currently available on how accurate VPE is in diagnosing malignant nodules, it is not possible to comment on its potential usefulness, Aya Kamaya, MD, a radiology professor at Stanford (Calif.) University Medical Center, said in an interview.

Ultrasound elastography for diagnosing thyroid disease has been in development for years. More than 100 reports have been published in the medical literature since 2005. Various devices are available commercially, but for now, elastography for thyroid nodules remains investigational, she said.

Another expert who was approached for comment was more critical.

Lisa Orloff, MD, a professor and director of endocrine head and neck surgery and the thyroid tumor program at Stanford University, noted that, in general, “elastography has not gained more traction in thyroid evaluation to date because it does not appear to reduce the need for [fine-needle aspiration] of suspicious nodules based on gray-scale ultrasound alone, without elastography.”

As for the French report, she said that “while the voice might be a convenient shear wave source, I am very skeptical at many levels. I get the impression that [this is] a laboratory-based concept that is fraught with confounding factors in attempting real-world application.

“One concern is that the thyroid gland and nodule stiffness are affected by factors including underlying goiter, autoimmune disease, fluid content of nodules, calcifications, and other variables that can be present in benign or malignant conditions. And there are so many variables that would affect an individual patient’s ability (or not) to phonate at 150 Hz,” Dr. Orloff said.

VPE is an extension of passive elastography, which extracts elasticity data from the natural vibrations caused by the heart, blood pulsatility, and muscle activity, the authors explained. The team turned to vocalization at 150 Hz in part to overcome the physiological background noise in the thyroid from carotid pulsation at about 1-10 Hz.

The group is exploring vocalizations at other frequencies and is working to improve the computer program interface. They are also exploring VPE for other organs, including the brain.

The source of funding for the study and the authors’ relevant financial relationships were not reported.

A version of this article first appeared on Medscape.com.

A 34-year-old woman with no significant past medical history presented as a new patient to our family medicine clinic with 2 weeks of intermittent lower abdominal and pelvic pain. She was sexually active with 1 partner and denied abnormal vaginal discharge or bleeding. She mentioned she’d had an intrauterine contraceptive device (IUD) placed a few weeks ago. The patient was afebrile, and her pelvic examination was unremarkable.

Physical examination showed mild tenderness to palpation over the lower abdomen without rebound tenderness or guarding. A complete metabolic panel revealed no significant abnormalities, and her human chorionic gonadotropin levels were normal.

Findings from the physical exam and her clinical history prompted the need for imaging. An abdominal radiograph (FIGURE 1) and noncontrast computed tomography (FIGURES 2A and 2B) were subsequently ordered.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The abdominal radiograph revealed a nonobstructive bowel gas pattern with an IUD overlaying the central lower abdomen and pelvis at the L5-S1 level (FIGURE 1). Computed tomography (CT) of her abdomen and pelvis showed that the IUD was outside the endometrial cavity (FIGURES 2A and 2B). There was no evidence of pneumoperitoneum or bowel perforation. Based on the work-up and imaging, the patient’s pain was due to intra-abdominal IUD malpositioning.

Diagnostic criteria for IUD malpositioning include device migration into 1 of several locations, such as the lower uterine segment or cervix. IUD malpositioning can involve the rotation or protrusion of the device into or through the myometrium. On imaging, a well-positioned IUD should have a straight stem contained within the endometrial cavity, with the arms of the IUD extending laterally at the uterine fundus.

For our patient, an abdominal radiograph showed that her IUD was superiorly displaced outside the expected region of the endometrial cavity. CT helped to confirm this.

Complications with IUDs are few

Using an IUD is an increasingly popular method of contraception because it is effective and generally well tolerated, with minimal adverse effects or complications. In a multicenter retrospective chart review of 2138 patients who had IUDs, Aoun et al found that serious complications included pelvic inflammatory disease (2%), IUD expulsion (6%), and pregnancy (1%).¹ In a retrospective cohort study examining complications among 90,489 women with IUDs, Berenson et al found ectopic pregnancy and uterine perforation affected < 1%.²

A less serious complication is IUD malpositioning. Although it does seem to occur more often than other, more serious complications, the exact incidence is unknown. In a retrospective case-control study, Braaten et al reported the rate for IUD malpositioning was 10.4% among 182 women.³ Malpositioned IUDs may be more likely to occur in those with suspected adenomyosis.³ In a study by de Kroon et al, the estimated prevalence rate for an abnormal IUD position ranged from 4% to 7.7% among 195 patients.⁴

Continue to: The clinical presentation of IUD migration

Identification of a malpositioned IUD is needed to avoid the possible increased risk for uterine perforation, IUD expulsion, or pregnancy.⁵

IUDs that have perforated the uterus float freely in the pelvis or abdomen and can result in injury to adjacent structures as well as peritonitis, fistulas, and hemorrhage.^5-7 In addition, adhesion formation over the IUD can lead to intestinal obstruction, infertility, and chronic pain.⁶

Common symptoms of IUD malpositioning include abdominal or pelvic pain and abnormal bleeding, although many patients may be asymptomatic.⁸ In a retrospective study of 167 patients with IUDs who underwent pelvic ultrasound, 28 patients were found to have an IUD in an abnormal position.⁸ Rates of bleeding and pain were higher in patients with malpositioned IUDs (35.7% and 39.3%, respectively) than in those with a normally positioned IUD (15.1% and 19.4%, respectively).⁸

The differential Dx includes endometriosis and fibroids

IUD malpositioning can be distinguished from other diagnoses that cause pelvic pain and have similar presentations—including endometriosis, ectopic pregnancy, and fibroids—through imaging study findings, clinical history, and presentation.

Other conditions that may need to be ruled out include pelvic inflammatory disease, acute appendicitis, and ovarian cysts.⁹ A thorough history and physical examination can help rule out these conditions by organ system, and laboratory and imaging studies can help to confirm the diagnosis.

Continue to: Which imaging tool to use, and when

Assessment of intrauterine contraception placement requires evaluation of the uterine cavity; gynecologic examination alone is not sufficient to fully evaluate for IUD position. Certain imaging studies are particularly helpful for revealing possible IUD migration.

Ultrasound—a widely available, radiation-free modality—is the first-line imaging tool for evaluation of an IUD’s position.¹⁰ In addition, ultrasound can provide effective evaluation of other pelvic structures, which is helpful in identifying or eliminating other causes of pain or abnormal bleeding.

Conventional radiography. If the IUD is not visualized on ultrasound, the American College of Obstetricians and Gynecologists (ACOG) recommends radiography to determine if the IUD has been expelled or has migrated to an extra-uterine position.⁶

CT may be best suited for the evaluation of more severe complications of IUD malpositioning, including visceral perforation, abscess formation, or bowel obstruction. CT should be considered if the patient’s clinical presentation is suspicious for a more serious intra-abdominal pathology.

Management depends on the IUD’s position

For patients whose IUD has an uncertain position or nonvisualized intravaginal strings, ACOG’s first-line recommendations include ruling out pregnancy, using an alternative method for contraception, and ordering pelvic ultrasonography.⁶ ACOG recommendations for the management of IUD malpositioning depend on the device’s location and the patient’s symptomatology.

Continue to: Management of low-lying IUDs

Management of low-lying IUDs is complex. An IUD that is malpositioned in the cervix is considered partially expelled and should be completely removed.⁶ For asymptomatic patients with an IUD located in the lower uterine segment and above the internal cervical os, there should be strong consideration given to leaving the IUD in place because removal is associated with higher rates of pregnancy given the low rates of initiation of effective contraception following removal.⁶

For asymptomatic patients with an IUD in the lower uterine segment and above the internal cervical os, consider leaving the IUD in place.

IUD malpositioning in the peritoneal cavity requires surgical intervention. Although ACOG’s first-line recommendation is laparoscopic intervention, laparotomy can be considered if laparoscopy does not result in the removal of the IUD or the patient has more severe complications (sepsis or bowel perforation).⁶ At the time of IUD removal, the clinician should also discuss and/or prescribe interim contraception.

Treatment for our patient included uncomplicated laparoscopic surgical removal of the intra-abdominal IUD. The patient’s symptoms went away following the procedure, and she was subsequently switched to an oral contraceptive.

A 34-year-old woman with no significant past medical history presented as a new patient to our family medicine clinic with 2 weeks of intermittent lower abdominal and pelvic pain. She was sexually active with 1 partner and denied abnormal vaginal discharge or bleeding. She mentioned she’d had an intrauterine contraceptive device (IUD) placed a few weeks ago. The patient was afebrile, and her pelvic examination was unremarkable.

Physical examination showed mild tenderness to palpation over the lower abdomen without rebound tenderness or guarding. A complete metabolic panel revealed no significant abnormalities, and her human chorionic gonadotropin levels were normal.

Findings from the physical exam and her clinical history prompted the need for imaging. An abdominal radiograph (FIGURE 1) and noncontrast computed tomography (FIGURES 2A and 2B) were subsequently ordered.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The abdominal radiograph revealed a nonobstructive bowel gas pattern with an IUD overlaying the central lower abdomen and pelvis at the L5-S1 level (FIGURE 1). Computed tomography (CT) of her abdomen and pelvis showed that the IUD was outside the endometrial cavity (FIGURES 2A and 2B). There was no evidence of pneumoperitoneum or bowel perforation. Based on the work-up and imaging, the patient’s pain was due to intra-abdominal IUD malpositioning.

Diagnostic criteria for IUD malpositioning include device migration into 1 of several locations, such as the lower uterine segment or cervix. IUD malpositioning can involve the rotation or protrusion of the device into or through the myometrium. On imaging, a well-positioned IUD should have a straight stem contained within the endometrial cavity, with the arms of the IUD extending laterally at the uterine fundus.

For our patient, an abdominal radiograph showed that her IUD was superiorly displaced outside the expected region of the endometrial cavity. CT helped to confirm this.

Complications with IUDs are few

Using an IUD is an increasingly popular method of contraception because it is effective and generally well tolerated, with minimal adverse effects or complications. In a multicenter retrospective chart review of 2138 patients who had IUDs, Aoun et al found that serious complications included pelvic inflammatory disease (2%), IUD expulsion (6%), and pregnancy (1%).¹ In a retrospective cohort study examining complications among 90,489 women with IUDs, Berenson et al found ectopic pregnancy and uterine perforation affected < 1%.²

A less serious complication is IUD malpositioning. Although it does seem to occur more often than other, more serious complications, the exact incidence is unknown. In a retrospective case-control study, Braaten et al reported the rate for IUD malpositioning was 10.4% among 182 women.³ Malpositioned IUDs may be more likely to occur in those with suspected adenomyosis.³ In a study by de Kroon et al, the estimated prevalence rate for an abnormal IUD position ranged from 4% to 7.7% among 195 patients.⁴

Continue to: The clinical presentation of IUD migration

Identification of a malpositioned IUD is needed to avoid the possible increased risk for uterine perforation, IUD expulsion, or pregnancy.⁵

IUDs that have perforated the uterus float freely in the pelvis or abdomen and can result in injury to adjacent structures as well as peritonitis, fistulas, and hemorrhage.^5-7 In addition, adhesion formation over the IUD can lead to intestinal obstruction, infertility, and chronic pain.⁶

Common symptoms of IUD malpositioning include abdominal or pelvic pain and abnormal bleeding, although many patients may be asymptomatic.⁸ In a retrospective study of 167 patients with IUDs who underwent pelvic ultrasound, 28 patients were found to have an IUD in an abnormal position.⁸ Rates of bleeding and pain were higher in patients with malpositioned IUDs (35.7% and 39.3%, respectively) than in those with a normally positioned IUD (15.1% and 19.4%, respectively).⁸

The differential Dx includes endometriosis and fibroids

IUD malpositioning can be distinguished from other diagnoses that cause pelvic pain and have similar presentations—including endometriosis, ectopic pregnancy, and fibroids—through imaging study findings, clinical history, and presentation.

Other conditions that may need to be ruled out include pelvic inflammatory disease, acute appendicitis, and ovarian cysts.⁹ A thorough history and physical examination can help rule out these conditions by organ system, and laboratory and imaging studies can help to confirm the diagnosis.

Continue to: Which imaging tool to use, and when

Assessment of intrauterine contraception placement requires evaluation of the uterine cavity; gynecologic examination alone is not sufficient to fully evaluate for IUD position. Certain imaging studies are particularly helpful for revealing possible IUD migration.

Ultrasound—a widely available, radiation-free modality—is the first-line imaging tool for evaluation of an IUD’s position.¹⁰ In addition, ultrasound can provide effective evaluation of other pelvic structures, which is helpful in identifying or eliminating other causes of pain or abnormal bleeding.

Conventional radiography. If the IUD is not visualized on ultrasound, the American College of Obstetricians and Gynecologists (ACOG) recommends radiography to determine if the IUD has been expelled or has migrated to an extra-uterine position.⁶

CT may be best suited for the evaluation of more severe complications of IUD malpositioning, including visceral perforation, abscess formation, or bowel obstruction. CT should be considered if the patient’s clinical presentation is suspicious for a more serious intra-abdominal pathology.

Management depends on the IUD’s position

For patients whose IUD has an uncertain position or nonvisualized intravaginal strings, ACOG’s first-line recommendations include ruling out pregnancy, using an alternative method for contraception, and ordering pelvic ultrasonography.⁶ ACOG recommendations for the management of IUD malpositioning depend on the device’s location and the patient’s symptomatology.

Continue to: Management of low-lying IUDs

Management of low-lying IUDs is complex. An IUD that is malpositioned in the cervix is considered partially expelled and should be completely removed.⁶ For asymptomatic patients with an IUD located in the lower uterine segment and above the internal cervical os, there should be strong consideration given to leaving the IUD in place because removal is associated with higher rates of pregnancy given the low rates of initiation of effective contraception following removal.⁶

For asymptomatic patients with an IUD in the lower uterine segment and above the internal cervical os, consider leaving the IUD in place.

IUD malpositioning in the peritoneal cavity requires surgical intervention. Although ACOG’s first-line recommendation is laparoscopic intervention, laparotomy can be considered if laparoscopy does not result in the removal of the IUD or the patient has more severe complications (sepsis or bowel perforation).⁶ At the time of IUD removal, the clinician should also discuss and/or prescribe interim contraception.

Treatment for our patient included uncomplicated laparoscopic surgical removal of the intra-abdominal IUD. The patient’s symptoms went away following the procedure, and she was subsequently switched to an oral contraceptive.

A 34-year-old woman with no significant past medical history presented as a new patient to our family medicine clinic with 2 weeks of intermittent lower abdominal and pelvic pain. She was sexually active with 1 partner and denied abnormal vaginal discharge or bleeding. She mentioned she’d had an intrauterine contraceptive device (IUD) placed a few weeks ago. The patient was afebrile, and her pelvic examination was unremarkable.

Physical examination showed mild tenderness to palpation over the lower abdomen without rebound tenderness or guarding. A complete metabolic panel revealed no significant abnormalities, and her human chorionic gonadotropin levels were normal.

Findings from the physical exam and her clinical history prompted the need for imaging. An abdominal radiograph (FIGURE 1) and noncontrast computed tomography (FIGURES 2A and 2B) were subsequently ordered.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The abdominal radiograph revealed a nonobstructive bowel gas pattern with an IUD overlaying the central lower abdomen and pelvis at the L5-S1 level (FIGURE 1). Computed tomography (CT) of her abdomen and pelvis showed that the IUD was outside the endometrial cavity (FIGURES 2A and 2B). There was no evidence of pneumoperitoneum or bowel perforation. Based on the work-up and imaging, the patient’s pain was due to intra-abdominal IUD malpositioning.

Diagnostic criteria for IUD malpositioning include device migration into 1 of several locations, such as the lower uterine segment or cervix. IUD malpositioning can involve the rotation or protrusion of the device into or through the myometrium. On imaging, a well-positioned IUD should have a straight stem contained within the endometrial cavity, with the arms of the IUD extending laterally at the uterine fundus.

For our patient, an abdominal radiograph showed that her IUD was superiorly displaced outside the expected region of the endometrial cavity. CT helped to confirm this.

Complications with IUDs are few

Using an IUD is an increasingly popular method of contraception because it is effective and generally well tolerated, with minimal adverse effects or complications. In a multicenter retrospective chart review of 2138 patients who had IUDs, Aoun et al found that serious complications included pelvic inflammatory disease (2%), IUD expulsion (6%), and pregnancy (1%).¹ In a retrospective cohort study examining complications among 90,489 women with IUDs, Berenson et al found ectopic pregnancy and uterine perforation affected < 1%.²

A less serious complication is IUD malpositioning. Although it does seem to occur more often than other, more serious complications, the exact incidence is unknown. In a retrospective case-control study, Braaten et al reported the rate for IUD malpositioning was 10.4% among 182 women.³ Malpositioned IUDs may be more likely to occur in those with suspected adenomyosis.³ In a study by de Kroon et al, the estimated prevalence rate for an abnormal IUD position ranged from 4% to 7.7% among 195 patients.⁴

Continue to: The clinical presentation of IUD migration

Identification of a malpositioned IUD is needed to avoid the possible increased risk for uterine perforation, IUD expulsion, or pregnancy.⁵

IUDs that have perforated the uterus float freely in the pelvis or abdomen and can result in injury to adjacent structures as well as peritonitis, fistulas, and hemorrhage.^5-7 In addition, adhesion formation over the IUD can lead to intestinal obstruction, infertility, and chronic pain.⁶

Common symptoms of IUD malpositioning include abdominal or pelvic pain and abnormal bleeding, although many patients may be asymptomatic.⁸ In a retrospective study of 167 patients with IUDs who underwent pelvic ultrasound, 28 patients were found to have an IUD in an abnormal position.⁸ Rates of bleeding and pain were higher in patients with malpositioned IUDs (35.7% and 39.3%, respectively) than in those with a normally positioned IUD (15.1% and 19.4%, respectively).⁸

The differential Dx includes endometriosis and fibroids

IUD malpositioning can be distinguished from other diagnoses that cause pelvic pain and have similar presentations—including endometriosis, ectopic pregnancy, and fibroids—through imaging study findings, clinical history, and presentation.

Other conditions that may need to be ruled out include pelvic inflammatory disease, acute appendicitis, and ovarian cysts.⁹ A thorough history and physical examination can help rule out these conditions by organ system, and laboratory and imaging studies can help to confirm the diagnosis.

Continue to: Which imaging tool to use, and when

Assessment of intrauterine contraception placement requires evaluation of the uterine cavity; gynecologic examination alone is not sufficient to fully evaluate for IUD position. Certain imaging studies are particularly helpful for revealing possible IUD migration.

Ultrasound—a widely available, radiation-free modality—is the first-line imaging tool for evaluation of an IUD’s position.¹⁰ In addition, ultrasound can provide effective evaluation of other pelvic structures, which is helpful in identifying or eliminating other causes of pain or abnormal bleeding.

Conventional radiography. If the IUD is not visualized on ultrasound, the American College of Obstetricians and Gynecologists (ACOG) recommends radiography to determine if the IUD has been expelled or has migrated to an extra-uterine position.⁶

CT may be best suited for the evaluation of more severe complications of IUD malpositioning, including visceral perforation, abscess formation, or bowel obstruction. CT should be considered if the patient’s clinical presentation is suspicious for a more serious intra-abdominal pathology.

Management depends on the IUD’s position

For patients whose IUD has an uncertain position or nonvisualized intravaginal strings, ACOG’s first-line recommendations include ruling out pregnancy, using an alternative method for contraception, and ordering pelvic ultrasonography.⁶ ACOG recommendations for the management of IUD malpositioning depend on the device’s location and the patient’s symptomatology.

Continue to: Management of low-lying IUDs

Management of low-lying IUDs is complex. An IUD that is malpositioned in the cervix is considered partially expelled and should be completely removed.⁶ For asymptomatic patients with an IUD located in the lower uterine segment and above the internal cervical os, there should be strong consideration given to leaving the IUD in place because removal is associated with higher rates of pregnancy given the low rates of initiation of effective contraception following removal.⁶

For asymptomatic patients with an IUD in the lower uterine segment and above the internal cervical os, consider leaving the IUD in place.

IUD malpositioning in the peritoneal cavity requires surgical intervention. Although ACOG’s first-line recommendation is laparoscopic intervention, laparotomy can be considered if laparoscopy does not result in the removal of the IUD or the patient has more severe complications (sepsis or bowel perforation).⁶ At the time of IUD removal, the clinician should also discuss and/or prescribe interim contraception.

Treatment for our patient included uncomplicated laparoscopic surgical removal of the intra-abdominal IUD. The patient’s symptoms went away following the procedure, and she was subsequently switched to an oral contraceptive.

THE CASE

A 60-year-old man with a past medical history of gastroesophageal reflux disease (GERD) and dyslipidemia presented to his family physician for evaluation of chronic cough. Five years prior, the patient had developed a high fever and respiratory symptoms, including a cough, and was believed to have had severe otitis media. He was treated with multiple courses of antibiotics and corticosteroids for persistent otitis media. Although the condition eventually resolved, his cough continued.

The persistent cough prompted the patient to consult a succession of specialists. First, he saw a gastroenterologist; following an esophagogastroduodenoscopy, he was prescribed pantoprazole. Despite the proton-pump inhibitor (PPI) therapy, the cough remained. Next, he had multiple visits with an otolaryngologist but that yielded no specific diagnosis for the cough. He also saw an allergist-immunologist, who identified a ragweed allergy, gave him a diagnosis of cough-variant asthma, and prescribed antihistamines and mometasone furoate and formoterol fumarate dihydrate. Neither was helpful.

After 5 years of frustration, the patient complained to his family physician that he still had a cough and “a tickle” in his throat that was worsened by speaking and drinking cold beverages. He denied fever, shortness of breath, nausea, vomiting, or any other associated symptoms.

THE DIAGNOSIS

The failed treatment attempts with antihistamines, corticosteroids, bronchodilators, and PPI therapy excluded multiple etiologies for the cough. The throat discomfort and feeling of a “tickle” prompted us to consider a nerve-related disorder on the differential. The diagnosis of laryngeal sensory neuropathy (LSN) was considered.

DISCUSSION

LSN is a relatively uncommon cause of chronic refractory cough that can also manifest with throat discomfort, dysphagia, and dysphonia.¹ It is thought to result from some type of insult to the recurrent laryngeal nerve or superior laryngeal nerve via viral infections, metabolic changes, or mechanical trauma, leading to a change in the firing threshold.² The hypothesis of nerve damage is supported by the increased incidence of LSN in patients with goiters and those with type 2 diabetes.^3,4 When there is a decrease in the laryngeal sensory threshold, dysfunctional laryngeal behavior results, leading to symptoms such as persistent cough and throat clearing.

Diagnosis. LSN is often diagnosed clinically, after GERD, allergies, asthma, angiotensin-converting enzyme inhibitor intake, and psychogenic disorders have been ruled out.¹ Our patient had a prior diagnosis or investigation of nearly all of these conditions. Other clues pointing to an LSN diagnosis include a cough lasting 8 weeks or more, recurrent sensory disturbances (such as a tickle) of instantaneous onset before each cough episode, triggers that can include talking or a change in air temperature, daily coughing episodes numbering in the 10s to 100s, and a nonproductive cough.^5,6

The throat discomfort and feeling of a “tickle” prompted us to consider a nerve-related disorder on the differential.

Beyond clinical clues, laryngeal electromyography, which evaluates the neuromuscular system in the larynx by recording action potentials generated in the laryngeal muscles during contraction, can be used for diagnosis.⁴ Videostroboscopy, which allows for an enlarged and slow motion view of the vocal cords, can also be used.

Continue to: Treatment

Treatment. To both confirm the diagnosis and treat the patient in a rapid, practical fashion, a trial of a neuromodulating agent such as pregabalin or gabapentin can be employed.^6-9 A study identifying 28 LSN patients found symptomatic relief in 68% of patients taking gabapentin 100 to 900 mg/d.² In another study, 12 LSN patients given pregabalin found relief after a 1-month regimen.¹ Another study of 12 patients showed amitriptyline hydrochloride and gabapentin provided a positive response in 2 months, and the addition of reflux precautions and acid-­suppression therapy was helpful.⁹ Finally, a group of 32 patients trialed on 3 different medications (amitriptyline, desipramine, and gabapentin) found similar efficacy among the 3.⁶

Another option. Aside from medications, botulinum toxin type A has been shown in a case series to directly decrease laryngeal hypertonicity and possibly reduce neurogenic inflammation and neuropeptide-mediated cough.¹⁰ Another study found that 18 patients with neurogenic cough who received superior laryngeal nerve blocks had cough severity index scores decrease from an average of 26.8 pretreatment to 14.6 posttreatment (P < .0001).¹¹

Our patient agreed to a trial of gabapentin 300 mg once a day, with titration up to a maximum of 900 mg tid. When the patient returned to the clinic 4 months later, he reported that when he reached 300 mg bid, the cough completely resolved.

THE TAKEAWAY

A persistent cough with minimal identifiable triggers is a huge disruption to a patient’s life; having to visit multiple specialists before receiving a diagnosis compounds that. In our patient’s case, the process took 5 years, which underscores how important it is that LSN be considered in the differential diagnosis. Since this is generally a diagnosis of exclusion, it is important to take a careful history of a patient with a chronic cough. If LSN seems likely, trialing a patient on neuromodulating medication is the next best step, with dose titration if necessary.

CORRESPONDENCE
Selena R. Pasadyn, 675 West 130th Street, Hinckley, OH, 44233; [email protected]

THE CASE

A 60-year-old man with a past medical history of gastroesophageal reflux disease (GERD) and dyslipidemia presented to his family physician for evaluation of chronic cough. Five years prior, the patient had developed a high fever and respiratory symptoms, including a cough, and was believed to have had severe otitis media. He was treated with multiple courses of antibiotics and corticosteroids for persistent otitis media. Although the condition eventually resolved, his cough continued.

The persistent cough prompted the patient to consult a succession of specialists. First, he saw a gastroenterologist; following an esophagogastroduodenoscopy, he was prescribed pantoprazole. Despite the proton-pump inhibitor (PPI) therapy, the cough remained. Next, he had multiple visits with an otolaryngologist but that yielded no specific diagnosis for the cough. He also saw an allergist-immunologist, who identified a ragweed allergy, gave him a diagnosis of cough-variant asthma, and prescribed antihistamines and mometasone furoate and formoterol fumarate dihydrate. Neither was helpful.

After 5 years of frustration, the patient complained to his family physician that he still had a cough and “a tickle” in his throat that was worsened by speaking and drinking cold beverages. He denied fever, shortness of breath, nausea, vomiting, or any other associated symptoms.

THE DIAGNOSIS

The failed treatment attempts with antihistamines, corticosteroids, bronchodilators, and PPI therapy excluded multiple etiologies for the cough. The throat discomfort and feeling of a “tickle” prompted us to consider a nerve-related disorder on the differential. The diagnosis of laryngeal sensory neuropathy (LSN) was considered.

DISCUSSION

LSN is a relatively uncommon cause of chronic refractory cough that can also manifest with throat discomfort, dysphagia, and dysphonia.¹ It is thought to result from some type of insult to the recurrent laryngeal nerve or superior laryngeal nerve via viral infections, metabolic changes, or mechanical trauma, leading to a change in the firing threshold.² The hypothesis of nerve damage is supported by the increased incidence of LSN in patients with goiters and those with type 2 diabetes.^3,4 When there is a decrease in the laryngeal sensory threshold, dysfunctional laryngeal behavior results, leading to symptoms such as persistent cough and throat clearing.

Diagnosis. LSN is often diagnosed clinically, after GERD, allergies, asthma, angiotensin-converting enzyme inhibitor intake, and psychogenic disorders have been ruled out.¹ Our patient had a prior diagnosis or investigation of nearly all of these conditions. Other clues pointing to an LSN diagnosis include a cough lasting 8 weeks or more, recurrent sensory disturbances (such as a tickle) of instantaneous onset before each cough episode, triggers that can include talking or a change in air temperature, daily coughing episodes numbering in the 10s to 100s, and a nonproductive cough.^5,6

The throat discomfort and feeling of a “tickle” prompted us to consider a nerve-related disorder on the differential.

Beyond clinical clues, laryngeal electromyography, which evaluates the neuromuscular system in the larynx by recording action potentials generated in the laryngeal muscles during contraction, can be used for diagnosis.⁴ Videostroboscopy, which allows for an enlarged and slow motion view of the vocal cords, can also be used.

Continue to: Treatment

Treatment. To both confirm the diagnosis and treat the patient in a rapid, practical fashion, a trial of a neuromodulating agent such as pregabalin or gabapentin can be employed.^6-9 A study identifying 28 LSN patients found symptomatic relief in 68% of patients taking gabapentin 100 to 900 mg/d.² In another study, 12 LSN patients given pregabalin found relief after a 1-month regimen.¹ Another study of 12 patients showed amitriptyline hydrochloride and gabapentin provided a positive response in 2 months, and the addition of reflux precautions and acid-­suppression therapy was helpful.⁹ Finally, a group of 32 patients trialed on 3 different medications (amitriptyline, desipramine, and gabapentin) found similar efficacy among the 3.⁶

Another option. Aside from medications, botulinum toxin type A has been shown in a case series to directly decrease laryngeal hypertonicity and possibly reduce neurogenic inflammation and neuropeptide-mediated cough.¹⁰ Another study found that 18 patients with neurogenic cough who received superior laryngeal nerve blocks had cough severity index scores decrease from an average of 26.8 pretreatment to 14.6 posttreatment (P < .0001).¹¹

Our patient agreed to a trial of gabapentin 300 mg once a day, with titration up to a maximum of 900 mg tid. When the patient returned to the clinic 4 months later, he reported that when he reached 300 mg bid, the cough completely resolved.

THE TAKEAWAY

A persistent cough with minimal identifiable triggers is a huge disruption to a patient’s life; having to visit multiple specialists before receiving a diagnosis compounds that. In our patient’s case, the process took 5 years, which underscores how important it is that LSN be considered in the differential diagnosis. Since this is generally a diagnosis of exclusion, it is important to take a careful history of a patient with a chronic cough. If LSN seems likely, trialing a patient on neuromodulating medication is the next best step, with dose titration if necessary.

CORRESPONDENCE
Selena R. Pasadyn, 675 West 130th Street, Hinckley, OH, 44233; [email protected]

THE CASE

A 60-year-old man with a past medical history of gastroesophageal reflux disease (GERD) and dyslipidemia presented to his family physician for evaluation of chronic cough. Five years prior, the patient had developed a high fever and respiratory symptoms, including a cough, and was believed to have had severe otitis media. He was treated with multiple courses of antibiotics and corticosteroids for persistent otitis media. Although the condition eventually resolved, his cough continued.

The persistent cough prompted the patient to consult a succession of specialists. First, he saw a gastroenterologist; following an esophagogastroduodenoscopy, he was prescribed pantoprazole. Despite the proton-pump inhibitor (PPI) therapy, the cough remained. Next, he had multiple visits with an otolaryngologist but that yielded no specific diagnosis for the cough. He also saw an allergist-immunologist, who identified a ragweed allergy, gave him a diagnosis of cough-variant asthma, and prescribed antihistamines and mometasone furoate and formoterol fumarate dihydrate. Neither was helpful.

After 5 years of frustration, the patient complained to his family physician that he still had a cough and “a tickle” in his throat that was worsened by speaking and drinking cold beverages. He denied fever, shortness of breath, nausea, vomiting, or any other associated symptoms.

THE DIAGNOSIS

The failed treatment attempts with antihistamines, corticosteroids, bronchodilators, and PPI therapy excluded multiple etiologies for the cough. The throat discomfort and feeling of a “tickle” prompted us to consider a nerve-related disorder on the differential. The diagnosis of laryngeal sensory neuropathy (LSN) was considered.

DISCUSSION

LSN is a relatively uncommon cause of chronic refractory cough that can also manifest with throat discomfort, dysphagia, and dysphonia.¹ It is thought to result from some type of insult to the recurrent laryngeal nerve or superior laryngeal nerve via viral infections, metabolic changes, or mechanical trauma, leading to a change in the firing threshold.² The hypothesis of nerve damage is supported by the increased incidence of LSN in patients with goiters and those with type 2 diabetes.^3,4 When there is a decrease in the laryngeal sensory threshold, dysfunctional laryngeal behavior results, leading to symptoms such as persistent cough and throat clearing.

Diagnosis. LSN is often diagnosed clinically, after GERD, allergies, asthma, angiotensin-converting enzyme inhibitor intake, and psychogenic disorders have been ruled out.¹ Our patient had a prior diagnosis or investigation of nearly all of these conditions. Other clues pointing to an LSN diagnosis include a cough lasting 8 weeks or more, recurrent sensory disturbances (such as a tickle) of instantaneous onset before each cough episode, triggers that can include talking or a change in air temperature, daily coughing episodes numbering in the 10s to 100s, and a nonproductive cough.^5,6

The throat discomfort and feeling of a “tickle” prompted us to consider a nerve-related disorder on the differential.

Beyond clinical clues, laryngeal electromyography, which evaluates the neuromuscular system in the larynx by recording action potentials generated in the laryngeal muscles during contraction, can be used for diagnosis.⁴ Videostroboscopy, which allows for an enlarged and slow motion view of the vocal cords, can also be used.

Continue to: Treatment

Treatment. To both confirm the diagnosis and treat the patient in a rapid, practical fashion, a trial of a neuromodulating agent such as pregabalin or gabapentin can be employed.^6-9 A study identifying 28 LSN patients found symptomatic relief in 68% of patients taking gabapentin 100 to 900 mg/d.² In another study, 12 LSN patients given pregabalin found relief after a 1-month regimen.¹ Another study of 12 patients showed amitriptyline hydrochloride and gabapentin provided a positive response in 2 months, and the addition of reflux precautions and acid-­suppression therapy was helpful.⁹ Finally, a group of 32 patients trialed on 3 different medications (amitriptyline, desipramine, and gabapentin) found similar efficacy among the 3.⁶

Another option. Aside from medications, botulinum toxin type A has been shown in a case series to directly decrease laryngeal hypertonicity and possibly reduce neurogenic inflammation and neuropeptide-mediated cough.¹⁰ Another study found that 18 patients with neurogenic cough who received superior laryngeal nerve blocks had cough severity index scores decrease from an average of 26.8 pretreatment to 14.6 posttreatment (P < .0001).¹¹

Our patient agreed to a trial of gabapentin 300 mg once a day, with titration up to a maximum of 900 mg tid. When the patient returned to the clinic 4 months later, he reported that when he reached 300 mg bid, the cough completely resolved.

THE TAKEAWAY

A persistent cough with minimal identifiable triggers is a huge disruption to a patient’s life; having to visit multiple specialists before receiving a diagnosis compounds that. In our patient’s case, the process took 5 years, which underscores how important it is that LSN be considered in the differential diagnosis. Since this is generally a diagnosis of exclusion, it is important to take a careful history of a patient with a chronic cough. If LSN seems likely, trialing a patient on neuromodulating medication is the next best step, with dose titration if necessary.

CORRESPONDENCE
Selena R. Pasadyn, 675 West 130th Street, Hinckley, OH, 44233; [email protected]