ORLANDO—RNA expression patterns are highly dynamic, even at the earliest stages of multiple sclerosis (MS) pathogenesis, according to research presented at the ACTRIMS 2017 Forum. Machine learning methods trained and validated with these gene targets are a highly accurate tool that could provide actionable data for health care providers who suspect MS.

RNA sequencing was performed to identify differentially expressed protein-coding and noncoding RNA genes at distinct stages of MS, compared with controls. Expression levels of these genes were validated by real-time polymerase chain reaction (PCR) across all 979 subjects recruited. Ratios of gene expression data were used as inputs to train machine learning classifiers capable of multicategory comparisons. An independent validation testing set consisting of individuals across each control and disease class was used to evaluate the performance of these classifiers. In contrast to protein-coding gene targets where gene expression differences were often twofold or less, lncRNAs were highly differentially expressed across each of the experimental groups compared. Training and validation of machine learning methods revealed that lncRNA gene expression inputs resulted in higher overall accuracy and confidence of machine learning predictions than did protein-coding genes, resulting in greater than 90% accuracy in the validation testing set. 

—Glenn S. Williams

ORLANDO—RNA expression patterns are highly dynamic, even at the earliest stages of multiple sclerosis (MS) pathogenesis, according to research presented at the ACTRIMS 2017 Forum. Machine learning methods trained and validated with these gene targets are a highly accurate tool that could provide actionable data for health care providers who suspect MS.

RNA sequencing was performed to identify differentially expressed protein-coding and noncoding RNA genes at distinct stages of MS, compared with controls. Expression levels of these genes were validated by real-time polymerase chain reaction (PCR) across all 979 subjects recruited. Ratios of gene expression data were used as inputs to train machine learning classifiers capable of multicategory comparisons. An independent validation testing set consisting of individuals across each control and disease class was used to evaluate the performance of these classifiers. In contrast to protein-coding gene targets where gene expression differences were often twofold or less, lncRNAs were highly differentially expressed across each of the experimental groups compared. Training and validation of machine learning methods revealed that lncRNA gene expression inputs resulted in higher overall accuracy and confidence of machine learning predictions than did protein-coding genes, resulting in greater than 90% accuracy in the validation testing set. 

—Glenn S. Williams

ORLANDO—RNA expression patterns are highly dynamic, even at the earliest stages of multiple sclerosis (MS) pathogenesis, according to research presented at the ACTRIMS 2017 Forum. Machine learning methods trained and validated with these gene targets are a highly accurate tool that could provide actionable data for health care providers who suspect MS.

RNA sequencing was performed to identify differentially expressed protein-coding and noncoding RNA genes at distinct stages of MS, compared with controls. Expression levels of these genes were validated by real-time polymerase chain reaction (PCR) across all 979 subjects recruited. Ratios of gene expression data were used as inputs to train machine learning classifiers capable of multicategory comparisons. An independent validation testing set consisting of individuals across each control and disease class was used to evaluate the performance of these classifiers. In contrast to protein-coding gene targets where gene expression differences were often twofold or less, lncRNAs were highly differentially expressed across each of the experimental groups compared. Training and validation of machine learning methods revealed that lncRNA gene expression inputs resulted in higher overall accuracy and confidence of machine learning predictions than did protein-coding genes, resulting in greater than 90% accuracy in the validation testing set. 

—Glenn S. Williams

Henri R. Ford, MD, MHA, FACS, FAAP, vice-president and surgeon-in-chief, Children’s Hospital Los Angeles; professor of surgery and vice-dean for medical education, Keck School of Medicine, University of Southern California; and member of the American College of Surgeons Board of Regents, was accorded Honorary Fellowship in the Royal College of Surgeons of England (RCSEng) on March 7 in London, U.K.

A world-renowned Haitian-American surgeon, Dr. Ford played a prominent role in organizing and leading medical teams in response to the catastrophic 2010 earthquake in Haiti. Born in Haiti, Dr. Ford regularly returns to his native country to teach, lead operating teams, and assist in developing surgical systems, which the island nation historically has lacked. His accomplishments there are myriad. For example, in May 2015, Dr. Ford led a team of health care professionals that made history by completing the first separation of conjoined twins in Haiti. (Read more about the operation at www.cbsnews.com/news/more-than-just-a-surgery-conjoined-twins-separated-in-haiti/.)

Dr. Ford and his family fled Haiti’s oppressive regime and came to the U.S. when he was 13 years old. He received his medical degree from Harvard Medical School, Boston, MA, and trained in general surgery at Weill Cornell Medical College, New York, NY. He completed his pediatric surgical training at Children’s Hospital of Pittsburgh, PA. Prior to joining Children’s Hospital Los Angeles in 2005, Dr. Ford was professor and chief, division of pediatric surgery, and surgeon-in-chief, Children’s Hospital of Pittsburgh and the University of Pittsburgh School of Medicine.

Su-Anna Boddy, MS, FRCS, council member for the RCSEng, introduced Dr. Ford at the ceremony and spoke of his accomplishments, and Clare Marx, CBE, DL, PRCS, RCSEng president, formally awarded him the honor.
 

Henri R. Ford, MD, MHA, FACS, FAAP, vice-president and surgeon-in-chief, Children’s Hospital Los Angeles; professor of surgery and vice-dean for medical education, Keck School of Medicine, University of Southern California; and member of the American College of Surgeons Board of Regents, was accorded Honorary Fellowship in the Royal College of Surgeons of England (RCSEng) on March 7 in London, U.K.

A world-renowned Haitian-American surgeon, Dr. Ford played a prominent role in organizing and leading medical teams in response to the catastrophic 2010 earthquake in Haiti. Born in Haiti, Dr. Ford regularly returns to his native country to teach, lead operating teams, and assist in developing surgical systems, which the island nation historically has lacked. His accomplishments there are myriad. For example, in May 2015, Dr. Ford led a team of health care professionals that made history by completing the first separation of conjoined twins in Haiti. (Read more about the operation at www.cbsnews.com/news/more-than-just-a-surgery-conjoined-twins-separated-in-haiti/.)

Dr. Ford and his family fled Haiti’s oppressive regime and came to the U.S. when he was 13 years old. He received his medical degree from Harvard Medical School, Boston, MA, and trained in general surgery at Weill Cornell Medical College, New York, NY. He completed his pediatric surgical training at Children’s Hospital of Pittsburgh, PA. Prior to joining Children’s Hospital Los Angeles in 2005, Dr. Ford was professor and chief, division of pediatric surgery, and surgeon-in-chief, Children’s Hospital of Pittsburgh and the University of Pittsburgh School of Medicine.

Su-Anna Boddy, MS, FRCS, council member for the RCSEng, introduced Dr. Ford at the ceremony and spoke of his accomplishments, and Clare Marx, CBE, DL, PRCS, RCSEng president, formally awarded him the honor.
 

Henri R. Ford, MD, MHA, FACS, FAAP, vice-president and surgeon-in-chief, Children’s Hospital Los Angeles; professor of surgery and vice-dean for medical education, Keck School of Medicine, University of Southern California; and member of the American College of Surgeons Board of Regents, was accorded Honorary Fellowship in the Royal College of Surgeons of England (RCSEng) on March 7 in London, U.K.

A world-renowned Haitian-American surgeon, Dr. Ford played a prominent role in organizing and leading medical teams in response to the catastrophic 2010 earthquake in Haiti. Born in Haiti, Dr. Ford regularly returns to his native country to teach, lead operating teams, and assist in developing surgical systems, which the island nation historically has lacked. His accomplishments there are myriad. For example, in May 2015, Dr. Ford led a team of health care professionals that made history by completing the first separation of conjoined twins in Haiti. (Read more about the operation at www.cbsnews.com/news/more-than-just-a-surgery-conjoined-twins-separated-in-haiti/.)

Dr. Ford and his family fled Haiti’s oppressive regime and came to the U.S. when he was 13 years old. He received his medical degree from Harvard Medical School, Boston, MA, and trained in general surgery at Weill Cornell Medical College, New York, NY. He completed his pediatric surgical training at Children’s Hospital of Pittsburgh, PA. Prior to joining Children’s Hospital Los Angeles in 2005, Dr. Ford was professor and chief, division of pediatric surgery, and surgeon-in-chief, Children’s Hospital of Pittsburgh and the University of Pittsburgh School of Medicine.

Su-Anna Boddy, MS, FRCS, council member for the RCSEng, introduced Dr. Ford at the ceremony and spoke of his accomplishments, and Clare Marx, CBE, DL, PRCS, RCSEng president, formally awarded him the honor.
 

Thomas E. Starzl, MD, PhD, FACS, known as the “father of transplantation” for his role as the first surgeon to perform a successful human liver transplant and for developing techniques for safe, standardized surgery in the field of transplantation, died March 4 at his home in Pittsburgh, PA. He was 90 years old.

After nearly a decade of laboratory research and surgical practice at institutions such as Northwestern Medical School, Chicago, IL, and Johns Hopkins Hospital, Baltimore, MD, Dr. Starzl performed the world’s first successful liver transplant while practicing at the University of Colorado, Boulder, in 1967. This achievement came at a time when the prevailing medical opinion on the feasibility of liver transplants was pessimistic, but Dr. Starzl’s monumental success led to a newfound clinical interest in the possibilities of allogenic human transplantation. In 1980, he introduced anti-lymphocyte globulin and cyclosporine to his previous development of azathioprine and corticosteroid immunosuppression to prevent organ rejection. It was this advancement that moved organ transplantation from being considered an experimental to a clinically accepted treatment modality.

Dr. Starzl joined the University of Pittsburgh School of Medicine in 1981 as professor of surgery; there, he launched the first liver transplant program in the U.S. Though he retired from clinical and surgical service in 1991 after serving as chief of transplantation services at various Pittsburgh hospitals, he remained at the University of Pittsburgh as distinguished service professor of surgery and director emeritus of the University of Pittsburgh Medical Center’s Thomas E. Starzl Transplantation Institute.

Read about Dr. Starzl’s storied career and a statement from his family at www.news.pitt.edu/news/starzl. For a more thorough account of Dr. Starzl’s accomplishments, visit the University of Pittsburgh’s Dr. Thomas E. Starzl website at www.starzl.pitt.edu/index.html.
 

Thomas E. Starzl, MD, PhD, FACS, known as the “father of transplantation” for his role as the first surgeon to perform a successful human liver transplant and for developing techniques for safe, standardized surgery in the field of transplantation, died March 4 at his home in Pittsburgh, PA. He was 90 years old.

After nearly a decade of laboratory research and surgical practice at institutions such as Northwestern Medical School, Chicago, IL, and Johns Hopkins Hospital, Baltimore, MD, Dr. Starzl performed the world’s first successful liver transplant while practicing at the University of Colorado, Boulder, in 1967. This achievement came at a time when the prevailing medical opinion on the feasibility of liver transplants was pessimistic, but Dr. Starzl’s monumental success led to a newfound clinical interest in the possibilities of allogenic human transplantation. In 1980, he introduced anti-lymphocyte globulin and cyclosporine to his previous development of azathioprine and corticosteroid immunosuppression to prevent organ rejection. It was this advancement that moved organ transplantation from being considered an experimental to a clinically accepted treatment modality.

Dr. Starzl joined the University of Pittsburgh School of Medicine in 1981 as professor of surgery; there, he launched the first liver transplant program in the U.S. Though he retired from clinical and surgical service in 1991 after serving as chief of transplantation services at various Pittsburgh hospitals, he remained at the University of Pittsburgh as distinguished service professor of surgery and director emeritus of the University of Pittsburgh Medical Center’s Thomas E. Starzl Transplantation Institute.

Read about Dr. Starzl’s storied career and a statement from his family at www.news.pitt.edu/news/starzl. For a more thorough account of Dr. Starzl’s accomplishments, visit the University of Pittsburgh’s Dr. Thomas E. Starzl website at www.starzl.pitt.edu/index.html.
 

Thomas E. Starzl, MD, PhD, FACS, known as the “father of transplantation” for his role as the first surgeon to perform a successful human liver transplant and for developing techniques for safe, standardized surgery in the field of transplantation, died March 4 at his home in Pittsburgh, PA. He was 90 years old.

After nearly a decade of laboratory research and surgical practice at institutions such as Northwestern Medical School, Chicago, IL, and Johns Hopkins Hospital, Baltimore, MD, Dr. Starzl performed the world’s first successful liver transplant while practicing at the University of Colorado, Boulder, in 1967. This achievement came at a time when the prevailing medical opinion on the feasibility of liver transplants was pessimistic, but Dr. Starzl’s monumental success led to a newfound clinical interest in the possibilities of allogenic human transplantation. In 1980, he introduced anti-lymphocyte globulin and cyclosporine to his previous development of azathioprine and corticosteroid immunosuppression to prevent organ rejection. It was this advancement that moved organ transplantation from being considered an experimental to a clinically accepted treatment modality.

Dr. Starzl joined the University of Pittsburgh School of Medicine in 1981 as professor of surgery; there, he launched the first liver transplant program in the U.S. Though he retired from clinical and surgical service in 1991 after serving as chief of transplantation services at various Pittsburgh hospitals, he remained at the University of Pittsburgh as distinguished service professor of surgery and director emeritus of the University of Pittsburgh Medical Center’s Thomas E. Starzl Transplantation Institute.

Read about Dr. Starzl’s storied career and a statement from his family at www.news.pitt.edu/news/starzl. For a more thorough account of Dr. Starzl’s accomplishments, visit the University of Pittsburgh’s Dr. Thomas E. Starzl website at www.starzl.pitt.edu/index.html.
 

Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.

Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.

Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.

In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.

The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.

The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.

Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.

—Erik Greb

Suggested Reading

Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.

Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.

Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.

Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.

Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.

In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.

The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.

The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.

Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.

—Erik Greb

Suggested Reading

Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.

Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.

Pitolisant, a histamine H3 receptor inverse agonist, is well tolerated and effectively reduces cataplexy, according to data published in the March issue of Lancet Neurology. If the drug’s effect is confirmed in long-term studies, pitolisant could become a first-line therapy for cataplexy in patients with narcolepsy, who currently have few treatment options, according to the authors.

Two types of drugs are used to treat cataplexy. Antidepressants are used off-label and not well supported by evidence. Sodium oxybate is effective, but may cause serious adverse events.

Zoltán Szakács, MD, a doctor at the State Health Center in Budapest, and colleagues enrolled patients with narcolepsy from 16 sleep centers in nine countries into a randomized, double-blind, placebo-controlled trial. Eligible participants were age 18, had narcolepsy with cataplexy, had at least three cataplexies per week, and had excessive daytime sleepiness. Patients were randomized to pitolisant or placebo once per day. During a three-week flexible dosing period, patients randomized to pitolisant received 5 mg for the first week, 10 mg for the second week, and for the third week, a dose of between 5 mg and 20 mg, on the basis of safety and efficacy. A four-week period of stable dosing followed. Finally, patients underwent a one-week withdrawal period.

In all, 54 patients received pitolisant, and 51 received placebo. During the stable dosing period, the weekly cataplexy rate was decreased by 75% in patients who received pitolisant and by 38% among controls. The effect was significant regardless of the patient’s stable dose of pitolisant. Use of concomitant anticataplectic treatment before study initiation did not affect the results. The drug also improved scores on the Epworth Sleepiness Scale and maintenance of wakefulness test.

The pitolisant group had a significantly higher rate of treatment-related adverse events than did the placebo group (28% vs 12%). The researchers recorded no serious adverse events, but observed one case of severe nausea in the pitolisant group.

The study’s main limitation is that the diagnosis of narcolepsy was based on nonspecific criteria, said Christian R. Baumann, Professor of Neurology at University Hospital Zurich, in an accompanying editorial. “The fact that reported mean sleep latencies in the cohort of Szakács and colleagues (4.2–4.7 min) were higher than those reported in other cohorts, including ours (2.6–2.9 min), leaves some uncertainty about patient inclusion,” he added.

Nevertheless, the study may contribute to the regulatory approval of pitolisant. “This is good news for clinicians, since we need more treatment options to better tailor individualized therapy for patients with narcolepsy,” said Dr. Baumann.

—Erik Greb

Suggested Reading

Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017;16(3):200-207.

Baumann CR. Wide implications of a trial on pitolisant for cataplexy. Lancet Neurol. 2017;16(3):173-174.

CASE Woman with fibroids seeks alternative to hysterectomy

A 42-year-old woman (G2P2) presents to the office for evaluation of heavy menstrual bleeding and known uterine fibroids. Physical examination reveals a 16-week-sized uterus, and ultrasonography shows at least 6 fibroids, 2 of which impinge on the uterine cavity. She does not want to have any more children, but she wishes to avoid a hysterectomy.

Abdominal myomectomy: A good option for many women

Abdominal myomectomy is an underutilized procedure. With fibroids as the indication for surgery, 197,000 hysterectomies were performed in the United States in 2010, compared with approximately 40,000 myomectomies.^1,2 Moreover, the rates of both laparoscopic and abdominal myomectomy have decreased following the controversial morcellation advisory issued by the US Food and Drug Administration.³

The differences in the hysterectomy and myomectomy rates might be explained by the many myths ascribed to myomectomy. Such myths include the beliefs that myomectomy, when compared with hysterectomy, is associated with greater risk of visceral injury, more blood loss, poor uterine healing, and high risk of fibroid recurrence, and that myomectomy is unlikely to improve patient symptoms.

Studies show, however, that these beliefs are wrong. The risk of needing treatment for new fibroid growth following myomectomy is low.⁴ Hysterectomy, compared with myomectomy for similar size uteri, is actually associated with a greater risk of injury to the bowel, bladder, and ureters and with a greater risk of operative hemorrhage. Furthermore, hysterectomy (without oophorectomy) can be associated with early menopause in approximately 10% of women, while myomectomy does not alter ovarian hormones. (See “7 Myomectomy myths debunked,” which appeared in the February 2017 issue of OBG Management.) Another myth debunked: Fibroids do not “degenerate” into leiomyosarcomas, and the risk of leiomyosarcoma in premenopausal women with presumed uterine fibroids is extremely low.^5,6

For women who have serious medical problems (severe anemia, ureteral obstruction) due to uterine fibroids, surgery usually is necessary. In addition, women may request surgery for fibroid-associated quality-of-life concerns, such as heavy menstrual bleeding, infertility, pelvic pressure, urinary frequency, or incontinence. In one prospective study, the authors found that when women were assessed 6 months after undergoing myomectomy, 75% reported experiencing a significant decrease in bothersome symptoms.⁷

Myomectomy may be considered even for women with large uterine fibroids who desire uterine conservation. In a systematic review of the perioperative morbidity associated with abdominal myomectomy compared with abdominal hysterectomy for fibroids, which included 1,520 women with uterine size up to 16 to 18 weeks, no difference was found in major morbidity rates.⁸ Investigators who studied 91 women with uterine size ranging from 16 to 36 weeks who underwent abdominal myomectomy reported 1 bowel injury, 1 bladder injury, and 1 reoperation for bowel obstruction; no women had conversion to hysterectomy.⁹

Since ObGyn residency training emphasizes hysterectomy techniques, many residents receive only limited exposure to myomectomy procedures. Increased exposure to and comfort with myomectomy surgical technique would encourage more gynecologists to offer this option to their patients who desire uterine conservation, including those who do not desire future childbearing.

Imaging techniques are essential in the preoperative evaluation

For women with fibroid-related symptoms who desire surgery with uterine preservation, determining the myomectomy approach (abdominal, laparoscopic/robotic, hysteroscopic) depends on accurate assessment of the size, number, and position of the fibroids. If abdominal myomectomy is planned because of uterine size, the presence of numerous fibroids, or patient choice, transvaginal/transabdominal ultrasonography usually is adequate for anticipating what will be found during surgery. Sonography is readily available and is the least costly imaging technique that can help differentiate fibroids from other pelvic pathology. Although small fibroids may not be seen on sonography, they can be palpated and removed at the time of open surgery.

If submucous fibroids need to be better defined, saline-infusion sonography can be performed. However, if laparoscopic/robotic myomectomy (which precludes accurate palpation during surgery) is being considered, magnetic resonance imaging (MRI) allows the best assessment of the size, number, and position of the fibroids.¹⁰ When adenomyosis is considered in the differential diagnosis, MRI is an accurate way to determine its presence and helps in planning the best surgical procedure and approach.

Correct anemia before surgery

Women with fibroids may have anemia requiring correction before surgery to reduce the need for intraoperative or postoperative blood transfusion. Mild iron deficiency anemia can be treated prior to surgery with oral elemental iron 150 to 200 mg per day. Vitamin C 1,000 mg per day helps to increase intestinal iron absorption. Three weeks of treatment with oral iron can increase hemoglobin concentration by 2 g/dL.

For more severe anemia or rapid correction of anemia, intravenous (IV) iron sucrose infusions, 200 mg infused over 2 hours and given 3 times per week for 3 weeks, can increase hemoglobin by 3 g/dL.¹¹ In our ObGyn practice, hematologists manage iron infusions.

Read about abdominal incision technique

Abdominal incision technique

Even a large uterus with multiple fibroids usually can be managed through use of a transverse lower abdominal incision. Prior to reaching the lateral borders of the rectus abdominis, curve the fascial incision cephalad to avoid injury to the ileoinguinal nerves (FIGURE 1). Detaching the midline rectus fascia (linea alba) from the anterior abdominal wall, starting at the pubic symphysis and continuing up to the umbilicus, frees the rectus muscles and allows them to be easily separated (see VIDEO 1). Since fascia is not elastic, these 2 steps are important to allow more room to deliver the uterus through the incision.

Illustration: Marcia Hartsock for OBG Management

Delivery of the uterus through the incision isolates the surgical field from the bowel, bladder, ureters, and pelvic nerves. Once the uterus is delivered, inspect and palpate it for fibroids. Identify the fundus and the position of the uterine cavity by locating both uterine cornua and imagining a straight line between them. It may be necessary to explore the endometrial cavity to look for and remove submucous fibroids. Then plan the necessary uterine incisions for removing all fibroids (see VIDEO 2).

Read about managing blood loss

4 approaches to managing intraoperative blood loss

In my practice, we employ misoprostol, tranexamic acid, vasopressin, and a uterine and ovarian vessel tourniquet to manage intraoperative blood loss.¹² Although no data exist to show that using these methods together is advantageous, they have different mechanisms of action and no negative interactions.

Misoprostol 400 μg inserted vaginally 2 hours before surgery induces myometrial contraction and compression of the uterine vessels. This agent can reduce blood loss by 98 mL per case.¹²

Tranexamic acid, an antifibrinolytic, is given IV piggyback at the start of surgery at a dose of 10 mg/kg; it can reduce blood loss by 243 mL per case.¹²

Vasopressin 20 U in 100 mL normal saline, injected below the vascular pseudocapsule, causes vasoconstriction of capillaries and small arterioles and venules and can reduce blood loss by 246 mL per case.¹² Intravascular injection should be avoided because rare cases of bradycardia and cardiovascular collapse have been reported.¹³ Using vasopressin to decrease blood loss during myomectomy is an off-label use of this drug.

Place a tourniquet around the lower uterine segment, including the infundibular pelvic ligaments. Tourniquet use is the most effective way to decrease blood loss during myomectomy, since it can reduce blood loss by 1,870 mL.¹² For women who wish to preserve fertility, take care to ensure that the tourniquet does not compromise the tubes. For women who are certain they do not want to preserve fertility, discuss the possibility of performing bilateral salpingectomy to decrease the risk of subsequent tubal (“ovarian”) cancer.

Some surgeons incise the broad ligaments bilaterally and pass the tourniquet through the broad ligaments to avoid compromising blood flow to the ovaries. Occluding the utero- ovarian ligaments with bulldog clamps to control collateral blood flow from the ovarian artery has been described, but the clamps can tear these often enlarged and fragile uterine veins during manipulation of the uterus. Release the tourniquet every 15 to 30 minutes to allow reperfusion of the ovaries. In women with ovarian torsion lasting hours to days, the ovary has been found to resist hypoxia and recover function.¹⁴ Antral follicle counts of detorsed and contralateral normal ovaries following a mean of 13 hours of hypoxia are similar 3 months following detorsion.¹⁵

Consider blood salvage. For women with multiple or very large fibroids, consider using a salvage-type autologous blood transfusion device, which has been shown to reduce the need for heterologous blood transfusion.¹⁶ This device suctions blood from the operative field, mixes it with heparinized saline, and stores the blood in a canister (FIGURE 2). If the patient requires blood reinfusion, the stored blood is washed with saline, filtered, centrifuged, and given back to the patient intravenously. Blood salvage, or cell salvage, avoids the risks of infection and transfusion reaction, and the oxygen transport capacity of salvaged red blood cells is equal to or better than that of stored allogeneic red cells.

Used with permission.

Additional surgical considerations

Previous teaching suggested that proper placement of the uterine incisions was an important factor in limiting blood loss. Some authors suggested that vertical uterine incisions would avoid injury to the ascending uterine vessels should inadvertent extension of the incision occur. Other authors proposed horizontal uterine incisions to avoid severing the arcuate vessels that branch off from the ascending uterine arteries and run transversely across the uterus. However, since fibroids distort the normal vascular architecture, it is not possible to entirely avoid severing vessels in the myometrium (FIGURE 3).¹⁷ Uterine incisions can therefore be made as needed based on the position of the fibroids and the need to avoid inadvertent extension to the ascending uterine vessels or cornua.¹⁷

Used with permission.

Fibroid anatomy and vascularity. Fibroids are entirely encased within the dense blood supply of a pseudocapsule (FIGURE 4),¹⁸ and no distinct “vascular pedicle” exists at the base of the fibroid.¹⁹ It is therefore important to extend the uterine incisions down through the entire pseudocapsule until the fibroid is clearly visible. This will identify a less vascular surgical plane, which is deeper than commonly recognized. Once the fibroid is reached, the pseudocapsule can be “wiped away” using a dry laparotomy sponge (see VIDEO 3). Staying under the pseudocapsule reduces bleeding and may preserve the tissue growth factors and neurotransmitters that are thought to promote wound healing.²⁰

Used with permission.

Adhesion prevention. Limiting the number of uterine incisions has been suggested as a way to reduce the risk of postoperative pelvic adhesions. To extract fibroids that are distant from an incision, however, tunnels must be created within the myometrium, and this makes hemostasis within these defects difficult. In that blood increases the risk of adhesion formation, tunneling may be counterproductive. If tunneling incisions are avoided and hemostasis is secured immediately, the risk of adhesion formation should be lessened.

Therefore, make incisions directly over the fibroids. Remove only easily accessed fibroids and promptly close the defects to secure hemostasis. Multiple uterine incisions may be needed; adhesion barriers may help limit adhesion formation.²¹

On final removal of the tourniquet, carefully inspect for bleeding and perform any necessary re-suturing. We place a pain pump (ON-Q* Pain Relief System, Halyard Health, Inc) for pain management and close the abdominal incision in the standard manner.

Read about postoperative care

Postoperative care: Manage pain, restore function

The pain pump infuser, attached to one soaker catheter above and one below the fascia, provides continuous infusion of bupivacaine to the incision at 4 mL per hour for 4 days. The pain pump greatly reduces the need for postoperative opioids.²² Use of a patient-controlled analgesia pump, with its associated adverse effects (sedation, need for oxygen saturation monitoring, slowing of bowel function) can thus be avoided. The patient’s residual pain is controlled with oral oxycodone or hydrocodone and scheduled nonsteroidal anti-inflammatory drugs.

In my practice, we use an enhanced recovery after surgery (ERAS) protocol designed to reduce postoperative surgical stress and expedite a return to baseline physiologic body functions.²³ Excellent well-researched, evidence-based studies support the effectiveness of ERAS in gynecologic and general surgery procedures.²⁴

Pre-emptive, preoperative analgesia (gabapentin and celecoxib) and end-of-case IV acetaminophen are given to reduce the inflammatory response and the need for postoperative opioids. Once it is confirmed that the patient is hemodynamically stable, add ketorolac 30 mg IV every 6 hours on postoperative day 1. Nausea and vomiting prophylaxis includes ondansetron and dexamethasone at the end of surgery, avoidance of bowel edema with restriction of intraoperative and postoperative fluids (euvolemia), early oral feeding, and gum chewing. On the evening of surgery, the urinary catheter is removed to reduce the risk of bladder infection and facilitate ambulation. Encourage sitting at the bedside and early ambulation starting the evening of surgery to reduce risk of thromboembolism and to avoid skeletal muscle weakness and postoperative fatigue.

Most women are able to be discharged on postoperative day 2. They return to the office on postoperative day 5 for removal of the pain pump.

CASE Continued: Fibroids removed via abdominal myomectomy

We performed an abdominal myomectomy through a Pfannenstiel incision. Nine fibroids—3 of which were not seen on MRI—ranging in size from 1 to 7 cm were removed. Intravaginal misoprostol, IV tranexamic acid, subserosal vasopressin, and a uterine vessel tourniquet limited the intraoperative blood loss to 225 mL. After surgery, a pain pump and ERAS protocol allowed the patient to be discharged on postoperative day 2, and she returned to the office on day 5 for removal of the pain pump. Oral pain medication was continued on an as-needed basis.

Acknowledgement

The author would like to thank Stanley West, MD, for generously teaching him the surgical techniques for performing abdominal myomectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE Woman with fibroids seeks alternative to hysterectomy

A 42-year-old woman (G2P2) presents to the office for evaluation of heavy menstrual bleeding and known uterine fibroids. Physical examination reveals a 16-week-sized uterus, and ultrasonography shows at least 6 fibroids, 2 of which impinge on the uterine cavity. She does not want to have any more children, but she wishes to avoid a hysterectomy.

Abdominal myomectomy: A good option for many women

Abdominal myomectomy is an underutilized procedure. With fibroids as the indication for surgery, 197,000 hysterectomies were performed in the United States in 2010, compared with approximately 40,000 myomectomies.^1,2 Moreover, the rates of both laparoscopic and abdominal myomectomy have decreased following the controversial morcellation advisory issued by the US Food and Drug Administration.³

The differences in the hysterectomy and myomectomy rates might be explained by the many myths ascribed to myomectomy. Such myths include the beliefs that myomectomy, when compared with hysterectomy, is associated with greater risk of visceral injury, more blood loss, poor uterine healing, and high risk of fibroid recurrence, and that myomectomy is unlikely to improve patient symptoms.

Studies show, however, that these beliefs are wrong. The risk of needing treatment for new fibroid growth following myomectomy is low.⁴ Hysterectomy, compared with myomectomy for similar size uteri, is actually associated with a greater risk of injury to the bowel, bladder, and ureters and with a greater risk of operative hemorrhage. Furthermore, hysterectomy (without oophorectomy) can be associated with early menopause in approximately 10% of women, while myomectomy does not alter ovarian hormones. (See “7 Myomectomy myths debunked,” which appeared in the February 2017 issue of OBG Management.) Another myth debunked: Fibroids do not “degenerate” into leiomyosarcomas, and the risk of leiomyosarcoma in premenopausal women with presumed uterine fibroids is extremely low.^5,6

For women who have serious medical problems (severe anemia, ureteral obstruction) due to uterine fibroids, surgery usually is necessary. In addition, women may request surgery for fibroid-associated quality-of-life concerns, such as heavy menstrual bleeding, infertility, pelvic pressure, urinary frequency, or incontinence. In one prospective study, the authors found that when women were assessed 6 months after undergoing myomectomy, 75% reported experiencing a significant decrease in bothersome symptoms.⁷

Myomectomy may be considered even for women with large uterine fibroids who desire uterine conservation. In a systematic review of the perioperative morbidity associated with abdominal myomectomy compared with abdominal hysterectomy for fibroids, which included 1,520 women with uterine size up to 16 to 18 weeks, no difference was found in major morbidity rates.⁸ Investigators who studied 91 women with uterine size ranging from 16 to 36 weeks who underwent abdominal myomectomy reported 1 bowel injury, 1 bladder injury, and 1 reoperation for bowel obstruction; no women had conversion to hysterectomy.⁹

Since ObGyn residency training emphasizes hysterectomy techniques, many residents receive only limited exposure to myomectomy procedures. Increased exposure to and comfort with myomectomy surgical technique would encourage more gynecologists to offer this option to their patients who desire uterine conservation, including those who do not desire future childbearing.

Imaging techniques are essential in the preoperative evaluation

For women with fibroid-related symptoms who desire surgery with uterine preservation, determining the myomectomy approach (abdominal, laparoscopic/robotic, hysteroscopic) depends on accurate assessment of the size, number, and position of the fibroids. If abdominal myomectomy is planned because of uterine size, the presence of numerous fibroids, or patient choice, transvaginal/transabdominal ultrasonography usually is adequate for anticipating what will be found during surgery. Sonography is readily available and is the least costly imaging technique that can help differentiate fibroids from other pelvic pathology. Although small fibroids may not be seen on sonography, they can be palpated and removed at the time of open surgery.

If submucous fibroids need to be better defined, saline-infusion sonography can be performed. However, if laparoscopic/robotic myomectomy (which precludes accurate palpation during surgery) is being considered, magnetic resonance imaging (MRI) allows the best assessment of the size, number, and position of the fibroids.¹⁰ When adenomyosis is considered in the differential diagnosis, MRI is an accurate way to determine its presence and helps in planning the best surgical procedure and approach.

Correct anemia before surgery

Women with fibroids may have anemia requiring correction before surgery to reduce the need for intraoperative or postoperative blood transfusion. Mild iron deficiency anemia can be treated prior to surgery with oral elemental iron 150 to 200 mg per day. Vitamin C 1,000 mg per day helps to increase intestinal iron absorption. Three weeks of treatment with oral iron can increase hemoglobin concentration by 2 g/dL.

For more severe anemia or rapid correction of anemia, intravenous (IV) iron sucrose infusions, 200 mg infused over 2 hours and given 3 times per week for 3 weeks, can increase hemoglobin by 3 g/dL.¹¹ In our ObGyn practice, hematologists manage iron infusions.

Read about abdominal incision technique

Abdominal incision technique

Even a large uterus with multiple fibroids usually can be managed through use of a transverse lower abdominal incision. Prior to reaching the lateral borders of the rectus abdominis, curve the fascial incision cephalad to avoid injury to the ileoinguinal nerves (FIGURE 1). Detaching the midline rectus fascia (linea alba) from the anterior abdominal wall, starting at the pubic symphysis and continuing up to the umbilicus, frees the rectus muscles and allows them to be easily separated (see VIDEO 1). Since fascia is not elastic, these 2 steps are important to allow more room to deliver the uterus through the incision.

Illustration: Marcia Hartsock for OBG Management

Delivery of the uterus through the incision isolates the surgical field from the bowel, bladder, ureters, and pelvic nerves. Once the uterus is delivered, inspect and palpate it for fibroids. Identify the fundus and the position of the uterine cavity by locating both uterine cornua and imagining a straight line between them. It may be necessary to explore the endometrial cavity to look for and remove submucous fibroids. Then plan the necessary uterine incisions for removing all fibroids (see VIDEO 2).

Read about managing blood loss

4 approaches to managing intraoperative blood loss

In my practice, we employ misoprostol, tranexamic acid, vasopressin, and a uterine and ovarian vessel tourniquet to manage intraoperative blood loss.¹² Although no data exist to show that using these methods together is advantageous, they have different mechanisms of action and no negative interactions.

Misoprostol 400 μg inserted vaginally 2 hours before surgery induces myometrial contraction and compression of the uterine vessels. This agent can reduce blood loss by 98 mL per case.¹²

Tranexamic acid, an antifibrinolytic, is given IV piggyback at the start of surgery at a dose of 10 mg/kg; it can reduce blood loss by 243 mL per case.¹²

Vasopressin 20 U in 100 mL normal saline, injected below the vascular pseudocapsule, causes vasoconstriction of capillaries and small arterioles and venules and can reduce blood loss by 246 mL per case.¹² Intravascular injection should be avoided because rare cases of bradycardia and cardiovascular collapse have been reported.¹³ Using vasopressin to decrease blood loss during myomectomy is an off-label use of this drug.

Place a tourniquet around the lower uterine segment, including the infundibular pelvic ligaments. Tourniquet use is the most effective way to decrease blood loss during myomectomy, since it can reduce blood loss by 1,870 mL.¹² For women who wish to preserve fertility, take care to ensure that the tourniquet does not compromise the tubes. For women who are certain they do not want to preserve fertility, discuss the possibility of performing bilateral salpingectomy to decrease the risk of subsequent tubal (“ovarian”) cancer.

Some surgeons incise the broad ligaments bilaterally and pass the tourniquet through the broad ligaments to avoid compromising blood flow to the ovaries. Occluding the utero- ovarian ligaments with bulldog clamps to control collateral blood flow from the ovarian artery has been described, but the clamps can tear these often enlarged and fragile uterine veins during manipulation of the uterus. Release the tourniquet every 15 to 30 minutes to allow reperfusion of the ovaries. In women with ovarian torsion lasting hours to days, the ovary has been found to resist hypoxia and recover function.¹⁴ Antral follicle counts of detorsed and contralateral normal ovaries following a mean of 13 hours of hypoxia are similar 3 months following detorsion.¹⁵

Consider blood salvage. For women with multiple or very large fibroids, consider using a salvage-type autologous blood transfusion device, which has been shown to reduce the need for heterologous blood transfusion.¹⁶ This device suctions blood from the operative field, mixes it with heparinized saline, and stores the blood in a canister (FIGURE 2). If the patient requires blood reinfusion, the stored blood is washed with saline, filtered, centrifuged, and given back to the patient intravenously. Blood salvage, or cell salvage, avoids the risks of infection and transfusion reaction, and the oxygen transport capacity of salvaged red blood cells is equal to or better than that of stored allogeneic red cells.

Used with permission.

Additional surgical considerations

Previous teaching suggested that proper placement of the uterine incisions was an important factor in limiting blood loss. Some authors suggested that vertical uterine incisions would avoid injury to the ascending uterine vessels should inadvertent extension of the incision occur. Other authors proposed horizontal uterine incisions to avoid severing the arcuate vessels that branch off from the ascending uterine arteries and run transversely across the uterus. However, since fibroids distort the normal vascular architecture, it is not possible to entirely avoid severing vessels in the myometrium (FIGURE 3).¹⁷ Uterine incisions can therefore be made as needed based on the position of the fibroids and the need to avoid inadvertent extension to the ascending uterine vessels or cornua.¹⁷

Used with permission.

Fibroid anatomy and vascularity. Fibroids are entirely encased within the dense blood supply of a pseudocapsule (FIGURE 4),¹⁸ and no distinct “vascular pedicle” exists at the base of the fibroid.¹⁹ It is therefore important to extend the uterine incisions down through the entire pseudocapsule until the fibroid is clearly visible. This will identify a less vascular surgical plane, which is deeper than commonly recognized. Once the fibroid is reached, the pseudocapsule can be “wiped away” using a dry laparotomy sponge (see VIDEO 3). Staying under the pseudocapsule reduces bleeding and may preserve the tissue growth factors and neurotransmitters that are thought to promote wound healing.²⁰

Used with permission.

Adhesion prevention. Limiting the number of uterine incisions has been suggested as a way to reduce the risk of postoperative pelvic adhesions. To extract fibroids that are distant from an incision, however, tunnels must be created within the myometrium, and this makes hemostasis within these defects difficult. In that blood increases the risk of adhesion formation, tunneling may be counterproductive. If tunneling incisions are avoided and hemostasis is secured immediately, the risk of adhesion formation should be lessened.

Therefore, make incisions directly over the fibroids. Remove only easily accessed fibroids and promptly close the defects to secure hemostasis. Multiple uterine incisions may be needed; adhesion barriers may help limit adhesion formation.²¹

On final removal of the tourniquet, carefully inspect for bleeding and perform any necessary re-suturing. We place a pain pump (ON-Q* Pain Relief System, Halyard Health, Inc) for pain management and close the abdominal incision in the standard manner.

Read about postoperative care

Postoperative care: Manage pain, restore function

The pain pump infuser, attached to one soaker catheter above and one below the fascia, provides continuous infusion of bupivacaine to the incision at 4 mL per hour for 4 days. The pain pump greatly reduces the need for postoperative opioids.²² Use of a patient-controlled analgesia pump, with its associated adverse effects (sedation, need for oxygen saturation monitoring, slowing of bowel function) can thus be avoided. The patient’s residual pain is controlled with oral oxycodone or hydrocodone and scheduled nonsteroidal anti-inflammatory drugs.

In my practice, we use an enhanced recovery after surgery (ERAS) protocol designed to reduce postoperative surgical stress and expedite a return to baseline physiologic body functions.²³ Excellent well-researched, evidence-based studies support the effectiveness of ERAS in gynecologic and general surgery procedures.²⁴

Pre-emptive, preoperative analgesia (gabapentin and celecoxib) and end-of-case IV acetaminophen are given to reduce the inflammatory response and the need for postoperative opioids. Once it is confirmed that the patient is hemodynamically stable, add ketorolac 30 mg IV every 6 hours on postoperative day 1. Nausea and vomiting prophylaxis includes ondansetron and dexamethasone at the end of surgery, avoidance of bowel edema with restriction of intraoperative and postoperative fluids (euvolemia), early oral feeding, and gum chewing. On the evening of surgery, the urinary catheter is removed to reduce the risk of bladder infection and facilitate ambulation. Encourage sitting at the bedside and early ambulation starting the evening of surgery to reduce risk of thromboembolism and to avoid skeletal muscle weakness and postoperative fatigue.

Most women are able to be discharged on postoperative day 2. They return to the office on postoperative day 5 for removal of the pain pump.

CASE Continued: Fibroids removed via abdominal myomectomy

We performed an abdominal myomectomy through a Pfannenstiel incision. Nine fibroids—3 of which were not seen on MRI—ranging in size from 1 to 7 cm were removed. Intravaginal misoprostol, IV tranexamic acid, subserosal vasopressin, and a uterine vessel tourniquet limited the intraoperative blood loss to 225 mL. After surgery, a pain pump and ERAS protocol allowed the patient to be discharged on postoperative day 2, and she returned to the office on day 5 for removal of the pain pump. Oral pain medication was continued on an as-needed basis.

Acknowledgement

The author would like to thank Stanley West, MD, for generously teaching him the surgical techniques for performing abdominal myomectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE Woman with fibroids seeks alternative to hysterectomy

A 42-year-old woman (G2P2) presents to the office for evaluation of heavy menstrual bleeding and known uterine fibroids. Physical examination reveals a 16-week-sized uterus, and ultrasonography shows at least 6 fibroids, 2 of which impinge on the uterine cavity. She does not want to have any more children, but she wishes to avoid a hysterectomy.

Abdominal myomectomy: A good option for many women

Abdominal myomectomy is an underutilized procedure. With fibroids as the indication for surgery, 197,000 hysterectomies were performed in the United States in 2010, compared with approximately 40,000 myomectomies.^1,2 Moreover, the rates of both laparoscopic and abdominal myomectomy have decreased following the controversial morcellation advisory issued by the US Food and Drug Administration.³

The differences in the hysterectomy and myomectomy rates might be explained by the many myths ascribed to myomectomy. Such myths include the beliefs that myomectomy, when compared with hysterectomy, is associated with greater risk of visceral injury, more blood loss, poor uterine healing, and high risk of fibroid recurrence, and that myomectomy is unlikely to improve patient symptoms.

Studies show, however, that these beliefs are wrong. The risk of needing treatment for new fibroid growth following myomectomy is low.⁴ Hysterectomy, compared with myomectomy for similar size uteri, is actually associated with a greater risk of injury to the bowel, bladder, and ureters and with a greater risk of operative hemorrhage. Furthermore, hysterectomy (without oophorectomy) can be associated with early menopause in approximately 10% of women, while myomectomy does not alter ovarian hormones. (See “7 Myomectomy myths debunked,” which appeared in the February 2017 issue of OBG Management.) Another myth debunked: Fibroids do not “degenerate” into leiomyosarcomas, and the risk of leiomyosarcoma in premenopausal women with presumed uterine fibroids is extremely low.^5,6

For women who have serious medical problems (severe anemia, ureteral obstruction) due to uterine fibroids, surgery usually is necessary. In addition, women may request surgery for fibroid-associated quality-of-life concerns, such as heavy menstrual bleeding, infertility, pelvic pressure, urinary frequency, or incontinence. In one prospective study, the authors found that when women were assessed 6 months after undergoing myomectomy, 75% reported experiencing a significant decrease in bothersome symptoms.⁷

Myomectomy may be considered even for women with large uterine fibroids who desire uterine conservation. In a systematic review of the perioperative morbidity associated with abdominal myomectomy compared with abdominal hysterectomy for fibroids, which included 1,520 women with uterine size up to 16 to 18 weeks, no difference was found in major morbidity rates.⁸ Investigators who studied 91 women with uterine size ranging from 16 to 36 weeks who underwent abdominal myomectomy reported 1 bowel injury, 1 bladder injury, and 1 reoperation for bowel obstruction; no women had conversion to hysterectomy.⁹

Since ObGyn residency training emphasizes hysterectomy techniques, many residents receive only limited exposure to myomectomy procedures. Increased exposure to and comfort with myomectomy surgical technique would encourage more gynecologists to offer this option to their patients who desire uterine conservation, including those who do not desire future childbearing.

Imaging techniques are essential in the preoperative evaluation

For women with fibroid-related symptoms who desire surgery with uterine preservation, determining the myomectomy approach (abdominal, laparoscopic/robotic, hysteroscopic) depends on accurate assessment of the size, number, and position of the fibroids. If abdominal myomectomy is planned because of uterine size, the presence of numerous fibroids, or patient choice, transvaginal/transabdominal ultrasonography usually is adequate for anticipating what will be found during surgery. Sonography is readily available and is the least costly imaging technique that can help differentiate fibroids from other pelvic pathology. Although small fibroids may not be seen on sonography, they can be palpated and removed at the time of open surgery.

If submucous fibroids need to be better defined, saline-infusion sonography can be performed. However, if laparoscopic/robotic myomectomy (which precludes accurate palpation during surgery) is being considered, magnetic resonance imaging (MRI) allows the best assessment of the size, number, and position of the fibroids.¹⁰ When adenomyosis is considered in the differential diagnosis, MRI is an accurate way to determine its presence and helps in planning the best surgical procedure and approach.

Correct anemia before surgery

Women with fibroids may have anemia requiring correction before surgery to reduce the need for intraoperative or postoperative blood transfusion. Mild iron deficiency anemia can be treated prior to surgery with oral elemental iron 150 to 200 mg per day. Vitamin C 1,000 mg per day helps to increase intestinal iron absorption. Three weeks of treatment with oral iron can increase hemoglobin concentration by 2 g/dL.

For more severe anemia or rapid correction of anemia, intravenous (IV) iron sucrose infusions, 200 mg infused over 2 hours and given 3 times per week for 3 weeks, can increase hemoglobin by 3 g/dL.¹¹ In our ObGyn practice, hematologists manage iron infusions.

Read about abdominal incision technique

Abdominal incision technique

Even a large uterus with multiple fibroids usually can be managed through use of a transverse lower abdominal incision. Prior to reaching the lateral borders of the rectus abdominis, curve the fascial incision cephalad to avoid injury to the ileoinguinal nerves (FIGURE 1). Detaching the midline rectus fascia (linea alba) from the anterior abdominal wall, starting at the pubic symphysis and continuing up to the umbilicus, frees the rectus muscles and allows them to be easily separated (see VIDEO 1). Since fascia is not elastic, these 2 steps are important to allow more room to deliver the uterus through the incision.

Illustration: Marcia Hartsock for OBG Management

Delivery of the uterus through the incision isolates the surgical field from the bowel, bladder, ureters, and pelvic nerves. Once the uterus is delivered, inspect and palpate it for fibroids. Identify the fundus and the position of the uterine cavity by locating both uterine cornua and imagining a straight line between them. It may be necessary to explore the endometrial cavity to look for and remove submucous fibroids. Then plan the necessary uterine incisions for removing all fibroids (see VIDEO 2).

Read about managing blood loss

4 approaches to managing intraoperative blood loss

In my practice, we employ misoprostol, tranexamic acid, vasopressin, and a uterine and ovarian vessel tourniquet to manage intraoperative blood loss.¹² Although no data exist to show that using these methods together is advantageous, they have different mechanisms of action and no negative interactions.

Misoprostol 400 μg inserted vaginally 2 hours before surgery induces myometrial contraction and compression of the uterine vessels. This agent can reduce blood loss by 98 mL per case.¹²

Tranexamic acid, an antifibrinolytic, is given IV piggyback at the start of surgery at a dose of 10 mg/kg; it can reduce blood loss by 243 mL per case.¹²

Vasopressin 20 U in 100 mL normal saline, injected below the vascular pseudocapsule, causes vasoconstriction of capillaries and small arterioles and venules and can reduce blood loss by 246 mL per case.¹² Intravascular injection should be avoided because rare cases of bradycardia and cardiovascular collapse have been reported.¹³ Using vasopressin to decrease blood loss during myomectomy is an off-label use of this drug.

Place a tourniquet around the lower uterine segment, including the infundibular pelvic ligaments. Tourniquet use is the most effective way to decrease blood loss during myomectomy, since it can reduce blood loss by 1,870 mL.¹² For women who wish to preserve fertility, take care to ensure that the tourniquet does not compromise the tubes. For women who are certain they do not want to preserve fertility, discuss the possibility of performing bilateral salpingectomy to decrease the risk of subsequent tubal (“ovarian”) cancer.

Some surgeons incise the broad ligaments bilaterally and pass the tourniquet through the broad ligaments to avoid compromising blood flow to the ovaries. Occluding the utero- ovarian ligaments with bulldog clamps to control collateral blood flow from the ovarian artery has been described, but the clamps can tear these often enlarged and fragile uterine veins during manipulation of the uterus. Release the tourniquet every 15 to 30 minutes to allow reperfusion of the ovaries. In women with ovarian torsion lasting hours to days, the ovary has been found to resist hypoxia and recover function.¹⁴ Antral follicle counts of detorsed and contralateral normal ovaries following a mean of 13 hours of hypoxia are similar 3 months following detorsion.¹⁵

Consider blood salvage. For women with multiple or very large fibroids, consider using a salvage-type autologous blood transfusion device, which has been shown to reduce the need for heterologous blood transfusion.¹⁶ This device suctions blood from the operative field, mixes it with heparinized saline, and stores the blood in a canister (FIGURE 2). If the patient requires blood reinfusion, the stored blood is washed with saline, filtered, centrifuged, and given back to the patient intravenously. Blood salvage, or cell salvage, avoids the risks of infection and transfusion reaction, and the oxygen transport capacity of salvaged red blood cells is equal to or better than that of stored allogeneic red cells.

Used with permission.

Additional surgical considerations

Previous teaching suggested that proper placement of the uterine incisions was an important factor in limiting blood loss. Some authors suggested that vertical uterine incisions would avoid injury to the ascending uterine vessels should inadvertent extension of the incision occur. Other authors proposed horizontal uterine incisions to avoid severing the arcuate vessels that branch off from the ascending uterine arteries and run transversely across the uterus. However, since fibroids distort the normal vascular architecture, it is not possible to entirely avoid severing vessels in the myometrium (FIGURE 3).¹⁷ Uterine incisions can therefore be made as needed based on the position of the fibroids and the need to avoid inadvertent extension to the ascending uterine vessels or cornua.¹⁷

Used with permission.

Fibroid anatomy and vascularity. Fibroids are entirely encased within the dense blood supply of a pseudocapsule (FIGURE 4),¹⁸ and no distinct “vascular pedicle” exists at the base of the fibroid.¹⁹ It is therefore important to extend the uterine incisions down through the entire pseudocapsule until the fibroid is clearly visible. This will identify a less vascular surgical plane, which is deeper than commonly recognized. Once the fibroid is reached, the pseudocapsule can be “wiped away” using a dry laparotomy sponge (see VIDEO 3). Staying under the pseudocapsule reduces bleeding and may preserve the tissue growth factors and neurotransmitters that are thought to promote wound healing.²⁰

Used with permission.

Adhesion prevention. Limiting the number of uterine incisions has been suggested as a way to reduce the risk of postoperative pelvic adhesions. To extract fibroids that are distant from an incision, however, tunnels must be created within the myometrium, and this makes hemostasis within these defects difficult. In that blood increases the risk of adhesion formation, tunneling may be counterproductive. If tunneling incisions are avoided and hemostasis is secured immediately, the risk of adhesion formation should be lessened.

Therefore, make incisions directly over the fibroids. Remove only easily accessed fibroids and promptly close the defects to secure hemostasis. Multiple uterine incisions may be needed; adhesion barriers may help limit adhesion formation.²¹

On final removal of the tourniquet, carefully inspect for bleeding and perform any necessary re-suturing. We place a pain pump (ON-Q* Pain Relief System, Halyard Health, Inc) for pain management and close the abdominal incision in the standard manner.

Read about postoperative care

Postoperative care: Manage pain, restore function

The pain pump infuser, attached to one soaker catheter above and one below the fascia, provides continuous infusion of bupivacaine to the incision at 4 mL per hour for 4 days. The pain pump greatly reduces the need for postoperative opioids.²² Use of a patient-controlled analgesia pump, with its associated adverse effects (sedation, need for oxygen saturation monitoring, slowing of bowel function) can thus be avoided. The patient’s residual pain is controlled with oral oxycodone or hydrocodone and scheduled nonsteroidal anti-inflammatory drugs.

In my practice, we use an enhanced recovery after surgery (ERAS) protocol designed to reduce postoperative surgical stress and expedite a return to baseline physiologic body functions.²³ Excellent well-researched, evidence-based studies support the effectiveness of ERAS in gynecologic and general surgery procedures.²⁴

Pre-emptive, preoperative analgesia (gabapentin and celecoxib) and end-of-case IV acetaminophen are given to reduce the inflammatory response and the need for postoperative opioids. Once it is confirmed that the patient is hemodynamically stable, add ketorolac 30 mg IV every 6 hours on postoperative day 1. Nausea and vomiting prophylaxis includes ondansetron and dexamethasone at the end of surgery, avoidance of bowel edema with restriction of intraoperative and postoperative fluids (euvolemia), early oral feeding, and gum chewing. On the evening of surgery, the urinary catheter is removed to reduce the risk of bladder infection and facilitate ambulation. Encourage sitting at the bedside and early ambulation starting the evening of surgery to reduce risk of thromboembolism and to avoid skeletal muscle weakness and postoperative fatigue.

Most women are able to be discharged on postoperative day 2. They return to the office on postoperative day 5 for removal of the pain pump.

CASE Continued: Fibroids removed via abdominal myomectomy

We performed an abdominal myomectomy through a Pfannenstiel incision. Nine fibroids—3 of which were not seen on MRI—ranging in size from 1 to 7 cm were removed. Intravaginal misoprostol, IV tranexamic acid, subserosal vasopressin, and a uterine vessel tourniquet limited the intraoperative blood loss to 225 mL. After surgery, a pain pump and ERAS protocol allowed the patient to be discharged on postoperative day 2, and she returned to the office on day 5 for removal of the pain pump. Oral pain medication was continued on an as-needed basis.

Acknowledgement

The author would like to thank Stanley West, MD, for generously teaching him the surgical techniques for performing abdominal myomectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

HOUSTON – Subspecialties such as urology and gynecology have seen a steady increase in robot-assisted surgery and an offsetting decline in open procedures, but in general surgery, robot-assisted procedures seem to be making gains at the expense of laparoscopy, according to researchers from the University of Nebraska.

In two specific operations, ventral and inguinal hernia repairs (VHR and IHR), the percentage of open procedures has increased or held steady over the 7-year study period while the share of laparoscopic operations declined and robot-assisted surgeries (RAS) increased, Priscila Rodrigues Armijo, MD, reported at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

HOUSTON – Subspecialties such as urology and gynecology have seen a steady increase in robot-assisted surgery and an offsetting decline in open procedures, but in general surgery, robot-assisted procedures seem to be making gains at the expense of laparoscopy, according to researchers from the University of Nebraska.

In two specific operations, ventral and inguinal hernia repairs (VHR and IHR), the percentage of open procedures has increased or held steady over the 7-year study period while the share of laparoscopic operations declined and robot-assisted surgeries (RAS) increased, Priscila Rodrigues Armijo, MD, reported at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

HOUSTON – Subspecialties such as urology and gynecology have seen a steady increase in robot-assisted surgery and an offsetting decline in open procedures, but in general surgery, robot-assisted procedures seem to be making gains at the expense of laparoscopy, according to researchers from the University of Nebraska.

In two specific operations, ventral and inguinal hernia repairs (VHR and IHR), the percentage of open procedures has increased or held steady over the 7-year study period while the share of laparoscopic operations declined and robot-assisted surgeries (RAS) increased, Priscila Rodrigues Armijo, MD, reported at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

The humanized monoclonal antibody ocrelizumab became the first drug to receive approval from the Food and Drug Administration for the treatment of primary progressive multiple sclerosis in adults, according to a March 29 announcement from the agency that also said it is approved for relapsing-remitting disease in adults.

The drug has a mechanism of action similar to rituximab (Rituxan) through its selective targeting of CD20-positive B cells, which depletes them from circulation. CD20-positive B cells are thought to be a key contributor to myelin and axonal damage.

[email protected]

The humanized monoclonal antibody ocrelizumab became the first drug to receive approval from the Food and Drug Administration for the treatment of primary progressive multiple sclerosis in adults, according to a March 29 announcement from the agency that also said it is approved for relapsing-remitting disease in adults.

The drug has a mechanism of action similar to rituximab (Rituxan) through its selective targeting of CD20-positive B cells, which depletes them from circulation. CD20-positive B cells are thought to be a key contributor to myelin and axonal damage.

[email protected]

The humanized monoclonal antibody ocrelizumab became the first drug to receive approval from the Food and Drug Administration for the treatment of primary progressive multiple sclerosis in adults, according to a March 29 announcement from the agency that also said it is approved for relapsing-remitting disease in adults.

The drug has a mechanism of action similar to rituximab (Rituxan) through its selective targeting of CD20-positive B cells, which depletes them from circulation. CD20-positive B cells are thought to be a key contributor to myelin and axonal damage.

[email protected]

Click here to download the PDF

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ORLANDO—Probiotic treatment is associated with the induction of an anti-inflammatory peripheral immune profile in patients with multiple sclerosis (MS), and discontinuing probiotics is associated with a decrease in immune regulatory cells, according to pilot study results presented at the ACTRIMS 2017 Forum. The results suggest that probiotics may be applicable as a therapy for MS. More studies, including controlled clinical trials, are needed to guide treatment decisions, said Howard L. Weiner, MD, Director of the MS Program at Brigham and Women’s Hospital in Newton, Massachusetts, and Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston.

The gut microbiome can modulate neuroimmune function, and studies have found that patients with MS have alterations in the gut microbiome, compared with healthy controls. These findings have led researchers to ask, “Can you treat MS by modulating the microbiome?” Dr. Weiner said. One way to modulate the microbiome is with probiotics, which can be taken as an oral, nontoxic treatment in combination with current therapies. He and his research colleagues conducted a pilot study to investigate the effect of probiotics in patients with MS. “We did not feel that we could do a clinically related study,” he said. Instead, the investigators focused on what happens to the gut microbiome and immune profiles in the blood of patients who receive probiotics.

Two Months of Treatment

The study included nine patients with MS and 13 controls. The investigators gave study participants the probiotic VSL#3. Some formulations of VSL#3 are available in stores. The company that markets the probiotic, Sigma-Tau HealthScience USA, based in Gaithersburg, Maryland, requires a prescription for VSL#3 DS, the double-strength formulation used in the study.

Prior studies of the probiotic have found that VSL#3 provides benefit in animal models of diabetes, colitis, and allergy. Kigerl et al reported that, in mice with spinal cord injury, dysbiosis induced by antibiotics exacerbates neurologic impairment and spinal cord pathology, whereas feeding mice VSL#3 enriched with lactic-acid-producing bacteria triggers a protective immune response, confers neuroprotection, and improves walking. In addition, some doctors prescribe VSL#3 to patients with ulcerative colitis, irritable bowel syndrome, and pouchitis, Dr. Weiner said.

In the pilot study, participants took VSL#3 DS sachets twice daily for two months. Researchers took blood and stool samples from participants before administering the probiotic, at discontinuation of therapy, and three months thereafter.

VSL#3 had no effect on alpha or phylogenetic diversity, but did change the gut microbiome composition. Researchers observed an increase in the relative abundance of specific organisms contained in the probiotic. Methanogens, which are increased in MS, decreased when patients received the probiotic. Administration of VSL#3 also was associated with a decrease in proinflammatory monocytes and decreased expression of activation markers on monocytes and dendritic cells.

When patients stopped probiotic treatment, the numbers of CD39 and IL10 T regulatory cells decreased, and proinflammatory monocytes increased. “We did see changes when you stop treatment, almost as if there is a rebound,” he said. “We are seeing an immune effect in the blood.”

The treatment was well tolerated. “I myself took some,” Dr. Weiner said. “It tastes a little chalky, but otherwise it is fine.” Some patients said they felt better after taking the probiotic. The study was not placebo-controlled, however. Future randomized clinical studies will include MRI scans, he said.

What should neurologists tell patients who want to take a probiotic and ask which probiotic they should take? “We are all asked those questions,” Dr. Weiner said. “I tell them, we really don’t know, but if you would like to take a probiotic, that is fine. But we have no particular recommendations at this time. We need a lot of science before we know what we are doing, as far as treatment, in this regard.”

Changes in the Gut Microbiome in MS

Prior to conducting the pilot study, Sushrut Jangi, MD, research fellow at Brigham and Women’s Hospital, Dr. Weiner, and colleagues studied the gut microbiome in 60 patients with MS and 43 healthy controls. They found that patients with MS had increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, compared with controls. Methanobrevibacter produces methane, and in another cohort, the researchers detected more methane in the breath of patients with MS than in controls.

In addition, Prevotella and Sutterella were increased, and Sarcina was decreased in patients with MS who were treated with disease-modifying therapy, compared with untreated patients with MS. “It gives us a whole series of targets to try to understand,” he said. The gut microbiome alterations in patients with MS correlated with variations in the expression of genes in circulating T cells and monocytes that have been implicated in MS pathogenesis.

How Are the Gut Microbiome and MS Related?

The nature of the relationship between the gut microbiome and MS is unclear. One possibility is that “the gut could be the key to MS,” Dr. Weiner said. An organism in the gut may trigger MS, and that organism potentially could be altered or used in vaccinations to treat or prevent the disease. Alternatively, the gut microbiome might relate to MS susceptibility. Environmental factors, including diet and antibiotics, could affect the microbiome and MS risk. It is also possible that MS disease-modifying therapies act in part through the gut, Dr. Weiner said.

Various treatments targeting the microbiome are under investigation. For example, researchers are asking whether a particular bacteria or fecal microbiome transplants might help treat MS. “I am very interested in the concept of oral tolerance, where we trigger immune responses in the mucosa,” said Dr. Weiner. “We are beginning a trial of anti-CD3 [monoclonal antibodies], which will be given mucosally to stimulate the gut immune response.”

—Jake Remaly

Suggested Reading

Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015.

Kigerl KA, Hall JC, Wang L, et al. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med. 2016;213(12):2603-2620.

Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2016 Sep 16 [Epub ahead of print].

Miyake S, Kim S, Suda W, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015;10(9):e0137429.

Tremlett H, Waubant E. The multiple sclerosis microbiome? Ann Transl Med. 2017;5(3):53.

ORLANDO—Probiotic treatment is associated with the induction of an anti-inflammatory peripheral immune profile in patients with multiple sclerosis (MS), and discontinuing probiotics is associated with a decrease in immune regulatory cells, according to pilot study results presented at the ACTRIMS 2017 Forum. The results suggest that probiotics may be applicable as a therapy for MS. More studies, including controlled clinical trials, are needed to guide treatment decisions, said Howard L. Weiner, MD, Director of the MS Program at Brigham and Women’s Hospital in Newton, Massachusetts, and Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston.

The gut microbiome can modulate neuroimmune function, and studies have found that patients with MS have alterations in the gut microbiome, compared with healthy controls. These findings have led researchers to ask, “Can you treat MS by modulating the microbiome?” Dr. Weiner said. One way to modulate the microbiome is with probiotics, which can be taken as an oral, nontoxic treatment in combination with current therapies. He and his research colleagues conducted a pilot study to investigate the effect of probiotics in patients with MS. “We did not feel that we could do a clinically related study,” he said. Instead, the investigators focused on what happens to the gut microbiome and immune profiles in the blood of patients who receive probiotics.

Two Months of Treatment

The study included nine patients with MS and 13 controls. The investigators gave study participants the probiotic VSL#3. Some formulations of VSL#3 are available in stores. The company that markets the probiotic, Sigma-Tau HealthScience USA, based in Gaithersburg, Maryland, requires a prescription for VSL#3 DS, the double-strength formulation used in the study.

Prior studies of the probiotic have found that VSL#3 provides benefit in animal models of diabetes, colitis, and allergy. Kigerl et al reported that, in mice with spinal cord injury, dysbiosis induced by antibiotics exacerbates neurologic impairment and spinal cord pathology, whereas feeding mice VSL#3 enriched with lactic-acid-producing bacteria triggers a protective immune response, confers neuroprotection, and improves walking. In addition, some doctors prescribe VSL#3 to patients with ulcerative colitis, irritable bowel syndrome, and pouchitis, Dr. Weiner said.

In the pilot study, participants took VSL#3 DS sachets twice daily for two months. Researchers took blood and stool samples from participants before administering the probiotic, at discontinuation of therapy, and three months thereafter.

VSL#3 had no effect on alpha or phylogenetic diversity, but did change the gut microbiome composition. Researchers observed an increase in the relative abundance of specific organisms contained in the probiotic. Methanogens, which are increased in MS, decreased when patients received the probiotic. Administration of VSL#3 also was associated with a decrease in proinflammatory monocytes and decreased expression of activation markers on monocytes and dendritic cells.

When patients stopped probiotic treatment, the numbers of CD39 and IL10 T regulatory cells decreased, and proinflammatory monocytes increased. “We did see changes when you stop treatment, almost as if there is a rebound,” he said. “We are seeing an immune effect in the blood.”

The treatment was well tolerated. “I myself took some,” Dr. Weiner said. “It tastes a little chalky, but otherwise it is fine.” Some patients said they felt better after taking the probiotic. The study was not placebo-controlled, however. Future randomized clinical studies will include MRI scans, he said.

What should neurologists tell patients who want to take a probiotic and ask which probiotic they should take? “We are all asked those questions,” Dr. Weiner said. “I tell them, we really don’t know, but if you would like to take a probiotic, that is fine. But we have no particular recommendations at this time. We need a lot of science before we know what we are doing, as far as treatment, in this regard.”

Changes in the Gut Microbiome in MS

Prior to conducting the pilot study, Sushrut Jangi, MD, research fellow at Brigham and Women’s Hospital, Dr. Weiner, and colleagues studied the gut microbiome in 60 patients with MS and 43 healthy controls. They found that patients with MS had increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, compared with controls. Methanobrevibacter produces methane, and in another cohort, the researchers detected more methane in the breath of patients with MS than in controls.

In addition, Prevotella and Sutterella were increased, and Sarcina was decreased in patients with MS who were treated with disease-modifying therapy, compared with untreated patients with MS. “It gives us a whole series of targets to try to understand,” he said. The gut microbiome alterations in patients with MS correlated with variations in the expression of genes in circulating T cells and monocytes that have been implicated in MS pathogenesis.

How Are the Gut Microbiome and MS Related?

The nature of the relationship between the gut microbiome and MS is unclear. One possibility is that “the gut could be the key to MS,” Dr. Weiner said. An organism in the gut may trigger MS, and that organism potentially could be altered or used in vaccinations to treat or prevent the disease. Alternatively, the gut microbiome might relate to MS susceptibility. Environmental factors, including diet and antibiotics, could affect the microbiome and MS risk. It is also possible that MS disease-modifying therapies act in part through the gut, Dr. Weiner said.

Various treatments targeting the microbiome are under investigation. For example, researchers are asking whether a particular bacteria or fecal microbiome transplants might help treat MS. “I am very interested in the concept of oral tolerance, where we trigger immune responses in the mucosa,” said Dr. Weiner. “We are beginning a trial of anti-CD3 [monoclonal antibodies], which will be given mucosally to stimulate the gut immune response.”

—Jake Remaly

Suggested Reading

Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015.

Kigerl KA, Hall JC, Wang L, et al. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med. 2016;213(12):2603-2620.

Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2016 Sep 16 [Epub ahead of print].

Miyake S, Kim S, Suda W, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015;10(9):e0137429.

Tremlett H, Waubant E. The multiple sclerosis microbiome? Ann Transl Med. 2017;5(3):53.

ORLANDO—Probiotic treatment is associated with the induction of an anti-inflammatory peripheral immune profile in patients with multiple sclerosis (MS), and discontinuing probiotics is associated with a decrease in immune regulatory cells, according to pilot study results presented at the ACTRIMS 2017 Forum. The results suggest that probiotics may be applicable as a therapy for MS. More studies, including controlled clinical trials, are needed to guide treatment decisions, said Howard L. Weiner, MD, Director of the MS Program at Brigham and Women’s Hospital in Newton, Massachusetts, and Robert L. Kroc Professor of Neurology at Harvard Medical School in Boston.

The gut microbiome can modulate neuroimmune function, and studies have found that patients with MS have alterations in the gut microbiome, compared with healthy controls. These findings have led researchers to ask, “Can you treat MS by modulating the microbiome?” Dr. Weiner said. One way to modulate the microbiome is with probiotics, which can be taken as an oral, nontoxic treatment in combination with current therapies. He and his research colleagues conducted a pilot study to investigate the effect of probiotics in patients with MS. “We did not feel that we could do a clinically related study,” he said. Instead, the investigators focused on what happens to the gut microbiome and immune profiles in the blood of patients who receive probiotics.

Two Months of Treatment

The study included nine patients with MS and 13 controls. The investigators gave study participants the probiotic VSL#3. Some formulations of VSL#3 are available in stores. The company that markets the probiotic, Sigma-Tau HealthScience USA, based in Gaithersburg, Maryland, requires a prescription for VSL#3 DS, the double-strength formulation used in the study.

Prior studies of the probiotic have found that VSL#3 provides benefit in animal models of diabetes, colitis, and allergy. Kigerl et al reported that, in mice with spinal cord injury, dysbiosis induced by antibiotics exacerbates neurologic impairment and spinal cord pathology, whereas feeding mice VSL#3 enriched with lactic-acid-producing bacteria triggers a protective immune response, confers neuroprotection, and improves walking. In addition, some doctors prescribe VSL#3 to patients with ulcerative colitis, irritable bowel syndrome, and pouchitis, Dr. Weiner said.

In the pilot study, participants took VSL#3 DS sachets twice daily for two months. Researchers took blood and stool samples from participants before administering the probiotic, at discontinuation of therapy, and three months thereafter.

VSL#3 had no effect on alpha or phylogenetic diversity, but did change the gut microbiome composition. Researchers observed an increase in the relative abundance of specific organisms contained in the probiotic. Methanogens, which are increased in MS, decreased when patients received the probiotic. Administration of VSL#3 also was associated with a decrease in proinflammatory monocytes and decreased expression of activation markers on monocytes and dendritic cells.

When patients stopped probiotic treatment, the numbers of CD39 and IL10 T regulatory cells decreased, and proinflammatory monocytes increased. “We did see changes when you stop treatment, almost as if there is a rebound,” he said. “We are seeing an immune effect in the blood.”

The treatment was well tolerated. “I myself took some,” Dr. Weiner said. “It tastes a little chalky, but otherwise it is fine.” Some patients said they felt better after taking the probiotic. The study was not placebo-controlled, however. Future randomized clinical studies will include MRI scans, he said.

What should neurologists tell patients who want to take a probiotic and ask which probiotic they should take? “We are all asked those questions,” Dr. Weiner said. “I tell them, we really don’t know, but if you would like to take a probiotic, that is fine. But we have no particular recommendations at this time. We need a lot of science before we know what we are doing, as far as treatment, in this regard.”

Changes in the Gut Microbiome in MS

Prior to conducting the pilot study, Sushrut Jangi, MD, research fellow at Brigham and Women’s Hospital, Dr. Weiner, and colleagues studied the gut microbiome in 60 patients with MS and 43 healthy controls. They found that patients with MS had increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, compared with controls. Methanobrevibacter produces methane, and in another cohort, the researchers detected more methane in the breath of patients with MS than in controls.

In addition, Prevotella and Sutterella were increased, and Sarcina was decreased in patients with MS who were treated with disease-modifying therapy, compared with untreated patients with MS. “It gives us a whole series of targets to try to understand,” he said. The gut microbiome alterations in patients with MS correlated with variations in the expression of genes in circulating T cells and monocytes that have been implicated in MS pathogenesis.

How Are the Gut Microbiome and MS Related?

The nature of the relationship between the gut microbiome and MS is unclear. One possibility is that “the gut could be the key to MS,” Dr. Weiner said. An organism in the gut may trigger MS, and that organism potentially could be altered or used in vaccinations to treat or prevent the disease. Alternatively, the gut microbiome might relate to MS susceptibility. Environmental factors, including diet and antibiotics, could affect the microbiome and MS risk. It is also possible that MS disease-modifying therapies act in part through the gut, Dr. Weiner said.

Various treatments targeting the microbiome are under investigation. For example, researchers are asking whether a particular bacteria or fecal microbiome transplants might help treat MS. “I am very interested in the concept of oral tolerance, where we trigger immune responses in the mucosa,” said Dr. Weiner. “We are beginning a trial of anti-CD3 [monoclonal antibodies], which will be given mucosally to stimulate the gut immune response.”

—Jake Remaly

Suggested Reading

Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;7:12015.

Kigerl KA, Hall JC, Wang L, et al. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med. 2016;213(12):2603-2620.

Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. 2016 Sep 16 [Epub ahead of print].

Miyake S, Kim S, Suda W, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015;10(9):e0137429.

Tremlett H, Waubant E. The multiple sclerosis microbiome? Ann Transl Med. 2017;5(3):53.

Two issues of emerging importance are being addressed in the literature: caring for patients with obesity and the concept of delivering value-based care. Value-based care does not mean providing the cheapest care; “value” places importance on quality as well as cost. In this Update, we present 3 practices that the evidence says will deliver value:

• endometrial biopsy in all obese women. Although performing more endometrial biopsies in younger women with a body mass index (BMI) in the obese range will not be less expensive initially, the procedure’s value likely will be in early diagnosis, which hopefully will translate to eventual health care system savings.
• use of the levonorgestrel-releasing intrauterine device (LNG-IUD) in obese patients experiencing abnormal uterine bleeding (AUB). This practice appears to add value in the context of AUB.
• performance of routine diagnostic hysteroscopy in the office setting. We should reconsider our current habits and traditions of performing routine diagnostic hysteroscopy in the operating room (OR) as we move toward providing value-based care.

Read about obesity as a risk factor for endometrial hyperplasia

Endometrial sampling and obesity: Forget the "age 45" rule 

Wise MR, Gill P, Lensen S, Thompson JM, Farquhar CM. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women. Am J Obstet Gynecol. 2016;215(5):598.e1-e8.

How do we bring more value to our patients with AUB? We are well aware that heavy menstrual bleeding places a burden on many women; AUB affects 30% of those of reproductive age. The condition often results in lost workdays and diminished quality of life. It also is associated with significant cost expenditures for hygiene products. It is important not only to bring value to women with heavy menstrual bleeding but also to consider our increasingly expensive health care system.

Obesity is a significant problem that likely will increase the number of women presenting with AUB to ObGyns. Recent studies from New Zealand--which has 33% of its population classified as obese--have provided valuable information.¹

Photo: Shutterstock

Obesity is a risk factor for endometrial hyperplasia

In a large retrospective cohort study, Wise and colleagues analyzed data from 916 premenopausal women referred for AUB who had an endometrial biopsy from 2008 to 2014. The setting was a single large urban secondary women's health service in New Zealand. This study challenges the concept of age-related biopsy guidelines.

Of the 916 women, half were obese. Almost 5% of the women had complex endometrial hyperplasia with atypia or cancer. This incidence had risen from 3% in the years 1995 to 1997, likely due to the rising incidence of obesity. Women with a BMI ≥30 kg/m2 were 4 times more likely to develop complex hyperplasia or cancer than normal-weight women.

Other factors associated with an increased risk for complex hyperplasia or cancer were nulliparity (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.25-5.05), anemia (OR, 2.38; 95% CI, 1.25-4.56), and a thickened endometrium on ultrasonography (defined as >12 mm; OR, 4.04; 95% CI, 1.69-9.65). Age was not a significant risk factor in this group.  

Read about using LNG-IUD to treat AUB in obese women

Small study shows LNG-IUD is effective for treating heavy menstrual bleeding in obese patients

Shaw V, Vandal AC, Coomarasamy C, Ekeroma AJ. The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding. Aust N Z J Obstet Gynaecol. 2016;56(6):619-623.

In another recent study from New Zealand, researchers set out to assess the efficacy of the LNG-IUD for the treatment of heavy menstrual bleeding in obese women. This study is important because there are very few studies of the LNG-IUD in the obese population, and none that have studied quality-of-life measures. 

Shaw and colleagues conducted the prospective observational study at a tertiary teaching hospital. Twenty obese (BMI >30 kg/m2) women with heavy menstrual bleeding agreed to treatment with an LNG-IUD, and 14 completed the study (2 had a device expulsion, 1 had a device removed for pain, and 1 had a device removed for infection; 2 were lost to follow-up). The women were aged 27 to 52 years (median, 40.5 years), and their BMI ranged from 30 to 68 kg/m2 (median, 40.6 kg/m2). At recruitment, 6 months, and 12 months, participants completed the Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment Chart--2 validated tools.

Photo: Shutterstock

Compared with baseline Pictorial Bleeding Assessment scores, the authors found the LNG-IUD to be effective in 73.2% (95% CI, 55.3%-83.9%) of women at 6 months and in 92.8% (95% CI, 80.0%-97.4%) of women at 12 months. Taking into consideration device failures, including removed and expelled LNG-IUDs (which occurred in 4 women, or 20%, in the intent-to-treat analysis), the actual efficacy rate was 67%. Similarly, there was significant improvement at 6 and 12 months in Menstrual Impact Questionnaire scores for social activities, work performance, tiredness, productivity, hygiene,  and depression.

Read about doing more diagnostic hysteroscopy in the office

Is it time to abandon diagnostic hysteroscopy in the OR?

Leung S, Leyland N, Murji A. Decreasing diagnostic hysteroscopy performed in the operating room: a quality improvement initiative. J Obstet Gynaecol Can. 2016;38(4):351-356.

Diagnostic hysteroscopy: Are we stuck in the 1990s? Why are we still performing so many diagnostic hysteroscopies in the OR, thus subjecting our patients to general anesthesia and using our precious OR time? That is the question asked by a group of researchers in Canada. 

According to data from the Ontario Ministry of Health and Long Term Care, diagnostic hysteroscopy was performed 10,027 times in the 2013-2014 fiscal year. Ontario researchers designed and implemented a quality improvement initiative at their institution and successfully decreased the number of diagnostic hysteroscopies performed in their hospital by 70% from their baseline 12-month period. The improvements resulted in a savings of 78 hours of case costing, or $126,984. When these data are extrapolated to the Ontario population (in which more than  10,000 diagnostic hysteroscopies were performed), potentially 7,000 women could avoid the risk of general anesthesia and the health care system could save $11 million. 

Re-education protocol was key to reducing OR procedures

How did the researchers accomplish their results? The multifaceted intervention had  3 key components:

Staff education and review. Many surgeons were performing diagnostic hysteroscopy in the OR because that is how they were trained, and they were unaware of less invasive options. An awareness campaign was conducted by e-mail, during staff meetings, and at rounds. 

Accessible sonohysterography. This diagnostic modality was made more accessible to referring physicians in a timely manner.

Initiation of an operative hysteroscopy education program. To allow more surgeons greater comfort with office hysteroscopy, the authors instituted didactic sessions, dry and wet lab simulations, and mentorship.  

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Two issues of emerging importance are being addressed in the literature: caring for patients with obesity and the concept of delivering value-based care. Value-based care does not mean providing the cheapest care; “value” places importance on quality as well as cost. In this Update, we present 3 practices that the evidence says will deliver value:

• endometrial biopsy in all obese women. Although performing more endometrial biopsies in younger women with a body mass index (BMI) in the obese range will not be less expensive initially, the procedure’s value likely will be in early diagnosis, which hopefully will translate to eventual health care system savings.
• use of the levonorgestrel-releasing intrauterine device (LNG-IUD) in obese patients experiencing abnormal uterine bleeding (AUB). This practice appears to add value in the context of AUB.
• performance of routine diagnostic hysteroscopy in the office setting. We should reconsider our current habits and traditions of performing routine diagnostic hysteroscopy in the operating room (OR) as we move toward providing value-based care.

Read about obesity as a risk factor for endometrial hyperplasia

Endometrial sampling and obesity: Forget the "age 45" rule 

Wise MR, Gill P, Lensen S, Thompson JM, Farquhar CM. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women. Am J Obstet Gynecol. 2016;215(5):598.e1-e8.

How do we bring more value to our patients with AUB? We are well aware that heavy menstrual bleeding places a burden on many women; AUB affects 30% of those of reproductive age. The condition often results in lost workdays and diminished quality of life. It also is associated with significant cost expenditures for hygiene products. It is important not only to bring value to women with heavy menstrual bleeding but also to consider our increasingly expensive health care system.

Obesity is a significant problem that likely will increase the number of women presenting with AUB to ObGyns. Recent studies from New Zealand--which has 33% of its population classified as obese--have provided valuable information.¹

Photo: Shutterstock

Obesity is a risk factor for endometrial hyperplasia

In a large retrospective cohort study, Wise and colleagues analyzed data from 916 premenopausal women referred for AUB who had an endometrial biopsy from 2008 to 2014. The setting was a single large urban secondary women's health service in New Zealand. This study challenges the concept of age-related biopsy guidelines.

Of the 916 women, half were obese. Almost 5% of the women had complex endometrial hyperplasia with atypia or cancer. This incidence had risen from 3% in the years 1995 to 1997, likely due to the rising incidence of obesity. Women with a BMI ≥30 kg/m2 were 4 times more likely to develop complex hyperplasia or cancer than normal-weight women.

Other factors associated with an increased risk for complex hyperplasia or cancer were nulliparity (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.25-5.05), anemia (OR, 2.38; 95% CI, 1.25-4.56), and a thickened endometrium on ultrasonography (defined as >12 mm; OR, 4.04; 95% CI, 1.69-9.65). Age was not a significant risk factor in this group.  

Read about using LNG-IUD to treat AUB in obese women

Small study shows LNG-IUD is effective for treating heavy menstrual bleeding in obese patients

Shaw V, Vandal AC, Coomarasamy C, Ekeroma AJ. The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding. Aust N Z J Obstet Gynaecol. 2016;56(6):619-623.

In another recent study from New Zealand, researchers set out to assess the efficacy of the LNG-IUD for the treatment of heavy menstrual bleeding in obese women. This study is important because there are very few studies of the LNG-IUD in the obese population, and none that have studied quality-of-life measures. 

Shaw and colleagues conducted the prospective observational study at a tertiary teaching hospital. Twenty obese (BMI >30 kg/m2) women with heavy menstrual bleeding agreed to treatment with an LNG-IUD, and 14 completed the study (2 had a device expulsion, 1 had a device removed for pain, and 1 had a device removed for infection; 2 were lost to follow-up). The women were aged 27 to 52 years (median, 40.5 years), and their BMI ranged from 30 to 68 kg/m2 (median, 40.6 kg/m2). At recruitment, 6 months, and 12 months, participants completed the Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment Chart--2 validated tools.

Photo: Shutterstock

Compared with baseline Pictorial Bleeding Assessment scores, the authors found the LNG-IUD to be effective in 73.2% (95% CI, 55.3%-83.9%) of women at 6 months and in 92.8% (95% CI, 80.0%-97.4%) of women at 12 months. Taking into consideration device failures, including removed and expelled LNG-IUDs (which occurred in 4 women, or 20%, in the intent-to-treat analysis), the actual efficacy rate was 67%. Similarly, there was significant improvement at 6 and 12 months in Menstrual Impact Questionnaire scores for social activities, work performance, tiredness, productivity, hygiene,  and depression.

Read about doing more diagnostic hysteroscopy in the office

Is it time to abandon diagnostic hysteroscopy in the OR?

Leung S, Leyland N, Murji A. Decreasing diagnostic hysteroscopy performed in the operating room: a quality improvement initiative. J Obstet Gynaecol Can. 2016;38(4):351-356.

Diagnostic hysteroscopy: Are we stuck in the 1990s? Why are we still performing so many diagnostic hysteroscopies in the OR, thus subjecting our patients to general anesthesia and using our precious OR time? That is the question asked by a group of researchers in Canada. 

According to data from the Ontario Ministry of Health and Long Term Care, diagnostic hysteroscopy was performed 10,027 times in the 2013-2014 fiscal year. Ontario researchers designed and implemented a quality improvement initiative at their institution and successfully decreased the number of diagnostic hysteroscopies performed in their hospital by 70% from their baseline 12-month period. The improvements resulted in a savings of 78 hours of case costing, or $126,984. When these data are extrapolated to the Ontario population (in which more than  10,000 diagnostic hysteroscopies were performed), potentially 7,000 women could avoid the risk of general anesthesia and the health care system could save $11 million. 

Re-education protocol was key to reducing OR procedures

How did the researchers accomplish their results? The multifaceted intervention had  3 key components:

Staff education and review. Many surgeons were performing diagnostic hysteroscopy in the OR because that is how they were trained, and they were unaware of less invasive options. An awareness campaign was conducted by e-mail, during staff meetings, and at rounds. 

Accessible sonohysterography. This diagnostic modality was made more accessible to referring physicians in a timely manner.

Initiation of an operative hysteroscopy education program. To allow more surgeons greater comfort with office hysteroscopy, the authors instituted didactic sessions, dry and wet lab simulations, and mentorship.  

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Two issues of emerging importance are being addressed in the literature: caring for patients with obesity and the concept of delivering value-based care. Value-based care does not mean providing the cheapest care; “value” places importance on quality as well as cost. In this Update, we present 3 practices that the evidence says will deliver value:

• endometrial biopsy in all obese women. Although performing more endometrial biopsies in younger women with a body mass index (BMI) in the obese range will not be less expensive initially, the procedure’s value likely will be in early diagnosis, which hopefully will translate to eventual health care system savings.
• use of the levonorgestrel-releasing intrauterine device (LNG-IUD) in obese patients experiencing abnormal uterine bleeding (AUB). This practice appears to add value in the context of AUB.
• performance of routine diagnostic hysteroscopy in the office setting. We should reconsider our current habits and traditions of performing routine diagnostic hysteroscopy in the operating room (OR) as we move toward providing value-based care.

Read about obesity as a risk factor for endometrial hyperplasia

Endometrial sampling and obesity: Forget the "age 45" rule 

Wise MR, Gill P, Lensen S, Thompson JM, Farquhar CM. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women. Am J Obstet Gynecol. 2016;215(5):598.e1-e8.

How do we bring more value to our patients with AUB? We are well aware that heavy menstrual bleeding places a burden on many women; AUB affects 30% of those of reproductive age. The condition often results in lost workdays and diminished quality of life. It also is associated with significant cost expenditures for hygiene products. It is important not only to bring value to women with heavy menstrual bleeding but also to consider our increasingly expensive health care system.

Obesity is a significant problem that likely will increase the number of women presenting with AUB to ObGyns. Recent studies from New Zealand--which has 33% of its population classified as obese--have provided valuable information.¹

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Obesity is a risk factor for endometrial hyperplasia

In a large retrospective cohort study, Wise and colleagues analyzed data from 916 premenopausal women referred for AUB who had an endometrial biopsy from 2008 to 2014. The setting was a single large urban secondary women's health service in New Zealand. This study challenges the concept of age-related biopsy guidelines.

Of the 916 women, half were obese. Almost 5% of the women had complex endometrial hyperplasia with atypia or cancer. This incidence had risen from 3% in the years 1995 to 1997, likely due to the rising incidence of obesity. Women with a BMI ≥30 kg/m2 were 4 times more likely to develop complex hyperplasia or cancer than normal-weight women.

Other factors associated with an increased risk for complex hyperplasia or cancer were nulliparity (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.25-5.05), anemia (OR, 2.38; 95% CI, 1.25-4.56), and a thickened endometrium on ultrasonography (defined as >12 mm; OR, 4.04; 95% CI, 1.69-9.65). Age was not a significant risk factor in this group.  

Read about using LNG-IUD to treat AUB in obese women

Small study shows LNG-IUD is effective for treating heavy menstrual bleeding in obese patients

Shaw V, Vandal AC, Coomarasamy C, Ekeroma AJ. The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding. Aust N Z J Obstet Gynaecol. 2016;56(6):619-623.

In another recent study from New Zealand, researchers set out to assess the efficacy of the LNG-IUD for the treatment of heavy menstrual bleeding in obese women. This study is important because there are very few studies of the LNG-IUD in the obese population, and none that have studied quality-of-life measures. 

Shaw and colleagues conducted the prospective observational study at a tertiary teaching hospital. Twenty obese (BMI >30 kg/m2) women with heavy menstrual bleeding agreed to treatment with an LNG-IUD, and 14 completed the study (2 had a device expulsion, 1 had a device removed for pain, and 1 had a device removed for infection; 2 were lost to follow-up). The women were aged 27 to 52 years (median, 40.5 years), and their BMI ranged from 30 to 68 kg/m2 (median, 40.6 kg/m2). At recruitment, 6 months, and 12 months, participants completed the Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment Chart--2 validated tools.

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Compared with baseline Pictorial Bleeding Assessment scores, the authors found the LNG-IUD to be effective in 73.2% (95% CI, 55.3%-83.9%) of women at 6 months and in 92.8% (95% CI, 80.0%-97.4%) of women at 12 months. Taking into consideration device failures, including removed and expelled LNG-IUDs (which occurred in 4 women, or 20%, in the intent-to-treat analysis), the actual efficacy rate was 67%. Similarly, there was significant improvement at 6 and 12 months in Menstrual Impact Questionnaire scores for social activities, work performance, tiredness, productivity, hygiene,  and depression.

Read about doing more diagnostic hysteroscopy in the office

Is it time to abandon diagnostic hysteroscopy in the OR?

Leung S, Leyland N, Murji A. Decreasing diagnostic hysteroscopy performed in the operating room: a quality improvement initiative. J Obstet Gynaecol Can. 2016;38(4):351-356.

Diagnostic hysteroscopy: Are we stuck in the 1990s? Why are we still performing so many diagnostic hysteroscopies in the OR, thus subjecting our patients to general anesthesia and using our precious OR time? That is the question asked by a group of researchers in Canada. 

According to data from the Ontario Ministry of Health and Long Term Care, diagnostic hysteroscopy was performed 10,027 times in the 2013-2014 fiscal year. Ontario researchers designed and implemented a quality improvement initiative at their institution and successfully decreased the number of diagnostic hysteroscopies performed in their hospital by 70% from their baseline 12-month period. The improvements resulted in a savings of 78 hours of case costing, or $126,984. When these data are extrapolated to the Ontario population (in which more than  10,000 diagnostic hysteroscopies were performed), potentially 7,000 women could avoid the risk of general anesthesia and the health care system could save $11 million. 

Re-education protocol was key to reducing OR procedures

How did the researchers accomplish their results? The multifaceted intervention had  3 key components:

Staff education and review. Many surgeons were performing diagnostic hysteroscopy in the OR because that is how they were trained, and they were unaware of less invasive options. An awareness campaign was conducted by e-mail, during staff meetings, and at rounds. 

Accessible sonohysterography. This diagnostic modality was made more accessible to referring physicians in a timely manner.

Initiation of an operative hysteroscopy education program. To allow more surgeons greater comfort with office hysteroscopy, the authors instituted didactic sessions, dry and wet lab simulations, and mentorship.  

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