Will Pass

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

Patients with stage III melanoma who have circulating tumor cells (CTCs) at baseline may benefit from adjuvant therapy, according to investigators.

A prospective study showed that patients with at least one CTC upon first presentation had increased risks of both short-term and long-term recurrence, reported lead author Anthony Lucci, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.

While previous studies have suggested that CTCs hold prognostic value for melanoma patients, no trials had evaluated the CellSearch CTC Test – a standardized technique approved by the Food and Drug Administration – in patients with stage III disease, the investigators wrote. Their report is in Clinical Cancer Research.

In the present study, the investigators tested the CellSearch system in 243 patients with stage III cutaneous melanoma who were treated at MD Anderson Cancer Center. Patients with uveal or mucosal melanoma, or distant metastatic disease, were excluded.

Baseline blood samples were drawn within 3 months of regional lymph node metastasis, determined by either lymphadenectomy or sentinel lymph node biopsy. CTC assay positivity required that at least one CTC was detected within a single 7.5 mL tube of blood.

Out of 243 patients, 90 (37%) had a positive test. Of these 90 patients, almost one-quarter (23%) relapsed within 6 months, compared with 8% of patients who had a negative CTC assay. Within the full follow-up period, which was as long as 64 months, 48% of patients with CTCs at baseline relapsed, compared with 37% of patients without CTCs.

Multivariable regression analysis, which was adjusted for age, sex, pathological nodal stage, Breslow thickness, ulceration, and lymphovascular invasion, showed that baseline CTC positivity was an independent risk factor for melanoma recurrence, both in the short term and the long term. Compared with patients who lacked CTCs, those who tested positive were three times as likely to have disease recurrence within 6 months (hazard ratio, 3.13; P = .018). For relapse-free survival within 54 months, this hazard ratio decreased to 2.25 (P = .006).

Although a Cochran-Armitage test suggested that recurrence risks increased with CTC count, the investigators noted that a minority of patients (17%) had two or more CTCs, and just 5% had three or more CTCs.

According to the investigators, CTCs at baseline could become the first reliable blood-based biomarker for this patient population.

“[CTCs] clearly identified a group of stage III patients at high risk for relapse,” the investigators wrote. “This would be clinically very significant as an independent risk factor to help identify the stage III patients who would benefit most from adjuvant systemic therapy.”

This study was funded by the Kiefer family, Sheila Prenowitz, the Simon and Linda Eyles Foundation, the Sam and Janna Moore family, and the Wintermann Foundation. The investigators reported no conflicts of interest.

SOURCE: Lucci et al. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-19-2670.

Patients with stage III melanoma who have circulating tumor cells (CTCs) at baseline may benefit from adjuvant therapy, according to investigators.

A prospective study showed that patients with at least one CTC upon first presentation had increased risks of both short-term and long-term recurrence, reported lead author Anthony Lucci, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.

While previous studies have suggested that CTCs hold prognostic value for melanoma patients, no trials had evaluated the CellSearch CTC Test – a standardized technique approved by the Food and Drug Administration – in patients with stage III disease, the investigators wrote. Their report is in Clinical Cancer Research.

In the present study, the investigators tested the CellSearch system in 243 patients with stage III cutaneous melanoma who were treated at MD Anderson Cancer Center. Patients with uveal or mucosal melanoma, or distant metastatic disease, were excluded.

Baseline blood samples were drawn within 3 months of regional lymph node metastasis, determined by either lymphadenectomy or sentinel lymph node biopsy. CTC assay positivity required that at least one CTC was detected within a single 7.5 mL tube of blood.

Out of 243 patients, 90 (37%) had a positive test. Of these 90 patients, almost one-quarter (23%) relapsed within 6 months, compared with 8% of patients who had a negative CTC assay. Within the full follow-up period, which was as long as 64 months, 48% of patients with CTCs at baseline relapsed, compared with 37% of patients without CTCs.

Multivariable regression analysis, which was adjusted for age, sex, pathological nodal stage, Breslow thickness, ulceration, and lymphovascular invasion, showed that baseline CTC positivity was an independent risk factor for melanoma recurrence, both in the short term and the long term. Compared with patients who lacked CTCs, those who tested positive were three times as likely to have disease recurrence within 6 months (hazard ratio, 3.13; P = .018). For relapse-free survival within 54 months, this hazard ratio decreased to 2.25 (P = .006).

Although a Cochran-Armitage test suggested that recurrence risks increased with CTC count, the investigators noted that a minority of patients (17%) had two or more CTCs, and just 5% had three or more CTCs.

According to the investigators, CTCs at baseline could become the first reliable blood-based biomarker for this patient population.

“[CTCs] clearly identified a group of stage III patients at high risk for relapse,” the investigators wrote. “This would be clinically very significant as an independent risk factor to help identify the stage III patients who would benefit most from adjuvant systemic therapy.”

This study was funded by the Kiefer family, Sheila Prenowitz, the Simon and Linda Eyles Foundation, the Sam and Janna Moore family, and the Wintermann Foundation. The investigators reported no conflicts of interest.

SOURCE: Lucci et al. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-19-2670.

Patients with stage III melanoma who have circulating tumor cells (CTCs) at baseline may benefit from adjuvant therapy, according to investigators.

A prospective study showed that patients with at least one CTC upon first presentation had increased risks of both short-term and long-term recurrence, reported lead author Anthony Lucci, MD, of the University of Texas MD Anderson Cancer Center, Houston, and colleagues.

While previous studies have suggested that CTCs hold prognostic value for melanoma patients, no trials had evaluated the CellSearch CTC Test – a standardized technique approved by the Food and Drug Administration – in patients with stage III disease, the investigators wrote. Their report is in Clinical Cancer Research.

In the present study, the investigators tested the CellSearch system in 243 patients with stage III cutaneous melanoma who were treated at MD Anderson Cancer Center. Patients with uveal or mucosal melanoma, or distant metastatic disease, were excluded.

Baseline blood samples were drawn within 3 months of regional lymph node metastasis, determined by either lymphadenectomy or sentinel lymph node biopsy. CTC assay positivity required that at least one CTC was detected within a single 7.5 mL tube of blood.

Out of 243 patients, 90 (37%) had a positive test. Of these 90 patients, almost one-quarter (23%) relapsed within 6 months, compared with 8% of patients who had a negative CTC assay. Within the full follow-up period, which was as long as 64 months, 48% of patients with CTCs at baseline relapsed, compared with 37% of patients without CTCs.

Multivariable regression analysis, which was adjusted for age, sex, pathological nodal stage, Breslow thickness, ulceration, and lymphovascular invasion, showed that baseline CTC positivity was an independent risk factor for melanoma recurrence, both in the short term and the long term. Compared with patients who lacked CTCs, those who tested positive were three times as likely to have disease recurrence within 6 months (hazard ratio, 3.13; P = .018). For relapse-free survival within 54 months, this hazard ratio decreased to 2.25 (P = .006).

Although a Cochran-Armitage test suggested that recurrence risks increased with CTC count, the investigators noted that a minority of patients (17%) had two or more CTCs, and just 5% had three or more CTCs.

According to the investigators, CTCs at baseline could become the first reliable blood-based biomarker for this patient population.

“[CTCs] clearly identified a group of stage III patients at high risk for relapse,” the investigators wrote. “This would be clinically very significant as an independent risk factor to help identify the stage III patients who would benefit most from adjuvant systemic therapy.”

This study was funded by the Kiefer family, Sheila Prenowitz, the Simon and Linda Eyles Foundation, the Sam and Janna Moore family, and the Wintermann Foundation. The investigators reported no conflicts of interest.

SOURCE: Lucci et al. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-19-2670.

A new ratio based on manometric esophageal length in relation to patient height could offer an objective means of preoperatively identifying shortened esophagus, which could improve surgical planning and outcomes with hiatal hernia repair, according to investigators.

In a retrospective analysis, patients with a lower manometric esophageal length-to-height (MELH) ratio had a higher rate of hiatal hernia recurrence, reported lead author Pooja Lal, MD, of the Cleveland Clinic, and colleagues.

A short esophagus increases tension at the gastroesophageal junction, which may necessitate a lengthening procedure in addition to hiatal hernia repair, the investigators wrote in the Journal of Clinical Gastroenterology. As lengthening may require additional expertise, preoperative knowledge of a short esophagus is beneficial; however, until this point, short esophagus could only be identified intraoperatively. Since previous attempts to define short esophagus were confounded by patient height, the investigators devised the MELH ratio to account for this variable.

The investigators evaluated data from 245 patients who underwent hiatal hernia repair by Nissen fundoplication, of whom 157 also underwent esophageal lengthening with a Collis gastroplasty. The decision to perform a Collis gastroplasty was made intraoperatively if a patient did not have at least 2-3 cm of intra-abdominal esophageal length with minimal tension.

For all patients, the MELH ratio was determined by dividing manometric esophageal length by patient height (both in centimeters).

On average, patients who needed a Collis gastroplasty had a shorter esophagus (20.2 vs. 22.4 cm; P less than .001) and a lower MELH ratio (0.12 vs. 0.13; P less than .001).

Multivariable hazard regression showed that regardless of surgical approach, for every 0.01 U-increment increase in MELH ratio, risk of hernia recurrence decreased by 33% (hazard ratio, 0.67; P less than .001). In contrast, regardless of MELH ratio, repair without Collis was associated with a 500% increased risk of recurrence (HR, 6.1; P less than .001). Over 5 years, the benefit of Collis gastroplasty translated to a significantly lower rate of both hernia recurrence (18% vs. 55%; P less than .001) and reoperations for recurrence (0% vs. 10%; P less than .001).

“We suggest that surgeons and gastroenterologists calculate the MELH ratio before repair of a hiatal hernia, and be cognizant of patients with a shortened esophagus,” the investigators concluded. “An esophageal lengthening procedure such as a Collis gastroplasty may reduce the risk of hernia recurrence and reoperation for recurrence, especially for patients with a MELH ratio less than 0.12.”The investigators reported no conflicts of interest.

SOURCE: Lal P et al. J Clin Gastroenterol. 2020 Jan 20. doi: 10.1097/MCG.0000000000001316.

A new ratio based on manometric esophageal length in relation to patient height could offer an objective means of preoperatively identifying shortened esophagus, which could improve surgical planning and outcomes with hiatal hernia repair, according to investigators.

In a retrospective analysis, patients with a lower manometric esophageal length-to-height (MELH) ratio had a higher rate of hiatal hernia recurrence, reported lead author Pooja Lal, MD, of the Cleveland Clinic, and colleagues.

A short esophagus increases tension at the gastroesophageal junction, which may necessitate a lengthening procedure in addition to hiatal hernia repair, the investigators wrote in the Journal of Clinical Gastroenterology. As lengthening may require additional expertise, preoperative knowledge of a short esophagus is beneficial; however, until this point, short esophagus could only be identified intraoperatively. Since previous attempts to define short esophagus were confounded by patient height, the investigators devised the MELH ratio to account for this variable.

The investigators evaluated data from 245 patients who underwent hiatal hernia repair by Nissen fundoplication, of whom 157 also underwent esophageal lengthening with a Collis gastroplasty. The decision to perform a Collis gastroplasty was made intraoperatively if a patient did not have at least 2-3 cm of intra-abdominal esophageal length with minimal tension.

For all patients, the MELH ratio was determined by dividing manometric esophageal length by patient height (both in centimeters).

On average, patients who needed a Collis gastroplasty had a shorter esophagus (20.2 vs. 22.4 cm; P less than .001) and a lower MELH ratio (0.12 vs. 0.13; P less than .001).

Multivariable hazard regression showed that regardless of surgical approach, for every 0.01 U-increment increase in MELH ratio, risk of hernia recurrence decreased by 33% (hazard ratio, 0.67; P less than .001). In contrast, regardless of MELH ratio, repair without Collis was associated with a 500% increased risk of recurrence (HR, 6.1; P less than .001). Over 5 years, the benefit of Collis gastroplasty translated to a significantly lower rate of both hernia recurrence (18% vs. 55%; P less than .001) and reoperations for recurrence (0% vs. 10%; P less than .001).

“We suggest that surgeons and gastroenterologists calculate the MELH ratio before repair of a hiatal hernia, and be cognizant of patients with a shortened esophagus,” the investigators concluded. “An esophageal lengthening procedure such as a Collis gastroplasty may reduce the risk of hernia recurrence and reoperation for recurrence, especially for patients with a MELH ratio less than 0.12.”The investigators reported no conflicts of interest.

SOURCE: Lal P et al. J Clin Gastroenterol. 2020 Jan 20. doi: 10.1097/MCG.0000000000001316.

A new ratio based on manometric esophageal length in relation to patient height could offer an objective means of preoperatively identifying shortened esophagus, which could improve surgical planning and outcomes with hiatal hernia repair, according to investigators.

In a retrospective analysis, patients with a lower manometric esophageal length-to-height (MELH) ratio had a higher rate of hiatal hernia recurrence, reported lead author Pooja Lal, MD, of the Cleveland Clinic, and colleagues.

A short esophagus increases tension at the gastroesophageal junction, which may necessitate a lengthening procedure in addition to hiatal hernia repair, the investigators wrote in the Journal of Clinical Gastroenterology. As lengthening may require additional expertise, preoperative knowledge of a short esophagus is beneficial; however, until this point, short esophagus could only be identified intraoperatively. Since previous attempts to define short esophagus were confounded by patient height, the investigators devised the MELH ratio to account for this variable.

The investigators evaluated data from 245 patients who underwent hiatal hernia repair by Nissen fundoplication, of whom 157 also underwent esophageal lengthening with a Collis gastroplasty. The decision to perform a Collis gastroplasty was made intraoperatively if a patient did not have at least 2-3 cm of intra-abdominal esophageal length with minimal tension.

For all patients, the MELH ratio was determined by dividing manometric esophageal length by patient height (both in centimeters).

On average, patients who needed a Collis gastroplasty had a shorter esophagus (20.2 vs. 22.4 cm; P less than .001) and a lower MELH ratio (0.12 vs. 0.13; P less than .001).

Multivariable hazard regression showed that regardless of surgical approach, for every 0.01 U-increment increase in MELH ratio, risk of hernia recurrence decreased by 33% (hazard ratio, 0.67; P less than .001). In contrast, regardless of MELH ratio, repair without Collis was associated with a 500% increased risk of recurrence (HR, 6.1; P less than .001). Over 5 years, the benefit of Collis gastroplasty translated to a significantly lower rate of both hernia recurrence (18% vs. 55%; P less than .001) and reoperations for recurrence (0% vs. 10%; P less than .001).

“We suggest that surgeons and gastroenterologists calculate the MELH ratio before repair of a hiatal hernia, and be cognizant of patients with a shortened esophagus,” the investigators concluded. “An esophageal lengthening procedure such as a Collis gastroplasty may reduce the risk of hernia recurrence and reoperation for recurrence, especially for patients with a MELH ratio less than 0.12.”The investigators reported no conflicts of interest.

SOURCE: Lal P et al. J Clin Gastroenterol. 2020 Jan 20. doi: 10.1097/MCG.0000000000001316.

Patients with inflammatory bowel disease (IBD) who receive opioids while hospitalized are three times as likely to be prescribed opioids after discharge, based on a retrospective analysis of more than 800 patients.

Awareness of this dose-dependent relationship and IBD-related risks of opioid use should encourage physicians to consider alternative analgesics, according to lead author Rahul S. Dalal, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

“Recent evidence has demonstrated that opioid use is associated with severe infections and increased mortality among IBD patients,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Despite these concerns, opioids are commonly prescribed to IBD patients in the outpatient setting and to as many as 70% of IBD patients who are hospitalized.”

To look for a possible relationship between inpatient and outpatient opioid use, the investigators reviewed electronic medical records of 862 IBD patients who were treated at three urban hospitals in the University of Pennsylvania Health System. The primary outcome was opioid prescription within 12 months of discharge, including prescriptions at time of hospital dismissal.

During hospitalization, about two-thirds (67.6%) of patients received intravenous opioids. Of the total population, slightly more than half (54.6%) received intravenous hydromorphone and about one-quarter (25.9%) received intravenous morphine. Following discharge, almost half of the population (44.7%) was prescribed opioids, and about 3 out of 4 patients (77.9%) received an additional opioid prescription within the same year.

After accounting for confounders such as IBD severity, preadmission opioid use, pain scores, and psychiatric conditions, data analysis showed that inpatients who received intravenous opioids had a threefold (odds ratio [OR], 3.3) increased likelihood of receiving postdischarge opioid prescription, compared with patients who received no opioids while hospitalized. This association was stronger among those who had IBD flares (OR, 5.4). Furthermore, intravenous dose was positively correlated with postdischarge opioid prescription.

Avoiding intravenous opioids had no impact on the relationship between inpatient and outpatient opioid use. Among inpatients who received only oral or transdermal opioids, a similarly increased likelihood of postdischarge opioid prescription was observed (OR, 4.2), although this was a small cohort (n = 67).

Compared with other physicians, gastroenterologists were the least likely to prescribe opioids. Considering that gastroenterologists were also most likely aware of IBD-related risks of opioid use, the investigators concluded that more interdisciplinary communication and education are needed.

“Alternative analgesics such as acetaminophen, dicyclomine, hyoscyamine, and celecoxib could be advised, as many of these therapies have been deemed relatively safe and effective in this population,” they wrote.The investigators disclosed relationships with Abbott, Gilead, Romark, and others.

SOURCE: Dalal RS et al. Clin Gastro Hepatol. 2019 Dec 27. doi: 10.1016/j.cgh.2019.12.024.

Patients with inflammatory bowel disease (IBD) who receive opioids while hospitalized are three times as likely to be prescribed opioids after discharge, based on a retrospective analysis of more than 800 patients.

Awareness of this dose-dependent relationship and IBD-related risks of opioid use should encourage physicians to consider alternative analgesics, according to lead author Rahul S. Dalal, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

“Recent evidence has demonstrated that opioid use is associated with severe infections and increased mortality among IBD patients,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Despite these concerns, opioids are commonly prescribed to IBD patients in the outpatient setting and to as many as 70% of IBD patients who are hospitalized.”

To look for a possible relationship between inpatient and outpatient opioid use, the investigators reviewed electronic medical records of 862 IBD patients who were treated at three urban hospitals in the University of Pennsylvania Health System. The primary outcome was opioid prescription within 12 months of discharge, including prescriptions at time of hospital dismissal.

During hospitalization, about two-thirds (67.6%) of patients received intravenous opioids. Of the total population, slightly more than half (54.6%) received intravenous hydromorphone and about one-quarter (25.9%) received intravenous morphine. Following discharge, almost half of the population (44.7%) was prescribed opioids, and about 3 out of 4 patients (77.9%) received an additional opioid prescription within the same year.

After accounting for confounders such as IBD severity, preadmission opioid use, pain scores, and psychiatric conditions, data analysis showed that inpatients who received intravenous opioids had a threefold (odds ratio [OR], 3.3) increased likelihood of receiving postdischarge opioid prescription, compared with patients who received no opioids while hospitalized. This association was stronger among those who had IBD flares (OR, 5.4). Furthermore, intravenous dose was positively correlated with postdischarge opioid prescription.

Avoiding intravenous opioids had no impact on the relationship between inpatient and outpatient opioid use. Among inpatients who received only oral or transdermal opioids, a similarly increased likelihood of postdischarge opioid prescription was observed (OR, 4.2), although this was a small cohort (n = 67).

Compared with other physicians, gastroenterologists were the least likely to prescribe opioids. Considering that gastroenterologists were also most likely aware of IBD-related risks of opioid use, the investigators concluded that more interdisciplinary communication and education are needed.

“Alternative analgesics such as acetaminophen, dicyclomine, hyoscyamine, and celecoxib could be advised, as many of these therapies have been deemed relatively safe and effective in this population,” they wrote.The investigators disclosed relationships with Abbott, Gilead, Romark, and others.

SOURCE: Dalal RS et al. Clin Gastro Hepatol. 2019 Dec 27. doi: 10.1016/j.cgh.2019.12.024.

Patients with inflammatory bowel disease (IBD) who receive opioids while hospitalized are three times as likely to be prescribed opioids after discharge, based on a retrospective analysis of more than 800 patients.

Awareness of this dose-dependent relationship and IBD-related risks of opioid use should encourage physicians to consider alternative analgesics, according to lead author Rahul S. Dalal, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

“Recent evidence has demonstrated that opioid use is associated with severe infections and increased mortality among IBD patients,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Despite these concerns, opioids are commonly prescribed to IBD patients in the outpatient setting and to as many as 70% of IBD patients who are hospitalized.”

To look for a possible relationship between inpatient and outpatient opioid use, the investigators reviewed electronic medical records of 862 IBD patients who were treated at three urban hospitals in the University of Pennsylvania Health System. The primary outcome was opioid prescription within 12 months of discharge, including prescriptions at time of hospital dismissal.

During hospitalization, about two-thirds (67.6%) of patients received intravenous opioids. Of the total population, slightly more than half (54.6%) received intravenous hydromorphone and about one-quarter (25.9%) received intravenous morphine. Following discharge, almost half of the population (44.7%) was prescribed opioids, and about 3 out of 4 patients (77.9%) received an additional opioid prescription within the same year.

After accounting for confounders such as IBD severity, preadmission opioid use, pain scores, and psychiatric conditions, data analysis showed that inpatients who received intravenous opioids had a threefold (odds ratio [OR], 3.3) increased likelihood of receiving postdischarge opioid prescription, compared with patients who received no opioids while hospitalized. This association was stronger among those who had IBD flares (OR, 5.4). Furthermore, intravenous dose was positively correlated with postdischarge opioid prescription.

Avoiding intravenous opioids had no impact on the relationship between inpatient and outpatient opioid use. Among inpatients who received only oral or transdermal opioids, a similarly increased likelihood of postdischarge opioid prescription was observed (OR, 4.2), although this was a small cohort (n = 67).

Compared with other physicians, gastroenterologists were the least likely to prescribe opioids. Considering that gastroenterologists were also most likely aware of IBD-related risks of opioid use, the investigators concluded that more interdisciplinary communication and education are needed.

“Alternative analgesics such as acetaminophen, dicyclomine, hyoscyamine, and celecoxib could be advised, as many of these therapies have been deemed relatively safe and effective in this population,” they wrote.The investigators disclosed relationships with Abbott, Gilead, Romark, and others.

SOURCE: Dalal RS et al. Clin Gastro Hepatol. 2019 Dec 27. doi: 10.1016/j.cgh.2019.12.024.

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

For elderly patients with chronic lymphocytic leukemia (CLL) and comorbidities, the anti-CD20 monoclonal antibody ofatumumab may be a safe and effective treatment option, according to a recent phase 2 trial.

Among 32 patients with a median age of 73 years, the overall response rate was 72%, and no grade 4 adverse events occurred, reported lead author Candida Vitale, MD, PhD, of the University of Torino (Italy) and colleagues.

These findings help fill in a knowledge gap created by clinical trial exclusions, which currently make treatment planning “a significant challenge,” the investigators wrote in Journal of Geriatric Oncology.

The study, which was conducted at MD Anderson Cancer Center in Houston, enrolled 34 treatment-naive patients with CLL who were 65 years or older. All patients had an Eastern Cooperative Oncology Group performance status of 2 or 3, or a Charlson comorbidity index of at least 2. Patients with other serious medical conditions and/or primary malignancies were eligible, given that they were not already receiving anticancer therapy.

More than half of the patients (53%) had advanced-stage disease and almost one-third (29%) had at least one other primary cancer diagnosis. Many patients also had high-risk disease characteristics, including a complex karyotype involving three or more chromosomal abnormalities (15%), and/or unmutated immunoglobulin heavy chain variable region (IGHV, 59%).

Among 32 patients eligible for efficacy analysis, the overall response rate was 72%, of which 53% were partial and 19% were complete. Six percent (6%) of patients achieved minimal residual disease negativity. The benefits of ofatumumab extended to patients with high-risk disease characteristics, including unmutated IGHV (65% response rate) and/or a complex karyotype (60% response rate).

Ofatumumab also demonstrated a favorable safety profile, according to the investigators.

With all 34 patients evaluable for safety data, 19 (56%) experienced a grade 1 or 2 infusion-related reaction, and 1 (3%) experienced a grade 3 infusion-related reaction. Twenty-one grade 2 infections were reported, and one grade 3 infection occurred. Other grade 3 treatment-related adverse events included gastrointestinal disturbances, pulmonary embolism, allergic reaction, and hyperglycemia, each of which occurred in one patient. No grade 4 adverse events, or grade 2 or higher hematologic toxicities occurred.

“Our findings show that older patients with poor performance status and comorbidities can safely undergo treatment with ofatumumab,” the investigators concluded. “[The results] also support the possibility of enrolling these patients in clinical trials, so that a larger number of patients will be included and their characteristics will more closely mirror those of typical patients seen in the community.”

The study was funded by Novartis, which markets the antibody. The investigators reported additional relationships with AbbVie, Roche, Celgene, and others.

SOURCE: Vitale et al. J Geriatr Oncol. 2019 Apr 18. doi: 10.1016/j.jgo.2019.04.002.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.

But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.

These findings provide clinical insight into a minimally researched patient population.

“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”

The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.

Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.

Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.

“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.

SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.

For men with prostate cancer, prostatectomy is more likely to cause long-term, clinically meaningful incontinence than are other treatment modalities, based on patient-reported outcomes from more than 2,000 men.

Patients with high-risk disease who underwent prostatectomy also reported worse sexual function at every time point over 5 years, reported Karen E. Hoffman, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues. Other functional differences between treatments faded over time, they said.

“These estimates of the long-term bowel, bladder, and sexual function after localized prostate cancer treatment may clarify expectations and enable men to make informed choices about care,” the investigators wrote. Their report is in JAMA.

The prospective, population-based cohort study involved 1,386 men with favorable-risk prostate cancer and 619 men with unfavorable-risk disease. For men with favorable-risk disease, treatments included low-dose brachytherapy, external beam radiation therapy (EBRT), nerve-sparing prostatectomy, and active surveillance. Men with unfavorable-risk disease were treated with either prostatectomy or EBRT plus androgen deprivation therapy (ADT).

At multiple time points for 5 years, patients completed the 26-item Expanded Prostate Index Composite questionnaire (EPIC; range, 0-100). Clinically significant functional differences between treatment modalities were defined for bowel and hormonal function (4-6), urinary irritative symptoms (5-7), urinary incontinence (6-9), and sexual function (10-12). All 2,005 men completed at least one questionnaire, with about 3 out of 4 men (77%) still responding after 5 years.

Across all patients, prostatectomy was associated with a relatively higher risk of long-term, clinically meaningful urinary incontinence.

For men with favorable-risk disease, the adjusted mean difference for incontinence between nerve-sparing prostatectomy and active surveillance was –10.9 (P less than .001). Patients in this group who elected prostatectomy over active surveillance had a higher rate of urinary leakage (10% vs. 7%; P = .04); however, there was no significant difference in rates of moderate or big problems with urinary function, which suggests that incontinence issues were typically mild.

For men with unfavorable risk disease, prostatectomy carried a higher risk of more severe incontinence. The adjusted mean difference between prostatectomy and EBRT plus ADT was –23.2 (P less than .001), and patients treated with prostatectomy were more likely to report moderate or big problems with urinary function (17% vs. 13%; P = .005). In addition to these urinary issues, men with unfavorable-risk disease who underwent prostatectomy were more likely to report worse sexual function at 5 years, compared with those who were treated with EBRT plus ADT (adjusted mean difference, –12.5).

While other clinically meaningful differences were found between treatments for other functional categories, these differences lost statistical significance by the 5-year time point.

The Agency for Healthcare Research and Quality, the Patient-Centered Outcomes Research Institute, and the National Cancer Institute funded the study. The investigators reported additional relationships with Dendreon, Bayer, AstraZeneca, and others.

SOURCE: Hoffman et al. JAMA. 2020 Jan 14. doi: 10.1001/jama.2019.20675.

For men with prostate cancer, prostatectomy is more likely to cause long-term, clinically meaningful incontinence than are other treatment modalities, based on patient-reported outcomes from more than 2,000 men.

Patients with high-risk disease who underwent prostatectomy also reported worse sexual function at every time point over 5 years, reported Karen E. Hoffman, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues. Other functional differences between treatments faded over time, they said.

“These estimates of the long-term bowel, bladder, and sexual function after localized prostate cancer treatment may clarify expectations and enable men to make informed choices about care,” the investigators wrote. Their report is in JAMA.

The prospective, population-based cohort study involved 1,386 men with favorable-risk prostate cancer and 619 men with unfavorable-risk disease. For men with favorable-risk disease, treatments included low-dose brachytherapy, external beam radiation therapy (EBRT), nerve-sparing prostatectomy, and active surveillance. Men with unfavorable-risk disease were treated with either prostatectomy or EBRT plus androgen deprivation therapy (ADT).

At multiple time points for 5 years, patients completed the 26-item Expanded Prostate Index Composite questionnaire (EPIC; range, 0-100). Clinically significant functional differences between treatment modalities were defined for bowel and hormonal function (4-6), urinary irritative symptoms (5-7), urinary incontinence (6-9), and sexual function (10-12). All 2,005 men completed at least one questionnaire, with about 3 out of 4 men (77%) still responding after 5 years.

Across all patients, prostatectomy was associated with a relatively higher risk of long-term, clinically meaningful urinary incontinence.

For men with favorable-risk disease, the adjusted mean difference for incontinence between nerve-sparing prostatectomy and active surveillance was –10.9 (P less than .001). Patients in this group who elected prostatectomy over active surveillance had a higher rate of urinary leakage (10% vs. 7%; P = .04); however, there was no significant difference in rates of moderate or big problems with urinary function, which suggests that incontinence issues were typically mild.

For men with unfavorable risk disease, prostatectomy carried a higher risk of more severe incontinence. The adjusted mean difference between prostatectomy and EBRT plus ADT was –23.2 (P less than .001), and patients treated with prostatectomy were more likely to report moderate or big problems with urinary function (17% vs. 13%; P = .005). In addition to these urinary issues, men with unfavorable-risk disease who underwent prostatectomy were more likely to report worse sexual function at 5 years, compared with those who were treated with EBRT plus ADT (adjusted mean difference, –12.5).

While other clinically meaningful differences were found between treatments for other functional categories, these differences lost statistical significance by the 5-year time point.

The Agency for Healthcare Research and Quality, the Patient-Centered Outcomes Research Institute, and the National Cancer Institute funded the study. The investigators reported additional relationships with Dendreon, Bayer, AstraZeneca, and others.

SOURCE: Hoffman et al. JAMA. 2020 Jan 14. doi: 10.1001/jama.2019.20675.

For men with prostate cancer, prostatectomy is more likely to cause long-term, clinically meaningful incontinence than are other treatment modalities, based on patient-reported outcomes from more than 2,000 men.

Patients with high-risk disease who underwent prostatectomy also reported worse sexual function at every time point over 5 years, reported Karen E. Hoffman, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues. Other functional differences between treatments faded over time, they said.

“These estimates of the long-term bowel, bladder, and sexual function after localized prostate cancer treatment may clarify expectations and enable men to make informed choices about care,” the investigators wrote. Their report is in JAMA.

The prospective, population-based cohort study involved 1,386 men with favorable-risk prostate cancer and 619 men with unfavorable-risk disease. For men with favorable-risk disease, treatments included low-dose brachytherapy, external beam radiation therapy (EBRT), nerve-sparing prostatectomy, and active surveillance. Men with unfavorable-risk disease were treated with either prostatectomy or EBRT plus androgen deprivation therapy (ADT).

At multiple time points for 5 years, patients completed the 26-item Expanded Prostate Index Composite questionnaire (EPIC; range, 0-100). Clinically significant functional differences between treatment modalities were defined for bowel and hormonal function (4-6), urinary irritative symptoms (5-7), urinary incontinence (6-9), and sexual function (10-12). All 2,005 men completed at least one questionnaire, with about 3 out of 4 men (77%) still responding after 5 years.

Across all patients, prostatectomy was associated with a relatively higher risk of long-term, clinically meaningful urinary incontinence.

For men with favorable-risk disease, the adjusted mean difference for incontinence between nerve-sparing prostatectomy and active surveillance was –10.9 (P less than .001). Patients in this group who elected prostatectomy over active surveillance had a higher rate of urinary leakage (10% vs. 7%; P = .04); however, there was no significant difference in rates of moderate or big problems with urinary function, which suggests that incontinence issues were typically mild.

For men with unfavorable risk disease, prostatectomy carried a higher risk of more severe incontinence. The adjusted mean difference between prostatectomy and EBRT plus ADT was –23.2 (P less than .001), and patients treated with prostatectomy were more likely to report moderate or big problems with urinary function (17% vs. 13%; P = .005). In addition to these urinary issues, men with unfavorable-risk disease who underwent prostatectomy were more likely to report worse sexual function at 5 years, compared with those who were treated with EBRT plus ADT (adjusted mean difference, –12.5).

While other clinically meaningful differences were found between treatments for other functional categories, these differences lost statistical significance by the 5-year time point.

The Agency for Healthcare Research and Quality, the Patient-Centered Outcomes Research Institute, and the National Cancer Institute funded the study. The investigators reported additional relationships with Dendreon, Bayer, AstraZeneca, and others.

SOURCE: Hoffman et al. JAMA. 2020 Jan 14. doi: 10.1001/jama.2019.20675.

For detection of recurrent colorectal cancer, circulating tumor DNA (ctDNA) may be more reliable than carcinoembryonic antigen (CEA), based on a recent Australian study.

Among 144 patients with a history of colorectal cancer, ctDNA testing offered a sensitivity of 66.0%, compared with 31.9% for CEA, reported lead author Erin L. Symonds, PhD, of Flinders University, Bedford Park, Australia, and colleagues, who noted that the two tests had comparable specificity.

According to the investigators, many patients with colorectal cancer who relapse are incurable because they have multiple unresectable metastases.

“This may be due to the poor sensitivity of the currently applied surveillance tools, with guidelines focused on radiological imaging (mostly yearly computed tomography [CT] scans) and regular blood tests for carcinoembryonic antigen (CEA),” the investigators wrote in Cancer. “There is a need to improve the timely detection of metastatic disease while it is still confined to a resectable state.”

To this end, the investigators compared ctDNA testing with CEA testing in a real-world setting. Initially, 548 patients were enrolled. The final dataset included 144 of these patients, all of whom were disease negative on CT or MRI after surgical resection or neoadjuvant therapy. Most exclusions were due to unavailability of imaging results. Circulating tumor DNA testing evaluated methylation levels of BCAT1 and IKZF1 (COLVERA test, Clinical Genomics Pty, North Ryde, New South Wales, Australia) . The LIAISON CEA test was used to measure CEA plasma concentration.

After a median follow-up of almost 4 years, 50 out of 144 patients had disease recurrence, most of which involved distant metastasis (74%). As described above, the sensitivity of ctDNA was higher than CEA by a wide and significant margin (66.0% vs. 31.9%; P less than .001). The superior sensitivity of ctDNA was observed regardless of whether recurrence was locoregional (76.9% vs. 15.4%; P = .006) or distant (62.1% vs. 38.2%; P = .044). Specificity was not statistically different between ctDNA (97.9%) and CEA (96.4%). Multivariate analysis showed that ctDNA was an independent predictor of recurrence, while CEA was not.

“In conclusion, the methylated BCAT1/IKZF1 ctDNA test is twice as sensitive as CEA for detecting recurrent CRC during the monitoring of patients after their initial treatment,” the investigators wrote.

The study was funded by the National Health and Medical Research Council, Clinical Genomics, Cancer Council SA’s Beat Cancer Project, and others. The investigators reported additional relationships with Eiken Chemical and the Commonwealth Scientific and Industrial Research Organisation.

*This story was updated on Jan. 10, 2020.

SOURCE: Symonds et al. Cancer. 2020 Jan 7. doi: 10.1002/cncr.32695.

For detection of recurrent colorectal cancer, circulating tumor DNA (ctDNA) may be more reliable than carcinoembryonic antigen (CEA), based on a recent Australian study.

Among 144 patients with a history of colorectal cancer, ctDNA testing offered a sensitivity of 66.0%, compared with 31.9% for CEA, reported lead author Erin L. Symonds, PhD, of Flinders University, Bedford Park, Australia, and colleagues, who noted that the two tests had comparable specificity.

According to the investigators, many patients with colorectal cancer who relapse are incurable because they have multiple unresectable metastases.

“This may be due to the poor sensitivity of the currently applied surveillance tools, with guidelines focused on radiological imaging (mostly yearly computed tomography [CT] scans) and regular blood tests for carcinoembryonic antigen (CEA),” the investigators wrote in Cancer. “There is a need to improve the timely detection of metastatic disease while it is still confined to a resectable state.”

To this end, the investigators compared ctDNA testing with CEA testing in a real-world setting. Initially, 548 patients were enrolled. The final dataset included 144 of these patients, all of whom were disease negative on CT or MRI after surgical resection or neoadjuvant therapy. Most exclusions were due to unavailability of imaging results. Circulating tumor DNA testing evaluated methylation levels of BCAT1 and IKZF1 (COLVERA test, Clinical Genomics Pty, North Ryde, New South Wales, Australia) . The LIAISON CEA test was used to measure CEA plasma concentration.

After a median follow-up of almost 4 years, 50 out of 144 patients had disease recurrence, most of which involved distant metastasis (74%). As described above, the sensitivity of ctDNA was higher than CEA by a wide and significant margin (66.0% vs. 31.9%; P less than .001). The superior sensitivity of ctDNA was observed regardless of whether recurrence was locoregional (76.9% vs. 15.4%; P = .006) or distant (62.1% vs. 38.2%; P = .044). Specificity was not statistically different between ctDNA (97.9%) and CEA (96.4%). Multivariate analysis showed that ctDNA was an independent predictor of recurrence, while CEA was not.

“In conclusion, the methylated BCAT1/IKZF1 ctDNA test is twice as sensitive as CEA for detecting recurrent CRC during the monitoring of patients after their initial treatment,” the investigators wrote.

The study was funded by the National Health and Medical Research Council, Clinical Genomics, Cancer Council SA’s Beat Cancer Project, and others. The investigators reported additional relationships with Eiken Chemical and the Commonwealth Scientific and Industrial Research Organisation.

*This story was updated on Jan. 10, 2020.

SOURCE: Symonds et al. Cancer. 2020 Jan 7. doi: 10.1002/cncr.32695.

For detection of recurrent colorectal cancer, circulating tumor DNA (ctDNA) may be more reliable than carcinoembryonic antigen (CEA), based on a recent Australian study.

Among 144 patients with a history of colorectal cancer, ctDNA testing offered a sensitivity of 66.0%, compared with 31.9% for CEA, reported lead author Erin L. Symonds, PhD, of Flinders University, Bedford Park, Australia, and colleagues, who noted that the two tests had comparable specificity.

According to the investigators, many patients with colorectal cancer who relapse are incurable because they have multiple unresectable metastases.

“This may be due to the poor sensitivity of the currently applied surveillance tools, with guidelines focused on radiological imaging (mostly yearly computed tomography [CT] scans) and regular blood tests for carcinoembryonic antigen (CEA),” the investigators wrote in Cancer. “There is a need to improve the timely detection of metastatic disease while it is still confined to a resectable state.”

To this end, the investigators compared ctDNA testing with CEA testing in a real-world setting. Initially, 548 patients were enrolled. The final dataset included 144 of these patients, all of whom were disease negative on CT or MRI after surgical resection or neoadjuvant therapy. Most exclusions were due to unavailability of imaging results. Circulating tumor DNA testing evaluated methylation levels of BCAT1 and IKZF1 (COLVERA test, Clinical Genomics Pty, North Ryde, New South Wales, Australia) . The LIAISON CEA test was used to measure CEA plasma concentration.

After a median follow-up of almost 4 years, 50 out of 144 patients had disease recurrence, most of which involved distant metastasis (74%). As described above, the sensitivity of ctDNA was higher than CEA by a wide and significant margin (66.0% vs. 31.9%; P less than .001). The superior sensitivity of ctDNA was observed regardless of whether recurrence was locoregional (76.9% vs. 15.4%; P = .006) or distant (62.1% vs. 38.2%; P = .044). Specificity was not statistically different between ctDNA (97.9%) and CEA (96.4%). Multivariate analysis showed that ctDNA was an independent predictor of recurrence, while CEA was not.

“In conclusion, the methylated BCAT1/IKZF1 ctDNA test is twice as sensitive as CEA for detecting recurrent CRC during the monitoring of patients after their initial treatment,” the investigators wrote.

The study was funded by the National Health and Medical Research Council, Clinical Genomics, Cancer Council SA’s Beat Cancer Project, and others. The investigators reported additional relationships with Eiken Chemical and the Commonwealth Scientific and Industrial Research Organisation.

*This story was updated on Jan. 10, 2020.

SOURCE: Symonds et al. Cancer. 2020 Jan 7. doi: 10.1002/cncr.32695.

In males but not females, hyperinsulinemia, insulin resistance, and metabolic syndrome are independently associated with a higher risk of Barrett’s esophagus (BE), based on a recent case-control study.

These findings offer some insight into why men have higher rates of BE and esophageal adenocarcinoma than do women, reported lead author Bradley J. Kendall, MBBS, PhD, of the University of Queensland in Brisbane, Australia, and colleagues.

“Esophageal adenocarcinoma (EA) and its precursor lesion, Barrett’s esophagus (BE), are more common in males than females,” the investigators wrote in the Journal of Clinical Gastroenterology. “In contrast, gastroesophageal reflux (GER), the major risk factor for BE and EA occurs at similar frequencies in both sexes. In addition, 10% to 20% of BE and EA cases report no history of GER symptoms. This suggests that non-GER factors are important in the development of BE and EA.”

To examine risk factors more closely, the investigators enrolled 227 patients with BE and 241 age- and sex-matched controls. Data were drawn from self-reported questionnaires, interviews, blood pressure readings, and anthropometric measurements, the latter of which included weight, height, and waist circumference. These patient characteristics were supplemented with fasted blood assays. The investigators looked for associations between BE and insulin level, Homeostatic Model Assessment of Insulin Resistance, metabolic syndrome, type 2 diabetes mellitus, insulin-like growth factors, and interleukin-6 (IL-6).

Across the entire population, independent associations were detected between BE and hyperinsulinemia (highest vs. lowest tertile; odds ratio, 1.9; P = .003), insulin resistance (OR, 1.9; P = .006) and metabolic syndrome (OR, 1.8; P = .004). For those with metabolic syndrome, risk of BE increased by 20% for each additional syndrome criterion (P = .02).

When stratifying by sex, however, all of the above risk factors remained statistically significant in men, but not in women. For male patients, compared with the population as a whole, risks were relatively higher for all three factors: hyperinsulinemia (OR, 2.1; P = .007), insulin resistance (OR, 2.1; P = .01), and metabolic syndrome (OR, 2.3; P = .001). Similarly, for men with metabolic syndrome, each additional syndrome criterion increased risk of BE by 40% (P = .005).

Regardless of sex stratification, the other evaluated characteristics (type 2 diabetes mellitus, insulin-like growth factors, and IL-6) were not associated with BE risk.

The investigators offered some possible mechanistic explanations for their findings.

“Hyperinsulinemia ... can result in increased insulin signaling, increased cellular proliferation, reduced apoptosis, oncogenic pathway activation, and enhanced cellular invasion,” they wrote. “In addition, abdominal obesity, which is the driver of these disorders of insulin homeostasis, also alters adipocytokine profiles and induces a chronic systemic inflammatory state. The inflammatory state can result in oncoprotein activation, angiogenesis, cellular proliferation, apoptosis, and metastasis.”

Concerning the difference between sexes, the investigators pointed to patterns of abdominal obesity. “[A]bdominal obesity and the associated metabolic sequelae are more common in males than females,” they wrote. “These observations give rise to the notion that the metabolic syndrome potentiates the inflammatory effects of the gastric refluxate in the distal esophagus and this may play a role in the male predominance of BE and EA.”

While these findings offer insight into the underlying processes that precipitate BE, the investigators suggested that more research is needed.

“The interactions of obesity hormones, GER, and the cells of the esophageal mucosa warrant further investigation,” they concluded.

The study was funded by the Queensland Cancer Fund, Queensland Government Smart State Fund, and the Princess Alexandra Hospital Research Foundation, and others. The investigators reported no disclosures.

SOURCE: Kendall BJ et al. J Clin Gastroenterol. 2019 Dec 24. doi: 10.1097/MCG.0000000000001307.

In males but not females, hyperinsulinemia, insulin resistance, and metabolic syndrome are independently associated with a higher risk of Barrett’s esophagus (BE), based on a recent case-control study.

These findings offer some insight into why men have higher rates of BE and esophageal adenocarcinoma than do women, reported lead author Bradley J. Kendall, MBBS, PhD, of the University of Queensland in Brisbane, Australia, and colleagues.

“Esophageal adenocarcinoma (EA) and its precursor lesion, Barrett’s esophagus (BE), are more common in males than females,” the investigators wrote in the Journal of Clinical Gastroenterology. “In contrast, gastroesophageal reflux (GER), the major risk factor for BE and EA occurs at similar frequencies in both sexes. In addition, 10% to 20% of BE and EA cases report no history of GER symptoms. This suggests that non-GER factors are important in the development of BE and EA.”

To examine risk factors more closely, the investigators enrolled 227 patients with BE and 241 age- and sex-matched controls. Data were drawn from self-reported questionnaires, interviews, blood pressure readings, and anthropometric measurements, the latter of which included weight, height, and waist circumference. These patient characteristics were supplemented with fasted blood assays. The investigators looked for associations between BE and insulin level, Homeostatic Model Assessment of Insulin Resistance, metabolic syndrome, type 2 diabetes mellitus, insulin-like growth factors, and interleukin-6 (IL-6).

Across the entire population, independent associations were detected between BE and hyperinsulinemia (highest vs. lowest tertile; odds ratio, 1.9; P = .003), insulin resistance (OR, 1.9; P = .006) and metabolic syndrome (OR, 1.8; P = .004). For those with metabolic syndrome, risk of BE increased by 20% for each additional syndrome criterion (P = .02).

When stratifying by sex, however, all of the above risk factors remained statistically significant in men, but not in women. For male patients, compared with the population as a whole, risks were relatively higher for all three factors: hyperinsulinemia (OR, 2.1; P = .007), insulin resistance (OR, 2.1; P = .01), and metabolic syndrome (OR, 2.3; P = .001). Similarly, for men with metabolic syndrome, each additional syndrome criterion increased risk of BE by 40% (P = .005).

Regardless of sex stratification, the other evaluated characteristics (type 2 diabetes mellitus, insulin-like growth factors, and IL-6) were not associated with BE risk.

The investigators offered some possible mechanistic explanations for their findings.

“Hyperinsulinemia ... can result in increased insulin signaling, increased cellular proliferation, reduced apoptosis, oncogenic pathway activation, and enhanced cellular invasion,” they wrote. “In addition, abdominal obesity, which is the driver of these disorders of insulin homeostasis, also alters adipocytokine profiles and induces a chronic systemic inflammatory state. The inflammatory state can result in oncoprotein activation, angiogenesis, cellular proliferation, apoptosis, and metastasis.”

Concerning the difference between sexes, the investigators pointed to patterns of abdominal obesity. “[A]bdominal obesity and the associated metabolic sequelae are more common in males than females,” they wrote. “These observations give rise to the notion that the metabolic syndrome potentiates the inflammatory effects of the gastric refluxate in the distal esophagus and this may play a role in the male predominance of BE and EA.”

While these findings offer insight into the underlying processes that precipitate BE, the investigators suggested that more research is needed.

“The interactions of obesity hormones, GER, and the cells of the esophageal mucosa warrant further investigation,” they concluded.

The study was funded by the Queensland Cancer Fund, Queensland Government Smart State Fund, and the Princess Alexandra Hospital Research Foundation, and others. The investigators reported no disclosures.

SOURCE: Kendall BJ et al. J Clin Gastroenterol. 2019 Dec 24. doi: 10.1097/MCG.0000000000001307.

In males but not females, hyperinsulinemia, insulin resistance, and metabolic syndrome are independently associated with a higher risk of Barrett’s esophagus (BE), based on a recent case-control study.

These findings offer some insight into why men have higher rates of BE and esophageal adenocarcinoma than do women, reported lead author Bradley J. Kendall, MBBS, PhD, of the University of Queensland in Brisbane, Australia, and colleagues.

“Esophageal adenocarcinoma (EA) and its precursor lesion, Barrett’s esophagus (BE), are more common in males than females,” the investigators wrote in the Journal of Clinical Gastroenterology. “In contrast, gastroesophageal reflux (GER), the major risk factor for BE and EA occurs at similar frequencies in both sexes. In addition, 10% to 20% of BE and EA cases report no history of GER symptoms. This suggests that non-GER factors are important in the development of BE and EA.”

To examine risk factors more closely, the investigators enrolled 227 patients with BE and 241 age- and sex-matched controls. Data were drawn from self-reported questionnaires, interviews, blood pressure readings, and anthropometric measurements, the latter of which included weight, height, and waist circumference. These patient characteristics were supplemented with fasted blood assays. The investigators looked for associations between BE and insulin level, Homeostatic Model Assessment of Insulin Resistance, metabolic syndrome, type 2 diabetes mellitus, insulin-like growth factors, and interleukin-6 (IL-6).

Across the entire population, independent associations were detected between BE and hyperinsulinemia (highest vs. lowest tertile; odds ratio, 1.9; P = .003), insulin resistance (OR, 1.9; P = .006) and metabolic syndrome (OR, 1.8; P = .004). For those with metabolic syndrome, risk of BE increased by 20% for each additional syndrome criterion (P = .02).

When stratifying by sex, however, all of the above risk factors remained statistically significant in men, but not in women. For male patients, compared with the population as a whole, risks were relatively higher for all three factors: hyperinsulinemia (OR, 2.1; P = .007), insulin resistance (OR, 2.1; P = .01), and metabolic syndrome (OR, 2.3; P = .001). Similarly, for men with metabolic syndrome, each additional syndrome criterion increased risk of BE by 40% (P = .005).

Regardless of sex stratification, the other evaluated characteristics (type 2 diabetes mellitus, insulin-like growth factors, and IL-6) were not associated with BE risk.

The investigators offered some possible mechanistic explanations for their findings.

“Hyperinsulinemia ... can result in increased insulin signaling, increased cellular proliferation, reduced apoptosis, oncogenic pathway activation, and enhanced cellular invasion,” they wrote. “In addition, abdominal obesity, which is the driver of these disorders of insulin homeostasis, also alters adipocytokine profiles and induces a chronic systemic inflammatory state. The inflammatory state can result in oncoprotein activation, angiogenesis, cellular proliferation, apoptosis, and metastasis.”

Concerning the difference between sexes, the investigators pointed to patterns of abdominal obesity. “[A]bdominal obesity and the associated metabolic sequelae are more common in males than females,” they wrote. “These observations give rise to the notion that the metabolic syndrome potentiates the inflammatory effects of the gastric refluxate in the distal esophagus and this may play a role in the male predominance of BE and EA.”

While these findings offer insight into the underlying processes that precipitate BE, the investigators suggested that more research is needed.

“The interactions of obesity hormones, GER, and the cells of the esophageal mucosa warrant further investigation,” they concluded.

The study was funded by the Queensland Cancer Fund, Queensland Government Smart State Fund, and the Princess Alexandra Hospital Research Foundation, and others. The investigators reported no disclosures.

SOURCE: Kendall BJ et al. J Clin Gastroenterol. 2019 Dec 24. doi: 10.1097/MCG.0000000000001307.

The American Gastroenterological Association recently released a clinical practice update for endoscopic treatment of Barrett’s esophagus with dysplasia and/or early esophageal adenocarcinoma.

The update offers best practice advice for a range of clinical scenarios based on published evidence, including guidelines and recent systematic reviews, reported lead author Prateek Sharma, MD, of the University of Kansas, Kansas City. Dr. Sharma was accompanied on the authoring review team by three other expert gastroenterologists from the United States and the Netherlands.

Beyond practice advice, the investigators highlighted a research focus for the future.

“Given the expense and time required for careful and continual surveillance after Barrett’s endoscopic therapy, the future must define improved means of risk-stratifying patients for therapy who are at highest risk for cancer development and for risk of recurrence after complete eradication of intestinal metaplasia,” they wrote in Gastroenterology. “Potentially, we may use a panel of patient characteristics (such as the [Progression in Barrett’s] score), preablation tissue characteristics (e.g., baseline grade of dysplasia) and the posttherapy molecular makeup of the epithelium to help risk stratify our patients.”

For now, many of the treatment principles in the update depend upon histologic features.

For instance, either endoscopic therapy or continued surveillance are reasonable options for patients with Barrett’s esophagus who have confirmed and persistent low-grade dysplasia. In contrast, the update recommends that all patients with high-grade dysplasia or esophageal adenocarcinoma (T1a) undergo endoscopic therapy, highlighting that this method is preferred over esophagectomy for patients with T1a cancer. Along the same lines, the investigators noted that endoscopic therapy is a “reasonable alternative” to esophagectomy in cases of T1b esophageal adenocarcinoma in the presence of minimal invasion and good to moderate differentiation, particularly in patients who are poor candidates for surgery.

During the decision-making process, patients with dysplasia should be advised that not undergoing endoscopic therapy may increase cancer risk, the investigators wrote, adding that patients should also be informed about endoscopic therapy–related risks of bleeding and perforation, which occur in less than 1% of patients, and the risk of postprocedural stricture formation, which occurs in approximately 6% of patients.

If endoscopic therapy is elected, the update suggests that the procedure be done by experts who perform at least 10 new cases per year.

Concerning specifics of therapy, the investigators advised that mucosal ablation be applied to all visible esophageal columnar mucosa, 5-10 mm proximal to the squamocolumnar junction, and 5-10 mm distal to the gastroesophageal junction. Ablation should only be performed in cases of flat Barrett’s esophagus in which no visible abnormalities or signs of inflammation are present, the review team wrote.

The investigators went on to lay out some “practical ground rules” for endoscopic therapy, including a potential pitfall.

“Ablation therapy may consist of multiple 2-3 monthly ablation sessions that may extend over a period of more than a year,” the investigators wrote. “The worst adverse outcome during the treatment period is failing to recognize and treat an invasive cancer while continuing the ablation sessions. This occurrence may place the patient outside of the window of opportunity for curative endoscopic treatment. Therefore, every ablation session starts with careful endoscopic inspection using [high-definition white-light endoscopy] and preferably optical chromoendoscopy to exclude the presence of visible abnormalities that require an endoscopic resection instead of the scheduled ablation. Routine biopsies of flat Barrett’s esophagus are not necessary or recommended prior to ablation at these sessions, as the blood may inhibit optimal energy transfer to the tissue.”

Following successfully achieved complete endoscopic and histologic eradication of intestinal metaplasia, the update calls for surveillance endoscopy with biopsies at intervals of 1 and 3 years for cases of low-grade dysplasia and at intervals of 3, 6, and 12 months for high-grade dysplasia or esophageal adenocarcinoma, followed by annual checks thereafter.

The investigators disclosed relationships with Olympus, Ironwood, Erbe, and others.

SOURCE: Sharma P et al. Gastroenterology. 2019 Nov 12. doi: 10.1053/j.gastro.2019.09.051.

The American Gastroenterological Association recently released a clinical practice update for endoscopic treatment of Barrett’s esophagus with dysplasia and/or early esophageal adenocarcinoma.

The update offers best practice advice for a range of clinical scenarios based on published evidence, including guidelines and recent systematic reviews, reported lead author Prateek Sharma, MD, of the University of Kansas, Kansas City. Dr. Sharma was accompanied on the authoring review team by three other expert gastroenterologists from the United States and the Netherlands.

Beyond practice advice, the investigators highlighted a research focus for the future.

“Given the expense and time required for careful and continual surveillance after Barrett’s endoscopic therapy, the future must define improved means of risk-stratifying patients for therapy who are at highest risk for cancer development and for risk of recurrence after complete eradication of intestinal metaplasia,” they wrote in Gastroenterology. “Potentially, we may use a panel of patient characteristics (such as the [Progression in Barrett’s] score), preablation tissue characteristics (e.g., baseline grade of dysplasia) and the posttherapy molecular makeup of the epithelium to help risk stratify our patients.”

For now, many of the treatment principles in the update depend upon histologic features.

For instance, either endoscopic therapy or continued surveillance are reasonable options for patients with Barrett’s esophagus who have confirmed and persistent low-grade dysplasia. In contrast, the update recommends that all patients with high-grade dysplasia or esophageal adenocarcinoma (T1a) undergo endoscopic therapy, highlighting that this method is preferred over esophagectomy for patients with T1a cancer. Along the same lines, the investigators noted that endoscopic therapy is a “reasonable alternative” to esophagectomy in cases of T1b esophageal adenocarcinoma in the presence of minimal invasion and good to moderate differentiation, particularly in patients who are poor candidates for surgery.

During the decision-making process, patients with dysplasia should be advised that not undergoing endoscopic therapy may increase cancer risk, the investigators wrote, adding that patients should also be informed about endoscopic therapy–related risks of bleeding and perforation, which occur in less than 1% of patients, and the risk of postprocedural stricture formation, which occurs in approximately 6% of patients.

If endoscopic therapy is elected, the update suggests that the procedure be done by experts who perform at least 10 new cases per year.

Concerning specifics of therapy, the investigators advised that mucosal ablation be applied to all visible esophageal columnar mucosa, 5-10 mm proximal to the squamocolumnar junction, and 5-10 mm distal to the gastroesophageal junction. Ablation should only be performed in cases of flat Barrett’s esophagus in which no visible abnormalities or signs of inflammation are present, the review team wrote.

The investigators went on to lay out some “practical ground rules” for endoscopic therapy, including a potential pitfall.

“Ablation therapy may consist of multiple 2-3 monthly ablation sessions that may extend over a period of more than a year,” the investigators wrote. “The worst adverse outcome during the treatment period is failing to recognize and treat an invasive cancer while continuing the ablation sessions. This occurrence may place the patient outside of the window of opportunity for curative endoscopic treatment. Therefore, every ablation session starts with careful endoscopic inspection using [high-definition white-light endoscopy] and preferably optical chromoendoscopy to exclude the presence of visible abnormalities that require an endoscopic resection instead of the scheduled ablation. Routine biopsies of flat Barrett’s esophagus are not necessary or recommended prior to ablation at these sessions, as the blood may inhibit optimal energy transfer to the tissue.”

Following successfully achieved complete endoscopic and histologic eradication of intestinal metaplasia, the update calls for surveillance endoscopy with biopsies at intervals of 1 and 3 years for cases of low-grade dysplasia and at intervals of 3, 6, and 12 months for high-grade dysplasia or esophageal adenocarcinoma, followed by annual checks thereafter.

The investigators disclosed relationships with Olympus, Ironwood, Erbe, and others.

SOURCE: Sharma P et al. Gastroenterology. 2019 Nov 12. doi: 10.1053/j.gastro.2019.09.051.

The American Gastroenterological Association recently released a clinical practice update for endoscopic treatment of Barrett’s esophagus with dysplasia and/or early esophageal adenocarcinoma.

The update offers best practice advice for a range of clinical scenarios based on published evidence, including guidelines and recent systematic reviews, reported lead author Prateek Sharma, MD, of the University of Kansas, Kansas City. Dr. Sharma was accompanied on the authoring review team by three other expert gastroenterologists from the United States and the Netherlands.

Beyond practice advice, the investigators highlighted a research focus for the future.

“Given the expense and time required for careful and continual surveillance after Barrett’s endoscopic therapy, the future must define improved means of risk-stratifying patients for therapy who are at highest risk for cancer development and for risk of recurrence after complete eradication of intestinal metaplasia,” they wrote in Gastroenterology. “Potentially, we may use a panel of patient characteristics (such as the [Progression in Barrett’s] score), preablation tissue characteristics (e.g., baseline grade of dysplasia) and the posttherapy molecular makeup of the epithelium to help risk stratify our patients.”

For now, many of the treatment principles in the update depend upon histologic features.

For instance, either endoscopic therapy or continued surveillance are reasonable options for patients with Barrett’s esophagus who have confirmed and persistent low-grade dysplasia. In contrast, the update recommends that all patients with high-grade dysplasia or esophageal adenocarcinoma (T1a) undergo endoscopic therapy, highlighting that this method is preferred over esophagectomy for patients with T1a cancer. Along the same lines, the investigators noted that endoscopic therapy is a “reasonable alternative” to esophagectomy in cases of T1b esophageal adenocarcinoma in the presence of minimal invasion and good to moderate differentiation, particularly in patients who are poor candidates for surgery.

During the decision-making process, patients with dysplasia should be advised that not undergoing endoscopic therapy may increase cancer risk, the investigators wrote, adding that patients should also be informed about endoscopic therapy–related risks of bleeding and perforation, which occur in less than 1% of patients, and the risk of postprocedural stricture formation, which occurs in approximately 6% of patients.

If endoscopic therapy is elected, the update suggests that the procedure be done by experts who perform at least 10 new cases per year.

Concerning specifics of therapy, the investigators advised that mucosal ablation be applied to all visible esophageal columnar mucosa, 5-10 mm proximal to the squamocolumnar junction, and 5-10 mm distal to the gastroesophageal junction. Ablation should only be performed in cases of flat Barrett’s esophagus in which no visible abnormalities or signs of inflammation are present, the review team wrote.

The investigators went on to lay out some “practical ground rules” for endoscopic therapy, including a potential pitfall.

“Ablation therapy may consist of multiple 2-3 monthly ablation sessions that may extend over a period of more than a year,” the investigators wrote. “The worst adverse outcome during the treatment period is failing to recognize and treat an invasive cancer while continuing the ablation sessions. This occurrence may place the patient outside of the window of opportunity for curative endoscopic treatment. Therefore, every ablation session starts with careful endoscopic inspection using [high-definition white-light endoscopy] and preferably optical chromoendoscopy to exclude the presence of visible abnormalities that require an endoscopic resection instead of the scheduled ablation. Routine biopsies of flat Barrett’s esophagus are not necessary or recommended prior to ablation at these sessions, as the blood may inhibit optimal energy transfer to the tissue.”

Following successfully achieved complete endoscopic and histologic eradication of intestinal metaplasia, the update calls for surveillance endoscopy with biopsies at intervals of 1 and 3 years for cases of low-grade dysplasia and at intervals of 3, 6, and 12 months for high-grade dysplasia or esophageal adenocarcinoma, followed by annual checks thereafter.

The investigators disclosed relationships with Olympus, Ironwood, Erbe, and others.

SOURCE: Sharma P et al. Gastroenterology. 2019 Nov 12. doi: 10.1053/j.gastro.2019.09.051.