Less Liver Cancer in HCV Patients Given Antiviral Therapy

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Less Liver Cancer in HCV Patients Given Antiviral Therapy

Antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with hepatitis C infections, Dr. Nina Kimer reported in the Oct. 22 issue of BMJ Open, published online.

Moreover, the effect seems to persist regardless of whether sustained virologic response is achieved.

Dr. Kimer, of Copenhagen University Hospital, Hvidovre, Denmark, and colleagues conducted a meta-analysis of trials looking at hepatitis C-related cirrhosis or fibrosis (BMJ Open 2012;2:e001313 [doi:10.1136/bmjopen-2012-001313]).

Courtesy US. Dept of Veterans Affairs
Researchers report that antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with Hepatitis C (shown here).

The primary analysis focused on randomized controlled trials, although prospective cohort studies with control groups were included in sensitivity analyses.

The authors searched the Cochrane Library, PubMed, EMBASE, and Web of Science databases, as well as reference lists from relevant papers, conference proceedings, and the World Health Organization Trial Search Portal.

Studies looking at HIV and chronic hepatitis B were excluded, for a total of eight randomized trials and five prospective cohort studies.

The duration of therapy (which included pegylated interferon in two trials, interferon plus ribavirin in one trial, and interferon monotherapy in the remaining trials) varied from 1 to 5 years. Follow-up ranged from 2 to 8.7 years.

Overall, the authors found that 81 of 1,156 patients who received antiviral therapy and 129 of 1,074 control patients who received no therapy developed hepatocellular carcinoma.

The relative risk for antiviral therapy, compared with no treatment, was 0.53 (95% confidence interval, 0.34-0.81).

"The corresponding number needed to treat to prevent one case of [hepatocellular carcinoma] was eight patients," added the researchers.

And while the effect of antivirals was more pronounced among patients with a virological response (RR 0.15; 95% CI, 0.05-0.45), there was nevertheless a clear reduction in risk for nonresponders to antivirals, with a relative risk of 0.57, compared with controls (95% CI 0.37-0.85).

"Although the intervention was more beneficial among sustained virological responders than nonresponders, there was a clear effect in both patient groups. ... Antiviral therapy may have beneficial effects on the risk of developing HCC that are unrelated to the virological response."

On the other hand, there was no reported effect of antiviral therapy on all-cause mortality, liver-related mortality, or liver-related morbidity in this population.

Dr. Kimer conceded several limitations to this analysis. "Only two of the included trials evaluated pegylated interferon, which is the current standard treatment for chronic hepatitis C."

Moreover, the duration of treatment in several included studies was "relatively long, which may increase the proportion of responders."

Finally, Dr. Kimer added that the researchers were unable to perform subgroup analysis to determine which treatment duration or dose is best.

"Based on the duration of follow-up and the lack of clear evidence concerning morbidity or mortality, we cannot exclude that interferon delays rather than prevents carcinogenesis," concluded the investigators.

Nevertheless, the "protection from HCC might be even better among patients in current antiviral therapy since the proportion of virological responders continues to increase with ongoing improvements in therapy," they wrote.

"Additional randomized trials with longer follow-up are still warranted to determine whether this is the case," they noted.

The authors disclosed having no outside funding and no competing interests related to this study.

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Antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with hepatitis C infections, Dr. Nina Kimer reported in the Oct. 22 issue of BMJ Open, published online.

Moreover, the effect seems to persist regardless of whether sustained virologic response is achieved.

Dr. Kimer, of Copenhagen University Hospital, Hvidovre, Denmark, and colleagues conducted a meta-analysis of trials looking at hepatitis C-related cirrhosis or fibrosis (BMJ Open 2012;2:e001313 [doi:10.1136/bmjopen-2012-001313]).

Courtesy US. Dept of Veterans Affairs
Researchers report that antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with Hepatitis C (shown here).

The primary analysis focused on randomized controlled trials, although prospective cohort studies with control groups were included in sensitivity analyses.

The authors searched the Cochrane Library, PubMed, EMBASE, and Web of Science databases, as well as reference lists from relevant papers, conference proceedings, and the World Health Organization Trial Search Portal.

Studies looking at HIV and chronic hepatitis B were excluded, for a total of eight randomized trials and five prospective cohort studies.

The duration of therapy (which included pegylated interferon in two trials, interferon plus ribavirin in one trial, and interferon monotherapy in the remaining trials) varied from 1 to 5 years. Follow-up ranged from 2 to 8.7 years.

Overall, the authors found that 81 of 1,156 patients who received antiviral therapy and 129 of 1,074 control patients who received no therapy developed hepatocellular carcinoma.

The relative risk for antiviral therapy, compared with no treatment, was 0.53 (95% confidence interval, 0.34-0.81).

"The corresponding number needed to treat to prevent one case of [hepatocellular carcinoma] was eight patients," added the researchers.

And while the effect of antivirals was more pronounced among patients with a virological response (RR 0.15; 95% CI, 0.05-0.45), there was nevertheless a clear reduction in risk for nonresponders to antivirals, with a relative risk of 0.57, compared with controls (95% CI 0.37-0.85).

"Although the intervention was more beneficial among sustained virological responders than nonresponders, there was a clear effect in both patient groups. ... Antiviral therapy may have beneficial effects on the risk of developing HCC that are unrelated to the virological response."

On the other hand, there was no reported effect of antiviral therapy on all-cause mortality, liver-related mortality, or liver-related morbidity in this population.

Dr. Kimer conceded several limitations to this analysis. "Only two of the included trials evaluated pegylated interferon, which is the current standard treatment for chronic hepatitis C."

Moreover, the duration of treatment in several included studies was "relatively long, which may increase the proportion of responders."

Finally, Dr. Kimer added that the researchers were unable to perform subgroup analysis to determine which treatment duration or dose is best.

"Based on the duration of follow-up and the lack of clear evidence concerning morbidity or mortality, we cannot exclude that interferon delays rather than prevents carcinogenesis," concluded the investigators.

Nevertheless, the "protection from HCC might be even better among patients in current antiviral therapy since the proportion of virological responders continues to increase with ongoing improvements in therapy," they wrote.

"Additional randomized trials with longer follow-up are still warranted to determine whether this is the case," they noted.

The authors disclosed having no outside funding and no competing interests related to this study.

Antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with hepatitis C infections, Dr. Nina Kimer reported in the Oct. 22 issue of BMJ Open, published online.

Moreover, the effect seems to persist regardless of whether sustained virologic response is achieved.

Dr. Kimer, of Copenhagen University Hospital, Hvidovre, Denmark, and colleagues conducted a meta-analysis of trials looking at hepatitis C-related cirrhosis or fibrosis (BMJ Open 2012;2:e001313 [doi:10.1136/bmjopen-2012-001313]).

Courtesy US. Dept of Veterans Affairs
Researchers report that antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with Hepatitis C (shown here).

The primary analysis focused on randomized controlled trials, although prospective cohort studies with control groups were included in sensitivity analyses.

The authors searched the Cochrane Library, PubMed, EMBASE, and Web of Science databases, as well as reference lists from relevant papers, conference proceedings, and the World Health Organization Trial Search Portal.

Studies looking at HIV and chronic hepatitis B were excluded, for a total of eight randomized trials and five prospective cohort studies.

The duration of therapy (which included pegylated interferon in two trials, interferon plus ribavirin in one trial, and interferon monotherapy in the remaining trials) varied from 1 to 5 years. Follow-up ranged from 2 to 8.7 years.

Overall, the authors found that 81 of 1,156 patients who received antiviral therapy and 129 of 1,074 control patients who received no therapy developed hepatocellular carcinoma.

The relative risk for antiviral therapy, compared with no treatment, was 0.53 (95% confidence interval, 0.34-0.81).

"The corresponding number needed to treat to prevent one case of [hepatocellular carcinoma] was eight patients," added the researchers.

And while the effect of antivirals was more pronounced among patients with a virological response (RR 0.15; 95% CI, 0.05-0.45), there was nevertheless a clear reduction in risk for nonresponders to antivirals, with a relative risk of 0.57, compared with controls (95% CI 0.37-0.85).

"Although the intervention was more beneficial among sustained virological responders than nonresponders, there was a clear effect in both patient groups. ... Antiviral therapy may have beneficial effects on the risk of developing HCC that are unrelated to the virological response."

On the other hand, there was no reported effect of antiviral therapy on all-cause mortality, liver-related mortality, or liver-related morbidity in this population.

Dr. Kimer conceded several limitations to this analysis. "Only two of the included trials evaluated pegylated interferon, which is the current standard treatment for chronic hepatitis C."

Moreover, the duration of treatment in several included studies was "relatively long, which may increase the proportion of responders."

Finally, Dr. Kimer added that the researchers were unable to perform subgroup analysis to determine which treatment duration or dose is best.

"Based on the duration of follow-up and the lack of clear evidence concerning morbidity or mortality, we cannot exclude that interferon delays rather than prevents carcinogenesis," concluded the investigators.

Nevertheless, the "protection from HCC might be even better among patients in current antiviral therapy since the proportion of virological responders continues to increase with ongoing improvements in therapy," they wrote.

"Additional randomized trials with longer follow-up are still warranted to determine whether this is the case," they noted.

The authors disclosed having no outside funding and no competing interests related to this study.

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Major Finding: Antiviral therapy for hepatitis C carried a relative risk of 0.53 for developing hepatocellular carcinoma, compared with no treatment (95% confidence interval, 0.34-0.81).

Data Source: A meta-analysis of randomized controlled trials.

Disclosures: The authors disclosed having no outside funding and no competing interests related to this study.

Postop Radiation Slows Prostate Cancer Progression

Selection of Patients Is Key
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Postop Radiation Slows Prostate Cancer Progression

Delivering radiation therapy immediately after radical prostatectomy resulted in fewer cases of biochemical progression of prostate cancer, compared with a "wait-and-see" approach, according to long-term data from a randomized phase III trial.

However, no such effect on overall survival was seen, with a possible detrimental effect in patients older than 70 years, investigators reported online Oct. 19 in the Lancet (doi: 10.1016/S0140-6736(12)61253-7).

Dr. Michel Bolla, of the Centre Hospitalier Universitaire A Michallon in Grenoble, France, and his colleagues looked at 1,005 men enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial, who were followed for a median of 10.6 years.

The cohort (median age 65 years) included patients with untreated adenocarcinoma of the prostate and at least one of the following: capsular perforation, positive surgical margins, or seminal vesicle invasion.

All patients underwent radical prostatectomy, and were then randomly assigned either to receive immediate postoperative external irradiation (within 16 weeks of surgery) or to a "wait-and-see" policy, whereby subsequent treatment was delayed until biochemical or clinical relapse.

Overall, Dr. Bolla and his coauthors found that 198 patients (39.4%) in the postoperative radiation group had biochemical progression (defined as an increase in prostate-specific antigen concentration to more than 0.2 mcg/L measured on two occasions at least 2 weeks apart), clinical progression, or died.

In contrast, the "wait-and-see" group recorded 311 patients (61.8%) who either progressed or died, for a hazard ratio of 0.49 for the radiation approach (P less than .0001).

Stratifying the results by age showed that patients under 70 years old had improved biochemical progression-free survival (hazard ratio, 0.44; P less than .0001) and clinical progression-free survival (HR, 0.67; P = .0013) in the radiation cohort compared with wait-and-see patients.

However, "excess mortality was seen in patients aged 70 years or older who had received immediate radiation compared with those aged 70 years or older who were on the wait-and-see policy," they wrote, with 40 deaths out of 94 older patients in the radiation group versus 20 deaths out of 102 patients in the wait-and-see group (HR, 2.94; P less than .0001).

Finally, looking at the entire cohort, the authors found that overall all-cause 10-year survival did not differ substantially, at 76.9% for the postoperative radiation patients and 80.7% for the wait-and-see group.

"Prostate cancer mortality did not differ significantly between groups either," added the authors.

Dr. Bolla and his colleagues said they had no conflicts of interest related to this study, which was funded by the Ligue Nationale contre le Cancer and the EORTC Charitable Trust.

Body

In a comment accompanying the article, Dr. Jason A. Efstathiou wrote that "the decision to treat [prostate cancer] needs multidisciplinary input" from the entire uro-oncology team, including surgical, radiation, and medical specialists (Lancet 2012 Oct. 19 [doi: 10.1016/S0140-6736(12)61253-7]).

"When surgery has probably not cured a patient, prospective data still support postoperative radiation. The onus is on the uro-oncology team (surgical, radiation, and medical) to discuss postoperative radiation with the patient, address optimal timing of initiation when it is used, and provide justification when it is not," he wrote.

Looking to the future, "novel imaging modalities, such as lymphotropic nanoparticle and multiparametric MRI and PET (18F-sodium fluoride, 18F-acetate, 11C-acetate, 18F-choline, 11C-choline, and others), are being explored extensively, and provide further promise," he added.

"Such advances might help discern which patients are most likely to benefit from postoperative radiation."

DR. EFSTATHIOU is with the department of radiation oncology at Massachusetts General Hospital in Boston. He declared that he had no conflicts of interest.

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Body

In a comment accompanying the article, Dr. Jason A. Efstathiou wrote that "the decision to treat [prostate cancer] needs multidisciplinary input" from the entire uro-oncology team, including surgical, radiation, and medical specialists (Lancet 2012 Oct. 19 [doi: 10.1016/S0140-6736(12)61253-7]).

"When surgery has probably not cured a patient, prospective data still support postoperative radiation. The onus is on the uro-oncology team (surgical, radiation, and medical) to discuss postoperative radiation with the patient, address optimal timing of initiation when it is used, and provide justification when it is not," he wrote.

Looking to the future, "novel imaging modalities, such as lymphotropic nanoparticle and multiparametric MRI and PET (18F-sodium fluoride, 18F-acetate, 11C-acetate, 18F-choline, 11C-choline, and others), are being explored extensively, and provide further promise," he added.

"Such advances might help discern which patients are most likely to benefit from postoperative radiation."

DR. EFSTATHIOU is with the department of radiation oncology at Massachusetts General Hospital in Boston. He declared that he had no conflicts of interest.

Body

In a comment accompanying the article, Dr. Jason A. Efstathiou wrote that "the decision to treat [prostate cancer] needs multidisciplinary input" from the entire uro-oncology team, including surgical, radiation, and medical specialists (Lancet 2012 Oct. 19 [doi: 10.1016/S0140-6736(12)61253-7]).

"When surgery has probably not cured a patient, prospective data still support postoperative radiation. The onus is on the uro-oncology team (surgical, radiation, and medical) to discuss postoperative radiation with the patient, address optimal timing of initiation when it is used, and provide justification when it is not," he wrote.

Looking to the future, "novel imaging modalities, such as lymphotropic nanoparticle and multiparametric MRI and PET (18F-sodium fluoride, 18F-acetate, 11C-acetate, 18F-choline, 11C-choline, and others), are being explored extensively, and provide further promise," he added.

"Such advances might help discern which patients are most likely to benefit from postoperative radiation."

DR. EFSTATHIOU is with the department of radiation oncology at Massachusetts General Hospital in Boston. He declared that he had no conflicts of interest.

Title
Selection of Patients Is Key
Selection of Patients Is Key

Delivering radiation therapy immediately after radical prostatectomy resulted in fewer cases of biochemical progression of prostate cancer, compared with a "wait-and-see" approach, according to long-term data from a randomized phase III trial.

However, no such effect on overall survival was seen, with a possible detrimental effect in patients older than 70 years, investigators reported online Oct. 19 in the Lancet (doi: 10.1016/S0140-6736(12)61253-7).

Dr. Michel Bolla, of the Centre Hospitalier Universitaire A Michallon in Grenoble, France, and his colleagues looked at 1,005 men enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial, who were followed for a median of 10.6 years.

The cohort (median age 65 years) included patients with untreated adenocarcinoma of the prostate and at least one of the following: capsular perforation, positive surgical margins, or seminal vesicle invasion.

All patients underwent radical prostatectomy, and were then randomly assigned either to receive immediate postoperative external irradiation (within 16 weeks of surgery) or to a "wait-and-see" policy, whereby subsequent treatment was delayed until biochemical or clinical relapse.

Overall, Dr. Bolla and his coauthors found that 198 patients (39.4%) in the postoperative radiation group had biochemical progression (defined as an increase in prostate-specific antigen concentration to more than 0.2 mcg/L measured on two occasions at least 2 weeks apart), clinical progression, or died.

In contrast, the "wait-and-see" group recorded 311 patients (61.8%) who either progressed or died, for a hazard ratio of 0.49 for the radiation approach (P less than .0001).

Stratifying the results by age showed that patients under 70 years old had improved biochemical progression-free survival (hazard ratio, 0.44; P less than .0001) and clinical progression-free survival (HR, 0.67; P = .0013) in the radiation cohort compared with wait-and-see patients.

However, "excess mortality was seen in patients aged 70 years or older who had received immediate radiation compared with those aged 70 years or older who were on the wait-and-see policy," they wrote, with 40 deaths out of 94 older patients in the radiation group versus 20 deaths out of 102 patients in the wait-and-see group (HR, 2.94; P less than .0001).

Finally, looking at the entire cohort, the authors found that overall all-cause 10-year survival did not differ substantially, at 76.9% for the postoperative radiation patients and 80.7% for the wait-and-see group.

"Prostate cancer mortality did not differ significantly between groups either," added the authors.

Dr. Bolla and his colleagues said they had no conflicts of interest related to this study, which was funded by the Ligue Nationale contre le Cancer and the EORTC Charitable Trust.

Delivering radiation therapy immediately after radical prostatectomy resulted in fewer cases of biochemical progression of prostate cancer, compared with a "wait-and-see" approach, according to long-term data from a randomized phase III trial.

However, no such effect on overall survival was seen, with a possible detrimental effect in patients older than 70 years, investigators reported online Oct. 19 in the Lancet (doi: 10.1016/S0140-6736(12)61253-7).

Dr. Michel Bolla, of the Centre Hospitalier Universitaire A Michallon in Grenoble, France, and his colleagues looked at 1,005 men enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial, who were followed for a median of 10.6 years.

The cohort (median age 65 years) included patients with untreated adenocarcinoma of the prostate and at least one of the following: capsular perforation, positive surgical margins, or seminal vesicle invasion.

All patients underwent radical prostatectomy, and were then randomly assigned either to receive immediate postoperative external irradiation (within 16 weeks of surgery) or to a "wait-and-see" policy, whereby subsequent treatment was delayed until biochemical or clinical relapse.

Overall, Dr. Bolla and his coauthors found that 198 patients (39.4%) in the postoperative radiation group had biochemical progression (defined as an increase in prostate-specific antigen concentration to more than 0.2 mcg/L measured on two occasions at least 2 weeks apart), clinical progression, or died.

In contrast, the "wait-and-see" group recorded 311 patients (61.8%) who either progressed or died, for a hazard ratio of 0.49 for the radiation approach (P less than .0001).

Stratifying the results by age showed that patients under 70 years old had improved biochemical progression-free survival (hazard ratio, 0.44; P less than .0001) and clinical progression-free survival (HR, 0.67; P = .0013) in the radiation cohort compared with wait-and-see patients.

However, "excess mortality was seen in patients aged 70 years or older who had received immediate radiation compared with those aged 70 years or older who were on the wait-and-see policy," they wrote, with 40 deaths out of 94 older patients in the radiation group versus 20 deaths out of 102 patients in the wait-and-see group (HR, 2.94; P less than .0001).

Finally, looking at the entire cohort, the authors found that overall all-cause 10-year survival did not differ substantially, at 76.9% for the postoperative radiation patients and 80.7% for the wait-and-see group.

"Prostate cancer mortality did not differ significantly between groups either," added the authors.

Dr. Bolla and his colleagues said they had no conflicts of interest related to this study, which was funded by the Ligue Nationale contre le Cancer and the EORTC Charitable Trust.

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Major Finding: Among postprostatectomy patients, 39.4% of patients who underwent immediate radiation had biochemical progression, versus 61.8% of patients who took a "wait-and-see" approach.

Data Source: This was a randomized trial of 1,005 patients in the European Organisation for Research and Treatment of Cancer 22911 study.

Disclosures: Dr. Bolla and his colleagues said they had no conflicts of interest related to this study, which was funded by the Ligue Nationale contre le Cancer and the EORTC Charitable Trust.

Long-Term Follow-Up Warranted After Gastric MALT Lymphoma Remission

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Long-Term Follow-Up Warranted After Gastric MALT Lymphoma Remission

As many as 80% of gastric MALT lymphoma patients achieve remission after Helicobacter pylori eradication, yet these patients remain at a significantly increased risk for second gastric cancers and lymphomas, reported Dr. Thomas Wündisch and his colleagues in Gastroenterology.

"The clinical consequence of this should be yearly lifelong endoscopic follow-up in all patients with a history of GML [gastric MALT lymphoma] to detect gastric cancer as early as possible," they wrote.

Dr. Wündisch, of Heinrich-Heine-Universität in Düsseldorf, Germany, and his colleagues studied 120 patients (63 female, mean age 62 years) recruited between June 1993 and July 1999 with stage EI1 gastric mucosa–associated lymphoid tissue (MALT) lymphoma according to the Ann Arbor system, where lymphoma is limited to the mucosa and submucosa of the stomach with no lymph node involvement.

Patients in this multicenter study underwent H. pylori eradication therapy consisting of a 2-week course of amoxicillin (750 mg three times daily) and omeprazole (40 mg three times daily).

Endoscopy was performed monthly until complete histologic remission, defined as macroscopic disappearance of lymphoma and absence of lymphoma on biopsy in two consecutive analyses, and then every 6-12 months. Patients were followed for a median of 122 months after H. pylori eradication (range, 1-171 months).

Dr. Wündisch and his colleagues reported that 96 of the 120 patients with complete follow-up (80%) achieved complete GML remission between 1 and 28 months after eradication therapy began, and 80% of them (77/96) remained disease free (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.06.035]).

Histologic residual disease was seen in 16 out of 96 patients; indeed, it was likely "ongoing histological residual disease rather than complete remission, as the microscopic lesions were small and often found only upon examination of serial sections of one of multiple biopsies."

A "watch and wait" approach was used in these cases, and all but one patient showed complete remission again at the last time point, with a median second remission duration of 46 months. There was also no progression.

"We strongly support this strategy," the investigators wrote.

Overall, the 96 patients with complete GML remission had a 5-year survival rate of 94%, and a 10-year survival of 87%.

Nevertheless, the researchers observed a morbidity ratio of 8.567 for gastric cancer among these patients (95% confidence interval, 3.566-20.582; P less than .001) and 18.621 for non-Hodgkin’s lymphoma (95% CI, 8.365-41.448; P less than 10–6), compared with the general population. The morbidity rate for all cancers was also elevated, at 1.689, but this was not statistically significant.

According to the researchers, although treatment-related factors often contribute to the development of second cancers in patients with lymphoma, the 2-week-long H. pylori regimen employed was unlikely to cause long-term toxic effects.

"Patient-related factors, such as gene polymorphisms, might play a more important role in the development of GML and second cancers in our patients, but these factors have yet to be identified," they said.

In any case, "currently, follow-up of patients without significant comorbidities should extend beyond 5 years for detecting reinfection, relapse, second lymphoma, and early gastric cancer."

The authors stated that the study was funded by a grant from Deutsche Krebshilfe, and they had no personal disclosures.

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As many as 80% of gastric MALT lymphoma patients achieve remission after Helicobacter pylori eradication, yet these patients remain at a significantly increased risk for second gastric cancers and lymphomas, reported Dr. Thomas Wündisch and his colleagues in Gastroenterology.

"The clinical consequence of this should be yearly lifelong endoscopic follow-up in all patients with a history of GML [gastric MALT lymphoma] to detect gastric cancer as early as possible," they wrote.

Dr. Wündisch, of Heinrich-Heine-Universität in Düsseldorf, Germany, and his colleagues studied 120 patients (63 female, mean age 62 years) recruited between June 1993 and July 1999 with stage EI1 gastric mucosa–associated lymphoid tissue (MALT) lymphoma according to the Ann Arbor system, where lymphoma is limited to the mucosa and submucosa of the stomach with no lymph node involvement.

Patients in this multicenter study underwent H. pylori eradication therapy consisting of a 2-week course of amoxicillin (750 mg three times daily) and omeprazole (40 mg three times daily).

Endoscopy was performed monthly until complete histologic remission, defined as macroscopic disappearance of lymphoma and absence of lymphoma on biopsy in two consecutive analyses, and then every 6-12 months. Patients were followed for a median of 122 months after H. pylori eradication (range, 1-171 months).

Dr. Wündisch and his colleagues reported that 96 of the 120 patients with complete follow-up (80%) achieved complete GML remission between 1 and 28 months after eradication therapy began, and 80% of them (77/96) remained disease free (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.06.035]).

Histologic residual disease was seen in 16 out of 96 patients; indeed, it was likely "ongoing histological residual disease rather than complete remission, as the microscopic lesions were small and often found only upon examination of serial sections of one of multiple biopsies."

A "watch and wait" approach was used in these cases, and all but one patient showed complete remission again at the last time point, with a median second remission duration of 46 months. There was also no progression.

"We strongly support this strategy," the investigators wrote.

Overall, the 96 patients with complete GML remission had a 5-year survival rate of 94%, and a 10-year survival of 87%.

Nevertheless, the researchers observed a morbidity ratio of 8.567 for gastric cancer among these patients (95% confidence interval, 3.566-20.582; P less than .001) and 18.621 for non-Hodgkin’s lymphoma (95% CI, 8.365-41.448; P less than 10–6), compared with the general population. The morbidity rate for all cancers was also elevated, at 1.689, but this was not statistically significant.

According to the researchers, although treatment-related factors often contribute to the development of second cancers in patients with lymphoma, the 2-week-long H. pylori regimen employed was unlikely to cause long-term toxic effects.

"Patient-related factors, such as gene polymorphisms, might play a more important role in the development of GML and second cancers in our patients, but these factors have yet to be identified," they said.

In any case, "currently, follow-up of patients without significant comorbidities should extend beyond 5 years for detecting reinfection, relapse, second lymphoma, and early gastric cancer."

The authors stated that the study was funded by a grant from Deutsche Krebshilfe, and they had no personal disclosures.

As many as 80% of gastric MALT lymphoma patients achieve remission after Helicobacter pylori eradication, yet these patients remain at a significantly increased risk for second gastric cancers and lymphomas, reported Dr. Thomas Wündisch and his colleagues in Gastroenterology.

"The clinical consequence of this should be yearly lifelong endoscopic follow-up in all patients with a history of GML [gastric MALT lymphoma] to detect gastric cancer as early as possible," they wrote.

Dr. Wündisch, of Heinrich-Heine-Universität in Düsseldorf, Germany, and his colleagues studied 120 patients (63 female, mean age 62 years) recruited between June 1993 and July 1999 with stage EI1 gastric mucosa–associated lymphoid tissue (MALT) lymphoma according to the Ann Arbor system, where lymphoma is limited to the mucosa and submucosa of the stomach with no lymph node involvement.

Patients in this multicenter study underwent H. pylori eradication therapy consisting of a 2-week course of amoxicillin (750 mg three times daily) and omeprazole (40 mg three times daily).

Endoscopy was performed monthly until complete histologic remission, defined as macroscopic disappearance of lymphoma and absence of lymphoma on biopsy in two consecutive analyses, and then every 6-12 months. Patients were followed for a median of 122 months after H. pylori eradication (range, 1-171 months).

Dr. Wündisch and his colleagues reported that 96 of the 120 patients with complete follow-up (80%) achieved complete GML remission between 1 and 28 months after eradication therapy began, and 80% of them (77/96) remained disease free (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.06.035]).

Histologic residual disease was seen in 16 out of 96 patients; indeed, it was likely "ongoing histological residual disease rather than complete remission, as the microscopic lesions were small and often found only upon examination of serial sections of one of multiple biopsies."

A "watch and wait" approach was used in these cases, and all but one patient showed complete remission again at the last time point, with a median second remission duration of 46 months. There was also no progression.

"We strongly support this strategy," the investigators wrote.

Overall, the 96 patients with complete GML remission had a 5-year survival rate of 94%, and a 10-year survival of 87%.

Nevertheless, the researchers observed a morbidity ratio of 8.567 for gastric cancer among these patients (95% confidence interval, 3.566-20.582; P less than .001) and 18.621 for non-Hodgkin’s lymphoma (95% CI, 8.365-41.448; P less than 10–6), compared with the general population. The morbidity rate for all cancers was also elevated, at 1.689, but this was not statistically significant.

According to the researchers, although treatment-related factors often contribute to the development of second cancers in patients with lymphoma, the 2-week-long H. pylori regimen employed was unlikely to cause long-term toxic effects.

"Patient-related factors, such as gene polymorphisms, might play a more important role in the development of GML and second cancers in our patients, but these factors have yet to be identified," they said.

In any case, "currently, follow-up of patients without significant comorbidities should extend beyond 5 years for detecting reinfection, relapse, second lymphoma, and early gastric cancer."

The authors stated that the study was funded by a grant from Deutsche Krebshilfe, and they had no personal disclosures.

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Major Finding: Of 120 participants, 96 (80%) achieved complete remission of gastric MALT lymphoma, and 80% of them (77/96) remained disease free.

Data Source: A prospective, multicenter trial of 120 patients over a median 10 years of follow-up.

Disclosures: The authors stated that the study was funded by a grant from Deutsche Krebshilfe, and they had no personal disclosures.

Ablation Cost Effective for High-Grade Dysplasia in Barrett's Esophagus

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Radiofrequency ablation for high-grade dysplasia in the setting of Barrett’s esophagus is more cost effective than endoscopic surveillance until progression to cancer, reported Dr. Chin Hur and his colleagues in the September issue of Gastroenterology.

Moreover, the use of radiofrequency ablation (RFA) for stable, confirmed low-grade dysplasia can also be cost effective, said the investigators.

Dr. Hur of Harvard University and Massachusetts General Hospital, both in Boston, and his colleagues conducted several analyses comparing three treatment strategies for each of three disease states: Barrett’s esophagus with high-grade dysplasia, Barrett’s esophagus with low-grade dysplasia, and Barrett’s esophagus with no dysplasia.

The treatment strategies consisted of surveillance followed by esophagectomy upon disease progression to cancer, RFA upon disease progression to a higher-grade dysplasia or cancer, or initial RFA before disease progression (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.05.010]).

Cost calculations were based on Medicare reimbursement rates for 2011. The cost estimate for RFA, for example, was $6,400, and the cost of esophagectomy was $25,882. Based on these values, the authors then conducted a base-case analysis.

They found that in high-grade dysplasia, the strategy of initial RFA resulted in 0.704 more quality-adjusted life-years (QALYs) and cost $25,609 less than the strategy of surveillance without RFA followed by esophagectomy upon disease progression to cancer, assuming a 1% disease progression rate.

Similarly, in low-grade dysplasia, RFA upon disease progression to high-grade dysplasia also bested the strategy of surveillance until cancer and esophagectomy, resulting in 0.17 more QALYs and costing $7,446 less, assuming a 0.5% progression rate.

However, in low-grade dysplasia, when comparing initial RFA versus surveillance until progression to high-grade dysplasia and then RFA, the authors found that the latter approach cost only $1,969 less than the former, and that the former was associated with a 0.108 gain in QALYs.

That amounted to an incremental cost-effectiveness ratio of $18,231 per QALY – "below our willingness-to-pay threshold of $100,000/QALY, making it the most plausible strategy in terms of cost-effectiveness."

Finally, in scenarios involving Barrett’s esophagus but no dysplasia, RFA upon progression of disease to high-grade dysplasia was still the most cost-effective strategy: It was associated with a savings of $7,709 as well as 0.194 additional QALYs, compared with esophagectomy upon disease progression to cancer, assuming a 0.33% progression rate.

The authors noted that their model relies on a stringent definition of low-grade dysplasia that assumes "review and agreement between more than one expert pathologist" as well as a consistent level of dysplasia found on more than one endoscopy spaced at least 6 months apart. In addition, the progression rates used in this analysis were based on the current literature, but were still estimates involving some uncertainty.

"We believe that a multicenter, randomized, controlled trial for initial RF ablation versus surveillance in patients with BE without dysplasia is needed to confirm our model results and to inform clinical decision making," they added.

Long-term follow-up data from such a study could "provide much needed data regarding cancer progression and the need for surveillance, which significantly impacts the cost-effectiveness and patients’ preferences for RFA."

The authors stated that they had no disclosures relevant to this study. The study was supported by grants from the National Institutes of Health.

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Radiofrequency ablation for high-grade dysplasia in the setting of Barrett’s esophagus is more cost effective than endoscopic surveillance until progression to cancer, reported Dr. Chin Hur and his colleagues in the September issue of Gastroenterology.

Moreover, the use of radiofrequency ablation (RFA) for stable, confirmed low-grade dysplasia can also be cost effective, said the investigators.

Dr. Hur of Harvard University and Massachusetts General Hospital, both in Boston, and his colleagues conducted several analyses comparing three treatment strategies for each of three disease states: Barrett’s esophagus with high-grade dysplasia, Barrett’s esophagus with low-grade dysplasia, and Barrett’s esophagus with no dysplasia.

The treatment strategies consisted of surveillance followed by esophagectomy upon disease progression to cancer, RFA upon disease progression to a higher-grade dysplasia or cancer, or initial RFA before disease progression (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.05.010]).

Cost calculations were based on Medicare reimbursement rates for 2011. The cost estimate for RFA, for example, was $6,400, and the cost of esophagectomy was $25,882. Based on these values, the authors then conducted a base-case analysis.

They found that in high-grade dysplasia, the strategy of initial RFA resulted in 0.704 more quality-adjusted life-years (QALYs) and cost $25,609 less than the strategy of surveillance without RFA followed by esophagectomy upon disease progression to cancer, assuming a 1% disease progression rate.

Similarly, in low-grade dysplasia, RFA upon disease progression to high-grade dysplasia also bested the strategy of surveillance until cancer and esophagectomy, resulting in 0.17 more QALYs and costing $7,446 less, assuming a 0.5% progression rate.

However, in low-grade dysplasia, when comparing initial RFA versus surveillance until progression to high-grade dysplasia and then RFA, the authors found that the latter approach cost only $1,969 less than the former, and that the former was associated with a 0.108 gain in QALYs.

That amounted to an incremental cost-effectiveness ratio of $18,231 per QALY – "below our willingness-to-pay threshold of $100,000/QALY, making it the most plausible strategy in terms of cost-effectiveness."

Finally, in scenarios involving Barrett’s esophagus but no dysplasia, RFA upon progression of disease to high-grade dysplasia was still the most cost-effective strategy: It was associated with a savings of $7,709 as well as 0.194 additional QALYs, compared with esophagectomy upon disease progression to cancer, assuming a 0.33% progression rate.

The authors noted that their model relies on a stringent definition of low-grade dysplasia that assumes "review and agreement between more than one expert pathologist" as well as a consistent level of dysplasia found on more than one endoscopy spaced at least 6 months apart. In addition, the progression rates used in this analysis were based on the current literature, but were still estimates involving some uncertainty.

"We believe that a multicenter, randomized, controlled trial for initial RF ablation versus surveillance in patients with BE without dysplasia is needed to confirm our model results and to inform clinical decision making," they added.

Long-term follow-up data from such a study could "provide much needed data regarding cancer progression and the need for surveillance, which significantly impacts the cost-effectiveness and patients’ preferences for RFA."

The authors stated that they had no disclosures relevant to this study. The study was supported by grants from the National Institutes of Health.

Radiofrequency ablation for high-grade dysplasia in the setting of Barrett’s esophagus is more cost effective than endoscopic surveillance until progression to cancer, reported Dr. Chin Hur and his colleagues in the September issue of Gastroenterology.

Moreover, the use of radiofrequency ablation (RFA) for stable, confirmed low-grade dysplasia can also be cost effective, said the investigators.

Dr. Hur of Harvard University and Massachusetts General Hospital, both in Boston, and his colleagues conducted several analyses comparing three treatment strategies for each of three disease states: Barrett’s esophagus with high-grade dysplasia, Barrett’s esophagus with low-grade dysplasia, and Barrett’s esophagus with no dysplasia.

The treatment strategies consisted of surveillance followed by esophagectomy upon disease progression to cancer, RFA upon disease progression to a higher-grade dysplasia or cancer, or initial RFA before disease progression (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.05.010]).

Cost calculations were based on Medicare reimbursement rates for 2011. The cost estimate for RFA, for example, was $6,400, and the cost of esophagectomy was $25,882. Based on these values, the authors then conducted a base-case analysis.

They found that in high-grade dysplasia, the strategy of initial RFA resulted in 0.704 more quality-adjusted life-years (QALYs) and cost $25,609 less than the strategy of surveillance without RFA followed by esophagectomy upon disease progression to cancer, assuming a 1% disease progression rate.

Similarly, in low-grade dysplasia, RFA upon disease progression to high-grade dysplasia also bested the strategy of surveillance until cancer and esophagectomy, resulting in 0.17 more QALYs and costing $7,446 less, assuming a 0.5% progression rate.

However, in low-grade dysplasia, when comparing initial RFA versus surveillance until progression to high-grade dysplasia and then RFA, the authors found that the latter approach cost only $1,969 less than the former, and that the former was associated with a 0.108 gain in QALYs.

That amounted to an incremental cost-effectiveness ratio of $18,231 per QALY – "below our willingness-to-pay threshold of $100,000/QALY, making it the most plausible strategy in terms of cost-effectiveness."

Finally, in scenarios involving Barrett’s esophagus but no dysplasia, RFA upon progression of disease to high-grade dysplasia was still the most cost-effective strategy: It was associated with a savings of $7,709 as well as 0.194 additional QALYs, compared with esophagectomy upon disease progression to cancer, assuming a 0.33% progression rate.

The authors noted that their model relies on a stringent definition of low-grade dysplasia that assumes "review and agreement between more than one expert pathologist" as well as a consistent level of dysplasia found on more than one endoscopy spaced at least 6 months apart. In addition, the progression rates used in this analysis were based on the current literature, but were still estimates involving some uncertainty.

"We believe that a multicenter, randomized, controlled trial for initial RF ablation versus surveillance in patients with BE without dysplasia is needed to confirm our model results and to inform clinical decision making," they added.

Long-term follow-up data from such a study could "provide much needed data regarding cancer progression and the need for surveillance, which significantly impacts the cost-effectiveness and patients’ preferences for RFA."

The authors stated that they had no disclosures relevant to this study. The study was supported by grants from the National Institutes of Health.

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Esophageal Cancers Reported After Radiofrequency Ablation

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Two cases of adenocarcinoma and one case of subsquamous high-grade dysplasia have been reported after radiofrequency ablation for Barrett’s esophagus, wrote Dr. Mohammad Titi and colleagues in the September issue of Gastroenterology.

The findings point to a need for "continued meticulous surveillance with biopsies of neosquamous epithelium, even after apparently successful eradication of intestinal metaplasia," the authors wrote.

The three cases of subsquamous neoplasia following "successful" radiofrequency ablation (RFA) are the only cases reported to date, said Dr. Titi of the Veterans Affairs Medical Center, Kansas City, Mo., and colleagues (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.051]).

The first case detailed by the investigators occurred in a 65-year-old patient with Barrett’s esophagus who had been undergoing surveillance for 2 years. An intramucosal adenocarcinoma was detected, and the patient underwent esophagectomy. The margins were positive for high-grade dysplasia.

RFA was performed in three sessions, "leading to complete eradication of dysplasia and intestinal metaplasia," the authors wrote, and for 2 years and over five surveillance biopsies, no endoscopic or histologic evidence of intestinal metaplasia was seen.

"Finally, almost two years post RFA, surveillance biopsies from the neosquamous epithelium 2 cm above surgical anastomosis showed subsquamous intestinal metaplasia with high-grade dysplasia."

In the second case, a 59-year-old patient with a 10-year Barrett’s history was found to have focal high-grade dysplasia and underwent two RFA sessions with complete eradication of dysplasia and intestinal metaplasia. Surveillance at 3 months was normal.

"Surveillance endoscopy at 6 months post RFA showed normal neosquamous epithelium; however, biopsies 1 cm above the gastroesophageal junction revealed subsquamous adenocarcinoma," wrote the authors. The patient underwent esophagectomy, revealing residual subsquamous carcinoma. The lymph nodes were negative.

The third and final case was a 76-year-old Barrett’s patient with focal, high-grade dysplasia initially treated with endoscopic mucosal resection (EMR) followed by four sessions of RFA, with complete eradication of dysplasia and intestinal metaplasia.

Two surveillance endoscopies at 3-month intervals showed no evidence of intestinal metaplasia. "The third surveillance endoscopy per protocol was at 9 months post RFA, and showed a nodular area in the neosquamous epithelium above the gastroesophageal junction, 1 cm distal to the site of previous EMR." Biopsies confirmed subsquamous adenocarcinoma; the patient underwent esophagectomy.

According to the authors, all patients were on twice-daily proton pump inhibitor therapy at the time of neoplasia occurrence. All patients underwent surveillance biopsies per the Seattle protocol.

"This report illustrates an important fact that must be remembered about any ablative therapy, including RFA: High-grade dysplasia or cancer can develop in some patients even after apparently successful eradication of neoplasia and intestinal metaplasia," the authors wrote.

"A prudent approach is performing surveillance every 3 months for the first year post ablation; every 6 months for the next year; and then annually," they wrote. "These reports should also temper our enthusiasm to apply ablation to all patients with Barrett’s esophagus."

The authors stated that they had no conflicts of interest related to this report, and no grant support.

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Two cases of adenocarcinoma and one case of subsquamous high-grade dysplasia have been reported after radiofrequency ablation for Barrett’s esophagus, wrote Dr. Mohammad Titi and colleagues in the September issue of Gastroenterology.

The findings point to a need for "continued meticulous surveillance with biopsies of neosquamous epithelium, even after apparently successful eradication of intestinal metaplasia," the authors wrote.

The three cases of subsquamous neoplasia following "successful" radiofrequency ablation (RFA) are the only cases reported to date, said Dr. Titi of the Veterans Affairs Medical Center, Kansas City, Mo., and colleagues (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.051]).

The first case detailed by the investigators occurred in a 65-year-old patient with Barrett’s esophagus who had been undergoing surveillance for 2 years. An intramucosal adenocarcinoma was detected, and the patient underwent esophagectomy. The margins were positive for high-grade dysplasia.

RFA was performed in three sessions, "leading to complete eradication of dysplasia and intestinal metaplasia," the authors wrote, and for 2 years and over five surveillance biopsies, no endoscopic or histologic evidence of intestinal metaplasia was seen.

"Finally, almost two years post RFA, surveillance biopsies from the neosquamous epithelium 2 cm above surgical anastomosis showed subsquamous intestinal metaplasia with high-grade dysplasia."

In the second case, a 59-year-old patient with a 10-year Barrett’s history was found to have focal high-grade dysplasia and underwent two RFA sessions with complete eradication of dysplasia and intestinal metaplasia. Surveillance at 3 months was normal.

"Surveillance endoscopy at 6 months post RFA showed normal neosquamous epithelium; however, biopsies 1 cm above the gastroesophageal junction revealed subsquamous adenocarcinoma," wrote the authors. The patient underwent esophagectomy, revealing residual subsquamous carcinoma. The lymph nodes were negative.

The third and final case was a 76-year-old Barrett’s patient with focal, high-grade dysplasia initially treated with endoscopic mucosal resection (EMR) followed by four sessions of RFA, with complete eradication of dysplasia and intestinal metaplasia.

Two surveillance endoscopies at 3-month intervals showed no evidence of intestinal metaplasia. "The third surveillance endoscopy per protocol was at 9 months post RFA, and showed a nodular area in the neosquamous epithelium above the gastroesophageal junction, 1 cm distal to the site of previous EMR." Biopsies confirmed subsquamous adenocarcinoma; the patient underwent esophagectomy.

According to the authors, all patients were on twice-daily proton pump inhibitor therapy at the time of neoplasia occurrence. All patients underwent surveillance biopsies per the Seattle protocol.

"This report illustrates an important fact that must be remembered about any ablative therapy, including RFA: High-grade dysplasia or cancer can develop in some patients even after apparently successful eradication of neoplasia and intestinal metaplasia," the authors wrote.

"A prudent approach is performing surveillance every 3 months for the first year post ablation; every 6 months for the next year; and then annually," they wrote. "These reports should also temper our enthusiasm to apply ablation to all patients with Barrett’s esophagus."

The authors stated that they had no conflicts of interest related to this report, and no grant support.

Two cases of adenocarcinoma and one case of subsquamous high-grade dysplasia have been reported after radiofrequency ablation for Barrett’s esophagus, wrote Dr. Mohammad Titi and colleagues in the September issue of Gastroenterology.

The findings point to a need for "continued meticulous surveillance with biopsies of neosquamous epithelium, even after apparently successful eradication of intestinal metaplasia," the authors wrote.

The three cases of subsquamous neoplasia following "successful" radiofrequency ablation (RFA) are the only cases reported to date, said Dr. Titi of the Veterans Affairs Medical Center, Kansas City, Mo., and colleagues (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.04.051]).

The first case detailed by the investigators occurred in a 65-year-old patient with Barrett’s esophagus who had been undergoing surveillance for 2 years. An intramucosal adenocarcinoma was detected, and the patient underwent esophagectomy. The margins were positive for high-grade dysplasia.

RFA was performed in three sessions, "leading to complete eradication of dysplasia and intestinal metaplasia," the authors wrote, and for 2 years and over five surveillance biopsies, no endoscopic or histologic evidence of intestinal metaplasia was seen.

"Finally, almost two years post RFA, surveillance biopsies from the neosquamous epithelium 2 cm above surgical anastomosis showed subsquamous intestinal metaplasia with high-grade dysplasia."

In the second case, a 59-year-old patient with a 10-year Barrett’s history was found to have focal high-grade dysplasia and underwent two RFA sessions with complete eradication of dysplasia and intestinal metaplasia. Surveillance at 3 months was normal.

"Surveillance endoscopy at 6 months post RFA showed normal neosquamous epithelium; however, biopsies 1 cm above the gastroesophageal junction revealed subsquamous adenocarcinoma," wrote the authors. The patient underwent esophagectomy, revealing residual subsquamous carcinoma. The lymph nodes were negative.

The third and final case was a 76-year-old Barrett’s patient with focal, high-grade dysplasia initially treated with endoscopic mucosal resection (EMR) followed by four sessions of RFA, with complete eradication of dysplasia and intestinal metaplasia.

Two surveillance endoscopies at 3-month intervals showed no evidence of intestinal metaplasia. "The third surveillance endoscopy per protocol was at 9 months post RFA, and showed a nodular area in the neosquamous epithelium above the gastroesophageal junction, 1 cm distal to the site of previous EMR." Biopsies confirmed subsquamous adenocarcinoma; the patient underwent esophagectomy.

According to the authors, all patients were on twice-daily proton pump inhibitor therapy at the time of neoplasia occurrence. All patients underwent surveillance biopsies per the Seattle protocol.

"This report illustrates an important fact that must be remembered about any ablative therapy, including RFA: High-grade dysplasia or cancer can develop in some patients even after apparently successful eradication of neoplasia and intestinal metaplasia," the authors wrote.

"A prudent approach is performing surveillance every 3 months for the first year post ablation; every 6 months for the next year; and then annually," they wrote. "These reports should also temper our enthusiasm to apply ablation to all patients with Barrett’s esophagus."

The authors stated that they had no conflicts of interest related to this report, and no grant support.

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Endoscopy Falls Short for Eosinophilic Esophagitis

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Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

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Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

Endoscopic findings alone are not sufficient to diagnose eosinophilic esophagitis and instead, biopsies are needed, reported Ms. Hannah P. Kim and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, while findings like rings, strictures, and linear furrows ought to raise suspicion, a meta-analysis of more than 4,600 patients confirms that "low sensitivity and variable predictive values make them inadequate both for the diagnosis of EoE [eosinophilic esophagitis] and for the decision of whether or not to obtain biopsies."

Ms. Kim of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, and her colleagues analyzed data from 80 articles and 20 abstracts that included a total of 4,678 patients with EoE and 2,742 patients without, who served as controls.

The studies were culled from PubMed, EMBASE, and gastroenterology meetings. All studies included in the analysis had more than 10 patients with EoE and provided information on the associated endoscopic findings. The mean age of participants ranged from 6 years to 55 years in the different studies.

In an analysis, the authors found that the overall pooled prevalence of esophageal rings in the sample was 44%. For strictures, the prevalence was 21%, and for linear furrows, 48% (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.04.019]).

Narrow-caliber esophagus findings had a pooled prevalence of only 9% of the total sample, while the presence of white plaques or exudates was 27%. Visible pallor or decreased vasculature on endoscopy was seen in 41% of patients, and erosive esophagitis in 17%.

"The endoscopic examination was normal in 17% of cases," added the authors.

They also found a difference in prevalence according to age of patients. For example, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

"On the other hand, white plaques and pallor or decreased vasculature were more prevalent in children (36% and 58%) than in adults (19% and 18%; P less than .05 for each)."

Finally, Ms. Kim and her associates assessed the overall sensitivity, specificity, pooled positive predictive value (PPV), and pooled negative predictive value (NPV) for each of the assessed endoscopic characteristics.

For rings, the overall sensitivity was 48%, the specificity was 91%, the PPV was 64%, and NPV was 84%. Strictures had an overall sensitivity of 15%, specificity of 95%, PPV of 51%, and NPV of 76%.

"The operating characteristics were slightly higher for linear furrows, with a sensitivity of 40%, specificity 95%, PPV 73%, and NPV 83%," wrote the authors.

And for the endoscopic finding of pallor and/or decreased vasculature, sensitivity was 43%, specificity 90%, PPV 65%, and NPV 79%.

"In contrast to the low sensitivity of individual endoscopic findings, when examining the presence of at least one endoscopic finding, an abnormal endoscopy had a sensitivity of 87%, specificity of 47%, PPV of 42%, and NPV of 89%," the authors added.

"Although endoscopic features of EoE such as esophageal rings, linear furrows, and white plaques or exudates are often considered to be typical features of EoE, these are not always identified by endoscopists," wrote the researchers.

And while most patients with EoE have abnormal findings on upper endoscopy examinations, "the sensitivity values of individual endoscopic findings were modest, and although the specificity values were higher, the predictive values were inadequate for diagnostic purposes."

"Esophageal biopsies should be obtained from all patients who present with symptoms of EoE, regardless of the endoscopic appearance of the esophagus."

The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

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Endoscopy Falls Short for Eosinophilic Esophagitis
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Major Finding: On endoscopy, rings and strictures were more prevalent in adults (57% and 25%, respectively) than in children (11% and 8%; P less than .05 for each).

Data Source: A systematic review and meta-analysis of studies including more than 4,600 EoE patients and 2,700 controls.

Disclosures: The authors stated that the study was supported by grants from the National Institutes of Health and the Doris Duke Charitable Foundation. They stated that they had no individual disclosures.

Robotic Device for Gastric Neoplasia Found Safe in Five Patients

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Robotic Device for Gastric Neoplasia Found Safe in Five Patients

A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

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A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

A novel robotic system designed to perform endoscopic submucosal dissection of early gastric neoplasia was safe and effective in a five-patient trial, reported Soo Jay Phee, Ph.D., and colleagues in Clinical Gastroenterology and Hepatology.

Indeed, the first human study of the robotic device showed that it achieved clear margins, no cases of major bleeding or perforation, and discharge within hours for several of the patients.

Dr. Phee of the School of Mechanical and Aerospace Engineering at Nanyang Technological University in Singapore and first author Dr. D. Nageshwar Reddy of the Asian Institute of Gastroenterology in Somajiguda, India, enrolled five patients from two centers in India and one in Hong Kong.

Only patients with gastric neoplasia limited to the mucosa, confirmed by biopsy and histopathology, were included.

All patients underwent endoscopic submucosal dissection with the assistance of a novel device called the Master and Slave Transluminal Endoscopic Robot (MASTER). The MASTER device has been described previously (Gastrointest. Endoscopy 2010;72:593-9).

According to the authors, the device is controlled by two operators, "one responsible for the steering of the endoscope while the other would be performing the submucosal dissection with the two robotic arms."

The investigators added, "The open edge of the mucosa with the tumor was grasped by one of the robotic arms to retract the mucosa and enhance exposure of the submucosa, while submucosal dissection was completed with the other L hook arm" (Clin. Gastroenterol. Hepatol. 2012 October [doi:10.1016/j.cgh.2012.05.019]).

All procedures were performed under general anesthesia and with ventilation by naso- or orotracheal intubation. All operators trained on porcine models prior to the study.

In the case of the first patient, a 41-year-old man with a 2-cm adenocarcinoma in the body of the stomach, "the submucosal dissection with the robotic system was successfully done in 19 minutes," reported the authors.

There was no bleeding for perforation, and histopathology of the specimen after retrieval showed intramucosal well-differentiated adenocarcinoma with clear resection margins. The patient was discharged after 12 hours.

The second case, a 60-year-old man, was found to have a 1.5-cm mucosal adenocarcinoma in the gastric antrum. "The submucosal dissection was completed in only 5 minutes," wrote the authors, with no complications, and clear margins on histopathology. The patient was discharged in 6 hours.

Similarly, the third patient (a 39-year-old man) had a 2-cm sessile lesion in the gastric antrum. Submucosal dissection with the MASTER was completed in 3 minutes, with no complications, clear margins, and discharge from the hospital 4 hours later.

The longest procedure was done in a 51-year-old woman with a 3-cm early gastric cancer; this procedure took 50 minutes. She had no major bleeding or perforation, had clear margins on histopathology, and had a 3-day hospital stay.

Finally, a 50-year-old man with a 2.5-cm sessile polypoid in the inferior wall of the prepyloric canal underwent a 16-minute dissection. "Severe bleeding was encountered during the procedure and required exchange of the MASTER-mounted endoscope for a waterjet endoscope to stop the bleeding with coagulation grapser," wrote the authors.

"The pathology showed hyperplastic polyp with clear margins. He was discharged from hospital on day 3 after the procedure."

At 30 days’ follow-up, no complications were reported by any of the patients, and the follow-up endoscopy showed "complete healing" of the resection site. At 6 months, the three patients with data available were "doing well," according to the authors.

The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

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Major Finding: Five patients who underwent endoscopic submucosal dissection of early-stage gastric neoplasia with the use of a novel robotic system had good 30-day outcomes and clear resection margins.

Data Source: The findings came from five case studies in India and Hong Kong.

Disclosures: The study was supported by a MedTech Seeding Fund from the National University of Singapore. The authors reported having no other relevant financial disclosures.

Bile Duct Stones: Adequate Dilation Time Cuts Pancreatitis Risk

Choosing EPBD Over ES
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Bile Duct Stones: Adequate Dilation Time Cuts Pancreatitis Risk

When treating choledocholithiasis, a shorter duration of endoscopic papillary balloon dilation increases, rather than decreases, the risk of postprocedure pancreatitis, reported Dr. Wei-Chih Liao and his colleagues in Clinical Gastroenterology and Hepatology.

"This meta-analysis contradicts the common belief that pancreatitis results from direct pancreatic duct compression during balloon dilation, and thus dilation duration should be short," he and his colleagues wrote. On the contrary, "[endoscopic papillary balloon dilation] with an adequate duration (around 5 minutes) has lower complication rates than the current standard of endoscopic sphincterotomy, and may be used as the first-line treatment for bile duct stones."

Dr. Liao, of the National Taiwan University College of Medicine, Taipei, conducted a systematic review of Medline, the Cochrane databases, and clinicaltrials.gov to identify randomized controlled trials of endoscopic papillary balloon dilation (EPBD), endoscopic sphincteroplasty, endoscopic balloon sphincter dilation, and endoscopic balloon dilation. Studies were excluded if dilation duration was not clearly reported.

Overall, 12 studies were included in the analysis: 11 compared EPBD with endoscopic sphincterotomy (EST); 4 compared short-duration EPBD (1 minute or less) with EST; and 7 looked at long-duration EPBD (more than 1 minute) versus EST.

Only one study compared long-duration EPBD with short-duration EPBD, they wrote (Clin. Gastroenterol. Hepatol. 2012 [doi: 10.1016/j.cgh.2012.05.017]).

First, the authors looked at the risk of pancreatitis when comparing EST to short-duration EPBD. They found that the latter had a significantly higher pancreatitis risk, with a pooled odds ratio of 3.87 for developing pancreatitis post procedure, compared with EST (95% confidence interval, 1.08-13.84).

However, long-duration EPBD did not pose a significantly higher risk compared with EST (OR, 1.14; 95% CI, 0.56-2.35).

Similarly, looking at overall complications, the researchers noted a trend toward a higher overall complication rate in short-duration EPBD compared with EST (OR, 1.71; 95% CI, 0.67-4.35). "By contrast, long EPBD seemed to have a lower overall complication rate (pooled OR, 0.61; 95% CI, 0.36-1.04)," wrote the authors.

The researchers also calculated the regression coefficient of dilation duration, and found it to be –0.69, "meaning that every 1-minute increase in dilation duration up to 3 minutes was associated with a 49.8% (95% CI, –9.4% –77.0%) reduction in OR," they wrote.

The finding was similar for overall complications, with every 1-minute increase in dilation duration up to 5 minutes associated with a 45.1% reduction in OR.

In an attempt to explain the findings, Dr. Liao noted that recent evidence suggests that EPBD with dilation duration of 1 minute or less "carries a higher risk of inadequate sphincter loosening, which increases the risks of pancreatitis and failed stone extraction."

"An inadequately loosened sphincter from short-duration EPBD may limit volume expansion of its encircled contents as in a compartment syndrome, thus [worsening] compression of the pancreatic duct from post-EPBD edema and [increasing] pancreatitis risk."

The researchers added that the longest reported EPBD duration is 5 minutes.

"It is unknown whether dilation duration longer than 5 minutes may further reduce pancreatitis risk, but the degree of sphincter loosening can only increase to a certain point. ... Further studies on EPBD with different durations will be helpful to corroborate our findings and determine the optimal duration."

The study was funded by grants from the Royal Society, London; the National Science Council, Taiwan; and the National Taiwan University Hospital, Taipei. The authors stated that they had no individual conflicts to disclose.

Body

Endoscopic papillary balloon dilation (EPBD) using small diameter balloons (less than 10 mm) as an alterative to endoscopic sphincterotomy (ES) for removal of small bile duct stones is not new. Potential advantages of EPBD over ES are avoidance of bleeding and perforation while preserving biliary sphincter function. Potential disadvantages are potential for post-ERCP pancreatitis (PEP) and recurrence of choledocholithiasis, particularly in patients with an intact gallbladder.

Data on EPBD has been accrued from Asian populations, where the short-term and long-term outcomes are favorable, though with a significantly higher but acceptable risk of PEP. Unfortunately, the one randomized study from the U.S. was stopped prematurely due to two deaths from PEP. This has led to divergence in acceptance of EPBD between endoscopists in the East and West leading to the need for ways to reduce PEP after EPBD, including varying the duration of balloon inflation. In the present meta-analysis by Dr. Liao and his colleagues, longer duration of balloon dilation was found to be associated with less PEP than shorter duration. This finding may seem counterintuitive as longer duration would be expected to lead increased edema and obstruction of the pancreatic duct.

One factor not considered was the rapidity of dilation from zero pressure to the maximum. I believe this factor may be more important than duration since it influences shearing stress and force, tearing of tissue and subsequent peripapillary edema. Could it be that rapid inflation was more common when shorter-duration of inflation was performed? In short, the findings of Dr. Liao and his associates might influence the technique of EPBD in the East, but a more important question might be will these findings increase acceptance of EPBD in the West? Perhaps, but other ways to prevent PEP after EPBD, including the use of pancreatic duct stents and rectally administered non-steroidal anti-inflammatory agents, are more likely.

Todd Baron, M.D., is a professor of medicine and director of pancreaticobiliary endoscopy at the Mayo Clinic, Rochester, Minn. He has no relevant disclosures.

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Endoscopic papillary balloon dilation (EPBD) using small diameter balloons (less than 10 mm) as an alterative to endoscopic sphincterotomy (ES) for removal of small bile duct stones is not new. Potential advantages of EPBD over ES are avoidance of bleeding and perforation while preserving biliary sphincter function. Potential disadvantages are potential for post-ERCP pancreatitis (PEP) and recurrence of choledocholithiasis, particularly in patients with an intact gallbladder.

Data on EPBD has been accrued from Asian populations, where the short-term and long-term outcomes are favorable, though with a significantly higher but acceptable risk of PEP. Unfortunately, the one randomized study from the U.S. was stopped prematurely due to two deaths from PEP. This has led to divergence in acceptance of EPBD between endoscopists in the East and West leading to the need for ways to reduce PEP after EPBD, including varying the duration of balloon inflation. In the present meta-analysis by Dr. Liao and his colleagues, longer duration of balloon dilation was found to be associated with less PEP than shorter duration. This finding may seem counterintuitive as longer duration would be expected to lead increased edema and obstruction of the pancreatic duct.

One factor not considered was the rapidity of dilation from zero pressure to the maximum. I believe this factor may be more important than duration since it influences shearing stress and force, tearing of tissue and subsequent peripapillary edema. Could it be that rapid inflation was more common when shorter-duration of inflation was performed? In short, the findings of Dr. Liao and his associates might influence the technique of EPBD in the East, but a more important question might be will these findings increase acceptance of EPBD in the West? Perhaps, but other ways to prevent PEP after EPBD, including the use of pancreatic duct stents and rectally administered non-steroidal anti-inflammatory agents, are more likely.

Todd Baron, M.D., is a professor of medicine and director of pancreaticobiliary endoscopy at the Mayo Clinic, Rochester, Minn. He has no relevant disclosures.

Body

Endoscopic papillary balloon dilation (EPBD) using small diameter balloons (less than 10 mm) as an alterative to endoscopic sphincterotomy (ES) for removal of small bile duct stones is not new. Potential advantages of EPBD over ES are avoidance of bleeding and perforation while preserving biliary sphincter function. Potential disadvantages are potential for post-ERCP pancreatitis (PEP) and recurrence of choledocholithiasis, particularly in patients with an intact gallbladder.

Data on EPBD has been accrued from Asian populations, where the short-term and long-term outcomes are favorable, though with a significantly higher but acceptable risk of PEP. Unfortunately, the one randomized study from the U.S. was stopped prematurely due to two deaths from PEP. This has led to divergence in acceptance of EPBD between endoscopists in the East and West leading to the need for ways to reduce PEP after EPBD, including varying the duration of balloon inflation. In the present meta-analysis by Dr. Liao and his colleagues, longer duration of balloon dilation was found to be associated with less PEP than shorter duration. This finding may seem counterintuitive as longer duration would be expected to lead increased edema and obstruction of the pancreatic duct.

One factor not considered was the rapidity of dilation from zero pressure to the maximum. I believe this factor may be more important than duration since it influences shearing stress and force, tearing of tissue and subsequent peripapillary edema. Could it be that rapid inflation was more common when shorter-duration of inflation was performed? In short, the findings of Dr. Liao and his associates might influence the technique of EPBD in the East, but a more important question might be will these findings increase acceptance of EPBD in the West? Perhaps, but other ways to prevent PEP after EPBD, including the use of pancreatic duct stents and rectally administered non-steroidal anti-inflammatory agents, are more likely.

Todd Baron, M.D., is a professor of medicine and director of pancreaticobiliary endoscopy at the Mayo Clinic, Rochester, Minn. He has no relevant disclosures.

Title
Choosing EPBD Over ES
Choosing EPBD Over ES

When treating choledocholithiasis, a shorter duration of endoscopic papillary balloon dilation increases, rather than decreases, the risk of postprocedure pancreatitis, reported Dr. Wei-Chih Liao and his colleagues in Clinical Gastroenterology and Hepatology.

"This meta-analysis contradicts the common belief that pancreatitis results from direct pancreatic duct compression during balloon dilation, and thus dilation duration should be short," he and his colleagues wrote. On the contrary, "[endoscopic papillary balloon dilation] with an adequate duration (around 5 minutes) has lower complication rates than the current standard of endoscopic sphincterotomy, and may be used as the first-line treatment for bile duct stones."

Dr. Liao, of the National Taiwan University College of Medicine, Taipei, conducted a systematic review of Medline, the Cochrane databases, and clinicaltrials.gov to identify randomized controlled trials of endoscopic papillary balloon dilation (EPBD), endoscopic sphincteroplasty, endoscopic balloon sphincter dilation, and endoscopic balloon dilation. Studies were excluded if dilation duration was not clearly reported.

Overall, 12 studies were included in the analysis: 11 compared EPBD with endoscopic sphincterotomy (EST); 4 compared short-duration EPBD (1 minute or less) with EST; and 7 looked at long-duration EPBD (more than 1 minute) versus EST.

Only one study compared long-duration EPBD with short-duration EPBD, they wrote (Clin. Gastroenterol. Hepatol. 2012 [doi: 10.1016/j.cgh.2012.05.017]).

First, the authors looked at the risk of pancreatitis when comparing EST to short-duration EPBD. They found that the latter had a significantly higher pancreatitis risk, with a pooled odds ratio of 3.87 for developing pancreatitis post procedure, compared with EST (95% confidence interval, 1.08-13.84).

However, long-duration EPBD did not pose a significantly higher risk compared with EST (OR, 1.14; 95% CI, 0.56-2.35).

Similarly, looking at overall complications, the researchers noted a trend toward a higher overall complication rate in short-duration EPBD compared with EST (OR, 1.71; 95% CI, 0.67-4.35). "By contrast, long EPBD seemed to have a lower overall complication rate (pooled OR, 0.61; 95% CI, 0.36-1.04)," wrote the authors.

The researchers also calculated the regression coefficient of dilation duration, and found it to be –0.69, "meaning that every 1-minute increase in dilation duration up to 3 minutes was associated with a 49.8% (95% CI, –9.4% –77.0%) reduction in OR," they wrote.

The finding was similar for overall complications, with every 1-minute increase in dilation duration up to 5 minutes associated with a 45.1% reduction in OR.

In an attempt to explain the findings, Dr. Liao noted that recent evidence suggests that EPBD with dilation duration of 1 minute or less "carries a higher risk of inadequate sphincter loosening, which increases the risks of pancreatitis and failed stone extraction."

"An inadequately loosened sphincter from short-duration EPBD may limit volume expansion of its encircled contents as in a compartment syndrome, thus [worsening] compression of the pancreatic duct from post-EPBD edema and [increasing] pancreatitis risk."

The researchers added that the longest reported EPBD duration is 5 minutes.

"It is unknown whether dilation duration longer than 5 minutes may further reduce pancreatitis risk, but the degree of sphincter loosening can only increase to a certain point. ... Further studies on EPBD with different durations will be helpful to corroborate our findings and determine the optimal duration."

The study was funded by grants from the Royal Society, London; the National Science Council, Taiwan; and the National Taiwan University Hospital, Taipei. The authors stated that they had no individual conflicts to disclose.

When treating choledocholithiasis, a shorter duration of endoscopic papillary balloon dilation increases, rather than decreases, the risk of postprocedure pancreatitis, reported Dr. Wei-Chih Liao and his colleagues in Clinical Gastroenterology and Hepatology.

"This meta-analysis contradicts the common belief that pancreatitis results from direct pancreatic duct compression during balloon dilation, and thus dilation duration should be short," he and his colleagues wrote. On the contrary, "[endoscopic papillary balloon dilation] with an adequate duration (around 5 minutes) has lower complication rates than the current standard of endoscopic sphincterotomy, and may be used as the first-line treatment for bile duct stones."

Dr. Liao, of the National Taiwan University College of Medicine, Taipei, conducted a systematic review of Medline, the Cochrane databases, and clinicaltrials.gov to identify randomized controlled trials of endoscopic papillary balloon dilation (EPBD), endoscopic sphincteroplasty, endoscopic balloon sphincter dilation, and endoscopic balloon dilation. Studies were excluded if dilation duration was not clearly reported.

Overall, 12 studies were included in the analysis: 11 compared EPBD with endoscopic sphincterotomy (EST); 4 compared short-duration EPBD (1 minute or less) with EST; and 7 looked at long-duration EPBD (more than 1 minute) versus EST.

Only one study compared long-duration EPBD with short-duration EPBD, they wrote (Clin. Gastroenterol. Hepatol. 2012 [doi: 10.1016/j.cgh.2012.05.017]).

First, the authors looked at the risk of pancreatitis when comparing EST to short-duration EPBD. They found that the latter had a significantly higher pancreatitis risk, with a pooled odds ratio of 3.87 for developing pancreatitis post procedure, compared with EST (95% confidence interval, 1.08-13.84).

However, long-duration EPBD did not pose a significantly higher risk compared with EST (OR, 1.14; 95% CI, 0.56-2.35).

Similarly, looking at overall complications, the researchers noted a trend toward a higher overall complication rate in short-duration EPBD compared with EST (OR, 1.71; 95% CI, 0.67-4.35). "By contrast, long EPBD seemed to have a lower overall complication rate (pooled OR, 0.61; 95% CI, 0.36-1.04)," wrote the authors.

The researchers also calculated the regression coefficient of dilation duration, and found it to be –0.69, "meaning that every 1-minute increase in dilation duration up to 3 minutes was associated with a 49.8% (95% CI, –9.4% –77.0%) reduction in OR," they wrote.

The finding was similar for overall complications, with every 1-minute increase in dilation duration up to 5 minutes associated with a 45.1% reduction in OR.

In an attempt to explain the findings, Dr. Liao noted that recent evidence suggests that EPBD with dilation duration of 1 minute or less "carries a higher risk of inadequate sphincter loosening, which increases the risks of pancreatitis and failed stone extraction."

"An inadequately loosened sphincter from short-duration EPBD may limit volume expansion of its encircled contents as in a compartment syndrome, thus [worsening] compression of the pancreatic duct from post-EPBD edema and [increasing] pancreatitis risk."

The researchers added that the longest reported EPBD duration is 5 minutes.

"It is unknown whether dilation duration longer than 5 minutes may further reduce pancreatitis risk, but the degree of sphincter loosening can only increase to a certain point. ... Further studies on EPBD with different durations will be helpful to corroborate our findings and determine the optimal duration."

The study was funded by grants from the Royal Society, London; the National Science Council, Taiwan; and the National Taiwan University Hospital, Taipei. The authors stated that they had no individual conflicts to disclose.

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Major Finding: Endoscopic papillary balloon dilation for a short duration was associated with a greater risk for pancreatitis post procedure, compared with endoscopic sphincterotomy (odds ratio, 3.87), but longer-duration EPBD was less likely to cause pancreatitis.

Data Source: This study was a meta-analysis of 12 randomized controlled trials.

Disclosures: The study was funded by grants from the Royal Society, London; the National Science Council, Taiwan; and the National Taiwan University Hospital, Taipei. The authors stated that they had no individual conflicts to disclose.

Upper GI Cancer Risk Elevated in AIDS

Gastroenterologists and the Cancer/AIDS Link
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Upper GI Cancer Risk Elevated in AIDS

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

Body

Over the 30 years of the HIV pandemic, the risk of cancer has been found to be significantly elevated in HIV-infected persons. These include the three “AIDS-defining” cancers (Kaposi Sarcoma [KS], non-Hodgkin lymphoma [NHL], and cervical cancer) and a variety of “non AIDS-defining” cancers. Gastroenterologists have been most likely to encounter either visceral KS or hepatocellular carcinoma.

Dr. Persson and her colleagues used large population-based HIV and cancer registries to describe an increased risk of two additional malignancies, esophageal cancer (both squamous cell and adenocarcinoma) and stomach cancer in persons with AIDS, in addition to mucosa-associated lymphomas (NHL). NHL decreased in the era of effective antiretroviral therapy, but esophageal and gastric cancers remained elevated, and none was correlated with CD4 count.

HIV-associated cancers are often attributed to an infectious etiology, which presumably in the setting of impaired immunity and increased inflammation leads to a greater risk of cancer. Both Epstein-Barr virus and Helicobacter pylori have been associated with gastric cancer and NHL, and the role they play in HIV-associated gastrointestinal malignancies needs to be further defined. Additionally, the high prevalence of tobacco and alcohol use in HIV patients may contribute to the risk of gastrointestinal malignancies.

Gastroenterologists clearly now need to be familiar with several malignancies in persons with HIV, including KS, NHL, and gastric and esophageal carcinoma. It remains unknown whether strategies such as earlier initiation of antiretroviral therapy, eradication of H. pylori, and reducing alcohol and tobacco use are effective in reducing the burden of cancer in HIV-infected persons.

COREY CASPER, M.D., M.P.H., is an associate member of the divisions of public health science and clinical research in the department of vaccine and infectious disease at the Fred Hutchinson Cancer Research Center, Seattle, and an associate professor of medicine, epidemiology, and global health at the University of Washington, Seattle. He also is medical director of infection control, Seattle Cancer Care Alliance.

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Body

Over the 30 years of the HIV pandemic, the risk of cancer has been found to be significantly elevated in HIV-infected persons. These include the three “AIDS-defining” cancers (Kaposi Sarcoma [KS], non-Hodgkin lymphoma [NHL], and cervical cancer) and a variety of “non AIDS-defining” cancers. Gastroenterologists have been most likely to encounter either visceral KS or hepatocellular carcinoma.

Dr. Persson and her colleagues used large population-based HIV and cancer registries to describe an increased risk of two additional malignancies, esophageal cancer (both squamous cell and adenocarcinoma) and stomach cancer in persons with AIDS, in addition to mucosa-associated lymphomas (NHL). NHL decreased in the era of effective antiretroviral therapy, but esophageal and gastric cancers remained elevated, and none was correlated with CD4 count.

HIV-associated cancers are often attributed to an infectious etiology, which presumably in the setting of impaired immunity and increased inflammation leads to a greater risk of cancer. Both Epstein-Barr virus and Helicobacter pylori have been associated with gastric cancer and NHL, and the role they play in HIV-associated gastrointestinal malignancies needs to be further defined. Additionally, the high prevalence of tobacco and alcohol use in HIV patients may contribute to the risk of gastrointestinal malignancies.

Gastroenterologists clearly now need to be familiar with several malignancies in persons with HIV, including KS, NHL, and gastric and esophageal carcinoma. It remains unknown whether strategies such as earlier initiation of antiretroviral therapy, eradication of H. pylori, and reducing alcohol and tobacco use are effective in reducing the burden of cancer in HIV-infected persons.

COREY CASPER, M.D., M.P.H., is an associate member of the divisions of public health science and clinical research in the department of vaccine and infectious disease at the Fred Hutchinson Cancer Research Center, Seattle, and an associate professor of medicine, epidemiology, and global health at the University of Washington, Seattle. He also is medical director of infection control, Seattle Cancer Care Alliance.

Body

Over the 30 years of the HIV pandemic, the risk of cancer has been found to be significantly elevated in HIV-infected persons. These include the three “AIDS-defining” cancers (Kaposi Sarcoma [KS], non-Hodgkin lymphoma [NHL], and cervical cancer) and a variety of “non AIDS-defining” cancers. Gastroenterologists have been most likely to encounter either visceral KS or hepatocellular carcinoma.

Dr. Persson and her colleagues used large population-based HIV and cancer registries to describe an increased risk of two additional malignancies, esophageal cancer (both squamous cell and adenocarcinoma) and stomach cancer in persons with AIDS, in addition to mucosa-associated lymphomas (NHL). NHL decreased in the era of effective antiretroviral therapy, but esophageal and gastric cancers remained elevated, and none was correlated with CD4 count.

HIV-associated cancers are often attributed to an infectious etiology, which presumably in the setting of impaired immunity and increased inflammation leads to a greater risk of cancer. Both Epstein-Barr virus and Helicobacter pylori have been associated with gastric cancer and NHL, and the role they play in HIV-associated gastrointestinal malignancies needs to be further defined. Additionally, the high prevalence of tobacco and alcohol use in HIV patients may contribute to the risk of gastrointestinal malignancies.

Gastroenterologists clearly now need to be familiar with several malignancies in persons with HIV, including KS, NHL, and gastric and esophageal carcinoma. It remains unknown whether strategies such as earlier initiation of antiretroviral therapy, eradication of H. pylori, and reducing alcohol and tobacco use are effective in reducing the burden of cancer in HIV-infected persons.

COREY CASPER, M.D., M.P.H., is an associate member of the divisions of public health science and clinical research in the department of vaccine and infectious disease at the Fred Hutchinson Cancer Research Center, Seattle, and an associate professor of medicine, epidemiology, and global health at the University of Washington, Seattle. He also is medical director of infection control, Seattle Cancer Care Alliance.

Title
Gastroenterologists and the Cancer/AIDS Link
Gastroenterologists and the Cancer/AIDS Link

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

AIDS patients have a greater risk of esophageal and stomach malignancies, compared with the general population, reported E. Christina Persson, Ph.D., and her colleagues in Gastroenterology.

The researchers, led by Dr. Persson of the division of cancer epidemiology and genetics at the National Cancer Institute, analyzed data from nearly 2 million person-years recorded in the HIV/AIDS Cancer Match Study. The HACM study links state and metropolitan HIV/AIDS registries to the corresponding cancer registries.

The investigators limited their search to primary invasive carcinomas or non-Hodgkin’s lymphomas (NHLs) of the esophagus and stomach that were diagnosed between 1980 and 2007 (Gastroenterology 2012 [doi: 10.1053/j.gastro.2012.07.013]).

"Individuals diagnosed with first malignancies other than esophageal and stomach cancers were censored at date of diagnosis, and any subsequent malignancy was excluded," they said.

Additionally, the first 3 months after AIDS diagnosis were excluded from analysis, since NHL is AIDS-defining, and also because intensive medical evaluation in this period could artificially inflate cancer diagnoses.

AIDS patients were followed up until earliest cancer diagnosis, death, date of last registry coverage, or 10 years after AIDS diagnosis, whichever came first.

The researchers then ascertained the standardized incidence ratio (SIR) for the 596,955 AIDS patients (predominantly male) included in the study. This was calculated by dividing the observed counts in AIDS patients by expected counts, which were in turn estimated by applying general population incidence rates to the AIDS population in strata defined by age, race, sex, calendar year, and cancer registry.

During 1,920,274 person-years, the SIR for esophageal carcinoma was 1.69 in AIDS patients, compared with the general population (95% confidence interval, 1.37-2.07).

When the data were broken down by specific type of esophageal cancer, the SIR was higher for esophageal adenocarcinoma at 1.91 (95% CI, 1.31-2.70), and lower for squamous cell carcinoma of the esophagus at 1.47 (95% CI, 1.10-1.92).

The authors added that the elevated risk applied to all sites, "although the elevated risk of carcinoma of the middle esophagus was of borderline statistical significance."

The results were similar for carcinomas of the stomach. Compared with the general population, AIDS patients had a SIR of 1.44 for all carcinomas (95% CI, 1.17-1.76).

"All types of adenocarcinoma were elevated, including diffuse adenocarcinoma (SIR, 1.65; 95% CI, 1.08-2.41) and intestinal adenocarcinoma (SIR, 1.96; 95% CI, 0.94-3.61)," wrote Dr. Persson.

Moreover, the risk was elevated for both cardia and noncardia sites, "though only the SIR for noncardia stomach carcinoma was significant (SIR, 1.53; 95% CI, 1.12-2.05)."

The risks of non-Hodgkin’s lymphomas of the esophagus and stomach were dramatically elevated in the AIDS population, which was "not surprising," according to the authors: For the esophagus, the SIR was 261 (95% CI, 190-349) and for the stomach, it was 35.5 (95% CI, 31.9-39.5).

The authors also examined the risk of carcinoma adjusted for demographics, calendar year, and AIDS status. They found that CD4 count was not associated with the risk of either esophageal or stomach cancer.

Nor was there any decrease in the incidence rate over the calendar period of the study, even after the introduction of highly active antiretroviral therapy (HAART) in 1996.

According to the authors, this confirms that while "extended immunosuppression plays a role in the development of these cancers, ... HAART use after the development of AIDS may not be effective in halting this process."

The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

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Major Finding: The risk of developing cancer of the esophagus and stomach is increased by 69% and 44%, respectively, in people with AIDS, compared with the general population.

Data Source: This study was a review of nearly 2 million person-years of data from the HIV/AIDS Cancer Match Study.

Disclosures: The research was funded by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. The authors declared no potential conflicts of interest.

Most IBD Patients Don't Meet Biologics Trial Criteria

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Most IBD Patients Don't Meet Biologics Trial Criteria

Participants in randomized controlled trials of biologics for inflammatory bowel disease do not adequately represent real-world patients because of stringent inclusion criteria for the trials, reported Dr. Christina Ha and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, among 125 Crohn’s disease (CD) patients seen in routine clinical practice at a tertiary care center, only 43 – just 34% – would have qualified for enrollment in at least one of seven randomized controlled trials (RCTs) for biologics, calling into question the generalizability of these trials’ results. The corresponding percentage for ulcerative colitis (UC) patients was only 25%.

Video Source: American Gastroenterological Association

Dr. Ha, of the division of gastroenterology at Johns Hopkins University, Baltimore, and her colleagues reviewed the medical records of 206 patients with moderate to severe CD or UC presenting to the Mount Sinai Medical Center in New York for adjustment of therapy during 2008-2009.

The researchers then looked at seven randomized controlled trials of biologics in CD as well as two trials of biologics in UC, and applied their inclusion and exclusion criteria to her real-world study population (Clin. Gastroenterol. Hepatol. 2012 September [doi: 10.1016/j.cgh.2012.02.004]).

Among the Crohn’s patients, "trial eligibility for the RCTs for infliximab, adalimumab, certolizumab pegol, and natalizumab ranged from 8% for the SONIC [Study of Biologic and Immunomodulator Naïve Patients in Crohn’s Disease] trial to 27% for the CHARM [Crohn’s Trial of the Fully Human Antibody Adalimumab for Remission Maintenance] and PRECISE [Pegylated Antibody Fragment Evaluation in Crohn’s Disease] trials," wrote the investigators.

Similarly, among the 81 UC patients, only 21 (25%) would have qualified for enrollment into the ACT (Active Ulcerative Colitis Trial) 1 or 2 trials.

Among the Crohn’s patients, the most common reasons for ineligibility were symptomatic strictures or abscesses (n = 51, 62.2%), recent exposure or prior nonresponse to anti–tumor necrosis factor drugs (n = 42, 51.2%), use of high-dose steroids (n = 15, 18.3%), and comorbid cardiovascular or pulmonary disease and malignancies (n = 21, 25.6%).

"The most common reason for trial ineligibility for UC was current rectal therapy usage (n = 34, 56.7%)," wrote the authors. Other reasons included steroid naivety (n = 27, 45.0%); new diagnoses of UC (n = 10, 16.7%); or need for colectomy due to age, comorbidity, or concomitant dysplasia found during colonoscopy (n = 9, 15.0%).

Finally, the authors assessed the outcomes of patients who would not have qualified for the biologics trials but initiated biologic therapy nevertheless. In the CD cohort, "ultimately, almost 50% of these ‘trial ineligible’ patients underwent surgery, either as a primary therapy or due to inadequate response to biologics or immunomodulators," wrote the authors. In the UC group, roughly one-quarter of would-be ineligible patients underwent colectomy at 4-12 weeks.

The authors conceded that if patients had been studied longitudinally, "with the inclusion and exclusion criteria applied at the time patients were first being considered for immunomodulators or biologics or at the time of diagnosis, a larger percentage of patients may have been eligible for trial participation."

Nevertheless, Dr. Ha and her colleagues concluded, "pragmatic trials of the major IBD therapeutics would not only serve to validate RCT findings, but provide additional insight regarding medication safety across a broader patient population."

Several of the authors disclosed financial relationships with pharmaceutical companies, including the makers of biologics. The authors stated that this study received no grant support.

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Participants in randomized controlled trials of biologics for inflammatory bowel disease do not adequately represent real-world patients because of stringent inclusion criteria for the trials, reported Dr. Christina Ha and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, among 125 Crohn’s disease (CD) patients seen in routine clinical practice at a tertiary care center, only 43 – just 34% – would have qualified for enrollment in at least one of seven randomized controlled trials (RCTs) for biologics, calling into question the generalizability of these trials’ results. The corresponding percentage for ulcerative colitis (UC) patients was only 25%.

Video Source: American Gastroenterological Association

Dr. Ha, of the division of gastroenterology at Johns Hopkins University, Baltimore, and her colleagues reviewed the medical records of 206 patients with moderate to severe CD or UC presenting to the Mount Sinai Medical Center in New York for adjustment of therapy during 2008-2009.

The researchers then looked at seven randomized controlled trials of biologics in CD as well as two trials of biologics in UC, and applied their inclusion and exclusion criteria to her real-world study population (Clin. Gastroenterol. Hepatol. 2012 September [doi: 10.1016/j.cgh.2012.02.004]).

Among the Crohn’s patients, "trial eligibility for the RCTs for infliximab, adalimumab, certolizumab pegol, and natalizumab ranged from 8% for the SONIC [Study of Biologic and Immunomodulator Naïve Patients in Crohn’s Disease] trial to 27% for the CHARM [Crohn’s Trial of the Fully Human Antibody Adalimumab for Remission Maintenance] and PRECISE [Pegylated Antibody Fragment Evaluation in Crohn’s Disease] trials," wrote the investigators.

Similarly, among the 81 UC patients, only 21 (25%) would have qualified for enrollment into the ACT (Active Ulcerative Colitis Trial) 1 or 2 trials.

Among the Crohn’s patients, the most common reasons for ineligibility were symptomatic strictures or abscesses (n = 51, 62.2%), recent exposure or prior nonresponse to anti–tumor necrosis factor drugs (n = 42, 51.2%), use of high-dose steroids (n = 15, 18.3%), and comorbid cardiovascular or pulmonary disease and malignancies (n = 21, 25.6%).

"The most common reason for trial ineligibility for UC was current rectal therapy usage (n = 34, 56.7%)," wrote the authors. Other reasons included steroid naivety (n = 27, 45.0%); new diagnoses of UC (n = 10, 16.7%); or need for colectomy due to age, comorbidity, or concomitant dysplasia found during colonoscopy (n = 9, 15.0%).

Finally, the authors assessed the outcomes of patients who would not have qualified for the biologics trials but initiated biologic therapy nevertheless. In the CD cohort, "ultimately, almost 50% of these ‘trial ineligible’ patients underwent surgery, either as a primary therapy or due to inadequate response to biologics or immunomodulators," wrote the authors. In the UC group, roughly one-quarter of would-be ineligible patients underwent colectomy at 4-12 weeks.

The authors conceded that if patients had been studied longitudinally, "with the inclusion and exclusion criteria applied at the time patients were first being considered for immunomodulators or biologics or at the time of diagnosis, a larger percentage of patients may have been eligible for trial participation."

Nevertheless, Dr. Ha and her colleagues concluded, "pragmatic trials of the major IBD therapeutics would not only serve to validate RCT findings, but provide additional insight regarding medication safety across a broader patient population."

Several of the authors disclosed financial relationships with pharmaceutical companies, including the makers of biologics. The authors stated that this study received no grant support.

Participants in randomized controlled trials of biologics for inflammatory bowel disease do not adequately represent real-world patients because of stringent inclusion criteria for the trials, reported Dr. Christina Ha and her colleagues in the September issue of Clinical Gastroenterology and Hepatology.

Indeed, among 125 Crohn’s disease (CD) patients seen in routine clinical practice at a tertiary care center, only 43 – just 34% – would have qualified for enrollment in at least one of seven randomized controlled trials (RCTs) for biologics, calling into question the generalizability of these trials’ results. The corresponding percentage for ulcerative colitis (UC) patients was only 25%.

Video Source: American Gastroenterological Association

Dr. Ha, of the division of gastroenterology at Johns Hopkins University, Baltimore, and her colleagues reviewed the medical records of 206 patients with moderate to severe CD or UC presenting to the Mount Sinai Medical Center in New York for adjustment of therapy during 2008-2009.

The researchers then looked at seven randomized controlled trials of biologics in CD as well as two trials of biologics in UC, and applied their inclusion and exclusion criteria to her real-world study population (Clin. Gastroenterol. Hepatol. 2012 September [doi: 10.1016/j.cgh.2012.02.004]).

Among the Crohn’s patients, "trial eligibility for the RCTs for infliximab, adalimumab, certolizumab pegol, and natalizumab ranged from 8% for the SONIC [Study of Biologic and Immunomodulator Naïve Patients in Crohn’s Disease] trial to 27% for the CHARM [Crohn’s Trial of the Fully Human Antibody Adalimumab for Remission Maintenance] and PRECISE [Pegylated Antibody Fragment Evaluation in Crohn’s Disease] trials," wrote the investigators.

Similarly, among the 81 UC patients, only 21 (25%) would have qualified for enrollment into the ACT (Active Ulcerative Colitis Trial) 1 or 2 trials.

Among the Crohn’s patients, the most common reasons for ineligibility were symptomatic strictures or abscesses (n = 51, 62.2%), recent exposure or prior nonresponse to anti–tumor necrosis factor drugs (n = 42, 51.2%), use of high-dose steroids (n = 15, 18.3%), and comorbid cardiovascular or pulmonary disease and malignancies (n = 21, 25.6%).

"The most common reason for trial ineligibility for UC was current rectal therapy usage (n = 34, 56.7%)," wrote the authors. Other reasons included steroid naivety (n = 27, 45.0%); new diagnoses of UC (n = 10, 16.7%); or need for colectomy due to age, comorbidity, or concomitant dysplasia found during colonoscopy (n = 9, 15.0%).

Finally, the authors assessed the outcomes of patients who would not have qualified for the biologics trials but initiated biologic therapy nevertheless. In the CD cohort, "ultimately, almost 50% of these ‘trial ineligible’ patients underwent surgery, either as a primary therapy or due to inadequate response to biologics or immunomodulators," wrote the authors. In the UC group, roughly one-quarter of would-be ineligible patients underwent colectomy at 4-12 weeks.

The authors conceded that if patients had been studied longitudinally, "with the inclusion and exclusion criteria applied at the time patients were first being considered for immunomodulators or biologics or at the time of diagnosis, a larger percentage of patients may have been eligible for trial participation."

Nevertheless, Dr. Ha and her colleagues concluded, "pragmatic trials of the major IBD therapeutics would not only serve to validate RCT findings, but provide additional insight regarding medication safety across a broader patient population."

Several of the authors disclosed financial relationships with pharmaceutical companies, including the makers of biologics. The authors stated that this study received no grant support.

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Most IBD Patients Don't Meet Biologics Trial Criteria
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biologics for inflammatory bowel disease, IBD, Dr. Christina Ha, Clinical Gastroenterology and Hepatology, Crohn’s disease, ulcerative colitis, gastroenterology, SONIC study, Study of Biologic and Immunomodulator Naïve Patients in Crohn’s Disease trial, CHARM, Crohn’s Trial of the Fully Human Antibody Adalimumab for Remission Maintenance, PRECISE, Pegylated Antibody Fragment Evaluation in Crohn’s Disease, ACT, Active Ulcerative Colitis Trial,
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biologics for inflammatory bowel disease, IBD, Dr. Christina Ha, Clinical Gastroenterology and Hepatology, Crohn’s disease, ulcerative colitis, gastroenterology, SONIC study, Study of Biologic and Immunomodulator Naïve Patients in Crohn’s Disease trial, CHARM, Crohn’s Trial of the Fully Human Antibody Adalimumab for Remission Maintenance, PRECISE, Pegylated Antibody Fragment Evaluation in Crohn’s Disease, ACT, Active Ulcerative Colitis Trial,
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