Damien Mallat

Role of Helicobacter pylori infection in gastroduodenal injury and gastric prostaglandin synthesis during long term/low dose aspirin therapy: a prospective placebo-controlled, double-blind randomized trial

OBJECTIVES:Whether gastric infection with Helicobacter pylori increases the risk of gastric mucosal injury during long term/low dose aspirin therapy is unknown. We examined whether H. pylori infection enhances upper GI mucosal damage, assessed endoscopically, in volunteers given low dose aspirin. We studied 61 healthy men and women, 29 with and 32 without active H. pylori infection.METHODS:We treated volunteers for 45 days with a placebo or aspirin (either 81 mg every day or 325 mg every 3 days). Gastroduodenal mucosal damage was then assessed by endoscopy, as was gastric histology and ex vivo gastric mucosal prostaglandin E2 and F2α synthesis rates.RESULTS:Erosive disease from low dose aspirin (erosions and/or ulcers) occurred in 50% of H. pylori–infected volunteers and in 16% of their noninfected counterparts (p = 0.02). Aspirin caused a significantly higher average mucosal injury score in the gastric antrum in H. pylori–infected participants than in noninfected subjects (p = 0.03), and two H. pylori–infected subjects developed antral gastric ulcers. Subjects with H. pylori gastritis treated with the placebo had nearly 50% higher gastric mucosal prostaglandin (E2 plus F2α) synthesis rates than their noninfected counterparts (108 ± 6 ng/g/min versus 75 ± 6 ng/g/min, p < 0.001). Aspirin reduced mucosal prostaglandin synthesis to similar levels in infected and noninfected participants.CONCLUSIONS:Long term/low dose aspirin therapy led to more gastric mucosal damage when H. pylori gastritis was present than when it was absent, despite similar degrees of gastric mucosal prostaglandin depletion.

The natural history of HCV infection in African Americans.

Worldwide the consequences of the hepatitis C virus (HCV) epidemic have been devastating. In the United States alone, about 4 million persons are infected with HCV. The prevalence of HCV appears to vary among racial groups. HCV infection is more prevalent in African Americans than in any other racial group. Seeff et al. (1) studied 8568 military recruit blood samples, frozen for about 45 yr, and found that the rate of HCV antibody was 1.8% among African Americans and 0.07% among whites. Moreover, in the United States Third National Health and Nutrition Examination Survey, HCV antibody was detected in 3.2% of African Americans but in only 1.5% of whites. The rate of viremia was 86% in African Americans and 68% in whites; genotype 1 was identified in the majority of African Americans infected with HCV (91%) (2). However, in a study from Johns Hopkins University (3), 2523 patients were recruited from an inner city hospital and were tested for HCV, hepatitis B virus, and HIV. Among African American males (age 35–44), the prevalence of HCV antibody was 51%.

The Duodenal Aspirate Volume Does Not Correlate With the PEAK Bicarbonate Concentration During Secretin Stimulated Endoscopic Pancreas Function Testing. A Note of Caution for Secretin MRCP

Background. Abnormal exocrine function precedes most imaging changes of CP so stimulated pancreas function tests (PFT) are used as a surrogate for early diagnosis as histology is rarely obtained. Endoscopic PFT (ePFT) have shown promise as a less technically challenging PFT but may last one hour and require special equipment. Peak pancreas exocrine output takes at least 30 minutes to occur after secretagogue stimulation so we tested if a shorter endoscopic aspiration could differentiate patients with and without chronic pancreatitis. Methods. Synthetic secretin 0.2 μg/kg (ChiRhoClin,Inc.,Burtonsville,MD) was administered IV, and sedation started 30 minutes afterwards. After gastric fluid aspiration the endoscope was advanced to the major papilla and four continuous duodenal aspirations were done at 5 minute intervals, starting 35 minutes after secretin administration, collected in a sealed polyp trap on ice, and delivered to the laboratory. The first four samples were analyzed by an autoanalyzer (Corning 965, USA) calibrated to a bicarbonate of 80 mEq/L and compared to pH back titration. Variance between the methods was ±0.02 mEq/L so subsequent measurements were done with the auto-analyzer only. Peak bicarbonate concentration (PBC) >80 mEq/L during any collection is normal. ERCP and EUS were compared to ePFT and all three to a final diagnosis of CP which was established by considering history, imaging, histology and ePFT. Results. Twenty seven ePFT have been performed (16 females). Indications were suspected CP (17), abdominal pain (7), steatorrhea (2), idiopathic recurrent acute pancreatitis (1). Nine patients (pts) received a final diagnosis of CP and 18 no CP. 15 pts had ERCP (two had one, 9 pts had 2, 2 pts had 3 and 2 pts had 5). Seven pts had a normal pancreatogram. Cambridge class was I in one pt, II in 4 pts, III in 2 pts and IV in one pt. Two pts with Cambridge II and one with Cambridge III had normal PBC. 23 pts had EUS (21 had one, one pt had two, and one pt had 3). Ten pts had > 4 criteria for CP, and 6/10 pts had an abnormal ePFT. 13 pts had a normal EUS, and 11/13 had normal PBC (one pt had PBC 78.9 mEq/L). PBC was 80 mEq/ L in 17/18 pts without CP. The sensitivity and specificity of ePFT compared to ERCP and EUS and of all three compared to a final diagnosis of CP are in the tables. Conclusion. The ePFT was as good as EUS and ERCP in predicting CP. ePFT and EUS were non-statistically superior to ERCP in ruling out CP. The final diagnosis of CP was enhanced by combining numerous tests, but this proposed shorter ePFT requires less expertise, involves routine upper endoscopy, and may be more practical for regular use. More data is needed to determine how well it predicts early chronic pancreatitis, and if results decrease the ordering of other tests when CP is suspected. Comparison of ePFT to ERCP and EUS

Interferon for postresection recurrence of hepatocellular carcinoma.

In a randomized, controlled trial, 30 hepatitis C virus-infected men who underwent hepatic resection for hepatocellular carcinoma (HCC) were subsequently randomized to receive either interferon (INF)-alpha (n = 15) or no interferon (n = 15). Eighty percent of patients had hepatitis C virus genotype 1b, and 20% of patients had genotype 2a. Patients in the treatment group were given IFN-alpha, 6 M IU i.m. daily for 2 wk, then three times weekly for 14 wk, and finally twice weekly for 88 wk. The investigators were blinded to the treatment assignment. The median duration of follow-up was approximately 3 and 2.5 yr for the IFN and control groups, respectively. Three patients (15%) did not complete IFN therapy as a result of side effects. In addition, four patients (20%) with recurrence of HCC had their IFN stopped before the end of the study to allow treatment of the tumor. In the IFN group, two patients had sustained viral response, and six had biochemical response. In a survival analysis that included all randomized patients, i.e., “intention to treat,” recurrent HCC was detected in five patients (30%) in the IFN-alpha group and in 12 control patients (80%) (p = 0.037). The difference in the rate of HCC between the groups became apparent only after the first 2 yr of follow-up. The authors concluded that IFN-alpha therapy appears to decrease the recurrence of HCC after resection in patients with chronic hepatitis C infection.

Surveillance for hepatocellular carcinoma: does it work?

(173) with the remainder (37) having malabsorption. A second, smaller group of 132 patients, again with negative histology but strong clinical suspicion for WD, had small intestinal biopsies submitted for PCR analysis. In a vindication for the academic pathologist, there was complete concordance between negative histology and negative PCR in all the specimens. The authors conclude that there is no reason for PCR-based T. whipplei testing in patients with negative histology, even for those in whom the clinical suspicion is high. What lessons can we learn from this study? Firstly, WD is extremely rare and is diagnosed infrequently, even in patients with malabsorption evaluated in specialized gastroenterology clinics. Secondly, PCR-based T. whipplei testing, as done by this group, is not associated with false positive results, thereby dispelling the notion that T. whipplei might be a commensal in the intestine. Lastly, WD might not involve the bowel in up to 15% of cases (so called dry forms of the disease) (2), and testing of a symptomatic extraintestinal site by PCR is indicated. Citing previous work from their institution, these authors describe patients with negative intestinal biopsies whose diagnosis of WD was made by PCR of other infected tissues. This included CSF, a lymph node, ocular vitreous fluid, and a heart valve. Most practicing physicians will never diagnose WD in their working lifetime, so it might seem such research will not repay the effort invested in it. However, it should be remembered that WD is uniformly fatal if left untreated and is a diagnosis never to be missed.

Interferon: benefit beyond hepatitis therapy?

In a randomized, controlled trial, 30 hepatitis C virus–infected men who underwent hepatic resection for hepatocellular carcinoma (HCC) were subsequently randomized to receive either interferon α (n = 15) or no interferon (n = 15). Eighty percent of patients had HCV genotype 1b and 20% had genotype 2a. Patients in the treatment group were given interferon α (6 million IU i.m.) daily for 2 wk, then three times weekly for 14 wk, and finally twice weekly for 88 wk. The investigators were blinded to the treatment assignment. The median durations of follow-up were approximately 3 and 2.5 yr for the interferon and control groups, respectively. Three patients (15%) did not complete interferon therapy as a result of side effects. In addition, four patients (20%) with recurrence of HCC had their interferon stopped before the end of the study to allow treatment of the tumor. In the interferon group, two patients had sustained viral response and six had biochemical response. In a survival analysis that included all randomized patients (i.e., intention to treat), recurrent HCC was detected in five patients (30%) in the interferon-α group and in 12 control patients (80%) (p = 0.037). The difference in the rate of HCC between the groups became apparent only after the first 2 yr of follow-up. The authors concluded that interferon-α therapy appears to decrease the recurrence of HCC after resection in patients with chronic hepatitis C infection.

Management of Patients With Pancreatic Cysts: Analysis of Possible False-Negative Cases of Malignancy.

Goals: To examine the utility of integrated molecular pathology (IMP) in managing surveillance of pancreatic cysts based on outcomes and analysis of false negatives (FNs) from a previously published cohort (n=492). Background: In endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of cyst fluid lacking malignant cytology, IMP demonstrated better risk stratification for malignancy at approximately 3 years’ follow-up than International Consensus Guideline (Fukuoka) 2012 management recommendations in such cases. Study: Patient outcomes and clinical features of Fukuoka and IMP FN cases were reviewed. Practical guidance for appropriate surveillance intervals and surgery decisions using IMP were derived from follow-up data, considering EUS-FNA sampling limitations and high-risk clinical circumstances observed. Surveillance intervals for patients based on IMP predictive value were compared with those of Fukuoka. Results: Outcomes at follow-up for IMP low-risk diagnoses supported surveillance every 2 to 3 years, independent of cyst size, when EUS-FNA sampling limitations or high-risk clinical circumstances were absent. In 10 of 11 patients with FN IMP diagnoses (2% of cohort), EUS-FNA sampling limitations existed; Fukuoka identified high risk in 9 of 11 cases. In 4 of 6 FN cases by Fukuoka (1% of cohort), IMP identified high risk. Overall, 55% of cases had possible sampling limitations and 37% had high-risk clinical circumstances. Outcomes support more cautious management in such cases when using IMP. Conclusions: Adjunct use of IMP can provide evidence for relaxed surveillance of patients with benign cysts that meet Fukuoka criteria for closer observation or surgery. Although infrequent, FN results with IMP can be associated with EUS-FNA sampling limitations or high-risk clinical circumstances.