Benjamin Avidan

Hiatal hernia size, Barrett's length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma.

OBJECTIVE:The reasons for the development of dysplasia and adenocarcinoma in Barretts mucosa are not well understood. The aims of this study were to characterize risk factors for the transition from Barretts esophagus without dysplasia to Barretts esophagus with high-grade dysplasia or esophageal adenocarcinoma.METHODS:A group of 131 patients with high-grade dysplasia or esophageal adenocarcinoma were selected as case subjects. A first population of 2170 patients without gastroesophageal reflux disease (GERD) and a second population of 1189 patients with Barretts esophagus served as two control groups. Logistic regression analyses were used to compare the risk factors associated with the occurrence of high-grade dysplasia or esophageal adenocarcinoma.RESULTS:Patients with high-grade dysplasia or esophageal adenocarcinoma shared many characteristics with other forms of severe GERD, such as older age, male gender, and white ethnicity. The length of Barretts esophagus and the size of hiatus hernia increased the risk for both conditions. Subjects with high-grade dysplasia and adenocarcinoma had more severe acid reflux than patients with other forms of GERD. Smoking and alcohol consumption did not affect the risk for developing high-grade dysplasia or adenocarcinoma in patients with Barretts esophagus.CONCLUSIONS:High-grade dysplasia and esophageal adenocarcinoma seem to stem from an extreme and unfavorable constellation of all risk factors that are generally held responsible for the development of GERD and Barretts esophagus.

Hiatal hernia and acid reflux frequency predict presence and length of Barrett's esophagus.

One third of the general population may experience reflux symptoms, yet only a small fraction of patients with gastroesophageal reflux disease (GERD) have Barretts esophagus. The aim of the present study was to compare the characteristics of GERD patients with and without Barretts esophagus and identify potential risk factors for the appearance of Barretts esophagus in reflux disease. Outpatients from a gastroenterology clinic who underwent upper gastrointestinal endoscopy, esophageal manometry, and 24-hr pH monitoring were recruited into a case-control study. A total of 256 case subjects with endoscopically and histologically proven Barretts esophagus were compared to a control group of 229 subjects with nonerosive reflux disease. As compared to nonerosive reflux disease, Barretts esophagus was strongly associated with more reflux episodes. Barretts esophagus occurred more frequently among subjects with hiatus hernia and among subjects who consumed large amounts of alcohol or cigarettes. Frequent reflux episodes, hiatus hernia, smoking, and alcohol consumption were also risk factors for an increased length of Barretts mucosa. Total esophageal mucosal acid contact time at pH < 4 was a significant risk factor for the length but not the presence of Barretts esophagus. Intake of aspirin or NSAIDs was similar in patients with and without Barretts esophagus. In conclusion, in comparison with nonerosive reflux disease, Barretts esophagus is characterized by risk factors usually indicative of severe types of GERD. Mechanisms in addition to acid reflux must contribute to the development of Barretts esophagus.

New occurrence and recurrence of neoplasms within 5 years of a screening colonoscopy

OBJECTIVE:The fear that colorectal adenomas were missed on initial colonoscopy or that new adenomas have developed is often a rationale for repeating a colonoscopic examination. The aim of this study was to delineate risk factors associated with recurrence of colorectal adenomas after an initial baseline screening colonoscopy.METHODS:The study population comprised 875 subjects who underwent a baseline screening colonoscopy followed by a second examination 1–5 yr later. Multiple logistic regression was used to assess the influence of potential risk factors on the occurrence or recurrence of colorectal adenomas, the strength of the influence being expressed as an OR with a 95% CI.RESULTS:Colorectal adenomas were detected in 484 of all patients (55%) at baseline colonoscopy. Within a 1- to 5-yr time interval, 181 patients (37%) had recurrent adenomas (adenomas were removed during the first colonoscopy) and 73 patients (19%) had newly developed adenomas (adenomas were absent on the first colonoscopy). The occurrence of adenomas at baseline screening colonoscopy was the only factor associated with an increased risk for the recurrence of adenomas at follow-up (OR = 2.51, 95% CI = 1.77–3.55). Recurrence was associated with multiple baseline adenomas (4.45, 2.98–6.64) and baseline adenomas larger than 1 cm (2.62, 1.99–3.11). Recurrence was not associated with histology type or family history of colorectal cancer. There was a significant trend for adenomas to recur in the same proximal or distal segment as the baseline adenomas (p = 0.02).CONCLUSIONS:Colon adenomas tend to recur with greater frequency if the adenomas removed at baseline were either large or multiple. Although patients with large adenomas or multiple adenomas at baseline screening colonoscopy are at a 2.6- to 4.5-fold risk for recurrence of adenomas, the rate of de novo adenoma formation in patients without baseline adenomas may be large enough to warrant repeat colonoscopy at some time in the future. The exact timing of the follow-up colonoscopy needs to be determined.

Risk factors for erosive reflux esophagitis: a case-control study

OBJECTIVES:It is presently not fully understood which risk factors contribute to the occurrence of reflux esophagitis and how such factors might influence the severity of the disease. The aim of this study was to delineate the clinical epidemiology of erosive reflux esophagitis.METHODS:Outpatients from a medicine and gastroenterology clinic who underwent upper GI endoscopy were recruited into a case-control study. A total of 1533 patients with and 3428 patients without endoscopically diagnosed reflux esophagitis were categorized as case and control subjects, respectively. Using multivariate logistic regressions for statistical analysis, the presence of esophageal erosions, ulcers or strictures, served as three separate outcome variables. Demographic characteristics, intake of nonsteroidal anti-inflammatory drugs (NSAIDs), consumption of alcohol and cigarettes, and the presence of hiatus hernia or peptic ulcer served as predictor variables.RESULTS:Erosive reflux esophagitis tended to occur more frequently in Caucasian male patients. Hiatus hernia was associated with a strong risk for developing esophageal erosions, ulcers, and strictures. Although statistical significance was demonstrated only for esophageal erosions, in all grades of reflux esophagitis alike, gastric and duodenal ulcer exerted a protective influence. Consumption of NSAIDs increased the risk for esophageal ulcers only. Smoking and alcohol were not associated with an increased risk of developing any type of erosive reflux esophagitis.CONCLUSIONS:The results stress the critical role played by hiatus hernia in all grades of erosive reflux esophagitis. NSAIDs may act through a mechanism of topically induced esophageal injury. Our data also suggest that the presence of either gastric or duodenal ulcer exerts a protective influence against the development of reflux disease.

Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial

BACKGROUND & AIMS The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumins efficacy in inducing remission in patients with active mild-to-moderate UC. METHODS We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy. Patients were randomly assigned to groups who were given curcumin capsules (3 g/day, n = 26) or an identical placebo (n = 24) for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (SCCAI ≤2) at week 4. Clinical and endoscopic responses were also recorded. RESULTS In the intention-to-treat analysis, 14 patients (53.8%) receiving curcumin achieved clinical remission at week 4, compared with none of the patients receiving placebo (P = .01; odds ratio [OR], 42; 95% confidence interval [CI], 2.3-760). Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. 3 patients (12.5%) in the placebo group (P < .001; OR, 13.2; 95% CI, 3.1-56.6). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with none of 16 patients evaluated in the placebo group (P = .043; OR, 20.7; 95% CI, 1.1-393). Adverse events were rare and comparable between the 2 groups. CONCLUSIONS Addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects. Curcumin may be a safe and promising agent for treatment of UC. Clinicaltrials.gov number: NCT01320436.

Endoscopic ultrasound staging of rectal cancer: Diagnostic value before and following chemoradiation

Background:  Endoscopic ultrasound (EUS) has been shown to be a reliable tool for staging rectal cancer. Nevertheless, the accuracy of EUS after chemoradiation remains unclear; therefore the purpose of the present paper was to compare the accuracy of EUS staging for rectal cancer before and following chemoradiation.

The Familial Mediterranean Fever ( MEVF ) Gene as a Modifier of Crohn's Disease

OBJECTIVES:Crohns disease (CD) has been reported to be more frequent among non-Ashkenazi Jewish patients suffering from familial Mediterranean fever (FMF). Interestingly, functional similarities between the CD susceptibility gene (NOD2/CARD15) and the FMF gene (MEFV) have been described: both belong to the death domain containing protein family, important in the regulation of apoptosis, cytokine processing and inflammation.AIMS:To investigate the prevalence of MEFV mutations in Jewish non-Ashkenazi CD patients and its putative effect on CD presentation.METHODS:Germline DNA of 105 Israeli CD patients of non-Ashkenazi and mixed Ashkenazi–non-Ashkenazi ethnic background was analyzed for three most common MEFV mutations: M694V, V726A, and E148Q. Five patients (4.7%) with a clinical diagnosis of FMF were included. Data obtained from each patient included: age of onset, disease location, and behavior, the presence of extraintestinal manifestations of CD and therapeutic regimens.RESULTS:The overall prevalence of mutation carriers among non-FMF-CD patients was 13% (13/100). A stricturing disease pattern was observed in 56% (10/18) of all carriers, FMF-CD, and non-FMF-CD patients, and in 25% (22/87) of noncarriers (OR: 3.7, 95% CI: 1.3–10.5, p = 0.015). The prevalence of fistulas was comparable in both groups. Extraintestinal manifestations were significantly more frequent among carriers than noncarriers (65%vs 32%, OR 3.9, 95% CI = 1.3–11.5, p = 0.015). No differences were observed in disease location and disease severity.CONCLUSIONS:MEFV mutations are not associated with CD susceptibility, yet the presence of these mutations appears to be associated with a stricturing disease pattern and extraintestinal disease manifestations of CD.

Risk Factors Regarding the Need for a Second Operation in Patients with Crohn’s Disease

Background/Aims: The majority of Crohn’s disease patients undergo surgery. However, the factors that predict post-operative recurrence remain controversial. The aim of the present study was to shed light on the potential predictors of such recurrence. Methods: 86 patients who underwent operative procedures for Crohn’s disease were retrospectively studied. Recurrence was defined as the need for a second operation. Life table and multivariate analysis were performed to find the predictors of recurrence. Results: In 26/86 (30%) of the patients, post-operative recurrence was diagnosed within a mean of 42 months of the follow-up. Logistic regression analysis revealed that smoking (OR 3.69, 95% CI 2.06–11.52) and perforating disease (OR 4.09, 95% CI 1.31–12.65) were associated with a risk of recurrence. However, survival analysis showed that only perforating disease was associated with an early post-operative recurrence (log-rank test, p < 0.001). Neither resected surgical specimen characteristics, nor the duration and the location of the disease were found to predict the need for a second operation. Conclusion: The risk for Crohn’s disease patients who undergo surgery is related to the presence of perforating disease and smoking, which predict the need for a second operation. The former is associated with an even earlier recurrence.

Acid reflux is a poor predictor for severity of erosive reflux esophagitis

It is unknown which factors determine the severity of mucosal damage in gastroesophageal reflux disease (GERD). Our aim was to test whether the amount of esophageal acid exposure could predict the severity of esophageal injury in erosive reflux esophagitis. A total of 644 outpatients with symptomatic GERD underwent an esophagogastroduodenoscopy followed by esophageal manometry and 24-h pH monitoring. GERD was graded according to the endoscopic severity of mucosal damage as no erosions, single erosions, confluent erosions, esophageal ulcers, and strictures. A multiple linear regression was used to assess the joint influences of demographic characteristics, social habits, endoscopic anatomy, and various parameters of esophageal function tests on the severity of erosive reflux disease. No clear-cut association between the amount of acid reflux and the severity of erosive reflux esophagitis could be established. All individual parameters of esophageal pH monitoring, such as upright or supine acid contact time, frequency of all or only long reflux episodes, and an overall summary score of pH-metry, revealed no or only a weak correlation with the severity grade of erosive reflux esophagitis. Similarly, the pressure of the lower esophageal sphincter was only slightly more decreased in patients with extensive erosive esophagitis as compared to subjects without esophageal erosions. In the multiple linear regression, the presence of hiatus hernia was a stronger predictor of disease severity than any of the other parameters. In conclusion, factors other than exposure of the esophageal mucosa to acid must contribute to the development of erosive esophagitis.

The outcome of a second preparation for colonoscopy after preparation failure in the first procedure

BACKGROUND There are scant data regarding the outcome of consecutive repeated procedures in patients who failed to adequately clean their colon for colonoscopy. OBJECTIVE To investigate the outcome of a second colonoscopy after preparation-associated failure of the first colonoscopy. DESIGN AND SETTING A retrospective study in a tertiary-referral center. PATIENTS All patients with failure of colonoscopy because of poor preparation within a 1-year period. RESULTS Of a total of 6990 colonoscopies performed during the study period, 307 procedures (4.4%) failed because of inadequate preparation. Data on subsequent repeated colonoscopies were available for 235 patients. The repeated procedure again failed because of unsatisfactory preparation in 54 of these patients (23%). The failure rate in subsequent third and fourth colonoscopies was also high (more than 25%). Of the various patient and procedure-related parameters examined, only the use of calcium channel blockers (CCB) was found to be predictive of a failed repeated preparation (odds ratio [OR] 3.2 [95% CI, 1.6-6.3], P < .001). In contrast, a next-day colonoscopy after failure of the index procedure was associated with a reduced risk of unsatisfactory second preparation (OR 0.31 [95% CI, 0.1-0.92], P = .03). LIMITATIONS Validated data on the specific bowel purgatives used were not available. CONCLUSIONS Almost a fourth of patients with an unacceptable colonic preparation will also fail the repeated colonoscopy, and patients who use CCB are at particular risk for failure. Strategies to manage this difficult-to-treat patient group should be investigated and may possibly include a preference for next-day colonoscopy.