The involvement of IgH enhancer HS1.2 in the pathogenesis of Crohn's disease: how the immune system can influence a multifactorial disease.

OBJECTIVE: To study the 3' immunoglobulin heavy-chain regulatory region (3'RR) enhancer complex, active in class switching recombination and in B-cells, in Crohn's disease. PATIENTS AND METHODS: A total of 167 patients [79 females (47.3%) and 88 males (52.7%)] affected by Crohn's disease were enrolled in the study. As a control, we included 64 healthy subjects, age and sex matched, from the same geographical area. Blood tests were performed on all subjects to determine their antibody levels and to detect the presence of any possible infections. We conducted a selective PCR, which amplified the hs1.2-A region. The nested second PCR to amplify the polymorphic core of the enhancer was performed. RESULTS: No differences between cases and controls were observed with respect to sex distribution (43.8% females among controls and 49.5% among cases), age, tTG IgA, RF, serum or secretory IgA, IgG1, IgG2 and IgG3. No correlation was found between both seric and secretory immunoglobulins levels, with except of statistically significant differences between cases and controls with respect to IgA and IgG ASCA positivity (p<0.001), serum IgG4 (p<0.001) and IgD (p=0.001). CONCLUSIONS: We have demonstrated that in Crohn's disease, the HS1,2 immunoglobulins enhancer is not implicated in the disease pathogenesis. Moreover, we have found that IgG4 levels are lower in Crohn's disease patients than in controls; these data may be related to an impairment of number and function of Tregs, further linked to the presence of tissue inflammation. Crohn's disease is a complex multifactorial disease. The pathogenesis of Crohn's disease is incompletely understood although it is clear that the disease involves multiple interacting agents.

Effect of immunosuppressive therapy on patients with inflammatory bowel diseases and hepatitis B or C virus infection.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

BACKGROUND AND AIM: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the choice amongst regimens available for cleansing the colon in preparation for colonoscopy. METHODS: This Guideline is based on a targeted literature search to evaluate the evidence supporting the use of bowel preparation for colonoscopy. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. RESULTS: The main recommendations are as follows. (1) The ESGE recommends a low-fiber diet on the day preceding colonoscopy (weak recommendation, moderate quality evidence). (2) The ESGE recommends a split regimen of 4 L of polyethylene glycol (PEG) solution (or a same-day regimen in the case of afternoon colonoscopy) for routine bowel preparation. A split regimen (or same-day regimen in the case of afternoon colonoscopy) of 2 L PEG plus ascorbate or of sodium picosulphate plus magnesium citrate may be valid alternatives, in particular for elective outpatient colonoscopy (strong recommendation, high quality evidence). In patients with renal failure, PEG is the only recommended bowel preparation. The delay between the last dose of bowel preparation and colonoscopy should be minimized and no longer than 4 hours (strong recommendation, moderate quality evidence). (3) The ESGE advises against the routine use of sodium phosphate for bowel preparation because of safety concerns (strong recommendation, low quality evidence).

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

Efficacy and safety of endoscopic submucosal dissection for colorectal neoplasia: a systematic review.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has been proposed for large colorectal lesions, due to the high risk of recurrence following endoscopic mucosal resection. However, data on the efficacy and safety of colorectal ESD are still controversial. The aim of the current systematic review was to assess the efficacy and safety of colorectal ESD. METHODS: A detailed Medline search of papers published during the period 1999-2010 was performed, using the search terms "Endoscopic submucosal dissection," "Colorectal neoplasia," "Colon," or "Rectum." Published studies that evaluated ESD for colorectal lesions were assessed using well-defined inclusion/exclusion criteria, including histological confirmation and surgery for complications. The process was independently performed by two authors. Forest plots on primary (i.e. histologically verified R0 resection and surgery for ESD complications) and secondary end-points were produced based on random-effect models. Heterogeneity was assessed using the I2 statistic. Risk for within-study bias was also ascertained. RESULTS: A total of 22 studies (20 Asian, two European) provided data on 2841 ESD-treated lesions. The per-lesion summary estimate of R0 resection rate was 88% (95%CI 82%-92%; I2=91%). At meta-regression, carcinoid vs. non-carcinoid series (R0 93% vs. 87%; P=0.04) and Asian vs. European series (R0 88% vs. 65%; P=0.03) appeared to explain the detected heterogeneity. The per-lesion summary estimate of surgery for ESD complications was 1% (95%CI 0%-1%) with a moderate degree of heterogeneity (I2=49%). However, subgrouping of these results according to histological tumor types was not available in the reviewed studies. CONCLUSIONS: ESD appeared to be an extremely effective technique to achieve R0 resection of large colorectal lesions. The very low rate of surgery for complications also shows the potential safety of this approach.

Impact of lifestyle factors on colorectal polyp detection in the screening setting.

BACKGROUND: Awareness of risk factors for colorectal neoplasia could address risk reduction strategies in asymptomatic subjects. METHODS: This is a post hoc analysis of a prospective, cross-sectional study of 1321 asymptomatic adults. All the subjects underwent same-day CT colonography and colonoscopy to determine the prevalence of colorectal neoplasia. The variables examined included body mass index, smoking, alcohol consumption, age, and gender. Univariate and logistic regression analyses were performed for detection of colorectal neoplasia and hyperplastic polyps. Odds ratios with 95% confidence intervals were calculated. RESULTS: Colorectal adenomas and hyperplastic polyps were detected in 378 (28.6%) and 157 (11.9%) participants, respectively. In both univariate and multivariate analysis, increasing age, male gender, and body mass index > or =25 were significantly associated with the detection of colorectal adenomas, with an odds ratio of 1.22 (95% CI,1.09-1.36), 1.28 (95% CI, 1.06-1.45), and 1.34 (95% CI, 1.02-1.77), respectively. A history of smoking was the only identifiable risk factor for hyperplastic polyps (odds ratio, 1.98; 95% CI, 1.41-2.78). CONCLUSIONS: Body mass index > or =25, increasing age, and male gender were all associated with an increased likelihood of colorectal adenomas at screening, whereas smoking was strongly associated with hyperplastic polyps.

Appropriateness of the indication for upper endoscopy: a meta-analysis.

BACKGROUND: Application of appropriate indications for upper endoscopy (EGD) should conserve limited endoscopic resources. To perform a systematic review and meta-analysis to assess the efficacy of American Society for Gastrointestinal Endoscopy and European Panel on the Appropriateness of Gastrointestinal Endoscopy guidelines in selecting patients referred for an upper endoscopy relative to the detection of gastro-oesophageal cancer. METHODS: Studies comparing the appropriateness of EGD indication according to American Society for Gastrointestinal Endoscopy or European Panel on the Appropriateness of Gastrointestinal Endoscopy guidelines and the detection of relevant endoscopic findings and cancer were identified by searching the Medline (1982 to September 2008). Pre-defined outputs of the meta-analysis were sensitivity, specificity, and positive and negative likelihood ratios (LR+, LR-). RESULTS: We included eight cohort studies comprising 13,856 patients; 10,643 EGD indications were categorized as appropriate, and 3010 (22%) as inappropriate. For relevant findings, the adjusted sensitivity, specificity, LR+, and LR- were 85% (95% CI, 84-86%), 28% (95% CI, 27-29%), 1.18 (95% CI, 1.1-1.3) and 0.6 (95% CI, 0.5-0.7), respectively. For cancer detection, the adjusted sensitivity, specificity, LR+, and LR- were 97% (95% CI, 94-98%), 22% (95% CI, 22-23%), 1.2 (95% CI, 1.1-1.4), and 0.2 (95% CI, 0.05-0.9), respectively. CONCLUSIONS: For inappropriate EGD, the very low likelihood of cancer argues against endoscopic referral, whereas the low specificity substantially reduces the predictive value of an appropriate indication for both cancer and relevant endoscopic findings.

Degree of concordance between double-balloon enteroscopy and capsule endoscopy in obscure gastrointestinal bleeding: a multicenter study.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is considered the diagnostic procedure of choice in patients with obscure gastrointestinal bleeding (OGIB). Double-balloon endoscopy (DBE) offers both diagnostic and therapeutic potential, but is invasive, complex, and time-consuming. The aim was to evaluate diagnostic agreement between capsule endoscopy and DBE in patients with OGIB, and secondarily the diagnostic gain of DBE when capsule endoscopy detected only blood or clots in the small-bowel lumen. METHODS: Multicenter prospective study carried out at six institutions in Italy. RESULTS: 193 patients (119 men, mean age 61.6 +/- 16.2) first underwent capsule endoscopy and then DBE. The most frequent positive findings at capsule endoscopy were vascular lesions (74 patients, 38.3 %), blood or clot in the lumen (34, 17.6 %), and tumor mass (20, 10.4 %). The most frequent findings at DBE were vascular lesions (72 patients, 37.3 %), neoplasia (30, 15.5 %) and ulcers/inflammatory lesions (12, 6.2 %). Overall kappa coefficient was 0.46 (95 %CI 0.38 - 0.54), with maximum concordance for vascular (0.72 [95 %CI 0.59 - 0.84]) and inflammatory (0.78 [0.58 - 0.99]) lesions and minimum for polyps (0.46 [0.16 - 0.80]). Blood in the lumen was the only positive finding at capsule endoscopy in 34 cases; of these, 12 had negative DBE findings whereas 10 had vascular lesions, 6 neoplasia, 1 ulcer, and 5 diverticula. CONCLUSION: Capsule endoscopy and DBE have good agreement for vascular and inflammatory lesions but not for polyps or neoplasia. DBE provides valuable adjunctive information, particularly in patients with neoplasia or polyp at capsule endoscopy. DBE clarified the origin of bleeding in two-thirds of patients with capsule endoscopy showing only blood in the lumen.

Acrylate glue injection for acutely bleeding oesophageal varices: A prospective cohort study.

BACKGROUND: Acrylate glue injection is seldom performed in patients with bleeding oesophageal varices. AIM: To assess efficacy and safety of acrylate glue injection in patients with bleeding oesophageal varices, as well as the impact of this technique on subsequent variceal ligation. METHODS: Prospective study on 133 consecutive cirrhotic patients treated by intravariceal injection of undiluted N-butyl-2-cyanoacrylate into the bleeding varix. Outcome measures were initial haemostasis, recurrent bleeding, complications and mortality at 6 weeks. RESULTS: 52 patients were actively bleeding at endoscopy and 81 showed stigmata of recent haemorrhage. Initial haemostasis was achieved in 49/52 active bleeders (94.2% [95% CI 85.1-98.5]). Overall, early recurrent bleeding occurred in 7 patients (5.2% [95% CI 2.3-10.1]). No major procedure-related complication was recorded. At 6 weeks, death occurred in 11 patients, with an overall bleeding-related mortality of 8.2% [95% CI 5.8-15.3]. Mortality was higher in active (15.4% [95% CI 6.9-28.1]) than non-active bleeders (3.7% [95% CI 0.8-10.4], OR 4.7 [95% CI 1.05-28.7], p=0.02). Of those surviving the first bleeding episode, 112 patients subsequently underwent ligation. No technical difficulties were encountered in performing the banding procedure which was successfully completed in all cases. CONCLUSIONS: Emergency injection of acrylate glue is safe and effective for the treatment of acute bleeding oesophageal varices and does not hamper subsequent variceal ligation.

Endoscopic palliation of malignant obstructive jaundice: an evidence-based review.

Endoscopic stent insertion is considered the method of choice for palliative treatment of malignant biliary obstruction. Nonetheless, relevant studies are often underpowered or outdated and do not compare actual surgical outcomes with latest stent technology. Purpose of this review was to assess, with an evidence-based methodology, the role of endoscopic versus surgical palliation of patients with malignant obstructive jaundice with special reference to clinical effectiveness, safety aspects and economic outcomes.

Predictive value of magnification chromoendoscopy for diagnosing invasive neoplasia in nonpolypoid colorectal lesions and stratifying patients for endoscopic resection or surgery.

BACKGROUND AND STUDY AIMS: In nonpolypoid colorectal lesions, the presence of irregular, distorted glands in the colon (a disrupted crypt pattern) on magnification chromoendoscopy (MCE) is strongly associated with submucosal invasive cancer. The aim of the present study was to evaluate the ability of MCE to differentiate between an invasive crypt pattern and a noninvasive crypt pattern, including nonneoplastic lesions, and to assess the ability of this MCE classification to predict invasiveness and allow patients to be selected for endoscopic resection or surgical resection. PATIENTS AND METHODS: In a prospective study including 1560 colonoscopies, 153 flat or depressed colorectal lesions were evaluated with MCE among 534 colorectal lesions; the remainder had a polypoid appearance. The pit pattern was classified as nonneoplastic (type II) or neoplastic (types III - V), and the latter was subdivided into noninvasive (types III or IV) or submucosally invasive (type V). Lesions with a nonneoplastic and noninvasive neoplastic appearance were resected endoscopically if technically feasible, whereas those with a type V pattern were resected surgically. The resection specimens were analyzed histologically in relation to the Vienna classification. RESULTS: Using this management strategy based on the pit pattern, 86 % (n = 70) of the type II lesions were hyperplastic; the remaining 11 had low-grade intraepithelial neoplasia. Type III and IV lesions (n = 58) represented either low-grade or high-grade intraepithelial neoplasia in 95 % of the cases. Three patients had sm1 (n = 2) or sm2/3 invasive cancers. Among the patients with type V lesions (n = 14), 11 had invasive cancers (four sm1 and seven sm2/3). Endoscopic differentiation based on the pit pattern thus had a positive predictive value (PPV) of 86 % and a negative predictive value of 96 % for distinguishing between nonneoplastic and neoplastic lesions. The pit pattern criteria for distinguishing between invasive and noninvasive neoplasia (including nonneoplastic lesions), and hence the choice between endoscopic and surgical resection, had a PPV of 79 % and a NPV of 98 %. Excluding nonneoplastic lesions, the NPV would be 95 %. CONCLUSIONS: The endoscopic pit pattern on MCE has only a moderate predictive value for nonneoplastic lesions, so that leaving these flat hyperplastic lesions in place on the basis of the endoscopic magnification appearance alone cannot be generally recommended. However, MCE has a good predictive value for guiding management toward either endoscopic resection (if technically feasible) or surgical resection.

Meta-analysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases.

BACKGROUND: Prospective trials support the role of capsule enteroscopy as an improvement in diagnosing mucosal lesions in the small bowel. AIM: To determine the diagnostic yield and safety of capsule enteroscopy vs. alternative diagnostic modalities (such as push enteroscopy, small bowel follow-through or enteroclysis) in patients with small bowel diseases. METHODS: A search for prospective studies comparing capsule enteroscopy vs. other diagnostic tests in adults was performed between 1966 and 2005. Selected articles were included in a meta-analysis. Three analyses were run separately, all included studies and studies having occult gastrointestinal bleeding or Crohn's disease as main outcome. RESULTS: Seventeen studies (526 patients) met inclusion criteria. The rate difference (i.e. the absolute pooled difference in the rate of positive findings) between capsule enteroscopy and alternative modalities for small bowel disease was 41% (95% CI 35.6-45.9); 37% (95% CI 29.6-44.1) for occult gastrointestinal bleeding; and 45% (95% CI 30.9-58.0) for Crohn's disease. Failure to visualize the caecum occurred in 13%, significantly more often in occult bleeders (17%) than in patients with Crohn's disease (8%) (P < 0.006). Adverse events were recorded in 29 patients (6%). Capsule retention was more frequent in patients with Crohn's disease (3% vs. 1%, OR 4.37). CONCLUSIONS: Capsule enteroscopy proved significantly superior to push enteroscopy and small bowel radiology in the diagnosis of ileal diseases. Capsule enteroscopy is safe, though prior radiology is still necessary to rule out small bowel strictures in patients with known or suspected Crohn's disease.

Long-term outcome of argon plasma coagulation therapy for bleeding caused by chronic radiation proctopathy.

BACKGROUND: Radiation-induced proctopathy is a serious complication of radiation therapy for pelvic malignancy. AIM: To assess the safety and efficacy of argon plasma coagulation in the treatment of haemorrhagic radiation-induced proctopathy. PATIENTS: Twenty-four patients with rectal bleeding due to radiation-induced proctopathy were prospectively enrolled in the study. METHODS: Indications for treatment were iron deficiency anaemia (n = 16) and persistent bleeding, despite pharmacotherapy (n = 8). Argon flow and power used were 0.8-1.2 l/min and 40 W, respectively. An interval of at least 4 weeks was allowed between treatment sessions. Haemoglobin level, bleeding severity score, number of admissions and transfusion requirements were recorded after endoscopic coagulation and before 12 and 24 months. RESULTS: A median of 2.5 therapeutic sessions per patient were performed (range 1-6). All patients reported clinical improvement and/or cessation of rectal bleeding. The mean value of the bleeding severity score decreased from 2.9 to 0.8 (P < 0.01), while average haemoglobin levels increased by a mean of 1.9 mg/dl at the end of the treatments (P < 0.05). During a minimum follow-up of 24 months (range 24-60), rectal bleeding recurred in two cases and was successfully retreated endoscopically. One patient developed a recto-vaginal fistula. CONCLUSIONS: Argon plasma coagulation appears to be a safe and effective technique for management of rectal bleeding caused by radiation-induced proctopathy.

Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C.

BACKGROUND: A high incidence of thyroid autoantibodies and/or disorders was observed in subjects with hepatitis C virus-related chronic hepatitis during interferon-alpha therapy. AIM: To evaluate whether thyroid autoimmunity and dysfunction, induced by interferon-alpha therapy, could be viewed as predictors for treatment response and as valid prognostic markers of liver disease progression. PATIENTS: A total of 136 subjects (96 males/40 females; median age 48 years; range 23-64) affected by biopsy-proven chronic hepatitis C (33.1% with compensated liver cirrhosis). METHODS: All subjects were treated with interferon-alpha therapy at 6 MU 3 times weekly for 12 months and then followed up for an average period of 60 months (range 12-108). Routine laboratory tests, virological assessment, liver ultrasound, thyroid function tests (serum free-triiodothyronine, free-thyroxine, serum thyrotropin), and autoimmunity were performed for all subjects. RESULTS: Percentage of thyroid autoimmunity and thyroid dysfunction in long-term responders was not significantly different compared to that in non-responders (47.0% and 11.8% vs 35.3% and 5.9%, respectively; non significant). The multivariate model demonstrated that the absence of cirrhosis was the only factor significantly related to successful response to therapy (odds ratio: 14.9; 95% confidence interval: 1.9-115.0 for chronic hepatitis C vs presence of cirrhosis). Moreover, the occurrence of thyroid autoimmunity during interferon therapy was similar both in patients with or without worsening of liver disease (33.3% and 39.8%, respectively; p = not significant). No subject with on-going liver disease developed thyroid dysfunction during treatment, as opposed to the 10/118 (8.4%) with a better course of liver disease; however, this difference was not statistically significant. The multivariate model showed that age was the only covariate significantly associated with unfavourable outcome of liver disease (odds ratio: 18.6; 95% confidence interval: 2.3-151.9, for those over 48 years vs younger patients). CONCLUSIONS: There is no evidence that the immune mechanism involved in the pathogenesis of thyroid autoimmune phenomena is the same as that regulating the therapeutic clearance of HCV or modulating the unfavourable course of HCV-related chronic hepatitis. However, our study confirmed that liver disease seems to progress more slowly in younger subjects.

Endoclips versus heater probe in preventing early recurrent bleeding from peptic ulcer: a prospective and randomized trial.

BACKGROUND: Endoscopic application of hemoclips (HC) was prospectively compared with heat probe (HP) treatment in patients with bleeding ulcers. METHODS: One hundred thirteen patients with major stigmata of ulcer hemorrhage were randomly assigned to receive HP (n = 57) or HC (n = 56). Clinical and endoscopic features were comparable in both groups. Recurrent bleeding was retreated with the modality previously used. Patients in whom treatment or retreatment was unsuccessful underwent emergency surgery. RESULTS: Hemostasis, adequate treatment of visible vessel, 30-day mortality, and emergency surgery rates were similar for both groups. Recurrent bleeding was 21% for HP and 1.8% for HC (p < 0.05). Length of hospital stay and transfusion requirements were significantly lower in the HC group. There was no evidence of clip-induced tissue injury or impaired ulcer healing. Clips dislodged spontaneously in most patients within 8 weeks of treatment. No further hemorrhage occurred on a median follow-up of 11 months (range 1-23). CONCLUSIONS: The hemoclip is safe and effective in the treatment of severe ulcer bleeding and is superior to HP in preventing early recurrent bleeding.

High prevalence of thrombophilic genotypes in patients with acute mesenteric vein thrombosis.

OBJECTIVES: Mesenteric vein thrombosis is a rare but severe abdominal emergency, often requiring intestinal resection. New genetic prothrombotic defects such as factor V Leiden, the prothrombin transition G20210A, and the methylenetetrahydrofolate reductase TT677 genotype have been described in association with venous thrombosis. Our goal was to assess prevalence and clinical significance of genetic thrombophilia in mesenteric vein thrombosis. METHODS: Twelve patients with acute mesenteric vein thrombosis were compared with 431 healthy people from the same geographical area. The factor V Leiden, the prothrombin transition G20210A, and the methylenetetrahydrofolate reductase TT677 genotype were identified by polymerase chain reaction and restriction analysis. RESULTS: A thrombophilic genotype was present in 9 patients (75%): the methylenetetrahydrofolate reductase TT677 genotype was present in 6 (50%), the factor V Leiden in 3 (25%), and the prothrombin transition G20210A in 3 (25%). Combined mutations were present in 4 (33%) patients. CONCLUSIONS: The factor V Leiden, the prothrombin transition G20210A, and the methylenetetrahydrofolate reductase TT677 genotype are important predisposing factors in the pathogenesis of mesenteric vein thrombosis. Their identification bears strong clinical implications for management of patients with mesenteric vein thrombosis.

Endoscopic clipping of perforation following pneumatic dilation of esophagojejunal anastomotic strictures.

Two patients with small perforations occurring after endoscopic balloon dilation of esophagojejunal anastomotic strictures were treated conservatively using metal clips. Closure of the perforation was achieved in both cases, using one and two clips in a single session. There was no procedure-related morbidity and no patient developed complications. Patients were discharged from hospital on days 4 and 5, respectively. In patients with esophagojejunal anastomotic strictures, endoscopic treatment of postdilation perforation by metal clips is safe and effective.