Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery.

BACKGROUND & AIMS: Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery. METHODS: We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn's & Colitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P < .05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration. RESULTS: A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI. CONCLUSIONS: Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort.

Labor-associated eosinophilic gastroenteritis.

A 30-year-old woman who was 2 weeks postpartum presented with intermittent dysphagia since delivery. Esophagogastroduodenoscopy (EGD) revealed linear furrowing, trachealization, and a B-type distal esophageal ring with normal appearing stomach and duodenum. Biopsies showed eosinophilic esophagitis. Over 3 weeks, she developed severe midepigastric pain. Laboratory studies revealed an elevated absolute eosinophil count of 990/dL (normal 0-450/dL), and a computed tomography scan showed proximal jejunal thickening. Repeat esophagogastroduodenoscopy showed gastric erythema and edema of the duodenal mucosa. Biopsies revealed greater than 50 eosinophils per high power field in the intraepithelial mucosa with extension into the muscularis and serosa, consistent with eosinophilic gastroenteritis (EG). EG represents an uncommon inflammatory disease marked by gastrointestinal symptoms, eosinophilic infiltration in one or more areas of the gastrointestinal tract, and absence of parasitic or extraintestinal disease. Approximately 300 cases have been reported since 1937. This case contains two unique aspects. First, the clinical and endoscopic progression of gastrointestinal eosinophilic disease from the esophagus to the stomach and small bowel was chronologically documented. This proximal to distal luminal progression has not been previously reported. The possible link to her pregnancy is also notable as only two previous cases of labor-associated EG have been published.

Hyperbaric Oxygen Therapy in Chronic Inflammatory Conditions of the Pouch.

BACKGROUND: Pouchitis can be a chronic complication of ileal pouch-anal anastomosis. We aimed to determine the efficacy and safety of hyperbaric oxygen therapy (HBOT) for chronic antibiotic-refractory pouchitis (CARP) and other inflammatory conditions of the pouch. METHODS: This was a retrospective case series of adults with inflammatory bowel disease (IBD) who underwent ileal pouch-anal anastomosis and then developed CARP and received HBOT between January 2015 and October 2019. A modified Pouchitis Disease Activity Index (mPDAI) score was used to quantify subjective symptoms (0-6) and endoscopic findings (0-6) before and after HBOT. RESULTS: A total of 46 patients were included, with 23 (50.0%) being males with a mean age of 43.6 ± 12.9 years. The median number of HBOT sessions was 30 (range 10-60). There was a significant reduction in the mean mPDAI symptom subscore from 3.19 to 1.91 after HBOT (P < 0.05). The pre- and post-HBOT mean mPDAI endoscopy subscores for the afferent limb were 2.31 ± 1.84 and 0.85 ± 1.28 (P = 0.006); for the pouch body, 2.34 ± 1.37 and 1.29 ± 1.38 (P < 0.001); and for the cuff, 1.93 ± 1.11 and 0.63 ± 1.12 (P < 0.001), respectively. Transient side effects included ear barotrauma in 5 patients (10.9%) and hyperbaric myopic vision changes in 5 patients (10.9%). CONCLUSIONS: Despite minor adverse events, HBOT was well tolerated in patients with CARP and significantly improved symptoms and endoscopic parameters.

Histopathologic variability between the right and left lobes of the liver in morbidly obese patients undergoing Roux-en-Y bypass.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) has been shown to occur in >90% of significantly obese patients. At present, diagnosis of the more severe form of NAFLD, nonalcoholic steatohepatitis (NASH), requires a liver biopsy. Conflicting data exist on the degree of sampling variability seen with percutaneous liver biopsy. Our aim was to assess for significant regional differences in histopathology between the right and left lobes of the liver in morbidly obese patients undergoing bariatric surgery. METHODS: Morbidly obese patients undergoing bariatric surgery at Wilford Hall Medical Center were eligible for study enrollment. Patients with chronic liver disease other than NAFLD were excluded. All patients underwent intraoperative liver biopsy, one from the right lobe and one from the left lobe, with a 14-gauge Tru-cut biopsy needle. Histopathologic features of NAFLD were compared by a hepatopathologist who examined biopsy specimens from the 2 hepatic lobes and was blinded to patient identification and site of origin of biopsy. Agreement between the 2 biopsy specimens was assessed by using the kappa coefficient. RESULTS: Forty-three patients (predominantly female) with body mass index median of 46.2 kg/m2 were enrolled. Agreement for steatosis was 93% (kappa = 0.91), inflammation 74% (kappa = 0.58), ballooning necrosis 84% (kappa = 0.73), fibrosis 98% (kappa = 0.96), and for the NAFLD activity score > or =5 was 93% (kappa = 0.83). CONCLUSIONS: Minimal variability was found for steatosis, NAFLD activity score > or =5, and fibrosis in samples of liver obtained from the right and left lobes of the liver in a group of morbidly obese, predominately female patients undergoing bariatric surgery. Histopathologic findings of necroinflammation appear to have the greatest degree of sampling variability. In contrast with previously published data, excellent agreement was seen for fibrosis in biopsy specimens obtained at surgery from right and left lobes of the liver.

Issues related to colorectal cancer and colorectal cancer screening practices in women.

Studies have shown that colorectal cancer (CRC) incidence is equal between men and women. However, several studies have demonstrated lower adenoma detection rates in women than in men. Many questions arise about differences in adenomas, CRC, and screening practices between men and women: should screening be the same for both sexes, are there differences in risk factors in the formation of colon cancer, should special groups of women be screened differently from the general population, are colonoscopies tolerated differently in women and why, and what determines if a woman will undergo colonoscopy? This article reviews these issues.

Clinical model for distinguishing nonalcoholic steatohepatitis from simple steatosis in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses both simple steatosis and nonalcoholic steatohepatitis (NASH). Differentiation of these two entities requires histopathologic evaluation. The aim of this study was to establish a reliable diagnostic model for differentiating steatosis from steatohepatitis utilizing both clinical characteristics and a panel of biochemical markers of lipid peroxidation and fibrosis. Eighty subjects with biopsy proven NAFLD were enrolled, 39 with simple steatosis and 41 with histopathologic evidence of NASH. Demographic and laboratory data to include serologic testing for 8-epi-PGF(2alpha), transforming growth factor-beta (TGF-beta), adiponectin, and hyaluronic acid (HA) were obtained and compared between the two groups. There were significant differences between the two groups with respect to age (P=0.004), female gender (P=0.024), aspartate aminotransferase (AST) (P=0.028), body mass index (BMI) (P=0.003), fasting insulin (0.018), AST/alanine aminotransferase (ALT) ratio (AAR) (P=0.017), quantitative insulin sensitivity check index (QUICKI) (P=0.002), and HA (P=0.029). A composite index for distinguishing steatosis from NASH was calculated by summing the risk factors of age >or=50 years, female gender, AST>or=45 IU/l, BMI >or=30 mg/kg2, AAR>or=0.80, and HA>or=55 microg/l, and its accuracy was determined by receiver operating characteristic (ROC) analysis to be 0.763 (95% CI: 0.650-0.876). The presence of three or more risk factors had a sensitivity, specificity, PPV, and NPV of 73.7%, 65.7%, 68.2%, and 71.4%, respectively. In addition, HA at a cutoff of 45.3 microg/l was a good predictor of advanced fibrosis. In conclusion, we propose a noninvasive screening model for distinguishing simple steatosis from NASH. Identifying patients at risk for NASH will allow clinicians to more accurately determine who may benefit from liver biopsy.

Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery.

OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is an increasingly prevalent problem. Treatment options are still under investigation. The primary aim of the study was to determine whether weight loss, achieved through Roux-en-Y gastric bypass (RYGBP), improved histopathology in obese patients with biopsy proven NASH. METHODS: One hundred and forty-nine patients were identified from a surgical database as having RYGBP for obesity and concomitant intra-operative liver biopsies from October 2001 to September 2003. Thirty-five patients were found to have evidence of NASH at the time of surgery. Nineteen patients were contacted and underwent repeat percutaneous liver biopsies. Biopsies were evaluated and compared in blinded fashion by an experienced hepatopathologist. Fasting lipid panel, insulin and glucose, hemoglobin A1c (HgbA1c), and liver enzymes were obtained. RESULTS: Significant differences were noted in the following variables pre- and post-bypass surgery: body mass index 46.8-28.8 kg/m2 (p < 0.001); body weight in kilograms 132.1-79.7 (p < 0.001); glucose 102.9-94.1 mg/dL (p = 0.015); Hgb A1c 5.79-5.15% (p = 0.026); high density lipoprotein 45.7-64.4 mg/dL (p < 0.001); low density lipoprotein 112-88.6 mg/dL (p = 0.003); triglycerides 132.1-97 mg/dL (p = 0.013). Significant improvements in steatosis, lobular inflammation, portal, and lobular fibrosis were noted. Histopathologic criteria for NASH were no longer found in 17/19 patients (89%). CONCLUSIONS: Weight loss after gastric bypass surgery in obese patients with NASH results in significant improvement in glucose, HgbA1c. and lipid profiles. Furthermore, RYGBP results in significant improvement in the histological features of NASH with resolution of disease in a majority of these patients.

Extrahepatic manifestations of hepatitis C.

Hepatitis C affects approximately 170 million people worldwide. Extrahepatic manifestations of chronic hepatitis C infection are clinically evident in nearly 40% of patients. Much research has been done over the last decade to better understand their incidence, clinical presentation, mechanism of disease, and the role of antiviral therapy in their treatment. Of the commonly reported manifestations, cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda remain the best understood manifestations. More recently, the association of insulin resistance and diabetes mellitus with chronic hepatitis C has been demonstrated. This paper serves to review the growing body of literature detailing the extrahepatic manifestations of chronic hepatitis C.

Safety of band ligator use in the small bowel and the colon.

BACKGROUND: Endoscopic band ligation for bleeding small-bowel vascular lesions has been reported as safe and efficacious based on small case series. There have been several other published case reports of band ligators used for bleeding lesions, usually Dieulafoy's lesions, in the stomach, the proximal small bowel, and the colon. In addition, this method has been used for postpolypectomy bleeding stalks. There has never been a critical look at the anatomic consequences of banding in the thinner sections of bowel. METHOD: The purpose of this study is to define the anatomic and histologic consequences of applying band ligator devices to the small and the large bowel. Fresh surgical specimens, both large and small bowel, that were excised because of neoplastic lesions were transported to our endoscopy unit where one end of the intact bowel was sutured shut. A standard upper endoscope was passed via the open end, and the bowel was closed tightly with rubber band ties. The bowel then was insufflated, and band ligators were applied to unaffected mucosa by using a standard technique. Photodocumentation from inside and outside the bowel was obtained. Some of the band polyps were cut above the band, and some were cut below the band in the fresh state. Some were fixed in formalin and examined microscopically. Histologic sectioning occurred at the level of the bands. RESULTS: The results were striking in that there were large holes (1 cm) in the fresh ileum specimen. There was gross serosal entrapment manifested by visible puckers on the outer surfaces of the specimens, especially in the small bowel and the right colon. The left colon, anatomically thicker, was less affected. The histologic evaluation revealed inclusion by the band ligator of the muscularis propria and serosa on the small bowel, the muscularis propria in the right colon, and the submucosa in the left colon. CONCLUSIONS: Based on these findings, we conclude that band ligator devices are not safe in the small bowel and the right colon but probably are safe in the thicker left colon.