Methylation study of tumor suppressor genes in human aberrant crypt foci, colorectal carcinomas, and normal colon.

BACKGROUND: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. METHODS: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. RESULTS: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear ß-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. CONCLUSIONS: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon.

Acinar cystic transformation of the pancreatic body and tail in an elderly male patient: A case report.

Acinar cystic transformation (ACT) is a rare benign cystic lesion of the pancreas reported in elderly women. ACT can be easily confused with other cystic lesions of the pancreas, such as intraductal papillary neoplasm and serous and mucinous neoplasms, on imaging, especially when detected radiologically in a male patient as the index case. A preoperative histological examination can establish a diagnosis and avoid extensive surgical resection. We hereby report a case of ACT in a 69-year-old male patient that affected the body and tail region of the pancreas.

Postoperative pulmonary complications with high versus standard FiO2 in adult patients undergoing major abdominal surgery: A noninferiority trial.

BACKGROUND: Despite the possible clinical benefit of high intraoperative oxygen therapy on surgical site infection, the effect on postoperative respiratory function is debatable. However, it remains yet to be elucidated whether hyperoxia due to a high fraction of inspired oxygen used in conjunction with lung protective ventilation can lead to increased incidence of postoperative pulmonary complications. METHODS: In this noninferiority randomized trial, an intraoperative high fraction of inspired oxygen of 0.8 (group H) was compared to a standard fraction of inspired oxygen of 0.3 to 0.4 (group S) in adult patients undergoing major elective or emergency surgery. A lung protective ventilation strategy was employed in all patients, including volume control ventilation with a tidal volume of 6 to 8 mL/kg of predicted body weight, respiratory rate of 12 beats per minute, and positive end-expiratory pressure of 5 to 8 cm H2O. Postoperative pulmonary complications were assessed on postoperative days 3 and 5 by the Melbourne group scale. RESULTS: In this trial, n = 226 patients were randomized; among them, 130 patients underwent routine surgery, and 96 patients underwent emergency surgery. The median (interquartile range) of the patients was 48 (35-58) years, and 47.3% were female. Melbourne group scale scores at postoperative day 3 (median [interquartile range] 2 [1-4] in group S vs 2 [1-3] in group H; the difference in median [95% confidence interval] 0 [0, -1]; P = .13) and day 5 (median [interquartile range] 1 (0-3) in group S vs 1 [0-3] in group H; the difference in median [95% confidence interval] 0 [0, 0.5]; P = .34) were statistically similar in both the groups and the upper margin was within the predefined margin of 1. Incidence of surgical site infection (P = .46), postoperative hospital stay (P = .29), and days alive without antibiotic therapy at postoperative day 28 (P = .95) were similar in both groups. CONCLUSION: High intraoperative fiO2 was noninferior to standard fiO2 in postoperative pulmonary complications in adult patients undergoing major surgery.

Management and outcomes of pseudoaneurysms presenting with late hemorrhage following pancreatic surgery: A six-year experience from a tertiary care center.

BACKGROUND/PURPOSE: Late hemorrhage following pancreatic surgery is associated with significant morbidity and mortality. Pseudoaneurysm (PSA) is an important source of late hemorrhage, which is effectively and safely managed by embolization. We aim to retrospectively review the outcomes of embolization for pseudoaneurysms causing late post-pancreatectomy hemorrhage over a period of six-years at our tertiary care center. METHODS: Between 2014 and 2020, 616 pancreatic surgeries were performed and 25 patients had late hemorrhage (occurring > 24 hours post-operatively). The clinical parameters related to late hemorrhage, associated complications, embolization details, treatment success and their short-and long-term outcomes were analyzed. RESULTS: Sixteen of 25 patients had PSA on digital subtraction angiography. Embolization was performed in these patients with technical and clinical success rates of 94.1% and 100%, respectively. Compared to patients without PSA, patients with PSA had significant hemoglobin drop (2.5 g/dL vs. 1.5 g/dL, p = 0.01), higher incidence of sentinel bleed (50% vs. 11.1%, p = 0.05) and lower requirement for surgery for bleeding (0% vs. 44.4%, p = 0.02). Clincally relevant postoperative pancreatic fistula and bile leak were seen in 72% and 52% of patients, respectively. Eight of these embolized patients died due to sepsis. The long-term outcome was good, once the patients were discharged. CONCLUSION: Late hemorrhage after pancreatic surgery was associated with high mortality due to complications such as pancreatic fistula and bile leak. Sentinel bleeding was an important clinical indicator of PSA. Angiographic embolization is safe and effective without any adverse short or long-term outcomes.

Compensated Advanced Chronic Liver Disease in Nonalcoholic Fatty Liver Disease: Two-Step Strategy is Better than Baveno Criteria.

BACKGROUND: Advanced fibrosis and cirrhosis (compensated advanced chronic liver disease [cACLD]) are clinically indistinguishable and increase risk of developing clinically significant portal hypertension. Baveno VII recommends using elastography to rule out and diagnose cACLD with liver stiffness measurement (LSM) cut-offs of 10/15 kPa. METHODS: In a retrospective analysis of 330 nonalcoholic fatty liver disease (NAFLD) patients, performance of the Baveno VII cut-offs for diagnosing cACLD was compared with newly suggested lower cut-offs (8/12 kPa). A model for detecting cACLD among those with LSM between 8 and 12 kPa was developed and compared with recently published models. RESULTS: Seventy (21.2%) of the 330 NAFLD patients had biopsy-proven cACLD. The Baveno VII cut-offs (10/15 kPa) had a lower sensitivity of 72.8% (60.9-82.8%) and a specificity of 93.4% (89.7-96.1%). Sensitivity and specificity of lower cut-offs (8/12 kPa) were 91.4% (82.3-96.8%) and 88.5% (83.9-92.1%), respectively. Modeling based on the presence of diabetes (odds ratio [OR] 3.625[1.161-11.320], p = 0.027) and serum aspartate aminotransferase (AST) levels (OR 1.636[1.098-2.436], p = 0.015) correctly identified 75.7% of patients with LSM between 8 and 12 kPa. Our model performed best with an area under receiver operator curve (AUROC) of 0.725 (95%CI 0.609-0.822), compared to Papatheodoridi (AUROC 0.626, CI 0.506-.736) and Zhou (AUROC 0.523, CI 0.403-0.640) models. A two-step strategy comprising application of lower LSM cut-offs followed by the predictive model correctly identified the presence of cACLD in 83% of the patients as compared to 75% by the Baveno VII cut-offs. CONCLUSION: A two-step strategy employing lower LSM cut-offs and modeling based on diabetes and AST levels outperforms Baveno VII cut-offs for identifying cACLD in NAFLD patients.

Outcome assessment of biliary stricture repair following cholecystectomy in a tertiary care centre.

PURPOSE: Bile duct injuries (BDIs) are the potential grievous complications of cholecystectomy that result in substantial morbidity and mortality. Outcomes of BDI management depend on multiple factors such as the type and extent of injury, timing of repair, and surgical expertise. The present retrospective study was conducted to analyse the risk factors associated with the BDI repair outcomes. METHODS: The data of patients having primary or recurrent bile duct stricture following BDI from 1985 to 2018 were retrospectively evaluated. RESULTS: A total of 268 patients underwent hepaticojejunostomy (HJ). Of the total, 218 patients had primary bile duct stricture, and 50 patients had HJ stricture. The most commonly performed procedure for primary BDI was Roux-en-Y HJ (RYHJ), followed by right hepatectomy, right posterior sectionectomy, and left hepatectomy. All patients with strictured HJ underwent RYHJ, except one who underwent a right hepatectomy. Outcome assessment using the McDonald grading system showed that 62%, 27%, 5%, and 6% of patients with primary bile duct stricture had grade A, grade B, grade C, and grade D complications, respectively, with a mortality rate of 3.21%, whereas 46%, 34%, and 18% patients with strictured HJ had grade A, grade B, and grade C complications, respectively, with a mortality rate of 2%. High-up biliary strictures, early repair, and blood loss > 350 mL are the surrogate markers for failure of repair. CONCLUSION: Management of BDI needs a multidisciplinary approach. The outcomes of both primary biliary stricture and strictured HJ can be improved with management of patients in a tertiary care centre. However, attempts to repair within 2 weeks of injury, Strasberg E4 and E5, and blood loss of > 350 mL may have an adverse effect on the outcome of HJ.

Monotherapy with thiopurines in stricturing Crohn's disease: A real-life experience from low- and middle-income countries.

BACKGROUND: Stricturing Crohn's disease (CD) is difficult to manage medically with limited treatment options, anti-tumor necrosis factor (TNF) therapy being the first-line therapy. Although thiopurines are also recommended first-line treatment option for maintenance of remission in steroid-dependent CD, evidence on their use in stricturing CD is lacking. We evaluated the efficacy of azathioprine (AZA) in patients with stricturing CD. METHODS: In this retrospective cohort study (January 2005 to July 2020), patients with stricturing CD who were managed with AZA as a primary therapy for at least 6 months, and had a follow-up of at least 6 months after AZA initiation were included. Disease characteristics, complications, long-term response, and adverse events were noted. RESULTS: One hundred and fifteen patients were included (mean age 33.8±14 years, 67.8% males, median disease duration 98 months [IQR: 60-158], median follow-up duration 60 months [IQR: 50-96]). 46.1% (n=53) patients had significant anemia at presentation, and 73% (n=84) had isolated small bowel involvement. Median dose of AZA was 100 mg (equivalent to 1.5 mg/kg). Median therapy and follow-up duration (after AZA initiation) was 17 (IQR: 9-42) and 33 months (IQR 18-60), respectively. The cumulative probability of maintaining response without treatment failure at 1, 2, and 5 years was 73.1%, 40.7%, and 18.5%, respectively. Among patients with AZA failure, 15.6% received methotrexate, 13% received anti-TNFs, and 9.5% underwent surgery. Significant anemia (<10 g/dL) at presentation and steroid dependence predicted AZA failure. 31.3% patients experienced adverse events, commonest being leukopenia (n=29, 25.2%). CONCLUSION: Azathioprine demonstrated good short-term and modest long-term response rates in patients with stricturing CD.

Prospective validation of AIIMS index as a predictor of steroid failure in patients with acute severe ulcerative colitis.

BACKGROUND: Optimal outcomes in acute severe ulcerative colitis (ASUC) are related to time-bound management based upon early prediction of response to intravenous (IV) steroids. In an earlier study, we described the All India Institute of Medical Sciences (AIIMS) index (baseline Ulcerative Colitis Endoscopic Index of Severity [UCEIS] ≥ 7 and day 3 fecal calprotectin [FCP] > 1000 µg/g) for predicting failure of IV steroids. The current study is designed to validate this index in a prospective cohort. METHODS: IV steroid-naïve patients with ASUC, satisfying Truelove and Witts' criteria, hospitalized from August 2018 to July 2019 were included. Patients' assessment included baseline sigmoidoscopy, day 1 and 3 FCP, hemogram, biochemistry and day 3 C-reactive protein. All patients received IV steroids, and the primary outcome was steroid failure, defined as the need for colectomy or rescue therapy with cyclosporine (CYC)/infliximab (IFX) during admission. RESULTS: Of the 47 patients, eight were excluded (four received steroids outside, two were directly taken for surgery/infliximab therapy, one had toxic megacolon, and one had infectious colitis), and 39 patients were included (mean age: 36.1 ± 12.6 years, male: 31%). Fifteen patients (38%) failed IV steroid and required rescue therapy (IFX: 9, CYC: 2, Colectomy: 3, IFX followed by colectomy: 1). On univariate analysis, UCEIS ≥ 7 at baseline (p = 0.006), day 1 FCP (p = 0.03), day 3 FCP > 1000 µg/g (p = 0.001), Oxford criteria (p = 0.04) and AIIMS index (p < 0.001) were significantly different between steroid responders and steroid failures. On multivariate analysis, day 3 FCP > 1000 µg/g (odds ratio (odds ratio (OR)= 6.4;(95% CI =2.2-196.1) and baseline UCEIS ≥ 7 (OR) = 10.1;(95% CI = 2.1-80.2) were independent predictors. The AIIMS index predicted steroid failure with a better specificity (100% vs. 83%, p = 0.04) and positive predictive value (100% vs. 64%, p = 0.03) than Oxford criteria. CONCLUSION: AIIMS index has been validated in 39 prospective ASUC patients as an effective early predictor of steroid failure (sensitivity = 53%, specificity = 100%).

Clinicopathological profile and outcomes of anorectal melanoma from a tertiary care center in India.

Background: Anorectal melanoma (AM) is a rare subtype of melanoma. Aim: To study the clinic-pathologic features and outcomes in patients with AM. Materials & methods: Clinical, pathologic findings and outcomes of patients with AM were recorded. Results: Twenty-seven patients with AM were identified with median age of 57 years. Most patients presented in stage III (44.4%). Lymph node involvement was seen in 70.4%. The response to chemotherapy and immunotherapy was 16.6 and 25.0%, respectively. At a median follow up of 11 months, median overall survival was 30 months. Ballantine stage 3 and weight loss at presentation were predictors of poor survival. Conclusion: AM presents at an advanced stage with lymph node and distant metastasis.

Real world analysis on the efficacy and safety of anti-tumor necrosis factor therapy in patients with stricturing Crohn's disease.

Crohn's disease (CD) is often complicated by strictures and associated with increased risk for surgery. Inflammatory strictures respond to medical therapy, and anti-tumor necrosis factor (TNF) therapy is often used after the failure of steroids. However, data on efficacy of anti-TNF therapy in stricturing CD is limited. We retrospectively analysed the records of patients with stricturing CD who were treated with anti-TNF therapy and were prospectively followed from January 2005 to July 2020. Treatment success was defined as continuation of anti-TNF without the requirement for steroids or parenteral nutrition, switch to other anti-TNF, endoscopic dilation, surgery and severe adverse events leading to the withdrawal of anti-TNF. Fifty-nine patients were included [50-infliximab, 9-adalimumab; mean age-30.1 ± 15 years; males-69.5%; median disease duration-124 (range 30-396) months; median follow-up duration-42 (range 8-180) months]. Ileum was the most common site of stricture (69.5%), 20.3% of patients had colonic strictures, and 64.4% had multiple strictures. 55.9% of patients were steroid dependent and 37.3% were steroid refractory. The median duration of anti-TNF therapy was 14 (range 2-96) months, and 54.2% (n = 32) patients received concomitant immunomodulators. 88% improved with induction (11.8% primary non-response), secondary loss of response was seen in 52.2%, and the cumulative probability of treatment success at 1, 2 and 5 years was 69%, 51%, and 28% respectively. Anaemia at presentation predicted poor response. Only 30% of patients retained biologics on long-term (lack of response, cost, adverse events). 16.9% had adverse events, the commonest being reactivation of tuberculosis (5.1%). Anti-TNF therapy is associated with good short-term treatment success with modest long-term response in stricturing CD.

Combination of sarcopenia and high visceral fat predict poor outcomes in patients with Crohn's disease.

BACKGROUND: Sarcopenia and visceral fat independently predict poor outcomes in Crohn's disease (CD). However, combined influence of these parameters on outcomes is unknown, and was investigated in the present study. METHODS: This retrospective study evaluated skeletal muscle index (SMI-cross-sectional area of five skeletal muscles normalized for height), visceral and subcutaneous fat area and their ratio (VF/SC) on single-slice computed tomography (CT) images at L3 vertebrae in CD patients (CT done: January 2012-December 2015, patients followed till December 2019). Sarcopenia was defined as SMI < 36.5 cm2/m2 and 30.2 cm2/m2 for males and females, respectively. Disease severity, behavior, and long-term outcomes (surgery and disease course) were compared with respect to sarcopenia and VF/SC ratio. RESULTS: Forty-four patients [age at onset: 34.4 ± 14.1 years, median disease duration: 48 (24-95) months, follow-up duration: 32 (12-53.5) months, males: 63.6%] were included. Prevalence of sarcopenia was 43%, more in females, but independent of age, disease severity, behavior and location. More patients with sarcopenia underwent surgery (31.6% vs 4%, p = 0.01). VF/SC was significantly higher in patients who underwent surgery (1.76 + 1.31 vs 0.9 + 0.41, p = 0.002), and a cutoff of 0.88 could predict surgery with sensitivity and specificity of 71% and 65% respectively. On survival analysis, probability of remaining free of surgery was lower in patients with sarcopenia (59.6% vs 94.1% p = 0.01) and those with VF/SC > 0.88 (66.1% vs 91.1%, p = 0.1), and still lower in those with both sarcopenia and VF/SC > 0.88 than those with either or none (38% vs 82% vs 100%, p = 0.01). CONCLUSIONS: Combination of sarcopenia and high visceral fat predict worse outcomes in CD than either.

Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A real-life cohort from northern India.

BACKGROUND: The decision to withdraw anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains controversial, especially in the developing world, where its long-term use is restrained by side effects and prohibitive cost. Present study evaluated the relapse rate and its predictors following anti-TNF withdrawal in a cohort of IBD patients from northern India. METHODS: Patients with IBD who received anti-TNF therapy (induction and beyond), and were under follow-up at All India Institute of Medical Sciences, New Delhi, from January 2005 to July 2018 were included. Demographic features, disease characteristics, duration, response to anti-TNF therapy, and relapse rate after its withdrawal were analyzed. RESULTS: Among 4600 patients with IBD under follow-up, 90 (1.9%) received anti-TNF therapy, of whom 11 were excluded (8-complete records unavailable; 3-received only single dose). Of 79 patients (mean age-40.1 ± 14.2 years; 53.2% males; 31 [39.2%] ulcerative colitis, 47 [59.5%] Crohn's disease; median follow-up-24 [12-39] months), 9 (11.4%) were primary non-responders, 19 (24.1%) had secondary loss of response, and 51 (64.5%) maintained clinical response on anti-TNF. Anti-TNF was withdrawn in 45 (57%) patients (major causes: financial burden-16.5%; tubercular reactivation-12.7%), of whom 33 were in clinical remission. Over a median follow-up of 26 (7.5-45) months, 15 patients (45.5%) relapsed. Most of them responded to antibiotics, steroids, or anti-TNF agents; only 3 required surgery. On Kaplan-Meier analysis, long disease duration prior to therapy was a significant predictor of relapse (hazard ratio [HR] = 1.33, p = 0.034). CONCLUSION: Almost 50% patients with IBD in clinical remission relapse within a year of anti-TNF withdrawal. However, most of these patients have a favorable disease course and respond to medical therapy.

Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma.

Background: Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and cathepsin B (CTSB) has been implicated in several tumorigenic processes. However, no such information in GBC was available. Therefore, the present study was planned to investigate the expression and clinical significance of these cathepsins in GBC. Methods: Activities of CTSL and CTSB were assayed in the gallbladder (GB) tissues obtained from GBC patients (n = 43) and control subjects (n = 69). Protein and mRNA levels were quantified using immunohistochemistry and real-time PCR (qPCR), respectively. Finally, serum levels of CTSL and CTSB were estimated by ELISA. Receiver operating characteristic (ROC) curve analysis was used for the assessment of sensitivity, specificity, and diagnostic accuracy of these cysteine cathepsins in GBC. The association of combined CTSL and CTSB activity with overall survival was assessed using Kaplan Meier survival analysis. Results: The expression and activity of both CTSL and CTSB were significantly increased (p < 0.050) in tumors of GBC patients as compared to controls. Enzymatic activity of CTSL+B and CTSB exhibited a strong positive association with tumor stage and lymph node involvement in GBC (p < 0.050). Interestingly, the elevated activity of combined CTSL+B was also associated with increased mortality in these patients. Furthermore, significantly enhanced levels of serum CTSL and CTSB were also observed in GBC (p < 0.050) as compared to controls. ROC analysis revealed high diagnostic significance of serum CTSB and CTSL for distinguishing GBC patients from controls with an area under the curve (AUC) of 82 and 77%, respectively. Conclusion: This study, for the first time, demonstrates the clinical significance of CTSL and CTSB overexpression in GBC. Our findings may help improve the clinical management of this carcinoma.

Gastrointestinal Stromal Tumor of the Jejunum With Active Bleeding Demonstrated on Dual-Energy MDCT Angiography: A Case Report.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and may occasionally present with acute gastrointestinal bleed (GIB). Multidetector computed tomography (MDCT) angiography is extremely useful in demonstrating the tumor as well as the presence of active hemorrhage, thereby guiding subsequent interventional or surgical management. We report a case of a 38-year-old man who presented with acute-onset melena and compensated shock, whose source of bleed remained elusive on endoscopy. MDCT angiography performed on a dual-energy scanner showed a jejunal tumor with active intraluminal contrast extravasation. The tumor was subsequently resected and the patient did well on follow-up. This was one of the few instances when MDCT angiography demonstrated active bleeding in a GIST and the first such case demonstrated on a dual-energy scanner.

Development and validation of a new score for measuring post-operative complications.

PURPOSE: Assigning a numerical value to post-operative morbidity may improve its usefulness as an outcome measure. The recently developed Comprehensive Complication Index (CCI) is a step forward in this process but assigns an inappropriately high score to a combination of complications. METHODS: We developed a new score called the complication severity score (CSS) using a mathematical process and compared it with the CCI using a questionnaire-based survey of 49 experienced gastrointestinal and hepato-pancreatico-biliary surgeons. The CSS was modified based on the results of this survey and was correlated with other patient-centered outcomes in a prospective cohort of consecutive patients undergoing elective surgery. RESULTS: Of the nine sets of scenarios, experienced surgeons' opinion matched with CSS in 6, CSS as well as CCI in 1, and neither CSS nor CCI in 2 scenarios. Of the total 441 responses, 281 matched with CSS while 143 matched with CCI (p = 0.0001, odds ratio: 3.7; 95% CI: 2.8 to 4.8). The modified CSS significantly correlated with the post-operative length of stay (r = 0.76; 95% CI: 0.68 to 0.82; p < 0.001), the length of ICU stay (r = 0.61; 95% CI: 0.50 to 0.70; p < 0.001) and with the difference between pre-operative and post-operative quality of life scores in the physical (r = 0.29; 95% CI: 0.14 to 0.42; p < 0.001) and social (r = 0.29; 95% CI: 0.14 to 0.43; p < 0.001) domains. CONCLUSIONS: The CSS more often matched the opinion of experienced senior surgeons compared to CCI. The modified CSS significantly correlated with other patient-centered outcomes.

Perioperative antiemetic efficacy of dexamethasone versus 5-HT3 receptor antagonists: a meta-analysis and trial sequential analysis of randomized controlled trials.

BACKGROUND: Dexamethasone has many desirable pharmacologic properties for perioperative use. Its antiemetic potential has been a focus of many recent trials. METHODS: Trials comparing dexamethasone to 5-HT3-receptor antagonists (5HT3-RA) for 24 h postoperative vomiting incidences published till August 2017 were searched in the medical database. Comparisons for antiemetic efficiency variables (vomiting incidence, nausea incidence, rescue antiemetic need, and patients with complete response) during early (until 6 h) and late postoperative phase were made. Comparative analgesic requirements were also evaluated. RESULTS: Twenty randomized controlled double-blinded trials were included in the final analysis. Twenty-four-hour vomiting incidence was similar (Fixed-effects, P = 0.86, I2 = 2.94%). Trial sequential analysis (TSA) confirmed non-inferiority of dexamethasone for 24-h vomiting incidence. (α = 5%, ß = 20%, δ = 10%) with "information size" being 1619 (required > 573). Equivalence was also verified from early and delayed nausea rate as well using TSA. Pooled results did not demonstrate superiority/inferiority of 5-HT3-RAs over dexamethasone in all other antiemetic efficacy variables (early and delayed). Heterogeneity was found to be low in all of the comparisons. Linear-positive dose-response curve for dexamethasone 24-h vomiting and nausea incidence was seen (correlation coefficient being 0.21 and 0.28, respectively). Dexamethasone reduced the analgesic need (MH-odds of 0.64 (95% CI being 0.44 to 0.93) P = 0.02, I2 = 0)). Possibility of publication bias could not be ruled out (Egger's test, X-intercept = 1.41, P = 0.04). CONCLUSIONS: Dexamethasone demonstrates equal antiemetic efficacy compared to 5-HT3 receptor antagonists. The agents perform equally well both in early postoperative phase and up to 24 h after surgery. Use of dexamethasone replacing 5-HT3 RAs offers an additional advantage of lowering the opioid requirements during the perioperative period.

Early colectomy in steroid-refractory acute severe ulcerative colitis improves operative outcome.

PURPOSE: Up to a third of patients with acute severe ulcerative colitis (ASUC) fail to respond to intensive steroid therapy and eventually require a salvage colectomy. We have previously reported that the mortality of emergency colectomy can be decreased by offering it within the first week of intensive medical therapy. We implemented this policy and report the results of our experience. METHODS: The clinical records of all patients with ASUC who underwent emergency colectomy after failure of medical therapy between January 2005 and July 2015 were extracted from a prospectively maintained database. The data were analysed with regard to duration of intensive medical therapy, timing of surgery, in-hospital mortality and post-operative complications. RESULTS: Eighty-eight patients underwent emergency surgery for ASUC after failed medical therapy. Of these, 75 (85.2%) were operated within 7 days of initiation of intensive medical therapy [n = 51 (58%) were operated < 5 days]. One patient who was operated on day 8 following steroid therapy died postoperatively. The current post-operative mortality of 1.1% (1/88) was significantly lower than the mortality noted in the previously recorded retrospective case series [8/51 (15.6%); p = 0.001]. In addition, the incidence of overall (9/13 vs. 23/75; p = 0.012) and clinically significant (12/75 vs. 6/13; p = 0.022) complications was significantly higher in patients operated after 7 days as compared to those operated within 7 days. CONCLUSION: The policy of early colectomy, within 7 days, in patients with ASUC who fail to respond to intensive steroid-based therapy improves perioperative outcomes with significantly low in-hospital mortality and morbidity.

Surgical Management of Life Threatening Bleeding after Endoscopic Cystogastrostomy.

Postprocedural bleeding is a rare but life threatening complication of endoscopic cystogastrostomy which may require surgical management in some patients. The presence of adhesions and inflammation due to antecedent acute pancreatitis, difficult location of the bleeding site and breach in the posterior wall of stomach pose significant challenges during the surgical management. Here we have described the surgical approach and technique that we used to manage three patients who required surgery for life threatening bleeding after endoscopic cystogastrostomy.

The International Study Group of Pancreatic Surgery definition of delayed gastric emptying and the effects of various surgical modifications on the occurrence of delayed gastric emptying after pancreatoduodenectomy.

BACKGROUND: A number of definitions have been used for delayed gastric emptying (DGE) after pancreatoduodenectomy and the reported rates varied widely. The International Study Group of Pancreatic Surgery (ISGPS) definition is the current standard but it is not used universally. In this comprehensive review, we aimed to determine the acceptance rate of ISGPS definition of DGE, the incidence of DGE after pancreatoduodenectomy and the effect of various technical modifications on its incidence. DATA SOURCE: We searched PubMed for studies regarding DGE after pancreatoduodenectomy that were published from 1 January 1980 to 1 July 2015 and extracted data on DGE definition, DGE rates and comparison of DGE rates among different technical modifications from all of the relevant articles. RESULTS: Out of 435 search results, 178 were selected for data extraction. The ISGPS definition was used in 80% of the studies published since 2010 and the average rates of DGE and clinically relevant DGE were 27.7% (range: 0-100%; median: 18.7%) and 14.3% (range: 1.8%-58.2%; median: 13.6%), respectively. Pylorus preservation or retrocolic reconstruction were not associated with increased DGE rates. Although pyloric dilatation, Braun's entero-enterostomy and Billroth II reconstruction were associated with significantly lower DGE rates, pyloric ring resection appears to be most promising with favorable results in 7 out of 10 studies. CONCLUSIONS: ISGPS definition of DGE has been used in majority of studies published after 2010. Clinically relevant DGE rates remain high at 14.3% despite a number of proposed surgical modifications. Pyloric ring resection seems to offer the most promising solution to reduce the occurrence of DGE.