Vikesh K. Singh

Flexible transgastric peritoneoscopy: a novel approach to diagnostic and therapeutic interventions in the peritoneal cavity

BACKGROUND A novel endoscopic peroral transgastric approach to the peritoneal cavity was tested in a porcine model in acute and long-term survival experiments. METHODS Transgastric peritoneoscopy was evaluated in 50-kg pigs. After upper endoscopy, the peritoneal cavity was accessed by needle-knife puncture of the gastric wall, followed by extension of the incision either with a pull-type sphincterotome or by balloon dilation. The peritoneal cavity was examined, and a liver biopsy specimen was obtained. The gastric wall incision was closed with clips. OBSERVATIONS Twelve acute and 5 survival experiments were performed. Both techniques of gastric wall incision were without complication. The acute experiments demonstrated the technical feasibility of the approach. In the survival experiments, all pigs recovered and gained weight. CONCLUSIONS The peroral transgastric approach to peritoneal cavity technically is feasible and has the potential to be an alternative to laparoscopy and laparotomy.

The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials.

BACKGROUND An increased intake of magnesium might lower blood pressure (BP), yet evidence from clinical trials is inconsistent, perhaps as a result of small sample size or heterogeneity in study design. METHODS We performed a meta-analysis of randomized trials that tested the effects of magnesium supplementation on BP. Twenty trials meeting the inclusion criteria were identified. Random effects models and meta-regression methods were used to pool study results and to determine the dose-response relationship of magnesium to BP. RESULTS The 20 studies included 14 of hypertensive and 6 of normotensive persons totaling 1220 participants. The doses of magnesium ranged from 10 to 40 mmol/day (median, 15.4 mmol/day). Magnesium supplementation resulted in only a small overall reduction in BP. The pooled net estimates of BP change (95% confidence interval [CI]) were -0.6 (-2.2 to 1.0) mm Hg for systolic BP and -0.8 (-1.9 to 0.4) mm Hg for diastolic BP. However, there was an apparent dose-dependent effect of magnesium, with reductions of 4.3 mm Hg systolic BP (95% CI 6.3 to 2.2; P < .001) and of 2.3 mm Hg diastolic BP (95% CI 4.9 to 0.0; P = .09) for each 10 mmol/day increase in magnesium dose. CONCLUSIONS Our meta-analysis detected dose-dependent BP reductions from magnesium supplementation. However, adequately powered trials with sufficiently high doses of magnesium supplements need to be performed to confirm this relationship.

A prospective evaluation of the bedside index for severity in acute pancreatitis score in assessing mortality and intermediate markers of severity in acute pancreatitis.

OBJECTIVES:Our aim was to prospectively evaluate the ability of the bedside index for severity in acute pancreatitis (BISAP) score to predict mortality as well as intermediate markers of severity in a tertiary center.METHODS:The BISAP score was evaluated among 397 consecutive cases of acute pancreatitis admitted to our institution between June 2005 and December 2007. BISAP scores were calculated on all cases using data within 24 h of presentation. The ability of the BISAP score to predict mortality was evaluated using trend and discrimination analysis. The optimal cutoff score for mortality from the receiver operating curve was used to evaluate the development of organ failure, persistent organ failure, and pancreatic necrosis.RESULTS:Among 397 cases, there were 14 (3.5%) deaths. There was a statistically significant trend for increasing mortality (P < 0.0001) with increasing BISAP score. The area under the receiver operating curve for mortality by BISAP score in the prospective cohort was 0.82 (95% confidence interval: 0.70, 0.95), which was similar to that of the previously published validation cohort. A BISAP score ≥3 was associated with an increased risk of developing organ failure (odds ratio=7.4, 95% confidence interval: 2.8, 19.5), persistent organ failure (odds ratio=12.7, 95% confidence interval: 4.7, 33.9), and pancreatic necrosis (odds ratio=3.8, 95% confidence interval: 1.8, 8.5).CONCLUSIONS:The BISAP score represents a simple way to identify patients at risk of increased mortality and the development of intermediate markers of severity within 24 h of presentation. This risk stratification capability can be utilized to improve clinical care and facilitate enrollment in clinical trials.

A comparative evaluation of radiologic and clinical scoring systems in the early prediction of severity in acute pancreatitis.

OBJECTIVES:The early identification of clinically severe acute pancreatitis (AP) is critical for the triage and treatment of patients. The aim of this study was to compare the accuracy of computed tomography (CT) and clinical scoring systems for predicting the severity of AP on admission.METHODS:Demographic, clinical, and laboratory data of all consecutive patients with a primary diagnosis of AP during a two-and-half-year period was prospectively collected for this study. A retrospective analysis of the abdominal CT data was performed. Seven CT scoring systems (CT severity index (CTSI), modified CT severity index (MCTSI), pancreatic size index (PSI), extrapancreatic score (EP), ‘‘extrapancreatic inflammation on CT’’ score (EPIC), ‘‘mesenteric oedema and peritoneal fluid’’ score (MOP), and Balthazar grade) as well as two clinical scoring systems: Acute Physiology, Age, and Chronic Health Evaluation (APACHE)-II and Bedside Index for Severity in AP (BISAP) were comparatively evaluated with regard to their ability to predict the severity of AP on admission (first 24 h of hospitalization). Clinically severe AP was defined as one or more of the following: mortality, persistent organ failure and/or the presence of local pancreatic complications that require intervention. All CT scans were reviewed in consensus by two radiologists, each blinded to patient outcome. The accuracy of each imaging and clinical scoring system for predicting the severity of AP was assessed using receiver operating curve analysis.RESULTS:Of 346 consecutive episodes of AP, there were 159 (46%) episodes in 150 patients (84 men, 66 women; mean age, 54 years; age range, 21–91 years) who were evaluated with a contrast-enhanced CT scan (n=131 episodes) or an unenhanced CT scan (n=28 episodes) on the first day of admission. Clinically severe AP was diagnosed in 29/159 (18%) episodes; 9 (6%) patients died. Overall, the Balthazar grading system (any CT technique) and CTSI (contrast-enhanced CT only) demonstrated the highest accuracy among the CT scoring systems for predicting severity, but this was not statistically significant. There were no statistically significant differences between the predictive accuracies of CT and clinical scoring systems.CONCLUSIONS:The predictive accuracy of CT scoring systems for severity of AP is similar to clinical scoring systems. Hence, a CT on admission solely for severity assessment in AP is not recommended.

Comparison of Existing Clinical Scoring Systems to Predict Persistent Organ Failure in Patients With Acute Pancreatitis

BACKGROUND & AIMS It is important to identify patients with acute pancreatitis who are at risk for developing persistent organ failure early in the course of disease. Several scoring systems have been developed to predict which patients are most likely to develop persistent organ failure. We head-to-head compared the accuracy of these systems in predicting persistent organ failure, developed rules that combined these scores to optimize predictive accuracy, and validated our findings in an independent cohort. METHODS Clinical data from 2 prospective cohorts were used for training (n = 256) and validation (n = 397). Persistent organ failure was defined as cardiovascular, pulmonary, and/or renal failure that lasted for 48 hours or more. Nine clinical scores were calculated when patients were admitted and 48 hours later. We developed 12 predictive rules that combined these scores, in order of increasing complexity. RESULTS Existing scoring systems showed modest accuracy (areas under the curve at admission of 0.62-0.84 in the training cohort and 0.57-0.74 in the validation cohort). The Glasgow score was the best classifier at admission in both cohorts. Serum levels of creatinine and blood urea nitrogen provided similar levels of discrimination in each set of patients. Our 12 predictive rules increased accuracy to 0.92 in the training cohort and 0.84 in the validation cohort. CONCLUSIONS The existing scoring systems seem to have reached their maximal efficacy in predicting persistent organ failure in acute pancreatitis. Sophisticated combinations of predictive rules are more accurate but cumbersome to use, and therefore of limited clinical use. Our ability to predict the severity of acute pancreatitis cannot be expected to improve unless we develop new approaches.

Hyperplastic polyps of the stomach: Associations with histologic patterns of gastritis and gastric atrophy

Hyperplastic polyps are common gastric lesions characterized by hyperplastic foveolae with variable amounts of inflamed stroma. Their pathogenesis is unknown, but they have been reported to occur in association with various forms of chronic gastritis, particularly autoimmune gastritis and Helicobacter pylori gastritis. Comprehensive histologic evaluation of the background mucosal pathology in patients with hyperplastic polyps has not been previously performed. We studied 160 patients with gastric hyperplastic polyps and characterized endoscopic and histologic features of the polyps (i.e., location, multiplicity, and presence of dysplasia and adenocarcinoma) and the background gastric mucosa (i.e., intestinal metaplasia, dysplasia, carcinoma, and presence and classification of gastritis). Hyperplastic polyps were most common in the antrum (60%) and were multiple in 20% of patients. Focal intestinal metaplasia of the polyp was present in 16% and dysplasia in 4% of patients. Only one patient (0.6%) had adenocarcinoma within the polyp. Evaluation of the surrounding gastric mucosa showed at least focal intestinal metaplasia in 37% of patients, adenoma or low-grade flat epithelial dysplasia in 2%, and synchronous or metachronous adenocarcinoma in 6%. Eighty-five percent of patients had inflammatory mucosal pathology, most commonly active chronic H. pylori gastritis (25%), reactive or chemical gastropathy (21%), and metaplastic atrophic gastritis of the autoimmune (12%) or environmental (8%) type. These results indicate a strong association between various forms of gastritis and the development of hyperplastic polyps and further emphasize the importance of biopsy of the nonpolypoid gastric mucosa during endoscopic examination.

Early systemic inflammatory response syndrome is associated with severe acute pancreatitis.

BACKGROUND & AIMS There have been few clinical studies of systemic inflammatory response syndrome (SIRS) in patients with acute pancreatitis. The aim of this study was to evaluate the role of SIRS in assessing severity of acute pancreatitis. METHODS We prospectively enrolled 252 consecutive patients with acute pancreatitis who were admitted directly to our institution between 2005-2007. The incidence and duration of SIRS (transient <or=48 hours vs persistent >48 hours) during the first 7 days of hospitalization, and the number of SIRS criteria (0-4) on the first day of hospitalization (day 1) were evaluated with individual markers of severity, including persistent organ failure, pancreatic necrosis, need for intensive care unit, and mortality. RESULTS SIRS occurred in 155/252 patients (62%) on day 1. SIRS on day 1 predicted severe disease with high sensitivity (85%-100%). The absence of SIRS on day 1 was associated with a high negative predictive value (98%-100%). Patients with a higher number of systemic inflammatory response (SIR) criteria on day 1 and persistent SIRS had an increased risk for severe disease (P < .01). CONCLUSIONS The majority of patients hospitalized with acute pancreatitis have SIRS on day 1. The severity of acute pancreatitis is greater among patients with SIRS on day 1 and, in particular, among those with 3 or 4 SIRS criteria, compared with those without SIRS on day 1.

A comparative evaluation of single-balloon enteroscopy and spiral enteroscopy for patients with mid-gut disorders.

BACKGROUND Single-balloon enteroscopy (SBE) and spiral enteroscopy (SE) are recently described device-assisted techniques in endoluminal evaluation of the small bowel. No studies comparing SBE and SE in patients with suspected small-bowel disorders have previously been reported. OBJECTIVE The aims of this study were to compare SBE and SE in terms of diagnostic yield, procedure time, depth of maximal insertion, and complications. DESIGN Retrospective cohort study. SETTING Tertiary-care referral center. PATIENTS A retrospective analysis was performed on all patients at our institution undergoing anterograde SBE or SE between 2007 and 2009. Patients with altered anatomy or prior small-bowel surgery were excluded. INTERVENTION Deep enteroscopy. MAIN OUTCOME MEASUREMENT Diagnostic yield. RESULTS During the study period, 92 patients underwent 105 procedures (52 SBE, 53 SE). The most common indication for small-bowel endoscopy was obscure GI bleeding (n = 42). The diagnostic yield was not statistically different between SBE and SE (59.6% and 43.4%, respectively, P = .12). The overall diagnostic yield in patients with obscure GI bleeding was 67%. There was no significant difference between mean SBE and SE procedure times (53 minutes [range 15-99 minutes] vs 47 minutes [range 20-125 minutes], respectively; P = .2). The mean depth of maximal insertion beyond the ligament of Treitz for SE was significantly higher than that for SBE (301 cm [range 175-400 cm] vs 222 cm [range 110-400 cm], respectively; P < .001). Perforation occurred in one SBE procedure. LIMITATIONS Retrospective design and nonstandardized gas insufflation. CONCLUSION This is the first report comparing SE and SBE. Although SE yielded greater depth of maximal insertion than SBE, both techniques had similar diagnostic yields and procedure times. In addition, both techniques were safe and were particularly useful in patients with obscure GI bleeding.

A Systematic Review of Solid-Pseudopapillary Neoplasms: Are these rare lesions?

Objective The aim of the study was to determine if there had been any change in the number of solid-pseudopapillary neoplasm (SPN) cases detected and their evaluation or management over time. Methods A systematic review of SPN was performed of all articles published in English in PubMed and Scopus. Results A total of 2744 patients with SPN were identified in 484 studies published between 1961 and 2012; 87.8% of the cases were reported between 2000 and 2012. A total of 2408 (87.8%) were females, and the mean age was 28.5 (SD, 13.7) years. The most common symptom was abdominal pain in 63.6% of the cases and incidentally detected in 38.1% of the cases. There were 2285 patients who underwent pancreatic resection. The mean tumor size was 8.6 (SD, 4.3) cm. Follow-up was reported for 1952 (90.5%) patients, with a mean follow-up of 36.1 (SD, 32.8) months. Disease-free survival was documented in 1866 (95.6%) patients with recurrence in 86 (4.4%) patients; the median time to recurrence was 50.5 months. Conclusions The number of SPNs reported in the literature has seen a 7-fold increase in the number of cases reported since 2000 compared with before. Solid-pseudopapillary neoplasms continue to be primarily found in young women and present with nonspecific symptoms. Surgery remains the mainstay of treatment with an excellent long-term prognosis.

Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells

Objectives Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of cancer. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of oesophageal adenocarcinoma (EAC) and its progression. Design lncRNAs that are abnormally upregulated in EACs were identified by RNA-sequencing analysis, followed by quantitative RT-PCR (qRTPCR) validation using tissues from 25 EAC patients. Cell biological assays in combination with small interfering RNA-mediated knockdown were performed in order to probe the functional relevance of these lncRNAs. Results We discovered that a lncRNA, HNF1A-AS1, is markedly upregulated in human primary EACs relative to their corresponding normal oesophageal tissues (mean fold change 10.6, p<0.01). We further discovered that HNF1A-AS1 knockdown significantly inhibited cell proliferation and anchorage-independent growth, suppressed S-phase entry, and inhibited cell migration and invasion in multiple in vitro EAC models (p<0.05). A gene ontological analysis revealed that HNF1A-AS1 knockdown preferentially affected genes that are linked to assembly of chromatin and the nucleosome, a mechanism essential to cell cycle progression. The well known cancer-related lncRNA, H19, was the gene most markedly inhibited by HNF1A-AS1 knockdown. Consistent to this finding, there was a significant positive correlation between HNF1A-AS1 and H19 expression in primary EACs (p<0.01). Conclusions We have discovered abnormal upregulation of a lncRNA, HNF1A-AS1, in human EAC. Our findings suggest that dysregulation of HNF1A-AS1 participates in oesophageal tumorigenesis, and that this participation may be mediated, at least in part, by modulation of chromatin and nucleosome assembly as well as by H19 induction.