Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Systematic review with meta-analysis: endoscopic retrograde cholangiopancreatography-based modalities for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis.

BACKGROUND: The accuracy of current endoscopic modalities for diagnosing cholangiocarcinoma in primary sclerosing cholangitis (PSC) is suboptimal. AIM: To evaluate the comparative effectiveness of endoscopic retrograde cholangiopancreatography (ERCP)-based modalities, independently or in combination, for the diagnosis of cholangiocarcinoma in patients with PSC-induced biliary strictures. METHODS: Searches of PubMed, EMBASE, Web of Science and the Cochrane Library databases were performed through December 2015. Measured outcomes included sensitivity and specificity of all diagnostic modalities independently or in combination. A bivariate model was used to compute the pooled sensitivity and specificity, and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). A logistic regression model was used to impute the incremental performance of combining two diagnostic tests. RESULTS: Twenty-one studies met inclusion criteria: 13 on bile duct brushing for cytology, 7 on fluorescence in situ hybridisation (FISH), 2 on probe-based confocal laser endomicroscopy, and 4 on single-operator cholangioscopy with targeted biopsies. Single-operator cholangioscopy with targeted biopsies was the most accurate diagnostic modality at 96% (95% CI, 94-97%). The pooled sensitivity and specificity of single-operator cholangioscopy for diagnosis of cholangiocarcinoma in patients with PSC was 65% (95% CI, 35-87%) and 97% (95% CI, 87-99%), respectively. The pooled diagnostic odds ratio to detect cholangiocarcinoma was 59 (95% CI, 10-341). CONCLUSIONS: Single-operator cholangioscopy with targeted biopsies appears to be the most accurate ERCP-based modality for diagnosing cholangiocarcinoma in primary sclerosing cholangitis. However, future large, well-designed comparative diagnostic studies are warranted to validate these findings.

The impact of ulcerative colitis on the long-term outcome of patients with primary sclerosing cholangitis.

BACKGROUND: The impact of ulcerative colitis (UC) on the outcome of primary sclerosing cholangitis (PSC) outcome remains unclear. AIM: To investigate whether the presence of UC is associated with a worse clinical of associated PSC. METHODS: A total of 222 patients with PSC (167 with UC and 55 without UC) seen and followed at a single centre from 1985 to 2011 were included. Clinical and demographic variables were obtained and patients were followed until the date of their last clinic visit. RESULTS: The median age at presentation of PSC with associated UC was 38 vs. 47 years without UC (P < 0.001). At presentation, median serum bilirubin (2.1 vs. 4.5, P < 0.001) and the Mayo PSC Risk Score (0.95 vs. 1.69, P < 0.001) were lower in those with UC vs. those without UC. A total of 55 of 167 (32.9%) patients with PSC-UC developed colon neoplasia in contrast to 1 of the 55 (1.8%) patients with PSC. (P < 0.001) On proportional hazards analysis, UC (hazard ratio (HR) = 0.90 [95% confidence interval (CI): 0.60-1.34, P = 0.60] was not associated with death or orthotopic liver transplantation (OLT), when adjusting for gender, Mayo risk score and year of PSC diagnosis; whereas the revised Mayo risk score [HR = 5.08, 95% CI: (2.62-9.86), P < 0.001] was associated with a greater risk of OLT or death. CONCLUSIONS: Primary sclerosing cholangitis often is recognised at an early stage in patients with concurrent ulcerative colitis; ulcerative colitis has no impact on long-term prognosis in terms of liver-related outcomes when adjusted for the severity of liver disease.

The effects of liver transplantation on the clinical course of colitis in ulcerative colitis patients with primary sclerosing cholangitis.

BACKGROUND: The course of ulcerative colitis (UC) following orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) is unclear. AIM: To investigate the clinical course of UC, before and after OLT for PSC. METHODS: From a historical cohort of 86 patients with PSC-UC who underwent OLT, 77 patients who were followed up at our institution both before and after OLT from 1985 to 2011 were included. RESULTS: Ulcerative colitis was diagnosed in 77 (97.5%) patients before OLT. Nineteen of 77 (24.7%) patients underwent colectomy before OLT. In the other 58 patients, the course of UC after OLT when compared to the last 5 years before OLT was quiescent in 48 patients (82.8%) while 9/58 (15.5%) of patients underwent colectomy post-OLT. There was a total of 97 colitis flares over a total of 621 years of follow-up from PSC/UC diagnosis to OLT (0.156 flares per patient year) whereas post-OLT, there were 31 flares over a total of 511 years of post-OLT follow-up (0.061 flares per patient year) (P < 0.001). On univariable analysis, the number of UC flares [Odds ratio (OR) 1.52; 95% Confidence interval (1.02-2.27), P = 0.04] and dysplasia [OR 47.00; 95% CI (6.48-340.66), P < 0.001] increased the risk of colectomy following OLT; the use of corticosteroids [OR 0.07; 95% CI (0.01-0.63), P = 0.008] and 5-aminosalicylate [OR 0.18; 95% CI (0.04-0.83), P = 0.04] was protective. CONCLUSIONS: Ulcerative colitis in the presence of primary sclerosing cholangitis remains quiescent, and may improve in most patients after orthotopic liver transplantation.

Awareness about clostridium difficile infection among internal medicine residents in the United States.

AIM: Clostridium difficile infection (CDI) is the leading infective cause of antibiotic associated diarrhea. The principal objective of this study was to assess the knowledge and awareness of internal medicine (IM) residents regarding the epidemiology, clinical recognition, diagnosis and management of CDI. METHODS: A 20-question survey was distributed to 90 IM residents in all three years of their post graduate training in a university-based program. The survey instrument assessed the resident's knowledge of the current epidemiological trend, clinical recognition and presentation, diagnosis and management of CDI. RESULTS: Forty two out of 90 (48%) residents completed the questionnaire. Only 10/42 (23.8%) of the residents recommended the gold standard investigation for diagnosing CDI. The majority of residents 29/42 (69%) were not aware of the existence of CDI in the outpatient setting and would not test for CDI. Only 50% of the residents were aware of the worse outcome of CDI in inflammatory bowel disease patients and only 12/42 (28.6%) would appropriately risk stratify and treat patients. Almost all of the residents (97.6%) knew about the appropriate time to consult surgery. There was no significant difference in the awareness with respect to the year of training (interns vs. residents), their career choices (primary care vs. fellowship) nor did the knowledge correlate with the United States medical licensing examination (USMLE) scores. CONCLUSION: IM residents had suboptimal knowledge of many aspects of the common problem of CDI. Educational efforts should be directed at IM residents, many of whom plan careers as primary care/hospitalists, who will encounter patients with CDI.

Pathogenesis of cholangitis in obstructive jaundice-revisited.

Obstructive jaundice produces a number of biochemical and physiologic alterations in the biliary tract. Acute cholangitis occurs in an infected, usually obstructed biliary system, at the level of the common bile duct. The most common cause of obstruction is stones. Bacterial reflux from the biliary tract to the systemic circulation is considered to be the primary etiologic factor in bacteremia and the development of sepsis in cholangitis. The main factors in the pathogenesis of acute cholangitis are biliary tract obstruction, elevated intraluminal pressure, and infection of bile. The bile is normally sterile. The route of infection may be ascending, hematogenous or by lymphatics. Bactibilia (presence of bacteria in the biliary tract) increases in the presence of biliary obstruction, particularly partial and in the presence of foreign bodies like stones. Obstruction produces local changes in the host defenses, both in chemotaxis and phagocytosis along with systemic changes. The absence of bile and secretary IgA from the gastrointestinal tract because of biliary obstruction produces changes in the bacterial flora, loss of mucosal integrity, decreased endotoxin inactivation and promotes bacterial overgrowth, portal bacteremia, endotoxemia and increased translocation of endotoxin (LPS) to the liver, resulting in sepsis and also serving to inhibit hepatic macrophage (Kupffer cell) function in these patients. Early intervention in relieving biliary decompression is imperative in restoring normal function of the Kupffer cells in the liver and to prevent functional alterations in the liver because of chronic obstruction and cholestasis and to decrease the postoperative morbidity and mortality.

Recent advancements in the pathogenesis of pain in chronic pancreatitis: the argument continues.

Chronic pancreatitis is a state of chronic inflammation characterized by progressive destruction of the pancreas. Pancreatic pain, a cardinal symptom in chronic pancreatitis patients has always been a subject of great interest and controversy. The precise mechanism of pain and its persistence in chronic pancreatitis patients remain unknown. Several pancreatic, neurogenic and central hypotheses have been proposed for the pathogenesis of pain. In patients with a dilated main pancreatic duct, increased intraductal pressure due to strictures/calculi, presence of interstitial hypertension, pancreatic ischemia and fibrosis and pseudocyst have been proposed to contribute to chronic pain. "Neurogenic" or "neuropathic" theory is based on the fact that patients with chronic pancreatitis have enlarged intrapancreatic nerves with microscopic damage to nerve sheaths (mediated by growth-associated protein 43 (GAP-43), that makes them more susceptible to mediators like brain derived neurotrophic factor, nerve growth factor and TrkA and artemin, the expression of which directly correlates with severity of pain frequency and intensity. The central theory proposes that reorganization of neurons in the insula may explain the chronic pain in these patients. However all these studies have been observational. Further studies are required in the future to characterize these immune response observed in the intrapancreatic neurons in chronic pancreatitis and the neuronal changes in the brain if we are to manage these patients with chronic pain and give them a better quality of life.

Nutritional support in acute pancreatitis: when to start oral feeds.

Nutritional support in acute pancreatitis had always been a subject of great controversy in the past. The results of the recently published meta-analysis however have shown improved outcome with enteral feeding when compared to parenteral nutrition in patients with severe acute pancreatitis. However the time of initiation of oral feeds in acute pancreatitis is still a subject of controversy, given the fact that a large number of patients have a recurrence of abdominal pain when the oral feeds are initiated based on subjective parameters and the incident rise in duration of hospitalization and hospital costs. This brief communication highlights the present literature in the nutrition support in acute pancreatitis patients and discusses the future studies required to study the often neglected topic of nutrition therapy in acute pancreatitis.

Risk factors for gastric cancer in South India.

INTRODUCTION: Stomach cancer is the third most common cancer in South India. A higher incidence has been reported from certain states in northern India, where potential risk factors have been identified. Similar data is available only to a limited extent from southern India. The aim of this case-control study was to evaluate the effects of lifestyle habits and dietary factors on the risk of gastric cancer in South Indians. METHODS: A hospital-based case-control study of matched pairs was conducted in Chennai, India, from 2002 to 2006 in a large tertiary care referral centre in South India. We studied 89 gastric cancer patients and 89 age- and gender-matched healthy controls of the same socioeconomic status. All subjects were interviewed face-to-face by a trained interviewer using a structured questionnaire to collect data about lifestyle habits, such as cigarette smoking, alcohol consumption, tobacco chewing and dietary factors, with special attention to known factors like salted fish, smoked and pickled foods as well as intake of vegetables and fruits. RESULTS: The response rate was 100 percent. There were 64 male and 25 female patients. The male to female ratio was 2.6:1. The demographic characteristics were similar in the case and control populations. Less than ten percent of patients were below the age of 30 years. Approximately 50 percent were between 30 and 60 years of age, and the rest were over 60 years of age. Multivariate logistic regression models indicated that alcohol consumption (odds ratio [OR] 2.3, 95 percent confidence interval [CI] 1.1-4.9, p-value is 0.04) and consumption of pickled food (OR 1.8, 95 percent CI 1.2-3.9, p-value is 0.05) are independent risk factors for the development of gastric cancer. A protective effect of the consumption of pulses (OR 0.4, 95 percent CI 0.2-0.9, p-value is 0.05), showing a 55 percent reduction in risk, was also identified; this could be of use for possible control and prevention of this cancer. Tobacco chewing and cigarette smoking did not emerge as high risk factors for stomach cancer. CONCLUSION: The study showed alcohol and pickled food consumption as independent risk factors for the development of gastric cancer, while consumption of pulses were protective. Cigarette smoking did not predict an increased risk of contracting the disease.

Acquired platelet dysfunction with spontaneous intramuscular hematoma and compartment syndrome in cirrhosis.

Cirrhosis patients are at high risk for bleeding as a result of decreased platelet counts and impaired function, defective production of coagulation factors and abnormalities in clot lysis. The authors report the case of a 58 year-old man with cryptogenic cirrhosis who presented initially with intramuscular hematoma in the thigh which progressed to compartment syndrome. The patient developed disseminated progressive intramuscular hematomas in the muscles of chest, abdomen and finally retroperitoneal hemorrhage secondary to probable accelerated intravascular coagulation and fibrinolysis (AICF) culminating in death. This case highlights many of the common coagulation abnormalities seen in cirrhosis. The authors speculate the sequence of events in our patient at every level of the coagulation cascade which could have lead to this fatal outcome.

Endoscopic management of biliary leaks. The answer for the future.

Bile duct diseases and biliary leaks are not uncommon complications and their management is challenging. Majority of bile leaks occur secondary to trauma, major liver, gallbladder and biliary tract surgeries. Early recognition of bile leaks by imaging combined with a high clinical suspicion is required. Bile leaks can be managed either conservatively, or through percutaneous drainage, or endoscopically or by surgical intervention. The innovations in endoscopic techniques have expanded the horizons for managing patients with bile leaks irrespective of their etiology. Endoscopic interventions through biliary sphincterotomy alone, biliary stenting with or without sphincterotomy, and nasobiliary drainage with or without sphincterotomy, use of self expanding covered metal stents and the recent use of biodegradable stents have been very effective in the management of all kinds of biliary leaks. All endoscopic techniques are based on the principle that eliminating the rise in pressure inside the bile duct by promoting decompression in the form of stent placement/sphincterotomy promotes healing of bile leaks. Further future developments in endoscopic techniques are expected to improve their effectiveness in managing patients with bile leaks.

Appropriateness of indications for diagnostic upper gastrointestinal endoscopy in India.

INTRODUCTION: Guidelines for an upper gastrointestinal endoscopy have been outlined for the Western population, but not yet for India. The study aimed to assess the appropriateness of upper gastrointestinal endoscopy for patients with dyspepsia and to identify the cut-off age for endoscopy from an Indian perspective. METHODS: Patients referred for upper digestive endoscopy to a university clinic in India were prospectively studied between January 2004 and June 2005. Patients who presented with dyspepsia and those with isolated alarm symptoms without dyspepsia who underwent endoscopy were included. The cut-off age for the detection of upper gastrointestinal tract carcinoma in dyspepsia was derived. RESULTS: A total of 3,432 endoscopies were performed during the study period. There were 2,068 men and 1,364 women. The overall mean age was 41.6+/-15 (range 7-85) years. 18.3 percent of 284 patients with malignancy were between 25 and 45 years of age. Using the receiver operator characteristic curve, the cut-off age for malignancy was between 35 and 44 years; specifically, the optimal cut-off age was 38 years for females and 43.5 years for males. CONCLUSION: In the south Indian population with dyspepsia, there were more normal and benign lesions at endoscopy. The optimal cut-off ages for detecting malignancy for both genders were also determined.