Ramprasad Jegadeesan

Progression of low-grade dysplasia to advanced neoplasia based on the location and morphology of dysplasia in ulcerative colitis patients with extensive colitis under colonoscopic surveillance

BACKGROUND The management of low-grade dysplasia (LGD) in ulcerative colitis (UC) patients remains unclear. AIM The aim of our study was to study the risk of progression of LGD to advanced neoplasia (AN), defined as high-grade dysplasia (HGD) or colorectal cancer (CRC) for UC patients undergoing surveillance based on location and morphology of LGD. METHODS 997 UC patients underwent 3152 surveillance colonoscopies from 1998 to 2011. Kaplan-Meier estimates and incidence rates calculated. RESULTS Of the 102 patients with LGD (65 raised and 37 flat), 5 (4.9%) patients progressed to AN (3 HGD and 2 CRC) after a median follow-up of 36 months (interquartile range 18-71 months). Initial location of dysplasia was in the proximal colon in 47, distal colon in 55 patients. Four of the 5 (80%) patients with AN had initial dysplasia in the distal colon. Distal colonic LGD had an incidence rate for AN of 2.1 cases per 100 person years at risk, while proximal LGD had an incidence of 0.5 cases per 100 person years. Flat LGD in the distal colon was more likely to progress to AN [hazard ratio=3.6; 95% confidence interval, CI (1.3-10.6)]. Twenty of the 102 patients (15 flat and 5 raised) underwent colectomy: 2 (10%) had evidence of AN in colectomy (1 HGD and 1 CRC), 9 had LGD and remaining 9 did not have dysplasia. CONCLUSIONS The frequency of progression of LGD to AN is low. Flat dysplasia located in the distal colon is associated with a greater risk of progression to AN.

Lipidomic profiling of bile in distinguishing benign from malignant biliary strictures: a single-blinded pilot study.

OBJECTIVES:Ascertaining the benign or malignant nature of biliary strictures may be challenging. Oxidized phospholipids (oxPLs) play an important role in tumor apoptosis and may be elevated in malignant biliary strictures. The objective of the study was to investigate whether oxPLs are enriched in the bile of malignant biliary strictures.METHODS:In this prospective single-blinded study, bile was obtained from 46 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and management of biliary strictures, including 17 with pancreatic cancer, 6 with primary sclerosing cholangitis (PSC), 8 with cholangiocarcinoma (CCA), and 15 with benign biliary conditions (sphincter of Oddi dysfunction (SOD) or choledocholithiasis or chronic pancreatitis). Bile samples were stored under conditions to minimize artificial oxidation. Levels of 10 different oxPLs were measured blindly by one investigator using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).RESULTS:Of the 10 different phospholipids measured, the levels of two phosphatidylcholines (PCs; i.e., ON-PC and S-PC) were elevated in CCA as compared with other biliary strictures. Among these, ON-PC was most useful and a cutoff value of 6,020.1 nm distinguished CCA from other biliary strictures with a sensitivity and specificity of 85.7% and 80.3%, respectively (area under curve (AUC) 0.86). A combination of ON-PC and S-PC at a cutoff value of 6,032.2 nm distinguished CCA from other biliary strictures with a sensitivity and specificity of (100% and 83.3%, respectively (AUC 0.91).CONCLUSIONS:The measurement of specific oxPL products may help to distinguish CCA from other biliary strictures. Measurement of these products in bile may enhance the endoscopic diagnosis of indeterminate biliary strictures.

Natural history of low grade dysplasia in patients with primary sclerosing cholangitis and ulcerative colitis

BACKGROUND AND AIM Patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) are at increased risk of colon cancer. The aim of this study was to determine the natural history of LGD and its progression to high grade dysplasia (HGD)/colorectal cancer (CRC) in PSC-UC patients. METHODS Ten PSC-UC patients with LGD who underwent surveillance colonoscopy from 1996 to 2011 were evaluated. Raised dysplasia was defined as a discrete raised lesion located in an area involved by either quiescent or active colitis that was endoscopically resected, while flat dysplasia was defined as the absence of documentation of a raised lesion. RESULTS Of the 10 patients with LGD, 3 (30%) progressed to raised HGD over a mean follow-up of 13±11 months. Three of 10 patients had initial raised LGD while 7 had flat LGD. The location of HGD was in the proximal colon in all 3 patients. However all 3 patients who progressed to HGD had initial dysplasia located in the distal colon and had flat morphology. The incidence rate for detection of HGD/CRC was 9.4 cases per 100 person years at risk. Patients with LGD with flat morphology had an incidence rate of 17.8 cases per 100 person years at risk. HGD occurred more frequently within the first year of initial detection of LGD (23.5 per 100 patient years of follow-up). CONCLUSIONS One-third of patients with LGD progressed to HGD/CRC in PSC-UC. Most patients progress within the first year of diagnosis of LGD supporting early colectomy in PSC-UC patients with LGD.

Delay in performing ERCP and adverse events increase the 30-day readmission risk in patients with acute cholangitis

BACKGROUND Readmission to the hospital within 30 days of discharge (30-day readmission rate) is used as a quality measure. OBJECTIVE To investigate the incidence and factors that contribute to readmissions in patients with acute cholangitis. DESIGN Retrospective cohort study. SETTING Tertiary-care referral center. PATIENTS Retrospective analysis of consecutive patients admitted to our center for acute cholangitis and ERCP. INTERVENTION ERCP MAIN OUTCOME MEASUREMENTS Incidence and variables associated with 30-day readmission and 1-year mortality. RESULTS ERCP was successful in 98.8% of patients during the index admission. The 30-day readmission rate was 22.0%. Recurrence of cholangitis was the most common etiology for readmissions (37.8%). Readmission within 30 days was independently associated with failed ERCP or ERCP delayed for >48 hours (odds ratio [OR] 2.47; 95% confidence interval [CI], 1.01-6.07), development of any after-ERCP adverse event (OR 11.0; 95% CI, 3.06-39.30), and the etiology of cholangitis (etiologies not related to stones) (OR 3.3; 95% CI, 1.17-9.18). Every 1-point increase in the Charlson Comorbidity Index score (OR, 1.33; 95% CI, 1.05-1.69) was associated significantly with 1-year mortality. In unadjusted analysis, 30-day readmission after ERCP was associated significantly with 1-year mortality (OR, 2.86; 95% CI, 1.16-7.07). This association, however, was not present after adjustment for other covariates. LIMITATIONS Retrospective study. CONCLUSION Delays in performing ERCP during the index admission, development of after-ERCP adverse events, and etiology of cholangitis not related to stones increased the risk of 30-day readmissions.

ERCP-related adverse events in patients with primary sclerosing cholangitis.

BACKGROUND ERCP is frequently used in patients with primary sclerosing cholangitis (PSC) for cancer surveillance and treatment of dominant strictures. OBJECTIVE To evaluate the prevalence and risk factors for ERCP-related adverse events in patients with PSC. DESIGN Retrospective analysis of ERCPs performed from 1998 to 2012. SETTING Referral center. PATIENTS A total of 294 consecutive patients with PSC who underwent a total of 657 ERCPs. INTERVENTIONS ERCP. MAIN OUTCOME MEASUREMENTS ERCP-related adverse events and predictive factors were determined by univariate and multivariate analyses. RESULTS ERCP use in patients with PSC showed a significant increase during the second half of the study period (2006-2012) compared with the first half (1998-2005) (437 vs 220 procedures; P = .04). Primary cannulation was successful in 634 procedures (96.6%) or in 271 of 294 patients (92.2%). Access to the bile duct was achieved with a needle-knife in 19 procedures (2.9%), whereas ERCP was unsuccessful in 4 of 657 procedures (0.6%), and successful percutaneous drainage was performed. Post-ERCP pancreatitis (PEP) was diagnosed in 8 (1.2%), cholangitis in 16 (2.4%), and bleeding in 4 (0.7%) procedures. Overall, risk of any adverse event was 28 of 657 (4.3%) procedures. On multivariate analysis, performing biliary sphincterotomy (odds ratio [OR] 5.04; 95% confidence interval [CI], 2.01-12.60; P = .001) and passage of a guidewire into the pancreatic duct (OR 4.54; 95% CI, 1.44-14.30; P = .010) were independently associated with an increased risk of any adverse event. LIMITATIONS Retrospective study. CONCLUSION Cholangitis appears to be the most common adverse event despite intraprocedural antibiotic use. There was a low risk of adverse events in patients with PSC undergoing ERCP.

Factors predicting adverse short-term outcomes in patients with acute cholangitis undergoing ERCP: A single center experience

AIM To identify potential factors that can predict adverse short-term outcomes in patients with acute cholangitis undergoing endoscopic retrograde cholangiopancreatography (ERCP). METHODS Retrospective analysis of consecutive patients admitted to our center for acute cholangitis and underwent ERCP from 2001 to 2012. Involvement of two or more organ systems was termed as organ failure (OF). Cardiovascular failure was defined based on a systolic blood pressure of < 90 mmHg despite fluid replacement and/or requiring vasopressor treatment; respiratory failure if the Pa02/Fi02 ratio was < 300 mmHg and/or required mechanical ventilation; coagulopathy if the platelet count was < 80; and renal insufficiency if serum creatinine was > 1.9 mg/dL. Variables associated with short term adverse clinical outcomes defined as persistent OF and/or 30-d mortality was determined. RESULTS A total of 172 patients (median age 62 years, 56.4% female) were included. The median door to ERCP time was 17 h. Bile duct stones were the most common etiology (n = 67, 39.2%). In multivariate analysis, factors that were independently associated with persistent OF and/or 30-d mortality included American Society of Anesthesiology (ASA) physical classification score > 3 (OR = 7.70; 95%CI: 2.73-24.40), presence of systemic inflammatory response syndrome (OR = 3.67; 95%CI: 1.34-10.3) and door to ERCP time greater than 72 h (OR = 3.36; 95%CI: 1.12-10.20). Door to ERCP time greater than 72 h was also associated with 70% increase in the mean length of stay (P < 0.001). Every one point increase in the ASA physical classification and every 1 mg/dL increase in the pre-ERCP bilirubin level was associated with a 34% and 2% increase in the mean length of hospital stay, respectively. Transfer status did not impact clinical outcomes. CONCLUSION Higher ASA physical classification and delays in ERCP are associated with adverse clinical outcomes and prolonged length of hospital stay in patients with acute cholangitis undergoing ERCP.

Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.

Predictors for detection of cancer in patients with indeterminate biliary stricture and atypical cells on endoscopic retrograde brush cytology

The management of atypical cells on endoscopic retrograde brush cytology (ERBC) in patients with indeterminate biliary stricture is unclear. This study aimed to investigate the detection of cancer (pancreatic and biliary carcinoma) in patients with atypical cells on ERBC and the factors predicting it.

Efficacy of peroral endoscopic myotomy vs other achalasia treatments in improving esophageal function

AIM To assess and compare the esophageal function after peroral endoscopic myotomy (POEM) vs other conventional treatments in achalasia. METHODS Chart review of all achalasia patients who underwent POEM, laparoscopic Heller myotomy (LHM) or pneumatic dilation (PD) at our institution between January 2012 and March 2015 was performed. Patient demographics, type of achalasia, prior treatments, pre- and post-treatment timed barium swallow (TBE) and high-resolution esophageal manometry (HREM) findings were compared between the three treatment groups. Patients who had both pre- and 2 mo post-treatment TBE or HREM were included in the final analysis. TBE parameters compared were barium column height, width and volume of barium remaining at 1 and 5 min. HREM parameters compared were basal lower esophageal sphincter (LES) pressures and LES-integrated relaxation pressures (IRP). Data are presented as mean ± SD, median [25(th), 75(th) percentiles] or frequency (percent). Analysis of variance, Kruskal-Wallis test, Pearsons χ(2) test and Fishers Exact tests were used for analysis. RESULTS A total of 200 achalasia patients were included of which 36 underwent POEM, 22 underwent PD and 142 underwent LHM. POEM patients were older (55.4 ± 16.8 years vs 46.5 ± 15.7 years, P = 0.013) and had higher BMI than LHM (29.1 ± 5.9 kg/m(2) vs 26 ± 5.1 kg/m(2), P = 0.012). More number of patients in POEM and PD groups had undergone prior treatments compared to LHM group (72.2% vs 68.2% vs 44.3% respectively, P = 0.003). At 2 mo post-treatment, all TBE parameters including barium column height, width and volume remaining at 1 and 5 min improved significantly in all three treatment groups (P = 0.01 to P < 0.001) except the column height at 1 min in PD group (P = 0.11) . At 2 mo post-treatment, there was significant improvement in basal LES pressure and LES-IRP in both LHM (40.5 mmHg vs 14.5 mmHg and 24 mmHg vs 7.1 mmHg respectively, P < 0.001) and POEM groups (38.7 mmHg vs 11.4 mmHg and 23.6 mmHg vs 6.6 mmHg respectively, P < 0.001). However, when the efficacy of three treatments were compared to each other in terms of improvement in TBE or HREM parameters at 2 mo, there was no significant difference (P > 0.05). CONCLUSION POEM, PD and LHM were all effective in improving esophageal function in achalasia at short-term. There was no difference in efficacy between the three treatments.

Comparison of outcomes for patients with primary sclerosing cholangitis associated with ulcerative colitis and Crohn’s disease

Background: The comparative outcomes of ulcerative colitis (UC) and Crohn’s disease (CD) in patients with primary sclerosing cholangitis (PSC) are unclear; the aim of our study was to make an objective comparison. Methods: A total of 273 patients with PSC and inflammatory bowel disease (223 with UC and 50 with CD) were included. Clinical and demographic variables were obtained. Results: The PSC risk score was similar for both groups. The median follow-up period in patients with PSC-UC was 12 years (range 0–38) and that for PSC-CD was 14 years (range 1–36). The median number of disease flares per year was higher in PSC-UC patients than in the PSC-CD group [1vs.0 (ranges 0–20 and 0–9, respectively); P < 0.001]. More patients with UC developed colon neoplasia than CD (35.9% vs.18%; P = 0.009). On proportional hazards analysis for the risk of colectomy, UC patients had a 12% higher risk for colectomy [hazard ratio (HR) = 0.88; 95% confidence interval (CI) 0.51–1.51; P = 0.64]. Liver transplantation for PSC was associated with decreased risk (HR = 0.57; 95% CI 0.37–0.89; P = 0.013), while colon neoplasia increased the risk (HR = 3.83; 95% CI 2.63–5.58; P < 0.001) for colectomy. On proportional hazards analysis for the risk of colon neoplasia, UC patients had 56% higher risk of developing colon neoplasia than CD (HR = 0.44; 95% CI 0.16–1.25; P = 0.12). Conclusions: PSC patients with CD appear to be associated with a lower risk of colon neoplasia and colectomy than PSC patients with UC.