Norma G. Gutierrez

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.

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.

Volatile organic compounds in bile can diagnose malignant biliary strictures in the setting of pancreatic cancer: a preliminary observation

BACKGROUND Ascertaining the nature of biliary strictures is challenging. The role of volatile organic compounds (VOCs) in bile in determining the cause of biliary strictures is not known. OBJECTIVE To identify potential VOCs in the headspaces (gas above the sample) of bile in patients with malignant biliary strictures from pancreatic cancer. DESIGN Prospective cross-sectional study. SETTING Referral center. PATIENTS Prospective study in which bile was aspirated in 96 patients undergoing ERCP for benign and malignant conditions. MAIN OUTCOME MEASUREMENTS Selected ion flow tube mass spectrometry (VOICE200R SIFT-MS instrument; Syft Technologies Ltd, Christchurch, New Zealand) was used to analyze the headspace and to build a predictive model for pancreatic cancer. RESULTS The headspaces from 96 bile samples were analyzed, including 24 from patients with pancreatic cancer and 72 from patients with benign biliary conditions. The concentrations of 6 compounds (acetaldehyde, acetone, benzene, carbon disulfide, pentane, and trimethylamine [TMA]) were increased in patients with pancreatic cancer compared with controls (P < .05). By using receiver-operating characteristic curve analysis, we developed a model for the diagnosis of pancreatic cancer based on the levels of TMA, acetone, isoprene, dimethyl sulfide, and acetaldehyde. The model [10.94 + 1.8229* log (acetaldehyde) + 0.7600* log (acetone) - 1.1746* log (dimethyl sulfide) + 1.0901* log (isoprene) - 2.1401 * log (trimethylamine) ≥ 10] identified the patients with pancreatic cancer (area under the curve = 0.85), with 83.3% sensitivity and 81.9% specificity. LIMITATIONS Sample size. CONCLUSIONS The measurement of biliary fluid VOCs may help to distinguish malignant from benign biliary strictures. Further studies are warranted to validate these observations. (Clinical Trial Registration Number NCT01565460.).

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.

IgG4 levels in bile for distinguishing IgG4-associated cholangiopathy from other biliary disorders: A single blinded pilot study

Background/Aims Immunoglobulin G4 (IgG4)-associated cholangiopathy (IAC) is an inflammatory disease and may mimic primary sclerosing cholangitis (PSC), cholangiocarcinoma (CCA), or pancreatic cancer on cholangiography. We investigated whether IgG4 levels in bile aspirated during endoscopic retrograde cholangiopancreatography (ERCP) can distinguish IAC from PSC, CCA, and pancreatic cancer. Methods Bile was aspirated directly from the common bile duct during ERCP in patients with IAC prior to steroid therapy. For control purposes, bile was obtained from patients with PSC, CCA, pancreatic cancer, and benign biliary conditions (sphincter of oddi dysfunction/choledocholithiasis). Results Biliary IgG4 levels were measured in 54 patients. The median bile IgG4 levels were markedly elevated in patients with IAC (5.5 mg/dL; interquartile range [IQR], 5.1 to 15.6) as compared to patients with benign biliary conditions (0 mg/dL; IQR, 0 to 0.1; p=0.003). The median biliary IgG4 levels in PSC, CCA, and pancreatic cancer were 1.2 (IQR, 0.2 to 3.8), 0.9 (IQR, 0.2 to 3.4), and 0.2 mg/dL (IQR, 0.1 to 0.8), respectively. A cutoff value of 3.8 mg/dL distinguished IAC from PSC and CCA patients with 100% and 76.9% sensitivity and specificity, respectively. Conclusions The results of this pilot study suggest that measurement of biliary IgG4 levels may have clinical value in distinguishing patients with IAC from biliary disorders that can mimic IAC.

New approach to decrease post-ERCP adverse events in patients with primary sclerosing cholangitis

Background and study aims  Endoscopic retrograde cholangiopancreatography (ERCP) is often performed in patients with primary sclerosing cholangitis (PSC). Our aim was to validate a treatment approach with the objective of decreasing ERCP related adverse events (AEs). Patients and methods  All patients who had undergone ERCP for PSC during the period from 2002 – 2012 were identified (group I). This group had traditional ERCP (no bile aspiration prior to contrast injection with balloon dilation and stent placement for treatment of dominant strictures). To decrease ERCP-related AEs, we changed the ERCP approach in which bile aspiration was performed prior to contrast injection and balloon dilation alone was performed for treatment of dominant strictures. This was tested prospectively in all patients undergoing ERCP for PSC from 2012 – 2014 (group II). Results  The risk of overall AEs and cholangitis was relatively less in group II compared with group I [(2.1 % vs. 10.3 %; P  = .38) and (0 % vs. 4.4 %; P  = .68)]. On bivariate analysis, change in ERCP approach was associated with decreased risk of post-procedure cholangitis (0 % vs. 10.2 %, P =  .03) and overall AE (0 % vs. 18.6 %, P =  .03). There were no AEs in 22/46 patients in group II who had bile aspiration with balloon dilation. On multivariate analysis, only biliary stent placement was associated with increased risk of AEs (OR 4.10 (1.32 – 12.71); P  = .02) and cholangitis (OR 5.43, 1.38 – 21.38; P = .02) respectively. Conclusion  Biliary aspiration and avoidance of stenting approach after dilation of strictures during ERCP in PSC patients appears to be associated with decreased risk of cholangitis and overall AEs. Future prospective randomized controlled trials are needed to validate our observation.