Jaundice, hepatosplenomegaly, and portal lymphadenopathy in a middle-aged female: Is it lymphoma?

Primary biliary cholangitis is a rare liver disease which often progresses to cirrhosis. It can be difficult to diagnose as patients are often asymptomatic initially or merely complain of fatigue or pruritus. We describe the case of a 56-year-old female who presented with a 2-month history of painless jaundice and constitutional symptoms. Computed tomography scan showed massive hepatosplenomegaly with abdominal lymphadenopathy. Liver biopsy and a strongly positive antimitochondrial antibody titer confirmed the diagnosis of primary biliary cholangitis.

NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1ß in Active Ulcerative Colitis.

A contributing factor in the development of ulcerative colitis (UC) and Crohn's disease (CD) is the disruption of innate and adaptive signaling pathways due to aberrant cytokine production. The cytokine, interleukin (IL)-1ß, is highly inflammatory and its production is tightly regulated through transcriptional control and both inflammasome-dependent and inflammasome- independent proteolytic cleavage. In this study, qRT-PCR, immunohistochemistry, immunofluorescence confocal microscopy were used to (1) assess the mRNA expression of NLRP3, IL-1ß, CASP1 and ASC in paired biopsies from UC and CD patient, and (2) the colonic localization and spatial relationship of NLRP3 and IL-1ß in active and quiescent disease. NLRP3 and IL-1ß were found to be upregulated in active UC and CD. During active disease, IL-1ß was localized to the infiltrate of lamina propria immune cells, which contrasts with the near-exclusive epithelial cell layer expression during non-inflammatory conditions. In active disease, NLRP3 was consistently expressed within the neutrophils and other immune cells of the lamina propria and absent from the epithelial cell layer. The disparity in spatial localization of IL-1ß and NLRP3, observed only in active UC, which is characterized by a neutrophil-dominated lamina propria cell population, implies inflammasome-independent processing of IL-1ß. Consistent with other acute inflammatory conditions, these results suggest that blocking both caspase-1 and neutrophil-derived serine proteases may provide an additional therapeutic option for treating active UC.

The impact of wire caliber on ERCP outcomes: a multicenter randomized controlled trial of 0.025-inch and 0.035-inch guidewires.

BACKGROUND AND AIMS: Wire-guided biliary cannulation has been demonstrated to improve cannulation rates and reduce post-ERCP pancreatitis (PEP), but the impact of wire caliber has not been studied. This study compares successful cannulation rates and ERCP adverse events by using a 0.025-inch and 0.035-inch guidewire. METHODS: A randomized, single blinded, prospective, multicenter trial at 9 high-volume tertiary-care referral centers in the Asia-Pacific region was performed. Patients with an intact papilla and conventional anatomy who did not have malignancy in the head of the pancreas or ampulla and were undergoing ERCP were recruited. ERCP was performed by using a standardized cannulation algorithm, and patients were randomized to either a 0.025-inch or 0.035-inch guidewire. The primary outcomes of the study were successful wire-guided cannulation and the incidence of PEP. Overall successful cannulation and ERCP adverse events also were studied. RESULTS: A total of 710 patients were enrolled in the study. The primary wire-guided biliary cannulation rate was similar in 0.025-inch and 0.035-inch wire groups (80.7% vs 80.3%; P = .90). The rate of PEP between the 0.025-inch and the 0.035-inch wire groups did not differ significantly (7.8% vs 9.3%; P = .51). No differences were noted in secondary outcomes. CONCLUSION: Similar rates of successful cannulation and PEP were demonstrated in the use of 0.025-inch and 0.035-inch guidewires. (Clinical trial registration number: NCT01408264.).

Right-sided adenoma detection with retroflexion versus forward-view colonoscopy.

BACKGROUND: Colonoscopy and polypectomy can prevent up to 80% of colon cancer; however, a significant adenoma miss rate still exists, particularly in the right side of the colon. OBJECTIVE: To assess whether retroflexion in the right side of the colon significantly improves the adenoma detection rate (ADR) over forward-view assessment. DESIGN: Multicenter prospective cohort study. SETTING: Three tertiary care public and 2 private hospitals. PATIENTS: A total of 1351 consecutive adult patients undergoing elective colonoscopy. INTERVENTION: Withdrawal from the cecum was performed in the forward view initially and identified polyps removed. Once the hepatic flexure was reached, the cecum was reintubated and the right side of the colon was assessed in the retroflexed view to the hepatic flexure. MAIN OUTCOME MEASUREMENTS: ADR in the retroflexed view when compared with forward-view examination of the right side of the colon. RESULTS: Retroflexion was successful in 95.9% of patients, with looping the predominant (69.6%) reason for failure. Forward-view assessment of the right side of the colon identified 642 polyps, of which 531 were adenomas yielding a polyp and ADR of 28.57% and 24.64%, respectively. Retroflexion identified a further 84 polyps of which 75 were adenomas, improving the polyp and ADR to 30.57% and 26.4%, respectively. LIMITATIONS: Observational study. CONCLUSION: Right-sided retroflexion was successful in most of our cohort with a statistically significant but small increase in ADR. Right-sided retroflexion is safe when performed by experienced endoscopists with no adverse events observed in this cohort. ( CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12613000424707.).

Circumferential location predicts the risk of high-grade dysplasia and early adenocarcinoma in short-segment Barrett's esophagus.

BACKGROUND: Whether early Barrett's neoplasia has a predilection for particular spatial locations in shorter segment disease is currently unknown. Anatomic factors may play a role in lesion location because of differing levels of mucosal acid exposure. OBJECTIVE: To identify high-risk lesion locations, which has important implications for surveillance strategies. DESIGN: We interrogated a prospectively maintained database of patients who underwent endoscopic resection (ER) for Barrett's neoplasia at 2 Australian tertiary centers. Lesions targeted for ER were characterized and their location in the distal esophagus was noted as on a clock face. A Z test of proportions was used to test for deviation from uniformity in the distribution of lesions. SETTING: Two Australian tertiary centers. PATIENTS: Patients who underwent ER for Barrett's neoplasia. MAIN OUTCOME MEASUREMENTS: Lesion location in the distal oesophagus, resected specimen histology. RESULTS: A total of 146 consecutive patients had ER for biopsy-proven high-grade dysplasia or esophageal adenocarcinoma. A total of 75 patients had Barrett's segment length of 5 cm or less and a visible lesion. Five patients had 2 visible lesions giving a total of 80 lesions. ER of 66 lesions (82.5%) led to the identification of advanced pathology: 37 high-grade dysplasia (46%), 24 mucosal adenocarcinoma (30%), 5 submucosal adenocarcinoma (6%). Of a total of 80 lesions, 43 (53.8%) (95% CI, 42.9%-64.7%) were centered within the 2- to 5-o'clock arc, comprising 25% of the circumference. This area also accounted for 36 (54.5%) of the 66 lesions with advanced histology (95% CI, 42.5%-66.5%). All confidence intervals lie wholly above the 25% expected in a uniform circular distribution (P < .05). LIMITATIONS: Observational study in a tertiary center. CONCLUSIONS: In Barrett's maximal segments of 5 cm or less, the 2- to 5-o'clock arc, accounts for approximately 50% of macroscopically visible lesions and associated early neoplasia. This finding has important implications for surveillance strategies.

Giant laterally spreading tumors of the duodenum: endoscopic resection outcomes, limitations, and caveats.

BACKGROUND: Giant hemicircumferential and greater nonampullary duodenal adenomas or laterally spreading tumors (LSTs) may be amenable to safe endoscopic resection, but little data exists on outcomes or risk stratification. DESIGN: We interrogated a prospectively maintained database of all patients who underwent endoscopic resection between January 2008 and November 2010. The resection technique was standardized. Major complications were defined as perforation, bleeding requiring readmission with hemoglobin drop of more than 20 g/L, or other substantial deviations from the usual clinical course. Outcomes were analyzed in 2 groups: giant lesions (>30 mm) and conventional duodenal polyps (<30 mm in diameter). Statistical evaluation was performed by using a χ(2) test. RESULTS: A total of 50 nonampullary duodenal polyps and LSTs were resected from 46 patients (23 men, mean age 59.4 years, range 35-83 years). Nineteen were giant hemicircumferential and greater LSTs (mean size 40.5 mm, range 30-80 mm), and 31 were less than 30 mm in diameter (mean size 14.5 mm, range 5-25 mm). Intraprocedural bleeding occurred more frequently in giant lesions (57.8% vs 19.3%, P = .005) and was treated with a combination of soft coagulation and endoscopic clips with hemostasis achieved in all cases. Major complications, mostly bleeding related, occurred in 5 patients (26.3%) with giant lesions and 1 patient (3.2%) with a smaller lesion (P = .014). There were no deaths. LIMITATION: Retrospective observational study in a tertiary center. CONCLUSIONS: Endoscopic resection of giant nonampullary duodenal LSTs is a successful treatment. However, it is hazardous and associated with significantly higher complication rates, primarily bleeding, when compared with conventional duodenal polypectomy. Safer and more effective hemostatic tools are required in this high-risk location.