Microscopic colitis: clinical characteristics, treatment and outcomes in an Irish population.

BACKGROUND AND AIMS: Many aspects of microscopic colitis remain poorly understood. Our aim was to report a single centre experience with this condition. METHODS: Two hundred and twenty-two patients (52 male, 170 female; median age 64 years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes were reviewed, and data on age, gender, clinical features, history of autoimmune diseases, medication use, cigarette smoking, histology and outcome were collected. RESULTS: There were 99 cases of lymphocytic and 123 of collagenous colitis. Diarrhoea was almost invariably present (98 %) while abdominal pain (24 %), weight loss (10 %), faecal incontinence (8 %) and blood PR (5 %) were also described. Twenty-eight percent had concomitant autoimmune diseases, most commonly coeliac disease. Patients were taking a variety of medications at diagnosis thought to be associated with microscopic colitis including NSAIDs (22 %), aspirin (19 %), statins (15 %), proton pump inhibitors (19 %) and SSRIs (10 %) at diagnosis. Prior to the widespread use of budesonide in our institution, 33 % of patients required two or more medications during therapy compared to 15 % following the introduction of budesonide (p = 0.001). Thirty-eight percent of patients achieved spontaneous remission with either no treatment or simple anti-diarrhoeals. Using a multivariate model, the only factor associated with spontaneous remission was male gender (RR 1.9; 95 % CI 1.0-3.6; p = 0.04). Two patients had refractory microscopic colitis; one required a colectomy while a more recent case has responded to anti-TNFα therapy. CONCLUSION: Microscopic colitis is predominantly a benign and self-limiting disorder. The introduction of budesonide has revolutionised treatment of this lesser studied inflammatory bowel disease.

Response to endoscopic therapy for biliary anastomotic strictures in deceased versus living donor liver transplantation.

BACKGROUND: Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT). LDLT is thought to be associated with higher rates of biliary complications, but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups. This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT. METHODS: This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) after liver transplantation. The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT. The response of anastomotic stricture to endoscopic therapy was also analyzed. RESULTS: A total of 362 patients underwent liver transplantation between 2003 and 2011, with 125 requiring ERCP to manage biliary complications. Thirty-three (9.9%) cases of DDLT and 8 (27.6%) of LDLT (P=0.01) were found to have anastomotic stricture. When comparing DDLT and LDLT, there was no difference in the mean time to the development of anastomotic strictures (98+/-17 vs 172+/-65 days, P=0.11), likelihood of response to ERCP [22 (66.7%) vs 6 (75.0%), P=0.69], mean time to the resolution of anastomotic strictures (268+/-77 vs 125+/-37 days, P=0.34), and the number of ERCPs required to achieve resolution (3.9+/-0.4 vs 4.7+/-0.9, P=0.38). CONCLUSIONS: Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation. Anastomotic strictures occur more frequently in LDLT compared with DDLT, with equivalent endoscopic treatment response and outcomes for both groups.

Endoscopic management of gastric variceal bleeding with cyanoacrylate glue injection: safety and efficacy in a Canadian population.

BACKGROUND:  Gastric variceal bleeding (GVB) is a major cause of morbidity and mortality among patients with portal hypertension. Endoscopic band ligation and standard sclerotherapy have been used but have significant limitations. Decompression through transjugular intrahepatic portosystemic shunt insertion has been shown to be effective. Gastric variceal injection therapy with a commercially available cyanoacrylate glue is less invasive than transjugular intrahepatic portosystemic shunt insertion and has recently been shown to be effective for acute hemostasis.  OBJECTIVE: To assess the immediate and long-term outcomes of cyanoacrylate glue injection therapy for GVB. METHODS: A retrospective chart review was conducted to identify patients treated with cyanoacrylate injection for GVB at two tertiary care hospitals over a period of six years. The outcomes assessed included complications, acute hemostasis, rebleeding rate and all-cause mortality. RESULTS: Thirty-seven patients (60% men) underwent cyanoacrylate glue injections for GVB. The median follow-up period was 14 months and included 29 patients (eight were lost to follow-up). Initial hemostasis was achieved in 35 patients (95%). No significant complications from cyanoacrylate injection were observed. Early rebleeding was rare (8%) and late rebleeding occurred in only 28% of patients. The all-cause mortality rate was 28.6% during the median follow-up period.  CONCLUSION: The data suggest that cyanoacrylate injection therapy is safe and effective for the prevention of short- and long-term bleeding from gastric varices. Furthermore, although these patients had significant comorbid disease, survival in the follow-up time period was greater than 70%.

Relapse of multiple myeloma presenting with biliary obstruction.

Pancreatic infiltration is a rare feature of multiple myeloma. A case of a 74-year-old man presenting with symptomatic biliary obstruction two years after the original diagnosis of myeloma is described. Confirmation of pancreatic infiltration with myeloma cells was performed by endoscopic ultrasound-guided fine-needle aspiration. Biliary stenting was performed at endoscopic retrograde cholangiopancreatography. Resolution of the pancreatic mass and the associated biliary stricture was observed after radiation and chemotherapy.

Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer.

Previous in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively. Epithelial nuclear staining percentage (p = 0.04) and intensity (p = 0.006) increased with advancing tumor stage, whereas stromal cytoplasmic staining decreased (p = 0.02). Using multivariate statistical analysis, survival was inversely associated with staining intensity in the epithelial cytoplasm (p = 0.01) and stromal nuclei (p = 0.007). In different colorectal cell lines and in vivo tumors, pro- and active Cathepsin L isoforms were present in both the cytoplasm and nuclear samples, with pro-Cathepsin L at 50 kDa and active Cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions from cell lines and tumors showed active Cathepsin L activity. The identification of nuclear Cathepsin L may play an important prognostic role in colorectal disease progression and patient outcome. Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression.

Preoperative biliary drainage in malignant obstruction: indications, techniques, and the debate over risk.

In patients with malignant biliary obstruction considered suitable for surgical resection, preoperative drainage might be expected to improve surgical outcomes by restoring liver function and improving nutritional status. In practice, however, the benefits of preoperative drainage are far from clear. Studies to date have reported differing outcomes, and some have suggested that morbidity and mortality are greater in patients undergoing drainage than in those proceeding directly to surgery. The development of clinical guidelines has been limited by the lack of convincing randomized data, which in turn has led to variations in practice. This article examines the arguments for and against preoperative biliary drainage, the conflicting data on the subject, and the techniques used.

The investigation of unexplained biliary dilatation.

The investigation of biliary dilatation forms a routine part of gastroenterology practice. In developed countries, biliary dilatation is usually the result of obstruction of bile flow by either stones or mitotic lesions of the pancreas or biliary tree, and standard radiologic and endoscopic techniques are used to identify and relieve the obstruction. In the absence of an obvious cause, however, the investigation and management of biliary dilatation can prove challenging, particularly while trying to minimize invasive studies. This review examines factors thought to influence bile duct size in the absence of obvious obstructing pathology and looks at some causes of biliary dilatation that are unusual and potentially difficult to diagnose.

Increased topoisomerase IIalpha expression in colorectal cancer is associated with advanced disease and chemotherapeutic resistance via inhibition of apoptosis.

Topoisomerase IIalpha is a nuclear enzyme that regulates the tertiary structure of DNA. The influence of topoisomerase IIalpha gene (TOP2A) or protein alterations on disease progression and treatment response in colorectal cancer (CRC) is unknown. The study investigated the clinical relevance of topoisomerase IIalpha in CRC using in vivo and in vitro models. Differentially expressed genes in early and late-stage CRC were identified by array comparative genomic hybridization (CGH). Cellular location of gene amplifications was determined by fluorescence in situ hybridization (FISH). Topoisomerase IIalpha levels, proliferation index, and HER2 expression were examined in 228 colorectal tumors by immunohistochemistry. Overexpression of topoisomerase IIalpha in vitro was achieved by liposome-based transfection. Cell growth inhibition and apoptosis were quantified using the crystal violet assay and flow cytometry, respectively, in response to drug treatment. Amplification of TOP2A was identified in 3 (7.7%) tumors using array CGH and confirmed using FISH. At the protein level, topoisomerase IIalpha staining was observed in 157 (69%) tumors, and both staining and intensity levels were associated with an aggressive tumor phenotype (p values 0.04 and 0.005, respectively). Using logistic regression analysis, topoisomerase IIalpha remained significantly associated with advanced tumor stage when corrected for tumor proliferation (p=0.007) and differentiation (p=0.001). No association was identified between topoisomerase IIalpha and HER2. In vitro, overexpression of topoisomerase IIalpha was associated with resistance to irinotecan (p=0.001) and etoposide chemotherapy (p=0.03), an effect mediated by inhibition of apoptosis. Topoisomerase IIalpha overexpression is significantly associated with alterations in tumor behavior and response to drug treatment in CRC. Our results suggest that gene amplification may represent an important mechanism underlying these changes.

Acute fulminant colitis caused by idiopathic mesenteric inflammatory veno-occlusive disease.

Mesenteric inflammatory veno-occlusive disease (MIVOD) is an uncommon but important cause of bowel inflammation. MIVOD is characterised by lymphocytic inflammation and non-thrombotic occlusion of the mesenteric venules and veins. We present the case of a young man who presented with acute fulminant colitis, requiring colectomy. The differential diagnosis, pathogenesis and treatment are discussed. This case illustrates the rapid progression from 'well' to 'colectomy' that can occur with MIVOD. MIVOD should be considered in the differential diagnosis of colitis that does not respond to conventional medical treatment.