De Novo Autoimmune Hepatitis Following Liver Transplantation.

INTRODUCTION: De novo autoimmune hepatitis, also known as plasma cell hepatitis, is an increasingly recognized entity following liver transplantation. The aim of this study is to investigate the long-term outcomes of patients with de novo autoimmune hepatitis. METHODS: Using transplant liver biopsy database, we identified all patients showing plasma cell hepatitis following liver transplantation between 2008 and 2013. The diagnosis of plasma cell hepatitis was based on the histologic features from liver biopsies. RESULTS: A total of 30 patients with plasma cell hepatitis were identified. Underling liver disease were hepatitis C virus (n = 11) and non-hepatitis C virus-related disease (n = 19). The interval period from liver transplantation to development of plasma cell hepatitis was 20 (2-246) months during 6 (1.5-25.8) years after liver transplantation. The mean international autoimmune hepatitis score and frequency of acute cellular rejection episode prior to the diagnosis of plasma cell hepatitis were lower in the patients with hepatitis C virus than those underlying non-hepatitis C virus-related disease. Twenty-seven patients (90.0%) showed complete biochemical response to plasma cell hepatitis treatment, but 10 (37.0%) patients relapsed. During the median 72 months' follow-up after liver transplantation, 9 (30.0%) patients progressed to cirrhosis (median 37 months) and 10 (33.3%) patients died or were retransplanted. CONCLUSIONS: This long-term clinical observation shows that de novo autoimmune hepatitis represents one cause of graft loss in patients with or without hepatitis C virus. Although most patients exhibit a good response to medical therapy, de novo autoimmune hepatitis is likely to recur and progress to liver cirrhosis.

Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation.

BACKGROUND: Fibrosis in ulcerative colitis has remained largely unexplored despite its clinical implications. AIMS: This cross-sectional study was aimed at characterising the presence, anatomical location and degree of ulcerative colitis-associated fibrosis and its possible link to clinical parameters. METHODS: Seven hundred and six individual tissue cross-sections derived every 10 cm along the length of 89 consecutive Ulcerative colitis colectomy specimens were examined and compared to Crohn's disease colitis, diverticular disease and uninvolved areas from colorectal cancer patients. Degree of inflammation, fibrosis and morphometric measurements of all layers of the intestinal wall were evaluated. Three gastrointestinal pathologists independently assessed colon sections stained with haematoxylin and eosin, Masson trichrome and Sirius red. Clinical data were collected prospectively. RESULTS: Submucosal fibrosis was detected in 100% of ulcerative colitis colectomy specimens, but only in areas affected by inflammation. Submucosal fibrosis was associated with the severity of intestinal inflammation (Spearman correlations rho (95% confidence interval): 0.58 (P < 0.001) and histopathological changes of chronic mucosal injury, but not active inflammation. Colectomy for refractory disease rather than presence of dysplasia was associated with increased fibrosis and a thicker muscularis mucosae, whereas a thinner muscularis mucosae was associated with anti-tumour necrosis factor therapy. No feature on endoscopic mucosal biopsies could predict the underlying amount of fibrosis or the thickness of the muscularis mucosae. CONCLUSIONS: A significant degree of fibrosis and muscularis mucosae thickening should be considered as common complications of chronic progressive ulcerative colitis. These features may have clinical consequences such as motility abnormalities and increased wall stiffness.

Inter-observer and intra-observer variability in the diagnosis of dysplasia in patients with inflammatory bowel disease: correlation of pathological and endoscopic findings.

AIM: Colonic epithelial dysplasia is deemed the precursor lesion of cancer arising in inflammatory bowel disease (IBD). It has been suggested that many dysplastic lesions could be endoscopically detected to obtain target biopsies, leading to better yield. However, the clinical impact of a diagnosis of dysplasia may be hampered by a significant degree of histological and endoscopic intra-observer and inter-observer variability. This study aimed to evaluate intra-observer and inter-observer variability in the microscopic diagnosis of dysplasia in IBD and correlate endoscopic and histological findings. METHOD: In total, 158 cases of ulcerative colitis and 14 of Crohn's disease with dysplasia were selected from a pathology database. Slides were blindly reviewed twice by two expert gastrointestinal pathologists. Results of endoscopic examinations were extracted from the reports. The degree of intra-observer and inter-observer variability was determined by kappa statistics. RESULTS: Overall, there was an excellent degree of histopathological inter-observer agreement (κ = 0.786). The lowest level of agreement in the dysplasia group was for indefinite dysplasia (κ = 0.251). Negative and high grade dysplasia diagnosis reached the highest level of agreement with κ values of 0.822 [95% confidence interval (CI) 0.673-0.971] and 1.00 (95% CI 0.850-1.149), respectively. Intra-observer agreement was good and increased during the latter period of the study (κ = 0.734, 95% CI 0.642-0.826). Endoscopic-histological correlation was poor among the negative endoscopies, as up to 43% of cases were diagnosed with at least focal high grade dysplasia. The endoscopic-histological correlation improved when evaluating suspicious endoscopic lesions. CONCLUSION: Dysplasia is reliably diagnosed by expert gastrointestinal pathologists but has poor correlation with an endoscopic diagnosis of dysplasia.

Esophageal squamous cell carcinoma arising after endoscopic ablation therapy of Barrett's esophagus with high-grade dysplasia. Report of a case.

Patients with Barrett's esophagus are at risk for dysplasia and esophageal adenocarcinoma. Although surgery was the mainstay treatment for Barrett's dysplasia and cancer, patients with high-grade dysplasia and early cancers now have several nonsurgical treatment options. Most of the endoscopic therapies are relatively safe but do carry a risk for complications. Treatment failure with progression of the disease is the most severe complication, especially among patients with low surgical risk. Cryoablation has been used with promising results in both high-grade dysplasia and early esophageal cancer. A patient with a well-documented history of Barrett's esophagus with high-grade dysplasia that underwent multiple sessions of photodynamic therapy and salvage cryoablation for residual high-grade dysplasia was presented. The patient was diagnosed with squamous cell carcinoma of the distal esophagus approximately 1 year after cryoablation. This is the first complete report of squamous cell carcinoma occurring after endoscopic ablation for Barrett's neoplasia. Careful follow up is necessary in any endoscopic ablation program due to the risk of recurrent neoplasia.

Factors influencing circumferential resection margin in rectal cancer.

AIM: Abdominoperineal excision (APR) has been associated with higher circumferential resection margin (CRM) involvement and local recurrence rates than extralevator APR for low rectal cancer. This study aimed to evaluate the CRMs in APR and low anterior resection (LAR) specimens and to identify factors influencing CRM involvement. METHOD: All pathological specimens from consecutive patients with rectal cancer who underwent curative resection at the Cleveland Clinic Florida, from January 2000 to July 2010, were reviewed by two pathologists. Demographics, tumour characteristics, operative data, postoperative pathology and Dworak's tumour regression grade were compared between specimens with positive and negative CRMs. RESULTS: One-hundred and fifty-four patients underwent curative APR (n = 65) or LAR (n = 69). Mean tumour size was 3.6 cm, and mean distance from the dentate line was 5.4 cm. Nine (6.8%) patients had a positive CRM (n = 6 APR, n = 3 LAR), which was associated with tumour size > 5.9 cm (P = 0.002), a distance of ≤ 2.6 cm from the dentate line (P = 0.013), microvascular invasion (P = 0.009), perineural invasion (P < 0.001), number of positive lymph nodes (P = 0.046) and incomplete total mesorectal excision (TME) (P < 0.001). APR specimens were three times more likely than LAR specimens to have an incomplete mesorectum (9.8%vs 2.9%, P = 0.322). CONCLUSIONS: Factors associated with a positive CRM were tumour size > 5.9 cm, a distance of ≤ 2.6 cm from the dentate line, incomplete TME, number of positive nodes and microvascular and perineural invasion. The incidence of a positive CRM was not significantly different between LAR and APR (n = 3 LAR and n = 6 APR).

Granulomas in Crohn's disease: does progression through the bowel layers affect presentation or predict recurrence?

AIM: The aim of the study was to correlate the presence and pattern of distribution of granulomas in resected specimens to clinical characteristics and outcome in patients undergoing surgery for Crohn's disease. METHOD: Patients with Crohn's disease who underwent surgical resection between 2001 and 2007 were identified. Pathology slides were reviewed for the presence, number and location of granulomas in four representative slides from each specimen. RESULTS: Two-hundred and seven patients were identified. At a mean follow up of 14 months, 39 patients had a recurrence, 22 (57%) of whom underwent reoperation. Ninety-four (45%) patients had granulomas present in the surgical specimen. Patients with granulomas were younger (P<0.001), had a lower preoperative body mass index (P=0.037), were more likely to be female (P=0.017) and were more likely to have extra-intestinal manifestations (P=0.026) or perianal disease (P=0.012). Sites of disease and procedures performed were similar in both groups. Disease recurrence and reoperative rates were similar in both groups, as were length of stay and morbidity rates. The average number of granulomas present in each sampled pathology slide was 7.2, and there was no correlation between number of granulomas and disease severity. No link was found between the depth of involvement of the granulomas and fistulizing or stricturing disease. CONCLUSION: Granulomas were associated with increased extra-intestinal manifestations and perianal disease, a lower body mass index and younger or female patients. There was no correlation between the presence of granulomas and disease progression or recurrence rates during the short follow-up period of this study.

Structure, composition, and peptide binding properties of detergent soluble bilayers and detergent resistant rafts.

Lipid bilayers composed of unsaturated phosphatidylcholine (PC), sphingomyelin (SM), and cholesterol are thought to contain microdomains that have similar detergent insolubility characteristics as rafts isolated from cell plasma membranes. We chemically characterized the fractions corresponding to detergent soluble membranes (DSMs) and detergent resistant membranes (DRMs) from 1:1:1 PC:SM:cholesterol, compared the binding properties of selected peptides to bilayers with the compositions of DSMs and DRMs, used differential scanning calorimetry to identify phase transitions, and determined the structure of DRMs with x-ray diffraction. Compared with the equimolar starting material, DRMs were enriched in both SM and cholesterol. Both transmembrane and interfacial peptides bound to a greater extent to DSM bilayers than to DRM bilayers, likely because of differences in the mechanical properties of the two bilayers. Thermograms from 1:1:1 PC:SM:cholesterol from 3 to 70 degrees C showed no evidence for a liquid-ordered to liquid-disordered phase transition. Over a wide range of osmotic stresses, each x-ray pattern from equimolar PC:SM:cholesterol or DRMs contained a broad wide-angle band at 4.5 A, indicating that the bilayers were in a liquid-crystalline phase, and several sharp low-angle reflections that indexed as orders of a single lamellar repeat period. Electron density profiles showed that the total bilayer thickness was 57 A for DRMs, which was approximately 5 A greater than that of 1:1:1 PC:SM:cholesterol and 10 A greater than the thickness of bilayers with the composition of DSMs. These x-ray data provide accurate values for the widths of raft and nonraft bilayers that should be important in understanding mechanisms of protein sorting by rafts.

A comparison of two methods to perform a breathing trial before extubation in pediatric intensive care patients.

OBJECTIVE: To compare the percentage of infants and children successfully extubated after a trial of breathing performed with either pressure support or T-piece. DESIGN: Prospective and randomized study. SETTING: Three medical-surgical pediatric intensive care units (PICUs). PATIENTS: Two hundred fifty-seven consecutive infants and children who received mechanical ventilation for at least 48 h and were deemed ready to undergo a breathing trial by their primary physician. INTERVENTIONS: Patients were randomly assigned to undergo a trial of breathing in one of two ways: pressure support of 10 cmH2O or T-piece. Bedside measurements of respiratory function were obtained immediately before discontinuation of mechanical ventilation and within the first 5 min of breathing through a T-piece. The primary physicians were unaware of those measurements, and the decision to extubate a patient at the end of the breathing trial was made by them. MEASUREMENTS AND MAIN RESULTS: Of the 125 patients in the pressure support group, 99 (79.2%) completed the breathing trial and were extubated, but 15 of them (15.1%) required reintubation within 48 h. Of the 132 patients in the T-piece group, 102 (77.5%) completed the breathing trial and were extubated, but 13 of them (12.7%) required reintubation within 48 h. The percentage of patients who remained extubated for 48 h after the breathing trial did not differ in the pressure support and T-piece groups (67.2% versus 67.4%, p=0.97). CONCLUSIONS: In infants and children mechanically ventilated, successful extubation was achieved equally effectively after a first breathing trial performed with pressure support of 10 cmH2O or a T-piece.

Defunctioning lateral colostomy or ileostomy.

A method of loop colostomy and ileostomy construction is described. The stoma provides complete diversion and can be either temporary or permanent.