Severity of coeliac disease and clinical management study when using a non-metabolised medication: a phase I pharmacokinetic study.

Objective: The non-metabolised antihistamine fexofenadine has oral absorption resulting from transporter activity. Uptake by enterocyte organic anion transporting polypeptides and efflux by an ATP-binding cassette transporter (P-glycoprotein) are primary determinants. Coeliac disease-mediated lesions to the small intestinal mucosa may alter oral absorption of the drug probe, fexofenadine.

Recurrent Hepatocellular Carcinoma After Liver Transplantation: Validation of a Pathologic Risk Score on Explanted Livers to Predict Recurrence.

Background: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation is a major cause of morbidity and mortality. To date, there is no widely accepted pathologic assessment tool to predict HCC recurrence. In 2007, we developed a pathologic risk score that stratified patients into low, intermediate, or high risk for recurrence based on explant pathology.

Globular glial tauopathy, a newly recognized white matter tauopathy, with depression/anxiety disorder: report and review of classification.

Several studies have recently described 4-repeat tauopathies that are characterized by the presence of globular glial inclusions. These inclusions are astrocytic or oligodendroglial, show extensive white matter involvement, and have a wide range of neuropathological and clinical presentations. Globular glial tauopathy (GGT) is classified into three subtypes according to clinical manifestations.

Severity of coeliac disease and clinical management study when using a CYP3A4 metabolised medication: a phase I pharmacokinetic study.

Objective: Severity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism.

Complete duodenal necrosis associated with non-traumatic duodenal hematoma requiring emergent pancreatico-duodenectomy.

Introduction: Duodenal necrosis is a rare complication of acute pancreatitis but can occur given the shared blood supply to the head of the pancreas and the duodenum.

Presentation Of Case: A 55-year-old male presented with acute-on-chronic pancreatitis and a duodenal hematoma. The hematoma expanded to occlude the biliary tree and, shortly after, the duodenum necrosed and perforated.

CDX2 and Muc2 immunohistochemistry as prognostic markers in stage II colon cancer.

The treatment for colorectal cancer is largely surgical followed by adjuvant chemotherapy in high-risk cases. In patients with stage II cancer, there is no clear benefit for chemotherapy, and the current tools for assessment of risk are inadequate. A recent study identified that colorectal cancer with a gene signature similar to undifferentiated colonic stem cells was associated with a worse outcome.

Grading of Total Mesorectal Excision Specimens: Assessment of Interrater Agreement.

Background: Total mesorectal excision is the standard of care for patients with rectal cancer. Pathological evaluation of the quality of the total mesorectal excision specimen is an important prognostic factor that correlates with local recurrence, but is potentially subjective.

Objective: This study aimed to determine the degree of variation in grading, both between assessors and between fresh and formalin-fixed specimens.

The impact of knowledge transfer on the detection of venous invasion in colorectal cancer.

Venous invasion (VI) is an independent predictor of hematogenous metastasis and mortality in colorectal cancer (CRC) yet remains widely underreported. Its detection may require recognition of subtle morphologic clues, which at times are only unmasked with an elastin stain. This study evaluates the impact of a knowledge transfer initiative (KTI) on VI detection in a "real-world" pathology practice setting.

The Future Liver Remnant in Patients Undergoing the Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) Maintains the Immunological Components of a Healthy Organ.

Background And Aims: A short-interval, two-stage approach termed associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) increases the number of patients with extensive malignant disease of the liver and a small future liver remnant (FLR) that can undergo liver resection. While this approach results in accelerated liver hypertrophy of the FLR, it remains unknown whether this phenomenon is restricted to liver parenchymal cells. In the current study, we evaluated whether ALPPS alters the immunological composition of the deportalized lobe (DL) and the FLR.

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

Background: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist.

Methods: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis.

Inflammatory pseudotumours of the oesophagus--histological and immunohistochemical findings.

Aims: Inflammatory oesophageal pseudotumours are rare lesions, thought to be reactive. Due to marked atypia of the stromal cells, these can be misdiagnosed as malignancies. The objective of this study was to characterize histological and immunohistochemical features of a series of inflammatory pseudotumours of the oesophagus.

Interobserver variability in assessing dysplasia and architecture in colorectal adenomas: a multicentre Canadian study.

Aims: Following the introduction of colorectal cancer screening programmes throughout Canada, it became necessary to standardise the diagnosis of colorectal adenomas. Canadian guidelines for standardised reporting of adenomas were developed in 2011. The aims of the present study were (a) to assess interobserver variability in the classification of dysplasia and architecture in adenomas and (b) to determine if interobserver variability could be improved by the adoption of criteria specified in the national guidelines.

Re-directing an alkylating agent to mitochondria alters drug target and cell death mechanism.

We have successfully delivered a reactive alkylating agent, chlorambucil (Cbl), to the mitochondria of mammalian cells. Here, we characterize the mechanism of cell death for mitochondria-targeted chlorambucil (mt-Cbl) in vitro and assess its efficacy in a xenograft mouse model of leukemia. Using a ρ° cell model, we show that mt-Cbl toxicity is not dependent on mitochondrial DNA damage.

Retrospective analysis of disease association and outcome in histologically confirmed ischemic colitis.

Objective: To identify risk factors, clinical features and complications in patients with ischemic colitis (IC).

Methods: All patients diagnosed with biopsy proven IC within a 2-year period were identified; clinical data were retrospectively collected and subsequently analyzed.

Results: In total, 72 IC patients with a mean age of 68 years were included in this study.

Venous invasion in colorectal cancer: impact of an elastin stain on detection and interobserver agreement among gastrointestinal and nongastrointestinal pathologists.

Venous invasion (VI) is an independent prognostic indicator in colorectal cancer and may prompt consideration for adjuvant chemotherapy in patients with stage II tumors. Recent evidence suggests that VI is underreported in colorectal cancer and that detection may be enhanced by an elastin stain. This study aimed (1) to determine the impact of an elastin stain on VI detection and on interobserver agreement between gastrointestinal (GI) and non-GI pathologists, and (2) to identify factors associated with increased VI detection.

A comparison of survival and pathologic features of non-alcoholic steatohepatitis and hepatitis C virus patients with hepatocellular carcinoma.

Aim: To compare the clinical outcome and pathologic features of non-alcoholic steatohepatitis (NASH) patients with hepatocellular carcinoma (HCC) and hepatitic C virus (HCV) patients with HCC (another group in which HCC is commonly seen) undergoing liver transplantation.

Methods: Patients transplanted for HCV and NASH at our institution from January 2000 to April 2011 were analyzed. All explanted liver histology and pre-transplant liver biopsies were examined by two specialist liver histopathologists.

Reduction of liver ischemia reperfusion injury by silencing of TNF-α gene with shRNA.

Background: Tumor necrosis factor-alpha (TNF-α) is a central mediator in the hepatic response to ischemia/reperfusion. Short hairpin RNA (shRNA) has been proven to be an effective means of harnessing the RNA interference pathway in mammalian cells. In the current study, we investigated whether silencing TNF-α gene with shRNA can prevent liver ischemic reperfusion injury (IRI).

Prospective study of clinical and histological safety of pure and uncontaminated Canadian oats in the management of celiac disease.

Background: Pure oats are safe for most patients with celiac disease, but concerns regarding contamination by other grains limit their consumption. The Canadian Celiac Association recently released guidelines governing the production of pure oats. The objective was to test the safety of a product manufactured under these guidelines.

Lobular capillary hemangioma of the liver.

Background: Lobular capillary hemangioma (LCH) is a benign vascular tumor that is rare in adults and has never been reported in the liver. This vascular lesion usually presents on the skin or mucous membranes, and predominantly affects children.

Methods: LCH as a large asymptomatic hepatic mass was seen in a 35-year-old female.

Mycophenolate mofetil-related gastrointestinal mucosal injury: variable injury patterns, including graft-versus-host disease-like changes.

Mycophenolate mofetil (MMF) is a commonly used immunosuppressive drug used in the management of transplant recipients. Although gastrointestinal (GI) toxicity is a known complication of MMF, the literature characterizing the pathologic features of MMF in the GI tract is sparse. This study characterizes the pathologic features of MMF toxicity in both the upper and lower GI tract, correlating it with clinical and endoscopic findings.

Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA).

The morphologic distinction between various serrated polyps of the colorectum may be challenging. The distinction between sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) may be difficult using currently available criteria mostly based on cytologic characteristics. We have evaluated 66 serrated polyps including 29 SSA, 18 TSA, and 19 hyperplastic polyps for overall shape of the polyps, architectural features of individual crypts, the presence of eosinophilic cytoplasm, size and distribution of the proliferation and maturation zones, as well as Ki-67 and CK20 expression.

Recurrent hepatocellular carcinoma after transplantation: use of a pathological score on explanted livers to predict recurrence.

Milan and University of California at San Francisco (UCSF) criteria are used to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). Recurrent HCC is a significant cause of death. There is no widely accepted pathological assessment strategy to predict recurrent HCC after transplantation.

Survivin and hedgehog protein expression in serrated colorectal polyps: an immunohistochemical study.

Sessile serrated adenomas and traditional serrated adenomas are pathogenetically related to inhibition of apoptosis. Survivin and hedgehog proteins, including sonic hedgehog, patched, and smoothened, inhibit apoptosis, with hedgehog proteins forming a signal transduction cascade implicated in digestive cancers. This study compares survivin and hedgehog protein expression in serrated polyps and tubulovillous adenomas.

Pathological effects of drugs on the gastrointestinal tract: a review.

Drug-induced injury of the gastrointestinal (GI) tract is increasingly common but generally under-recognized. Although there is an overwhelming number of drugs that are associated with adverse GI effects, there is a limited number of characteristic injury patterns that should prompt consideration of drug-induced GI pathology. These include the following: erosions, ulcers, and strictures; crystal deposition; parietal cell changes; reactive gastropathy; pseudodysplastic changes; microscopic colitis; infectious or necrotizing enterocolitis; ischemic colitis; focal active colitis; and increased epithelial apoptosis.

Comparison of ThinPrep and conventional smears in salivary gland fine-needle aspiration biopsies.

Background: ThinPrep (TP) cytology for evaluation of nongynecological specimens is being increasingly used. There are few studies comparing TP with conventional smears (CS) in salivary gland (SG) fine-needle aspiration biopsies (FNAB). This study compares diagnostic accuracy and morphology of TP and CS in SG FNABs.