Integrative multi-omics characterization of hepatocellular carcinoma in Hispanic patients.

Background: The incidence and mortality rates of hepatocellular carcinoma among Hispanic individuals in the United States are much higher than in non-Hispanic White people. We conducted multi-omics analyses to elucidate molecular alterations in hepatocellular carcinoma among Hispanic patients.

Methods: Paired tumor and adjacent nontumor samples were collected from 31 Hispanic hepatocellular carcinomas in South Texas for genomic, transcriptomic, proteomic, and metabolomic profiling.

Reconstitution of human PDAC using primary cells reveals oncogenic transcriptomic features at tumor onset.

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations.

Integrin alpha 6 is upregulated and drives hepatocellular carcinoma progression through integrin α6β4 complex.

Integrin α6 (ITGA6) forms integrin receptors with either integrin β1 (ITGB1) or integrin β4 (ITGB4). How it functions to regulate hepatocellular carcinoma (HCC) progression is not well-elucidated. We found that ITGA6 RNA and protein expression levels are significantly elevated in human HCC tissues in comparison with paired adjacent nontumor tissues by RNA sequencing, RT-qPCR, Western blotting and immunofluorescence staining.

Cholangiolytic Changes in Statin-Induced Liver Injury.

Atorvastatin is a commonly used oral cholesterol-lowering agent. Side effects associated with statin therapy include arthralgia, myalgia, dyspepsia, weakness, and headache. Prospective and retrospective studies of drug-induced liver injury have identified statin-induced hepatotoxicity, with atorvastatin being the most commonly cited.

Activation of the intrinsic fibroinflammatory program in adult pancreatic acinar cells triggered by Hippo signaling disruption.

Damaged acinar cells play a passive role in activating pancreatic stellate cells (PSCs) via recruitment of immune cells that subsequently activate PSCs. However, whether acinar cells directly contribute to PSC activation is unknown. Here, we report that the Hippo pathway, a well-known regulator of proliferation, is essential for suppression of expression of inflammation and fibrosis-associated genes in adult pancreatic acinar cells.

Intrathecal Methotrexate-Induced Necrotizing Myelopathy: A Case Report and Review of Histologic Features.

Central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL) is associated with a poor prognosis. However, prophylactic measures, including intrathecal (IT) methotrexate, reduce the incidence of CNS relapse in these patients considerably. Unfortunately, IT methotrexate can cause several neurologic complications, including transverse myelopathy; ie, the development of isolated spinal cord dysfunction over hours or days following the IT infusion of methotrexate, but in the absence of a compressive lesion.

Case Report: Fulminant Murine Typhus Presenting with Status Epilepticus and Multi-Organ Failure: an Autopsy Case and a Review of the Neurologic Presentations of Murine Typhus.

Murine typhus (MT) is an important cause of febrile illness in endemic areas, and there is an epidemiologic resurgence of this infection currently transpiring in Texas and California. Fatal cases and severe neurological complications are rare. A fatal case of MT in a middle-aged man is reported with a course culminating in multi-organ failure and refractory status epilepticus.

Leukocyte Cell-Derived Chemotaxin-2 Amyloidosis (ALECT2) in a Patient With Lung Adenocarcinoma: An Autopsy Report and Literature Review.

Amyloidosis caused by deposition of leukocyte cell-derived chemotaxin-2 amyloidosis (ALECT2) is the most recently described form of systemic amyloidosis and has quickly emerged as a common and possibly underdiagnosed cause of slowly declining renal function, particularly in patients of Hispanic ancestry. We describe the autopsy findings in a 70-year-old Hispanic woman who died of metastatic lung adenocarcinoma and was incidentally found to have extensive amyloid deposition in the kidneys, liver, spleen, adrenal glands, small intestine, gallbladder, lungs, bilateral ovaries, and uterus. The type of amyloid was confirmed to be ALECT2 by mass spectrometry.

Steatohepatitis in laboratory opossums exhibiting a high lipemic response to dietary cholesterol and fat.

Plasma VLDL and LDL cholesterol were markedly elevated (>40-fold) in high-responding opossums, but moderately elevated (6-fold) in low-responding opossums after they had consumed a high-cholesterol and high-fat diet for 24 wk. In both high- and low-responding opossums, plasma triglycerides were slightly elevated, threefold and twofold, respectively. Dietary challenge also induced fatty livers in high responders, but not in low responders.

Progression of morphological changes after transplantation of a liver with heterozygous α-1 antitrypsin deficiency.

Inadvertent transplantation of an α-1 antitrypsin-deficient liver into an adult man provided a unique opportunity to follow the natural history of morphological changes in serial liver biopsies. After doing well initially, the patient developed liver function test abnormalities 6 years posttransplant, but biopsies at that time and 2 years later revealed only chronic hepatitis with no specific features. It was only upon repeat biopsy 10 years posttransplant that characteristic cytoplasmic inclusions appeared.

High-grade microsteatosis and delay in hepatic function after orthotopic liver transplantation.

Macrovesicular steatosis may be used to exclude potential donor livers from use in transplantation. Livers with more than 50% macrovesicular steatosis are believed to be at risk for delayed graft function and primary graft nonfunction. However, the significance of even extensive microsteatosis is uncertain.

Periodic review of pathology training program teaching files: a quality improvement study.

Pathology training programs typically retain teaching files of classic and unusual diagnostic cases. Since diagnostic criteria and terminology are mutable, we reviewed a surgical pathology teaching archive to determine if the materials continued to be acceptable for educational purposes. Each case (from 2001-2003) consisted of 1 to 3 slides and a 3 x 5 card with clinical information and the diagnosis.

Morphologic features resembling transplant rejection in core biopsies of native livers from patients with Hepatitis C.

Morphologic differentiation of recurrent Hepatitis C from transplant rejection is a major problem in posttransplant liver biopsies. Although biopsies of the native livers from patients with Hepatitis C are known to display bile duct damage, other morphologic features similar to those seen in rejection, such as endotheliitis, portal eosinophils, and pericentral fibrosis, are not generally acknowledged. To determine the frequency with which features morphologically similar to rejection might be present, we examined 50 cases of core-needle biopsy from the native livers of patients with Hepatitis C for the presence of the following: bile duct damage, portal eosinophils, portal or central vein endotheliitis, ductopenia, vascular obliteration, pericentral fibrosis, and pericentral mononuclear cell infiltrate.

Diagnostic efficacy of additional step-sections in colorectal biopsies originally diagnosed as normal.

Multiple "step-sections" are prepared for many diagnostic biopsies, but tissue is usually left in the block for possible additional studies. We sought to determine the frequency with which sampling the remaining tissue with additional step-sections would reveal pathologic abnormality in a series of colorectal biopsies originally diagnosed as normal. Slides of 232 cases were reviewed and classified into 7 standard diagnostic categories.

Interobserver agreement in hepatitis C grading and staging and in the Banff grading schema for acute cellular rejection: the "hepatitis C 3" multi-institutional trial experience.

Context: Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials.

Objective: To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the "Hepatitis C 3" trial.

Design: The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV.

Colorectal cancer in Hispanics: a population at risk for earlier onset, advanced disease, and decreased survival.

Background: While colorectal cancer (CRC) incidence and mortality rates have declined slightly over the past decade, there remain marked differences by ethnicity. Our aim was to investigate ethnic differences in occurrence, clinical presentation and outcome of CRC at a tertiary university center that serves a predominantly Hispanic population.

Methods: Prospectively collected data from the tumor registry on patients diagnosed with colorectal cancer from 1985 through 2001 was examined.

Alcohol biomarker screening in medical and surgical settings.

This article highlights the proceedings of a symposium presented at the 28th Annual Meeting of the Research Society on Alcoholism in Santa Barbara, CA, on June 28, 2005, organized and chaired by Peter Miller. The presentations included (1) Screening for Alcohol Use Disorders in Surgical and Trauma Patients, presented by Claudia Spies; (2) Are Serum Levels of %CDT and GGT Related to Severity of Liver Biopsy Inflammation, Fibrosis, and Steatohepatitis in Patients with Hepatitis C? by Martin Javors; (3) Biochemical Alcohol Screening in the Treatment of Hypertension, presented by Peter Miller; and (4) The Cost-Effectiveness of a New Biomarker, CDT, in a Primary Care Sample, by Michael Fleming. Presentations were discussed by Raymond Anton.

The etiology and epidemiology of anal cancer.

The anatomic definitions for anal cancer (canal versus margin) are made based on the relationship of the tumor to the anal verge. This method had led to confusion for some providers. A modification in the terminology is proposed that includes intra-anal, perianal, and skin as categories.

Acute hepatic allograft rejection: a comparison of patients with and without centrilobular alterations during first rejection episode.

The histologic diagnosis of acute hepatic allograft rejection is usually based upon the identification of characteristic portal tract features. In addition to these, centrilobular alterations such as central vein endothelialitis, zone 3 inflammation, and hepatocyte necrosis may also be seen during episodes of acute rejection. The purpose of this study was to identify any differences in the subsequent clinical course of patients with and without centrilobular alterations during their first biopsy-proven episode of acute rejection.

Radiofrequency tissue ablation: effect of hepatic blood flow occlusion on thermal injuries produced in cirrhotic livers.

Background: Radiofrequency thermal ablation has been used as a treatment for several types of hepatic malignancies. Many of these lesions exist in the presence of cirrhosis. Limitations exist to the size of the ablations and, subsequently, the efficacy of treatment.

Myxoma of the small bowel in a 47-year-old woman with a left atrial myxoma.

Although atrial myxoma is the most common primary tumor of the heart, the synchronous occurrence of myxomas of the intestine and the heart has not been reported in the English literature. We report a case of a 47-year-old woman who presented with small bowel obstruction by a pedunculated mass that was found to be a myxoma after resection. A left atrial mass was found incidentally by a computed tomographic scan, and a diagnosis of atrial myxoma was confirmed after a second surgery.