Role of liver biopsy in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease

Intermittent Inflammatory Bowel Disease and Microscopic Colitis: Variant or Epiphenomenon?

Background: Idiopathic inflammatory bowel disease and microscopic colitis are distinct entities; however, some clinical features overlap. Aims: To identify if these alternative diagnoses may direct clinical therapy more effectively.Methods: We describe seven patients who had intermittent phases of either inflammatory bowel disease or microscopic colitis in at least two separate occasions with matching clinical and endoscopic pictures. Results: Diarrhea was the presenting symptom in all cases. In two of seven cases, the initial diagnosis was microscopic colitis, and in five cases it was inflammatory bowel disease. Addition of medication specific to diagnosis had resulted in improvement in six out of seven cases. Among the seven patients we reported, three had used nonsteroidal antiinflammatory drugs, a well-known trigger, before the onset of microscopic colitis. Conclusions: Inflammatory bowel disease and microscopic colitis are distinct clinicopathologic entities that may coexist in the same patient. Triggering factors for microscopic colitis in the general population can also be the culprit in inflammatory bowel disease patients. Microscopic colitis may present as an epiphenomenon which is superimposed on predisposing inflammatory bowel disease patients. A thorough synthesis of all clinical, medication, endoscopic, radiology, and pathological data is crucial in these patients

The microscopic anatomy of the esophagus including the individual layers, specialized tissues, and unique components and their responses to injury

The esophagus, a straight tube that connects the pharynx to the stomach, has the complex architecture common to the rest of the gastrointestinal tract with special differences that relate to its function as a conduit of ingested substances. For instance, it has submucosal glands that are unique and have a specific protective function. It has a squamous lining that exists nowhere else in the gut except the anus and it has a different submucosal nerve plexus when compared to the stomach and intestines. All of the layers of the esophageal wall and the specialized structures including blood and lymphatic vessels and nerves have specific responses to injury. The esophagus also has unique features such as patches of gastric mucosa called inlet patches at the very proximal part and it has a special sphincter mechanism at the most distal aspect. This review covers the normal microscopic anatomy of the esophagus and the patterns of reaction to stress and injury of each layer and each special structure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147079/1/nyas13705_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147079/2/nyas13705.pd

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer

The RNA-binding protein Apobec1 complementation factor (A1CF) regulates posttranscriptional ApoB mRNA editing, but the range of RNA targets and the long-term effect of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf-transgenic (A1cf+/Tg), A1cf+/Tg Apobec1-/-, and A1cf-/- mice fed chow or high-fat/high-fructose diets using RNA-Seq, RNA CLIP-Seq, and tissue microarrays from human hepatocellular cancer (HCC). A1cf+/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution. Aged A1cf+/Tg mice developed spontaneous fibrosis, dysplasia, and HCC, and this development was accelerated on a high-fat/high-fructose diet and was independent of Apobec1. RNA-Seq revealed increased expression of mRNAs involved in oxidative stress (Gstm3, Gpx3, Cbr3), inflammatory response (Il19, Cxcl14, Tnfα, Ly6c), extracellular matrix organization (Mmp2, Col1a1, Col4a1), and proliferation (Kif20a, Mcm2, Mcm4, Mcm6), and a subset of mRNAs (including Sox4, Sox9, Cdh1) were identified in RNA CLIP-Seq. Increased A1CF expression in human HCC correlated with advanced fibrosis and with reduced survival in a subset with nonalcoholic fatty liver disease. In conclusion, we show that hepatic A1CF overexpression selectively alters polysomal distribution and mRNA expression, promoting lipogenic, proliferative, and inflammatory pathways leading to HCC

Gastrointestinal Parasitosis: Histopathological Insights to Rare But Intriguing Lesions of the Gastrointestinal Tract

WOS: 000376535000003PubMed ID: 27136106Objective: Gastrointestinal parasitosis is a significant cause of morbidity and mortality. Definitive diagnosis is usually made by stool tests and/or serology but may require tissue evaluation. Although pathologists are usually familiar with common parasites, it is not well established whether the diagnosis could be suspected without seeing the "parasite" itself. Material and Method: Resection or biopsy specimens of 32 cases with Giardia intestinalis (n= 20), Enterobius vermicularis (n= 5), Entamoeba histolytica (n= 4), Fasciola hepatica (n= 1), Strongyloides spp. (n= 1) and Taenia saginata (n= 1) infections were retrospectively re-evaluated for accompanying mucosal changes, and compared with nonparametric tests. Results: The most common changes were congestion (65.6%) and eosinophilic infiltration (50%). Chronic active mucosal inflammation accompanied 37.5% of the cases. More than 10 eosinophils/HPF were present in 43.8%. Only one case of G. intestinalis, E. vermicularis, E. histolytica, and F. hepatica showed more than 50 eosinophils/HPF. Mucosal architectural abnormalities were present in 34.4%. Granulomas, giant cells and Charcot-Leyden crystals were only seen accompanying F. hepatica. No statistically significant difference was found between parasite subspecies regarding presence of inflammation, lymphoid aggregates, architectural distortion, congestion, ulceration and increase of eosinophils. Conclusion: Parasites induce nonspecific inflammation, slight mucosal architectural changes, mild eosinophilic infiltrate or granuloma formation. They may cause ulceration, bowel obstruction or perforation. Parasitosis should also be considered when evaluating cases mimicking inflammatory bowel disease, celiac disease or those that do not fulfill diagnostic criteria

Comparison between staple and vessel sealing device for parynchemal transection in laparoscopic liver surgery in a swine model

Background. Advancements in technology have allowed laparoscopic surgery to expand into advanced procedures such as liver resection; however, the transection method is debatable. This study was designed to evaluate the feasibility and outcome of laparoscopic liver resection comparing the vessel sealing device (VSD) versus endomechanical stapling devices for parenchymal transection in a swine model. Materials and methods. Laparoscopic left hepatectomy was performed in two groups (n=7 in each group) comparing the stapler device with the VSD. The cut surfaces of the liver were evaluated for bleeding and biliary leakage at the time of the operation and 1 week later. The animals were sacrificed 1 week after the operation to determine hemorrhage and bile leakage, and to allow histological evaluation of the liver. Serum liver enzymes were checked before, after, and 1 week postoperatively. Results. No evidence of biliary leakage or hemorrhage was noted at the time of the operation and 1 week later for both groups. There was a trend toward an increase in blood loss in the stapled group compared with LigaSure (40±16.4 cc vs 17±3.7 cc, p>0.05). There was also a trend toward shorter transection time in the stapled group compared with the LigaSure group (15±4.1 min vs 21.8±5.3, p>0.05). The instrument cost was significantly higher in the stapled group (720±110 vs 400±50; p<0.05). There was no difference in serial liver enzymes and liver histopathology in the two groups. Conclusions. The VSD and endomechanical stapler can be safely and effectively used for parenchymal transection during laparoscopic liver resection. However, using endomechanical staplers is associated with an increase in cost

ARE THE PAIRED IMPLANT BIOPSIES FROM CADAVERIC DONORS NECESSARY?

WOS: 00020863350136

Positron Emission Tomography with [18F]-3′-Deoxy-3′fluorothymidine (FLT) as a Predictor of Outcome in Patients with Locally Advanced Resectable Rectal Cancer: a Pilot Study

PurposeThis pilot study was performed to evaluate whether tumor uptake of (18)F-labeled 3'-deoxy-3'fluorothymidine (FLT), a proliferative radiotracer, at baseline and early during therapy, is predictive of outcome in locally advanced rectal cancer.ProceduresFourteen patients underwent positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and FLT before therapy and PET with FLT approximately 2&nbsp;weeks after initiating neoadjuvant chemoradiotherapy. FLT and FDG uptake were evaluated qualitatively and by maximum standardized uptake value (SUV(max)). Tumor FLT and FDG uptake were correlated with disease-free survival (DFS).ResultsThirteen patients underwent surgery after therapy, one died before surgery with progressive disease. FDG-PET/computed tomography detected regional lymph node metastases in five and FLT-PET was positive in one. High pretherapy FDG uptake (SUV(max) ≥ 14.3), low during-therapy FLT uptake (SUV(max) &lt; 2.2), and high percentage change in FLT uptake (≥60&nbsp;%) were predictive of improved DFS (p &lt; 0.05 for all three values).ConclusionPretherapy FDG uptake, during-therapy FLT uptake, and percentage change in FLT uptake were equally predictive of DFS