A New Glutamine Synthetase Index to Evaluate Hepatic Lobular Restoration in Advanced Fibrosis During Anti-HBV Therapy

Background Hepatic lobular architecture distortion is a deleterious turning point and crucial histological feature of advanced liver fibrosis in chronic liver diseases. Regression of fibrosis has been documented in chronic hepatitis B (CHB) patients. However, the restoration of lobular architecture after antiviral therapy is still unclear. Here, we propose a new glutamine synthetase (GS) index (GS-index) to evaluate the extent of architectural disruption and restoration. Methods We evaluated 43 pre-and post-treatment liver biopsies of CHB patients with advanced fibrosis (Ishak stage≥4). Glutamine synthetase (GS) is normally expressed by perivenular hepatocytes around hepatic veins (HV). When GS expression is observed in the vicinity of portal tracts (PT), it denotes parenchymal extinction and lobular collapse. We propose the new glutamine synthetase index (GS-index), defined as the percentage of GSHV/(GSHV+ GSPT), to evaluate the extent of architectural disruption and restoration. Results The median GS-index improved from 7% at baseline to 36% at week 78 (P<0.001). When GS-index78w≥50% used to define hepatic lobular restoration, 37% patients (16/43) achieved lobular restoration, with improvement in ALT and AST levels. More importantly, GS-index correlated with fibrosis regression, one stage fibrosis improvement in restored group and no change in non-restored patients (P=0.030). Conclusion In the era of antiviral therapy for CHB, restoration of hepatic lobular architecture is achievable. GS-index gives a new evaluation tool to quantitively assess hepatic lobular status and therapeutic benefits in CHB patients.

The Voronoi theory of the normal liver lobular architecture and its applicability in hepatic zonation

The precise characterization of the lobular architecture of the liver has been subject of investigation since the earliest historical publications, but an accurate model to describe the hepatic lobular microanatomy is yet to be proposed. Our aim was to evaluate whether Voronoi diagrams can be used to describe the classic liver lobular architecture. We examined the histology of normal porcine and human livers and analyzed the geometric relationships of various microanatomic structures utilizing digital tools. The Voronoi diagram model described the organization of the hepatic classic lobules with overall accuracy nearly 90% based on known histologic landmarks. We have also designed a Voronoi-based algorithm of hepatic zonation, which also showed an overall zonal accuracy of nearly 90%. Therefore, we have presented evidence that Voronoi diagrams represent the basis of the two-dimensional organization of the normal liver and that this concept may have wide applicability in liver pathology and research.

Hidden Patterns: The Voronoi Theory of the Normal Liver Lobular Architecture and its Applicability in Hepatic Zonation.

The precise characterization of the lobular architecture of the liver has been subject of investigation since the earliest historical publications, but an accurate model to describe the hepatic lobular microanatomy is yet to be proposed. Our aim was to evaluate whether Voronoi diagrams can be used to describe the classic liver lobular architecture. We examined the histology of normal porcine and human livers and analyzed the geometric relationships of various microanatomic structures utilizing digital tools. The Voronoi diagram model described the organization of the hepatic classic lobules with overall accuracy nearly 90% based on known histologic landmarks. We have also designed a Voronoi-based algorithm of hepatic zonation, which also showed an overall zonal accuracy of nearly 90%. Therefore, we have presented evidence that Voronoi diagrams represent the basis of the two-dimensional organization of the normal liver and that this concept may have wide applicability in liver pathology and research.

Spontaneous Regression of a Large Nasal Hemangioma in a 55-Year-Old Male

Lobular capillary hemangiomas (LCHs) are benign vascular lesions of the skin, oral cavity, and, rarely, the nasal cavity that are histologically characterized by capillary proliferation and a lobular architecture. The etiology of LCH is not well understood, but the possible underlying factors include trauma, hormonal influences, and angiogenic growth factors. This case report describes the spontaneous complete regression of an LCH without further surgery although it was incompletely excised. To our knowledge, this is a rare case for a middle-aged man.

Kuttner’s tumour: chronic sclerosing sialadenitis- a mimicker of malignancy

Background: Kuttner’s tumour is a condition of the submandibular gland which is underreported as a distinct entity. Also called as the chronic sclerosing sialadenitis it resembles a plasmocytic and lymphocytic inflammatory process and presents as a hard and painful mass which clinically mimics a malignancy and raises significant concerns. The objective of the present study was to evaluate cases of Kuttner’s tumor and discuss its clinical and pathological aspects to distinguish it from a definite malignancy and create a grown acceptance of the presence of such an entity in our setting.Methods: We collected 170 cases of submandibular swellings and evaluated in detail the clinical and pathological aspects of eight cases out of them which were later diagnosed to as Kuttner’s tumour.Results: The age of the patients varied between 23 to 61 years (mean age 42.5 years) with 3 males and 5 females. 6 patients reported with a firm to hard painless submandibular mass (5 left sided; 3 right sided) while 2 patients experienced intermittent discomfort. The mean duration of presentation of symptoms was 5.3 months. Fine needle aspiration cytology was done in 6 cases preoperatively. Following submandibular sialadenectomy histopathology showed salivary gland tissue with preserved lobular architecture, but with marked fibrosis, acinar atrophy, and a dense lymphoplasmacytic infiltrates.Conclusions: Kuttner’s tumor may be pre operatively distinguished from a malignancy with improved imaging and a good image guided FNA Cytology saving the clinician and the patient from a lot of dilemma. However, histopathology and immunohistochemistry would be the key in establishing the diagnosis.

Esophageal Pyogenic Granuloma: A Case Report and Review of the Literature

Pyogenic granuloma (PG) is a capillary hemangioma mainly found in the skin and oral mucosa, but rarely described in the esophagus. We report the case of a 66-year-old man who consulted for retrosternal pain. Endoscopic studies showed a 28-mm polypoid mass located at the distal esophageal mucosa. The patient underwent endoscopic resection, and the histopathological examination showed a neoplastic proliferation of small blood vessels growing in a lobular architecture, with edematous stroma and prominent inflammatory infiltrate. Special stains for fungus showed pseudohyphae compatible with Candida spp. Findings were consistent with those of an esophageal PG associated with Candida infection. This case is a reminder that PG can be found in the esophagus, can be associated with other entities such as Candida infection, and is one of the differential diagnoses of neoplastic vascular proliferations that may mimic malignancy. In addition, we reviewed previously reported cases of esophageal PG.

How Normal Is the Liver in Which the Inflammatory Type Hepatocellular Adenoma Develops?

The inflammatory type hepatocellular adenoma (IHCA) is a subtype of HCA which is a benign liver tumor, predominantly occurring in young women in an otherwise normal liver. IHCA contains either a mutation of gp130 or STAT3. Both mutations lead to a similar morphologic phenotype and to increased expression of C-reactive protein (CRP) and/or serum amyloid-A (SAA). IHCA comprised about 40% of all HCAs and is associated with obesity. We investigated the histomorphological and immunophenotypical changes of the nontumorous liver of 32 resected IHCA specimens. Similar types of changes are present in samples taken adjacent to tumor and distant ones. The lobular architecture is well preserved. Mild/moderate steatosis is found in a high frequency which is in accordance with the median BMI of 32 in our cases. Of note are the regular findings of sinusoidal dilatation, single arteries, and minute CRP foci which are all features of HCA. These distinct CRP foci are mostly found in cases of multiple IHCA which indicates that the remnant liver may also contain IHCA foci. These findings show that the nonlesional liver in IHCA does contain abnormalities, and this may have consequences for the followup, especially since it is known that obesity may stimulate malignant growth.

Protective Role ofPhyllanthus niruriExtract against Thioacetamide-Induced Liver Cirrhosis in Rat Model

A preclinical study was performed to determine if the extract fromPhyllanthus niruri(PN) plays a protective role against liver cirrhosis induced by thioacetamide (TAA) in rats. Initially, acute toxicity was tested and the results showed that the extract was benign when applied to healthy rats. Next, the therapeutic effect of the extract was investigated using five groups of rats: control, TAA, silymarin, and PN high dose and low dose groups. Significant differences were observed between the TAA group and the other groups regarding body and liver weights, liver biochemical parameters, total antioxidant capacity, lipid peroxidation, and oxidative stress enzyme levels. Gross visualization indicated coarse granules on the surface of the hepatotoxic rats’ livers, in contrast to the smoother surface in the livers of the silymarin and PN-treated rats. Histopathological analysis revealed necrosis, lymphocytes infiltration in the centrilobular region, and fibrous connective tissue proliferation in the livers of the hepatotoxic rats. But, the livers of the treated rats had comparatively minimal inflammation and normal lobular architecture. Silymarin and PN treatments effectively restored these measurements closer to their normal levels. Progression of liver cirrhosis induced by TAA in rats can be intervened using the PN extract and these effects are comparable to those of silymarin.