Hepatic Involvement in Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome which results in uncontrolled systemic proliferation of benign macrophages in all reticuloendothelial organs producing worsening peripheral blood cytopenia(s); hypercytokinemia leading to hepatic injury producing hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia; and if not diagnosed and treated early may lead to disseminated intravascular coagulation (DIC), multiorgan dysfunction, and death in nearly all individuals. It is postulated that hepatic injury/dysfunction starts early in the course of the disease which may mimic nonspecific hepatitis like prodrome to fulminant hepatic failure; possibly requiring liver transplant. While HLH as an entity is being increasingly recognized nowadays across wide specialties (both pediatric and adults); hepatic involvement in this setting has been poorly characterized. This chapter is aimed to highlight on the diagnosis and classification of HLH with a special emphasis on the pathophysiology of hepatic dysfunction, histomorphology of liver; and the current concept and controversies on the role of liver transplantation in this clinical setting

Intestinal mitochondrial dysfunction in surgical stress

Background: Surgical stress is associated with altered intestinal function. Our earlier study using a rat model indicated that oxidative stress plays an important role in this process. Since mitochondria are crucial to cellular function and survival and are both a target as well as a source of reactive oxygen species, the present study looks at the changes in enterocyte mitochondria during surgical stress. Methods: Surgical stress was induced by opening the abdominal wall and handling the intestine as done during laparotomy. Mitochondria were prepared from the isolated enterocytes at different time periods after surgical stress. The effect of surgical stress on enterocyte mitochondrial ultrastructure, respiration, anti-oxidant enzyme activity, thiol redox status, calcium flux, permeability, and matrix enzymes was then studied. Results: Surgical stress resulted in alterations in mitochondrial respiration and thiol redox status. It was also associated with altered mitochondrial matrix enzyme activity, decreased superoxide dismutase activity, induction of mitochondrial permeability transition, and swelling, as well as impairment of mitochondrial calcium flux. These alterations were seen at a maximum of 60 min following surgical stress and were reversed by 24 h. Conclusions: Laparotomy and mild intestinal handling itself results in enterocyte mitochondrial damage. Since mitochondria are important cellular organelles, this damage can probably lead to compromised intestinal function

Phlebolith in arteriovenous malformation in buccal fat pad masquerading sialolith: A rare case report

Arteriovenous malformations (AVMs) are rare vascular lesion in the buccal fat pad (BFP). One of the important complications associated with these lesions is phlebolith formation within it. To the best of authors′ knowledge, there is no medical literature on AVM with phlebolith formation in BFP till date. The present case is a 12-year-old boy who presented with a swelling in the right side of the face, clinically diagnosed to be sialocele with sialolith. Excision of the mass was done, and histopathology revealed AVM with the formation of phlebolith. This rare entity needs to be kept in mind while evaluating a case of calcification in BFP. The first case of AVM with phlebolith formation in BFP is reported here along with brief review of literature

Multicentric papillary and chromophobe renal cell carcinomas in a patient with autosomal dominant polycystic kidney disease: Report of a rare case

The causal relationship of autosomal dominant polycystic kidney disease (ADPKD) with the development of renal cell carcinoma (RCC) is still not known. We describe a case of bilateral PKD complicated with a large enhancing mass and multiple small nodules in the left kidney. The histopathological study of the nephrectomy specimen revealed the synchronous occurrence of eosinophilic variant of chromophobe RCC (EVCRCC) and multicentric papillary RCC (PRCC) in a background of ADPKD. To the best of our knowledge, this case is the first to describe the collision tumor of EVCRCC and multicentric PRCC in ADPKD

Nitric oxide protects the intestine from the damage induced by laparotomy and gut manipulation

Background: The intestine is highly susceptible to free radical-induced damage, and our earlier work has shown that surgical stress induces the generation of oxygen free radicals in enterocytes, resulting in intestinal damage along with ultrastructural changes. Since nitric oxide (NO) is an important mediator of gastrointestinal function, this study looked at the effect of NO on surgical stress-induced intestinal alterations. Materials and methods: Control rats and rats pretreated with the NO donor l-arginine were subjected to surgical stress by opening the abdominal wall and handling the intestine as done during laparotomy. Enterocytes were isolated and homogenate prepared, and the protection offered by l-arginine against damage due to surgical stress was determined and compared with normal controls. Protection to structural as well as functional aspects of the intestine was also examined. Results: Intestinal manipulation affected intestinal structure as assessed by electron microscopy. Functional impairment of the enterocyte was also evident, with increased xanthine oxidase activity resulting in production of superoxide anion. This impairment is more dramatic in the crypt cells. Increased protease activity was also seen following laparotomy and handling. Pretreatment with the NO synthase substrate l-arginine prevented these damaging effects. Arginine protection was abolished in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester, indicating the role of NO. Conclusion: Stress in the small intestine due to any surgery can affect enterocyte structure and function. These damaging effects can be prevented by NO, an important modulator of cellular function

Adherent Escherichia coli in colorectal mucosal biopsies: A histological and ultrastructural evaluation

Background: Colorectal mucosal biopsies occasionally demonstrate the presence of bacteria adherent to the epithelium. This study evaluated the histological and ultrastructural correlates of such bacterial adherence. Materials and Methods: Rectal mucosal biopsies from eight patients in whom histopathological examination of biopsies had earlier demonstrated adherent bacteria were examined by electron microscopy and by bacterial culture. Colorectal biopsies of 69 patients with adherent bacteria detected histologically were retrospectively evaluated for histological changes at sites proximal and distant to adherent bacteria. Results: Escherichia coli of different serogroups were isolated from 7 of 8 rectal biopsies demonstrating bacterial adherence. All isolates showed diffuse or focal adherence to HEp-2 cell monolayers. Ultrastructural changes noted included microvillus damage, pedestal formation, actin web condensation, and protrusions of the apical cytoplasm of epithelial cells into the lumen towards the bacteria. Histological changes noted at light microscopy included reduction in epithelial cell height, focal epithelial cell degeneration, cryptitis and neutrophil infiltration at sites of bacterial adherence whereas these were usually absent at sites distant to adherent bacteria. Bacterial adherence was noted more often in biopsies from Crohn′s disease patients than in patients without this diagnosis (P < 0.001). Conclusion: Adherent Escherichia coli in colorectal biopsies were associated with focal epithelial damage and showed an association with Crohn′s disease

Malignant phyllodes tumor with heterologous differentiation: Clinicopathological spectrum of nine cases in a tertiary care institute in Eastern India

Phyllodes tumors are uncommon fibroepithelial neoplasms of breast. Heterologous sarcomatous differentiation of malignant phyllodes tumor (MPT) is a rare phenomenon as shown in the literature. Herein we report a series of nine cases from a tertiary care centre in Eastern India. Patients demographic data and clinical details were obtained from the medical records. Histopathology and immunohistochemical studies were analysed and diagnosed accordingly. Out of 38 cases of PT, 13 were found to be MPT, of which 9 cases showed heterologous differentiation in the form of angiosarcoma, fibrosarcoma, undifferentiated sarcoma, extensive squamous differentiation and with lipomatous metaplasia. Proper diagnosis and subtyping of the sarcomatous component is essential for deciding the correct treatment modality and prognostication of the disease. However there is no clear cut treatment protocol is available because of paucity of data