Co-occurrence of cytomegalovirus-induced vanishing bile duct syndrome with papillary stenosis in HIV infection.

Jaundice in patients with AIDS can be a result of diverse conditions ranging from opportunistic infections to drug-related hepatotoxicity. With the advent of antiretroviral therapy (ART), the prevalence of AIDS cholangiopathy as a cause of jaundice has decreased; on the other hand, ART-related hepatotoxicity has become one of the commonest causes of jaundice in these patients. AIDS cholangiopathy is a rare condition of extrahepatic biliary obstruction in patients with advanced HIV infection, usually due to opportunistic infections. Vanishing bile duct syndrome (VBDS) is an acquired disorder characterized by progressive destruction and loss of interlobular bile ducts causing intrahepatic cholestasis. Herein, we report co-occurrence of fatal cytomegalovirus (CMV)-induced VBDS along with papillary stenosis, as a component of AIDS cholangiopathy, which to the best of our knowledge has not been documented earlier. This is perhaps the third case of VBDS in a patient with AIDS, and the second in association with CMV infection. VBDS in AIDS has a poor outcome, and liver transplantation may be considered only in a suitable candidate.

Multicentric extranodal Rosai Dorfman disease--a cytological diagnosis, with histological corroboration.

BACKGROUND: Rosai Dorfman disease (RDD) typically presents with massive bilateral cervical lymphadenopathy, a viral-like prodrome, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Other lymph nodes may be less commonly involved. Extranodal RDD is quite rare, and orbital disease accounts for only 10% of the extranodal sites of involvement. Multicentric disease has also been described, which is usually accompanied by lymphadenopathy either initially or later in the disease course. CASE: We report an extremely rare extranodal multicentric disease in a diabetic patient, presenting with bilateral orbital involvement, causing ocular motility restriction, which was diagnosed on aspiration cytology of the orbital mass. This was followed in quick succession by new mass lesions in the lower back and infratemporal fossa. On extensive work-up, no lymphadenopathy was detected. The patient responded well to surgical debulking of the orbital lesions and systemic steroids. CONCLUSION: Fine needle aspiration cytology can be effectively applied for early diagnosis of multicentric extranodal RDD. Surgical debulking in such cases may be supplemented by systemic steroids.

High viral load and deregulation of the progesterone receptor signaling pathway: association with hepatitis E-related poor pregnancy outcome.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection is associated with high maternal and fetal mortalities. A prospective study was undertaken to evaluate the role of viral and host factors in HEV related pregnancy outcomes. METHODS: The study included HEV infected pregnancy cases; acute viral hepatitis (AVH), n=100 and fulminant hepatic failure (FHF), n=43, and healthy pregnancy cases, n=50. HEV genotypes and viremia were studied by nucleotide sequencing and real time PCR, respectively. Progesterone receptor (PR) gene mutations (PROGINS) were studied by PCR, PR expression at the mRNA and protein levels in the placenta were studied by semi-quantitative RT-PCR and immunohistochemistry, respectively. Progesterone induced blocking factor (PIBF) expression was studied by RT-PCR in blood. Serum interleukin-10 (IL-10) and interleukin-12 (IL-12) levels were assayed by ELISA. RESULTS: HEV viral load was significantly higher in FHF than AVH (p<0.001) and in cases with fetal mortality in AVH (p=0.001) and FHF (p=0.018). PROGINS were predominant in FHF compared to AVH (p=0.26) and showed reduced mRNA and protein expression. The risk of fetal mortality in AVH was two times higher (OR, 2.190; CI, 0.303-15.85) and maternal and fetal mortalities in FHF were 4-fold (OR, 4.0; CI, 0.363-44.113) increased in PROGINS carriers. PR and PIBF expression was lower in AVH and even lower in FHF compared to healthy controls. The higher IL-12/IL-10 ratio observed in FHF compared to other groups correlated with fetal mortality in AVH and FHF (p<0.001). CONCLUSIONS: In conclusion, reduced expression of PR and PIBF, a higher IL-12/IL-10 ratio, and a high viral load results in poor pregnancy outcome in Hepatitis E.

Evaluation of adefovir & lamivudine in chronic hepatitis B: correlation with HBV viral kinetic, hepatic-necro inflammation & fibrosis.

BACKGROUND & OBJECTIVES: Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B. METHODS: This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months. RESULTS: Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P<0.001) and after therapy (r=0.713, P<0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histology activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively. INTERPRETATION & CONCLUSIONS: Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured.

Coeliac disease and the liver: spectrum of liver histology, serology and treatment response at a tertiary referral centre.

BACKGROUND: Coeliac disease (CD) is a gluten-sensitive enteropathy diagnosed on the basis of ESPGHAN criteria and clinical response to gluten-free diet (GFD). Histological abnormalities on liver biopsy have been noted in CD but have seldom been described. AIMS: To assess the histological spectrum of 'coeliac hepatitis' and possibility of reversal of such features after a GFD. METHODS: Twenty-five patients with concomitant CD and hepatic derangement were analysed for clinical profile, laboratory investigations and duodenal and liver biopsy. A histological comparison of pre- and post-GFD duodenal and liver biopsies was carried out, wherever possible. RESULTS: Fifteen patients presenting with CD subsequently developed abnormal liver function tests; 10 patients presenting with liver disease were found to have tissue positive transglutaminase in 70% and antigliadin antibodies in 60%. Serological markers for autoimmune liver disease (AILD) were positive in eight patients. Liver histology ranged from mild reactive hepatitis, chronic hepatitis, steatosis to cirrhosis. Liver biopsies after a GFD were available in six cases, of which five showed a decrease in steatosis, portal and lobular inflammation and fibrosis score. CONCLUSION: Coeliac hepatitis could be a distinct entity and the patients may present with either CD or secondary hepatic derangement. Evaluation for the presence of CD is recommended for patients presenting with AILD, unexplained transaminasaemia or anaemia. This is one of the very few studies demonstrating the continuum of liver histological changes in 'coeliac hepatitis'. Trial of a GFD may result in clinicopathological improvement of 'coeliac hepatitis'.

Primary intracardiac leiomyoma arising from cardiomyocyte progenitors at the right ventriculoseptal interface: case report with literature review.

Primary cardiac neoplasms are rare and are usually benign myxomas and rhabdomyomas. Cardiac leiomyomas are usually seen as a part of the spectrum of intravenous leiomyomatosis or benign metastasizing leiomyoma. De novo occurrence of primary intracardiac leiomyomas (PICL) is a rarity. Herein we describe a 14-year-old boy presenting with intermittent dyspnea for 2 years, with a large right ventricular mass suggestive of myxoma on transthoracic echocardiography, without any extracardiac lesions. Histology and immunohistochemistry of the tumor excised under cardiopulmonary bypass confirmed a PICL arising at the cardiomyocyte-smooth muscle septal interface. A review of existing literature highlights an increased incidence in young patients and an overwhelming right ventricular anatomical predilection. Abnormalities in the multipotent cardiac progenitor cells of the second heart field may provide a potential microenvironment for the histogenesis of PICL.

Cystic ductal adenocarcinoma of pancreas: an unusual variant.

Cystic lesions of the pancreas are usually pseudocysts (90%); only 10% of them are cystic tumors. These cystic tumors constitute less than 10% of all pancreatic neoplasms, making them an extremely uncommon type of pancreatic malignancy. What is more important is that these tumors are very easily misdiagnosed as pseudocysts because their characteristics are very similar to those of the benign pseudocysts. This gains importance as the cystic tumors have a high cure rate and good prognosis if diagnosed and treated on time. Of all the cystic tumors, the most common are the benign serous cystadenomas, mucinous cystic tumors, intraductal papillary mucinous neoplasms etc. Ductal adenocarcinoma of pancreas presenting in cystic form is an uncommon type of cystic tumor, making it extremely rare among all pancreatic malignancies (solid or cystic). We present the following case report. The review of literature concerning the diagnosis and management has also been discussed.

Atypical presentation of calvarial metastasis of renal cell carcinoma in an adolescent: A rare case diagnosed on fine needle aspiration cytology with literature review.

Renal cell carcinoma (RCC) is a complex and challenging neoplasm both in terms of treatment as well as diagnosis. Its unpredictable biological behavior and many deceptive appearances can sometimes bewilder the pathologist. We hereby report a rare case of a 17 year old girl presenting with an occipital swelling and importantly no prior documents at the time of aspiration. Fine needle aspiration cytology showed features of metastatic carcinoma with the following possibilities; metastatic RCC, melanoma, and hepatocellular carcinoma. Further detailed history of the patient and investigations were advised. Intraoperative squash smears also showed similar features. Histopathology of the lesion showed features of metastatic RCC. This case highlights the fact that a skull lesion in rare cases may be the presenting sign of an underlying malignancy. In the absence of key documents, providing the correct diagnosis may become very challenging and cytomorphology alone can be extremely helpful.

Clear cell hepatocellular carcinoma: Back to the basics for diagnosis.

Hepatocellular carcinoma (HCC) is a common cancer world-wide with a higher incidence in Asia. Clear cell variant of HCC (CCHCC) has a frequency ranging from 0.4% to 37%. The presence of 90-100% clear cells is rare. In the present case, a 35-year-old female patient presented with fever and a large abdominal mass in the right hypochondrium. Histology of the tumor revealed >95% clear cells and after taking multiple sections from different areas of tumor only few scattered cells with eosinophilic cytoplasm were found. Immunohistochemistry with Hep Par 1, Glypican 3 and polyclonal carcinoembryonic antigen were negative as were all other markers for metastatic clear cell tumors. Histological diagnosis was based on routine H and E sections showing a histological pattern of architecture with thickened trabeculae. We describe a rare case of CCHCC with >95% clear cells and no immunoreactivity in tumor cells in a non-cirrhotic liver.

Infant gastroesophageal reflux disease score: reproducibility and validity in a developing country.

A 25-point infant gastro-oesophageal reflux disease (GERD) score based on 11 signs and symptoms of gastrooesophageal reflux (GER), to diagnose GERD has been suggested in infant. We carried out this study to test the reproducibility and validity of this scoring system in the cross-cultural settings of Indian infants. Caretakers of 610 apparently healthy infants, between the ages of 1 month and 24 months were administered the Orenstein's infant GER questionnaire and assigned a GERD score. Of these, 95 infants were taken up for a 24-hours oesophageal pH monitoring study. Before the pH study, each subject was again tested by the infant GER questionnaire by another independent observer and assigned an infant GERD score. The 24-hours oesophageal pH study was done using the Synectics Digitrapper MK III portable pH recording device. Reflux index (RI) >10% in infants up to 1 year of age and >5% in children more than 1 year of age was taken as pathological. Upper gastrointestinal endoscopy and oesophageal biopsies were performed in 35 cases, after taking informed consent. A good correlation was seen between the scores evaluated independently by the two workers, with a Pearson correlation coefficient of 0.906. The mean GERD score in infants with GER (as diagnosed by pH-metry) was 4.64 +/- 3.99 compared to 3.54 +/- 3.96 in those with no documented GER (p>0.05). A GERD score of 5 had a sensitivity of 43% and specificity of 79%, compared to 86% and 85% observed by Orenstein et al. in their series. The infant GER Questionnaire is easily adaptable and reproducible in the settings of developing countries. However, its diagnostic validity appears to be much less than that obtained by Orenstein et al. in their study on American infants.

Surgical management of obstructive gastroduodenal tuberculosis.

BACKGROUND: Gastroduodenal tuberculosis is a rare but potentially curable condition. The aim of the present study was to evaluate the clinical presentation, pre-operative status, management and outcome in patients with histologically proven diagnosis of gastroduodenal obstruction due to tuberculosis. METHODS: We retrospectively reviewed the records of 17 patients managed surgically for gastroduodenal obstruction due to tuberculosis. RESULTS: The site of obstruction was the pyloroduodenal canal in 53% of patients, second part of the duodenum in 24%, third part of the duodenum in 12% and duodenjojejunal flexure in 12%. The obstruction was caused by fibrotic stricture formation in 59% of patients and extrinsic compression by a lymph nodal mass in 41%. Endoscopic biopsy was diagnostic in only 29% of the patients in whom it was performed. Overall, a pre-operative diagnosis of gastroduodenal tuberculosis was suspected in only 35% of patients. All the patients underwent surgical drainage procedures and the diagnosis was confirmed by histopathological examination of biopsies taken at the time of laparotomy. CONCLUSIONS: In view of its rarity and non-specific findings on clinical, radiological and endoscopic evaluation, tuberculosis as a cause of gastroduodenal obstruction is seldom diagnosed pre-operatively. Hence, a high index of suspicion is required in young patients residing in endemic areas. Surgical intervention helps not only in relieving obstruction but also in confirming the diagnosis.

Fine-needle aspiration cytology, frozen section, and open biopsy: relative significance in diagnosis of musculoskeletal tumors.

Fine-needle aspiration cytology (FNAC) is a minimally invasive technique used extensively in diagnosis of various tumors. Frozen section biopsy is known for its usefulness in assessing adequacy of margins of resection intraoperatively. This study assesses the usefulness and significance of these procedures in tumors of musculoskeletal origin. This study includes 91 patients and all the patients were subjected to a preoperative FNAC test on an outpatient basis. An open biopsy was done in every case under appropriate anesthesia and representative tumor tissue was sent for frozen section analysis. Out of 91 patients, FNAC was feasible in 78 patients. Out of the 78 patients aspirated, a type-specific diagnosis was made in 79.5% of cases (62 out of 78). Frozen section was possible in 85 cases. The percentage of specific diagnosis by frozen section in this study is 85.9% (73 out of 85) and overall diagnostic accuracy of 96.5% (82 out of 85). FNAC and frozen section are reliable diagnostic modalities, in the presence of clinico-radiological correlation, in the diagnosis of musculoskeletal tumors.

Histological spectrum of chronic hepatitis in precore mutants and wild-type hepatitis B virus infection.

This study compares the histology of liver biopsies in precore mutant (PCM) and wild-type hepatitis B virus (HBV) infection. Thirty cases of PCM and 60 cases of wild-type HBV infection were included. Patients were diagnosed on the basis of serological profile and HBV DNA assessment. Liver biopsies in each case were assessed for histological activity and stage of fibrosis using a modification of Knodell's scoring system. There was no statistically significant (P=0.14) difference in histological activity in the two groups. The difference in stage of fibrosis in the two groups was statistically significant (P=0.001). Quantitative estimation of viral load did not show any correlation with liver histology. PCM HBV showed greater stage of fibrosis compared with wild-type infection, and this may be related to disease progression and lack of response to therapy.

Histological profile of liver disease in patients with dual hepatitis B and C virus infection.

UNLABELLED: There is limited information on the histological profile of chronic liver disease due to dual infection with hepatitis B virus and hepatitis C virus infection. Few studies have indicated higher histological activity with dual infection as compared to HBV and HCV infection present alone. This study aims at reviewing the histological profile of liver biopsies in the three groups. Liver biopsies of 25 patients serologically diagnosed as HBV and HCV dual infection (Group I), were compared with 25 age and sex matched cases of HBV infection (Group II) and HCV infection (Group III). RESULTS: Mean Histological Activity Score in group I was 8, which was higher than the scores of group II (6.2) and group III (7.3). The mean stage of fibrosis was also slightly higher in group I (2.3) as compared to group II (1.9) and group III (1.7). However, when stage 3 and 4 fibrosis (extensive fibrosis) were combined and compared with the number of patients with stage 1 and 2 fibrosis in each group, we found Group I (dual infection) had larger number of patients with extensive fibrosis (48%) than in Groups II and III (20% and 36% respectively). In addition, there was no significant difference in presence of features like fatty change, bile duct injury and lymphoid aggregates in the three groups. CONCLUSION: Patients with dual HBV and HCV infection are more likely to have an advanced stage of disease than those with a single infection, however there is no significant difference in histologic activity or any other histological parameter between these groups.

Improvement in myocardial function by Terminalia arjuna in streptozotocin-induced diabetic rats: possible mechanisms.

Vascular complications are a leading cause of mortality and morbidity in diabetic patients. Herbal drugs are increasingly being used in the treatment of cardiovascular disorders. The present study was designed to examine the therapeutic potential of Terminalia arjuna bark extract in improving myocardial function in streptozotocin (STZ)-induced diabetic rats. After 8 weeks of STZ administration, rats showed a decline in left ventricular pressure (LVP), maximal rate of rise and fall in LVP (LV [dP/dt] max and LV [dP/dt] min), cardiac contractility index (LV [dP/dt] max/LVP), and rise in LV end-diastolic pressure. Altered lipid profile, oxidative stress, and increased levels of endothelin 1 (ET-1), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) along with histological changes in heart and pancreas were observed in diabetic rats. T arjuna significantly attenuated cardiac dysfunction and myocardial injury in diabetic rats. It also reduced oxidative stress, ET-1, and inflammatory cytokine levels. The decreased body weight, heart rate blood pressure, and raised blood sugar in diabetic rats did not improve after T arjuna therapy. Results suggest that T arjuna bark extract improves the altered myocardial function in diabetic rats possibly through maintaining endogenous antioxidant enzyme activities, decreasing ET-1 and cytokine levels.