A retrospective clinico-pathological analysis of neuroendocrine tumors of the gastrointestinal tract.

AIM: Gastrointestinal tract is the commonest site for neuroendocrine tumors. Appendix, ileum and rectum were considered to be common sites for these tumors. However, there has been change in pattern of gastrointestinal neuroendocrine tumors over last few years. There is limited data available on epidemiology and patterns of these tumors in India. METHODS: Analysis of 74 patients with gastrointestinal and pancreatic neuroendocrine tumors over a period of 7 years at a single center in Mumbai, India was done. Clinical details, surgical outcome with follow up and treatment were reviewed. All these patients were analyzed with special emphasis on the site of the tumor. RESULTS: The results showed a male preponderance (ratio of 2.5:1) with a mean age of 53.01 +/- 15.13 years. Of the 74 tumors, the commonest site was found to be stomach 22 (30.2%), followed by pancreas 17 (23.3%) and duodenum 14 (18.9%). Only 3 (4.1%) patients presented with carcinoid syndrome. The disease was localized in 46 (62.2%), regional spread was seen in 14 (18.9%) and distant spread in 14 (18.9%). Majority of gastric and duodenal tumors had localized disease while pancreatic NETs led to most of the cases with distant disease. CONCLUSION: This analysis showed that gastrointestinal and pancreatic neuroendocrine tumors are not rare. Pattern of these tumors has definitely changed over last few years. Stomach was found to be commonest site for gastrointestinal neuroendocrine tumors followed by pancreas and duodenum.

Intrinsic factor antibody negative atrophic gastritis; is it different from pernicious anaemia?

INTRODUCTION: H. pylori gastritis and autoimmune gastritis are the two main types of chronic atrophic gastritis. Parietal cell antibody (PCA) and intrinsic factor antibody (IFA) are characteristic of autoimmune gastritis, of which IFA is more specific. Patients who are IFA negative are considered under the category of chronic atrophic gastritis. AIM: To differentiate IFA positive from IFA negative chronic atrophic gastritis. METHODS: Fifty consecutive patients of biopsy proven chronic atrophic gastritis were included in this study. All patients underwent haematological and biochemical tests including serum LDH, vitamin B12 and fasting serum gastrin levels. PCA and IFA antibodies were tested in all patients. Multiple gastric biopsies from body and antrum of the stomach were taken and evaluated for presence of intestinal metaplasia, endocrine cell hyperplasia, carcinoid and H. pylori infection. Patients were grouped as group A (IFA positive) and group B (IFA negative). The mean laboratory values and histological parameters were compared between the two groups using appropriate statistical methods. RESULTS: Eighteen patients were in group A (mean age 55.5 +/- 13 years, male: female = 16:2) and thirty-two in group B (mean age 49.7 +/- 13 years, male: female = 25:7). There was no statistically significant difference between median values of haemoglobin, MCV, LDH, Vitamin B12 and serum gastrin in both the groups. None of the histological parameters showed any significant difference. CONCLUSION: There was no statistically significant difference in haematological, biochemical and histological parameters in IFA positive and negative gastritis. These may be the spectrum of the same disease, where H. pylori may be responsible for initiating the process.

Hepatic changes in fatal malaria: an emerging problem.

Over the last few years there has been a rise in the incidence of fatal malaria in urban areas of India, and this worrying trend is a major cause of concern for the national health authorities. The spectrum of histopathological changes that occur in the livers of Indian subjects with fatal malaria has recently been investigated, in a retrospective autopsy-based study. This investigation involved the 151 fatal cases of malaria seen at a tertiary-care hospital in Mumbai between January 2001 and December 2007. The diagnosis of malaria was made on the basis of the examination of a smear of peripheral blood (81 cases) or a histopathological examination (70 cases). For each subject of the present study, at least two blocks were prepared, using routine histological methods, from a liver sample collected at autopsy. The sections produced from these blocks were stained with various compounds, including Prussian Blue (which was used to distinguish malarial pigment from non-malarial). The pattern of liver necrosis seen in the malaria cases was compared with that seen in 11 cases of acute viral hepatitis, and with the liver histology seen in 50 control subjects, who had died of causes other than malaria or liver disease. The most common clinical presentation of the subjects who died of malaria was fever (85%), followed by jaundice (68%). The presence of jaundice often led to an initial misdiagnosis of acute viral hepatitis. In the livers of the fatal malaria cases, Kupffer-cell hyperplasia and the retention of haemozoin pigment were the two most common histological features. Necrosis was seen in 63 (41%) of these cases, with predominant centrilobular haemorrhagic necrosis in 16 (10%). The inflammation in the sections of liver from the malaria cases with hepatic necrosis was sparse compared with that in the corresponding sections from patients with acute viral hepatitis, although mixed portal inflammation was frequently noted in the malaria cases. None of the liver sections from the 50 control subjects showed evidence of pigment, necrosis or any other pathology. In conclusion, jaundice was one of the commonest clinical presentations of the fatal cases of malaria and could mimic viral hepatitis on clinical examination. The characteristic histopathological features of the livers of those with fatal malaria were Kupffer-cell hyperplasia, malarial pigment within the Kupffer cells, and liver-cell necrosis, with portal inflammation, steatosis and cholestasis also observed.

Utilization of antihepatocyte clone OCH1E5 (Hep Par 1) in histological evaluation of liver tumors.

Diagnosis of hepatocellular carcinoma (HCC) is not always easy on simple hematoxylin and eosin (H&E) stain. The diagnostic problems arise when tumor shows pseudoglandular, pleomorphic or clear cell differentiation. Various tumors markers have been described with varying sensitivity and specificity. Monoclonal antibody Hep Par 1 (OCH1E5) which is specific for hepatocytes offers great help in separation of these tumors. The aim of the present study was to determine utility of Hep Par 1 (OCH1E5) in differentiating HCC from metastatic tumors and cholangiocarcinoma. Total of 62 cases of liver tumors obtained from biopsies, resected or autopsy specimens were included in the study. Slides having representative sections were subjected to immunohistochemistry with monoclonal antibody Hep Par 1 (Dako Corp) using avidin biotin technique with primary antibody dilution of 1:40. Adjacent nontumorous hepatocytes were taken as positive control. Slides were examined by experienced pathologist without any information of clinical or H&E diagnosis. Cases were considered positive for Hep Par 1 if tumor cells showed cytoplasmic brown colored granules. The intensity and distribution (diffuse/ focal) of immunoreactivity was noted. Subsequently immunohistochemistry results were correlated with histology and clinical diagnosis. Hep Par 1 antibody was positive in 26 (42 %) and negative in 36 (58 %) liver tumors. On correlating with H&E sections, out of 26 positive cases, 25 (89.2%) were HCC and one was the case of metastasis of mucin secreting adenocarcinoma. From 36 tumors with negative staining 3 were cases of HCC, 27 metastatic adenocarcinomas and 6 cholangiocarcinomas. Only one case of liver metastasis of mucin secreting adenocarcinoma showed positivity. None of the cases of cholangiocarcinoma showed positivity for Hep Par 1. The three HCCs which did not take up staining for Hep Par 1 were 2 cases of moderately differentiated HCC having pseudoglandular pattern and a case of well differentiated HCC with trabecular arrangement. In 11(44%) cases staining was diffuse while in 14 (56%) it was focal but intense. Hep Par 1 is a useful marker in differentiating HCC from metastaic tumors and cholangiocarcinoma with sensitivity and specificity of 89 % and 97 % respectively and positive predictive value of 96 %. However one should be aware of limitations of immunohistochemistry.

Nonalcoholic steatohepatitis (NASH) with diabetes: predictors of liver fibrosis.

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is common cause of chronic liver disease strongly associated with insulin resistance leading to fibrosis. No factors that determine increasing fibrosis have been well recognized. Liver biopsy is considered as gold standard for diagnosis and prognosis of this disease. AIM: To identify independent predictive factors of liver fibrosis in patients of NASH with diabetes. MATERIAL AND METHODS: During the year 2001 and 2002 total 36 patients of NASH associated with diabetes were included in the study. The diagnosis of NASH was based on 1) presence of steatosis, inflammation and ballooning on liver biopsy 2) Intake of alcohol < 20 gm of ethanol per week 3) Exclusion of other liver diseases. Patients were labeled as diabetic if random glucose was > 200 mg/dL or fasting glucose more than 140 mg/dL on 2 occasion or having documented use of oral hypoglycemic medications or insulin. Clinical and biochemical variables such as age, sex, obesity, hypercholesterolemia, AST, ALT and AST: ALT were examined for predictors of fibrosis using univariate and multiple regression statistical analysis. Obesity was defined as BMI > 30 for both males and females. Hypercholesterolemia was considered when fasting cholesterol level was above 95th percentile of normal on at least 2 occasions. Fibrosis was noted as present or absent on histology. RESULTS: Of 36 patients 17 were females and 19 males with age range of 25 to 75 years, mean age 50.8 years. Fibrosis was present in 11 (30.5%) and absent in 25 (69.4%) patients. Univariate and multiple correlations co-efficient failed to detect significant association of fibrosis with above mentioned variables. However multiple regression and logistic regression analysis (MLR) detected statistical significance for AST, ALT levels and AST: ALT ratio between fibrosis and no fibrosis in 80.6% patients. CONCLUSION: There is no definite noninvasive test that helps to predict liver fibrosis however AST, ALT levels and AST: ALT ratio may help to determine the fibrosis in patients of NASH with diabetes in majority of cases.

Insulinoma--a case report.

Insulinoma is a rare pancreatic endocrine tumour characterised by hyperinsulinemic hypoglycemia. It is important to surgically remove this tumour as it can cause potentially lethal hypoglycemia. We report a case of insulinoma presenting with unconsciousness following repeated episodes of inability to arise from sleep and convulsions. Biochemical investigation revealed hypoglycemia and hyperinsulinemia. The diagnosis of Insulinoma is often delayed due to misattribution of symptoms to psychiatric or neurological disorders. In this case, same delay lead to fatal outcome for this patient.

Tissue polymerase chain reaction in diagnosis of intestinal tuberculosis and Crohn's disease.

AIMS AND OBJECTIVES: 1) To evaluate the utility of PCR in differentiating intestinal tuberculosis from Crohn's disease. 2) To compare histological features of tuberculosis and Crohn's disease. MATERIAL AND METHODS: A total of 60 cases of diagnosed intestinal tuberculosis and 20 Crohn's disease were included in the study. Clinical data, radiological and endoscopic findings and response to treatment were taken into consideration. Endoscopic biopsies from affected areas were subjected to histopathological examination and polymerase chain reaction (PCR) assay. Acid fast staining on tissue and culture was done whenever possible. RESULTS: Clinical symptoms, radiological and endoscopic findings were almost similar between intestinal tuberculosis and Crohn's disease. PCR was positive in 21.6% cases of intestinal tuberculosis and 5% Crohn's disease. Nine out of 42 cases (21.4%) without granuloma were also positive by PCR. There was no statistical difference for PCR positivity between patients with intestinal tuberculosis with or without granuloma on histology and also between caseating and non-caseating granuloma. CONCLUSION: PCR assay showed high specificity (95%) for the diagnosis of intestinal tuberculosis hence may be valuable method to differentiate intestinal tuberculosis from Crohn's disease.

A rare cause of steatohepatitis.

We present a rare case of steatohepatitis due to neutral lipid storage disorder in a 1.5-year-old male presenting with intermittent fever, hepatomegaly and dark-coloured urine. On examination, there was ichthyosis involving both the limbs. Liver biopsy showed steatohepatitis. The peripheral blood smear revealed fat vacuoles in the cytoplasm of leucocytes, characteristic of the Dorfman-Chanarin syndrome. Awareness of this condition helps in prompt diagnosis and avoids unnecessary further investigations.

Hepatolithiasis with biliary ascariasis--a case report.

BACKGROUND: Biliary ascariasis is regarded as possible etiological factor for hepatolithiasis. Here we report one case of a patient with hepatolithiasis with biliary ascariasis who developed a liver abscess, which was treated with partial hepatectomy. CASE PRESENTATION: A young adult female presented with epigastric pain and vomiting with repeated attacks of cholangitis. ERCP showed evidence of multiple intrahepatic calculi with the development of abscess in the left lobe of liver. The patient underwent partial hepatectomy and was found to have biliary ascariasis on histology. She was treated with antihelmenthic therapy and has had an uneventful postoperative period of 2 years. CONCLUSION: Biliary ascariasis with hepatolithiasis, although rare, should be considered in endemic countries.

Hepatic sarcoidosis.

We describe six cases of hepatic sarcoidosis. Clinical presentation was with weight loss, hepatomegaly and abnormal liver function tests. In addition there was fever, itching, splenomegaly and abdominal lymphadenopathy in some. CT scan revealed mediastinal lymphadenopathy in all. Liver biopsy showed noncaseating epithelioid granulomas. Serum angiotensin converting enzyme was elevated in four cases. All patients had received anti-tuberculosis treatment with clinical diagnosis of hepatic tuberculosis. None of them improved, while some showed clinical deterioration. All patients responded to corticosteroids with disappearance of symptoms and normalization of liver function tests.

Extrahepatic manifestations of viral hepatitis.

UNLABELLED: Viral hepatitis has been shown to be associated with various extrahepatic manifestations. These can be seen in both acute and chronic liver disease, may precede or follow overt liver disease. AIMS AND OBJECTS: To study the prevalence of extrahepatic manifestations of viral hepatitis and follow the course of the disease in response to antiviral therapy whenever indicated. METHODS: Prospectively 448 patients of viral hepatitis were evaluated for extrahepatic manifestations and patients of glomerulonephritis (GN), polyarteritis nodosa (PAN) and cryoglobulinemia were tested for viral markers. All patients were investigated for liver and kidney function tests, hematological workup and viral markers such as HBsAg, HBeAg, Anti HBeAg, HCV RNA, IgM anti HAV and IgM anti HEV. Serum electrophoresis and kidney biopsies were done whenever indicated. In 10 cases of hepatitis B glomerulonephritis immunohistochemistry was done on kidney biopsies for demonstration of hepatitis B surface and core antigen. RESULTS: Of total 448 cases 181 (40.4%) had hepatitis B infection, 142 (31.6%) had hepatitis C infection, 86 (19.1%) hepatitis E and 39 (8.7%) had hepatitis A infection. Extrahepatic manifestations were seen in 29 (6.4%) cases and these were cases of GN, PAN, cryoglobulinemia, thrombocytopenia, agranulocytosis, aplastic anemia and pancreatitis. Patients with hepatitis A with extrahepatic manifestations showed complete recovery in both hepatitis and extrahepatic manifestations. Six patients with PAN were treated with interferon of which 4 showed excellent response. Three patients of hepatitis B and hepatitis C related GN were given interferon and 4/6 responded well to treatment. CONCLUSION: Prevalence of extrahepatic manifestations with viral hepatitis was found to be 6.4%. These manifestations recover completely with recovery from viral hepatitis.

Prevalence of short segments of specialized columnar epithelium in distal esophagus: association with gastroesophageal reflux.

BACKGROUND AND AIMS: Recent studies have reported high prevalence rates of short segments of specialized columnar epithelium (SCE) in the distal esophagus. The association of SCE with gastroesophageal reflux disease is not well established. We studied the prevalence and associations of short segments of SCE in the distal esophagus amongst Indians. METHODS: 271 patients (mean age 36 [14] y; 160 men) undergoing diagnostic upper gastrointestinal endoscopy were interviewed regarding symptoms of gastroesophageal reflux, and history of medications, smoking or chewing tobacco and alcohol ingestion. At endoscopy, presence and grade of esophagitis and hiatus hernia were recorded. One biopsy each was taken from the squamocolumnar junction and 2 cm proximal to it. Biopsies were stained with hematoxylin/eosin and alcian blue/periodic acid-Schiff. The pathologist was blinded to the clinical and endoscopic data. RESULTS: Short segments of SCE in the distal esophagus were present in 16/271 (6%; CI 5.03-6.97) patients. Increasing age (p<0.01), and endoscopic (p<0.01) and histologic (p<0.001) esophagitis were associated with its presence, whereas symptoms of gastroesophageal reflux, smoking, tobacco chewing, use of alcohol or non-steroidal anti-inflammatory drugs, and hiatus hernia were not. One patient with SCE had dysplasia. CONCLUSION: Prevalence of short segments of SCE in the distal esophagus amongst Indians is low and is usually associated with inflammation in the esophagus.

Neuroendocrine differentiation in hepatocellular carcinoma.

A patient with hepatocellular carcinoma with neuroendocrine features is reported. Identification of this tumor is essential due to its aggressive behavior and the differences in the treatment and clinical control of the patient.

Nonalcoholic steatohepatitis: clinicopathological profile.

AIMS: To evaluate clinicopathological spectrum of nonalcoholic steatohepatitis (NASH) METHODOLOGY: Total 210 patients with chronic liver disease were evaluated. Detailed history has taken with clinical examination, laboratory investigations, radiological findings and liver biopsy whenever possible. RESULTS: From 210 patients of chronic liver disease, 13 (6.19%) were diagnosed to have NASH (M:F = 9:4, age range 37-72 years, mean age 55.4 +/- 9 years). Of 13 patients, four were referred for asymptomatic enzyme elevation, nine had right hypochondriac pain. Risk factors were diabetes in four cases, obesity four, steroid treatment two and hyperlipidemia in three cases. Laboratory investigations showed abnormal liver enzymes in all the cases. Ultrasonography and CT scan was helpful in predicting fatty liver. Liver biopsy showed steatosis with inflammation in all, fibrosis in two and cirrhosis in one patient. CONCLUSION: NASH is an important form of chronic liver disease, and is characterised by hepatomegaly, elevated liver enzymes. It is essential to diagnose this condition due to its progression to liver fibrosis and cirrhosis in some patients.

Role of autoimmunity in nonviral chronic liver disease.

OBJECTIVE: To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. METHODS: Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. RESULTS: Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50%). CONCLUSION: Autoimmune liver disease is not uncommon in India and should be suspected in all patients with chronic liver disease, especially in non-viral, non-alcoholic, female patients. The diagnosis of AIH should however be made on the composite scoring system given by international group and not only on the presence or absence of autoimmune markers.

Fine needle aspiration cytology of adenomatoid tumor. A case report.

BACKGROUND: Adenomatoid tumor is a benign neoplasm of the male and female genital tract. The epididymis is the most common site. CASE: A 25-year-old male presented with a swelling in the left side of the epididymis. Cytology showed monotonous cells arranged in sheets, cords and glandular patterns. The cell showed eccentric vesicular nuclei with fine chromatin and abundant, vacuolated cytoplasm. CONCLUSION: With the help of fine needle aspiration cytology, an accurate diagnosis of adenomatoid tumor is possible and can relieve anxiety and uncertainty in both the patient and physician.

Barrett's esophagus.

Contrary to earlier definition of Barrett's oesophagus which referred to the presence of metaplastic columnar epithelium of either gastric or intestinal type, the new definition lays stress on presence of specialised columnar epithelium (SEC) with goblet cells. Hence this study was carried out to determine the frequency of specialised columnar epithelium in Indian population. 150 cases of dyspepsia underwent esophagogatro duodenoscopy with esophageal biopsy. Slides were stained with routine H and E stain and alcian blue-PAS stain. Histologically, esophagitis was found in 75 (50%) and columnar epithelium-gastric type in 63 (42%) cases only 4 (2.6%) cases showed presence of specialised columnar epithelium which were labelled as Barrett's esophagus, giving an incidence of 2.6% in this study.