Matrix metalloproteinase 7 expression in ampullary carcinoma.

Background: Matrix metalloproteinase 7 (MMP7) has largely been studied in pancreatic cancer which is the most common component of periampullary cancer in the western population. In India, the ampullary carcinoma is seen as the most common periampullary cancer in resected pancreaticoduodenectomies. We aimed to study the expression of MMP7 and its correlation with clinicopathological features in ampullary cancer. Materials and Methods: Consecutive cases of all ampullary cancer in a 3-year period were reviewed for histological differentiation (intestinal and pancreatobiliary) by morphology and immunohistochemistry (CDX2, MUC2, cytokeratin 20 [CK20], MUC1, cytokeratin 7 [CK7], and cytokeratin 17 [CK17]). All cases were stained for MMP7 and expression was correlated with histological variables, differentiation, and overall survival. Results: There were a total of 91 ampullary carcinomas (36 intestinal, 44 pancreatobiliary and 6 other types). Ampullary carcinoma showed MMP7 expression in 63.7% cases. Two-third of intestinal type and half of the pancreatobiliary type cancers showed MMP7 expression. MMP7 expression was signifi cantly higher in low pathological T-stage of total ampullary carcinomas; however, it was seen more commonly in higher overall stage of the pancreatobiliary type compared to intestinal type of ampullary carcinoma. Overall survival in patients with MMP7 expression was lower compared to MMP7 negative patients. Conclusions: This is the fi rst study on MMP7 expression in ampullary cancer. MMP7 expression was seen in nearly 64 % of ampullary cancer and showed a signifi cant correlation with low pathological (T-) stage and high overall stage with a shorter survival. MMP7 can be explored as a target for MMP inhibitor therapy in the future.

Mutation profiling in gallbladder cancer in Indian population.

Aim: Gallbladder cancer is an aggressive malignancy usually diagnosed at late stage. The molecular genetics of this cancer is heterogeneous and not well established. Mutation profi ling of gallbladder cancer was performed through massarray technology with an aim to identify molecular markers involved in the tumor pathogenesis that can be helpful as markers for early diagnosis and targets for therapy. Materials and Methods: Forty nine cases of gallbladder cancer were screened through Sequenom Massarray technology for 390 mutations across 30 genes in formalin fi xed paraffi n embedded archived tissues and the results of mutation profi ling was correlated with tumor characteristics. Mutations were observed in 9 of 49 cases across four genes – TP53 (four cases), CTNNB1 (two cases), PIK3CA (two cases), and KRAS (one case). Six of these cases were well differentiated but of eight of them belonged to stage II to IV disease. Six cases had associated gallstones. Conclusion: The mutation frequency found in gallbladder cancer is comparable to the data available in literature. Identifi cation of PIK3CA and KRAS mutations would help in formulating more effi cacious targeted approach for management. Studies with large number of cases would help in exploring more targets and better classifi cation of these cancers at genetic level.

Spectrum of adrenal lesions on fine needle aspiration cytology.

Background: Fine needle aspiration (FNA) cytology of adrenal gland is not a commonly performed technique and is limited primarily to tertiary care centers. However, it is a sensitive and specific procedure in the workup of patients with adrenal gland's mass lesions. Though cytomorphological features for various lesions have been described, there are a limited number of studies in cytologic literature. Aims: We report our 7 years of experience in FNAC of adrenal lesions. We have not only described the cytomorphological details of different lesions, but also tried to discuss the various diagnostic difficulties encountered during reporting of adrenal fine needle aspirations. Materials and Methods: All ultrasound-guided percutaneous aspirations of adrenal gland received in the department between the years 2002 and 2009 were reviewed. There were a total of 52 FNA samples of adrenal masses from 35 patients in 7 years. The lesions were categorized as non-neoplastic and neoplastic categories. Neoplastic lesions were further divided into benign and malignant lesions. Results: In our study, FNA proved to be 100% specific for diagnosing malignant lesions. The overall inadequacy rate was 11.4% with no major complications of the procedure. A wide variety of non-neoplastic as well as neoplastic lesions were identified.

Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease & tropical malabsorption.

Background & objectives: Aetiology of malabsorption syndrome (MAS) differs in tropical and temperate countries over time; clinical and laboratory parameters may differentiate between various causes. This study was undertaken to investigate the spectrum of MAS among Indian adults and to find out the features that may help to differentiate between TM and celiac disease. Methods: Causes of MAS, and factors differentiating tropical malabsorption (TM) from celiac disease (CD) were determined in 275 patients. Results: Using standard criteria, causes in 275 patients [age 37.5+13.2 yr, 170, (61.5%) male] were, TM 101 (37%), CD 53 (19%), small intestinal bacterial overgrowth 28 (10%), AIDS 15 (5.4%), giardiasis 13 (5%), hypogammaglobulinemia 12 (4%), intestinal tuberculosis 7 (2.5%), strongyloidiasis 6 (2%), immunoproliferative small intestinal disease 5 (2%), Crohn's disease 6 (2%), amyloidosis 4 (1.5%), intestinal lymphangiectasia 3 (1%) and unknown 22 (8%). On univariate analysis, patients with CD were younger than TM (30.6+12 vs. 39.3+12.6 yr, P<0.001), had lower body weight (41.3+11.8 vs. 49.9+11.2 kg, P<0.001), longer diarrhoea duration (median 36 inter-quartile range 17.8-120 vs. 24-months, 8-48, P<0.01), lower stool frequency (6/day, 5-8 vs. 8, 5-10, P<0.05), lower haemoglobin (9.4+3.2 vs. 10.4+2.7 g/dl, P<0.05), higher platelet count (2,58,000, range 1,35,500-3,23,500 vs. 1,60,000, 1,26,000-2,58,000/mm3, P<0.05), and more often had hepatomegaly (9/53, 17% vs. 4/101, 4%, P<0.01), and subtotal or partial villous atrophy (36/50, 72% vs. 28/87, 32%, P<0.001). Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were significant on multivariate analysis. Interpretation & conclusions: TM and CD are common causes of MAS among Indian adults. Younger age (<35 yr), longer diarrhoea duration, higher platelet count and villous atrophy were found to be associated with CD.

Role of C-erbB2 expression in gallbladder cancer.

Background: Gallbladder cancer (GBC) is a lethal malignancy presenting at an advanced stage. The pathogenesis is not well categorized, and surgery is the only treatment available at the early stage of the disease. There have been few reports on role of growth factor receptors in GBC. C-erbB2 is one such receptor whose over-expression is being explored in GBC as one of the factors involved in carcinogenesis and possible target for therapy. Materials and Methods: One hundred and four consecutive cases of GBC were retrospectively studied with regard to clinical features, histological type, grade and stage of tumor. Immunohistochemistry for C-erbB2 was done and expression was correlated with different clinic-pathological parameters and survival. Results: C-erbB2 overexpression was seen in 9.4% cases with complete staining and both complete and incomplete staining (2+ and 3+) was seen in 13.4% cases. Eighty percent of the C-erbB2 over-expressed cases were well differentiated and in stage II to stage IV disease. Dysplasia adjacent to carcinoma did not show any expression. No correlation was found with tumor grade, stage, gall stones, and patient survival. Xanthogranulomatous inflammation was inversely correlated with C-erbB2 over-expression. Median survival was 30 months in C-erbB2 over-expressed cases, and 12 months in C-erbB2 negative cases. Conclusion: We found complete membranous staining of C-erbB2 in 9.4% of GBC which was frequent in well differentiated and stage II to stage IV tumors. C-erbB2 tumors had longer median survival than C-erbB2 negative tumors. C-erbB2 is not involved early in the carcinogenetic process as none of the dysplasia showed expression. C-erbB2 over-expression may be considered as target for therapy in advanced stage of GBC.

Epstein-Barr virus DNA load and its association with Helicobacter pylori infection in gastroduodenal diseases

Helicobacter pylori and Epstein-Barr virus (EBV) infections are common worldwide. Although H. pylori infection is a major factor in gastroduodenal diseases, its role in association with EBV infection is unknown. Objective: To study the association of H. pylori infection and EBV DNA load in patients with gastroduodenal diseases. Methods: Biopsy samples were collected from 200 adult patients [non-ulcer dyspepsia (NUD) 100, peptic ulcer disease (PUD) 50, gastric carcinoma (GC) 50] undergoing upper gastrointestinal endoscopy. H. pylori infection was diagnosed by rapid urease test, culture, histopathology, PCR and Q-PCR. EBV DNA was detected by non-polymorphic Epstein-Barr nuclear antigen-1 (EBNA-1) gene based Q-PCR. Results: In patients with GC and PUD, EBV DNA was detected more often than NUD (GC versus NUD = 90 percent versus 37 percent, p < 0.001; PUD versus NUD = 70 percent versus 37 percent, p < 0.001). The dual prevalence of H. pylori infection and EBV DNA was significantly higher in patients with GC and PUD than in those with NUD. Median copy number of EBV DNA was considerably higher in GC and PUD than NUD (p < 0.01). The copy number of EBV DNA was significantly higher in H. pylori infected patients (p = 0.015). The number of ureA gene copies was also found to be significantly higher in PUD and NUD with presence of EBV DNA. However, in GC no significant difference was seen between EBV positive and negative status. Conclusion: There was a trend for higher EBV DNA load in H. pylori positive individuals suggesting a probable role of H. pylori in modulating the conversion of EBV to its lytic phase.

Serological assessment of gastric intestinal metaplasia and atrophy using pepsinogen-I, pepsinogen-II and gastrin-17 levels in a low incidence area of gastric cancer endemic for H. pylori infection.

Background: Intestinal metaplasia (IM), a precursor of gastric cancer (GC), may be amenable to non-invasive assessment. Aims:We evaluated the diagnostic utility of serum PG-I, PG-II, PG-I/PG-II ratio and gastrin-17 (G-17) to detect IM and atrophy. Methods: The study was conducted at a tertiary care center located in a low-incidence area of GC, endemic for H. pylori infection. Patients with GC and dyspepsia were evaluated by endoscopy, histology for IM (H&E, PAS and Alcian blue stains), gastritis and H. pylori (H&E and Giemsa stains) infection, which was considered to be present if two of three tests (rapid urease test, IgG antibody and histology) were positive. Serum levels of PG-I, PG-II and G-17 were estimated using ELISA. Results: Of 98 patients with GC and 62 with dyspepsia, 35 (36%) and 9 (14%) had IM, respectively (p=0.004). Patients with IM (n=44) had lower PG-I/PG-II ratio than those without IM (n=116; median 4.4, 0.37-23.6 vs. 6.3, 0.19-38.6, respectively; p=0.005). A cut-off value of PG-I/PG-II ratio of 6.0 had 64% sensitivity and 52% specificity for detecting IM (area under ROC curve 0.64). 26/44 (60%) patients with IM and 52/98 (53%) with GC had PG-I/PG-II ratio <6. Serum G-17 was comparable among patients with and without IM. Conclusions: Though PG-I/PG-II ratio was lower in patients with IM, only 60% had a lower ratio suggesting that this test and G-17 may not be useful to detect IM in a low-incidence area of GC, endemic for H. pylori infection.

Patients with Helicobacter pylori infection have less severe gastroesophageal reflux disease: a study using endoscopy, 24-hour gastric and esophageal pH metry.

Background and aim The relationship between gastroesophageal reflux disease (GERD) and Helicobacter pylori is controversial. We evaluated endoscopic, 24-h gastric and esophageal acid profile among patients with GERD in relation to H. pylori, as the latter might alter gastric acid secretion. Methods Patients with GERD (n=123), who were not on acid-suppressive drugs, and had not received anti-H. pylori therapy, underwent gastroduodenoscopy and tests for H. pylori detection. Esophageal manometry, 24-h pH metry, serum pepsinogen-I (PG-I), PG-II and gastrin-17 ELISA were done in all these patients. Univariate and multivariate analyses were performed to assess independent predictors for erosive esophagitis (EE). Results Of 123 patients (mean age 40.5 [13.1] years, 85 [69.1%] men), 59 (47.9%) had H. pylori infection. EE was more common in H. pylori non-infected than infected (49 vs. 32, p<0.001). Among patients older than 40 years, absence of H. pylori was associated with lower esophageal pH and longer reflux (p=0.02 and p<0.001, respectively). PG-I/PG-II ratio was lower in H. pylori infected subjects (p <0.001). In patients with higher LA grade of esophagitis, elevated PG-I levels and PG-I/PG-II ratio were associated with more acidic stomach (p=0.04 and p=0.01, respectively). Multivariate analyses showed low gastrin-17 (p=0.016), higher age (p=0.013), hiatus hernia (p=0.004) and absence of H. pylori (p=0.03) were independent predictors for risk of EE. Conclusion H. pylori infection is associated with less acidic stomach and less severe GERD. Low gastrin-17, higher age, hiatus hernia and absence of H. pylori were the best predictors for EE risk.

Meningeal chondroma in a young female.

Meningeal chondroma is a rare intracranial neoplasm. It is usually diagnosed clinically as meningioma. Histologically it may have a differential diagnosis of chordoid meningioma, a malignant lesion, and needs radiotherapy. A chondroma is a benign lesion where surgical removal is the treatment. A 20-year-old female presented with symptoms of space occupying lesion which was clinically and radiologically considered meningioma. On histopathology, the lesion turned out to be a chondroma. Meningeal chondroma is a benign lesion for which surgical removal is the curative treatment. No further treatment in the form of radiation is required.

Gliosarcoma: an audit from a single institution in India of 24 post-irradiated cases over 15 years.

BACKGROUND: Gliosarcomas (GS) are biphasic brain tumors composed of glioblastoma multiforme (GBM) and sarcomatous component. Therapeutic approaches include maximum surgical decompression with postoperative radiotherapy. Outcomes in gliosarcoma are poor despite multimodality management. AIMS: To analyze the outcome in patients of GS treated in our institute over a period of 15 years and compare it with GBM treated during the same period. SETTINGS AND DESIGN: Clinical records of the post-irradiated GS patients and GBM patients seen between 1990 and 2004 were retrieved. MATERIALS AND METHODS: Demographic and treatment variables were evaluated for their influence on overall survival (OS). The survival outcomes of GBM and GS treated during the same period were also compared. STATISTICAL ANALYSIS: Univariate analysis was carried out using the Kaplan-Meier method and tested using log-rank test for significance. RESULTS: During these 15 years, 24 evaluable GS patients were treated as compared to 251 evaluable patients of GBM. There was a slight male preponderance in GS (14 males vs.10 females) with a median age of 50 years. All patients underwent surgery followed by post-operative radiotherapy (median dose of 60 Gy). None of the patient or treatment related factors were found to be significantly influencing their OS. Median OS in GS was 7.3 months compared to 7.5 months in GBM patients (P = 0.790). CONCLUSIONS: The OS appears to be similar for GS and GBM. None of the demographic variables appeared to prognosticate the survivals of GS.

Role of IgG anti-beta-lactoglobulin antibody in the diagnosis of cow's milk protein intolerance in India.

OBJECTIVE: Little is known about cow's milk protein intolerance (CMPI) in India. This study was aimed at finding CMPI cases and determining the role of IgG anti-beta-lactoglobulin antibody in the diagnosis of this condition in India. METHODS: From June 2004 to December 2005, 30 children with presumptive diagnosis of CMPI, based on endoscopic rectal or duodenal biopsy showing excess eosinophils and response to milk withdrawal, were enrolled and studied prospectively. Definite diagnosis was made in 20 children on the basis of positive milk challenge. IgG anti-beta-lactoglobulin antibodies were tested in children with CMPI before and after stopping milk and after milk challenge. Antibody levels were also studied in 27 age-matched disease controls and 50 healthy adults. RESULTS: The median age of 20 children (16 boys) with CMPI was 16.5 (6-36) months. Of them, 18 presented with diarrhea (12 bloody) and 2 had rectal bleeding. The presumptive diagnosis was most often (85%) based on colonic or rectal biopsy findings. Rectal biopsy was diagnostic in all 20 cases irrespective of the mode of presentation compared with duodenal biopsy which was diagnostic in 3 cases (p< 0.0001). There was no difference in antibody levels between cases and controls; the antibody level decreased significantly after milk withdrawal (p< 0.005), but did not rise significantly after milk re-challenge. CONCLUSIONS: CMPI is a common cause of chronic diarrhea in children in northern India. Sigmoidoscopy and rectal biopsy help in establishing the diagnosis in most cases. IgG anti-lactoglobulin antibody test is not useful in diagnosing CMPI in the Indian setting.

Dubin-Johnson syndrome--a clinicopathologic study of twenty cases.

Dubin-Johnson syndrome (DJS) is a rare benign chronic disorder of bilirubin metabolism, characterized by conjugated hyperbilirubinemia, darkly pigmented liver and presence of abnormal pigment in hepatic parenchymal cells. This is a retrospective study of twenty cases of DJS highlighting their major clinical and pathological findings. Liver biopsies were available in all the cases, obtained during a fourteen-year period (January 1991 to March 2005). The patients' age ranged from 7-63 years (median 21 years). These twenty cases comprised 13 males and 7 females. Major clinical manifestations were recurrent or persistent jaundice, abdominal pain and fever. Duration of illness ranged from 9 months to 58 years (median 10 years). All of them had conjugated hyberbilirubinemia and total serum bilirubin levels ranged between 1.4-13 mg/dl (mean 4.4 mg/dl). Liver biopsies revealed presence of coarse granular brown pigment in the cytoplasm of hepatocytes more concentrated in the pericanalicular region and more prominent in centrilobular hepatocytes. Associated findings were presence of hepatitis B virus related chronic hepatitis (1), history of tubercular lymphadenitis (1), chronic cholecystitis in (2), coronary heart disease (1) and exacerbation during pregnancy (1).

Oxyphilic cell adenoma of parathyroid resulting in primary hyperparathyroidism and osteitis fibrosa cystica--a case report.

Adenomas of the parathyroid gland, the majority of which are of the solitary chief cell type, are the most frequent cause of primary hyperparathyroidism (pHPT). Parathyroid adenomas composed predominantly or exclusively of oxyphil cells are rare and most oxyphil cell adenomas of this organ remain clinically silent. We present here a case of hyperfunctioning oxyphil cell adenoma of the parathyroid gland resulting in pHPT, osteitis fibrosa cystica and simultaneous bilateral fractures upper shafts of femora.

Role of adjuvant radiotherapy in metaplastic matrix producing breast cancer: a case study with review of literature.

A rare and unique variant of breast cancer--metaplastic matrix producing carcinoma, is presented. Surgery has been the mainstay of treatment. The role of adjuvant postoperative radiotherapy, as has been used in this patient, has been reviewed.

Strongyloides stercoralis infestation in a patient with severe ulcerative colitis.

Asymptomatic infestation with Strongyloides stercoralis, common in the tropics, may result in potentially fatal hyperinfection during treatment with immunosuppressive drugs used to treat patients with severe ulcerative colitis (UC). Hence, importance of early recognition and treatment of this nematode in patients with UC before starting immunosuppressive drugs can not be overemphasized. We report a 23-yrs old man with UC who presented with acute severe attack. Since his UC did not respond to intravenous hydrocortisone over 6 days, oral cyclosporine was started on 7th day after repeating stool microscopy, which revealed larvae of Strongyloides stercoralis. Duodenal aspirate also confirmed presence of multiple larvae. He responded to treatment for Strongyloides stercoralis , continuation of hydrocortisone and cyclosporine. Importance of early diagnosis of infestation with Strongyloides stercoralis while on treatment with immunosuppressive drugs for severe UC is emphasized. Difficulties in diagnosis and management of Strongyloides stercoralis infestation in patients with UC are discussed.

Parotid Gland Enlargement as a Presenting Manifestation of Acute Lymphoblastic Leukemia

A young female presented with symmetric polyarthritis, generalized lymphadenopathy, hepatosplenomegaly and bilateral parotid gland enlargement without sicca symptoms. A second case of 15 months old child presented with short duration pyrexia with generalized lymphadenopathy, hepatosplenomegaly and bilateral parotid gland enlargement. Both the patients had out of proportion anemia on examination. Investigations confirmed CD 10+ B-cell acute lymphoblastic leukemia (ALL) in both the cases. Fine needle aspiration cytology of parotid glands in both the cases showed infiltration by lymphoblasts.We propose that ALL should be included in the differential diagnosis of bilateral parotid gland enlargement especially if associated with lymphadenopathy and hepato-splenomegaly.