Intraductal papillary neoplasm of the bile duct: A case report of a rare tumor with a brief review of literature.

INTRODUCTION AND IMPORTANCE: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare neoplasm, mostly found in patients from far Eastern areas where hepatolithiasis and clonorchiasis are endemic. Very few cases are reported from India. CASE PRESENTATION: We present a case of recurrent cholangitis in a 59-year-old male, initially suspected to have IPNB based on preoperative imaging. Confirmation occurred intraoperatively, with mucin-filled bile ducts and papillary lesions in the resected hepatic duct. Treatment included left hepatectomy, extrahepatic bile duct excision, and Roux-en-Y hepaticojejunostomy. Histopathology indicated invasive pancreatobiliary-type IPNB with clear margins. The patient experienced post-hepatectomy hepatic insufficiency and superficial incisional surgical site wound infection, managed conservatively. Discharge occurred on postoperative day 21, with satisfactory recovery at the 16-month follow-up. CLINICAL DISCUSSION: IPNB is recognized as the biliary equivalent of intraductal papillary mucinous neoplasm, as these two conditions exhibit multiple commonalities in terms of clinical and histopathological characteristics. The unique aspect of our case lies in the intricacies associated with its diagnosis. Initially, imaging modalities did not yield a definitive characterization of the lesion. Notably, the endoscopist misinterpreted mucin expression emanating from the papilla as purulent material, primarily due to the patient's concurrent cholangitis. Subsequent repetitions of both CT scan and MRI provided some valuable insights that contributed to the diagnostic clarity of the IPNB. CONCLUSION: In cases of symptoms like biliary obstruction with bile duct dilation, wall nodules, papillary/solid-cystic masses, and upstream-downstream dilation, IPNB should be considered. Striving for R0 resection is crucial for enhanced long-term patient survival.

Differentiating biliary atresia from other causes of infantile cholestasis: An appraisal of the histomorphological changes on liver biopsy.

Background: Cholestatic disorders are a significant cause of morbidity and mortality in infants. Characterization of these disorders and differentiating biliary atresia (BA) from other causes of intrahepatic cholestasis is an age-old problem. Objectives: To study the spectrum of different infantile cholestatic disorders in our population, to differentiate BA from other causes of neonatal cholestasis (NC) on a liver biopsy, and validation of the available scoring system for the characterization of these disorders. Materials and Methods: This is an observational cross-sectional study performed over a period of 3 years between 2018 and 2021, done on neonates and infants presenting with cholestatic jaundice. The changes on liver biopsy were evaluated by different histological parameters and available scoring systems to differentiate BA from non-BA causes. Correlation with clinical, biochemical, and imaging findings was done in all cases. Results: This study included 87 cases of NC, of which BA comprised 28 cases (32%), whereas idiopathic neonatal hepatitis (INH) comprised only 12 cases (14%). Portal neutrophilic inflammation (P = 0.000053), ductal cholestasis (P < 0.001), neoductular bile plugs (P < 0.001) and bile ductular proliferation (P < 0.0001) were significantly more in BA, whereas lobular lymphocytic inflammation (P = 0.001) and giant cell transformation of hepatocytes (P = 0.0024) were more frequent in the non-BA group. Using the Lee and Looi scoring system, a histologic score ≥7 was helpful in identifying BA with 85.7% sensitivity, 92.6% specificity, and 90.6% accuracy. Conclusion: BA is the commonest cause of NC in neonates, whereas the frequency of INH is declining. Detailed histomorphologic analysis of liver biopsy, aided with IHC, is the cornerstone for the diagnosis of these disorders.

Primary hepatic leiomyosarcoma masquerading as focal nodular hyperplasia of liver: A wolf in sheep's clothing.

ABSTRACT: Primary hepatic leiomyosarcoma is a rare hepatic malignancy which requires exclusion of other primary site of origin. Clinical presentation and imaging of this tumor is nonspecific and mimics many other hepatic neoplasms. A 62-year-old female patient presents here with right hepatic mass with insidious onset and radiological features favoring a benign solid lesion suggestive of focal nodular hyperplasia. On right hepatectomy, an encapsulated mass identified about 11 cm in maximum dimension with pushing margin and central scar-like area. Histopathological examination reveals a spindle cell tumor and panel of immunohistochemical markers is required to distinguish it from other morphological mimickers. Diagnosis of primary hepatic leiomyosarcoma requires histopathology along with immunohistochemical examination. It is thus advisable to do preoperative biopsy with immunohistochemistry in all patients having atypical imaging and clinical features.

Multifaceted Defects in Monocytes in Different Phases of Chronic Hepatitis B Virus Infection: Lack of Restoration after Antiviral Therapy.

Monocytes play an important role in the control of microbial infection, but monocyte biology during chronic hepatitis B virus (HBV) infection (CHI) remains inadequately studied. We investigated the frequency, phenotype, and functions of monocyte subsets in different phases of CHI, namely, immune tolerance (IT), hepatitis B early antigen (HBeAg)-positive/HBeAg-negative chronic hepatitis B (EP-/EN-CHB, respectively), and inactive carrier (IC), identified factors responsible for their functional alterations, and determined the impact of antiviral therapy on these cells. Flow cytometric analysis indicated that HLA-DR+ CD14++ CD16- classical monocytes were significantly reduced while HLA-DR+ CD14++ CD16+ intermediate and HLA-DR+ CD14+ CD16++ nonclassical monocytes were expanded in IT and EP-/EN-CHB compared with those in IC and healthy controls (HC). In comparison to IC/HC, monocytes in IT and CHB exhibited diminished expression of Toll-like receptor 2 (TLR-2)/TLR-4/TLR-9 and cytokines interleukin-12 (IL-12)/tumor necrosis factor alpha (TNF-α)/IL-6 but produced higher levels of IL-10/transforming growth factor ß (TGF-ß). Further, monocytes in CHB/IT showed impaired phagocytosis and oxidative response relative to those in IC/HC. In vitro assays indicated that high titers of hepatitis B surface antigen (HBsAg) present in IT/CHB and of IL-4 in CHB triggered the functional defects in monocytes via induction of ß-catenin. Additionally, monocyte-derived M1 macrophages of CHB/IT produced fewer proinflammatory and more anti-inflammatory cytokines than those of IC/HC, while in CHB/IT, the monocytes skewed the differentiation of CD4+ T cells more toward regulatory T cells and a Th2 phenotype. Moreover, monocytes in CHB and IT overexpressed chemokine receptor CCR2, which coincided with increased intrahepatic accumulation of ß-catenin+ CD14+ cells. One year of tenofovir therapy failed to normalize monocyte functions or reduce serum HBsAg/IL-4 levels. Taken together, monocytes are functionally perturbed mostly in IT and EP-/EN-CHB phases. Targeting intramonocytic ß-catenin or reducing HBsAg/IL-4 levels might restore monocyte function and facilitate viral clearance. IMPORTANCE Chronic HBV infection (CHI) is a major cause of end-stage liver disease for which pharmacological treatments currently available are inadequate. Chronically HBV-infected patients fail to mount an efficient immune response to the virus, impeding viral clearance and recovery from hepatitis. Monocytes represent a central part of innate immunity, but a comprehensive understanding on monocyte involvement in CHI is still lacking. We here report a multitude of defects in monocytes in chronically HBV-infected patients that include alteration in subset distribution, Toll-like receptor expression, cytokine production, phagocytic activity, oxidative response, migratory ability, polarization of monocyte-derived macrophages, and monocyte-T-cell interaction. We demonstrated that high levels of hepatitis B virus surface antigen and IL-4 potentiate these defects in monocytes via ß-catenin induction while therapy with the nucleotide analog tenofovir fails to restore monocyte function. Our findings add to the continuing effort to devise new immunotherapeutic strategies that could reverse the immune defects in CHI.

Outcome of Whipple's procedure for Groove pancreatitis: A retrospective cross-sectional study.

Background: Groove pancreatitis (GP) is a rare form of chronic pancreatitis primarily affecting the pancreatoduodenal groove. Very few studies have been published from India. The aim of the present study is to report our experience with Whipple's procedure for GP. Methodology: In this cross-sectional study, data of all patients who underwent Whipple's procedure for GP between August 2007 and July 2021 were retrospectively reviewed. Results: Of the total 504 Whipple's procedures, histopathologically proven GP was identified in 9 patients. All of them were male. Mean age at presentation was 42.66 ± 4.35 years. All of them had history of alcohol abuse. Eight (88.8%) of them had history of smoking. Postprandial abdominal discomfort and pain (n = 9, 100%) was the most common presenting symptom. Three (33.3%) patients had solid variety and six (66.6%) patients had cystic dystrophy of the duodenal wall. Two (22.2%) patients had mass in the head of the pancreas which was thought to be malignant. None of the patients underwent prior endoscopic management (stenting). Duration of surgery and blood loss was 330 (range, 300-379) minutes, and 250 (range, 200-750) ml respectively. There was no postoperative mortality. Postoperative complications developed in 5 (55.5%) patients. All the complications were managed conservatively. Median postoperative hospital stay was 10 (range, 9-16) days. Over a median follow-up of 41 (range, 12-120) months, complete remission of symptoms was achieved in 7 (78%) patients. Conclusion: Whipple's procedure is safe with acceptable perioperative outcomes and good long-term symptom control.

Clinical profile and outcome of solid pseudopapillary neoplasm of the pancreas: A retrospective study on 28 patients.

BACKGROUND: Solid pseudopapillary neoplasms (SPN) of the pancreas are rare tumors accounting for 0.9-2.7% of all exocrine pancreatic tumors. Very few studies comprising of more than 10 patients have been published. The aim of the present study is to report on our experience with SPNs over a period of 14 years from a tertiary center of Eastern India. METHODOLOGY: Data of all patients whose histopathology reports of surgically resected specimen confirmed SPN were retrospectively reviewed in the present study. RESULTS: Twenty-eight patients had a pathologically confirmed diagnosis of SPN. Twenty-five (89.3%) patients were females with a median age of 26 (15-45) years. Abdominal pain (89.2%) was the most common presenting symptom. Abdominal mass was palpable in 12 (42.8%) patients. The mean size of the tumor was 9.03 cm (range, 4-25 cm). The most common location of the tumor was in the body and tail of pancreas (35.7%). The most commonly performed operation was distal pancreaticosplenectomy (n = 17, 60.7%), followed by Whipple's procedure (n = 8, 28.5%). Thirty postoperative complications developed in 23 (82.1%) patients. The operative mortality was 3.5% (n = 1). The median hospital stay was 10 (5-25) days. Over a median follow-up period of 36 months (range), no patient developed recurrence. CONCLUSION: Although the size of tumor was quite large at the time of initial presentation, complete surgical resection was possible in all the patients. In experienced hand, surgery can be performed with acceptable perioperative mortality and excellent long-term outcomes.

Extrahepatic mucinous biliary cystadenoma: A rare cause of gastric outlet obstruction.

Extrahepatic mucinous biliary cystadenoma is an extremely rare clinical entity that can present with varieties of vague clinical signs and symptoms. Gastric outlet obstruction caused due to this has never been reported before. We highlighted the diagnostic dilemma we faced when radiological investigations could not suggest the accurate organ of origin.

Diverse facets of MDSC in different phases of chronic HBV infection: Impact on HBV-specific T-cell response and homing.

BACKGROUND AND AIMS: Chronic HBV infection (CHI) is associated with a diverse natural history that includes immune-tolerant (IT), HBeAg-positive chronic hepatitis B (CHB) (EP-CHB), inactive carrier, and HBeAg-negative CHB (EN-CHB) phases. A hallmark of CHI is impairment of HBV-specific T-cell response. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as key regulator of T cells, and their properties are sculpted by their microenvironment. Here, we investigated the distinctive features of MDSCs during CHI, identified factors responsible for their functional discrepancies, and studied their impact on HBV-specific T-cell response and homing. Influence of antiviral therapy on MDSC profile and T-cell response was also assessed. APPROACH AND RESULTS: Flow cytometric analysis indicated that MDSCs in EP-CHB/EN-CHB patients had profound suppressive ability, expressing arginase 1 (Arg1)/inducible nitric oxide synthase (iNOS)/programmed death ligand 1 (PD-L1)/cytotoxic T lymphocyte-associated protein 4 (CTLA-4)/CD40 at significantly greater levels relative to healthy controls (HC). However, in IT, only Arg1+ MDSCs and in inactive carrier, iNOS+ and PD-L1+ MDSCs were higher than HC. In vitro assays demonstrated that high HBsAg titer in IT/CHB induced Arg1+ MDSC. Furthermore, elevated serum TNF-α and IL-4 in CHB potentiated Arg1/PD-L1/CD40/CTLA-4 expression, whereas increased IL-1ß in CHB/IC triggered the expansion of PD-L1+ MDSCs and iNOS+ MDSCs. MDSCs, sorted from CHB/IC, greatly attenuated IL-2/interferon gamma (IFN-γ) production by HBV-specific CD8+ /CD4+ T cells, the effect being more pronounced in CHB. However, MDSCs of IT minimally affected the cytokine production by T cells. Adding Arg1-/iNOS-inhibitor restored only IFN-γ production, while neutralizing PD-L1 recovered both IL-2 and IFN-γ secretion by T cells. Moreover, MDSCs from IT/CHB disrupted virus-specific T-cell trafficking by down-regulating chemokine receptor type 5 on them via TGF-ß signaling. One year of tenofovir therapy failed to normalize MDSC phenotype and HBV-specific T-cell response. CONCLUSIONS: Diversity of MDSCs during CHI affects HBV-specific T-cell response and homing. Hence, therapeutic targeting of MDSCs could boost anti-HBV immunity.

Surgical Outcome of Brunner's Gland Hamartoma: A Single-Centre Experience.

Introduction Brunner's gland hamartomas (BGH) are rare benign lesions with an incidence of <0.01%, accounting for 5 to 10% of all benign tumors of the duodenum. It requires expeditious management by a multidisciplinary team. The aim of the study is to report our experience with surgery for BGH. Methodology Data of all patients who underwent surgical intervention for duodenal polypoidal mass between August 2007 and March 2020 were retrieved from our prospectively maintained gastrointestinal (GI) surgery database. All patients whose histopathology report of the resected specimen confirmed BGH ( n = 9) were included in the present study. Other pathological diagnosis like duodenal lipoma ( n = 2), ganglioneuroma ( n = 1), adenoma ( n = 10), and adenocarcinoma ( n = 4) were excluded. Results Nine patients had confirmatory histopathological diagnosis of BGH and met our inclusion criteria. Three (33.3%) of them were men with a median age of 45 (range: 24-61) years. The median interval between onset of symptoms and diagnosis of duodenal polyp was 14 (range: 4-180) days. Five patients (55.5%) presented with upper GI hemorrhage. Three (33.3%) patients presented with abdominal pain, and one (11.1%) patient presented with episodes of bilious vomiting. Diagnostic endoscopy could detect the lesion in all (100%) patients. Contrast-enhanced computed tomography detected duodenal polypoidal lesion in five (55.5%) patients. The mean size of tumor was 4.78 ± 1.36 cm. These lesions were symptomatic in all the patients and warranted intervention. In view of failed endoscopic intervention ( n = 7, 77.7%), or extramural extension of the tumor ( n = 2, 22.2%), surgical intervention was considered. Most commonly performed operation was duodenal polypectomy ( n = 6, 66.6%). Three postoperative complications developed in two (22.2%) patients. There was no surgery-related mortality. After a median follow-up of 60 (12 -78) months, no patient developed GI bleed or intestinal obstruction. Conclusion In this study, the clinical profile of BGH was explored from the surgeon's point of view. Although endoscopic management is the first-line treatment, surgery plays an important role, particularly, if this fails or is not feasible. In experienced hand, surgery can be performed with acceptable perioperative morbidity and mortality and long-term satisfactory outcomes.

Immunohistochemistry as a Surrogate Marker of Underlying Molecular Derangements in Sporadic Colorectal Carcinoma in Children - A Series of Three Cases.

Background: Colorectal carcinomas (CRCs) are uncommon tumors in children. Here, we elucidate three cases of childhood CRCs with their underlying molecular derangements using immunohistochemistry (IHC) with emphasis on BRAF mutation. Case summary: All three CRCs were sporadic tumors involving the left colon with two of them having a mucinous phenotype. We performed IHC for BRAF, p53 and ß-catenin along with markers of microsatellite instability (MSI) in all three tumors. All the tumors had diffuse strong cytoplasmic BRAF positivity, with focal p53 positivity in two cases and cytoplasmic ß-catenin staining in one case. One case showed CpG island hypermethylation with isolated loss of PMS2 staining. None of the cases had any family history of CRC. Conclusions: IHC can be used as a surrogate marker for determining the underlying molecular derangements in CRC. Sporadic CRCs in children are a cumulative effect of multiple mutations, of which BRAF mutation is significant and critical for planning targeted therapy.

Abdominal tuberculosis: Clinical profile and outcome.

Background: Tuberculosis (TB) is common form of communicable disease in India. Abdominal TB is one of the most common yet misdiagnosed forms of extrapulmonary TB. It is missed due to its similarity to other conditions such as Crohn's disease and nonspecific clinical presentation. Methods: Medical records of 317 patients who were diagnosed with abdominal TB from August 2015 to December 2020 were reviewed retrospectively from our prospectively maintained database. Results: Among 317 patients, 167 (52.7%) were male. Median age of presentation was 45 (8-85) years. Luminal involvement was seen in most of the patients (n = 157, 49.5%), followed by peritoneal (n = 63, 19.8%), mixed (n = 42, 13.2%), solid visceral (n = 30, 9.4%), and nodal (n = 25, 7.8%) involvement. Two hundred and sixty-one (82.3%) showed complete response. Seven (2.2%) patients died and 5 (1.6%) patients lost to follow-up. Median duration of treatment was 28 (25-52) weeks. Drug-induced liver injury was identified in 30 (9.5%) patients. Median follow-up duration was 32 (1-70) months. Conclusion: Abdominal TB is quite a diagnostic challenge due its vague clinical symptoms, nonspecific radiological features, and poor sensitivity and specificity of diagnostic tests. Hence, clinicians should have a high index of suspicion to diagnose and treat this treatable yet lethal condition promptly. Most cases respond very well to medical management and a small fraction requires surgical intervention if diagnosed early.

A combination of circulating microRNA-375-3p and chemokines CCL11, CXCL12, and G-CSF differentiate Crohn's disease and intestinal tuberculosis.

Differentiation of Crohn's disease (CD) from intestinal tuberculosis (ITB) is a big challenge to gastroenterologists because of their indistinguishable features and insensitive diagnostic tools. A non-invasive biomarker is urgently required to distinguish ITB/CD patients particularly in India, a TB endemic region, where CD frequency is increasing rapidly due to urbanization. Among the three differentially expressed miRNAs obtained from small RNA transcriptomic profiling of ileocaecal/terminal ileal tissue of ITB/CD patients (n = 3), only two down-regulated miRNAs, miR-31-5p, and miR-215-5p showed comparable data in qRT-PCR. Out of which, only miR-215-5p was detectable in the patient's plasma, but there was no significant difference in expression between ITB/CD. On the other hand, miR-375-3p, the pulmonary TB specific marker was found in higher amount in the plasma of ITB patients than CD while reverse expression was observed in the ileocaecal/terminal ileal tissues of the same patients. Next, using Bioplex pro-human cytokine 48-plex screening panel, only three chemokines, Eotaxin-1/CCL11, SDF-1α/CXCL12, and G-CSF have noted significantly different levels in the serum of ITB/CD patients. ROC analysis has revealed that compared to a single molecule, a combination of miR-375-3p + Eotaxin-1/CCL11 + SDF-1α /CXCL12 + G-CSF showed a better AUC of 0.83, 95% CI (0.69-0.96) with 100% specificity and positive predictive value while sensitivity, negative predictive value, and accuracy were 56%, 69%, and 78% respectively in distinguishing ITB from CD. This study suggests that a combination of plasma markers shows better potential in differentiating ITB from CD than a single marker and this panel of markers may be used for clinical management of ITB/CD patients.

Mixed neuroendocrine-non-neuroendocrine tumour of pancreas mimicking groove pancreatitis: Case report.

INTRODUCTION: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare tumour of the pancreas which can mimic groove pancreatitis. CASE REPORT: We present a 49-year-old Indian male presented with constant, dull-aching epigastric pain for last 6 months radiating to back, not associated with jaundice, gastrointestinal bleed, fever or weight loss. He also had history of alcohol abuse for last 15 years. Physical examination was unremarkable. Laboratory investigations were within normal limits. Contrast enhanced computed tomography (CT) of the abdomen was suggestive of groove pancreatitis. CA 19.9, CEA and IgG4 levels were normal. Upper gastrointestinal endoscopy revealed an oedematous mucosa with narrowing of second part of duodenum. Endoscopic ultrasound (EUS) showed bulky pancreas with ill-defined heteroechoic head with periduodenal soft tissue thickening. EUS guided fine needle aspiration revealed chronic inflammatory cells. Based on the endoscopic findings and imaging, we suspected the diagnosis to be groove pancreatitis. He underwent open Whipple's pancreaticoduodenectomy. Histopathological evaluation revealed well differentiated neuroendocrine tumour and immunohistochemistry revealed features which was consistent with mixed neuroendocrine-non-neuroendocrine tumour (MiNEN). Post-operative period was uneventful and he was discharged on post-op day 7. A PET-CT scan was done to look for any silent metastasis and it was negative. He recieved 4 cycles of cisplatin-based chemotherapy. He was symptom free and doing well on 12 months follow up with no evidence of recurrence in surveillance CT imaging. DISCUSSION: Pancreatic MiNEN is characterised by presence of two malignant tissues, adenocarcinoma and NET, with one constituent involving at least 30% of the tumour. We report the pitfalls in diagnostic work-up which can lead to misdiagnosis of this rare entity. Specially due to admixture of different kinds of tissue, radiological investigations can be misleading. CONCLUSION: Our case highlights the fact that MiNEN of pancreas can mimic a benign condition like groove pancreatitis. If routine histopathological and immunohistochemical evaluation is not done on the resected samples, relying on radiological and fine-needle aspiration cytology evidences, the actual diagnosis could be missed.

Primary tubercular granulomatous hepatitis presenting as fluctuating jaundice.

Granulomatous hepatitis is an uncommon presentation of tuberculosis (TB). It is even more peculiar to have TB confined to the liver alone with no pulmonary or a disseminated form. In either form, there is the usual presentation of nonprogressive cholestatic jaundice, but no documented case with fluctuating jaundice in the literature was found. In order to highlight this rare presentation aiding the right diagnosis, we present one such case of a 46-year-old woman with no known comorbidities, who complained of fluctuating and painless type of jaundice, associated with fatiguability, pruritus, and weight loss. Preliminary blood investigations showed anemia and cholestatic pattern of jaundice. Ultrasonography and computed tomography imaging showed hepatomegaly with heterogeneous texture. Magnetic resonance cholangiopancreatography further revealed features of cholecystitis with hepatic ducts near proximal common bile duct showing postinflammatory change. The periampullary region was normal. Sputum acid-fast staining and cartridge-based nucleic acid amplification test were negative. Eventually, liver biopsy was done which showed caseating granulomas with Langhans giant cells. The tissue was abundant in acid-fast bacilli. The patient was started on a 9-month course of first-line Antitubercular treatment (ATT) and responded well. Fluctuating jaundice is a rare and undocumented presentation of primary hepatic TB and can cause diagnostic dilemmas.

Duodenal Ganglioneuroma: A Rare Tumor Causing Upper Gastrointestinal Bleed.

Neuroblastic tumors (NTs) include neuroblastoma, ganglioneuroblastoma, and ganglioneuroma (GN). They are very rare in adults. The Surveillance, Epidemiology, and End Results identified 144 patients ≥20 years old at diagnosis (6.1%) from 1973 to 2002. GNs account for 14% of all localized NT. Since 1957, a total of four cases of GN of the duodenum have been reported. We report a novel case of GN of the periampullary region in the duodenum in a 41-year-old man presenting with chronic upper gastrointestinal bleed. Given the rarity of GNs in this age group and the nonspecificity of radiological features, this diagnosis is often missed until histopathology is done. This may negatively affect the prognosis of an otherwise well-prognosticated disease.

Endoscopic ultrasonographic diagnosis of pancreatic tuberculosis in immunocompetent patients-A case series from eastern India.

Tubercular involvement of pancreas is rare. It presents as a focal lesion of pancreas on cross sectional imaging. Endosonography with fine-needle aspiration (EUS-FNA) is crucial for a timely presurgical diagnosis. A retrospective review was conducted on 117 cases of pancreatic focal mass undergoing EUS-FNA at our institution over a period of 3 years, and 5 cases with pancreatic tuberculosis (TB) were detected. The clinical presentation varied from obstructive jaundice, recurrent acute pancreatitis to incidentaloma of pancreas. All patients received antitubercular therapy and were followed up for at least 6 months. In conclusion, pancreatic tuberculosis is a differential of a pancreatic focal lesion and EUS-FNA is the method for diagnosis of this condition that may obviate surgical exploration.

Massive Upper Gastrointestinal Hemorrhage in Brunner's Gland Hamartoma of Duodenum.

Brunner's gland hamartoma (BGH) is a rare benign small bowel tumor, mostly encountered in the duodenum. Massive upper gastrointestinal (UGI) hemorrhage is an unusual presentation rarely reported in English literature. Symptomatic patients mostly present with features of gastric outlet obstruction, occult bleeding, or intussusception. Herein, we report a case of BGH presenting with overt UGI bleed and features of gastric outlet obstruction. Esophagogastroduodenoscopy revealed a smooth polypoidal swelling in the posterior wall of the duodenal bulb. An endoscopic ultrasound (EUS) guided fine-needle-aspiration was performed, which was inconclusive. Contrast-enhanced computed tomography showed the absence of any extraluminal component of the lesion. Endoscopic polypectomy was attempted but failed due to the broad base of the lesion, and hence the patient was managed by open surgical excision. Histological examination of the resected specimen confirmed the diagnosis to be BGH. The patient had an uneventful recovery and was doing well at the 15-month follow-up. BGH should be considered as a differential diagnosis of a polypoidal lesion of the duodenum. Any lesion larger than 2 cm or symptomatic should be removed either by endoscopic or surgical intervention.

Reciprocal interplay between asporin and decorin: Implications in gastric cancer prognosis.

Effective patient prognosis necessitates identification of novel tumor promoting drivers of gastric cancer (GC) which contribute to worsened conditions by analysing TCGA-gastric adenocarcinoma dataset. Small leucine-rich proteoglycans, asporin (ASPN) and decorin (DCN), play overlapping roles in development and diseases; however, the mechanisms underlying their interplay remain elusive. Here, we investigated the complex interplay of asporin, decorin and their interaction with TGFß in GC tumor and corresponding normal tissues. The mRNA levels, protein expressions and cellular localizations of ASPN and DCN were analyzed using real-time PCR, western blot and immunohistochemistry, respectively. The protein-protein interaction was predicted by in-silico interaction analysis and validated by co-immunoprecipitation assay. The correlations between ASPN and EMT proteins, VEGF and collagen were achieved using western blot analysis. A significant increase in expression of ASPN in tumor tissue vs. normal tissue was observed in both TCGA and our patient cohort. DCN, an effective inhibitor of the TGFß pathway, was negatively correlated with stages of GC. Co-immunoprecipitation demonstrated that DCN binds with TGFß, in normal gastric epithelium, whereas in GC, ASPN preferentially binds TGFß. Possible activation of the canonical TGFß pathway by phosphorylation of SMAD2 in tumor tissues suggests its role as an intracellular tumor promoter. Furthermore, tissues expressing ASPN showed unregulated EMT signalling. Our study uncovers ASPN as a GC-promoting gene and DCN as tumor suppressor, suggesting that ASPN can act as a prognostic marker in GC. For the first time, we describe the physical interaction of TGFß with ASPN in GC and DCN with TGFß in GC and normal gastric epithelium respectively. This study suggests that prevention of ASPN-TGFß interaction or overexpression of DCN could serve as promising therapeutic strategies for GC patients.

Refractory hypoglycaemia in a localised gastrointestinal stromal tumour: Case report.

INTRODUCTION: GIST and NICTH are mesenchymal in origin however there are very few reports of GIST associated with NICTH which is a para neoplastic syndrome, generally diagnosed when a tumour induced hypoglycaemia is noted. CASE PRESENTATION: A 46 years old female with prime complain of awareness of a mass in the upper abdomen was admitted for evaluation and further management. Detailed investigation revealed the mass to be gastrointestinal stromal tumour. On the day of admission patient was found to be hypoglycaemic which didn't resolve even after 10% glucose infusion. A growth hormone releasing peptide-2 (GHRP-2) assay was carried out which showed an excessive reaction of basal growth hormone however corticotropin releasing hormone (CRH) tests were within normal limits. She was suspected to be Non Islet cell tumour hypoglycaemia (NICTH) and hypoglycaemia resolved upon administering dexamethasone. Later she underwent chemotherapy and surgical resection after which her blood sugar levels were within normal limits. DISCUSSION: Expression of big IGF-II on the surface of GIST be it metastatic or nonmetastatic can cause refractory hypoglycaemia and can be fatal if left untreated. CONCLUSION: Clinicians should be aware of refractory hypoglycaemia in patients with large GIST's as glucocorticoid therapy may prove to be extremely useful and lifesaving even before considering any forms of definitive management of the tumour.