Reduced expression of Ankyrin-G and E-cadherin in duodenal mucosal biopsy of subjects with celiac disease.

Confirmatory diagnosis of celiac disease (CD) include histopathology of duodenal biopsy and tissue trans-glutaminase-IgA. Identification of tissue-specific histological markers is warranted to improve the diagnosis. A genetic study in CD identified the association of ankyrin-G that connects E-cadherin with ß2-spectrin in epithelial cells of the duodenal tissue. We attempted to investigate the differential expression of ankyrin-G, E-cadherin and ß2-spectrin in duodenal biopsy of CD subjects compared to non-CD controls. Duodenal tissue was collected from 83 study participants, of which 50 were CD, and 33 were non-CD controls. Whole RNA was isolated from 32 CD and 23 non-CD controls from available tissues, and differential mRNA expression was measured using real-time PCR. Tissue sections from 18 CD cases and 10 non-CD controls were immunostained using monoclonal antibodies. Tissue immunohistochemistry were evaluated for differential expression and pattern of expression. RT-PCR revealed significantly reduced expression of ankyrin-G (fold change=0.63; p=0.03) and E-cadherin (fold change=0.50; p=0.02) among CD subjects compared to non-CD controls. Tissue immunohistochemistry confirmed the reduced expression of ankyrin-G and E-cadherin in CD. Differential expression is grossly limited within the outer columnar epithelial cell layer. Expression fold change of E-cadherin was seen to partially correlate with the serum tTG level (r=0.4; p=0.04). In CD, reduced expression of two key cytoskeletal proteins (ankyrin-G and E-cadherin) in duodenum mucosa was observed, which indicates its implication in disease biology and could be tested as a tissue-specific biomarker for CD. Functional studies may unravel the specific contribution of these proteins in CD pathophysiology.

A duodenal mucosa transcriptome study identified reduced expression of a novel gene CDH18 in celiac disease.

BACKGROUND: Celiac disease (CD) a complex immune disease that affects duodenal mucosa. Identification of tissue specific biomarkers is expected to improve the existing biopsy based CD diagnosis. AIMS: To investigate the differentially expressed genes (DEGs) in duodenal mucosa tissue to identify clinically relevant gene expression pattern in CD. METHODS: Whole RNA extracted from the duodenal biopsies of three CD patients and four non-CD controls were sequenced. Significant DEGs were identified. Prioritized DEGs were validated using qRT-PCR in an independent group (CD=23; Control=26). Enriched pathways were analyzed, protein-protein interaction networks were evaluated. RESULTS: 923 DEGs comprising of 135 up-regulated, and 788 down-regulated genes, with p-value≤0.05; log2FC>2 or <-2 were identified. A novel down-regulated gene CDH18 (p = 0.03; log2FC=-0.74) was identified. Previously known CXCL9 was replicated. CDH18, a trans-membrane protein was found to interact with other CDH proteins, α/ß catenins, and other membrane transporters such as SLC and ABCB. Pathways and protein networks contributing in channel activity (p = 2.15E-12), membrane transporters (p = 2.15E-12), and cellular adhesion (p = 8.05E-6) were identified. CONCLUSIONS: CDH18, a novel DEG identified in the present study is a pivotal gene involved in maintaining epithelial membrane organization and integrity. The functional significance of lower expression of CDH18 in pathogenesis of CD warranted to be investigated. CDH18 expression could be tested for its effectiveness in diagnostic, prognostic and therapeutic purposes.

Prevalence and spectrum of haemoglobinopathies in females of reproductive age group- A first tertiary care center experience in Punjab, North India.

Background: Thalassemia and hemoglobinopathies are a group of inherited conditions characterized by abnormalities in the synthesis or structure of hemoglobin (Hb). According to estimates, approximately 7% of the world population is a carrier of Hb disorders, leading to high morbidity and mortality. To reduce the burden of these highly prevalent monogenic disorders, detecting them in the carrier stage is crucial to prevent disease progression. Aim: We aimed to estimate the prevalence and spectrum of hemoglobinopathies in females in the reproductive (20-40 years) age group. Settings and Design: It was a retrospective observational study carried out for 2.5 years (from January 2018 till June 2020). Materials and Methods: All the females in the age group of 20-40 years age whose blood samples were received in the department for High-Performance Liquid Chromatography (HPLC) were included. The cases with abnormal HPLC findings were analyzed for hematological parameters including hemoglobin, RBC count, and RBC indices [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), & red cell distribution width - coefficient of variation (RDW-CV)]. Statistical Analysis: Statistical package for social science (SPSS) statistics 21 version for Microsoft Windows (Chicago, USA) was used for statistical analysis of data. The data were described in terms of range, mean ± standard deviation (SD), frequencies (number of cases), and relative frequencies (percentage) as appropriate. Results: During the study period, 72.2% of the females were affected with ß-thalassemia trait, followed by HbD Punjab trait (17.8%), HbQ India trait (2.9%), ß-thalassemia major (1.8%), and two cases (1.2%) each of HbS trait, HbD Iran trait, and compound heterozygous of HbD Punjab and ß-thalassaemia, whereas HbE trait, compound heterozygous of HbQ and ß-thalassemia, compound heterozygous of HbJ-variant and ß-thalassemia had one case each (0.6%). Conclusion: Preventive strategies are cost-effective and include population screening, premarital screening, screening of spouses, genetic counseling, and prenatal diagnosis. Educating the carrier females about the potential risk and various screening methods may help in controlling the disease.

Secondary amyloidosis with concomitant gastric GIST and gastric adenocarcinoma - A case report.

Secondary amyloidosis is a well-established entity and has been described in association with chronic inflammatory conditions such as rheumatoid arthritis, ankylosing spondylitis, bronchiectasis, tuberculosis, etc., It has also been reported in association with neoplasms such as Hodgkin's lymphoma, Waldenstrom's macroglobulinemia, renal cell carcinoma, lung carcinoma, etc. However, only a few case reports documenting the association of amyloidosis with gastrointestinal tumor (GIST) and gastric adenocarcinoma are available in the literature. Hereby, we report a case of a 74-year-old male who presented with colicky abdominal pain and vomiting. Ultrasonography revealed a common bile duct (CBD) stone and a small extra-luminal gastric mass. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to remove the CBD stone which revealed an incidental finding of gastric ulcer. A biopsy was taken from the gastric ulcer which on histopathological examination was confirmed as adenocarcinoma leading onto total gastrectomy. During total gastrectomy, an inadvertent injury to the spleen led to simultaneous splenectomy. Multiple samples from the gastric ulcer, the extra-luminal gastric mass, and the spleen were subjected to histopathological examination. Gastric ulcer was confirmed as adenocarcinoma, gastric extra-luminal mass was confirmed as GIST, and splenic examination revealed widespread deposition of amyloid which on Congo-red stain imparted an apple-green birefringence on polarizing microscopy. To the best of our knowledge, this is the first-ever case of such an association where gastric adenocarcinoma occurred with concomitant gastric GIST and secondary amyloidosis of the spleen.

Fibrolamellar hepatocellular carcinoma presenting as cholestatic jaundice: An unusual presentation of a rare disease.

Fibrolamellar hepatocellular carcinoma is a rare primary hepatic tumor that usually occurs in youth. The common presenting features are vague abdominal pain, nausea, vomiting and weight loss. We present a case report of a young male who presented with cholestatic jaundice and on evaluation was diagnosed to have fibrolamellar hepatocellular carcinoma. He underwent successful surgical resection of the tumor. In young individuals presenting with unexplained cholestasis, fibrolamellar hepatocellular carcinoma should be considered.

Distinctive Attributes of Indian Patients With Classical BCR::ABL1 Negative Myeloproliferative Neoplasms: Unified Clinical and Laboratory Data.

INTRODUCTION: We report one of the largest single center data from a mixed referral setting in India describing baseline characteristics and outcomes of patients with classical BCR::ABL1 negative myeloproliferative neoplasms (MPNs). MATERIALS AND METHODS: Patients diagnosed from June 2019 to 2022 were included. Workup and treatment was as per current guidelines. RESULTS: Diagnosis comprised polycythemia vera (PV) in 51(49%), ET in 33(31.7%) and prefibrotic primary myelofibrosis (MF) pre fibrotic myelofibrosis (prePMF) and myelofibrosis in 10(9.6%) patients each. Median age at diagnosis was 52 years for PV and ET, 65.5 for MF and 79 years for prePMF. Diagnosis was incidental in 63(56.7%) and after thrombosis in 8(7.2%) patients. Baseline next generation sequencing (NGS) was available for 63(60.5%) patients. Driver mutations in PV: JAK2 in 80.3%; in ET: JAK2 in 41%, CALR in 26%, MPL in 2.9%; in prePMF JAK2 in 70%, CALR in 20%, MPL in 10%, and in MF: JAK2 in 10%, MPL in 30% and CALR in 40%. Seven novel mutations were detected of which 5 were potentially pathogenic on computational analysis. After median follow up of 30 months, 2 patients had disease transformation and none had new episodes of thrombosis. Ten patients died, most commonly with cardiovascular events(n = 5,50%). Median overall survival was not reached. Mean OS time was 10.19 years(95%CI, 8.6 to 11.74) and mean time to transformation was 12.2 years(95% CI,11.8 to 12.6). CONCLUSION: Our data indicates comparatively indolent presentation of MPNs in India with younger age and lower risk of thrombosis. Further follow up will enable correlation with molecular data and guide modification of age based risk stratification models.

Low prevalence of primary sclerosing cholangitis in patients with inflammatory bowel disease in India.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Limited data exist on PSC in patients with IBD from India. We aimed to assess the prevalence and disease spectrum of PSC in Indian patients with IBD. METHODS: Database of IBD patients at 5 tertiary care IBD centers in India were analyzed retrospectively. Data were extracted and the prevalence of PSC-IBD was calculated. RESULTS: Forty-eight patients out of 12,216 patients with IBD (9,231 UC, 2,939 CD, and 46 IBD unclassified) were identified to have PSC, resulting in a prevalence of 0.39%. The UC to CD ratio was 7:1. Male sex and pancolitis (UC) or colonic CD were more commonly associated with PSC-IBD. The diagnosis of IBD preceded the diagnosis of PSC in most of the patients. Majority of the patients were symptomatic for liver disease at diagnosis. Eight patients (16.66%) developed cirrhosis, 5 patients (10.41%), all UC, developed malignancies (3 colorectal cancer [6.25%] and 2 cholangiocarcinoma [4.16%]), and 3 patients died (2 decompensated liver disease [4.16%] and 1 cholangiocarcinoma [2.08%]) on follow-up. None of the patients mandated surgical therapy for IBD. CONCLUSIONS: Concomitant PSC in patients with IBD is uncommon in India and is associated with lower rates of development of malignancies.

Clinical spectrum of elderly-onset inflammatory bowel disease in India.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India. METHODS: A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD. RESULTS: During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn's disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD. CONCLUSIONS: Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.

Liposarcoma of tongue: A case report.

ABSTRACT: Liposarcoma (LS) is one of the most common malignant tumors. However, oral LS is an extremely rare lesion that is often clinically misdiagnosed as a benign lesion because of its asymptomatic and indolent clinical course. In oral cavity, the tongue is the most frequent site for its occurrence.

Correlation between magnetic resonance enterography and ileo-colonoscopy for assessment of disease activity in terminal ileal Crohn's disease.

BACKGROUND: Magnetic resonance enterography (MRE) has emerged as a novel tool for the assessment of disease activity in Crohn's disease (CD). Real world data from Indian subcontinent on performance of MRE in terminal ileal CD are lacking. METHODS: Retrospective analysis of patients with terminal ileal CD who underwent both ileo-colonoscopy and MRE was performed. Ileo-colonoscopy was considered the gold standard for assessment of disease activity. On ileo-colonoscopy, a simple endoscopic score for Crohn's disease (SES-CD) ≥2 was considered active disease; presence of ulcers indicated severe disease. MRE scoring of the disease activity was performed using magnetic resonance index of activity (MARIA) and simplified MARIA (MARIAs). The measure of agreement between ileo-colonoscopy and MRE and comparison of MARIA and MARIAs for assessment of disease activity and sensitivity of MRE to detect mucosal ulcerations were calculated. RESULTS: Seventy patients with terminal ileal CD (mean age 40.74±15.56 years; 71.4% males [n=50]) were evaluated. The sensitivities of MARIA and MARIAs scores to detect active disease were 0.76 and 0.84, respectively. The area under the receiver operating characteristic curve (AUROC) for detecting severe disease was 0.836 (p<0.0001) for MARIA and 0.861 (p<0.0001) for MARIAs. For mild active disease, there was no agreement between SES-CD and MARIA or MARIAs; however, for severe disease, the agreement was fair and moderate for MARIA and MARIAs, respectively. MARIA and MARIAs were comparable for identification of active and severe disease (κ 0.759, p<0.0001 and κ 0.840, p<0.0001, respectively). MRE was 68.18% sensitive to detect mucosal ulcers. CONCLUSION: MRE is a reliable and sensitive tool for detection of endoscopically severe, but not mild, terminal ileal CD.

Intranasal glioma (Nasal heterotopia): A rare cause of nasal polyp in neonates.

A 3-month-old boy presented with an intranasal polypoidal mass protruding out of the nostril which was present since birth and growing slowly. The mass was non-pulsatile and soft to firm in consistency. It did not increase in size on coughing, crying, or compression of the jugular vein. Magnetic resonance imaging and contrast-enhanced computed tomography (CT) revealed a lobulated well-circumscribed soft tissue mass in the left nasal cavity with no intracranial communication. Complete surgical excision of the mass was carried out via an intranasal endoscopic approach. Histopathological examination confirmed the diagnosis of intranasal glioma.

Isolated pancreatic myeloid sarcoma: A potential mimicker of pancreatic adenocarcinoma.

Myeloid sarcoma (MS) is an extramedullary proliferation of immature myeloid cells which may occur as a progression of myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) and as acute myeloid leukemia (AML) relapse. Rarely may it be de novo. Lymph nodes, skin, lungs, intestine are the commonly involved sites. However, an isolated pancreatic MS is seldom reported in the literature. Herein, we report one such case which was misdiagnosed as pancreatic adenocarcinoma on the clinico-radiological examination which misled us away from preoperative diagnostic sampling, and a Whipple pancreaticoduodenectomy was performed. Histopathological examination in conjunction with immunohistochemistry revealed the final diagnosis of isolated MS of the pancreas. We emphasize that although rare, a clinical suspicion along with preoperative histopathological examination may lead to early diagnosis, targeted management, and a better clinical outcome in such cases.

Case 300: Ruptured Mucinous Cystadenoma of the Pancreas.

History Part one of this case appeared 4 months previously and may contain larger images. A 40-year-old woman presented to the outpatient department of our hospital with a 2-year history of abdominal pain, which had worsened in the past few days. There were no other constitutional symptoms; in particular, there was no weight loss or loss of appetite. The serum amylase and serum lipase levels were always within normal limits, even during the current episode. There was no history of pancreatitis, alcohol abuse, drug use, or trauma. The patient was evaluated at an outside clinic 2 years ago and underwent imaging, including US and dedicated pancreatic CT, which revealed a complex multiseptated noncalcified pancreatic cystic lesion. After CT, the patient underwent endoscopic US, which showed the lesion was suspected to be an infected parasitic cyst; fine-needle aspiration and cytology were not attempted due to the risk of iatrogenic rupture. The patient was advised to undergo surgical resection but declined the procedure and was lost to follow-up for 2 years before her current visit to our facility. On clinical examination, there were no clinically important findings, aside from mild to moderate pain on deep palpation and some shifting dullness that was suggestive of ascites. The patient always remained hemodynamically stable. US-guided ascitic fluid analysis was performed, which revealed amylase levels of 869 IU/L (normal range, 4-234 IU/L). Considering prior CT and endoscopic US reports, the patient was further evaluated with a pancreatic MRI protocol for lesion characterization and to explain the new-onset abdominal pain.

Diagnostic Accuracy of Calculated Tumor Volumes and Apparent Diffusion Coefficient Values in Predicting Endometrial Cancer Grade.

Background: Magnetic resonance imaging (MRI) has been shown to be an accurate imaging technique for the preoperative assessment of local staging of endometrial cancer and for evaluating the depth of myometrial invasion. Materials and Methods: This was a single-center retrospective study performed on patients with histopathologically proven endometrial carcinoma who underwent an MRI examination of the pelvis between October 2017 and May 2020. Results: In the present analysis, mean apparent diffusion coefficient (ADC) values for each histologic grade were 0.72 ± 0.13 × 10-3 mm2/s (G1), 0.76 ± 0.17 × 10-3 mm2/s (G2), and 0.74 ± 0.12 × 10-3 mm2/s (G3), respectively, showing no significant correlation between ADC values and tumor grade (P = 0.73). Overall, ADC minimum was significant in differentiating grades of endometrial carcinoma (P = 0.02) with the ability to differentiate Grade I and II lesions (P = 0.01). A mean tumor volume of 25.2 cc could differentiate low-grade tumors (Grade I and Grade II) from high-grade tumors (Grade III) with a sensitivity and specificity of 88% and specificity of 89%. The tumor volume/uterine volume ratio (TV/UV) differentiates high-grade tumors from low-grade tumors (P < 0.001), however, no significant difference in the ratio was observed among Grade I and II lesions (P = 0.48). The area under the curve of tumor volume was 0.875 (95% confidence interval 0.0-1.00) (P = 0.001), indicating that tumor volume was an effective tool for distinguishing high-grade and low-grade endometrioid adenocarcinomas. The corresponding sensitivity and specificity were 88.0% and 89.0%, respectively. Conclusion: Preoperative noninvasive radiological assessment for tumor volume, TV/ UV or tumor volume/uterine volume is important surrogate markers for preoperative prognostication of endometrial carcinoma.

Prevalence of Molecular Subtypes in Operated Cases of Breast Cancer and Its Clinicopathological Correlation: A Single Institute Study from a Tertiary Cancer Centre in North India.

Breast cancer has emerged as a major health problem among women in India. There are few Indian studies which have looked at prevalence of molecular subtypes of breast cancer in Indian population. The primary objective of our study was to find out the prevalence of various molecular subtypes in operated cases of breast cancer patients presenting to us. Three hundred sixty patients who were operated in our department were analysed. Clinicopathological features of all cases were recorded. Classification into various molecular subtypes was done using St. Gallen 2013 criteria. Luminal B HER2 negative was the predominant molecular subtype in our study population constituting 30.3% of patients. The percentage of aggressive subtypes, viz. triple negative breast cancer and HER2 enriched, were 21.7% and 11.4% respectively. Only 19.4% of patients in our study population had tumour size ≤ 2 cm with nodes being positive in 56.9% of our patients at presentation. Data from our study and other studies published from India show that the two most aggressive subtypes of, viz. triple negative breast cancer and HER2 enriched, may be more prevalent in our population as compared to western population.