Publications by authors named "Rajni Yadav"

67 Publications

Safety and Efficacy of Bariatric Surgery in Advanced Liver Fibrosis.

Obes Surg 2020 Nov 3;30(11):4359-4365. Epub 2020 Jul 3.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Background: There is limited data on the safety and efficacy of metabolic and bariatric (MBS) surgery in patients with advanced liver fibrosis.

Methods: This is a retrospective analysis of data of patients with advanced liver fibrosis undergoing MBS at a tertiary care centre. Weight loss and complications were analysed. Transient elastography and liver biopsy findings 1 year after surgery were compared with baseline.

Results: Twenty-two patients had cirrhosis and 16 had stage 3 fibrosis; all were Child Pugh A. Majority (76%) underwent sleeve gastrectomy. Mean excess BMI loss was 65.8 ± 18.9%. There were no leaks or 30-day mortality. One patient with cirrhosis had late mortality due to liver decompensation. Preoperative and postoperative median LSM were 15.5 kPa (interquartile range IQR = 24.4-11.6) and 10.9 kPa (IQR 19.3-7.6), respectively. Preoperative and postoperative median CAP were 352.5 dB/m (IQR = 372-315.5) and 303 dB/m (IQR 331-269.5), respectively. On follow-up biopsy, nine of twelve patients had improvement in fibrosis, while three had no change. Four out of five patients in the cirrhotic cohort had improvement in fibrosis stage and LSM improved in all of them. Five out of seven patients with stage 3 fibrosis had an improvement in fibrosis stage and none progressed to cirrhosis. LSM improved in three of these five patients.

Conclusion: MBS has the potential to ameliorate advanced liver fibrosis, including cirrhosis. Transient elastography can be used as an effective tool for screening and follow-up of liver disease in patients undergoing MBS.
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http://dx.doi.org/10.1007/s11695-020-04827-3DOI Listing
November 2020

Determinants of Outcomes in Autoimmune Hepatitis Presenting as Acute on Chronic Liver Failure Without Extrahepatic Organ Dysfunction upon Treatment With Steroids.

J Clin Exp Hepatol 2021 Mar-Apr;11(2):171-180. Epub 2020 Aug 22.

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.

Background And Aims: Autoimmune hepatitis presenting as acute on chronic liver failure (AIH-ACLF) is a novel entity with limited data on clinical course and management. We assessed outcomes in patients of AIH-ACLF with no extrahepatic organ dysfunction/failure when administered steroids.

Methods: In this retrospective analysis, clinical data, laboratory parameters, liver biopsy indices and prognostic scores such as model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores at baseline were computed for patients with AIH-ACLF and compared across strata of incident infections and transplant-free survival. The primary outcome was 90-day transplant-free survival. Biochemical remission was assessed, and predictors of end points were identified.

Results: Twenty-nine patients of AIH-ACLF were included with a median follow-up of 4 months. The 90- and 180-day transplant-free survival rates of 55.2 [95% confidence interval (CI): 39.7-76.6]% and 30.2(95% CI: 16.7-54.6)%, respectively, were attained on steroids. Three patients (10.3%) underwent liver transplant while 16 (55.2%) deaths occurred. Infections developed in 12 patients (41.3%), leading to worsening prognostic scores, new onset organ dysfunction/failure and 11 deaths. Seven of ten patients (70%) in the transplant-free survivor group attained biochemical remission on follow-up. The MELD score<24 (sensitivity: 68.4%; specificity: 80%) and CTP<11 (sensitivity: 78.9%; specificity: 90%) had best predictive value for survival, in addition to decrease in the MELD score at 2 weeks (sensitivity: 78.9%; specificity: 70%).

Conclusion: Patients with AIH-ACLF have a morbid disease course despite treatment with steroids. Patients with no extrahepatic organ failure with good baseline prognostic scores may be administered steroids with close monitoring for change in MELD over 2 weeks.
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http://dx.doi.org/10.1016/j.jceh.2020.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953011PMC
August 2020

Comparison of Non-Operative Mesotherapy and Surgery in the Management of Superficial Lipomas.

Malays J Med Sci 2021 Feb 24;28(1):51-58. Epub 2021 Feb 24.

Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India.

Background: Lipomas are benign adipocytic tumours. Surgical excision is the gold standard for treating such lipomas, but it results in unaesthetic scarring.

Methods: A total of 126 patients were randomised into two groups. The patients in Group A underwent mesotherapy ( = 66) and those in Group B underwent surgery ( = 60). The patients in Group A group received six sessions of mesotherapy treatment at 2-week intervals. Both groups were followed up for 12 weeks, during which they were assessed for complications arising from treatment, reduction of the size of the lipoma and cosmetic outcomes.

Results: The overall mean age of the patients was 32.93 (± 10.1) years old and the mean volume of the lipomas was 2.29 (± 3.8) mL. A 55.86% ( = 0.0032) mean reduction in the volume of lipomas was noted in the patients who received mesotherapy, while one patient showed a gain of 16% by volume. The patients in Group A (cosmetic score ≥ 4: 63%) were happier with the treatment than those in Group B (cosmetic score ≥ 4: 21%).

Conclusion: Our findings indicate that mesotherapy modestly reduces the volume of lipomas with very few and minor complications and excellent cosmetic outcomes.
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http://dx.doi.org/10.21315/mjms2021.28.1.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909353PMC
February 2021

Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 May 12;1866(5):158905. Epub 2021 Feb 12.

CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

Inflammation is a constant in Non-Alcoholic Fatty Liver Disease (NAFLD), although their relationship is unclear. In a transgenic zebrafish system with chronic systemic overexpression of human IL6 (IL6-OE) we show that inflammation can cause intra-hepatic accumulation of triglycerides. Transcriptomics and proteomics analysis of the IL6-OE liver revealed a deregulation of glycolysis/gluconeogenesis pathway, especially a striking down regulation of the glycolytic enzyme aldolase b. Metabolomics analysis by mass spectrometry showed accumulation of hexose monophosphates and their derivatives, which can act as precursors for triglyceride synthesis. Our results suggest that IL6-driven repression of glycolysis/gluconeogenesis, specifically aldolase b, may be a novel mechanism for fatty liver. This mechanism may be relevant for NAFLD in lean individuals, an emerging class of NAFLD prevalent more in Asian Indian populations.
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http://dx.doi.org/10.1016/j.bbalip.2021.158905DOI Listing
May 2021

Presence and type of decompensation affects outcomes in autoimmune hepatitis upon treatment with corticosteroids.

JGH Open 2021 Jan 13;5(1):81-90. Epub 2020 Nov 13.

Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India.

Background And Aims: Decompensated cirrhosis in autoimmune hepatitis has poor prognosis. Besides liver transplant, treatment for this entity is undefined. We explored the outcomes of autoimmune hepatitis (AIH)-related decompensated cirrhosis with active disease on treatment with steroids.

Methods: In this retrospective analysis, clinical data, laboratory parameters, and prognostic scores, such as baseline model for end-stage liver disease (MELD) scores, were compared among patients of AIH with decompensated cirrhosis with mild/no ascites ( = 38), gross ascites ( = 24), and compensated cirrhosis ( = 32) when administered steroids. The primary outcome was transplant-free survival at 12 months. Biochemical remission rates and other adverse events were also assessed and compared between these groups.

Results: Steroids were initiated at lower doses (25 mg/day-mild/no ascites, 20 mg/day-gross ascites) in patients with decompensated cirrhosis and at 40 mg/day in those with compensated cirrhosis. Transplant-free survival was 25.4%, 74.6%, and 96.9% ( = 0.001), and biochemical remission occurred in 5.1%, 49.0%, and 64.1% ( = 0.001) at 12 months in patients with gross ascites, mild/no ascites, and compensated cirrhosis, respectively. Infections were seen more frequently in decompensated cirrhosis, while other adverse events were comparable. Among decompensated cirrhosis, those with mild/no ascites had better prognostic scores, fewer posttreatment infections, and more frequent biochemical remission than those with gross ascites, achieving rates comparable to compensated cirrhosis. On multivariate analysis, the MELD score (subdistributional hazards ratio [sHR]; 95% confidence interval: 1.153 [1.07-1.24]; = 0.001) and ascites (sHR: 2.556 [1.565-5.65]; = 0.020) predicted survival.

Conclusion: Type and severity of decompensation affect outcomes in patients with AIH-related cirrhosis. Those with mild/no ascites have comparable outcomes to those with compensated cirrhosis upon treatment with low-dose steroids.
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http://dx.doi.org/10.1002/jgh3.12451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812520PMC
January 2021

FibroScan-aspartate aminotransferase score in an Asian cohort of non-alcoholic fatty liver disease and its utility in predicting histological resolution with bariatric surgery.

J Gastroenterol Hepatol 2021 May 16;36(5):1309-1316. Epub 2020 Dec 16.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, New Delhi, India.

Background And Aim: The FibroScan-aspartate aminotransferase (FAST) score was developed for identifying patients with non-alcoholic steatohepatitis, who also have an elevated non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥ 4 and significant fibrosis (F ≥ 2). We aimed to validate it in our NAFLD cohort and assess if it correlates with the histological changes after bariatric surgery.

Methods: Patients with NAFLD, including those undergoing bariatric surgery, were included. The FAST score was calculated using liver stiffness measure, controlled attenuation parameter, and aspartate aminotransferase. Calibration and discrimination of the model were assessed by calibration plots and area under the receiver operating characteristic curve, respectively. Sensitivity and specificity were assessed at the rule-out and rule-in cutoffs (≤0.35 and ≥0.67), respectively. Changes in the NAS and FAST scores were compared in the bariatric cohort 1 year after surgery.

Results: The cohort composed of 309 patients, of which 48 patients underwent repeat liver biopsy at 1 year. The model showed good discrimination with area under the receiver operating characteristic curve of 0.79 (0.74-0.84); however, it was not satisfactorily calibrated (Hosmer-Lemeshow test, P = 0.008). The sensitivity and specificity at the rule-out and rule-in cutoffs were 0.90 and 0.84, respectively. A significant correlation was seen between the 1-year reduction in the NAS and FAST scores (r = 0.38, P = 0.009). A significant reduction in the median FAST score was seen in patients who had ≥2-point reduction in NAS after bariatric surgery.

Conclusion: FibroScan-aspartate aminotransferase score demonstrated good discrimination for fibrotic non-alcoholic steatohepatitis in our cohort. However, a miscalibration resulted in overprediction. The score correlated well with the histological response to interventions for NAFLD.
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http://dx.doi.org/10.1111/jgh.15358DOI Listing
May 2021

Bariatric Surgery in Nonalcoholic Fatty Liver Disease (NAFLD): Impact Assessment Using Paired Liver Biopsy and Fibroscan.

Obes Surg 2021 02 17;31(2):617-626. Epub 2020 Sep 17.

Departments of Internal Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Background: Bariatric surgery is associated with a positive impact on the degree of hepatic steatosis and inflammation in nonalcoholic associated fatty liver disease (NAFLD), although its effect on fibrosis is contentious. The role of Fibroscan in the post-bariatric assessment of hepatic steatosis and fibrosis is unclear.

Objectives: This work aims to study the impact of bariatric surgery on the course of NAFLD using both invasive (liver biopsy) and non-invasive tests (biochemical parameters and Fibroscan).

Methods: In this prospective study, the impact of bariatric surgery on the course of NAFLD was assessed using paired liver biopsy (intra-operative and post-bariatric surgery 1-year follow-up). The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) cutoffs for the assessment of hepatic fibrosis and steatosis, respectively, were calculated in both pre- and post-bariatric settings.

Results: Fifty-eight patients (70.7% females, mean age 39.2 years) underwent paired liver biopsy. Post-bariatric surgery 1-year liver biopsy showed significant improvement in all the histopathological parameters of NAFLD. The mean NAFLD Activity Score declined from 2.81 (± 1.08) to 1.31 (± 1.39) post-bariatric surgery. Thirty (51.7%) patients showed improvement in fibrosis, eighteen (31%) no change, and ten (17.2%) had worsening. Worsening of fibrosis was associated with a higher median age of 44.5 versus 38 years (p value = 0.033). The CAP cutoff values for the various stages of hepatic steatosis were higher pre-operatively as compared with those obtained post-bariatric surgery.

Conclusions: Bariatric surgery is associated with significant improvement in histopathological parameters of NAFLD. Fibroscan shows good diagnostic accuracy in detecting advanced stage and grade of NAFLD.
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http://dx.doi.org/10.1007/s11695-020-04977-4DOI Listing
February 2021

Primary urethral small cell melanoma with neuroendocrine differentiation: a case report.

J Egypt Natl Canc Inst 2020 Oct 12;32(1):40. Epub 2020 Oct 12.

Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Background: Primary malignant melanoma of the female urethra is an exceedingly rare tumor. It represents 0.2% of all malignant melanomas. Divergent differentiation towards non-melanocytic lineages has not been reported in urethral melanoma.

Case Presentation: We report a rare case of neuroendocrine differentiation in a large primary small cell malignant melanoma involving the urethra, in a 62-year-old lady, who presented with obstructive urinary symptoms. Clinical and radiological workup revealed a large urethral mass with liver and lymph nodal metastases. A biopsy was performed from the urethral and liver lesions which showed poorly differentiated tumor cells with small cell morphology and presence of melanin pigment. These cells were immunopositive for melanocytic and neuroendocrine markers. Ultrastructural examination showed presence of melanosomes and neurosecretory granules in the tumor cells.

Conclusions: Although malignant melanoma with neuroendocrine differentiation is exceptionally rare, it needs to be recognized among the other well-known variants of malignant melanoma.
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http://dx.doi.org/10.1186/s43046-020-00051-3DOI Listing
October 2020

Giant Gastric Polyp in Peutz-Jeghers Syndrome: Report of a Case.

J Indian Assoc Pediatr Surg 2020 Jul-Aug;25(4):236-238. Epub 2020 Jun 24.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Peutz-Jeghers syndrome (PJS) is inherited as an autosomal dominant disorder presenting as hamartomatous polyps in the small bowel, mucocutaneous pigmentation and with a predisposition to develop cancer. We report a case of PJS, with an adenomatous giant gastric polyp. The purpose is to highlight that adenomatous giant gastric polyp may be an extremely rare presentation of PJS. Awareness of this possibility will help us in not missing out these atypical cases of PJS.
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http://dx.doi.org/10.4103/jiaps.JIAPS_54_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478285PMC
June 2020

Hypoxia aggravates non-alcoholic fatty liver disease in presence of high fat choline deficient diet: A pilot study.

Life Sci 2020 Nov 10;260:118404. Epub 2020 Sep 10.

Non-communicable Disease Group, Translational Health Science and Technology Institute (THSTI), Faridabad 121001, Haryana, India; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781101, Assam, India. Electronic address:

Aim: NAFLD is a chronic and progressive disease for which there are no FDA-approved drugs available in the market. Drug discovery is a time-consuming procedure and requires screening of hundreds of small molecules to find new chemical entities (NECs) for a particular disease. Current preclinical NAFLD animal models take a longer time, which enhances the duration and expenses of the screening procedure. Hence to shorten the duration, we have proposed a preclinical animal model for rapid induction of non-alcoholic steatohepatitis (NASH), an advanced stage of NAFLD in rats.

Methodology: The animals were divided into three groups; control, high fat choline deficient (HFCD) and high fat choline deficient diet with sodium nitrite (40 mg/kg b.w. i.p. per day) (HFCD + NaNO) respectively. Four weeks later physical and serum biochemical parameters were assessed, intraperitoneal glucose tolerance test was performed, and histopathology and gene expression were analysed.

Key Findings: Hypoxic stress aggravates the lipid accumulation, ballooning, lobular inflammation and fibrosis in hepatic tissue in presence of HFCD diet.

Significance: This novel rodent model could be a useful NAFLD model to screen small molecules rapidly for treatment of NASH.
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http://dx.doi.org/10.1016/j.lfs.2020.118404DOI Listing
November 2020

Gangliocytic Paraganglioma of Ampulla Masquerading as a Neuroendocrine Tumor.

J Gastrointest Cancer 2020 Sep 8. Epub 2020 Sep 8.

Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12029-020-00507-8DOI Listing
September 2020

Tuberculosis presenting as a liver mass in a pregnant lady.

Liver Int 2021 01;41(1):204-205

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1111/liv.14651DOI Listing
January 2021

Effect of -eradication therapy on hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomized-controlled pilot study.

Gastroenterol Rep (Oxf) 2020 Apr 25;8(2):104-110. Epub 2019 Nov 25.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Background: infection has been associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD). This study was done to evaluate the effect of -eradication therapy (HPET) in patients with NAFLD compared to standard management therapy (SMT).

Methods: Eighty NAFLD patients with co-infection were randomized into SMT (diet and exercise, =36) and HPET (SMT plus amoxicillin, clarithromycin, and pantoprazole, =44) groups. The controlled attenuation parameter (CAP), anthropometric parameters, liver enzymes, lipid profile, and glycemic parameters including homeostasis model assessment-insulin resistance (HOMA-IR) were measured and compared between two groups at the baseline and 24 weeks.

Results: Sixty-four participants (SMT group [=28] and HPET group [=36]) were included in a modified intention-to-treat analysis. Both the SMT group and the HPET group had a significant reduction in CAP scores at 24 weeks (=0.002 and <0.001, respectively), but the change between the groups was insignificant (=0.213). Successful eradication of occurred in 68% of the HPET group and led to greater improvement in HOMA-IR at 24 weeks compared to SMT or non-responder patients (=0.007). The liver enzymes reduced significantly at 24 weeks in both groups, but the changes between the groups were similar. The lipid parameters remained unchanged within the groups and between the groups at 24 weeks. A significant increase in the levels of reduced glutathione was noted in the HPET group, but the change between the two groups was not statistically different.

Conclusions: HPET was found to be comparable to SMT alone in reducing hepatic steatosis and liver enzymes at 24 weeks in NAFLD patients. However, successful eradication of led to greater improvement in HOMA-IR (Trial registration CTRI/2017/05/008608).
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http://dx.doi.org/10.1093/gastro/goz058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261206PMC
April 2020

Clear Cell Sarcoma of Sigmoid Colon: a Rare Malignancy with Common Clinical Manifestations.

J Gastrointest Cancer 2020 Sep;51(3):1070-1073

Department of Surgical Oncology, Dr. BRA-IRCH, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1007/s12029-020-00413-zDOI Listing
September 2020

Uterine tumor resembling ovarian sex cord tumor: A series of six cases displaying varied histopathological patterns and clinical profiles.

Indian J Pathol Microbiol 2020 Feb;63(Supplement):S81-S86

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Uterine tumors resembling ovarian sex cord tumor (UTROSCT) are a unique group of neoplasms with diverse morphology and immunophenotypic characteristics, coexpressing sex cord, epithelial, and smooth-muscle markers. To date, less than 100 cases have been reported and there is paucity of data concerning their clinical behavior.

Materials And Methods: All cases of uterine body tumors diagnosed over a period of two and a half years (2016-2018) were retrieved. Histopathological features were reviewed and extended panel of immunohistochemistry was performed to identify cases of UTROSCTs.

Results: Six cases of UTROSCTs were identified with a median age of 46.5 years. Four of them presented with menorrhagia, while two with postmenopausal bleeding including one with a history of carcinoma breast. Three of these cases were initially misdiagnosed as endometrial stromal sarcoma and adenocarcinomas. They all underwent hysterectomy with bilateral salpingo-oophorectomy.

Conclusion: It is considered a tumor with low malignant potential; however, one out of six cases (16.7%) in our study showed metastasis, within 1 year of diagnosis. It is important to recognize this entity as it mimics a wide range of both benign and malignant tumors. Molecular pathogenesis and exact management protocols remain elusive due to rarity,hence, multi-institutional studies are warranted.
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http://dx.doi.org/10.4103/IJPM.IJPM_340_19DOI Listing
February 2020

Primary Multifocal Hepatic PEComa: A Rarely Encountered Diagnostic Dilemma.

J Gastrointest Cancer 2020 Jun;51(2):667-672

Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12029-019-00352-4DOI Listing
June 2020

Cytomorphology of hepatoblastoma with histological correlation and role of SALL4 immunocytochemistry in its diagnosis, subtyping, and prognostication.

Cancer Cytopathol 2020 03 27;128(3):190-200. Epub 2019 Dec 27.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Background: Hepatoblastoma (HB) is the most common malignant pediatric liver tumor, and cytology material is often the only tissue available for evaluation before definitive therapy. Subcategorization of HB based on cytomorphological features thus carries an important role in its prognostication. Spalt-like transcription factor 4 (SALL4), a marker of embryonic stem cells that is also found in the fetal liver, is reactivated in certain liver tumors. Limited studies have evaluated its role in HB. This study was aimed at evaluating the cytomorphological features of HB and assessing the utility of SALL4 immunocytochemistry (ICC) in its subtyping and prognostication.

Methods: Pretherapy fine-needle aspiration smears from patients diagnosed with HB over a period of 9 years were retrieved. Aspirates were subclassified on the basis of the cytomorphology and were correlated with the histology wherever it was available. ICC for SALL4 was performed in 33 cases, and nuclear staining was considered positive.

Results: A total of 53 HB cases were included with 30 available postchemotherapy resection specimens. All the patients were diagnosed as epithelial HB on cytology, and the cases were subclassified as pure fetal (9 of 53), pure embryonal (2 of 53), or combined epithelial HB (42 of 53). There was good concordance between cytology and histology for subtyping. SALL4 immunostaining displayed strong and diffuse nuclear positivity in the embryonal component while focal and weak to negative staining in fetal cells.

Conclusions: Fine-needle aspiration cytology serves as a rapid and effective tool for a correct diagnosis of HB before the implementation of chemotherapy, and SALL4 may serve as a useful diagnostic and prognostic marker.
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http://dx.doi.org/10.1002/cncy.22231DOI Listing
March 2020

Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma.

Front Oncol 2019 22;9:1239. Epub 2019 Nov 22.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.

Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and cathepsin B (CTSB) has been implicated in several tumorigenic processes. However, no such information in GBC was available. Therefore, the present study was planned to investigate the expression and clinical significance of these cathepsins in GBC. Activities of CTSL and CTSB were assayed in the gallbladder (GB) tissues obtained from GBC patients ( = 43) and control subjects ( = 69). Protein and mRNA levels were quantified using immunohistochemistry and real-time PCR (qPCR), respectively. Finally, serum levels of CTSL and CTSB were estimated by ELISA. Receiver operating characteristic (ROC) curve analysis was used for the assessment of sensitivity, specificity, and diagnostic accuracy of these cysteine cathepsins in GBC. The association of combined CTSL and CTSB activity with overall survival was assessed using Kaplan Meier survival analysis. The expression and activity of both CTSL and CTSB were significantly increased ( < 0.050) in tumors of GBC patients as compared to controls. Enzymatic activity of CTSL+B and CTSB exhibited a strong positive association with tumor stage and lymph node involvement in GBC ( < 0.050). Interestingly, the elevated activity of combined CTSL+B was also associated with increased mortality in these patients. Furthermore, significantly enhanced levels of serum CTSL and CTSB were also observed in GBC ( < 0.050) as compared to controls. ROC analysis revealed high diagnostic significance of serum CTSB and CTSL for distinguishing GBC patients from controls with an area under the curve (AUC) of 82 and 77%, respectively. This study, for the first time, demonstrates the clinical significance of CTSL and CTSB overexpression in GBC. Our findings may help improve the clinical management of this carcinoma.
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http://dx.doi.org/10.3389/fonc.2019.01239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883407PMC
November 2019

SPARC expression in desmoplastic and non desmoplastic pancreatic carcinoma and cholangiocarcinoma.

Pathol Res Pract 2019 Dec 21;215(12):152685. Epub 2019 Oct 21.

Departments of Pathology, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Background: The pancreatobiliary carcinomas are characterized by presence of desmoplastic stroma. Overexpression of secreted protein acid and rich in cysteine (SPARC), a matrix producing agent has been documented in pancreatic ductal adenocarcinomas, with survival benefits. This study was targeted to see if SPARC expression in pancreatobiliary carcinomas is responsible for stromal desmoplasia and its prognostic significance.

Methods: In this retrospective study 48 cases of pancreatic cancer and 27 cases of cholangiocarcinoma were analyzed. The expression pattern of SPARC and vascular endothelial growth factor (VEGF) (angiogenic factors) was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. Immunoreactivity was scored semi quantitatively based on stain intensity and stain distribution. SPARC expression was correlated with tumor histology, stromal desmoplasia, VEGF expression, various histological parameters and overall survival in patients. Real time polymerase chain reaction was performed in few cases to validate the immunohistochemistry expression pattern.

Results: SPARC expression was high in peritumoral stroma in pancreatic carcinoma than in pancreatic controls; however, SPARC expression pattern was not grossly different in desmoplastic and non-desmoplastic pancreatobiliary carcinomas and in cholangiocarcinomas. No definite correlation was noted between SPARC expression and histological markers of severity and overall survival data.

Conclusions: The relevance of SPARC expression in pancreato-biliary carcinomas though may still be important for therapeutic decision making, it is not responsible for peritumoral stromal desmoplasia in these tumors and it does not have any significant prognostic implication.
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http://dx.doi.org/10.1016/j.prp.2019.152685DOI Listing
December 2019

Melanotic neuroectodermal tumour of infancy presenting as a lytic lesion in femur: a rare tumour at a rare site with an unusual behaviour.

BMJ Case Rep 2019 Oct 5;12(10). Epub 2019 Oct 5.

Orthopaedics, All India Institute of Medical Sciences, New Delhi, India.

Melanotic neuroectodermal tumour of infancy (MNTI) is an uncommon tumour, predominantly occurring in head and neck, mostly maxilla, but also in skull and mandible. Although a benign lesion, it is known to recur in 15%-27% of cases, and rarely, may undergo malignant transformation. We present a case of a 5-month-old female patient, who presented with a gradually progressive swelling in the right thigh. On imaging, an osteolytic lesion was seen, involving the metadiaphysis of shaft of right femur. A biopsy was performed, on which diagnosis of MNTI was made. MNTI is rarely seen in extremities. To the best of our knowledge, only six cases have been reported in femur, the present case being the seventh. The tumour showed spontaneous regression on follow-up in our patient, which has rarely been described. A knowledge of characteristic morphology and immunohistochemistry is the key to differentiate it from other tumours.
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http://dx.doi.org/10.1136/bcr-2019-231959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782039PMC
October 2019

Synchronous Inflammatory Myofibroblastic Tumour of Liver and Carcinoma Head of Pancreas in a Young Male: a Diagnostic Dilemma.

J Gastrointest Cancer 2020 Jun;51(2):620-623

Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12029-019-00302-0DOI Listing
June 2020

Cytological diagnosis of Langerhans cell histiocytosis: A series of 47 cases.

Cytopathology 2019 07 23;30(4):413-418. Epub 2019 May 23.

Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Objective: Langerhans cell histiocytosis (LCH) is a rare disease affecting predominantly children and young adults but can be found in any age group. Diagnosis of LCH is often difficult and can be delayed because of its rarity. The present study highlights the cytomorphological features in a large cohort of cases. An accurate cytological diagnosis may avoid unnecessary biopsy and guide appropriate management.

Method: Fourty seven (47) cases of LCH diagnosed on cytological material & fine-needle aspiration (FNA) over a period of 14 years (2003-2016) were retrieved from the archives. The cytological smears were evaluated and microscopic findings collected by semi-quantitative assessment done by two different pathologists RESULT: The age at the diagnosis of the patients ranged from 9 months to 28 years. The majority of cases were in the age group of 0-5 years. The most common site was head and neck region, which included cervical lymphadenopathy and scalp swelling. Two cases were diagnosed each from inguinal lymph node and bronchio-alveolar lavage (BAL). Cytological smears in the majority of the cases were moderate to highly cellular (58%) and showing abundant Langerhans cell in (72%) of cases. Areas of necrosis were seen in 38%, while 78% of cases showed giant cells. The majority of cases showed mild eosinophilia (61%), sparse lymphocytosis (83%) and mild neutrophilic infiltration (64%). There were 1-2 mitoses per 10 high power field in 12 cases (25.5%). No abnormal mitoses were identified.

Conclusion: The presence of cells with features of Langerhans cells associated with the expression of selected immunohistochemical markers allow the diagnosis of LCH on cytological samples, sparing more invasive procedure as a biopsy.
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http://dx.doi.org/10.1111/cyt.12709DOI Listing
July 2019

Quantitative histology-based classification system for assessment of the intestinal mucosal histological changes in patients with celiac disease.

Intest Res 2019 Jul 22;17(3):387-397. Epub 2019 Apr 22.

Departments of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Background/aims: The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies.

Methods: We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists.

Results: Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%-85.03%) and interobserver (24.6%-71.5%) agreements.

Conclusions: Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD. (Intest Res, Published online).
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http://dx.doi.org/10.5217/ir.2018.00167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667359PMC
July 2019

Controlled Attenuation Parameter for Assessment of Hepatic Steatosis in Indian Patients.

J Clin Exp Hepatol 2019 Jan-Feb;9(1):13-21. Epub 2018 Mar 14.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Background/aims: The gold standard method for measurement of hepatic steatosis is liver histology. Controlled Attenuation Parameter (CAP) can measure hepatic steatosis non-invasively. We aimed to assess the accuracy of CAP for detection of hepatic steatosis.

Methods: A total of 462 patients (May 2012-January 2017)-89 non-alcoholic fatty liver disease, 182 chronic hepatitis B, 88 chronic hepatitis C and 103 patients with other etiologies who underwent simultaneous liver biopsy and CAP estimation using Transient Elastography (TE) were included. Steatosis was graded as S0: steatosis in 0-5% of hepatocytes, S1: 6-33%, S2: 34-66% and S3: 67-100%. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the accuracy of CAP in detecting hepatic steatosis. Predictors of CAP were assessed by multivariate linear regression model.

Results: The mean age ± SD was 33.8 ± 11.6 years; 296 (64.1%) were males. On liver histology, steatosis grades S0, S1, S2 and S3 were seen in 331 (71.6%), 74 (16.0%), 39 (8.4%) and 18 (3.9%), respectively. The median CAP (IQR) values for S0, S1, S2, and S3 steatosis were 206 (176-252) dB/m, 295 (257-331) dB/m, 320 (296-356) dB/m, and 349 (306-363) dB/m, respectively. For estimation of ≥S1, ≥S2, and ≥S3 using CAP, AUROC were 0.879, 0.893, and 0.883, respectively. In multivariate analysis, only BMI (OR 1.18; CI, 1.11-1.26,  < 0.001) and grade of hepatic steatosis (grade 1, OR, 3.94; 95% CI, 1.58-9.84,  = 0.003; grade 2, OR 42.04; 95% CI, 4.97-355.31,  = 0.001 and grade 3, OR 35.83; 95% CI 4.31-297.61,  = 0.001) independently predicted CAP.

Conclusions: CAP detects hepatic steatosis with good accuracy in Indian patients with various etiologies.
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http://dx.doi.org/10.1016/j.jceh.2018.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363949PMC
March 2018

Synchronous endometrioid carcinoma of the endometrium and small cell neuroendocrine carcinoma of the cervix: a rare combination.

BMJ Case Rep 2018 Nov 8;2018. Epub 2018 Nov 8.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Synchronous multiple primaries of female genital tract are uncommon, with the most frequently encountered combination being of endometrium and ovary. Concurrent primary tumours of endometrium and cervix are rare. We report a case of coexistent endometrioid carcinoma of the endometrium and small cell neuroendocrine carcinoma of the cervix in 48-year-old woman who presented with menometrorrhagia and was detected to have metastases to distant sites on imaging. She underwent multimodality treatment which resulted in a significant reduction in the tumour bulk.
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http://dx.doi.org/10.1136/bcr-2018-227155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6229213PMC
November 2018

Mucinous adenocarcinoma of gallbladder: Subcategorisation on fine-needle aspiration cytology.

Diagn Cytopathol 2019 Feb 30;47(2):110-113. Epub 2018 Oct 30.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Background: Mucinous adenocarcinoma (MC) of gallbladder is a rare histological subtype of gallbladder carcinoma (CaGB) which presents at an advanced stage and is associated with a poor prognosis compared to the conventional CaGB. This variant has been described mostly as reports or series, except for a single detailed histological and immunohistochemical analysis. Till date, there are no studies describing the cytomorphology of MC in detail. Hence, we undertook this study to analyse the cytomorphological features of MC.

Methods: A retrospective cytomorphological analysis was performed on MC identified out of all CaGB diagnosed on cytology over a period of last 4 years. The architectural and cellular features were recorded in a structured proforma.

Results: Thirty-three cases (33/987, 3.3%) were identified as MC. Extracellular mucin >90% was seen only in 3 cases whereas the remaining 30 had 50%-90% mucin. The predominant architectural pattern was tight epithelial fragments (14/33). The tumour cells were mostly of intermediate size (31/33) and had moderate amount of cytoplasm (31/33). Majority of the cases showed moderate nuclear pleomorphism (28/33) and nuclear chromatin was fine granular (17/33) or vesicular (14/33). Most of the cases had single and small nucleoli (26/33). Presence of inflammation composed predominantly of polymorphs was noted in 25 cases. Majority of the cases showed no (15/33) or scant necrosis (13/33).

Conclusion: The morphological features of MC can very well be demonstrated on cytology. As they are associated with poor prognosis compared to conventional CaGB, cytopathologists should try to document the subtype.
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http://dx.doi.org/10.1002/dc.24102DOI Listing
February 2019

Histological assessment & use of immunohistochemical markers for detection of dysplasia in Barrett's esophageal mucosa.

Pathol Res Pract 2018 Jul 16;214(7):993-999. Epub 2018 May 16.

Departments of Pathology and Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Background: Histological assessment of dysplasia in Barrett's esophagus (BE) has high inter-observer variability. Hence, use of ancillary markers for early detection of dysplasia in BE is an important clinical question.

Methods: In this retrospective study consecutive cases of BE (n = 59), over a period of 4 years were included. Hematoxylin and eosin stained sections were reviewed independently by 3 senior qualified pathologists, who graded the dysplasia according to the Vienna Classification system and inter-observer agreement was analysed using the Kappa statistics. Subsequently Alpha-Methyl Acyl-CoA Racemase (AMACR), p53, CyclinD1, β-catenin, H2AX and M30 immunohistochemical (IHC) stains were examined on the following disease categories: BE with no dysplasia [NFD] (45), BE with indefinite for dysplasia (IFD) (4), low grade dysplasia (LGD) (3), high grade dysplasia (HGD) (2) and in adenocarcinomas (5). H score was calculated by adding up products of different grades of stain distribution and stain intensities (range of scores 0-300).

Results: Among the 3 pathologists, overall agreement was poor (k 0.06; 95% CI -0.089 to 0.145), with highest disagreement noted for differentiating the LGD and IFDs (k = 0.21). After revising the histological criteria, the kappa improved to 0.53. Among the IHC stains performed, p53, β-catenin, H2AX and M30 stains were significantly useful to differentiate between IFD and LGD (P values: 0.04, 0.004, 0.05 & 0.04, respectively). AMACR and β-catenin stains though were up-regulated in HGD/adenocarcinomas than in other categories, their expression were not statistically different between the IFD and LGDs.

Conclusions: A detail histological scoring system may bring uniformity in histological interpretation of dysplasia in BE. Using a combined panel of IHC stains seems helpful in detection of dysplasia in BE, especially to differentiate the IFD and LGD changes in BE.
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http://dx.doi.org/10.1016/j.prp.2018.05.006DOI Listing
July 2018

Mucosal Schwann cell hamartoma of gall bladder: a novel observation.

Pathology 2018 Jun 5;50(4):480-482. Epub 2018 May 5.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

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http://dx.doi.org/10.1016/j.pathol.2017.11.095DOI Listing
June 2018

Spectrum of hepatobiliary cystic lesions: A 7-year experience at a tertiary care referral center in North India and review of literature.

Indian J Pathol Microbiol 2017 Oct-Dec;60(4):487-500

Department of Pathology, AIIMS, New Delhi, India.

Context: Cysts arising from the hepatobiliary tree are a group of heterogeneous lesions with regard to pathogenesis, clinical presentation, and radiological finding. They can be intrahepatic or extrahepatic, developmental, secondary to infective/inflammatory etiologies, as well as neoplastic. This study was conducted to determine the spectrum of hepatobiliary cysts in surgically intervened cases, with regard to their prevalence, histological spectrum, and clinicoradiological correlation, wherever possible.

Methods: In this retrospective observational study, hematoxylin and eosin stained slides of all cases of hepatobiliary cystic lesions, operated between 2009 and 2016 were reviewed. Special stains as reticulin, Masson's trichrome, and periodic acid Schiff were done wherever necessary. Overall prevalence, age-sex distribution, clinical presentation and histopathological patterns were studied. Relevant imaging findings were correlated wherever possible.

Results: A total of 312 cases of hepatobiliary cysts were identified, the majority in females. Choledochal cysts (CCs) were the most common type (n = 198,63.5%), followed by hydatid cysts (n = 73,23.3%), simple hepatic cysts (n = 10,3.2%), congenital hepatic fibrosis (n = 10,3.2%), biliary cystadenomas (n = 4,1.2%) hepatic mesenchymal hamartomas (n = 7,2.2%), and cavernous hemangiomas (n = 3,0.9%). Fibropolycystic liver disease (n = 2,0.6%), Caroli's disease (n = 1, 0.3%), liver abscess (n = 2, 0.6%), infantile hemangioendothelioma (n = 1,0.3%), and biliary cystadenocarcinomas (n = 1,0.3%) were rare. Lesions noted mostly in 1st decade of life were: CCs, fibrocystic liver disease, Caroli's syndrome, cystic mesenchymal hamartoma, and infantile hemangioendotheliomas.

Conclusion: In our cohort of surgically intervened cases of hepatobiliary cystic lesions from a tertiary care hospital in North India, the CCs, followed by hydatid cyst were the most common lesions. Histology can play vital role in characterization, as often clinical findings and radiology can overlap.
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http://dx.doi.org/10.4103/IJPM.IJPM_691_16DOI Listing
July 2018

Utility of transient elastography (fibroscan) and impact of bariatric surgery on nonalcoholic fatty liver disease (NAFLD) in morbidly obese patients.

Surg Obes Relat Dis 2018 01 11;14(1):81-91. Epub 2017 Sep 11.

Department of Internal Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Background: Controlled attenuation parameter (CAP) is a novel, noninvasive technique for assessing hepatic steatosis. However, its role in morbidly obese individuals is unclear. The effect of bariatric surgery on inflammation and fibrosis needs to be explored.

Objectives: To assess the utility of CAP for assessment of hepatic steatosis in morbidly obese individuals and evaluate the effect of bariatric surgery on hepatic steatosis and fibrosis.

Setting: A tertiary care academic hospital.

Methods: Baseline details of anthropometric data, laboratory parameters, FibroScan (XL probe), and liver biopsy were collected. Follow-up liver biopsy was done at 1 year.

Results: Of the 124 patients screened, 76 patients were included; mean body mass index was 45.2 ± 7.1 kg/m. FibroScan success rate was 87.9%. The median liver stiffness measurement (LSM) and CAP were 7.0 (5.0-9.5) kPa and 326.5 (301-360.5) dB/m, respectively. On liver histopathology, severe steatosis and nonalcoholic steatohepatitis were present in 5.3% and 15.8%; significant fibrosis (≥stage 2) and cirrhosis in 39.5% and 2.6%, respectively. Area under receiver operator characteristic curve of LSM for prediction of significant fibrosis (F2-4 versus F0-1) and advanced fibrosis (F3-4 versus F0-2) was .65 (95% confidence interval [CI]: .52-.77) and .83 (95% CI: .72-.94), respectively. The area under receiver operator characteristic curve of CAP for differentiating moderate hepatic steatosis (S2-3 versus S0-1) and severe hepatic steatosis (S3 versus S0-2) was .74 (95% CI: .62-.86) and .82 (95% CI: .73-.91), respectively. At 1-year follow-up, 32 patients underwent liver biopsy. In these patients, there was significant improvement in hepatic steatosis (P = .001), lobular inflammation (P = .033), ballooning (P<.001), and fibrosis (P = .003). Nonalcoholic steatohepatitis was resolved in 3 of 4 (75%) patients. LSM and CAP significantly declined.

Conclusions: LSM and CAP are feasible and accurate at diagnosing advanced fibrosis and severe hepatic steatosis in morbidly obese individuals. Bariatric surgery is associated with significant improvement in LSM, CAP, steatohepatitis, and fibrosis.
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http://dx.doi.org/10.1016/j.soard.2017.09.005DOI Listing
January 2018