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

Prasenjit Das,Gaurav PS Gahlot,Alka Singh,Vandana Baloda,Ramakant Rawat,Anil K Verma,Gaurav Khanna,Maitrayee Roy,Archana George,Ashok Singh,Aasma Nalwa,Prashant Ramteke,Rajni Yadav,Vineet Ahuja,Vishnu 대한장연구학회 2019 Intestinal Research Vol.17 No.3

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.

Bendamustine in combination with ifosfamide, etoposide, and vinorelbine (VIBE) is an effective salvage regimen for heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma: a single-center experience

Gaurav Prakash,Arihant Jain,Kamalkant Sahu,Amanjit Bal,Charanpreet Singh,Rajender Basher,Harmandeep Singh,Kundan Mishra,Aditya Jandial,Deepesh Lad,Alka Khadwal,Radhika Srinivasan,Ashim Das,Neelam Varm 대한혈액학회 2021 Blood Research Vol.56 No.3

Background This study evaluated the outcomes of patients with refractory/relapsed Hodgkin lymphoma (RRHL) treated with a bendamustine-based regimen in combination with ifosfamide, etoposide, and vinorelbine (VIBE). Methods Consecutive RRHL patients who were treated with the VIBE regimen were identified and studied for clinicopathologic characteristics, response to VIBE regimen, event-free survival (EFS), and feasibility of an autologous stem-cell transplant (autoSCT). Results In total, 24 patients received the VIBE regimen, and a median of 3 cycles were administered. In this cohort, 80% of the patients had received ≥2 prior lines of therapy. The overall and complete response rates with VIBE were 79% and 42%, respectively. After a median follow-up (following VIBE regimen) of 14 months (range, 3‒76), the 3-year EFS and OS were 46% and 74%, respectively. Of the eligible patients, 92% underwent successful AutoSCT. The mean CD34+ cell count in the autograft was 5.5×106 /kg (SD 2.07). Neutropenia was the commonest hematologic toxicity and it was observed in 42% of the patients. However, only 9% of the patients developed grade III/IV febrile neutropenia. Chemotherapy-induced nausea and vomiting were the second most common grade III/IV toxicities in our cohort of patients. Conclusion In this retrospective analysis, the combination regimen, VIBE, has shown good efficacy in heavily pre-treated patients with RRHL without compromising stem cell collection. These encouraging results provide a rationale for further development of this regimen.

Programmed death-ligand 1 expression and tumor-infiltrating lymphocytes in non-small cell lung cancer: association with clinicopathologic parameters

Gaurav Garg,Kuruswamy Thurai Prasad,Navneet Singh,Parul Gupta,Valliappan Muthu,Ashim Das,Amanjit Bal 대한병리학회 2021 Journal of Pathology and Translational Medicine Vol.55 No.6

Background: Data on the prevalence of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in non–small cell lung cancer (NSCLC) and their clinical significance in Indian patients are limited. Methods: Newly diagnosed NSCLC cases (adenocarcinoma or squamous cell carcinoma [SqCC] histology) were included in the present study. The TILs were evaluated based on morphology on hematoxylin and eosin–stained slides. PD-L1 expression in tumors was assessed using immunohistochemistry with rabbit monoclonal antibody (SP263) on the Ventana automated immunostainer. Tumors with PD-L1 expression > 50% on tumor cells were considered PD-L1–positive. Tumors in which TILs occupy > 25% of stroma were considered to have high TILs. The association of PD-L1 expression and TILs with various clinical parameters including overall survival (OS) was investigated. Results: The present study included 128 cases of NSCLC (67 adenocarcinoma, 61 SqCC). PD-L1 positivity was observed in 17.2% of the patients with NSCLC. Baseline characteristics of PD-L1–positive subjects were similar to PD-L1–negative subjects except for a higher prevalence of liver metastasis (18.2% vs. 2.8%; p = .018) and a higher probability of diagnosis from extrapulmonary biopsies. High TILs were observed in 26.6% of the subjects. However, PD-L1 expression and high TIL did not affect OS. Conclusions: PD-L1 positivity and high TILs were observed in 20% and 25% of the patients with NSCLC, respectively, however, neither were predictors of survival in SqCC.

Atypical presentation of hairy cell leukemia: a report and comprehensive review

Pattnaik Sandeep Abhijit,Padhi Somanath,Chhabra Gaurav,Panigrahi Manoj Kumar,Das Prabodh Kumar,Bhola Rajesh Kumar,Mishra Shruti 대한혈액학회 2020 Blood Research Vol.55 No.2

Feasibility and Outcomes of Multivisceral Resection in Locally Advanced Colorectal Cancer: Experience of a Tertiary Cancer Center in North-East India

Joydeep Purkayastha,Pritesh Rajeev Singh,Abhijit Talukdar,Gaurav Das,Jitin Yadav,Srinivas Bannoth 대한대장항문학회 2021 Annals of Coloproctolgy Vol.37 No.3

Purpose: Locally advanced colorectal cancer may require an en bloc resection of surrounding organs or structures to achieve complete tumor removal. This decision must weigh the risk of complications of multivisceral resection against the potential survival benefit. The purpose of this study is to review a single-center experience of feasibility of en bloc multiv- isceral resections for locally advanced colorectal carcinoma and to examine the effect of surgical experience on immediate outcome and rate of R0 resections. Methods: This is a study of 27 patients who underwent multivisceral resection for locally advanced colorectal carcinoma which was performed at our institute from January 2016 to December 2019. Among the 27 patients aged between 21 and 76 years (mean age, 48.67±7.3 years), 13 were males and 14 were females. Overall 18 patients had primary colon carci- noma and 9 had primary rectal carcinoma. All rectal cancer patients received neoadjuvant chemoradiation. All patients underwent surgery with curative intent. All patients underwent open surgery of which 66.7% underwent colectomy, 14.8% underwent anterior resection, 11.1% underwent Miles procedure, and 7.4% underwent pelvic exenteration. Results: The mean operative time was 268.14±72.2 minutes and the median amount of blood units transfused was 2.07 units. The mean hospital stay was 13.67±3.4 days. Histologically, 44.4% of patients had well-differentiated adenocarci- noma and 55.6% had moderately differentiated adenocarcinoma. The final histopathological examinatio n revealed ma- lignant infiltration of the adjacent organs in 19/27 patients (70.4%). Pathological complete response was seen in 2 patients. R0 resection rate achieved was 96.3%. Lymph node metastasis was seen in 66.7% of patients with colon cancer and 11.1% with rectal cancer with overall mean number of harvested lymph nodes being 12.44±3.01. Postoperative complications were identified in 7 patients (25.9%), while mortality was seen in 2 (7.4%). Conclusion: Multivisceral resection for advanced colorectal cancer invading into the adjacent organ may be performed with acceptable morbidity and mortality.

Comparable outcomes with low-dose and standard-dose horse anti-thymocyte globulin in the treatment of severe aplastic anemia

Arihant Jain,Aditya Jandial,Thenmozhi Mani,Kamal Kishore,Charanpreet Singh,Deepesh Lad,Gaurav Prakash,Alka Khadwal,Reena Das,Neelam Varma,Subhash Varma,Pankaj Malhotra 대한혈액학회 2024 Blood Research Vol.59 No.1

Background The standard dose (SD) of horse anti-thymocyte globulin (hATG) ATGAM (Pfizer, USA) or its biosimilar thymogam (Bharat Serum, India) for the treatment of Aplastic Anemia (AA) is 40 mg/kg/day for 4 days in combination with cyclosporine. Data on the impact of hATG dose on long-term outcomes are limited. Here, we describe our comparative experience using 25 mg/kg/day (low-dose [LD]) hATG for 4 days with SD for the treatment of AA. Methods We retrospectively studied patients with AA (age > 12 years) who received two doses of hATG combined with cyclosporine. Among 93 AA patients who received hATG, 62 (66.7%) and 31 (33.3%) patients received LD and SD hATG with cyclosporine, respectively. Among these,seventeen(18.2%) patients also received eltrombopag with hATG and cyclosporine. Overall response rates [complete response (CR) and partial response (PR)] of LD and SD hATG groups at 3 months (50% vs. 48.4%; p = 0.88), 6 months (63.8% vs. 71.4%; p = 0.67), and 12 months (69.6% vs. 79.2%; p = 0.167) were comparable. The mean (Standard Deviation) 5-year Kaplan–Meier estimate of overall survival and event-free survival was 82.1 (4.6)% and 70.9 (5.5)% for the study population. The mean (standard deviation) 5-year Kaplan–Meier estimate of overall survival and event-free survival of those who received LD hATG versus SD hATG dose was 82.9 (5·3)% versus 74.8 (10·3)% (P = 0·439), and 75.2 (6.2)% versus 61.4(11.2)% (P = 0·441). Conclusion Our study revealed that the response rates of patients with AA and LD were similar to those of patients with SD to hATG combined with cyclosporine in a real-world setting.

Exploring the neural mechanisms of aversion to bitter gourd phytochemicals in insects using Drosophila

Chakraborty Rusha,Thakur Tamanna Singh,Chauhan Riti,Manzar Zeba,Das Gaurav,Mitra Aniruddha 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.3

Bitter gourd (Momordica charantia L.) has compounds that repel insect pests. Unlike conventional pesticides, these compounds are eco-friendly and beneficial for human health. However the mechanisms by which these compounds repel insects and affect their physiology remains poorly known. Here we used Drosophila melanogaster (Meigen) to address these issues. We tested a wild strain, and a laboratory bred Canton S strain. Bitter gourd extract reduced the viability of developing flies, but did not affect survival in adults. Flies avoided bitter gourd extract in a food choice assay, and consumed a significantly low amount of food mixed with bitter gourd – indicating that it acts as an antifeedant. Transgenic flies with impaired aversive taste sensitive neurons showed a reduced aversion towards bitter gourd extract showing that these compounds act through the bitter sensitive gustatory neurons. Finally, flies also retained the memory of consuming bitter gourd extract for at least 24 hours, suggesting an additional cognitive mechanism for long term aversion. Our study provides the first evidence of bitter gourd compounds acting as antifeedants and also as potent reinforcers of aversive memory in drosophilids. We suggest that flies can be used to understand the physiological and neural mechanisms underlying the mode of action of other such phyto-extracts with the goal of developing potent but less harmful pest control formulations.

A Universal Craniometric Index for Establishing the Diagnosis of Basilar Invagination

Jayesh Sardhara,Sanjay Behari,Suyash Singh,Arun K. Srivastava,Gaurav Chauhan,Hira Lal,Kuntal K. Das,Kamlesh Singh Bhaisora,Anant Mehrotra,Prabhakar Mishra,Awadhesh K. Jaiswal 대한척추신경외과학회 2021 Neurospine Vol.18 No.1

Objective: The conventional criteria for defining the basilar invagination (BI) focus on the relationship of odontoid tip to basion and opisthion, landmarks that are intrinsically variable especially in presence of occipitalised atlas. A universal single reference line is proposed that helps in unequivocally establishing the diagnosis of BI, may be relevant in establishing both Goel types A and B BI, as well as in differentiating a ‘very high’ from ‘regular’ BI. Methods: Study design – case-control study. In 268 patients (group I with BI [n=89] including Goel type A BI [n=66], Goel type B BI [n=23], and group II controls [n=179]), the perpendicular distance between odontoid tip and line subtended between posterior tip of hard palate-internal occipital protuberance (P-IOP line) was measured. Logistic regression analysis determined factors influencing the proposed parameter (p<0.05). Results: In patients with a ‘very high’ BI (n=5), the odontoid tip intersected/or was above the P-IOP line. In patients with a ‘regular’ BI (n=84), the odontoid tip was 6.56±3.9mm below the P-IOP line; while in controls, this distance was 12.53±4.28 mm (p<0.01). In Goel type A BI, the distance was 7.01±3.78 mm and in type B BI, it was 5.07±4.19 mm (p=0.004). Receiver-operating characteristic curve analysis identified 9.0 mm (8.92–9.15 mm) as the cut-point for diagnosing BI using the odontoid tip-P-IOP line distance as reference. Conclusion: The odontoid tip either intersecting the P-IOP line (very high BI) or being <9 mm below the P-IOP line (Goel types A and B BI) is recommended as highly applicable criteria to establish the diagnosis of BI. This parameter may be useful in establishing the diagnosis in all varieties of BI.

Plasma cell leukemia in North India: retrospective analysis of a distinct clinicohematological entity from a tertiary care center and review of literature

Karthik Bommannan,Man Updesh Singh Sachdeva,Pankaj Malhotra,Narender Kumar,Prashant Sharma,Shano Naseem,Jasmina Ahluwalia,Reena Das,Neelam Varma,Gaurav Prakash,Alka Khadwal,Radhika Srinivasan,Subhash 대한혈액학회 2016 Blood Research Vol.51 No.1

BackgroundPlasma cell leukemia (PCL) is a rare and aggressive plasma cell neoplasm. In PCL, clonal plasma cells comprise ≥20% of the peripheral blood (PB) leukocytes and/or the absolute clonal PB plasma cell count is ≥2×109/L. Primary PCL (PPCL) originates de novo, whereas, secondary PCL (SPCL) evolves from pre-existing multiple myeloma.MethodsClinicohematological features, immunophenotypic profile, and survival of PCL patients were analyzed retrospectively.ResultsBetween January 2007 and December 2014, ten PPCL and four SPCL patients were inves-tigated (8 PPCLs and 3 SPCLs had complete clinical data). All were North Indians, sharing common geography and ethnicity. Our cohort showed less frequent renal failure, more frequent hepatomegaly, and non-secretory type disease. In contrast to western literature, flow cytometric immunophenotyping of our cohort revealed altered expression of CD138 (67%), CD56 (33%), and CD20 (0%). With novel therapeutic agents, these PPCL patients had a median overall survival of 15 months.ConclusionWe highlight that our PPCL patients from North India had distinct clinicohematological and immunophenotypic profiles. The significance of our findings must be tested in a larger patient cohort and must be supported by molecular and cytogenetic investigations to un-mask possible significant effects on pathogenesis.

Plasma cell leukemia in North India: retrospective analysis of a distinct clinicohematological entity from a tertiary care center and review of literature

Karthik Bommannan,Man Updesh Singh Sachdeva,Pankaj Malhotra,Narender Kumar,Prashant Sharma,Shano Naseem,Jasmina Ahluwalia,Reena Das,Neelam Varma,Gaurav Prakash,Alka Khadwal,Radhika Srinivasan,Subhash 대한혈액학회 2016 Blood Research Vol.51 No.1

BackgroundPlasma cell leukemia (PCL) is a rare and aggressive plasma cell neoplasm. In PCL, clonal plasma cells comprise ≥20% of the peripheral blood (PB) leukocytes and/or the absolute clonal PB plasma cell count is ≥2×109/L. Primary PCL (PPCL) originates de novo, whereas, secondary PCL (SPCL) evolves from pre-existing multiple myeloma.MethodsClinicohematological features, immunophenotypic profile, and survival of PCL patients were analyzed retrospectively.ResultsBetween January 2007 and December 2014, ten PPCL and four SPCL patients were inves-tigated (8 PPCLs and 3 SPCLs had complete clinical data). All were North Indians, sharing common geography and ethnicity. Our cohort showed less frequent renal failure, more frequent hepatomegaly, and non-secretory type disease. In contrast to western literature, flow cytometric immunophenotyping of our cohort revealed altered expression of CD138 (67%), CD56 (33%), and CD20 (0%). With novel therapeutic agents, these PPCL patients had a median overall survival of 15 months.ConclusionWe highlight that our PPCL patients from North India had distinct clinicohematological and immunophenotypic profiles. The significance of our findings must be tested in a larger patient cohort and must be supported by molecular and cytogenetic investigations to un-mask possible significant effects on pathogenesis.