Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).

BACKGROUND: Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India). METHODS: A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively. RESULTS: FHIT mRNA expression showed significantly decreased expression in ALL cases with mean fold change of 9.24 ± 5.44 as compared to healthy controls (p = 0.01). The pattern of FHIT deregulation in ALL cases differed significantly between decreased and increased expression (p < 0.0001). A threefold decreased expression was observed in 75% of ALL cases than healthy controls (- 3.58 ± 2.32). ALL patients with FHIT gene promoter hypermethylation presented significantly higher in 80% (53/66) of cases (p = 0.0005). The association of FHIT gene hypermethylation and its subsequent expression showed FHIT mRNA expression as significantly lower in ALL cases with hypermethylation (p = 0.0008). B-ALL cases exhibited a highly significant association between the methylation pattern and its mRNA expression (p = 0.000). In low range WBC group, a significant association was found between increased expression (26%) of the cases and methylated (4%)/unmethylated group 86% (p = 0.0006). CONCLUSION: The present study conclude that FHIT gene hypermethylation and its altered expression may be linked in the pathogenesis of ALL and provide an evidence for the role of FHIT in the development of ALL.

Left ventricular diastolic function and cardiotoxic chemotherapy.

BACKGROUND: Left ventricular ejection fraction falls when the myocardium has already lost a significant portion of its functional capacity. There are conflicting data on whether diastolic dysfunction precedes systolic dysfunction after cardiotoxic chemotherapy. We aimed to study systolic and diastolic dysfunction after cardiotoxic chemotherapy and whether diastolic dysfunction can predict subsequent risk of systolic dysfunction. It was an observational prospective cohort study, and patients receiving cardiotoxic chemotherapy were included. Baseline, demographic, and clinical details were recorded. Echocardiographic measurements of left ventricular systolic function, global longitudinal strain, and diastolic function were noted at baseline, three months, and 6 months. RESULTS: We included eighty patients. The mean age of the patients was 54.92 ± 7.6 years, predominantly females (80%). The mean left ventricular ejection fraction fell from 64.92 ± 1.96 to 60.97 ± 4.94 at 6 months. Low ejection fraction was seen in 8 (10%) patients at 6 months. The mean global longitudinal strain (GLS) at baseline was - 18.81 ± 0.797 and fell to - 17.65 ± 2.057 at 6 months, with 12 (15%) patients having low GLS (< - 18). Grade 1 diastolic dysfunction was seen in 22 (27.5%) patients, and grade 2 diastolic dysfunction was seen in 3 (3.8%) patients at 6 months. There was a significant decrease in E/A ratio (inflow early diastolic velocity/Inflow late diastolic velocity), mitral tissue Doppler velocity, and an increase in isovolumic relaxation time, mitral valve deceleration time, and E/e' (inflow early diastolic velocity/tissue Doppler mitral annular velocity), at three months and 6 months. Ejection fraction at 6 months was significantly and negatively correlated with diastolic dysfunction at three months (r = - 0.595, p = 0.02). CONCLUSIONS: Cardiotoxic chemotherapy is associated with early diastolic dysfunction. Early diastolic dysfunction predicts subsequent left ventricular systolic dysfunction.

Nosocomial SARS-COVID-19 Outbreak During the Third Wave of COVID-19 in an Oncology Facility at a Tertiary Care Hospital in Kashmir, India.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged as a life-threatening respiratory condition, especially in immunocompromised patients, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially detected in China in December 2019, the first case in India was diagnosed on January 30, 2020. Here we report a nosocomial COVID-19 outbreak among cancer patients and healthcare workers (HCWs) in a medical oncology unit of a tertiary care hospital from our region. MATERIALS AND METHODS: This was a descriptive study of the nosocomial COVID-19 outbreak and was conducted in the month of January 2022 at the medical oncology unit of a tertiary care hospital in Srinagar, Jammu and Kashmir (J&K), India. The study included 25 COVID-19 cases, including patients and HC/non-HCWs (NHCWs). The confirmation of diagnosis was done through real-time polymerase chain reaction (RT-PCR) using nasopharyngeal/oropharyngeal swabs as the test sample. RESULTS: Twenty-five COVID-19 cases, including 14 admitted patients, nine HCWs, and two NHCWs were confirmed by COVID-19 RT-PCR in a span of 11 days. The first case was a positive HCW. The patients were admitted for management of various hematological as well as solid organ malignancies. Of the 14 patients, eight were in the pediatric age group with a mean age of 6.9 years, and six were adults with a mean age of 55.2 years. Thirteen patients were on different chemotherapy protocols, and one was undergoing an autologous stem cell transplant. Of the 14 patients, four were asymptomatic for COVID-19 symptoms, eight had mild disease, and two had severe disease with respiratory failure. Two patients with severe diseases needed COVID-19-designated high-dependency unit (HDU) admission. There was one COVID-19-related death. Among the healthcare workers, the mean age was 33.8 years, of which six were males and three were females. All the HCWs and NHCWs had mild disease, and all of them recovered completely. CONCLUSION: Nosocomial COVID-19 illness is a new entity and is preventable. COVID-19 illness will remain in society after the pandemic is over, like the influenza B viral illness, and there can be seasonal flares in the future. Proper measures should be taken to prevent its clustering in hospital settings.

Evaluation of chromosome 1p/19q deletion by Fluorescence in Situ Hybridization (FISH) as prognostic factors in malignant glioma patients on treatment with alkylating chemotherapy.

BACKGROUND: Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better prognosis and enhanced response to therapy. Information of 1p/19q status is now regarded as the standard of care when managing oligodendroglial tumors for therapeutic options in anticipation of the increased survival and progression-free survival times associated with it. Keeping this in view, we first time attempted to establish the FISH based detection of 1p/19q deletion in glioma tissue samples to evaluate its role and involvement in the disease. METHOD: Overall 39 glioma cases of different histologies were evaluated by fluorescence in situ hybridization (FISH) technique using specific FISH probes with Olympus BX43 fluorescent microscope to detect chromosomes 1p and 19q or co-deletions therein. RESULTS: Of the 39 glioma samples, overall 27 (69.2%) were found to have deletion either in 1p, 19q or both. Deletions were observed in 23.0%, 7.6% and 38.4% in 1p, 19q and 1p/19q co-deletions respectively. Overall oligidendrioglioma presented with 53.8% (21 of 39) deletions, astrocytoma group showed 12.8% and GBM accounted for 2.5% deletions. Overall survival and disease free survival was seen significantly better in oligidendrioglioma and astrocytoma with deleted tumors as compared to non-deleted ones (p<0.05). CONCLUSION: Allelic losses on 1p and 19q, either discretely or shared, were more frequent in classic oligodendrogliomas than in either astrocytoma or Glioblastoma with better survival and response to therapy.

Long-Term Outcomes of Autologous Hematopoietic Stem Cell Transplant (HSCT) for Multiple Myeloma: While New Horizons Emerge, It Is Still Only a Silver Lining for Resource-Constrained Settings.

Background Significant hurdles impede the optimal implementation of hematopoietic stem cell transplantation (HSCT) in low-middle income countries (LMICs). Herein, we highlight the challenges faced in LMICs while performing HSCT and report the long-term outcomes of patients with newly diagnosed multiple myeloma (MM) who underwent autologous HSCT (AHSCT) at our center. Besides, we provide a comprehensive review of studies reporting long-term outcomes of AHSCT in MM from the Indian subcontinent. Methodology This study was conducted at the State Cancer Institute, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India. Case records of all patients with MM who received AHSCT from December 2010 to July 2018 were reviewed retrospectively. A non-systematic literature search was performed using PubMed and Google Scholar databases. Data regarding clinicopathological parameters and long-term follow-up were extracted from relevant studies and for patients included in our study. Results At our center, 47 patients (median age 52.0 years) with MM underwent AHSCT. Majority of patients had stage III disease (ISS) and median time to transplant was 11.5 months. The five-year progression free survival (PFS) and overall survival (OS) were 59.1% and 81.2%, respectively. Studies from the Indian subcontinent have observed a five-year OS of ~50% to ~85%. However, a greater variability in the five-year PFS has been reported, ranging from ~20% to ~75%. The median time to transplant has ranged from seven to 17 months (indicating time delays) with median CD34 cell counts of 2.7-6.3×106 cells/kg (lower than developed countries). Conclusions Despite significant resource limitations in LMICs, AHSCT is increasingly been performed in MM with encouraging long-term outcomes.

Patterns of Treatment and Outcomes in Epithelial Ovarian Cancer: A Retrospective North Indian Single-Institution Experience.

PURPOSE: Ovarian cancer (OC) is ranked as the third most common gynecologic cancer in various Indian cancer registries. In India, OC is seen in the younger age group, with a median age < 55 years being reported by most of the studies. The majority of patients are diagnosed in advanced stage (70%-80%), where the long-term (10-year) survival rate is poor, estimated at 15%-30%. The aim of this study was to evaluate clinical epidemiology, treatment patterns, and survival outcomes in patients with epithelial OC. METHODS: This was a retrospective analysis of patients with epithelial OC who were treated at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, over a period of 9 years, from January 2010 to December 2018. RESULTS: OC constituted 2.94% of all cancers registered. Epithelial OC constituted 88.4% of all OCs, with a median age 50 years. More than two third of patients belonged to rural background and the majority (76.9%) of the patients were in stage III or IV at the time of diagnosis. The main presenting symptoms were abdominal distension/bloating (46.5%) and gastrointestinal disturbances (35.2%). The most common histologic types were serous (65.9%) followed by mucinous carcinoma (15%). Median overall survival for the whole study cohort was 30 months (95% CI, 28.0 to 31.9). Median overall survival for stage I, II, III, and IV was 72, 60, 30, and 20 months, respectively. CONCLUSION: Most of the patients presented in advanced stage of the disease and have poor outcome. Delay in diagnosis and improper management before registering in tertiary cancer center and lack of tertiary care facilities are the root causes of poor outcomes. The general population and primary care physicians need to be made aware of OC symptoms.

Squamous Cell Carcinoma Lung with Skeletal Muscle Involvement: A 8-year Study of a Tertiary Care Hospital in Kashmir.

AIMS: Lung cancer is the most common malignancy throughout the world. Nonsmall cell lung cancer (NSCLC) is the most common type, and squamous cell type is most common in India. Mostly, patients present with chest-related symptoms and signs. Isolated skeletal muscle metastasis (ISMM) is rarely seen. The aim was to see muscle metastasis and its prognosis. MATERIALS AND METHODS: We are presenting our data of 8 years about this common malignancy with relation to muscle metastasis, either alone or with other system metastasis. RESULTS: Muscle metastasis is seen 1.5% of patients, with male: female of 8:1. Overall median survival was 15 months and progression-free survival was 12 months. CONCLUSION: One peculiarity seen was ISMM with no pulmonary system and severe paraneoplastic hypercalcemia. Local therapy may be having an impact on overall survival in metachronous muscle involvement.

Experience of 100 solid organ transplants over a five-yr period from the first successful pediatric multi-organ transplant program in India.

To analyze the clinical profile and outcome of pediatric patients who had undergone a liver and/or RT at our center over a five yr period, case records of all the patients who had undergone a liver or RT were analyzed retrospectively. One hundred solid organ transplants were performed at our center between January 2007 and January 2012. These included 50 liver, 44 renal, one sequential liver and renal, and two CLKT. BA was the most common indication for an LT (38%). At a median follow-up of two yr three months, the patient survival was 88%. The most common indication for an RT was chronic glomerulonephritis (54.5%). At a median follow-up of three yr, the survival was 91%. The CLKT were performed for hyperoxaluria. Two yr post LT, a sequential RT was performed for ESRD resulting from transplant associated microangiopathy. All patients received a living related graft. The common post-operative complications were infections, vascular complications, and graft dysfunction. Survival rates for liver and RT at our center are comparable to those in the established centers in the West.