The Tata Memorial Hospital is situated in Parel, Mumbai, in India. Also popularly known as TMH. It is a specialist cancer treatment and research centre, closely associated with the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC). The Centre is the national comprehensive cancer centre for the prevention, treatment, education and research in cancer and is recognized as one of the leading cancer centres in this part of the world. It is an autonomous body funded and controlled by Department of Atomic Energy, Government of India which also oversees the administration of institute since 1962.The Tata Memorial Hospital was initially commissioned by the Sir Dorabji Tata Trust on 28 February 1941 as a center with enduring value and a mission for concern for the Indian people. Current Director of the hospital is Dr. Rajendra A Badwe, who took over from for director Dr. K. A. Dinshaw. K.
Background Chimeric Antigen Receptor T-cell (CAR T-cell) therapy is a promising treatment option for patients with refractory or relapsed B-cell malignancies. The success of this therapy depends on the efficient collection of lymphocytes (CD3+ T cells) through apheresis. This study analyzed the factors influencing CD3+ cell counts in apheresis products for CAR T-cell therapy. Methods This exploratory analysis evaluated patients enrolled in the registration phase I/II trials of talicabtagene autoleucel at a tertiary care oncology centre in Western India. Patients were enrolled after obtaining informed consent. The study was approved by the Institutional Ethics Committee and the Central Drugs Standard Control Organisation (CDSCO), and registered with the Clinical Trials Registry of India. A total of 48 autologous lymphocytapheresis procedures were performed on 44 patients with refractory or relapsed lymphoma (predominantly diffuse large B-cell lymphoma) or B-acute lymphoblastic leukemia. Pre-apheresis hematological parameters and flow cytometry were used to estimate absolute lymphocyte counts and peripheral blood CD3+ cell counts. Predictive factors for CD3+ cells in the product were analyzed using the Pearson correlation coefficient and regression models by the Statistical Package for Social Sciences software (Version 25.0, Armonk, NY: IBM Corp.), and p-values <0.05 were considered statistically significant. Results Pre-apheresis parameters like total leukocyte count, absolute lymphocyte count, and circulating CD3⁺ cell count were all positively correlated with the absolute CD3+ cell yield in the apheresis product (p < 0.05). Importantly, these associations remained significant in multivariate analysis, highlighting their independent predictive value for the harvested CD3+ count. Additionally, lower pre-apheresis hematocrit and higher platelet levels were independently associated with reduced CD3+ recovery. Notably, the targeted CD3+ cell dose was successfully achieved in 96 % (46/48) of collections. Conclusion Pre-apheresis total leukocyte count, absolute lymphocyte counts, CD3+ cells, hematocrit, and platelet counts are key factors influencing the successful collection of CD3+ cells during apheresis. Understanding these variables is crucial for optimizing lymphocyte collection for CAR T-cell manufacturing.
Obesity is a global health challenge. An increasing number of patients with obesity are admitted to an intensive care unit. Airway management in these patients represents a unique challenge due to significant anatomical and physiological alterations. Increased adipose tissue in the face, cheeks, pharynx, hypopharynx, and neck narrows the upper airway, renders soft tissues more collapsible, and complicates airway management. In addition, the functional residual capacity is reduced, resulting in markedly shortened safe apnea time, contributing to severe hypoxemia during intubation. Non-invasive ventilation is effective in mitigating this risk and should be applied from pre-induction to laryngoscopy. Peri-intubation physiological optimization should include assessment of preload and cardiac contractility, with careful consideration of right ventricular strain. The transition from negative to positive intrathoracic pressure should be closely monitored, with cautious titration of positive end-expiratory pressure. Recognition of these anatomical and physiological challenges may prompt clinicians to consider awake intubation in selected patients. When rapid sequence induction is performed, both ketamine and etomidate are appropriate options; the choice between them should be guided by the clinical context, patient characteristics, local practice patterns and availability. Videolaryngoscopy increases the incidence of successful intubation on the first attempt and should be adopted routinely in the population with obesity. Several questions remain unanswered, including the safety and efficacy of pre-emptive vasopressor use to prevent post-intubation cardiovascular collapse and the optimal dosing of hypnotic agents to achieve ideal intubation conditions, while minimizing adverse events.
The clinicopathological spectrum of FET-CREB sarcomas is evolving with several distinct tumors entities described across various body sites, apart from the soft tissues. Lately, there are tumors primarily identified in the abdominal and extra-abdominal sites, including the soft tissues with an epithelioid morphology and displaying FET-CREB fusions, which are different from the established tumors showing the similar underlying gene fusions. An 18-year-old female patient presented with pain in her upper back. She underwent An An 18-year-old female patient presented with pain in her upper back. She underwent magnetic resonance imaging (MRI), which revealed a large lobulated, intraspinal, extra-axial mass, measuring 4.1 cm in the largest dimension. Histopathological examination of the biopsy revealed a tumor composed of moderate to focally, markedly pleomorphic, round to polygonal to spindle-shaped cells, including vacuolated forms in a myxoid-rich stroma with intervening branching blood vessels. By immunohistochemistry, the tumor cells were patchily positive for epithelial membrane antigen (EMA), and focally for pan keratin (AE1/AE3), S100 and desmin. A 43-year-old lady presented with a gradual, left-sided hearing loss of one year duration. On clinical examination, there was a soft palatal bulge. Computed tomogram (CT) scan showed a 4.9 cm-sized mass in the left parapharyngeal space. Microscopic examination of the excised mass revealed an infiltrating tumor composed of round to oval cells arranged in solid sheets, cords and cribriform pattern in a densely hyalinized and myxoid stroma. Few mitotic figures were noted. By immunohistochemistry, the tumor cells were focally positive for EMA, ALK and diffusely positive for S100 and SOX10. Fluorescence in-situ hybridization (FISH) revealed EWSR1 rearrangement. Next-generation sequencing (NGS) revealed EWSR1::CREB1 fusion in the former and EWSR1::ATF1 fusion in the latter tumor. The former patient is alive with the disease and the latter patient in on maintenance chemotherapy. The two tumors, occurring at distinct sites, histopathologically exhibiting a relatively atypical immunophenotype, including “myoepithelial-like” differentiation seem to further expand the clincopathological spectrum of tumors with epithelioid morphology and underlying FET-CREB fusions.
The 6th Edition of the WHO Classification of Digestive System Tumours represents a significant update to the 5th edition. It integrates pathological, new molecular, and clinical insights to refine the taxonomy of digestive system neoplasms. The revised classification continues to emphasise standardisation in terminology, coding, and diagnostic criteria to facilitate global consistency in diagnosis, treatment, epidemiological reporting and research. Structural reorganisation of book chapters describes epithelial tumours by anatomical site, while separating neuroendocrine, mesenchymal and haematolymphoid tumours into dedicated chapters that are aligned with other WHO tumour volumes. Genetic tumour syndromes are classified by mechanisms, pathways and genes, whereas metastatic disease is comprehensively covered under other tumours and metastases. Key structural and diagnostic refinements include consolidation of gastric dysplasia entities; separation of duodenal/ampullary from jejuno-ileal tumours; clearer categorisation of colorectal serrated polyps and novel carcinoma grading; introduction of small- and large-duct intrahepatic cholangiocarcinoma as separate entities, and redefinition of undifferentiated carcinoma to include 'carcinoma with mesenchymal differentiation'. Several new entities are introduced, including oesophageal epidermoid metaplasia, colorectal intramucosal adenocarcinoma, low-grade tubuloglandular adenocarcinoma and lymphoglandular complex-like adenocarcinoma, intraductal tubulopapillary and intraductal oncocytic papillary neoplasms of the bile ducts and sonic hedgehog hepatocellular adenoma. The concept of amphicrine-like carcinoma (ALC) is distinguished from MiNEN and broadens the understanding of tumours with dual neuroendocrine-non-neuroendocrine differentiation. Grading systems are simplified to two-tier classifications (low/high grade) across precursor lesions, with enhanced criteria for neuroendocrine tumour grading. Anal canal neoplasia terminology is harmonised with human papillomavirus (HPV) related Lower Anogenital Squamous Terminology (LAST) and mass-forming biliary and gallbladder cancer precursors share similar terminology. Finally, carcinoma of unknown primary (CUP) is included in a separate section for the first time, classified by molecular and immunophenotypic profiles to guide therapy. Overall, the 6th edition strengthens tumour diagnostic precision and molecular alignment across the digestive system.
