Tata Memorial Hospital

About: Tata Memorial Hospital is a healthcare organization based out in Mumbai, India. It is known for research contribution in the topics: Cancer & Breast cancer. The organization has 3187 authors who have published 4636 publications receiving 109143 citations.

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

Abstract: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Tubulocystic Carcinoma of the Kidney With Poorly Differentiated Foci: A Frequent Morphologic Pattern of Fumarate Hydratase-deficient Renal Cell Carcinoma

Abstract: An emerging group of high-grade renal cell carcinomas (RCCs), particularly carcinomas arising in the hereditary leiomyomatosis renal cell carcinoma syndrome (HLRCC), show fumarate hydratase (FH) gene mutation and loss of function. On the basis of similar cytomorphology and clinicopathologic features between these tumors and cases described as tubulocystic carcinomas with poorly differentiated foci (TC-PD) of infiltrative adenocarcinoma, we hypothesized a relationship between these entities. First, 29 RCCs with morphology of TC-PD were identified retrospectively and assessed for FH expression and aberrant succination (2SC) by immunohistochemistry (IHC), with targeted next-generation sequencing of 409 genes-including FH-performed on a subset. The 29 TC-PD RCCs included 21 males and 8 females, aged 16 to 86 years (median, 46), with tumors measuring 3 to 21 cm (median, 9) arising in the right (n=16) and left (n=13) kidneys. Family history or stigmata of HLRCC were identifiable only retrospectively in 3 (12%). These tumors were aggressive, with 79% showing perinephric extension, nodal involvement in 41%, and metastasis in 86%. Of these, 16 (55%) demonstrated loss of FH by IHC (14/14 with positive 2SC). In contrast, 5 (17%) showed a wild-type immunoprofile of FH+/2SC-. An intriguing group of 8 (28%) showed variable FH± positivity, but with strong/diffuse 2SC+. Next-generation sequencing revealed 8 cases with FH mutations, including 5 FH-/2SC+ and 3 FH±/2SC+ cases, but none in FH+/2SC- cases. Secondly, we retrospectively reviewed the morphology of 2 well-characterized cohorts of RCCs with FH-deficiency determined by IHC or sequencing (n=23 and n=9), unselected for TC-PD pattern, identifying the TC-PD morphology in 10 (31%). We conclude that RCCs with TC-PD morphology are enriched for FH deficiency, and we recommend additional workup, including referral to genetic counseling, for prospective cases. In addition, based on these and other observations, we propose the term "FH-deficient RCC" as a provisional term for tumors with a combination of suggestive morphology and immunophenotype but where genetic confirmation is unavailable upon diagnosis. This term will serve as a provisional nomenclature that will enable triage of individual cases for genetic counseling and testing, while designating these cases for prospective studies of their relationship to HLRCC.

Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial

Abstract: Summary Background Several large randomised studies from western Europe and the USA have shown that accelerated fractionation of radiotherapy might be beneficial in the treatment of squamous-cell carcinoma of the head and neck (HNSCC). The aim of this study—the International Atomic Energy Agency (IAEA) ACC trial—was to determine whether accelerated fractionation could be applied in developing countries, where there are fewer therapeutic resources and where tumour burdens can be heavier. Methods Between Jan 6, 1999, to March 31, 2004, nine centres from Asia, Europe, the Middle East, Africa, and South America recruited patients with HNSCC of the larynx, pharynx, and oral cavity who were eligible for curative radiotherapy. Patients were randomly assigned in this open-label trial to receive an accelerated regimen of six fractions of radiotherapy per week (n=458) or to receive a conventional radiotherapy regimen of five fractions per week (n=450), receiving a total dose of 66–70 Gy in 33–35 fractions. Patients were stratified by tumour localisation, T classification, histopathological grade, and institution. Randomisation was done by a central computer-generated balanced randomisation algorithm. The primary endpoint was locoregional control, analysed for all eligible patients, irrespective of whether or not they had completed the course of radiotherapy. This trial is registered with ClinicalTrials.gov, number NCT00120211. Findings Six patients in the accelerated group and two in the conventional group were excluded from analyses because of withdrawal of consent or missing data. The planned total radiotherapy dose was received by 418 (92%) of the 452 eligible patients in the accelerated radiotherapy group and 413 (92%) of the 448 patients in the conventional radiotherapy group. Median treatment time was 40 days in the accelerated group and 47 days in the conventional group. The 5-year actuarial rate of locoregional control was 42% in the accelerated group versus 30% in the conventional group (hazard ratio [HR] 0·63, 95% CI 0·49–0·83; p=0·004). Acute morbidity in the form of confluent mucositis was noted in 45 patients in the accelerated group and 22 patients in the conventional group (2·15, 1·27–3·35); severe skin reactions were noted in 87 patients in the accelerated group and 50 patients in the conventional group (1·91, 1·31–2·79). There were no significant differences in late radiation side-effects. Interpretation An accelerated schedule of radiotherapy for HNSCC was more effective than conventional fractionation, and since it does not require additional resources, might be a suitable new worldwide standard baseline treatment for radiotherapy of HNSCC. Funding International Atomic Energy Agency, Coordinated Research Project (IAEA-CRP E.3.30.18), the Danish Cancer Society, the Danish Strategic Research Council, and the Lundbeck Centre for Interventional Research in Radiation Oncology (CIRRO).

Cholelithiasis in gallbladder cancer: coincidence, cofactor, or cause!

Abstract: Background While gallstones are associated with cancers of the gallbladder, the actual nature of their relationship needs to be clarified. This would aid the recommendations on the need for prophylactic cholecystectomy. Methods A systematic search of the scientific literature was carried out using the Medline, the Embase, and the Cochrane Central Register of Controlled Trials for the years 1891–2009 to obtain access to all publications involving gallstones in gallbladder cancer. Results While some epidemiological evidence supports a causal relationship for gallstones in gallbladder cancer, other studies have demonstrated a relatively low incidence of gallbladder cancer in countries reporting a high incidence of gallstones as a whole. In those studies where gallstones appear to have a causative role for cancer, the risk increases with increasing size, volume and weight, and number of the stones. The impact of duration of the stone or its composition is not clear. Experimental evidence from studies examining the impact of artificially introducing gallstones in the gallbladder has failed to lead to carcinogenesis. Conclusions The evidence at the current time indicates that gallstones are a cofactor in the causation of gallbladder cancer. Absolute proof of their role as a cause for gallbladder cancer is lacking. The recommendation for prophylactic cholecystectomy in countries reporting a high incidence of gallbladder cancer and associated gallstones needs to be tailored to the epidemiological profile of the place.

Revisiting chordoma with brachyury, a "new age" marker: analysis of a validation study on 51 cases.

Abstract: Context.—Chordoma is a rare, notochordal tumor with a characteristic histomorphology and immunohistochemical profile. At times, it presents a diagnostic challenge, especially in small biopsies. Brachyury, a nuclear transcription factor, is a recently described immunohistochemical marker for diagnosing chordomas. Objective.—To study the sensitivity and specificity of brachyury in diagnosing chordomas by comparing its expression in axial chordomas with nonchordomatous tumors. Design.—Fifty-one axial chordomas, accessioned during a 10-year period, and 58 nonchordomatous tumors were subjected to brachyury staining by immunohistochemistry. Results.—The 51 chordomas occurred in 36 men and 15 women. Sitewise, 34 cases (66.7%) occurred in the sacrococcyx, 9 (17.6%) in the spine, and 8 (15.7%) in the skull base. Histologically, 34 cases (66.7%) were classical chordomas, 13 cases (25.5%) had a dominant chondroid component, and 2 cases each (3.9%) were chondroid chordomas and dedifferentiated chordomas, res...