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.

Global Retinoblastoma Presentation and Analysis by National Income Level

Abstract: Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma—an International Atomic Energy Agency study

Abstract: Background: Previous studies from South Africa have established that fractionated high-dose-rate (HDR) brachytherapy gives the best results in terms of palliation and survival in advanced esophageal cancer. A multicenter, prospective randomized study was therefore conducted under the auspices of the International Atomic Energy Agency to evaluate two HDR regimens. Methods and Materials: Surgically inoperable patients with histologically proven squamous cell cancer of the esophagus, tumor >5 cm in length on barium swallow and/or endoscopy, Karnofsky performance score >50, age 17–70 years, primary disease in the thoracic esophagus, no prior malignancy within the past 5 years, and any N or M status were included in the study. Exclusion criteria included cervical esophagus location, tumor extending Results: A total of 232 patients were entered into the study (112 in Group A and 120 in Group B). There was no difference between the groups for any of the prognostic variables. All patients were followed until death. The dysphagia-free survival for the whole group was 7.1 months (Group A, 7.8 months; Group B, 6.3 months; p >0.05). The overall survival was 7.9 months for the whole group (Group A, 9.1 months; Group B, 6.9 months; p >0.05). On univariate analysis, the presenting weight (p = 0.0083), gender (p = 0.0038), race (p = 0.0105), the presenting dysphagia score (p = 0.0083), the treatment center (p = 0.0029), and tumor grade (p = 0.0029) had an impact on the dysphagia-free survival, and gender (p = 0.0011) and performance score (p = 0.0060) had an impact on dysphagia-free survival on multivariate analysis. Only age had an impact on overall survival on both univariate (p = 0.0430) and multivariate (p = 0.0331) analysis. The incidence of strictures (Group A, n = 12; Group B, n = 13; p >0.05) and fistulas (Group A, n = 11; Group B, n = 12; p >0.05) was similar in both groups. Conclusion: Fractionated HDR brachytherapy alone is an effective method of palliating advanced esophageal cancers, surpassing the results of any other modality of treatment presently available. Dose fractions of 6 Gy × 3 and 8 Gy × 2 give similar results for dysphagia-free survival, overall survival, strictures, and fistulas and are equally effective in palliation of advanced esophageal cancer.

Withholding and Withdrawal of Life-Sustaining Treatments in Intensive Care Units in Asia

Abstract: Importance Little data exist on end-of-life care practices in intensive care units (ICUs) in Asia. Objective To describe physicians’ attitudes toward withholding and withdrawal of life-sustaining treatments in end-of-life care and to evaluate factors associated with observed attitudes. Design, Setting, and Participants Self-administered structured and scenario-based survey conducted among 1465 physicians (response rate, 59.6%) who manage patients in ICUs (May-December 2012) at 466 ICUs (response rate, 59.4%) in 16 Asian countries and regions. Results For patients with no real chance of recovering a meaningful life, 1029 respondents (70.2%) reported almost always or often withholding whereas 303 (20.7%) reported almost always or often withdrawing life-sustaining treatments; 1092 respondents (74.5%) deemed withholding and withdrawal ethically different. The majority of respondents reported that vasopressors, hemodialysis, and antibiotics could usually be withheld or withdrawn in end-of-life care, but not enteral feeding, intravenous fluids, and oral suctioning. For severe hypoxic-ischemic encephalopathy after cardiac arrest, 1201 respondents (82.0% [range between countries, 48.4%-100%]) would implement do-not-resuscitate orders, but 788 (53.8% [range, 6.1%-87.2%]) would maintain mechanical ventilation and start antibiotics and vasopressors if indicated. On multivariable analysis, refusal to implement do-not-resuscitate orders was more likely with physicians who did not value families’ or surrogates’ requests (adjusted odds ratio [AOR], 1.67 [95% CI, 1.16-2.40];P = .006), who were uncomfortable discussing end-of-life care (AOR, 2.38 [95% CI, 1.62-3.51];P Conclusions and Relevance Whereas physicians in ICUs in Asia reported that they often withheld but seldom withdrew life-sustaining treatments at the end of life, attitudes and practice varied widely across countries and regions. Multiple factors related to country or region, including economic, cultural, religious, and legal differences, as well as personal attitudes, were associated with these variations. Initiatives to improve end-of-life care in Asia must begin with a thorough understanding of these factors.

Cancer of the esophagus: esophagogastric anastomotic leak--a retrospective study of predisposing factors.

Abstract: An esophagogastric anastomotic leak, especially in the mediastinum or the chest, is a life-threatening complication of surgery for cancer of the esophagus. Of 617 patients who underwent esophageal resection and esophagogastric anastomosis between January 1980 and December 1989, 39 (6.32%) had anastomotic leakage; of these, 25 (64.10%) died. Various biologic parameters, operative techniques, and the management of leaks were analysed. Albumin concentration below 3 gm/dL (chi 2 = 3.9; P = 0.047), neoplastic permeation of the anastomotic cut margin (chi 2 = 4.7; P = 0.04), and cervical anastomosis (chi 2 = 12.32; P = 0.0004) were associated with a higher incidence of anastomotic leakage. Hemoglobin level, type of suture material used for the anastomosis, preoperative radiotherapy, and the experience of the operating surgeon under supervision were found to be statistically insignificant factors and did not influence anastomotic leakage. Mortality due to leak in the first postoperative week was 85% and was statistically significant as compared to the mortality occurring in the second postoperative week (chi 2 = 6.04; P = 0.013). Surgical or conservative management of the leak did not influence mortality (chi 2 = 1.2; P = 0.27). The salvage rates for cervical and intrathoracic anastomotic leakage were 80% and 29.4%, respectively. This difference is statistically significant (chi 2 = 29; P = 0.088).

Integrative analysis of genomic aberrations associated with prostate cancer progression

Abstract: Integrative analysis of genomic aberrations in the context of trancriptomic alterations will lead to a more comprehensive perspective on prostate cancer progression. Genome-wide copy number changes were monitored using array comparative genomic hybridization of laser-capture microdissected prostate cancer samples spanning stages of prostate cancer progression, including precursor lesions, clinically localized disease, and metastatic disease. A total of 62 specific cell populations from 38 patients were profiled. Minimal common regions (MCR) of alterations were defined for each sample type, and metastatic samples displayed the most number of alterations. Clinically localized prostate cancer samples with high Gleason grade resembled metastatic samples with respect to the size of altered regions and number of affected genes. A total of 9 out of 13 MCRs in the putative precursor lesion, high-grade prostatic intraepithelial neoplasia (PIN), showed an overlap with prostate cancer cases (amplifications in 3q29, 5q31.3-q32, 6q27, and 8q24.3 and deletions in 6q22.31, 16p12.2, 17q21.2, and 17q21.31), whereas postatrophic hyperplasia (PAH) did not exhibit this overlap. Interestingly, prostate cancers that do not overexpress ETS family members (i.e., gene fusion-negative prostate cancers) harbor differential aberrations in 1q23, 6q16, 6q21, 10q23, and 10q24. Integrative analysis with matched mRNA profiles identified genetic alterations in several proposed candidate genes implicated in prostate cancer progression.