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.

Early documentation of therapeutic response at 6 weeks following corticosteroid therapy in extensive sarcoidosis: promise of FDG-PET.

Abstract: A 52-year-old man, who was treated with antitubercular drugs for 1 year without any benefit for an initial diagnosis of tuberculosis, and was referred for further evaluation. An FDG-PET study was performed to evaluate the whole-body disease status, which showed multiple abnormal foci in bilateral neck nodes, mediastinal, axillary, and multiple abdominal (para-aortic and inguinal) nodes, and the liver, spleen, and thyroid. A rebiopsy of the inguinal nodes for a definitive diagnosis was confirmatory of sarcoidosis. He had a history of hypothyroidism, which is a frequent accompaniment of sarcoidosis due to the association of autoimmunity in this population. He was treated with oral corticosteroids and was referred for reassessment of his disease status with FDG-PET following 6 weeks of therapy. The FDG-PET images showed remarkable improvement with near total resolution of the FDG hypermetabolism at the initially involved sites. The present case underscores the value of FDG-PET imaging in whole-body monitoring of early response to therapy in patients of sarcoidosis (particularly those with extensive disease) that can be of substantial benefit and indicates the promise of this powerful molecular imaging technique in managing this multisystem disorder.

Radiotherapeutic management of locally advanced head and neck cancer.

Abstract: Head and neck cancer management has undergone several paradigm shifts for several relevant reasons. From the dismal experience with the use of radiotherapy as the sole modality in the treatment of this group of patients with advanced disease, radiotherapy has been evaluated as an adjuvant for the same group of patients who had undergone successful surgery. Although there is no level 1 evidence to support postoperative adjuvant radiation, several studies have demonstrated that adjuvant radiotherapy reduces the local failures and, thereby, improves survival. Predictors of recurrence after surgical resection are: positive margins of resection; extranodal spread in involved nodes; perineural invasion; and presence of two or more involved regional lymph nodes. Realization of the advantages of a combination of chemotherapy with radiotherapy has had a major impact on the management of these cancers. There is emerging evidence for the use of adjuvant concurrent chemoradiotherapy in the group with high-risk features. Multiple organ conservation strategies in the management of locally advanced head and neck cancers have evolved over the years. However, the meta-analyses of impact of chemotherapy in various settings reveal that concomitant chemoradiotherapy is superior to any of the other regimens. Increasing use of computed tomography, magnetic resonance imaging and positron emission tomography scan images has resulted in better visualization of target volumes and critical structures. Delineation of these structures is of paramount importance and has resulted in a profound change in conformal treatment planning. Better understanding of the physical aspects of delivery of radiotherapy and the advent of modern treatment planning systems have led to the development of conformal techniques. Although the benefit of these techniques on survival have yet to be demonstrated, there is evidence to suggest that they reduce treatment-related toxicities significantly and facilitate dose escalation. Increased knowledge of radiobiology has led to the development of various altered fractionation regimens in the management of locally advanced head and neck cancers. Discovery of cell-cycle kinetics and signal transduction pathways has led to the unearthing of several potential targets for targeted therapy. The epidermal growth factor receptor gene has emerged as the most promising target. The role of biological radiation response modifiers is evolving. All of these approaches to improve the therapeutic gain would be incomplete without evaluating their effect on the quality of life of these patients.

Extracellular 2'5'-oligoadenylate synthetase 2 mediates T-cell receptor CD3-ζ chain down-regulation via caspase-3 activation in oral cancer.

Abstract: Decreased expression of CD3-ζ chain, an adaptor protein associated with T-cell signalling, is well documented in patients with oral cancer, but the mechanistic justifications are fragmentary. Previous studies in patients with oral cancer have shown that decreased expression of CD3-ζ chain was associated with decreased responsiveness of T cells. Tumours are known to induce localized as well as systemic immune suppression. This study provides evidence that oral tumour-derived factors promote immune suppression by down-regulating CD3-ζ chain expression. 2'5'-Oligoadenylate synthetase 2 (OAS2) was identified by the proteomic approach and our results established a causative link between CD3-ζ chain down-regulation and OAS2 stimulation. The surrogate situation was established by over-expressing OAS2 in a HEK293 cell line and cell-free supernatant was collected. These supernatants when incubated with T cells resulted in down-regulation of CD3-ζ chain, which shows that the secreted OAS2 is capable of regulating CD3-ζ chain expression. Incubation of T cells with cell-free supernatants of oral tumours or recombinant human OAS2 (rh-OAS2) induced caspase-3 activation, which resulted in CD3-ζ chain down-regulation. Caspase-3 inhibition/down-regulation using pharmacological inhibitor or small interfering RNA restored down-regulated CD3-ζ chain expression in T cells induced by cell-free tumour supernatant or rh-OAS2. Collectively these results show that OAS2 leads to impairment in CD3-ζ chain expression, so offering an explanation that might be applicable to the CD3-ζ chain deficiency observed in cancer and diverse disease conditions.

Anorectal melanoma: a large clinicopathologic study from India.

Abstract: Anorectal melanoma is a rare tumor. It has dismal prognosis; only 10% of patients live longer than 5 years. It commonly presents as bleeding from the rectum or as a hemorrhoidal mass. The management of this tumor is controversial. Some authors believe that a palliative local excision is the treatment of choice, whereas others recommend radical surgery in localized disease. We present a retrospective analysis of 72 patients who were managed at our center between 1990 and 2001. This is the largest series from India. Most patients (48/72; 66%) presented with distant metastases. Twenty-four patients (24/72; 33%) underwent an abdomino-perineal resection. Nineteen patients (19/24) had positive lymph node disease, and the mean disease-free survival in these patients was 10.3 months. Disease-free survival in the node-negative patients was 26.5 months. A subset of patients with localized disease can benefit from radical surgery. In patients with large bulky localized disease, radical surgery provides better palliation than local excision.

Radical radiation vs surgery plus post-operative radiation in advanced (resectable) supraglottic larynx and pyriform sinus cancers: a prospective randomized study

Abstract: Aim: Survival in head and neck cancers reflect loco-regional control. With an aim of organ and function preservation the present study was undertaken to compare local failure and survivals. Material and methods: Between August 1991–December 1995, 72 patients with resectable advanced supraglottic cancers, were randomized to radical surgery followed by post-operative radiation therapy (Sx+PORT) (Arm I) or radical radiation therapy followed by salvage surgery (RRT+/−SSx) (Arm II). Results: Sixty-four of 72 patients were evaluable, 55 were T3 (86%) and 9 were T4 (14%) tumors. In Arm I ( n =35) with a mean follow-up of 24 months (2–86 months), 21 patients were alive without disease. Six patients had recurrence, one each at local and tracheostomy stoma, four had nodal recurrence only, and two developed 2nd primary in soft palate/tonsil and parotid at 15 and 18 months respectively. In Arm II ( n =29), with a mean follow-up of 24 months (3–81 months), 14 patients were alive without disease. Thirteen patients had recurrence, eight had local (one patient had persistent disease), two nodal only, three loco-regional and two patients developed distant metastasis (lung). One out of eight local recurrence and 2/2 nodal recurrences were salvaged with Sx. There was a significant difference in disease-free survival between the two treatment arms, DFS (5 years) of 70% in Arm I vs 50% in Arm II ( p =0.04), but did not have any impact on overall survival OAS (5 years); 73% vs 77% ( p =0.79). Voice/laryngeal preservation was possible in 18/29 patients (62%) treated with RRT+/− Sx, without significantly affecting the OAS. ‘Pathological upstaging’ was another significant finding seen in 64% of clinical T3 after radical surgery. Conclusion: RRT+/−SSx can be a feasible option in low volume, favourable resectable stage III and IV supraglottic lesions for better quality of life.