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1.
Ann Surg Oncol ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014164

ABSTRACT

BACKGROUND: Outside of clinical trials, real-world data of advanced gastric cancers (AGCs) managed with perioperative or adjuvant chemotherapy with a backbone of D2 lymphadenectomy is limited. PATIENTS AND METHODS: Curative resections for gastric adenocarcinoma between January 2003 and January 2020 at the Tata Memorial Centre were analyzed, comparing three time periods marking major increments in annual gastric resections (GRs). RESULTS: 1657 radical gastric resections were performed with a morbidity and mortality rate of 34.9% and 1.4%, respectively. Over three consecutive periods, the number of annual GRs increased from 56/year to 97/year to 156/year (P < 0.001) with a significant escalation in surgical magnitude and complexity. Improvement in surgical quality indicators (median lymph node yield from 15 to 25, P < 0.001 and margin negativity from 8.2 to 5.5%, P = 0.002) was observed with no corresponding increase in severe complications (6.9%) or mortality (1.4%). The proportion of distal and signet ring cancers was found to decrease over time, with an increase in proximal cancers and younger age at presentation. Overall, 90% of GRs were for AGCs with a median overall survival (OS) of 4.4 years (± 6 months), and 5-year OS rate of 47.6% (± 1.9%). CONCLUSIONS: Change in pattern of tumor characteristics was observed. Aggressive treatment options for AGC were employed progressively with excellent survival. With increase in volumes, improvements in surgical quality indicators, and a relative improvement in postoperative mortality was observed. These results provide a roadmap for developing dedicated gastric cancer centers.

2.
Int J Cancer ; 139(4): 869-81, 2016 08 15.
Article in English | MEDLINE | ID: mdl-27062572

ABSTRACT

Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients. In the current prospective study, we investigated the role of IL17 producing TCRγδ(+) (Tγδ17), CD4(+) (Th17), CD8(+) (Tc17) and regulatory T cells (Tregs) in pathogenesis of GBC. Analysis by multi-color flow cytometry revealed that compared to healthy individuals (HI), Tγδ17, Th17 and Tc17 cells were increased in peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TIL) of GBC patients. Tregs were decreased in PBMCs but increased in TILs of GBC patients. The suppressive potential of Tregs from GBC patients and HI were comparable. Serum cytokines profile of GBC patients showed elevated levels of cytokines (IL6, IL23 and IL1ß) required for polarization and/or stabilization of IL17 producing cells. We demonstrated that Tγδ17 cells migrate toward tumor bed using CXCL9-CXCR3 axis. IL17 secreted by Tγδ17 induced productions of vascular endothelial growth factor and other angiogenesis related factors in GBC cells. Tγδ17 cells promote vasculogenesis as studied by chick chorioallantoic membrane assay. Survival analysis showed that Tγδ17, Th17 and Treg cells in peripheral blood were associated with poor survival of GBC patients. Our findings suggest that Tγδ17 is a protumorigenic subtype of γδT cells which induces angiogenesis. Tγδ17 may be considered as a predictive biomarker in GBC thus opening avenues for targeted therapies.


Subject(s)
Gallbladder Neoplasms/etiology , Gallbladder Neoplasms/pathology , Interleukin-17/biosynthesis , Neovascularization, Pathologic , Receptors, Antigen, T-Cell, gamma-delta/metabolism , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Biomarkers , Cytokines/metabolism , Female , Gallbladder Neoplasms/mortality , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Middle Aged , Prognosis , Tumor Microenvironment
3.
Dig Surg ; 33(2): 146-56, 2016.
Article in English | MEDLINE | ID: mdl-26820472

ABSTRACT

BACKGROUND: There are no data on surgical outcomes of major gastrointestinal cancer resections in the expanding Indian oncogeriatric population. METHODS: A prospective database of patients who underwent major gastrointestinal cancer resections during varying time periods (2006-2014) was analyzed retrospectively. RESULTS: Two thousand six hundred and forty three patients with a median age of 53 were analyzed. Four hundred and seventy two (17.9%) patients were aged ≥65 years and 235 (8.9%) patients were ≥70 years. Mortality rates were not significantly higher in the elderly (≥65 years) or the very elderly (≥70 years) when compared to younger controls, being 2.8 vs. 1.6% (p = 0.09) and 3.0 vs. 1.7% (p = 0.162) respectively. Overall morbidity was similar for patients ≥65 or <65 years (24.2 vs. 21.7%, p = 0.253), but was higher in patients ≥70 years (29.8 vs. 21.4%, p = 0.003). The incidence of severe complications, however, was not significantly greater in this age group (13.2 vs. 12.5%, p = 0.74). CONCLUSIONS: Major gastrointestinal cancer resections in the elderly Indian population, though uncommon, are safe when performed at experienced high volume centres. These results should serve as a starting point for the gradual development of dedicated oncogeriatric programs in the Indian subcontinent.


Subject(s)
Digestive System Surgical Procedures/statistics & numerical data , Gastrointestinal Neoplasms/surgery , Adult , Age Factors , Aged , Aged, 80 and over , Databases, Factual , Digestive System Surgical Procedures/mortality , Female , Gastrointestinal Neoplasms/mortality , Humans , India , Logistic Models , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Treatment Outcome
4.
Indian J Gastroenterol ; 33(3): 258-64, 2014 May.
Article in English | MEDLINE | ID: mdl-24214581

ABSTRACT

BACKGROUND: The reported incidence of postoperative liver failure in cirrhotic patients is highly varied with diverse risk factors identified to predict risk, mainly drawn from organ or disease-specific studies. We aimed to assess risk factors for the development of postoperative liver failure in a specific cohort of patients with cirrhosis undergoing abdominal cancer resection. METHODS: From November 2007 to October 2012, 30 cirrhotic patients who underwent curative resection for abdominal cancer were analyzed. The postoperative trends in liver function were followed and the incidence of postoperative liver failure was demonstrated. RESULTS: Among the 30 patients, the tumors were located in the stomach (n = 5), pancreas (n = 5), colon/rectum (6), liver (n = 11), gallbladder (n = 1), and retroperitoneum (n = 2). Eighteen (60 %) patients experienced postoperative liver failure of which 7 (23 %) patients required deviation from the clinical course or management. There was one mortality due to grade C liver failure and hepatorenal syndrome. On multivariate analysis, only age (>55 years) was found to be statistically significant to predict postoperative liver failure (p = 0.024). CONCLUSION: Liver dysfunction remains a major problem during the postoperative phase of major gastrointestinal cancer resections. However, less than one fourth of well-selected patients will develop significant postoperative liver failure. This incidence may be further reduced if the selection is restricted to younger patients.


Subject(s)
Abdominal Neoplasms/complications , Abdominal Neoplasms/surgery , Liver Cirrhosis/complications , Liver Failure/etiology , Postoperative Complications/etiology , Adult , Age Factors , Aged , Cohort Studies , Female , Forecasting , Humans , Incidence , India/epidemiology , Liver Cirrhosis/etiology , Liver Failure/epidemiology , Male , Middle Aged , Multivariate Analysis , Patient Selection , Postoperative Complications/epidemiology , Prospective Studies , Risk Factors
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