Preoperative Diabetes Mellitus and Long-Term Survival After Resection of Pancreatic Adenocarcinoma

Chu, Carrie K.; Mazo, Ashley; Goodman, Michael; Egnatashvili, Vasili; Sarmiento, Juan M.; Staley, Charles A.; Galloway, John R.; Adsay, Volkan; Jacobs, Sol; Kooby, David A.

doi:10.1245/s10434-009-0789-6

Cited by 93 publications

(107 citation statements)

References 43 publications

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“…9 In a related study using a similar patient population, although assessing longterm outcomes, this group did find that new-onset DM (<24 months before the diagnosis of PDAC) was predictive of poorer OS, independent of tumor characteristics and related comorbidities, such as BMI. 15 Interestingly, preoperative DM, regardless of time of onset, was also independently associated with increased tumor size. Our novel finding that preoperative insulin use is an independent predictor of both early postoperative mortality and OS suggests that hyperinsulinemia itself may be responsible for some of the findings described above.…”

Section: Discussionmentioning

confidence: 90%

Medically Managed Hypercholesterolemia and Insulin-Dependent Diabetes Mellitus Preoperatively Predicts Poor Survival after Surgery for Pancreatic Cancer

Chagpar

Martin

Ahmad

et al. 2011

Journal of Gastrointestinal Surgery

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Section: Discussionmentioning

confidence: 90%

Medically Managed Hypercholesterolemia and Insulin-Dependent Diabetes Mellitus Preoperatively Predicts Poor Survival after Surgery for Pancreatic Cancer

Chagpar

Martin

Ahmad

et al. 2011

Journal of Gastrointestinal Surgery

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“…This survival benefit of metformin was particularly notable because patients with a preoperative diagnosis with diabetes have been shown to have worse outcomes and thus a worse OS. 29,30 After accounting for differences in baseline risk factors including nodal status, metformin use was associated with a 21 % improved survival. Interestingly, we also observed a dose-effect with an increasing daily dose of metformin associated with improved survival.…”

Section: Discussionmentioning

confidence: 99%

Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer

Cerullo

Gani

Chen

et al. 2016

Journal of Gastrointestinal Surgery

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Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD = 9.1 years). Roughly one half of patients were female (n = 1735, 51.1 %); 49.1 % (n = 1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n = 664) had diabetes. At the time of surgery, 60.0 % (n = 2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n = 1212) a partial/distal pancreatectomy, while 4.3 % (n = 147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p = 0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4-67.3 %] vs. 69.2 % [95 % CI 64.2-73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR] = 0.79, 95 % CI 0.67-0.93, p = 0.005). Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand its role in modifying cancer-specific and overall health outcomes.

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“…Chu et al examined the records of resected PC patients and found that preexisting diabetes is associated with reduced survival in patients who underwent resection for PC. Additionally, PC with new-onset diabetes may exhibit increased tumor size and decreased postresection survival [34]. When hamster H2T pancreatic carcinoma cells were implanted into the cheek pouches of Syrian hamsters, the tumor size, weight, and total DNA content were significantly greater in animals with diabetes, demonstrating that diabetes appears to promote the growth of PC cells in the hamster [35].…”

Section: Hyperglycemia and Cancer Cell Proliferationmentioning

confidence: 99%

Hyperglycemia, a Neglected Factor during Cancer Progression

Duan

Shen

Liu

et al. 2014

BioMed Research International

193

157

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Recent evidence from large cohort studies suggests that there exists a higher cancer incidence in people with type 2 diabetes (DM2). However, to date, the potential reasons for this association remain unclear. Hyperglycemia, the most important feature of diabetes, may be responsible for the excess glucose supply for these glucose-hungry cells, and it contributes to apoptosis resistance, oncogenesis, and tumor cell resistance to chemotherapy. Considering associations between diabetes and malignancies, the effect of hyperglycemia on cancer progression in cancer patients with abnormal blood glucose should not be neglected. In this paper, we describe the role that hyperglycemia plays in cancer progression and treatment and illustrate that hyperglycemia may contribute to a more malignant phenotype of cancer cells and lead to drug resistance. Therefore, controlling hyperglycemia may have important therapeutic implications in cancer patients.

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Preoperative Diabetes Mellitus and Long-Term Survival After Resection of Pancreatic Adenocarcinoma

Abstract: Preexisting DM is associated with reduced survival in patients undergoing resection for PDAC. PDAC with new-onset DM may exhibit increased tumor size and decreased postresection survival. Additional investigation is needed to clarify etiology and impact of PDAC-associated DM.

Cited by 93 publications

References 43 publications

Medically Managed Hypercholesterolemia and Insulin-Dependent Diabetes Mellitus Preoperatively Predicts Poor Survival after Surgery for Pancreatic Cancer

Medically Managed Hypercholesterolemia and Insulin-Dependent Diabetes Mellitus Preoperatively Predicts Poor Survival after Surgery for Pancreatic Cancer

Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer

Hyperglycemia, a Neglected Factor during Cancer Progression

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