Impact of Preoperative Diabetes on Long-Term Survival After Curative Resection of Pancreatic Adenocarcinoma: A Systematic Review and Meta-Analysis

Walter, Ulrike; Kohlert, Tobias; Rahbari, Nuh N.; Weitz, Juergen; Welsch, Thilo

doi:10.1245/s10434-013-3415-6

Cited by 32 publications

(18 citation statements)

References 36 publications

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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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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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“…In the field of PDAC, the prognostic relevance of preoperative DM is still controversial. In retrospective studies DM was associated with reduced survival in patients undergoing resection for PDAC [21, 26, 29, 41–45]; on the other hand, DM had no impact on overall survival in other studies [46–50] or was unexpectedly associated to a reduced risk of death [51–53]. Inconsistent findings were also reported when DM was stratified by duration of diabetes: recent-onset DM, but not long-standing DM was associated with reduced PDAC survival in some studies [10, 29], while others did not find this association [23, 24, 43, 54, 55].…”

Section: Discussionmentioning

confidence: 99%

Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study

et al. 2016

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AimTo investigate the effect of diabetes mellitus (DM) on disease-free and overall post-resection survival of patients with pancreatic ductal adenocarcinoma (PDAC)MethodsProspective observational study on patients admitted for pancreatic disease from January 2008 to October 2012. DM was classified as recent-onset (<48 months before PDAC diagnosis), longstanding (≥48 months before PDAC) or new onset (after surgery).ResultsOf 296 patients, 140 had a diagnosis of DM prior to surgery (26 longstanding, 99 recent-onset, 15 with unknown duration). Median follow-up time was 5.4 ± 0.22 years. Patients with recent onset DM had poorer postoperative survival than patients without DM: disease-free survival and overall survival were 1.14±0.13 years and 1.52±0.12 years in recent onset DM, versus 1.3±0.15 years and 1.87±0.15 years in non-diabetic patients (p = 0.013 and p = 0.025, respectively). Longstanding DM and postoperative new onset DM had no impact on prognosis. Compared to cases without DM, patients with recent onset DM were more likely to have residual disease after surgery and to develop liver metastases during follow-up. Multivariate analysis confirmed recent onset DM was independently associated with PDAC relapse (hazard ratio 1.45 [1.06–1.99]).ConclusionPreoperative recent onset DM has an impact on survival after the resection of PDAC.

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“…Patients with PC often have concurrent diabetes or impaired glucose tolerance. Diabetes has been suggested to have a negative impact on the clinical outcome of PC 21 , 22 . In this study, we did not detect an association between TE and history of diabetes or initial blood glucose level.…”

Section: Discussionmentioning

confidence: 99%

ABO non‐O type as a risk factor for thrombosis in patients with pancreatic cancer

Pise

Overman

et al. 2015

Cancer Medicine

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ABO blood type has previously been identified as a risk factor for thrombosis and pancreatic cancer (PC). The aim of the study is to demonstrate the associations between ABO blood type and other clinical factors with the risk of thromboembolism (TE) in patients with PC. We conducted a retrospective study in 670 patients with pathologically confirmed pancreatic adenocarcinoma at the University of Texas MD Anderson Cancer Center. Clinical information was retrieved from medical records. ABO blood type was determined serologically and/or genetically. Logistic regression models, Kaplan–Meier plot, log-rank test, and Cox proportional hazard regression models were employed in data analysis. The incidence of TE was 35.2% in 670 patients who did not have TE prior to cancer diagnosis. Pulmonary embolism (PE) and deep vein thrombosis (DVT) consisted 44.1% of the TE events. Non-O blood type, pancreatic body/tail tumors, previous use of antithrombotic medication, and obesity (body mass index >30 kg/m2) were significant predictors for TE in general. Blood type A and AB, low hemoglobin level (≤10 g/dL), obesity, metastatic tumor, and pancreatic body/tail tumors were significant predictors for PE and DVT. Patients with metastatic tumor or pancreatic body/tail tumors had a much higher frequency of early TE events (≤3 months after cancer diagnosis); and early TE occurrence was a significant independent predictor for increased risk of death. These observations suggest that ABO non-O blood type is an independent predictor for TE in PC. A better understanding of the risk factors for TE in PC may help to identify patients who are most likely to benefit from prophylactic anticoagulation therapy.

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Impact of Preoperative Diabetes on Long-Term Survival After Curative Resection of Pancreatic Adenocarcinoma: A Systematic Review and Meta-Analysis

Cited by 32 publications

References 36 publications

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

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

Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study

ABO non‐O type as a risk factor for thrombosis in patients with pancreatic cancer

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