Diabetes mellitus is associated with unfavorable pathologic features, increased postoperative mortality, and worse long-term survival in resected pancreatic cancer

Hank, Thomas; Sandini, Marta; Qadan, Motaz; Weniger, Maximilian; Ciprani, Debora; Li, Annie; Ferrone, Cristina R.; Warshaw, Andrew L.; Lillemoe, Keith D.; Castillo, Carlos Fernández‐del

doi:10.1016/j.pan.2019.10.007

Cited by 22 publications

(32 citation statements)

References 53 publications

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“…These would also imply that abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or even overt diabetes) is actually present long before the onset of PDAC and may be a contributor to its development. Consistent with this assumption and suggestive of a possible causal role of impaired glucose homeostasis, PDAC incidence [36,37] and mortality [38][39][40] have been recently shown to increase with increasing fasting glucose levels, even within the normal range [36,37]. Moreover, in a recent case-control study, Sharma et al provided evidence that blood sugar levels in PDAC patients were elevated for up to three years prior to PDAC diagnosis [41].…”

Section: Figurementioning

confidence: 79%

Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress

Menini

Iacobini

Vitale

et al. 2021

Cancers

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Both type 2 (T2DM) and type 1 (T1DM) diabetes mellitus confer an increased risk of pancreatic cancer in humans. The magnitude and temporal trajectory of the risk conferred by the two forms of diabetes are similar, suggesting a common mechanism. Carbonyl stress is a hallmark of hyperglycemia and dyslipidemia, which accompanies T2DM, prediabetes, and obesity. Accumulating evidence demonstrates that diabetes promotes pancreatic ductal adenocarcinoma (PDAC) in experimental models of T2DM, a finding recently confirmed in a T1DM model. The carbonyl stress markers advanced glycation end-products (AGEs), the levels of which are increased in diabetes, were shown to markedly accelerate tumor development in a mouse model of Kras-driven PDAC. Consistently, inhibition of AGE formation by trapping their carbonyl precursors (i.e., reactive carbonyl species, RCS) prevented the PDAC-promoting effect of diabetes. Considering the growing attention on carbonyl stress in the onset and progression of several cancers, including breast, lung and colorectal cancer, this review discusses the mechanisms by which glucose and lipid imbalances induce a status of carbonyl stress, the oncogenic pathways activated by AGEs and their precursors RCS, and the potential use of carbonyl-scavenging agents and AGE inhibitors in PDAC prevention and treatment, particularly in high-risk diabetic individuals.

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Section: Figurementioning

confidence: 79%

Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress

Menini

Iacobini

Vitale

et al. 2021

Cancers

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“…Earlier studies had shown that DM was associated with increased abdominal complication and was an independent risk factor of POPF in patients undergoing PD for pancreatic cancer. 6 , 7 , 32 Recent study by Hank et al 33 also showed DM was associated with increased postoperative mortality after PD in pancreatic cancer. Various factors like advanced age, high BMI, malnutrition, coexisting co-morbidities were considered to be contributory.…”

Section: Discussionmentioning

confidence: 95%

Impact of diabetes mellitus on morbidity and survival after pancreaticoduodenectomy for malignancy

Deo

Kulkarni

Kumar‐M

et al. 2021

Ann Hepatobiliary Pancreat Surg

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Backgrounds/Aims: Diabetes mellitus (DM) is a known risk factor for morbidity, length of hospital stay, or mortality after surgery, however, its impact on postoperative course and long-term survival after pancreaticoduodenectomy (PD) is not clear. Methods: This is a retrospective analysis of prospectively maintained database of 141 patients with periampullary and pancreatic head adenocarcinoma operated between January 2001 and March 2019. Clinico-pathological records and follow-up data were retrieved and analyzed. Cumulative hazard was computed for comparing the survival between DM and non-DM. Results: DM was present in 31/141 (21.9%) patients, while 16/31 (51.6%). were new-onset DM (NODM). Tumor size, lymphovascular & perineural invasion, type of surgery, lymph node positivity and R0 resection rate were comparable between diabetic and non-diabetic. There was no significant difference in postoperative pancreatic fistula, delayed gastric emptying, infectious complication, hospital stay and mortality between DM and nondiabetics. Patients with DM had worse survival at 3 years

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“…The median time from DM diagnosis to PC development was shorter than 2 years. More recently, another study reported that patients with DM have more aggressive tumors and higher surgical morbidity, concluding that they have significantly shorter survival than those without DM and this effect is more pronounced in patients undergoing neoadjuvant CT [22]. Similarly, in a meta-analysis involving 6 studies, survival was significantly shorter in PC patients with DM who received adjuvant CT, compared those without DM [23].…”

Section: Discussionmentioning

confidence: 96%

Effect of type 2 diabetes mellitus on survival in metastatic pancreatic cancer

Şahin¹,

Sakin²,

Atçı³

et al. 2021

Journal of Surgery and Medicine

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Background/Aim: Many epidemiological studies describe a relationship between pancreatic cancer (PC) and Diabetes mellitus (DM). However, there are not enough studies investigating the effect of DM on survival of patients with metastatic PC. The purpose of this retrospective study was to investigate the effect of DM and its treatment on survival of patients with metastatic PC who received chemotherapy (CT) as first line treatment. Methods: Patients with metastatic PC who were followed up at the department of medical oncology between 2006 and 2018 were enrolled in this retrospective cohort study. Patients aged 18 years and over, who had metastatic disease at diagnosis and were treated with CT were analyzed. Patients with DM were stratified into two groups based on the history of medical treatments used for DM as follows: Oral antidiabetic (OAD) and OAD + insulin combination. Results: Following results were obtained after analyzing the medical records of 372 patients with metastatic PC, among which 125 (33.6%) had type II DM at the time diagnosis: The median age of the patients was 61 (range: 28-83) years. There were 136 (36.6%) female patients, and the median overall survival (OS) was 9.0 months in patients without DM, and 7.0 months (P=0.023) in those with DM. OS was 8.0 months in diabetic patients using OAD+insulin combination compared to 7.0 months in those receiving OAD (P=0.614) only. Multivariate analysis revealed that the presence of DM [Hazard ratio (HR), 1.43)], Eastern Cooperative Oncology Group Performance Status 3 (HR, 1.62), treatment with gemcitabine+Nab-paclitaxel (HR, 0.29) or folfirinox (HR, 0.46), and CA 19-9 level (HR, 1.01) were factors related to OS. Conclusion: In our study, we observed that the presence of DM adversely affected survival in metastatic PC patients who received CT as first line treatment; however, whether these patients used OAD or OAD+insulin combination did not affect survival.

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Diabetes mellitus is associated with unfavorable pathologic features, increased postoperative mortality, and worse long-term survival in resected pancreatic cancer

Cited by 22 publications

References 53 publications

Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress

Diabetes and Pancreatic Cancer—A Dangerous Liaison Relying on Carbonyl Stress

Impact of diabetes mellitus on morbidity and survival after pancreaticoduodenectomy for malignancy

Effect of type 2 diabetes mellitus on survival in metastatic pancreatic cancer

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