Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest of all common malignancies. Treatment is difficult and often complicated by the presence of cachexia. The clinical portrait of cachexia contributes to the poor prognosis experienced by PDAC patients and worsens therapeutic outcomes. We propose that low bone mineral density is a component of cachexia, which we explore herein through a retrospective review of all patients at our facility that underwent surgery for PDAC between 2011 and 2018 and compared to sex-, age- and comorbidity-matched control individuals. Data were abstracted from the medical record and pre-operative computed tomography scans. Muscle mass and quality were measured at the L3 level and bone mineral density was measured as the radiation attenuation of the lumbar vertebral bodies. Patients with PDAC displayed typical signs of cachexia such as weight loss and radiologically appreciable deterioration of skeletal muscle. Critically, PDAC patients had significantly lower bone mineral density than controls, with 61.2% of PDAC patients categorized as osteopenic compared to 36.8% of controls. PDAC patients classified as osteopenic had significantly reduced survival (1.01 years) compared to patients without osteopenia (2.77 years). The presence of osteopenia was the strongest clinical predictor of 1- and 2-year disease-specific mortality, increasing the risk of death by 107% and 80%, respectively. Osteopenia serves as a test of 2-year mortality with sensitivity of 76% and specificity of 58%. These data therefore identify impaired bone mineral density as a key component of cachexia and predictor of postoperative survival in patients with PDAC. The mechanisms that lead to bone wasting in tumor-bearing hosts deserve further study.
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http://dx.doi.org/10.1002/cam4.4416 | DOI Listing |
Nutrients
December 2024
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10-20 years), prevention strategies represent an effective means to improve outcomes.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
The gut microbiome plays an important role in the carcinogenesis of luminal gastrointestinal malignancies and response to antineoplastic therapy. Preclinical studies have suggested a role of intratumoral gammaproteobacteria in mediating response to gemcitabine-based chemotherapy in pancreatic ductal adenocarcinoma (PDAC). To our knowledge, this is the first study to evaluate the impact of the PDAC microbiome on chemotherapy response using samples from human pancreatic tumor resections.
View Article and Find Full Text PDFUpdates Surg
January 2025
Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Da Hua Road, Dong Dan, Beijing, 100730, People's Republic of China.
Mod Pathol
January 2025
Department of Pathology, Research Institute for Medical Innovation, Radboud university medical center, Nijmegen, The Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. About 10% of affected individuals have an inherited component. Deleterious germline variants increase the lifetime risk for PDAC and are often associated with an elevated risk for extra-pancreatic malignancies.
View Article and Find Full Text PDFGastro Hep Adv
August 2024
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, Florida.
Background And Aims: Enzyme insufficiency (EPI) is common in chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and after pancreatic resection. 40%-50% of CP patients and 70%-80% of PDAC patients develop EPI. 1/3rd of these patients are prescribed Pancreatic enzyme replacement therapy (PERT), often at an inadequate dose, with evidence that this leads to increased morbidity and mortality.
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