Safety and efficacy of combination chemotherapy regimens in older adults with pancreatic ductal adenocarcinoma: a systematic review.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is often diagnosed in older adults. However, most published studies investigating chemotherapy for PDA include a predominantly younger population, and the standard of care for the older adult population is not defined. It is our goal to review the literature available about the safety and efficacy of combination chemotherapy for locally advanced or metastatic PDA in older adults ≥65 years. METHODS: We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting checklist. We searched PubMed, EMBASE and MEDLINE databases to identify retrospective and prospective studies published until October 2018 that assessed the survival outcomes and adverse events in patients 65 years and older diagnosed with PDA and treated with combination chemotherapy. RESULTS: A total of 1,479 studies were screened. Twenty-four full-text studies were assessed for eligibility. Nineteen were excluded due to wrong study design (n=4) or abstract only with no further publication (n=15). A total of 5 full text studies met eligibility and were included in the present review. Combination chemotherapy is associated with similar survival to that reported in younger populations with advanced PDA. The most common toxicities across studies included: sensory neuropathy and neutropenia. Two studies each reported one death related to treatment-associated sepsis. DISCUSSION: Papers examined in this systematic review concluded that the use of combination chemotherapy regimens is safe and effective for older adults with minimal comorbidities and adequate performance status. Prospective data is needed to confirm these findings, provided that the most significant limitation of these studies was a small sample size.

Spontaneous regression of pancreatic cancer with liver metastases.

Spontaneous cancer regression is a rare event, scarcely reported among gastrointestinal malignancies. Pancreatic adenocarcinoma regression has been documented in five previous cases, none of which included liver metastases, and the mechanism by which this occurs is not known. A 56-year-old woman with history of discoid lupus, homocysteinemia and peripheral vascular disease was diagnosed with stage IV pancreatic ductal adenocarcinoma (PDA) metastatic to the liver. She received palliative chemotherapy with 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) for 6 months, complicated by mucositis, diarrhoea, vomiting and two Clostridium difficile colitis episodes. Cancer initially responded to chemotherapy. However, due to substantial toxicities, she decided to discontinue cytotoxic chemotherapy and focus on palliation alone. Thereafter, CT and carbohydrate antigen (CA) 19-9 showed further response and ultimately complete cancer regression that has persisted for 33 months after cessation of chemotherapy. This is the first report in the English literature showing spontaneous regression of a PDA with liver metastases. Two possible mechanisms are proposed: antitumoral autoimmunity and tumour hypoxia related to vascular disease.

White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging.

Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline.