Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it is a disease of dismal prognosis. While immunotherapy has revolutionized the treatment of various solid tumors, it has achieved little success in PDAC. Hypoxia within the stroma-rich tumor microenvironment is associated with resistance to therapies and promotes angiogenesis, giving rise to a chaotic and leaky vasculature that is inefficient at shuttling oxygen and nutrients. Hypoxia and its downstream effectors have been implicated in immune resistance and could be contributing to the lack of response to immunotherapy experienced by patients with PDAC. Paradoxically, increasing evidence has shown hypoxia to augment genomic instability and mutagenesis in cancer, suggesting that hypoxic tumor cells could have increased production of neoantigens that can potentially enable their clearance by cytotoxic immune cells. Strategies aimed at relieving this condition have been on the rise, and one such approach opts for normalizing the tumor vasculature to reverse hypoxia and its downstream support of tumor pathogenesis. An important consideration for the successful implementation of such strategies in the clinic is that not all PDACs are equally hypoxic, therefore hypoxia-detection approaches should be integrated to enable optimal patient selection for achieving improved patient outcomes.

Successful surgery combines quality (achievement of a positive outcome) with safety (avoidance of a negative outcome). Outcome assessment serves the purpose of quality improvement in health care by establishing performance indicators and allowing the identification of performance gaps. Novel surgical quality metric tools (benchmark cutoffs and textbook outcomes) provide procedure-specific ideal surgical outcomes in a subgroup of well-defined low-risk patients, with the aim of setting realistic and best achievable goals for surgeons and centers, as well as supporting unbiased comparison of surgical quality between centers and periods of time. Validated classification systems have been deployed to grade adverse events during the surgical journey: (1) the ClassIntra classification for the intraoperative period; (2) the Clavien–Dindo classification for the gravity of single adverse events; and the (3) Comprehensive Complication Index (CCI) for the sum of adverse events over a defined postoperative period. The failure to rescue rate refers to the death of a patient following one or more potentially treatable postoperative adverse event(s) and is a reliable proxy of the institutional safety culture and infrastructure. Complication assessment is undergoing digital transformation to decrease resource-intensity and provide surgeons with real-time pre- or intraoperative decision support. Standardized reporting of complications informs patients on their chances to realize favorable postoperative outcomes and assists surgical centers in the prioritization of quality improvement initiatives, multidisciplinary teamwork, surgical education, and ultimately, in the enhancement of clinical standards.