Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection. New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. .

VHRs continue to rise in incidence and cost. By reducing recurrence rate alone, a cost saving of US $32 million dollars for each 1% reduction in operations would result. Further research is necessary for improved understanding of ventral hernia etiology and treatment and is critical to cost effective healthcare.

Objective: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019). Summary Background Data: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking. Methods: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology. Results: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety. Conclusion: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

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Objective To use a large population-based cohort to determine age-dependent short-term outcomes after pancreatic resection. Methods We identified all pancreatic resections in Texas from 1999 to 2005. Patients were stratified into 4 age groups (<60, 60–69, 70–79, and 80+ years). Bivariate and multivariate analyses were performed to determine the effect of age on mortality, discharge to home versus requiring inpatient nursing care, and length of stay. Results Three thousand seven hundred and thirty-six patients underwent pancreatic resection. Unadjusted in-hospital mortality increased with each increasing age group from 2.4% in patients <60 to 11.4% in patients 80 years and older (P < 0.0001). Likewise, postoperative lengths of stay increased with each increasing age group (P = 0.02). Age group independently predicted the need for discharge to an inpatient nursing unit rather than home (P < 0.0001), with the odds ration (OR) increasing with each increasing age group. With each increasing age group, patients were less likely to be resected at high-volume (H-V) hospitals (>10 pancreatic resections/y). Whereas low-volume (L-V) hospitals (≤10 pancreatic resections/y) had higher mortality rates (3.2% versus 7.3%, P < 0.0001), the difference in mortality between H- and L-V hospitals was more striking in older patients. With increasing age group, mortality increased from 3.0% to 9.5% to 11.4% to 14.7% at L-V hospitals. It increased from 2.0% to 3.5% to 4.5% to 8.7% at H-V hospitals (P < 0.0001). In the multivariate model controlling for gender, race, hospital volume, year of surgery, diagnosis, risk of mortality, severity of illness, admission status, and procedure type, older age group independently predicted increased mortality. The OR for patients 60–69 years was 2.5 (P = 0.0003), the OR for patients 70–79 years was 1.8 (P = 0.02), and the OR for patients 80+ years was 4.4 (P < 0.0001) when compared with patients <60 years. Conclusions In contrast to some previous single-institution studies, we found that increased age is an independent risk factor for mortality after pancreatic resection. For all ages, mortality rates were higher at L-V hospitals, but the difference worsened significantly with increasing age. Older patients had longer lengths of stay, were less likely to be discharged home, and more likely to require care at an inpatient nursing or acute care facility at the time of discharge.