Objective Advances in multimodality treatment paralleled increasing numbers of complex pancreatic procedures with major vascular resections. The aim of this meta-analysis was to evaluate the current outcomes of arterial resection (AR) in pancreatic surgery. Methods A systematic literature search was carried out from January 2011 until January 2020. MOOSE guidelines were followed. Predefined outcomes were morbidity, pancreatic fistula, postoperative bleeding and delayed gastric emptying, reoperation rate, mortality, hospital stay, R0 resection rate, and lymph node positivity. Duration of surgery, blood loss, and survival were also analyzed. Results Eight hundred and forty-one AR patients were identified in a cohort of 7111 patients. Morbidity and mortality rates in these patients were 66.8% and 5.3%, respectively. Seven studies (579 AR patients) were included in the meta-analysis. Overall morbidity (48% vs 39%, p = 0.1) and mortality (3.2% vs 1.5%, p = 0.27) were not significantly different in the groups with or without AR. R0 was less frequent in the AR group, both in patients without (69% vs 89%, p < 0.001) and with neoadjuvant treatment (50% vs 86%, p < 0.001). Weighted median survival was shorter in the AR group (18.6 vs 32 months, range 14.8–43.1 months, p = 0.037). Conclusions Arterial resections increase the complexity of pancreatic surgery, as demonstrated by relevant morbidity and mortality rates. Careful patient selection and multidisciplinary planning remain important.

Current therapies for treating pancreatic ductal adenocarcinoma (PDAC) are largely ineffective, with the desmoplastic environment established within these tumors being considered a central issue. We established a 3D spheroid co-culture in vitro model using a PDAC cell line (either PANC-1 or Capan-2), combined with stellate cells freshly isolated from pancreatic tumors (PSC) or hepatic lesions (HSC), and human type I collagen to analyze the efficiency of the chemotherapeutic gemcitabine (GEM) as well as two novel drug candidates derived from natural products: pseudopterosin (PsA-D) and O-methyltylophorinidine (TYLO). Traditional 2D in vitro testing of these agents for cytotoxicity on PANC-1 demonstrated IC50 values of 4.6 (±0.47) nM, 34.02 (±1.35) µM, and 1.99 (±0.13) µM for Tylo, PsA-D, and GEM, respectively; these values were comparable for Capan-2: 5.58 (±1.74) nM, 33.94 (±1.02) µM, and 0.41 (±0.06) µM for Tylo, PsA-D, and GEM, respectively. Importantly, by assessing the extent of viable cells within 3D co-culture spheroids of PANC-1 with PSC or HSC, we could demonstrate a significant lack of efficacy for GEM, while TYLO remained active and PsA-D showed slightly reduced efficacy: GEM in PANC-1/PSC (IC50 = >100 µM) or PANC-1/HSC (IC50 = >100 µM) spheroids, TYLO in PANC-1/PSC (IC50 = 3.57 ± 1.30 nM) or PANC-1/HSC (IC50 = 6.39 ± 2.28 nM) spheroids, and to PsA-D in PANC-1/PSC (IC50 = 54.42 ± 12.79 µM) or PANC-1/HSC (IC50 = 51.75 ± 0.60 µM). Microscopic 3D rendering supported these cytotoxicity outcomes, showing little or no morphological spheroid structure change during this period of rapid cell death. Our results support the use of this 3D spheroid co-culture in vitro model having a desmoplastic microenvironment for the identification of possible novel chemotherapeutic drug candidates for PDAC, such as TYLO and PsA-D.

No abstract

Pancreatic cancer is predicted to become the second-leading cause of cancer-related deaths in the United States by 2030. Less than 9% of patients with pancreatic cancer achieve long-term survival. The majority of pancreatic cancer patients develop recurrence, even after surgical resection. At the molecular level, malignant transformation involves several oncogenes and tumour suppressor genes regulating a variety of signalling pathways. Aberrant activation of epigenetic pathways also contributes to the pathogenesis of pancreatic cancer. This chapter provides an overview on genetics, signalling pathways, and epigenetics such as promoter methylation, histone modifications, and chromatin remodelling in pancreatic cancer. Further, the chapter summarizes the data on cancer stem cells, as well as on the tumour microenvironment. Continuous research effort and progress in the understanding of the molecular basis of pancreatic cancer are essential for further improving the outcomes of patients.