Circulating tumor cells (Ctc) and kras mutant circulating free Dna (cfdna) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer.

BACKGROUND: Pancreatic cancer remains one of the most difficult cancers to treat with the poorest prognosis. The key to improving survival rates in this disease is early detection and monitoring of disseminated and residual disease. However, this is hindered due to lack reliable diagnostic and predictive markers which mean that the majority of patients succumb to their condition within a few months. METHODS: We present a pilot study of the detection circulating free DNA (cfDNA) combined with tumor specific mutation detection by digital PCR as a novel minimally invasive biomarker in pancreatic ductal adenocarcinoma (PDAC). This was compared to the detection of CTC by the CellSearch® system and a novel CTC enrichment strategy based on CD45 positive cell depletion. The aim of the study was to assess tumor specific DNA detection in plasma and CTC detection as prognostic markers in PDAC. RESULTS: We detected KRAS mutant cfDNA in 26% of patients of all stages and this correlated strongly with Overall Survival (OS), 60 days (95% CI: 19-317) for KRAS mutation positive vs 772 days for KRAS mutation negative (95% CI: 416-1127). Although, the presence of CTC detected by the CellSearch® system did correlate significantly with OS, 88 days (95% CI: 27-206) CTC positive vs 393 days CTC negative (95% CI: 284-501), CTC were detected in only 20% of patients, the majority of which had metastatic disease, whereas KRAS mutant cfDNA was detected in patients with both resectable and advanced disease. CONCLUSIONS: Tumor specific cfDNA detection and CTC detection are promising markers for the management of patients with PDAC, although there is a need to validate these results in a larger patient cohort and optimize the detection of CTC in PDAC by applying the appropriate markers for their detection.

Impact of Standard Versus Low Pneumoperitoneum Pressure on Peritoneal Environment in Laparoscopic Cholecystectomy. Randomized Clinical Trial.

BACKGROUND: High CO 2 pneumoperitoneum pressure during laparoscopy adversely affects the peritoneal environment. This study hypothesized that low pneumoperitoneum pressure may be linked to less peritoneal damage and possibly to better clinical outcomes. MATERIALS AND METHODS: One hundred patients undergoing scheduled laparoscopic cholecystectomy were randomized 1:1 to low or to standard pneumoperitoneum pressure. Peritoneal biopsies were performed at baseline time and 1 hour after peritoneum insufflation in all patients. The primary outcome was peritoneal remodeling biomarkers and apoptotic index. Secondary outcomes included biomarker differences at the studied times and some clinical variables such as length of hospital stay, and quality and safety issues related to the procedure. RESULTS: Peritoneal IL6 after 1 hour of surgery was significantly higher in the standard than in the low-pressure group (4.26±1.34 vs. 3.24±1.21; P =0.001). On the contrary, levels of connective tissue growth factor and plasminogen activator inhibitor-I were higher in the low-pressure group (0.89±0.61 vs. 0.61±0.84; P =0.025, and 0.74±0.89 vs. 0.24±1.15; P =0.028, respectively). Regarding apoptotic index, similar levels were found in both groups and were 44.0±10.9 and 42.5±17.8 in low and standard pressure groups, respectively. None of the secondary outcomes showed differences between the 2 groups. CONCLUSIONS: Peritoneal inflammation after laparoscopic cholecystectomy is higher when surgery is performed under standard pressure. Adhesion formation seems to be less in this group. The majority of patients undergoing surgery under low pressure were operated under optimal workspace conditions, regardless of the surgeon's expertise.

Relevance of positive resection margins in ductal pancreatic adenocarcinoma and prognostic factors. / Relevancia del margen de resección positivo en adenocarcinoma ductal de páncreas y otros factores pronósticos.

INTRODUCTION: Currently, R1 resection is defined by the presence of tumor cells within <1mm of the resection margin. The main aim of this study was to analyze the impact of positive margins (R1) on survival outcomes in pancreatic cancer. METHODS: We performed a retrospective analysis with multivariate regression analysis of a prospective database from 2008-2017, which included resection margin status, expanded resection margin (R1<1mm), vascular resection, lymphatic involvement, surgical complications, tumor differentiation grade and adjuvant treatment. RESULTS: A total of 80 patients were analyzed: 42 (52%) R1; 38 (48%) R0. No differences were found in the composition of the two groups except for the vascular resection, which was more frequent in the R1 group: 12 (21%) vs 2 (3%). Overall survival in the R0 group was 19 months vs 24 months in the R1 group (p=0.13). Wide R1 (R1<1mm) had an overall survival of 21 months versus 31 months in wide R0 (p=0.55). In the multivariate analysis, only lymph node involvement (p=0.02, HR=2.88), tumor differentiation (p=0.02, HR=3.2) and adjuvant therapy (p<0.01; HR=0.21) were found to be factors related to survival. CONCLUSIONS: R1 resection is not an independent risk factor. Lymph node involvement, differentiation grade and adjuvant treatment are prognostic factors. The benefit of expanding the resection margins should be demonstrated. More studies are needed to assess the impact of the resection margin.