Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic tumor spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in pancreatic CTC and corresponding tumors, and evaluated their significance as prognostic markers. Samples from 68 individuals (58 PDAC patients, 10 healthy donors) were analyzed; CTCs were present in patients with UICC stage IA-IV tumors and none of the controls (p < 0.001). Patients with >3 CTC/ml had a trend for worse median overall survival (OS) than patients with 0.3–3 CTC/ml (P = 0.12). Surprisingly, CTCs harbored various KRAS mutations in codon 12 and 13. Patients with a KRAS^G12V mutation in their CTC (n = 14) had a trend to better median OS (24.5 months) compared to patients with other (10 months), or no detectable KRAS mutations (8 months; P = 0.04). KRAS mutations in CTC and corresponding tumor were discordant in 11 of 26 “tumor-CTC-pairs” (42%), while 15 (58%) had a matching mutation; survival was similar in both groups (P = 0.36). Genetic characterization, including mutations such as KRAS, may prove useful for prognosis and understanding of tumor biology.

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis.” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch^© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.

Perioperative mortality after pancreaticoduodenectomy has decreased significantly in high-volume centers, but morbidity remains high. Restrictive perioperative fluid management may contribute to reduced complication rates after various surgical procedures. The aim of this study was to determine whether there is a correlation between the amount of fluid administered and postoperative complications. We hypothesized that higher amounts of intra- and total fluid is associated with greater postoperative morbidity. We retrospectively examined data of 553 patients who underwent pancreaticoduodenectomy at University of Freiburg Medical Center between 2001 and 2013. Data on intra - and postoperative fluid administration (until postoperative day 5) were obtained from anesthesiological and surgical records. Data on complications were retrieved from our institutional pancreatic database. The median values for intra- and total fluid administered were 6000 ml (range 400-15,000 ml) and 13,600 ml (range 5000-57,700 ml), respectively. The overall in-hospital mortality was 1.9% (no correlation with fluid administration). Patients who received more than 6000 ml intraoperative fluid had more wound infections (P = 0.049), intra-abdominal abscesses (P = 0.020) and postoperative interventions (P = 0.007). In patients who received more than 14000 ml fluid until postoperative day 5 all evaluated types of postoperative complications (infectious, fistula, delayed gastric emptying, bleeding) and re-interventions occurred significantly more frequently than in patients who received less than 14,000 ml (P < 0.05-0.001). Higher amounts of fluids may contribute to postoperative complications. More studies are needed to adequately assess the use of intra/postop fluid therapy.

Restrictive intraoperative fluid management is increasingly recommended for patients undergoing esophagectomy. Controversy still exists about the impact of postoperative fluid management on perioperative outcome. We retrospectively examined 335 patients who had undergone esophagectomy for esophageal cancer at the University Hospital Freiburg between 1996 and 2014 to investigate the relation between intra- and postoperative fluid management and postoperative morbidity after esophagectomy. Perioperative morbidity was 75%, the in-hospital mortality 8%. A fluid balance above average on the operation day was strongly associated with a higher rate of postoperative mortality (21% vs 3%, p < 0.001) and morbidity (83% vs 66%, p = 0.001). Univariate analysis for risk factors for adverse surgical outcome (Clavien ≥ III) identified ASA-score (p = 0.002), smoking (p = 0.036), reconstruction by colonic interposition (p = 0.036), cervical anastomosis (p = 0.017), blood transfusion (p = 0.038) and total fluid balance on the operation day and on POD 4 (p = 0.001) as risk factors. Multivariate analysis confirmed only ASA-score (p = 0.001) and total fluid balance (p = 0.001) as independent predictors of adverse surgical outcome. Intra- and postoperative fluid overload is strongly associated with increased postoperative morbidity. Our results suggest restrictive intra- and especially postoperative fluid management to optimize the outcome after esophagectomy.