To analyze pancreatic cancer patients who developed metachronous pulmonary metastases (MPM) as a first site of recurrence after the curative-intent surgery. One-hundred-fifty-nine consecutive pancreatic ductal adenocarcinoma (PDAC) patients who underwent radical pancreatic surgery between 2006 and 2013 were included in this retrospective analysis. The clinical data including age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered, and follow-up were all obtained from medical records. Further analysis covered only patients with metachronous metastases. Clinical and histopathological data (age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered and follow-up) of patients with metachronous non-pulmonary metastases and patients with metachronous pulmonary metastases were statistically assessed. Disease-free survival (DFS) from pancreas resection until metastases onset and overall survival (OS) were calculated. Wilcoxon test, χ² test and survival functions computed by the Kaplan-Meier method were used. Statistical significance was evaluated by the log-rank test using SPSS. A P-value of less than 0.05 was considered statistically significant. Metachronous pulmonary metastases were observed in 20 (16.9%) and were operable in 3 (2.5%) of PDAC patients after a prior curative-intent surgery. Patients with isolated pulmonary metastases (oligometastases and multiple metastases) had estimated prior DFS and OS of 35.4 and 81.4 mo, respectively, and those with metachronous pulmonary metastases accompanied by other metastases had prior DFS and OS of 17.3 and 23.4 mo, respectively. Patients with non-pulmonary metastases had prior DFS and OS of 9.4 and 15.8 mo, respectively. Different clinical scenarios according to the presentation of MPM were observed and patients could be divided to three subgroups with different prognosis which could be used for the selection of treatment strategy: isolated pulmonary oligometastases, isolated multiple pulmonary metastases and pulmonary metastases accompanied by other metastases. Surgery should be considered for all patients with isolated pulmonary oligometastases, but the risk of intervention has to be individually weighted for each patient.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and aggressive cancers with a less than 6% five-year survival rate. Circulating microRNAs (miRNAs) are emerging as a useful tool for non-invasive diagnosis and prognosis estimation in the various cancer types, including PDAC. Our study aimed to evaluate whether miRNAs in the pre-operative blood plasma specimen have the potential to predict the prognosis of PDAC patients. In total, 112 PDAC patients planned for surgical resection were enrolled in our prospective study. To identify prognostic miRNAs, we used small RNA sequencing in 24 plasma samples of PDAC patients with poor prognosis (overall survival (OS) < 16 months) and 24 plasma samples of PDAC patients with a good prognosis (OS > 20 months). qPCR validation of selected miRNA candidates was performed in the independent cohort of PDAC patients (n = 64). In the discovery phase of the study, we identified 44 miRNAs with significantly different levels in the plasma samples of the group of good and poor prognosis patients. Among these miRNAs, 23 showed lower levels, and 21 showed higher levels in plasma specimens from PDAC patients with poor prognosis. Eleven miRNAs were selected for the validation, but only miR-99a-5p and miR-365a-3p were confirmed to have significantly lower levels and miR-200c-3p higher levels in plasma samples of poor prognosis cases. Using the combination of these 3-miRNA levels, we were able to identify the patients with poor prognosis with sensitivity 85% and specificity 80% (Area Under the Curve = 0.890). Overall, 3-miRNA prognostic score associated with OS was identified in the pre-operative blood plasma samples of PDAC patients undergoing surgical resection. Following further independent validations, the detection of these miRNA may enable identification of PDAC patients who have no survival benefit from the surgical treatment, which is associated with the high morbidity rates.

The morbidity of pancreatic resection remains high, with pancreatic fistula being the most common cause. The important question is whether any postoperative treatment adjustment may prevent the development of clinically significant postoperative pancreatic fistulae. Recent studies have shown that intraabdominal drains and manipulation using them are of great importance. Although authors of a few retrospective reports have described good results of pancreatic resection without the use of intraabdominal drains, a recent prospective randomized trial showed that routine elimination of drains in pancreaticoduodenectomy is associated with poor outcome. An important issue arises as to which type of drain is most suitable for pancreatic resection. Two types of surgical drains exist: open drains and closed drains. Open drains are considered obsolete nowadays because of frequent retrograde infection. Closed drains include two types: passive gravity drains and closed-suction drains. Closed-suction drains are more effective, as they remove fluid from the abdominal cavity under light pressure. However, some surgeons believe that closed-suction drains represent a potential hazard to patients and that negative pressure might increase the risk of pancreatic fistulae. Nobody has yet specifically dealt with the question of which kind of drainage is most appropriate in pancreatic surgery. The aim of the DRAins in PAncreatic surgery (DRAPA) trial is to compare the closed-suction drain versus the closed passive gravity drain in pancreatic resection. DRAPA is a dual-centre, prospective, randomized controlled trial. The primary endpoint is the rate of postoperative pancreatic fistula; the secondary endpoint is postoperative morbidity with follow-up of 3 months. No study to date has compared different types of drains in pancreatic surgery. This study is designed to answer the question whether any particular type of drain might lower the rate of postoperative pancreatic fistula or other complications. ClinicalTrials.gov Identifier: NCT01988519 . Registered 13 November 2013.

Background: The aim of this study is to identify the incidence trends of primary and secondary peritoneal surface malignancies in a representative Czech population. Methods: Data were obtained from patients registered in the Czech National Cancer Registry between 1979 and 2016. The incidence rates were analyzed between 2012 and 2016. To observe the incidence trends, we analyzed the data from two time periods, 1979–2005 and 2006–2016. The analyzed data included age, sex, and the histological types and primary origins of the malignancies. The Cochrane-Armitage test for linear trends was used for verification of the null hypothesis. The significance level established for hypothesis testing was p = 0.05. Results: Between 2012 and 2016, 230 patients with primary peritoneal tumors were identified and divided into the following groups according to their “International Statistical Classification of Diseases and Related Health Problems, 10th revision” codes: malignant neoplasm of specified parts of the peritoneum (C48.1); malignant neoplasm of the peritoneum, unspecified (C48.2); and malignant neoplasm of overlapping sites of the retroperitoneum and peritoneum (C48.8). Moreover, 549 primary tumors of the appendix (C18.1, encompassing all appendiceal malignancies) and 3137 secondary synchronous peritoneal carcinomatoses of other primary origins were documented. The age-adjusted incidence of primary peritoneal tumors in 2012–2016 was 4.36/year/1,000,000 inhabitants. The age-adjusted incidence of synchronous secondary peritoneal malignancies in 2014–2016 was 99.0/year/1,000,000 inhabitants. The diagnoses of primary peritoneal malignancies followed a stable trend between 1979 and 2016. However, the incidences of primary tumors of the appendix increased by 76.7%. Conclusions: The data produced in our study ought to clarify the status of peritoneal surface malignancies in the Czech Republic, which can lead to improved planning and development of therapeutic interventions as well as physician training.

Postpancreatectomy hemorrhage (PPH) and pancreatic fistula are main and serious complications following pancreaticoduodenectomy. Postpancreatectomy hemorrhage is considered life-threatening for its high rate of mortality. Postpancreatectomy hemorrhage is defined as early, occurring within 24 h...

Background: The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC etiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNP) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported. Methods: We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using Multi-marker Analysis of GenoMic Annotation (MAGMA) software. Results: In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P < 0.05). In the second phase, none of the findings were replicated. In the gene-level analysis, we observed that three genes (TERT, SUGCT, and SURF1) involved in the mitochondrial metabolism showed an association below the Bonferroni-corrected threshold of statistical significance (P = 0.05/1588 = 3.1 × 10−5). Conclusions: Even though the mitochondrial metabolism might be involved in PDAC etiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk. Impact: This large case–control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.