Major iatrogenic bile duct injury during elective cholecystectomy: a Czech population register-based study.

PURPOSE: Bile duct injury (BDI) remains the most serious complication following cholecystectomy. However, the actual incidence of BDI in the Czech Republic remains unknown. Hence, we aimed to identify the incidence of major BDI requiring operative reconstruction after elective cholecystectomy in our region despite the prevailing modern 4 K Ultra HD laparoscopy and Critical View of Safety (CVS) standards implemented in daily surgical practice among the Czech population. METHODS: In the absence of a specific registry for BDI, we analysed data from The Czech National Patient Register of Reimbursed Healthcare Services, where all procedures are mandatorily recorded. We investigated 76,345 patients who were enrolled for at least a year and underwent elective cholecystectomy during the period from 2018-2021. In this cohort, we examined the incidence of major BDI following the reconstruction of the biliary tract and other complications. RESULTS: A total of 76,345 elective cholecystectomies were performed during the study period, and 186 major BDIs were registered (0.24%). Most elective cholecystectomies were performed laparoscopically (84.7%), with the remaining open (15.3%). The incidence of BDI was higher in the open surgery group (150 BDI/11700 cases/1.28%) than in laparoscopic cholecystectomy (36 BDI/64645 cases/0.06%). Furthermore, the total hospital stays with BDI after reconstruction was 13.6 days. However, the majority of laparoscopic elective cholecystectomies (57,914, 89.6%) were safe and standard procedures with no complications. CONCLUSION: Our study corroborates the findings of previous nationwide studies. Therefore, though laparoscopic cholecystectomy is reliable, the risks of BDI cannot be eliminated.

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells.

The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM+ cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.

Trends in peritoneal surface malignancies: evidence from a Czech nationwide population-based study.

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.

Current status of cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC) in the multimodal treatment of peritoneal surface malignancies.

The tumors of the peritoneal surface, both primary and secondary, are associated with a very poor prognosis and rapid progression through conventional oncology treatment including systemic chemotherapy, targeted treatment, radiotherapy, surgery, and symptomatic treatment. Until recently, most of them were considered incurable. In the 1980s, the first cytoreductive surgery ("CRS") combined with intraperitoneal hyperthermic chemotherapy ("HIPEC") became the standard of treatment for selected tumor peritoneal tumor (pseudomyxoma peritonei and primary peritoneal malignant mesothelioma). In some cases of other peritoneal carcinomatosis associated with colorectal cancer, gastric cancer and ovarian cancer in the subgroup of well selected patients, this treatment can lead to a significant prolongation of overall survival and good standard of quality of life. This method is safe in specialized centers with an acceptable rate of morbidity and mortality comparable to foreign workplaces and is also available for patients in the Czech Republic. Key words surgery, oncology, cytoreduction, intraperitoneal chemotherapy, hyperthermia.

Preoperative nutritional support in patients undergoing pancreatic surgery affects PREPARE score accuracy.

Background: This study aimed to validate the accuracy of the Preoperative Pancreatic Resection (PREPARE) risk score in pancreatic resection patients. Patients and methods: This prospective study included 216 patients who underwent pancreatic resection between January 2015 and December 2018. All patients in our cohort with weight loss or lack of appetite received dietary advice and preoperative oral nutritional supplementation (600 kcal/day). Demographic, clinicopathological, operative, and postoperative data were collected prospectively. The PREPARE score and the predicted risk of major complications were computed for each patient. Differences in major postoperative complications were analyzed using a multivariate Cox proportional hazards regression model. The predicted and observed risks of major complications were tested using the C-statistic. Results: The study included 216 patients [117 men (54.2%)] with a median age of 65.0 (30.0-83.0) years. The majority of patients were classified as American Society of Anesthesiologists (ASA)' Physical Status score II (N = 164/216; 75.9%) and as "low risk" PREPARE score (N = 185/216; 85.6%) before the surgery. Only 4 (1.9%) patients were malnourished, with albumin levels of less than 3.5 g/dl. The most common type of pancreatic resection was a pylorus-preserving pancreaticoduodenectomy (N = 122/216; 56.5%). Major morbidity and 30-day mortality rates were 11.1% and 1.9%, respectively. The type of surgical procedure (hazard ratio [HR]: 3.849; 95% confidence interval [CI]: 1.208-12.264) and ASA score (HR: 3.089; 95% CI: 1.067-8.947) were significantly associated with the incidence of major postoperative complications in multivariate analysis. The receiver operating characteristic curve was 0.657 for incremental values and 0.559 for risk categories, indicating a weak predictive model. Conclusion: The results of the present study suggest that the PREPARE risk score has low accuracy in predicting the risk of major complications in patients with consistent preoperative nutritional support. This limits the use of PREPARE risk score in future preoperative clinical routines.

Fluorescence In Situ Hybridization in Primary Diagnosis of Biliary Strictures: A Single-Center Prospective Interventional Study.

Background and aims: Diagnosis of the biliary stricture remains a challenge. In view of the low sensitivity of brush cytology (BC), fluorescence in situ hybridization (FISH) has been reported as a useful adjunctive test in patients with biliary strictures. We aimed to determine performance characteristics of BC and FISH individually and in combination (BC + FISH) in the primary diagnosis of biliary strictures. Methods: This single-center prospective study was conducted between April 2019 and January 2021. Consecutive patients with unsampled biliary strictures undergoing first endoscopic retrograde cholangiopancreatography in our institution were included. Tissue specimens from two standardized transpapillary brushings from the strictures were examined by routine cytology and FISH. Histopathological confirmation after surgery or 12-month follow-up was regarded as the reference standard for final diagnosis. Results: Of 109 enrolled patients, six were excluded and one lost from the final analysis. In the remaining 102 patients (60.8% males, mean age 67.4, range 25-92 years), the proportions of benign and malignant strictures were 28 (27.5%) and 74 (72.5%), respectively. The proportions of proximal and distal strictures were 26 (25.5%) and 76 (74.5%), respectively. In comparison to BC alone, FISH increased the sensitivity from 36.1% to 50.7% (p = 0.076) while maintaining similar specificity (p = 0.311). Conclusions: Dual-modality tissue evaluation using BC + FISH showed an improving trend in sensitivity for the primary diagnosis of biliary strictures when compared with BC alone.

Morphine Analgesia, Cannabinoid Receptor 2, and Opioid Growth Factor Receptor Cancer Tissue Expression Improve Survival after Pancreatic Cancer Surgery.

Pancreatic cancer (PDAC) has a poor prognosis despite surgical removal and adjuvant therapy. Additionally, the effects of postoperative analgesia with morphine and piritramide on survival among PDAC patients are unknown, as are their interactions with opioid/cannabinoid receptor gene expressions in PDAC tissue. Cancer-specific survival data for 71 PDAC patients who underwent radical surgery followed by postoperative analgesia with morphine (n = 48) or piritramide (n = 23) were therefore analyzed in conjunction with opioid/cannabinoid receptor gene expressions in the patients' tumors. Receptor gene expressions were determined using the quantitative real-time polymerase chain reaction. Patients receiving morphine had significantly longer cancer-specific survival (CSS) than those receiving piritramide postoperative analgesia (median 22.4 vs. 15 months; p = 0.038). This finding was supported by multivariate modelling (p < 0.001). The morphine and piritramide groups had similar morphine equipotent doses, receptor expression, and baseline characteristics. The opioid/cannabinoid receptor gene expression was analyzed in a group of 130 pancreatic cancer patients. Of the studied receptors, high cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) gene expressions have a positive influence on the length of overall survival (OS; p = 0.029, resp. p = 0.01). Conversely, high delta opioid receptor gene expression shortened OS (p = 0.043). Multivariate modelling indicated that high CB2 and OGFR expression improved OS (HR = 0.538, p = 0.011, resp. HR = 0.435, p = 0.001), while high OPRD receptor expression shortened OS (HR = 2.264, p = 0.002). Morphine analgesia, CB2, and OGFR cancer tissue gene expression thus improved CSS resp. OS after radical PDAC surgery, whereas delta opioid receptor expression shortened OS.

Isolated Gastric Metastases of Pancreatic Ductal Adenocarcinoma following Radical Resection-Impact of Endosonography-Guided Fine Needle Aspiration Tract Seeding.

BACKGROUND: Endosonography-guided fine needle aspiration biopsy (EUS-FNA)-associated metachronous gastric seeding metastases (GSM) of pancreatic ductal adenocarcinoma (PDAC) represent a serious condition with insufficient evidence. METHODS: Retrospective analysis of PDAC resections with a curative-intent, proven pathological diagnosis of PDAC, preoperative EUS-FNA and post-resection follow-up of at least 60 months. The systematic literature search of published data was used for the GSM growth evaluation using Pearson correlation and the linear regression analyses. RESULTS: The inclusion criteria met 59/134 cases, 16 (27%) had retained needle tract (15 following distal pancreatectomy, 1 following pylorus-sparing head resection). In total, 3/16 cases (19%) developed identical solitary GSM (10-26th month following primary surgery) and were radically resected. A total of 30 published cases of PDAC GSM following EUS-FNA were identified. Lesion was resected in 20 distal pancreatectomy cases with complete information in 14 cases. A correlation between the metastasis size and time (r = 0.612) was proven. The regression coefficient b = 0.72 expresses the growth of 0.72 mm per month. CONCLUSIONS: The GSM represent a preventable and curable condition. A remarkably high number of GSM following EUS-FNA was identified, leading to follow-up recommendation of EUS-FNA sampled patients. Multimodal management (gastric resection, adjuvant chemotherapy) may prolong survival.

The short- and long-term outcomes of pancreaticoduodenectomy for distal cholangiocarcinoma.

BACKGROUND: The aim of the study was to calculate the short-term and long-term outcomes of curative-intent surgery in distal cholangiocarcinoma (DCC) patients to identify potential prognostic factors. PATIENTS AND METHODS: A retrospective cohort study of 32 consecutive DCC patients treated with pancreaticoduodenectomy between 2009-2017. The clinicopathological and histopathological data were evaluated for prognostic factors using the univariable Cox regression analysis. The Overall Survival (OS) was estimated using the Kaplan-Meier analysis. RESULTS: The study comprised a total of 32 patients, with a mean age of 65.8 (± 9.0) years at the time of surgery. R0 resection was achieved in 25 (86.2%) patients, 19 (65.5%) patients received adjuvant oncological therapy. The OS rates at 1, 3 and 5 years were 62.5%, 37.5% and 21.9%, respectively. The 90-day mortality was 3/32 (9.4%) accounting for one-fourth of the first-year mortality rate. The median OS was 28.5 months. The only statistically significant prognostic factor was vascular resection, which was associated with worse OS in the univariable analysis (HR: 3.644; 95%-CI: 1.179-11.216, P=0.025). An age less than 65 years, ASA grade I/II, hospital stay of fewer than 15 days, R0 resection, lymph node ratio less than 0.2 and adjuvant oncological therapy tended to be associated with better OS but without statistically significant relevance. CONCLUSION: The main factor directly influencing the survival of DCC patients is surgical complications. Surgical mortality comprises a significant group of patients, who die in the first year following pancreaticoduodenectomy. Vascular resection is the most important negative prognostic factor for long-term survival.

Surgical treatment of duodenal adenocarcinoma: ampullary vs. non-ampullary, short- and long-term outcomes.

BACKGROUND: The aim of this study was to evaluate symptoms, diagnostic methods, short- and long-term outcomes of surgical treatment in patients with duodenal adenocarcinoma. PATIENTS AND METHODS: A single center, retrospective, observational study of 52 consecutive patients with duodenal adenocarcinoma operated on with curative intent between 2006 - 2019. Duodenectomy as part of a hemipancreatoduodenectomy or total pancreatectomy procedure was performed for ADAC (ampullary duodenal/intestinal adenocarcinoma) or NADAC (non-ampullary duodenal adenocarcinoma). RESULTS: Prevailing symptoms were obstructive jaundice in the ADAC group (P<0.0001) and bleeding in the NADAC group (P=0.005), with larger tumor size in patients with NADAC (P=0.001). Complication rate, morbidity and mortality were comparable. Primary total pancreatoduodenectomy predominated in the NADAC group, 16.6% vs. 2.9%, and salvage completion pancreatectomy in the ADAC group, 6% vs. 0%. Significant prognostic factors for OS were perineural invasion (P=0.006) and adjuvant chemotherapy (P=0.045) in the ADAC group, and for DFS the total number of resected lymph nodes (P=0.042) and lymph node ratio (P=0.031) in the NADAC group. Median OS is 21 months and 5-year survival 27.3% in the NADAC group and 41.5 months and 52% in the ADAC group. CONCLUSION: Ampullary duodenal/intestinal adenocarcinomas are smaller than non-ampullary at diagnosis, with a higher rate of lymph node metastases, but with a better prognosis and long-term outcome in the presented cohort. Oral localisation of NADAC prevailed in the present cohort. Perineural invasion and postoperative oncological therapy are significant prognostic factors for OS in ADAC, but the total number of lymph nodes and lymph node ratio are significant prognostic factors for DFS in NADAC.

Silver-Based Dressings in the Prevention of the Incisional Surgical Site Infection: A Prospective Multicenter Observational Controlled Trial.

Background: A new silver-based dressing has been designed to reduce surgical sited infections. Patients and Methods: A prospective multicenter observational study was conducted from January 2020 to October 2021. Patients with and without silver-based dressing after surgical incision were observed and their data analyzed. The study aimed to assess the incidence of incisional surgical site infection and primary healing after general surgery procedures. Results: Overall, 218 patients with silver-based (n = 109) and conventional silver-free dressing (n = 109) were analyzed. Surgical site infection (SSI) and primary incision healing were reported in 10 (9.2%) versus 21 (19.3%) (p = 0.037) and in 95 (87.2%) versus 86 (78.9%) (p = 0.107) patients treated with and without silver-based dressing, respectively. Conclusions: Silver-based dressing demonstrated a lower incidence of incisional SSI and improved primary healing in comparison with patients in whom conventional non-silver-based dressing has been used.

Cyclomodulins and Hemolysis in E. coli as Potential Low-Cost Non-Invasive Biomarkers for Colorectal Cancer Screening.

The frequent occurrence of E. coli positive for cyclomodulins such as colibactin (CLB), the cytotoxic necrotizing factor (CNF), and the cytolethal distending factor (CDT) in colorectal cancer (CRC) patients published so far provides the opportunity to use them as CRC screening markers. We examined the practicability and performance of a low-cost detection approach that relied on culture followed by simplified DNA extraction and PCR in E. coli isolates recovered from 130 CRC patients and 111 controls. Our results showed a statistically significant association between CRC and the presence of colibactin genes clbB and clbN, the cnf gene, and newly, the hemolytic phenotype of E. coli isolates. We also observed a significant increase in the mean number of morphologically distinct E. coli isolates per patient in the CRC cohort compared to controls, indicating that the cyclomodulin-producing E. coli strains may represent potentially preventable harmful newcomers in CRC patients. A colibactin gene assay showed the highest detection rate (45.4%), and males would benefit from the screening more than females. However, because of the high number of false positives, practical use of this marker must be explored. In our opinion, it may serve as an auxiliary marker to increase the specificity and/or sensitivity of the well-established fecal immunochemical test (FIT) in CRC screening.

Effect of hemorrhoidectomy on anorectal physiology.

PURPOSE: The aim of this study was to determine whether overactivity of the anal sphincter in patients with hemorhhoids is primary or secondary and thus assess indication of lateral internal sphincterotomy to surgical treatment of hemorrhoids. Tonic contraction of the sphincter muscle in patients with advanced stages of hemorrhoids is considered by many authors as a primary cause, and therefore, they complete hemorrhoid surgery with lateral internal sphincteroomy. If hypertension of anal sphincter is secondary during hemorrhoid disease, lateral internal sphincterotomy is not indicated. Although examinations made immediately after sphincterotomy proved no changes of anal continence, certain sequelae of lateral internal sphincterotomy cannot be excluded and may later negatively affect patient's anal continence. PATIENTS AND METHODS: The prospective study comprised 385 patients treated in 2002-2006 by Hemoron or surgery according to Milligan-Morgan or Longo. Patients with history of another disease of the anal canal, radiotherapy of pelvis, Crohn's disease or ulcerous colitis were excluded. Manometry was performed before and after surgery at intervals of 1, 3, 6 and 12 months after operation using a perfusion flow method, six-channels catheter with radial arrangement of channel tips. RESULTS: In all three groups (Hemoron, sec. Milligan-Morgan, sec. Longo), there were 60-65% of patients with third degree hemorrhoids. Normal resting anal pressure before surgery was recorded in only 25% of men and 30% of women. Patients with advanced hemorrhoid degrees were found to have significant hypertension of the anal sphincter. The most significantly improved state of sphincter overactivity was observed after surgery according to Longo and application of Hemoron. After surgery, according to Milligan-Morgan, recovery of anal sphincter tension was the longest; even 6 months after operation, a mean increased resting anal pressure persisted (91-110 mmHg) in 25% of men and 19% of women. After 12 months, recovery of anal tension occurred in this group also--mean increased anal pressure was recorded in only three patients (1.67%). CONCLUSION: Overactivity of the anal sphincter in patients with hemorrhoids is secondary and according to our results. Hypertension of the sphincter muscle in patients with hemorrhoids is significantly increased in patients with advanced degrees of hemorrhoids. Therefore, it is not recommended to postpone surgery and indicate patients with advanced degrees of hemorrhoids to hemorrhoidectomy.

Candida albicans culture from a rectal swab can be associated with newly diagnosed colorectal cancer.

Plenty of metagenomic studies have suggested possible associations between microbiome composition and colorectal cancer (CRC). However, these techniques are not economic enough for routine use so far. Therefore, we explored the possibility to detect species associated with colorectal cancer by conventional culture from rectal swab. Fifty-two patients newly diagnosed for adenoma/CRC and 52 age-matched controls were recruited and sampled. Rectal swabs were inoculated on several types of plates and incubated appropriately under both aerobic and anaerobic conditions. All colonial morphotypes were subcultured and identified using MALDI-ToF MS. Although no bacterial species was significantly associated with CRC in our study, we surprisingly observed a strong and significant overrepresentation of the yeast Candida albicans in cases (P = 0.0066, odds ratio 5.444 [95% CI 1.449-20.462]). Potential confounding factors were associated neither with CRC (history of CRC in first-degree relatives, a personal history of appendectomy and cholecystectomy, increased BMI (body mass index), and the percentage of males) nor with C. albicans presence (preexisting diabetes and PPI medication) in our cohort. A growing body of evidence supports the view that C. albicans does cause cancer in humans. We hypothesize that presence of C. albicans in the gut may induce or facilitate some part of the sporadic CRC cases. Our observation should be a strong incentive to verify the potential usefulness of the easily culturable C. albicans yeast as a screening marker for patients at risk of CRC or those suffering an early asymptomatic stage of CRC.

Cost analysis of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and the risk factors for their increased cost in a public insurance health care system - Single centre study.

INTRODUCTION: This study aimed to evaluate the costs of CRS and HIPEC and treatment of the related postoperative complications in the public healthcare system. We also aimed to identify the risk factors that increase the cost of CRS and HIPEC. MATERIALS AND METHODS: We retrospectively evaluated 80 patients who underwent CRS and HIPEC between February 2016 and November 2018 in the Department of Surgery, University Hospital of Olomouc, Czech Republic. Intraoperative factors and postoperative complications were assessed. The treatment cost included the surgery, hospital stay, intensive care unit (ICU) admission, pharmaceutical charges including medication, hospital supplies, pathology, imaging, and allied healthcare services. RESULTS: The postoperative morbidity rate was 50%, and the mortality rate was 2.5%. The mean length of hospitalisation and ICU admission was 15.44 ± 8.43 and 6.15 ± 4.12 for all 80 patients and 10.73 ± 2.93 and 3.73 ± 1.32, respectively, for 40 patients without complications, and 20.15 ± 13.93 and 8.58 ± 6.92, respectively, for 40 patients with complications. The total treatment cost reached €606,358, but the total reimbursement was €262,931; thus, the CRS and HIPEC profit margin was €-343,427. Multivariate analysis showed that blood loss ≥1.000 ml (p = 0.03) and grade I-V Clavien-Dindo complications (p < 0.001) were independently associated with increased costs. CONCLUSION: The Czech public health insurance system does not fully compensate for the costs of CRS and HIPEC. Hospital losses remain the main limiting factor for further improving these procedures. Furthermore, treatment costs increase with increasing severity of postoperative complications.

Identification and Validation of Circulating Micrornas as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Patients Undergoing Surgical Resection.

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.

Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations.

BACKGROUND: The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background. PATIENTS AND METHODS: A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients. RESULTS: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively. CONCLUSION: This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis.

Results of a randomized controlled trial comparing closed-suction drains versus passive gravity drains after pancreatic resection.

BACKGROUND: This dual-center, randomized controlled trial aimed to compare 2 types of intra-abdominal drains after pancreatic resection and their effect on the development of pancreatic fistulae and postoperative complications. METHODS: Patients undergoing pancreatic resection were randomized to receive either a closed-suction drain or a closed, passive gravity drain. The primary endpoint was the rate of postoperative pancreatic fistula. A secondary endpoint was postoperative morbidity during follow-up of 3 months. The planned sample size was 223 patients. RESULTS: A total of 294 patients were assessed for eligibility, 223 of whom were randomly allocated. One patient was lost during follow-up, and 111 patients in each group were analyzed. The rate of postoperative pancreatic fistula (closed-suction 43.2%, passive 36.9%, P = .47) and overall morbidity (closed-suction 51.4%, passive 40.5%, P = .43) were not different between the groups. We did not find any differences between the groups in reoperation rate (P = .45), readmission rate (P = .27), hospital stay (P = .68), or postoperative hemorrhage (P = .11). We found a significantly lesser amount of drain fluid in the passive gravity drains between the second and fifth postoperative days and also on the day of drain removal compared with closed-suction drains. CONCLUSION: The type of drain (passive versus closed suction) had no influence on the rate of postoperative pancreatic fistulae. The closed-suction drains did not increase the rate of postoperative complications. We found that the passive gravity drains are more at risk for obstruction, whereas the closed-suction drains kept their patency for greater duration.

Are we any closer to screening for colorectal cancer using microbial markers?A critical review.

The role of gut microbiota in the development of sporadic colorectal cancer (CRC) is supported by a number of studies, however, the conclusiveness of published metagenomic studies is questioned by technical pitfalls and limited by small cohort sizes. In this review, we evaluate the current knowledge critically and outline practical solutions. We also list candidate CRC risk markers that are - in our opinion - well supported by available data and thus deserve clinical validation. Last but not least, we summarise available knowledge useful for improving care for patients immediately.

Different clinical presentations of metachronous pulmonary metastases after resection of pancreatic ductal adenocarcinoma: Retrospective study and review of the literature.

AIM: To analyze pancreatic cancer patients who developed metachronous pulmonary metastases (MPM) as a first site of recurrence after the curative-intent surgery. METHODS: 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. RESULTS: 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. CONCLUSION: Surgery should be considered for all patients with isolated pulmonary oligometastases, but the risk of intervention has to be individually weighted for each patient.