Search

Aim: Sufficient liver function is crucial in extracellular matrix growth, hemostasis, and wound healing. Repeated abdominal surgery is a known risk factor for the development of wound complications. This study aimed to evaluate this high-risk constellation in patients undergoing associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) and repeated liver resections (RLR) in comparison to single liver resection (SLR). Method: Forty patients who underwent ALPPS between 2011 and 2020 were evenly matched with patients undergoing RLR or SLR (n = 40 per group) using propensity scores. Postoperative outcomes were compared and factors associated with wound complications were analyzed. Results: Postoperative wound complications were significantly more frequent in ALPPS group (p = 0.001). The reoperation rate was not significantly different between the three groups (p = 0.143). However, surgical reintervention due to wound complications occurred more frequently in the ALPPS group in relation to RLR and SLR (17.5% vs. 7.5% and 5% respectively). Length of stay was significantly longer in the ALPPS group (p = 0.033). ALPPS was an independent risk factor for postoperative wound complication (OR = 8.55, 95% CI:1.07–68.44, p = 0.043). Risk factor analysis identified age ≥ 60 years (OR = 27.64, 95% CI:3.09-246.75, p = 0.003), BMI ≥ 30 kg/m2 (OR = 30.21, 95% CI:3.35-271.83, p = 0.002), and low postoperative albumin levels (OR = 168.41, 95% CI:7.76-3651.18, p = 0.001) as independent predictors of postoperative wound complications after major liver resection. Conclusion: Patients undergoing ALPPS and RLR are faced with a high risk of developing wound complications. Older age, obesity, a history of previous abdominal surgery, and a decreased postoperative albumin level were independent risk factors for wound complications. [ABSTRACT FROM AUTHOR]

Background: This monocentric randomized controlled pilot trial investigates the impact of virtual reality (VR) hypnosedation on perioperative anxiety, pain, patient satisfaction, and medication usage during port implantation under local anesthesia. Methods: A total of 120 patients undergoing elective port implantation between January 2022 and August 2023 were enrolled and randomized in a 1:1 ratio to either a VR hypnosedation group or a control group. The VR group used a commercially available VR headset with the HypnoVR application, providing various environments, musical backgrounds, and a guiding voice, while the control group underwent the procedure without VR. Patients with ASA > 3, chronic pain, cognitive issues, and contraindications against VR use were excluded. The main outcomes measured were perioperative pain and anxiety scores, with secondary outcomes including perioperative medication usage. Due to the nature of the interventions, blinding of patients and physicians was not feasible. Statistical analysis was primarily descriptive and exploratory, focusing on estimating effect sizes for future trials. Results: The study found no significant differences in immediate postoperative pain with 1.43 ± 1.63 vs. 1.6 ± 2.05 (p = 0.62) or anxiety scores 30.65 ± 9.13 vs. 31.78 ± 13.34 (p = 0.60) between the no VR and VR group, respectively. Additionally, there was a trend to less usage of certain medications, particularly remifentanil (mean dose of 200 mg vs. 100 mg (p = 0.12)) and novaminsulfon (mean dose of 1250 mg vs. 900 mg (p = 0.26)) in the VR group vs. no VR group, respectively. However, these differences were not statistically significant and therefore no definitive conclusions can be drawn regarding medication usage based on this data. Conclusion: While VR hypnosedation did not significantly reduce perioperative pain or anxiety in this pilot trial, the observed trends in reduced medication usage suggest potential benefits. These findings warrant further investigation in larger, confirmatory trials to better understand the role of VR in enhancing patient comfort and potentially reducing reliance on pharmacological interventions during surgical procedures. Trial registration: German Clinical Trials Register: DRKS00028508; registration date 15 March 2022; Universal Trial Number: U1111-1275–4995. [ABSTRACT FROM AUTHOR]

Copyright of Chirurgie (2731-6971) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Radiotherapy is an important treatment option for esophageal cancer, in addition to surgery and chemotherapy. Ionizing radiation can cause alterations in the patient's anatomy, particularly in the larynx area, which may make advanced airway management more challenging for anesthetists. The existing literature contains data on other entities of cancer and radiotherapy and their impact on advanced airway management. However, there is a lack of data on esophageal cancer. We retrospectively analyzed patients with esophageal cancer who underwent radiotherapy followed by surgery between 2012 and 2023 in our university hospital. It has been shown in the literature that post-radiotherapy effects can increase the risk of difficult endotracheal intubation and airway complications in anesthesiology. However, our study did not indicate any evidence of impaired advanced airway management in patients with esophageal cancer after radiotherapy. (1) Background: Currently, no data are available in the literature investigating the influence of radiotherapy (RT) on endotracheal intubation success in patients with esophageal cancer. This study aims to evaluate the impact of RT on endotracheal intubation quality metrics in patients with esophageal cancer. (2) Methods: Patients with esophageal cancer who underwent RT followed by surgery between 2012 and 2023 at the University Hospital Heidelberg, Germany, were retrospectively analyzed. (3) Results: Fifty-five patients, predominantly males 65.5% with a mean age of 64 years, were enrolled. Overall, 81.8% of the patients had an ASA class of III, followed by 27.2% ASA II. The mean prescribed cumulative total dose to the primary tumor and lymph node metastasis was 48.2 Gy with a mean single dose of 1.8 Gy. The mean laryngeal total dose was 40.0 Gy. Direct laryngoscopy was performed in 80.0% of cases, followed by 12.1% videolaryngoscopy, and 7.2% required fiberoptic intubation. Overall, 96.4% of patients were successfully intubated on the first attempt. (4) Conclusions: It has been demonstrated that post-RT effects can increase the risk of airway management difficulties and complications. The results of our study did not indicate any evidence of impaired advanced airway management in patients with esophageal cancer who had undergone RT. [ABSTRACT FROM AUTHOR]

Exocrine and endocrine pancreas are interconnected anatomically and functionally, with vasculature facilitating bidirectional communication. Our understanding of this network remains limited, largely due to two-dimensional histology and missing combination with three-dimensional imaging. In this study, a multiscale 3D-imaging process was used to analyze a porcine pancreas. Clinical computed tomography, digital volume tomography, micro-computed tomography and Synchrotron-based propagation-based imaging were applied consecutively. Fields of view correlated inversely with attainable resolution from a whole organism level down to capillary structures with a voxel edge length of 2.0 µm. Segmented vascular networks from 3D-imaging data were correlated with tissue sections stained by immunohistochemistry and revealed highly vascularized regions to be intra-islet capillaries of islets of Langerhans. Generated 3D-datasets allowed for three-dimensional qualitative and quantitative organ and vessel structure analysis. Beyond this study, the method shows potential for application across a wide range of patho-morphology analyses and might possibly provide microstructural blueprints for biotissue engineering. [ABSTRACT FROM AUTHOR]

Background: Aim of the current study was to present the results of the implementation phase of a robotic liver surgery program and to assess the validity of the IWATE difficulty score in predicting difficulty and postoperative complications in robotic liver surgery. Methods: Based on the prospective database of the Interdisciplinary Robotic Center of Ulm University Hospital, the first 100 robotic liver surgeries were identified and analyzed. Perioperative parameters (duration of surgery and blood loss) and postoperative parameters including morbidity, mortality, and length of hospital stay were assessed and the results were compared between different IWATE difficulty categories. Results: From November 2020 until January 2023, 100 robotic liver surgeries were performed (41 female, 59 male; median age 60.6 years, median BMI 25.9 kg/m2). Median duration of surgery was 180 min (IQR: 128.7), and median blood loss was 300 ml (IQR: 550). Ninety-day mortality was 2%, and overall morbidity was 21%, with major complications occurring in 13% of patients (≥ grade 3 according to Clavien/Dindo). A clinically relevant postoperative biliary leakage was observed in 3 patients. Posthepatectomy liver failure occurred in 7% (4 Grade A, 3 Grade B). Duration of surgery (p < 0.001), blood loss (p < 0.001), CCI (p = 0.004), overall morbidity (p = 0.004), and length of hospital stay (p < 0.001) were significantly increased in the IWATE 'expert' category compared to lower categories. Discussion: Robotic surgery offers a minimally invasive approach for liver surgery with favorable clinical outcomes, even in the implementation phase. In the current study the IWATE difficulty score had the ability to predict both difficulty of surgery as well as postoperative outcomes when assessing the complexity of robotic liver surgery. Therefore, the role of the IWATE score in predicting these outcomes highlights its importance as a tool in surgical planning and decision-making. [ABSTRACT FROM AUTHOR]

Pancreatic exocrine insufficiency (PEI) is common after gastric resection for cancer or ulcers but is under-recognized and undertreated. Although pancreatic enzyme replacement therapy (PERT) is the mainstay of PEI management, robust evidence supporting its use after gastric surgery is limited. In the absence of guideline recommendations specific for patients with pancreatic insufficiency after gastrectomy, a panel of experts from different geographical regions convened in a virtual meeting to discuss their approach to patient management. Pancreatic insufficiency after gastrointestinal surgery is not a simple post-surgical complication as several factors contribute to its development. Although the pancreas is unimpaired after gastrectomy, it cannot function normally in the altered environment. Pancreatic insufficiency can be challenging to diagnose in gastrectomy patients due to nonspecific symptoms and the absence of a simple diagnostic test. Fecal elastase appears to be the default test, although it is not sufficiently sensitive nor reliable for diagnosing or monitoring PEI. Patients with maldigestion symptoms after gastrectomy are treated pragmatically: those with clinical suspicion of pancreatic insufficiency receive a trial of PERT and are monitored for symptom improvement. There is a clear need for high-quality evidence from clinical trials to guide the management of this patient population. [ABSTRACT FROM AUTHOR]

Introduction: Geriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge. Methods: A digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process. Discussion: The outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults. Trial registration: German clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022. [ABSTRACT FROM AUTHOR]

Background: The treatment of complicated intra-abdominal infections remains a challenge. Both optimal medical and surgical therapy (i.e., source control) are needed to achieve low mortality and morbidity. The objective of this systematic review and meta-analysis is to determine the impact of carbapenem antibiotic therapy compared to other antibiotics in complicated intra-abdominal infections (secondary peritonitis) with an emphasis on mortality and postoperative complications. Methods: A systematic literature search from PubMed/Medline and Web of Science databases was carried out. The last search was conducted in August 2022. PRISMA guidelines were followed. Pre-defined outcomes were mortality, treatment success, treatment failure, and adverse events. Results: Ten randomized controlled trials, published from 1983 to 2013 with a total of 2377 patients (1255 patients in the carbapenem antibiotics group and 1122 in the control group), were identified. A meta-analysis comparing patients undergoing carbapenem antibiotic therapy and patients receiving other antibiotics was performed. No significant difference regarding mortality (OR 1.19, 95% CI [0.79; 1.82], p = 0.40), treatment success (OR 1.17, 95% CI [0.72; 1.91], p = 0.53), and treatment failure (OR 0.84, 95% CI [0.48; 1.45], p = 0.52) was observed. Carbapenem therapy was associated with fewer adverse events compared to therapy with other antibiotics (OR 0.79, 95% CI [0.65; 0.97], p = 0.022). Conclusion: There is currently no evidence that carbapenem antibiotics are superior in terms of mortality, and success or failure for the treatment of complicated intra-abdominal infections (secondary peritonitis). The rate of adverse events is lower under carbapenem therapy compared to control antibiotics. Trial Registration: PROSPERO 2018 CRD42018108854. [ABSTRACT FROM AUTHOR]

The article discusses the ongoing research priorities in the field of pancreatic surgery, highlighting the need for further studies to reduce mortality and complications. The International Study Group of Pancreatic Surgery has developed an Evidence Map of Pancreatic Surgery to identify research gaps and prioritize topics for future projects. A survey among 149 pancreatic surgeons from 30 countries revealed the top research priorities, such as vascular resection and radical antegrade modular pancreatosplenectomy, aiming to improve oncological outcomes. The study emphasizes the importance of addressing evidence gaps and conducting relevant trials to advance the field of pancreatic surgery. [Extracted from the article]

Background Perioperative steroid administration may improve postoperative outcomes in major abdominal surgery by reducing the systemic inflammatory response. The aim of this systematic review was to evaluate the impact of perioperative steroid administration on outcomes after elective liver resection. Methods PubMed, Cochrane Library, and Web of Science were systematically searched for randomized clinical trials (RCTs) comparing perioperative steroid administration with placebo, standard of care, or no steroids with respect to postoperative outcomes, particularly postoperative complications. Two independent reviewers critically appraised the studies and extracted data. Meta-analyses were performed using a random-effects model with ORs calculated for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Results Ten RCTs comprising 930 patients were included. Perioperative steroid administration significantly reduced the overall postoperative complication rate (OR 0.61, 95 per cent c.i. 0.43 to 0.87; P = 0.006; I 2 = 26 per cent). No significant differences were shown for individual complications. Several postoperative laboratory parameters were positively affected, like total serum bilirubin (MD −0.46; 95 per cent c.i. −0.74 to −0.18; P = 0.001; I 2 = 80 per cent), interleukin 6 (MD −48.99; 95 per cent c.i. −60.72 to −37.27; P < 0.001; I 2 = 0 per cent) and C-reactive protein (MD −5.20; 95 per cent c.i. −7.62 to −2.77; P < 0.001; I 2 = 71 per cent). There were no signs of an increase in potential steroid-induced adverse events, namely infectious complications, thromboembolic events, or bleeding. Conclusions Perioperative steroid administration significantly reduces the overall complication rate after elective liver resection without an increased risk of adverse effects. [ABSTRACT FROM AUTHOR]

Alveolar echinococcosis (AE) is a rare disease caused by Echinococcosis multilocularis, which usually requires multidisciplinary management including surgery as the only curative approach. In recent years, minimally invasive strategies have been increasingly adopted for liver surgery. In particular, robotic surgery enables surgeons to perform even complex liver resections using a minimally invasive approach. However, there are only a few reports on robotic liver surgery for AE. Consecutive patients undergoing robotic liver surgery for AE were analysed based on the prospective database of the Interdisciplinary Robotic Centre of Ulm University Hospital. Between January 2021 and August 2022, a total of 16 patients with AE underwent robotic hepatectomy at our institution. Median age was 55.5 years (23–73), median body mass index (BMI) was 25.8 kg/m2 (20.2–36.8) and 12 patients (75%) were female. Anatomic resections were performed in 14 patients (87.5%), of which 4 patients (25%) underwent major hepatectomies (i.e., resection of >3 segments) including two right hemihepatectomies, one left hemihepatectomy and one extended right hemihepatectomy performed as associating liver partition with portal vein ligation staged (ALPPS) hepatectomy. There was no 90-day mortality, no postoperative bile leakage and no posthepatectomy haemorrhage. One patient developed posthepatectomy liver failure grade B after extended right hemihepatectomy using an ALPPS approach. One patient had to be converted to open surgery and developed an organ-space surgical site infection, for which he was re-admitted and underwent intravenous antibiotic therapy. Median length of postoperative hospital stay was 7 days (4–30). To our knowledge, this is the largest series of robotic liver surgeries for AE. The robotic approach seems safe with promising short-term outcomes in this selected cohort for both minor as well as major resections. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is increasingly treated with chemotherapy before surgery, but this does not improve prognosis for every patient. On a cellular level, pancreatic cancer tissue is usually mixed with a dense matrix called the stroma which interacts with the tumor and contains fibers, large molecules and cells. The role of this stroma in chemotherapy and subsequent surgical tumor resection is unclear, especially for current first-line chemotherapy regimens. We analyzed two of the main stromal components, activated fibroblasts and collagen, and found that treatment with gemcitabine + nab-paclitaxel reduced collagen content while FOLFIRINOX had no quantitative effect. Meanwhile, a higher number of activated fibroblasts was beneficial for prognosis after chemotherapy. These findings will serve to further elucidate mechanisms of response and chemoresistance in pancreatic cancer and potentially to stratify patients for different treatment pathways. Neoadjuvant therapy (NT) for advanced PDAC is an emerging concept, affecting both stroma and tumor. The Activated Stroma Index (ASI; ratio of activated cancer-associated fibroblasts (CAF) to collagen deposition) is a prognostic marker in upfront resected pancreatic adenocarcinoma (PDAC). We assessed ASI and its prognostic relevance after NT. Tissue from resection specimens of n = 48 PDAC patients after neoadjuvant chemotherapy with FOLFIRINOX (FOL; n = 31), gemcitabine + nab-paclitaxel (GEM; 7) or combination treatment (COMB; 10) was compared with upfront resected matched controls (RES; 69). Activated CAFs were assessed by immunohistochemistry for α-SMA, and collagen was stained with aniline blue; the stained area was then determined by computational imaging analysis and ASI was calculated. In GEM, ASI was significantly higher and collagen deposition lower than in controls and FOL. The lowest quartile of ASI values had significantly longer overall survival (OS) in RES, whereas in FOL, the highest quartile had the best prognosis. After NT, OS was significantly improved in the α-SMA-high group; in RES, however, survival was independent of α-SMA. Reversed prognostic association of ASI thus points to the differing significance of stromal composition after FOL, while improved prognosis with high CAF abundance suggests a synergistic effect of myofibroblasts with chemotherapy. These divergences impede usability of ASI after NT. [ABSTRACT FROM AUTHOR]

Sca-1 is a surface marker for murine hematopoietic stem cells (HSCs) and type-I interferon is a key regulator for Lin-Sca-1+ HSCs expansion through Ifnar/Stat-1/Sca-1-signaling. In this study we aimed to characterize the role and regulation of Sca-1+ cells in pancreatic regeneration. To characterize Sca-1 in vivo, immunohistochemistry and immunofluorescence staining of Sca-1 was conducted in normal pancreas, in cerulein-mediated acute pancreatitis, and in Kras-triggered cancerous lesions. Ifnar/Stat-1/Sca-1-signaling was studied in type-I IFN-treated epithelial explants of adult wildtype, Ifnar-/-, and Stat-1-/- mice. Sca-1 induction was analyzed by gene expression and FACS analysis. After isolation of pancreatic epithelial Lin-Sca-1+cells, pancreatosphere-formation and immunofluorescence-assays were carried out to investigate self-renewal and differentiation capabilities. Sca-1+ cells were located in periacinar and periductal spaces and showed an enrichment during cerulein-induced acute pancreatitis (23.2/100 μm2 ± 4.9 SEM) and in early inflammation-mediated carcinogenic lesions of the pancreas of KrasG12D mice (35.8/100 μm2 ± SEM 1.9) compared to controls (3.6/100 μm2 ± 1.3 SEM). Pancreatic Lin-Sca-1+ cells displayed a small population of 1.46% ± 0.12 SEM in FACS. In IFN-β treated pancreatic epithelial explants, Sca-1 expression was increased, and Lin-Sca-1+ cells were enriched in vitro (from 1.49% ± 0.36 SEM to 3.85% ± 0.78 SEM). Lin-Sca-1+ cells showed a 12 to 51-fold higher capacity for clonal self-renewal compared to Lin-Sca-1- cells and generated cells express markers of the acinar and ductal compartment. Pancreatic Sca-1+ cells enriched during parenchymal damage showed a significant capacity for cell renewal and in vitro plasticity, suggesting that corresponding to the type I interferon-dependent regulation of Lin-Sca-1+ hematopoietic stem cells, pancreatic Sca-1+ cells also employ type-I-interferon for regulating progenitor-cell-homeostasis. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) harbors mutant KRAS as the most common driver mutation. Studies on mouse models have uncovered the tumorigenic characteristics of the Kras oncogene driving pancreatic carcinogenesis. Similarly, Ewing sarcoma predominantly depends on the occurrence of the EWSR1-FLI1 fusion oncogene. The expression of EWSR1-FLI1 affects pro-tumorigenic pathways and induces cell transformation. In this study, we investigated whether mutant Kras could be exchanged by another potent oncogene, such as EWSR1-FLI1 , to initiate pancreatic cancer development. We generated two conditional mouse models expressing mutant Kras G12D (KC) or the EWSR1-FLI1 oncogene (E/F) in pancreas cells. Pancreatic tissue was collected from the mice at 4–6 weeks and 11–13 weeks of age as well as from survival cohorts to determine the development of spontaneous acinar-to-ductal metaplasia (ADM) and neoplastic lesions. Immunohistochemistry and immunofluorescence staining were performed to characterize and quantify changes in tissue morphology. The expression of the EWSR1-FLI1 fusion protein in pancreas cells was confirmed by positive FLI1 immunohistochemistry staining. Notably, the EWSR1-FLI1 expression in pancreas cells resulted in a strong depletion of the acinar cell mass and an extensive lipomatosis. Although the E/F mice exhibited spontaneous ADM formation and a shorter overall survival rate compared to KC mice, no development of neoplastic lesion was observed in aging E/F mice. The expression of the EWSR1-FLI1 oncogene leads to a strong pancreatic atrophy and lipomatosis. ADM formation indicates that pancreatic acinar cells are susceptible for EWSR1-FLI1-mediated oncogenic transformation to a limited extent. However, the EWSR1-FLI1 oncogene is insufficient to induce pancreatic cancer development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The benefit of preoperative biliary stenting in the treatment of pancreatic ductal adenocarcinoma is controversially debated. Data from recent meta-analyses favor primary surgery for the majority of resectable pancreatic cancers. Regardless of this evidence, preoperative biliary stenting via endoscopy (EBS) is commonly performed, often before involvement of a surgeon. The goal of this study was to elucidate the association of bile duct stenting, microbiological dislocation of gut flora to the biliary compartment, and major postoperative complications. Methods: Patient data was derived from a prospectively maintained database including all pancreatic resections between January 2006 and December 2014. Patients receiving pancreaticoduodenectomy for malignant disease in the head of the pancreas with prior EBS were included. Microbiological data were obtained through conventional culture from intraoperative bile duct swabs. Results: Two hundred ninety-eight patients were enrolled in this study. Severe postoperative complications were associated with stent colonization: Postoperative pancreatic fistula type C occurred more frequently in E. coli–colonized patients (sample estimated odds ratio (OR) = 4.07), and the rate of lymphatic fistula was elevated in Enterococcus-colonized patients (OR = 3.25). Longer stenting duration (> 16 days) was associated with the prevalence of these bacteria. Conclusion: Major surgical complications following pancreaticoduodenectomy, including severe pancreatic fistula, are associated with bacterobilia after EBS. The indication for bile duct stenting should be evaluated in a multidisciplinary setting. [ABSTRACT FROM AUTHOR]

Incidence of wound complications after kidney transplantation (KTx) is still considerable. Here, we report the impact of prophylactic absorbable polyglactin (Vicryl®) mesh reinforcement on the incidence of short‐term post‐KTx wound complications. Sixty‐nine patients were analyzed; 23 with and 46 without preventive onlay mesh reinforcement. Surgical site infections (SSI) were seen in six (26%) patients in the mesh group and in 17 (37%) patients in no‐mesh group. A lower, but not statistically significant, rate of early postoperative wound complications occurred in the mesh group. Wound complications were observed in seven (30%) patients in the mesh group and in 23 (50%) patients in the no‐mesh group. There was no association between mesh placement and SSI incidence (odds ratios [OR] 0.60, 95% confidence interval [CI] 0.20–1.82, p = 0.369) and wound complications (OR 0.44, 95% CI 0.15–1.26, p = 0.126). Therefore, we conclude that mesh reinforcement does not increase the risk of SSI and overall wound complications. Long‐term outcomes have to be evaluated in a randomized trial setting. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:67–72, 2020. [ABSTRACT FROM AUTHOR]

Pancreatitis is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). Previous studies in mice have demonstrated that pancreatitis contributes to oncogenic Kras‐driven carcinogenesis, probably initiated in acinar cells; however, oncogenic Kras alone or in combination with caerulein‐induced pancreatitis is not sufficient in initiating PDAC from the ductal compartment. We thus introduced ductal obstruction – which induces a more severe form of pancreatitis – by pancreatic ductal ligation in mice harbouring oncogenic Kras. This induced a particular phenotype with highly proliferative nonmucinous cells with nuclear atypia. Around these lesions, there was a significant proliferation of activated fibroblasts and infiltration of immune cells, corroborating the pathological features of preneoplastic lesions. Lineage‐tracing experiments revealed that these preneoplastic cells derived from two distinctive cellular sources: acinar and ductal cells. Phenotypic characterisation revealed that the duct‐derived preneoplastic lesions show a high proliferative potential with persistent activation of tumour‐promoting inflammatory pathways while the acinar‐derived ones were less proliferative with persistent p53 activation. Furthermore, the duct‐derived preneoplastic cells have a particularly high nuclear‐to‐cytoplasmic ratio. These data demonstrate that ductal obstruction promotes preneoplastic lesion formation from the pancreatic ductal compartment. What's new? Pancreatic inflammation contributes to oncogenic Kras‐driven pancreatic ductal adenocarcinoma (PDAC). Little is known, however, about differences between pancreatic acinar cells and ductal cells regarding susceptibility to oncogenic Kras. Here, initiation of pre‐neoplastic lesions from the acinar or ductal cellular compartment was found to be related to inflammation type and extent. In oncogenic Kras mice, ductal obstruction caused severe pancreatitis with transient ductal cell proliferation and further induced a proliferative phenotype in oncogenic Kras‐expressing ductal cells, with pathological features resembling those of pre‐neoplastic lesions. The findings highlight the significance of cell type‐dependent diversity in PDAC malignant transformation pathways. [ABSTRACT FROM AUTHOR]

Background: Site-specific outcomes of resection for periampullary cancer have not been analyzed on a large, registry-based scale.Methods: We assessed data on periampullary cancers from the SEER database. Site- and stage-specific outcomes were analyzed. Resection was compared to no resection.Results: Resection was the main therapy in stages 1 and 2 (resection vs. no resection, 8644 vs. 7208 patients), was less frequent in stage 3 (1248 vs. 2783 patients) and was rarely-but still-used in stage 4 disease (541 vs. 11,212 patients). Pancreatic head (75.7%), 11.4% distal bile duct, 7.7% ampullary, and 5.3% duodenal cancers. Cancer subtype-independent median survival was 22.0 (resection) vs. 7.0 months (no resection) in stages 1 and 2, 21.0 vs. 8.0 months in stage 3, and 10.0 vs. 3.0 months in stage 4. Subtype-dependent median survival (resection vs. no resection) was 18.0 vs. 5.0 months in pancreatic head, 19.0 vs 4.0 months in distal bile duct, 41.0 vs 7.0 months in ampullary, and 38.0 vs 4.0 months in duodenal adenocarcinoma. On multivariable analysis, patient comorbidities, marital and insurance status, and income all influenced the decision to undergo resection.Conclusions: Surgery is still underutilized in the treatment of periampullary cancers. Patients with cancers originating from the duodenum or the ampulla of Vater benefit most from resectional surgery. [ABSTRACT FROM AUTHOR]

Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene‐disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case–control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58–0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21–0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19–0.89, and OR = 0.73, 95%CI 0.53–1.00, respectively). Several inflammatory‐related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC. What's new? Deaths from pancreatic cancer are increasing making it a public health emergency to define the molecular causes of this deadly disease. Here the authors show that autoimmune diseases share genetic components with pancreatic cancer and further corroborate this association in a case‐control study. This could bring new mechanistic understanding of pancreatic cancer, potentially impacting its prevention and treatment in the future. [ABSTRACT FROM AUTHOR]

Abstract Background Acute pancreatitis is accompanied by acinar cell damage releasing potential toll-like receptor 3 (TLR3) ligands. So far, TLR3 is known as a pattern recognition receptor in the immune signaling cascade triggering a type I interferon response. In addition, TLR3 signaling contributes to programmed cell death through the activation of caspase 8. However, the functional role of TLR3 and its downstream toll-like receptor adaptor molecule 1 (TICAM1) in the inflamed pancreas is unknown. Methods To uncover the role of TLR3 signaling in acute pancreatitis, we induced a cerulein-mediated pancreatitis in Tlr3 and Ticam1 knockout (KO) mice and in wildtype animals. The exocrine damage was determined by blood serum analysis and histological examination. Immunohistochemistry, gene expression and immunoblot analysis were conducted to study TLR3 function. Results After the induction of an acute pancreatitis, wildtype mice showed a high endosomal TLR3 expression in acinar cells. In comparison to wildtype and Ticam1 KO mice, Tlr3 KO mice exhibited the highest severity of pancreatitis with an increased NF-κB activation and elevated expression of the pro-inflammatory cytokines Il6 and Tnf , although the amount of infiltrating immune cells was unaffected. Additionally, we detected a strong elevation of acinar cell necrosis and reduced levels of cleaved caspase 8 in Tlr3 and Ticam1 KO mice. Conclusions TLR3 and its downstream adaptor TICAM1 are important mediators of acinar cell damage in acute pancreatitis. They possess a critical role in programmed cell death and our data suggest that TLR3 signaling controls the onset and severity of acute pancreatitis. [ABSTRACT FROM AUTHOR]

Introduction: Numerous extended donor criteria (EDC) have been identified in liver transplantation (LT), but different EDC have different impacts on graft and patient survival. This study aimed to identify major EDC (maEDC) that were best able to predict the outcome after LT and to examine the plausibility of an allocation algorithm based on these criteria.Methods: All consecutive LTs between 12/2006 and 03/2014 were included (n = 611). We analyzed the following EDC: donor age > 65 years, body mass index > 30, malignancy and drug abuse history, intensive care unit stay/ventilation > 7 days, aminotransferases > 3 times normal, serum bilirubin > 3 mg/dL, serum Na+ > 165 mmol/L, positive hepatitis serology, biopsy-proven macrovesicular steatosis (BPS) > 40%, and cold ischemia time (CIT) > 14 h. We analyzed hazard risk ratios of graft failure for each EDC and evaluated primary non-function (PNF). In addition, we analyzed 30-day, 90-day, 1-year, and 3-year graft survival. We established low- and high-risk graft (maEDC 0 vs. ≥ 1) and recipient (labMELD < 20 vs. ≥ 20) groups and compared the post-LT outcomes between these groups.Results: BPS > 40%, donor age > 65 years, and CIT > 14 h (all p < 0.05) were independent predictors of graft failure and patient mortality and increased PNF, 30-day, 90-day, 1-year, and 3-year graft failure rates. Three-year graft and patient survival decreased in recipients of ≥ 1 maEDC grafts (all p < 0.05) and LT of high-risk grafts into high-risk recipients yielded worse outcomes compared with other groups.Conclusion: Donor age > 65 years, BPS > 40%, and CIT > 14 h are major EDC that decrease short and 3-year graft survival, and 3-year patient survival. An allocation algorithm based on maEDC and labMELD is therefore plausible. [ABSTRACT FROM AUTHOR]

This statement was developed to promote international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) which was adopted by the National Comprehensive Cancer Network (NCCN) in 2006, but which has changed yearly and become more complicated. Based on a symposium held during the 20th meeting of the International Association of Pancreatology (IAP) in Sendai, Japan, in 2016, the presenters sought consensus on issues related to BR-PDAC. We defined patients with BR-PDAC according to the three distinct dimensions: anatomical (A), biological (B), and conditional (C). Anatomic factors include tumor contact with the superior mesenteric artery and/or celiac artery of less than 180° without showing stenosis or deformity, tumor contact with the common hepatic artery without showing tumor contact with the proper hepatic artery and/or celiac artery, and tumor contact with the superior mesenteric vein and/or portal vein including bilateral narrowing or occlusion without extending beyond the inferior border of the duodenum. Biological factors include potentially resectable disease based on anatomic criteria but with clinical findings suspicious for (but unproven) distant metastases or regional lymph nodes metastases diagnosed by biopsy or positron emission tomography-computed tomography. This also includes a serum carbohydrate antigen (CA) 19–9 level more than 500 units/ml. Conditional factors include the patients with potentially resectable disease based on anatomic and biologic criteria and with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. The definition of BR-PDAC requires one or more positive dimensions (e.g. A, B, C, AB, AC, BC or ABC). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumor and vessels, but that biological and conditional dimensions are also important. The aim in presenting this consensus definition is also to highlight issues which remain controversial and require further research. [ABSTRACT FROM AUTHOR]

Introduction The risk of malignancy in branch duct intraductal papillary mucinous neoplasia of the pancreas (BD-IPMN) is controversially debated. An increasing number of studies report on outcomes using the Sendai or Fukuoka consensus criteria for treatment decision-making. The objective of this work was to evaluate the diagnostic accuracy of the Sendai and Fukuoka criteria. Methods We systematically reviewed studies on Sendai or Fukuoka criteria-guided management of BD-IPMN. Pooled sensitivity, specificity and diagnostic odds ratios as compound measures of diagnostic accuracy were calculated from studies matching the inclusion criteria. The meta-analysis was performed using a random effects model. Results Fifteen studies with a total of 2710 patients were included. Twelve of these used the Sendai criteria. In these studies, 23% of Sendai-negative patients had a high grade dysplastic lesion or an invasive carcinoma in final histology. Pooled sensitivity was 56%, specificity was 74% and the diagnostic odds ratio for malignancy in Sendai-positive lesions was 7.45. When the results of follow-up examinations were included, diagnostic accuracy improved significantly (14.66, p < 0.001). Three studies were identified that used the Fukuoka criteria for decision making. Of 200 patients with Fukuoka-negative lesions who underwent surgery, 22 had a malignant lesion in final histology (11%). Pooled sensitivity was 83%, specificity was 53% and the diagnostic odds ratio was 8.76. Conclusion The Fukuoka criteria have considerably improved sensitivity but still lack adequate specificity. For further reduction of a potential surgical overtreatment of BD-IPMN, the development of criteria with an increased specificity is required. [ABSTRACT FROM AUTHOR]

These parameters were regarded as maEDC, and their effects on graft and patient survival were analyzed." These parameters were regarded as maEDC, and their effects on graft and patient survival were analyzed." The original article can be found online at https://doi.org/10.1007/s00423-018-1704-z B Correction to: Langenbeck's Archives of Surgery (2018) 403:719-731 b https://doi.org/10.1007/s00423-018-1704-z The original version of this article unfortunately contained a small error on pages 722-723 of the manuscript (paragraph "Major EDC"). [Extracted from the article]

Background: Pancreatic acinar cell carcinoma (ACC) is a rare tumor entity with an unfavorable prognosis. Recent whole-exome sequencing identified p53 mutations in a subset of human ACC. Activation of the mammalian target of rapamycin (mTOR) pathway is associated with various pancreatic neoplasms. We thus aimed at analyzing whether activation of mTOR with a concomitant loss of p53 may initiate ACC. Methods: We generated transgenic mouse models in which mTOR was hyperactivated through pancreas-specific, homozygous tuberous sclerosis 1 (Tsc1) deficiency, with or without deletion of p53 (Tsc1-/- and Tsc1-/-; p53-/-). Activity of mTOR signaling was investigated using mouse tissues and isolated murine cell lines. Human ACC specimens were used to corroborate the findings from the transgenic mouse models. Results: Hyperactive mTOR signaling in Tsc1-/- mice was not oncogenic but rather induced a near-complete loss of the pancreatic acinar compartment. Acinar cells were lost as a result of apoptosis which was associated with p53 activation. Concomitantly, ductal cells were enriched. Ablation of p53 in Tsc1-deficient mice prevented acinar cell death but promoted formation of acinar cells with severe nuclear abnormalities. One out of seven Tsc1-/-; p53-/- animals developed pancreatic tumors showing a distinctive tumor morphology, reminiscent of human ACC. Hyperactive mTOR signaling was also detected in a subset of human ACC. Conclusion: Hyperactive mTOR signaling combined with loss of p53 in mice induces tumors similar to human ACC. [ABSTRACT FROM AUTHOR]

Type I interferon constitutes an essential component of the combinational therapy against viral disease. Acute pancreatitis is one side effect of type I interferon-based therapy, implying that activation of type I interferon signaling affects the homeostasis and integrity of pancreatic acinar cells. Here, we investigated the role of type I interferon signaling in pancreatic acinar cells using a caerulein-induced murine model of acute pancreatitis. Pancreas-specific ablation of interferon (alpha and beta) receptor 1 (Ifnar1) partially protected animals from caerulein-induced pancreatitis, as demonstrated by reduced tissue damage. Profiling of infiltrating immune cells revealed that this dampened tissue damage response correlated with the number of macrophages in the pancreas. Pharmacologic depletion of macrophages reversed the protective effect of Ifnar1 deficiency. Furthermore, expression of chemokine (C-C motif) ligand 2 (Ccl2), a potent factor for macrophage recruitment, was significantly increased in the Ifnar1-deficient pancreas. Thus, type I interferon signaling in pancreatic acinar cells controls pancreatic homeostasis by affecting the macrophage-mediated inflammatory response in the pancreas. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) patients frequently present with borderline resectable disease, which can be due to invasion of the portal/superior mesenteric vein (PV/SMV). Here, we analyzed this group of patients, with emphasis on short and long-term outcomes. Methods: 156 patients who underwent a resection for PDAC were included in the analysis and sub-stratified into a cohort of patients with PV/SMV resection (n = 54) versus those with standard surgeries (n = 102). Results: While venous resections could be performed safely, there was a trend towards shorter median survival in the PV/SMV resection group (22.7 vs. 15.8 months, p = 0.157). These tumors were significantly larger (3.5 vs 4.3 cm; p = 0.026) and margin-positivity was more frequent (30.4 % vs 44.4 %, p = 0.046). Conclusion: Venous resection was associated with a higher rate of margin positivity and a trend towards shorter survival. However, compared to non-surgical treatment, resection offers the best chance for long term survival. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) patients frequently present with borderline resectable disease, which can be due to invasion of the portal/superior mesenteric vein (PV/SMV). Here, we analyzed this group of patients, with emphasis on short and long-term outcomes. Methods: 156 patients who underwent a resection for PDAC were included in the analysis and sub-stratified into a cohort of patients with PV/SMV resection (n = 54) versus those with standard surgeries (n = 102). Results: While venous resections could be performed safely, there was a trend towards shorter median survival in the PV/SMV resection group (22.7 vs. 15.8 months, p = 0.157). These tumors were significantly larger (3.5 vs 4.3 cm; p = 0.026) and margin-positivity was more frequent (30.4 % vs 44.4 %, p = 0.046). Conclusion: Venous resection was associated with a higher rate of margin positivity and a trend towards shorter survival. However, compared to non-surgical treatment, resection offers the best chance for long term survival. [ABSTRACT FROM AUTHOR]

Background: Previous studies identified microRNAs (miRNAs) and messenger RNAs with significantly different expression between normal pancreas and pancreatic cancer (PDAC) tissues. Due to technological limitations of microarrays and real-time PCR systems these studies focused on a fixed set of targets. Expression of other RNA classes such as long intergenic non-coding RNAs or sno-derived RNAs has rarely been examined in pancreatic cancer. Here, we analysed the coding and non-coding transcriptome of six PDAC and five control tissues using next-generation sequencing. Results: Besides the confirmation of several deregulated mRNAs and miRNAs, miRNAs without previous implication in PDAC were detected: miR-802, miR-2114 or miR-561. SnoRNA-derived RNAs (e.g. sno-HBII-296B) and piR-017061, a piwi-interacting RNA, were found to be differentially expressed between PDAC and control tissues. In silico target analysis of miR-802 revealed potential binding sites in the 3' UTR of TCF4, encoding a transcription factor that controls Wnt signalling genes. Overexpression of miR-802 in MiaPaCa pancreatic cancer cells reduced TCF4 protein levels. Using Massive Analysis of cDNA Ends (MACE) we identified differential expression of 43 lincRNAs, long intergenic non-coding RNAs, e.g. LINC00261 and LINC00152 as well as several natural antisense transcripts like HNF1A-AS1 and AFAP1-AS1. Differential expression was confirmed by qPCR on the mRNA/miRNA/lincRNA level and by immunohistochemistry on the protein level. Conclusions: Here, we report a novel lncRNA, sncRNA and mRNA signature of PDAC. In silico prediction of ncRNA targets allowed for assigning potential functions to differentially regulated RNAs. [ABSTRACT FROM AUTHOR]

Background Nodal (nodal growth differentiation factor) and its inhibitor Lefty (left right determination factor), which are ligands of the TGF (transforming growth factor) β superfamily, are responsible for the determination of left-right asymmetry in vertebrates. Nodal/Lefty signaling has been suggested to play a role in the development of metastatic melanoma and breast cancer. However, it remains unclear whether this pathway is also involved in human pancreatic ductal adenocarcinoma (PDAC). Methods Pancreatic cancer patient specimens with clinical data (n = 54) were used to investigate the clinical significance of Nodal-Lefty signaling. A set of in vitro assays were carried out in a human pancreatic cancer cell line (Colo-357) to assess the functional relevance of Nodal-Lefty signaling. Results Nodal was absent in the human normal pancreas, while Lefty was present in islet cells. Though Nodal and Lefty expression were found in cancer cells at various expression levels, the cancer-associated tubular complexes were particularly positive for Lefty. Survival analysis revealed that high expression of Nodal correlated with reduced patient survival (median survival 17.8 vs 33.0 months, p = 0.013). Cultured pancreatic cancer cell lines expressed Nodal and Lefty at different levels. In vitro functional assays revealed that treatment with human recombinant Nodal inhibited cell growth and increased invasion of Colo-357 pancreatic cancer cells whereas no effect was found upon treatment with recombinant Lefty. Conclusion Nodal-Lefty signaling might be involved in the pathogenesis of PDAC as Nodal expression marks a subtype of PDAC with unfavorable prognosis. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease without clearly known disease causes. Recent epidemiological and animal studies suggest that the supplementation of dietary antioxidants (e.g., vitamins C and E) decreases cancer risk, implying that increased reactive oxygen species (ROS) may play a role in pancreatic carcinogenesis. However, oncogenic Kras mutations (e.g., KrasG12D), which are present in more than 90% of PDAC, have been proven to foster low intracellular ROS levels. Here, oncogenic Kras activates expression of a series of anti-oxidant genes via Nrf2 (nuclear factor, erythroid derived 2, like 2) and also mediates an unusual metabolic pathway of glutamine to generate NADPH. This can then be used as the reducing power for ROS detoxification, leading collectively to low ROS levels in pancreatic pre-neoplastic cells and in cancer cells. In adult stem cells and cancer stem cells, low ROS levels have been associated with the formation of a proliferation-permissive intracellular environment and with perseverance of self-renewal capacities. Therefore, it is conceivable that low intracellular ROS levels may contribute significantly to oncogenic Kras-mediated PDAC formation. [ABSTRACT FROM AUTHOR]

Our understanding of pancreatic ductal adenocarcinoma (PDAC) is shifting away from a disease of malignant ductal cells-only, toward a complex system where tumor evolution is a result of interaction of cancer cells with their microenvironment. This change has led to intensification of research focusing on the fibrotic stroma of PDAC. Pancreatic stellate cells (PSCs) are the main fibroblastic cells of the pancreas which are responsible for producing the desmoplasia in chronic pancreatitis (CP) and PDAC. Clinically, the effect of desmoplasia is two-sided; on the negative side it is a hurdle in the diagnosis of PDAC because the fibrosis in cancer resembles that of CP. It is also believed that PSCs and pancreatic fibrosis are partially responsible for the therapy resistance in pancreatic cancer. On the positive side, a fibrotic pancreas is safer to operate on compared to a fatty and soft pancreas which is prone for postoperative pancreatic fistula. In this review the impact of pancreatic fibrosis on diagnosis of pancreatic cancer and surgical decisions are discussed from a clinical point of view. [ABSTRACT FROM AUTHOR]