Mortality and postoperative complications after different types of surgical reconstruction following pancreaticoduodenectomy-a systematic review with meta-analysis.

BACKGROUND: Pancreaticoduodenectomy/PD is a technically demanding pancreatic resection. Options of surgical reconstruction include (1) the child reconstruction defined as pancreatojejunostomy/PJ followed by hepaticojejunostomy/HJ and the gastrojejunostomy/GJ "the standard/s-Child," (2) the s-child reconstruction with an additional Braun enteroenterostomy "BE-Child," or (3) Isolated-Roux-En-Y-pancreaticojejunostomy "Iso-Roux-En-Y," in which the pancreas anastomosis is reconstructed in a separate loop after the GJ. Yet, the impact of these reconstruction methods on patients' outcome has not been sufficiently compared in a systematic manner. METHODS: A systematic review and meta-analysis were conducted according to the Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines by screening Pubmed/Medline, Scopus, Cochrane Library and Web-of-Science. Articles meeting predefined criteria were extracted and meta-analysis was performed. RESULTS: Nineteen studies were identified comparing BE-Child or Isolated-Roux-En-Y vs. s-Child. Compared to s-Child neither BE-Child (p = 0.43) nor Iso-Roux-En-Y (p = 0.94) displayed an impact on postoperative mortality, whereas BE-Child showed less postoperative complications (p = 0.02). BE-Child (p = 0.15) and Iso-Roux-En-Y (p = 0.61) did not affect postoperative pancreatic fistula/POPF in general, but BE-Child was associated with a decrease of clinically relevant POPF (p = 0.005), clinically relevant delayed gastric emptying/DGE B/C (p = 0.004), bile leaks (p = 0.01), and hospital stay (p = 0.06). BE-Child entailed also an increased operation time (p = 0.0002) with no impact on DGE A/B/C, hemorrhage, surgical site infections and pulmonary complications. CONCLUSION: BE-Child is associated with a decreased risk for postoperative complications, particularly a decreased risk for clinically relevant DGE, POPF, and bile leaks, whereas Iso-Roux-En-Y does not seem to affect the clinical course after PD. Therefore, BE seems to be a valuable surgical method to improve patients' outcome after PD.

R0 Versus R1 Resection Matters after Pancreaticoduodenectomy, and Less after Distal or Total Pancreatectomy for Pancreatic Cancer.

OBJECTIVE: The aim of this study was to decipher the true importance of R0 versus R1 resection for survival in pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: PDAC is characterized by poor survival, even after curative resection. In many studies, R0 versus R1 does not result in different prognosis and does not affect the postoperative management. METHODS: Pubmed, Embase, and Cochrane databases were screened for prognostic studies on the association between resection status and survival. Hazard ratios (HRs) were pooled in a meta-analysis. Furthermore, our prospective database was retrospectively screened for curative PDAC resections according to inclusion criteria (n = 254 patients) between July 2007 and October 2014. RESULTS: In the meta-analysis, R1 was associated with a decreased overall survival [HR 1.45 (95% confidence interval, 95% CI 1.37-1.52)] and disease-free survival [HR 1.44 (1.30-1.59)] in PDAC when compared with R0. Importantly, this effect held true only for pancreatic head resection both in the meta-analysis [R0 ≥0 mm: HR 1.21 (1.05-1.39) vs R0 ≥1 mm: HR 1.66 (1.46-1.89)] and in our cohort (R0 ≥0 mm: 31.8 vs 14.5 months, P < 0.001; R0 ≥1 mm, 41.2 vs 16.8 months; P < 0.001). Moreover, R1 resections were associated with advanced tumor disease, that is, larger tumor size, lymph node metastases, and extended resections. Multivariable Cox proportional hazard model suggested G3, pN1, tumor size, and R1 (0 mm/1 mm) as independent predictors of overall survival. CONCLUSION: Resection margin is not a valid prognostic marker in publications before 2010 due to heterogeneity of cohorts and lack of standardized histopathological examination. Within standardized pathology protocols, R-status' prognostic validity may be primarily confined to pancreatic head cancers.

Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).

The impact of surgically placed, intraperitoneal drainage on morbidity and mortality after pancreas resection- A systematic review & meta-analysis.

BACKGROUND: Although routinely used, the benefit of surgically placed intraperitoneal drains after pancreas resection is still under debate. To assess the true impact of intraperitoneal drains in pancreas resection, a systematic review with meta-analysis was performed. METHODS: For this, the Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines were conducted and Pubmed/Medline, Embase, Scopus and The Cochrane Library were screened for relevant studies. RESULTS: 8 retrospective and 3 prospective studies were included in the systematic review. No difference was found between patients with or without intraperitoneal drains in mortality (Risk-ratio/RR 0.74, 95%-Confidence-interval/CI: 0.47-1.18, p = 0.20), in Grade B/C-postoperative pancreatic fistulas/POPF (RR 1.31, 95%-CI: 0.74-2.32, p = 0.35), in intraabdominal abscesses (RR 0.92, 95%-CI: 0.65-1.30, p = 0.64), in surgical site infection (RR 1.20, 95%-CI: 0.85-1.70, p = 0.30), in delayed gastric emptying (RR 1.11, 95%-CI: 0.65-1.90, p = 0.71), in postoperative haemorrhages (RR 0.92 95%-CI: 0.63-1.33, p = 0.65), in reoperations (RR 1.15, 95%-CI: 0.87-1.52, p = 0.33), or in radiological reinterventions (RR 0.95, 95%-CI: 0.69-1.31, p = 0.76). The risk for overall morbidity (RR 1.16, 95%-CI: 1.04-1.29, p = 0.008), of any POPF (RR 2.15, 95%-CI: 1.52-3.04, p < 0.0001) and of readmissions (RR 1.23, 95%-CI: 1.04-1.45, p = 0.01) was increased for patients with intraperitoneal drain compared to patients without following pancreatic resection. CONCLUSION: Regarding the controversial results of the recent prospective, randomized trials this meta-analysis revealed no difference in mortality but an increased risk for postoperative morbidity, POPF and readmissions of patients with intraperitoneal drains after pancreatic resection. Therefore, the indication for intraperitoneal drains should be critically weighed in patients undergoing pancreatic resections.

Endoluminal perforation of a magnetic antireflux device.

BACKGROUND: The history of surgical antireflux treatment is coined by the search for better alternatives to Nissen fundoplication. Implantable devices are one option, beginning with the "Angelchik" prosthesis 30 years ago. However, this procedure was left soon because of the high rate of foreign body connected problems (migration, perforation). A modern approach is a magnetic sphincter augmentation device (LINX Reflux Management System, Torax Medical, Shoreview, MN, USA), a magnetic chain which is implanted laparoscopically. Advantages reported are simplicity to apply and good results in reflux control, with up to now only rare complication rates as reported in the literature (Lipham et al. in Dis Esophagus, 2014). METHODS: We report one case of erosion of the esophagus by a LINX system resulting in severe dysphagia. RESULTS: A complete endoluminal removal could be achieved by a prototype OTSC-clip remover. Complete remission could be achieved. The technique is presented in detail (video). CONCLUSIONS: In principle, total endoscopic removal of the LINX device is feasible in case of major erosion.

Multicenter double-blinded randomized controlled trial of standard abdominal wound edge protection with surgical dressings versus coverage with a sterile circular polyethylene drape for prevention of surgical site infections: a CHIR-Net trial (BaFO; NCT01181206).

OBJECTIVE: To determine whether circular plastic wound edge protectors (CWEPs) significantly reduce the rate of surgical site infections (SSIs) in comparison to standard surgical towels in patients undergoing laparotomy. BACKGROUND: SSIs cause substantial morbidity, prolonged hospitalization, and costs and remain one of the most frequent surgical complications. CWEPs have been proposed as a measure to reduce the incidence of SSIs. METHODS: In this randomized controlled, multicenter, 2-arm, parallel-group design, patient- and observer-blinded trial patients undergoing open elective abdominal surgery were assigned to either intraoperative wound coverage with a CWEP or standard coverage with surgical towels. Primary endpoint was superiority of intervention over control in terms of the incidence of SSIs within a 30-day postoperative period. RESULTS: Between September 2010 and November 2012, 608 patients undergoing laparotomy were randomized at 16 centers across Germany. Three patients in the device group and 11 patients in the control group did not undergo laparotomy. Patients' and procedural characteristics were well balanced between the 2 groups. Forty-eight patients discontinued the study prematurely, mainly because of relaparotomy (control, n=9; intervention, n=9) and death (control, n=4; intervention, n=7). A total of 79 patients experienced SSIs within 30 days of surgery, 27 of 274 (9.9%) in the device group and 52 of 272 (19.1%) in the control group (odds ratio=0.462, 95% confidence interval: 0.281-0.762; P=0.002). Subgroup analyses indicate that the effect could be more pronounced in colorectal surgery, and in clean-contaminated/contaminated surgeries. CONCLUSIONS: Our trial shows that CWEPs are effective at reducing the incidence of SSIs in elective and clean or clean-contaminated open abdominal surgery.

Novel Histologic Categorization Based on Lauren Histotypes Conveys Prognostic Information for Gastroesophageal Junction Cancers-Analysis from a Large Single Center Cohort in Germany.

Adenocarcinoma of the gastroesophageal junction (AEG) ranks among the most common cancers in the Western world with increasing incidence. However, the prognostic influence and applicability of the Lauren classification was not examined in detail before. The purpose of this analysis was to analyze the oncologic outcomes of GE-junction cancer related to the Lauren histotype in a large single center cohort. Data from the prospectively documented database of the Klinikum Rechts der Isar (TUM School of Medicine) for patients undergoing curatively intended oncologic resection for GE-junction cancer between 1984 and 2018 were extracted. Univariate and multivariate regression analyses were performed to identify predictors for overall survival. Kaplan-Meier analyses were done to investigate the survival rates according to the Lauren histotype. After identification of two distinct histologic categories with prognostic implications, propensity score matching (PSM) was performed to balance for confounders and evaluate its oncologic outcomes retrospectively. In the time period indicated, 1710 patients were treated for GE-junction cancer. Exclusion criteria were: R2-resections (n = 134), metastatic disease (n = 296), 30-day mortality (n = 45), Siewert type I (n = 21), and missing/incomplete data (n = 61). Finally, 1153 patients were analyzed. In a multiple variable analysis, age, UICC-stage, all Lauren histotypes, R-stage, and postoperative complications were significant predictors of overall survival. Kaplan Meier analysis demonstrated significant survival differences between intestinal, diffuse, and mixed Lauren-histotypes (p = 0.001 and p = 0.029). Survival rates were comparable between non-classifiable and intestinal Lauren-types (p = 0.16) and between diffuse and mixed types (p = 0.56). When combining non-classifiable, well, and moderately differentiated Lauren-types and combining poorly differentiated intestinal, diffuse, and mixed types, two highly prognostic groups were identified (p < 0.0001). This was confirmed after PSM for possible confounders. The Lauren histotypes demonstrate highly prognostic value after oncologic resection of GE-junction cancer (Siewert type II and type III) in a single center Western patient cohort. A simplified histotype classification based on Lauren subtypes revealed a clear distinction of prognostic groups and should be considered for further evaluation.

Significance of Lauren Classification in Patients Undergoing Neoadjuvant/Perioperative Chemotherapy for Locally Advanced Gastric or Gastroesophageal Junction Cancers-Analysis from a Large Single Center Cohort in Germany.

BACKGROUND: the purpose of this analysis was to analyze the outcomes of multimodal treatment that are related to Lauren histotypes in gastro-esophageal cancer (GEC). METHODS: patients with GEC between 1986 and 2013 were analyzed. Uni- and multivariate regression analysis were performed to identify predictors for overall survival. Lauren histotype stratified overall survival (OS)-rates were analyzed by the Kaplan-Meier method. Further, propensity score matching (PSM) was performed to balance for confounders. RESULTS: 1290 patients were analyzed. After PSM, the median survival was 32 months for patients undergoing primary surgery (PS) and 43 months for patients undergoing neoadjuvant chemotherapy (nCTx) ahead of surgery. For intestinal types, median survival time was 34 months (PS) vs. 52 months (nCTx+surgery) p = 0.07, 36 months (PS) vs. (31) months (nCTx+surgery) in diffuse types (p = 0.44) and 31 months (PS) vs. 62 months (nCTx+surgery) for mixed types (p = 0.28). Five-/Ten-year survival rates for intestinal, diffuse, and mixed types were 44/29%, 36/17%, and 43/33%, respectively. After PSM, Kaplan-Meier showed a survival benefit for patients undergoing nCTx+surgery in intestinal and mixed types. CONCLUSION: the Lauren histotype might be predictive for survival outcome in GEC-patients after neoadjuvant/perioperative chemotherapy.

Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging.

BACKGROUND: PDAC remains a tumor entity with poor prognosis and a 5-year survival rate below 10%. Recent research has revealed invasive biomarkers, such as distinct molecular subtypes, predictive for therapy response and patient survival. Non-invasive prediction of individual patient outcome however remains an unresolved task. METHODS: Discrete cellularity regions of PDAC resection specimen (n = 43) were analyzed by routine histopathological work up. Regional tumor cellularity and CT-derived Hounsfield Units (HU, n = 66) as well as iodine concentrations were regionally matched. One-way ANOVA and pairwise t-tests were performed to assess the relationship between different cellularity level in conventional, virtual monoenergetic 40 keV (monoE 40 keV) and iodine map reconstructions. RESULTS: A statistically significant negative correlation between regional tumor cellularity in histopathology and CT-derived HU from corresponding image regions was identified. Radiological differentiation was best possible in monoE 40 keV CT images. However, HU values differed significantly in conventional reconstructions as well, indicating the possibility of a broad clinical application of this finding. CONCLUSION: In this study we establish a novel method for CT-based prediction of tumor cellularity for in-vivo tumor characterization in PDAC patients.

Histopathologic Response Is a Positive Predictor of Overall Survival in Patients Undergoing Neoadjuvant/Perioperative Chemotherapy for Locally Advanced Gastric or Gastroesophageal Junction Cancers-Analysis from a Large Single Center Cohort in Germany.

There is conflicting evidence regarding the efficacy of neoadjuvant/perioperative chemotherapy (NCT) for gastro-esophageal cancer (GEC) on overall survival. This study aimed to analyze the outcomes of multimodal treatments in a large single center cohort. We performed a retrospective analysis of patients treated with NCT, followed by intended curative oncological surgery for locally advanced gastric cancer. Uni- and multivariate regression analysis were performed to identify the predictors of overall survival. From over 3000 patients, 702 eligible patients were analyzed. In the univariate analysis clinical stage, application of preoperative PLF, requirement of surgical extension, UICC-stage, grading, R-status, Lauren histotype, and HPR were the prognostic survival factors. In multivariate analysis PLF regimen, UICC-stages, R-status, Lauren histotype, and histopathologic regression (HPR) were significant predictors of overall survival. Overall HPR-rate was 26.9%. HPR was highest in the cT2cN0 stage (55.9%), and lowest in the cT3/4 cN+ stage (21.6%). FLOT demonstrated the highest HPR (37.5%). Independent predictors for HPR were the clinical stage and grading. Kaplan Meier analyses demonstrated significant survival benefits for the responding patients (p < 0.0001). HPR after NCT was an important prognostic factor to predict overall survival for locally advanced GEC. FLOT should be the preferred regimen in patients undergoing NCT ahead of surgery.

Multiparametric Modelling of Survival in Pancreatic Ductal Adenocarcinoma Using Clinical, Histomorphological, Genetic and Image-Derived Parameters.

RATIONALE: Pancreatic ductal adenocarcinoma (PDAC) remains a tumor entity of exceptionally poor prognosis, and several biomarkers are under current investigation for the prediction of patient prognosis. Many studies focus on promoting newly developed imaging biomarkers without a rigorous comparison to other established parameters. To assess the true value and leverage the potential of all efforts in this field, a multi-parametric evaluation of the available biomarkers for PDAC survival prediction is warranted. Here we present a multiparametric analysis to assess the predictive value of established parameters and the added contribution of newly developed imaging features such as biomarkers for overall PDAC patient survival. METHODS: 103 patients with resectable PDAC were retrospectively enrolled. Clinical and histopathological data (age, sex, chemotherapy regimens, tumor size, lymph node status, grading and resection status), morpho-molecular and genetic data (tumor morphology, molecular subtype, tp53, kras, smad4 and p16 genetics), image-derived features and the combination of all parameters were tested for their prognostic strength based on the concordance index (CI) of multivariate Cox proportional hazards survival modelling after unsupervised machine learning preprocessing. RESULTS: The average CIs of the out-of-sample data were: 0.63 for the clinical and histopathological features, 0.53 for the morpho-molecular and genetic features, 0.65 for the imaging features and 0.65 for the combined model including all parameters. CONCLUSIONS: Imaging-derived features represent an independent survival predictor in PDAC and enable the multiparametric, machine learning-assisted modelling of postoperative overall survival with a high performance compared to clinical and morpho-molecular/genetic parameters. We propose that future studies systematically include imaging-derived features to benchmark their additive value when evaluating biomarker-based model performance.

Negative Pressure Wound Therapy vs Conventional Wound Treatment in Subcutaneous Abdominal Wound Healing Impairment: The SAWHI Randomized Clinical Trial.

Importance: Negative pressure wound therapy (NPWT) is an established treatment option, but there is no evidence of benefit for subcutaneous abdominal wound healing impairment (SAWHI). Objective: To evaluate the effectiveness and safety of NPWT for SAWHI after surgery in clinical practice. Design, Setting, and Participants: The multicenter, multinational, observer-blinded, randomized clinical SAWHI study enrolled patients between August 2, 2011, and January 31, 2018. The last follow-up date was June 11, 2018. The trial included 34 abdominal surgical departments of hospitals in Germany, Belgium, and the Netherlands, and 539 consecutive, compliant adult patients with SAWHI after surgery without fascia dehiscence were randomly assigned to the treatment arms in a 1:1 ratio stratified by study site and wound size using a centralized web-based tool. A total of 507 study participants (NPWT, 256; CWT, 251) were assessed for the primary end point in the modified intention-to-treat (ITT) population. Interventions: Negative pressure wound therapy and conventional wound treatment (CWT). Main Outcomes and Measures: The primary outcome was time until wound closure (delayed primary closure or by secondary intention) within 42 days. Safety analysis comprised the adverse events (AEs). Secondary outcomes included wound closure rate, quality of life (SF-36), pain, and patient satisfaction. Results: Of the 507 study participants included in the modified ITT population, 287 were men (56.6%) (NPWT, 155 [60.5%] and CWT, 132 [52.6%]) and 220 were women (43.4%) (NPWT, 101 [39.5%] and CWT 119 [47.4%]). The median (IQR) age of the participants was 66 (18) years in the NPWT arm and 66 (20) years in the CWT arm. Mean time to wound closure was significantly shorter in the NPWT arm (36.1 days) than in the CWT arm (39.1 days) (difference, 3.0 days; 95% CI 1.6-4.4; P < .001). Wound closure rate within 42 days was significantly higher with NPWT (35.9%) than with CWT (21.5%) (difference, 14.4%; 95% CI, 6.6%-22.2%; P < .001). In the therapy-compliant population, excluding study participants with unauthorized treatment changes (NPWT, 22; CWT, 50), the risk for wound-related AEs was higher in the NPWT arm (risk ratio, 1.51; 95% CI, 0.99-2.35). Conclusions and Relevance: Negative pressure wound therapy is an effective treatment option for SAWHI after surgery; however, it causes more wound-related AEs. Trial Registration: ClinicalTrials.gov Identifier: NCT01528033.

Borderline-resectable pancreatic adenocarcinoma: Contour irregularity of the venous confluence in pre-operative computed tomography predicts histopathological infiltration.

PURPOSE: The purpose of the current study was to compare CT-signs of portal venous confluence infiltration for actual histopathological infiltration of the vein or the tumor/vein interface (TVI) in borderline resectable pancreatic ductal adenocarcinoma (PDAC). METHODS AND MATERIALS: 101 patients with therapy-naïve, primarily resected PDAC of the pancreatic head without arterial involvement were evaluated. The portal venous confluence was assessed for contour irregularity (defined as infiltration) and degree of contact. The sensitivity and specificity of contour irregularity versus tumor to vein contact >180° as well as the combination of the signs for tumor cell infiltration of the vessel wall or TVI was calculated. Overall survival (OS) was compared between groups. RESULTS: Sensitivity and specificity of contour irregularity for identification of tumor infiltration of the portal venous confluence or the TVI was higher compared to tumor to vessel contact >180° for tumor cell infiltration (96%/79% vs. 91%/38% respectively, p<0.001). The combination of the signs increased specificity to 92% (sensitivity 88%). Patients with contour irregularity/ tumor to vein contact >180°/ both signs had significantly worse overall survival (16.2 vs. 26.5 months/ 17.9 vs. 37.4 months/ 18.5 vs. 26.5 months respectively, all p<0.05). CONCLUSION: Portal venous confluence contour irregularity is a strong predictor of actual tumor cell infiltration of the vessel wall or the TVI and should be noted as such in radiological reports.

Pancreatic stump closure techniques and pancreatic fistula formation after distal pancreatectomy: Meta-analysis and single-center experience.

BACKGROUND: Pancreatic fistula/PF is the most frequent and feared complication after distal pancreatectomy/DP. However, the safest technique of pancreatic stump closure remains an ongoing debate. Here, we aimed to compare the safety of different pancreatic stump closure techniques for preventing PF during DP. METHODS: We performed a PRISMA-based meta-analysis of all relevant studies that compared at least two techniques of stump closure during DP with regard to PF rates/PFR. We further performed a retrospective analysis of our institutional PFR in correlation with stump closure techniques. RESULTS: 8301 studies were initially identified. From these, ten randomized controlled trials/RCTs, eleven prospective and 59 retrospective studies were eligible. Stapler closure (26%vs.31%, OR:0.73, p = 0.02), combination of stapler and suture (30%vs.33%, OR:0.70, p = 0.05), or stump anastomosis (14%vs.28%, OR:0.51, p = 0.02) were associated with lower PFR than suture closure alone. Spleen preservation/splenectomy, or laparoscopic/open DP, TachoSil®, fibrin-like glue-application, or bioabsorbable-stapler-reinforcements (Seamguard®) did not influence PFR after DP. In contrast, autologous patches (falciform ligament/seromuscular patches) resulted in lower PFR than no patch application (21.9%vs.25,8%, OR:0.60, p = 0.006). In our institution, the major three techniques of stump closure resulted in comparable PFR (suture:27%, stapler:29%, or combination:24%). However, selective suturing/clipping of the main pancreatic duct during pancreatic stump closure prevented severe PF (p = 0.02). CONCLUSION: After DP, stapler closure, pancreatic anastomosis, or falciform/seromuscular patches lead to lower PFR than suture closure alone. However, the differences are rather small, and further RCTs are needed to test these effects. Selective closure of the main pancreatic duct during stump closure may prevent severe PF.

Intraoperative wound irrigation to prevent surgical site infection after laparotomy (IOWISI): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative surgical site infection (SSI) is one of the most common hospital infections and contributes substantially to postoperative morbidity and mortality. In addition, SSIs dramatically increase the treatment cost and length of hospital stay. Following visceral surgery by laparotomy, SSI rates are especially high (14-25%). Therefore, measures to prevent SSI in this field are urgently needed. Prophylactic intraoperative wound irrigation (IOWI) of the subcutaneous soft tissue before skin closure hypothetically represents an easy and economical option to reduce SSI rates and is already frequently used in clinical practice. However, there are currently no definite recommendations on the use of IOWI since high-level evidence supporting its use is lacking. Consequently, clinical practice varies widely. Antiseptic polyhexanide (PHX)-based solutions are approved for soft-tissue wound irrigation in surgery but have not been specifically evaluated in randomized clinical trials for the prevention of SSI following laparotomy for visceral surgery. METHODS/DESIGN: The IOWISI trial is a multicentre, randomized, observer- and patient-blinded clinical trial with three parallel treatment groups, comparing IOWI with a 0.04% PHX solution to no irrigation (test 1) or saline (test 2) before skin closure after laparotomy for visceral surgery (contamination level II-IV). The primary endpoint of the trial is the SSI rate within 30 days postoperatively. Statistical analysis of the primary endpoint measure will be based on the intention-to-treat population. The global level of significance is set at 2.5% for test 1 and 5% for test 2 and the sample size (n = 540) is determined to assure a power of 94% (test 1) and 85% (test 2). DISCUSSION: The IOWISI trial will provide high-level evidence as a basis for clinical recommendations regarding the use of IOWI with PHX or saline and will potentially impact on future clinical guidelines and practice. The pragmatic trial design guarantees high external validity. TRIAL REGISTRATION: Registered at the German Clinical Trials Register, DRKS00012251 . Registered on 3 July 2017.

Parenteral nutrition during neoadjuvant chemotherapy for patients with non-metastatic gastric or esophago-gastric cancer to reduce postoperative morbidity (PERCOG): study protocol for a randomized controlled trial.

BACKGROUND: The majority of patients with gastric or esophago-gastric cancer are at risk for malnutrition. Preoperative malnutrition was shown to increase the incidence of postoperative complications following abdominal surgery. However, it remains unclear if preoperative parenteral nutritional support during neoadjuvant chemotherapy (NACT) may be effective to reduce the rate of postoperative complications in these patients. METHODS/DESIGN: The PERCOG trial is a randomized controlled multicenter observer-blinded trial, investigating if the improvement of the general condition of patients with non-metastasized gastric cancer or cancer of the esophago-gastric junction during NACT by supplemental parenteral nutrition can decrease the postoperative Comprehensive Complication Index (CCI). Statistical analysis of the primary endpoint measure (CCI on postoperative day 30) will be based on the intention-to-treat population. The global level of significance is set at 5% and the sample size (n = 150) is determined to assure a power of 80%. DISCUSSION: The results of the PERCOG trial will provide high-level evidence for clinical recommendations regarding the administration of preoperative supportive parenteral nutrition and provide all participating patients the opportunity of an improved treatment. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00009451 . Registered on 3 July 2017.

The impact of neoadjuvant therapy on the histopathological features of pancreatic ductal adenocarcinoma - A systematic review and meta-analysis.

BACKGROUND: Due to increased rates of curative tumor resections exceeding 60% after FOLFIRINOX-treatment, neoadjuvant therapy/NTx is increasingly recognized as an effective therapy option for downstaging borderline or locally advanced pancreatic ductal adenocarcinoma/PDAC. Yet, the effects of NTx on the common histopathological features of PDAC have not been systematically analysed. Therefore, the aim of the current study was to assess the impact of NTx on relevant histopathological features of PDAC. PATIENTS AND METHODS: Biomedical databases were systematically screened for predefined searching terms related to NTx and PDAC. The Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines were used to perform a systematic review and meta-analysis. Articles meeting the predefined criteria were analysed on relevance, and a meta-analysis was performed. RESULTS: A total of 9031 studies could be identified that analysed the effect of NTx on PDAC. Only 35 studies presented comparative data on the histological features of neoadjuvantly treated vs. upfront resected PDAC patients. In meta-analyses, the beneficial effect of NTx was reflected by reduced tumor size (T1/2: RR 2.87, 95%-CI: 1.52-5.42, P=0.001, T3/4: RR 0.78, 95%-CI: 0.69-0.89, P=0.0002), lower N-Stage (N0: RR 2.14, 95%-CI: 1.85-2.46, P<0.00001, N1: RR 0.59, 95%-CI: 0.53-0.65, P<0.00001), higher R0-rates (R0: RR 1.13, 95%-CI: 1.08-1.18, P<0.00001, R1: RR 0.66, 95%-CI: 0.58-0.76, P<0.00001), less perineural invasion (Pn1: RR 0.78, 95%-CI: 0.73-0.83, P<0.00001), less lymphatic vessel invasion (RR: 0.50, 95%-CI: 0.36-0.70, P<0.0001) and fewer G3-tumors (RR 0.82, 95%-CI: 0.71-0.94, P=0.005). CONCLUSIONS: NTx in PDAC seems to exert its beneficial effect in borderline or locally advanced PDAC over genuine tumor downstaging. Thus, although at least 40% of all NTx treated patients remain unresectable even with modern NTx regimes, neoadjuvantly treated PDAC showed not only increasing resectability rates especially after FOLFIRINOX, but even reach a lower tumor stage than primarily resected PDAC.

Perioperative transfusion of leukocyte depleted blood products in gastric cancer patients negatively influences oncologic outcome: A retrospective propensity score weighted analysis on 610 curatively resected gastric cancer patients.

The influence of perioperative transfusion (PT) on outcome following surgery for gastric cancer (GC) remains controversial, with randomized trials lacking and observational series confounded by patient risk factors. This analysis determines the association between reception of leukocyte-depleted blood products and post-operative survival for GC.Data from 610 patients who underwent curative surgery for GC in a German tertiary care clinic from 2001 to 2013 were included. Kaplan-Meier survival curves and Cox proportional hazards regression were applied to determine the association of PT and clinical and patient risk factors for overall and relapse-free survival. Propensity score analysis was performed to adjust for observational biases in reception of PT.Higher Union International Contre le Cancer/American Joint Committee on Cancer (UICC/AJCC)-stages (P <0.001), postoperative complications and severity according to the Clavien-Dindo (CD) classification (P <0.001), PT (P = 0.02), higher age (P <0.001), and neoadjuvant chemotherapy (P <0.001) were related to increased mortality rates. Higher UICC-stages (P <0.001), neoadjuvant chemotherapy (P <0.001), and type of surgery (P = 0.02) were independently associated with increased relapse rates. Patients were more likely to receive PT with higher age (P = 0.05), surgical extension to adjacent organs/structures (P = 0.002), tumor location (P = 0.003), and female gender (P = 0.03). In the adjusted propensity score weighted analysis, PT remained associated with an increased risk of death (hazard ratio (HR): 1.31, 95% CI: 1.01-1.69, P = 0.04).Because of the association of PT with negative influence on patient survival following resection for GC, risks from application of blood products should be weighed against the potential benefits.

Adjuvant and/or neoadjuvant therapy for gastric cancer? A perspective review.

Surgery is still the only curative therapy for locoregional gastric cancer. Hereby it is important to achieve negative margins (R0 resection) and to perform an adequate lymph-node dissection (D2 lymphadenectomy). Unfortunately most cases of gastric cancer are diagnosed in a locally advanced tumor stage. The poor prognosis of patients with these tumors is due to the frequent recurrences after primary resection in curative intent. This observation led to the development of (neo)adjuvant treatment concepts. Beginning with the end of the 1980s, more and more patients with locally advanced tumors were subjected to a preoperative, perioperative, or postoperative treatment in order to improve the prognosis after curative resection. However, in different regions of the world, different regiments are preferred. While adjuvant chemotherapy is the established treatment in Asia, adjuvant chemoradiotherapy is favored in the USA and perioperative chemotherapy is considered the treatment of choice in Europe. However, recently a certain convergence of the different philosophies is to be observed. This article covers the relevant studies dealing with neoadjuvant and adjuvant treatment concepts and gives an overview on the latest developments in this field.

Developments in flexible endoscopic surgery: a review.

Flexible endoscopy is increasingly developing into a therapeutic instead of a purely diagnostic discipline. Improved visualization makes early lesions easily detectable and allows us to decide ad hoc on the required treatment. Deep enteroscopy allows the exploration of even the small bowel - for long a "white spot" for gastrointestinal endoscopy - and to perform direct treatment. Endoscopic submucosal dissection is a considerable step forward in oncologically correct endoscopic treatment of (early) malignant lesions. Though still technically challenging, it is increasingly facilitated by new manipulation techniques and tools that are being steadily optimized. Closure of wall defects and hemostasis could be improved significantly. Even the anatomy beyond the gastrointestinal wall is being explored by the therapeutic use of endoluminal ultrasound. Endosonographic-guided surgery is not only a suitable fallback solution if conventional endoscopic retrograde cholangiopancreatography fails, but even makes necrosectomy procedures, abscess drainage, and neurolysis feasible for the endoscopist. Newly developed endoscopic approaches aim at formerly distinctive surgical domains like gastroesophageal reflux disease, appendicitis, and cholecystitis. Combined endoscopic/laparoscopic interventional techniques could become the harbingers of natural orifice transluminal endoscopic surgery, whereas pure natural orifice transluminal endoscopic surgery is currently still in its beginnings.