Prospective Validation of the Pancreatic Fistula Risk Classification by the International Study Group for Pancreatic Surgery (PARIS trial).

OBJECTIVE: The aim of this study was a prospective validation of the recently established ISGPS pancreas classification as a parenchymal risk classification system for pancreatic fistula after pancreatoduodenectomy. SUMMARY BACKGROUND DATA: Postoperative pancreatic fistula (POPF) is the major driver for complications after partial pancreatoduodenectomy (PD). Recently, the International Study Group for Pancreatic Surgery (ISGPS) published a pancreas classification containing the parameters main pancreatic duct diameter (MPD) and pancreatic texture to help assess the risk of POPF development following pancreatoduodenectomy. METHODS: From January 2020 to July 2021, 271 patients receiving elective PD were included after informed consent. The postoperative course was documented prospectively up to postoperative day 30. Among the pancreas characteristics, MPD and pancreatic texture were assessed intraoperatively at the pancreatic resection margin and the pancreatic glands were assigned to one of the four pancreas classes according to the ISGPS (A to D). The primary endpoint was POPF according to the updated ISGPS definition. Secondary endpoints comprised other post-PD morbidity and mortality. RESULTS: Of 271 patients, 264 had available data according to the ISGPS pancreas classification. Of those, 78 were assigned to class A (30%), 53 to class B (20%), 50 to class C (19%) and 83 to class D (31%). POPF occurred in 54 of 271 patients (19.9%). The 30-day mortality was 7/271 (2.6%), with 6/7 having developed POPF (86%). POPF rates within the classes A, B, C and D were 9.0%, 11.3%, 20.0% and 37.4%, respectively (P<0.001). In the univariable regression analysis, only patients in pancreas class D demonstrated a significantly higher risk for POPF when compared to class A (OR 6.05, 95%-CI: 2.6-15.9, P<0.001). In the multivariable regression model, patients in class D had a significantly higher risk for POPF compared to class A (OR 3.45, 95%-CI: 1.15-11.3, P=0.032). The model comprised Body Mass Index, surgery duration, microscopic fibrosis and the ISGPS pancreas classification, demonstrating an AUC-value of approximately 0.82 when tested on the PARIS dataset. CONCLUSION: This prospective trial shows that the ISGPS pancreas classification is valid. Patients in risk class D are prone to POPF independently of other factors. Therefore, all future publications on pancreatic surgery should report the risk class according to the ISGPS pancreas classification to allow for a better comparison of reported cohorts.

Postoperative Complications and Mobilization Following Major Abdominal Surgery With Versus Without Fitness Tracker-based Feedback (EXPELLIARMUS): A Student-led Multicenter Randomized Controlled Clinical Trial of the CHIR-Net SIGMA Study Group.

OBJECTIVE: To determine whether daily postoperative step goals and feedback through a fitness tracker (FT) reduce the rate of postoperative complications after surgery. BACKGROUND: Early and enhanced postoperative mobilization has been advocated to reduce postoperative complications, but it is unknown whether FT alone can reduce morbidity. METHODS: EXPELLIARMUS was performed at 11 University Hospitals across Germany by the student-led clinical trial network SIGMA. Patients undergoing major abdominal surgery were enrolled, equipped with an FT, and randomly assigned to the experimental (visible screen) or control intervention (blackened screen). The experimental group received daily step goals and feedback through the FT. The primary end point was postoperative morbidity within 30 days using the Comprehensive Complication Index (CCI). All trial visits were performed by medical students in the hospital with the opportunity to consult a surgeon-facilitator who also obtained informed consent. After discharge, medical students performed the 30-day postoperative visit through telephone and electronic questionnaires. RESULTS: A total of 347 patients were enrolled. Baseline characteristics were comparable between the 2 groups. The mean age of patients was 58 years, and 71% underwent surgery for malignant disease, with the most frequent indications being pancreatic, colorectal, and hepatobiliary malignancies. Roughly one-third of patients underwent laparoscopic surgery. No imputation for the primary end point was necessary as data completeness was 100%. There was no significant difference in the CCI between the 2 groups in the intention-to-treat analysis (mean±SD CCI experimental group: 23±24 vs. control: 22±22; 95% CI: -6.1, 3.7; P=0.628). All secondary outcomes, including quality of recovery, 6-minute walking test, length of hospital stay, and step count until postoperative day 7 were comparable between the 2 groups. CONCLUSIONS: Daily step goals combined with FT-based feedback had no effect on postoperative morbidity. The EXPELLIARMUS shows that medical students can successfully conduct randomized controlled trials in surgery.

[Cancer of the Esophagogastric Junction: Double Tract Reconstruction - Evidence and Technique]. / Adenokarzinome des ösophagogastralen Überganges: Double-Tract-Rekonstruktion ­ Evidenz und Technik.

Adenocarcinoma of the esophagogastric junction (AEG) still represent a certain surgical challenge. In contrary to the trend of thoracoabdominal surgery for AEG I and AEG II cancer, the proximal gastrectomy is regaining popularity through new reconstruction methods such as the double tract reconstruction. Proximal gastrectomy followed by double tract reconstruction represents an alternative for the thoracoabdominal approach for suitable AEG II cancer and an alternative to the total gastrectomy for AEG III cancers. Latest studies suggest a functional benefit of proximal gastrectomy and double tract reconstruction in comparison to total gastrectomy. The accurate indication for proximal gastrectomy for locally advanced cancers has to be established in the near future as well as the influence of the size of the remnant stomach on the outcome, as Asian techniques for early lesions sometimes significantly differ from European. The following article reflects the present evidence on proximal gastrectomy and double tract reconstruction as well as technical aspects in the context of cancer of the esophagogastric junction.

Long-term recurrence-free survival following pancreatic surgery with HIPEC treatment for locally advanced pancreatic adenocarcinoma.

More than 5 years previous to this report, a female patient in her 60s underwent oncological left-sided pancreatic resection and adrenalectomy including splenectomy for locally advanced pancreatic adenocarcinoma (PDAC), recommended by a multidisciplinary tumour board (MDT). Additionally, she was treated with gemcitabine-containing hyperthermic intraperitoneal chemotherapy (HIPEC) for 60 minutes in the framework of a clinical trial (PanHIPEC), aiming to determine the safety and feasibility (not efficacy) of this approach. Following the postoperative MDT recommendation, she subsequently received adjuvant chemotherapy consisting of six cycles of gemcitabine and cisplatin for a histopathologically confirmed PDAC of the pancreatic tail with infiltration of the left-sided adrenal gland (pT3, pN1 (3/16), cM0, L0, V0, Pn1, R0, G2). Five years and five months after pancreatic surgery and HIPEC, the patient has no signs of tumour recurrence as determined by follow-up examination including CT scan and CA19-9 tumour marker serology.

Intraoperative Wound Irrigation for the Prevention of Surgical Site Infection After Laparotomy: A Randomized Clinical Trial by CHIR-Net.

Importance: Surgical site infections frequently occur after open abdominal surgery. Intraoperative wound irrigation as a preventive measure is a common practice worldwide, although evidence supporting this practice is lacking. Objective: To evaluate the preventive effect of intraoperative wound irrigation with polyhexanide solution. Design, Setting, and Participants: The Intraoperative Wound Irrigation to Prevent Surgical Site Infection After Laparotomy (IOWISI) trial was a multicenter, 3-armed, randomized clinical trial. Patients and outcome assessors were blinded to the intervention. The clinical trial was conducted in 12 university and general hospitals in Germany from September 2017 to December 2021 with 30-day follow-up. Adult patients undergoing laparotomy were eligible for inclusion. The main exclusion criteria were clean laparoscopic procedures and the inability to provide consent. Of 11 700 screened, 689 were included and 557 completed the trial; 689 were included in the intention-to-treat and safety analysis. Interventions: Randomization was performed online (3:3:1 allocation) to polyhexanide 0.04%, saline, or no irrigation (control) of the operative wound before closure. Main Outcome and Measures: The primary end point was surgical site infection within 30 postoperative days according to the US Centers for Disease Control and Prevention definition. Results: Among the 689 patients included, 402 were male and 287 were female. The median (range) age was 65.9 (18.5-94.9) years. Participants were randomized to either wound irrigation with polyhexanide (n = 292), saline (n = 295), or no irrigation (n = 102). The procedures were classified as clean contaminated in 92 cases (8%). The surgical site infection incidence was 11.8% overall (81 of 689), 10.6% in the polyhexanide arm (31 of 292), 12.5% in the saline arm (37 of 295), and 12.8% in the no irrigation arm (13 of 102). Irrigation with polyhexanide was not statistically superior to no irrigation or saline irrigation (hazard ratio [HR], 1.23; 95% CI, 0.64-2.36 vs HR, 1.19; 95% CI, 0.74-1.94; P = .47). The incidence of serious adverse events did not differ among the 3 groups. Conclusions and Relevance: In this study, intraoperative wound irrigation with polyhexanide solution did not reduce surgical site infection incidence in clean-contaminated open abdominal surgical procedures compared to saline or no irrigation. More clinical trials are warranted to evaluate the potential benefit in contaminated and septic procedures, including the emergency setting. Trial Registration: drks.de Identifier: DRKS00012251.

Robotic versus open partial pancreatoduodenectomy (EUROPA): a randomised controlled stage 2b trial.

Background: Open partial pancreatoduodenectomy (OPD) represents the current gold standard of surgical treatment of a wide range of diseases of the pancreatic head but is associated with morbidity in around 40% of cases. Robotic partial pancreatoduodenectomy (RPD) is being used increasingly, yet, no randomised controlled trials (RCTs) of RPD versus OPD have been published, leaving a low level of evidence to support this practice. Methods: This investigator-initiated, exploratory RCT with two parallel study arms was conducted at a high-volume pancreatic centre in line with IDEAL recommendations (stage 2b). Patients scheduled for elective partial pancreatoduodenectomy (PD) for any indication were randomised (1:1) to RPD or OPD with a centralised web-based tool. The primary endpoint was postoperative cumulative morbidity within 90 days, assessed via the Comprehensive Complication Index (CCI). Biometricians were blinded to the intervention, but patients and surgeons were not. The trial was registered prospectively (DRKS00020407). Findings: Between June 3, 2020 and February 14, 2022, 81 patients were randomly assigned to RPD (n = 41) or OPD (n = 40), of whom 62 patients (RPD: n = 29, OPD: n = 33) were analysed in the modified intention to treat analysis. Four patients in the OPD group were randomised, but did not undergo surgery in our department and one patient was excluded in the RPD group due to other reason. Nine patients in the RPD group and 3 patients in the OPD were excluded from the primary analysis because they did not undergo PD, but rather underwent other types of surgery. The CCI after 90 days was comparable between groups (RPD: 34.02 ± 23.48 versus OPD: 36.45 ± 27.65, difference in means [95% CI]: -2.42 [-15.55; 10.71], p = 0.713). The RPD group had a higher incidence of grade B/C pancreas-specific complications compared to the OPD group (17 (58.6%) versus 11 (33.3%); difference in rates [95% CI]: 25.3% [1.2%; 49.4%], p = 0.046). The only complication that occurred significantly more often in the RPD than in the OPD group was clinically relevant delayed gastric emptying. Procedure-related and overall hospital costs were significantly higher and duration of surgery was longer in the RPD group. Blood loss did not differ significantly between groups. The intraoperative conversion rate of RPD was 23%. Overall 90-day mortality was 4.8% without significant differences between RPD and OPD. Interpretation: In the setting of a very high-volume centre, both RPD and OPD can be considered safe techniques. Further confirmatory multicentre RCTs are warranted to uncover potential advantages of RPD in terms of perioperative and long-term outcomes. Funding: Federal Ministry of Education and Research (BMBF: 01KG2010).

Results of robotic liver surgery in association with IWATE criteria - the first 100 cases.

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.

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement vs. primary suture only in midline laparotomies (PRIMA): long-term outcomes of a multicentre, double-blind, randomised controlled trial.

Background: Incisional hernia occurs approximately in 40% of high-risk patients after midline laparotomy. Prophylactic mesh placement has shown promising results, but long-term outcomes are needed. The present study aimed to assess the long-term incisional hernia rates of the previously conducted PRIMA trial with radiological follow-up. Methods: In the PRIMA trial, patients with increased risk of incisional hernia formation (AAA or BMI ≥27 kg/m2) were randomised in a 1:2:2 ratio to primary suture, onlay mesh or sublay mesh closure in three different countries in eleven institutions. Incisional hernia during follow-up was diagnosed by any of: CT, ultrasound and physical examination, or during surgery. Assessors and patients were blinded until 2-year follow-up. Time-to-event analysis according to intention-to-treat principle was performed with the Kaplan-Meier method and Cox proportional hazard models. Trial registration: NCT00761475 (ClinicalTrials.gov). Findings: Between 2009 and 2012, 480 patients were randomized: 107 primary suture, 188 onlay mesh and 185 sublay mesh. Five-year incisional hernia rates were 53.4% (95% CI: 40.4-64.8), 24.7% (95% CI: 12.7-38.8), 29.8% (95% CI: 17.9-42.6), respectively. Compared to primary suture, onlay mesh (HR: 0.390, 95% CI: 0.248-0.614, p < 0.001) and sublay mesh (HR: 0.485, 95% CI: 0.309-0.761, p = 0.002) were associated with a significantly lower risk of incisional hernia development. Interpretation: Prophylactic mesh placement remained effective in reducing incisional hernia occurrence after midline laparotomy in high-risk patients during long-term follow-up. Hernia rates in the primary suture group were higher than previously anticipated. Funding: B. Braun.

Efficacy of Different Oncolytic Vaccinia Virus Strains for the Treatment of Murine Peritoneal Mesothelioma.

Effective treatment options for peritoneal surface malignancies (PSMs) are scarce. Oncolytic virotherapy with recombinant vaccinia viruses might constitute a novel treatment option for PSM. We aimed to identify the most effective oncolytic vaccinia virus strain in two murine mesothelioma cell lines and the oncolytic potential in a murine model of peritoneal mesothelioma. Cell lines AB12 and AC29 were infected in vitro with vaccinia virus strains Lister (GLV-1h254), Western Reserve (GLV-0b347), and Copenhagen (GLV-4h463). The virus strain GLV-0b347 was shown most effective in vitro and was further investigated by intraperitoneal (i.p.) application to AB12 and AC29 mesothelioma-bearing mice. Feasibility, safety, and effectiveness of virotherapy were assessed by evaluating the peritoneal cancer index (PCI), virus detection in tumor tissues and ascites, virus growth curves, and comparison of overall survival. After i.p. injection of GLV-0b347, virus was detected in both tumor cells and ascites. In comparison to mock-treated mice, overall survival was significantly prolonged, ascites was less frequent and PCI values declined. However, effective treatment was only observed in animals with limited tumor burden at the time point of virus application. Nonetheless, intraperitoneal virotherapy with GLV-0b347 might constitute a novel therapeutic option for the treatment of peritoneal mesothelioma. Additional treatment modifications and combinational regimes will be investigated to further enhance treatment efficacy.