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Septic complications after pancreatic surgery are common. However, it remains unclear if and how a shift of the microbiological spectrum affects morbidity. The aim of the present study was to assess the microbiological spectrum and antibiotic resistance patterns and their impact on outcome.We conducted a retrospective study including patients undergoing pancreatic surgery at our center between 2005 and 2018. A systematic literature review and descriptive meta-analysis of the published and original data was performed according to the PRISMA guidelines.A total of 318 patients were included in the analysis. Patients with biliary drainage had a significantly higher incidence of bacterobilia (93% vs. 25%) and received preoperative antibiotics (46% vs. 12%). The analyzed bile cultures showed no resistance to piperacillin/tazobactam, fluoroquinolones, or carbapenems. Resistance to cefuroxime was seen in 58% of the samples of patients without biliary drainage (NBD) and 93% of the samples of those with drainage (BD). In general, there was no significant difference in overall postoperative morbidity. However, superficial surgical site infections (SSIs) were significantly more common in the BD group. We included a total of six studies and our own data (1627 patients) in the descriptive meta-analysis. The percentage of positive bile cultures ranged from 53 to 81%. In patients with BD, the most frequent microorganisms were Enterococcus spp. (58%), Klebsiella spp. (29%), and E. coli (27%). Almost all studies demonstrated resistance to first- and second-generation cephalosporins and to third- and fourth-generation cephalosporins for patients with BD.A change in perioperative antibiotic strategy according to local resistance patterns, especially after BD, might be useful for patients undergoing pancreatic surgery. Appropriate perioperative antibiotic coverage may help to prevent abdominal infectious complications and especially superficial SSIs.

Purpose Anastomotic leakage (AL) and surgical site infection (SSI) account for most postoperative complications in colorectal surgery. The aim of this retrospective trial was to investigate whether perioperative selective decontamination of the digestive tract (SDD) reduces these complications and to provide a cost-effectiveness model for elective colorectal surgery. Methods All patients operated between November 2016 and March 2020 were included in our analysis. Patients in the primary cohort (PC) received SDD and those in the historical control cohort (CC) did not receive SDD. In the case of rectal/sigmoid resection, SDD was also applied via a transanally placed Foley catheter (TAFC) for 48 h postoperatively. A propensity score-matched analysis was performed to identify risk factors for AL and SSI. Costs were calculated based on German diagnosis-related group (DRG) fees per case. Results A total of 308 patients (154 per cohort) with a median age of 62.6 years (IQR 52.5–70.8) were analyzed. AL was observed in ten patients (6.5%) in the PC and 23 patients (14.9%) in the CC (OR 0.380, 95% CI 0.174–0.833; P = 0.016). SSI occurred in 14 patients (9.1%) in the PC and 30 patients in the CC (19.5%), representing a significant reduction in our SSI rate (P = 0.009). The cost-effectiveness analysis showed that SDD is highly effective in saving costs with a number needed to treat of 12 for AL and 10 for SSI. Conclusion SDD significantly reduces the incidence of AL and SSI and saves costs for the general healthcare system.

Abstract Purpose Robotic-assisted minimally invasive esophagectomy (RAMIE) has become one standard approach for the operative treatment of esophageal tumors at specialized centers. Here, we report the results of a prospective multicenter registry for standardized RAMIE. Methods The German da Vinci Xi registry trial included all consecutive patients who underwent RAMIE at five tertiary university centers between Oct 17, 2017, and Jun 5, 2020. RAMIE was performed according to a standard technique using an intrathoracic circular stapled esophagogastrostomy. Results A total of 220 patients were included. The median age was 64 years. Total minimally invasive RAMIE was accomplished in 85.9%; hybrid resection with robotic-assisted thoracic approach was accomplished in an additional 11.4%. A circular stapler size of ≥28 mm was used in 84%, and the median blood loss and operative time were 200 (IQR: 80–400) ml and 425 (IQR: 335–527) min, respectively. The rate of anastomotic leakage was 13.2% (n=29), whereas the two centers with >70 cases each had rates of 7.0% and 12.0%. Pneumonia occurred in 19.5% of patients, and the 90-day mortality was 3.6%. Cumulative sum analysis of the operative time indicated the end of the learning curve after 22 cases. Conclusions High-quality multicenter registry data confirm that RAMIE is a safe procedure and can be reproduced with acceptable leak rates in a multicenter setting. The learning curve is comparably low for experienced robotic surgeons.

Zusammenfassung Hintergrund Es gibt Hinweise, dass die roboterassistierte minimal-invasive Ösophagektomie (RAMIE) die Morbidität im Vergleich zur konventionellen Operationstechnik verringern kann. Ziel der Arbeit Es erfolgte eine Vergleichsanalyse eines Single-Center-Strategiewechsels des Standards von offener Ösophagektomie zu RAMIE mit perioperativer, enteraler, selektiver Darmdekontamination (SDD). Material und Methoden Patienten- und Morbiditätsdaten nach elektiver RAMIE entsprechend dem neuen Standardmanagement zwischen Juli 2018 und September 2020 wurden retrospektiv mit einer historischen Kontrollkohorte nach offener Ösophagektomie zwischen Januar 2014 und Juni 2018 verglichen. Es erfolgte eine 1:1-Propensity-Score-Matching(PSM)-Analyse. Ergebnisse Insgesamt 75 Patienten konnten nach PSM in beiden Gruppen analysiert werden. Etwa zwei Drittel der Operationen erfolgte aufgrund eines Adenokarzinoms und ein Drittel bei Plattenepithelkarzinom. Im Median wurden 22 bzw. 21 Lymphknoten reseziert. Die intrathorakale Ösophagogastrostomie erfolgte in der RAMIE-Gruppe in 97 % mit einem Zirkularstapler mit ≥28 mm Durchmesser (offen: 25 mm in 90 % der Fälle). Die Operationszeit war länger (Median 490 vs. 339 min, p p p = 0,004), Wundinfektions- (4,0 % vs. 17,3 %, p = 0,008) und pulmonale Komplikationsrate (29,3 % vs. 44,0 %, p = 0,045) sowie die mediane Krankenhausverweildauer (14 vs. 20 Tage, p p = 0,039). Diskussion Ein konsequenter Wechsel des perioperativen Managements u. a. mit RAMIE und SDD kann zu einer stabilen Reduktion der Morbidität ohne Einschränkungen der onkologischen Radikalität führen.

Introduction: Patients with advanced gastric cancer (AGC) frequently show peritoneal carcinomatosis (PC). PC reduces life expectancy and quality of life. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve overall survival. Nevertheless, it has been reported that CRS and HIPEC are accompanied by an increase in postoperative complications. The purpose of this study was to investigate the complications associated with CRS and HIPEC and overall and disease-free survival. Methods: Patients with AGC and PC, who received complete CRS and HIPEC, were included in the HIPEC group (n = 15). Patients with AGC but without PC, who received resection of the primary tumor alone, constituted the control group (n = 43). Results: Patients enrolled in the HIPEC group presented with a median PCI of 7. In comparison with the control group, no differences were found in patient characteristics, risk factors, pathological findings, and operative procedures. Twenty-five percentage of the patients in both groups suffered from serious postoperative complications (CDC ≥3a). Surgical and medical complications, rate of reoperation, and mortality did not differ. Also, the recurrence pattern, median survival, and 1- and 2-year survival rates showed no differences. Conclusion: CRS and HIPEC do not lead to an increased postoperative morbidity and mortality in AGC with PC. Albeit the poorer prognosis of patients with PC, survival of both groups was comparable.

Introduction The aim of this study was to develop a reliable objective structured assessment of technical skills (OSATS) score for linear-stapled, hand-sewn closure of enterotomy intestinal anastomoses (A-OSATS). Materials and methods The Delphi methodology was used to create a traditional and weighted A-OSATS score highlighting the more important steps for patient outcomes according to an international expert consensus. Minimally invasive novices, intermediates, and experts were asked to perform a minimally invasive linear-stapled intestinal anastomosis with hand-sewn closure of the enterotomy in a live animal model either laparoscopically or robot-assisted. Video recordings were scored by two blinded raters assessing intrarater and interrater reliability and discriminative abilities between novices (n = 8), intermediates (n = 24), and experts (n = 8). Results The Delphi process included 18 international experts and was successfully completed after 4 rounds. A total of 4 relevant main steps as well as 15 substeps were identified and a definition of each substep was provided. A maximum of 75 points could be reached in the unweighted A-OSATS score and 170 points in the weighted A-OSATS score respectively. A total of 41 anastomoses were evaluated. Excellent intrarater (r = 0.807–0.988, p p Conclusion With the weighted and unweighted A-OSATS score, we propose a new reliable standard to assess the creation of minimally invasive linear-stapled, hand-sewn anastomoses based on an international expert consensus. Validity evidence in live animal models is provided in this study. Future research should focus on assessing whether the weighted A-OSATS exceeds the predictive capabilities of patient outcomes of the unweighted A-OSATS and provide further validity evidence on using the score on different anastomotic techniques in humans.

Purpose Postoperative pancreatic fistula (POPF) is a major complication of pancreatic surgery and can be fatal. Better stratification of patients into risk groups may help to select those who might benefit from strategies to prevent complications. The aim of this study was to validate ten prognostic scores in patients who underwent pancreatic head surgery. Methods A total of 364 patients were included in this study between September 2012 and August 2017. Ten risk scores were applied to this cohort. Univariate and multivariate analyses were performed considering all risk factors in the scores. Furthermore, the stratification of patients into risk categories was statistically tested. Results Nine of the scores (Ansorge et al., Braga et al., Callery et al., Graham et al., Kantor et al., Mungroop et al., Roberts et al., Yamamoto et al. and Wellner et al.) showed strong prognostic stratification for developing POPF (p Conclusion Most risk scores tend to stratify patients correctly according to risk for POPF. Nevertheless, except for the fistula risk score (Callery et al.) and its alternative version (Mungroop et al.), many of the published risk scores are obscure even for the dedicated pancreatic surgeon in terms of their clinical practicability. There is a need for future studies to provide strategies for preventing POPF and managing patients with high-risk stigmata.

Background Postpancreatectomy morbidity remains significant even in high-volume centers and frequently results in delay or suspension of indicated adjuvant oncological treatment. This study investigated the short-term and long-term outcome after primary total pancreatectomy (PTP) and pylorus-preserving pancreaticoduodenectomy (PPPD) or Whipple procedure, with a special focus on administration of adjuvant therapy and oncological survival. Methods Patients who underwent PTP or PPPD/Whipple for periampullary cancer between January 2008 and December 2017 were retrospectively analyzed. Propensity score-matched analysis was performed to compare perioperative and oncological outcomes. Correspondingly, cases of rescue completion pancreatectomy (RCP) were analyzed. Results In total, 41 PTP and 343 PPPD/Whipple procedures were performed for periampullary cancer. After propensity score matching, morbidity (Clavien-Dindo classification (CDC) ≥ IIIa, 31.7% vs. 24.4%; p = 0.62) and mortality rates (7.3% vs. 2.4%, p = 0.36) were similar in PTP and PPPD/Whipple. Frequency of adjuvant treatment administration (76.5% vs. 78.4%; p = 0.87), overall survival (513 vs. 652 days; p = 0.47), and progression-free survival (456 vs. 454 days; p = 0.95) did not significantly differ. In turn, after RCP, morbidity (CDC ≥ IIIa, 85%) and mortality (40%) were high, and overall survival was poor (median 104 days). Indicated adjuvant therapy was not administered in 77%. Conclusions In periampullary cancers, PTP may provide surgical and oncological treatment outcomes comparable with pancreatic head resections and might save patients from RCP. Especially in selected cases with high-risk pancreatic anastomosis or preoperatively impaired glucose tolerance, PTP may provide a safe treatment alternative to pancreatic head resection.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer deaths with a best median survival of only 40 to 50 months for localized disease despite multimodal treatment. The standard tissue differentiation method continues to be pathology with histological staining analysis. Microscopic discrimination between inflammatory pancreatitis and malignancies is demanding.We aim to accurately distinguish native pancreatic tissue using infrared (IR) spectroscopy in a fast and label-free manner.Twenty cryopreserved human pancreatic tissue samples were collected from surgical resections. In total, more than 980,000 IR spectra were collected and analyzed using aMATLAB package. For differentiation of PDAC, pancreatitis, and normal tissue, a three-class training set for supervised classification was created with 25,000 spectra and the principal component analysis (PCA) score values for each cohort. Cross-validation was performed using the leaveone- out method. Validation of the algorithm was accomplished with 13 independent test samples.Reclassification of the training set and the independent test samples revealed an overall accuracy of more than 90% using a discrimination algorithm.IR spectroscopy in combination with PCA and supervised classification is an efficient analytical method to reliably distinguish between benign and malignant pancreatic tissues. It opens up a wide research field for oncological and surgical applications.

Sarcopenia is a known risk factor for adverse outcomes after esophageal cancer (EC) surgery. Robot-assisted minimally invasive esophagectomy (RAMIE) offers numerous advantages, including reduced morbidity and mortality. However, no evidence exists to date comparing the development of sarcopenia after RAMIE and open esophagectomy (OE). The objective was to evaluate whether the development of sarcopenia within the first postoperative year after esophagectomy is associated with the surgical approach: RAMIE versus OE.A total of 168 patients with EC were analyzed who either underwent total robotic or fully open Ivor Lewis esophagectomy in a propensity score-matched analysis. Sarcopenia was assessed using the skeletal muscle index (cmAfter 1-to-1 propensity score matching for confounders, 67 patients were allocated to RAMIE and OE groups, respectively. Skeletal muscle index in the OE group was significantly lower compared with the RAMIE group at the third (43.2 ± 7.6 cmTo our knowledge, this study is the first to suggest a substantial benefit of RAMIE compared with open esophagectomy in terms of postoperative sarcopenia. These results add further evidence to support the implementation of the robotic approach in multimodal therapy of EC.

Postoperative pulmonary embolism (PE) after pancreatic surgery is a potentially life-threatening complication. However, the magnitude of morbidity and mortality of PE is still uncertain. The present study aims to assess the incidence of PE after pancreatic surgery and analyze its impact on the outcome. We conducted a retrospective study including all patients who underwent pancreatic resections between 2005 and 2017. The development of PE was analyzed for a 90-day period following surgery. Risk factors were evaluated using regression models. The study investigated 947 patients undergoing pancreatic surgery. Overall, 26 (2.7%) patients developed PE. The median body mass index (BMI) of patients with PE was significantly higher (28.1 kg/m2 [24.7–31.8] vs. 24.8 kg/m2 [22.4–27.8], p

Purpose Postpancreatectomy hemorrhage (PPH) is one of the leading causes of mortality after pancreatic resection. Late onset PPH is most often treated using a transarterial approach. The aim of this study was to analyze risk factors for in-hospital mortality after endovascular treatment. Methods Between 2012 and 2017, patients who were treated endovascular due to PPH were identified from a retrospective analysis of a database. Risk factors for mortality were identified by univariate analysis. Results In total, 52 of the 622 patients (8.4%) underwent endovascular treatment due to PPH. The primary technical success achieved was 90.4%. In 59.6% of patients, bleeding control was achieved by placing a stent graft and in 40.4% by coil embolization. The primary 30-day and 1-year patency of the placed covered stents was 89.3% and 71.4%, respectively. The 60-day mortality was 34.6%. The reintervention rate was higher after stent graft placement compared to coiling (39.3% vs. 21.1%, P = 0.012). In the univariate analysis the need for reintervention was associated with a higher in-hospital mortality (21.2% vs. 7.7%, P = 0.049). The use of an antiplatelet agent was associated with a decreased in-hospital mortality in the univariate (11.5% vs. 25%, P = 0.024) and multivariate analysis (HR 3.1, 95% CI 1.1-9, P = 0.034), but did not increase the risk of rebleeding. Conclusion Endovascular management of delayed PPH has a high technical success rate. Stent graft placement showed a higher reintervention rate. The need for reintervention was associated with a higher in-hospital mortality but did not differ between coiling and stent graft placement.

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to checkpoint blockade, such as anti-CTLA-4 and anti-PD-1. Galectin-9, a β-galactoside-binding lectin, promotes immune suppression through T-cell inhibition, and programming of tolerogenic macrophages. Of all cancers tested, PDAC showed the highest expression of LGALS9 (galectin-9) mRNA. We analyzed formalin-fixed and paraffin-embedded specimens from 83 patients with PDAC stained for galectin-9. Using flow cytometry, we determined galectin-9 expression on immune cells from tumor and matched blood samples from 12 patients with resectable PDAC. Furthermore, we analyzed galectin-9 serum levels by enzyme-linked immunosorbent assay using serum samples from 70 patients with PDAC, from 36 individuals with benign pancreatic disease, and from 28 healthy controls. Galectin-9 was highly expressed in human PDAC compared with normal pancreas and present on both tumor and immune cells. Tumor-infiltrating immune cells, especially CD3+ T cells, showed upregulation of galectin-9 compared with immune cells from matched blood. Blood γδ T cells from PDAC patients had higher galectin-9 expression than γδ T cells from healthy individuals. Galectin-9 polarized macrophages toward a protumoral M2 phenotype leading to suppressed T-cell cytokine secretion. Furthermore, serum concentration of galectin-9 was able to discriminate PDAC from benign pancreatic disease and healthy individuals, and was prognostic for stage IV patients. Galectin-9 is a new biomarker for the detection of PDAC.

Drug combination therapies for cancer treatment show high efficacy but often induce severe side effects, resulting in dose or cycle number reduction. We investigated the impact of neoadjuvant chemotherapy (neoCTx) adaptions on treatment outcome in 59 patients with pancreatic ductal adenocarcinoma (PDAC). Resections with tumor-free margins were significantly more frequent when full-dose neoCTx was applied. We determined if patient-derived organoids (PDOs) can be used to personalize poly-chemotherapy regimens by pharmacotyping of treatment-naïve and post-neoCTx PDAC PDOs. Five out of ten CTx-naïve PDO lines exhibited a differential response to either the FOLFIRINOX or the Gem/Pac regimen. NeoCTx PDOs showed a poor response to the neoadjuvant regimen that had been administered to the respective patient in 30% of cases. No significant difference in PDO response was noted when comparing modified treatments in which the least effective single drug was removed from the complete regimen. Drug testing of CTx-naïve PDAC PDOs and neoCTx PDOs may be useful to guide neoadjuvant and adjuvant regimen selection, respectively. Personalizing poly-chemotherapy regimens by omitting substances with low efficacy could potentially result in less severe side effects, thereby increasing the fraction of patients receiving a full course of neoadjuvant treatment. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Background: Chronic pancreatitis (CP) often leads to recurrent pain as well as exocrine and/or endocrine pancreatic insufficiency. This study aimed to investigate the effect of pancreatic head resections on glucose metabolism in patients with CP. Methods: Patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD), Whipple procedure (cPD), or duodenum-preserving pancreatic head resection (DPPHR) for CP between January 2011 and December 2020 were retrospectively analyzed with regard to markers of pancreatic endocrine function including steady-state beta cell function (%B), insulin resistance (IR), and insulin sensitivity (%S) according to the updated Homeostasis Model Assessment (HOMA2). Results: Out of 141 pancreatic resections for CP, 43 cases including 31 PPPD, 2 cPD and 10 DPPHR, met the inclusion criteria. Preoperatively, six patients (14%) were normoglycemic (NG), 10 patients (23.2%) had impaired glucose tolerance (IGT) and 27 patients (62.8%) had diabetes mellitus (DM). In each subgroup, no significant changes were observed for HOMA2-%B (NG: p = 0.57; IGT: p = 0.38; DM: p = 0.1), HOMA2-IR (NG: p = 0.41; IGT: p = 0.61; DM: p = 0.18) or HOMA2-%S (NG: p = 0.44; IGT: p = 0.52; DM: p = 0.51) 3 and 12 months after surgery, respectively. Conclusion: Pancreatic head resections for CP, including DPPHR and pancreatoduodenectomies, do not significantly affect glucose metabolism within a follow-up period of 12 months.

There are indications that robot-assisted minimally invasive esophagectomy (RAMIE) can reduce the morbidity compared with the conventional operative technique.A comparative analysis of a single-center change in strategy of the standard from open esophagectomy to RAMIE with perioperative, enteral, selective bowel decontamination (SBD) was carried out.Patient and morbidity data after elective RAMIE treated according to the novel standard management between July 2018 and September 2020 were compared retrospectively with an historical control cohort after open esophagectomy between January 2014 and June 2018. A 1:1 propensity score matching (PSM) analysis was performed.A total of 75 patients could be analyzed in both groups after PSM. Approximately two thirds of the operations were carried out due to an adenocarcinoma and one third due to a squamous cell carcinoma. The median number of resected lymph nodes was 22 and 21, respectively. In the RAMIE group the intrathoracic esophagogastrostomy was performed using a circular stapler with a diameter of ≥28 mm in 97%, whereas a 25 mm stapler was used in 90% in the control group. The operative time was longer (median 490min vs. 339 min, p 0.001) but in contrast blood loss (median 300ml vs. 500 ml, p 0.001), anastomotic leaks (8.0% vs. 25.3%, p = 0.004), surgical site infections (4.0% vs. 17.3%, p = 0.008) and pulmonary complication rates (29.3% vs. 44.0%, p = 0.045) as well as the median hospital stay (14 days vs. 20 days, p 0.001) and 90-day mortality were significantly reduced compared with the open control group (4.0% vs. 13.3%, p = 0.039).A consistent change of the perioperative management including RAMIE and SBD can lead to a stable reduction of morbidity without compromising oncological radicalness.HINTERGRUND: Es gibt Hinweise, dass die roboterassistierte minimal-invasive Ösophagektomie (RAMIE) die Morbidität im Vergleich zur konventionellen Operationstechnik verringern kann.Es erfolgte eine Vergleichsanalyse eines Single-Center-Strategiewechsels des Standards von offener Ösophagektomie zu RAMIE mit perioperativer, enteraler, selektiver Darmdekontamination (SDD).Patienten- und Morbiditätsdaten nach elektiver RAMIE entsprechend dem neuen Standardmanagement zwischen Juli 2018 und September 2020 wurden retrospektiv mit einer historischen Kontrollkohorte nach offener Ösophagektomie zwischen Januar 2014 und Juni 2018 verglichen. Es erfolgte eine 1:1-Propensity-Score-Matching(PSM)-Analyse.Insgesamt 75 Patienten konnten nach PSM in beiden Gruppen analysiert werden. Etwa zwei Drittel der Operationen erfolgte aufgrund eines Adenokarzinoms und ein Drittel bei Plattenepithelkarzinom. Im Median wurden 22 bzw. 21 Lymphknoten reseziert. Die intrathorakale Ösophagogastrostomie erfolgte in der RAMIE-Gruppe in 97 % mit einem Zirkularstapler mit ≥28 mm Durchmesser (offen: 25 mm in 90 % der Fälle). Die Operationszeit war länger (Median 490 vs. 339 min, p 0,001), hingegen waren der Blutverlust (Median 300 vs. 500 ml, p 0,001), die Anastomoseninsuffizienz- (8,0 % vs. 25,3 %, p = 0,004), Wundinfektions- (4,0 % vs. 17,3 %, p = 0,008) und pulmonale Komplikationsrate (29,3 % vs. 44,0 %, p = 0,045) sowie die mediane Krankenhausverweildauer (14 vs. 20 Tage, p 0,001) und die 90-Tage-Mortalität signifikant geringer verglichen mit der offenen Kontrollkohorte (4,0 % vs. 13,3 %, p = 0,039).Ein konsequenter Wechsel des perioperativen Managements u. a. mit RAMIE und SDD kann zu einer stabilen Reduktion der Morbidität ohne Einschränkungen der onkologischen Radikalität führen.

(1) Background: The postoperative morbidity rate after pancreatic head resection remains high, partly due to infectious complications. The primary aim of this study was to analyze the influence of selective decontamination of the digestive tract (SDD) on the postoperative infection rate after pancreatic surgery. (2) Methods: From January 2019, the standard of care for patients undergoing pancreatic head resections at the Department for Visceral, Thoracic, and Vascular Surgery, University Hospital Dresden was the preoperative oral administration of SDD. The influence of SDD was evaluated for patients operated on between January 2019 and June 2020 in comparison to a propensity score-matched cohort, extracted from an existing database including all pancreatic resections from 2012 to 2018. The primary endpoint of the study was the shift of the bacterial load on the intraoperative bile swab test. The secondary endpoint was the association of SDD with postoperative complications. (3) Results: In total, 200 patients either with SDD (n = 100; 50%) or without SDD (non-SDD, n = 100; 50%) were analyzed. In the patient group without a preoperative biliary stent, 44% (n = 11) of the non-SDD group displayed positive bacterial results, whereas that was the case for only 21.7% (n = 10) in the SDD group (p = 0.05). Particularly, Enterobacter species (spp.) were reduced from 41.2% (n = 14) (non-SDD group) to 23.5% (n = 12) (SDD group) (p = 0.08), and Citrobacter spp. were reduced by 13.7% (p = 0.09) from the non-SDD to the SDD cohort. In patients with a preoperative biliary stent, the Gram-negative Enterobacter spp. were significantly reduced from 52.2% (n = 12) in the non-SDD group to 26.8% (n = 11) in the SDD group (p = 0.04). Similarly, Citrobacter spp. decreased by 20.6% from 30.4% (n = 7) to 9.8% (n = 4) in the non-SDD compared to the SDD group (p = 0.04). In general, deep fluid collection and abscesses occurred more frequently in the non-SDD group (36%; n = 36 vs. 27%; n = 27; p = 0.17). (4) Conclusions: Adoption of SDD before pancreatic head surgery may reduce the bacterial load in bile fluid. SDD administration does not significantly affect the postoperative infectious complication rate after pancreatic head resections.

Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels.In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH.Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively).A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy.NCT02588066 (http://www.clinicaltrials.gov).

Background Resection of the para-aortic lymph node (PALN) group Ln16b1 during pancreatoduodenectomy remains controversial because PALN metastases are associated with a worse prognosis in pancreatic cancer patients. The present study aimed to analyze the impact of PALN metastases on outcome after non-pancreatic periampullary cancer resection. Methods One hundred sixty-four patients with non-pancreatic periampullary cancer who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005 and 2016 were retrospectively investigated. The data were supplemented with a systematic literature review on this topic. Results In 67 cases, the PALNs were clearly assigned and could be histopathologically analyzed. In 10.4% of cases (7/67), tumor-infiltrated PALNs (PALN+) were found. Metastatic PALN+ stage was associated with increased tumor size (P = 0.03) and a positive nodal stage (P < 0.001). The median overall survival (OS) of patients with metastatic PALN and non-metastatic PALN (PALN–) was 24.8 and 29.5 months, respectively. There was no significant difference in the OS of PALN+ and pN1 PALN patients (P = 0.834). Patients who underwent palliative surgical treatment (n = 20) had a lower median OS of 13.6 (95% confidence interval 2.7–24.5) months. Including the systematic literature review, only 23 cases with PALN+ status and associated OS could be identified; the average survival was 19.8 months. Conclusion PALN metastasis reflects advanced tumor growth and lymph node spread; however, it did not limit overall survival in single-center series. The available evidence of the prognostic impact of PALN metastasis is scarce and a recommendation against resection in these cases cannot be given.

Summary Background & aims Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can rapidly progress into acute respiratory distress syndrome accompanied by multi-organ failure requiring invasive mechanical ventilation and critical care treatment. Nutritional therapy is a fundamental pillar in the management of hospitalized patients. It is broadly acknowledged that overfeeding and underfeeding of intensive care unit (ICU) patients are associated with increased morbidity and mortality. This study aimed to assess the energy demands of long-term ventilated COVID-19 patients using indirect calorimetry and to evaluate the applicability of established predictive equations to estimate their energy expenditure. Methods We performed a retrospective, single-center study in 26 mechanically ventilated COVID-19 patients with resolved SARS-CoV-2 infection in three independent intensive care units. Resting energy expenditure (REE) was evaluated by repetitive indirect calorimetry (IC) measurements. Simultaneously the performance of 12 predictive equations was examined. Patient's clinical data were retrieved from electronic medical charts. Bland-Altman plots were used to assess agreement between measured and calculated REE. Results Mean mREE was 1687 kcal/day and 20.0 kcal relative to actual body weight (ABW) per day (kcal/kg/day). Longitudinal mean mREE did not change significantly over time, although mREE values had a high dispersion (SD of mREE ±487). Obese individuals were found to have significantly increased mREE, but lower energy expenditure relative to their body mass. Calculated REE showed poor agreement with mREE ranging from 33 to 54%. Conclusion Resolution of SARS-CoV-2 infection confirmed by negative PCR leads to stabilization of energy demands at an average 20 kcal/kg in ventilated critically ill patients. Due to high variations in mREE and low agreement with calculated energy expenditure IC remains the gold standard for the guidance of nutritional therapy.

Physiological liver cell replacement is central to maintaining the organ's high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon (C-14) birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age

Weltweit erkranken jahrlich 572.000 Menschen an einem Osophaguskarzinom, 509.000 Patienten sterben daran. Die Osophagektomie ist der entscheidende Faktor in der kurativen multimodalen Therapie des lokal fortgeschrittenen Osophaguskarzinoms. Die roboterassisistierte minimal-invasive Osophagektomie (RAMIE) ist als Weiterentwicklung der minimal-invasiven Osophagektomie (MIE) anzusehen, reduziert wie diese im Vergleich zum offenen Vorgehen das operative Trauma sowie die postoperative Morbiditat. Sie verringert die Limitationen der MIE durch eine 3-dimensionale Sicht, eine wiederhergestellte Auge-Hand-Achse, die Filterung des naturlichen Tremors und eine hervorragende Bewegungsfreiheit der Instrumente, deren Gelenke dem menschlichen Handgelenk nachempfunden sind. In diesem Kapitel beschreiben wir unsere Technik der roboterassistierten minimal-invasiven Osophagektomie im Detail und benennen notwendige Voraussetzungen zur erfolgreichen Implementierung.

Background Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. Methods In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. Results Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). Conclusion A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. Registration number: NCT02588066 (http://www.clinicaltrials.gov).

Die Osophagusperforation ist eine lebensgefahrliche Erkrankung mit einer Mortalitat von 10–15 %. Der Allgemeinzustand des Patienten, das Zeitfenster bis zur Diagnosestellung, die Ursache, das Ausmas und die Lokalisation der Osophagusperforation sind entscheidend fur Prognose und Wahl des therapeutischen Verfahrens. Eine fruhe Diagnose – innerhalb von 24 h – ist fur ein optimales Therapieergebnis entscheidend. Die chirurgische Therapie einer Osophagusperforation umfasst die Versorgung des Defektes sowie die Drainage des Mediastinums und der Pleurahohlen. Die Primarnaht ist das klassische nichtresezierende Verfahren, wahrend die Osophagektomie als das wichtigste resezierende Verfahren gilt. Aufgrund des komplexen Krankheitsbildes, einer hohen Mortalitat und der Moglichkeit der multidisziplinaren Therapie sollte die Behandlung der Osophagusperforation in spezialisierten Zentren erfolgen.

Background The present study aimed to examine the impact of microscopically tumour-infiltrated resection margins (R1) in pancreatic ductal adenocarcinoma (PDAC) patients with advanced lymphonodular metastasis (pN1–pN2) on overall survival (OS). Methods This retrospective, multi-institutional analysis included patients undergoing surgical resection for PDAC at three tertiary university centres between 2005 and 2018. Subcohorts of patients with lymph node status pN0–N2 were stratified according to the histopathological resection status using Kaplan-Meier survival analysis. Results The OS of the entire cohort (n = 620) correlated inversely with the pN status (26 [pN0], 18 [pN1], 11.8 [pN2] months, P < 0.001) and R status (21.7 [R0], 12.5 [R1] months, P < 0.001). However, there was no statistically significant OS difference between R0 versus R1 in cases with advanced lymphonodular metastases: 19.6 months (95% CI: 17.4–20.9) versus 13.6 months (95% CI: 10.7–18.0) for pN1 stage and 13.7 months (95% CI: 10.7–18.9) versus 10.1 months (95% CI: 7.9–19.1) for pN2, respectively. Accordingly, N stage–dependent Cox regression analysis revealed that R status was a prognostic factor in pN0 cases only. Furthermore, there was no significant survival disadvantage for patients with R0 resection but circumferential resection margin invasion (≤ 1 mm; CRM+; 10.7 months) versus CRM-negative (13.7 months) cases in pN2 stages (P = 0.5). Conclusions An R1 resection is not associated with worse OS in pN2 cases. If there is evidence of advanced lymph node metastasis and a re-resection due to an R1 situation (e.g. at venous or arterial vessels) may substantially increase the perioperative risk, margin clearance in order to reach local control might be avoided with respect to the OS.

Anemia affects the postoperative course of patients undergoing a major surgical procedure. However, it remains unclear whether anemia has a different impact on the long-term outcome of patients with malignant or benign pancreatic disease. A retrospective analysis of patients undergoing pancreatic surgery for pancreatic malignancies or chronic pancreatitis was conducted between January 2012 and June 2018 at the University Hospital Dresden, Germany. The occurrence of preoperative anemia and the administration of pre-, intra-, and postoperative blood transfusions were correlated with postoperative complications and survival data by uni- and multivariate analysis. A total of 682 patients were included with 482 (70.7%) undergoing surgical procedures for pancreatic malignancies. Univariate regression analysis confirmed preoperative anemia as a risk factor for postoperative complications > grade 2 according to the Clavien-Dindo classification. Multivariate regression analyses indicated postoperative blood transfusion as an independent risk factor for postoperative complications in patients with a benign (OR 20.5; p value < 0.001) and a malignant pancreatic lesion (OR 4.7; p value < 0.01). Univariate and multivariate analysis revealed preoperative anemia and pre-, intra-, and postoperative blood transfusions as independent prognostic factors for shorter overall survival in benign and malignant patients (p value < 0.001–0.01). Preoperative anemia is a prevalent, independent, and adjustable factor in pancreatic surgery, which poses a significant risk for postoperative complications irrespective of the entity of the underlying disease. It should therefore be understood as an adjustable factor rather than an indicator of underlying disease severity.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a mostly immunosuppressive microenvironment. Tumor-draining lymph nodes (TDLN) are a major site for priming of tumor-reactive T cells and also tumor metastasis. However, the phenotype and function of T cells in TDLNs from PDAC patients is unknown. In this study, lymph nodes from the pancreatic head (PH), the hepatoduodenal ligament (HDL) and the interaortocaval (IAC) region were obtained from 25 patients with adenocarcinoma of the pancreatic head. Additionally, tumors and matched blood were analyzed from 16 PDAC patients. Using multicolor flow cytometry, we performed a comprehensive analysis of T cells. CD4+ T cells were the predominant T cell subset in PDAC-draining lymph nodes. Overall, lymph node CD4+ and CD8+ T cells had a similar degree of activation, as measured by CD69, inducible T cell co-stimulator (ICOS) and CD137 (4-1BB) expression and interferon-&gamma, (IFN&gamma, ) secretion. Expression of the inhibitory receptor programmed death 1 (PD-1) by lymph node and tumor-infiltrating regulatory T cells (Tregs) correlated with lymph node metastasis. Collectively, Treg cells and PD-1 are two relevant components of the immunosuppressive network in PDAC-draining lymph nodes and may be particularly attractive targets for combinatorial immunotherapeutic strategies in selected patients with node-positive PDAC.

Introduction The immunosuppressive tumor microenvironment promotes progression of pancreatic ductal adenocarcinoma (PDAC). γδ T cells infiltrate the pancreatic tumor stroma and support tumorigenesis through αβ T cell inhibition. Pancreatic stellate cell (PSC) activation contributes to pancreatic fibrosis in PDAC, limiting the delivery and efficacy of therapeutic agents. Whether γδ T cells have direct effects on PSC activation is unknown. Methods In this study, we analyzed tumor tissue from 68 patients with PDAC and determined the frequency and location of γδ T cells using immunohistochemistry and immunofluorescence. PDAC samples from the TCGA database with low and high TRGC2 expression were correlated with the expression of extracellular matrix genes. Further, PSCs were isolated from pancreatic tumor tissue and co-cultured with γδ T cells for 48 hours and cytokine production was measured using a cytometric bead array. Results γδ T cells infiltrated the pancreatic tumor stroma and were located in proximity to PSCs. A high infiltration of γδ T cells was associated with increased expression of several extracellular matrix genes in human PDAC. In vitro, γδ T cells stimulated IL-6 production by PDAC-derived PSCs. Conclusion γδ T cells activated PSCs and modulation of this interaction may enhance the efficacy of combinational therapies in human PDAC.

Electroporation is a common method for transfection with different kinds of molecules by electrical permeabilization of the plasma membrane. With the increasing use of organoids as a culturing method for primary patient material in the last years, efficient transfer methods of components for genetic engineering in this 3D culture system are in need. Especially for organoids, the efficiency of genetic manipulations depends on a successful transfection. Thus, this protocol was developed to facilitate the electroporation of organoids and to prove its universal functionality in different entities. Human colorectal, pancreatic, hepatic and gastric cancer organoids were successfully electroporated with small and large plasmids in comparison. Based on GFP encoding vectors, the transfection efficiency was determined by FACS. No extensive preparation of the cells or special, cost-intensive electroporation buffers are necessary, and the protocol can be performed within one day.