Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis.

The gastroesophageal squamocolumnar junction (GE-SCJ) is a critical tissue interface between the esophagus and stomach, with significant relevance in the pathophysiology of gastrointestinal diseases. Despite this, the molecular mechanisms underlying GE-SCJ development remain unclear. Using single-cell transcriptomics, organoids, and spatial analysis, we examine the cellular heterogeneity and spatiotemporal dynamics of GE-SCJ development from embryonic to adult mice. We identify distinct transcriptional states and signaling pathways in the epithelial and mesenchymal compartments of the esophagus and stomach during development. Fibroblast-epithelial interactions are mediated by various signaling pathways, including WNT, BMP, TGF-ß, FGF, EGF, and PDGF. Our results suggest that fibroblasts predominantly send FGF and TGF-ß signals to the epithelia, while epithelial cells mainly send PDGF and EGF signals to fibroblasts. We observe differences in the ligands and receptors involved in cell-cell communication between the esophagus and stomach. Our findings provide insights into the molecular mechanisms underlying GE-SCJ development and fibroblast-epithelial crosstalk involved, paving the way to elucidate mechanisms during adaptive metaplasia development and carcinogenesis.

Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial.

PURPOSE: This trial evaluates the addition of the PD-L1 antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA). METHODS: DANTE started as multicenter, randomized phase II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B). RESULTS: Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .032), and the difference was more pronounced in the PD-L1 CPS ≥10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups. CONCLUSION: Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.

Endoscopic Submucosal Dissection in the Upper Gastrointestinal Tract and the Need for Rescue Surgery-A Multicenter Analysis.

Endoscopic submucosal dissection (ESD) has become the standard treatment for early malignant lesions in the upper gastrointestinal (GI) tract. Its clinical results have been reported to be as good as surgery. The outcomes of rescue surgery after non-curative ESD have been reported to be as good as first-line surgery. The aim of this study was to evaluate the outcomes of ESD in the upper GI tract and the outcomes of rescue surgery after non-curative ESD performed in Linz, Austria, between 2009 and January 2023. A total of 193 ESDs were included and divided into 104 esophageal ESD and 89 gastric ESD procedures. The criteria for curative ESD were in line with established guidelines' recommendations. For esophageal lesions, the mean lesion size was 40.3 mm and the rate of curative ESD was 56.7%. In the non-curative ESD, the rate of technical failure as the reason for non-curative ESD was 13.3% and the oncological failure rate was 86.7%. Only 48.7% of indicated rescue surgeries were performed. The main reason for not performing surgery was interdisciplinary consensus due to comorbidity. Perioperative complications Dindo-Clavien ≥ 3 occurred in 22.2% of cases with an in-hospital mortality rate of 0. In gastric lesions, the mean size was 39 mm and the rate of curative ESD was 69.7%. The rate of technical failure as a reason for non-curative ESD was 25.9% and the oncological failure rate was 74.1% for non-curative ESD. Rescue surgery was performed in 48.2% of indicated cases. The perioperative rate for major complications was 0. The outcome of ESD in the upper GI tract is in line with the published literature, and non-curative ESD does not worsen surgical outcomes. The available follow-up data are in line with the international published literature, showing a low rate of residual malignancy in surgical resection specimens. Therefore, the indication of rescue surgery for oncological failure remains challenging. Furthermore, the learning curve of ESD has shown a trend towards improving outcomes over time.

Response prediction by mutation- or methylation-specific detection of ctDNA dynamics in pretreated metastatic colorectal cancer.

Background: Serial analysis of circulating tumor DNA (ctDNA) levels is a promising tool for both relapse prediction in the curative setting, as well as predicting clinical benefit from systemic treatment in metastasic colorectal cancer (mCRC). Most data in this context are derived from treatment naive patients. Objective: To predict progressive disease (PD) as early as possible through monitoring of changes in ctDNA levels during systemic treatment in pretreated patients with mCRC. Design: A prospective, single-center, observational study. Methods: Patients treated beyond first-line were prospectively included between February 2020 and September 2021. Blood for ctDNA detection was taken before every treatment cycle from start of treatment until first restaging by CT-scan. ctDNA was detected by mutation- (mut-ctDNA) and methylation-specific ddPCR. Receiver Operating Characteristic (ROC)-analysis was used to describe sensitivity and specificity for prediction of PD at restaging for all time points. Results: A total of 42 patients were included who all carried a mutation in tumor tissue. Detection rate of mut-ctDNA was 88.1% and 74.4% for meth-ctDNA. Absolute ctDNA levels before treatment were prognostic in terms of overall survival. Levels of ctDNA were significantly higher in patients with PD at restaging. Median time from start of treatment to restaging was 93 days (95% CI 88.8-96). After a median of 19 days of treatment (95% CI 16.1-20.2), a decline of either mutation- or methylation-specific ctDNA levels of ⩽58% predicted PD at restaging with a sensitivity/specificity of 92.9/85.7% and 85.7/100%, respectively. Median time to restaging was 66 days (95% CI 56.8-75.2). There was no significant increase of sensitivity/specificity at later time points of ctDNA measurements. Conclusion: Monitoring early changes of ctDNA levels either by mut- or meth-ctDNA allows for early prediction of PD in pretreated patients with mCRC. This has the potential to complement RECIST-based treatment assessment with the aim to switch potentially insufficient treatments as early as possible, which is of particular interest in higher treatment lines.

Textbook Outcome after Gastrectomy for Gastric Cancer Is Associated with Improved Overall and Disease-Free Survival.

(1) Background: The complexity of the perioperative outcome for patients with gastric cancer is not well reflected by single quality metrics. To study the effect of the surgical outcome on survival, we have evaluated the relationship between textbook outcome (TO)-a new composite parameter-and oncological outcome. (2) Methods: All patients undergoing total gastrectomy or trans-hiatal extended gastrectomy for gastric cancer with curative intent between 2017 and 2021 at our institution were included. TO was defined by negative resection margins (R0); collection of ≥25 lymph nodes; the absence of major perioperative complications (Clavien-Dindo ≥ 3); the absence of any reintervention; absence of unplanned ICU re-admission; length of hospital stay < 21 days; absence of 30-day readmission and 30-day mortality. We evaluated factors affecting TO by multivariate logistic regression. The correlation between TO and long-term survival was assessed using a multivariate cox proportional-hazards model. (3) Results: Of the patients included in this study, 52 (52.5 %) achieved all TO metrics. Open surgery (p = 0.010; OR 3.715, CI 1.334-10.351) and incomplete neoadjuvant chemotherapy (p = 0.020, OR 4.278, CI 1.176-15.553) were associated with failure to achieve TO on multivariate analysis. The achievement of TO significantly affected overall survival (p = 0.015). TO (p = 0.037, OD 0.448, CI 0.211-0.954) and CCI > 4 (p = 0.034, OR 2.844, CI 1.079-7.493) were significant factors affecting DFS upon univariate analysis. In multivariate analysis, CCI > 4 (p = 0.035, OR 2.605, CI 0.983-6.905) was significantly associated with DFS. (4) Conclusions: We identified patient- and procedure-related factors influencing TO. Importantly, achieving TO is strongly associated with improved long-term survival in gastric cancer patients and merits further focus on surgical quality improvement efforts.

Pancreatic Fistulas: Current Evidence and Strategy-A Narrative Review.

Pancreatic fistulas are highly feared complications following surgery on or near the pancreas, abdominal trauma, or severe inflammation. These fistulas arise from leaks in the pancreatic ductal system, leading to various complications such as abscesses, delayed gastric emptying, and hemorrhage. Severe cases present with sepsis or organ failure, dramatically increasing mortality and morbidity. Risk factors include smoking, high BMI, male gender, age, and surgery-related factors like prolonged operation time and non-ligation of the main pancreatic duct. Therefore, treatment options and preventive measurements have become a hot topic in recent years. Studies have investigated the use of fibrin sealants, different closure methods, and less invasive surgical techniques. Treatment options consist of conservative measurements and the use of percutaneous drainage, prophylactic transpapillary stenting, and surgery in severe cases. As EUS has become widely available, transmural stenting started to influence the management of pancreatic fluid collections (PFCs). However, studies on its use for the management of pancreatic fistulas are lacking. Medical treatment options like somatostatin analogs and pasireotide have been investigated but yielded mixed results.

Endoscopic Transmural Therapy of Pancreatic Fistulas in an Interdisciplinary Setting-A Retrospective Data Analysis.

Pancreatic fistulas belong to the most feared complications after surgery on or near the pancreas, abdominal trauma, or severe pancreatitis. The majority occur in the setting of operative interventions and are called postoperative pancreatic fistulas (POPF). They can lead to various complications, including abscesses, delayed gastric emptying or hemorrhages with a significant impact on morbidity and mortality. Several risk factors have been identified, including smoking, high BMI, male gender, and age. Prophylactic measures and treatment options have been explored but with limited success. This study aimed to analyze the incidence and management of pancreatic fistulas treated in a tertiary referral center, particularly focusing on an endoscopic approach. The data of 60 patients with clinically relevant pancreatic fistulas were analyzed between 2018 and 2021. Different treatment approaches, including conservative management, percutaneous drainage, transpapillary stenting, and endoscopic transmural drainage, were evaluated. An endoscopic transmural approach using lumen-apposing metal stents (LAMS) was used in almost half of this cohort showing promising results, with a high rate of fistula closure in refractory cases and a mean time until closure of 2.7 months. The findings suggest that an endoscopic approach, particularly using LAMS, can be effective in the management of pancreatic fistulas.

Hybrid laparoscopic versus fully robot-assisted minimally invasive esophagectomy: an international propensity-score matched analysis of perioperative outcome.

BACKGROUND: Currently, little is known regarding the optimal technique for the abdominal phase of RAMIE. The aim of this study was to investigate the outcome of robot-assisted minimally invasive esophagectomy (RAMIE) in both the abdominal and thoracic phase (full RAMIE) compared to laparoscopy during the abdominal phase (hybrid laparoscopic RAMIE). METHODS: This retrospective propensity-score matched analysis of the International Upper Gastrointestinal International Robotic Association (UGIRA) database included 807 RAMIE procedures with intrathoracic anastomosis between 2017 and 2021 from 23 centers. RESULTS: After propensity-score matching, 296 hybrid laparoscopic RAMIE patients were compared to 296 full RAMIE patients. Both groups were equal regarding intraoperative blood loss (median 200 ml versus 197 ml, p = 0.6967), operational time (mean 430.3 min versus 417.7 min, p = 0.1032), conversion rate during abdominal phase (2.4% versus 1.7%, p = 0.560), radical resection (R0) rate (95.6% versus 96.3%, p = 0.8526) and total lymph node yield (mean 30.4 versus 29.5, p = 0.3834). The hybrid laparoscopic RAMIE group showed higher rates of anastomotic leakage (28.0% versus 16.6%, p = 0.001) and Clavien Dindo grade 3a or higher (45.3% versus 26.0%, p < 0.001). The length of stay on intensive care unit (median 3 days versus 2 days, p = 0.0005) and in-hospital (median 15 days versus 12 days, p < 0.0001) were longer for the hybrid laparoscopic RAMIE group. CONCLUSIONS: Hybrid laparoscopic RAMIE and full RAMIE were oncologically equivalent with a potential decrease of postoperative complications and shorter (intensive care) stay after full RAMIE.

The Rate of Avoidable Pancreatic Resections at a High-Volume Center: An Internal Quality Control and Critical Review.

BACKGROUND: The incidence of benign diseases among pancreatic resections for suspected malignancy still represents a relevant issue in the surgical practice. This study aims to identify the preoperative pitfalls that led to unnecessary surgeries at a single Austrian center over a twenty-year period. METHODS: Patients undergoing surgery for suspected pancreatic/periampullary malignancy between 2000 and 2019 at the Linz Elisabethinen Hospital were included. The rate of "mismatches" between clinical suspicion and histology was considered as primary outcome. All cases that, despite that, fulfilled the indication criteria for surgery were defined as minor mismatches (MIN-M). Conversely, the true avoidable surgeries were identified as major mismatches (MAJ-M). RESULTS: Among the 320 included patients, 13 (4%) presented with benign lesions at definitive pathology. The rate of MAJ-M was 2.8% (n = 9), and the most frequent causes of misdiagnoses were autoimmune pancreatitis (n = 4) and intrapancreatic accessory spleen (n = 2). In all MAJ-M cases, various mistakes within the preoperative workup were detected: lack of multidisciplinary discussion (n = 7, 77.8%); inappropriate imaging (n = 4, 44.4%); lack of specific blood markers (n = 7, 77.8%). The morbidity and mortality rates for mismatches were 46.7% and 0. CONCLUSION: All avoidable surgeries were the result of an incomplete pre-operative workup. The adequate identification of the underlying pitfalls could lead to minimize and, potentially, overcome this phenomenon with a concrete optimization of the surgical-care process.

Coping with a lack of evidence: living-donor kidney transplantation in the initial phase of the SARS-CoV-2 pandemic.

Due to immunosuppressive therapy, transplant patients are more susceptible to viral and bacterial infections. A potentially deadly new virus haunted us in 2020: SARS-CoV­2, causing coronavirus disease 19 (COVID-19). We analyzed the consequences of this previously unknown risk for our living-donor transplant program in the first year of the pandemic. After the complete lockdown in spring 2020, our transplant center in Linz resumed the living-donor kidney transplantation program from June to September 2020, between the first and second waves of COVID-19 in Austria. We compared the outcomes of these living-donor kidney transplantations with the transplant outcomes of the corresponding periods of the three previous years. From June 4 to September 9, 2020, five living-donor kidney transplantations were performed. All donors and recipients were screened for COVID 19 infection by PCR testing the day before surgery. Kidney transplant recipients remained isolated in single rooms until discharge from hospital. All recipients and donors remained SARS-CoV­2 negative during the follow-up of 10 months and have been fully vaccinated to date. The number of living transplants in the studied period of 2020 was constant compared to the same months of 2017, 2018, and 2019. Living-donor kidney transplantation can be continued using testing for SARS-CoV­2 and meticulous hygienic precautions in epidemiologically favorable phases of the SARS-CoV­2 pandemic. Donors and recipients should be carefully selected and informed about risks and benefits.

A 25 mm Circular Stapler Anastomosis Is Associated with Higher Anastomotic Leakage Rates Following Minimally Invasive Ivor Lewis Operation.

(1) Background: Minimally invasive oesophagectomy (MIE) with intrathoracic anastomosis is increasingly used in treating patients with oesophageal cancer. Anastomotic leakage (AL) remains a critical perioperative complication, despite recent advances in surgical techniques. It remains unclear to what extent the size of the circular stapler (CS), a 25 mm CS or a bigger CS, may affect the incidence of AL. This study aimed to evaluate whether the CS size in oesophagogastrostomy affects the postoperative AL rates and related morbidity in MIE. (2) Methods: We conducted a retrospective review of consecutive patients who had undergone thoracic MIE between August 2014 and July 2019 using a CS oesophagogastric anastomosis at the level of the Vena azygos. The patients were grouped according to CS size (mm): small-sized (SS25) and large-sized (LS29). The patient demographics, data regarding morbidity, and clinical outcomes were compared. The primary outcome measure was the AL rate related to the stapler size. (3) Results: A total of 119 patients were included (SS25: n = 65; LS29: n = 54). Except for the distribution of squamous cell carcinoma, the demographics were similar in each group. The AL rate was 3.7% in the LS29 group and 18.5% in the SS25 group (p = 0.01). The major morbidity (CD ≥ 3a) was significantly more frequent in the SS25 group compared with the LS29 group (p = 0.02). CS size, pulmonary complications, and cardiovascular disease were independent risk factors for AL in the multivariate analysis. (4) Conclusions: A 29 mm CS is associated with significantly improved surgical outcomes following standard MIE at the level of the azygos vein and should be conducted whenever technically feasible.

The Learning Curve for Hand-Assisted Laparoscopic Total Gastrectomy in Gastric Cancer Patients.

(1) Background: Hand-assisted laparoscopic total gastrectomy (LTG) for patients with gastric cancer (GC) has been established as the standard surgical treatment at our center. This study aims to quantify the learning curve for surgeons performing minimally invasive total gastrectomy at a high-volume single center. (2) Methods: One hundred and eighteen consecutive patients who underwent minimally invasive total gastrectomy between January 2014 and December 2020 at a single high-volume center were included and reviewed retrospectively. Risk-adjusted cumulative sum analysis (RA-CUSUM) was used to monitor the surgical outcomes for patients with different risks of postoperative mortality using varying-coefficient logistic regression models. Patients were ordered by the sequential number of the procedure performed and divided into two groups according to the degree of surgeon proficiency as determined by RA-CUSUM analysis (group A: 45; group B: 73 patients). Age, gender, body mass index (BMI), tumor location, pathology, and comorbidities were compared while primary endpoints comprised surgical parameters, postoperative course, and survival outcomes. (3) Results: Forty-four cases were required for the completion of the learning curve. During this time, the mean operating time decreased. Hand-assisted laparoscopic total gastrectomy performed after a learning curve was associated with a shorter median operating time (OT) (360 min vs. 289 min, <0.001), and a reduced length of stay (A = 18.0 vs. B = 14.0 days) (p = 0.154), while there was a trend toward less major complications (Clavien−Dindo (CD) 3−5 within 90 days (12 (26.67%) vs. 10 (13.70%) p = 0.079). Our results showed no difference in anastomotic leakage between the two groups (group A vs. group B, 3 (6.67%) vs. 4 (5.48%) p = 0.99). Similarly, 30-day (0 (0%) vs. 1 (1.7%), p = 0.365) and 90-day mortality (1 (2.08%) vs. 2 (3.39%), p = 0.684) were comparable. Following multivariate analysis, the level of surgical proficiency was not a significant prognostic factor for overall survival. (4) Conclusions: A minimum of 44 cases are required for experienced laparoscopic surgeons to achieve technical competence for performing LTG. While operation time decreased after completion of the learning curve, quality criteria such as achievement of R0 resection, anastomotic leakage, and perioperative mortality remained unaltered. Of note, the level of surgical training showed no significant impact on the 2 year OS or DFS.

Prediction of response to systemic treatment by kinetics of circulating tumor DNA in metastatic pancreatic cancer.

Introduction: Pretherapeutic detectable circulating tumor DNA (ctDNA) represents a promising prognostic biomarker for predicting relapse and overall survival in patients with metastatic pancreatic cancer. However, the prognostic value of ctDNA dynamics during treatment has not been studied thus far. We aimed to investigate the correlation between the change of ctDNA levels and response to treatment in patients treated by systemic therapy. Material and methods: CtDNA detection using liquid biopsy (droplet digital PCR (ddPCR) utilizing KRAS G12/13 and, if negative, Q61 commercial test kits) was prospectively performed on patients with stage IV pancreatic cancer i) prior to initiation of systemic chemotherapy and ii) serially every 2 weeks until restaging. Detection rates, levels of ctDNA, and the course of the relative ctDNA change (ctDNA kinetics) were correlated to treatment response and clinical outcome. Results: The detection rate at baseline was 64.3% (45/70), and complete serial measurement records were available for 32 ctDNA-positive patients. Reduction of ctDNA levels below 57.9% of its baseline value at week 2 after treatment initiation was significantly predictive of response to treatment (area under the curve (AUC) = 0.918, sensitivity 91.67%, and specificity 100%) and was associated with prolonged overall survival (OS) (5.7 vs. 11.4 months, p = 0.006) and progression-free survival (PFS) (2.5 vs. 7.7 months, p < 0.000) regardless of treatment line. Pretherapeutic ctDNA detection was independently associated with worse OS in patients receiving a first-line regimen (7 vs. 11.3 months, p = 0.046) and regardless of treatment line (11.4 vs. 15.9 months, p = 0.045) as well as worse PFS (3.4 vs. 10.8 months, p = 0.018). Conclusion: The change in magnitude of ctDNA during systemic treatment allows the prediction of treatment response and is associated with both OS and PFS. This finding adds significant clinical potential to the already established prognostic value of ctDNA positivity in metastatic pancreatic cancer.

The Association between Neoadjuvant Radio-Chemotherapy and Prolonged Healing of Anastomotic Leakage after Esophageal Resection Treated with EndoVAC Therapy.

(1) Background: Endoscopic vacuum therapy (EVT) has become the mainstay in the treatment of early anastomotic leakage (AL) after esophageal resection. The effect of nRCT on the efficacy of EVT is currently unknown. (2) Methods: Data of 427 consecutive patients undergoing minimally invasive esophagectomy between 2013 and 2022 were analyzed. A total of 26 patients received EVT for AL after esophagectomy between 2010 and 2021. We compared a cohort of 13 patients after treatment with EVT for anastomotic leakage after neoadjuvant radiochemotherapy (nRCT) with a control group of 13 patients after neoadjuvant chemotherapy (nCT) using inverse propensity score weighting to adjust for baseline characteristics between the groups. EVT therapy was assessed regarding patient survival, treatment failure as defined by a change in treatment to stent/operation, duration of treatment, and secondary complications. Statistical analysis was performed using linear regression analysis. (3) Results: Time to EVT after initial tumor resection did not vary between the groups. The duration of EVT was longer in patients after nRCT (14.69 days vs. 20.85 days, p = 0.002) with significantly more interventions (4.38 vs. 6.85, p = 0.001). The success rate of EVT did not differ between the two groups (nCT n = 8 (61.54%) vs. nCT n = 5 (38.46%), p = 0.628). The rate of operative revision did not vary between the groups. Importantly, no mortality was reported within 30 days and 90 days in both groups. (4) Conclusions: EVT is a valuable tool for the management of AL after esophageal resection in patients after nRCT. While the success rates were comparable, EVT was associated with a significantly longer treatment duration. Anastomotic leakages after nRCT often require prolonged and multimodal treatment strategies while innovative strategies such as prophylactic endoVAC placement or use of a VAC-Stent may be considered.

Robotic-assisted minimally invasive Ivor Lewis esophagectomy within the prospective multicenter German da Vinci Xi registry trial.

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.

Robotic vs. laparoscopic liver surgery: a single-center analysis of 600 consecutive patients in 6 years.

BACKGROUND: While laparoscopic liver surgery has become a standard procedure, experience with robotic liver surgery is still limited. The aim of this prospective study was to evaluate safety and feasibility of robotic liver surgery and compare outcomes with conventional laparoscopy. METHODS: We here report the results of a single-center, prospective, post-marketing observational study (DRKS00017229) investigating the safety and feasibility of robotic liver surgery. Baseline characteristics, surgical complexity (using the IWATE score), and postoperative outcomes were then compared to laparoscopic liver resections performed at our center between January 2015 and December 2020. A propensity score-based matching (PSM) was applied to control for selection bias. RESULTS: One hundred twenty nine robotic liver resections were performed using the da Vinci Xi surgical system (Intuitive) in this prospective study and were compared to 471 consecutive laparoscopic liver resections. After PSM, both groups comprised 129 cases with similar baseline characteristics and surgical complexity. There were no significant differences in intraoperative variables, such as need for red blood cell transfusion, duration of surgery, or conversion to open surgery. Postoperative complications were comparable after robotic and laparoscopic surgery (Clavien-Dindo ≥ 3a: 23% vs. 19%, p = 0.625); however, there were more bile leakages grade B-C in the robotic group (17% vs. 7%, p = 0.006). Length of stay and oncological short-term outcomes were comparable. CONCLUSIONS: We propose robotic liver resection as a safe and feasible alternative to established laparoscopic techniques. The object of future studies must be to define interventions where robotic techniques are superior to conventional laparoscopy.

Prognostic Relevance of Weight and Weight Loss during Multimodal Therapy for Oesophagogastric Tumours.

The prognostic meaning of weight loss (WL) during standard treatment for operable oesophagogastric cancer is still unclear. The aim of this study is to analyse the prognostic effect of WL during perioperative chemotherapy (PC) for gastric cancer (GC) and oesophageal adenocarcinomas (OAC). We retrospectively analysed data from 128 patients (pts) with GC and OAC who underwent surgery in the context of multimodal treatment with PC. We collected data on WL during different steps of therapy together with other histopathologic and demographic information. We analysed the effects on overall survival (OS) and disease-free survival (DFS). Results: Pts with WL ≥ 5% during neoadjuvant chemotherapy exhibited significantly worse OS compared with pts with WL < 5% (median OS: 23.6 months [95% CI: 4.4−42.9] vs. 63.5 months [95% CI: 50.7−76.2], p = 0.007) and DFS (median DFS: 12.5 months [95% CI: 2.9−22.1] vs. 63.5 months [95% CI: 31.6−95.4], p = 0.016). Pts with WL ≥ 14% during the whole treatment exhibited significantly worse OS compared with pts with WL < 14% (median OS: 43.7 months [95% CI: 13.2−74.2] vs. not reached, p = 0.028) and DFS (median DFS: 34.3 months [95% CI: 14.0−54.5] vs. not reached, p = 0.038). Conclusion: WL patterns during neoadjuvant chemotherapy and during the whole treatment correlate with a significantly worse prognosis in operated pts with curative GC or OAC in the context of a multimodal treatment with PC. A validation of this prognostic effect in prospective studies is warranted.

Ten years of live surgical broadcast at Charité-MAYO conferences (2010-2019): a systematic evaluation of the surgical outcome.

OBJECTIVE: The international Charité-MAYO Conference aims to promote international dialog on diagnostics, management, scientific breakthroughs, and state-of-the-art surgical procedures in gynecology and gynecologic oncology and senology. Live surgeries are a fundamental tool of interdisciplinary and international exchange of experts in their respective fields. Currently, there is a controversial and emotional debate about the true value, risks, and safety of live surgical broadcasts. The aim of the current study is to analyze peri-operative risks in patients who were operated live during the Charité-MAYO Conferences. METHODS: Live surgeries were performed by the core Charité team consisting of gynecologic oncologic surgeons, breast and plastic surgeons, partly in collaboration with visiting gynecologic oncologic surgeons. We performed a retrospective analysis of live surgeries performed during seven Charité-MAYO Conferences from 2010 to 2019 held in Berlin, Germany. Patients' files and tumor databases were analyzed as required and patients were contacted to update their long-term follow-up. RESULTS: Sixty-nine patients who were operated live were included. The types of surgery were as follows: urogynecologic procedures (n=13), breast surgery (n=21), and gynecologic oncology surgery for ovarian, uterine, vulvar or cervical cancer (n=35). Peri-operative complications were assessed according to the Clavien-Dindo classification. Despite a high rate of complete resection and the high frequency of multivisceral procedures, the rate of peri-operative complications was within the range published in the literature. Time of surgery and length of intensive unit care and hospital stay did not differ from data acquired at the home institution. CONCLUSIONS: Based on our analysis, live surgeries appear to be safe when performed within a multidisciplinary setting without an increase in surgical morbidity and mortality compared with historical controls and without compromise of patients' outcome. This is the first analysis of its kind to set the basis for patient information and consent for this type of surgeries.

Body Mass Index Thresholds and the Use of Bariatric Surgery in the Field of Kidney Transplantation in Germany.

BACKGROUND: Obesity in the recipient is linked to inferior transplant outcome. Consequently, access to kidney transplantation (KT) is often restricted by body mass index (BMI) thresholds. Bariatric surgery (BS) has been established as a superior treatment for obesity compared to conservative measures, but it is unclear whether it is beneficial for patients on the waiting list. METHODS: A national survey consisting of 16 questions was sent to all heads of German KT centers. Current situation of KT candidates with obesity and the status of BS were queried. RESULTS: Center response rate was 100%. Obesity in KT candidates was considered an important issue (96.1%; n = 49/51) and 68.6% (n = 35/51) of departments responded to use absolute BMI thresholds for KT waiting list access with ≥ 35 kg/m2 (45.1%; n = 23/51) as the most common threshold. BS was considered an appropriate weight loss therapy (92.2%; n = 47/51), in particular before KT (88.2%; n = 45/51). Sleeve gastrectomy was the most favored procedure (77.1%; n = 37/51). Twenty-one (41.2%) departments responded to evaluate KT candidates with obesity by default but only 11 (21.6%) had experience with ≥ n = 5 transplants after BS. Concerns against BS were malabsorption of immunosuppressive therapy (39.2%; n = 20/51), perioperative morbidity (17.6%; n = 9/51), and malnutrition (13.7%; n = 7/51). CONCLUSIONS: Obesity is potentially limiting access for KT. Despite commonly used BMI limits, only few German centers consider BS for obesity treatment in KT candidates by default. A national multicenter study is desired by nearly all heads of German transplant centers to prospectively assess the potentials, risks, and safety of BS in KT waitlisted patients.

Systematic literature review and meta-analysis of Clostridium septicum aortitis.

BACKGROUND: Clostridium septicum bacteremia is often associated with occult malignancies (approximately 80%), especially of the right colon. Furthermore, inflammation of the aortic wall can rapidly lead to aneurysm induction through bacterial seeding into atheromatous lesions with consecutive life-threatening rupture. We summarize all published data on this rare and lethal disease to evaluate therapeutic approaches and give valid treatment recommendations because there are no guidelines. METHODS: A systematic review of the literature was conducted screening EMBASE and MEDLINE databases following the PRISMA guidelines with search period from first description to August 25, 2021. RESULTS: There were 72 cases of C septicum aortitis reported in 64 publications. Endovascular aortic repair (EVAR) was performed in a minority of patients (n = 6) unfit for surgery but lacked long-term survivors. Antibiotic treatment was beneficial in a bridge to surgery concept, but up to now harbored a 6-month mortality rate of 100% (median overall survival, 0.5 months) when no additional aortic repair was performed. Open aortic repair was the only potential curative approach but was accompanied with a 90-day-mortality of 26.7% (4/15). CONCLUSIONS: Open aortic repair combined with perioperative antibiotic treatment should be offered to all patients as the only potentially curative approach. If applicable, resection of a coexisting colonic tumor should be performed after successful aortic repair. Alternatively, long-term antibiotic treatment can be offered to patients unfit for surgery in a palliative setting. Endovascular aortic repair has been performed on a minority of patients with a high risk for stent graft infection and should remain a salvage strategy when therapeutic pressure demands acute intervention in patients unfit for surgery.