PURPOSE:The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers. METHODS:In this cross-sectional case-based survey study, 5 anonymized patient cases with imaging data of localized STS were presented to MTBs of 21 German-speaking tertiary referral hospitals. Centers provided recommendations on treatment sequence and modalities, along with the consensus level within their MTB. Agreement percentages were calculated, and consensus levels were rated on a scale of 1 to 10. RESULTS:Five patient cases were discussed resulting in 105 recommendations. Agreement percentages for case 1 to 5 were 14.3%, 61.9%, 33.3%, 52.4% and 9.3%, with a median agreement percentage of 33.3%. Grouping pre- and postoperative therapies as "perioperative" and including recommendations with and without regional hyperthermia raised the median agreement to 47.6%. The mean consensus level within each center across all 5 cases was 9.5. CONCLUSION:This first case-based analysis of inter-center agreement for STS management in German-speaking countries reveals low inter-center agreement but high intra-center consensus. Our study includes nearly all tertiary sarcoma centers in German-speaking countries, affirming its strong external validity. These findings suggest potential and clinically very relevant differences in treatment standards among sarcoma centers. Enhanced case-based exchanges and collaborative efforts are needed to reduce discrepancies and standardize the management of STS patients.

Previous studies have shown that surgical residents can safely perform a variation of complex abdominal surgeries when provided with adequate training, proper case selection, and appropriate supervision. Their outcomes are equivalent when compared to experienced board-certified surgeons. Our previously published training curriculum for robotic assisted minimally invasive esophagectomy already demonstrated a possible reduction in time to reach proficiency. However, esophagectomy is a technically challenging procedure and comes with high morbidity rates of up to 60%, making it difficult to provide opportunities to train surgical residents. We aimed to investigate if a surgical resident could safely perform complex esophageal surgery when a structured modular teaching curriculum is applied. A structured teaching program based on our previously published modular step-up approach was applied by two experienced board-certified esophageal surgeons. Our IRB-approved (Institutional Review Board) database was searched to identify all Ivor-Lewis esophagectomies performed by the selected surgical resident from August 2019 to July 2021. The cumulative sum method was used to analyze the learning curve of the surgical resident. Outcomes of patients operated by the resident were then compared to our overall cohort of open, hybrid, and robotic Ivor-Lewis esophagectomies from May 2016 to May 2020. The total cohort included 567 patients, of which 65 were operated by the surgical resident and 502 patients were operated by experienced esophageal cancer surgeons as the control group. For baseline characteristics, a significant difference for BMI (Body mass index) was observed, which was lower in the resident's group (25.5 kg/m2 vs. 26.8 kg/m2 (P = 0.046). A significant difference of American Society of Anesthesiologists- and Eastern Cooperative Oncology Group-scores was seen, and a subgroup analysis including all patients with American Society of Anesthesiologists I and Eastern Cooperative Oncology Group 0 was performed revealing no significant differences. Postoperative complications did not differ between groups. The anastomotic leak rate was 13.8% in the resident's cohort and 12% in the control cohort (P = 0.660). Major complications (Clavien-Dindo >= IIIb) occurred in 16.9% of patients in both groups. Oncological outcome, defined by harvested lymph nodes (35 vs. 32.33, P = 0.096), proportion of lymph node compliant performed operations (86.2% vs. 88.4%, P = 0.590), and R0-resection rate (96.9% vs. 96%, P = 0.766), was not compromised when esophagectomies were performed by the resident. The resident completed the learning curves after 39 cases for the total operating time, 38 cases for the thoracic operating time, 26 cases for the number of harvested lymph nodes, 29 cases for anastomotic leak rate, and finally 58 cases for the comprehensive complication index. For postoperative complications, no significant difference was seen between patients operated in the resident group versus the control group, with a third of patients being discharged with a textbook outcome in both cohorts. Furthermore, no difference in oncological quality of the resection was found, emphasizing safety and feasibility of our training program. A structured modular step-up for training a surgical resident to perform complex esophageal cancer surgery can successfully maintain patient safety and outcomes.

Background: In contrast to the well-established multimodal therapy for localized oesophageal cancer, the metastatic stage is commonly treated only with systemic therapy as current international guidelines recommend. However, evidence suggesting that multimodal therapy including surgery could benefit selected patients with metastasized oesophageal cancer is increasing. The aim of this study was to investigate the survival of patients diagnosed with metastatic oesophageal cancer after different treatment regimens. Methods: This was a retrospective single-centre study of patients with adenocarcinoma or squamous cell carcinoma of the oesophagus with synchronous or metachronous metastases who underwent Ivor Lewis oesophagectomy between 2010 and 2021. Each patient received an individual treatment for their metastatic burden based on an interdisciplinary tumour board conference. Survival differences between different treatments were assessed using the Kaplan-Meier method, as well as univariable and multivariable Cox regression models. Results: Out of 1791 patients undergoing Ivor Lewis oesophagectomy, 235 patients diagnosed with metastases were included. Of all of the included patients, 42 (17.9%) only underwent surgical resection of their metastatic disease, 37 (15.7%) underwent multimodal therapy including surgery, 78 (33.2%) received chemotherapy alone, 49 (20.9%) received other therapies, and 29 (12.3%) received best supportive care. Patients who underwent resection or multimodal therapy including surgery of their metastatic burden showed superior overall survival compared with chemotherapy alone (median overall survival of 19.0, 18.0, and 11.0 months respectively) (P < 0.001). This was confirmed in subcohorts of patients with metachronous solid-organ metastases and with a single metastasis. In multivariable analyses, resection with or without multimodal therapy was an independent factor for favourable survival. Conclusion: Surgical resection could be a feasible treatment option for metastasized oesophageal cancer, improving survival in selected patients. Further prospective randomized studies are needed to confirm these findings and define reliable selection criteria.

This study evaluates the H2AX/γ-H2AX expression in soft tissue sarcomas (STS), its implications for biological behavior and immune environment, and its potential as a prognostic biomarker. RNA-Seq data from 237 STS were obtained from The Cancer Genome Atlas project. Patients were stratified by H2AX mRNA expression using a survival-associated cutoff. Differentially expressed genes and pathways as well as immune signatures between H2AXhigh- and H2AXlow tumors were identified with DESeq2 analysis, gene set enrichment analyses (GSEA), Enrichr pathway analysis and CIBERSORTx. Tissue microarrays of a different cohort of 291 STS were generated for immunohistochemical staining to assess γ-H2AX protein expression, followed by statistical evaluation. High H2AX mRNA expression was associated with shorter overall survival (OS) in STS (p = 0.02), particularly in leiomyosarcomas (LMS) (p < 0.001), and was a negative prognostic factor in LMS (HR 11.15, p < 0.001). H2AXhigh LMS tumors showed upregulation of cell cycle-related pathways, while H2AXlow LMS exhibited increased inflammatory activity, including elevated M1 macrophage signatures and resting mast cell signatures (both p < 0.001). High γ-H2AX protein levels were an independent negative prognostic factor in the total LMS cohort (HR 12.12, p = 0.025) and in the subgroup of non-uterine LMS (HR 153.80, p = 0.013). Consistent with CIBERSORTx analysis, γ-H2AXlow LMS showed higher mast cell infiltration than γ-H2AXhigh LMS (p = 0.038). In conclusion, H2AX mRNA and γ-H2AX protein expression are associated with distinct biological behavior, differences in the immune cell environment, and might serve as useful prognostic biomarkers in LMS.

While the sentinel lymph node concept is routinely applied in other surgical fields, no established and valid modality for lymph node mapping for esophageal cancer surgery currently exists. Near-infrared light fluorescence (NIR) using indocyanine green (ICG) has been recently proven to be a safe technology for peritumoral injection and consecutive lymph node mapping in small surgical cohorts, mostly without the usage of robotic technology. The aim of this study was to identify the lymphatic drainage pattern of esophageal cancer during highly standardized RAMIE and to correlate the intraoperative images with the histopathological dissemination of lymphatic metastases. Patients with clinically advanced stage squamous cell carcinoma or adenocarcinoma of the esophagus undergoing a RAMIE at our Center of Excellence for Surgery of the Upper Gastrointestinal Tract were prospectively included in this study. Patients were admitted on the day prior to surgery, and an additional EGD with endoscopic injection of the ICG solution around the tumor was performed. Intraoperative imaging procedures were performed using the Stryker 1688 or the FIREFLY fluorescence imaging system, and resected lymph nodes were sent to pathology. A total of 20 patients were included in the study, and feasibility and safety for the application of NIR using ICG during RAMIE were shown. NIR imaging to detect lymph node metastases can be safely performed during RAMIE. Further analyses in our center will focus on pathological analyses of ICG-positive tissue and quantification using artificial intelligence tools with a correlation of long-term follow-up data.

In der Chirurgie des oberen Gastrointestinaltrakts kommen zunehmend minimal-invasive Verfahren zum Einsatz. Bereits 2003 konnte die erste roboterassistierte Ösophagektomie durchgeführt werden. Seit dieser Zeit zeigten etliche Studien die Vorteile der robotischen Chirurgie am oberen Gastrointestinaltrakt. Ziel dieses Übersichtsartikels ist die Darstellung unterschiedlicher Operationsroboter, innovativer Operationstechniken und Anwendung künstlicher Intelligenz in der Ösophagus- und Magenchirurgie. Diese Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed unter Verwendung der Suchbegriffe „RAMIE“, „minimally invasive esophagectomy“, „gastrectomy“, „virtual reality“ und „ergonomics“. Bereits im TIME Trial ergab der Einsatz minimal-invasiver Verfahren eine Reduktion von pulmonalen Komplikationen, des Blutverlusts und der Krankenhausverweildauer in der Ösophaguschirurgie zeigen. Darauf baute die ROBOT-Studie auf, darin führte der robotisch durchgeführte thorakale Teil der Ösophagektomie – ebenso wie im TIME Trial – zu einer Reduktion von postoperativen Schmerzen sowie pulmonalen Komplikationen im Vergleich zur offenen Methode. Dieser Übersichtsartikel geht auf die Robotersysteme Da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA), Hugo™ RAS System (Medtronic plc, Dublin, Irland), Versius, Dexter® (Fa. Distalmotion, Lausanne, Schweiz), Senhance® Surgical System (Asensus Surgical US, Inc., Durham, NC, USA) sowie ArtiSential (Fa. LivsMed, Seongnam, Republic of Korea) ein. Neue robotische Operationsmethoden haben das Potenzial, das Patientenoutcome, aber auch die Arbeitsbedingungen von Chirurgen weiter signifikant zu verbessern. Zukünftige Entwicklungen, wie der Einsatz von künstlicher Intelligenz sowie die vermehrte Verbreitung von robotischen Systemen, werden dieses Feld weiter voranbringen.

BACKGROUND:Histopathologic regression following neoadjuvant treatment (NT) of oesophageal cancer is a prognostic factor of survival, but the nodal status is not considered. Here, a score combining both to improve prediction of survival after neoadjuvant therapy is developed. METHODS:Seven hundred and fifteen patients with oesophageal squamous cell (SCC) or adenocarcinoma (AC) undergoing NT and esophagectomy were analysed. Histopathologic response was classified according to percentage of vital residual tumour cells (VRTC): complete response (CR) without VRTC, major response with <10% VRTC, minor response with >10% VRTC. Nodal stage was classified as ypN0 and ypN+. Kaplan-Meier and Cox regression were used for survival analysis. RESULTS:Survival analysis identified three groups with significantly different mortality risks: (1) low-risk group for CR (ypT0N0) with 72% 5-year overall survival (5y-OS), (2) intermediate-risk group for minor/major responders and ypN0 with 59% 5y-OS, and (3) high-risk group for minor/major responders and ypN+ with 20% 5y-OS (p < 0.001). Median survival in AC and SCC cohorts were comparable (3.8 (CI 95%: 3.1, 5.3) vs. 4.6 years (CI 95%: 3.3, not reached), p = 0.3). CONCLUSIONS:Histopathologic regression and nodal status should be combined for estimating AC and SCC prognosis. Poor survival in the high-risk group highlights need for adjuvant therapy.

Background: The risk of an anastomotic leakage (AL) following Ivor-Lewis esophagectomy is increased in patients with calcifications of the aorta or a stenosis of the celiac trunc. Ischemic conditioning (ISCON) of the gastric conduit prior to esophagectomy is supposed to improve gastric vascularization at the anastomotic site. The prospective ISCON trial was conducted to proof the safety and feasibility of this strategy with partial gastric devascularization 14 days before esophagectomy in esophageal cancer patients with a compromised vascular status. This work reports the results from a translational project of the ISCON trial aimed to investigate variables of neo-angiogenesis.Methods: Twenty esophageal cancer patients scheduled for esophagectomy were included in the ISCON trial. Serum samples (n = 11) were collected for measurement of biomarkers and biopsies (n = 12) of the gastric fundus were taken before and after ISCON of the gastric conduit. Serum samples were analyzed including 62 different cytokines. Vascularization of the gastric mucosa was assessed on paraffin-embedded sections stained against CD34 to detect the degree of microvascular density and vessel size.Results: Between November 2019 and January 2022 patients were included in the ISCON Trial. While serum samples showed no differences regarding cytokine levels before and after ISCON biopsies of the gastric mucosa demonstrated a significant increase in microvascular density after ISCON as compared to the corresponding gastric sample before the intervention.Conclusion: The data prove that ISCON of the gastric conduit as esophageal substitute induces significant neo-angiogenesis in the gastric fundus which is considered as surrogate of an improved vascularization at the anastomotic site.

Background Robotic-assisted minimally invasive esophagectomy (RAMIE) was first introduced in 2003 and has since then shown to significantly improve the postoperative course. Previous studies have shown that a structured training pathway based on proficiency-based progression using individual skill levels as measures of reach of competence can enhance surgical performance. The aim of this study was to evaluate and help understand our pathway to reach surgical expert levels using a proficiency-based approach introducing RAMIE at our German high-volume center. Methods All patients undergoing RAMIE performed by two experienced surgeons for esophageal cancer since the introduction of the robotic technique in 2017 was included in this analysis. Intraoperative outcomes and postoperative outcomes were included in the analysis. The cumulative sum method was used to analyze how many cases are needed to reach expert levels for different performance characteristics and skill sets during robotic-assisted minimally invasive esophagectomy. Results From 06/2017 to 03/2022, a total of 154 patients underwent RAMIE at our facility and were included in the analysis. An advancement in performance level was observed for total operating time after 70 cases and for thoracic operative time after 79 cases. Lymph node yield showed an increase up until case 60 in the CUSUM analysis. Length of hospital stay stabilized after case 55. The CCI score inflection point was at case 55 in both CUSUM and regression analyses. Anastomotic leak rate stabilized at case 38 and showed another inflection point after case 83. Conclusion Our data and analysis showed the progression from proficient to expert performance levels during the implementation of RAMIE at a European high-volume center. Further analysis of surgeons, especially with a different training status has yet to reveal if the caseloads found in this study are universally applicable. However, skill acquisition and respective measures of such are diverse and as a great range of number of cases was observed, we believe that the learning curve and ascent in performance levels cannot be defined by one parameter alone.

Einleitung Für das lokal begrenzte Ösophaguskarzinom ist die multimodale Therapie aktuell der Goldstandard. Im Gegensatz dazu ist das metastasierte Ösophaguskarzinom als palliative Erkrankung definiert. Aktuell wird diesen Patienten lediglich eine Systemtherapie empfohlen. Dennoch steigt die Evidenz für den Nutzen einer multimodalen Therapie inklusive chirurgischer Resektion für das metastasierte Ösopohaguskarzinom.

Abstract Background The goal of the present study was to develop a convolutional neural network for the detection of bleedings in capsule endoscopy videos using realistic clinical data from one single-centre. Methods Capsule endoscopy videos from all 133 patients (79 male, 54 female; meanage = 53.73 years, SDage = 26.13) who underwent capsule endoscopy at our institution between January 2014 and August 2018 were screened for pathology. All videos were screened for pathology by two independent capsule experts and confirmed findings were checked again by a third capsule expert. From these videos, 125 pathological findings (individual episodes of bleeding spanning a total of 5696 images) and 103 non-pathological findings (sections of normal mucosal tissue without pathologies spanning a total of 7420 images) were used to develop and validate a neural network (Inception V3) using transfer learning. Results The overall accuracy of the model for the detection of bleedings was 90.6% [95%CI: 89.4%–91.7%], with a sensitivity of 89.4% [95%CI: 87.6%–91.2%] and a specificity of 91.7% [95%CI: 90.1%–93.2%]. Conclusion Our results show that neural networks can detect bleedings in capsule endoscopy videos under realistic, clinical conditions with an accuracy of 90.6%, potentially reducing reading time per capsule and helping to improve diagnostic accuracy.