Cologne ergonomic measurement for robotic surgery (CEMRobSurg) using the Hugo™ RAS System.

BACKGROUND: The ergonomic advantages and potential challenges that robotic surgery poses to the well-being of surgeons are mainly unexplored. The most recent surgical robot introduced on the European market is the Hugo™ RAS System by Medtronic. This study aims to evaluate the ergonomic benefits of the Hugo™ RAS System, which is available in our training laboratory, CeMIT (Center for Medical Innovation and Technology Cologne). METHODS AND PROCEDURES: Using the previously established Cologne Ergonomic Measurement Setup for Robotic Surgery (CEMRobSurg), we measured three parameters related to ergonomic posture from subjects with different levels of surgical expertise (laypeople, medical students, surgical residents, and expert robotic surgeons). The heart rate was measured continuously using a polar band. The noise level was measured while using the Hugo™ RAS System, and automated photographs using our locally developed methodology were captured of the participant every 2 s to assess body posture. The ergonomic measurements were conducted while the subject performed the same standardized robotic training exercises (Peg Board, Rope Walk, and Ring Walk). RESULTS: A total of 53 participants were enrolled in this study. The average noise level during all measurements was 54.87 dB. The highest stress level was measured in surgical residents with a sympathetic nervous system index (SNS index) of 1.15 (min - 1.43, max 3.56). The lowest stress level was measured in robotic experts with an SNS index of 0.23 (min - 0.18, max 0.91). We observed a risk-prone positioning of the neck and elbow in medical students (mean 39.6° and 129.48°, respectively). Robotic experts showed a risk positioning in the knee and hip region (mean 107.89° and 90.31°, respectively). CONCLUSION: This is the first study to analyze and objectify the ergonomic posture of medical students, surgical trainees, surgeons, and laypeople using the open console, modular Hugo™ RAS System. Our findings offer recommendations for operating surgeons and allow for a comparative analysis between the different robotic systems. Further evaluations in real-time operative scenarios will follow.

Deep Learning Histology for Prediction of Lymph Node Metastases and Tumor Regression after Neoadjuvant FLOT Therapy of Gastroesophageal Adenocarcinoma.

BACKGROUND: The aim of this study was to establish a deep learning prediction model for neoadjuvant FLOT chemotherapy response. The neural network utilized clinical data and visual information from whole-slide images (WSIs) of therapy-naïve gastroesophageal cancer biopsies. METHODS: This study included 78 patients from the University Hospital of Cologne and 59 patients from the University Hospital of Heidelberg used as external validation. RESULTS: After surgical resection, 33 patients from Cologne (42.3%) were ypN0 and 45 patients (57.7%) were ypN+, while 23 patients from Heidelberg (39.0%) were ypN0 and 36 patients (61.0%) were ypN+ (p = 0.695). The neural network had an accuracy of 92.1% to predict lymph node metastasis and the area under the curve (AUC) was 0.726. A total of 43 patients from Cologne (55.1%) had less than 50% residual vital tumor (RVT) compared to 34 patients from Heidelberg (57.6%, p = 0.955). The model was able to predict tumor regression with an error of ±14.1% and an AUC of 0.648. CONCLUSIONS: This study demonstrates that visual features extracted by deep learning from therapy-naïve biopsies of gastroesophageal adenocarcinomas correlate with positive lymph nodes and tumor regression. The results will be confirmed in prospective studies to achieve early allocation of patients to the most promising treatment.

Learning curve of achieving competency in emergency endoscopy in upper gastrointestinal bleeding: how much experience is necessary?

OBJECTIVES: The management of upper gastrointestinal bleeding (UGIB) has seen rapid advancements with revolutionising innovations. However, insufficient data exist on the necessary number of emergency endoscopies needed to achieve competency in haemostatic interventions. DESIGN: We retrospectively analysed all oesophagogastroduodenoscopies with signs of recent haemorrhage performed between 2015 and 2022 at our university hospital. A learning curve was created by plotting the number of previously performed oesophagogastroduodenoscopies with signs of recent haemorrhage against the treatment failure rate, defined as failed haemostasis, rebleeding and necessary surgical or radiological intervention. RESULTS: The study population included 787 cases with a median age of 66 years. Active bleeding was detected in 576 cases (73.2%). Treatment failure occurred in 225 (28.6%) cases. The learning curve showed a marked decline in treatment failure rates after nine oesophagogastroduodenoscopies had been performed by the respective endoscopists followed by a first plateau between 20 and 50 procedures. A second decline was observed after 51 emergency procedures followed by a second plateau. Endoscopists with experience of <10 emergency procedures had higher treatment failure rates compared with endoscopists with >51 emergency oesophagogastroduodenoscopies performed (p=0.039) or consultants (p=0.041). CONCLUSIONS: Our data suggest that a minimum number of 20 oesophagogastroduodenoscopies with signs of recent haemorrhage is necessary before endoscopists should be considered proficient to perform emergency procedures independently. Endoscopists might be considered as advanced-qualified experts in managing UGIB after a minimum of 50 haemostatic procedure performed. Implementing recommendations on minimum numbers of emergency endoscopies in education programmes of endoscopy trainees could improve their confidence and competency in managing acute UGIB.

Timing of endoscopy in patients with elevated lactate levels and acute upper gastrointestinal bleeding; a retrospective comparative study.

BACKGROUND/AIMS: While current guidelines recommend performing endoscopy within 24 h in case of acute upper gastrointestinal bleeding (AUGIB), the precise timing remains an issue of debate. Lactate is an established parameter for risk stratification in a variety of medical emergencies. This study evaluated the predictive ability of elevated lactate levels in identifying patients with UGIB, who may benefit from emergent endoscopy. METHODS: We retrospectively analyzed all patients with elevated lactate levels, who presented to our emergency department between 01 January 2015 and 31 December 2019 due to suspected AUGIB. RESULTS: Of 134 included cases, 81.3% had an Charlson comorbidity index of ≥3 and 50.4% presented with shock. Fifteen (11.2%) patients died and mortality rates rose with increasing lactate levels. Emergent endoscopy within 6 h (EE) and non-EE were performed in 64 (47.8%) and 70 (52.2%) patients, respectively. Patients who underwent EE had lower systolic blood pressure (107.6 mmHg vs. 123.2 mmHg; p = 0.001) and received blood transfusions more frequently (79.7% vs 64.3%; p = 0.048), but interestingly need for endoscopic intervention (26.6% vs 20.0%; p = 0.37), rebleeding (17.2% vs. 15.7%; p = 0.82) and mortality (9.4% vs. 11.4%; p = 0.7) did not differ significantly. CONCLUSION: In conclusion, our findings support the recommendations of current guidelines to perform non-EE after sufficient resuscitation and management of comorbid illnesses.

Postesophagectomy Diaphragmatic Prolapse after Robot-Assisted Minimally Invasive Esophagectomy (RAMIE).

BACKGROUND: Postesophagectomy diaphragmatic prolapse (PDP) is a major complication after esophagectomy with significant mortality and morbidity. However, in the current literature, treatment and outcomes are not evaluated for patients undergoing an Ivor Lewis Robot-assisted minimally invasive esophagectomy (IL-RAMIE). The aim of this study is to evaluate the incidence of PDP after IL-RAMIE. Moreover, the study aims to determine whether using a minimally invasive approach in the management of PDP after an IL-RAMIE procedure is safe and feasible. MATERIALS AND METHODS: This study includes all patients who received an IL-RAMIE at our high-volume center (>200 esophagectomies/year) between April 2017 and December 2022 and developed PDP. The analysis focuses on time to prolapse, symptoms, treatment, surgical method, and recurrence rates of these patients. RESULTS: A total of 185 patients underwent an IL-RAMIE at our hospital. Eleven patients (5.9%) developed PDP. Patients presented with PDP after a medium time of 241 days with symptoms like reflux, nausea, vomiting, and pain. One-third of these patients did not suffer from any symptoms. In all cases, a CT scan was performed in which the colon transversum always presented as the herniated organ. In one patient, prolapse of the small intestine, pancreas, and greater omentum also occurred. A total of 91% of these patients received a revisional surgery in a minimally invasive manner with a mean hospital stay of 12 days. In four patients, PDP recurred (36%) after 13, 114, 119 and 237 days, respectively. CONCLUSION: This study shows that a minimally invasive approach in repositioning PDP is a safe and effective option after IL-RAMIE.

Long-Term Postsurgical Outcomes of Neoadjuvant Chemoradiation (CROSS) Versus Chemotherapy (FLOT) for Multimodal Treatment of Adenocarcinoma of the Esophagus and the Esophagogastric Junction.

BACKGROUND: The question of the ideal neoadjuvant therapy for locally advanced esophagogastric adenocarcinoma has not been answered to date. Multimodal treatment has become a standard treatment for these adenocarcinomas. Currently, perioperative chemotherapy (FLOT) or neoadjuvant chemoradiation (CROSS) is recommended. METHODS: A monocentric retrospective analysis compared long-term survival after CROSS versus FLOT. The study enrolled patients with adenocarcinoma of the esophagus (EAC) or the esophagogastric junction type I or II undergoing oncologic Ivor-Lewis esophagectomy between January 2012 and December 2019. The primary objective was to determine the long-term outcome in terms of overall survival. The secondary objectives were to determine differences regarding the histopathologic categories after neoadjuvant treatment and the histomorphologic regression. RESULTS: The findings showed no survival advantage for one or the other treatment in this highly standardized cohort. All the patients underwent open (CROSS: 9.4% vs. FLOT: 22%), hybrid (CROSS: 82% vs. FLOT: 72%), or minimally invasive (CROSS: 8.9% vs. FLOT: 5.6%) thoracoabdominal esophagectomy. The median post-surgical follow-up period was 57.6 months (95% confidence interval [CI] 23.2-109.7 months), and the median survival was longer for the CROSS patients (54 months) than for the FLOT patients (37.2 months) (p = 0.053). The overall 5-years survival was 47% for the entire cohort (48% for the CROSS and 43% for the FLOT patients). The CROSS patients showed a better pathologic response and fewer advanced tumor stages. CONCLUSION: The improved pathologic response after CROSS cannot be translated into longer overall survival. To date, the choice of which neoadjuvant treatment to use can be made only on the basis of clinical parameters and the patient's performance status.

Extension of resection after positive intraoperative pathology during surgery for gastric and gastroesophageal junction adenocarcinoma: a retrospective cohort study.

BACKGROUND: Residual tumor at the resection margins after surgery for gastric and gastroesophageal junction (GEJ) adenocarcinoma is a known prognostic factor. In this single-center, retrospective cohort study in a tertiary referral center, the authors aimed to evaluate the relevance of intraoperative pathology consultation (IOC) and consecutive extension of surgery on patient survival. STUDY DESIGN: Of 737 consecutive patients undergoing (sub)total gastrectomy for gastric or GEJ adenocarcinoma, 679 cases with curative intent surgery between 05/1996 and 03/2019 were included. Patients were categorized into: R0 without further resection (direct R0), R0 after positive IOC and extension of resection (converted R0), and R1. RESULTS: IOC was performed in 242 (35.6%) patients, in 216 (89.3%) at the proximal resection margin. Direct R0-status was achieved in 598 (88.1%), converted R0 in 26 (3.8%) of 38 (5.6%) patients with positive IOC and R1 in 55 (8.1%) patients. The median follow-up was 29 months for surviving patients. 3-year survival rate (3-YSR) was significantly higher for direct R0 compared to converted R0 with 62.3% compared to 21.8% (hazard ratio=0.298; 95% CI=0.186-0.477, P <0.001). 3-YSR was similar between converted R0 and R1 (21.8 vs. 13.3%; hazard ratio =0.928; 95% CI=0.526-1.636, P =0.792). In multivariate analysis, advanced T ( P <0.001), N ( P <0.001), R ( P =0.003), and M1 status ( P <0.001) were associated with worse overall survival. CONCLUSION: IOC and consecutive extended resection for positive resection margins in gastrectomy for the proximal gastric and GEJ adenocarcinoma does not achieve long-term survival benefits in advanced tumor stages.

Mapping the Lymphatic Drainage Pattern of Esophageal Cancer with Near-Infrared Fluorescent Imaging during Robotic Assisted Minimally Invasive Ivor Lewis Esophagectomy (RAMIE)-First Results of the Prospective ESOMAP Feasibility Trial.

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.

Efficacy of endoscopic therapy and long-term outcomes of upper gastrointestinal tumor bleeding in patients with esophageal cancer.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) from malignancies is associated with a poor outcome. Only a small number of studies on gastrointestinal tumor bleeding have been published so far, focusing mainly on bleeding from gastric cancer. Since the information on patients with UGIB from esophageal cancer appears insufficient, this study aimed to present clinical and endoscopic findings, treatment options as well as clinical outcomes such as rebleeding and survival of those patients. METHODS: This retrospective analysis included all patients admitted with UGIB from esophageal cancer at our university hospital during a 10-year period. RESULTS: 45 patients were analyzed of whom 26 (57.8%) already had cancer stage IV at index bleeding. 22 (48.9%) patients presented with hemodynamic instability and 30 (66.7%) patients received blood transfusions. Active bleeding was present in 24 (53.3%) patients, of whom 20 (83.3%) received endoscopic therapy. Successful hemostasis was achieved in 18 (90%) of 20 patients with Argon plasma coagulation used most frequently (52.4%). Early and delayed rebleeding occurred in 5 (12.5%) and 11 (27.5%) of all inoperable patients, respectively. Intake of anticoagulation or anti-platelet drugs were risk factors for delayed rebleeding and the median overall survival after index bleeding was 1.2 months. CONCLUSION: UGIB from esophageal cancer occurred most frequently in advanced tumor stages and was associated with significant blood loss. Even though initial endoscopic therapy was effective, rebleeding occurred in a significant number of patients. Those taking anticoagulants or anti-platelet drugs should be closely monitored for rebleeding. The overall survival after index bleeding was poor.

Two decades of gastric and gastroesophageal junction cancer surgery.

PURPOSE: Diagnosis and treatment of gastric and gastroesophageal junction cancer have undergone many critical changes during the last two decades. We addressed the question of how clinical reality outside of clinical trials has changed for gastric and gastroesophageal junction cancer patients in a European center for upper gastrointestinal surgery. METHODS: In this retrospective cohort study, patients undergoing (sub)total gastrectomy for gastric or gastroesophageal junction adenocarcinoma between 1996 and 2017 in a tertiary upper gastrointestinal center were included. The time was divided into a) before (1996-2006) (pre-CTx) and b) after (2006-2017) (CTx) the MAGIC trial. Data were comprehensively analyzed for demographics, tumor stage, perioperative treatment, surgery, histopathology, and survival rates (SR). RESULTS: 737 patients (32% female) underwent gastrectomy, 255 patients in the pre-CTx era and 482 patients in the CTx era. The median age was 65 years and the median follow-up was 27.5 months for surviving patients. Around 16.9% of patients received neoadjuvant treatment in the pre-CTx era versus 46.3% in the CTx era. The 3-year survival rate (3-YSR) was 46.4% in the pre-CTx and 60.9% in the CTx era (p < 0.001). For pretreated patients, 3-YSR was 39.0% (pre-CTx) versus 55.3% (CTx) (p = 0.168). Survival rate (SR) for locally advanced tumor stages (cT3/cT4) was higher when neoadjuvant therapy was administered (3-YSR: 56.7% vs 40.6%; p = 0.022). There were no significant differences according to sex (p = 0.357), age (p = 0.379), pT category (p = 0.817), pN stage (p = 0.074), cM stage (p = 0.112), Laurén classification (p = 0.158), and SRs (3-YSR: 60.3% vs 59.4%; p = 0.898) between the MAGIC and FLOT regimens. CONCLUSIONS: Survival rates have dramatically improved for gastric cancer patients during the last two decades. MAGIC and FLOT regimens showed similar results in the postsurgical follow-up.

Assessment of pyloric sphincter physiology after Ivor-Lewis esophagectomy using an endoluminal functional lumen imaging probe.

OBJECTIVE OF THE STUDY: The most common functional complication after Ivor-Lewis esophagectomy is the delayed emptying of the gastric conduit (DGCE) for which several diagnostic tools are available, e.g. chest X-ray, upper esophagogastroduodenoscopy (EGD) and water-soluble contrast radiogram. However, none of these diagnostic tools evaluate the pylorus itself. Our study demonstrates the successful measurement of pyloric distensibility in patients with DGCE after esophagectomy and in those without it. METHODS AND PROCEDURES: Between May 2021 and October 2021, we performed a retrospective single-centre study of all patients who had an oncological Ivor-Lewis esophagectomy and underwent our post-surgery follow-up programme with surveillance endoscopies and computed tomography scans. EndoFlip™ was used to perform measurements of the pylorus under endoscopic control, and distensibility was measured at 40 ml, 45 ml and 50 ml balloon filling. RESULTS: We included 70 patients, and EndoFlip™ measurement was feasible in all patients. Successful application of EndoFlip™ was achieved in all interventions (n = 70, 100%). 51 patients showed a normal postoperative course, whereas 19 patients suffered from DGCE. Distensibility proved to be smaller in patients with symptoms of DGCE compared to asymptomatic patients. For 40 ml, 45 ml and 50 ml, the mean distensibility was 6.4 vs 10.1, 5.7 vs 7.9 and 4.5 vs 6.3 mm2/mmHg. The differences were significant for all three balloon fillings. No severe EndoFlip™ treatment-related adverse events occurred. CONCLUSION: Measurement with EndoFlip™ is a safe and technically feasible endoscopic option for measuring the distensibility of the pylorus. Our study shows that the distensibility in asymptomatic patients after esophagectomy is significantly higher than that in patients suffering from DGCE. However, more studies need to be conducted to demonstrate the general use of EndoFlip™ measurement of the pylorus after esophagectomy.

Outcome of endoscopic vacuum therapy for duodenal perforation.

BACKGROUND: Duodenal defects are complex clinical situations, and their management is challenging and associated with high mortality. Besides surgery, endoscopic treatment options exist, but the size and location of the perforation can limit their application. We present a retrospective study, demonstrating a successful application of endoscopic vacuum therapy (EVT) for duodenal leaks. METHODS: We performed a retrospective study of all patients who underwent EVT for duodenal perforations between 2016 and 2021 at two tertiary centers. We analyzed demographic and clinical patient characteristics, surgical outcomes, leak characteristics, sponge-related complications, and success rate. RESULTS: Indications for treatment with EVT in the duodenum consisted of leak after duodenal suture of a perforated ulcer (n = 4), iatrogenic perforation after endoscopic resection (n = 2), iatrogenic perforation during surgery (n = 2), and anastomotic leak after upper gastrointestinal surgery (n = 2). EVT was used as a first-line treatment in seven patients and as a second-line treatment in three patients. EVT was successfully applied in all interventions (n = 10, 100%). Overall, EVT lead to definitive closure of the defects in eight out of ten patients (80%). No severe EVT-related adverse events occurred. CONCLUSION: EVT is safe and technically feasible, so it emerges as a promising endoscopic treatment option for duodenal leaks. However, multidisciplinary collaboration and management are important to reduce the occurrence of postoperative complications, and to improve recovery rates.

Time to endoscopic vacuum therapy-lessons learned after > 150 robotic-assisted minimally invasive esophagectomies (RAMIE) at a German high-volume center.

OBJECTIVE OF THE STUDY: In esophageal surgery, anastomotic leak (AL) remains one of the most severe and critical adverse events after oncological esophagectomy. Endoscopic vacuum therapy (EVT) can be used to treat AL; however, in the current literature, treatment outcomes and reports on how to use this novel technique are scarce. The aim of this study was to evaluate the outcomes of patients with an AL after IL RAMIE and to determine whether using EVT as an treatment option is safe and feasible. MATERIAL AND METHODS: This study includes all patients who developed an Esophagectomy Complications Consensus Group (ECCG) type II AL after IL RAMIE at our center between April 2017 and December 2021. The analysis focuses on time to EVT, duration of EVT, and follow up treatments for these patients. RESULTS: A total of 157 patients underwent an IL RAMIE at our hospital. 21 patients of these (13.4%) developed an ECCG type II AL. One patient died of unrelated Covid-19 pneumonia and was excluded from the study cohort. The mean duration of EVT was 12 days (range 4-28 days), with a mean of two sponge changes (range 0-5 changes). AL was diagnosed at a mean of 8 days post-surgery (range 2-16 days). Closure of the AL with EVT was successful in 15 out of 20 patients (75%). Placement of a SEMS (Self-expandlable metallic stent) after EVT was performed in four patients due to persisting AL. Overall success rate of anastomotic sealing independently of the treatment modality was achieved in 19 out of 20 Patients (95%). No severe EVT-related adverse events occurred. CONCLUSION: This study shows that EVT can be a safe and effective endoscopic treatment option for ECCG type II AL.

Using an Endoluminal Functional Lumen Imaging Probe (EndoFLIP™) to Compare Pyloric Function in Patients with Gastroparesis to Patients After Esophagectomy.

BACKGROUND: Gastroparesis (GP) occurs in patients after upper gastrointestinal surgery, in patients with diabetes or systemic sclerosis and in idiopathic GP patients. As pyloric dysfunction is considered one of the underlying mechanisms, measuring this mechanism with EndoFLIP™ can lead to a better understanding of the disease. METHODS: Between November 2021 and March 2022, we performed a retrospective single-centre study of all patients who had non-surgical GP, post-surgical GP and no sign of GP after esophagectomy and who underwent our post-surgery follow-up program with surveillance endoscopies and further exams. EndoFLIP™ was used to perform measurements of the pylorus, and distensibility was measured at 40 ml, 45 ml and 50 ml balloon filling. RESULTS: We included 66 patients, and successful application of the EndoFLIP™ was achieved in all interventions (n = 66, 100%). We identified 18 patients suffering from non-surgical GP, 23 patients suffering from GP after surgery and 25 patients without GP after esophagectomy. At 40, 45 and 50 ml balloon filling, the mean distensibility in gastroparetic patients was 8.2, 6.2 and 4.5 mm2/mmHg; 5.4, 5.1 and 4.7 mm2/mmHg in post-surgical patients suffering of GP; and 8.5, 7.6 and 6.3 mm2/mmHg in asymptomatic post-surgical patients. Differences between symptomatic and asymptomatic patients were significant. CONCLUSION: Measurement with EndoFLIP™ showed that asymptomatic post-surgery patients seem to have a higher pyloric distensibility. Pyloric distensibility and symptoms of GP seem to correspond.

Integrin beta1 (ITGB1) as a prognostic marker in esophageal adenocarcinoma.

Today, individual prognosis in patients with adenocarcinoma of the esophagus (EAC) is based on post-surgical TNM staging and valid biomarkers are still not implemented. Integrin beta1 (ITGB1) is widely expressed in epithelial cells and promotes cell adhesion and growth. Its impact on tumor progression was described for different tumor entities before, data on its function as a potential biomarker in EAC is not available. Aim of the study is to evaluate the expression level of ITGB1 in a large collective of EAC and its impact on patients´ prognosis. 640 patients with esophageal adenocarcinoma were analyzed immunohistochemically for ITGB1. The data was correlated with long term outcome, clinical, pathological and molecular data (TP53, HER2/neu, c-myc, GATA6, PIK3CA and KRAS). Of 640 patients to be analyzed, 127 (19.8%) showed expression of ITGB1. ITGB1 expression was associated with lymph node metastasis, expression of integrin alphaV and KRAS mutation status. Patients with high ITGB1 expression showed impaired overall survival (22.5 months (95% CI 15.3-29.7 months), vs. 34.1 months (95% CI 25.3-42.4 months), P = 0.024). This effect was particularly evident in the group of patients undergoing primary surgery without prior neoadjuvant therapy (10.2 months (95% CI 1.9-41.7 months) vs. 31.4 months (95% CI 21.1-144.2 months, P = 0.008). ITGB1 was also an independent prognostic marker in multivariable analysis (HR 1.696 (95% CI 1.084-2.653, P = 0.021) in patients that underwent primary surgery. We demonstrate for the first time the prognostic significance of ITGB1 expression in a large EAC patient population.

Management of intra-thoracic anastomotic leakages after esophagectomy: updated systematic review and meta-analysis of endoscopic vacuum therapy versus stenting.

Despite a significant decrease of surgery-related mortality and morbidity, anastomotic leakage still occurs in a significant number of patients after esophagectomy. The two main endoscopic treatments in case of anastomotic leakage are self-expanding metal stents (SEMS) and the endoscopic vacuum therapy (EVT). It is still under debate, if one method is superior to the other. Therefore, we performed a systematic review and meta-analysis of the existing literature to compare the effectiveness and the related morbidity of SEMS and EVT in the treatment of esophageal leakage. We systematically searched for studies comparing SEMS and EVT to treat anastomotic leak after esophageal surgery. Predefined endpoints including outcome, treatment success, endoscopy, treatment duration, re-operation rate, intensive care and hospitalization time, stricture rate, morbidity and mortality were assessed and included in the meta-analysis. Seven retrospective studies including 338 patients matched the inclusion criteria. Compared to stenting, EVT was significantly associated with higher healing (OR 2.47, 95% CI [1.30 to 4.73]), higher number of endoscopic changes (pooled median difference of 3.57 (95% CI [2.24 to 4.90]), shorter duration of treatment (pooled median difference - 11.57 days; 95% CI [- 17.45 to - 5.69]), and stricture rate (OR 0.22, 95% CI [0.08 to 0.62]). Hospitalization and intensive care unit duration, in-hospital mortality rate, rate of major and treatment related complications, of surgical revisions and of esophago-tracheal fistula failed to show significant differences between the two groups. Our analysis indicates a high potential for EVT, but because of the retrospective design of the included studies with potential biases, these results must be interpreted with caution. More robust prospective randomized trials should further investigate the potential of the two procedures.

Subculture and Cryopreservation of Esophageal Adenocarcinoma Organoids: Pros and Cons for Single Cell Digestion.

The lack of suitable translational research models reflecting primary disease to explore tumorigenesis and therapeutic strategies is a major obstacle in esophageal adenocarcinoma (EAC). Patient-derived organoids (PDOs) have recently emerged as a remarkable preclinical model in a variety of cancers. However, there are still limited protocols available for developing EAC PDOs. Once the PDOs are established, the propagation and cryopreservation are essential for further downstream analyses. Here, two different methods have been standardized for EAC PDOs subculture and cryopreservation, i.e., with and without single cell digestion. Both methods can reliably obtain appropriate cell viability and are applicable for a diverse experimental setup. The current study demonstrated that subculturing EAC PDOs with single cell digestion is suitable for most experiments requiring cell number control, uniform density, and a hollow structure that facilitates size tracking. However, the single cell-based method shows slower growth in culture as well as after re-cultivation from frozen stocks. Besides, subculturing with single cell digestion is characterized by forming hollow structures with a hollow core. In contrast, processing EAC PDOs without single cell digestion is favorable for cryopreservation, expansion, and histological characterization. In this protocol, the advantages and disadvantages of subculturing and cryopreservation of EAC PDOs with and without single cell digestion are described to enable researchers to choose an appropriate method to process and investigate their organoids.

Robot-assisted minimally invasive esophagectomy (RAMIE) vs. hybrid minimally invasive esophagectomy: propensity score matched short-term outcome analysis of a European high-volume center.

INTRODUCTION: Transthoracic esophagectomy is a highly complex and sophisticated procedure with high morbidity rates and a significant mortality. Surgical access has consistently become less invasive, transitioning from open esophagectomy to hybrid esophagectomy (HE) then to totally minimally invasive esophagectomy (MIE), and most recently to robot-assisted minimally invasive esophagectomy (RAMIE), with each step demonstrating improved patient outcomes. Aim of this study with more than 600 patients is to complete a propensity-score matched comparison of postoperative short-term outcomes after highly standardized RAMIE vs. HE in a European high volume center. PATIENTS AND METHODS: Six hundred and eleven patients that underwent transthoracic Ivor-Lewis esophagectomy for esophageal cancer between May 2016 and May 2021 were included in the study. In January 2019, we implemented an updated robotic standardized anastomotic technique using a circular stapler and ICG (indocyanine green) for RAMIE cases. Data were retrospectively analyzed from a prospectively maintained IRB-approved database. Outcomes of patients undergoing standardized RAMIE from January 2019 to May 2021 were compared to our overall cohort from May 2016-April 2021 (HE) after a propensity-score matching analysis was performed. RESULTS: Six hundred and eleven patients were analyzed. 107 patients underwent RAMIE. Of these, a total of 76 patients underwent a robotic thoracic reconstruction using the updated standardized circular stapled anastomosis (RAMIE group). A total of 535 patients underwent HE (Hybrid group). Seventy patients were propensity-score matched in each group and analysis revealed no statistically significant differences in baseline characteristics. RAMIE patients had a significantly shorter ICU stay (p = 0.0218). Significantly more patients had no postoperative complications (Clavien Dindo 0) in the RAMIE group [47.1% vs. 27.1% in the HE group (p = 0.0225)]. No difference was seen in lymph node yield and R0 resection rates. Anastomotic leakage rates when matched were 14.3% in the hybrid group vs. 4.3% in the RAMIE group (p = 0.07). CONCLUSION: Our analysis confirms the safety and feasibility of RAMIE and HE in a large cohort after propensity score matching. A regular postoperative course (Clavien-Dindo 0) and a shorter ICU stay were seen significantly more often after RAMIE compared to HE. Furthermore it shows that both procedures provide excellent short-term oncologic outcomes, regarding lymph node harvest and R0 resection rates. A randomized controlled trial comparing RAMIE and HE is still pending and will hopefully contribute to ongoing discussions.

[GERD and Barett: Natural Course of One Disease - Update Diagnostics and Therapy]. / GERD und Barrett.

GERD and Barett: Natural Course of One Disease - Update Diagnostics and Therapy Abstract. The gastroesophageal reflux disease (GERD) represents a relatively frequent condition, which clinically includes orocervical, thoracic and abdominal complaints. GERD is defined as pathological gastroesophageal acidic reflux, which consecutively leads to mucosal damage of the esophagus such as reflux esophagitis. The most common symptom of GERD is heartburn but GERD symptoms include various complaints, which need to be considered in diagnosis and therapy. Besides endoscopy, barium swallow, pH metry and manometry are counted among the routine diagnostics for GERD patients. For therapy, dietary and lifestyle measures come along with medication such as proton pump inhibitors (PPI) as daily medication and antacids on demand. It has been demonstrated that anti-reflux surgery, minimally invasive fundoplication or magnet augmentation of the lower esophageal sphincter, produces an equal and lasting effect on GERD compared to PPI. Surgery is preferred in case of large hiatal hernia of voluminous reflux. Success of therapy is given if esophageal exposure to acid is reduced, which shows in remission of esophagitis or which can be demonstrated through pH-metry control. Additionally, improvement of quality of life stands in the focus of GERD treatment, which is to be considered for every therapeutic step. Barrett esophagus represents a subtype of GERD with rising incidence in Western countries. As potential precancerous lesion, the Barrett's esophagus is to be diagnosed early and needs to undergo a risk stratified surveillance in order to prevent dysplasia or carcinoma. Patients with low grade dysplasia, high grade dysplasia or early Barrett's carcinoma should be treated endoscopically. Soon artificial intelligence might contribute to improvement of Barrett's esophagus surveillance and treatment.