A senior surgical resident can safely perform complex esophageal cancer surgery after surgical mentoring program-experience of a European high-volume center.

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.

[The "surgical track"-Innovative approaches to counteract the shortage of young recruits in surgery]. / Der "Surgical Track" ­ innovative Ansätze gegen den Nachwuchsmangel in der Chirurgie.

Surgery faces significant challenges resulting from changes in medical education and the declining attractiveness of the surgical career path for aspiring doctors in the western world. For example, students' expectations of their future workplace have changed, with issues such as career planning uncertainties, an unbalanced work-life balance, and a lack of compatibility of family and occupation becoming increasingly more relevant. The entry of Generation Z into the workforce will also impact surgery. Although women comprise the largest proportion of graduates only a few opt for a career in surgery. The resulting shortage of young surgeons will negatively impact medical care in German surgical units. Intense competition for talents is already emerging in all medical specialties. Thus, hospitals and academic centers are taking various measures to counteract the impending staff shortage, such as summer schools or scholarships with work commitments. Furthermore, regional funding laws are being established. In addition, as there is a declining interest in surgical training, particularly during the course of medical studies, early integration of surgical skills is crucial to counteract this trend. For this reason, we have developed the "surgical track", designed to offer targeted innovative teaching concepts to get students attracted to surgery at an early stage. The "surgical track" is based on virtual reality (VR) and robotics. Students can practice operations and emergency scenarios through VR simulations and complete practical exercises with robotic systems. High-quality training concepts such as the "surgical track" can help to promote enthusiasm for surgery and impart knowledge at the same time, even if the long-term benefits still need to be evaluated. Through virtual simulations, robotic surgery and innovative teaching, students gain insights into visceral surgery that combine theoretical understanding and practical experience.

Predicting the HER2 status in oesophageal cancer from tissue microarrays using convolutional neural networks.

BACKGROUND: Fast and accurate diagnostics are key for personalised medicine. Particularly in cancer, precise diagnosis is a prerequisite for targeted therapies, which can prolong lives. In this work, we focus on the automatic identification of gastroesophageal adenocarcinoma (GEA) patients that qualify for a personalised therapy targeting epidermal growth factor receptor 2 (HER2). We present a deep-learning method for scoring microscopy images of GEA for the presence of HER2 overexpression. METHODS: Our method is based on convolutional neural networks (CNNs) trained on a rich dataset of 1602 patient samples and tested on an independent set of 307 patient samples. We additionally verified the CNN's generalisation capabilities with an independent dataset with 653 samples from a separate clinical centre. We incorporated an attention mechanism in the network architecture to identify the tissue regions, which are important for the prediction outcome. Our solution allows for direct automated detection of HER2 in immunohistochemistry-stained tissue slides without the need for manual assessment and additional costly in situ hybridisation (ISH) tests. RESULTS: We show accuracy of 0.94, precision of 0.97, and recall of 0.95. Importantly, our approach offers accurate predictions in cases that pathologists cannot resolve and that require additional ISH testing. We confirmed our findings in an independent dataset collected in a different clinical centre. The attention-based CNN exploits morphological information in microscopy images and is superior to a predictive model based on the staining intensity only. CONCLUSIONS: We demonstrate that our approach not only automates an important diagnostic process for GEA patients but also paves the way for the discovery of new morphological features that were previously unknown for GEA pathology.

Effect of phone call distraction on the performance of medical students in an OSCE.

BACKGROUND: The usage of smartphones in the daily clinical routine is an essential aspect however it seems that they also present an important distractor that needs to be evaluated. The aim of this prospective study was the evaluation of the influence of phone calls as distractors on the performance levels of medical students during an objective structured clinical examination (OSCE), simulating the normal clinical practice. METHODS: As the goal of an OSCE presents the examination of clinical skills of medical students in a realistic setting, more than 100 students recruited from the university hospital of Cologne participated in either OSCE I or II. During the OSCE I intravenous cannulation was simulated while OSCE II simulated an acute abdominal pain station. Participants had to perform each of these stations under two circumstances: a normal simulated OSCE and an OSCE station with phone call distraction. Their performance during both simulations was then evaluated. RESULTS: In OSCE I students achieved significantly more points in the intravenous cannulation station if they were not distracted by phone calls (M=6.44 vs M=5.95). In OSCE II students achieved significantly more points in the acute abdominal pain station if they were not distracted by phone calls (M=7.59 vs M=6.84). While comparing only those students that completed both stations in OSCE I/II participating students achieved significantly more points in both OSCE I and II if they were not distracted by phone calls. CONCLUSION: The presented data shows that phone call distraction decreases the performance level of medical students during an OSCE station. Therefore, it is an indicator that distraction especially for younger doctors should be held to a minimum. On a second note distraction should be integrated in the medical education system as it plays an important role in clinical routine.

Post-transplant Malignancies Show Reduced T-cell Abundance and Tertiary Lymphoid Structures as Correlates of Impaired Cancer Immunosurveillance.

PURPOSE: An increased risk to develop cancer is one of the most challenging negative side effects of long-term immunosuppression in organ transplant recipients and impaired cancer immunosurveillance is assumed as underlying mechanism. This study aims to elucidate transplant-related changes in the tumor immune microenvironment (TME) of cancer. EXPERIMENTAL DESIGN: Data from 123 organ transplant recipients (kidney, heart, lung, and liver) were compared with historic data from non-immunosuppressed patients. Digital image analysis of whole-section slides was used to assess abundance and spatial distribution of T cells and tertiary lymphoid structures (TLS) in the TME of 117 tumor samples. Expression of programmed cell death 1 ligand 1 (PD-L1) and human-leucocyte-antigen class I (HLA-I) was assessed on tissue microarrays. RESULTS: We found a remarkably reduced immune infiltrate in the center tumor (CT) regions as well as the invasive margins (IM) of post-transplant cancers. These differences were more pronounced in the IM than in the CT and larger for CD8+ T cells than for CD3+ T cells. The Immune-score integrating results from CT and IM was also lower in transplant recipients. Density of TLS was lower in cancer samples of transplant recipients. The fraction of samples with PD-L1 expression was higher in controls whereas decreased expression of HLA-I was more common in transplant recipients. CONCLUSIONS: Our study demonstrates the impact of immunosuppression on the TME and supports impaired cancer immunosurveillance as important cause of post-transplant cancer. Modern immunosuppressive protocols and cancer therapies should consider the distinct immune microenvironment of post-transplant malignancies.

Gender benefit in laparoscopic surgical performance using a 3D-display system: data from a randomized cross-over trial.

BACKGROUND: The use of 3D technique compared to high-resolution 2D-4K-display technique has been shown to optimize spatial orientation and surgical performance in laparoscopic surgery. Since women make up an increasing amount of medical students and surgeons, this study was designed to investigate whether one gender has a greater benefit from using a 3D compared to a 4K-display system. METHODS: In a randomized cross-over trial, the surgical performance of male and female medical students (MS), non-board certified surgeons (NBCS), and board certified surgeons (BCS) was compared using 3D- vs. 4K-display technique at a minimally invasive training parkour with multiple surgical tasks and repetitions. RESULTS: 128 participants (56 women, 72 men) were included. Overall parkour time in seconds was 3D vs. 4K for all women 770.7 ± 31.9 vs. 1068.1 ± 50.0 (p < 0.001) and all men 664.5 ± 19.9 vs. 889.7 ± 31.2 (p < 0.001). Regarding overall mistakes, participants tend to commit less mistakes while using the 3D-vision system, showing 10.2 ± 1.1 vs. 13.3 ± 1.3 (p = 0.005) for all women and 9.6 ± 0.7 vs. 12.2 ± 1.0 (p = 0.001) for all men. The benefit of using a 3D system, measured by the difference in seconds, was for women 297.3 ± 41.8 (27.84%) vs. 225.2 ± 23.3 (25.31%) for men (p = 0.005). This can be confirmed in the MS group with 327.6 ± 65.5 (35.82%) vs. 249.8 ± 33.7 (32.12%), p = 0.041 and in the NBCS group 359 ± 52.4 (28.25%) vs. 198.2 ± 54.2 (18.62%), p = 0.003. There was no significant difference in the BCS group. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 2D-4K technique for both women and men. The greatest 3D benefit was found for women with less surgical experience. As a possible result of surgical education, this gender specific difference disappears with higher grade of experience. Using a 3D-vision system could facilitate surgical apprenticeship, especially for women.

[Impact of COVID-19 on oncological surgery of the upper gastrointestinal tract]. / Auswirkungen von COVID-19 auf die onkologische Chirurgie des oberen Gastrointestinaltrakts.

BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) pandemic imposed limitations for elective surgery, impacting the associated hospital standards worldwide. As certain treatment windows must be adhered to in oncological surgery, the limited intensive care unit (ICU) capacity had to be critically distributed in order to do justice to both acutely ill and oncology patients. This manuscript summarizes the impact of COVID-19 on the management of oncological surgery of the upper gastrointestinal tract and particularly esophageal surgery in German medical centers. MATERIAL AND METHODS: A survey of German centers for esophageal surgery was performed on the impact of COVID-19 on operative management for esophageal surgery during the first lockdown. After inspection, assessment, critical analysis and interpretation, the results were compared to the international literature. RESULTS AND DISCUSSION: Initial recommendations of international societies warned for caution and restraint regarding interventions of the upper gastrointestinal tract that were not absolutely necessary. Oncological surgery should be performed under strict restrictions, especially only after negative testing for COVID-19 and only with sufficiently available personal protective equipment for the personnel. Furthermore, minimally invasive procedures were preferably not recommended. In diseases with alternative treatment options, such as definitive chemoradiotherapy of esophageal squamous cell carcinoma, these should be given priority when possible. In the further development of the pandemic, it was shown that due to a high standardization of preoperative management, postoperative results comparable to pre-pandemic times could be achieved particularly with respect to the diagnostics of infections.

Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (n = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (p = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.

Gastrointestinal function testing model using a new laryngopharyngeal pH probe (Restech) in patients after Ivor-Lewis esophagectomy.

BACKGROUND: There is no established correlation between 24-h esophageal pH-metry (Eso-pH) and the new laryngopharyngeal pH-monitoring system (Restech) as only small case series exist. Eso-pH was not designed to detect laryngopharyngeal reflux (LPR) and Restech may detect LPR better. We have previously published a dataset using the two techniques in a large patient collective with gastroesophageal reflux disease. Anatomically, patients after esophagectomy were reported to represent an ideal human reflux model as no reflux barrier exists. AIM: To use a human reflux model to examine our previously published correlation in these patients. METHODS: Patients after Ivor Lewis esophagectomy underwent our routine follow-up program with surveillance endoscopies, computed tomography scans and further exams following surgery. Only patients with a complete check-up program and reflux symptoms were offered inclusion into this prospective study and evaluated using Restech and simultaneous Eso-pH. Subsequently, the relationship between the two techniques was evaluated. RESULTS: A total of 43 patients from May 2016 - November 2018 were included. All patients presented with mainly typical reflux symptoms such as heartburn (74%), regurgitation (84%), chest pain (58%), and dysphagia (47%). Extraesophageal symptoms such as cough, hoarseness, asthma symptoms, and globus sensation were also present. Esophageal 24-hour pH-metry was abnormal in 88% of patients with a mean DeMeester Score of 229.45 [range 26.4-319.5]. Restech evaluation was abnormal in 61% of cases in this highly selective patient cohort. All patients with abnormal supine LPR were also abnormal for supine esophageal reflux measured by conventional Eso-pH. CONCLUSION: Patients following esophagectomy and reconstruction with gastric interposition can ideally serve as a human reflux model. Interestingly, laryngopharyngeal reflux phases occur mainly in the upright position. In this human volume-reflux model, results of simultaneous esophageal and laryngopharyngeal (Restech) pH-metry showed 100% correlation as being explicable by one of our reflux scenarios.

Learning curve of surgical novices using the single-port platform SymphonX: minimizing OR trauma to only one 15-mm incision.

BACKGROUND: Minimally invasive single-port surgery is always associated with large incisions up to 2-3 cm, complicated handling due to the lack of triangulation, and instrument crossing. The aim of this prospective study was to report how medical students without any laparoscopic experience perform several laparoscopic tasks (rope pass, paper cut, peg transfer, recapping, and needle threading) with the new SymphonX single-port platform and to examine the learning curves in comparison to the laparoscopic multi-port technique. METHODS: A set of 5 laparoscopic skill tests (Rope Pass, Paper cut, Peg Transfer, Recapping, Needle Thread) were performed with 3 repetitions. Medical students performed all tests with both standard laparoscopic instruments and the new platform. Time and errors were recorded. RESULTS: A total of 114 medical students (61 females) with a median age of 23 years completed the study. All subjects were able to perform the skill tests with both standard laparoscopic multi-port and the single-port laparoscopic system and were able to significantly improve their performance over the three trials for all five tasks-rope pass (p < 0.001), paper cut (p < 0.001), peg transfer (p < 0.001), needle threading (p < 0.001), and recapping (p < 0.001). In 3 out of 5 tasks, medical students performed the tasks faster using the standard multi-port system-rope pass (p < 0.001), paper cut (p < 0.001), and peg transfer (p < 0.001). In the task recapping, medical students performed the task faster using the new single-port system (p = 0.003). In the task needle threading, there was no significant difference between the standard multi-port system and the new single-port system (p > 0.05). CONCLUSION: This is the first study analyzing learning curves of the commercially available SymphonX platform for abdominal laparoscopic surgery when used by novices. The learning curve and the error rate are promising.

True single-port cholecystectomy with ICG cholangiography through a single 15-mm trocar using the new surgical platform "symphonX": first human case study with a commercially available device.

BACKGROUND: Minimally invasive single-port surgery is often associated with large incisions up to 2-3 cm, complicated handling due to the lack of triangulation, and instrument crossing. Aim of this prospective study was to perform true single-port surgery (cholecystectomy) without the use of assisting trocars using a new surgical platform that allows for triangulation incorporating robotic features, and to measure the perioperative outcome and cosmetic results. METHODS: As the first European site after FDA and CE-mark approval, the new device has been introduced to our academic center. In patients with cholecystitis and cholecystolithiasis, the operation was performed through only one 15-mm trocar. For patients safety, intraoperative cholangiography using intravenous ICG and a standard Stryker 1588 system was routinely performed. RESULTS: Symphonx was used in n = 12 patients for abdominal surgery (6 females, mean age 42.5 [30-77], mean BMI 26.2 [19.3-38.9]. A total of 8 patients underwent surgery using no additional ports besides the 15-mm trocar; in the remaining patients, one assisting instrument (3-5 mm) was used. Mean OR time was 107 [72-221] minutes. The postoperative course was uneventful in 11 patients; in one patient, a seroma at the surgical site required interventional drainage 1 month postoperatively. No intraoperative complications occurred. CONCLUSION: This is the first human case series using the commercially available symphonX platform for abdominal laparoscopic surgery and the first series using the system without assisting instruments. Laparoscopic cholecystectomy in patients with cholecystitis and cholecystolithiasis using the symphonX platform through only one 15-mm trocar is feasible, safe, and more cost-efficient compared to robotic platforms.

FABP1 and FABP3 Have High Predictive Values for Renal Replacement Therapy in Patients with Acute Kidney Injury.

BACKGROUND/AIMS: Early initiation of renal replacement therapy (RRT) is recommended in order to improve the clinical outcome of patients who develop an acute kidney injury (AKI). However, markers that guide an early RRT initiation do not really exist currently. METHODS: Urine and serum samples were prospectively collected from 120 AKI patients. Depending on the necessity of initiating RRT, patients were divided into 2 different groups: dialysis (n = 52) and non-dialysis (n = 68). RESULTS: Comparative urinary proteomic analyses identified 4 different proteins (fatty acid binding proteins 1 and 3 (FABP1 and FABP3), ß-2-microglobulin (B2M), cystatin-M (CST6)) that discriminate AKI patients with high risk for RRT. Western blot analysis confirmed the proteomics data for FABP1 and FABP3 but not for B2M and CST6. Validation analysis confirmed that the FABP1 and FABP3 fulfilled the requirement of functioning as markers for AKI patients with risk to dialysis (p < 0.001). CONCLUSION: The release of high amounts of FABP1 and FABP3 in urine of AKI patients could serve as a diagnostic/prognosis marker for RRT initiation in these patients.

Predictors of renal replacement therapy in acute kidney injury.

BACKGROUNDS: Criteria that may guide early renal replacement therapy (RRT) initiation in patients with acute kidney injury (AKI) currently do not exist. METHODS: In 120 consecutive patients with AKI, clinical and laboratory data were analyzed on admittance. The prognostic power of those parameters which were significantly different between the two groups was analyzed by receiver operator characteristic curves and by leave-1-out cross validation. RESULTS: Six parameters (urine albumin, plasma creatinine, blood urea nitrogen, daily urine output, fluid balance and plasma sodium) were combined in a logistic regression model that estimates the probability that a particular patient will need RRT. Additionally, a second model without daily urine output was established. Both models yielded a higher accuracy (89 and 88% correct classification rate, respectively) than the best single parameter, cystatin C (correct classification rate 74%). CONCLUSIONS: The combined models may help to better predict the necessity of RRT using clinical and routine laboratory data in patients with AKI.