Combined regression score predicts outcome after neoadjuvant treatment of oesophageal cancer.

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.

Introduction of laparoscopic nephrectomy for autosomal dominant polycystic kidney disease as the standard procedure.

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder and accounts for 5-10% of all cases of kidney failure. 50% of ADPKD patients reach kidney failure by the age of 58 years requiring dialysis or transplantation. Nephrectomy is performed in up to 20% of patients due to compressive symptoms, renal-related complications or in preparation for kidney transplantation. However, due to the large kidney size in ADPKD, nephrectomy can come with a considerable burden. Here we evaluate our institution's experience of laparoscopic nephrectomy (LN) as an alternative to open nephrectomy (ON) for ADPKD patients. MATERIALS AND METHODS: We report the results of the first 12 consecutive LN for ADPKD from August 2020 to August 2021 in our institution. These results were compared with the 12 most recent performed ON for ADPKD at the same institution (09/2017 to 07/2020). Intra- and postoperative parameters were collected and analyzed. Health related quality of life (HRQoL) was assessed using the SF36 questionnaire. RESULTS: Age, sex, and median preoperative kidney volumes were not significantly different between the two analyzed groups. Intraoperative estimated blood loss was significantly less in the laparoscopic group (33 ml (0-200 ml)) in comparison to the open group (186 ml (0-800 ml)) and postoperative need for blood transfusion was significantly reduced in the laparoscopic group (p = 0.0462). Operative time was significantly longer if LN was performed (158 min (85-227 min)) compared to the open procedure (107 min (56-174 min)) (p = 0.0079). In both groups one postoperative complication Clavien Dindo ≥ 3 occurred with the need of revision surgery. SF36 HRQol questionnaire revealed excellent postoperative quality of life after LN. CONCLUSION: LN in ADPKD patients is a safe and effective operative procedure independent of kidney size with excellent postoperative outcomes and benefits of minimally invasive surgery. Compared with the open procedure patients profit from significantly less need for transfusion with comparable postoperative complication rates. However significant longer operation times need to be taken in account.

The ISCON-trial protocol: laparoscopic ischemic conditioning prior to esophagectomy in patients with esophageal cancer and arterial calcifications.

BACKGROUND: Anastomotic leakage is the most important surgical complication following esophagectomy. A major cause of leakage is ischemia of the gastric tube that is used for reconstruction of the gastrointestinal tract. Generalized cardiovascular disease, expressed by calcifications of the aorta and celiac axis stenosis on a pre-operative CT scan, is associated with an increased risk of anastomotic leakage. Laparoscopic ischemic conditioning (ISCON) aims to redistribute blood flow and increase perfusion at the anastomotic site by occluding the left gastric, left gastroepiploic and short gastric arteries prior to esophagectomy. This study aims to assess the safety and feasibility of laparoscopic ISCON in selected patients with esophageal cancer and concomitant arterial calcifications. METHODS: In this prospective single-arm safety and feasibility trial based upon the IDEAL recommendations for surgical innovation, a total of 20 patients will be included recruited in 2 European high-volume centers for esophageal cancer surgery. Patients with resectable esophageal carcinoma (cT1-4a, N0-3, M0) with "major calcifications" of the thoracic aorta accordingly to the Uniform Calcification Score (UCS) or a stenosis of the celiac axis accordingly to the modified North American Symptomatic Carotid Endarterectomy Trial (NASCET) score on preoperative CT scan, who are planned to undergo esophagectomy are eligible for inclusion. The primary outcome variables are complications grade 2 and higher (Clavien-Dindo classification) occurring during or after laparoscopic ISCON and before esophagectomy. Secondary outcomes include intra- and postoperative complications of esophagectomy and the induction of angiogenesis by biomarkers of microcirculation and redistribution of blood flow by measurement of indocyanine green (ICG) fluorescence angiography. DISCUSSION: We hypothesize that in selected patients with impaired vascularization of the gastric tube, laparoscopic ISCON is feasible and can be safely performed 12-18 days prior to esophagectomy. Depending on the results, a randomized controlled trial will be needed to investigate whether ISCON leads to a lower percentage and less severe course of anastomotic leakage in selected patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03896399 . Registered 4 January 2019.

Two-stage hybrid Ivor-Lewis esophagectomy as surgical strategy to reduce postoperative morbidity for high-risk patients.

BACKGROUND: Ivor-Lewis esophagectomy (ILE) is the standard surgical care for esophageal cancer patients but postoperative morbidity impairs quality of life and reduces long-term oncological outcome. Two-stage ILE separating the abdominal and thoracic phase into two distinct surgical procedures has proven to enhance microcirculation of the gastric conduit and therefore most likely reduces complications. However, two-stage ILE has not been evaluated systematically in selected groups of patients scheduled for this procedure. This investigation aims to demonstrate the feasibility of two-stage ILE in high-risk patients. PATIENTS AND METHODS: In this retrospective analysis of data obtained from a prospective database, a consecutive series of 275 hybrid ILE (hILE) were included. Patients were divided into two groups based on one- or two-stage hILE. Postoperative complications were assessed according to ECCG (Esophageal Complication Consensus Group) criteria and compared using the Clavien-Dindo score. Indication for two-stage esophagectomy was classified as pre- or intraoperative decision. RESULTS: 34 out of 275 patients (12.7%) underwent two-stage hILE. Patients of the two-stage group were significantly older. In 21 of 34 patients (61.8%) the decision for a two-stage procedure was made prior to esophagectomy, in 13 (38.2%) patients intraoperatively after completion of the laparoscopic gastric mobilization. The most frequent preoperative reason to select the two-stage procedure was a stenosis of the coeliac trunc and superior mesenteric artery (n = 10). The predominant cause for an intraoperative change of strategy was a laparoscopically diagnosed hepatic fibrosis/cirrhosis (n = 5).Overall morbidity and major' complications (CD > IIIa) were comparable for both groups (11.7% in both groups). The overall anastomotic leak rate was 12.4% and was non-significant lower for the two-stage procedure. CONCLUSION: Two-stage hILE is a feasible concept to individualize the surgical treatment of patients with well-defined clinical risk factors for postoperative morbidity. It can also be applied after completion of the abdominal phase of IL esophagectomy without compromising the patient safety.

Navigated laparoscopic microwave ablation of tumour mimics in pig livers: a randomized ex-vivo experimental trial.

BACKGROUND: In order to efficiently perform laparoscopic microwave ablation of liver tumours precise positioning of the ablation probe is mandatory. This study evaluates the precision and ablation accuracy using the innovative laparoscopic stereotactic navigation system CAS-One-SPOT in comparison to 2d ultrasound guided laparoscopic ablation procedures. METHODS: In a pig liver ablation model four surgeons, experienced (n = 2) and inexperienced (n = 2) in laparoscopic ablation procedures, were randomized for 2d ultrasound guided laparoscopic or stereotactic navigated laparoscopic ablation procedures. Each surgeon performed a total of 20 ablations. Total attempts of needle placements, time from tumor localization till beginning of ablation and ablation accuracy were analyzed. RESULTS: The use of the laparoscopic stereotactic navigation system led to a significant reduction in total attempts of needle placement. The experienced group of surgeons reduced the mean number of attempts from 2.75 ± 2.291 in the 2d ultrasound guided ablation group to 1.45 ± 1.191 (p = 0.0302) attempts in the stereotactic navigation group. Comparable results could be observed in the inexperienced group with a reduction of 2.5 ± 1.50 to 1.15 ± 0.489 (p = 0.0005). This was accompanied by a significant time saving from 101.3 ± 112.1 s to 48.75 ± 27.76 s (p = 0.0491) in the experienced and 165.5 ± 98.9 s to 66.75 ± 21.96 s (p < 0.0001) in the inexperienced surgeon group. The accuracy of the ablation process was hereby not impaired as postinterventional sectioning of the ablation zone revealed. CONCLUSION: The use of a stereotactic navigation system for laparoscopic microwave ablation procedures of liver tumors significantly reduces the attempts and time of predicted correct needle placement for novices and experienced surgeons without impairing the accuracy of the ablation procedure.

Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial.

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.

ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.

Stenosis of the celiac trunk is associated with anastomotic leak after Ivor-Lewis esophagectomy.

Transthoracic esophagectomy with gastric tube formation is the surgical treatment of choice for esophageal cancer. The surgical reconstruction induces changes of gastric microcirculation, which are recognized as potential risk factors of anastomotic leak. This prospective observational study investigates the association of celiac trunk (TC) stenosis with postoperative anastomotic leak. One hundred fifty-four consecutive patients with esophageal cancer scheduled for Ivor-Lewis esophagectomy were included. Preoperative staging computed tomography (CT) was used to identify TC stenosis. Any narrowing of the lumen due to atherosclerotic changes was classified as stenosis. Percentage of stenotic changes was calculated using the North American Symptomatic Carotid Endarterectomy Trial formula. Multivariable analysis was used to identify possible risk factors for leak. The overall incidence of TC stenosis was 40.9%. Anastomotic leak was identified in 15 patients (9.7%). Incidence of anastomotic leak in patients with stenosis was 19.4% compared to 2.3% in patients without stenosis. Incidence of stenosis in patients with leak was 86.7% (13 of 15 patients) and significantly higher than 38.8% (54 of 139 patients) in patients without leak (P < 0.001). There was a significant difference in median degree of TC stenosis (50.0% vs 39.4%; P = 0.032) in patients with and without leak. In the multivariable model, TC stenosis was an independent risk factor for anastomotic leak (odds ratio: 5.98, 95% CI: 1.58-22.61). TC stenosis is associated with postoperative anastomotic leak after Ivor-Lewis esophagectomy. Routine assessment of TC for possible stenosis is recommended to identify patients at risk.

Impact of the Weekday of Surgery on Outcome in Gastric Cancer Patients who Underwent D2-Gastrectomy.

BACKGROUND: The impact of the weekday of surgery in major elective cases of the upper-GI has been discussed controversially. The objective of this study was to assess whether weekday of surgery influences outcome in patients undergoing D2-gastrectomy. MATERIALS AND METHODS: Patients who underwent D2-gastrectomy for gastric adenocarcinoma between 1996 and 2016 were included. Weekday of surgery was recognized, and subgroups were analyzed regarding clinical and histopathological differences. Survival analysis was performed based on weekday of surgery, and early weekdays (Monday-Tuesday) were compared with late weekdays (Wednesday-Friday). RESULTS: In total, 460 patients, 71% male and 29% female, were included into analysis. The median age was 65 years. Distribution to each weekday was equal and ranged from 86 cases (Wednesday) to 96 cases (Tuesday). The pT, pN and M category and the rate of patients who underwent neoadjuvant treatment did not show significant differences (p = 0.641; p = 0.337; p = 0.752; p = 0.342, respectively). The subgroups did not differ regarding the number of dissected lymph nodes and rate of R-1/2 resections (p = 0.590; p = 0.241, respectively). Survival analysis showed a median survival of 43 months (95% CI 31-55 months), and there was no single weekday or a combination of weekdays (Mon/Tue vs Wed/Thu/Fri) with a significant favorable or worse outcome (p = 0.863; p = 0.30, respectively). The outcome did not differ regarding mortality within the first 90 days after surgery (p = 0.948). CONCLUSIONS: The present study does not show any evidence for a significant impact of weekday of surgery on short- and long-term outcome of patients undergoing gastrectomy for gastric adenocarcinoma.

Simultaneous laryngopharyngeal pH monitoring (Restech) and conventional esophageal pH monitoring-correlation using a large patient cohort of more than 100 patients with suspected gastroesophageal reflux disease.

24-hour esophageal pH-metry is not designed to detect laryngopharyngeal reflux (LPR). The new laryngopharyngeal pH-monitoring system (Restech) may detect LPR better. There is no established correlation between these two techniques as only small case series exist. The aim of this study is to examine the correlation between the two techniques with a large patient cohort. All patients received a complete diagnostic workup for gastroesophageal reflux including symptom evaluation, endoscopy, 24-hour pH-metry, high resolution manometry, and Restech. Consecutive patients with suspected gastroesophageal reflux and disease-related extra-esophageal symptoms were evaluated using 24-hour laryngopharyngeal and concomitant esophageal pH-monitoring. Subsequently, the relationship between the two techniques was evaluated subdividing the different reflux scenarios into four groups. A total of 101 patients from December 2013 to February 2017 were included. All patients presented extra-esophageal symptoms such as cough, hoarseness, asthma symptoms, and globus sensation. Classical reflux symptoms such as heartburn (71%), regurgitation (60%), retrosternal pain (54%), and dysphagia (32%) were also present. Esophageal 24-hour pH-metry was positive in 66 patients (65%) with a mean DeMeester Score of 66.7 [15-292]. Four different reflux scenarios were detected (group A-D): in 39% of patients with abnormal esophageal pH-metry, Restech evaluation was normal (group A, n = 26, mean DeMeester-score = 57.9 [15-255], mean Ryan score = 2.6 [2-8]). In 23% of patients with normal pH-metry (n = 8, group B), Restech evaluation was abnormal (mean DeMeester-score 10.5 [5-13], mean Ryan score 63.5 [27-84]). The remaining groups C and D showed corresponding results. Restech evaluation was positive in 48% of cases in this highly selective patient cohort. As demonstrated by four reflux scenarios, esophageal pH-metry and Restech do not necessarily need to correspond. Especially in patients with borderline abnormal 24-hour pH-metry, Restech may help to support the decision for or against laparoscopic anti-reflux surgery.

A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition.

BACKGROUND: Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy. METHODS: Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg-1 body weight) or high (5 mg kg-1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared. RESULTS: ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy. CONCLUSIONS: Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

[Teamwork in the operating theatre: the German Observational Teamwork Assessment for Surgery (OTAS-D) and its first application in Germany]. / Interdisziplinäre Teamarbeit im Operationssaal: Das Beobachtungsverfahren OTAS-D und erste Anwendungsergebnisse aus Deutschland.

BACKGROUND: The quality of surgical teamwork contributes to performance of the operating theatre team, service quality and patient safety in surgery. Observational tools are a feasible and reliable way to capture and evaluate teamwork in the operating theatre (OT). We introduce the German version of the Observational Teamwork Assessment for Surgery (OTAS-D) and present the first observational results from German OTs. METHODS: Quality of surgical teamwork was assessed with observational teamwork assessment for surgery (OTAS-D). It evaluates five dimensions of OT teamwork: communication, coordination, cooperation/backup behaviour, leadership, and team monitoring/situation awareness. Each dimension is evaluated for each profession (surgical, nursing, and anaesthesia team) as well for each phase of the procedure (pre-, intra-, and post-operative). We observed n = 63 procedures, mainly in abdominal/general and orthopaedic surgery. Additionally, all OT team members scored their individual evaluation of the intra-operative teamwork (standardised 1-item questions). RESULTS: The OTAS-D evaluations showed meaningful results and differences for the OT professions as well as across the different phases of the procedures. Overall, a medium to good level of the OT teamwork was observed. There were no differences in regard to type of surgery (minimally invasive vs. open) or surgical specialties. With an increased coordination of the surgical team we observed a significantly increased cooperation of the nursing team (r = 0.36, p = 0.004). Concerning the OT staffs self-reports, the surgical and nursing teams reported higher scores for quality of surgical teamwork during the procedure than their anaesthesia team members. No significant relationships between observed quality of OT teamwork and self-reports were found. CONCLUSIONS: The German version of OTAS-D is a psychometrically robust method to capture the quality of teamwork in operating theatres. It enables the analyses of teamwork between the surgical, nursing and anaesthesia professions in acute surgical care. Limitations of the first application results are considered. Finally, potential applications for surgical teaching, research and quality management are discussed.

[Structured teaching of surgery the LMU model in Munich]. / Strukturierte Lehre in der Chirurgie am Beispiel des Humanmedizinstudiums an der Ludwig-Maximilians-Universität München.

The medical curriculum (MeCuM) of the Ludwig Maximilian University (LMU) in Munich is a dynamic curriculum aimed to support the learning process of all students with their different learning styles. It is based on interactive, activating teaching methods in order to increase students' interest, and on repetitive evaluation of teaching units to modify the teaching in order to meet students' needs and wishes. In this context the teaching of surgery at our faculty takes place. Besides interdisciplinary lessons where diseases are taught in cooperation with our colleagues from internal medicine, indications for surgery, complications and consequences of surgery for the patients are analysed in PBL tutorials, online cases, bedside teachings and practical teaching on the ward. Surgical skills like suturing are demonstrated in videos, practiced on models or during practical teaching on the ward and they are tested in OSCEs. During the "praktisches Jahr", the students in the last year of their medical studies are supposed to apply their practical skills besides repeating theoretical knowledge in order to pass the final examination. For this purpose they are taught in a revision course called "LMU-StaR" (revision course for the Staatsexamen). In this paper we describe in detail the teaching of surgery at our faculty.

[Management and treatment of liver injuries after blunt abdominal trauma]. / Management und Versorgung von Leberverletzungen nach stumpfem Bauchtrauma.

The liver is involved in about 20% of cases of blunt abdominal trauma. The management of liver trauma has changed significantly in the past three decades towards conservative treatment. Up to 80% of all liver trauma patients can now be successfully treated by nonoperative management. Decisive for this is the adequate screening and assessment of the patient and the injury pattern as well as the provision of the appropriate infrastructure. Hemodynamically unstable patients require immediate exploratory surgery. In hemodynamically stable patients, a contrast-enhanced computed tomography (CT) should be performed. If active bleeding is detected angiographic imaging and embolization should be performed to stop the bleeding. Even after initially successful conservative management of liver trauma, subsequent complications can occur that make surgical inpatient treatment necessary.

Laparoscopic ischemic conditioning of the stomach prior to esophagectomy induces gastric neo-angiogenesis.

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.

Mismatch repair deficiency, chemotherapy and survival for resectable gastric cancer: an observational study from the German staR cohort and a meta-analysis.

PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

Clinical implication of targeting of cancer stem cells.

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers.

[Non-curable tumours of the female genital tract: therapeutic options in bowel stenosis and bleeding]. / Inoperable Genitaltumoren der Frau: Therapeutische Optionen bei Darmstenose und -blutung.

BACKGROUND: Tumours of the female genital tract are often diagnosed at an advanced stage or re-lapse after initial curative therapy. Ovarian cancer is in particular associated with peritoneal carcinomatosis or local tumour progression entailing different intestinal complications. MATERIAL AND METHODS: Based on our own results and a systemic PubMed search, different intestinal complications in non-curable tumours of the female genital tract were defined and different surgical and non-surgical therapeutic options were analysed. RESULTS: Stenosis of the small bowel is often caused by direct infiltration of the tumour. Peritoneal carcinomatosis or postoperative abdominal adhesions may lead to an acute or even more often chronic recurrent obstruction. The rectum or sigmoid colon is in particular affected by stenosis caused by tumour masses within the pelvis, occurring fistulas or direct tumour infiltration which may lead to bleeding complications or a large bowel obstruction. Radiation-induced abdominal adhesions or stenosis of the small bowel as well as radiation-induced chronic proctocolitis are further common abdominal complications. Special attention with regard to a well balanced indication towards surgical, oncological or conservative management must be given in the palliative setting of the genital tract. CONCLUSION: In particular the dictum of "primum nihil nocere" has to be followed in consideration of the patient's declared intention, the patient's prognosis, general condition, psychological strain as well as the expected complications.

[Statement of the surgical working group upper gastrointestinal tract (CAOGI) and the quality committee of the German Society for General and Visceral Surgery (DGAV) on the modified minimum caseload requirements for esophagus resection]. / Stellungnahme der Chirurgischen Arbeitsgemeinschaft oberer Gastrointestinaltrakt (CAOGI) sowie der Qualitätskommission der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV) zu der geänderten Mindestmenge für die Ösophagusresektion.

A positive association between the number of operations and postoperative hospital mortality, the so-called caseload-treatment result relation, has been confirmed many times in the literature; however, the definition of the underlying volumes is not uniform. The number of 26 resections/year/institution, which has now been established by the Federal Joint Committee as the future minimum caseload requirement, is discussed in this statement of the surgical working group upper gastrointestinal tract (CAOGI) and the quality committee of the German Society for General and Visceral Surgery (DGAV), taking the treatment situation in Germany and the current data situation into account.

[Esophagotracheal and esophagobronchial fistulas]. / Ösophagotracheobronchiale Fisteln.

Esophagobronchial and esophagotracheal fistulas are rare but complex diseases with a heterogeneous spectrum of underlying etiologies. Common causes are locally advanced tumors of the esophagus and larynx, traumatic perforation from the esophageal or tracheal side as well as postoperative fistulas. The management of esophagotracheal and esophagobronchial fistulas always involves different health care providers and in most cases patients require a multidisciplinary treatment on the intensive care unit. The therapeutic concept primarily depends on the underlying cause, localization and size of the fistula but decision making is also influenced by the severity of the course of sepsis and the extent of the respiratory dysfunction. Endoscopic management with esophageal and/or tracheobronchial stenting is the most common treatment. Surgical reconstructive procedures are predominantly reserved for patients with a treatment refractory fistula or a septic multiple organ failure. The prognosis is particularly influenced by the underlying disease.

[Evidence in minimally invasive oncological surgery of the esophagus]. / Evidenz in der minimal-invasiven onkologischen Chirurgie des Ösophagus.

BACKGROUND: Thoracoabdominal esophagectomy still plays a major role in the oncological treatment for esophageal cancer. Minimally invasive procedures were developed to reduce the high rate of postoperative morbidity and mortality without negatively affecting the oncological outcome. OBJECTIVE: What evidence supports minimally invasive oncological surgery of the esophagus? Do patients benefit from minimally invasive esophagectomy compared to an open approach? Is the reduction of surgical access trauma specifically advantageous? MATERIAL AND METHODS: Review, evaluation and critical analysis of the international literature. RESULTS: A reduction in postoperative morbidity by decreasing surgical trauma was confirmed by three prospective randomized clinical trials, while showing at least similar oncological outcomes. Diverse retrospective analyses and meta-analyses also came to the same result. CONCLUSION: A minimization of surgical access trauma during thoracoabdominal esophagectomy reduces postoperative morbidity compared to conventional open surgery. Recent evidence suggests that oncological outcomes are not altered depending on the surgical approach.