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Early stage carcinomas of the esophagus are histologically differentiated into adenocarcinomas and squamous cell carcinomas and subdivided into mucosal (m1-3) and submucosal (sm1-3) carcinomas depending on the infiltration depth. While the prevalence of lymph node metastases in mucosal carcinomas is very low, the probability of lymph node metastases increases from submucosal infiltration with increasing depth. According to the current German S3 guidelines endoscopic resection is the recommended treatment strategy for mucosal adenocarcinoma without histological risk factors (lymphatic invasion [L1], venous invasion [V1], poorly differentiated [>G2], microscopic residual disease [R1] at the deep resection margin). For superficial submucosal infiltration (sm1) without histological risk factors endoscopic resection can also be carried out, whereby in this case the guidelines make a stronger recommendation for esophagectomy. For squamous cell carcinoma endoscopic resection is indicated for an infiltration depth up to middle layer mucosal carcinoma (m2) without histological risk factors. Outside of these criteria an esophageal resection should always be carried out. The surgical gold standard is a subtotal abdominothoracic esophagectomy with two-field lymphadenectomy. Alternative procedures are total esophagectomy in proximal esophageal carcinoma and transhiatal extended gastrectomy for carcinoma of the cardia. Limited proximal or distal esophageal resections can be performed in proximal or distal mucosal carcinoma without the possibility of endoscopic resection; however, partial resections are not superior in terms of functional results and are not oncologically equivalent due to limited lymphadenectomy. Minimally invasive procedures show good oncological results and reduce the morbidity of radical esophagectomy. Reduced morbidity might be an argument for surgical resection in borderline cases between endoscopic and surgical resection. Ösophagusfrühkarzinome werden histologisch in Adeno- und Plattenepithelkarzinome und abhängig von der Tiefeninfiltration in m1–3(Mukosa)-und sm1–3(Submukosa)-Karzinome unterteilt. Während die Prävalenz von Lymphknotenmetastasen bei Mukosakarzinomen sehr gering ist, steigt die Wahrscheinlichkeit von Lymphknotenmetastasen ab Infiltration der Submukosa mit zunehmender Tiefe an. Nach der aktuellen deutschen S3-Leitlinie wird bei intramukosalen Adenokarzinomen ohne histologische Risikofaktoren (Lymphgefäßinvasion [L1], Blutgefäßinvasion [V1], gering differenziert [>G2], mikroskopischer Residualtumor [R1] basal) eine endoskopische Resektion empfohlen. Bei oberflächlicher Submukosainfiltration (sm1) ohne histologische Risikofaktoren kann ebenfalls eine endoskopische Resektion erfolgen, wobei die Leitlinie in diesem Fall eine stärkere Empfehlung für eine Ösophagektomie gibt. Bei Plattenepithelkarzinomen ist bis zur Infiltrationstiefe m2 und ohne histologische Risikofaktoren eine endoskopische Resektion indiziert. Außerhalb dieser Kriterien sollte immer eine Ösophagusresektion erfolgen. Das chirurgische Standardverfahren ist eine subtotale abdominothorakale Ösophagektomie mit Zweifeldlymphadenektomie. Alternative Verfahren sind die totale Ösophagektomie bei proximalen Karzinomen und die transhiatal erweiterte Gastrektomie bei Kardiakarzinomen. Limitierte proximale oder distale Ösophagusresektionen können bei proximal oder distal gelegenen und endoskopisch nicht resezierbaren Mukosakarzinomen durchgeführt werden, sind aber der radikalen Resektion funktionell nicht überlegen und onkologisch aufgrund der eingeschränkten Lymphadenektomie nicht gleichwertig. Minimalinvasive Verfahren zeigen gute onkologische Ergebnisse und vermindern die Morbidität der radikalen Ösophagusresektion. Dies sollte in Zukunft bei der Entscheidungsfindung in Grenzfällen zwischen endoskopischer und chirurgischer Resektion berücksichtigt werden.

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. 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). 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). 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.

IMPORTANCE: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. RESULTS: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P

In den aktuell gültigen deutschen S3-Leitlinien wird bei metastasierten Magenkarzinomen und metastasierten Adenokarzinomen des ösophagogastralen Übergangs eine chirurgische Therapie in der Regel nicht empfohlen. In der täglichen Praxis findet jedoch schon heute in Einzelfällen eine Erweiterung der Indikation statt, sodass auch solche Patienten in kurativer Zielsetzung im Rahmen eines multimodalen Therapiekonzepts ausgedehnt und radikal operiert werden. Diese Arbeit stellt die wissenschaftliche Rationale eines solchen Vorgehens anhand der vorliegenden Literatur und unter Einbeziehung moderner, multimodaler Konzepte dar und verweist auf Kriterien, die für eine Erweiterung der Indikation gegeben sein sollten. Bislang existieren lediglich retrospektive Untersuchungen und wenige aktuelle Metaanalysen, die eine chirurgische Behandlung bei metastasierten Adenokarzinomen rechtfertigen. Es liegen zudem erste Ergebnisse der als Abstract publizierten FLOT-3-Studie vor, die eine Patientensubgruppe identifizieren konnte, die von einer Resektion im metastasierten Stadium profitiert. Ob die chirurgische Therapie zukünftig ein fester Bestandteil in der Behandlung des begrenzt metastasierten Adenokarzinoms des Magens und des Ösophagus wird, müssen große prospektiv randomisierte Studien wie die RENAISSANCE/FLOT-5-Studie zeigen. In the current German S3 guidelines surgical treatment is not recommended for metastatic gastric cancer or metastatic adenocarcinoma of the esophagogastric junction; however, in routine practice the indications can be extended so that there may be occasions in which radical surgical intervention for specific individuals may be appropriate as part of a multimodal therapy with curative intent. This article presents the scientific rationale of such an approach based on the available literature considering modern, multimodal therapy concepts including criteria to be met for radical surgery. Currently only retrospective trials and limited current meta-analysis data are available for justifying surgical treatment for metastatic adenocarcinoma. The recently published initial results of the FLOT-3 study identified a patient subgroup that benefits from a resection even though metastasis has occurred. Whether surgical therapy will become an integral part of the treatment of limited metastatic adenocarcinoma of the stomach and esophagus in the future, has to be demonstrated by large prospective randomized studies, such as the RENAISSANCE/FLOT-5 study.

Background: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection.Methods: In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres. Patients with resectable gastric or gastro-oesophageal junction cancer who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both were randomly assigned (1:1) to either three preoperative and three postoperative 3-week cycles of intravenous epirubicin 50 mg/m2on day 1, intravenous cisplatin 60 mg/m2on day 1, and either fluorouracil 200 mg/m2as continuous intravenous infusion or capecitabine 1250 mg/m2orally (two doses of 625 mg/m2per day) on days 1 to 21 (ECF/ECX group) or four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m2, intravenous oxaliplatin 85 mg/m2, intravenous leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2as a 24 h infusion, all on day 1 (FLOT group). Randomisation was done centrally with an interactive web-response system based on a sequence generated with blocks (block size 2) stratified by Eastern Cooperative Oncology Group performance status, location of primary tumour, age, and nodal status. No masking was done. Central assessment of pathological regression was done according to the Becker criteria. The primary endpoint was pathological complete regression (tumour regression grade TRG1a) and was analysed in the modified intention-to-treat population, defined as all patients who were randomly assigned to treatment excluding patients who had surgery but did not provide resection specimens for central evaluation. The study (including the phase 3 part) has completed enrolment, but follow-up is ongoing and this is an interim analysis. The trial is registered with ClinicalTrials.gov, number NCT01216644. Findings: Between Aug 18, 2010, and Aug 10, 2012, 300 patients (152 patients in the ECF/ECX group; 148 patients in the FLOT group) were enrolled into the phase 2 part of the study, 265 of whom (137 in the ECF/ECX group; 128 in the FLOT group) were assessable on a modified intention-to-treat basis. 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 patients in the ECF/ECX group were given all planned preoperative cycles of treatment. FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX (20 [16%; 95% CI 10-23] of 128 patients vs eight [6%; 3-11] of 137 patients; p=0·02). 44 (40%) of 111 patients in the ECF/ECX group and 30 (25%) of 119 patients in the FLOT group had at least one serious adverse event involving a perioperative medical or surgical complication. The most common non-surgical grade 3-4 adverse events were neutropenia (52 [38%] of 137 patients in the ECF/ECX group vs 67 [52%] of 128 patients in the FLOT group), leucopenia (28 [20%] vs 36 [28%]), nausea (23 [17%] vs 12 [9%]), infection (16 [12%] vs 15 [12%]), fatigue (19 [14%] vs 11 [9%]), and vomiting (13 [10%] vs four [3%]). Interpretation: Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-eosophageal junction adenocarcinoma.

Background: Esophagectomy with gastric tube reconstruction and extended transhiatal gastrectomy with Roux-en-Y reconstruction are alternative procedures in current therapeutic concepts for adenocarcinoma of the esophagogastric junction (AEG). The impact of these operations on long-term health-related quality of life (HRQL) is incompletely understood.Methods: Patients with cancer-free survival of at least 24 months after esophagectomy (ESO) or extended gastrectomy (GAST) for AEG were identified from a prospectively maintained database. EORTC questionnaires were sent out to assess health-related general (QLQ-C30) and cancer-specific (OG-25) quality of life. Numeric scores were calculated for each conceptual area and compared with those of healthy reference populations.Results: 123 patients (ESO n = 71; GAST n = 52) completed the self-rated questionnaires. HRQL was consistently lower in surgical patients (GAST and ESO) compared with healthy reference populations. Also, there was a general trend for a better HRQL in GAST compared with ESO patients. This trend was statistically significant for physical function (p = 0.04), dyspnea (p = 0.02), and reflux (p = 0.03). Subgroup analysis revealed no significant differences between patients with or without prior neoadjuvant therapy.Conclusions: After mid- and long-term follow-up, HRQL after extended gastrectomy with Roux-en-Y reconstruction is superior to that after esophagectomy and gastric tube reconstruction. Improved HRQL after gastrectomy is mainly due to less pulmonary and reflux-related symptoms. Our findings may influence the choice of the surgical strategy for patients with AEG.