Die Inzidenz der Adenokarzinome des Ösophago-gastralen Übergangs (AEG) zeigt eine starke Zunahme in den letzten Dekaden mit einer hohen Tumor-bedingten Sterblichkeit. Die radikale Resektion ist der Hauptbestandteil jedweder Therapie. Es ist bis dato unklar, ob die abdomino-thorakale Resektion im Sinne eines Zweihöhleneingriffes der transhiatal erweiterten Gastrektomie (TH) über einen rein abdominellen Zugang überlegen ist. Die hier vorliegende Untersuchung hat zum Ziel, die perioperativen Ergebnisse sowie das Langzeitüberleben dieser beiden operativen Modalitäten zu vergleichen.

Introduction: It is still a matter of debate whether subtotal esophagectomy via a right thoracoabdominal approach (RTA) or extended gastrectomy using a transhiatal-abdominal approach (TH) is the favorable technique in the treatment of Siewert type II esophago-gastric junction adenocarcinoma (EJA). Materials and methods: Patients undergoing RTA or TH for EJA at our institution between 2000 and 2013 were extracted from a prospective database. Of 270 patients 91 (33.7%) underwent RTA and 179 (66.3%) were treated by TH. Differences in baseline characteristics, 30d mortality and complications were investigated using the chi 2-test or exact testing. Survival analysis was performed using the Kaplan-Meier method and log rank testing. Median survival and hazard ratios were calculated and multivariable analysis of predictors was performed using a Cox model. Confounders were balanced using propensity score matching (PSM). Results: No significant difference between the two procedures was detected regarding overall-survival (OS) and disease-free survival (DFS). 30d mortality rates were 1.1% in the RTA group and 4.5% in the TH group (p = 0.134). Morbidity was 34.1% in the RTA and 24.6% in the TH group (p = 0.006). Cox regression analysis identified age, ASA class and UICC stage as independent prognostic factors for OS. After PSM survival curves (OS + PFS) showed no significant difference. Conclusion: The present study could not detect a difference between RTA and TH from the oncologic point of view; RTA was not associated with higher 30d mortality. RTA for Siewert Type II EJA is justified whenever the oral tumor margin cannot be safely reached via a transhiatal approach. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background: Patients who suffer from malignant tumors of the esophagus and esophagogastric junction have 5-year survival rates of up to 83%, something that is documented in the early stages of cancer. Too often, weight loss is an underestimated sign for patients suffering from cancer on the upper gastrointestinal tract. Weight loss is associated with different adverse outcomes. Even after tumor resection, malnutrition remains a severe problem that still affects long-term disease free survivors.Material and methods: This study included the clinical courses of 205 patients suffering from cancer of the esophagus or the esophagogastric junction who were operated on between July 2007 and December 2009. On admission, the nutrition risk score was evaluated. Follow-up data were collected routinely. The aim of the underlying study was to show the prevalence of an elevated nutrition risk score (NRS) and to demonstrate its influence on perioperative mortality and morbidity. Furthermore, the relevance of an elevated nutrition risk score on the postoperative survival was analyzed.Results: More than a third (35.8%) of the patients included in this study had a nutrition risk score of at least three. A preoperative elevated nutrition risk score did not have a significant influence on perioperative morbidity or on 30-days mortality rate. In patients with early tumor stage UICC stage I a/b, an elevated risk score of 3 or more had a significant influence on postoperative survival. In contrast, in advanced tumor stages an increased NRS did not have a significant negative influence on survival within both UICC II a/b and UICC IIII a/b. Conclusions: Further studies are required to demonstrate whether a nutritional intervention can improve the survival rates of patients suffering from malignant tumors within the esophagus and in whom an operation has to be performed.Keywords: Weight loss, esophageal cancer, NRS

Neoadjuvant chemotherapy (neoCTx) improves the prognosis of patients (pts) with localized esophagogastric adenocarcinoma (EGC). This retrospective analysis evaluates the predictive value of histopathology on neoCTX. 461 pts with locally advanced EGC (T2/T3 and/or N+) who received neoCTx followed by surgery between 2000 and 2013 were analyzed from four institutions: 314 (68.1%) with intestinal, 94 (20.4%) with diffuse and 53 (11.5%) with mixed histological type according to Laurens classification. Taxane-platinum-fluoropyrimidine (5FU) based triplet or platinum-FU based doublet neoCTX was administered preoperatively to 185 (40.1%) and 276 (59.9%) pts, respectively. Pathological response evaluation according to Becker was performed locally. Median patients' age was 63 years, 79.8% were male. Tumors were localized in the stomach in 32.5% and EG junction in 67.5%. 96.5% had clinical stage T3/T4 and 93.7% were N+. With a median follow up of 39.6 months (mos), median overall survival (OS) was 66.4 mos. For pts with intestinal type, median OS was 77.9 mos compared to 34.6 mos for diffuse (p < 0.001) and 64.4 mos for mixed type (p = 0.657). Median disease-free survival (DFS) was 48.7 mos for intestinal compared to 17.3 for diffuse (p = 0.002) and 29.2 mos for mixed type (p = 0.327). Pathological complete response (pCR) was 9.1% and combined complete und subtotal response (pCR + pSR) was 26.7% for all pts. 25/261 (9.6%) of pts with intestinal type had a pCR compared to 4/65 pts (6.2%) with diffuse and 4/37 (10.8%) with mixed type. pCR + pSR rate was significantly higher in intestinal (30.3%) compared to diffuse (15.4%; p = 0.024), but not compared to mixed type (21.6%; p = 0.373). Pts with pCR had a mean OS of 124.1 compared to 89.4 mos for pts with other regression grades (p = 0.004). For pts with intestinal type, 3-yr OS was 87.5% with pCR and 68.4% with other regression grades (p = 0.091). All pts with diffuse and mixed type and pCR were alive after 3 yrs compared to 41.9% and 68.9% with other regression grades (p = 0.043). Pathologic complete response is associated with long-term survival in EGC independent of histopathological subtype. Efforts to increase the rate of pCR by more effective neoCTX are warranted.

Tumor budding has prognostic significance in many carcinomas and is defined as the presence of detached isolated single cells or small cell clusters up to 5 cells at the invasion front (peritumoral budding [PTB]) or within the tumor (intratumoral budding [ITB]). For esophageal adenocarcinomas (EACs), there are currently only few data about the impact of this morphological feature. We investigated tumor budding in a large collective of 200 primarily resected EACs. Pancytokeratin staining was demonstrated to be superior to hematoxylin and eosin staining for the detection of buds with substantial to excellent interobserver agreement and used for subsequent analysis. PTB and ITB were scored across 10 high-power fields (HPFs). The median count of tumor buds was 130/10 HPFs for PTB (range, 2-593) and 80/10 HPFs for ITB (range, 1-656). PTB and ITB correlated significantly with each other (r = 0.9; P < .001). High PTB and ITB rates were seen in more advanced tumor categories (P < .001 each); tumors with lymph node metastases (P < .001/P = .002); and lymphatic, vascular, and perineural invasion and higher tumor grading (P < .001 each). Survival analysis showed an association with worse survival for high-grade ITB (P = .029) but not PTB (P = .385). However, in multivariate analysis, lymph node and resection status, but not ITB, were independent prognostic parameters. In conclusion, PTB and ITB can be observed in EAC to various degrees. High-grade budding is associated with aggressive tumor phenotype. Assessment of tumor budding, especially ITB, may provide additional prognostic information about tumor behavior and may be useful in specific cases for risk stratification of EAC patients.

In the last years, the impact of weight loss in patients with malignant tumors has come more and more into the focus of clinical research, as the occurrence of weight loss is often associated with a reduced survival. Weight loss can be a hint for metastases in patients suffering from malignant tumors; furthermore, these patients are usually not able to be treated with chemotherapy. The aim of the study was to show the influence of weight loss and an elevated nutrition risk score on survival following tumor resection in patients suffering from gastric cancer. In 99 patients in whom a gastrectomy due to gastric cancer was performed, the nutrition risk score was calculated and its influence on mortality, morbidity and survival was analyzed. Of the included patients, 45 % of the patients gave a history of weight loss; they had significantly more often a NRS ≥ 3. In UICC stage 1a/b, a NRS ≥ 3 was associated with a significantly reduced survival compared to patients with a NRS < 3. In early tumor stages (UICC 1a/b), a NRS ≥ 3 was associated with a significantly reduced survival, while in progressed tumor stage, the influence of a poor NRS was not significant. This seems to show that in progressed stages in patients with gastric cancer, the influence of a reduced NRS is negligible.

Background: Oesophageal adenocarcinoma or Barrett's adenocarcinoma (EAC) is increasing in incidence and stratification of prognosis might improve disease management. Multi-colour Fluorescence in situ hybridisation (FISH) investigating ERBB2, MYC, CDKN2A and ZNF217 has recently shown promising results for the diagnosis of dysplasia and cancer using cytological samples.Methods: To identify markers of prognosis we targeted four selected gene loci using multi-colour FISH applied to a tissue microarray containing 130 EAC samples. Prognostic predictors (P1, P2, P3) based on genomic copy numbers of the four loci were statistically assessed to stratify patients according to overall survival in combination with clinical data.Results: The best stratification into favourable and unfavourable prognoses was shown by P1, percentage of cells with less than two ZNF217 signals; P2, percentage of cells with fewer ERBB2- than ZNF217 signals; and P3, overall ratio of ERBB2-/ZNF217 signals. Median survival times for P1 were 32 vs 73 months, 28 vs 73 months for P2; and 27 vs 65 months for P3. Regarding each tumour grade P2 subdivided patients into distinct prognostic groups independently within each grade, with different median survival times of at least 35 months.Conclusions: Cell signal number of the ERBB2 and ZNF217 loci showed independence from tumour stage and differentiation grade. The prognostic value of multi-colour FISH-assays is applicable to EAC and is superior to single markers.

Background: Oesophageal adenocarcinomas often show resistances to chemotherapy (CTX), therefore, it would be of high interest to better understand the mechanisms of resistance. We examined the expression of heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) in pretherapeutic biopsies of oesophageal adenocarcinomas to assess their potential role in CTX response.Methods: Ninety biopsies of locally advanced adenocarcinomas before platin/5-fluorouracil (FU)-based CTX were investigated by reverse phase protein arrays (RPPAs), immunohistochemistry (IHC) and quantitative RT-PCR.Results: CTX response strongly correlated with survival (P = 0.001). Two groups of tumours with specific protein expression patterns were identified by RPPA: Group A was characterised by low expression of HSP90, HSP27 and p-HSP27((Ser15, Ser78, Ser82)) and high expression of GRP78, GRP94, HSP70 and HSP60; Group B exhibited the inverse pattern. Tumours of Group A were more likely to respond to CTX, resulting in histopathological tumour regression (P = 0.041) and post-therapeutic down-categorisation from cT3 to ypT0-T2 (P = 0.040). High HSP60 protein (IHC) and mRNA expression were also associated with tumour down-categorisation (P = 0.016 and P = 0.004).Conclusion: Our findings may enhance the understanding of CTX response mechanisms, might be helpful to predict CTX response and might have translational relevance as they highlight the role of potentially targetable cellular stress proteins in the context of CTX response.

In dieser Arbeit wird der Einfluss des chirurgischen Zugangs und der neoadjuvanten Therapie auf die Entwicklung eines Chylothorax (CT) nach Oesophagusresektion bei Patienten mit Adenokarzinom des oesophago-gastralen Übergangs (AEG I/II) und Plattenepithelkarzinom des Oesophagus analysiert und ein Behandlungsalgorithmus dargestellt. Der Auswertung zugrunde liegen Zentrumsdaten mit 1856 operierten Patienten sowie eine Literaturanalyse (Medline 1982–2011, n=9794 Patienten). Die statistische Auswertung erfolgte mittels Fisher's Test (Signifikanzniveau 0,05), Überlebenszeiten wurden mit der Kaplan-Meier Methode und log- rank Test bestimmt. Die Chylothorax Rate unseres Zentrums lag bei 2% (n=39). Eine Revisions- Operation wurde in 69% der Patienten durchgeführt, 31% wurden konservativ behandelt. Zwischen dem transthorakalen und transhiatalen Zugangsweg zeigte sich kein signifikanter Unterschied in der Entwicklung eines CT. Beim Vergleich der Gruppen cervikale vs. intrathorakale Anastomose zeigte sich in der cervikalen Gruppe eine deutlich höhere CT Rate (AEG: 4% vs. 0%, RR=9,96, 95%-CI: (1,69, 58,52), p=0,018). Neoadjuvante Therapiekonzepte führten zu keiner vermehrten CT Entwicklung (RR=0,92, 95%-CI: (0,46, 1,84), p>0,999). Im 8- Jahres Follow-up ergab sich ein verbessertes Überleben der re- operierten (45%) gegenüber der konservativ behandelten (30%) Patienten. 12 Studien wurden bei der systematischen Literaturanalyse ausgewertet. Die CT Rate lag bei 2,6% (0,9–9,0%), 5 Studien favorisierten ein primär operatives (70–100%) und 5 Studien ein primär konservatives (58–72%) Therapiekonzept mit gleichen Mortalitätsraten. Zwischen dem transthorakalen und transhiatalen Zugangsweg zeigt sich kein statistisch signifikanter Unterschied, allerdings war die CT Rate in letzterer Gruppe leicht erhöht (n=2 vs. 4 Studien).

Hintergrund: Gewichtsverlust ist ein häufiges Symptom bei Patienten mit malignen Erkrankungen im oberen Gastrointestinaltrakt. Dieser ist bedingt durch eine reduzierte Möglichkeit der Nahrungsaufnahme wegen Stenosen, eingeschränkter Motilität und Inappetenz. Zusätzlich lässt sich bei Tumorpatienten ein erhöhter Ruheenergieumsatz nachweisen.

The new International Union Against Cancer (UICC) classification in its seventh version has been out since January 2010. It included some important changes for the classification of esophageal and gastric carcinomas compared to the sixth version.For esophageal carcinomas this means a more detailed subdivision of the T and N stages which should, together with the newly introduced prognostic grouping (separate for squamous cell carcinoma and adenocarcinoma) enable a more precise and individualized prediction of prognosis. Another innovation is that positive lymph nodes in the esophageal drainage area, including celiac axis nodes and paraesophageal lymph nodes in the neck, are classified as regional lymph node metastases rather than distant metastatic spread, irrespective of tumor location. Hereby the lymphadenectomy specimen should include >= 6 lymph nodes (LN).The most controversial improvement is that adenocarcinomas of the esophagogastric junction (AEG) are all classified as esophageal carcinomas. This should acknowledge the similar prognosis of AEGs and esophageal carcinomas, which is worse compared to gastric carcinomas in other locations.Regarding the classification of gastric carcinomas the T-stages were redefined and lymph node staging (N-stage) was refined to allow for a better prediction of prognosis. The lymphadenectomy specimen after gastrectomy should hereby include >= 16 LNs.As the primary aim of the UICC classification is a preferably accurate prognosis prediction, the impact on a surgeon's therapeutic decision is low. For decisions regarding the type of resection the endoscopic AEG classification with the aim of R0 resections is still the instrument of choice. The value of the UICC classification is that it enables sophisticated comparisons between different treatment regimens and strategies.

Einleitung: Der Behandlungsalgorithmus und die Prognose werden bei Patienten mit Frühkarzinomen des oberen Gastrointestinaltraktes durch das Lymphknotenmetastasierungsrisiko bestimmt.

BACKGROUND AND STUDY AIMS:The endoscopic-laparoscopic interdisciplinary training entity (ELITE) is one of the first training models for the training of natural orifice transluminal endoscopic surgery (NOTES) and conventional laparoscopic and endoscopic skills. The current study was designed to assess whether the effect of surgical simulation with an ex vivo training unit is relevant to surgical practice in the operating room and who, in particular, might benefit from this training.PATIENTS AND METHODS:A group of 30 participants (gastroenterologists, laparoscopists, and novices) performed a standardized NOTES cholecystectomy via a trans-sigmoidal approach. Fifteen participants performed the cholecystectomy following training with ELITE and 15 participants performed the procedures without previous training. The parameters studied were task times, quality and safety of the surgical procedure, and subjective evaluation of the ELITE trainer as a teaching model.RESULTS:During the training courses all participants showed a significant learning curve, with a total time needed on the first pass of 32 minutes vs. 18 minutes for the fourth pass ( P < 0.001). For the cholecystectomy in the pig model, participants with prior training needed less time to complete the procedure than participants without training. In the group without training, more complications/difficulties occurred than in the group with prior training (16 vs. 8). The video analyses by two independent NOTES experts showed an inter-rater validity of 1.0. Subjective evaluation showed that participants considered ELITE to be a suitable and recommendable simulator for NOTES.CONCLUSIONS:The ELITE model is suitable for training in the NOTES cholecystectomy procedure. This type of simulator training leads to fewer intraoperative complications.

Seit Januar 2010 liegt die neue TNM-Klassifikation der UICC (International Union Against Cancer) in ihrer 7. Auflage vor. Für die Klassifikation der Ösophagus- und Magenkarzinome haben sich im Vergleich zur 6. Auflage einige entscheidende Änderungen ergeben.

Hintergrund: Beim Pankreaskarzinom hat ein Gewichtsverlust, der 10% des stabilen Körpergewichts überschreitet, einen signifikanten Einfluss auf das Überleben. Gewichtsverlust lässt sich bei bis zu 80% der Patienten mit malignem Tumoren im Gastrointestinaltrakt nachweisen.