ZusammenfassungNeuroendokrine Neoplasien (NEN) umfassen eine seltene Tumorentität mit heterogener Biologie, Prognose und therapeutischen Optionen. In Zusammenhang mit der kürzlichen Publikation der ersten deutschen Leitlinie zur Diagnostik und Therapie von NEN erfolgte die Analyse der Kohorte des Deutschen NET-Registers der Deutschen Gesellschaft für Endokrinologie (DGE). Hierzu wurden 2686 Fälle extrahiert und ihre Patientencharakteristika wie Alter, Geschlecht, Primärtumorlokalisation, Grading und Staging dargestellt sowie das Gesamtüberleben berechnet. Zusätzlich wurden die systemischen Behandlungsstrategien in den beiden größten Untergruppen, NEN des Dünndarms und Pankreas, im Stadium der Metastasierung analysiert.Die Verteilung der Primärtumoren, die histopathologische Charakterisierung, das Tumorstadium sowie das Gesamtüberleben waren vergleichbar mit den Ergebnissen internationaler Registerstudien. Somatostatinanaloga (SSA) und die Peptid-Rezeptor-Radionuklid-Therapie (PRRT) waren die häufigsten systemischen Therapieverfahren bei Dünndarm-NEN. Hingegen wurde eine Chemotherapie – in Übereinstimmung mit der neuen Leitlinie – vor allem bei pankreatischen NEN eingesetzt und kam in der Erstlinie in ähnlicher Frequenz wie die SSA-Therapie bzw. in der Zweitlinie ähnlich häufig wie eine PRRT zum Einsatz. Prognostisch relevante Parameter waren die WHO-Klassifikation 2010 und das TNM-Staging.Die aktuelle Analyse des deutschen NET-Registers charakterisiert damit eine multizentrische, interdisziplinäre, deutschlandweite Kohorte von NEN-Patienten und beschreibt die angewendeten systemischen Therapieverfahren, das Gesamtüberleben und die prognostische Bedeutung der WHO-Klassifikation 2010 sowie des TNM-Stadiums.

Background and ObjectivesThe management of R1-resected adenocarcinoma of the esophagogastric junction (AEG) is unclear. We aimed to identify risk factors and prevalence of R1 resections, their recurrence and prognosis, and efficacy of postoperative therapy.MethodsA single center cohort of 766 consecutive patients undergoing curative intent resection for AEG was analyzed retrospectively.ResultsR1-resection rate was 13%. Poorer tumor differentiation, higher T-, N-, and UICC/AJCC-stages were associated with R1-resections. Compared to R0-resected patients, R1-resected patients had a higher incidence of tumor recurrence (77% vs. 32%; P<0.001) and worse overall survival (5-year overall survival 43% vs. 10%; P<0.001). The pattern of recurrence did not differ between R0- and R1-resections with distant metastases in 90% and 87% of patients with tumor recurrence. We found a trend towards better overall survival for R1-resected patients receiving postoperative therapy compared to R1-resected patients without postoperative therapy (median 17.4 vs. 14.6 months, P=0.056).ConclusionsThe association of R1-resections with poor tumor characteristics allows for identification of patients at risk for R1-resection. As in R0-resections, tumor recurrence in R1-resections is mainly systemic, not local. The potential benefit of additive local postoperative therapies in R1-resected patients must be balanced against overall prognosis and therapy-specific morbidity and mortality. J. Surg. Oncol. 2016;114:428-433. (c) 2016 Wiley Periodicals, Inc.

OBJECTIVE:To determine the prevalence and localization of lymph node metastases in patients with pT1 carcinoma of the esophagus, esophagogastric junction, and stomach.BACKGROUND:Retrospective analysis and topographic description.METHODS:We included 793 consecutive patients with pT1 carcinomas who underwent primary surgery for squamous cell carcinoma (SCC) of the esophagus, adenocarcinomas of the esophagogastric junction (AEG), or gastric cancer (GC). Clinical records and pathology reports were reviewed, and the prevalence and topography of lymph node metastases were identified.RESULTS:The prevalence of lymph node metastases in SCC, AEG, and GC was 7%, 0%, and 5% for pT1a tumors and 24%, 18%, and 14% for pT1b tumors, respectively. Positive lymph node status was associated with worse overall survival (P<0.001). Not only infiltration of the submucosa (P=0.002) but also lymphatic vessel invasion (P<0.001), multifocal tumor growth (P=0.001), lower patient age (P=0.001), and poor tumor differentiation (P=0.05) were associated with nodal disease. These 5 parameters allowed the compilation of a nomogram to estimate the individual risk of lymph node metastases. In SCC, lymph node metastases were found from the neck to the celiac axis. In AEG, nodal disease was limited to the lower mediastinum and the D1 compartment. In GC, lymphatic spread exceeded the D1 compartment in 7% of node positive patients.CONCLUSIONS:Risk estimation for lymph node metastases should not be based on depth of tumor infiltration alone but additional clinicopathological parameters should also be considered. The extent of lymphadenectomy in surgical procedures should respect the presented topography of lymph node metastases.

For esophageal adenocarcinoma treated with neoadjuvant chemotherapy, postoperative staging classifications initially developed for non-pretreated tumors may not accurately predict prognosis. We tested whether a multifactorial TNM-based histopathologic prognostic score (PRSC), which additionally applies to tumor regression, may improve estimation of prognosis compared with the current Union for International Cancer Control/American Joint Committee on Cancer (UICC) staging system.

In this case report we present a 60-year-old male patient with overt midgastrointestinal bleeding of a primary ileal pleomorphic liposarcoma diagnosed by video capsule endoscopy (VCE). Clinical work-up for final diagnosis and the pathological background of this uncommon tumorous entity of the small bowel will be discussed in this paper.

Esophagectomy is a challenging operation with considerable potential for postoperative complications, including chylothorax.

Preoperative radio(chemo)therapy (pR(C)T) significantly reduces the local recurrence risk and is therefore recommended in stage II/III rectal cancer. However, this multimodal treatment approach may be associated with late adverse effects. To determine the impact of pR(C)T on long-term anorectal, sexual, and urinary function, we performed a systematic review and meta-analysis.

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).

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

BACKGROUND & AIMS: There is controversy about the best way to treat esophageal anastomotic leakage. We evaluated the effects of treatment with self-expanding metal stents in patients with esophageal anastomotic leakage after esophagectomy or gastrectomy for cancer. METHODS: We investigated outcomes and procedure-related complications of 115 patients who received endoscopic stents for anastomotic leakage after esophagectomy or gastrectomy at a university hospital from 2004 to 2009. We also performed a systematic literature review on stent therapy and compared outcomes with that of other treatment regimens for esophageal anastomotic leakage. RESULTS: Among the 115 patients who received stents, the in-hospital mortality rate was 9% and complete anastomotic healing was achieved in 70% (95% confidence interval [CI], 64%-76%). Stent dislocation occurred in 53% of the patients (95% CI, 43%-62%), in all patients with esophagocolonostomy, in 61% with esophagojejunostomy, and in 49% with esophagogastrostomy. Three percent of patients (95% CI, 1%-5%) needed laparotomy to remove dislocated stents. Elective endoscopic stent removal was performed in 80% of the patients after a median of 54 days (range 17-427 d); 12% of these patients developed symptomatic anastomotic strictures after stent removal. CONCLUSIONS: Anastomoses completely heal in 70% of patients that receive endoscopic stents for anastomotic leakage after esophagectomy or gastrectomy. Stent therapy should be used in the management of patients with adequately perfused esophageal anastomotic leakage. However, stent dislocation remains a common problem after surgery.

64 Background: In the new 7th edition of the TNM classification for cancers of the esophagus, the UICC stage groups are still based on the anatomic extent of the tumor alone. In contrast, the AJCC prognostic groupings is the first staging system for esophageal cancer to add histologic tumor type, tumor site and grade. Methods: Data of a single center cohort of 2,920 patients operated for cancers of the esophagus were analyzed. Statistical methods to evaluate survival of the patients and the prognostic performance of the new staging systems included Kaplan-Meier analyzes and time dependent ROC-analysis. Results: UICC stage, R-status, histologic tumor type and age were identified as independent prognostic factors for cancers of the esophagus. Grade and tumor site, additional parameters in the new AJCC prognostic groupings, were not significantly correlated with survival. Patients with esophageal adenocarcinoma had a significantly better long-term prognosis after resection than patients with squamous cell carcinoma (p < 0.0001). The new number-dependent N- classification proved superior to the former site-dependent classification with significantly decreasing prognosis with increasing number of lymph node metastases (p < 0.001). The new subclassification of T1 tumors also revealed significant differences in prognosis between pT1a and pT1b patients (p < 0.001). However, the multiple new UICC and AJCC subgroupings did not prove distinctive for survival between stages IIA and IIB, IIIA and IIIB, and between IIIC and IV. Conclusions: The new 7th edition of the TNM classification improved the predictive ability for cancers of the esophagus, however, stage groups could be condensed to a clinically relevant number. Differences in patient characteristics, pathogenesis and especially survival clearly identify adenocarcinomas and squamous cell carcinoma of the esophagus as two separate tumor entities requiring differentiated therapeutic concepts. No significant financial relationships to disclose.

BACKGROUND:To evaluate whether so-called cardiac adenocarcinomas (adenocarcinomas of the esophagogastric junction type II and III, ie AEG II and III) are better staged as cancers of the esophagus or as cancers of the stomach.METHODS:A single-center cohort of 1141 patients operated for AEG II and III is staged according to the seventh edition of the TNM classification for cancers of the esophagus and cancers of the stomach. Kaplan-Meier and Cox regression analyses are used to evaluate the prognostic performance of these 2 staging schemes.RESULTS:For so-called cardiac adenocarcinomas, the esophageal T classification is monotone. That is, it defines subgroups with continuous decreasing survival with increasing T stage. And it is distinct. That is, survival of these monotonic subgroups differs significantly. The gastric T classification is monotone but not distinct for pT2 versus pT3 (P=0.641) and for pT4a versus pT4b tumors (P=0.130). The type of infiltrated adjacent structure matters with significant differences in prognosis between the esophageal subgroups T4a and T4b (P<0.001). For the N classification, both the esophageal and gastric schemes are monotone and distinct, with decreasing prognosis with increasing number of lymph node metastases. The subclassification of N3a and N3b disease according to the gastric scheme defines 2 subgroups with significant differences in prognosis (P<0.01). Both the gastric and esophageal schemes include heterogeneous stage groups (2 and 1, respectively) and are not distinctive between several stage groups (4 and 3, respectively).CONCLUSIONS:Neither the esophageal nor the gastric scheme proves to be clearly superior over the other, and neither is perfect for AEG II and III. Our analysis includes further hints that so-called cardiac adenocarcinomas have different biological properties compared with genuine gastric and genuine esophageal cancers.

Background. The costimulatory molecule B7-H1 (programmed death-1 ligand-1, PD-L1) has been implicated as a potential regulator of antitumor immunity in various human cancers. To date, no data are available on the role of B7-H1 in Barrett carcinoma. Therefore, we investigated the expression pattern and clinical significance of B7-H1 in a large cohort of patients with Barrett carcinoma.Methods. Expression of B7-H1 was evaluated by immunohistochemistry in 101 patients with Barrett carcinoma. Expression data were correlated with clinicopathologic features, including TNM stage, UICC (Union Internationale Contre le Cancer) tumor stage, tumor grade, resection status, and survival, and with the number of tumor-infiltrating CD3(+), CD8(+), and CD45RO(+) T lymphocytes.Results. Aberrant B7-H1 expression was found in Barrett carcinoma cells. High tumor B7-H1 expression was significantly associated with advanced T stage (p = 0.002), advanced UICC tumor stage (p = 0.022), and incomplete resection status (p = 0.009). The median survival of patients with high tumor B7-H1 expression was 38 months compared with 136 months for patients with no or low tumor B7-H1 expression. In the multivariable analysis, high tumor B7-H1 expression was significantly associated with an increased risk of death from Barrett carcinoma (hazard ratio, 3.50; 95% confidence interval, 1.66 to 7.38; p < 0.001).Conclusions. Our data suggest that B7-H1 may represent a new prognostic marker for patients with Barrett carcinoma. Furthermore, given its immune-inhibitory function, B7-H1 may represent a potential target in the treatment of Barrett carcinoma. (Ann Thorac Surg 2011;91:1025-31) (C) 2011 by The Society of Thoracic Surgeons

OBJECTIVE:We analyzed the long-term outcome of patients operated for esophageal cancer and evaluated the new seventh edition of the tumor-node-metastasis classification for cancers of the esophagus.BACKGROUND:Retrospective analysis and new classification.METHODS:Data of a single-center cohort of 2920 patients operated for cancers of the esophagus according to the seventh edition are presented. Statistical methods to evaluate survival and the prognostic performance of the staging systems included Kaplan-Meier analyses and time-dependent receiver-operating-characteristic-analysis.RESULTS:Union Internationale Contre le Cancer stage, R-status, histologic tumor type and age were identified as independent prognostic factors for cancers of the esophagus. Grade and tumor site, additional parameters in the new American Joint Cancer Committee prognostic groupings, were not significantly correlated with survival. Esophageal adenocarcinoma showed a significantly better long-term prognosis after resection than squamous cell carcinoma (P < 0.0001). The new number-dependent N-classification proved superior to the former site-dependent classification with significantly decreasing prognosis with the increasing number of lymph node metastases (P < 0.001). The new subclassification of T1 tumors also revealed significant differences in prognosis between pT1a and pT1b patients (P < 0.001). However, the multiple new Union Internationale Contre le Cancer and American Joint Cancer Committee subgroupings did not prove distinctive for survival between stages IIA and IIB, between IIIA and IIIB, and between IIIC and IV.CONCLUSION:The new seventh edition of the tumor-node-metastasis classification improved the predictive ability for cancers of the esophagus; however, stage groups could be condensed to a clinically relevant number. Differences in patient characteristics, pathogenesis, and especially survival clearly identify adenocarcinomas and squamous cell carcinoma of the esophagus as 2 separate tumor entities requiring differentiated therapeutic concepts.

BACKGROUND:Preoperative chemotherapy has been shown to improve outcome of patients with adenocarcinoma of the esophagogastric junction (AEG) and gastric cancer (GC), and histopathologic response has been identified as an independent prognostic parameter in these patients. A recent meta-analysis has identified patients with AEG as benefiting more from preoperative chemotherapy than patients with GC. The aim of this retrospective analysis was to prove these findings in an experienced single-center large patient cohort because there are currently no recruiting prospective clinical trials.METHODS:In a single center, 551 patients underwent preoperative platin-based chemotherapy followed by oncologic surgery for locally advanced AEG and GC. Pretherapeutic clinical parameters were correlated with histopathologic response to preoperative chemotherapy.RESULTS:Histopathologic response (<10% of residual tumor) was found in 130 patients (24%) and was significantly correlated with overall survival (P<0.0001). Tumor localization at the esophagogastric junction (GE junction), lower baseline cT stage, and baseline cN0 stage were significantly associated with histopathologic response (P=0.034, P=0.015, and P=0.002, respectively). In subgroup analyses, the latter two predictive parameters were confirmed only for AEG (n=378) but not for other GC (n=173). AEG patients who were pretherapeutically staged as having cT3/4, cN0 disease (n=73) were identified as the subgroup with the highest rate of histopathologic response (48%).CONCLUSIONS:AEG is more likely to respond to preoperative chemotherapy than GC, a finding that might help identify patients who would benefit from preoperative chemotherapy.

1Department of Surgery, Klinikum rechts der Isar, Technischen Universität München, Chirurgische Klinik und Poliklinik, Munich, Germany 2Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Correspondence: Ralf Gertler, MD, Department of Surgery, Klinikum rechts der Isar, Technischen Universität München, Chirurgische Klinik und Poliklinik, Ismaningerstrasse 22, München 81675, Germany. E-mail: [email protected]