Christoph Treese

High Impact of Histopathological Remission for Prognosis after Perioperative Chemotherapy with ECF and ECF-Like Regimens for Gastric and Gastroesophageal Adenocarcinoma.

Background: Perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (5-FU) (ECF)-like regimens is the European standard for patients with adenocarcinoma of the gastroesophageal junction (GEJ) or gastric body (GaCa) stage UICC II/III (staged according to the Union for International Cancer Control). However, limited data exist on the histopathological response and relevance of prognosis for patients homogeneously treated with ECF(-like) therapies. Methods: All patients with GEJ/GaCa treated from September 2004 to September 2008 by perioperative ECF(-like) chemotherapy were retrospectively analyzed. Cisplatin and 5-FU were substituted with oxaliplatin or capecitabine when indicated. The histopathological response was assessed using the Becker score. Results: Seventy-seven patients were analyzed with a median follow-up of 72.3 months. R0 resection was achieved in 53 of 68 operated patients. Recurrence was observed in 25 (32.5%) of these curatively treated patients, whereas 53/77 patients (68.8%) died, 39 (50.6%) of whom tumor related. The 5-year overall survival (OS) for the intention-to-treat population was 36.3%, and the 5-year tumor-specific survival was 42.2%. Pathological complete response (pCR) was seen in 10 patients (13.0%) and near pCR in 3 patients (3.9%). Patients with pCR had a significantly prolonged 5-year OS of 80.0 versus 29.7% compared to the nonhistopathological complete remission group (p = 0.01). Conclusion: In our retrospective analysis, ECF(-like) pretreatment resulted in a (near) pCR rate of 16.9%. In line with other regimens, our data suggest that histopathological response predicts the OS in patients treated with ECF(-like) regimens.

Uncommon case of ulcerative esophagitis.

Gastroente Question: A 60-yearold woman with a 10yearhistoryofmultiple myeloma presented to our hospital with progressive dysphagia, retrosternal pain, and a 5-kg weight loss over a 4-week period. As part of hematologic therapy, the patient had been treated with rituximab 4 months prior. Dysphagia and pain were not responsive to high-dose proton pump inhibitor (PPI) treatment (pantoprazole 40 mg bid for 14 days). On arrival at the hospital, the patient was in reduced general condition. Physical examination did not show any specific pathologic findings. Laboratory studies showed a leucocyte count in normal range (6/nL); however, there was microcytic anemia (11.7 g/dL; mean corpuscular volume, 77 fL), and a slightly elevated C-reactive protein (4.3 mg/dL; normal, <0.5). Upper endoscopy revealed a fibrin-covered esophageal ulcer at 30–36 cm (Figure A). The endoscopic view suggested the presence of esophageal cancer. However, repeated biopsies including large forceps biopsies revealed inflammation with infiltration of neutrophils without any evidence of malignancy (Figure B). Computed tomography and endoscopic ultrasonography demonstrated an increased wall thickness (8 mm) with loss of contrast between the wall layers (a sign of inflammation), but no signs of a tumor was described. Intravenous therapy with pantoprazole was initiated to achieve an adequate acid suppression. Efficacy was proven by 24-hour pH monitoring, indicating an average pH of 7.0. Common pathogens for ulcerative esophagitis like cytomegalovirus, herpes simplex virus, HIV, and Mycobacterium tuberculosis or a fungal infection were excluded. Despite these measures, symptoms were ongoing for 4 weeks. What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

FLOT ist Chemotherapiestandard bei Adenokarzinomen des gastroösophagealen Übergangs und Magens in der Neoadjuvanz

Al-Batran S et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 2016; 17(12): 1697 –1708 Al-Batran S et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): A multicenter, randomized phase 3 trial. J Clin Oncol 2017; 35, no. 15 suppl. (May 2017) 4004 – 4004

Arzt und Wissenschaftler – Das Clinical Scientist Programm der Charité

Abb. 19Gruppenfoto auf demClinical Scientist Retreat im Januar 2016 auf Schloss Genshagen schaftlichen Tätigkeit in den noch verbleibenden Feierabend zu einer abnehmenden Qualität der Forschung an Universitätskliniken. Für den medizinischen Fortschritt und die Realisation translationaler Forschung ist jedoch die wissenschaftliche Aktivität klinisch arbeitender Mediziner essentiell. DieCharité Berlin stellt sich seit 5 Jahren mit der Einführung eines eigenen strukturierten, wissenschaftlichen Ausbildungsprogramm für klinisch aktive Mediziner gegen diesen Trend. Das Pilotprogrammwurde gegründet durchdie Gruppe „Junge Charité“, unter führender Leitung von Frau Prof. Dr. Duska Dragun und Frau Prof. Dr. Britta Siegmund. Durch die finanzielle Unterstützung der Volkswagenstiftung und der Stiftung Charité wurden 2011 im Rahmen dieses Programms zunächst acht MedizinerInnen über drei Jahre zu 50 Prozent für wissenschaftliche Projekte freigestellt, davon beschlossen alle ihre Facharztausbildung während dieser Förderperiode und vier davon habilitierten sich bereits. Aufgrund des großen Erfolges dieses Projektes und der steigenden Bewerberzahl wurde inzwischen die Zahl der Stellen deutlich erhöht. Für das Jahr 2016 wird das Erreichen der maximal förderbaren Zahl von 100Clinical Scientists erwartet. Das Clinical-Scientist Programm

Poorly Differentiated Medullary Phenotype Predicts Poor Survival in Early Lymph Node-Negative Gastro-Esophageal Adenocarcinomas.

Background 5-year survival rate in patients with early adenocarcinoma of the gastro-esophageal junction or stomach (AGE/S) in Caucasian patients is reported to be 60–80%. We aimed to identify prognostic markers for patients with UICC-I without lymph-node involvement (N0). Methods Clinical data and tissue specimen from patients with AGE/S stage UICC-I-N0, treated by surgery only, were collected retrospectively. Tumor size, lymphatic vessel or vein invasion, grading, classification systems (WHO, Lauren, Ming), expression of BAX, BCL-2, CDX2, Cyclin E, E-cadherin, Ki-67, TP53, TP21, SHH, Survivin, HIF1A, TROP2 and mismatch repair deficiency were analyzed using tissue microarrays and correlated with overall and tumor related survival. Results 129 patients (48 female) with a mean follow-up of 129.1 months were identified. 5-year overall survival was 83.9%, 5-year tumor related survival was 95.1%. Poorly differentiated medullary cancer subtypes (p<0.001) and positive vein invasion (p<0.001) were identified as risk factors for decreased overall—and tumor related survival. Ki-67 (p = 0.012) and TP53 mutation (p = 0.044) were the only immunohistochemical markers associated with worse overall survival but did not reach significance for decreased tumor related survival. Conclusion In the presented study patients with AGE/S in stage UICC-I-N0 had a better prognosis as previously reported for Caucasian patients. Poorly differentiated medullary subtype was associated with reduced survival and should be considered when studying prognosis in these patients.

Inflammatory bowel disease (IBD)-like disease in a case of a 33-year old man with glycogenosis 1b

BackgroundInflammatory bowel disease (IBD)-like conditions in glycogen storage disease (GSD) type Ib have been predominantly described in children. Signs and symptoms of GSD type Ib are hypoglycemia, pancytopenia and hepatosplenomegaly. Based on few published cases, there is evidence that granulocyte-colony stimulating factor (G-CSF) in patients with glycogenosis–related pancytopenia might ameliorate the IBD-like disease through leukocyte increase.Case presentationHere we firstly describe a case of an adult 33-year-old Caucasian male patient with GSD type Ib accompanied with IBD-like disease with persistent pancytopenia despite moderate-dose G-CSF treatment. Recent vomiting and abdominal discomfort were due to a high-grade stenosis in the transverse colon. A dose increase of the G-CSF successfully normalized his leukocyte count. However, the stenosis worsened and surgical therapy was needed.ConclusionWe suggest that symptomatic patients with GSD type Ib should undergo endoscopic examination in order to detect IBD-like disease and to initiate early treatment.

Molekulare Prognosefaktoren für Patienten mit Adenokarzinomen des Ösophagus und des Magens im Stadium T1/2N0

Einleitung: Das 5-jahres Uberleben von Patienten mit einem Adenokarzinom des gastroosophagealen Ubergangs und des Magens (AGO) im Stadium UICC I liegt nach Literaturangaben zwischen 60 – 80% (Holscher et al, 2009; Siewert et al. 1998). Ein Weg die Prognose dieser Patienten zu verbessern, konnte die Identifizierung von Hochrisiko-Tumoren mit entsprechender Intensivierung der Therapie sein. Ziel dieser Studie ist die Identifizierung molekularer prognostischer Marker bei AGO Patienten in einem moglichst homogenem Stadium (UICC I ohne Lymphknotenbeteiligung). Methode: In die Studie wurden retrospektiv Patienten mit AGO UICC I-N0, die zwischen 1993 und 2010 an der Charite-Universitatsmedizin Berlin operativ behandelt wurden, eingeschlossen. Die Expression von BAX, CDX2, Cyclin E, E-Cadherin, KI67, MACC1, p53, PTEN, S100, SHH, SURVIVIN und TROP2 wurden mittels Gewebemicroarray untersucht und mit bekannten prognostischen Markern wie Tumorgrose, Lymphgefas- (L1) und Veneninvasion (V1) sowie Grading und Klassifikationssystemen (WHO, Lauren und Ming) korreliert. Die statistische Analyse erfolgte mittels Marker one-sample T-test oder ANOVA. Ergebnisse: Eingeschlossen wurden 129 Patienten (w = 48, mittleres Alter 63 Jahre) mit einem Beobachtungszeit zwischen 6 und 224 Monaten und einem 5-Jahres Uberleben von 94,57%. Fur die immunhistologische Untersuchung standen die Gewebsproben von 75 Patienten zur Verfugung. Signifikante Unterschiede konnten zwischen T1a- und T1b-Tumoren mit einer hoheren Expression von SURVIVIN (p = 0,008) in T1a gefunden werden. Weiterhin war die Expression von p53 (p < 0,001), SHH (p < 0,001) und Trop2 (p < 0,001) in der Subgruppe der V1 positiven Karzinome erhoht. BAX war in der V1-Gruppe signifikant niedriger exprimiert (p 0,001). Fur die Expression von p53 zeigte sich eine positive Korrelation mit L1-positiven Karzinomen. Diskussion: Diese retrospektive Analyse zeigt eine exzellente Prognose fur Patienten mit AGO im Stadium UICC I-N0 von 95% 5-JUR. Die Uberexpression von p53, SHH und Trop2 deutet auf mogliche Mechanismen in der Tumorprogression hin. Diese Ergebnisse mussen prospektiv bestatigt werden und konnen auch relevant bei fortgeschrittenen Stadien sein. Diese Studie wird von der Berliner Krebsgesellschaft gefordert (DAFF201101).

Perioperative chemotherapy with epirubicin, cisplatin, and 5-FU (ECF) for gastroesophageal cancer: A retrospective analysis.

e14623 Background: Perioperative chemotherapy with ECF is the recommended treatment in Europe. We report our experience with this treatment. Methods: In this retrospective analysis all the pts from 09.2004 to 09.2008 with adenocarcinoma of the distal esophagus, gastroesophageal junction (GEJ) and gastric body who received preoperative ECF (Cunningham et al., 2006) with curative intent were included. Cisplatin and 5-FU were substituted with oxaliplatin or capecitabine, if indicated. Preop staging included MSCT-scan of chest and abdomen, endoscopy and endosonograpy. Pts were planned to receive 3 preop and 3 postop cycles of ECF. Results: 55 pts were analysed. Median age 64 (range 32- 79), male 43 pts. Tumor site: distal esophagus 5, GEJ: 26, gastric 24 pts. Surgery: none: 4 pts, curative: 43 pts, palliative: 8 pts; esophageal resection: 16 pts, total gastrectomy: 29 pts, subtotal gastrectomy: 3pts, other: 3 pts. D2 lymph node dissection: 43 pts. Preop chemotherapy: ECF 50 pts, EOF 4 pts, ECX 1 pt. All 3 pla...