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Zusammenfassung. Die moderne Diagnostik des Ösophagus ist hochgradig technisiert. Sie schliesst schwerpunktmässig endoskopische, radiologische, nuklearmedizinische, funktionelle und elektrochemische Untersuchungen ein. So kommen je nach Fragestellung Ösophagogastroduodenoskopie mit Chromoendoskopie, Endosonographie, Mano- und pH-Metrie oder radiologische Untersuchungen, wie Röntgenbreischluck, CT, MRT oder PET-CT, zur Anwendung. Die Anamnese und die körperliche Untersuchung stehen vor Beginn der Diagnostik und sind für die Indikationsstellung der anschliessenden Untersuchungen wichtig. Die Ösophagogastroduodenoskopie hat einen hohen Stellenwert in der Standarddiagnostik und die Indikation kann aufgrund der geringen Komplikationsrate grosszügig gestellt werden. Zusätzlich zu makroskopischen Beurteilung, Abstrich und Biopsie bietet sie die Möglichkeit, therapeutische Interventionen anzuschliessen. Zur Verbesserung der Diagnostik von Dysplasien können die klassische und virtuelle Chromoendoskopie eingesetzt werden. Die Endosonographie ist für das Staging von Ösophaguskarzinomen zwingend erforderlich, zusätzlich können endosonographisch gesteuerte Biopsien erfolgen. Eine CT ergänzt das Staging und ist notwendig zur Metastasendiagnostik. Für Motilitätsstörungen ist die HR-Manometrie heutzutage Goldstandard, welche um Bariumbreischluckuntersuchungen erweitert werden kann. Die pH-Metrie-Impedanz-Messung wird für die Diagnostik von Refluxerkrankungen eingesetzt. MRT-Schluckuntersuchungen sind klinisch noch kein Standard, werden aber im Rahmen von klinischen Studien bereits durchgeführt.

PDF file 2546K, Supplementary Figure 1 refers to Figure 1 and shows additional morphological and expression changes in KrasG12D mice upon caerulein challenge

PDF file 3772K, Supplementary Figure refers to Figure 6 and displays additional data on NFATc1 knockout mice

PDF file 1592K, Supplementary Figure 4 refers to Figure 4 and provides additional information about the ChIP-Seq analysis performed in KrasG12D;NFATc1 primary cancer cell lines

PDF file 2319K, Supplementary Figure 2 refers to Figure 2 and displays further information about KrasG12D;NFATc1 mice

PDF file 184K, This file contains Supplementary Methods, Tables (referring to the human TMA analyses as shown in Figure 3) and Supplementary References

PDF file 1914K, Supplementary Figure 5 refers to Figure 5 and provides further mechanistical insights into the NFATc1-STAT3-mediated target gene expression

PDF file 788K, Supplementary Figure 3 refers to Figure 3 and shows STAT3 and NFATc1 expression levels in human and murine pancreatic cancer cell lines as well as NFATc1-dependent STAT3 expression

Background Brain metastases represent a severe complication in many gastrointestinal malignancies especially those arising from the upper gastrointestinal tract, including cancer of the esophagus, gastroesophageal junction, and stomach (GEC). However, there is little knowledge about the onset or potential risk factors for brain metastases (BRMs) in upper gastrointestinal cancers resulting in a lack of screening guidelines for BRMs. Methods We analyzed 827 patients from our cancer registry suffering from gastroesophageal cancer (GEC) and treated at the University Medical Center Göttingen between January 2013 and December 2019 for the presence of BRMs. Results From 827 patients with GEC we found 54 patients with BRMs, resulting in an incidence of 6.5%. BRMs are more frequent in male patients (90.74% vs 9.26%, p = 0.0051) and in adenocarcinomas (90.74% vs 9.26%, p = 0.0117). Mean duration for the onset of BRMs from initial cancer diagnoses was 20.9 months in limited disease (curative approach) and 9.3 months in advanced disease (palliative approach) (p = 0.0026). However, early detection of BRMs is a prognostic factor since patients with successful resection of BRMs have a better prognosis compared to those with unresectable BRMs (5.93 vs 2.07 months, p = 0.0091). Conclusion In this single-center retrospective study, brain metastases (BRMs) occur with a high frequency (6.5%) in gastroesophageal cancer (GEC), significantly more often in male patients and adenocarcinomas. Since survival of these patients considerably correlates with successful BRMs resection, our observations propose further prospective trails to validate our hypothesis and ultimately the implementation of routine screening procedures to detect asymptomatic brain metastases.

State of the Art Diagnostics of the Esophagus

Cancer-associated inflammation is a molecular key feature in pancreatic ductal adenocarcinoma. Oncogenic KRAS in conjunction with persistent inflammation is known to accelerate carcinogenesis, although the underlying mechanisms remain poorly understood. Here, we outline a novel pathway whereby the transcription factors NFATc1 and STAT3 cooperate in pancreatic epithelial cells to promote KrasG12D-driven carcinogenesis. NFATc1 activation is induced by inflammation and itself accelerates inflammation-induced carcinogenesis in KrasG12D mice, whereas genetic or pharmacologic ablation of NFATc1 attenuates this effect. Mechanistically, NFATc1 complexes with STAT3 for enhancer–promoter communications at jointly regulated genes involved in oncogenesis, for example, Cyclin, EGFR and WNT family members. The NFATc1–STAT3 cooperativity is operative in pancreatitis-mediated carcinogenesis as well as in established human pancreatic cancer. Together, these studies unravel new mechanisms of inflammatory-driven pancreatic carcinogenesis and suggest beneficial effects of chemopreventive strategies using drugs that are currently available for targeting these factors in clinical trials. Significance: Our study points to the existence of an oncogenic NFATc1–STAT3 cooperativity that mechanistically links inflammation with pancreatic cancer initiation and progression. Because NFATc1–STAT3 nucleoprotein complexes control the expression of gene networks at the intersection of inflammation and cancer, our study has significant relevance for potentially managing pancreatic cancer and other inflammatory-driven malignancies. Cancer Discov; 4(6); 688–701. ©2014 AACR. This article is highlighted in the In This Issue feature, p. 621