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Simple Summary Inflammation caused by acidic reflux contributes to disease progression in Barrett’s esophagus. Little is known, whether esophageal cancer cells are influenced by acidic reflux and whether reflux influences cancer cell physiology, targeting the Nrf2/Kepa1- and the NFκB-pathway. The understanding mechanisms of the acidic susceptibility in cells from advanced stages of Barrett’s esophagus will provide further evidence, whether it should be prevented during chemotherapy for EAC treatment. Abstract Chronic acid reflux causes cellular damage and inflammation in the lower esophagus. Due to these irritating insults, the squamous epithelium is replaced by metaplastic epithelium, which is a risk factor for the development of esophageal adenocarcinoma (EAC). In this study, we investigated the acid susceptibility in a Barrett’s cell culture in vitro model, using six cell lines, derived from squamous epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B), and EAC (OE33 and OE19) cells. Cells exposed to acidic pH showed a decreased viability dependent on time, pH, and progression status in the Barrett’s sequence, with the highest acid susceptibility in the squamous epithelium (EPC1 and EPC2), and the lowest in EAC cells. Acid pulsing was accompanied with an activation of the Nrf2/Keap1- and the NFκB-pathway, resulting in an increased expression of HO1—independent of the cellular context. OE33 showed a decreased responsiveness towards 5-FU, when the cells were grown in acidic conditions (pH 6 and pH 5.5). Our findings suggest a strong damage of squamous epithelium by gastroesophageal reflux, while Barrett’s dysplasia and EAC cells apparently exert acid-protective features, which lead to a cellular resistance against acid reflux.

Highlights • Exact preoperative diagnosis and surgery of retroperitoneal schwannoma (RS) is sophisticated. • Due to heterogeneity of the entity, preoperative negative biopsy does not exclude malignancy. • A curative (R0) resection must be achieved in order to avoid local recurrence, always under consideration of multivisceral resections., Introduction The differential diagnosis and therapy of retroperitoneal masses suspicious for soft tissue tumors remains difficult and needs individual decisions as to the best management of patients. We report an unusual case of retroperitoneal schwannoma (RS). Presentation of case We report on a 57-year-old female patient with a retroperitoneal space-occupying lesion with displacement, but no infiltration of surrounding vessels, especially the inferior vena cava. As presence of malignancy could not be completely excluded by imaging and biopsy, we performed an open resection of the tumor with plastic reconstruction of the right renal vein. Curative resection of the tumor could be achieved and benign RS verified. Discussion Preoperative work-up, including a broad spectrum of differential diagnoses, and consecutive appropriate surgical resection are challenging. Characteristic features of the pre-therapeutic diagnostics of retroperitoneal schwannomas are discussed and differential diagnostic considerations as well as surgical therapeutic options are outlined. Conclusion Deeper understanding of retroperitoneal schwannomas gained from preoperative radiologic diagnostics may serve to underline the need for targeted biopsy. This and its histopathological examination necessitate expert interventional radiologists and pathologists. Thus, even the pre-therapeutic diagnostic management should be performed in a specialized center. If doubts remain regarding the entity of the retroperitoneal lesion and findings are still controversial after thorough assessment, surgical oncologic resection represents the therapy of choice, if the surgical risk is adequate.

Figure S1. Phosphoryation of Akt, GSK3β and β-catenin after Wnt3a treatment in EPC1, EPC2, CP-A, CP-B, OE33 and OE19 cells. Representative Westernblots related to the analysis shown in Fig. 5. (PPTX 10686 kb)

Introduction. Incisional negative pressure wound therapy (iNPWT) has been of recent interest in different surgical fields as beneficial outcomes on high-risk wounds have been reported. Nevertheless, its mechanisms of function are not widely studied to date. Methods. We established two ex vivo setups of iNPWT in porcine and human abdominal wall for measuring pressures within the wound which result from iNPWT application. For pressure measurements, a high-resolution manometry catheter and a balloon catheter probe were used in a wound sealed with either a commercially available PREVENA VAC kit or a self-made iNPWT kit. Furthermore, we evaluated seroma evacuation by iNPWT. Results. Both setups showed similar characteristics of pressure curves within the wound when applying increasing negative pressures. Application of high pressures did not result in a similar increase in wound pressure. Only subtotal evacuation of seroma by iNPWT application (about 75% of volume) could be detected. Conclusion. Our ex vivo model of iNPWT in porcine and human abdominal wall could show reproducible measurements of pressures within the wounds in both types of tissue. As intrawound pressures did not increase in the same way as the applied negative pressure, we suggest that our results do not advocate the idea of using iNPWT for wound care especially as seroma evacuation remains insufficient.