Objective: The aim of this study was to determine the clinical role of the systemic immune-inflammation index in patients with resectable adenocarcinoma of the gastroesophageal junction treated with or without neoadjuvant therapy. Background: Adenocarcinoma of the gastroesophageal junction is an aggressive disease, with less than 20% of overall patients surviving more than 5 years after diagnosis, while currently available clinical staging for esophageal cancer is lacking necessary accuracy. The systemic immune-inflammation index (SII) based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in various malignancies. Methods: Data of consecutive patients undergoing esophagectomy (n = 320, 1992 to 2016) were abstracted. The cut point for high and low SII before neoadjuvant treatment and before surgery was calculated for illustration of the Kaplan-Meier curves. SII was used for the correlation with patients’ clinicopathological characteristics as a continuous variable. Survival was analyzed with Cox proportional hazards models using clinical or pathological staging, adjusting for other known survival predictors. Results: In both neoadjuvantly treated and primarily resected patients, high SII was significantly associated with diminished overall [hazard ratio (HR) 1.3, 95% confidence interval (95% CI) 1.2–1.4; HR 1.2, 95% CI 1.2–1.3, respectively] and disease-free survival (HR 1.3, 95% CI 1.2–1.3; HR 1.2, 95% CI 1.2–1.3, respectively). In multivariable survival analysis, SII remained an independent prognostic factor for overall survival (HR 1.3, 95% CI 1.2–1.4; HR 1.2, 95% CI 1.2–1.3, respectively) and disease-free survival (HR 1.3, 95% CI 1.2–1.3; HR 1.2, 95% CI 1.2–1.3, respectively) in primarily resected and neoadjuvantly treated patients. Conclusion: Elevated SII is an independent adverse prognostic factor in patients with resectable gastroesophageal adenocarcinomas with and without neoadjuvant treatment.

Ulcerative colitis (UC) and Crohn's disease (CD) are two presentations of inflammatory bowel diseases (IBDs). Whereas the inflammation in UC is confined to the mucosa/submucosa, CD is considered a transmural disease with characteristic lymphoid aggregates with or without epithelioid granulomas in the subserosa. Here we examined and quantified the distribution of lymphatic capillaries in small-and large-bowel resection specimens (non-IBD n=8; CD n=20 and UC n=13) using immunohistochemical staining with anti-human podoplanin antibody, an established marker for lymphatic endothelium. In normal small intestine, the lymphatic network originated in the capillaries beneath the surface epithelial cells, whereas it started in the lower third of the mucosa of the large intestine. Lymphatic microvessel counts revealed a statistically highly significant increase (P<0.005 in the muscularis mucosae, P=0.012 in the tunica submucosa and P=0.012 in the tunica subserosa) in IBDs when compared with normal intestine. Numerical differences between CD and UC samples were not significant. Prominence of lymphatic capillaries could also be observed in areas where fibrosis replaced chronic inflammation. These findings suggested that lymph-vessel proliferation in IBDs may be triggered by chronic inflammation irrespective of its organization and is maintained in fibrotic end-stage disease.

Lymphatic vessels play a crucial role in a variety of human cancers, since invasion of lymphatic vessels by tumor cells and subsequent development of lymph node metastases significantly influences prognosis of cancer patients and therefore represent an integral part of tumor staging. Recent evidence on the important influence of lymphangiogenetic growth factors on intralymphatic cancer growth and metastasis raises hopes that lymphatic vessels and factors inducing their growth could serve as an additional target for tumor therapy. Nevertheless, in contrast to blood vessel angiogenesis, the mechanisms of new lymphatic vessel formation in human cancers, i.e. lymphangiogenesis, are still relatively unclear. In addition, only little data exist so far on the quantification and impact of this lymphangiogenesis, evident by lymphatic microvessel density (LMVD), on the prognosis of cancer patients. With expectation of possible anti-lymphangiogenic therapies, this review focuses on the mechanisms of lymphangiogenesis in general, and especially on the role of lymphatic vessels in gynecological and breast cancer, which are the so far most detailed investigated malignancies with regard to lymphangiogenesis.

These data indicate for the first time that CUL-4 might play a relevant role in the development and progression of ovarian carcinoma, warranting further investigations. Degradation of wild-type p53 might be a key mechanism to explain why CUL-4 leads to more aggressive clinical behaviour. Not only CUL-4 itself, but also its associated proteins might represent targets for novel, selective therapeutic strategies.

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Even though distinctive advances in the field of esophageal cancer therapy have occurred over the last few years, patients’ survival rates remain poor. FGF8, FGF18, and FGFR4 have been identified as promising biomarkers in a number of cancers; however no data exist on expression of FGF8, FGF18, and FGFR4 in adenocarcinomas of the esophago-gastric junction (AEG). A preliminary analysis of the Cancer Genome Atlas (TCGA) database on FGF8, FGF18, and FGFR4 mRNA expression data of patients with AEG was performed. Furthermore, protein levels of FGF8, FGF18, and FGFR4 in diagnostic biopsies and post-operative specimens in neoadjuvantly treated and primarily resected patients using immunohistochemistry were investigated. A total of 242 patients was analyzed in this study: 87 patients were investigated in the TCGA data set analysis and 155 patients in the analysis of protein expression using immunohistochemistry. High protein levels of FGF8, FGF18, and FGFR4 were detected in 94 (60.7%), 49 (31.6%) and 84 (54.2%) patients, respectively. Multivariable Cox proportional hazard regression models revealed that high expression of FGF8 was an independent prognostic factor for diminished overall survival for all patients and for neoadjuvantly treated patients. By contrast, FGF18 overexpression was significantly associated with longer survival rates in neoadjuvantly treated patients. In addition, FGF8 protein level correlated with Mandard regression due to neoadjuvant therapy, indicating potential as a predictive marker. In summary, FGF8 and FGF18 are promising candidates for prognostic factors in adenocarcinomas of the esophago-gastric junction and new potential targets for new anti-cancer therapies.

Background Magnetic sphincter augmentation (MSA) is a surgical intervention for gastroesophageal reflux disease (GERD) which has been evaluated in numerous studies and has shown beneficial effects. Long-term effectiveness data for MSA as well as laparoscopic fundoplication (LF) in patients with GERD are needed. Objective The objective of this study was to evaluate the 3-year outcomes for MSA and LF in patients with GERD. Methods This prospective, multi-center, observational registry study evaluated MSA and LF in clinical practice over 3 years (ClinicalTrials.gov identifier: NCT01624506). Data collection included baseline characteristics, reflux symptoms, medication use, satisfaction and complications. Post-surgical evaluations were collected at yearly intervals. Results Between December 2009 and December 2014, 631 patients (465 MSA and 166 LF) were enrolled in the registry. Both MSA and LF resulted in improvements in total GERD-HRQL score (mean reduction in GERD-HRQL from baseline to 3 years post-surgery: MSA 22.0 to 4.6 and LF 23.6 to 4.9) and in satisfaction (GERD-HRQL satisfaction increase from baseline to 3 years: MSA 4.6% to 78.2% and LF 3.7% to 76.5%). Most patients were able to belch as needed with both therapies (MSA 97.6% and LF 91.7% at 3 years). MSA allowed a higher percentage of patients the ability to vomit as needed (MSA 91.2% and LF 68.0% at 3 years). PPI usage declined from baseline to 3 years for both groups after surgery (MSA 97.8% to 24.2% and LF 95.8% to 19.5%). The mean procedure time was shorter for MSA than for LF. Intraoperative and procedurerelated complication rates (≤ 2%) were low for both therapies. Conclusions This 3-year prospective observational registry study contributes to the mounting evidence for the effectiveness of MSA and LF. Despite the more severe nature of GERD in the LF group, the clinical outcomes for MSA and LF were favorable from an effectiveness and safety standpoint.

Immunotherapy with checkpoint inhibitors serves as a promising treatment strategy in patients with upper gastrointestinal (GI) tumors. Human epidermal growth factor receptor 2 (HER2) is the only identified therapeutic target in upper GI tumors, whose potential interaction with programmed death-ligand 1 (PD-L1) is unknown. The aim of this study was the investigation of PD-L1 and HER2 in upper GI tumors. We retrospectively identified patients with HER2 positive gastroesophageal cancers and matched them with a HER2 negative group. We investigated the tumor specimens for HER2 status and PD-L1 expression, with the following assessments being performed: i) staining of tumor cells in terms of tumor proportion score (TPS), ii) staining for tumorassociated immune cells (TAIs), iii) interface pattern and iv) combined positive score (CPS). Both HER2 positive and negative group consisted of 59 patients. Expression of PD-L1 in TAIs and interface pattern were associated with a favorable outcome (p = 0.02, HR = 0.8; p = 0.04, HR = 0.39; respectively) in patients with localized disease, whereas TPS was associated with an unfavorable outcome in patients with advanced tumor (p = 0.02, HR = 1.4). These effects were HER2 independent. PD-L1 expression in its different assessment is equally observed in HER2 positive and negative patients. Future studies will show whether dual inhibition of HER2 and PD-L1 improves survival of this selected patient population.