Search

Background. A number of studies have revealed that inflammation-based prognostic scores, such as Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein and albumin ratio (C/A ratio), are associated with poor outcome in cancer patients. However, until now, no study has investigated the role of these prognostic scores in a cohort of neoadjuvant-treated esophageal adenocarcinomas (nEAC) and squamous cell carcinomas (nESCC). Methods. Patients had laboratory measurements within three days before resection. GPS, mGPS, and C/A ratio were tested together with established clinicopathological factors in simple and multiple Cox regression analysis of overall survival (OS) and disease-free survival (DFS). Results. A total of 283 patients (201 EAC and 82 ESCC) with locally advanced esophageal cancer were enrolled. 167 patients received neoadjuvant treatment (59.0%). Simple analysis revealed that there were significant differences in cancer-specific survival in relation to elevated C-reactive protein (p=0.011), lymph node status (p

FGF8, ALK, and EML4 have been identified as promising biomarkers in a number of malignancies. The aim of this study was to examine the prognostic role of FGF8, ALK, and EML4 in esophageal squamous cell carcinoma (ESCC). Methods: Consecutive patients with ESCC who underwent upfront resection were included in this study. ALK and EML4 gene status was evaluated by fluorescence in situ hybridization (FISH) using a triple-color break-apart single-fusion probe and a probe against 2p11. FGF8, ALK, and EML4 protein expression was determined by immunohistochemistry. Results: A total of 122 patients were included in this study. Multivariate analysis revealed that FGF8 overexpression is an independent negative prognostic factor for patients' overall survival (OS) ( p = 0.04). Furthermore, a significant correlation between the expression of FGF8, and ALK ( p = 0.04) and EML4 ( p = 0.01) alteration was found. Conclusions: FGF8 overexpression is an adverse independent prognostic factor in patients with upfront resected ESCC. Furthermore, FGF8 expression significantly correlates with ALK and EML4 amplification and may therefore qualify as a future therapeutic target.

Purpose: Serum fibrinogen and albumin play important roles in systemic inflammation and are implicated in tumor progression. The fibrinogen-to-albumin ratio (FAR) has shown a prognostic impact in several malignancies. This study aims to assess the prognostic value of the pretherapeutic FAR in patients with adenocarcinoma of the gastroesophageal junction (AEG) who underwent upfront resection., Methods: Consecutive patients who underwent surgical resection at the Department of Surgery at the Medical University of Vienna between 1992 and 2014 were included into this study. Optimal cut-off values were determined with the receiver-operating characteristic (ROC) curve, uni- and multivariate analyzes were calculated by the Cox proportional hazard regression model for overall survival (OS)., Results: Among 135 included patients, the majority were male (79.26%), with a mean age of 66.53 years. Elevated FAR correlated significantly (p = 0.002) with shorter OS in univariate analysis, also confirmed as independent prognostic factor (p = 0.005) in multivariable analysis. The ROC curve of FAR (AUC = 0.744) outperformed fibrinogen (AUC = 0.738) and albumin (AUC = 0.378) in predicting OS for AEG patients., Conclusion: The FAR serves as an independent prognostic factor for OS in patients undergoing primarily resection for AEG. Given its routine availability and ease of calculation, FAR could help in diagnosis and treatment selection for AEG patients. Further validation studies are warranted to confirm these findings conclusively., (© 2024. The Author(s).)

Introduction: The role of the family history in the development and prognosis of gastroesophageal cancer is a controversially discussed topic as appropriate data from western cohorts are lacking. This study aims to explore its associations with disease and outcome parameters in a large European cohort., Methods: We retrospectively analyzed self-reported family history in patients with gastroesophageal cancer treated between 1 January 1990 and 31 December 2021 at the Medical University of Vienna. Association analyses with patient characteristics, tumor characteristics, symptoms and overall survival (OS) were performed., Results: In our cohort of 1762 gastroesophageal cancer patients, 592 (34%) reported a positive family history of cancer (159, 9%, gastroesophageal cancer). No associations were found with histopathological parameters or initial symptoms; however, a positive family history correlated with female gender (cancer in general: p = 0.011; gastroesophageal cancer: p = 0.015). Family history of cancer in general was associated with earlier cancer stages (p = 0.04), higher BMI (p = 0.005), and alcohol consumption (p = 0.010), while a positive history for gastroesophageal cancer was associated with higher age at diagnosis (p = 0.002) and stomach cancer (p = 0.002). There was no statistically significant association of positive family history with OS (p = 0.1, p = 0.45), also not in subgroups for histology (adeno and squamous cell), number of family members and degree of relative., Conclusion: Our results emphasize that a positive family history is neither statistically significantly associated with prognosis nor with specific histopathological features in patients with gastroesophageal cancer. Yet, associations with distinct patient characteristics and positive family history indicate that specific subgroups might profit from endoscopic surveillance. Prospective studies are warranted to investigate these findings further., (© 2024. The Author(s).)

AF1q associates with tumor progression and metastases upon WNT signaling. The downstream WNT target CD44 has demonstrated prognostic significance in gastric cancer (GC). This study evaluates the impact of AF1q on tumor stage and survival in GC patients. Immunohistochemical marker expression was analyzed and data were processed to correlation and survival analysis. Out of 182 GC samples, 178 (97.8%) showed moderate to high AF1q expression (p < 0.001), these samples correlated with positive lymph node stage (p = 0.036). In a subgroup analysis of patients with nodal-positive GC (n = 129, 70.9%), enhanced tumoral AF1q expression resulted in impaired recurrence-free survival (RFS, p = 0.030). Enhanced tumoral CD44 expression resulted in impaired disease-specific survival (DSS) in the subgroup of patients with nodal-positive GC (p = 0.031) as well as in the overall GC group (p = 0.005). AF1q demonstrated as an independent prognostic marker for RFS (p = 0.035) and CD44 for DSS (p = 0.036). AF1q has shown potential for prognostication of RFS in GC patients and is predominantly expressed in nodal-positive GC. Testing AF1q provides a possibility of identifying patients with locoregional (and advanced) disease, particularly at risk for disease recurrence. Implementing AF1q into the diagnostic process may facilitate screening, prognosis estimation as well as consideration of preoperative multimodal treatment in patients qualifying for elective upfront surgery., (© 2024. The Author(s).)

Aim of the Study: Mean corpuscular volume (MCV) has shown mounting evidence as a prognostic indicator in a number of malignancies. The aim of this study was to examine the prognostic potential of pretherapeutic MCV among patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection after neoadjuvant treatment (NT)., Patients and Methods: Consecutive patients with PDAC who underwent pancreatic resection between 1997 and 2019 were included in this study. Neoadjuvantly treated patients' serum MCV was measured before NT and before surgery. In patients undergoing upfront resection serum MCV was measured before surgery. Median MCV values were used as cut-off to distinguish high from low MCV values., Results: Five hundred and forty-nine (438 upfront resected and 111 neoadjuvantly treated) patients were included in this study. Multivariate analysis revealed, that high MCV before and after NT, were independent negative prognostic factors for overall survival (P<0.01, respectively). Furthermore, the median MCV value from before to after NT increased significantly (P<0.001, Wilcoxon signed-rank test) and was (P=0.03, Wilcoxon rank sum test) associated with tumor response to NT., Conclusion: High MCV is an independent adverse prognostic factor in patients with resectable neoadjuvantly treated PDAC and may qualify as useful indicator to help physicians to provide personalized prognostication., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1 mm) after neoadjuvant therapy (NAT)., Background: The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1 mm margin clearance after NAT remains controversial., Methods: Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases. Clinicopathological and survival data were analyzed. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), and pattern of recurrence in association with R 0 >1 mm and R 1 ≤1 mm resections., Results: Three hundred fifty-seven patients with PDAC were included after NAT and subsequent pancreatic resection. Two hundred eight patients (58.3%) received FOLFIRINOX, 41 patients (11.5%) received gemcitabine-based regimens, and 299 individuals (83.8%) received additional radiotherapy. R 0 resections were achieved in 272 patients (76.2%) and 85 patients (23.8%) had R 1 resections. Median OS after R 0 was 41.0 months, compared with 20.6 months after R 1 resection ( P = 0.002), and even longer after additional adjuvant chemotherapy ( R 0 44.8 vs R1 20.1 months; P = 0.0032). Median RFS in the R 0 subgroup was 17.5 months versus 9.4 months in the R 1 subgroup ( P < 0.0001). R status was confirmed as an independent predictor for OS ( R 1 hazard ratio: 1.56, 95% CI: 1.07-2.26) and RFS ( R 1 hazard ratio: 1.52; 95% CI: 1.14-2.0). In addition, R 1 resections were significantly associated with local but not distant recurrence ( P < 0.0005)., Conclusions: The revised R status is an independent predictor of postresection survival and local recurrence in PDAC after NAT. Achieving R 0 resection with a margin of at least 1 mm should be a primary goal in the surgical treatment of PDAC after NAT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Gastroesophageal adenocarcinoma is associated with poor prognosis, even in resectable stages. Systemic inflammation plays a key role in cancer progression. Yet, information on prognostic values of systemic inflammatory parameters in European cohorts is scarce., Methods: We analysed systemic inflammatory biomarkers (neutrophil-to-lymphocyte ratio (NLR), leucocyte-to-lymphocyte ratio (LLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIRI) and modified Glasgow Prognostic Score (mGPS)) at the time of cancer diagnosis and their association with overall survival (OS) in patients with gastroesophageal adenocarcinoma treated at the Medical University of Vienna between 1990 and 2020., Results: In this analysis of 769 patients with gastroesophageal adenocarcinoma, higher mGPS (0-2) scores were associated with shorter OS in the overall cohort (24.9 versus 11.9 versus 7.6 months; HR 1.74, 95% CI 1.549-1.056; p < 0.001), in locally advanced (31.1 versus 19.8 versus 13.9 months, HR 1.561, 95% CI 1.274-1.912; p < 0.001) and in advanced/metastatic settings (12.3 versus 7.3 versus 5.8 months; HR 1.377, 95% CI 1.777-1.611; p < 0.001). In multivariate analyses, the association of mGPS with the OS stayed statistically significant in the locally advanced cohort (HR 1.397, 95% CI 1.068-1.828; p = 0.015), whereas NLR, LLR, PLR and SIRI did not. mGPS was associated with more advanced stages (p < 0.001) and weight loss (p = 0.002)., Conclusion: mGPS poses a feasible prognostic tool in patients with locally advanced gastroesophageal cancer., (© 2023. The Author(s).)

Objective: The aim of this study was to investigate the prognostic role of plasma platelet count (PLT), mean platelet volume (MPV), and the combined COP-MPV score in patients with resectable adenocarcinomas of the gastroesophageal junction., Background: Platelet activation, quantified by PLT and elevated MPV, plays an essential part in the biological process of carcinogenesis and metastasis. An increased preoperative COP-MPV is associated with poor survival in various tumor entities., Methods: Data of 265 patients undergoing surgical resection for adenocarcinoma of the gastroesophageal junction were abstracted. COP-MPV score was defined for each patient. Utilizing univariate and multivariate Cox proportional hazard analyses, survival was determined., Results: In univariate analysis, elevated PLT (HR 3.58, 95% CI 2.61-4.80, p<0.001) and increased COP-MPV (HR 0.27, 95% CI 0.17-0.42, p<0.001 and HR 0.42, 95% CI 0.29-0.60, p<0.001) significantly correlated with shorter patients' overall and disease-free survival, for all 256 patients, as well as in the subgroups of neoadjuvantly treated (p<0.001) and primarily resected patients (p<0.001). COP-MPV remained a significant prognostic factor in multivariate analysis for OS. However, PLT alone showed significant diminished OS and DFS in all subgroups (p<0.001) in univariate and multivariate analysis., Conclusion: PLT is a potent independent prognostic biomarker for survival in a large prospective cohort of patients with resectable adenocarcinoma of the gastroesophageal junction. Additionally, we confirm that the COP-MPV score is significantly associated with worse outcome in these patients, but has no benefit in comparison to PLT., (© 2023. The Author(s).)

Background: Diminished systemic serum butyrylcholinesterase (BChE), a biomarker for chronic inflammation, cachexia, and advanced tumor stage, has shown to play a prognostic role in various malignancies. The aim of this study was to investigate the prognostic value of pretherapeutic BChE levels in patients with resectable adenocarcinoma of the gastroesophageal junction (AEG), treated with or without neoadjuvant therapy., Methods: Data of a consecutive series of patients with resectable AEG at the Department for General Surgery, Medical University of Vienna, were analyzed. Preoperative serum BChE levels were correlated to clinic-pathological parameters as well as treatment response. The prognostic impact of serum BChE levels on disease-free (DFS) and overall survival (OS) was evaluated by univariate and multivariate cox regression analysis, and Kaplan-Meier curves used for illustration., Results: A total of 319 patients were included in this study, with an overall mean (standard deviation, SD) pretreatment serum BChE level of 6.22 (± 1.91) IU/L. In univariate models, diminished preoperative serum BChE levels were significantly associated with shorter overall (OS, p < 0.003) and disease-free survival (DFS, p < 0.001) in patients who received neoadjuvant treatment and/or primary resection. In multivariated analysis, decreased BChE was significantly associated with shorter DFS (HR: 0.92, 95% CI: 0.84-1.00, p 0.049) and OS (HR: 0.92, 95% CI: 0.85-1.00, p < 0.49) in patients receiving neoadjuvant therapy. Backward regression identified the interaction between preoperative BChE and neoadjuvant chemotherapy as a predictive factor for DFS and OS., Conclusion: Diminished serum BChE serves as a strong, independent, and cost-effective prognostic biomarker for worse outcome in patients with resectable AEG who had received neoadjuvant chemotherapy., (© 2023. The Author(s).)

Background: Incidental discovery of pancreatic cystic neoplasms (PCLs) is a common and steadily increasing occurrence. The aim of this study was to investigate a cohort of patients presenting with incidentally detected PCLs which were not included in a surveillance protocol, and to compare their risk of malignant evolution with that of systematically surveilled lesions., Materials and Methods: A population of PCLs which did not receive surveillance over a period >10 years (population A) was selected at the Medical University of Vienna. A group of "low risk" branch duct intraductal papillary mucinous neoplasm ≤15 mm in size upon diagnosis undergoing a regular follow-up of at least 5 years at the University of Verona was selected as control (population B). The incidence of pancreatic cancer (PC), cumulative risk of PC and disease-specific survival were compared., Results: Overall, 376 patients with non-surveilled PCLs were included in study group A and compared to 299 patients in group B. This comparison resulted in similar incidence rates of PC (1.6% vs 1.7%, p = 0.938), a strong similarity in terms of disease-specific mortality rates (1.3% vs 0.3%, p = 0.171) and the 5- and 10-year cumulative risk of PC (≅ 1% and 2%, p = 0.589) and DSS (≅ 100% and 98%, p = 0.050)., Conclusion: The "price to pay" for a negligence-based policy in the population of non-surveilled PCLs was reasonable, and the incidence of PC was comparable to that reported for a population of low-risk cysts enrolled to a standardized surveillance protocol., Competing Interests: Declaration of competing interest The authors have no conflict of interest to be declared., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Electrical stimulation therapy (EST) of the lower esophageal sphincter (LES) is a novel technique in antireflux surgery. Due to the minimal alteration at the LES during surgery, LES-EST is meant to be ideal for patients with gastroesophageal reflux disease (GERD) and ineffective esophageal motility (IEM). The aim of this prospective trial (NCT03476265) is to evaluate health-related quality of life and esophageal acid exposure after LES-EST in patients with GERD and IEM., Methods: This is a prospective non-randomized open-label study. Patients with GERD and IEM undergoing LES-EST were included. Follow-up (FUP) at 12 months after surgery included health-related quality of life (HRQL) assessment with standardized questionnaires (GERD-HRQL) and esophageal functional testing., Results: According to the study protocol, 17 patients fulfilled eligibility criteria. HRQL score for heartburn and regurgitation improved from 21 (interquartile range (IQR) 15-27) to 7.5 (1.25-19), p = 0.001 and from 17 (11-23.5) to 4 (0-12), p = 0.003, respectively. There was neither significant improvement of esophageal acid exposure nor reduction of number of reflux events in pH impedance measurement. Distal contractile integral improved from 64 (11.5-301) to 115 (IQR 10-363) mmHg s cm, p = 0.249. None of the patients showed any sign of dysphagia after LES-EST. One patient needed re-do surgery and re-implantation of the LES-EST due to breaking of the lead after one year., Conclusion: Although patient satisfaction improved significantly after surgery, this study fails to demonstrate normalization or significant improvement of acid exposure in the distal esophagus after LES-EST., (© 2020. The Author(s).)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The clinical behaviour and outcome of young patients with gastroesophageal tumours (GET) is surmised to differ from older patients, yet data on the comparison of these two patient subgroups is scarce. This study focuses on the investigation of the clinical characteristics and survival outcome of younger-age people with GET, when compared to older patients., Methods: Patients diagnosed with GET at the Medical University of Vienna between 2004 and 2016 were included in this study. Clinical parameters and the overall survival (OS) were compared between young (≤ 45 years) and elderly (≥ 65 years) patients., Results: Among 796 patients, who were eligible for this analysis, fifty-eight patients (7%) were ≤ 45 years at the initial onset of the disease. These 58 young patients were then matched to elderly patients based on the gender, tumour stage, histology and tumour location. The number of metastatic lesions was significantly higher among young patients (p < 0.05). In a non-metastatic setting younger patients showed a significant longer OS than older patients (median 1226 versus 801 days, p = 0.028). Furthermore, young patients with extensive metastatic disease (2 or more metastatic site) had a significantly poorer OS than elderly patients (median 450 versus 646 days, p = 0.033)., Conclusion: These results indicate that young patients might be diagnosed very late, which might lead to the development of a more aggressive disease compared to older patients, but a relatively long OS when diagnosed and treated in a non-metastatic setting. Thus, screening methods for younger patients might be considerable to enhance the outcome of young patients with GET.

Purpose: Long-term follow-up after sleeve gastrectomy (SG) revealed a high incidence of gastroesophageal reflux disease (GERD) frequently caused by preoperative silent pathologic reflux. We aimed to evaluate prevalence and phenotypes of GERD in asymptomatic patients with morbid obesity prior to metabolic surgery according to modern objective testing., Material and Methods: Prospective collection of data including consecutive patients with morbid obesity (body mass index (BMI) ≥ 35 kg/m 2 ) prior to metabolic surgery was applied for this study between 2014 and 2019. Patients underwent clinical examinations, endoscopy, pH metry, and high-resolution manometry and were analyzed according to the Lyon consensus., Results: Of 1379 patients undergoing metabolic surgery, 177 (12.8%, females = 105) asymptomatic individuals with a median age of 42.6 (33.8; 51.6) years and a median BMI of 44.6 (41.3; 50.8) kg/m 2 completed objective testing and were included during the study period. GERD was diagnosed in 55 (31.1%), whereas criteria of borderline GERD were met in another 78 (44.1%). GERD was mediated by a structural defective lower esophageal sphincter (p = 0.004) and highlighted by acidic (p = 0.004) and non-acidic (p = 0.022) reflux episodes. Esophageal motility disorders were diagnosed in 35.6% (n = 63) of individuals with a novel hypercontractile disorder found in 7.9% (n = 14) of patients., Conclusion: GERD affects a majority of asymptomatic patients with morbid obesity prior to primary bariatric surgery. Future longitudinal trials will have to reveal the clinical significance of esophageal motility disorders in patients with morbid obesity.

Immunotherapy with check-point 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 tumor-associated 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.

Purpose: Neoadjuvant radiochemotherapy (RCTH) is proven to be highly effective in the treatment of esophageal cancer (EC). We investigated oncological outcome and morbidity in patients treated with a modified CROSS protocol followed by esophagectomy at our institution., Methods: Patients with EC receiving neoadjuvant RCTH with paclitaxel and carboplatin and concurrent radiotherapy (46 Gy) followed by esophagectomy were included in this retrospective analysis. Histopathological response, overall survival (OS) and recurrence-free interval (RFI) as well as perioperative morbidity were investigated., Results: Thirty-six patients (86.1% male, mean age 61.3 years, standard deviation 11.52) received neoadjuvant RCTH before surgery. Sixteen patients (44.4%) were treated for squamous cell cancer, whereas 20 patients (55.6%) had adenocarcinoma. The majority (75%) underwent abdominothoracic esophageal resection. Major complications occurred in 7 patients (19.5%) including anastomotic leakage in 4 patients (11.1%). A R0 resection was achieved in 97.2%. A complete pathological remission was seen in 13 patients (36.1%). Major response, classified as Mandard tumor regression grade 1 and 2, was found in 26 patients (72.2%). Median OS and RFI were not reached., Conclusions: Neoadjuvant radiotherapy with 46 Gy and concomitant chemotherapy with paclitaxel and carboplatin for the treatment of locally advanced esophageal carcinoma is safe and effective. The results of this modified radiotherapy protocol are encouraging and should be considered in future patient treatment and study designs.

Background: Cancer-related inflammation is associated with tumour proliferation, maintenance and dissemination. It therefore impacts pancreatic cancer survival. The goal of this study was to examine the Prognostic Index (PI) as a prognostic biomarker for survival in patients with pancreatic ductal adenocarcinoma (PDAC). In addition, we explored factors known to interact with the immune and inflammation cascade that might interfere with the PI's strength for prognostication., Methods: Patients with PDAC undergoing resection were analysed retrospectively. The PI was calculated from preoperatively derived C-reactive protein levels and white blood count. Data were subject to correlation and survival analysis., Results: Of 357 patients, 235 (65.8%) patients had a PI 0, 108 (30.3%) PI 1, and 14 (3.9%) PI 2. Median (quartiles) survival with a high PI (group 1 + 2) was 13.2 months (7.7-27.0), compared with 18.7 months (10.2-35.4) with a low PI (group 0; p = 0.012). The PI proved to be an independent prognostic factor for cancer-specific survival (p = 0.003) adjusted for conventional prognostic factors. Prognostic strength was influenced by the presence of a bile stent (p = 0.032)., Conclusions: The PI is a strong and solid independent prognostic tool for survival in patients with PDAC undergoing resection. Preoperative survey of inflammatory activity as provided by the use of a biomarker like the PI may help to identify those patients at risk of a poor prognosis.

Background: The systemic immune-inflammation index based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in several malignancies. The aim of this study was to determine the prognostic role of systemic immune-inflammation index in patients with pancreatic ductal adenocarcinoma undergoing resection., Methods: Consecutive patients who underwent surgical resection at the department of surgery at the Medical University of Vienna between 1995 and 2014 were included into this study. The systemic immune-inflammation index was calculated by the formula platelet*neutrophil/lymphocyte. Optimal cutoffs were determined using Youden's index. Uni- and multivariate analyses were calculated by the Cox proportional hazard regression model for overall survival., Results: Three hundred twenty-one patients were included in this study. Clinical data was achieved from a prospective patient database. In univariate survival analysis, elevated systemic immune-inflammation index was found to be significantly associated with shortened patients' overall survival (p = 0.007). In multivariate survival analysis, systemic immune-inflammation index remained an independent prognostic factor for overall survival (p = 0.004). No statistical significance could be found for platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in multivariate analysis. Furthermore, area under the curve analysis showed a higher prognostic significance for systemic immune-inflammation index, compared to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio., Conclusion: A high systemic immune-inflammation index is an independent, preoperative available prognostic factor in patients with resectable pancreatic ductal adenocarcinoma and is superior to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio for predicting overall survival in pancreatic ductal adenocarcinoma patients.

Introduction: The prognostic value of symptoms at disease presentation of advanced gastro-oesophageal cancer is unknown. Thus, the aim of this study was to characterise these symptoms and correlate them with the outcome, so new prognostic markers can be defined., Methods: We analysed clinical data including symptoms, therapies and survival of patients with stage IV gastro-oesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. Initial symptoms as well as stenosis in endoscopy and HER2 positivity were evaluated in a cross-validation model to ascertain the impact of each variable on patient survival., Results: In total, 258 patients were evaluated. Five factors (stenosis in endoscopy, weight loss, HER2 positivity, dyspepsia, ulcer or active bleeding) have proven to be statistically relevant prognostic factors and were given a count of +1 and -1, if applicable. The resulting score ranges between -3 and +2. The survival probability for 180 days with a score of -3/-2, -1, 0, +1 and +2 is 90%, 80%, 73%, 72% and 42%, whereas for 2 years, it is 30%, 30%, 8%, 7% and 3%, respectively. The median overall survival of a score of -3/-2, -1, 0, +1 and +2 was 579 (95% CI 274 to not measurable), 481 (95% CI 358 to 637), 297 (95% CI 240 to 346), 284 (95% CI 205 to 371), 146 (95% CI 120 to 229) days, respectively., Conclusion: The data from this retrospective study indicate that the Viennese risk prediction score for Advanced Gastroesophageal carcinoma based on Alarm Symptoms score provides independent prognostic information that may support clinical decision making at diagnosis of advanced gastro-oesophageal cancer. Our findings should be evaluated in prospective studies., Competing Interests: Competing interests: HCP has received travel support from Eli Lilly, MSD, Novartis, Pfizer and Roche. ASB has research support from Daiichi Sankyo and Roche, honoraria for lectures, consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo as well as travel support from Roche, Amgen, Daiichi Sankyo and AbbVie. MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo and Merck Sharp & Dome. AI-M participated in advisory boards from MSD and Servier, received lecture honoraria from Eli Lilly and Servier and is the local principal investigator for clinical trials sponsored by BMS and Astellas., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background/aim: A standard treatment recommendation for advanced stage gastroesophageal cancer is still missing., Patients and Methods: We retrospectively analyzed clinical data of patients with inoperable locally advanced or metastatic gastroesophageal cancer treated between 2001 and 2017 at the Vienna General Hospital, Austria., Results: Administration of systemic therapy was positively associated with overall survival (OS) (469 days vs. 185 days; p<0.001), while palliative gastrectomy or radiotherapy showed no correlation. OS was significantly longer in patients receiving capecitabine/oxaliplatin (XELOX) vs. leucovorin/5-FU/oxaliplatin (FOLFOX) (600 days vs. 327 days, p<0.05). Comparison of doublet vs. triplet chemotherapies showed no difference in OS, but triplet chemotherapy resulted in more adverse events. The anti-HER2-antibody trastuzumab doubled OS (836 days vs. 399 days, p=0.053)., Conclusion: Capecitabine may be preferably used over infused 5-FU and doublet chemotherapy over triplet chemotherapy in the first-line palliative setting of advanced gastroesophageal cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The implementation of high-resolution manometry (HRM) and the Lyon Consensus statement facilitate evaluation of gastroesophageal reflux disease and motility disorders in morbidly obese patients. Therefore, we aimed to investigate prevalence and phenotype of (borderline) GERD and esophageal motility disorders in this population., Methods: Consecutive morbidly obese (BMI ≥ 35 kg/m 2 ) patients were offered evaluation by means of HRM, ambulatory 24-h pH impedance monitoring, endoscopy, and a clinical examination at our tertiary academic center. Data were collected prospectively., Results: Out of 448 eligible individuals, 147 patients (females = 75, 51%) with a median age of 41.6 (33.4; 52.3) years and a BMI of 44 (40.9; 49.4) kg/m 2 were included during the study period. The Chicago Classification revealed motility disorders in 50 (34%) patients, dominated by outflow obstruction (18.4%, n = 27) and a novel disorder (7.5%, n = 11), nicknamed jackhammer esophagus (JE). According to the Lyon Consensus, 52 (35.4%) patients had evidence of true GERD, whereas borderline GERD was noted in another 60 (40.8%). Hypersensitive esophagus was observed in 6.8% (n = 10). Sensitivity and specificity of symptoms for GERD were 53.8% and 68.4%, respectively., Conclusions: The current gold standard of assessment revealed that the prevalence of esophageal motility disorders and (borderline) GERD is high in the morbidly obese population. Further longitudinal data are needed to delineate the natural course of novel motility disorders like JE in obesity and to identify risk factors for adverse outcomes following bariatric surgery.

Background: Laparoscopic fundoplication (LF), even if performed in specialized centers, can be followed by long-term side effects such as dysphagia, gas bloating or inability to belch. Patients with an ineffective esophageal motility (IEM) and concurrent GERD are prone to postoperative dysphagia after LF. The aim of this study is to evaluate the safety and efficacy of electrical lower esophageal sphincter stimulation in patients with IEM and GERD., Methods: This is a prospective, open-label single center study. Patients with PPI-refractory GERD and ineffective esophageal motility were included for lower esophageal sphincter electrical stimulation (LES-EST). Patients underwent prospective follow-up including physical examination, interrogation of the device and were surveyed for changes in the health-related quality of life score., Results: According to power analysis, 17 patients were included in this study. Median distal contractile integral (DCI) was 64 mmHg s cm (quartiles 11.5-301). Median total % pH < 4 was 8.9 (quartiles 4-21.6). Twelve patients (70.6%) underwent additional hiatal repair. At 1-month follow-up, none of the patients showed any clinical or radiological signs of dysphagia. There were no procedure related severe adverse events. Mean total HQRL improved from baseline 37.53 (SD 15.07) to 10.93 (SD 9.18) at follow-up (FUP) (mean difference 24.0 CI 15.93-32.07) p < 0.001., Conclusions: LES-EST was introduced as a potential technique to avoid side effects of LF. LES-EST significantly improved health related quality of life and does not impair swallowing in patients with GERD and ineffective esophageal motility.

AF1q impairs survival in hematologic and solid malignancies. AF1q expression is associated with tumor progression, migration, and chemoresistance, and acts as a transcriptional co-activator in WNT and STAT signaling. This study evaluates the role of AF1q in patients with resectable esophageal cancer (EC). A total of 278 patients operated on for esophageal cancer were retrospectively included, and the expression of AF1q, CD44, and pYSTAT3 was analyzed following immunostaining. Quantified data were processed to correlational and survival analysis. In EC patients, an elevated expression of AF1q was associated with CD44 ( p = 0.004), and pYSTAT3 ( p = 0.0002). High AF1q expression in primary tumors showed high AF1q expression in the corresponding lymph nodes ( p = 0.016). AF1q expression was higher after neoadjuvant therapy ( p = 0.0002). Patients with AF1q-positive EC relapsed and died earlier compared to patients with AF1q-negative EC (disease-free survival (DFS), p = 0.0005; disease-specific survival (DSS), p = 0.003); in the multivariable Cox regression model, AF1q proved to be an independent prognostic marker (DFS, p = 0.01; DSS, p = 0.03). AF1q is associated with WNT and STAT signaling; it impairs and independently predicts DFS and DSS in patients with resectable EC. The testing of AF1q could facilitate prognosis estimation and provide a possibility of identifying the patients responsive to the therapeutic blockade of its oncogenic downstream targets., Competing Interests: M.G. has received institutional research support from AstraZeneca, Roche, Novartis, and Pfizer, and has received lecture fees, honoraria for participation on advisory boards, and travel support from Amgen, AstraZeneca, Celgene, EliLilly, Invectys, Pfizer, Nanostring, Novartis, Roche, and Medison. He has served as a consultant for AstraZeneca and EliLilly, and an immediate family member is employed by Sandoz. None of the other authors have financial and personal relationships with individuals or organizations that could inappropriately influence their work.

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., Competing Interests: The authors declare no conflict of interest.

Background: Incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are on the rise. Sarcopenia and sarcopenic obesity have proven to be prognostic factors in different types of cancers. In the context of previous findings, we evaluated the impact of body composition in patients undergoing surgery in a national pancreatic center., Methods: Patient's body composition (n = 133) was analyzed on diagnostic CT scans and defined as follows: Skeletal muscle index ≤38.5 cm2/m2 (women), ≤52.4 cm2/m2 (men); obesity was classified as BMI ≥25kg/m2., Results: Sarcopenia showed a negative impact on overall survival (OS; 14 vs. 20 months, p = 0.016). Sarcopenic patients suffering from obesity showed poorer OS compared to non-sarcopenic obese patients (14 vs. 23 months, p = 0.007). Both sarcopenia and sarcopenic obesity were associated with sex (p<0.001 and p = 0.006; males vs. females 20% vs. 38% and 12% vs. 38%, respectively); sarcopenia was further associated with neoadjuvant treatment (p = 0.025), tumor grade (p = 0.023), weight loss (p = 0.02) and nutritional depletion (albumin, p = 0.011) as well as low BMI (<25 kg/m2, p = 0.038). Sarcopenic obese patients showed higher incidence of major postoperative complications (p<0.001). In addition, sarcopenia proved as an independent prognostic factor for OS (p = 0.031) in the multivariable Cox Regression model., Conclusion: Patients with sarcopenia and sarcopenic obesity undergoing resection for PDAC have a significantly shorter overall survival and a higher complication rate. The assessment of body composition in these patients may provide a broader understanding of patients' individual condition and guide specific supportive strategies in patients at risk., Competing Interests: The authors have declared that no competing interests exist.

Background: Elevated mean corpuscular volume (MCV) is associated with a diminished prognosis for various tumor entities. This study aimed to evaluate the association between preoperative serum MCV levels and both overall (OS) and disease-free survival (DFS) for patients with resectable adenocarcinomas of the esophagogastric junction (AEG)., Methods: This study included consecutive patients undergoing surgical resection between 1992 and 2016. Measured preoperative MCV levels were stratified into quintiles and correlated with patients' survival and clinicopathologic characteristics., Results: The study analyzed 314 patients with a median OS of 36.8 months and a median DFS of 20.6 months. The multivariate analysis showed that preoperatively elevated MCV is a significant prognostic factor for OS (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.03-1.08; P < 0.001) and DFS (HR, 1.05; 95% CI, 1.03-1.08; P < 0.001). In the subgroup analysis of neoadjuvantly treated and untreated patients, MCV remained an independent prognostic factor for OS (HR, 1.08; 95% CI, 1.04-1.12; P < 0.001) and DFS (HR, 1.07; 95% CI, 1.03-1.12; P < 0.001) in both groups. In the univariate analysis, tumor stage and differentiation, adjuvant chemotherapy, MCV, mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were significantly correlated with diminished OS and DFS., Conclusion: Preoperatively elevated MCV is an independent prognostic factor for patients with adenocarcinomas of the esophagus and the gastroesophageal junction.

Purpose: Therapy response to neoadjuvant radiochemotherapy (nRCT) of locally advanced rectal cancer varies widely so that markers predicting response are urgently needed. Fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling is involved in pro-survival signaling and thereby may result in radiation resistance., Methods: In a cohort of 43 rectal cancer patients, who received nRCT, we analyzed protein levels of FGF 8 and its downstream target Survivin by immunohistochemistry to assess their impact on nRCT response. In vitro resistance models were created by exposing colorectal cancer cell lines to fractionated irradiation and selecting long-term survivors., Results: Our findings revealed significantly higher FGF8 and Survivin staining scores in pre-treatment biopsies as well as in surgical specimens of non-responsive compared to responsive patients. Functional studies demonstrated dose-dependent induction of FGF8 mRNA expression in mismatch-incompetent DLD1 cells already after one dose of irradiation. Surviving clones after one or two series of radiation were more resistant to an additional radiation fraction than non-irradiated controls and showed a significant increase in expression of the FGF8 receptor FGFR3 and of Survivin on both the RNA and the protein levels., Conclusion: The results of this study suggest that FGF8 and Survivin contribute to radiation resistance in rectal cancer and may serve as markers to select patients who may not benefit from neoadjuvant radiotherapy.

This trial was designed to assess the prevalence and characteristics of Jackhammer esophagus (JE), a novel hypercontractile disorder associated with progression to achalasia and limited outcomes following anti-reflux surgery in patients with typical symptoms of GERD and responsiveness to proton pump inhibitor (PPI) therapy. Consecutive patients, who were referred for surgical therapy because of PPI responsive typical symptoms of GERD, were prospectively assessed between January 2014 and May 2017. Patients diagnosed with JE subsequently underwent rigorous clinical screening including esophagogastroduodenoscopy (EGD), ambulatory pH impedance monitoring off PPI and a PPI trial. Out of 2443 evaluated patients, 37 (1.5%) subjects with a median age of 56.3 (51.6; 65) years were diagnosed with JE and left for final analysis. Extensive testing resulted in 16 (43.2%) GERD positive patients and 5 (13.9%) participants were observed to have an acid hypersensitive esophagus. There were no clinical parameters that differentiated phenotypes of JE. The prevalence of JE in patients with typical symptoms of GERD and response to PPI therapy is low. True GERD was diagnosed in less than half of this selected cohort, indicating the need for objective testing to stratify phenotypes of JE. (NCT03347903).

Background: Dysphagia and non-cardiac chest pain are common symptoms associated with a novel hypercontractile disorder, namely Jackhammer esophagus (JE). The aim of this study was to explore these symptoms in patients with JE and to elucidate associations with disease defining metrics, crucial for subsequent therapies., Methods: All consecutive patients, who were referred between January 2014 and December 2016 and fulfilled the criteria for JE were included in this study. Exclusion criteria were opioid intake, previous gastrointestinal surgery, mechanical esophageal obstruction and diseases explaining their symptoms., Key Results: Of 2205 examined subjects, thirty patients (females: n = 17, 56.7%) with a median age of 58 (51.6-64.9) years were finally enrolled. Dysphagia was noted in 53.3% (n = 16), whereas non-cardiac chest pain was specified within 40% (n = 12) with symptom duration of up to 10 years. Perception of dysphagia (P = .03) and presence of both symptoms (P = .008) increased to the end of the study period. Dysphagia was significantly associated with distal contractile integral (DCI) scores of all (P = .023), hypercontractile (P = .011) and maximum DCI swallows (P = .008). Symptoms duration influenced hypercontractile DCI scores (P = .015, r = .438) and significantly correlated with the intensity of perceived dysphagia (P = .01, r = .585). Presence of non-cardiac chest pain was not associated with any of these metrics., Conclusions & Interferences: The DCI mediates dysphagia in patients with JE. Duration of symptoms affected hypercontractile DCI scores and aggravated perception of dysphagia indicating a progressive character of disease., (© 2017 John Wiley & Sons Ltd.)

Background . The outcome of patients with adenocarcinoma of the esophagogastric junction (AEG) remains poor. The programmed cell-death-protein-1 (PD-1), a co-inhibitory receptor primarily expressed by T-cells, represents a potential new therapeutic target. PD-1, PD-1 ligand 1 (PD-L1), and PD-L2 expression have all been described as prognostic factors in a variety of cancers. Their expression patterns in AEG, however, are poorly understood. We analyzed PD-L1, PD-L2 and PD-1 expression by tumor-infiltrating lymphocytes (TILs) and cancer-cells in tumor-biospecimens in AEG-patients. Methods . 168 patients who underwent esophagectomy because of AEG between 1992-2011 were included in this study. PD-L1, PD-L2 and PD-1 expression were evaluated by immunohistochemistry and correlated with various clinicopathological parameters, disease-free survival (DFS) and long-term overall survival (OS). Results . PD-L1 expression by cancer-cells (cancer-cell-PD-L1 + ) was found in 43.5% of patients whereas PD-L1 expression by TILs (TILs-PD-L1 + ) was observed in 69%. PD-L2 expression by cancer-cells and TILs was only found in 3.5% and 1.8%, respectively. Additionally, 77.4% of tumors contained PD-1 + -cancer-cells and 81% PD-1 + -TILs. Patients with increased expression of PD-1 by cancer-cells and TILs showed significantly reduced OS and DFS, as determined by univariate, but not multivariate analysis. Expression of PD-L1 by cancer-cells was found to be an independent predictor for improved DFS (p = 0.038) and OS (p = 0.042) in multivariate analysis. Conclusions . Cancer cells and TILs displayed PD-L1 expression in around 50% and PD-1 expression in around 80% of tumor-biospecimens obtained from AEG patients. Expression of PD-L1 is an independent predictor of favorable outcome in AEG, whereas PD-1 expression is associated with worse outcome and advanced tumor stage.

Background and Aim: Symptomatic cervical heterotopic gastric mucosa, also known as cervical inlet patch (CIP), may present in various shapes and causes laryngopharyngeal reflux (LPR). Unfortunately, argon plasma coagulation, standard treatment of small symptomatic CIP, is limited in large CIP mainly because of concerns of stricture formation. Therefore, we aimed to investigate radiofrequency ablation (RFA), a novel minimally invasive ablation method, in the treatment of CIP focusing on large symptomatic patches., Methods: Consecutive patients with macroscopic and histological evidence of large (≥20 mm diameter) heterotopic gastric mucosa were included in this prospective trial. Primary outcome was complete macroscopic and histological eradication rate of CIP. Secondary outcome measures were symptom improvement, quality of life, severity of LPR and adverse events., Results: Ten patients (females, n = 5) underwent RFA of symptomatic CIP. Complete histological and macroscopic eradication of CIP was observed in 80% (females, n = 4) of individuals after two ablations. Globus sensations significantly improved from median visual analog scale score 8 (5-9) at baseline to 1.5 (1-7) after first ablation and 1 (1-2) after final evaluation (P < 0.001). Mental health scores significantly increased from 41.4 (± 8.5) to 54.4 (± 4.4) after RFA (P = 0.007). LPR improved significantly (P = 0.005) with absence of strictures after a mean follow up of 1.9 (± 0.5) years., Conclusions: This is the first study on RFA focusing on therapy of large symptomatic heterotopic gastric mucosa. Hereby, we demonstrate that this new technique can be successfully implemented in patients where treatment was limited so far (NCT03023280)., (© 2017 Japan Gastroenterological Endoscopy Society.)

The modified Glasgow Prognostic Score (mGPS) combines the indicators of decreased plasma albumin and elevated CRP. In a number of malignancies, elevated mGPS is associated with poor survival. Aim of this study was to investigate the prognostic role of mGPS in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction 256 patients from a prospective database undergoing surgical resection after neoadjuvant treatment between 2003 and 2014 were evaluated. mGPS was scored as 0, 1, or 2 based on CRP (>1.0 mg/dl) and albumin (<35 g/L) from blood samples taken prior (preNT-mGPS) and after (postNT-mGPS) neoadjuvant therapy. Scores were correlated with clinicopathological patients' characteristics. From 155 Patients, sufficient data was available. Median follow-up was 63.8 months (33.3-89.5 months). In univariate analysis, Cox proportional hazard model shows significant shorter patients OS ( p = 0.04) and DFS ( p = 0.02) for increased postNT-mGPS, preNT-hypoalbuminemia (OS: p = 0.003; DFS: p = 0.002) and post-NT-CRP (OS: p = 0.03; DFS: p = 0.04). Elevated postNT-mGPS and preNT-hypoalbuminemia remained significant prognostic factors in multivariate analysis for OS ( p = 0.02; p = 0.005,) and DFS ( p = 0.02, p = 0.004) with tumor differentiation and tumor staging as significant covariates. PostNT-mGPS and preNT-hypoalbuminemia are independent prognostic indicators in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction and significantly associated with diminished OS and DFS., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

Background . Esophageal cancer is ranked in the top ten of diagnosed tumors worldwide. Even though improvements in survival could be noticed over the last years, prognosis remains poor. ETS translocation variant 1 (ETV1) is a member of a family of transcription factors and is phosphorylated by mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2). Aim of this study was to evaluate the prognostic role of MK2 and ETV1 in esophageal cancer. Methods. Consecutive patients that underwent surgical resection at the department of surgery at the Medical University of Vienna between 1991 and 2012 were included into this study. After microscopic analysis, tissue micro arrays (TMAs) were created and immunohistochemistry was performed with antibodies against MK2 and ETV1. Results. 323 patients were included in this study. Clinical data was achieved from a prospective patient data base. Nuclear overexpression of MK2 was observed in 143 (44.3%) cases for nuclear staining and in 142 (44.0%) cases a cytoplasmic overexpression of MK2 was observed. Nuclear and cytoplasmic ETV1 overexpression was detected in 20 cases (6.2%) and 30 cases (9.3%), respectively. In univariate survival analysis, cMK2 and nETV1 were found to be significantly associated with patients' overall survival. Whereas overexpression of cMK2 was associated with shorter, nETV1 was associated with longer overall survival. In multivariate survival analysis, both cMK2 and nETV1 were found to be independent prognostic factors for the subgroup of EAC as well. Discussion. Expression of MK2 and ETV1 are prognostic factors in patients, with esophageal adenocarcinoma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG., Methods: Patients with AEG who underwent esophagectomy from 1992 to 2011 were included in the study. Expression of PD1was evaluated by immunohistochemistry and correlated with long-term overall survival (OS), disease-free survival (DFS), and various clinicopathologic parameters., Results: Tumor biospecimens from 168 patients were analyzed. In the analysis, 81% of the patients showed high tumoral frequencies (>5%) of PD1-expressing TILs (TIL-PD1 + ), and 77% of patient tumors harbored high levels (>5%) of PD1 + cancer cells (cancer-PD1 + ). Expression of PD1 by TILs and cancer cells correlated significantly (p < 0.05) with patients' tumor stage and lymph node involvement. Compared with the patients who had low tumoral frequencies of PD1 + TILs or cancer cells, the TIL-PD1 + and cancer-PD1 + patients demonstrated significantly reduced DFS in the univariate analysis (5-year DFS: 73.3 vs. 41.9%, log-rank 0.008 and 71.3 vs. 41.6%, p = 0.008, respectively). Additionally, the cancer-PD1 + patients showed significantly decreased OS in the univariate analysis compared with the cancer-PD1 - patients (5-year OS: 68.8 vs. 43.5%; p = 0.047). However, these correlations did not reach significance in the multivariate analysis., Conclusions: The PD1 receptor is expressed by both TILs and cancer cells in AEG. High expression of PD1 is associated with advanced tumor stage and lymph node involvement, but not with survival.

Early detection of anastomotic leakage (AL) after oesophageal resection for malignancy is crucial. This retrospective study validates a risk score, predicting AL, which includes C-reactive protein, albumin and white cell count in patients undergoing oesophageal resection between 2003 and 2014. For validation of the NUn score a receiver operating characteristic (ROC) curve is estimated. Area under the ROC curve (AUC) is reported with 95% confidence interval (CI). Among 258 patients (79.5% male) 32 patients showed signs of anastomotic leakage (12.4%). NUn score in our data has a median of 9.3 (range 6.2-17.6). The odds ratio for AL was 1.31 (CI 1.03-1.67; p = 0.028). AUC for AL was 0.59 (CI 0.47-0.72). Using the original cutoff value of 10, the sensitivity was 45.2% an the specificity was 73.8%. This results in a positive predictive value of 19.4% and a negative predictive value of 90.6%. The proportion of variation in AL occurrence, which is explained by the NUn score, was 2.5% (PEV = 0.025). This study provides evidence for an external validation of a simple risk score for AL after oesophageal resection. In this cohort, the NUn score is not useful due to its poor discrimination.

In colorectal cancer (CRC), fibroblast growth factor receptor 4 (FGFR4) is upregulated and acts as an oncogene. This study investigated the impact of this receptor on the response to neoadjuvant radiotherapy by analyzing its levels in rectal tumors of patients with different responses to the therapy. Cellular mechanisms of FGFR4-induced radioresistance were analyzed by silencing or over-expressing FGFR4 in CRC cell line models. Our findings showed that the FGFR4 staining score was significantly higher in pre-treatment biopsies of non-responsive than responsive patients. Similarly, high expression of FGFR4 inhibited radiation response in cell line models. Silencing or inhibition of FGFR4 resulted in a reduction of RAD51 levels and decreased survival in radioresistant HT29 cells. Increased RAD51 expression rescued cells in the siFGFR4-group. In radiosensitive SW480 and DLD1 cells, enforced expression of FGFR4 stabilized RAD51 protein levels resulting in enhanced clearance of γ-H2AX foci and increased cell survival in the mismatch repair (MMR)-proficient SW480 cells. MMR-deficient DLD1 cells are defective in homologous recombination repair and no FGFR4-induced radioresistance was observed. Based on our results, FGFR4 may serve as a predictive marker to select CRC patients with MMR-proficient tumors who may benefit from pre-operative radiotherapy.

Background: Colorectal cancer (CRC) is the fourth most common cause of death worldwide. Approximately 30 % of all CRC occurs in the rectum. Improvements in survival rates were achieved thanks to multimodal therapy, combining surgery and chemoradiation. Nevertheless, the prognosis of patients suffering from rectal cancer (RC) remains poor. Programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) regulate tumor immune response. The aim of this study was to analyze the expression of PD-L1 in RC pre- and post-neoadjuvant therapy and evaluate PD-L1 as a biomarker and potential target for therapy., Methods: In all, 29 patients with RC treated at the Medical University Vienna who received preoperative chemoradiation were retrospectively enrolled in this study. Expression of PD-L1 was investigated by immunohistochemistry with two different anti-PD-L1 antibodies., Results: No PD-L1 expression on cancer cells could be observed in all 29 cases in the specimens before chemoradiation as well as in the surgical specimens after neoadjuvant therapy. In one of the two staining methods performed, five (17.24 %) post-chemoradiation cases showed faint lymphohistiocytic staining., Conclusion: No expression of PD-L1 in RC cells before and after chemoradiation was found in our collective of 29 patients. Further investigations to evaluate the role of PD-L1 as a potential therapeutic target in RC are urgently needed., Competing Interests: Conflict of interestG.Jomrich, G.R.Silberhumer, B.Marian, A.Beer, L.Müllauer declare that they have no competing interests.

Gastric cancer is one of the most commonly diagnosed and the second leading cause of cancer death worldwide. Surgery combined with multimodal therapy remains the only curative therapy. However, local relapse or distant metastases occur in more than 50% of radically resected patients. Due to molecular therapies, targeting HER2 and angiogenesis, major advances in the treatment of gastric cancer could be achieved. Nevertheless, development of resistance to monoclonal antibodies, such as trastuzumab, is arising. Currently a number of promising new therapeutic are under investigation, combining chemotherapy with newly developed agents to overcome cancer resistance. In this review we report current clinical applications of targeted therapies and overview ongoing trials, investigating the use of monoclonal antibodies in (HER2 positive) gastric cancer.