Preoperative BChE serves as a prognostic marker in patients with resectable AEG after neoadjuvant chemotherapy.

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.

Platelets as a prognostic factor for patients with adenocarcinoma of the gastroesophageal junction.

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.

Additional fundophrenicopexia, after Nissen fundoplication, reduces postoperative dysphagia and re-operation rate in the long-term follow up.

BACKGROUND: Various technical modifications of Nissen fundoplication (NF) that aim to improve patients' outcomes have been discussed. This study aims to evaluate the effect of division of the short gastric vessels (SGV) and the addition of a standardized fundophrenicopexia on the postoperative outcome after NF. METHODS: 283 consecutive patients with GERD treated with NF were divided into four groups following consecutive time periods: with division of the SGV and without fundophrenicopexia (group A), with division of the SGV and with fundophrenicopexia (group B), without division of the SGV and with fundophrenicopexia (group C) and without division of the SGV and without fundophrenicopexia (group D). Postoperative contrast swallow, dysphagia scoring, GEDR-HRQL and proton pump inhibitor intake were evaluated. A comparative analysis of patients with division of the SGV and those without (161 A + B vs. 122 C + D), and patients with fundophrenicopexia and those without (78 A vs. 83 B and 49 C vs. 73 D) was performed. RESULTS: Fundophrenicopexia reduced postoperative dysphagia rates (0 group C vs. 5 group D, p = 0.021) in patients where the SGV were preserved and reoperation rates (1 group B vs. 7 group A, p = 0.017) in patients where the SGV were divided. There was no significant difference in the postoperative rates of heartburn relief, dysphagia, gas bloating syndrome, interventions, re-fundoplication and the GERD-HRQL score between groups A + B and C + D, respectively. CONCLUSION: Standardized additional fundophrenicopexia in patients undergoing Nissen fundoplication significantly reduces postoperative dysphagia in patients without division of the SGV and reoperation rates in patients with division of the SGV. Division of the SGV has no influence on the postoperative outcome of NF.

High Systemic Immune-Inflammation Index is an Adverse Prognostic Factor for Patients With Gastroesophageal Adenocarcinoma.

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.

Effect of electrical stimulation therapy of the lower esophageal sphincter in GERD patients with ineffective esophageal motility.

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.

Modification of preoperative radiochemotherapy for esophageal cancer (CROSS protocol) is safe and efficient with no impact on surgical morbidity.

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.

Ineffective Esophageal Motility in Patients with GERD is no Contraindication for Nissen Fundoplication.

BACKGROUND: Patients with preoperative ineffective esophageal motility (IEM) are thought to be at increased risk for postoperative dysphagia leading to the recommendations for tailoring or avoiding anti-reflux surgery in these patients. The aim of this study was to evaluate if IEM has an influence on postoperative outcome after laparoscopic Nissen fundoplication (LNF). METHODS: Seventy-two consecutive patients with IEM underwent LNF and were case-matched with 72 patients without IEM based on sex, age, BMI, HH size, total pH percentage time, total number of reflux episodes and the presence of BE. Standardized interview assessing postoperative gastrointestinal symptoms, proton pump inhibitor intake, GERD-health-related-quality-of-life (GERD-HRQL), alimentary satisfaction and patients' overall satisfaction was evaluated. RESULTS: Although a higher rate of preoperative dysphagia was observed in patients with IEM (29% IEM vs. 11% no IEM, p = 0.007), there was no significant difference in rates of dysphagia postoperatively (2 IEM vs. 1 no IEM, p = 0.559). Furthermore, no distinction was found in the postoperative outcome regarding symptom relief, quality of life, gas bloating syndrome, ability to belch and/or vomit or revision surgery between the two groups. CONCLUSION: Although preoperative IEM has an influence on GERD presentation, it has no effect on postoperative outcome after LNF. IEM should not be a cause for avoiding LNF, as is has been shown as the most effective and safe anti-reflux treatment.

High Mean Corpuscular Volume Predicts Poor Outcome for Patients With Gastroesophageal Adenocarcinoma.

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.

Swallowing MRI-a reliable method for the evaluation of the postoperative gastroesophageal situs after Nissen fundoplication.

PURPOSE: To evaluate the diagnostic performance of swallowing MRI of the gastroesophageal junction (GEJ) in the postoperative care of patients after laparoscopic antireflux surgery (LARS) MATERIAL AND METHODS: In this institutional review board-approved prospective study, 79 symptomatic patients (mean age, 52.3 years; range, 26-80 years) were evaluated after laparoscopic Nissen fundoplication. MRI findings were correlated with revision surgery, endoscopy, and high-resolution manometry (HRM) as standard of reference. MRI was performed on a 3.0-T unit using T2-weighted half-Fourier acquisition single-shot turbo spin echo (HASTE) sequences for anatomical assessment of the GEJ followed by dynamic MR swallowing (fast low-angle shot sequences). Four independent readers (two radiologists, two surgeons) rated 83 MR scans according to defined criteria, such as wrap disruption, slipping, recurrent hiatal hernia, and esophageal motility disorder. RESULTS: Wrap disruption was correctly diagnosed concordantly with the standard of reference in 87.8%, slipping in 81.5%, and recurrent hiatal hernia in 84.9% of the cases. For esophageal motility disorder, MRI interpretation was consistent with manometry in 66.2% of the subjects. Interobserver analysis showed substantial agreement for recurrent hiatal hernia (k = 0.703), moderate agreement for wrap disruption (k = 0.585), and fair agreement for motility disorder and slipping (k = 0.234 and k = 0.200, respectively). CONCLUSION: MR swallowing readily depicts the major failure mechanisms of LARS and has good reliability even in non-experienced readers. KEY POINTS: • MR swallowing accurately readily depicts the major failure mechanisms of laparoscopic antireflux surgery and has good reliability even in non-experienced readers. • It should be included in the preoperative workup for revision surgery after fundoplication. • It will be of great benefit to surgeons in considering and planning a reoperation.

Electrical lower esophageal sphincter augmentation in patients with GERD and severe ineffective esophageal motility-a safety and efficacy study.

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.

Radiofrequency ablation in patients with large cervical heterotopic gastric mucosa and globus sensation: Closing the treatment gap.

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).

Electrical Stimulation of the Lower Esophageal Sphincter to Treat Gastroesophageal Reflux After POEM.

As per-oral endoscopic myotomy (POEM) is not followed by any anti-reflux procedure, a common concern is the risk of postoperative gastro-esophageal reflux disease (GERD). Electrical stimulation of the lower esophageal sphincter (LES-EST) could be an option for post-POEM GERD. A 68-year old male obese patient underwent successful POEM but developed GERD not responsive to proton pump inhibitors. Consecutively, the patient had implanted an electrical LES stimulation device, consisting of bipolar LES-electrodes connected to a subcutaneous pulse generator. POEM reduced the Eckardt score (9 vs. 0), the LES resting pressure (52.0 vs. 16.4 mmHg), and the Integrated Relaxation Pressure (62.0 vs. 10.0 mmHg). LES-EST substantially reduced post-POEM GERD symptoms. GERD-HRQL scores indicated the elimination of heartburn (26 vs. 7) and regurgitation (24 vs. 3) at three months. A reduced total number refluxes (82 vs. 14) was observed. The %-time of pH below 4 was only slightly reduced (8.6% to 6.2%).LES-EST appears to be a feasible option to symptomatically treat post-POEM GERD for patients not ideal for conventional anti-reflux surgery.

Expression of Programmed Cell Death Protein 1 by Tumor-Infiltrating Lymphocytes and Tumor Cells is Associated with Advanced Tumor Stage in Patients with Esophageal Adenocarcinoma.

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.

Markers of sarcopenia quantified by computed tomography predict adverse long-term outcome in patients with resected oesophageal or gastro-oesophageal junction cancer.

OBJECTIVES: To assess the impact of sarcopenia and alterations in body composition parameters (BCPs) on survival after surgery for oesophageal and gastro-oesophageal junction cancer (OC). METHODS: 200 consecutive patients who underwent resection for OC between 2006 and 2013 were selected. Preoperative CTs were used to assess markers of sarcopenia and body composition (total muscle area [TMA], fat-free mass index [FFMi], fat mass index [FMi], subcutaneous, visceral and retrorenal fat [RRF], muscle attenuation). Cox regression was used to assess the primary outcome parameter of overall survival (OS) after surgery. RESULTS: 130 patients (65%) had sarcopenia based on preoperative CT examinations. Sarcopenic patients showed impaired survival compared to non-sarcopenic individuals (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.15-3.03, p = 0.011). Furthermore, low skeletal muscle attenuation (HR 1.91, 95% CI 1.12-3.28, p = 0.019) and increased FMi (HR 3.47, 95% CI 1.27-9.50, p = 0.016) were associated with impaired outcome. In the multivariate analysis, including a composite score (CSS) of those three parameters and clinical variables, only CSS, T-stage and surgical resection margin remained significant predictors of OS. CONCLUSION: Patients who show signs of sarcopenia and alterations in BCPs on preoperative CT images have impaired long-term outcome after surgery for OC. KEY POINTS: • Sarcopenia is associated with impaired OS after surgery for oesophageal cancer. • Other body composition parameters are also associated with impaired survival. • This influence on survival is independent of established clinical parameters. • Sarcopenia provides a better estimation of cachexia than BMI. • Sarcopenia assessment could be considered in risk/benefit stratification before oesophagectomy.

Change in volume parameters induced by neoadjuvant chemotherapy provide accurate prediction of overall survival after resection in patients with oesophageal cancer.

OBJECTIVES: To assess the prognostic value of volumetric parameters measured with CT and PET/CT in patients with neoadjuvant chemotherapy (NACT) and resection for oesophageal cancer (EC). METHODS: Patients with locally advanced EC, who were treated with NACT and resection, were retrospectively analysed. Data from CT volumetry and (18) F-FDG PET/CT (maximum standardized uptake [SUVmax], metabolic tumour volume [MTV], and total lesion glycolysis [TLG]) were recorded before and after NACT. The impact of volumetric parameter changes induced by NACT (MTVRATIO, TLGRATIO, etc.) on overall survival (OS) was assessed using a Cox proportional hazards model. RESULTS: Eighty-four patients were assessed using CT volumetry; of those, 50 also had PET/CT before and after NACT. Low post-treatment CT volume and thickness, MTV, TLG, and SUVmax were all associated with longer OS (p < 0.05), as were CTthicknessRATIO, MTVRATIO, TLGRATIO, and SUVmaxRATIO (p < 0.05). In the multivariate analysis, only MTVRATIO (Hazard ratio, HR 2.52 [95% Confidence interval, CI 1.33-4.78], p = 0.005), TLGRATIO (HR 3.89 [95%CI 1.46-10.34], p = 0.006), and surgical margin status (p < 0.05), were independent predictors of OS. CONCLUSIONS: MTVRATIO and TLGRATIO are independent prognostic factors for survival in patients after NACT and resection for EC. KEY POINTS: • Change in PET parameters shows close correlation to survival in oesophageal cancer. • Association with OS is independent of changes in SUVmax and CT volume. • Metabolic parameters after NACT correlate with pathologic response and nodal status. • Metabolic parameters may be better suited than SUVmax for response assessment.

Tumor cell budding in preoperative biopsies of esophageal and gastroesophageal junction carcinoma independently predicts survival in a grade-dependent manner.

BACKGROUND: Tumor budding is a prognostic factor in biopsies of different tumor entities. Recent evidence suggests that this also applies to esophageal squamous cell carcinomas. Since esophageal cancer is diagnosed by biopsy, the aim of this study was to investigate whether tumor budding in pretherapeutic biopsies of a mixed tumor population of the esophagus and gastroesophageal junction might predict survival. METHODS: In this retrospective analysis, samples of 78 patients were analyzed (55 adenocarcinomas, 17 squamous cell carcinomas, 5 adenosquamous carcinomas, 1 carcinosarcoma). In addition to preoperative biopsies, budding foci in corresponding resection specimens were assessed and related to overall and relapse-free survival. RESULTS: The main finding was that the number of budding foci in preoperative biopsies predicted overall survival independent of the patient's age and disease stage in a grade-specific (P = .009) manner. In patients with grade 2 tumors, each additional budding focus was associated with an increased chance of death by a factor of 1.28 (hazard ratio 95% confidence interval 1.06-1.55, P = .011). There was no significant association between survival and the number of budding foci in patients with grade 3 tumors, and no budding was observed in grade 1 tumors. Budding foci in resection specimens also showed a certain association with survival, but to a lesser degree. CONCLUSION: Budding foci in preoperative biopsies might serve to improve prognostic accuracy in esophageal carcinomas.

Oncostatin M-enhanced vascular endothelial growth factor expression in human vascular smooth muscle cells involves PI3K-, p38 MAPK-, Erk1/2- and STAT1/STAT3-dependent pathways and is attenuated by interferon-γ.

The pleiotropic cytokine oncostatin M (OSM), a member of the glycoprotein (gp)130 ligand family, plays a key role in inflammation and cardiovascular disease. As inflammation precedes and accompanies pathological angiogenesis, we investigated the effect of OSM and other gp130 ligands on vascular endothelial growth factor (VEGF) production in human vascular smooth muscle cells (SMC). Human coronary artery SMC (HCASMC) and human aortic SMC (HASMC) were treated with different gp130 ligands. VEGF protein was determined by ELISA. Specific mRNA was detected by RT-PCR. Western blotting was performed for signal transducers and activators of transcription1 (STAT1), STAT3, Akt and p38 mitogen-activated protein kinase (p38 MAPK). OSM mRNA and VEGF mRNA expression was analyzed in human carotid endaterectomy specimens from 15 patients. OSM increased VEGF production in both HCASMC and HASMC derived from different donors. OSM upregulated VEGF and OSM receptor-specific mRNA in these cells. STAT3 inhibitor WP1066, p38 MAPK inhibitors SB-202190 and BIRB 0796, extracellular signal-regulated kinase1/2 (Erk1/2) inhibitor U0126, and phosphatidylinositol 3-kinase (PI3K) inhibitors LY-294002 and PI-103 reduced OSM-induced VEGF synthesis. We found OSM expression in human atherosclerotic lesions where OSM mRNA correlated with VEGF mRNA expression. Interferon-γ (IFN-γ), but not IL-4 or IL-10, reduced OSM-induced VEGF production in vascular SMC. Our findings that OSM, which is present in human atherosclerotic lesions and correlates with VEGF expression, stimulates production of VEGF by human coronary artery and aortic SMC indicate that OSM could contribute to plaque angiogenesis and destabilization. IFN-γ reduced OSM-induced VEGF production by vascular SMC.

Thyroid Hormone Replacement Therapy Is Associated with Longer Overall Survival in Patients with Resectable Gastroesophageal Cancer: A Retrospective Single-Center Analysis.

INTRODUCTION: As thyroid hormones modulate proliferative pathways it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined. MATERIAL AND METHODS: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria, including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS). RESULTS: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, n = 647: median OS 29.7 months; hyperthyroid, n = 50: 23.1 months; hypothyroid, n = 70: 47.9 months; p = 0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, n = 53: median OS 30.6 months; with, n = 67: 51.3 months; p = 0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within the limit of normal: 23.4, above: 32.4, below: 9.6 months; p = 0.045). CONCLUSIONS: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.

Silent Gastroesophageal Reflux Disease in Patients with Morbid Obesity Prior to Primary Metabolic Surgery.

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/m2) 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/m2 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.

Modern Esophageal Function Testing and Gastroesophageal Reflux Disease in Morbidly Obese Patients.

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/m2) 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/m2 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.