MK2 and ETV1 Are Prognostic Factors in Esophageal Adenocarcinomas

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

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

n/

Alternative therapies for GERD : a way to personalized antireflux surgery

Gastroesophageal reflux disease (GERD) is a commondisorder, known to affect about20%of theWestern population. Although conventional medical or surgical treatment has proven effective, there is certainly room for improvements. As only 10% of GERD patients are finally treated by antireflux surgery, a large therapeutic window exists. This treatment gap consists of patients who are not effectively treated with proton pump inhibitor but do not want to run the potential risks of conventional surgery. During the last two decades, several novel and intriguing options for the surgical treatment of GERD have been introduced and found their way into clinical use. The following summary will give an update of certain alternative therapeutic options to treat GERD or its pathological consequences

Scientific Reports / External validation of the NUn score for predicting anastomotic leakage after oesophageal resection

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 6.217.6). The odds ratio for AL was 1.31 (CI 1.031.67; p=0.028). AUC for AL was 0.59 (CI 0.470.72). 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.(VLID)461590

Surgical Endoscopy / 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 11.5301). Median total % pH<4 was 8.9 (quartiles 421.6). 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 15.9332.07) 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.(VLID)365980

Oncotarget / The modified glasgow prognostic score is an independent prognostic indicator in neoadjuvantly treated adenocarcinoma of the esophagogastric junction

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 (33.389.5 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.(VLID)471339

European Surgery / Morbidity in open versus minimally invasive hybrid esophagectomy (MIOMIE) : Long-term results of a randomized controlled clinical study

Background The minimally invasive esophagectomy (MIE) for esophageal cancer was introduced assuming a reduction of morbidity and operation time. After implementation of MIE at our institution, a randomized controlled trial was designed. Methods This is a prospective randomized controlled study comparing open (OE) and laparoscopic gastric tube (MIE) formation in Ivor Lewis esophagectomy. Primary endpoints were morbidity and 30-day mortality. Secondary endpoints included the duration of intensive care unit stay, length of hospital stay, operative time as well as relapse-free and overall survival. Results Twenty patients (76.9%) were male, median age was 63 years (4077). Median operation time was 290 (215385) minutes in OE and 292.5 (200450) minutes in MIE group, p = 0.421. Major complications occurred in 4 (33.3%) patients in the OE group and in 6 (35.7%) patients in the MIE group. Anastomotic leakage was seen in 2 (16.6%) and 3 (21.4%) patients, respectively (OR 1.364; CI = 0.1889.912; p = 0.759). Due to an alarming number of consecutive anastomotic leakages, the trial was stopped after inclusion of 26 patients. Median follow-up was 41.5 (162.6) months. 5year survival rate was 50%. Thirty-eight percent developed recurrence of disease in the study period. There was no significant difference in overall and relapse-free survival regarding the type of surgery. Conclusion This study shows that hybrid MIE is a feasible alternative for esophageal resection. Morbidity, mortality, and oncological long-term results were equal in both groups, but the interpretation has to be done carefully due to premature termination of the trial. Interrupting a trial because of patient benefit should not be a reason to discard results but rather to improve technical aspects and strive for novel studies.(VLID)361607

Scientific Reports / Phenotypes of Jackhammer esophagus in patients with typical symptoms of gastroesophageal reflux disease responsive to proton pump inhibitors

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)(VLID)464183

Swallowing MRIa 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, 2680 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.(VLID)364367