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.

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.

Severe Dysphagia is Rare After Magnetic Sphincter Augmentation.

BACKGROUND: Dysphagia remains the most significant concern after anti-reflux surgery, including magnetic sphincter augmentation (MSA). The aim of this study was to evaluate postoperative dysphagia rates, its risk factors, and management after MSA. METHODS: From a prospectively collected database of all 357 patients that underwent MSA at our institution, a total of 268 patients were included in our retrospective study. Postoperative dysphagia score, gastrointestinal symptoms, proton pump inhibitor intake, GERD-HRQL, Alimentary Satisfaction, and serial contrast swallow imaging were evaluated within standardized follow-up appointments. To determine patients' characteristics and surgical factors associated with postoperative dysphagia, a multivariable logistic regression analysis was performed. RESULTS: At a median follow-up of 23 months, none of the patients presented with severe dysphagia, defined as the inability to swallow solids or/and liquids. 1% of the patients underwent endoscopic dilatation, and 1% had been treated conservatively for dysphagia. 2% of the patients needed re-operation, most commonly due to recurrent hiatal hernia. Two patients underwent device removal due to unspecific discomfort and pain. No migration of the device or erosion by the device was seen. The LINX® device size ≤ 13 was found to be the only factor associated with postoperative dysphagia (OR 5.90 (95% CI 1.4-24.8)). The postoperative total GERD-HRQL score was significantly lower than preoperative total score (2 vs. 19; p = 0.001), and daily heartburn, regurgitations, and respiratory complains improved in 228/241 (95%), 131/138 (95%) and 92/97 (95%) of patients, respectively. CONCLUSIONS: Dysphagia requiring endoscopic or surgical intervention was rare after MSA in a large case series. LINX® devices with a size < 13 were shown to be an independent risk factor for developing postoperative dysphagia.

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.

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.

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.

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.

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.

Persistent dysphagia is a rare problem after laparoscopic Nissen fundoplication.

BACKGROUND: Although around 30% of patients with gastroesophageal reflux disease (GERD) are insufficiently treated with medical therapy, only 1% opt for surgical therapy. One of the reasons behind this multifactorial phenomenon is the described adverse effect of long-term dysphagia or gastric bloating syndrome after surgical treatment. Aim of this study was to evaluate the most common side effects associated with anti-reflux surgery, as well as long-term outcomes in a large cohort of highly surgically standardized patients after laparoscopic Nissen fundoplication (LNF). METHODS: Out of a prospective patients' database including all patients that underwent anti-reflux surgery between 01/2003 and 01/2017 at our institution, 350 consecutive patients after highly standardized LNF were included in this study. A standardized interview was performed by one physician assessing postoperative gastrointestinal symptoms, proton pump inhibitor intake (PPI), GERD-Health-Related-Quality-of-Life (GERD-HRQL), Alimentary Satisfaction (AS), and patients' overall satisfaction. RESULTS: After a median follow-up of 4 years, persistent dysphagia (PD) after LNF was observed in 8 (2%) patients, while postoperative gas-bloat syndrome in 45 (12.7%) cases. Endoscopic dilatation was needed in 7 (2%) patients due to dysphagia, and 19 (5%) patients underwent revision surgery due to recurrence of GERD. The postoperative GERD-HRQL total score was significantly reduced (2 (IQR 0-4.3) vs. 19 (IQR 17-32); p < 0.000) and the median AS was 9/10. Heartburn relief was achieved in 83% of patients. Eighty-three percent of patients were free of PPI intake after follow-up, whereas 13% and 4% of the patients reported daily and irregular PPI use, respectively. CONCLUSION: LNF is a safe and effective surgical procedure with low postoperative morbidity rates and efficient GERD-related symptom relief. PD does not represent a relevant clinical issue when LNF is performed in a surgical standardized way. These results should be the benchmark to which long-term outcomes of new surgical anti-reflux procedures are compared.

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 (40-77). Median operation time was 290 (215-385) minutes in OE and 292.5 (200-450) 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 = 0.188-9.912; 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 (1-62.6) 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.

PD-L1 expression is an independent predictor of favorable outcome in patients with localized esophageal adenocarcinoma.

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.

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 (33.3-89.5 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.

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).

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) - a rare recently described gastric polyposis syndrome - report of a case.

In rare cases with multiple gastric polyps in the corpus and fundus, a recently described gastric polyposis syndrome called gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) has to be considered. We report on the findings in a patient fulfilling the criteria of this disease.A female patient born in 1977 underwent gastroscopy in 2005 due to recurrent abdominal pain. Endoscopy revealed more than 100 fundic gland polyps in the corpus and fundus. An ileocolonoscopy was inconspicuous. The patient did not take proton pump inhibitors. In follow-up biopsies, fundic gland polyps with low-grade dysplasia were observed. In 2015 gastroscopy with biopsy revealed for the first time high-grade dysplasia in a polyp, and the patient underwent prophylactic gastrectomy.Macroscopic examination of the gastrectomy specimen revealed hundreds of polyps predominantly measuring 3 mm in diameter covering the fundus and corpus. Histology showed fundic gland polyps, mainly covered by normal appearing foveolae. However, several of them were covered by lesions reminiscent of gastric foveolar adenomas with low- and focally high-grade dysplasia. Molecular pathology revealed a point mutation in the adenomatous polyposis coli promotor 1B. These findings in conjunction with the knowledge that the patient's father had died of gastric carcinoma in his 50 s led to the diagnosis of the autosomal dominant syndrome GAPPS, which has hitherto been described in 9 families.

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 6.2-17.6). 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.

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.

Tension-Free Inlay Repair of Large Hiatal Hernias Using Dual-Sided Composite PTFE/ePTFE Meshes in Laparoscopic Surgery for Gastroesophageal Reflux Disease.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) also frequently suffer from concomitant hiatal hernia. It has been described that a preoperative hiatal hernia of ≥3 cm is associated with a more than threefold relative risk for reflux symptom recurrence after fundoplication without mesh reinforcement. In this report, we describe our experience with the implantation of dual-sided composite PTFE/ePTFE meshes in a tension-free fashion during laparoscopic antireflux surgery (LARS). METHODS: A prospective database containing data of all patients undergoing LARS and hiatal hernia repair with mesh implantation from January 2009 until December 2014 was interrogated. Ten patients with preoperative esophageal high resolution manometry and 24-hour pH impedance monitoring because of symptoms suggestive of GERD who received hiatal repair using dual-sided meshes in inlay technique were identified and included in this analysis. RESULTS: There were no conversions to open surgery in the study group. Median operative time was 138 minutes (interquartile range Q1-Q3: 119-151 minutes) and average length of postoperative stay was 3.5 days (interquartile range Q1-Q3: 2.3-4.0 days). During a median follow-up period of 43.3 months (interquartile range Q1-Q3: 18.9-47.1 months), no redo operations had to be performed. Noteworthy, 2 patients complained about dysphagia (20%) during follow-up, but symptoms resolved after endoscopic interventions. CONCLUSIONS: Tension-free inlay repair of large hiatal hernias using dual-sided composite PTFE/ePTFE meshes during LARS provides promising results. It provides satisfactory symptom relief and prolonged control of GERD. Further studies to validate its efficiency in a larger collective are needed.

A retrospective study on the safety, diagnostic yield, and therapeutic effects of endoscopic unroofing for small gastric subepithelial tumors.

BACKGROUND AND AIMS: Accurate diagnosis of small gastric subepithelial tumors (SETs) is essential to assess their malignant potential. Endoscopic unroofing has been reported to yield sufficient tissue samples for histologic evaluation. This study aimed to evaluate the safety, diagnostic yield, and potential therapeutic effects of this technique over time. METHODS: This retrospective analysis of prospectively collected clinical data identified patients who underwent endoscopic unroofing at the Medical University of Vienna from January 2003 to December 2012. Demographic data, indications for endoscopic unroofing, intraprocedural adverse events, hospital stay, histologic results, and follow-up procedures were reviewed. RESULTS: A total of 14 patients (7 men; 7 women; median age, 70 years; range, 51-95 years) underwent endoscopic unroofing of 14 gastric SETs with a mean diameter of 26 ± 13 mm at EUS. In 9 of 14 cases, endoscopic unroofing was done exclusively for diagnostic purposes; in the remaining cases, it was performed with therapeutic intent because of bleeding from the gastric SETs. Unroofing was technically successful in 13 of 14 cases and revealed 8 cases of GI stromal tumor (GIST) and 1 case each of leiomyoma, fibroid polyp, glomus tumor, pancreatic rest, and nondiagnostic material at histology. Intraprocedural bleeding was the only adverse event (4 cases) and could be managed endoscopically. A follow-up EUS was available (median, 8 months) for 10 of the 14 patients. Notably, most patients showed complete regression of their gastric SETs after unroofing (on white light and EUS), including the glomus tumor, the leiomyoma, and 6 of the 8 cases of GIST. CONCLUSIONS: Endoscopic unroofing was safe and had a very favorable diagnostic yield in this study. Unexpectedly, it led to complete regression in most gastric SETs. Although it is not an oncologically curative treatment, endoscopic unroofing can be a valuable option to treat local adverse events in patients unfit for surgical therapy. (Clinical trial registration number: NCT02587923.).