Improving the Diagnostic Yield of High-Resolution Esophageal Manometry for GERD: The "Straight Leg-Raise" International Study.

BACKGROUND & AIMS: The straight leg raise (SLR) maneuver during high-resolution manometry (HRM) can assess esophagogastric junction (EGJ) barrier function by measuring changes in intraesophageal pressure (IEP) when intra-abdominal pressure is increased. We aimed to determine whether increased esophageal pressure during SLR predicts pathologic esophageal acid exposure time (AET). METHODS: Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%. RESULTS: The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P < .001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected. CLINICALTRIALS: gov ID: NCT04813029.

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.

Performance of a new natural oral contrast agent (LumiVision®) in dynamic MR swallowing.

OBJECTIVES: To evaluate image quality by first use of LumiVision® in dynamic MR swallowing, a contrast medium consisting of biological substances versus a gadolinium-buttermilk mixture in patients who underwent Nissen fundoplication due to gastroesophageal reflux disease (GERD). METHODS: The protocol of this retrospective study was approved by the local Institutional Review Board. A hundred twenty-nine patients (146 examinations) underwent a dynamic MR swallowing study (at 1.5 T or 3.0 T) and received an oral contrast agent. Two readers evaluated the distention of the esophagus, contrast, and traceability of the bolus in a 3-point scale. A steady-state coherent sequence (B-FFE, TrueFISP) was used. The patients were divided into 3 different groups: 53 patients received gadolinium chelate (Dotarem®)-buttermilk mixture (GBM) in a dilution of 1:40 as an oral contrast agent; 44 patients received LumiVision® water mixture (LWM) in a dilution of 1:1 and 49 patients received LumiVision® (L) undiluted. RESULTS: GBM showed significantly better results in overall evaluation for both readers in contrast to LWM (p = .003, p = .002). L also reached significantly better results in overall evaluation than LWM in both readers (p = .004, p = .042). There was no significant difference in the overall evaluation between L and GBM (p = .914, p = .376).According to Landis and Koch, interobserver agreement was "substantial" (Cohen's kappa = 0.738) between both readers. CONCLUSION: LumiVision® undiluted showed equal image quality compared to gadolinium-buttermilk mixture. The constellation of LumiVision® water mixture led to a clearly negative result in relation to the image quality compared to LumiVision® undiluted. Therefore, oral ingestion of LumiVision® undiluted is recommended for MR swallowing examinations. KEY POINTS: • LumiVision® undiluted shows significantly better image quality in comparison to LumiVision® diluted in oral application in swallowing MRI. • LumiVision® undiluted shows equal image quality in comparison to gadolinium-buttermilk mixture in oral application. • Oral ingestion of LumiVision® undiluted can replace gadolinium-buttermilk mixture in oral MR examinations.

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.

Allograft rejection is associated with development of functional IgE specific for donor MHC antigens.

BACKGROUND: Donor-specific antibodies of the IgG isotype are measured routinely for diagnostic purposes in renal transplant recipients and are associated with antibody-mediated rejection and long-term graft loss. OBJECTIVE: This study aimed to investigate whether MHC-specific antibodies of the IgE isotype are induced during allograft rejection. METHODS: Anti-MHC/HLA IgE levels were measured in sera of mice grafted with skin or heart transplants from various donor strains and in sera of kidney transplant patients with high levels of HLA IgG. Mediator release was triggered in vitro by stimulating basophils that were coated with murine or human IgE-positive serum, respectively, with specific recombinant MHC/HLA antigens. Kidney tissue samples obtained from organ donors were analyzed by using flow cytometry for cells expressing the high-affinity receptor for IgE (FcεRI). RESULTS: Donor MHC class I- and MHC class II-specific IgE was found on acute rejection of skin and heart grafts in several murine strain combinations, as well as during chronic antibody-mediated heart graft rejection. Anti-HLA IgE, including donor HLA class I and II specificities, was identified in a group of sensitized transplant recipients. Murine and human anti-MHC/HLA IgE triggered mediator release in coated basophils on stimulation with specific MHC/HLA antigens. HLA-specific IgE was not linked to atopy, and allergen-specific IgE present in allergic patients did not cross-react with HLA antigens. FcεRI+ cells were found in the human renal cortex and medulla and provide targets for HLA-specific IgE. CONCLUSION: These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms.

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.

Results of Magnetic Sphincter Augmentation for Gastroesophageal Reflux Disease.

BACKGROUND: Magnetic sphincter augmentation (MSA) is a modern treatment option for gastroesophageal reflux disease (GERD); however, laparoscopic fundoplication remains the gold standard. The aim of the study was to evaluate outcomes of MSA patients at a reflux center. METHODS: A retrospective review was performed of all patients that underwent MSA between March 2012 and November 2017. Out of 110 patients, 68 with a follow-up >3 months were included. Postoperative gastrointestinal symptoms, proton pump inhibitor (PPI) intake, GERD-Health-related Quality of Life (GERD-HRQL) and alimentary satisfaction (AS) were assessed. Postoperative esophageal functioning tests were performed in 50% of patients. RESULTS: Sixty-eight patients underwent MSA; hiatal repair was performed in 31 cases. The median OR time was 27 min, and no intraoperative complications occurred. The median follow-up was 13 months (IQR 4.2-45). Endoscopic dilatation was performed in 2 patients (3%) and device removal in another 2 cases. The postoperative GERD-HRQL score was significantly reduced (3 vs. 24; p < 0.001) and the median AS was 8/10. Preoperative experienced heartburn, regurgitations and dysphagia were eliminated in 92, 96 and 100%. Postoperative new-onset difficulties swallowing with solids only were reported to occur occasionally by 16% and rarely by 21% of patients. Satisfaction with heartburn relief was 95%, and the overall outcome was rated excellent/good in 89%. PPI dependency was eliminated in 87%. The median total percentage pH < 4 and number of reflux episodes were significantly reduced. Postoperative pH results were negative or slightly above the norm in 79% and 12%, respectively. CONCLUSION: Sphincter augmentation results in significantly reduced reflux symptoms, increased GERD-specific Quality of Life and excellent alimentary satisfaction with low perioperative morbidity. This procedure should be considered an excellent alternative to fundoplication in the treatment of GERD.

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.

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.).

Minimal-invasive approach for penetrating Crohn's disease is not associated with increased complications.

BACKGROUND: Laparoscopic surgery for penetrating Crohn's disease (CD) still remains highly conflicting due to a lack of sufficient data. Therefore, the following large study was designed to compare postoperative outcomes after minimal-invasive resections for penetrating and non-penetrating CD. METHODS: Consecutive patients, who underwent laparoscopic intestinal resection for symptomatic CD at a tertiary academic referral center, were included. Patients were divided according to perioperative findings in penetrating and non-penetrating type of disease. All clinical data were obtained from an institutional database and analyzed retrospectively. RESULTS: Of 234 patients enrolled, 101 patients [females: n = 54 (53.5 %)] were operated on for non-penetrating CD and 133 patients [females: n = 50 (37.6 %)] for penetrating CD. Fistulas (p < 0.001), inflammatory mass (p < 0.001) and abscess formation (p < 0.001) were observed more frequently in the perforating group. Ileocolic resections were performed predominantly in both groups [perforating CD: n = 110 (82.7 %), non-perforating CD: n = 82 (81.2 %)], with more complex resections (>1 intestinal resection) found in perforating CD (p < 0.001). Conversion rates did not differ significantly. Notably, 30-day postoperative morbidity was comparable for both groups [perforating CD: n = 20 (15 %), non-perforating CD: n = 19 (18.8 %), p = 0.44]. Postoperative complication rates graded according to the Clavien-Dindo classification showed no difference too (p = 0.49). CONCLUSION: Laparoscopic surgery can be conducted safely in selected patients with penetrating CD without increasing the risk of postoperative complications. This finding needs to be implemented in future guidelines.

Diagnosis and Management of the Largest Documented Appendicolith in Literature: A Case Report.

This case report depicts the diagnosis and management of the largest documented appendicolith found in the medical literature so far, measuring 4.5 cm. A 44-year-old male patient presented with a distended abdomen, right lower quadrant (RLQ) pain, constipation, and the inability to consume solid food. Laboratory tests revealed leukocytosis and elevated C-reactive protein (CRP) levels. Abdominal X-rays showed a densely calcified structure in the right lower quadrant, and further imaging confirmed the diagnosis of appendicolithiasis. The surgical indication for appendectomy was determined, and an open surgical procedure was performed due to the severity of inflammation, minimal perforation, and extensive adhesions. The surgically removed appendix with the appendicolith was analyzed histologically, confirming appendicolithiasis, periappendicitis, perforation, and serositis. The patient was discharged in stable condition after postoperative management. Giant appendicoliths are rare and associated with an increased risk of complications. Diagnosis is typically clinical but can be enhanced by imaging modalities.

The Milan score: A novel manometric tool for a more efficient diagnosis of gastro-esophageal reflux disease.

OBJECTIVE: A definitive diagnosis of gastroesophageal reflux disease (GERD) depends on endoscopic and/or pH-study criteria. However, high resolution manometry (HRM) can identify factors predicting GERD, such as ineffective esophageal motility (IEM), esophago-gastric junction contractile integral (EGJ-CI), evaluating esophagogastric junction (EGJ) type and straight leg raise (SLR) maneuver response. We aimed to build and externally validate a manometric score (Milan Score) to stratify the risk and severity of the disease in patients undergoing HRM for suspected GERD. METHODS: A population of 295 consecutive patients undergoing HRM and pH-study for persistent typical or atypical GERD symptoms was prospectively enrolled to build a model and a nomogram that provides a risk score for AET > 6%. Collected HRM data included IEM, EGJ-CI, EGJ type and SLR. A supplemental cohort of patients undergoing HRM and pH-study was also prospectively enrolled in 13 high-volume esophageal function laboratories across the world in order to validate the model. Discrimination and calibration were used to assess model's accuracy. Gastroesophageal reflux disease was defined as acid exposure time >6%. RESULTS: Out of the analyzed variables, SLR response and EGJ subtype 3 had the highest impact on the score (odd ratio 18.20 and 3.87, respectively). The external validation cohort consisted of 233 patients. In the validation model, the corrected Harrel c-index was 0.90. The model-fitting optimism adjusted calibration slope was 0.93 and the integrated calibration index was 0.07, indicating good calibration. CONCLUSIONS: A novel HRM score for GERD diagnosis has been created and validated. The MS might be a useful screening tool to stratify the risk and the severity of GERD, allowing a more comprehensive pathophysiologic assessment of the anti-reflux barrier. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT05851482).