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).

Efficacy of esophageal stents as a primary therapeutic option in spontaneous esophageal perforations: a systematic review and meta-analysis of observational studies.

Background: Spontaneous esophageal perforation traditionally mandates urgent surgical treatment. Lately, esophageal stents have been used to reduce the associated morbidity and mortality. The current systematic review aimed to assess the efficacy of stents as a primary treatment option in this scenario. Methods: A systematic search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library for studies published in the English language between 2000 and 2023. We included observational studies reporting on the use of stents, alongside conservative measures and drainage procedures, in patients with spontaneous esophageal perforations. Primary outcomes were sealing rate (persistent leak occlusion) and failure rate (mortality or conversion to a major surgical operation). Secondary outcomes included patients' presentation, sepsis, drainage procedures, and reinterventions. Results for primary outcomes were presented as pooled rates with 95% confidence intervals (CIs), using a random-effects model. Methodological quality was assessed using the MINORS score. Results: Eighteen studies involving 171 patients were included. Sealing rate was 86% (95%CI 77-93%) and failure rate was 14% (95%CI 7-22%). Weighted mortality rate was 6% (95%CI 2-13%), while conversion to surgical treatment was 2% (95%CI 0-9%). Late presentation was not related to a statistically significant increase in treatment failure (odds ratio 1.85, 95%CI 0.37-9.30; P=0.72). Drainage procedures were required for the majority of patients, with a high rate of surgical and endoscopic reinterventions. Conclusions: Our results imply that stents may offer an effective and safe alternative treatment for patients with spontaneous esophageal perforations. Additional endoscopic and surgical drainage procedures are frequently needed.

Life-threatening urosepsis because of ureteral entrapment within a large inguinal hernia.

Ureteral hernias are an uncommon entity that are usually incidentally discovered during inguinal hernia repair. However, when symptomatic, they could cause severe symptoms from the urinary system and even affect renal function. We aim to report a rare case of a 91-year-old male patient with urosepsis because of ureteral entrapment within an inguinal hernia, and further discuss proper management of such cases.

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.

miRNAs expression pattern and machine learning models elucidate risk for gastric GIST.

BACKGROUND: Gatrointestinal stromal tumors (GISTs) are the main mesenchymal tumors found in the gastrointestinal system. GISTs clinical phenotypes differ significantly and their molecular basis is not yet completely known. microRNAs (miRNAs) have been involved in carcinogenesis pathways by regulating gene expression at post-transcriptional level. OBJECTIVE: The aim of the present study was to elucidate the expression profiles of miRNAs relevant to gastric GIST carcinogenesis, and to identify miRNA signatures that can discriminate the GIST from normal cases. METHODS: miRNA expression was tested by miScript™miRNA PCR Array Human Cancer PathwayFinder kit and then we used machine learning in order to find a miRNA profile that can predict the risk for GIST development. RESULTS: A number of miRNAs were found to be differentially expressed in GIST cases compared to healthy controls. Among them the hsa-miR-218-5p was found to be the best predictor for GIST development in our cohort. Additionally, hsa-miR-146a-5p, hsa-miR-222-3p, and hsa-miR-126-3p exhibit significantly lower expression in GIST cases compared to controls and were among the top predictors in all our predictive models. CONCLUSIONS: A machine learning classification approach may be accurate in determining the risk for GIST development in patients. Our findings indicate that a small number of miRNAs, with hsa-miR218-5p as a focus, may strongly affect the prognosis of GISTs.

Eosinophilic Esophagitis and Achalasia: Two Distinct Nosologic Entities or a Possible Etiopathogenic Association?

BACKGROUND: Despite the fact that researchers have made significant progress in elucidating the pathophysiology of esophageal diseases, the understanding of esophageal motility alterations in patients with eosinophilic esophagitis (EoE) is in its infancy and current published medical literature remains rather scarce on this topic. A growing body of scientific data regarding associations between esophageal motor disorders, such as achalasia and EoE, exists nowadays. SUMMARY: It seems that the association of EoE and achalasia does not constitute a cause and effect relationship, as it is not clear whether esophageal motility abnormalities are the result of EoE or vice versa. As such, there is no universally accepted treatment algorithm for patients presenting with both of these entities. Key Messages: The aim of this article is to review the existing data on achalasia-like motility disorders in patients with EoE, highlighting a possible association between these 2 esophageal disorders. Moreover, we seek to describe the clinical presentation in such cases, diagnostic modalities to be used, and current treatment strategies in patients suspected to suffer from both disorders.

Effect of video games playing on surgical simulation training: a systematic review.

INTRODUCTION: Video games have a positive impact on the skills required for laparoscopic surgery. Several studies have assessed the impact of video games on laparoscopic skills. AIM: This study aims to systematically review the existing evidence. MATERIALS AND METHODS: A search strategy was implemented to retrieve relevant articles from MEDLINE and SCOPUS databases. The retrieved articles were reviewed for further evaluation according to the predetermined inclusion/exclusion criteria. RESULTS: Twenty-six studies were included in this systematic review. These included prospective (n=9), retrospective (n=5) and interventional (n=12). Other review papers were cited in the discussion section. Studies with positive outcomes significantly outweighed the negative ones (21 vs. 5, respectively). CONCLUSIONS: Although there is some evidence that video game experience could give some advantage in laparoscopy no firm conclusions could be drawn yet. The reasons for that lay in the various aims, approaches and results of different study reports. Gaming could be used as a daily warm-up or as a tool to speed-up mastering new skills. A standardized protocol is needed for answering the different questions regarding the impact of video game exposure to laparoscopic skills development and progression.

Esophageal cancer: challenges, concerns, and recommendations for management amidst the COVID-19 pandemic.

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, raising great concern, particularly in immunosuppressed cancer patients. The pandemic situation remains extremely dynamic, which necessitates proactive management decisions from oncologists and oncologic surgeons in effort to mitigate the risk of both SARS-CoV-2 infection and cancer metastasis. Esophageal cancer, in particular, is one of the deadliest types of malignancy worldwide, reflecting both aggressive biology and a lack of adequate treatment. Several challenges and concerns regarding the management of esophageal cancer have been raised in light of the ongoing viral pandemic. The primary aim of this review is to summarize the salient evidence for recommendations and optimal treatment strategies for patients with esophageal cancer amidst the COVID-19 pandemic.

Acute esophageal necrosis: A systematic review and pooled analysis.

BACKGROUND: Acute esophageal necrosis (AEN) is a rare entity with multifactorial etiology, usually presenting with signs of upper gastrointestinal bleeding. AIM: To systematically review all available data on demographics, clinical features, outcomes and management of this medical condition. METHODS: A systematic literature search was performed with respect to the PRISMA statement (end-of-search date: October 24, 2018). Data on the study design, interventions, participants and outcomes were extracted by two independent reviewers. RESULTS: Seventy-nine studies were included in this review. Overall, 114 patients with AEN were identified, of whom 83 were males and 31 females. Mean patient age was 62.1 ± 16.1. The most common presenting symptoms were melena, hematemesis or other manifestations of gastric bleeding (85%). The lower esophagus was most commonly involved (92.9%). The most widely implemented treatment modality was conservative treatment (75.4%), while surgical or endoscopic intervention was required in 24.6% of the cases. Mean overall follow-up was 66.2 ± 101.8 d. Overall 29.9% of patients died either during the initial hospital stay or during the follow-up period. Gastrointestinal symptoms on presentation [Odds ratio 3.50 (1.09-11.30), P = 0.03] and need for surgical or endoscopic treatment [surgical: Odds ratio 1.25 (1.03-1.51), P = 0.02; endoscopic: Odds ratio 1.4 (1.17-1.66), P < 0.01] were associated with increased odds of complications. A sub-analysis separating early versus late cases (after 2006) revealed a significantly increased frequency of surgical or endoscopic intervention (9.7 % vs 30.1% respectively, P = 0.04). CONCLUSION: AEN is a rare condition with controversial pathogenesis and unclear optimal management. Although the frequency of surgical and endoscopic intervention has increased in recent years, outcomes have remained the same. Therefore, further research work is needed to better understand how to best treat this potentially lethal disease.

Enhanced recovery pathways vs standard care pathways in esophageal cancer surgery: systematic review and meta-analysis.

Enhanced recovery after surgery (ERAS) protocols vs standard care pathways after esophagectomy for malignancy have gained wide popularity among surgeons. However, the current literature is still lacking level-I evidence to show a clear superiority of one approach. The present study is a detailed systematic review and meta-analysis of the published trials. A systematic review of literature databases was conducted for randomized controlled trials (RCTs) and non-randomized, prospective, comparative studies between January 1990 and September 2019, comparing ERAS pathway group with standard care for esophageal resection for esophageal cancer. Mean difference (MD) for continuous variables and odds ratio (OR) or risk difference (RD) for dichotomous variables with 95% confidence interval (CI) were used. Between-study heterogeneity was evaluated. Eight studies with a total of 1133 patients were included. Hospital stay [Standard mean difference (Std. MD) = - 1.92, 95% CI - 2.78, - 1.06, P < 0.0001], overall morbidity (OR 0.68, CI 0.49, 0.96, P = 0.03), pulmonary complications (OR 0.45, CI 0.31, 0.65, P < 0.0001), anastomotic leak rate (OR 0.37, CI 0.18, 0.74, P = 0.005), time to first flatus and defecation (Std. MD = -5.01, CI - 9.53, - 0.49, P = 0.03), (Std. MD = - 1.36, CI - 1.78, - 0.94, P < 0.00001) and total hospital cost (Std. MD = - 1.62, CI - 2.24, - 1.01, P < 0.00001) favored the ERAS group. Patients who undergo ERAS have a clear benefit over the standard care protocol. However, existing protocols in different centers are followed by great variability, while the evaluated parameters suffer from significant heterogeneity. A well-formulated, standardized protocol should be standard-of-care at all centers.

The 100 most cited manuscripts in esophageal motility disorders: a bibliometric analysis.

BACKGROUND: The use of bibliometrics can help us identify the most impactful articles on a topic or scientific discipline and their influence on clinical practice. We aimed to identify the 100 most cited articles covering esophageal motility disorders and examine their key characteristics. METHODS: The Web of Science database was utilized to perform the search, using predefined search terms. The returned dataset was filtered to include full manuscripts written in the English language. After screening, we identified the 100 most cited articles and analyzed them for title, year of publication, names of authors, institution, country of the first author, number of citations and citation rate. RESULTS: The initial search returned 29,521 results. The top 100 articles received a total of 20,688 citations. The most cited paper was by Inoue et al. (665 citations) who first described peroral endoscopic myotomy (POEM) for treating achalasia. The article with the highest citation rate was the third version of the Chicago Classification system, written by Kahrilas and colleagues. Gastroenterology published most papers on the list (n=32) and accrued the highest number of citations (6,675 citations). Peter Kahrilas was the most cited author (3,650 citations) and, along with Joel Richter, authored the highest number of manuscripts (n=14). Most articles were produced in the USA (n=66) between the years 1991 and 2000 (n=32). CONCLUSIONS: By analyzing the most influential articles, this work is a reference on the articles that shaped our understanding of esophageal motility disorders, thus serving as a guide for future research.

Long-term outcome of myotomy and fundoplication based on intraoperative real-time high-resolution manometry in achalasia patients.

BACKGROUND: Current treatment options for achalasia of the esophagus predominantly consist of endoscopic myotomy or laparoscopic myotomy combined with a partial fundoplication. The intraoperative use of conventional manometry has previously been proposed with various results. The aim of the present study was to introduce the use of high-resolution manometry (HRM) during surgical treatment for achalasia and to assess the long-term outcome of this technique. METHODS: We enrolled achalasia patients within the time period November 2013 to July 2016 who underwent HRM and evaluation of Eckardt scores (ES) before and after tailored laparoscopic myotomy and fundoplication with intraoperative recording using HRM. RESULTS: Twenty patients were classified as having achalasia type I (20%), type II (55%), or type III (25%). During surgery, 9 myotomies were extended and 13 fundoplications were modified according to HRM findings. Mean resting (16.1 vs. 41.9 mmHg) and residual (9 vs. 28.7 mmHg) pressures of the lower esophageal sphincter and ES (0.7 vs. 6.9) were significantly eliminated postoperatively over a mean follow-up time of 17.7 months. CONCLUSIONS: The use of intraoperative HRM gives us the advantage of simultaneous real-time estimation of intraluminal pressures of the esophagus and the ability to identify the exact points that produce pressure during laparoscopy. Consequently, it may be the key to the tailoring of the Heller-Dor technique and improving the outcomes for achalasia patients.

Can the upper esophageal sphincter contractile integral help classify achalasia?

BACKGROUND: The use of high-resolution manometry (HRM) in achalasia patients has revealed abnormal findings concerning upper esophageal sphincter (UES) function. The introduction of the UES contractile integral (UES-CI), as with the distal contractile integral (DCI), may complement the interpretation of the manometric study of achalasia subtypes, defined by the Chicago Classification v3.0. METHODS: Patients were classified into achalasia subtypes based on HRM. UES length (cm), UES resting pressure (mmHg), and UES residual pressure (mmHg) were recorded. UES-CI (mmHg·sec·cm) was calculated in a manner similar to that used for the DCI measurement at rest (landmark CI), corrected for respiration, and its relation to achalasia subtypes was evaluated. RESULTS: Twenty-four achalasia patients with mean age 55.29 years were included. Of these, 16.6% (n=4) were diagnosed with achalasia type I, 58.3% (n=14) with type II, and 25% (n=6) with type III. The landmark UES-CI, mean UES-CI, UES-CI corrected for respiration, and UES resting pressure were found to be significantly higher among patients with achalasia type II compared to the other types (1768.9 vs. 677.1, P=0.03; 1827.1 vs. 3555.1, P=0.036; 174.2 vs. 72.8, P=0.027; and 108.1 vs. 55.8, P=0.009, respectively). CONCLUSIONS: We introduce the CI index as a tool for the manometric evaluation of the UES in achalasia. UES resting pressure, landmark UES-CI and mean UES-CI were significantly higher in achalasia patients with panesophageal pressurization compared to types I and III. This finding may reflect a protective reaction against the risk of aspiration in this group, but further studying and clinical correlation is required.

Acid and nonacid gastroesophageal reflux after single anastomosis gastric bypass. An objective assessment using 24-hour multichannel intraluminal impedance-pH metry.

BACKGROUND: Single anastomosis gastric bypass (SaGB) was introduced in 2001 as an alternative to "loop" gastric bypass. It was considered as a procedure that would eliminate alkaline reflux and associated esophagitis. OBJECTIVES: Existing evidence about the postoperative incidence of gastroesophageal reflux (GERD) after SaGB is based on studies using symptom questionnaires. The aim of our study was to evaluate GERD 12 months after SaGB by using 24-hour multichannel intraluminal impedance pH metry (24-h MIIpH). SETTING: Surgical department of a university hospital METHODS: Morbidly obese candidates for SaGB underwent 24-hour MIIpH prior and 12 months after their bariatric procedure. RESULTS: There were 11 patients included in this prospective study. Results of 24-hour MIIpH revealed that DeMeester score (40.48 versus 24.16, P = .339) had an increasing trend 12 months after SaGB. Acid reflux episodes decreased, whereas nonacid reflux episodes increased postoperatively, both in proximal and distal esophagus. Total median bolus clearance time and acid clearance time increased. De novo GERD developed in 2 patients (28.6%) and worsening of already existing GERD developed in all patients with preoperative evidence of GERD. CONCLUSION: The use of symptom questionnaires to assess postoperative GERD after SaGB may not accurately depict the real image. Twenty-four-hour MIIpH in 12 months after SaGB revealed an increase of total number of nonacid reflux episodes and a decrease of total number of acid reflux episodes, with longer duration of each acid reflux episode. Close postoperative follow-up with reflux testing and possibly endoscopy could eliminate the risk of complicated GERD.

Real-time Continuous Esophageal High-resolution Manometry (HRM) During Laparoscopic Heller Myotomy and Dor Fundoplication for the Treatment of Achalasia. A Promising Novelty in Regards of Perfecting Surgical Technique: Could It Guide Surgical Technique Toward Excellent Results?

High-resolution manometry (HRM) is the gold-standard diagnostic tool for achalasia of the esophagus. Laparoscopic Heller-Dor technique is the preferred surgical approach with success rate estimated 90%. The use of intraoperative HRM provides real-time estimation of intraluminal esophageal pressures and identifies the exact points of esophageal luminal pressure during laparoscopy. Ten patients with achalasia underwent surgery. All patients preoperatively completed 1 manometric study and Quality of Life questionnaires (EORTC QLQ-C30 version 3.0) with Eckardt scores. We collected intraoperative manometry data and repeated manometric studies, EORTC QLQ-C30, and Eckardt scores postoperatively. Median Eckardt score was decreased from 7.5 to 0.5, mean resting pressure decreased from 51.4 to 11.9 mm Hg, whereas mean residual pressure diminished from 45.9 to 9.5 mm Hg postoperatively. The simultaneous use of HRM during the Heller-Dor technique may lead to an individualized management of the disease.