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  1. Siboni S, Kristo I, Rogers BD, De Bortoli N, Hobson A, Louie B, et al.
    Clin Gastroenterol Hepatol, 2023 Jul;21(7):1761-1770.e1.
    PMID: 36270615 DOI: 10.1016/j.cgh.2022.10.008
    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.

    Matched MeSH terms: Esophagogastric Junction/pathology
  2. Derakhshan MH, Robertson EV, Yeh Lee Y, Harvey T, Ferrier RK, Wirz AA, et al.
    Gut, 2015 Nov;64(11):1705-14.
    PMID: 25753030 DOI: 10.1136/gutjnl-2014-308914
    INTRODUCTION: Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine whether it may be due to columnar metaplasia of the distal oesophagus.

    METHODS: We used the squamocolumnar junction (SCJ), antral and body biopsies from the 52 Helicobacter pylori-negative healthy volunteers who had participated in our earlier physiological study and did not have hiatus hernia, transsphincteric acid reflux, Barrett's oesophagus or intestinal metaplasia (IM) at cardia. The densities of inflammatory cells and reactive atypia were scored at squamous, cardiac and oxyntocardiac mucosa of SCJ, antrum and body. Slides were stained for caudal type homeobox 2 (CDX-2), villin, trefoil factor family 3 (TFF-3) and liver-intestine (LI)-cadherin, mucin MUC1, Muc-2 and Muc-5ac. In addition, biopsies from 15 Barrett's patients with/without IM were stained and scored as comparison. Immunohistological characteristics were correlated with parameters of obesity and high-resolution pH metry recording.

    RESULTS: Cardiac mucosa had a similar intensity of inflammatory infiltrate to non-IM Barrett's and greater than any of the other upper GI mucosae. The immunostaining pattern of cardiac mucosa most closely resembled non-IM Barrett's showing only slightly weaker CDX-2 immunostaining. In distal oesophageal squamous mucosa, expression of markers of columnar differentiation (TFF-3 and LI-cadherin) was apparent and these correlated with central obesity (correlation coefficient (CC)=0.604, p=0.001 and CC=0.462, p=0.002, respectively). In addition, expression of TFF-3 in distal oesophageal squamous mucosa correlated with proximal extension of gastric acidity within the region of the lower oesophageal sphincter (CC=-0.538, p=0.001).

    CONCLUSIONS: These findings are consistent with expansion of cardia in healthy volunteers occurring by squamo columnar metaplasia of distal oesophagus and aggravated by central obesity. This metaplastic origin of expanded cardia may be relevant to the substantial proportion of cardia adenocarcinomas unattributable to H. pylori or transsphincteric acid reflux.

    Matched MeSH terms: Esophagogastric Junction/pathology*
  3. Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, et al.
    Nat Med, 2023 Aug;29(8):2133-2141.
    PMID: 37524953 DOI: 10.1038/s41591-023-02465-7
    There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .
    Matched MeSH terms: Esophagogastric Junction/pathology
  4. Siow SL, Mahendran HA, Wong CM, Milaksh NK, Nyunt M
    BMC Surg, 2017 Mar 20;17(1):25.
    PMID: 28320382 DOI: 10.1186/s12893-017-0221-2
    BACKGROUND: In recent years, staging laparoscopy has gained acceptance as part of the assessment of resectability of upper gastrointestinal (UGI) malignancies. Not infrequently, we encounter tumours that are either locally advanced; requiring neoadjuvant therapy or occult peritoneal disease that requires palliation. In all these cases, the establishment of enteral feeding during staging laparoscopy is important for patients' nutrition. This review describes our technique of performing laparoscopic feeding jejunostomy and the clinical outcomes.

    METHODS: The medical records of all patients who underwent laparoscopic feeding jejunostomy following staging laparoscopy for UGI malignancies between January 2010 and July 2015 were retrospectively reviewed. The data included patient demographics, operative technique and clinical outcomes.

    RESULTS: Fifteen patients (11 males) had feeding jejunostomy done when staging laparoscopy showed unresectable UGI maligancy. Eight (53.3%) had gastric carcinoma, four (26.7%) had oesophageal carcinoma and three (20%) had cardio-oesophageal junction carcinoma. The mean age was 63.3 ± 7.3 years. Mean operative time was 66.0 ± 7.4 min. Mean postoperative stay was 5.6 ± 2.2 days. Laparoscopic feeding jejunostomy was performed without intra-operative complications. There were no major complications requiring reoperation but four patients had excoriation at the T-tube site and three patients had tube dislodgement which required bedside replacement of the feeding tube. The mean duration of feeding tube was 127.3 ± 99.6 days.

    CONCLUSIONS: Laparoscopic feeding jejunostomy is an important adjunct to staging laparoscopy that can be performed safely with low morbidity. Meticulous attention to surgical techniques is the cornerstone of success.

    Matched MeSH terms: Esophagogastric Junction/pathology
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