Esophagogastric junction outflow obstruction: Characterization of a new entity? Clinical, manometric, and neuroimmunological description

Abstract

Objective To determine the differences between clinical, manometric, and neuroimmunological profile of esophagogastric junction outflow obstruction (EGJOO) and achalasia patients. Methods Seven EGJOO and 27 achalasia patients were enrolled in a blind cross‐sectional study. Peripheral blood (PB) of 10 healthy donors and 10 lower esophageal sphincter (LES) muscle biopsies from organ transplant donors were included as controls. The presence of ganglion cells, cells of Cajal, Th22/Th7/Th2/Th1/Tregs/Bregs/pDCregs in tissue, and PB was assessed by immunohistochemistry and flow cytometry. Serum concentration of IL‐22/IL‐17A/IL‐17F/IL‐4/IFN‐γ/IL‐1β/IL‐6/IL‐23/IL‐33/TNF‐α/IL‐10 was determined using bioplex plates. ANAs and antineuronal antibodies were evaluated by immunofluorescence and Western blot. Key Results EGJOO and achalasia patients had lower ganglion cells and cells of Cajal percentage vs. controls, while fibrosis was present only in achalasia patients. EGJOO and controls had lower cell percentage of Th22/Th17/Th2 vs. achalasia. EGJOO tissue had lower Th1/Treg cell number vs. achalasia, but higher levels vs. control group. Bregs and pDCregs percentage was higher in EGJOO vs. control group. Percentage of PB subpopulations in EGJOO was not significantly different from control group. Serum cytokine levels were higher for IL‐1β/IL‐6/TNF‐α, while IL‐17A levels were lower in EGJOO vs. achalasia and control group. EGJOO group was negative for ANAs, while in achalasia group, 54% were positive. GAD65 and PNMa/Ta2 antibodies were present in achalasia, whereas Yo and recoverin were positive in EGJOO group. Conclusions and Inferences Although EGJOO shares some clinical characteristics with achalasia, the neuroimmunological profile is completely different, suggesting that EGJOO might be a different entity.

Detection of cytokine storm in patients with achalasia using ELISA

“…The number of IL-22 + and TGF-β1 + cells observed in the myenteric plexus of esophageal biopsies are significantly higher in patients with achalasia than in control subjects (5,13). Moreover, serum levels of IL-22, IL-17A and IFN-γ were higher in 27 patients with achalasia compared with those in healthy volunteers (46). In the present study, IL-22 and TGF-β levels were not evaluated, as these cytokines could not be detected using the ELISA kit employed.…”

Lower esophageal sphincter muscle of patients with achalasia exhibits profound mast cell degranulation

“…19,40,41 Furthermore, most of those studies either included no control tissues, 3,5,40,41 or used the suboptimal control of muscle in esophagi resected because of cancer. 2,4,19,38,42 Few studies have done as we did, 35,39,43,44 comparing LES muscle samples taken from achalasia patients undergoing Heller myotomy with LES muscle from organ donors with no important esophageal disease.…”

“…Quantitative data are expressed as mean ± standard error of the mean patients clinically were indistinguishable from the 10 achalasia patients, patients with EGJOO recently were found to have a neuroimmunological profile distinct from that of achalasia. 35 Therefore, we analyzed our EGJOO patients as an independent group. Age, sex, and cause of death for the 7 organ donors are listed in Table 2.…”

Esophagogastric Junction Outflow Obstruction and Hiatal Hernia: Is Hernia Repair Alone Sufficient?

“…Because of manometric, clinical, and histologic overlap between EGJOO and achalasia, many experts consider primary EGJOO as a precursor or variant of achalasia. 1 , 8 , 9 The rate of conversion to achalasia is unknown, though numerous studies cite examples of patient progression from EGJOO to achalasia. 4 , 10 Secondary EGJOO, also termed “structural” or “mechanical” EGJOO, is caused by the presence of an anatomic abnormality leading to outflow obstruction.…”