A132 SMOOTH MUSCLE BIOPSIES FROM POEM PROCEDURES FOR ACHALASIA SHOW LACK OF FUNCTIONAL INNERVATION
Bibliographic record
Abstract
Abstract Background Idiopathic achalasia is a disease of the esophagus causing impaired peristalsis and absent lower esophageal sphincter relaxation. The etiopathogenesis of the disease is unclear but most histopathologic studies from surgical resections show an absence of nitric oxide-producing neurons in the myenteric plexus. The peroral endoscopic myotomy (POEM) procedure has evolved in the last decade to treat achalasia and has provided a unique way to sample diseased tissue from an otherwise inaccessible tissue compartment. Aims To study the effects of achalasia on innervation of smooth muscle and smooth muscle phenotype. Methods Patients with a diagnosis of achalasia based on high resolution manometry undergoing a POEM at Kingston general hospital were approached for enrollment between June 2017 to September 2018. Demographic information including age, symptom duration, previous treatments, and Eckhardt score was collected. Intraoperatively, biopsies of the circular smooth muscle (CSM) layer were taken at the proximal and distal extents of the myotomy and placed in formalin. Tissue was embedded in wax, sectioned and stained using immunocytochemistry (ICC) for neuronal, axonal and smooth muscle cell markers. This was compared to control tissue from patients undergoing gastroesophagectomy for adjacent malignancy. Results Control tissue from 3 separate esophagectomies were obtained. Samples were obtained from a total of 25 patients (13 males), with a median age of 50 (IQR 38–67). Most patients had Type 2 achalasia (19 [76%]) followed by Type 1 and 3 (2, [8%] respectively). Two cases had conflicting manometric findings. The median duration of symptoms was 3 years (IQR 1.5–10.5) and the median Eckhardt score was 6.5 (IQR 5–9). In sample tissues, no neuronal cell bodies were detected in the CSM layer. ICC for the axonal marker PGP9.5 showed that CSM of achalasia samples were almost completely devoid of axon structure, independent of the subtype of achalasia, compared to abundant axon presence in control tissues. In parallel, ICC showed that cholinergic (ChAT) or nitrergic (nNOS) axonal subtypes were absent in biopsy CSM while abundant in controls. CSM cells displayed hypertrophy with no detection of proliferation by ICC (KI67) or alterations in the phenotypic marker SM-22. Conclusions Preliminary results from advanced immunohistochemical techniques show the absence of functional innervation of the CSM layer of all patients with achalasia. This is characterized by a depleted excitatory and inhibitory axon population. Further studies are focused on defining differences in smooth muscle phenotype and the presence or absence of inflammatory cells within the CSM. Funding Agencies None
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".