難治性胃潰瘍―難治化の要因をさぐる―胃粘膜の病態から

Refractory Gastric Ulcers-lts Pathophysiology Focused on Gastric Mucosa

要旨　127例の胃潰瘍患者のうち26％がH₂受容体拮抗剤（H₂RA）抵抗性潰瘍であった．これらの難治化の要因について検討した．H₂RA抵抗性潰瘍はH₂RA易治性潰瘍に比べて再生粘膜の腺管係数が有意に低値で，再生腺管が未熟であることが示唆された．Helicobacter pyloriの感染率には有意差はなく，難治化の要因としての，Helicobacter pyloriの関与は少ないと思われた．H₂RA抵抗性潰瘍のうち半数の患者ではH₂RAによる酸分泌抑制が不十分であり，これらの例ではH₂RAを続行することにより，その後3か月以内に治癒した（H₂RA治癒遅延型潰瘍）．残りの半数の例では，H₂RAを継続しても3か月以内に治癒に至らなかったが（H₂RA治癒不能型潰瘍），これらの例では，H₂RAによって酸は十分に抑制されていた．H₂RA治癒不能型潰瘍ではH₂RA易治性潰瘍に比して潰瘍辺縁のprostaglandin E₂（PG）量が有意に減少しており，PGの減少も難治化の要因の1つであると思われた．

　Of 127 patients with gastric ulcer treated with H₂-receptor antagonists (H₂RAs), 26% were refractory to the treatment. Computer analysis for percentage of regenerated gland area per regenerated mucosa showed less glands in the rim of the H₂RA-refractory ulcers than in that of the H₂RA-tractable ulcers (good responders). Sixty percent of patients with H₂RA-refractory gastric ulcers were infected with Helicobacter pylori. The percentage was the same as that was found in H₂RA-tractable ulcer patients, suggesting no association of this bacterium with the refractoriness. H₂RAs did not raise intraluminal pH as expected in half of the patients with refractory ulcers. In these cases, ulcers healed by treatment with an H₂RA continued for the next 3 months (slow responders). Contrary to expectations, continuous treatment did not affect ulcers of the other half (non-responders) in whom H₂RA raised luminal pH. Prostaglandin (PG) E₂ levels were lower in the ulcer rim of the nonresponders than in that of the good responders. A PG analogue administered together with an H₂RA healed ulcers of the non-responders by 60%, suggesting that the reduced PGE₂, in part, causes the refractoriness. A proton-pump inhibitor (PPI) healed the ulcers by 88% because of its strong effect on acid suppression overcoming the effect of H₂RA. However, the higher intraluminal acidity itself may not cause the refractoriness for the reason that similar acidity was observed in patients with H₂RA-refractory ulcers.

　These results shows that morphological and functional disorder of the gastric mucosa is involved in the pathophysiology of H₂RA-refractory gastric ulcers.