Lee Y Y, McColl K E L
School of Medical Sciences, Universiti Sains Malaysia, Kota Bahru, Kelantan, Malaysia; Department of Medicine, Section of Gastroenterology and Hepatology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, USA.
Dis Esophagus. 2015 May-Jun;28(4):318-25. doi: 10.1111/dote.12202. Epub 2014 Feb 28.
Obesity is a major reason for the recent increase in incidence of reflux disease and cancers at the distal esophagus and gastroesophageal junction (GOJ) and is mediated through a rise in the intra-abdominal pressure (IAP) but the exact mechanisms are unclear. Raised IAP from obesity and with application of waist belt produces mechanical distortion of the GOJ through formation of partial hiatus hernia. Even though there is no trans-sphincteric acid reflux, there is increased ingress of acid into the lower sphincter (intra-sphincteric reflux) as a consequence of raised IAP. In addition, short segment acid reflux is more evident in obese subjects with a belt on. Acid pocket is also enlarged in hiatus hernia, and acts as a reservoir of acid available to reflux whenever the sphincter fails. Above mechanisms may explain the common occurrence of cardiac lengthening and inflammation found in asymptomatic obese subjects. The inflamed cardia is also immunohistochemically similar to non-intestinal Barrett's mucosa, which is of etiological importance for cancers at the GOJ. Interventions that can reduce the mechanical distortion and acid exposure at the GOJ, including diet, exercise, drugs, sphincter augmentation therapy, and surgery, are clinically relevant in the treatment of gastroesophageal reflux disease but more data are needed whether if these strategies are also effective in preventing cancer. As a conclusion, raised IAP produces silent mechanical disruption of the GOJ, which may explain the high occurrence of cancers in this region and it is potentially reversible with early interventions.
肥胖是近期反流性疾病以及食管远端和胃食管交界处(GOJ)癌症发病率上升的主要原因,其通过腹内压(IAP)升高介导,但确切机制尚不清楚。肥胖导致的IAP升高以及佩戴腰带会通过形成部分食管裂孔疝对GOJ产生机械性扭曲。即使没有跨括约肌酸反流,但由于IAP升高,酸进入下括约肌(括约肌内反流)的情况会增加。此外,在佩戴腰带的肥胖受试者中,短段酸反流更为明显。食管裂孔疝中的酸袋也会扩大,并且在括约肌功能失调时充当酸反流的储存库。上述机制可能解释了无症状肥胖受试者中常见的心底部延长和炎症。发炎的心底部在免疫组织化学上也与非肠化生的巴雷特黏膜相似,这对GOJ处的癌症具有病因学意义。能够减少GOJ处机械性扭曲和酸暴露的干预措施,包括饮食、运动、药物、括约肌增强治疗和手术,在胃食管反流病的治疗中具有临床相关性,但这些策略是否也能有效预防癌症还需要更多数据。总之,IAP升高会对GOJ产生无声的机械性破坏,这可能解释了该区域癌症的高发病率,并且早期干预可能使其逆转。