Wehrmann T, Seifert H, Seipp M, Lembcke B, Caspary W F
Dept. of Internal Medicine II, J. W. Goethe University Hospital, Frankfurt am Main, Germany.
Endoscopy. 1998 Oct;30(8):702-7. doi: 10.1055/s-2007-1001392.
Endoscopic sphincterotomy is not without risks, and is also ineffective in about half of patients with type III sphincter of Oddi dysfunction (SOD), i.e. those without clinical evidence of biliary obstruction (normal liver tests, normal bile duct diameter, and regular drainage time at endoscopic retrograde cholangiography). The present study therefore investigated the efficacy and safety of endoscopic botulinum toxin (BTX) injection into the papilla of Vater, and analyzed whether the symptomatic response to BTX injection might be a predictor of outcome for endoscopic sphincterotomy.
Twenty-two patients who had undergone cholecystectomy and had manometrically confirmed type III SOD were enrolled during a three-year study period. All patients received treatment with an endoscopic single-shot injection of 100 mouse units of BTX into the papilla of Vater. Initial symptomatic responses were analyzed six weeks later. If the BTX injection had been ineffective, or if biliary symptoms recurred after initial benefit during the follow-up period, endoscopic manometry and endoscopic sphincterotomy were performed. All patients then received further prospective clinical follow-up examinations.
With the exception of one patient with mild pancreatitis (4.5%), no side effects were observed after endoscopic BTX injection. Six weeks after BTX injection, 12 SOD patients (55%) were symptom-free, but ten patients (45%) were not. However five of these ten SOD patients who did not experience symptomatic benefit from BTX injection had normal basal sphincter of Oddi pressures (< 40 mmHg) at this time, and none of these five patients was free of complaints after subsequent endoscopic sphincterotomy. Two of the remaining five patients with sustained sphincter hypertension after BTX injection benefitted from endoscopic sphincterotomy. Eleven of the 12 SOD patients who had initially responded to BTX injection developed recurrent symptoms after a median period of six months. Manometry revealed sphincter hypertension in all 11 cases, and all patients became free of complaints again after endoscopic sphincterotomy during a median follow-up of a further 15 months. Overall, 11 of the 12 patients who responded to BTX injection, versus two of the ten patients who did not gain pain relief after BTX injection, later benefitted from endoscopic sphincterotomy (p < 0.01).
Endoscopic injection of botulinum toxin into the papilla of Vater is a safe procedure and provides short-term relief of symptoms in half of patients with type III SOD. Our results also indicate that the clinical response to BTX injection can predict whether SOD patients will gain long-term benefit from endoscopic sphincterotomy.
内镜下括约肌切开术并非毫无风险，对于约半数的Ⅲ型Oddi括约肌功能障碍（SOD）患者也无效，即那些无胆道梗阻临床证据的患者（肝功能检查正常、胆管直径正常且内镜逆行胆管造影时引流时间正常）。因此，本研究调查了内镜下向 Vater 乳头注射肉毒杆菌毒素（BTX）的疗效和安全性，并分析了对 BTX 注射的症状反应是否可能是内镜下括约肌切开术预后的预测指标。
在为期三年的研究期间，纳入了 22 例已行胆囊切除术且经测压确诊为Ⅲ型 SOD 的患者。所有患者均接受内镜下单次向 Vater 乳头注射 100 鼠单位 BTX 的治疗。六周后分析初始症状反应。如果 BTX 注射无效，或者在随访期间初始症状改善后胆道症状复发，则进行内镜测压和内镜下括约肌切开术。然后所有患者均接受进一步前瞻性临床随访检查。
除 1 例发生轻度胰腺炎的患者（占 4.5%）外，内镜下注射 BTX 后未观察到其他副作用。注射 BTX 六周后，12 例 SOD 患者（占 55%）症状消失，但 10 例患者（占 45%）仍有症状。然而，这 10 例未从 BTX 注射中获得症状改善的 SOD 患者中有 5 例此时 Oddi 括约肌基础压力正常（<40 mmHg），这 5 例患者在随后的内镜下括约肌切开术后均仍有不适。其余 5 例注射 BTX 后括约肌持续高血压的患者中有 2 例从内镜下括约肌切开术中获益。12 例最初对 BTX 注射有反应的 SOD 患者中有 11 例在中位期为六个月后出现症状复发。测压显示所有这 11 例均存在括约肌高血压，并且在进一步中位随访 15 个月期间，所有患者在内镜下括约肌切开术后再次症状消失。总体而言，12 例对 BTX 注射有反应的患者中有 11 例，而 10 例未从 BTX 注射中获得疼痛缓解的患者中有 2 例，后来从内镜下括约肌切开术中获益（p<0.01）。
内镜下向 Vater 乳头注射肉毒杆菌毒素是一种安全的操作，可为半数Ⅲ型 SOD 患者提供短期症状缓解。我们的结果还表明，对 BTX 注射的临床反应可预测 SOD 患者是否将从内镜下括约肌切开术中获得长期益处。
