Objective: To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer. Methods: A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat-sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non-stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory(BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long-acting opioids were administered, which included sustained-release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ(2) test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non-stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two-tailed test was established as the alpha significance level. Result: A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty-two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non-stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non-stoma group located in other sites. Compared with non-stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non-stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non-stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)](χ(2)=10.023, P=0.002) in the non-stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI: 0.102-0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709-18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non-stoma group (49.3%, 35/71) (χ(2)=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123-0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033-6.687, P=0.045) were independent factors affecting the use of lactulose laxatives. Conclusions: Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.
目的： 探讨造口状态对晚期消化道肿瘤患者镇痛模式的影响。 方法： 采用回顾性队列研究方法，本研究经中山大学附属第六医院伦理委员会审核通过（E2018026）。病例纳入标准：（1）年龄性别不限；（2）经组织学明确诊断为消化道恶性肿瘤，经过CT或者MR证实存在局部复发或转移；（3）疼痛数字评价量表（NRS）疼痛评分≥4分，需使用阿片类镇痛药物；（4）自愿签署知情同意书。排除标准：（1）早期恶性肿瘤；（2）研究者认为可能存在影响服药依从性的不良精神状态；（3）对阿片类药物超敏反应或过敏性反应。收集2016年9月至2017年4月期间于中山大学附属第六医院肿瘤科进行综合治疗的晚期消化道肿瘤患者临床资料，将患者有无进行肠造口分为造口组和无造口组，分析两组患者的临床特征，包括年龄、性别、造口状态、疼痛部位、有无肠梗阻以及疼痛特点、镇痛药物的选择、镇痛剂不良反应的处理。疼痛的评估采用简明疼痛评估量表（BPI）和NRS疼痛评分。疼痛的治疗主要为强阿片类药物；不耐受阿片类的患者首次用药进行阿片类药物滴定，滴定药物包括盐酸吗啡片、羟考酮和吗啡针。疼痛控制稳定后，换缓释制剂维持治疗，缓释制剂包括硫酸吗啡缓/控释片、盐酸羟考酮缓释片和芬太尼透皮贴。镇痛治疗效果的评价需同时满足NRS评分≤3分、爆发痛<3次/d及持续3 d以上。采用χ(2)检验和Wilcoxon符号秩和检验进行造口组和无造口组患者临床特征的分析，对比造口组与无造口组患者的一般临床资料、疼痛特点、镇痛药物选择和应用缓泻剂预防或治疗便秘的情况，应用多元回归模型进行多因素logistic回归分析造口状态对镇痛治疗以及缓泻剂使用的影响。 结果： 共计123例患者符合入组条件纳入研究。男性79例，女性44例，中位年龄51岁。造口组52例，包括回肠造口30例，结肠造口22例；无造口组71例。造口组中，40例（76.9%）疼痛部位为腹盆腔疼痛；无造口组中，44例为（62.0%）为其他部位疼痛。造口组和无造口组患者治疗前NRS疼痛评分中位数分别为5.7分和5.6分，两组比较，差异无统计学意义（P=0.741）；治疗后则分别降为2.1分和2.3分，两组差异仍无统计学意义（P=0.092）。镇痛治疗有效者共计111例（90.2%），造口组49例（94.2%），无造口组62例（87.3%），两组差异也无统计学意义（P=0.202）。在镇痛维持治疗中，选用芬太尼透皮贴者造口组更多[34.6%（18/52）比9.8%（7/71）]；而选用口服缓释制剂者以无造口组更多[78.9%（56/71）比61.5%（32/52）]（χ(2)=10.023，P=0.002）。多因素分析结果显示，造口状态（OR=0.290，95%CI：0.102~0.824，P=0.009）和疼痛部位（OR=5.691，95%CI：1.709~18.948，P=0.005）是影响一线维持治疗药物选择的独立因素。123例患者在维持镇痛治疗中，98例有缓泻剂使用与否的记载，其中46例使用了缓泻剂预防或治疗便秘，造口组应用缓泻剂的比例（21.2%，11/52）明显低于无造口组（49.3%，35/71），差异有统计学意义（χ(2)=6.957，P=0.008）。影响缓泻剂使用与否的多因素分析结果显示，造口状态（OR=2.621，95%CI：1.033~6.687，P=0.045）和年龄（OR=0.281，95%CI：0.123~0.684，P=0.010）是影响缓泻剂使用与否的独立因素。 结论： 造口可影响晚期消化道肿瘤患者的癌痛治疗模式；有造口的年轻患者，不需要预防性使用缓泻剂。.
Keywords: Analgesic pattern; Laxatives; Opioids; Stoma.