胆囊癌根治性目的切除术后并发症对不良结局影响的全国多中心真实世界研究

Impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer: a national multicenter real-world study

  • 摘要:
    探讨胆囊癌根治性目的切除术后并发症对不良结局的影响。
    采用多中心真实世界研究方法。收集2020年4月至2024年4月中华消化外科菁英荟胆道外科学组全国多中心数据库中陆军军医大学第一附属医院等14家医学中心收治的629例胆囊癌患者的临床病理资料;男225例,女404例;年龄为(64±10)岁。患者均行开腹胆囊癌根治性目的切除术。观察指标:(1)手术及术后并发症和不良结局发生情况。(2)影响患者术后不良结局发生的危险因素及人群归因分数分析。采用链式方程多重插补法处理预测变量的缺失数据,对结局变量缺失的患者采用多重插补后删除策略。采用方差膨胀因子检验评估自变量间多重共线性的严重程度。构建含对数链接和稳健误差方差的多变量泊松回归模型,通过限制性立方样条(3节点)处理连续变量的非线性关系,计算调整后的相对危险度(RR)及95%可信区间(CI)。使用R软件中AF软件包对每个插补数据集计算调整后人群归因分数,并依据Rubin规则进行合并。
    (1)手术及术后并发症和不良结局发生情况。629例患者均行胆囊癌根治性目的切除术,143例发生术后并发症,其中腹腔积液68例,肺部感染39例,胆漏21例,腹腔出血12例,肝衰竭11例,胰瘘、切口感染、胃瘫各10例,胆管炎、脓毒症各7例;同一例患者可发生≥1种并发症。629例患者术后90 d内死亡19例,缺失11例;术后90 d内再手术42例,缺失7例;术后90 d内再入院44例,缺失3例;术后住院时间延长155例,缺失3例。(2)影响患者术后不良结局发生的危险因素及人群归因分数分析。多因素分析结果显示:肺部感染、肝衰竭是影响患者术后90 d内死亡的独立危险因素(RR=3.74、12.15,95%CI为1.18~11.83、1.98~74.48,P<0.05);肺部感染人群归因分数最高为4.61%(95%CI为3.94%~5.28%,P<0.05)。腹腔积液、肺部感染、胆漏、腹腔出血是影响患者术后90 d内再手术的独立危险因素(RR=4.80、3.62、3.46、4.99,95%CI为2.49~9.26、1.42~9.21、1.34~8.92、1.55~16.06,P<0.05);腹腔积液人群归因分数最高为8.65%(95%CI为8.22%~9.08%,P<0.05)。腹腔积液、胆漏、肝衰竭是影响患者术后90 d内再入院的独立危险因素(RR=6.20、3.33、14.33,95%CI为3.21~11.95、1.33~8.35、3.72~55.28,P<0.05);腹腔积液人群归因分数最高为9.11%(95%CI为8.85%~9.37%,P<0.05)。腹腔积液、肺部感染、胆漏、肝衰竭、切口感染是影响患者术后住院时间延长的独立危险因素(RR=2.29、2.21、2.26、2.14、3.35,95%CI为1.63~3.23、1.41~3.46、1.32~3.86、1.11~4.13、1.70~6.60,P<0.05);腹腔积液人群归因分数最高为6.03%(95%CI为5.71%~6.35%,P<0.05)。
    肺部感染是胆囊癌根治性目的切除术后90 d内死亡最重要危险因素,腹腔积液是术后90 d再手术、术后90 d再入院及术后住院时间延长最重要危险因素。

     

    Abstract:
    Objective To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).
    Methods The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk (RR) with corresponding 95% confidence interval (CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules.
    Results (1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality (RR=3.74, 12.15, 95%CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95%CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation (RR=4.80, 3.62, 3.46, 4.99, 95%CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95%CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission (RR=6.20, 3.33, 14.33, 95%CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95%CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay (RR=2.29, 2.21, 2.26, 2.14, 3.35, 95%CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95%CI as 5.71%-6.35%, P<0.05).
    Conclusion Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.

     

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