基于多学科诊断与治疗的肝门部胆管癌外科手术疗效和预后影响因素分析

Surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multi-disciplinary diagnosis and treatment

  • 摘要:
    目的 探讨基于多学科诊断与治疗的肝门部胆管癌外科手术疗效和预后影响因素。
    方法 采用回顾性队列研究方法。收集2004年4月至2021年4月南京大学医学院附属鼓楼医院收治的91例行手术切除肝门部胆管癌患者的临床病理资料;男59例,女32例;年龄为(61±10)岁。2004年4月至2014年3月收治的患者采用传统外科诊断与治疗模式,2014年4月至2021年4月收治的患者采用多学科诊断与治疗模式。观察指标:(1)手术情况。(2)术后情况。(3)术后病理学检查情况。(4)术后预后分析。(5)术后预后影响因素分析。采用电话和门诊方式进行随访,术后每6个月随访1次,了解患者术后生存情况。随访时间截至2023年4月。正态分布的计量资料以x±s表示,组间比较采用独立样本t检验;偏态分布的计量资料以M(范围)表示,组间比较采用Mann⁃Whitney U检验。等级资料比较采用秩和检验。计数资料以绝对数或百分比表示,组间比较采用χ²检验或Fishe确切概率法。采用 Kaplan‑Meier法绘制生存曲线并计算生存率,Log‑Rank检验进行生存分析。单因素和多因素分析采用COX比例风险模型。
    结果 (1)手术情况。91例患者中,65例行半肝或扩大半肝切除术,13例行肝三区切除术,9例行部分肝切除术,4例仅行肝外胆管切除术;24例联合门静脉切除重建,8例联合胰十二指肠切除术,6例联合肝动脉切除重建;24例行扩大根治术(包括肝三区切除、肝动脉切除重建和肝胰十二指肠切除)。91例患者手术时间为(590±124)min,术中出血量为800(500~1 200)mL,术中输血率为75.8%(69/91)。2004年4月至2014年3月收治的31例和2014年4月至2021年4月收治的60例患者扩大根治术、术中出血量分别为4例、650(300~1 000)mL和20例、875(500~1 375)mL,两者比较,差异均有统计学意义(χ²=4.39,Z=0.31,P<0.05)。(2)术后情况。91例患者术后住院时间为(27±17)d,术后发生感染性并发症50例(腹腔感染43例、切口感染7例、菌血症5例、肺部感染8例,同一例患者可合并≥1种感染性并发症),胆漏30例,胃排空延迟和乳糜漏均为9例,肝衰竭6例,胰瘘5例,腹腔出血3例,二次手术6例,术后90 d内死亡3例。2004年4月至2014年3月收治的31例和2014年4月至2021年4月收治的60例患者术后腹腔感染分别为10例和33例,两者比较,差异有统计学意义(χ²=4.24,P<0.05);术后90 d内死亡分别为3例和0例,两者比较,差异有统计学意义(P<0.05)。(3)术后病理学检查情况。91例患者中,Bismuth分型Ⅰ~Ⅱ型、Ⅲ型、Ⅳ型分别为15、46、30例,T分期Tis期、T1期、T2a~2b期、T3期、T4期分别为1、9、25、30、26例,N分期N0期、N1期、N2期分别为49、36、6例,M分期M0期、M1期分别为85、6例,TNM分期0期、Ⅰ期、Ⅱ期、Ⅲ期、ⅣA期、ⅣB期分别为1、7、13、58、6、6例,根治性切除R0切除、R1或R2切除分别为63、28例。2004年4月至2014年3月收治的31例和2014年4月至2021年4月收治的60例患者根治性切除(R0切除、R1或R2切除)分别为15、16例和48、12例,两者比较,差异有统计学意义(χ²=9.59,P<0.05)。(4)术后预后分析。91例患者中,剔除3例术后90 d内死亡患者,88例患者5年总生存率为44.7%,中位总生存时间为55个月。2004年4月至2014年3月收治的28例和2014年4月至2021年4月收治的60例患者5年总生存率分别为33.5%和50.4%,两者比较,差异有统计学意义(χ²=5.31,P<0.05)。进一步分析:2004年4月至2014年3月收治的16例和2014年4月至2021年4月收治的31例无淋巴结转移患者5年总生存率分别为43.8%和61.6%,两者比较,差异有统计学意义(χ²=3.98,P<0.05)。2004年4月至2014年3月收治的12例和2014年4月至2021年4月收治的29例发生淋巴结转移患者5年总生存率分别为18.5%和37.7%,两者比较,差异无统计学意义(χ²=2.25,P>0.05)。(5)术后预后影响因素分析。多因素分析结果显示:肿瘤分化程度为低分化、R1或R2切除是影响肝门部胆管癌切除术后预后的独立危险因素(风险比=2.62,2.71,95%可信区间为1.30~5.29,1.30~5.69,P<0.05)。
    结论 与传统外科诊断与治疗模式比较,基于多学科诊断与治疗的肝门部胆管癌手术指征扩大、术后90 d内死亡比例降低,根治性切除比例和长期生存率均提高。肿瘤分化程度为低分化和非根治性切除是影响肝门部胆管癌切除术后预后的独立危险因素。

     

    Abstract:
    Objective To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.
    Methods The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model.
    Results (1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500‒1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300‒1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500‒1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them (χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them (χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them (P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ‒Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a‒2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R0 radical resection, cases with R1 or R2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R0 radical resection, cases with R1 or R2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them (χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them (χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis (χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis (χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R1 or R2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma (hazard ratio=2.62, 2.71, 95% confidence interval as 1.30‒5.29, 1.30‒5.69, P<0.05).
    Conclusions Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R1 or R2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

     

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