新辅助化疗对联合脏器切除胃癌根治术安全性及预后的影响

Influence of neoadjuvant chemotherapy on safety and prognosis of patients undergoing multi-visceral resection for gastric cancer

  • 摘要:
    目的 探讨新辅助化疗对联合脏器切除胃癌根治术安全性及预后的影响。
    方法 采用倾向评分匹配及回顾性队列研究方法。收集2011年12月至2020年12月复旦大学附属肿瘤医院收治的144例行联合脏器切除胃癌根治术患者的临床病理资料;男95例,女49例;年龄为(56±13)岁。144例患者中,27例行新辅助化疗和术后辅助化疗,设为新辅助化疗组;117例行术后辅助化疗,设为辅助化疗组。观察指标:(1)倾向评分匹配情况及匹配后两组患者一般资料比较。(2)手术及术后情况。(3)预后情况。倾向评分匹配按1∶1最近邻匹配法匹配,卡钳值设定为0.02。正态分布的计量资料以x±s表示;偏态分布的计量资料以M(范围)表示,组间比较采用秩和检验。计数资料以绝对数表示,组间比较采用χ²检验。等级资料比较采用非参数检验。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。
    结果 (1)倾向评分匹配情况及匹配后两组患者一般资料比较。144例患者中,46例配对成功,新辅助化疗组和辅助化疗组各23例。倾向评分匹配后消除术前血红蛋白、临床TNM分期因素混杂偏倚,具有可比性。(2)手术及术后情况。46例患者中,26例行胃联合1个脏器切除术,16例行胃联合2个脏器切除术,4例行胃联合3个脏器切除术;联合脏器切除中,联合脾脏切除、胰体尾切除、结肠切除、肝切除、小肠切除比例分别为69.6%(32/46)、39.1%(18/46)、32.6%(15/46)、8.7%(4/46)、2.2%(1/46)。新辅助化疗组和辅助化疗组患者行D1淋巴结清扫、D2淋巴结清扫,R0切除、R1切除分别为1、22例,23、0例和0、23例,23、0例,两组比较,差异均无统计学意义(P>0.05);淋巴结清扫数目、术中出血量、术后住院时间分别28(22~37)枚、150(100~200)mL、11(8~16)d和25(18~32)枚、150(100~200)mL、11(9~18)d,两组比较,差异均无统计学意义(Z=-1.13,-0.32,-0.50,P>0.05)。新辅助化疗组患者术后30 d发生≥Clavien‑Dindo Ⅱ级并发症2例,其中腹腔脓肿、肺炎各1例;辅助化疗组患者术后30 d发生≥Clavien‑Dindo Ⅱ级并发症8例,其中3例腹腔脓肿,2例吻合口瘘,肺炎、胰瘘、胃排空障碍各1例;两组患者发生≥Clavien‑Dindo Ⅱ级并发症比较,差异有统计学意义(χ²=4.60,P<0.05);腹腔脓肿、吻合口瘘、肺炎、胰瘘、胃排空障碍比较,差异均无统计学意义(P>0.05);两组患者均无死亡情况。(3)预后情况。46例患者中,43例完成随访,随访时间为15.4(3.0~84.0)个月。新辅助化疗组和辅助化疗组患者总生存时间分别为(14±10)个月和(24±22)个月,两组患者比较,差异无统计学意义(风险比=0.82,95%可信区间为0.28~2.40,P>0.05)。
    结论 与术后辅助化疗比较,新辅助化疗不增加行联合脏器切除胃癌根治术局部进展期患者的手术风险,可降低术后30 d≥Clavien‑Dindo Ⅱ级并发症发生率,但未能改善患者生存。

     

    Abstract:
    Objective To investigate the influence of neoadjuvant chemotherapy on safety and prognosis of patients undergoing multivisceral resection for gastric cancer.
    Methods The pro-pensity score matching (PSM) and retrospective cohort study was conducted. The clinicopathological data of 144 patients with gastric cancer who underwent multivisceral resection in the Fudan University Shanghai Cancer Center from December 2011 to December 2020 were collected. There were 95 males and 49 females, aged (56±13)years. Of 144 patients, 27 cases undergoing neoadjuvant chemotherapy and postoperative adjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, and 117 cases undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) PSM and comparison of general data of patients between the two groups after matching; (2) surgical and postoperative conditions; (3) prognosis. PSM was done by the 1∶1 nearest neighbor matching method, with the caliper setting as 0.02. Measurement data with normal distribution were expressed as Mean±SD. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the rank sum test. Count data were expressed as absolute numbers, comparison between groups was conducted using the chi‑square test. Comparison of ordinal data was conducted using the non-parameter test. The Kaplan‑Meier method was used to draw survival curves and calculate survival rate, and the Log‑Rank test was used for survival analysis.
    Results (1) PSM and comparison of general data of patients between the two groups after matching. Of 144 patients, 46 cases were successfully matched, including 23 cases in the neoadjuvant chemotherapy group and 23 cases in the adjuvant chemotherapy group, respectively. The elimination of preoperative hemoglobin, clinical TNM staging confounding bias ensured comparability between the two groups after PSM. (2) Surgical and postoperative conditions. Of 46 patients, 26 cases underwent gastrectomy with one organ resection, 16 cases underwent gastrectomy with two organs resection, and 4 cases underwent gastrectomy with three organs resection. Of the patients with multivisceral resection, the proportion of patients undergoing combined splenectomy, pancreatectomy, colon resection, liver resection, and small intes-tinal resection was 69.6%(32/46), 39.1%(18/46), 32.6%(15/46), 8.7%(4/46), 2.2%(1/46), respectively. Cases with D1 lymph node dissection, cases with D2 lymph node dissection, cases with R0 resection, cases with R1 resection in the neoadjuvant chemotherapy group and the adjuvant chemotherapy group were 1, 22, 23, 0 and 0, 23, 23, 0, respectively, showing no significant difference in the above indicators between the two groups (P>0.05). The number of lymph node dissected, the volume of intraoperative blood loss, duration of postoperative hospital stay in the neoadjuvant chemotherapy group and the adjuvant chemotherapy group were 28(range, 22-37), 150 (range, 100-200)mL, 11(range, 8-16)days and 25(range, 18-32), 150(range, 100-200)mL, 11(range, 9-18)days, respec-tively, showing no significant difference in the above indicators between the two groups (Z=-1.13, -0.32, -0.50, P>0.05). Cases with complications ≥grade Ⅱ of Clavien‑Dindo classification during the postoperative 30 days were 2 in the neoadjuvant chemotherapy group, including 1 case of abdominal abscess and 1 case of pneumonia. Cases with complications ≥grade Ⅱ of Clavien‑Dindo classification during the postoperative 30 days were 8 in the adjuvant chemotherapy group, including 3 cases of abdominal abscess, 2 cases of anastomotic fistula, 1 case of pneumonia, 1 case of pancreatic fistula, 1 case of gastric emptying disability. There were significant differences in the complications ≥grade Ⅱ of Clavien‑Dindo classification between the neoadjuvant chemotherapy group and the adjuvant chemotherapy group (χ²=4.60, P<0.05). There was no significant difference in the abdominal abscess, anastomotic fistula, pneumonia, pancreatic fistula, gastric emptying disability between the two groups (P>0.05). None of patient died in either of the neoadjuvant chemotherapy group and the adjuvant chemotherapy group. (3) Prognosis. Of 46 patients, 43 cases were followed up for 15.4(range, 3.0-84.0)months. The overall survival time of patients in the neoadjuvant chemotherapy group and the adjuvant chemotherapy group were (14±10)months and (24±22)months, showing no significant difference between them (hazard ratio=0.82, 95% confidence interval as 0.28-2.40, P>0.05).
    Conclusion Compared with postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not increase the surgical risk of locally advanced gastric cancer patients undergoing multivisceral and radical resection, and can reduce the incidence of complications ≥grade Ⅱ of Clavien-Dindo classification during the postoperative 30 days, but does not improve patient survival.

     

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