Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.
目的： 腹膜癌是一类原发或继发于腹膜表面的恶性肿瘤，肿瘤细胞减灭术（CRS）加腹腔热灌注化疗（HIPEC）是针对腹膜癌发展的一套综合治疗策略。本文旨在分析CRS+HIPEC治疗腹膜癌的疗效和安全性，并探讨影响其生存的预后因素。 方法： 采用描述性病例系列研究方法，回顾性收集2004年1月至2020年1月武汉大学中南医院（330例）和首都医科大学附属北京世纪坛医院（1 054例）腹膜肿瘤外科连续治疗的1 384例腹膜癌患者的临床病理资料。分析本组患者CRS+HIPEC治疗情况（手术时间、器官切除数量、腹膜切除数量、吻合口数量、HIPEC方案等）、安全性[术中出血量、术后严重不良事件（SAE）及发生时间、治疗情况]、生存情况及影响生存的预后因素。SAE依照国际腹膜癌联盟不良事件定义进行分级，将Ⅲ~Ⅳ级不良事件定义为SAE。围手术期定义为CRS+HIPEC治疗日至术后30 d。OS定义为CRS+HIPEC手术当日至死亡或末次随访时间，采用Kaplan-Meier法进行生存结果描述，组间比较采用Log-rank检验。影响生存的独立预后因素则采用Cox比例风险回归模型单因素和多因素分析。 结果： 全组患者中男529例（38.2%），中位年龄55（10~87）岁，中位体质指数为22.6 kg/m(2)。1 384例腹膜癌患者中来源于胃癌164例（11.8%），结直肠癌287例（20.7%），腹膜假黏液瘤356例（25.7%），腹膜恶性间皮瘤90例（6.5%），卵巢癌、宫颈癌、子宫内膜癌及原发性腹膜癌等共计300例（21.7%），腹膜后肉瘤、肺癌、乳腺癌等少见来源肿瘤187例（13.5%）。本组患者中位手术时间595（90~1 170）min，中位脏器切除数2（0~10）个，中位腹膜切除区域数4（0~9）个，中位腹膜癌指数（PCI）评分21（1~39）分，细胞减灭程度（CC）评分0~1分达61.9%（857/1 384）。HIPEC方案：顺铂+多西他赛917例（66.3%）、顺铂+丝裂霉素183例（13.2%）、阿霉素+异环磷酰胺43例（3.1%）及其他方案240例（17.3%）。331例（23.9%）腹膜癌患者发生围手术期严重不良事件500例次，其中21例（1.5%）患者因治疗无效于围手术期内死亡，其余患者经积极治疗后痊愈。全组患者中位随访时间为8.6（0.3~182.7）个月，414例（29.9%）死亡，mOS为38.2个月（95% CI：30.6~45.8），1、3、5年生存率分别为73.5%、50.4%、39.3%。其中，胃癌腹膜转移、结直肠癌腹膜转移、腹膜假黏液瘤、恶性腹膜间皮瘤和妇科肿瘤及原发性腹膜癌患者mOS分别为11.3个月（95% CI：8.9~13.8）、18.1个月（95% CI：13.5~22.6）、59.7个月（95% CI：48.0~71.4）、19.5个月（95% CI：6.0~33.0）和51.7个月（95% CI：14.6~88.8），组间比较差异有统计学意义（P<0.001）。Cox单因素和多因素分析显示，原发肿瘤为胃癌（HR=4.639，95% CI：1.692~12.724）、结直肠癌（HR=4.292，95% CI：1.957~9.420）和恶性腹膜间皮瘤（HR=2.741，95% CI：1.162~6.466）；卡氏功能状态（KPS）评分为60分（HR=4.606，95% CI：2.144~9.895）、70分（HR=3.434，95% CI：1.977~5.965）；CC评分为1分（HR=2.683，95% CI：1.440~4.999）、2~3分（HR=3.661，95% CI：1.956~6.852）以及围手术期发生SAE（HR=2.588，95% CI：1.846~3.629）均是影响本组腹膜癌患者生存的独立危险因素，差异均有统计学意义（均P<0.05）。 结论： CRS+HIPEC是针对腹膜癌有效的整合治疗技术，可延长生存，围手术期安全性可接受。术前需要严格筛选病例，KPS评分<80分者应慎重选择接受CRS+HIPEC治疗；术中应在保证安全的前提下，努力达到满意细胞减灭程度；另还要应积极预防围手术期SAE以降低腹膜癌患者死亡风险。.
Keywords: Cytoreductive surgery; Efficacy; Hyperthermic intraperitoneal chemotherapy; Peritoneal carcinomatosis; Prognosis; Safety.