进展期胃癌术后腹腔热灌注化疗的研究进展

胃癌为临床常见恶性肿瘤之一, 外科手术是其重要治疗方案, 进展期胃癌患者术后5年生存率较低, 而术后癌灶复发成为影响患者预后的重要因素。随着国内医学水平不断发展, 腹腔热灌注化疗技术得以不断改进, 其在进展期胃癌患者术后辅助治疗中的应用日益广泛, 长期临床实践表明预防性运用腹腔热灌注化疗可明显降低进展期胃癌术后复发率并提高其5年生存率, 在改善患者生存质量及总体临床疗效方面的作用明确。本文旨在对中国进展期胃癌术后腹腔热灌注化疗的临床应用进展进行综述。      

胃癌术后腹腔热灌注联合全身化疗的临床应用

为研究胃癌术后腹腔热灌注化疗联合全身化疗的治疗效果。对140例胃癌根治术后患者随机分为腹腔热灌注化疗组(n=72)和全身化疗组(n=68)。腹腔热灌注化疗组患者在全身化疗同时应用腹腔热灌注化疗,观察两组术后并发症、不良反应、术后生存率及腹腔复发率。两组在术后并发症及不良反应差异无统计学意义。腹腔热灌注化疗组和全身化疗组术后3、5年生存率分别为86.1%(62/72)、60.2%(41/68)和58.3%(42/72)、29.4%(20/68)(P<0.05)。腹腔热灌注化疗组和全身化疗组术后3、5年腹腔复发率分别为5.6%(4/72)、27.8%(19/68)和20.6%(15/72)、53%(36/68),差异有统计学意义,P<0.05。初步研究结果提示,胃癌术后腹腔热灌注联合全身化疗可有效控制肿瘤的复发和转移,提高胃癌术后患者的生存率。     

进展期胃癌腹腔热灌注化疗临床疗效与安全性Meta分析

目的:探讨进展期胃癌患者围术期腹腔热灌注化疗的临床疗效和安全性。方法:检索CNKI、中国生物医学文献光盘数据库(CBN)和维普中文期刊数据库中文资料库,以及MEDLINE、EMBASE、BIOSIS previews和Cochrane图书馆临床对照试验资料库,发表时间为1985-01-2011-01,文献语种为英文和中文;以"胃癌、胃肿瘤、进展期、热灌注化疗和胃癌根治术"为检索词,应用Meta分析的方法,对国内外12篇随机对照研究文献进行定量综合,以胃癌根治术后行围术期腹腔热灌注化疗的患者为治疗组,以仅行胃癌根治术的患者为对照组,比较两组患者3年生存率的RR作为结局变量,分析腹腔热灌注化疗临床应用的安全性。结果:入选12篇文献,共2 307例患者,其中治疗组991例,对照组1 316例,合计RR=1.42,95%CI:1.30~1.55,胃癌根治术后行围术期腹腔热灌注化疗治疗组患者比仅行胃癌根治术的对照组患者3年生存率高1.42倍,敏感性分析证实本结论较为可靠。现有资料出现的潜在安全性问题较小,胃癌根治术后行围术期腹腔热灌注化疗的治疗组并发症发生率与仅行胃癌根治术的对照组均为19%,差异无统计学意义,P=0.96;两组死亡率均为4%,差异无统计学意义,P=0.98。结论:进展期胃癌围术期腹腔热灌注化疗可以提高生存率,并不增加术后并发症的发生率和死亡率,临床应用安全有效。     

进展期胃癌术后腹腔热灌注化疗的临床观察

1997年2月～1999年5．月,我们对45例住院胃癌患进行联合腹腔热灌注化疗(Continuous Hyperthemic Peritoneal Perfusion,CHPP)与单纯全身化疗的临床观察,探讨腹腔热灌注化疗在进展期胃癌术后的治疗作用。     

进展期胃癌术中腹腔热灌注化疗临床研究

目的探讨进展期胃癌术中腹腔热灌注化疗对防治腹膜转移的疗效及安全性。方法对40例进展期胃癌患者进行回顾性分析,热化疗组(实验组)20例行根治性手术联合术中腹腔热灌注化疗(H IPEC),采用奥沙利铂350 mg溶于右旋糖酐4000 m l中,加热至41.5℃~42.5℃腹腔内循环灌注40~60 m in;选择同期单纯根治性手术治疗的20例胃癌患者作为对照组,对比分析两组患者的临床指标及预后。结果热化疗组仅少数病例治疗后出现短期血压降低、心率增快及肝肾功能、凝血功能指标异常,两组并发症发生率无明显差异;术后腹腔种植转移率热化疗组为5.0%(1/20),对照组15.0%(3/20);1,2年生存率热化疗组分别为90.0%(18/20)和75.0%(15/20),对照组分别为80.0%(16/20)和60.0%(12/20)。结论 H IPEC可有效防治腹膜转移、提高生存率,且并发症少,可作为进展期胃癌术中的辅助治疗。     

围手术期腹腔热灌注化疗治疗胃癌25例

[目的]探讨胃癌围手术期(术中和术后早期)腹腔热灌注化疗的可行性、安全性、毒副作用、并发症。[方法]对25例进展期胃癌患者行根治性或姑息性切除术;术中行腹腔热灌注化疗(5-氟尿嘧啶 丝裂霉素)1次,术后前4天,每日腹腔热灌注化疗(5-氟尿嘧啶)1次。[结果]术中及术后早期行腹腔热灌注化疗成功率为100%,热灌注化疗期间患者生命体征无明显异常。治疗后亦无明显毒副作用和并发症,无治疗相关性死亡。随访8～26个月,2例发生腹腔转移(8%);1例发生肝转移,2例分别于术后8、15个月死于全身广泛转移。[结论]胃癌围手术期腹腔热灌注化疗安全可行,毒副作用小,并发症少。     

腹腔热灌注化疗在胃癌治疗中的应用研究

目的研究腹腔热灌注化疗对胃癌的治疗效果.方法选行规范根治术的胃癌病人70例,随机分为:术后腹腔内热灌注化疗组(A组,n=35)和全身化疗组(B组,n=35),观察两组病人在治疗过程中肝、肾功能、体温、血细胞计数改变及术后生存率等.结果 B组病人术后所出现的毒副反应人数和程度都较A组多且重;术后1、3、5年A组生存率分别为88.5﹪、65.4﹪、53.8﹪,B组为73.3﹪、36.7﹪、26.7﹪.A组术后3、5年的生存率均明显高于B组,差异有显著性意义(P＜0.05).结论腹腔热灌注化疗能明显提高胃癌术后病人的生存率和生存质量.     

进展期胃癌术中温热灌洗及置泵术后灌注化疗的临床研究

目的探讨进展期胃癌手术切除后腹腔及肝转移的防治方法。方法将282例进展期胃癌切除术后患者分成术中腹腔温热低渗灌洗化疗及术后动脉灌注化疗组169例(简称治疗组)和单纯术后静脉化疗组113例(简称对照组),并对其腹腔转移率、肝转移率及3年生存率进行对照研究。结果治疗组腹腔转移率为21.9%,肝脏转移率12.4%,3年生存率74.6%;对照组腹腔转移率46.0%,肝脏转移率27.4%,3年生存率46.8%。结论术中温热低渗灌洗化疗及术后动脉灌注化疗对进展期胃癌术后腹腔复发和肝转移有良好的防治作用。     

胃癌术后腹腔热灌注化疗的临床评价

目的:探讨胃癌术后早期腹腔热灌注化疗的临床效果。方法:284例胃癌术后患者随机分为两组:治疗组(160例)应用ELFP方案化疗,静脉化疗的第5天用顺铂60mg/m2 0.9%生理盐水1500ml~2000ml(40℃~44℃) 地塞米松10mg 利多卡因20mg行腹腔灌注化疗,对照组(124例)仅做ELFP方案静脉化疗,两组4周为一化疗周期,均实行4~6个周期。结果:1、3、5年生存率分别为治疗组84%、72.3%、45%,对照组78%、44.5%、27%,有显著性差异;5年中肝转移率、腹腔转移率、腹水发生率,治疗组分别是26%、22%,36%,对照组分别为44%、42%、63%,两组有显著性差异;两组化疗的毒副作用比较无显著性差异。结论:术后早期腹腔热灌注化疗是提高进展期胃癌生存率的有效措施。     

腹腔热灌注化疗在进展期胃癌中的应用进展

胃癌是世界上最常见的五大癌症之一,死亡率排第三位。根治性切除术虽是目前唯一可治愈胃癌的方法,但进展期胃癌术后5年生存率仅为23%。研究表明,多数患者死于术后复发和转移,主要原因是术前腹腔内微小转移灶或游离癌细胞导致的腹腔种植转移。近年来,国内外学者针对如何改善胃癌患者预后做了大量研究,进展期胃癌需要多学科的综合性治疗。腹腔热灌注化疗是将热疗、腹腔化疗及腹腔灌洗三者有机结合的一种新技术,在预防与治疗多种腹腔恶性肿瘤及腹膜种植转移、恶性腹水方面具有独特的疗效。作者对近年来腹腔热灌注化疗在进展期胃癌中的应用情况进行了综述。     

Hyperthermic intraperitoneal chemoperfusion in combined treatment of locally advanced and disseminated gastric cancer: Results of a single-centre retrospective study

Background: Patients with locally advanced gastric cancer (GC) and/or peritoneal metastases have a poor prognosis despite systemic chemotherapy or palliative surgery. The aim of this retrospective comparative non-randomised study was to evaluate aggressive cytoreduction in combination with hyperthermic intraperitoneal chemoperfusion (HIPEC) as a novel treatment strategy for patients with intraperitoneal disseminated and locally advanced GC.

Patients and methods: Forty-nine GC patients with serosal invasion (n?=?19), limited peritoneal metastases (n?=?20), or disseminated peritoneal metastases and tense ascites (n?=?10) underwent combination therapy with HIPEC. Three matched control groups undergoing standard therapies were retrospectively identified.

Results: Combination therapy for serosa-invasive GC reduced the level of metachronous peritoneal carcinomatosis and increased median survival from 12 months to 22.5 months (p?=?0.001). The median and 1-year survival rates for intraperitoneal disseminated GC patients undergoing therapy with the use of HIPEC were 12 months and 68.8% compared with 8 months and 25%, respectively (p?=?0.004) for control subgroup patients (palliative chemotherapy). The symptomatic use of HIPEC allows effective elimination of recurrent ascites in GC patients.

Conclusion: HIPEC is a well-tolerated and effective method of adjuvant therapy for gastric cancer with high risk of intraperitoneal progression. Cytoreduction followed by HIPEC improves survival in patients with limited peritoneal carcinomatosis of gastric origin.     

Prognostic impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients: A meta-analysis of randomized controlled trials

Backgroundgastric cancer patients frequently develop peritoneal metastases (PM) with a poor long-term prognosis. A solid body of evidence underlines the beneficial role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is a lack of consensus regarding the optimal strategy in the treatment of locally advanced primary tumors with or without peritoneal metastasis. The present meta-analysis aims to assess the impact of CRS + HIPEC on survival analyzing the results of randomized studies only.MethodsA systematic review of articles was conducted according to PRISMA guidelines. Twelve studies were included in qualitative and quantitative analysis.ResultsA survival benefit for patients treated with CRS + HIPEC at all time points was highlighted. However, difference in survival was significant at all time points for patients treated for prophylaxis of PM, but no difference was found when considering resection with a curative intent. The 1, 2, 3 and 5-year survival rates (SR) for patients undergoing CRS + HIPEC were 86.9%, 70.5%, 63.7% and 55.7% respectively. CRS + HIPEC for the treatment rather than prophylaxis of PM was the only predictor of a reduced 3y SR.ConclusionsCRS + HIPEC may lead to improved prognosis for patients suffering from locally advanced gastric cancer in both prophylactic and curative settings. However, due to far from negligible postoperative morbidity and mortality rates, a strict patient selection is crucial to achieve the best results. The presence of extraperitoneal disease strongly limits the indication of this kind of surgery.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer and other less common disease histologies: is it time?

Gastric cancer is the fourth most commonly diagnosed cancer worldwide, and once spread to the peritoneum, has a 5-year survival of less than 5%. Recent years have demonstrated advances in the use of cytoreductive surgery (CRS) in combination with heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis due to various malignancies. The frequent desmoplastic stroma and poor vascularization impeding drug delivery particularly in the diffuse form of gastric cancer is thought to provide a sound rationale for a regionalized treatment approach in this disease. Here, we seek to review the available data to define the role of CRS and HIPEC in gastric cancer metastatic to the peritoneal surface, and furthermore, analyze the use of CRS and HIPEC in malignancies less commonly treated with the regionalized perfusion approach.     

MUC2 protein expression status is useful in assessing the effects of hyperthermic intraperitoneal chemotherapy for peritoneal dissemination of colon cancer

We conducted a molecular biological investigation to determine the outcomes of hyperthermic intraperitoneal chemotherapy (HIPEC) treatment, and whether it is effective in all cases for patients with peritoneal dissemination of colon cancer. In the HIPEC group, the 3-year survival rate was 39.2%, whereas in the non-HIPEC group the 3-year survival rate was 15.6%. MUC2 expression was investigated in the HIPEC group, in patients positive for MUC2 expression, and the 3-year survival rate was 0.0%, while in patients negative for MUC2 expression, the 3-year survival rate was 61.1%. In addition, as a result of introducing MUC2-siRNA into a colon cancer cell line with high expression of the MUC2 gene, the cell death rate from heat and anticancer agents increased 40% in comparison with colon cancer cells in which scrambled siRNA had not been introduced. HIPEC therapy is thought to be effective in prolonging survival in patients with peritoneal dissemination of colon cancer, and MUC2 expression is thought to be useful as an indicator to assess its effectiveness in colon cancer cells.     

腹腔热灌注化疗对不同病理类型和Borrmann分型进展期胃癌患者的预后分析

目的:回顾性分析行手术联合术后腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)与同期单纯手术胃癌患者的临床病理资料,以期了解HIPEC对局部进展期胃癌患者预后的影响。方法:回顾性分析2009年1月~2014年1月在天津医科大学肿瘤医院行HIPEC的80例Ⅲb期胃癌患者与同期单纯手术90例Ⅲb期胃癌患者。根据术后是否使用腹腔热灌注化疗分为HIPEC组(研究组)和单纯手术组(对照组)。研究组:印戒细胞癌24例,非印戒细胞癌56例;BorrmannⅠ型12例,BorrmannⅡ型28例,BorrmannⅢ型23例,BorrmannⅣ型17例。对照组:印戒细胞癌26例,非印戒细胞癌64例;BorrmannⅠ型15例,BorrmannⅡ型30例,BorrmannⅢ型26例子,BorrmannⅣ型19例。两组患者术后4周均予以SOX方案化疗8个疗程。分析比较不同病理类型及Borrmann分型的胃癌患者术后生存情况,并对两组患者手术相关并发症进行对比。结果:研究组和对照组患者5年生存率分别为36.25%和28.89%(P<0.05);印戒细胞癌患者中,研究组和对照组患者5年生存率分别为25.00%和15.38%(P<0.05);非印戒细胞癌患者中,研究组和对照组患者5年生存率分别为41.07%和34.38%(P>0.05);BorrmannⅠ型胃癌患者中,研究组和对照组患者5年生存率分别为41.67%和40.00%(P>0.05);BorrmannⅡ型胃癌患者中,研究组和对照组患者5年生存率分别为35.71%和33.33%(P>0.05);BorrmannⅢ型胃癌患者中,研究组和对照组患者5年生存率分别为39.13%和26.92%(P<0.05);BorrmannⅣ型胃癌患者中,研究组和对照组患者5年生存率分别为29.41%和15.79%(P<0.05)。两组患者手术相关并发症的差异无统计学意义(P>0.05)。结论:手术联合HIPEC安全可行,有利于提高患有印戒细胞癌、BorrmannⅢ型及BorrmannⅣ型进展期胃癌患者术后的5年生存率,延长生存期。     

Prophylactic hyperthermic intraperitoneal chemotherapy for patients with clinical T4 gastric cancer

IntroductionPatients with clinical T4 gastric cancers have high recurrence rates and low 5-year overall survival (OS) despite radical gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy. The invisible peritoneal metastasis may result in local recurrence due to the tumor invading the serosa and nearby organs. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested as an adjuvant treatment strategy in these patients. We evaluated the efficacy of prophylactic HIPEC post-gastrectomy for patients with clinical T4 gastric cancer.Materials and methodsWe retrospectively reviewed data from 132 patients with clinical T4 gastric cancer who underwent gastrectomy + D2 lymphadenectomy between 2014 and 2020. Thirty-five of these patients also underwent prophylactic HIPEC perioperatively. We used propensity score matching (PSM) to reduce selection bias. We evaluated the risk factors for recurrence and compared the OS and disease-free survival (DFS) between the gastrectomy and prophylactic HIPEC groups.ResultsA total of 132 eligible patients were included in the study. Seventy preoperative patient characteristics were homogeneous post-PSM. Prophylactic HIPEC seemed to reduce the risk of postoperative peritoneal recurrence but did not influence the risk of distant metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion. OS (adjusted hazard ratio, 0.37; 95% CI, 0.17 to 0.81; p = 0.035) and DFS (adjusted hazard ratio, 0.33; 95% CI, 0.15 to 0.72; p = 0.017) were better in the prophylactic HIPEC group than in the gastrectomy alone group.ConclusionsProphylactic HIPEC plus radical gastrectomy can reduce peritoneal recurrence and improve OS and DFS in patients with clinical T4 gastric cancer.     

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer

BackgroundFew prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).Materials and methodsBetween 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.ResultsA complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.ConclusionsA novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.     

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗同时性胃癌腹膜癌*

目的:分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery,CRS ）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy ,HIPEC）治疗同时性胃癌腹膜癌（peritoneal carcinoma,PC）的疗效及安全性。方法:50例胃癌PC患者接受52次CRS+HIPEC治疗,药物为洛铂100 mg、多西他赛120 mg,加入12000 mL生理盐水加热至（43± 0.5）℃ 持续灌注60min。主要终点指标为总生存期,次要终点评价指标为围手术期安全性。结果:患者中位随访期22.5 个月,中位生存期14.3 个月（95%CI:7.6～21.0）,1、2、3 年生存率分别为58% 、40% 、32% 。无围手术期死亡,12例（23.1%）出现严重不良事件。多因素分析显示,完全细胞减灭、术前肿瘤标记物水平正常、术后化疗≥ 6 个周期为影响预后的独立因素。结论:对于同时性胃癌PC患者,洛铂联合多西他赛行CRS+HIPEC可延长患者的总生存期,安全可行。      

改良HIPEC对预防局部进展期胃癌复发的作用及安全性评价

  目的  分析真实世界中改良腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）在预防进展期胃癌复发中的作用并评价其安全性。  方法  选取2017 年 8 月至 2020 年 11 月就诊于江南大学附属医院并行根治术后HIPEC的48 例ⅡB～ⅢC期胃癌患者作为HIPEC组;将同期80例根治术后仅接受静脉化疗的ⅡB～ⅢC期胃癌患者作为对照组,比较两组患者肿瘤无病生存期及不良反应的差异。  结果  HIPEC组3年复发率显著优于对照组（37.5% vs. 72.5%,P<0.05 ）;对照组中位无病生存期（disease-free survival,DFS）显著低于HIPEC组（ 17.2 vs. 25.4,P<0.05 ）。多因素Cox回归分析结果显示:HIPEC是预防进展期胃癌复发的独立保护因素（ HR=0.465,95%CI:0.269～0.803;P<0.01 ）;在热灌注治疗中选择白蛋白紫杉醇可显著减少肿瘤复发率（HR=0.385 ,95%CI:0.178～0.831;P=0.015）,HIPEC组骨髓抑制发生率更低 （HR=0.305,95%CI:0.136 ～ 0.682;P<0.05）。HIPEC主要的急性期不良反应为无菌性腹膜炎,部分患者远期出现肝功能异常,但两组间差异无统计学意义（P>0.05）。  结论  根治术后行改良HIPEC可以改善中晚期胃癌患者的预后,其骨髓抑制的发生率更低,且该置管方法不良事件的发生可控,能满足治疗需要。而使用白蛋白紫杉醇作为HIPEC的药物似乎更能改善患者的预后。