腹腔热灌注化疗的研究进展

腹膜是腹腔恶性肿瘤的常见转移部位,腹膜表面的血液供应很少,加之血浆-腹膜屏障的存在,使得静脉化疗药物很难到达腹膜表面.腹腔热灌注化疗则可直接作用于腹膜,从而有效地治疗腹膜转移癌及其引起的恶性腹水.本文将不同的腹腔热灌注化疗方法进行了分类,并综述了近几年腹腔热灌注化疗的研究进展.     

Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy

Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options.     

大肠癌术后腹腔低渗温热化疗

目的研究腹腔低渗温热化疗对大肠癌术后腹腔内及肝转移的预防效果.方法收集自1996年7月～1999年12月大肠癌手术病例,随机分为两组A组腹腔低渗温热化疗组.B组常规静脉化疗组.观察腹腔复发率、肝转移率、生存率.结果A组腹腔复发率7.5%(4/53),肝转移率5.7%(3/53),1年、2年生存率分别为96.8%(60/62)、88.7%(55/62).B组腹腔复发率11.8%(6/51),肝转移率15.7%(8/51),1年、2年生存率分别为82.8(48/58)、74.1%(43/58).结论腹腔低渗温热化疗对预防大肠癌术后腹腔内复发、肝转移、提高生存率有显著疗效.     

The approval process for hyperthermic intraoperative intraperitoneal chemotherapy

AimsTo clarify the requirements for Food and Drug Administration approval in the United States for hyperthermic intraoperative intraperitoneal chemotherapy administration. Also, to review the status of the approval process in Europe.MethodsThe obstacles to be overcome for approval by the Food and Drug Administration for a new drug approval and for a new device approval were reviewed. Drugs approved in the past were examined for their potential for current application in this technology.ResultsThe likelihood that the approval of a heater circulator along with the approval for specific chemotherapy agents for heated intraoperative intraperitoneal chemotherapy was judged to be remote. Rather, the continued use of “homemade heater circulators” and the off-label use of appropriate chemotherapy agents augmented by heat will continue to be the standard of care. The European community currently has several heater circulators approved for hyperthermic intraoperative intraperitoneal chemotherapy administration. These devices have been specifically approved for oncologic indications.ConclusionsContinued research and development of heated intraoperative intraperitoneal chemotherapy is necessary. As the requirement for prevention and treatment of the peritoneal surface component of gastrointestinal and gynecologic oncology expands, new investigations into the approval process in the United States will be necessary. Publication of results from institutions pioneering these new treatment strategies will, of necessity, continue.     

Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy

BACKGROUND: In recent years surgical cytoreduction followed by intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced as treatment modality in patients with peritoneal surface malignancy. In the current review the rational for this approach, the prerequisites and the different techniques used are discussed. METHODS: A literature search through PubMed was performed. RESULTS: Pharmacokinetic studies have shown an important dose advantage for intraperitoneal versus intravenous application. Hyperthermia enhances the penetration of cytostatic drugs into tumour tissue and also shows synergism with various cytostatic drugs. The penetration depth of drugs into tissue is limited, therefore HIPEC can only be effective in patients with minimal residual disease after (aggressive) surgery. HIPEC can be conducted in various ways, without clear proven advantage of one method over the others. Local complications after this combined treatment approach are mainly surgery related. Intraperitoneal chemotherapy may cause systemic toxicity, dependent on the drug used. In randomised studies cytoreductive surgery followed by HIPEC has proven its value in the prevention of peritoneal dissemination in gastric cancer. Phase II data on HIPEC in peritoneal carcinomatosis of colorectal origin and pseudomyxoma peritonei are promising, but randomised studies are still not available. CONCLUSION: Aggressive surgical cytoreduction and HIPEC in patients with peritoneal surface malignancy has a clear rational and seems to have clinical value.     

Applications of hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer

Introduction: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) plays a pivotal role in the current treatment of peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Since the first demonstration, benefits for patients and especially an increase in survival have been described. In recent years, feasibility, efficacy and safety of HIPEC have been improved and progress has been made in understanding its oncological mechanism.

Areas covered: In this article, leading publications have been reviewed including clinical trials to describe the clinical presentation of PC due to CRC and present recent evidence of the CRS/HIPEC procedure. The surgical approach including evaluation of the extent of PC is described and, in addition, the article reports about different HIPEC techniques as well as several protocols. Furthermore, the development and prognostic benefit of the combination of intraperitoneal and intravenous chemotherapy are outlined. Consideration has been given in particular to patient selection and the use of HIPEC if complete cytoreduction is not feasible.

Expert commentary: The CRS/HIPEC procedure represents a curative approach to treat patients with PC from CRC. However, surgical skills and the HIPEC technique still require specialized oncological centers.     

腹腔热灌注化疗操作参数的研究进展

综述腹腔热灌注化疗操作参数的研究进展，系统性回顾分析截止2018年9月在CNKI、PubMed上搜寻的相关文献，从灌注化疗中的药物选择、时间及温度、压力和/或容量和流速等方面阐述热灌注化疗的具体操作研究进展。提供灌注参数选择对治疗腹膜癌疗效、安全性和毒副作用的相关信息。     

腹腔热灌注化疗对腹腔游离癌细胞杀灭效果的评价*

目的：评估腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy ,HIPEC）对腹腔游离癌细胞的杀灭作用,探索腹膜癌细胞学根治的可行性。方法：收集 45例腹膜转移癌患者 HIPEC 前、后的腹腔灌洗液（或腹水）样本,分别行腹腔灌洗液细胞学（periton eal lavage cytology ,PLC ）检查;普通RT-PCR 及实时定量RT-PCR 检测CEA mRNA 、CK20mRNA ;化学发光法检测HIPEC 前、后患者血清肿瘤标志物CEA 、CA125 、CA19- 9 ;分析各项指标HIPEC 前、后的变化特点。结果：HIPEC 前、后PLC 检查阳性率分别为93.3% vs. 24.4%（P < 0.001）;CEAmRNA 阳性率分别为97.8% vs. 84.4%（P = 0.058）;CK20mRNA 阳性率HIPEC前、后均为95.6%（P = 1.000）。 分别有32.5% 和30.0% 的患者HIPEC 后CEAmRNA 表达量、CK20mRNA 表达量较HIPEC 前显著下降（均P < 0.001）。 HIPEC 前、后CEA 、CA125、CA19- 9 阳性率分别为50.0% vs. 23.6%（P = 0.016）、52.6% vs. 47.4%（P = 0.409）、36.8% vs.26.3%（P = 0.121）。结论：HIPEC 可有效杀灭腹腔游离癌细胞,为实现腹膜癌的细胞学根治提供了一个可行的方法。     

Prophylactic hyperthermic intraperitoneal chemotherapy in patients with epithelial appendiceal neoplasms

Background Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising approach for preventing peritoneal carcinomatosis in high-risk patients. We report our initial experience with prophylactic HIPEC in a series of patients with appendiceal neoplasms. Methods We retrospectively reviewed our prospectively maintained database to identify patients who underwent HIPEC in the absence of peritoneal disease. Patients with previously documented peritoneal surface disease were excluded. Data regarding clinical, operative and pathological features were analysed. Results Out of 322 HIPEC procedures performed between March 2007and August 2015, we identified 16 patients who underwent surgery with prophylactic intent. Primary diagnoses included high-grade and low-grade appendiceal neoplasms. Most patients presented originally with appendiceal perforation; all patients underwent initial surgery during which the appendix or right colon were resected. Following a median time interval of 2.2 months, a second surgery performed at our institution consisted of completion of omentectomy, partial colectomy and oophorectomy, with administration of prophylactic HIPEC (using mitomycin C). A totally laparoscopic approach was attempted and achieved in 11 patients in whom the median duration of surgery, estimated intraoperative blood loss and length of hospitalisation were 251?min, 100?cm³ and 4 days, respectively. There were no cases of major perioperative morbidity or mortality. Conclusions Prophylactic HIPEC for appendiceal neoplasms is feasible, safe and may be performed laparoscopically. Larger studies with long-term follow-up are needed to determine whether a survival benefit is associated with this treatment.     

胃癌患者术中腹腔热灌注化疗的临床研究

目的：探讨胃癌根治术中一次性腹腔温热灌注化疗的临床疗效。方法：将术中行一次性腹腔温热灌注化疗的50例胃癌患者（治疗组）与未行此方法治疗的100例患者（对照组）的腹腔游离癌细胞检出率及预后等情况进行对比。结果：治疗组的温热灌注液游离癌细胞检出率为7．4％；对照组冲洗液的癌细胞检出率为30．8％。治疗组与对照组术后两年内腹腔复发率分别为14．6％和38．7％（P〈0．01）。治疗组术后1、2、3年生存率分别为100％、79％和60％；对照组则为95．1％、50．2％和35．2％，两组2、3年生存率比较，差异有显著性（P〈0．01）。结论：一次性腹腔温热灌注化疗简便、高效、安全，具有杀灭腹腔游离癌细胞的作用，可降低患者术后腹腔复发率和提高生存率。     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignant disease

Peritoneal Malignant Disease (PMD) is the presence of tumoral tissue on the peritoneal surface from primary tumors or tumors from other locations (e.g. digestive or gynecologic). It is a regional disease with poor prognosis when treated with repeated “debulking” and traditional systemic chemotherapy. Cytoreduction plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a combined multimodal regional procedure aimed at reducing the macroscopic tumoral mass as much as possible and treating with chemotherapy the microscopic disease that is out of the scope of the surgeon. This combined treatment may change the natural history of PMD, it is translated into a higher overall survival and cancer-free survival and it offers the option of cure in selected cases. The high-complexity procedure is also associated with complications and mortality, but in similar rates as other major oncologic procedures.     

Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy

At the Fifth International Workshop on Peritoneal Surface Malignancy, in Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal surface malignancy was obtained through the Delphi process. Conflicting points concerning drugs, carrier solution and optimal temperature for hyperthermic intraperitoneal chemotherapy (HIPEC) were discussed.     

妇科恶性肿瘤腹腔热灌注化疗的研究进展

腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)主要通过腹腔内灌注治疗系统实现对腹腔内热化疗的精准控温、循环灌注,目前主要用于治疗和预防消化道肿瘤腹膜种植转移、腹膜假性黏液瘤以及控制恶性腹水.近年来,HIPEC逐渐成为治疗晚期、复发或转移性妇科恶性肿瘤的辅...     

胃癌患者术中腹腔热灌注化疗的临床研究

目的:探讨胃癌根治术中一次性腹腔温热灌注化疗的临床疗效.方法:将术中行一次性腹腔温热灌注化疗的50例胃癌患者(治疗组)与未行此方法治疗的100例患者(对照组)的腹腔游离癌细胞检出率及预后等情况进行对比.结果:治疗组的温热灌注液游离癌细胞检出率为7.4%;对照组冲洗液的癌细胞检出率为30.8%.治疗组与对照组术后两年内腹腔复发率分别为14.6%和38.7%(P＜0.01).治疗组术后1、2、3年生存率分别为100%、79%和60%;对照组则为95.1%、50.2%和35.2%,两组2、3年生存率比较,差异有显著性(P＜0.01).结论:一次性腹腔温热灌注化疗简便、高效、安全,具有杀灭腹腔游离癌细胞的作用,可降低患者术后腹腔复发率和提高生存率.