中国大陆腹腔热灌注化疗治疗胃肠癌腹膜转移癌的现状

对于胃、结直肠癌患者来说, 腹膜转移是肿瘤晚期的标志性事件。既往的全身化疗及姑息性手术治疗模式对其疗效很差, 细胞减灭术联合腹腔热灌注化疗可改善部分腹膜转移癌患者的生活质量、延长生存期, 已经成为结直肠癌腹膜转移的标准治疗策略。但是, 该方案在我国并未获得统一认识和广泛应用。本文在分析我国胃、结肠癌腹膜转移癌的诊治现状同时, 就我国未来开展胃肠癌腹膜转移瘤的规范治疗提出建议。      

腹腔热灌注化疗在胃癌腹膜转移治疗中的作用

胃癌发生腹膜转移预后极差,中位生存期小于6个月.全身化疗并没有明显增加这些患者的生存期.腹腔热灌注化疗是目前常用的治疗腹膜转移的方法.全文系统回顾分析了腹腔热灌注化疗在胃癌腹膜转移治疗、进展期胃癌术后辅助治疗以及术前新辅助治疗的疗效.     

腹腔灌注化疗治疗恶性腹水疗效观察

晚期恶性肿瘤患者常可出现腹水,减少或消除腹水并防止其复发是临床医师面临的一个重要课题。收集１９９７年～１９９８年本院收治的恶性腹水患者５７例,以探讨其治疗方法和疗效。１资料和方法１．１临床资料１．１．１患者性别和年龄男２５例,女３２例,年龄最小７岁,最大７５岁,其中４０岁以下８例,４０～６０岁２９例,６０岁以上２０例。１．１．２原发疾病肝癌１６例,卵巢癌６例,胃癌２０例,肠癌１０例,其他５例。１．２治疗方法１．２．１化疗前常规作心电图,血常规、肝肾功能、腹部Ｂ超或ＣＴ检查,符合化疗要求后开始化疗。１．２．２患…     

胃肠癌根治术中持续循环腹腔热灌注化疗的应用效果

目的 探讨胃肠癌根治术术中持续循环腹腔热灌注化疗的应用效果.方法 120例胃肠癌患者根据随机抽签法分为观察组和对照组,各60例.对照组给予腹腔镜下胃肠癌根治术;观察组给予腹腔镜下胃肠癌根治术,术中持续循环腹腔热灌注化疗.记录2组预后情况.结果 所有患者都完成手术,无中转开腹情况.2组的手术时间、术中出血量对比无明显差异,但观察组的术后住院时间明显少于对照组(P＜0.05).观察组术后1个月的吻合口瘘、肺部感染、深静脉栓塞、切口感染等并发症总发生率为3.3％,而对照组为5.0％,2组差异无统计学意义(P＜0.05).观察组与对照组术后1个月的血清IL-6表达分别为(33.32±16.06) ng/ml和(76.58±16.44) ng/ml,都明显低于术前的(174.90±12.24) ng/ml和(175.38±11.05) ng/ml,观察组术后IL-6表达明显低于对照组(P＜0.05).随访至今,观察组与对照组的中位生存时间分别为(19.32±3.81)个月和(14.20±4.10)个月,观察组的中位生存时间明显长于对照组(t=4.221,P＜0.05).结论 胃肠癌根治术术中持续循环腹腔热灌注化疗的应用并不会增加手术复杂度,具有很好的安全性,能促进患者预后的改善,延长生存时间,其作用机制可能与降低炎症反应有关.     

腹腔热灌注治疗癌性腹水的护理体会

腹腔热灌注治疗癌性腹水具有控制腹水、减少局部复发、延长生存期的作用,已广泛、安全、有效的应用于抗肿瘤治疗中[1]。腹腔热灌注是利用物理热能加热人体腹腔的一种治疗方法。温热可以通过改变肿瘤细胞膜通透性和细胞内外环境以及影响细胞增殖周     

热灌注化疗联合体外高频热疗治疗胃癌腹腔转移23例

[目的]观察胃癌腹腔转移患者应用腹腔热灌注化疗联合体外高频热疗的临床疗效和不良反应。[方法]应用5-Fu﹑DDP行腹腔热灌注,化疗第2d行腹腔局部热疗60min,温度控制在43℃。[结果]实体肿瘤治疗有效率57.14%(12/21),腹水控制有效率85.71%(6/7),腹痛症状缓解率90.00%(9/10)。不良反应为Ⅱ度白细胞下降17.39%(4/23),化学性腹膜炎8.70%(2/23),胃肠道反应17.39%(4/23)。[结论]腹腔热灌注化疗联合高频热疗治疗胃癌腹腔转移,近期疗效好,不良反应小。     

德国胃癌腹膜转移腹腔热灌注化疗的实践和进展

本文系统介绍了德国胃癌腹膜转移治疗和预防方面的临床试验结果和治疗经验。肿瘤细胞减灭术（cytoreductive surgery,CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）和（或）胃切除术可以在有潜在治愈性的情况下实施,但仅能在经验丰富的中心并根据多学科诊疗团队的临床决策开展。目前,德国正在进行有关CRS+HIPEC治疗胃癌腹膜转移的有效性和安全性的高质量临床试验,也进行着有关胃癌切除术后辅助HIPEC治疗的临床试验。德国发明的加压腹腔气溶胶化疗（pressurized intraperitoneal aerosol chemotherapy,PIPAC）技术联合系统性化疗可作为姑息性治疗手段处理及预防腹水等并发症,期待有更多临床研究结果证实其有效性。      

免疫检查点抑制剂联合全身化疗及腹腔热灌注化疗治疗恶性腹膜间皮瘤1例

<正>恶性腹膜间皮瘤(malignant peritoneal mesothelioma,MPM)是一种临床罕见且高度侵袭性的恶性肿瘤,死亡率高,预后较差,早期诊断困难,多数患者确诊时已属晚期^[1]。MPM目前尚无标准治疗方案。本文报告1例联合应用全身化疗、腹腔热灌注化疗(heated intraperitoneal chemotherapy,HIPEC)及免疫治疗的MPM患者的治疗效果,以期为该类患者的治疗提供借鉴。     

德国胃癌腹膜转移腹腔热灌注化疗的实践和进展

本文系统介绍了德国胃癌腹膜转移治疗和预防方面的临床试验结果和治疗经验。肿瘤细胞减灭术（cytoreductive surgery,CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）和（或）胃切除术可以在有潜在治愈性的情况下实施,但仅能在经验丰富的中心并根据多学科诊疗团队的临床决策开展。目前,德国正在进行有关CRS+HIPEC治疗胃癌腹膜转移的有效性和安全性的高质量临床试验,也进行着有关胃癌切除术后辅助HIPEC治疗的临床试验。德国发明的加压腹腔气溶胶化疗（pressurized intraperitoneal aerosol chemotherapy,PIPAC）技术联合系统性化疗可作为姑息性治疗手段处理及预防腹水等并发症,期待有更多临床研究结果证实其有效性。      

腹腔灌注治疗在晚期胃癌腹膜转移患者中的应用效果

目的：探讨腹腔灌注治疗对胃癌腹膜转移患者生存的影响。方法：回顾性分析2014年1月至2020年12月哈尔滨医科大学附属肿瘤医院收治的353例晚期胃癌合并腹膜转移患者临床资料。根据是否腹腔灌注给药分为灌注治疗组和未灌注治疗组,并对患者进行生存随访。Kaplan-Meier法绘制生存曲线,Cox风险比例模型分析影响患者预后的因素,根据病灶部位、分化程度等进行亚组分析。结果：灌注治疗组和未灌注治疗组中位总生存（overall survival,OS）期为9.50个月（95%CI:7.39～11.61）和7.83个月（95%CI:5.74～9.92,P=0.022）。体质量指数（BMI）>25及伴有腹水的胃癌腹膜转移患者更易从腹腔灌注中获益。多因素分析显示：腹腔积液（HR=1.52,95%CI:1.18～1.94）、全身系统治疗（HR=0.43,95%CI:0.33～0.56）、手术（HR=0.52,95%CI:0.39～0.70）、腹腔灌注治疗（HR=0.65,95%CI:0.52～0.82）是影响患者生存的因素。结论：胃癌伴有腹膜转移患者可进行腹腔灌注治疗,与未灌注治疗患者相比,其生...     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of gastrointestinal cancers with peritoneal metastases: Progress toward a new standard of care

Peritoneal metastases from gastrointestinal cancer was, in the past, accepted as an inevitable component of the natural history of these diseases. It is a major cause of intestinal obstruction, fistula formation, and bowel perforation as the recurrent malignancy progresses to a terminal condition. Peritoneal metastases may be caused by full thickness penetration of the bowel wall by the primary cancer or by spilled cancer cells released into the peritoneal space by surgical trauma. Two new surgical technologies that have evolved to manage peritoneal metastases are cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This combined treatment strategy uses peritonectomy procedures and visceral resections to reduce the disease in the abdomen and pelvis to a macroscopic volume. Then, HIPEC is used to preserve the complete cytoreduction by controlling the minimal residual disease. Since the extent of peritoneal metastases, as measured by the peritoneal cancer index (PCI), is crucial to a favorable outcome, prognostic indicators are used to select patients for treatment. The combined treatment may be used to prevent peritoneal metastases in gastrointestinal cancer patients having a resection of the primary malignancy. This is especially important in gastric cancer patients with serosal invasion. The combined treatment may be used synchronously with the primary cancer resection if peritoneal metastases are already apparent. The treatment is most frequently used with metachronous peritoneal metastases diagnosed in follow-up. Cure of peritoneal metastases is an option in selected patients and its knowledgeable use is progressing towards a new standard of care.     

细胞减灭术联合腹腔热灌注化疗治疗结直肠癌腹膜转移的临床应用与展望

结直肠癌为我国常见恶性肿瘤之一, 其发病率逐年上升。腹膜为结直肠癌第2常见转移部位, 早期诊断困难, 预后不良。既往多采取全身性系统静脉化疗作为腹膜转移的主要治疗策略, 其全身不良反应明显, 且不能有效控制肿瘤进展。近年来, 外科技术、理念、设备的不断发展以及新的化疗药物与靶向药物的出现改善了结直肠癌腹膜转移患者的生存质量及预后。细胞减灭术(CRS)联合腹腔热灌注化疗(HIPEC)可在有效清除腹腔内游离癌细胞与亚临床病灶的同时, 减轻化疗药物带来的全身不良反应, 最大程度上实现宏观与微观的肿瘤根治, 目前, CRS+HIPEC已被国内外作为结直肠癌腹膜转移的一线治疗方案。文章分析总结了CRS+HIPEC治疗结直肠癌腹膜转移的生存疗效、预后因素分析、化疗安全性等问题, 探讨了HIPEC治疗目前存在的问题与争议。     

Role of hyperthermic intraoperative peritoneal chemotherapy in the management of peritoneal metastases

The peritoneal cavity must be oncologically considered as an organ in its own right and peritoneal metastases (PM) must be treated with the same curative intent (and the same results) as liver metastases. The package combining complete cytoreductive surgery (CCRS) (treating the visible disease) plus hyperthermic intraoperative peritoneal chemotherapy (HIPEC) (treating the remaining non-visible disease) achieves cure in many patients. Twenty years of publication allow us to assemble sufficient background information and data to point out the good and poor indications for CCRS + HIPEC.HIPEC is the standard of care for the treatment of peritoneal pseudomyxomas and peritoneal mesotheliomas and also, recently for the treatment of colorectal PM with limited peritoneal extension.HIPEC is in the evaluation phase for gastric PM and ovarian PM after initially disappointing results, but it is highly probable that it will be useful in particular settings. PM from neuroendocrine tumours are in the same situation.HIPEC is not currently indicated for the treatment of PM from sarcomas, from GIST, and for small round-cell desmoplastic tumours, given the poor results obtained.HIPEC can be useful, on a case-by-case basis, to treat rare tumours complicated by isolated peritoneal diffusion (e.g. Frantz’s tumours).HIPEC can be used in the prophylactic setting to prevent PM in patients with a high risk of developing PM, and the first results of the ‘second-look’ approach are promising.Finally, CCRS + HIPEC appear to be indispensable tools in the oncologist’s armentarium.     

Advanced gastric cancer with or without peritoneal carcinomatosis treated with hyperthermic intraperitoneal chemotherapy: A single western center experience

Introduction

The aim of this article was to evaluate the role of hyperthermic intraperitoneal chemotherapy (HIPEC), associated or not to cytoreductive surgery (CS) in the treatment of different stages of advanced gastric cancer (AGC).

Patients and methods

Thirty seven patients with AGC who underwent 43 HIPEC from June 1992 to February 2007 were included. HIPEC used Mitomycin-C and Cisplatin for 60–90 min at 41–43 °C intra-abdominal temperature. The main endpoints were long-term survivals, morbidity and mortality rates.

Results

Eleven patients had no demonstrable sign of PC and constituted the Prophylactic-group, while 26 patients had macroscopic PC (PC-group). Five patients were Gilly 1 or 2 (nodules <0.5 cm) and 21 Gilly 3 or 4 (nodules ≥0.5 cm). In the PC-group a complete curative CS was achieved before HIPEC in 8 (PC-curative subgroup) and a palliative HIPEC in 18 patients (PC-palliative subgroup). The overall 30-days mortality was 5% (2 patients). Two patients in the Prophylactic group died within 6 months after hospital discharge (overall mortality 11%). The estimated risk of death per procedure was 9%. Ten patients (27%) presented one or more complications. The median survival was 23.4 months in the Prophylactic group, and 6.6 months in the PC-group (p < 0.05). The median survival in the PC-curative subgroup was 15 vs 3.9 months in the PC-palliative subgroup (p = 0.007). The median survival according to Gilly classification was significantly different (Gilly 1&2 vs Gilly 3&4, 15 vs 4 months respectively, p = 0.014). The global recurrence rates between the Prophylactic group and the PC-curative subgroup at 2 years were 36% vs 50% respectively. The median delay to recurrence was 18.5 vs 9.7 months respectively.

Conclusion

HIPEC might be useful to improve the survival in selected patients with ACG only when a complete cytoreduction can be achieved. Despite encouraging data, prospective studies, based on larger cohorts of patients are required to assess the role of this procedure as a prophylactic treatment in patients with AGC.     

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。     

腹腔内贝伐珠单抗联合腹腔热灌注化疗治疗卵巢癌腹腔积液的临床观察

目的 观察腹腔内贝伐珠单抗联合腹腔热灌注化疗治疗卵巢癌腹腔积液的疗效和安全性,分析腹水内血管内皮生长因子（VEGF）水平对贝伐珠单抗治疗卵巢癌腹腔积液的临床意义。方法 将46例卵巢癌伴腹腔积液患者随机分为治疗组（n=25）和对照组（n=21）,均应用TC方案（紫杉醇135mg／m2静脉注射d1+卡铂 AUC=5 静脉注射d1）全身化疗,3周重复1次;同时腹腔内给予顺铂40mg／m2+43～45℃ 0.9%生理盐水1500～3000ml热灌注化疗,每2周重复1次,连续治疗6周。治疗组在上述治疗基础上每次热灌注化疗后腹腔内注入贝伐珠单抗300mg,治疗6周。评价患者疗效、生活质量改善及不良反应。酶联免疫吸附法（ELISA）检测46例患者治疗前、后腹水中VEGF水平。结果 治疗组治疗后腹水VEGF水平为（468.30±42.80）pg/ml,明显低于治疗前的（2785.89±305.22）pg/ml（P＜0.05）;治疗组治疗后腹水VEGF水平明显低于对照组治疗后的（820.20±61.49）pg/ml（P＜0.05）。治疗组的有效率（RR）为92.0％（23／25）,对照组为61.9％（13／21）,差异有统计学意义（P＜0.05）。治疗组中VEGF阳性者的RR达1000％,VEGF阴性者为50.0％,差异有统计学意义（P＜0.05）。治疗组的生活质量（QOL）改善率为92.0％,对照组为57.1％,差异有统计学意义（P＜0.05）。46例患者对治疗的耐受良好,无严重不良反应。结论 腹腔内贝伐珠单抗联合腹腔热灌注化疗治疗卵巢癌腹腔积液的疗效优于单纯腹腔热灌注化疗,生活质量明显改善,安全性好,尤其对于腹水VEGF阳性卵巢癌患者更加适合。     

Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of malignant ascites secondary to unresectable peritoneal carcinomatosis from advanced gastric cancer

Aims

To review our experience of laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of malignant ascites from advanced gastric cancer in order to discuss benefits, problems and possible indications.

Methods

From June 2000 to May 2003 laparoscopic approach was used to perform HIPEC on five patients affected by malignant ascites secondary to unresectable peritoneal carcinomatosis of gastric origin, in order to associate the benefits of a definitive palliation of ascites with a minimal invasiveness. All patients had ascites related symptoms requiring iterative paracenteses. Intraperitoneal perfusion of mitomycin-C and cisplatin was delivered for 60–90 min with an inflow temperature of 45 °C.

Results

Complete clinical regression of ascites and related symptoms was achieved in all the five patients treated. Intraoperative course was uneventful in all cases. Mean operative time was 181 min. No postoperative deaths, related to the procedure, occurred. Only a case of delayed gastric empting was recorded as a minor postoperative complication.

Conclusions

Laparoscopic HIPEC appears to be a safe and effective procedure to treat debilitating malignant ascites from unresectable peritoneal carcinomatosis.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal and gastrointestinal origin shows acceptable morbidity and high survival

Background

Peritoneal carcinomatosis from colorectal origin carries a poor prognosis. Recent clinical studies show that cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival of selected patients with a colorectal carcinoma and isolated peritoneal carcinomatosis in the absence of extra-abdominal metastases. Here, we report the clinical outcomes and survival after cytoreductive surgery and HIPEC of the first cohort of patients treated in our institution.

Methods

Sixty-seven patients underwent a laparotomy. Complete cytoreduction could be performed in 49 patients, who underwent a total of 53 CS–HIPEC procedures. All had peritoneal carcinomatosis originating from primary colorectal, cecal, appendiceal, and gastric tumors.

Results

In patients who underwent CS–HIPEC, an R0 resection could be achieved in 4%, R1 in 88%, and R2 in 8%. The 30-day mortality was 0; one patient died in-hospital after 10 weeks. The median hospital stay was 12 days (range 4–56). The overall morbidity was 43%, including extended gastroparesis (11%), anastomotic failure (11%) and intra-abdominal abscess (9%). Mean time to clinical recurrence was 12 months (range 4–22). The actuarial 1-year survival was 88% and 2-year survival was 75%.

Conclusion

In well-selected patients referred to a specialized institution, CS–HIPEC has an accep table morbidity and high survival rate.     

Treatment and prevention of peritoneal carcinomatosis from gastric cancer by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Overview and rationale

Peritoneal carcinomatosis (PC) from gastric cancer is a condition with a very bleak prognosis. Most authors consider it to be a terminal disease and recommend palliative therapy only. Multimodal therapeutic approaches to PC have emerged in the last decades, combining cytoreductive surgery (CRS) and peritonectomy procedures with perioperative intraperitoneal chemotherapy (IPEC), including hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC).