结直肠癌腹膜转移治疗的临床研究进展

腹膜是结直肠癌转移的第三常见部位。结直肠癌腹膜转移通常被认为是终末期疾病,预后差。随着系统性药物治疗的进展,转移性结直肠癌患者预后明显改善,但腹膜转移患者生存获益仍然较少。腹膜肿瘤细胞减灭术和腹腔热灌注化疗能够显著改善腹膜转移患者的预后。新型治疗方法如腹腔加压气溶胶化疗、腹腔MOC31PE抗毒素治疗等也随之出现。本文将对结直肠癌腹膜转移治疗的临床研究进行综述。     

结直肠癌伴腹膜转移治疗的研究进展

结直肠癌是全球第三大常见癌症，也是与癌症相关死亡的第四大常见原因。转移性疾病仍然是结直肠癌死亡的主要原因，除了淋巴和血源传播途径外，结直肠癌还会引起肿瘤细胞的腹腔传播，最终导致腹膜癌。随着各种治疗的进展，转移性结直肠癌患者的预后明显改善，但对伴有腹膜转移的患者疗效并不理想。最近越来越多的研究表明，肿瘤细胞减灭术(CRS)和腹腔热灌注化疗(HIPEC)可使结直肠癌伴腹膜转移患者受益，预后较好，腹腔内加压气溶胶化疗(PIPAC)、新辅助化疗、Radspherin短距离辐射等新型疗法也相继出现。本文就结直肠癌伴腹膜转移的治疗研究进展作一综述。     

结直肠癌腹膜转移伴卵巢转移的治疗现状与挑战

腹膜是结直肠癌转移的好发部位。出现腹膜转移的女性结直肠癌患者常伴有卵巢转移。通常认为出现腹膜转移和卵巢转移的女性结直肠癌进展迅速且预后极差,目前仍无有效的治疗手段。虽然结直肠癌患者接受化疗及靶向药物后可显著改善预后,但同时伴有腹膜转移和卵巢转移的女性结直肠癌患者却无法明显获益。许多研究证实肿瘤细胞减灭术（CRS） 联合腹腔内热灌注化疗（HIPEC）可延长这类患者的生存期,改善生活质量。本文综述了结直肠癌腹膜转移和卵巢转移患者的诊治现状和相关进展。     

肿瘤细胞减灭术联合腹腔热灌注化疗治疗结直肠癌腹膜转移癌

结直肠癌(colorectal cancer,CRC)发病率呈上升趋势,虽然诊疗技术不断进步,仍有较多患者确诊时已经出现腹腔种植转移或根治性切除术后很快出现腹膜转移癌(peritoneal carcinomatosis,PC)。目前针对这种情况的治疗方法,主要有全身化疗、肿瘤细胞减灭术(cytoredu:tive surgery,CRS)联合全身化疗、CRS联合腹腔热灌注化疗(hyperthermie intraperitonealchemotherapy,HIPEC)等,其中CRS+HIPEC被认为是目前治疗CRC腹膜种植转移的有效方法。本文综述了该技术的治疗进展。1 HIPEC防治CRC PC的理论基础HIPEC是将大量含化疗药物的灌注液体持续、循环、充盈患者腹腔,预防和治疗PC。1980年Spratt等     

细胞减灭术加腹腔热灌注化疗治疗结直肠癌腹膜转移癌病例对照研究

  目的  分析细胞减灭术（CRS）加术中腹腔热灌注化疗术（HIPEC）对结直肠癌腹膜转移癌的疗效及安全性。  方法  课题设计为回顾性病例对照研究, 收集结直肠癌腹膜转移癌（CRC PC）患者资料, 按临床病理参数匹配原则, 分为CRS组（CRS+术后全身化疗）29例, HIPEC组（CRS+HIPEC+术后全身化疗）33例。分析两组的总体生存期（OS）及严重不良事件（SAE）。  结果  两组患者临床病理学特征均衡可比, 术中PCI评分及器官/腹膜切除情况相似。两组中位随访时间分别为41.9个月（6.5~110.0个月）和32.0个月（10.5~95.9个月）, OS分别为8.5个月（95% CI: 4.9~12.1个月）和14.5个月（95% CI: 11.9~17.1月）（P=0.007）。术后30天内CRS组3例发生SAE, HIPEC组9例（P=0.126）。多因素分析显示, HIPEC、CC 0~1分、术后化疗周期≥6个周期为改善生存的独立预后因素。  结论  CRS+HIPEC可改善CRCPC患者生存期, SAE无显著增加, 安全性可接受。      

结直肠癌腹膜转移的治疗:新事实、新知识和新未来

结直肠癌腹膜转移（colorectal cancer peritoneal metastasis,CRCPM）一直是荷兰临床肿瘤学研究的重点领域之一,对比系统化疗加姑息手术治疗,CRCPM患者更易从肿瘤细胞减灭术（cytoreductive surgery,CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）中获益,CRS+HIPEC在治疗CRCPM中已具有稳定的临床基础。目前,荷兰建立了全国肿瘤登记处,对所有腹膜癌病例进行详细登记和分析。本文重点介绍了荷兰CRCPM最新研究,包括流行病学研究、多中心随机临床试验、基础和转化研究的新成果,给出了国际热点问题和学术争鸣的荷兰答案,提出了腹膜肿瘤学未来发展的新机遇和新方向。      

结直肠癌腹膜转移的治疗: 新事实、新知识和新未来

腹膜转移是结直肠癌的常见转移方式,即使进行积极治疗,结直肠癌腹膜转移患者的预后仍较差。近年来,腹腔加压气溶胶化疗（pressurized intraperitoneal aerosol chemotherapy,PIPAC）作为一种新的腹腔内化疗方式受到了广泛关注,全球多个国家的研究者开展了大量与PIPAC相关的前瞻性研究和临床试验,对于腹膜癌患者来说,PIPAC已成为一种安全有效的且有前景的治疗方式,多个医疗中心已经将其用于治疗腹膜癌患者。随着PIPAC相关的临床证据越来越多,其在临床中的应用越发受到重视。本文就PIPAC治疗结直肠癌腹膜转移的理论基础、发展历程、操作流程、适应证、禁忌证、药物方案和临床应用的最新进展进行综述,以期为临床实践和研究提供参考。     

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。     

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.     

Peritoneal carcinomatosis of colorectal origin

Peritoneal carcinomatosis is, after liver metastases, the second most frequent cause of death in colorectal cancer patients and at the present time, is commonly inserted and treated as a stage IV tumour. Because there is no published data that outlines the impact of new therapeutic regimens on survival of patients with peritoneal surface diffusion, the story of carcinomatosis can be rewritten in light of a new aggressive approach based on the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Also if these treatment perhaps allow to obtain better results than standard therapies, we suggest, that a large prospective randomised control trial is needed to compare long-term and progression-free survival under the best available systemic therapy with or without cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.     

Peritoneal metastases from colorectal cancer: Patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment modality for patients with pseudomyxoma peritonei. The majority of patients with pseudomyxoma who have complete tumour removal and HIPEC are cured.     

Peritoneal cancer index (PCI) based patient selecting strategy for complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in gastric cancer with peritoneal metastasis: A single-center retrospective analysis of 125 patients

ObjectiveThe role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer with peritoneal metastasis (GCPM) is still controversial, mainly due to the limited survival benefit and uncertain patient selection. This study aims to construct a selecting strategy in GCPM for CRS + HIPEC.MethodsFrom a prospective established database, 125 patients were enrolled. All these patients were pathologically confirmed as GCPM and treated with CRS + HIPEC with or without preoperative or postoperative chemotherapy. The clinical documents and follow-up results were collected and analyzed with the primary endpoint of overall survival (OS) and the secondary endpoint of perioperative serious adverse events (SAEs).ResultsThe median OS of 125 GCPM patients treated with CRS + HIPEC was 10.7 months, with 1-, 2-, 3-, and 5-year survival rates of 43.8%, 24.7%, 18.6%, and 15.7%, respectively. The multivariate analysis identified completeness of cytoreduction (CC), SAEs, HIPEC drugs, and adjuvant chemotherapy as independent prognostic factors on OS. The median OS was 30.0 (95%CI: 16.8–43.3) months in CC-0 group, significantly better than 7.3 (95%CI: 5.8–8.8) months in CC1-3 group (P < 0.001). The median OS showed no significant difference among CC-1 (8.5, 95%CI: 6.7–10.2, months), CC-2 (5.6, 95%CI: 3.0–8.2, months) and CC-3 (6.5, 95%CI: 5.2–7.7, months) groups (P > 0.05 for all pairwise comparations). The nomogram based on peritoneal metastasis timing, preoperative tumor marker (TM), and peritoneal cancer index (PCI), with AUC of 0.985, showed a good accuracy and consistency between actual observation and prediction of the probability of complete CRS. The cutoffs of PCI were 16 for synchronous GCPM with normal TM, 12 for synchronous GCPM with abnormal TM, 10 for metachronous GCPM with normal TM, and 5 for metachronous GCPM with abnormal TM, setting the probability to achieve complete CRS as 50%.ConclusionsOnly complete CRS + HIPEC (CC-0) could improve survival for high selected GCPM patients with acceptable safety. An incomplete CRS (CC1-3) should be avoided for GCPM patients. Synchronous GCPM with PCI ≤16 and normal TM, synchronous GCPM with PCI ≤12 and abnormal TM, metachronous GCPM with PCI ≤10 and normal TM, or metachronous GCPM with PCI ≤5 and abnormal TM maybe potential indications for complete CRS + HIPEC treatment.     

Peritoneal carcinomatosis and liver metastases from colorectal cancer treated with cytoreductive surgery perioperative intraperitoneal chemotherapy and liver resection

Background

An aggressive therapy comprising of cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) and liver resection/ablation is generally not offered to patients with both colorectal peritoneal carcinomatosis (CRPC) and liver metastases (LM) as it no longer represents a loco-regional disease. We review the outcomes of patients who underwent an aggressive treatment with a curative intent for both CRPC and LM as a prelude towards determining the suitability of this treatment.

Methods

Patients with CRPC were treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy in our institution. Patients with LM underwent additional treatment of liver resection/ablation. The characteristics and survival of patients with isolated CRPC and those with both CRPC and LM were compared.

Results

Fifty-five patients underwent complete cytoreductive surgery for treatment of CRPC, amongst which 16 patients had LM. The overall median survival was 36 months. Fourteen of the 16 patients treated for CRPC and LM underwent synchronous treatment. When patients with CRPC alone or CRPC with LM were compared, patients with CRPC and LM had a lower PCI (p = 0.03), received less HIPEC infusion (p < 0.001), received less of both HIPEC and EPIC infusion (p = 0.007), had a shorter procedural duration (p = 0.001) and required less blood transfusion (p = 0.02). There was no difference in survival between patients who had CRPC alone or CRPC with LM who underwent aggressive treatment (p = 0.77).

Conclusions

A curative procedure may be offered to selected patients with CRPC and LM, especially in those with a low peritoneal cancer index.     

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).