活性碳吸附丝裂霉素C腹腔化疗预防进展期胃癌术后复发

目的　探讨活性碳吸附丝裂霉素C(MMC)腹腔化疗治疗和预防进展期胃癌术后腹腔复发的效果。　方法　通过随机临床试验 ,将 12 4例进展期胃癌病例随机分为 2组 ,实验组于手术结束时腹腔内给予经医用活性碳吸附的MMC 5 0mg ,术后 3个月开始常规静脉化疗。对照组仅于手术后 3周开始静脉化疗。全部病例均采取根治性手术治疗。　结果　实验组和对照组总的 3、5年生存率分别为 70 16 % ,44 5 1%和 2 7 0 9% ,14 4 5 % ,P <0 0 1。实验组较对照组 3、5年生存率分别提高 43 0 7%及 30 0 6 %。　结论　活性碳吸附MMC腹腔化疗能提高进展期胃癌根治性手术后无瘤生存率。其作用仅限于杀死腹腔内游离的癌细胞和淋巴结内微转移癌灶 ,因此主要适用于经根治手术的高危患者。     

Factors predicting survival after intraperitoneal hyperthermic chemotherapy with mitomycin C after cytoreductive surgery for patients with peritoneal carcinomatosis

HYPOTHESIS: Certain clinicopathologic factors predict improved survival after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. DESIGN: Prospective clinical trial. SETTING: Surgical oncology service at a university academic hospital. PATIENTS: A population of 109 consecutive patients with peritoneal carcinomatosis treated between December 1991 and November 1997. INTERVENTION: All patients underwent resection of gross disease followed by 2-hour intraoperative perfusion of mitomycin C (20-40 mg) into the peritoneal cavity at a temperature of 40.5 degrees C. MAIN OUTCOME MEASURES: Clinicopathologic factors that independently predicted improved overall survival rates. RESULTS: Overall survival at 1 and 3 years was 61% and 33%, respectively. With median follow-up of 52 months, median overall survival was 16 months. Four factors were significant independent predictors of improved survival by multivariate analysis: nonadenocarcinoma histologic features (P =.001), the appendix as a primary site (P =.003), the absence of hepatic parenchymal metastases (P =.01), and complete resection of all gross disease (R1/0 resection) (P<.001). Patients with an R1/0 resection vs an incomplete resection of gross disease (R2 resection) had 3-year overall survival of 68% vs 21% (P<.001). CONCLUSIONS: Patients with peritoneal carcinomatosis have a uniformly poor prognosis. However, in select patients, the natural history of this disease condition may be altered by using the multimodality approach of cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. These results require confirmation in prospective randomized studies.     

Intraperitoneal hyperthermic perfusion with mitomycin C for colorectal cancer with peritoneal metastases

Background: Intraperitoneal (i.p.) metastases pose a special problem for surgical treatment because of their multiplicity and microscopic size. This study was designed to examine the feasibility and safety of i.p. hyperthermic perfusion (IPHP) with mitomycin C (MMC) for treating recurrent colorectal cancer. Methods: Fifteen patients with metastatic colon cancer were treated. All patients underwent cytoreductive procedures leaving only residual i.p. metastases <1 cm in diameter. All patients had received prior systemic chemotherapy, but their disease had progressed. Intraperitoneal chemotherapy was administered through three large catheters (28 French) using a closed system of two pumps, a heat exchanger, and two filters. After the patient’s abdominal temperature reached 41°C, 45–60 mg of MMC was circulated intraperitoneally for 1 h. Results: The majority of patients had various anastomoses: small bowel (n=11), large bowel (n=5), and urologic (n=5). No anastomotic complications occurred in any of the patients. One patient experienced severe systemic MMC toxicity, which caused cytopenia and respiratory depression. In all patients the carcinoembryonic antigen (CEA) level decreased after surgery and IPHP. Median follow-up was 10 months, and recurrence was defined as an elevation in CEA level. Disease recurred in three patients within 5 months, and disease recurred in seven other patients over the next 3 months; one patient remains clinically free of disease after 8 months. Conclusion: Our data suggest that IPHP is a safe palliative method of treatment for patients with peritoneal carcinomatosis. The median patient response duration of 6 months may warrant consideration of a repeat IPHP procedure at that time. Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

Treatment of peritoneal carcinomatosis by intraperitoneal chemo-hyperthermia with mitomycin C. Initial experience

Intra-peritoneal chemo-hyperthermia with mitomycin C was used to treat 9 patients with very advanced gastrointestinal cancers with peritoneal seedings. Resection of the primary tumor was possible in 3 cases. After temporary of closure of the abdominal wall, 90 to 120 minutes of intra-peritoneal chemo-hyperthermia was performed under general anaesthesia with 32 degrees C of systemic hypothermia, via 3 intra-peritoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 61 of peritoneal dialysate warmed at the inflow temperature of 46 to 49 degrees C. We observed no mortality or morbidity. There were only minor and temporary laboratory side effects and for 6 patients, no malignant cells could be found in the ascitic fluid after intra-peritoneal chemo-hyperthermia. In six patients, we conserved an improvement in the Karnofsky index 3 to 7 months after intra-peritoneal chemo-hyperthermia. These results show that intraperitoneal chemo-hyperthermia with mitomycin C is a safe and reliable treatment for peritoneal seedings in severely advanced gastrointestinal cancers and encourage us to proceed with this new therapeutic modality.     

Hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis of digestive and peritoneal origin: rationale

Up to a few years ago peritoneal carcinomatosis was considered as an "incurable" disease. The aim of this paper is to review the surgical approach with curative intent to carcinomatosis: it consists of complete resection of macroscopic disease (R1), associated with hyperthermic intraperitoneal chemotherapy (HIPEC) to treat residual microscopic disease, and to evaluate its indications. Overall 5-year survival of patients with peritoneal carcinomatosis treated by HIPEC is similar to that of patients with hepatic metastases treated with curative intent. Those patients should no longer be considered as patients with a terminal disease but as patients with a potentially treatable localized disease.     

Intraperitoneal chemohyperthermia and attempted cytoreductive surgery in patients with peritoneal carcinomatosis of colorectal origin

BACKGROUND: Colorectal cancer with peritoneal carcinomatosis is usually considered incurable. The purpose of this study was to evaluate the efficacy of intraperitoneal chemohyperthermia (IPCH) following cytoreductive surgery in patients with colorectal carcinomatosis. METHODS: Between January 1989 and August 2002, 53 patients (mean age 48.6 years) were treated by IPCH with mitomycin C. IPCH was performed in 34 patients following extensive cytoreductive surgery (more than two peritonectomy procedures). Five patients underwent two operations and one patient three operations. RESULTS: Operative morbidity and mortality rates were 23 and 4 per cent respectively. At a median follow-up of 59.5 months, the overall median survival was 12.8 months. The extent of carcinomatosis, completeness of cytoreduction and histological differentiation were significant prognostic indicators by univariate analysis. The median survival was 32.9 months for patients whose resection was classified as completeness of cancer resection (CCR) 0 (complete cytoreduction), 12.5 months for those whose operation was CCR-1 (diameter of residual nodules 5 mm or less) and 8.1 months for patients who had a CCR-2 resection (diameter of residual nodules more than 5 mm) (P < 0.001). Completeness of cytoreduction was the only significant independent predictor of survival by multivariate analysis. CONCLUSION: IPCH combined with cytoreductive surgery seems to be an effective therapy for carefully selected patients with carcinomatosis from colorectal cancer. This strategy was most effective in patients with carcinomatosis of limited tumour volume or when cytoreductive surgery allowed sufficient downstaging (residual tumour nodules smaller than 5 mm).     

Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Pinto Peritoneal carcinomatosis (PC) had for long been regarded as a terminal disease, characterized by a very poor survival and worthy of being treated with palliative therapy only. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide a promising additional treatment option for patients with peritoneal carcinomatosis, resulting in recently published series enable to obtain long-term survival. In spite of the need for more high quality studies, there is now a consensus among many international experts about the use of this new strategy as gold standard for treating with intent of cure selected patients with PC. We summarized the present status and possible future progress of this treatment modality, in particular outlining its rationale, current practice and general outcomes.     

Surgical treatment of peritoneal carcinomatosis: current treatment modalities

Background

Selected patients with peritoneal surface malignancies (PSM) have been treated effectively by the combination of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Purpose

The purpose of this study is to summarize the treatment outcomes and general considerations regarding definitions and staging systems of current CRS and HIPEC modalities in malignant peritoneal mesothelioma and in secondary peritoneal malignancies such as peritoneal metastasis from appendiceal, colorectal, gastric, and epithelial ovarian cancers.

Conclusion

Disease progression within the peritoneal cavity has in the past been regarded as a terminal event. Accumulating evidence underlines the therapeutic potential and the acceptable morbidity and mortality rates of CRS and HIPEC in selected patients.     

Resectional treatment of peritoneal carcinomatosis followed by intraperitoneal chemotherapy, practical aspects

Surgical resection with curative intent for peritoneal carcinomatosis (PC) requires the excision of all macroscopic disease followed by immediate intraperitoneal chemotherapy to treat the residual microscopic metastases. Hyperthermia improves the effectiveness of this approach. The techniques for excision of PC are rather specific and are not undertaken unless it is possible to remove all visible disease larger than 1 mm. and to assure a post-operative quality of life which is more or less normal. Intraperitoneal hyperthermic chemotherapy techniques must be draconian in order to be effective. If these conditions can be met, peritoneal metastases can be definitively cured in two thirds of colorectal PC and pseudomyxoma peritonei, and in nearly half of mesotheliomas.     

新辅助腹腔内联合全身化疗应用于胃癌腹膜转移的临床价值和实施要点

胃癌腹膜转移可分为两类:①仅腹腔内游离癌细胞(free cancer cell, FCC)阳性(CY1),无肉眼可见的转移病灶(P0);②腹腔内可见肉眼转移病灶(P1).细胞学病理检查是目前诊断 CY1胃癌的金标准.FCC检查多需在手术时迸行,且需一定时间等待结果.     

Effect on immunological response of host by mitomycin C adsorbed into activated carbon particles (MMC-CH) in mice

Mitomycin C adsorbed onto activated carbon particles (MMC-CH) has been administered intraperitoneally for C57BL/6 mice. The weight of the spleen and thymus of the mice given MMC-CH was decreased lesser than those of the mice given mitomycin C aqueous solution (MMC-AQ). The number of peritoneal exudate cells (PEC) in the mice given MMC-AQ was decreased remarkably on 1st day after MMC-AQ administration and recovered within normal range on the 7th day. On the other hand, the number of PEC in the mice given MMC-CH was increased remarkably on the 1st day and then gradually decreased to normal range on the 7th day. Reactivity of spleen cells by Con A was inhibited in the spleen cells from the mice given MMC-AQ more than those from the mice given MMC-CH. Fifth percent lethal dose was 8.0mg/kg in the mice given MMC-AQ, and 18.2mg/kg in the mice given MMC-CH.     

Intraperitoneal treatment with dimethylthioampal (DIMATE) combined with surgical debulking is effective for experimental peritoneal carcinomatosis in a rat model

The goal was to evaluate the efficiency of intraperitoneal administration of dimethylthioampal (DIMATE), a cellular apoptosis inducer, combined, or not, with cytoreductive surgery on rats with peritoneal adenocarcinomatosis. Peritoneal carcinomatosis was induced in rats by intraperitoneal injection of adenocarcinoma cell line DHD/K12/pro B. Intraperitoneal DIMATE was given at 17.3 mg/kg. Rats were randomized into five groups of eight animals, regarding the day of treatment (2 days or 20 days after peritoneal carcinomatosis induction) and the combination with cytoreductive surgery. All rats were killed at 30 days to evaluate carcinomatosis extent (quantitative score) and ascites volume. The quantitative score of carcinomatosis and the ascites volume were significantly reduced in the groups treated with DIMATE at day 2 (P = 0.005 and P < 0.001, respectively) and when DIMATE was used with cytoreductive surgery at day 20 (P = 0.009 and P < 0.001, respectively). Cytoreductive surgery or DIMATE used alone at day 20 had no significant influence. The intraperitoneal DIMATE administration at day 20, when not combined with surgery, had no significant influence on carcinomatosis extent or on ascites volume. Intraperitoneal DIMATE appeared to be an efficient drug in the prevention or treatment of peritoneal carcinomatosis when combined with cytoreductive surgery or when it was given by intraperitoneal route, before the development of macroscopic peritoneal carcinomatosis. It appears to be a promising therapeutic agent to be investigated in a human phase I trial in peritoneal carcinomatosis.     

Surgical treatment of peritoneal carcinomatosis: 1988 Du Pont lecture

Tumour spread onto peritoneal surfaces is frequent in patients who have recurrent gastrointestinal cancer. In this study the author describes (a) a cytoreductive surgical technique of ball-tipped electrocautery dissection, which can rapidly and definitively remove large volumes of intra-abdominal tumour, (b) a procedure for immediate postoperative lavage of the abdominal cavity to remove blood and tissue debris, and (c) a regimen of early and delayed intraperitoneal chemotherapy to destroy small quantities of residual cancer cells on intra-abdominal surfaces. Forty-seven patients underwent cytoreductive surgery to remove large volumes of adenocarcinoma widely disseminated through the abdomen. Most patients had intraperitoneal chemotherapy to destroy small volumes of cancer remaining within the abdomen. In the absence of previous radiotherapy, one patient died and the morbidity was acceptable. In eight patients who received radiotherapy, seven had bowel perforation and one died. Surprisingly, the majority of patients who had cytoreductive surgery plus intraperitoneal chemotherapy had disease-free long-term survival. In patients with peritoneal carcinomatosis, long-term disease-free survival correlated with low tumour aggressiveness, adequate cytoreductive surgery and the use of intraperitoneal chemotherapy.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: initial experience in oaxaca, Mexico

Peritoneal carcinomatosis (PC) has been traditionally considered a terminal disease with median survivals reported in the literature of 6 to 12 months. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are playing an ever increasing role in the treatment of these patients. Excellent results have been achieved in well-selected patients but there is a very steep learning curve when starting a new program. A program for peritoneal surface malignancies in which patients with PC of gastrointestinal or gynecological origin were treated using multimodality therapy with combinations of systemic therapy, cytoreductive surgery (CRS), and HIPEC was initiated in December 2007 at "Hospital Regional de Alta Especialidad de Oaxaca," Mexico. We present the results of our initial experience. From December 2007 to February 2011, 26 patients were treated with CRS and HIPEC. There were 21 female patients. Most common indication (46%) was recurrent ovarian cancer. Mean duration of surgery was 260 minutes. Mean Peritoneal Cancer Index was 9. Twenty-three (88.5%) patients had a complete cytoreduction. Major morbidity and mortality rates were 19.5 and 3.8 per cent, respectively. Mean hospital stay was 8 days. At a mean follow-up of 20 months, median survival has not been reached. Rigorous preoperative workup, strict selection criteria, and mentoring from an experienced cytoreductive surgeon are mandatory and extremely important when starting a center for PC.     

Evolution of locoregional treatment for peritoneal carcinomatosis: single-center experience of 308 procedures of cytoreductive surgery and perioperative intraperitoneal chemotherapy

Background

Peritoneal carcinomatosis imposes an enormous clinical burden to the oncologic community. This study reports the patterns of care of the locoregional approach of cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy as a curative procedure for peritoneal carcinomatosis from the experience of a single tertiary center in Australia.

Methods

We performed a review of clinical records from a prospective database of patients who were treated at the St George Hospital Peritoneal Surface Malignancy Program according to a standard protocol.

Results

A total of 308 CRS were performed in 249 patients with peritoneal surface malignancy; the mean age was 53 years and 55% were women. Over the years, we expanded the age limit for treatment (P = .03), reduced intensive care unit stays (P = .04), reduced amount of blood transfusion (P = .03), treated patients with a higher peritoneal cancer index (P < .001), achieved higher rates of complete cytoreduction (P = .003), increased use of PIC (P < .001), and improved complication rate (P = .02) and mortality rate (P = .01). The median survival of patients treated over the years also improved (P = .001).

Conclusions

We show the maturity of the treatment of peritoneal carcinomatosis with CRS and perioperative intraperitoneal chemotherapy in our institution after an initial learning curve with expansion of the selection criteria, improved perioperative outcomes, improved surgical results, and long-term survival outcomes.