Long-term results of peritonectomy on the patients with peritoneal carcinomatosis

Peritonectomy was done for 125 patients with peritoneal carcinomatosis (PC): 19-pseudomyxomaperitonei (PMP), 15-appendiceal carcinoma (AC), 20-colorectal cancer, 67-gastric cancer, 2-small bowel cancer and 2-peritoneal mesothelioma. Cytoreduction by the standard techniques was done in 130 patients with PC. Complete cytoreduction (CC-0) was achieved in 85 of 125 (68%) patients, who have undergone peritonectomy, but was performed only in 28 of 130 (21%) by the standard surgical techniques. CC-0 could be done to patients with peritoneal cancer indices (PCI) of less than 14. A Cox model showed that significant prognostic factors are CC-0, and the patients were younger than 66 years old. Accordingly, peritonectomy increased the incidence of CC-0, and may have improved the prognosis of patients with PC. Peritonectomy is recommended for patients with PMP, AC and colorectal cancer. In gastric cancer, it is indicated for patients with PCI less than 14.     

Treatment of peritoneal carcinomatosis from colorectal cancer by cytoreductive surgery and hyperthermic perioperative intraperitoneal chemotherapy.

PURPOSE: Peritoneal carcinomatosis from colorectal cancer is resistant to standard treatments and median survival time for patients ranges between 6 and 8 months. Aggressive cytoreductive surgery with hyperthermic intraperitoneal perioperative chemotherapy may increase median survival. METHOD: Patients undergoing cytoreductive surgery and perioperative hyperthermic chemotherapy (mitomycin C, intraoperatively; 5-fluorouracil early post-operatively) for peritoneal carcinomatosis from colorectal cancer from 1996 to 2003 were evaluated retrospectively. RESULTS: From 1996 to 2003, 18 cytoreductive procedures were performed. The post-operative morbidity rate was 44.4% with no treatment related mortality. The median total operation time was 5 h 28 min (range: 3 h 20 min to 7 h 10 min). The median follow-up was 21 months. The median survival was 15 months. CONCLUSION: Surgical debulking and perioperative intraperitoneal chemotherapy improved survival with acceptable morbidity and mortality. Completeness of the resection was the most important prognostic indicator.     

Comparative analysis of perioperative intraperitoneal chemotherapy regimen in appendiceal and colorectal peritoneal carcinomatosis

Background

Perioperative intraperitoneal chemotherapy (PIC) is delivered by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC). The relative survival benefits of each or both regimens are explored in this large series of patients undergoing cytoreduction at a single institution.

Methods

Patients with a complete (CCR0) or optimal (CCR1) cytoreduction who received intraperitoneal chemotherapy for appendiceal and colorectal peritoneal carcinomatosis were included for analysis. PIC regimens were delivered according to the treatment protocol. Standardized statistical analyses were performed.

Results

Of 262 patients, 98 patients (37%) had colorectal peritoneal carcinomatosis, 108 patients (41%) had low-grade pseudomyxoma peritonei and 56 patients (21%) had appendiceal peritoneal carcinomatosis. For pseudomyxoma peritonei, recurrence-free survival (RFS) did not vary with PIC regimen, 5-year survival was 86% in the HIPEC and EPIC group and 64% in the HIPEC or EPIC group (P = 0.070). For appendiceal peritoneal carcinomatosis, RFS and overall survival (OS) did not vary with PIC regimen. For colorectal peritoneal carcinomatosis, the median RFS was 33 months in the HIPEC and EPIC group, 19 months in the HIPEC alone group and 20 months in the EPIC alone group (P = 0.046). OS did not vary with PIC regimen.

Conclusion

From our experience, without compromising the perioperative morbidity and mortality, PIC consisting of HIPEC and EPIC appears to be associated with potential survival benefits of improved OS in pseudomyxoma peritonei and RFS in colorectal peritoneal carcinomatosis.     

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.     

腹腔热灌注化疗治疗结直肠癌腹膜癌

结直肠癌局域性进展可形成腹膜癌,大约10％的患者初诊即发现腹膜癌,有4％～19％的患者在根治术后随访期发生腹膜癌,25％～35％的复发患者以腹膜癌为唯一表现。全身化疗对此类腹膜癌只是姑息性治疗,中位生存期不足6个月。缩瘤术加腹腔热灌注化疗则可清除宏观和微观癌细胞。荷兰癌症中心的Ⅰ、Ⅱ、Ⅲ期临床试验总结分析表明,接受完全缩瘤术加腹腔热灌注化疗者的中位生存期可达42．9个月,1、3、5年生存率分别是95％、56％和43％,明显高于传统治疗方法,已成为英国、法国、意大利、荷兰、西班牙和澳大利亚等国的标准治疗。     

腹腔热灌注化疗治疗结直肠癌腹膜癌

结直肠癌局域性进展可形成腹膜癌，大约10％的患者初诊即发现腹膜癌，有4％～19％的患者在根治术后随访期发生腹膜癌，25％～35％的复发患者以腹膜癌为唯一表现。全身化疗对此类腹膜癌只是姑息性治疗，中位生存期不足6个月。缩瘤术加腹腔热灌注化疗则可清除宏观和微观癌细胞。荷兰癌症中心的Ⅰ、Ⅱ、Ⅲ期临床试验总结分析表明，接受完全缩瘤术加腹腔热灌注化疗者的中位生存期可达42．9个月，1、3、5年生存率分别是95％、56％和43％，明显高于传统治疗方法，已成为英国、法国、意大利、荷兰、西班牙和澳大利亚等国的标准治疗。     

Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma.

AIMS: The prognosis of patients with peritoneal carcinomatosis from gastrointestinal malignancies is poor. The aim of this study was to analyse the results of multimodality treatment for peritoneal carcinomatosis of appendiceal carcinoma. PATIENTS AND METHODS: From 07/95 to 01/00, 17 patients (13 males, 4 female, median age 58 years) underwent peritonectomy procedures in combination with intraperitoneal hyperthermic chemotherapy. Surgical, pathological and survival data were analysed retrospectively. RESULTS: All patients had undergone previous surgical treatment and one patient had received chemotherapy. In all patients peritonectomy procedures, as described by Sugarbaker, were performed with the aim of achieving a macroscopically complete cytoreduction (range 2-6, median 4 procedures per patient). Following resection, open hyperthermic intraperitoneal chemotherapy with cisplatin was performed. Eleven patients had postoperative complications (predominantly "non-surgical") and two patients died postoperatively. The 4-year survival rate was 75%. Complete cytoreducion had a statistically significant positive influence on long-term survival. CONCLUSIONS: In selected patients (WHO status 0/1, minimal residual disease, no distant metastases, complete cytoreduction), the prognosis for patients with peritoneal carcinomatosis of appendiceal origin can be improved by peritonectomy procedures and hyperthermic intraperitoneal chemotherapy. Postoperative morbidity may be increased due to "non-surgical" complications. Copyright Harcourt Publishers Limited.     

Treatment of peritoneal carcinomatosis from colorectal cancer with cytoreductive surgery and perioperative intraperitoneal chemotherapy: state of the art and future prospects

Peritoneal carcinomatosis (PC), a malignancy limited to the peritoneal surface, has a severe prognosis, but a new therapeutic approach has resulted in cure in some cases. The treatment consists of complete cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy or early postoperative intraperitoneal chemotherapy. At present, only about 25 centers in the United States offer this treatment, and only a few have treated more than 100 cases. This approach may be the most promising new therapy for PC from colorectal cancer but requires collaboration among medical oncologists, colorectal surgeons, and peritoneal surface malignancy treatment centers.     

Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

BACKGROUND:

Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival.

METHODS:

A retrospective, multicenter cohort study was performed in French‐speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies.

RESULTS:

The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N = 523), pseudomyxoma peritonei (N = 301), gastric adenocarcinoma (N = 159), peritoneal mesothelioma (N = 88), and appendiceal adenocarcinoma (N = 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement.

CONCLUSIONS:

A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long‐term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC. Cancer 2010. © 2010 American Cancer Society.     

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour associated with an improved survival

AIMS: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been reported as a treatment option for patients with peritoneal carcinomatosis from colorectal carcinoma. METHODS: Thirty patients with colorectal peritoneal carcinomatosis underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. All appendiceal cancers were excluded. All patients were followed until January 2006 or death. Univariate analysis was performed to evaluate significant prognostic factors for overall survival, defined from the time of surgery. RESULTS: There were 13 male patients. The mean age at the time of surgery was 54years. There was no hospital mortality. The mean duration of hospital stay was 27days. The overall median survival was 29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one patients had complete cytoreduction and their 1- and 2-year survival rates were 85% and 71%, respectively. Univariate analysis demonstrated that patients with non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13, and complete cytoreduction were associated with an improved survival. CONCLUSIONS: This study reported on 30 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. Patients with mucinous tumour had relatively more extensive intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13, and complete cytoreduction were associated with an improved survival.     

腹膜转移癌内科治疗新进展

腹膜转移癌因发现较晚且预后差,目前正成为研究热点。随着细胞减灭术及腹腔热灌注治疗的推广,部分经选择的患者获益。针对不同肿瘤的不同时期,大量的临床研究显示,用药选择、用药时机、用药方法方面均取得进展,尤其是加压腹腔内气溶胶化疗的使用减轻了治疗相关不良反应,并提高了疗效。本文就近年来腹膜转移癌的内科治疗进展进行阐述。     

Cisplatin combined with prostaglandin E1 chemotherapy in rat peritoneal carcinomatosis

Cisplatin intraperitoneal (i.p.) chemotherapy is frequently performed for patients with peritoneal carcinomatosis. However, cisplatin penetrates only the surface of the peritoneal tumor and has serious side effects on renal cells. Thus, cisplatin i.p. chemotherapy had been limited to use for these patients. Prostaglandin E1 (PGE1) has been used for reducing the toxic effects of anticancer drugs because of its cytoprotective effects and has been reported to enhance tumoricidal activity of anticancer drugs. In our study, the effects of PGE1 on the rat peritoneal carcinomatosis model treated with cisplatin i.p. chemotherapy were evaluated. Cisplatin (5 mg/kg) was given in an i.p. administration to 70 tumor-free rats. PGE1 was administered to 35 rats through the tail vein at an infusion rate of 0.1 microg/kg/min (1 ml/hr), and the remaining 35 rats were injected with physiological saline. Forty rats were given an i.p. injection of 1 x 10(7) AH100B cells. Ten days after injection, cisplatin (5 mg/kg) was administered with PGE1 to 20 and the remaining 20 were injected with physiological saline. The accumulation of platinum in the tissues and apoptotic renal cells were analyzed. The maximum concentrations of platinum in the kidneys of PGE1 untreated rats (tumor-free: 10.11 microg/g; tumor-bearing: 11.45 microg/g) did not differ from those of platinum in the kidneys of PGE1-treated rats (tumor-free: 10.28 microg/g; tumor-bearing: 13.28 microg/g). The number of apoptotic renal cells was significantly reduced by PGE1 administration in both tumor-free and tumor-bearing rats. Moreover, PGE1 increased the maximum platinum concentration in tumor masses (5.31 microg/g) of the treated group compared with that in tumor mass of the control group (2.72 microg/g, p = 0.009). These results indicate that PGE1 may increase the anticancer effect of cisplatin by increasing tumor platinum concentration and may reduce the chance of cisplatin-induced renal failure. Intraperitoneal cisplatin chemotherapy combined with PGE1 treatment may have a therapeutic benefit for patients with peritoneal carcinomatosis.     

Significance of peritonectomy for peritonitis carcinomatosis

We analyzed patients who underwent multimodal treatment with peritonectomy as an aggressive treatment for peritonitis carcinomatosis. Peritonectomy was treated in eighteen cases (eleven gastric cancer, seven colon cancer). Out of these eighteen cases, nine were initial operation, six were recurrence after first operation and three were for relief after palliative operation for peritoneal dissemination. Five cases of recurrence included ileus. Of all eighteen patients, ten had received preoperative chemotherapies. Peritonectomy made complete resection possible principle, and the procedure included resection of the primary lesion, subtotal colectomy and peritonectomy. An intestinal stoma was needed in nine cases, consequently. All patients cases underwent continuous hyperthermic peritoneal perfusion (CHPP). Early postoperative peritoneal chemotherapy was given in five cases. By peritonectomy for a first time operation, macroscopically complete resection was possible in six cases. In relief and recurrence cases few tumor cells remained in five cases. Ileus due to peritoneal carcinomatosia was eliminated in all cases, and caloric intake became possible. Fourteen cases had postoperative complication (morbidity 78%), and treatment-related death occurred in three cases (mortality 17%). It became possible to resect even the peritoneal dissemination that was inoperable by conventional surgery, and improvement of QOL was achieved by peritonectomy in cases of carcinomatous peritonitis. However, postoperative care is important since aggression becomes more intense.     

Treatment and prevention of peritoneal carcinomatosis from colorectal cancer

PC from colorectal cancer is a terminal illness for which intravenous chemotherapy is the current standard treatment. However, a recent Dutch randomized study established the efficacy of maximal cytoreductive surgery plus IPCH to achieve statistically significant prolonged survival of these patients. In the near future, improvements of IPCH techniques and progress in selecting patients by radiologic imaging, by molecular biologic studies or further refinement of quantitative prognostic indicators will permit better results. Prospective studies must be conducted in the prevention of carcinomatosis in well-defined high-risk patients.     

Cytoreductive surgery and intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis from colorectal origin

Peritoneal carcinomatosis (PC) is a common form of tumour metastasis stemming from gastrointestinal and colorectal cancers. For a long time, PC has been considered a terminal clinical condition treated only with palliative systemic chemotherapy and associated with very limited results. During the last decade, the treatment of advanced colorectal disease has greatly improved with the emergence of new chemotherapy drugs and biological agents. However, the median survival rates still do not surpass 24 months, even though most of these studies correspond to groups of patients with metastatic disease to the liver and/or lung. The approach and development of cytoreductive radical surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) are based on performing radical surgery of the entire visible tumour within the abdomen/peritoneum, followed immediately by HIPEC, which acts upon microscopic tumour that remains present after surgery and which is responsible for the persistence or relapse of peritoneal disease. Peritonectomy procedures are demanding surgical techniques that permit elimination of the tumour present in the peritoneal lining and any other organs and/or structures that are infiltrated. The synergistic effect of hyperthermia and chemotherapy has been well documented. Hyperthermia increases the cytotoxicity of some cytostatic agents and increases the penetration of certain drugs into the neoplastic cells. The prognosis for patients with PC who undergo combined treatment correlates with the volume of PC (tumour burden) measured as the Peritoneal Cancer Index (PCI) and the ability to perform a CRS, to completely eliminate the gross tumour. At least one phase III study and an important number of phase II studies have shown that CRS + HIPEC provides important survival benefits for patients with PC of colorectal origin. The combination of CRS + HIPEC is indicated for patients with good general health, a low PCI, absence of extra-abdominal metastasis and who can, technically, undergo CRS. The early identification of this group of patients, rapid referral to centres specialised in CRS + HIPEC, together with the correct application of this treatment, are key in achieving the best results.     

Surgery combined with peritonectomy procedures and intraperitoneal chemohyperthermia in abdominal cancers with peritoneal carcinomatosis: a phase II study.

PURPOSE: To evaluate the tolerance of peritonectomy procedures (PP) combined with intraperitoneal chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis (PC), a phase II study was carried out from January 1998 to September 2001. PATIENTS AND METHODS: Fifty-six patients (35 females, mean age 49.3) were included for PC from colorectal cancer (26 patients), ovarian cancer (seven patients), gastric cancer (six patients), peritoneal mesothelioma (five patients), pseudomyxoma peritonei (seven patients), and miscellaneous reasons (five patients). Surgeries were performed mainly on advanced patients (40 patients stages 3 and 4 and 16 patients stages 2 and 1) and were synchronous in 36 patients. All patients underwent surgical resection of their primary tumor with PP and IPCH (with mitomycin C, cisplatinum, or both) with a closed sterile circuit and inflow temperatures ranging from 46 degrees to 48 degrees C. Three patients were included twice. RESULTS: A macroscopic complete resection was performed in 27 cases. The mortality and morbidity rates were one of 56 and 16 of 56, respectively. The 2-year survival rate was 79.0% for patients with macroscopic complete resection and 44.7% for patients without macroscopic complete resection (P =.001). For the patients included twice, two are alive without evidence of disease, 54 and 47 months after the first procedure. CONCLUSION: IPCH and PP are able to achieve unexpected long-term survival in patients with bulky PC. However, one must be careful when selecting the patients for such an aggressive treatment, as morbidity rate remains high even for an experienced team.     

Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy

Background

Although systemic therapies have shown to result in survival benefit in patients with metastatic colorectal cancer (mCRC), outcomes in patients with peritoneal carcinomatosis (PC) are poor. No data are available on outcomes of current chemotherapy schedules plus targeted agents in mCRC patients with PC.

Methods

Previously untreated mCRC patients treated with chemotherapy in the CAIRO study and with chemotherapy and targeted therapy in the CAIRO2 study were included and retrospectively analysed according to presence or absence of PC at randomisation. Patient demographics, primary tumour characteristics, progression-free survival (PFS), overall survival (OS), and occurrence of toxicity were evaluated.

Results

Thirty-four patients with PC were identified in the CAIRO study and 47 patients in the CAIRO2 study.Median OS was decreased for patients with PC compared with patients without PC (CAIRO: 10.4 versus 17.3 months, respectively (p ≤ 0.001); CAIRO2: 15.2 versus 20.7 months, respectively (p < 0.001)).Median number of treatment cycles did not differ between patients with or without PC in both studies. Occurrence of major toxicity was more frequent in patients with PC treated with sequential chemotherapy in the CAIRO study as compared to patients without PC. This was not reflected in reasons to discontinue treatment. In the CAIRO2 study, no differences in major toxicity were observed.

Conclusion

Our data demonstrate decreased efficacy of current standard chemotherapy with and without targeted agents in mCRC patients with PC. This suggests that the poor outcome cannot be explained by undertreatment or increased susceptibility to toxicity, but rather by relative resistance to treatment.