Review of patients with peritoneal malignancy treated with peritonectomy and heated intraperitoneal chemotherapy

BACKGROUND: Peritoneal dissemination of malignancy is usually considered incurable. The purpose of the present study was to evaluate the efficacy of intraperitoneal chemohyperthermia and cytoreductive surgery. METHODS: The present article is a retrospective review of prospectively recorded data in 60 patients who underwent 71 peritonectomy procedures between January 1996 and May 2004. Hospital records, a database and department notes were studied. Conditions treated were pseudomyxoma peritoneii (PMP) and appendiceal cancer (23), mesothelioma (7), colorectal cancer (CRC, 15), ovarian cancer (6) and other forms of malignancy (9). Following cytoreductive surgery, early postoperative intraperitoneal chemotherapy (EPIC) was given in 47 procedures, five with added i.v. mitomycin C. In 34 procedures, heated intraperitoneal chemotherapy (HIPEC) was administered. A policy change was made from intravenous to intraperitoneal mitomycin C chemotherapy in December 2001. Peritoneal cancer index (PCI) was calculated for all procedures. RESULTS: Of the procedures, 23 had PCI < or = 10, 37 had PCI of 11-20, and 11 had PCI > 20. The median operation time was 9 h. Blood units transfused and length of hospital stay have declined. Mortality was 4/60 patients (6.7%), caused by pancytopenia and sepsis. Morbidity occurred in 28/71 procedures. The 3-year survival rate for the HIPEC group was 71% compared with 28% for the no HIPEC group. In the complete excision group, the 3-year survival rate was 52% compared with 13% for the incomplete excision group. The 3-year survival rate for PMP and appendiceal cancer was 74%. The 2-year survival rate for ovarian cancer was 67%, mesothelioma 57%, and CRC 50%, respectively. CONCLUSIONS: Morbidity is significantly associated with duration of surgery and units of blood transfused. Our findings are consistent with the international experience in patients treated with combined peritonectomy and HIPEC.     

Operability and early outcome in 100 consecutive laparotomies for peritoneal malignancy

BACKGROUND: Peritoneal malignancy is common at the terminal stages of many intra-abdominal neoplasms. In selected patients a novel approach of complete macroscopic tumour removal by extensive surgical cytoreduction, combined with intraperitoneal chemotherapy, provides a possibility of cure. Initial experience with 100 consecutive laparotomies is reported. METHODS: Between 1994 and 2002, 218 patients with peritoneal malignancy were referred to a specialized unit. One hundred underwent laparotomy, of whom 85 had a primary appendiceal tumour. Treatment aims were complete macroscopic tumour excision combined with intraoperative intraperitoneal chemotherapy. RESULTS: Sixty-five patients had complete macroscopic tumour excision, 28 palliative major cytoreduction and seven were inoperable. The overall mortality rate was 8 per cent. The most common complications were pulmonary (25 per cent) and wound (14 per cent) infection. At a median follow-up of 30 (range 3-113) months, 44 of 51 patients with primary appendiceal tumours who had complete macroscopic cytoreduction were alive and 36 were disease free. CONCLUSION: Cytoreduction combined with intraperitoneal chemotherapy is an emerging technique with promising results in selected patients with peritoneal malignancy.     

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures

BACKGROUND: Peritoneal dissemination of abdominal malignancy (PSD) has a clinical course marked by bowel obstruction and death. We have been using aggressive cytoreductive surgery with intraperitoneal hyperthermic chemotherapy (IPHC) to treat PSD. The purpose of this article was to review our experience with IPHC. STUDY DESIGN: A prospective database of patients undergoing IPHC has been maintained since 1991. Patients were uniformly evaluated and treated. Demographics, performance status, resection status, primary site, and experience quartile were compared with outcomes. Univariate and multivariate analyses were performed. RESULTS: A total of 460 patients underwent 501 IPHC procedures. Average age was 53.0 years, and 50.4% were women. The 30-day mortality rate was 4.8%, the complication rate was 43%, and median hospital stay was 9 days. Median followup was 55.4 months, median survival was 22.2 months, and 5-year survival rate was 27.8%. Factors correlating with improved survival were performance status (p=0.0001), primary tumor (p=0.0001), resection status (p=0.0001), complications (p=0.002), previous IPHC (p=0.006), and experience quartile (p=0.031). On multivariate analysis, primary tumor site, performance status, resection status, and development of complications (p < 0.001) predicted outcomes. CONCLUSIONS: Our experience demonstrated that preoperative criteria for better outcomes include primary tumor site and performance status. Completeness of resection and development of postoperative complications are also crucial, and outcomes have improved over time. Cytoreductive surgery and IPHC represent substantial improvements in outcomes compared with historic series and best-available systemic therapy. Longterm survival is possible for selected patients who undergo the procedure.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in recurrent epithelial ovarian cancer with peritoneal metastases: a single centre experience

Background

This investigation aims to assess morbidity, mortality and postoperative outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (REOC) with peritoneal metastases (PM).

Methods

Consecutive patients with radiographic evidence of REOC with PM were scheduled for CRS and HIPEC at the Comprehensive Cancer Center, University Hospital Tübingen, Germany. Clinical data were retrospectively analyzed.

Results

In total, 90 patients were analyzed. Complete cytoreduction and HIPEC could be performed in 69 % of patients. When categorizing patients with respect to the completeness of cytoreduction (CC-0/1 vs CC-2/3), there was no difference considering baseline demographic characteristics. Cumulative morbidity was 42 %. Morbidity rates did not statistically differ between CC-0/1 patients with HIPEC and CC-2/3 patients without HIPEC. No surgery-related and 90-day postoperative mortality was observed. In CC-0/1 patients, median overall survival was 35 months as opposed to 14 months in CC-2/3 patients. There was no difference in survival with respect to the peritoneal carcinomatosis index (PCI) as long as complete cytoreduction could be achieved.

Conclusions

CRS and HIPEC can be performed with acceptable morbidity and low mortality in specialized centres. Our data do not suggest that HIPEC necessarily increases the risk of postoperative adverse events.     

Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy.

OBJECTIVE: A treatment plan to be used in patients with peritoneal carcinomatosis was devised and tested as a Phase II study. BACKGROUND: Peritoneal carcinomatosis from appendical or colorectal cancer has been regarded as a fatal clinical entity. Treatment protocols have not been reported previously. METHODS: The authors used cytoreductive surgery and intraperitoneal chemotherapy to treat 181 consecutive patients with peritoneal carcinomatosis. There were 51 patients with colorectal cancer and 130 patients with appendiceal cancer. Mean follow-up is 24 months, with a range of 0 to 149 months. RESULTS: Clinical features that showed prognostic significance included appendiceal versus colorectal primary tumors (p = 0.0001), grade 1 versus grades 2 and 3 histopathology (p = 0.0003), complete versus incomplete cytoreductions (p = 0.0001), lymph node-negative versus lymph node-positive primary tumors (p = 0.0001), and volume of peritoneal carcinomatosis present preoperatively for colon cancer (p = 0.0006). Features with no statistical prognostic significance included preoperative tumor volume for appendiceal cancer, age, sex, number of cycles of chemotherapy, operative time, complications, blood loss, and institution providing treatment. From these prognostic features, four prognostic groups were identified, and 3-year survival was estimated by the product-limit survival method. Group I patients (n = 76) were those with grade 1 histology, no lymph node metastases, and complete cytoreductions (survival at 3 years = 99%). Group II patients (n = 23) were those with grade 2 or 3 histology, no lymph node metastases, and complete cytoreductions (65%). Group III patients (n = 24) had any histology, lymph node metastases, and complete cytoreductions (66%). Group IV patients (n = 58) had incomplete cytoreductions (20%).     

Treatment of peritoneal surface malignancy by peritonectomy and intraperitoneal chemotherapy: a novel therapy with curative potential!

Peritoneal carcinomatosis has always been regarded to have a poor prognosis. Surgery is usually limited to palliation of bowel obstruction by performing an intestinal bypass or ostomy. This severe disease has been considered as equal to distant metastasis and intravenous (i.v.) chemotherapy is commonly used in order to achieve a regression of the tumour. However, resistance to cytotoxic drugs, a poor vascular supply and high osmotic pressure might prevent the efficient uptake of i.v. chemotherapeutic agents into tumour tissues. A new concept in dissemination of gastrointestinal cancer and gynecologic cancer now require that peritoneal implants are regarded in a different way. In many patients peritoneal dissemination is a locoregional spread of disease with no manifestation of systemic disease. A locoregional therapeutic approach combining cytoreductive surgery with hyperthermic intraperitoneal intraoperative chemotherapy evolved. This new treatment option seems to be an effective therapeutic approach in carefully selected patients, and offers a chance for cure or palliation in this condition with few alternative treatment options.     

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.     

Laparoscopic cytoreductive surgery and early postoperative intraperitoneal chemotherapy for patients with colorectal cancer peritoneal carcinomatosis: initial results from a single center

Background

In recent decades, a combination of cytoreductive surgery and intraperitoneal chemotherapy has yielded improvements in the survival of patients with peritoneal carcinomatosis. Laparoscopic cytoreductive surgery and intraperitoneal chemotherapy comprise a challenging and rarely reported surgical procedure.

Methods

Between November 2004 and February 2010, 29 patients underwent cytoreductive surgery and early postoperative intraperitoneal chemotherapy for peritoneal carcinomatosis secondary to colorectal cancer. Of the 29 patients, 15 underwent laparoscopic surgery and 14 underwent open surgery.

Results

The patient characteristics did not differ significantly between the two groups. Synchronous peritoneal carcinomatosis with a primary tumor was more common in the laparoscopic group, and the Gilly stage of peritoneal carcinomatosis was found more frequently in the open group. Complication rate and hospital stay were less in the laparoscopic group. However, the outcomes for the patients undergoing the combined treatment were similar between the two groups with respect to completeness of cytoreduction, operation morbidity, and overall survival. The laparoscopic group had a cytoreduction completeness of 86.7 % and an operative morbidity of 13.3 %. Operative mortality occurred for one patient after open surgery.

Conclusions

Laparoscopic cytoreductive surgery and early postoperative intraperitoneal chemotherapy can be performed safely for selected patients with peritoneal carcinomatosis from colorectal cancer to a limited extent. Further studies with longer follow-up periods and larger numbers of patients are warranted to confirm the study findings.     

Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

OBJECTIVE: To evaluate the survival of patients with pseudomyxoma peritonei (PMP) treated by cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), and to identify factors with prognostic value. SUMMARY BACKGROUND DATA: PMP is a clinical syndrome characterized by progressive intraperitoneal accumulation of mucous and mucinous implants, usually derived from a ruptured mucinous neoplasm of the appendix. Survival is dominated by pathology. METHODS: A total of 103 patients (34 men and 69 women) treated at The Netherlands Cancer Institute between 1996 and 2004 were identified. Survival was calculated from date of initial treatment and corrected for a second procedure. PMP was pathologically categorized into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and an intermediate subtype (PMCA-I). Clinical and pathologic factors were analyzed to identify their prognostic value for survival. RESULTS: Median follow-up was 51.5 months (range, 0.1-99.5 months). Recurrence developed in 44%. A second procedure for recurrence was performed in 11 patients. The median disease-free interval was 25.6 months (95% confidence interval [CI], 14.8-43.6 months). The 3-year and 5-year disease-free survival probability was 43.6% (95% CI, 34.4%-55.2%) and 37.4% (95% CI, 28.2%-49.5%), respectively. The disease-specific 3-year and 5-year survival probability was 70.9% (95% CI, 62.0%-81.2%) and 59.5% (95% CI 48.7%-72.5%), respectively. Factors associated with survival were pathological subtype, completeness of cytoreduction, and degree and location of tumor load (P < 0.05). The main prognostic factor, independently associated with survival, was the pathologic subtype (P < 0.01). CONCLUSION: Cytoreductive surgery in combination with intraoperative HIPEC is a feasible treatment strategy for PMP in terms of survival. The pathologic subtype remains the dominant factor in survival. Patients should be centralized to improve survival by a combination of surgical experience and adequate patient selection.     

Predicting the survival of patients with peritoneal carcinomatosis of colorectal origin treated by aggressive cytoreduction and hyperthermic intraperitoneal chemotherapy

BACKGROUND: Peritoneal carcinomatosis in the absence of distant metastasis occurs in approximately 8 per cent of patients with colorectal cancer. Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a new treatment option. Patient selection is crucial to outcome. METHODS: Cytoreduction followed by HIPEC was performed in 102 patients with peritoneal carcinomatosis. The following factors were studied for association with survival: perforation and obstruction of the primary lesion, location of the primary lesion, obstruction associated with carcinomatosis, presentation, tumour differentiation and histological type. Extent of disease and completeness of cytoreduction were also studied. Hazard ratios (HRs) were used to study these factors. RESULTS: Location of the primary tumour in rectum (HR 3.14 (95 per cent confidence interval (c.i.) 1.11 to 8.91); P = 0.069), poor differentiation (HR 1.73 (95 per cent c.i. 1.04 to 2.88); P = 0.031) and signet cell histological type (HR 2.24 (95 per cent c.i. 1.21 to 4.16); P = 0.008) were associated with shorter survival. Important factors predicting survival were the number of affected regions (HR 1.38 (95 per cent c.i. 1.20 to 1.59); P < 0.001), the simplified peritoneal cancer score (HR 1.19 (95 per cent c.i. 1.12 to 1.26); P < 0.001) and completeness of cytoreduction (HR 8.54 (95 per cent c.i. 4.01 to 18.18); P < 0.001). No other factor correlated with survival. CONCLUSION: The survival of patients with peritoneal carcinomatosis of colorectal origin is dominated by the extent of disease and the amount of residual tumour after cytoreduction.     

肿瘤细胞减灭术联合腹腔内热灌注化疗术后谵妄发生的危险因素分析

目的筛选肿瘤细胞减灭术联合腹腔内热灌注化疗术后谵妄发生的危险因素。方法全麻下行肿瘤细胞减灭术联合腹腔内热灌注化疗患者150例,年龄18~75岁,性别不限,美国麻醉医师协会(ASA)分级Ⅰ~Ⅲ级,体重40~70 kg。根据术后72小时内是否发生谵妄分为谵妄组和非谵妄组。记录患者性别、年龄、体重、ASA分级、术前空腹血糖和糖化血红蛋白;既往史包括肿瘤切除术史、化疗和放疗史;合并症包括抑郁症、高血压、冠状动脉粥样硬化性心脏病、慢性主观性头晕、慢性阻塞性肺疾病、腔隙性脑梗死和慢性肾功能衰竭;手术相关因素包括腹腔内热灌注时间、手术时间和术后机械通气时间;术后镇痛补救情况。将组间比较差异有统计学意义的因素进行多因素Logistic回归分析,筛选术后谵妄发生的危险因素。结果 139例患者中42例发生术后谵妄,发生率为30.2%。Logistic回归分析结果显示,年龄≥65岁、术前抑郁、长时间腹腔内热灌注化疗和术后ICU长时间机械通气是肿瘤细胞减灭术联合腹腔内热灌注化疗术后谵妄的独立危险因素。结论年龄≥65岁、术前抑郁、长时间腹腔内热灌注化疗和术后ICU长时间机械通气是肿瘤细胞减灭术联合腹腔内热灌注化疗术后谵妄的独立危险因素。     

Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for disseminated peritoneal cancer of gastrointestinal origin

No standard effective treatment exists for peritoneal carcinomatosis of gastrointestinal origin. The pharmacokinetic advantage of intraperitoneal chemotherapy and the synergy of heat and certain anticancer agents have prompted researchers to investigate intraperitoneal hyperthermic chemotherapy in treating disseminated peritoneal cancers. We have conducted a large Phase II trial to determine the safety and efficacy of aggressive cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC) in treating peritoneal carcinomatosis of gastrointestinal origin. Patients with disseminated peritoneal carcinomatosis of gastrointestinal origin with or without malignant ascites were eligible. After aggressive surgical debulking, patients were administered a 2-hour heated (40.5 degrees C) intraperitoneal perfusion with mitomycin C. The major response variable monitored was overall survival. Patients were assessed for toxicity after IPHC administration using the National Cancer Institute Common Toxicity Criteria. Eighty-four patients with peritoneal carcinomatosis of gastrointestinal origin were evaluated for survival and toxicity (colon, n = 38; appendix, n = 22; stomach, n = 19; other gastrointestinal, n = 5). Thirty-nine (46%) patients had malignant ascites at the time of therapy. The operative mortality (30-day) was 6 per cent. Hematologic toxicity was the most common toxicity but was of mild to moderate severity (7 and 4% of patients had grade 3/4 white blood cell or platelet toxicity, respectively). The overall median survival was 14.3 months. The median survival of patients with peritoneal carcinomatosis of appendiceal, colorectal, and gastric origins were 31.1+, 14.6, and 10.1 months, respectively. Significant differences in median survival were seen in patients without and with malignant ascites (27.7 vs 7.6 months; P = 0.0004) and R0/R1 (complete gross tumor resection) versus R2 (gross residual tumor) surgical resection status (28.5+ vs 10.8 months, P = 0.0002). These data suggest that aggressive cytoreductive surgery with IPHC using mitomycin C is safe and effective in treating peritoneal carcinomatosis of gastrointestinal origin. Additional studies and broader applications of this treatment are encouraged.     

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.     

Hyperthermic intraperitoneal chemotherapy and cytoreductive surgery for peritoneal carcinomatosis of colorectal origin: a novel treatment strategy with promising results in selected patients

Peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer with few options for treatment. Recent reports, including a single randomized trial, suggest that localized peritoneal carcinomatosis, in the absence of other metastases, could be considered regional metastatic disease analogous to liver metastases, and thus amenable to locoregional therapy. Optimal treatment involves complete tumour removal by complex surgical techniques, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment strategy has significant morbidity and mortality risks and careful selection is essential to avoid futile procedures. The best results are achieved in patients with limited disease who have complete macroscopic tumour removal, when the primary and peritoneal metastases are removed synchronously, and when the primary tumour is a cancer of the appendix. Improvements in cross-sectional imaging and increasing utilization of laparoscopy in colorectal cancer surgery may help in detecting suitable cases for these techniques. Selected patients with localized disease have been shown to have good outcomes with prolonged survival and perhaps a possibility of cure.