[Hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis arising from gastric cancer]. / Chimiohyperthermie intrapéritonéale dans le traitement des carcinoses péritonéales d'origine gastrique.

Since 20 years, treatment of peritoneal carcinomatosis has been developed in expert centers. Cytoreductive surgery and perioperative intraperitoneal chemotherapy, especially hyperthermic intraperitoneal chemotherapy, was assessed by many nonrandomised studies for the treatment of peritoneal carcinomatosis arising from gastric cancer. Results described increased survival, especially for the most favourable cases: limited carcinomatosis and complete cytoreductive surgery. A strict selection of the patients is necessary because of the important morbidity of those treatments. Only patients with good general health, able to tolerate a threatening treatment, with possible complete cytoreduction, may benefit from those treatments. Many japanese studies had demonstrated the efficacy of hyperthermic intraperitoneal chemotherapy for the prophylactic treatment of carcinomatosis in advanced-gastric cancers. These results have to be confirmed by european randomised studies.

[Peritoneal mesothelioma: treatment with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy]. / Mésothéliome péritonéal: traitement par l'association chirurgie de cytoréduction et chimiothérapie hyperthermique intrapéritonéale.

UNLABELLED: Diffuse malignant peritoneal mesothelioma is a rare and lethal disease. Locoregional treatments combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) seem to improve prognosis. METHODS: Cytoreductive surgery and HIPEC was performed in 22 patients at the Centre Hospitalier-Lyon Sud between 1989 and 2006. A retrospective analysis of survival was carried out to assess clinical and histological prognostic factors. RESULTS: Nineteen patients with diffuse malignant peritoneal mesothelioma were included (16 epithelial, 3 biphasic and 3 multicystic forms). Sixteen patients presented stage 3 or 4 peritoneal mesothelioma according to the Gilly classification. Optimal cytoreductive surgery was performed for 11 patients (complete macroscopic resection or residual tumor nodules less than 2.5mm). No post-operative deaths occurred but 9 patients (47%) presented grade III or IV post-operative complications. The overall median survival was 36.9 months; completeness of cytoreduction was the only significant prognostic factor. CONCLUSION: Cytoreductive surgery combined with HIPEC may improve the length of survival for patients with diffuse malignant peritoneal mesothelioma; such patients should be treated in specialized centers.

Quantitative prognostic indices in peritoneal carcinomatosis.

Five different descriptions quantitating peritoneal carcinomatosis are available: the Lyon staging system, the Peritoneal Cancer Index (PCI), the Japanese Research Society for Gastric Cancer carcinomatosis staging (JRSGS), the Dutch simplified peritoneal carcinomatosis assessment and the Completeness of Cytoreduction Score (CCR). These five staging systems are described and discussed. Combinations of these to achieve a complete description of peritoneal lesions prior to and following treatment assist in a correct prognostic assessment for these patients and in a selection of treatment options.

Peritoneal carcinomatosis in digestive cancers: cytoreductive surgery combined with intraperitoneal chemohyperthermia. The experience in Centre Hospitalier et Universitaire Lyon Sud (CHLS).

Intraperitoneal chemohyperthermia (IPCH) with Cytoreductive surgery (CS) has been used in Centre Hospitalier et Universitaire Lyon Sud (CHLS) since 1989. Up to 2005, 420 patients were involved in different phase II studies for peritoneal carcinomatosis (PC) from colorectal, gastric or ovarian origin, as well as for pseudomyxoma peritonei and peritoneal mesothelioma. Encouraging results were achieved in case of optimal PC cytoreduction. The CHLS experience, as well as the Dutch randomized trial and the international registration, underline the advantage of such an aggressive combined therapy for selected patients in experienced multidisciplinary centers.

[Therapeutic innovations in the management of peritoneal carcinomatosis from digestive origin: cytoreductive surgery and intraperitoneal chemotherapy]. / Nouveautés thérapeutiques dans la prise en charge des carcinoses péritonéales d'origine digestive: chirurgie de cytoréduction et chimiothérapie intrapéritonéale.

PURPOSE: Peritoneal carcinomatosis and particularly those from digestive origin has long been considered as an automatically terminal disease in abdominal cancer patients. CURRENT KNOWLEDGE AND KEY POINTS: Over the past decade, new locoregional treatments combining cytoreductive surgery, peritonectomy procedures with perioperative intraperitoneal chemotherapy (with or without hyperthermia) have been developed by specialized teams. Because of its high but acceptable mortality and morbidity, this aggressive but comprehensive therapeutic strategy requires accurate and strict patient's selection into multidisciplinary and specialized teams. It may allow prolonged survival and cure for patients with pseudomyxoma peritonei, peritoneal mesothelioma, carcinomatosis from colorectal or gastric cancer. Qualitative and quantitative prognostic indicators are needed to assess a patient's eligibility, including tumor histopathology, assessment of carcinomatosis extent or completeness of cytoreduction which appears to be the most important. PERSPECTIVES: Combination of cytoreductive surgery with perioperative intraperitoneal chemotherapy appears to be an adapted therapeutic approach for patients strictly selected, with peritoneal carcinomatosis. Phase III studies are now needed for the validation and the evaluation of the type of intraperitoneal chemotherapy.

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.

Pattern of failures in gastric cancer patients with lymph node involvement treated by surgery, intraoperative and external beam radiotherapy.

AIMS: High local failure rates in gastric cancer have been reported, up to 67%. To achieve a better local control, we evaluated intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT) in association with surgery for gastric cancer patients with lymph node involvement. We report here the analysis of the patterns of failure for patients involved in this IORT protocol. MATERIAL AND METHODS: Forty-two positive lymph node (N+) gastric cancer patients were operated on (31 total, three subtotal and eight extended gastrectomies) with IORT procedure between 1985 and 1997 (33 males, nine females, mean age 61.3 years). IORT was focused on coeliac area (mean dose 15 Gy), followed by EBRT (46 Gy) in 36 patients. Ten patients were pN1 and 32 were pN2. A concurrent systemic chemotherapy (five Fluoro-Uracil and Cisplatinum) was performed in 14 patients. RESULTS: One patient died postoperatively. Actuarial pN+ 10 year survival rate was 44.8%. The 5 year actuarial local control and disease-free survival rates were 78.8 and 47.5%, respectively. As far as patterns of failure were explored, 5 patients have a local coeliac recurrence (12%) and 12 have distant metastases with no evidence of coeliac recurrence. CONCLUSION: This retrospective analysis suggests a potential effect of IORT and/or EBRT in promoting local control and long-term survival in gastric cancer patients with lymph node involvement.

Cytoreductive surgery and intraperitoneal chemohyperthermia for peritoneal carcinomatosis arising from gastric cancer.

HYPOTHESIS: The most common cause of palliative resection and recurrence in gastric cancer is peritoneal seeding. This study evaluates the efficacy of intraperitoneal chemohyperthermia after cytoreductive surgery in patients with peritoneal carcinomatosis arising from gastric cancer. DESIGN: Prospective clinical trial. SETTING: Surgical department at a university academic hospital. PATIENTS: Forty-nine consecutive patients with peritoneal carcinomatosis treated between January 1, 1989, and February 29, 2000. INTERVENTIONS: All patients underwent intraperitoneal chemohyperthermia with mitomycin C (40-60 mg); 21 patients had previously undergone extensive cytoreductive surgery. MAIN OUTCOME MEASURES: Clinicopathologic factors that affect overall survival rates. RESULTS: With median follow-up of 99 months, overall median survival was 10.3 months. Two factors were significant independent predictors of survival by multivariate analysis: preoperative ascites (P =.04) and completeness of cancer resection (CCR) by cytoreductive surgery (P<.001). Median survival was 21.3 months for patients with CCR-0 (macroscopic complete resection) or CCR-1 (diameter of residual nodules <5 mm) and 6.1 months for patients with CCR-2 (diameter of residual nodules >5 mm) (P<.001). Four patients survived longer than 5 years. CONCLUSIONS: An aggressive management strategy combining intraperitoneal chemohyperthermia with cytoreductive surgery is effective for patients with peritoneal carcinomatosis arising from gastric cancer. In highly selected patients (good general status, resectable primary tumor, resectable peritoneal carcinomatosis), this therapy may result in long-term survival.

Intraoperative radiotherapy and external beam radiation therapy in gastric adenocarcinoma with R0-R1 surgical resection.

INTRODUCTION: The aims of this study were to evaluate the results of intraoperative radiotherapy (IORT) and external beam therapy (EBRT) in the treatment of gastric adenocarcinoma. METHODS: From 1986 to 1999, 87 patients who underwent surgical resection for gastric adenocarcinoma combined with IORT were reviewed. A R0 surgical resection was performed in 82 patients and five underwent R1 resection. The stage was: pT1 in 12, pT2 in 19, pT3 in 44 and pT4 in seven. Thirteen patients were pN1 and 43 were pN2, The IORT dose ranged from 12 to 23 Gy. Patients with pT3 and/or pN tumours underwent EBRT with a standard dose of 44-46 Gy. RESULTS: The post-operative mortality and morbidity rates were 2.3 and 6.8%, respectively. The 5-year survival rate for R0 patients was 60%, for R0-pN0 was 90% and for R0-pN+ patients was 55%. The local failure rate in the 19 pN+ patients was 21%. CONCLUSION: IORT and EBRT combined with surgical resection may provide overall survival, improving the local control after gastrectomy.

Population pharmacokinetics of cisplatin in patients with advanced ovarian cancer during intraperitoneal hyperthermia chemotherapy.

The objective of this study was to determine the pharmacokinetic profile of total platinum administered by hyperthermic peritoneal perfusion (HPP) in 16 patients with ovarian cancer. The patients had a performance status of lIIalpha/b/c on the FIGO scale. They received 60, 80 or 100 mg of cisplatin. The percent of cisplatin remaining in the body after the peritoneum was emptied averaged 65% (41.7-85.4%). The average ratio between peritoneal drug concentrations and plasma concentrations was 73. A Bayesian estimation of individual phamacokinetic parameters was carried out using the non-linear mixed-effect modeling approach as implemented in the NONMEM computer program. A two-compartment model with an additional peritoneal cavity compartment was used to fit the data. Large interindividual variability of the pharmacokinetic parameters occurred The maximum platinum concentration in plasma was reached between 1 and 1.5 hours after the beginning of administration; it ranged from 0.37 to 1.7 microg/ml (1.9 to 8.72 microM). The elimination half-life was 80 hours (48-152 hours and the area under the plasma concentration time curve normalized to a 100 mg cisplatin dose was 79 mg/liter x hours. The simultaneous fit of perfusate and plasma concentrations allowed us to estimate the percent of cisplatin that reached the systemic circulation at about 20%. At time infinity, the urinary cisplatin recovery accounted for only 20% of the administered dose. The results in this study showed that a high proportion of the cisplatin dose was absorbed by target tumor cells. In spite of the advanced disease of patients at the time of HPP, 37.5% of them were still alive three years after HPP (ie., 3-6 years after cancer diagnosis) and 12.5%, 7 years after HPP (i.e., 8 years after cancer diagnosis).

Peritonectomy combined with intraperitoneal chemohyperthermia in abdominal cancer with peritoneal carcinomatosis: phase I-II study.

OBJECTIVE: To evaluate the feasibility and the tolerance of Peritonectomy Procedure (PP) combined with Intraperitoneal Chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis, a phase I-II study has been realised from January 1997 to September 1998. METHODS: Eighteen patients were included for peritoneal carcinomatosis from colorectal cancer (13), ovarian cancer (2), gallbladder cancer (1), gastric cancer (1) and peritoneal mesothelioma (1). Peritoneal carcinomatosis were mainly advanced disease (16 stage 3 and 4, 2 stage 2). All the patients underwent surgical resection of their primary tumor with PP as described by Sugarbaker and IPCH (with Mitomycin C, Cisplatinum or both). IPCH used in this study was a "closed sterile circuit" device with inflow temperatures ranging from 46 to 48 degrees C. IPCH was performed on the same day as PP (8118) or delayed (10/18). RESULTS: Significant down-staging of peritoneal carcinomatosis was achieved for 16 patients. One patient died postoperatively, while the morbidity rate was 6/18 (long postoperative ileus, grade 3 leucopenia and anastomotic leakage). CONCLUSIONS: Combination of PP and IPCH could achieve significant tumoral volume reduction in peritoneal carcinomatosis. This aggressive treatment must be employed selectively because of its morbidity. Larger phase III studies are now needed.

Intraperitoneal chemo-hyperthermia with mitomycin C for gastric cancer patients with peritoneal carcinomatosis.

OBJECTIVE: This study evaluates the tolerance and efficacy of Intraperitoneal Chemo-hyperthermia (IPCH) with Mitomycin C (MMC) associated with surgery, in peritoneal carcinomatosis of gastric origin. BACKGROUND: Most patients with peritoneal carcinomatosis of gastric origin die within 6 months, and IPCH associated with surgery has been reported as a possible new therapeutic approach. METHODS: A prospective non randomized trial was carried out on 42 patients with gastric cancers and peritoneal carcinomatosis. Fourty-three IPCH with MMC were used as complementary treatment after surgery (peritoneal perfusate with a 10 mg/l dose of MMC, inflow temperature 46 to 49 degrees C, use of a closed circuit, duration 90 minutes). Fourteen primary tumors were unresectable ones and 12 patients had large malignant preoperative ascites. RESULTS: Mortality and morbidity rates were 2/42 and 4/42 respectively. For resectable gastric cancers with stage 1 and 2 carcinomatosis (malignant granulations less than 5 mm in diameter), one, two and three year survival rates were 80, 61 and 41% respectively. For unresectable primary tumors and for stage 3 and 4 carcinomatosis (granulations larger than 5 mm in diameter), six and twelve month survival rates were 50% and 10% respectively. CONCLUSIONS: IPCH appears as a safe new therapeutic approach in gastric cancers with peritoneal carcinomatosis with small malignant granulations (stage 1 and 2) and randomized trials are now needed to clearly evaluate its efficacy.

Liver cystadenocarcinoma originating in cystadenoma without mesenchymal stroma. Therapeutic strategy in case of atypical radiological criteria. A case report.

Optimal treatment of cystadenoma if diagnosed consists of complete resection of the tumor. In case of atypical radiological criteria, therapeutic strategy is not well defined. The attitude we adopt is to regularly monitor the lesion. Surgical removal of the tumor is of course indicated facing any significant change on sonography or tomodensiometry.

[Intraperitoneal chemo-hyperthermia with mitomycin C in cancer of the stomach with peritoneal carcinosis]. / Chimiohyperthermie intrapéritonéale avec mitomycine C dans les cancers de l'estomac avec carcinose péritonéale.

We report 42 cases of gastric cancer with peritoneal carcinosis treated with intraperitoneal chemohyperthermia. Intraperitoneal chemohyperthermia was achieved with a closed sterile circuit containing mitomycin C, 10 mg/l producing an input temperature varying from 46 to 49 degrees C for 90 minutes. There were three postoperative deaths: one pulmonary embolism at day 4, one multiple organ failure et day 4, and one septic shock at day 25 due to a colonic fistula. Two patients suffered complications: one opening of the duodenal stump requiring reoperation on day 5, and one prolonged postoperative ileus lasting to day 10. Of the 12 patients with ascites, resorption was achieved in 8. In patients with early-stage peritoneal carcinosis (granulations less than 5 mm) survival at 1, 2 and 3 years was 90%, 61% and 41% respectively. For those with more extensive carcinosis, survival at 1 year was 10%. Five patients survived more than 30 months, three have survived to 34, 43 and 73 months. Intraperitoneal chemohyperthermia is a new treatment for carcinosis of gastric origin. These early results must be assessed further with larger controlled.

Peritoneal mesothelioma treated by cytoreductive surgery and intraperitoneal hyperthermic chemotherapy: results of a prospective study.

BACKGROUND: Peritoneal mesothelioma is a rare disease with few therapeutic options. Recently, the combination of cytoreductive surgery with intraperitoneal hyperthermic chemotherapy (HIPEC) has shown promising results. METHODS: Fifteen patients with peritoneal mesothelioma who were treated by cytoreductive surgery and HIPEC between 1989 and 2004 were identified from a prospective database. HIPEC was performed with cisplatin and mitomycin C for 90 minutes by using the closed-abdomen technique. RESULTS: All patients but one (multicystic) had malignant disease of the following pathologic types: 12 epithelial and 2 biphasic. After surgical resection, 11 patients were considered to have a CC-0 or CC-1 resection (macroscopic complete resection or diameter of residual nodules <2.5 mm). No postoperative death occurred, and six postoperative complications were recorded. All but one patient had resolution of ascites. The overall median survival for the 14 patients with malignant mesothelioma was 35.6 months. The median survival was 37.8 months for patients treated with a CC-0 or CC-1 resection, whereas it was 6.5 months for those treated with a CC-2 or CC-3 resection (diameter of residual nodules >2.5 mm; P < .001). In a univariate analysis, the only other significant prognostic factor was the carcinomatosis extent (P = .02). CONCLUSIONS: A therapeutic strategy combining cytoreductive surgery with HIPEC seems to provide an adequate and efficient locoregional treatment for peritoneal mesothelioma. It is associated with acceptable morbidity when performed by an experienced surgical team. The completeness of cytoreduction is the major determinant of survival.

Intraperitoneal chemohyperthermia with mitomycin C for digestive tract cancer patients with peritoneal carcinomatosis.

BACKGROUND: Most patients with peritoneal carcinomatosis of digestive tract origin die within 6 months. Intraperitoneal chemohyperthermia (IPCH) associated with surgery has been reported as a possible new therapeutic approach. METHODS: A prospective Phase II trial was carried out with 83 patients who had digestive tract cancer and peritoneal carcinomatosis to evaluate the tolerance and efficacy of IPCH with mitomycin C (MMC) associated with surgery. Eighty-six IPCH treatments with MMC were given as complementary therapy after surgery (peritoneal perfusate with a 10 mg/L dose of MMC; inflow temperature, 46-49 degrees C; use of a closed circuit; duration, 90 minutes). Primary tumors were mainly gastric (in 42 cases) or colorectal (in 27 cases). RESULTS: Mortality and morbidity occurred in 3 of 83 cases and 8 of 83 cases, respectively. For patients with resectable tumors, the median survival time was 16 months when carcinomatosis was Stage I and II (malignant granulations less than 5 mm in greatest dimension), whereas it was 6 months when carcinomatosis was Stage III and IV (malignant granulations more than 5 mm in greatest dimension). For patients with resectable gastric cancer and Stage I and II carcinomatosis, 1-, 2-, and 3-year actuarial survival rates were 80%, 61%, and 41%, respectively, whereas the rate was 10% at 1 year for patients with bulky disease (Stage III and IV). CONCLUSIONS: IPCH appears to be a promising new approach to treating patients with digestive tract cancers and peritoneal carcinomatosis with small, malignant granulations (Stage I and II).