Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study.

BACKGROUND: Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM. METHODS: Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS). RESULTS: Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1-5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS. CONCLUSION: E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM.

The RENAPE observational registry: rationale and framework of the rare peritoneal tumors French patient registry.

BACKGROUND: Rare peritoneal cancers represent complex clinical situations requiring a specific and multidisciplinary management. Because of their rarity, lack of awareness and knowledge often leads to diagnostic delays and misdiagnosis. And patients are not systematically referred to expert centers as they should be. Clinicians and researchers also face unique challenges with these rare cancers, because it is hard to conduct adequately powered, controlled trials in such small patient population. This is how an observational patient registry constitutes a key instrument for the development of epidemiological and clinical research in the field of these rare cancers. It is the appropriate tool to pool scarce data for epidemiological research and to assess the impact of diagnostic and therapeutic strategies. We aimed to provide the outlines and the framework of the RENAPE observational registry and share our experience in the establishment of a national patient registry. RESULTS: The RENAPE observational registry has been launched in 2010 thanks to institutional supports. It concerns only patients with a histological diagnosis confirming a peritoneal surface malignancy. A web secured clinical database has been implemented based on data management procedures according to the principles of international recommendations and regulatory statements. A virtual tumor bank is linked in order to the conduct translational studies. Specialized working groups have been established to continuously upgrade and evolve the common clinical and histological data elements following the last classifications and clinical practices. They contribute also to standardize clinical assessment and homogenize practices. CONCLUSIONS: The RENAPE Registry may improve awareness and understanding of the rare peritoneal tumors into the incidence, prevalence, recurrence, survival and mortality rates, as well as treatment practices thereby enabling therapeutic intervention to be evaluated and ultimately optimized. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02834169.

Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study.

PURPOSE: Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network. PATIENTS AND METHODS: From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC). RESULTS: All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033). CONCLUSION: This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.

Frequent intragenic rearrangements of DPYD in colorectal tumours.

Dihydropyrimidine dehydrogenase is a crucial enzyme for the degradation of 5-fluorouracil (5FU). DPYD, which encodes dihydropyrimidine dehydrogenase, is prone to acquire genomic rearrangements because of the presence of an intragenic fragile site FRA1E. We evaluated DPYD copy number variations (CNVs) in a prospective series of 242 stage I-III colorectal tumours (including 87 patients receiving 5FU-based treatment). CNVs in one or more exons of DPYD were detected in 27% of tumours (deletions or amplifications of one or more DPYD exons observed in 17% and 10% of cases, respectively). A significant relationship was observed between the DPYD intragenic rearrangement status and dihydropyrimidine dehydrogenase (DPD) mRNA levels (both at the tumour level). The presence of somatic DPYD aberrations was not associated with known prognostic or predictive biomarkers, except for LOH of chromosome 8p. No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer.

Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study.

BACKGROUND: To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours. METHODS: This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH. RESULTS: The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR. CONCLUSIONS: Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy.

Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the only curative treatment for many peritoneal surface malignancies. The purpose of this study was to evaluate feasibility and safety of CRS combined with HIPEC by laparoscopy for patients with limited peritoneal disease and to compare postoperative outcomes with those for an open procedure. METHODS: Between January 2011 and November 2012, all patients with low-grade pseudomyxoma peritonei (PMP) or multicystic mesothelioma (MM) and limited peritoneal disease (Peritoneal Cancer Index [PCI] less than 10) underwent CRS and HIPEC by a laparoscopic approach. The study cohort was matched with a historical cohort of patients with the same characteristics (completeness of cytoreduction, HIPEC agent, PCI ± 11 and age ± 20 years) treated with CRS and HIPEC by laparotomy. RESULTS: Eight patients (five low-grade PMP and three MM) treated by a laparoscopic approach were compared to eight patients treated by laparotomy. All patients underwent complete cytoreductive surgery with HIPEC, and no conversion to laparotomy was needed. The median surgical length was 210 min (150-300) vs 240 (210-360), with a median hospital stay of 12 days (9-18) vs 19 (13-33). One patient had a postoperative complication (intraperitoneal haematoma treated by radiological drainage) vs four in the laparotomy group. CONCLUSION: Laparoscopic CRS combined with HIPEC is feasible and safe for curative treatment of strictly selected patients with peritoneal surface malignancy and might reduce postoperative complications and length of hospital stay.

Intraperitoneal vascular endothelial growth factor burden in peritoneal surface malignancies treated with curative intent: the first step before intraperitoneal anti-vascular endothelial growth factor treatment?

INTRODUCTION: Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors in solid tumours and plays an important role in ascites development in peritoneal surface malignancies (PSM). The main goal of this study was to determine the evolution and factors influencing intraperitoneal (IP) VEGF burden during cytoreductive surgery (CRS) with curative intent. PATIENTS AND METHODS: Ninety-seven consecutive patients with PSM were treated with CRS at a single centre with curative intent. Patient data were collected prospectively between February 2012 and October 2012. An enzyme-linked immunosorbent assay technique was used to assess VEGF levels in intravenous (IV) systemic blood samples before incision and after abdominal closure, and in IP samples during abdominal cavity exploration, after completion of CRS, after hyperthermic IP chemotherapy, and at 1 and 24h after abdominal closure. RESULTS: The IP VEGF burden increased significantly after CRS, and then decreased progressively (p<0.005). In multivariate analysis, neoadjuvant IV bevacizumab significantly decreased the preoperative IP VEGF burden, tumour load according to Peritoneal Cancer Index value increased significantly the preoperative IP VEGF burden and a low preoperative IP VEGF burden was associated with significantly increased postoperative complications. Neoadjuvant IV bevacizumab is the only factor that influences the preoperative IV VEGF concentration. CONCLUSION: For patients with PSM who were treated with curative intent, the IP VEGF burden increased after CRS, and was reduced prior to surgery by the administration of neoadjuvant IV bevacizumab.

Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients.

INTRODUCTION: Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have demonstrated promising results in the treatment of peritoneal carcinomatosis (PC). The purpose of this study was to assess the impact of this combined procedure on quality of life (QoL). MATERIALS AND METHODS: A prospective single centre study of 216 consecutive patients treated with CRS and HIPEC was conducted using the Gastro-Intestinal Quality of Life Index questionnaire (GIQLI), completed preoperatively and at 1, 3, 6 and 12 months. RESULTS: Questionnaire compliance was 81%, 90%, 89%, 89% and 74% at baseline, 1, 3, 6 and 12 months respectively. QoL was significantly decreased up to 6 months and returned to baseline at 12 months. In multivariate analysis, factors decreasing QoL were origin of PC at 3 months, presence of stoma at 6 months and length of surgery over 270 min and disease recurrence at 12 months. CONCLUSIONS: Despite morbidity associated with CRS and HIPEC, QoL returned to baseline at one year after surgery. This treatment strategy should be considered for the treatment of peritoneal carcinomatosis.

Malignant peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is GLUT1 expression a major prognostic factor? A preliminary study.

PURPOSE: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare primary peritoneal malignancy. Its prognosis has been improved by an aggressive locoregional treatment combining extensive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic factors are currently poorly defined for this disease but are essential if treatment is to be standardized. METHODS: Twenty-eight patients with DMPM, who were considered preoperatively to be candidates for CRS and HIPEC between June 1998 and August 2010 at our institution, were selected for this study. Medical records and histopathological features were retrospectively reviewed and 24 clinical, histological, and immunohistochemical parameters were assessed for their association with overall survival by univariate and multivariate analyses. RESULTS: The following factors were significantly associated with overall survival by univariate analysis: predominant histological growth pattern in the epithelioid areas, nuclear grooves in the epithelioid areas, atypical mitoses, and calretinin and GLUT1 expression by immunohistochemistry in the epithelioid areas. Expression of the facilitative glucose transporter protein GLUT1 in the epithelioid areas was the only factor independently associated with overall survival by multivariate analysis. CONCLUSIONS: GLUT1 expression appears to be an indicator of poor prognosis in DMPM. Standard histological classification of DMPM may not be adequate to select patients for aggressive locoregional treatments, such as CRS and HIPEC. Multicenter validation of the prognostic factors identified in this preliminary study is needed to refine patient selection for potential cure.

Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancers: results of EVOCAPE 2 multicentre prospective study.

AIM: In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC. METHODS: This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival. RESULTS: Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology (p<0.0001). By multivariate analysis, IPCC was not an independent prognostic factor. No relationship between cytology and recurrence was found. CONCLUSION: The presence of IPCC was not an independent prognostic and didn't add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didn't appear to predict development of PC. Peritoneal cytology using conventional staining doesn't seem to be a useful tool for the staging of colorectal and gastric cancers.

Primary peritoneal serous carcinoma treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. A multi-institutional study of 36 patients.

AIM: Primary peritoneal serous carcinoma (PPSC) is a rare condition, histologically identical to ovarian serous carcinoma and often diagnosed at late stage. There is not any standardized treatment for PPSC. A retrospective multicentric study was performed in French speaking centers to evaluate cytoreduction surgery and Hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis from different origins. The manuscript's aim was to study the particular population with PPSC. METHODS: Between September 1997 and July 2007, 36 patients with PPSC from 9 institutions underwent 39 procedures. RESULTS: Mortality and morbidity rates were 5.6% and 20.6% respectively. The overall survival at 1, 3 and 5 years are respectively 93.6, 71.5 and 57.4%. The median overall survival was not reached. By univariate analysis, the only factor that had prognostic value was PCI (p = 0.03). CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with HIPEC may achieve long-term survival in patients with PPSC.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for persistent and recurrent advanced ovarian carcinoma: a multicenter, prospective study of 246 patients.

BACKGROUND: Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed. RESULTS: An optimal cytoreductive surgery was possible in 92.2 % of patients. Mortality and morbidity rates were 0.37 % and 11.6 %, respectively. The overall median survival was 48.9 months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10). CONCLUSIONS: Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.

Intraperitoneal free cancer cells in non-gynaecological adenocarcinomas: a reproducibility study.

OBJECTIVE: In recent years, therapeutic approaches including cytoreductive surgery followed by intraperitoneal chemotherapy have proven effective in peritoneal carcinomatosis of colorectal origin. If cytology is to be used to include patients in aggressive treatment regimens, it is necessary to evaluate its performance, particularly in terms of specificity. The aim of this study was to assess interobserver agreement for the detection of intraperitoneal free cancer cells (IFCCs) in patients with non-gynaecological adenocarcinomas. METHODS: Over a 5-year period, 1223 patients were recruited in 19 French surgery departments. Peritoneal samples were examined in 14 dispersed pathology laboratories. Giemsa-stained slides were sent to a control reader blind to the previous diagnosis. Discordant cases, concordant positive results and a random selection of negative concordant cases were reviewed by a panel of seven cytopathologists. The 'final diagnosis' was that of the consensus meetings but took into account locally-processed slides. RESULTS: Gathering dubious cases with negative results, a 95.6% concordance was achieved between local readers and the control reader. IFCCs were ascertained by the panel in 85 cases (7.0%). Eight of 873 colorectal cancers cases viewed locally were falsely positive (0.9%). Radiotherapy and neoadjuvant therapy had no impact on the false-positive rate as assessed by final validation by the panel (P > 0.05). Samples initially considered as dubious were reclassified as negative by the panel in 24 of 25 cases (96.0%). CONCLUSIONS: The panel consensus allowed reclassification of most dubious/equivocal peritoneal cytology cases, whereas clearcut distinction between benign and malignant cases was correctly achieved in almost all cases.

Pseudomyxoma peritonei: role of 18F-FDG PET in preoperative evaluation of pathological grade and potential for complete cytoreduction.

INTRODUCTION: For pseudomyxoma peritonei (PMP), survival depends on pathological grade and completeness of cytoreductive surgery. The aim of the study was to assess the ability of preoperative 18F-FDG PET to determine these 2 prognosis indicators. MATERIAL AND METHODS: In this prospective single centre study, all patients presenting with PMP were included. They underwent a preoperative 18F-FDG PET with a double radiological evaluation and an explorative laparotomy with the objective of optimal cytoreduction followed by a hyperthermic intra-operative intraperitoneal chemotherapy (HIPEC). Patients with non resectable disease underwent debulking surgery without HIPEC. The Completeness of Cytoreduction was assessed by CC score. RESULTS: Thirty-four patients were included. PET scanning was positive for 19 patients with grade II (hybrid form) or III (Peritoneal Mucinous Carcinomatosis) and for 2 patients with grade I (disseminated peritoneal adenomucinosis), and negative for 3 patients with grade II - III and for 10 patients with grade I. PET scanning was positive for 6 patients with CC score 2 - 3 and for 16 patients with CC score 0, and negative for 2 patients with CC score 2 - 3 and for 10 patients with CC score 0. The 18F-FDG PET interpretation distinguished 2 patients groups (grade I and grade II - III) with a sensitivity of 90% and a specificity of 77%. Moreover, probability of complete cytoreduction when PET was negative was over 80%. CONCLUSION: Preoperative 18F-FDG PET may predict pathological grade and completeness of cytoreduction which are the two main prognostic factors in patients with PMP.

[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.

Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer.

BACKGROUND: In advanced colorectal cancer, K-Ras somatic mutations predict resistance to mAbs targeting epidermal growth factor receptor (EGFR). Relationships between K-Ras mutations and EGFR status have not been examined so far. We analyzed relationships between K-Ras mutations and EGFR tumoral status based on EGFR germinal polymorphisms, gene copy number and expression. METHODS: Eighty colorectal tumors (stage 0-IV) and 39 normal mucosas were analyzed. K-Ras mutations at codons 12 and 13 were detected by a sensitive enrichment double PCR-restriction fragment length polymorphism (RFLP) assay. EGFR gene polymorphisms at positions -216G>T, -191C>A and 497Arg>Lys were analyzed (PCR-RFLP), along with CA repeat polymorphism in intron 1 (fluorescent genotyping) and EGFR gene copy number (PCR amplification). EGFR expression was quantified by Scatchard binding assay. RESULTS: The number of EGFR high-affinity sites, dissociation constant (Kd), gene copy number, intron 1, -216G>T, -191C>A or 497Lys>Arg genotypes was not different between K-Ras-mutated or K-Ras-non-mutated tumors. No relationship was observed between any of the analyzed EGFR genotypes and EGFR expression. EGFR expression was not related to gene copy number. EGFR gene copy number in tumor and normal tissue was not correlated. The mean value of the tumor/normal mucosa gene copy number ratio was 1.16. CONCLUSIONS: Present data clearly show that EGFR status is independent of K-Ras mutations in colorectal tumors.

[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 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.