Search

Background: Pancreatic cancer, predominantly characterized by ductal adenocarcinoma (PDAC) accounts for 90% of cases and is the fourth leading cause of cancer-related deaths globally. Its incidence is notably increasing. This poor prognosis is primarily due to late-stage diagnosis (approximately 70% to 80% of patients are diagnosed at an advanced stage), aggressive tumor biology, and low sensitivity to chemotherapy. Consequently, it is crucial to identify and develop a simple, feasible and reproducible blood-based signature (i.e., combination of biomarkers) for early detection of PDAC., Methods: The PANLIPSY study is a multi-center, non-interventional prospective clinical trial designed to achieve early detection of PDAC with high specificity and sensitivity, using a combinatorial approach in blood samples. These samples are collected from patients with resectable, borderline or locally advanced, and metastatic stage PDAC within the framework of the French Biological and Clinical Database for PDAC cohort (BACAP 2). All partners of the BACAP consortium are eligible to participate. The study will include 215 PDAC patients, plus 25 patients with benign pancreatic conditions from the PAncreatic Disease Cohort of TOuLouse (PACTOL) cohort, and 115 healthy controls, totaling 355 individuals. Circulating biomarkers will be collected in a total volume of 50 mL of blood, divided into one CellSave tube (10 mL), two CELL-FREE DNA BCT® preservative tubes (18 mL), and five EDTA tubes (22 mL in total). Samples preparation will adhere to the guidelines of the European Liquid Biopsy Society (ELBS). A unique feature of the study is the AI-based comparison of these complementary liquid biopsy biomarkers. Main end-points: i) to define a liquid biopsy signature that includes the most relevant circulating biomarkers, ii) to validate the multi-marker panel in an independent cohort of healthy controls and patients, with resectable PDAC, and iii) to establish a unique liquid biopsy biobank for PDAC study., Discussion: The PANLIPSY study is a unique prospective non-interventional clinical trial that brings together liquid biopsy experts. The aim is to develop a biological signature for the early detection of PDAC based on AI-assisted detection of circulating biomarkers in blood samples (CTCs, ctDNA, EVs, circulating immune system, circulating cell-free nucleosomes, proteins, and microbiota)., Trial Registration: ClinicalTrials.gov Identifier: NCT06128343 / NCT05824403. Registration dates: June 8,2023 and April 21, 2023., (© 2024. The Author(s).)

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments. In this article, we revisit the conventional serum markers that are enjoying a 'come back' thanks to the development of high-performance scores based on biological, cytological, clinical, or radiological criteria., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Perturbations in circulating metabolites prior to a breast cancer diagnosis are not well characterised. We aimed to gain more detailed knowledge to help understand and prevent the disease., Methods: Baseline plasma samples from 791 breast cancer cases and 791 matched controls from the E3N (EPIC-France) cohort were profiled by nuclear magnetic resonance (NMR)-based untargeted metabolomics. Partial least-squares discriminant analysis (PLS-DA) models were built from NMR profiles to predict disease outcome, and odds ratios and false discovery rate (FDR)-adjusted CIs were calculated for 43 identified metabolites by conditional logistic regression., Results: Breast cancer onset was predicted in the premenopausal subgroup with modest accuracy (AUC 0.61, 95% CI: 0.49-0.73), and 10 metabolites associated with risk, particularly histidine (OR = 1.70 per SD increase, FDR-adjusted CI 1.19-2.41), N-acetyl glycoproteins (OR = 1.53, FDR-adjusted CI 1.18-1.97), glycerol (OR = 1.55, FDR-adjusted CI 1.11-2.18) and ethanol (OR = 1.44, FDR-adjusted CI 1.05-1.97). No predictive capacity or significant metabolites were found overall or for postmenopausal women., Conclusions: Perturbed metabolism compared to controls was observed in premenopausal but not postmenopausal cases. Histidine and NAC have known involvement in inflammatory pathways, and the robust association of ethanol with risk suggests the involvement of alcohol intake.

We aimed to determine whether pretherapeutic assessment of HPV circulating tumoral DNA (HPV ctDNA) by droplet-based digital PCR (ddPCR) could constitute a predictive and prognostic biomarker for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). A mono-institutional prospective biomarker study on 66 patients with p16+/HPV16-positive oropharyngeal squamous cell carcinoma (OPSCC) was conducted in European Georges Pompidou Hospital, Paris, France. Blood samples were collected at the time of diagnosis before any treatment. Optimized digital PCR assays were used to quantify HPV16 ctDNA. Forty-seven (71%) patients showed a positive pretherapeutic HPV ctDNA at time of diagnosis. Interestingly, the quantity of HPV16 ctDNA at baseline, as assessed by ddPCR, was significantly correlated with the T/N/M status or OPSCC stages according to the 2018 new staging criteria for high-risk human papillomavirus (HR HPV) related OPSCC from American Joint Committee on Cancer (AJCC). Moreover, all recurrences and the majority (83%) of death reported events occurred in patients with positive HPV16 ctDNA at baseline. Finally, when posttreatment blood samples were available (n = 6), the kinetic of pretreatment/posttreatment HPV16 ctDNA was clearly associated with treatment success or failure. HPV ctDNA monitoring by ddPCR could constitute a useful and noninvasive dynamic biomarker to select HR HPV-related OPSCC patients eligible for potential treatment de-escalation and to monitor treatment response., (© 2019 UICC.)

Background: Adjuvant treatment for stage II colon cancer remains debated. Finding a tool to select patients at risk for disease recurrence may help the clinical decision. Circulating tumor DNA (ctDNA) has been reported recently as a potential predictive marker for disease recurrence. We thus aim to test its ability to better select stage II colon cancer patients for adjuvant therapy., Methods: This national, phase III trial (NCT00002019-000935-15) conducted in more than 100 centers in France, plans to screen around 2640 patients in order to randomize (2:1; minimization method) 198 ctDNA positive patients. Patients aged 18 to 75 years with ECOG performance status ≤1 with R0 surgical resection of a pT3-T4aN0 colon or high rectum adenocarcinoma will be randomized within 63 days after curative-intent surgery, to adjuvant mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², and 5-FU bolus 400 mg/m2 then 5FU Continuous infusion 2.4 g/m²) every two weeks for 12 cycles or observation. Patients will be followed for maximum 7 years. A gain of 17.5% in 3-yr disease free survival (DFS) is expected (42.5% in the experimental arm vs. 25% in the control arm; HR:0.62; α, 5% [two-sided log-rank test]; 1-β, 80%). Secondary endpoints include 2-yr DFS, overall survival, and toxicity. Recruitement began End of January 2020., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925-1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05-4.69]; 4th quartile: OR = 2.33 [CI = 1.11-4.90]); P trend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07-5.65]; 4th quartile: OR = 2.76 [CI = 1.21-6.30]; P trend = 0.02). When considering receptor-negative tumors, only the 2nd quartile of PFOS was associated with risk (ER-: OR = 15.40 [CI = 1.84-129.19]; PR-: OR = 3.47 [CI = 1.29-9.15]). While there was no association between PFOA and receptor-positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER-: OR = 7.73 [CI = 1.46-41.08]; PR-: OR = 3.44 [CI = 1.30-9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC., (© 2019 UICC.)

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B)., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate the diagnostic value of serum/urinary biomarkers and the operability diagnosis strategy to make management recommendations., Methods: Bibliographical search in French and English languages by consultation of Pubmed, Cochrane and Embase databases., Results: For the diagnosis of a suspicious adnexal mass on imaging: Serum CA125 antigen is recommended (grade A). Serum CAE is not recommended (grade C). The low evidence in literature concerning diagnostic value of CA19.9 does not allow any recommendation concerning its use. Serum Human epididymis protein 4 (HE4) is recommended (grade A). Comparison of data concerning diagnosis value of CA125 and HE4 show similar results for the prediction of malignancy in case of a suspicious adnexal mass on imaging (NP1). Urinary HE4 is not recommended (grade A). The use of circulating tumor DNA is not recommended (grade A). Tumor associated antigen-antibodies (AAbs) is not recommended (grade B). The use of ROMA score (Risk of Ovarian Malignancy Algorithm) is recommended (grade A). The use of Copenhagen index (CPH-I), R-OPS score, OVA500 is not recommended (grade C). For the prediction of resectability of an ovarian cancer with peritoneal carcinomatosis in the context of a primary debulking surgery: It is not recommendend to use serum CA125 (grade A). The low evidence in literature concerning diagnostic value of HE4 does not allow any recommendation concerning its use in this context. No recommendation can be given concerning CA19.9 and CAE. For the prediction of resectability of an ovarian cancer with peritoneal carcinomatosis in the context of surgery after neoadjuvant chemotherapy: the low evidence in literature concerning diagnostic value of serum markers in this context does not allow any recommendation concerning their use in this context. Place of laparoscopy for the prediction of resectability in case of upfront surgery of an ovarian cancer with peritoneal carcinomatosis robust data shows that the use of laparoscopy significantly reduce futile laparotomies (LE1). Laparoscopy is recommended in this context (grade A). Fagotti score is a reproducible tool (LE1) permitting the evaluation of feasibility of an optimal upfront debulking (NP4), its use is recommended (grade C). A Fagotti score≥8 is correlated to a low probability of complete or optimal debulking surgery (LE4) (grade C). There is no sufficient evidence to recommend the use of the modified Fagotti score or any other laparoscopic score (LE4). In case of laparotomy for an ovarian cancer with peritoneal carcinomatosis, the use of Peritoneal Cancer Index (PCI) is recommended (grade C). For the prediction of overall survival, disease free survival and the prediction of postoperative complications, the clinical and statistical of actually available tools do not allow any recommendation., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: To assess the nutritional status and its role in the outcome of patients operated for retroperitoneal liposarcoma (RLS)., Material and Methods: Retrospective study on consecutive patients operated with en bloc compartment resection for primary or local recurrence of RLS between 2016 and 2017. Preoperative nutritional and laboratory assessment comprising serum albumin, serum transthyretin, orosomucoid, and CRP was systematically performed. The following preoperative parameters were analysed: weight, body mass index (BMI), significant weight loss (>5% in one month and/or >10% in 6 months), serum albumin, transthyretin, CRP, orosomucoid. PINI (prognostic inflammatory and nutritional index) was calculated., Results: There were 40 patients operated for RLS: 22 women and 18 men with a median age of 61 years (34-90). Median tumour was 280 mm (80-530). Median preoperative BMI was 24.8 (18-42) and median postoperative BMI was 23 (17.8-44). Twenty-one patients (52.5%) were considered to be malnourished: 3 with biological signs of malnutrition and 18 with weight loss. Eleven (47.6%) in the group of malnourished patients and 4 (26.3%) in the group with satisfactory nutritional status developed postoperative complications (p = 0.042). A PINI score>1 was related to significantly longer hospitalisation time 21.8 days (10-58) in comparison with 14.9 [9-30] in patients with PINI < 1, p = 0.003., Conclusions: The malnourished patients with RLS experienced more postoperative complications and longer hospitalisation. Nutritional status and biological markers contribute to the global management of RLS with improved postoperative behaviour including fewer complications and shorter hospitalisation. A prospective larger study with longer follow-up is necessary to refine these results., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Study Objective: To develop a predictive score for ovarian malignancy to avoid unnecessary adnexectomy in cases of adnexal mass in pediatric and adolescent girls., Design: A population-based retrospective study on girls who underwent surgery for an ovarian mass with normal levels of human chorionic gonadotrophin and alpha fetoprotein between 1996 and 2016., Setting: Rennes University Hospital, Rennes, France., Participants: Eighty-one patients who received surgery for ovarian tumor., Main Outcome Measures: The main outcome measure was the rate of malignant and borderline tumor. A preoperative scoring system was constructed after multivariate analysis., Results: The rate of malignant ovarian tumor was 6/81 (7%), borderline tumor was 7/81 (9%) (ie, outcome measure: 16%), and benign tumor was 84%. In a univariate analysis, the characteristics significantly associated with malignancy were early puberty, palpable mass, size and content of the tumor, and positive epithelial tumor markers (carcinoma antigen 125, carcinoembryonic antigen, and carcinoma antigen 19-9). The predictive malignancy score was on the basis of 2 variables obtained after multivariate analysis: tumor size and cystic content. The score defined 3 groups at risk for malignancy: low risk, middle-risk, and high-risk. The sensitivity for detecting malignancy was 1.3% (95% confidence interval [CI], 0.1-18.4), 26.2% (95% CI, 11.6-49.0), and 53.1% (95% CI, 29.1-75.8), respectively., Conclusion: We set up a simple predictive score of malignancy on the basis of objective criteria to help decision-making on whether or not ovarian-sparing surgery is feasible in case of children and adolescents with ovarian tumors and normal human chorionic gonadotrophin and alpha fetoprotein levels while ensuring oncologic safety., (Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Objectives: To define follow-up modalities after an epithelial ovarian, tubal or primitive peritoneal cancer. To define possibilities of hormone replacement therapy (HRT) and contraceptive use after treatment., Methods: Systematic review of the literature in French and English langage conducted on Pubmed/Medline and the Cochrane Library., Results: After the treatment of an epithelial ovarian, tubal or primitive peritoneal cancer, symptoms evaluation for follow-up is recommended at 3 months, 6 months, 12 months, 18 months, 24 months, and then yearly (Grade B). Only patients with an initial complete surgery (CC0, without any macroscopic signs of disease), and with a good general condition (ECOG 0) should be followed with paraclinic tests, with a serum HE4 or CA125 concentration measurement, from 6 months after the end of treatments (GradeC). Systematic follow-up with CT of the chest, abdomen, and pelvis is not recommended (GradeC). Imaging test is recommended in case of an increased serum concentration of HE4 or CA125 (Grade B). An HRT should be proposed to women younger than 45 after a non-conservative treatment for a high grade serous (GradeC) or for a mucinous (GradeC) ovarian, tubal or primitive peritoneal adenocarcinoma. HRT is not contra-indicated in women older than 45 presenting a climacteric syndrome after the treatment of a high grade serous (Grade B) or of a mucinous (GradeC) ovarian, tubal or primitive peritoneal adenocarcinoma., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: In adults' non-seminomatous germ cell tumours (NS-GCT), alpha-fetoprotein (AFP) decline was identified as an important prognostic factor. We investigated its prognostic value in the French TGM95 study for childhood NS-GCT., Patients and Methods: Three risk groups were defined: low risk (LR: localised and completely resected pS1, AFP<15000 ng/ml), with a 'wait-and-see' strategy; intermediate-risk (IR: localised incompletely resected, AFP<15000 ng/ml) with 3-5 vinblastine-bleomycine-cisplatin courses; high risk (HiR: AFP≥15000 ng/ml and/or metastatic) with 4-6 etoposide-ifosfamide-cisplatin courses. The multivariable prognostic analysis for progression-free survival (PFS) included age (±10 years), primary tumour site (1-testis, 2-ovary, 3-extragonadal), extent of disease (1-pS1, 2-loco-regional dissemination, 3-metastasis) and AFP (±10,000 ng/ml). AFP decline prognostic value was investigated in IR + HiR groups using predicted time to normalisation (TTN), AFP change, and difference between observed and expected (based on AFP half-life) area under the curve (O-E AUC)., Results: From January 1995 to December 2005, 239 patients (median age = 3years, 60 LR, 65 IR, 114 HiR) were included. Main sites were testis (n = 66), ovary (n = 77) and sacrococcygeal (n = 57). Five-year PFS and OS were 85% (95% confidence interval [CI] = 80-89%) and 93% (89-95%), respectively. Age ≥ 10 years (hazard ratio [HR] = 4.6, 95% CI = 2.1-10.1, p = 0.0001) and extragonadal primary (HR = 6.3, 95% CI = 2.0-19.9, p = 0.005) were significant prognostic factors. In AFP decline analysis (n = 151, 17 events), TTN (p = 0.61) and AFP change (p = 0.10) were not prognostic, whereas we showed a significant effect of O-E AUC (HR = 2.1, 95% CI = 1.0-4.2, p = 0.05)., Conclusion: Age ≥ 10 years and extragonadal tumours remain as poor prognostic factors. Contrary to adults, TTN is not reliable in paediatric NS-GCT. The prognostic value of O-E AUC should be investigated in larger studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase., Patients and Methods: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival., Results: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001)., Conclusion: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Research of predictive factors of biochemical recurrence to guide the establishment of an adjuvant treatment after radical prostatectomy for cancer with positive surgical margins., Methodology: A retrospective cohort of 1577 afro-caribbean patients undergoing radical prostatectomy operated between 1st January 2000 and 1st July 2013 was analyzed. In this cohort, 406 patients had positive surgical margin, we excluded 11 patients who received adjuvant therapy (radiotherapy, hormonotherapy, radio-hormonotherapy) and 2 patients for whom histological analysis of the surgical specimen was for a pT4 pathological stage. After a descriptive analysis, we used a Cox model to look for predictors of survival without biochemical recurrence then, depending on the significant variables, we separated our population into six groups: stage pT2 with Gleason score≤3+4 (group 1), stage pT2 with a score of Gleason≥4+3 (group 2), stage pT3a with a Gleason core≤3+4 (group 3), pT3a stage with a score of Gleason≥4+3 (group 4), stage pT3b with a Gleason score≤3+4 (group 5) and stage pT3b Gleason≥with a score of 4+3 (group 6) and compared survival without biochemical recurrence using a log rank test. After radical prostatectomy with surgical margins with an anatomopathological stage≤pT3b, a Gleason score≥4+3 had a pejorative survival without biochemical recurrence than pathological stage (P<0.001)., Results: In multivariate analysis, predictors of survival without biochemical recurrence after radical prostatectomy with positive surgical margins were the majority Gleason postoperative (P<0.0001), pathological stage (P=0.049) adjusted preoperative PSA (P=0.826), with the body mass index (BMI) (P=0.59) and tumor volume (P=0.95)., Conclusion: A high postoperatively Gleason score (≥4+3) has a better predictive value of biochemical recurrence than pathological stage pT2 or pT3 at the patients having been treated for prostate cancer by radical prostatectomy with positive surgical margins., Level of Evidence: 4., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: To develop a risk scoring system (RSS) for predicting recurrence in women with borderline ovarian tumours (BOTs)., Design: Cohort study of women with BOTs., Setting: French multicentre tertiary care centres., Population: A cohort of 360 women with BOTs who received primary surgical treatment between January 2000 and December 2013., Methods: Clinical and pathological factors affecting recurrence in women with BOTs., Main Outcome Measure: The development of a model for the prediction of recurrence in women with BOTs., Results: Overall the recurrence rate was 20.0% (72/360). Recurrence was associated with five variables: age < 45 years; preoperative serum tumour marker CA125 > 150 IU/mL; a serous histological subtype; International Federation of Gynecology and Obstetrics (FIGO) stage other than IA; and ovarian surgery other than bilateral salpingo-oophorectomy (BSO; i.e. cystectomy and unilateral salpingo-oophorectomy). These variables were included in the RSS and assigned scores ranging from 0 to 6. The discrimination of the RSS was 0.82 (95% confidence interval, 95% CI 0.79-0.85). A total score of 8 points corresponded to the optimal threshold of the RSS, with a rate of recurrence of 11.8% (35/297) and 58.7% (37/63) for women at low risk (<8 points) and women at high risk (≥8 points), respectively. The diagnostic accuracy was 85.0%., Conclusions: This study shows that the risk of BOT recurrence can be accurately predicted so that women at high risk can benefit from adapted surgical treatment., Tweetable Abstract: Our RSS permitted women with BOTs at low risk to be distinguished from women with BOTs at high risk of recurrence., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Objectives: To compare the cost effectiveness of adding a pancreatitis-associated protein (PAP) assay to common immunoreactive trypsinogen (IRT) and DNA cystic fibrosis (CF) newborn screening strategies., Methods: Using data collected on 553,167 newborns, PAP cut-offs were calculated based on non-inferiority of the detection rates of classical forms of CF. Cost effectiveness was considered from the third-party payer's perspective using only direct medical costs, and the unit costs of PAP assays were assessed based on a micro-costing study. Robustness of the cost-effectiveness estimates was assessed, taking the secondary outcomes of screening (ie. detecting mild forms and CF carriers) into account., Results: IRT/DNA, IRT/PAP, and IRT/PAP/DNA strategies had similar detection rates for classical forms of CF, but the strategies involving PAP assays detected smaller numbers of mild forms of CF. The IRT/PAP strategy was cost-effective in comparison with either IRT/DNA or IRT/PAP/DNA. IRT/PAP/DNA screening was cost-effective in comparison with IRT/DNA if relatively low value was assumed to be attached to the identification of CF carriers., Conclusions: IRT/PAP strategies could be strictly cost-effective, but dropping DNA would mean the test could not detect CF carriers. IRT/PAP/DNA strategies could be a viable option as they are significantly less costly than IRT/DNA, but still allow CF carrier detection., (© The Author(s) 2015.)

Background: The Glass model developed in 2003 uses prognostic factors for noncastrate metastatic prostate cancer (NCMPC) to define subgroups with good, intermediate, and poor prognosis., Objective: To validate NCMPC risk groups in a more recently diagnosed population and to develop a more sensitive prognostic model., Design, Setting, and Participants: NCMPC patients were randomized to receive continuous androgen deprivation therapy (ADT) with or without docetaxel in the GETUG-15 phase 3 trial. Potential prognostic factors were recorded: age, performance status, Gleason score, hemoglobin (Hb), prostate-specific antigen, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), metastatic localization, body mass index, and pain., Outcome Measurements and Statistical Analysis: These factors were used to develop a new prognostic model using a recursive partitioning method. Before analysis, the data were split into learning and validation sets. The outcome was overall survival (OS)., Results and Limitations: For the 385 patients included, those with good (49%), intermediate (29%), and poor (22%) prognosis had median OS of 69.0, 46.5 and 36.6 mo (p=0.001), and 5-yr survival estimates of 60.7%, 39.4%, and 32.1%, respectively (p=0.001). The most discriminatory variables in univariate analysis were ALP, pain intensity, Hb, LDH, and bone metastases. ALP was the strongest prognostic factor in discriminating patients with good or poor prognosis. In the learning set, median OS in patients with normal and abnormal ALP was 69.1 and 33.6 mo, and 5-yr survival estimates were 62.1% and 23.2%, respectively. The hazard ratio for ALP was 3.11 and 3.13 in the learning and validation sets, respectively. The discriminatory ability of ALP (concordance [C] index 0.64, 95% confidence interval [CI] 0.58-0.71) was superior to that of the Glass risk model (C-index 0.59, 95% CI 0.52-0.66). The study limitations include the limited number of patients and low values for the C-index., Conclusion: A new and simple prognostic model was developed for patients with NCMPC, underlying the role of normal or abnormal ALP., Patient Summary: We analyzed clinical and biological factors that could affect overall survival in noncastrate metastatic prostate cancer. We showed that normal or abnormal alkaline phosphatase at baseline might be useful in predicting survival., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Aggressive histopathologic subtypes of differentiated thyroid cancer (DTC) are fluorodeoxyglucose (FDG)-avid tumors and are at high risk for persistent/recurrent disease. In these patients, fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is performed in cases of suspicion of recurrence based on thyroglobulin (Tg) levels or thyroglobulin antibodies (TgAb). The goals of this study were to evaluate the sensitivity of systematic postoperative FDG-PET/CT and to identify risk factors for abnormal FDG-PET/CT., Methods: Single-center retrospective study of 38 consecutive patients (16 males, 22 females; mean age, 57 years) with aggressive histology DTC, without known persistent disease at the time of postoperative radioactive iodine (RAI) ablation. The most frequent aggressive histologic subtypes were tall cell papillary carcinoma (45%) and poorly differentiated carcinoma (42%)., Results: A total of 86 lesions were found in 20 (53%) patients, distributed in 33 organs. FDG-PET/CT and the postablation whole-body scan (RAI WBS) showed persistent disease in 15 and 12 patients, respectively. FDG-PET/CT was more sensitive than WBS for the detection of individual lesions (69% vs. 59%). Both imaging techniques were complementary with 41% of the lesions detected only by FDG-PET/CT and 31% only by RAI WBS. The only risk factor of abnormal FDG-PET/CT was a stimulated Tg level (Tg/TSH) measured at ablation >10 ng/mL with persistent disease showing FDG uptake in 72% of the patients with a Tg/TSH >10 ng/mL and in 10% of the patients with Tg/TSH ≤10 ng/mL., Conclusion: Postoperative FDG-PET/CT should be performed routinely in patients with aggressive histology DTC.

Background & Aims: Prothrombin induced by vitamin K absence-II (PIVKA-II) is a diagnostic and surveillance marker for HCC mainly used in Asia, and has also been shown to be a predictor of microvascular invasion (MVI), a major prognostic factor in HCC. However, experience with PIVKA-II in Europe remains limited., Methods: In a French cohort, we conducted a case-control study to compare the performances of α-fetoprotein (AFP) and PIVKA-II serum levels for diagnosis of early stage HCC, and we determined the value of PIVKA-II serum and tissue expression in pre-operative detection of MVI. 43 cirrhotic control patients and 85 HCC cases were included, of which 54 (63.5%) had early stage HCC (n=22 very early, n=32 early). PIVKA-II tissue expression was assessed by immunohistochemistry in HCC surgical samples., Results: For the diagnosis of early HCC, PIVKA-II had a sensitivity of 77% and a specificity of 82% at a cut-off of 42 mAU/ml, vs. 61% and 50% for AFP at a cut-off of 5.5 ng/ml (AUC 0.81 vs. 0.58, respectively). A PIVKA-II level >90 mAU/ml was an independent predictor of MVI (HR 3.5; 95% CI 1.08-11.8; p=0.043). High PIVKA-II tissue expression was significantly associated with the presence of MVI (p=0.001). When combining PIVKA-II immunostaining with the PIVKA-II serum level, sensitivity and specificity for the diagnosis of MVI increased from 70% to 87% and 63% to 90%, respectively., Conclusions: PIVKA-II was more efficient than AFP for the diagnosis of early HCC, and could be used as a predictive biomarker of MVI., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Context and Aims: Breast cancer prognosis and predictive biomarkers development would allow sparing some patients from chemotherapy or identifying patients for whom chemotherapy would be indicated. In this context, in 2009, the French National Cancer Institute, a National Health and Science Agency dedicated to cancer, in collaboration with the French society of senology and breast pathology (SFSPM) published a report on the assessment of the prognostic and the predictive clinical validity of tissular biomarkers, uPA/PAI-1, Oncotype DX™ and MammaPrint(®), in breast cancer management. They concluded that only the uPA/PAI-1 prognosis value reached the highest level of evidence (LOE I according to Hayes 1998 classification). In 2012, it was decided to update this report since new data have emerged and because information disparities among clinicians have been identified. This article aims to present the main conclusions together with the levels of evidence associated with those conclusions., Methods: The updating process was based on literature published since 2009 appraisal and on multidisciplinary and independent experts' opinion. The levels of evidence (LOE) used are those of the classification defined by Simon in 2009 (updated Hayes 1998 classification): LOE IA and LOE IB: high level of evidence; LOE IIB and LOE IIC: intermediate level of evidence; LOE IIIC and LOE IV-VD: low level of evidence., Conclusions: Among patients without lymph-node involvement, uPA/PAI-1, invasion process biomarkers, reach the highest level of evidence for 10 years recurrence free survival prognosis (LOE IA according to Simon). The predictive value to anthracyclins chemotherapy remains to be confirmed. Oncotype DX™ and MammaPrint(®) prognosis and predictive value do not reach the LOE I level. This updating' process confirms the 2009 levels of evidence for all the three biomarkers prognosis value. Besides, concerning Oncotype DX™ and MammaPrint(®), new data do not allow to conclude neither to their complementary clinical information to other clinicopathological existing biomarkers nor to a favorable cost-efficiency ratio in therapeutic decision making and this because of the methodological weakness and uncertainty that are identified in the selected studies. Practically, beyond the prognosis and predictive biomarkers validity, the clinical utility of a new biomarker for chemotherapy indication depends on its clinical added information with regard to validated biomarkers (HR, HER2 and Ki67) and to clinicopathological parameters. Since they are the sole validated biomarkers of the invasion process, uPA/PAI-1 could complete clinical information of other clinicopathological factors and consequently could confer an added clinical value. However, data concerning the impact of this information on chemotherapy clinical indication are lacking., (Copyright © 2014. Published by Elsevier Masson SAS.)

Objectives: Study the interest of addition of PSA density (PSAD), to the selection criteria of the French protocol for inclusion patients Afro-Caribbean on active surveillance prostate cancer., Methods: A retrospective analysis of 1505 patients who had, in turn, a radical prostatectomy for cancer between 2000 and 2012, in a single reference center. One hundred and forty-one patients was eligible, at the time of their diagnosis, for active surveillance by the criteria of the French protocol. This population was divided into 2 groups according to the histological analysis of the prostatectomy specimen confirmed indolent cancer or overturned. The median PSAD of each group was calculated to be compared. Secondarily, the most discriminating PSAD was investigated by the method of ROC after constitution tables intrinsic validity in this population. This threshold has secondary conducting a comparative analysis of the underestimation of cancer in terms of aggressiveness and/or extension between patients selected according to the criteria of the French protocol and "on-selected" patients according to these criteria and their PSAD., Results: Of the 141 patients identified for analysis, histological examination of the prostatectomy specimen has to show that 42 patients (29.7 %) were actually more aggressive cancer (20.6 % of Gleason ≥ 7), wider (4.2 % ≥ pT3) or larger and more aggressive (4.9 %) than foreshadowed criteria French protocol. The median PSAD these 42 patients were significantly higher than the median PSAD patients correctly estimated (0.18 vs. 0.14, p-value=0.046). The application of the most discriminating threshold: 0.15 ng/ml/cm(3) in this population allowed to significantly improve the selection of candidates of the 79 "on-selected" patients, six (20.2 %) were actually more aggressive cancer (13.9 % of Gleason ≥ 7), wider (2.5 % ≥ pT3) or larger and more aggressive (3.8 %)., Conclusion: The criteria for the French protocol for active surveillance, applied to the Caribbean population underestimate 29 % of non-latent cancers. Adjuvants criteria that must be inexpensive, sensitive and specific seem necessary in this population. A PSAD<0.15 ng/ml/cm(3) could be one of these criteria., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: To assess clinical practice of intermittent hormone therapy (IHT) among urologists members of the French Association of Urology., Methods: Internet-based observational survey evaluating IHT modalities in prostate cancer using questionnaire sent to 941 urologists., Results: Two hundred and sixty nine urologists participated in the survey (response rate 28.6 %) including 90.3 % prescribing IHT. The main reasons for IHT were improvement of quality of life in 94.2 %, clinical tolerance in 73.7 %, decreased costs and oncological equivalence in 44 %. The indications were localized prostate cancer (low risk 22.6 %, intermediate 19.8 %, high 14 %), locally advanced (59.7 %), metastatic (63.4 %), biochemical recurrence after local treatment (prostatectomy 62.1 %, radiotherapy 73.7 %). A PSA <2 ng/mL was considered as the threshold for androgen deprivation therapy break in 70 % of cases regardless of the IHT indication. The PSA threshold selected for the re-initiation of treatment was 4 ng/mL in 37.9 % and 10 ng/mL in 36.6 % of cases. The cycle of IHT was 6 months in 60 % of cases., Conclusion: This survey provided a snapshot of the practice of IHT in France. Even in the absence of level of evidence 1 trials in the literature, most urologists used IHT in their clinical practice, for many indications, especially in case of biochemical recurrence after local treatment., Level of Proof: 3., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Purpose: Mutated isocitrate dehydrogenases (IDHs) 1 and 2 produce high levels of 2-hydroxyglutarate (2-HG). We investigated whether, in acute myeloid leukemia (AML), serum 2-HG would predict the presence of IDH1/2 mutations at diagnosis and provide a marker of minimal residual disease (MRD)., Patients and Methods: Serum samples from 82 patients at diagnosis of de novo AML (IDH1/2 mutated, n = 53) and 68 patients without AML were analyzed for total 2-HG and its ratio of D to L stereoisomers by mass spectrometry. We measured 2-HG levels and molecular markers of MRD (WT1 and NPM1) in serial samples of 36 patients with IDH1/2 mutations after induction therapy., Results: In patients with AML with IDH1/2 mutations, 2-HG serum levels were significantly higher than in patients with IDH1/2 wild type (P < .001). Area under the receiver operating characteristic curve was 99%. The optimum diagnostic cutoff between IDH1/2 mutated and normal was 2 μmol/L (sensitivity, 100%; specificity, 79%). Quantification of the D/L stereoisomers increased specificity (100%; 95% CI, 83% to 100%) compared with total 2-HG (P = .031). In patients with IDH2 R172 mutations, 2-HG levels were higher relative to those with other IDH1/2 mutations (P < .05). During follow-up, serum 2-HG levels showed strong positive correlation with WT1 and NPM1 (P < .001). After induction therapy, total 2-HG serum levels < 2 μmol/L were associated with better overall (P = .008) and disease-free survival (P = .005)., Conclusion: Serum 2-HG is a predictor of the presence of IDH1/2 mutations and outcome in these patients. Discrimination between D/L stereoisomers improved specificity.

Background: Although dietary fatty acids may influence colorectal carcinogenesis, few studies have examined the association with adenoma risk. We assessed the association between biomarkers of dietary fatty acids or metabolism of fatty acids and the risk of colorectal adenomas in a nested case-control study from the French E3N-EPIC cohort., Methods: Among 13,106 women without prevalent cancer who completed the diet history questionnaire and who provided blood samples, 328 cases of adenomatous polyp were identified during an average of 6.6-year follow-up and randomly matched to 619 polyp-free colonoscopy controls. Erythrocyte membrane phospholipid fatty acid concentrations were determined by gas chromatography. Adjusted ORs for risk of colorectal adenomas with increasing concentrations of fatty acids were calculated using conditional logistic regression, separately for advanced and nonadvanced adenomas., Results: Associations were stronger with advanced than nonadvanced adenomas. High concentration of pentadecanoate plus heptadecanoate acids were inversely associated with the risk of advanced adenomas [highest vs. lowest tertile: OR(T3vsT1) = 0.40 (95% confidence interval (CI) 0.20-0.79); P(trend) = 0.009]. Oleic acid was associated with an increased risk of advanced adenomas [OR(T3vsT1) = 2.32 (1.16-4.64); P(trend) = 0.018]. Some polyunsaturated fatty acids were associated with the risk of advanced adenomas, either positively for di-homo-γ-linolenate [OR(T3vsT1) = 2.07 (1.15-3.72); P(trend) = 0.013], or negatively for eicosapentaenoic and docosahexaenoic acids [OR(T3vsT1) = 0.50 (0.27-0.93); P(trend) = 0.044 and OR(T3vsT1) = 0.50 (0.26-0.96); P(trend) = 0.028, respectively]., Conclusion: A specific erythrocyte membrane phospholipid fatty acid profile, presumably reflecting both a complex dietary pattern and altered fatty acid metabolism, is associated with advanced colorectal adenoma risk., Impact: Adenomas could be a target for primary prevention of colorectal cancer, using interventional strategy based on lipidomic profile of patients., (©2013 AACR)

Background: In patients with low-risk prostate cancer (PCa) the standard therapies carry a risk of overtreatment with potentially preventable side effects whereas restrained therapeutic strategies pose a risk of underestimation of the individual cancer risk. Alternative treatment options include thermal ablation strategies such as high-intensity focused ultrasound (HIFU)., Patients and Methods: 96 patients with low-risk PCa (D'Amico) were treated at 2 HIFU centres with different expertise (n=48, experienced centre Lyon/France; n=48 inexperienced centre Charité Berlin/Germany). Matched pairs were formed and analysed with regard to biochemical disease-free survival (BDFS) as well as postoperative functional parameters (micturition, erectile function). The matched pairs were discriminated as to whether they had received HIFU treatment alone or a combination of HIFU with transurethral resection of the prostate (TURP). Patients of the Lyon group were retrospectively matched through the @-registry database whereas patients of the Berlin group were prospectively evaluated. In the latter patients quality of life assessment was additionally inquired., Results: Postoperative PSA-Nadir was lower in the Berlin group for patients with HIFU only (0.007 vs. Lyon 0.34 ng/ml; p=0.037) and HIFU+TURP (0.25 vs. Lyon 0.42 ng/ml; p=0.003). BDFS was comparable in both groups for HIFU only (Berlin 4.77, Lyon 5.23 years; p=0.741) but patients with combined HIFU+TURP in the Berlin group showed an unfavourable BDFS as compared to the Lyon group (Berlin 3.02, Lyon 4.59 years; p=0.05). In an analysis of Berlin subgroups especially patients who had received HIFU and TURP (n=4) within the same narcosis had an unfavourable BDFS (p=0.009). Median follow-up was 3.36 years for HIFU only and 2.26 years for HIFU+TURP. Neither HIFU only (p=0.117) nor HIFU+TURP (p=0.131) showed an impact on postoperative micturition. Erectile function was negatively influenced (HIFU: p=0.04; HIFU+TURP: p=0.036). There was no measurable change in quality of life after the treatment., Conclusion: The 4-year BDFS after HIFU and HIFU+TURP is comparable to that of the standard therapies. The erectile function is sustainably negatively influenced whereas postoperative micturition and quality of life were not affected by HIFU or HIFU+TURP. These results are strongly limited by the low patient count and the short follow-up period and require validation in prospective multicentre studies with higher number of cases., (© Georg Thieme Verlag KG Stuttgart · New York.)

Granulosa tumors (GT) are rare neoplasms, difficult to diagnose in a preoperative stage. We report a set of seven patients affected by GT admitted in Amiens University Hospital, collated with a review of the literature (n=379). Our aim was to report the clinical and radiological characteristics of GT, in order to improve preoperative diagnosis. The average age of the subjects was 50.8 years old among the bibliographical search, and 37years old for the observations reported in Amiens. The principal circumstances of diagnosis were vaginal bleeding, abdominal pain and infertility. Ultrasound was the most frequently investigation, revealing GT as a large unilateral solid and cystic mass. The computed tomodensitometry (CT) allowed to precise the locoregional extension. Magnetic Resonance Imaging (MRI) appeared to be interesting to clarify lesions, showing GT as a solid mass with a cystic component or as a multicystic mass. Hormonal assays (inhibin B and/or anti-Müllerian hormone) can provide valuable assistance in diagnosis, despite their cost and lack of availability. In view of the clinical and radiological presentation of the reported and literature review cases, we suggest hormonal assays among perimenopausal women presenting with an unusual radiological aspect of an annexial mass., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: With PSA screening, the incidence of prostate cancer (PCa) has increased. Moreover, age and clinical stage have decreased as a result of earlier diagnosis. In this context, the risk of over-treatment including surgery may be important. The objective was to assess the evolution of pathological stages of radical prostatectomy (PR) to 5years apart., Materials and Methods: Nine hundred and six PR were conducted in two French centers (503 in 2005 and 403 in 2010). Preoperative data (age, PSA, clinical stage, number of biopsies, Gleason score) and postoperative (pTNM, Gleason score, prostate weight) were analyzed and compared (Student test and Chi(2))., Results: In 2005 and 2010, the median age was respectively 62.85 and 62.52years (NS). The median PSA was 8.55 and 8.99ng/ml (NS). The number of positive biopsies increased significantly (2.30 to 2.88, P<0.0001), but not the biopsy Gleason score (6.34 to 6.43, NS). Clinical stage was significantly changed with T1c: 77.8 to 73%, T2a: 16.6 to 14.2%, T2b: 4 to 7.8%, T2c: 0 to 1%, T3: 1 to 3.9% T4: 0.4 to 0% in 2005 and 2010, respectively (P<0.0006). The average weight of prostate decreased significantly (55.6g versus 48.8g, P<0.0001), pathological Gleason score was unchanged (6.86 versus 6.80, NS). However, the pathological stage has changed significantly to tumours with higher stages pT2: 66.5 to 51.8% and pT3 33.5 to 48.1% (15%) (P=0.02)., Conclusion: These results have shown that the number of PT performed for pT3 tumours has increased. This increase in patients with high-risk disease has been probably due to change in the selection of patients (surgery for more advanced clinical stages) and allows to consider the radical prostatectomy as a treatment of high risk PCa., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: To assess the frequency, circumstances, and possible medico-legal consequences of the pT0 prostate cancer, defined by the absence of tumor in a radical prostatectomy specimen., Methods: Six centers retrospectively identified all cases of pT0 and selectionned those that occurred without prior hormone therapy or prostate resection. Preoperative data, histological report and clinical and biological outcome were analyzed. The lawsuits' registry in pathology were consulted at insurance companies., Results: Thirty cases of pT0 prostate cancer (0.4%) were reported on 7693 patients. The median age was 63years, PSA 7.4ng/mL. The number of positive preoperative biopsies ranged from one to four for a median tumor length of 1mm (0.3 to 18mm). The biopsy Gleason score was 3+3 for 23 patients, less than 5 for six others and included a contingent of grade 4 in two patients. With a median follow-up of 82months, no clinical or biochemical recurrence was observed. One patient complaint for pT0 prostate was found in the insurances registry., Conclusion: The occurrence of a prostate pT0 called into question all the diagnostic procedures and surgical indication. To avoid a forensic procedure, urologists should inform patients of the possibility of this situation before radical prostatectomy., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aim: To examine the relationships between pre-diagnostic biomarkers and colorectal cancer risk and assess their relevance in predictive models., Methods: A nested case-control study was designed to include all first primary incident colorectal cancer cases diagnosed between inclusion in the SUpplémentation en VItamines et Minéraux AntioXydants cohort in 1994 and the end of follow-up in 2007. Cases (n = 50) were matched with two randomly selected controls (n = 100). Conditional logistic regression models were used to investigate the associations between pre-diagnostic levels of hs-CRP, adiponectin, leptin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1, E-selectin, monocyte chemoattractant protein-1 and colorectal cancer risk. Area under the receiver operating curves (AUC) and relative integrated discrimination improvement (RIDI) statistics were used to assess the discriminatory potential of the models., Results: Plasma adiponectin level was associated with decreased colorectal cancer risk (P for linear trend = 0.03). Quartiles of sVCAM-1 were associated with increased colorectal cancer risk (P for linear trend = 0.02). No association was observed with any of the other biomarkers. Compared to standard models with known risk factors, those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction (P for AUC improvement = 0.01, RIDI = 26.5%)., Conclusion: These results suggest that pre-diagnostic plasma adiponectin and sVCAM-1 levels are associated with decreased and increased colorectal cancer risk, respectively. These relationships must be confirmed in large validation studies.

Background: Mechanistic data suggest that n-3 PUFAs and endothelial function may interact and play a role in carcinogenesis, but epidemiologic evidence is lacking., Objective: Our objective was to investigate whether the prospective association between soluble intercellular adhesion molecule-1 (sICAM-1) and cancer risk is modulated by n-3 PUFA intake., Design: A nested case-control study was designed to include all first-incident cancer cases diagnosed in the SUpplémentation en VItamines et Minéraux AntioXydants cohort between 1994 and 2007, with available dietary data from 24-h records (n = 408). Cases were matched with 1 or 2 randomly selected controls (n = 760). Conditional logistic regression was used to estimate ORs and 95% CIs for the association between prediagnostic plasma concentrations of sICAM-1 and cancer risk, stratified by n-3 PUFA intake. The interactions between sICAM-1 and n-3 PUFA intake were tested., Results: An interaction was observed between sICAM-1 and n-3 PUFA intake, which was consistent across the studied cancer locations (P-interaction = 0.036 for overall, 0.038 for breast, and 0.020 for prostate cancer risk). sICAM-1 concentrations were positively associated with cancer risk among subjects with n-3 PUFA intakes below the median (multivariate OR(Tertile3vsTertile1): 2.8; 95% CI: 1.5, 5.2; P-trend = 0.001), whereas this association was not observed for subjects with n-3 PUFA intakes above the median (OR(Tertile3vsTertile1): 1.3; 95% CI: 0.8, 2.3; P-trend = 0.3)., Conclusion: These findings suggest that n-3 PUFA intake may counteract the procarcinogenic actions of sICAM-1.

Each year, 13,000 newly gynecologic cancers are diagnosed in France. Gynecologic cancers were specifically heterogeneous (localisations, histologic subgroups, age class, etc). This work was delineated for a national call dedicated to gynecologic cancers. This review reports the major needs in terms of scientific research dedicated to gynecologic cancers in the biologic, epidemiology, human and sociologic fields. For example, medico-economic strategies adapted to ethnosociologic context, specifically for cervix cancer, took important part of the epidemiologic research. Impact of gynecologic cancer in terms of symptoms and late effects, quality of life after treatments and fertility needs to be specifically explored. For fundamental research, molecular characterisation, biologic markers, impact of immunology and genetics represent the major part of the field need to be explored. Finally, therapeutic and diagnosis innovations, optimization of treatments strategies and development of predictive models in order to perform individual prediction taking into account several risk factors (clinical and molecular) to offer help in management of gynecologic cancers are required.

Purpose: A new human polyomavirus, Merkel cell polyomavirus (MCV), was identified in 2008 in tumor tissue of patients with Merkel cell carcinoma (MCC), a relatively rare human skin cancer. In this study, we investigated patients with MCC and controls for the presence of antibodies against MCV and their association with clinical characteristics., Patients and Methods: Antibodies against MCV were investigated by enzyme-linked immunosorbent assay in 68 patients with MCC and 82 controls using VP1 virus-like particles produced in insect cells., Results: Antibodies against MCV were detected in all patients with MCC and in 85% of controls. However, high antibody titers (> 10,000) were rarely observed in controls (7.3%) and they were detected in 64.7% of patients with MCC (P < .001) in contrast to the absence of VP1 expression in tumor samples. In addition, the geometric mean titer of anti-MCV in patients with MCC was around 14 times higher than that observed in MCV-positive controls (P < .001) and was not correlated with tumor viral load. High antibody titers were not found to be associated with any subject or tumor characteristics, but better progression-free survival was observed in patients with high antibody titers (hazard ratio, 4.6; 95% CI, 1.7 to 12.2; P = .002)., Conclusion: High titers of MCV antibodies in a much higher proportion of patients with MCC than in controls confirmed the association between MCV infection and MCC. The findings also indicated that a better progression-free survival occurred in patients with high MCV antibody titers and suggested that there are at least two distinct etiologic causes of MCC.

Background: Ecological studies have suggested that vitamin D production through ultraviolet (UV) solar irradiance could reduce breast cancer (BC) risk. Although studies restricted to dietary vitamin D intake have provided inconsistent results, little is known about the relationship between pre- and postmenopausal BC and combined intakes from diet, supplements, and sun exposure., Methods: Cox proportional hazards regression models evaluated the association between vitamin D intakes, mean daily ultraviolet radiation dose (UVRd) at the place of residence and risk of BC among 67,721 women of the French E3N cohort. All analyses were stratified on menopausal status taking into account important confounders including calcium consumption., Results: During 10 years of follow-up, a total of 2,871 BC cases were diagnosed. Dietary and supplemental vitamin D intakes were not associated with BC risk; however, in regions with the highest UVRd, postmenopausal women with high dietary or supplemental vitamin D intake had a significantly lower BC risk as compared with women with the lowest vitamin D intake (HR = 0.68, 95% CI: 0.54-0.85, and HR = 0.57, 95% CI: 0.36-0.90, respectively)., Conclusion: Our results suggest that a threshold of vitamin D exposure from both sun and diet is required to prevent BC and this threshold is particularly difficult to reach in postmenopausal women at northern latitudes where quality of sunlight is too poor for adequate vitamin D production., Impact: Prospective studies should further investigate associations between BC risk, vitamin D status and sunlight exposure., (©2011 AACR.)

Prostate cancer (CaP) has become the most frequent cancer in France and represents the 4th cause of mortality by cancer. Main risk factors include age, family history, black ethnic origin and carcinogenesis results from interaction between environmental and endogen factors. This work aimed to review main data and strategic trends about evolution of prevention and early diagnosis of CaP. Research topics considered as priorities results from the main objective including definition of most efficient medico-economic strategies according to epidemiology, diagnostic and therapeutic modalities and ethno-sociologic particularities, including in the schema presently used (PSA/biopsies): 1) new markers (genetic, serum and urinary), measurable environmental risk factors and potential prevention actions; 2) functional imaging (new techniques including contrast echography, dynamic MRI, spectro-MRI) in order to avoid unnecessary biopsies (60-70% biopsies are negative); 3) optimization of biopsies technique in identifying tumor zones in order to decrease false negative biopsies (about 15% of CaP < 0,5 cm3 but of high grade are missed in the first set of biopsies) and in improving the representativity of the tumor sample biopsied (discordance of about 40% between biopsy data and complete pathological analysis of prostatectomy specimen); 4) development of predictive models in order to perform individual prediction taking into account several risk factors (clinical and molecular) and genes/environment interactions in order to offer rational help in diagnostic and primary prevention procedures.

Objective: To evaluate the contribution of preoperative serum tumor markers to manage borderline ovarian tumors (BOT)., Study Design: Retrospective multicentre study including 317 BOT. Serum tumor marker levels of CA125, CA19-9, CEA, and CA15-3 were determined by radio-immunoassay., Results: Among 181 women with serous BOT and 136 women with mucinous BOT, respectively 55 of 114 (48.2%) and 38 of 91 (41.8%) had at least one abnormal value. Women with preoperative tumor marker assays were more likely to have radical treatment (p=0.0001), full staging (p=0.004), and intra-operative histology (p<0.0001). Women with at least one abnormal tumor marker were more likely to undergo laparotomy (p=0.007), to have intra-operative histology (p=0.04) and complete staging (p=0.0008). In multivariate analysis, first-line laparoscopy was associated with abnormal tumor marker levels (OR=9.63; 95%CI=1.40-66.39; p=0.02), while laparotomy was associated with large tumors, bilateral tumors, and ascitis visible on sonography., Conclusion: Serum tumor marker assays modified both preoperative assessment and surgical management of BOT., (Copyright © 2009. Published by Elsevier Ltd.)

Background: High 25-hydroxyvitamin D [25(OH)D] serum concentrations have been found to be associated with reduced breast cancer risk. However, few studies have further investigated this relationship according to menopausal status, nor have they taken into account factors known to influence vitamin D status, such as dietary and serum calcium, parathyroid hormone, and estradiol serum levels., Methods: We designed a nested case-control study within the French E3N cohort. Cases were women diagnosed with incident breast cancer (n = 636). Controls (n = 1,272) were matched with cases on age, menopausal status at blood collection, age at menopause, and center and year of blood collection. Multivariate logistic regression models were established., Results: We found a decreased risk of breast cancer with increasing 25(OH) vitamin D(3) serum concentrations (odds ratio, 0.73; 95% confidence interval, 0.55-0.96; P trend = 0.02) among women in the highest tertile. We also observed a significant inverse association restricted to women under 53 years of age at blood sampling [odds ratio (T(3) versus T(1)), 0.60; 95% confidence interval, 0.37-0.98; P trend = 0.04]. In premenopausal women, the risk was also decreased, although not significantly., Conclusion: Our findings support a decreased risk of breast cancer associated with high 25(OH) vitamin D(3) serum concentrations, especially in younger women, although we were unable to confirm a direct influence of age or menopausal status., Impact: Randomized intervention trials with vitamin D supplementation are required to confirm its benefits on breast cancer risk, but the maintenance of adequate vitamin D levels should be encouraged by public health policy., ((c)2010 AACR.)

PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

Introduction: Mass screening modalities remained controversial and made necessary large studies. The European Randomized study of Screening for Prostate cancer (ERSPC) was initiated in 1994. Eight countries including France are participating., Methods: ERSPC is a multicentric randomised study and started with the aim to determine whether a 20% reduction in prostate cancer mortality can be achieved with PSA-based screening. Men aged 50-74 and living in the Tarn or Hérault were included. After randomization and exclusion of men who died or had a prostate cancer were invited to participate by giving their consent and had a PSA test. In case of PSA greater than or equal to 3 ng/ml, biopsy was recommended. Included men in both screening and control group were followed through cancer registries. Objective was to present first round results of French participation to ERSPC, to determine factors of participation and to compare detected cancers cases between both groups., Results: Population of men included was 84,781 and were randomized in screening (n=42,590) or control (n=42,191) group. Participation rate was 36.9% in Tarn and 24.3% in Hérault. PSA was greater than or equal to 3 ng/ml in 15,4% of cases (n=1812) and 45.9% of men (n=832) who were biopsied. Age, previous PSA performed within two years prior to invitation, health insurance and department of residence were significantly associated to participation rate. Cumulated incidence with a four years follow-up was 2.48% (n=1053) in screening and 1.99% (n=840) in control group, with a relative risk (RR) of 1.242. Corresponding RR for Tarn and Hérault were 1.37 and 1.20 respectively. Clinical parameters and treatments modalities were similar between both screening and control groups (radical prostatectomy 68% and radiation therapy 20%)., Conclusion: Participation rate at first round was modest. Profile of men who participated compared to men who did not were different. The control group was probably contaminated by PSA testing outside study protocol. Consequences at ERSPC level of this low participation rate on final analysis remain to be determined.

The authors assessed the association between serum phospholipid fatty acids as biomarkers of fatty acid intake and breast cancer risk among women in the E3N Study (1989-2002), the French component of the European Prospective Investigation into Cancer and Nutrition. During an average of 7 years of follow-up, 363 cases of incident invasive breast cancer were documented among 19,934 women who, at baseline (1995-1998), had completed a diet history questionnaire and provided serum samples. Controls were randomly matched to cases by age, menopausal status at blood collection, fasting status at blood collection, date, and collection center. Serum phospholipid fatty acid composition was assessed by gas chromatography. Adjusted odds ratios for risk of breast cancer with increasing levels of fatty acids were calculated using conditional logistic regression. An increased risk of breast cancer was associated with increasing levels of the trans-monounsaturated fatty acids palmitoleic acid and elaidic acid (highest quintile vs. lowest: odds ratio = 1.75, 95% confidence interval: 1.08, 2.83; p-trend = 0.018). cis-Monounsaturated fatty acids were unrelated to breast cancer risk. A high serum level of trans-monounsaturated fatty acids, presumably reflecting a high intake of industrially processed foods, is probably one factor contributing to increased risk of invasive breast cancer in women.

We present the phase I development of an integrative platform for the analysis of clinical, gene expression, protein expression and pre-analytical data. The platform is aimed at providing transparent access and analysis tools to researchers investigating new biomarkers and prognosis factors in the particular field of lymphoma diseases. In this article, we report on the data integration phase. The platform's principal advantage is its completeness as it integrates in a single environment clinical, genomic and proteomic data, allowing for their combined analysis. The architecture consists in a data warehouse including data on patients, clinical trials and array platforms and a DeMilitarized Zone for data exchange. A secure web-based platform allows any collaborative team to request the data warehouse and access basic statistics on integrated data. The presented system is currently in use.

Objective: The measurement of PSA serum levels is central to all early detection programs for prostate cancer. Although individual PSA values were known to fluctuate in the short and long term, the influence of insolation and seasons on PSA had not been addressed to date. To assert the relationship between total and free PSA and meteorological data in 8644 participants (55-70 years) in the French arm of the ERSPC study., Methods: Blood sample was taken at the local laboratory after informed consent and frozen sera were sent for central testing of total and free PSA. PSA measurement was performed within 7 days on the Access 1.0 automat with Hybritech reagents. Monthly meteorological data -- insolation, daily temperatures and rain precipitations -- were obtained from the local branches of the National Meteorology Agency., Results: Total PSA -- but not free PSA -- was correlated with insolation, that is the monthly accrual in hours of sunshine during which the intensity was higher than 120 Watt x m(-2) (r = 0.05 (95%CI: 0.03-0.07; p < 0.0001)) while no relationships were shown between insolation and percent-free PSA (free PSA divided by the total PSA). Interdependence between total PSA and insolation was also apparent with respect to the 3 ng/mL ERSPC cutoff for recommending biopsies (213.1 vs. 206.2 hours, p = 0.004). Such relationship was even more evident in summer when the tested participants more often had a PSA > 3 ng/mL (17.1% vs. 14.3%, p = 0.0006) than in the rest of the year, resulting in 23% more chances of being referred for biopsies (Odds ratio 1.23, 95%CI: 1.10-1.40)., Conclusions: Total PSA was shown to be strongly associated with insolation and seasons while the percent-free PSA was not influenced., (European Association of Urology)

Objective: Genetic diagnosis available since 1993 established germinal mutations of the RET proto-oncogene at codon 634 as the main cause of inherited medullary thyroid carcinoma (MTC). International guidelines established in 1999 recommend that children with such mutations undergo a total thyroidectomy before age 5, with unspecified cervical neck dissection. Since 1993, only 41 of 275 thyroidectomies reported in RET 634 children were performed before age 5 (15%). The aim of this study was to evaluate the implementation of these guidelines in a single centre., Design and Patients: Genetic diagnosis was proposed to the parents of all eight children born after 1992 from two RET 634 families. Total thyroidectomy was proposed before age 5 if the child carried a mutation., Results: Genetic diagnosis was performed in all the children (aged 1-3) and thyroidectomy in the five who carried a mutation (aged 2-5). Cervical lymph node dissection varied from lymphadenectomy of central and lateral compartments in the eldest child to pickings in the youngest. There was no permanent hypoparathyroidism or recurrent nerve paralysis. C-cell hyperplasia, medullary thyroid carcinoma and lymph node metastasis were present in 5/5, 3/5 and 0/5, respectively. Undetectable pentagastrin-stimulated CT levels were achieved and maintained postoperatively in all five children (average follow-up 3.6 years)., Conclusions: MEN 2 guidelines on thyroidectomy can be efficiently and safely implemented by a multidisciplinary team operating in a single centre. The lack of guidelines on cervical neck dissection remains a problem; this could be solved by determining an age under which this procedure would be deemed unnecessary.

Objectives: We performed a retrospective analysis of first relapses after cisplatin-based chemotherapy in patients with advanced germ-cell tumors, in order to better define the appropriate follow-up., Methods: These patients were treated between 1986 and 1998 in two institutions. They were either followed after first-line chemotherapy at the same center or referred for relapse., Results: Ninety-six patients relapsed (17.5% of the total number of patients treated in the same time period). Thirty-five (36.4%) patients had serum tumor marker levels (AFP, hCG and LDH) normal values. Sites of relapse were: abdominal in 47 (49%) patients, thoracic in 17 (17.7%), thoraco-abdominal in 15 (15.6%), and brain in 8 (8.3). Seven (7.3%) patients had elevated markers only, 1 (1%) had isolated supra-clavicular lymph node, 1 (1%) had bone metastasis only. Eighty-two patients (85%) relapsed during the first 18 months of follow-up. All patients with brain metastases at relapse and those who obtained sCR after chemotherapy relapsed within 8 months of follow-up. Sixteen patients underwent resection of growing teratoma., Conclusions: These results allow to recommend extensive follow-up during the first two years after response to first line treatment. It includes marker level determination and whole body CT scan and less intensive work-up there after.

Dermatomyositis and polymyositis patients have an increased risk of developing cancers. We have assessed the diagnostic values of serum tumor markers for the detection of solid cancer in dermatomyositis/polymyositis patients. Serum carcinoembryonic antigen, CA15-3, CA19-9, and CA125 were assayed by immunoradiometric methods in 102 dermatomyositis/polymyositis patients. All the patients had complete physical examination, chest X-ray, echocardiogram, gastrointestinal tract endoscopic explorations, thoracoabdomino-pelvic computed tomography scan, and all women had gynecologic examination and mammogram. Exclusion criteria for study were childhood dermatomyositis, inclusion body myositis, myositis associated with a connective tissue disease, prior history of cancer, and the presence of benign conditions known to elevate serum tumor markers. After a median follow-up of 59 months, 10 (9.8%) patients had a solid cancer. Initial elevation of CA125 was associated with an increased risk of developing solid cancer [P = 0.0001 by Fisher's exact test; odds ratio (OR), 29.7; 95% confidence interval (95% CI), 8.2-106.6]. For CA19-9, there was a trend towards a significant association (P = 00.7; OR, 4.5; 95% CI, 1-18.7, respectively). Diagnostic values of elevated CA125 and CA19-9 at screening increased when the study analysis was restricted to patients who developed a cancer within 1 year (P < 0.0001 and P = 0.018, respectively) or to patients without interstitial lung disease (P = 0.00001; OR, 133; 95% CI, 6.5-2733 and P = 0.027; OR, 9; 95% CI, 1.5-53, respectively). Individual comparisons of the baseline and the second CA125 value showed that three of the eight patients with cancers versus 3 of the 76 patients without, displayed an increase of their CA125 level (P = 0.01 by Fisher's exact test). We conclude that CA125 and CA19-9 assessment could be useful markers of the risk of developing tumors for patients with dermatomyositis and polymyositis and should therefore be included in the search for cancer in dermatomyositis/polymyositis patients, especially for patients without interstitial lung disease.

Purpose: We performed a prospective oncological evaluation of laparoscopic radical prostatectomy in regard to local tumor control and biochemical recurrence., Materials and Methods: Between January 1998 and March 2002, 1,000 consecutive patients with a mean age +/- SD of 63 +/- 6.2 years and clinically localized prostate cancer underwent laparoscopic radical prostatectomy at 1 institution. Preoperative 1997 TNM clinical stage was T1a in 6 patients (0.6%), T1b in 3 (0.3%), T1c in 660 (66.5%), T2a in 304 (30.4%) and T2b in 27 (2.7%). Mean preoperative prostate specific antigen (PSA) +/- SD was 10 +/- 6.1 ng./ml. (range 1.5 to 55). Postoperatively, surgical specimens were assessed and positive surgical margins recorded. Factors that could influence the surgical margins status were evaluated. Irrespective of pathological stage or surgical margin status, no adjuvant treatment was proposed before an increasing PSA. PSA recurrence was defined as PSA greater than 0.1 ng./ml. and was confirmed by a second increase. Recurrence time was defined as the time of the first increase in PSA., Results: Postoperative pathological stage was pT2aN0/Nx in 203 patients (20.3%), pT2bN0/Nx in 572 (57.2%), pT3aN0/Nx in 142 (14.2%), pT3bN0/Nx in 77 (7.7%) and pT1-3 N1 in 6 (0.6%). Positive surgical margin rate was 6.9%, 18.6%, 30% and 34% for pathological stages pT2a, pT2b, pT3a and pT3b, respectively (p <0.001). The main predictors of a positive surgical margin were preoperative PSA (p <0.001), clinical stage (p = 0.001), pathological stage (p <0.001) and Gleason score (p = 0.003). The overall actuarial biochemical progression-free survival rate was 90.5% at 3 years. According to the pathological stage, the progression-free survival rate was 91.8% for pT2aN0/Nx, 88% for pT2bN0/Nx, 77% for pT3aN0/Nx, 44% for pT3bN0/Nx and 50% for pT1-3N1 (p <0.001). Of the patients 94% with negative surgical margins and 80% with positive margins had progression-free survival (p <0.001). Preservation of the neurovascular bundles in patients with localized tumors had no significant effect on the subsequent risk of positive surgical margins or progression-free survival., Conclusions: Based on followup, our evaluation confirms that laparoscopic radical prostatectomy provides satisfactory results in regard to local tumor control and biochemical recurrence.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the French National Federation of Comprehensive Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public University or General Hospitals, and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome of cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in colorectal cancer and their potential role in the management of patients with this malignancy., Methods: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 117 independent reviewers, and to the medical committees of the 20 French Cancer Centers., Results: The main recommendations for the tumor markers in colorectal cancer are: 1) The carcinoembryonic antigen (CEA) is the reference serum marker (standard). 2) All the analyses for a given patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 3) CEA or CA 19-9 should not be used for screening or diagnosis (standard, level of evidence B2). 4) High initial serum concentration of CEA is of bad predictive value (standard, level of evidence C). CEA is an independent prognostic factor of survival in colorectal cancers with lymph node metastases (standard, level of evidence B2). 5) CEA is the most sensitive biological parameter for the screening of hepatic metastases (standard, level of evidence B2). 6) CEA serum concentration before palliative chemotherapy is an independent prognostic factor of survival (standard, level of evidence B2). The combination of CEA assay with imagery techniques and clinical examination can help monitor the response to palliative chemotherapy (standard), in particular in non measurable disease (standard, expert agreement). 7) In 65% of the cases, CEA is the first indicator of relapse (standard, level of evidence B2). CEA is the choice marker for monitoring patients with colorectal cancer (standard, level of evidence B2). 8) A sustained biological follow-up including CEA assay can be used to predict the operability of recurring tumors (standard, level of evidence B2). Nevertheless, no survival advantage has been shown (standard).

Background: In patients with hepatitis C virus (HCV) infection and cirrhosis, long term outcome and the incidence of hepatocellular carcinoma (HCC) are still debated., Design: From January 1987 to January 1997, 416 patients (240 male, median age 57 years) with uncomplicated Child-Pugh A HCV related cirrhosis were followed in two Paris area centres from diagnosis of cirrhosis until death or reference date (1 June 1998). The analysis used a three state disability model generalising the Cox model., Results: Of the 416 patients, 60 developed HCC with a five year rate of 13.4% (95% confidence interval (CI) 9.0-17.8%) and 83 died (including 34 with HCC), with a five year death rate of 15.3% (95% CI 12.6-18.0%). By multivariable analysis, time to HCC relied on age (hazard ratio (HR) 1.05 per year; p=0.0005), male sex (HR 2.13; p=0.01), oesophageal varices (HR 2.36; p= 0.008), decreased platelet count (HR 0.99; p=0. 03), and bilirubin level (HR 1.01; p=0.003), while death after HCC was mainly related to tobacco consumption (HR 1.04; p=0.0006). In contrast, death free of HCC was dependent on age (HR 1.04; p=0.01), oesophageal varices (HR 2.75; p=0.001), low platelet count (HR 0.99; p=0.006), and albumin level (HR 0.90; p=0.0001)., Conclusion: The incidence of HCC and mortality should be higher in these patients than previously stated, and prognostic factors of HCC and death are closely related age and symptoms of portal hypertension.