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Gestational trophoblastic diseases derived from the chorionic-type intermediate trophoblast include benign placental site nodule (PSN) and malignant epithelioid trophoblastic tumor (ETT). Among PSN, the WHO classification introduced a new entity named atypical placental site nodule (APSN), corresponding to an ETT precursor, for which the diagnostic criteria remain unclear, leading to a risk of over-diagnosis and difficulties in patient management. We retrospectively studied 8 PSN, 7 APSN and 8 ETT to better characterize this new entity. We performed an immunohistochemical analysis (p63, hPL, Cyclin E, and Ki67), a transcriptional analysis using the Nanostring method to quantify the expression of 760 genes involved in the main tumorigenesis pathways, and a RNA sequencing to identify fusion transcripts. The immunohistochemical analysis did not reveal any significant difference in Cyclin E expression between the three groups (p = 0.476), whereas the Ki67 index was significantly (p LPCAT1-TERT fusion transcripts previously reported in ETT. The transcriptomic analysis allowed robust clustering of ETT distinct from the APSN/PSN group but failed to distinguish APSN from PSN. Indeed, only seven genes were differentially-expressed between PSN and APSN samples, CCL19 upregulation and EPCAM downregulation were the most discriminating features of APSN. In contrast, 80 genes discriminated ETT from APSN, establishing a molecular signature for ETT. Gene set analysis identified significant enrichments in the DNA damage repair, immortality and stemness, and cell cycle signaling pathways when comparing ETT and APSN. These results suggested that APSN might not represent a distinct entity but rather a variant of PSN or a transitional stage between PSN and ETT. RNA sequencing and the transcriptional signature of ETT described herein could serve as triage for APSN from curettage or biopsy material, enabling the identification of the cases that need further clinical investigations.

International audience; Objective: Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamide, Vincristine) and EMA-EP(Etoposide, Cisplatine)] regimens.Methods: We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma.Results: We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p < 0.05). In polychemoresistant choriocarcinoma (n = 20) we did not identify differentially expressed genes with an FDR adjusted p-value ≤ 0.05 when compared to polychemosensitive choriocarcinoma (n = 15). Gene pathway analysis revealed a predicted activation of IFN ᵞ in monochemoresistant choriocarcinoma and inhibited IL2 and TNF in polychemoresistant choriocarcinoma. The main biological functions predicted to be altered in chemoresistant choriocarcinoma were related to immunological homeostasis and leukopoiesis.Conclusion: HLA-G is a strong candidate gene to predict choriocarcinoma resistance to monochemotherapy and that further studies are required to implement its routine quantification in the decision process for the management of gestational choriocarcinoma.

p57 immunostaining is performed on hydropic products of conception to diagnose hydatidiform moles (HMs), which can progress to gestational trophoblastic neoplasia. Partial hydatidiform mole (PHM) and hydropic abortion (HA) display positive staining in stromal and cytotrophoblastic cells, whereas complete hydatidiform mole (CHM) is characterized by loss of p57 expression in both cell types. In some cases, an aberrant pattern is observed, called discordant p57 expression, with positive cytotrophoblast staining and negative stromal staining, or vice versa. The aim of this study was to describe the clinical, biological, and pathological characteristics of p57-discordant villi (p57DV) and other associated populations in cases of divergent p57 expression and to compare the evolutions of p57DV-associated and classic CHMs. Seventy cases of p57DV diagnosed by referent pathologists were divided into two groups, G1: p57DV ± non-CHM component (n = 22) and G2: p57DV + CHM component (n = 48). p57DV morphology was similar in the two groups. Observation of more than two populations and hybrid villi on p57 immunostaining were significantly more frequent in G2. The clinical, ultrasound, and biological presentations of p57DV-associated and classic CHMs were similar. The initial pathological diagnosis was more frequently incorrect, missing the CHM component, for the p57DV-associated CHMs. Molecular genotyping was informative in seven cases and identified as androgenetic/biparental mosaicism in four cases. These results show that p57DV are a diagnostic challenge for pathologists and that most are associated with a CHM component. However, the clinical management of p57DV-associated CHMs should be the same as that of classic CHMs.

In a low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX), the modeled hCG (human chorionic gonadotropin) residual concentration (hCGres), calculated with NONMEM program® (NM) during the first 50 treatment days, is a predictor of MTX-resistance risk. This model was implemented with another algorithm on https://www.biomarker-kinetics.org/hCG . The objective was to confirm the validity of the website estimations with respect to NM. The consistencies of modeled hCGres estimated by NM and by the website were assessed in a dataset of 60 fictive patients with simulated hCG profiles, as well as in an independent database of 531 actual patients. Moreover, the hCGres predictive values regarding MTX failure-risk were assessed. The values of hCGres obtained with both methods were highly consistent in the fictive patient and in the actual patient datasets: median relative prediction errors (RPE) were − 0.059 and 9.9 × 10–7, respectively. The ROC AUCs for predictions of MTX failure-risk were 0.90 (95% CI 0.87,0.93) with both NM and the website. The gradual association between increasing hCGres and the 2-year MTX failure-free survival was confirmed. There is a high consistency of hCGres estimates obtained with the two methods. The website is meant to help clinicians in the interpretation of hCG decline curves of MTX-treated GTN patients. hCGres is now validated for more than 1690 patients in four independent datasets, and its recognition as an early predictor of MTX resistance for treatment adjustment and for the future studies should be considered.

Placental mesenchymal dysplasia (PMD) and complete hydatidiform mole (CHM) with a coexisting fetus are 2 rare placental abnormalities characterized by lacunar placenta and presence of an embryo on ultrasound examination. We report the case of a 34-yr-old woman referred at 32.6 weeks of gestation because of a multicystic placenta. A caesarean section was performed at 39.1 weeks of gestation giving birth to a 2905 g normal female infant. Pathological examination revealed macroscopic and microscopic morphological, and immunohistological features of PMD in the main placenta, and features of CHM in a separate placental mass. Fluorescent in situ hybridization and molecular genotyping analyses showed diandric diploidy in the CHM component and androgenetic/biparental mosaicism in the PMD component, confirming the association of PMD and CHM with a live infant. There was no progression to gestational trophoblastic neoplasia during follow-up for the mother, or any sign of Beckwith-Wiedemann syndrome or hepatic tumor in the child.

Background The risk of malignant transformation of molar pregnancies after human chorionic gonadotropin levels return to normal is low, roughly 0.4%, but may justify an adaptation of monitoring strategies for certain patients. Objective This study aimed to determine the risk of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization in women with molar pregnancy and identify risk factors for this type of malignant transformation to optimize follow-up protocols after human chorionic gonadotropin normalization. Study Design This was a retrospective observational national cohort study based at the French National Center for Trophoblastic Diseases of 7761 patients, treated between 1999 and 2020 for gestational trophoblastic disease, whose human chorionic gonadotropin levels returned spontaneously to normal. Results Among 7761 patients whose human chorionic gonadotropin levels returned to normal, 20 (0.26%) developed gestational trophoblastic neoplasia. The risk of malignant transformation varied with the type of mole, from 0% (0 of 2592 cases) for histologically proven partial mole to 0.36% for complete mole (18 of 5045) and 2.1% (2 of 95) for twin molar pregnancy. The median time to diagnosis of malignant transformation after human chorionic gonadotropin normalization was 11.4 months (range, 1–34 months). At diagnosis, 16 of 20 patients (80%) had the International Federation of Gynecology and Obstetrics stage I tumor, and 10 of 20 patients (50%) had a tumor classified as low risk in terms of the International Federation of Gynecology and Obstetrics score. In 9 of 20 patients (45%), the most common first-line treatment was combination chemotherapy. A quarter of these tumors (5 of 20) were histologically proven placental site or epithelioid trophoblastic tumors. In univariate analysis, the factors significantly associated with a higher risk of developing gestational trophoblastic neoplasia after the end of the normal human chorionic gonadotropin monitoring period were age of ≥45 years (odds ratio, 8.3; 95% confidence interval, 2.0–32.7; P=.004) and time to human chorionic gonadotropin normalization of ≥8 weeks (odds ratio, 7.7; 95% confidence interval, 1.1–335; P=.03). The risk was even higher for human chorionic gonadotropin normalization times of ≥17 weeks (odds ratio, 19.5; 95% confidence interval, 3.3–206; P Conclusion In this group of patients with gestational trophoblastic disease, none of the those with pathologically verified partial mole had malignant transformation, supporting the current recommendation of stopping human chorionic gonadotropin monitoring after 3 successive negative tests. In cases of complete mole or twin molar pregnancy, we proposed to extend the monitoring period with quarterly human chorionic gonadotropin measurements for an additional 30 months in patients with the identified risk factors for late malignant transformation (age, ≥45 years; time to human chorionic gonadotropin normalization, ≥8 weeks).

Molar pregnancies are benign trophoblastic diseases associated with a risk of malignant transformation. If aetiology remains mostly unknown, the risk of recurrent molar pregnancy is around 1.5% after one molar pregnancy and around 25% after 2 molar pregnancies. In the later situation, genetic mutations have been described, increasing hugely this risk. In case of mutations, probability to obtain a normal pregnancy is estimated around 1.8%. We report the case of a Caucasian 30-year-old woman whose previous five spontaneous pregnancies had a negative outcome: a spontaneous miscarriage and then 4 complete hydatidiform moles. Genetic testing revealed that the patient carried two heterozygous mutations in the NLRP7 gene (c.2982-2A > G and Y318CfsX7). According to this, counselling was conducted to advocate for oocyte donation in order to obtain a normal pregnancy. This technique enabled a complication-free, singleton pregnancy that resulted in a healthy term live birth of a 2900 g female. Few months after delivery, the patient presented a new complete hydatidiform mole. Women presented with mutations in the NLRP7, KHDC3L or PADI6 genes are unlikely to obtain normal pregnancies, with a major risk of reproductive failure. In such a context, oocyte donation may be the best option. Only 4 normal pregnancies and deliveries have been published in this situation through this technique to our knowledge.

To evaluate the survival and functional outcome of patients with brain metastasis due to gestational trophoblastic neoplasia (GTN). A 17-year retrospective study based on case review of women with brain metastasis from GTN identified by the electronic databases held in the French Reference Centre. Primary outcome measure: 5-year overall survival calculated with the Kaplan–Meier method. Secondary outcome measures: causes of death, prognostic factors and functional outcomes. 21 patients had GTN brain metastasis and were treated with multidrug chemotherapy without concomitant whole-brain radiation therapy. Three patients died early (

Background Low-risk gestational trophoblastic neoplasia (GTN) patients (FIGO score ≤6) are generally treated with single agent chemotherapy (methotrexate or dactinomycin) resulting in a 5-year mortality rate of 0.3%. However, despite these encouraging survival rates, chemotherapy is associated with significant adverse events in most patients. Although it is generally accepted that patients who no longer wish to conceive may be treated by hysterectomy for a hydatidiform mole, the evidence to support this strategy in low-risk GTN patients is lacking. Objectives To describe the survival, efficacy, and tolerance associated with first-line hysterectomy in low-risk non-metastatic GTN patients. Study design. Seventy-four of 1072 low-risk GTN patients treated in the French Center underwent first-line hysterectomy. Patients data with successful first-line hysterectomy were retrospectively compared to those requiring further salvage chemotherapy. Results First-line hysterectomy was followed by hCG normalization in 61 patients (82.4%, 95% confidence interval [CI] 71.8–90.3) without any further salvage chemotherapy, whereas 13 patients required salvage chemotherapy. After multivariate analysis, a FIGO score of 5–6 (exact OR 8.961, 95%CI 1.60–64.96), and the presence of choriocarcinoma (exact OR 14.295, 95%CI 1.78–138.13) were associated with the risk of requiring salvage chemotherapy. Conclusion Hysterectomy as a first-line treatment is effective without salvage chemotherapy in 82.4% of women with low-risk non-metastatic GTN and can be presented as an alternative to single-agent chemotherapy when childbearing considerations have been fulfilled. In young patients, this therapeutic option should not be considered because single-agent chemotherapies are curative in nearly 100% of patients while maintaining fertility.

Resume Les tumeurs trophoblastiques gestationnelles correspondent a un spectre de lesions malignes d’origine placentaire, compose majoritairement de la mole invasive et du choriocarcinome, mais integrant egalement les tumeurs rares du site d’implantation placentaire et trophoblastique epithelioide. Le diagnostic de tumeur trophoblastique gestationnelle postmolaire est base sur les dosages des hormones chorioniques gonadotrophiques plasmatiques, et non sur l’imagerie ou l’histologie. L’imagerie est par contre cruciale pour faire le bilan d’extension tumorale, participer au suivi, et traiter les complications. Les caracteristiques des tumeurs trophoblastiques gestationnelles en imagerie pelvienne sont peu specifiques, mais il existe certaines specificites comme leur caractere hypervasculaire. L’echographie reste l’examen de premiere intention pour le diagnostic initial, et peut predire le caractere invasif ou recurrent de la pathologie trophoblastique persistante. L’IRM pelvienne est en passe de devenir systematique, permettant une analyse plus fiable de l’extension locoregionale et du risque de complications locales. Le scanner thoraco-abdominopelvien et l’IRM cerebrale sont les techniques de choix pour le bilan d’extension a distance. L’arteriographie est indispensable pour prevenir les risques hemorragiques ou traiter certaines complications vasculaires comme les malformations arterioveineuse. L’objectif de cette revue est d’aider a optimiser la prise en charge multidisciplinaire de ces patientes en donnant aux radiologues diagnostiques et interventionnels des cles de comprehension de la prise en charge oncologique de ces lesions et en developpant la place et l’apport des differentes techniques d’imagerie.

ObjectiveThe objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate.MethodsFrom 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure.ResultsA total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3–83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post–dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98–50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%).ConclusionGiven a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.

International audience; The human placenta shares properties with solid tumors, such as rapid growth, tissue invasion, cell migration, angiogenesis, and immune evasion. However, the mechanisms that drive the evolution from premalignant proliferative placental diseases—called hydatidiform moles—to their malignant counterparts, gestational choriocarcinoma, as well as the factors underlying the increased aggressiveness of choriocarcinoma arising after term delivery compared to those developing from hydatidiform moles, are unknown. Using a 730-gene panel covering 13 cancer-associated canonical pathways, we compared the transcriptomic profiles of complete moles to those of postmolar choriocarcinoma samples and those of postmolar to post-term delivery choriocarcinoma. We identified 33 genes differentially expressed between complete moles and postmolar choriocarcinoma, which revealed TGF-β pathway dysregulation. We found the strong expression of SALL4, an upstream regulator of TGF-β, in postmolar choriocarcinoma, compared to moles, in which its expression was almost null. Finally, there were no differentially expressed genes between postmolar and post-term delivery choriocarcinoma samples. To conclude, the TGF-β pathway appears to be a crucial step in the progression of placental malignancies. Further studies should investigate the value of TGF- β family members as biomarkers and new therapeutic targets.

The prenatal examination of the placenta is often an afterthought to that of the fetus in ultrasonography. Not giving the placenta its due may however result in potentially serious placental pathologies remaining undiscovered, notably in the presence of anechoic zones. These latter have earned numerous names, including "placental lakes", "placental venous lakes", "placental lacunae" or "placental caverns" among others, but they have received little attention in the literature. We thus feel that it is essential to review the various pathologies that placental lakes may signal, since any one of them may greatly affect patient management. The difficulty resides in the diversity of these pathologies, sometimes oncological, other times fetal, and in the potential need for multidisciplinary surgery. Some of these causes of placental lakes may result in maternal or fetal complications and/or necessitate increased and casespecific surveillance. The diagnosis and treatment of such cases requires close collaboration between sonographers, obstetricians, geneticists and pathologists. The work we present here focuses on the different etiologies to consider in the presence of a lacunar placenta and the necessary diagnostic measures. Our objective is to propose a diagnostic flowchart to aid clinicians in this dense differential diagnosis.

Resume But Elaborer une collection biologique reunissant des echantillons de qualite optimale pour inciter la recherche fondamentale sur les maladies trophoblastiques gestationnelles (MTG). Materiel et methodes Trois axes prioritaires de recherche ont ete definis afin d’optimiser la nature, les conditions de prelevement et de stockage des echantillons biologiques de patientes atteintes de MTG au sein d’une biobanque dediee : la comprehension de la physiopathologie des MTG, le developpement de nouveaux outils diagnostiques et l’identification de nouvelles cibles therapeutiques. Le protocole d’inclusion de chaque patiente a ete elabore a la lumiere d’une revue extensive de la litterature et d’echanges avec de nombreux experts internationaux en recherche sur les MTG. Resultats Cette biobanque rassemble ainsi pour chaque patiente des echantillons tissulaires (frais, conserves en RNALater® et fixes en formol), sanguins (serum, plasma, ARN sanguin et lymphocytes sanguins), urinaires (surnageants) ainsi que des cultures cellulaires selectives de cytotrophoblastes villeux. Les echantillons sont collectes prospectivement et sont associes a de nombreuses donnees cliniques et biologiques dont la decroissance de l’hormone chorionique gonadotropique sanguine en cas de mole hydatiforme. Conclusion La qualite des echantillons et des donnees cliniques constituant cette biobanque ouvre la possibilite de nombreux projets de recherche dans le cadre de collaborations scientifiques nationales et internationales.

LBA6008 Background: Patients with gestational trophoblastic tumors (GTT) resistant to monochemotherapy are treated with historic chemotherapy regimens known to be effective, but toxic. PD-L1 is constitutively expressed in all GTT subtypes (Bolze et al. Int J Gynecol Cancer 2017). HLA-G and natural killer (NK) cells are involved in GTT immune-surveillance. The anti-PD-L1 monoclonal antibody avelumab (Pfizer & Merck KGaA) triggers cytotoxicity through NK cells. The objective of TROPHIMMUN trial was to assess the efficacy of avelumab in patients with chemoresistant GTT. Methods: In the cohort A of this academic multicenter trial (NCT03135769), avelumab was given at 10 mg/kg Q2W in patients with GTT resistant to monochemotherapy. Avelumab was prescribed until hCG normalization, and then for 3 consolidation cycles. The primary objective was the rate of patients with hCG normalization, with a 2 step Simon design. Results: 15 patients (median 34 y old) followed by the French Gestational Trophoblastic Center were treated from Dec 2016 to Sept 2019 (stage I/III: 53%/47%; FIGO score 0-4: 33%; score 5-6: 47%; score >6: 20%). They all had progressed with previous methotrexate, and 1 patient with actinomycin-D. They received median 8 avelumab cycles (range: 2-11). The tolerability was favorable. 93 % of patients developed drug-related grade 1-2 toxicities (86% grade 1), mainly including fatigue (33% patients); nausea-vomiting (33%); infusion-related reactions (27%); thyroid disorder (20%); dry eyes (20%) & diarrhea (20%). A grade 3 uterus bleeding (treatment unrelated) was observed in 1 patient. Median follow-up was 30 months. Successful hCG normalizations were obtained in 8 patients (53%, median 9 avelumab cycles), either during avelumab treatment in 7 patients, or after avelumab discontinuation in 1 patient. None presented relapse afterwards, and 1 patient had a subsequent healthy pregnancy. Avelumab resistances requiring switch to chemotherapy were observed in 7 patients (47%), who normalized hCG with subsequent actinomycin-D (42%), or surgery/polychemotherapy (57%). The likelihood of success with avelumab was not related to the FIGO score, or disease stages. Conclusions: TROPHIMMUN is the first trial of immunotherapy in GTT patients. The anti-PD-L1 monoclonal antibody avelumab was effective, with a favorable safety profile compared to chemotherapy, in patients with resistance to mono-chemotherapy. About 50 % patients could be cured of their chemoresistant diseases. Avelumab may be a new therapeutic option. Clinical trial information: NCT03135769 .

Dans les tumeurs trophoblastiques gestationnelles (TTG) de bas risque, la determination precoce du risque de resistance a la chimiotherapie de premiere ligne serait utile. Les strategies fondees sur l’observation d’un point de concentration d’hCG a la premiere ou a la septieme semaine de traitement manquent de reproductibilite. Les approches fondees sur la modelisation permettant de calculer les equations mathematiques des cinetiques individuelles d’hCG semblent prometteuses. La reproductibilite de la valeur predictive precoce de parametres modelises a ete demontree dans trois larges etudes internationales. Il devrait etre possible de definir pour chaque patiente son risque de resistance en integrant dans un programme informatique les valeurs d’hCG mesurees durant les 50 premiers jours de traitement. Une validation prospective internationale de cette approche est prevue.

Le traitement recommande des tumeurs trophoblastiques gestationnelles (TTG) a bas risque est une monochimiotherapie, habituellement par methotrexate. La place de l’hysterectomie en premiere intention est mal definie dans cette indication. Evaluation de la normalisation des hCG des TTG a bas risque apres hysterectomie initiale, enregistrees par le Centre francais des maladies trophoblastiques de Lyon, France, entre 1999 et 2013. Sur les 54 patientes incluses, 43 (80 %) ont ete gueries definitivement par une hysterectomie. Aucun critere d’echec n’a pu etre mis en evidence de facon significative. Une hysterectomie est une option therapeutique possible des TTG a bas risque en cas de demande de la patiente.

Objective The risk of gestational trophoblastic neoplasia (GTN) after a hydatidiform mole (HM) is well known. However, the risk of GTN after normalisation of hCG in HM is poorly reported. The aim of this study was to evaluate the risk of GTN after normalisation of hCG according to HM types. Methods This prospective cohort study carried out between 2000 and 2010 used the database of the French Trophoblastic Disease Centre (FTDC). A total of 2008 registered patients with ascertained types of HM were analysed. Cases of GTN occurring after normalisation of hCG were analysed. Results A GTN developed in 239 out of 1980 HMs (12.1%) and 6 out of these 239 post-molar GTN (2.5%) were diagnosed after normalisation of hCG. The risk of GTN after normalisation of hCG was 0.34% (6/1747) following a HM, 0% (0/593) after a partial HM (PHM), 0.36% (4/1122) after a complete HM (CHM), and 9.5% (2/21) after a multiple pregnancy with HM. Conclusions The risk of post-molar GTN justifies hCG monitoring in all women with HM. However, after normalisation of hCG, monitoring of PHM can be stopped safely while it should be maintained for CHM and more importantly for multiple pregnancies with HM.

Background HELLP syndrome is a combination of symptoms described as hemolysis, elevated liver enzymes and low platelets, that complicates 0.01–0.6 % of pregnancies. HELLP syndrome has been scarcely reported associated with partial moles, another rare complication of pregnancy. This manuscript describes the only reported case of HELLP syndrome associated with a complete invasive hydatiform mole. Case presentation We report a perimenopausal patient in prolonged remission from an uncommon high-risk invasive complete mole. The diagnosis was set in a context of early onset preeclampsia and HELLP syndrome. The development of life-threatening complications required primary hysterectomy. Postoperative hCG quickly returned to normal with EMA/CO multi-agent chemotherapy. Conclusion Our patient is in prolonged remission from a complete mole complicated with EOP and HELLP syndrome. This exceptional case of complicated gestational trophoblastic neoplasia reflects a very rare condition in which several risk factors for placental ischemia are associated. Emergency hysterectomy should be considered as salvage initial treatment in such life-threatening situations.

Background In randomized clinical trials or observational studies, it is common to collect biomarker values longitudinally on a cohort of individuals. The investigators may be interested in grouping individuals that share similar changes of biomarker values and use these groups for diagnosis or therapeutic purposes. However, most classical model-based classification methods rely mainly on empirical models such as splines or polynomials and do not reflect the physiological processes. Methods A model-based classification method was developed for longitudinal biomarker measurements through a pharmacokinetic model that describes biomarker changes over time. The method is illustrated using data on human Chorionic Gonadotrophic Hormone measurements after curettage of hydatidiform moles. Results The resulting classification was linked to the evolution toward gestational trophoblastic neoplasia and may be used as a tool for early diagnosis. The diagnostic accuracy of the pharmacokinetic model was more reproducible than the one of a purely mathematical model that did not take into account the biological processes. Conclusion The use of pharmacokinetic models in model-based classification approaches can lead to clinically useful classifications. Electronic supplementary material The online version of this article (doi:10.1186/s12874-015-0106-y) contains supplementary material, which is available to authorized users.

The gestational trophoblastic diseases are a spectrum of different clinical and pathological-defined affections. Treatment of complete and partial hydatidiform moles is dilatation-suction evacuation. It is necessary to control the evolution of hCG thereafter. In case of gestational trophoblastic neoplasia (GTN), defined on abnormal evolution of hCG or on a pathological diagnosis of choriocarcinoma, a medical treatment will be necessary. Choice of regimen will be done after different radiological exams, through a FIGO score assessment. In case of low risk GTN, methotrexate will be the usual treatment. High risk GTN will need polychemotherapy regimens. This article tries to give the essential points on diagnosis and treatment in gestational trophoblastic diseases, but also on more rare diseases such as placental site tumor or twin pregnancy with normal fetus and complete mole.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 39 - N° 3S - p. F25-F32

Objective: Twin pregnancy with complete hydatidiform mole and coexistent fetus (CHM&CF) is a rare situation and a challenge for diagnosis. Results related to fetal outcome and maternal risk of subsequent gestational trophoblastic neoplasia (GTN) are controversial. We here display a series from the French Trophoblastic Disease Reference Center, which is to date the third in number of cases registered by the same center. Study design: By retrospective method based on patients from the French Trophoblastic Disease Reference Center data base between November 1999 and December 2006, 17 assumed cases were reviewed. In 14 cases the diagnosis of CHM&CF was ascertained. All files were reviewed to confirm diagnosis. Methods of initial diagnosis, outcome of pregnancy and evolution to GTN were studied. Results: In 10 cases (71%) diagnosis was made by ultrasonography. Differential diagnoses were partial hydatidiform mole and mesenchymal dysplasia. Three patients in 14 (21%) delivered a healthy child. In only one case, delivery occurred after 37 weeks of gestation. Seven patients (50%) had a diagnosis of GTN. No patient had fatal evolution. Clinical events, such as vaginal bleeding, pre-eclampsia or hyperthyroidism, had no effect on the evolution to GTN. Continuation of the pregnancy did not increase the risk of GTN. Conclusion: In case of prenatal diagnosis of CHM&CF, and even if delivery of a healthy child is possible, patients should be aware of a possibly higher risk of GTN than in CHM.

Resume Objectifs Les deux objectifs de cette etude etaient d'evaluer, sur les tumeurs trophoblastiques gestationnelles declarees au centre francais de reference des maladies trophoblastiques de Lyon, si les criteres diagnostiques de la FIGO 2000 (evolution anormale des HCG et/ou histologie de choriocarcinome) etaient respectes et si les chimiotherapies etaient adaptees au stade-score FIGO. Patientes et methode Etude descriptive, retrospective, portant sur 167 tumeurs trophoblastiques declarees de 1999 a 2005 au centre de reference de l'Hotel-Dieu a Lyon. Resultats Les criteres diagnostiques de tumeur trophoblastique ont ete conformes a ceux de la FIGO dans 66 % des cas (104/158 patientes traitees). Pour 34 % des patientes (n = 54) le diagnostic de tumeur etait donc premature ou errone, lors de la mise en route du traitement. Aucun element justificatif de ce diagnostic premature n'a ete retrouve pour 26 patientes. La decouverte de metastases pulmonaires ou vaginales (n = 9) et le diagnostic histologique de mole invasive (n = 9) sont apparus comme les criteres diagnostiques inappropries les plus frequemment avances. La chimiotherapie a semble adapter au stade-score FIGO dans 91,5 % des cas (150/164). Douze tumeurs a bas risque ont ete surtraitees par polychimiotherapie, et deux tumeurs a haut risque ont ete sous-traitees par monochimiotherapie. De plus, 29 % des patientes (49/164) ont recu une chimiotherapie non conforme du fait d'ecarts au protocole prevu. Discussion et conclusion Le non-respect des criteres diagnostiques FIGO de tumeur trophoblastique gestationnelle expose a des diagnostics errones de tumeurs. La presence de metastases pulmonaires ou vaginales ou le diagnostic de mole invasive ne peuvent en eux-memes justifier automatiquement le diagnostic de tumeur trophoblastique gestationnelle si la decroissance des HCG se fait de facon conforme. Le respect des criteres diagnostiques de la FIGO et l'adaptation de la chimiotherapie au stade-score FIGO permettent d'eviter les sur- ou sous-traitements des tumeurs trophoblastiques gestationnelles.

Introduction Up to 20% of hydatidiform moles are followed by malignant transformation in gestational trophoblastic neoplasia and require chemotherapy. Syncytin-1 is involved in human placental morphogenesis and is also expressed in various cancers. We assessed the predictive value of the expression of Syncytin-1 and its interactants in the malignant transformation process of hydatidiform moles. Methods Syncytin-1 glycoprotein was localized by immunohistochemistry in hydatidiform moles, gestational trophoblastic neoplasia and control placentas. The transcription levels of its locus ERVWE1, its interaction partners (hASCT1, hASCT2, TLR4 and DC-SIGN) and two loci (ERVFRDE1 and ERV3) involved the expression of other placental envelopes were assessed by real-time PCR. Results Syncytin-1 glycoprotein was expressed in syncytiotrophoblast of hydatidiform moles with an apical enhancement when compared with normal placentas. Moles with further malignant transformation had a higher staining intensity of Syncytin-1 surface unit C-terminus but the transcription level of its locus ERVWE1 was not different from that of moles with further remission and normal placentas. hASCT1 and TLR4, showed lower transcription levels in complete moles when compared to normal placentas. ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia. Conclusions Variations of Syncytin-1 protein localization and down-regulation of hASCT1 and TLR4 transcription are likely to reflect altered functions of Syncytin-1 in the premalignant context of complete moles. The reduced transcription in gestational trophoblastic diseases of ERVWE1, ERVFRDE1 and ERV3, which expression during normal pregnancy is differentially regulated by promoter region methylation, suggest a joint dysregulation mechanism in malignant context.

Contains fulltext : 155306.pdf (Publisher’s version ) (Closed access) Gestational trophoblastic disease (GTD) is a spectrum of cellular proliferations arising from trophoblast. Their invasive and metastatic potential sometimes requires chemotherapy and/or surgery. Current management is generally associated with favourable prognosis. Therefore, treatments must be chosen according to the desire for further childbearing of each patient. The European Organisation for Treatment of Trophoblastic Diseases (EOTTD) is dedicated to optimise diagnosis, treatment, follow-up and research in GTD by bringing together knowledge of clinicians and researchers from 29 countries working in the field of GTD in Europe. This study assessed the level of agreement among an expert panel of the EOTTD in order to rationalise the management of patients in Europe. The RAND/UCLA Appropriateness Method was used to combine the best available scientific evidence with the collective judgment of experts to yield a statement regarding the appropriateness of performing a procedure at the level of patient-specific symptoms, medical history and test results. There was an agreement for 54 statements while the experts showed a disagreement for two statements. As there is little evidence from randomised trials on which to base recommendations about management of GTD, many of these recommendations are based on expert opinion derived from changes in management fact that have improved outcomes from nearly 100% fatality to nearly 100% cure rates. However, a large agreement among experts is invaluable to the individual clinician who is struggling to decide whether a fertility-sparing treatment of hydatidiform mole or a low-risk GTN can be chosen and how it must be conducted.

Rationale Hip fractures can be separated into cervical and trochanteric fractures. Trochanteric fractures have been associated with up to twice the short-term mortality of cervical fractures in the elderly. There is also evidence suggesting that the mechanisms are different. Evidence from the literature remains limited on the predictive power of bone mineral density (BMD) and quantitative ultrasounds (QUS) for both types of hip fractures. Methods 5703 elderly women aged 75 years or more, who were recruited from the voting lists in the EPIDOS study, and had baseline calcaneal ultrasounds (QUS) and DXA measurements at the hip and the whole body, were analyzed in this paper. Among those, 192 hip fractures occurred during an average follow-up of 4 years, 108 cervical and 84 trochanteric fractures. Results Femoral neck, trochanteric and whole body BMD were able to predict trochanteric hip fracture (RR’s and 95% CI were, respectively, 3.2 (2.4–4.2); 4.8 (3.5–6.6); and 2.8 (2.2–3.6)) more accurately than cervical fractures (respectively, 2.1 (1.7–2.7); 2.3 (1.8–3.0); 1.2 (1.0–1.6)). All ultrasound parameters, SOS, BUA, and stiffness index (SI) were significant predictors of trochanteric (RR’s respectively 3.0 (2.2–4.1), 2.5(2.0–3.1), and 3.5(2.6–4.7)) but not cervical fractures. After adjustment for femoral neck or trochanteric BMD ultrasound parameters were still significant predictors of trochanteric fracture, and stiffness tended to be a better predictor of trochanteric fractures than either BUA or SOS with a relative risk of 2.25 (1.6–3.1). Conclusions A significant decrease of all bone measurements, BMD and QUS, was highly predictive of trochanteric fractures, whereas a decrease of femoral neck and trochanteric BMD were only associated with a slight increase in cervical fracture risk and a low total body BMD or QUS parameters were not significant predictors of cervical fractures. In women who sustained a hip fracture, the decrease of BMD and QUS values increases the risk of trochanteric fracture as compared to cervical fracture. Trochanteric fractures were mostly a consequence of a generalized low BMD and QUS, whereas other parameters might be involved in cervical fractures.

Resume Objectifs. – Etude descriptive de l’effet a long terme de la viscosupplementation par hylane GF-20 au cours de la gonarthrose et recherche de facteurs predictifs de l’efficacite. Patients et methodes. – Cent cinquante-cinq patients (80 femmes, 75 hommes, âge moyen 69 ans) ont ete revus en consultation puis interroges (questionnaire en 5 points) sur l’efficacite, la tolerance et la satisfaction globale, en moyenne 7 et 14 mois apres 3 injections d’hylane GF-20 pour une gonarthrose symptomatique. Les donnees radiologiques (topographie et stade du pincement), l’existence d’un epanchement (absent, modere, important), la voie d’injection (anterieure, laterorotulienne interne ou externe) et les effets secondaires ont ete notes. La recherche des facteurs predictifs d’efficacite a ete faite par analyse univariee puis multivariee tenant compte de l’âge, de l’index de masse corporelle, du sexe et du delai entre traitement et administration du questionnaire. Resultats. – Le pourcentage de patients satisfaits du traitement lors de la consultation et de l’administration du questionnaire etait respectivement de 78 et 58,9 %. La tolerance a ete consideree excellente ou bonne dans 96,2 % des cas. Les facteurs influencant positivement le resultat du traitement (p Conclusion. – Certains facteurs apparaissent associes a la reussite du traitement par hylane GF-20. Leur role doit etre precise et quantifie par des etudes prospectives.

Chemotherapy is the reference treatment for gestational trophoblastic neoplasia. In case of chemoresistance, hysterectomy has to be considered even in women wishing to conceive. A 31-year-old nulliparous patient presented a recurrent invasive mole, despite two regimens of chemotherapy. She underwent a partial uterine resection of an intramyometrial choriocarcinoma followed by a third-line regimen. Two years later she gave birth by cesarean section at 32 weeks of amenorrhea to a healthy child after a spontaneous pregnancy. In order to preserve patient's fertility, conservative uterine surgery is an alternative to hysterectomy for selected chemoresistant gestational trophoblastic neoplasia.

Background Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients. Objective This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone. Study Design Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients. Results The 5-year recurrence rate of low-risk gestational trophoblastic neoplasia patients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86–8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40–25.4, P = .016), a number of methotrexate courses superior to 5 courses (5–8 courses vs 1–4: HR = 6.19; 95% CI, 1.43–26.8, P = .015; 9 courses and more vs 1–4: HR = 6.80; 95% CI, 1.32–35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09–1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia (95% CI, 1.98–37.9], P = .0042). A patient who received 5–8 courses of methotrexate had a 6.7 times higher relapse risk than a patient who received 1–4 courses (95% CI, 1.54–29.2, P = .011). A patient who received 9 courses or more had an 8.1 times higher relapse risk than a patient who received 1–4 courses of methotrexate (95% CI, 1.54–42.6, P = .014). Conclusion Low-risk gestational trophoblastic neoplasia following a delivery and patients who need more than 4 courses of methotrexate to normalization are at a higher risk of relapse than other low-risk patients. Allotting a higher score to the "antecedent pregnancy" FIGO item should be considered for postdelivery gestational trophoblastic neoplasia. Further analysis of the need for consolidation courses is warranted.

Background Gestational trophoblastic diseases include premalignant (partial and complete hydatidiform moles) and malignant entities referred to as gestational trophoblastic neoplasia. Use of the International Federation of Gynecology and Obstetrics prognostic score is encouraged in cases of gestational trophoblastic neoplasia to predict the potential for the development of resistance to single-agent chemotherapy. An International Federation of Gynecology and Obstetrics score of ≥7 defines a high-risk patient and requires combination chemotherapy. Appropriate and rapid diagnosis, treatment by specialized centers, and reduction of early deaths at the time of chemotherapy initiation have led to significant improvements in survival for patients with high-risk gestational trophoblastic neoplasia. There is a crucial need for the early identification of high-risk patients with gestational trophoblastic neoplasia who have an increased death risk to organize their treatment in highly specialized centers. Objectives The purpose of this study was to describe cases of gestational trophoblastic neoplasia that have resulted in death, particularly in a subgroup with an International Federation of Gynecology and Obstetrics prognostic score of ≥13, for whom low-dose etoposide and cisplatin induction chemotherapy recently was shown to reduce early death rate. Study Design We identified 974 patients from the French Center for Trophoblastic Diseases who had a diagnosis of gestational trophoblastic neoplasia from November 1999 to March 2014. Among 140 patients who were at high risk of resistance to single-agent chemotherapy (International Federation of Gynecology and Obstetrics score, ≥7), 29 patients (21%) had a score of ≥13. Mortality rate was estimated with the use of the Kaplan-Meier method. Results The 5-year overall mortality rate, after the exclusion of placental site trophoblastic tumors and epithelioid trophoblastic tumors, was 2% for patients with gestational trophoblastic neoplasia (95% confidence interval, 1.25–3.13%). High-risk patients had a 5-year mortality rate of 12% (95% confidence interval, 7.49–18.9%). Patients with an International Federation of Gynecology and Obstetrics score of ≥13 had a higher 5-year mortality rate (38.4%; 95% confidence interval, 23.4–58.6%) and accounted for 52% of the deaths in the entire cohort. Early deaths, defined as those that occur within 4 weeks after treatment initiation, occurred in 8 patients of the entire cohort. Six of them had an International Federation of Gynecology and Obstetrics score of ≥13 at presentation, of whom 5 patients had brain and/or liver metastases. Conclusion Gestational trophoblastic diseases with an International Federation of Gynecology and Obstetrics score of ≥13 have an increased risk of early death. We suggest that an International Federation of Gynecology and Obstetrics score of ≥13 becomes a consensual criterion for prediction of patients with gestational trophoblastic neoplasia with increased risk of death, particularly early death. These patients justify treatment in highly specialized gestational trophoblastic disease centers and may benefit from the use of induction low-dose etoposide and cisplatin.

Objective To describe the clinical and histological pitfalls in the diagnosis of placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT), two rare types of gestational trophoblastic neoplasia (GTN). Methods This retrospective, observational, study was carried out in the French Trophoblastic Disease Reference Centre, Lyon, between 2000 and 2011. Due to the many similarities in the diagnosis, treatment and prognosis of PSTT and ETT, these two types of tumour were investigated together. Twenty-two patients with PSTT or ETT were analysed. Results The clinical presentation of these two types of tumour was irregular vaginal bleeding (55%) or amenorrhoea (27%), with a median plasma hCG level of 205IU/L. Seven of the 22 patients (32%) were initially misdiagnosed as an ectopic pregnancy. Median age at presentation was 35-years, with a median interval of 12months between the antecedent pregnancy and diagnosis of PSTT or ETT. The initial histological diagnosis was incorrect in 7/18 (39%) patients; there was a major disagreement with the referral pathologist in five of these seven patients (28%). Conclusions PSTT and ETT are the most difficult types of GTN to diagnose clinically and histologically. An incorrect diagnosis can lead to significant therapeutic deviations from the recommended first-line treatment, namely hysterectomy. Clinical and histological expertise is essential to avoid the pitfalls in the diagnosis of PSTT and ETT.

OBJECTIVE To evaluate the contribution of referent pathologists (RPs) to the quality of diagnosis of trophoblastic diseases and to study the level of diagnostic agreement between the initial pathologists and the RPs. METHODS This observational retrospective study was carried between 1 November 1999 and 11 January 2011 using the database of the French Trophoblastic Disease Reference Centre in Lyon. All files for hydatiform moles (HMs), trophoblastic tumours and non-molar pregnancies for which there was an initial suspicion of trophoblastic disease were included, whenever there was rereading of the slides by an RP. A total of 1851 HMs and 150 gestational trophoblastic tumours were analysed. RESULTS When the initial pathologist diagnosed a complete mole, the RP confirmed the diagnosis in 96% of cases. When the initial pathologist diagnosed a partial mole, the RP confirmed the diagnosis in only 64% of cases. For trophoblastic tumours, when the initial pathologist diagnosed a choriocarcinoma, the RP confirmed the diagnosis in 86% of cases. When the initial anatomopathology suggested an invasive mole, the diagnosis was confirmed in 96% of cases. Finally, when the initial diagnosis was a placental site trophoblastic tumour or an epithelioid trophoblastic tumour, the RP confirmed the diagnosis in 60 and 100% of cases, respectively. CONCLUSION A systematic policy of rereading of slides for all suspicious moles improves the quality of management of trophoblastic diseases at a national level.

International audience; BACKGROUND: Early identification of patients at high risk for chemoresistance among those treated with methotrexate (MTX) for low-risk gestational trophoblastic neoplasia (GTN) is needed. We modeled human chorionic gonadotropin (hCG) decline during MTX therapy using a kinetic population approach to calculate individual hCG clearance (CL(hCG)) and assessed the predictive value of CL(hCG) for MTX resistance. PATIENTS AND METHODS: A total of 154 patients with low-risk GTN treated with 8-day MTX regimen were retrospectively studied. NONMEM was used to model hCG decrease equations between day 0 and day 40 of chemotherapy. Receiver operating characteristic curve analysis defined the best CL(hCG) threshold. Univariate/multivariate survival analyses determined the predictive value of CL(hCG) and compared it with published predictive factors. RESULTS: A monoexponential equation best modeled hCG decrease: hCG(t) = 3900 x e(-0.149 x t). Median CL(hCG) was 0.57 l/day (quartiles: 0.37-0.74). Only choriocarcinoma pathology [yes versus no: hazard ratio (HR) = 6.01; 95% confidence interval (CI) 2.2-16.6; P < 0.001] and unfavorable CL(hCG) quartile (< or =0.37 versus >0.37 l/day: HR = 6.75; 95% CI 2.7-16.8; P < 0.001) were significant independent predictive factors of MTX resistance risk. CONCLUSION: In the second largest cohort of low-risk GTN patients reported to date, choriocarcinoma pathology and CL(hCG) < or =0.37 l/day were major independent predictive factors for MTX resistance risk.

Twin pregnancy with complete hydatidiform mole and coexistent fetus (CHMCF) is a rare situation and a challenge for diagnosis. Results related to fetal outcome and maternal risk of subsequent gestational trophoblastic neoplasia (GTN) are controversial. We here display a series from the French Trophoblastic Disease Reference Center, which is to date the third in number of cases registered by the same center.By retrospective method based on patients from the French Trophoblastic Disease Reference Center data base between November 1999 and December 2006, 17 assumed cases were reviewed. In 14 cases the diagnosis of CHMCF was ascertained. All files were reviewed to confirm diagnosis. Methods of initial diagnosis, outcome of pregnancy and evolution to GTN were studied.In 10 cases (71%) diagnosis was made by ultrasonography. Differential diagnoses were partial hydatidiform mole and mesenchymal dysplasia. Three patients in 14 (21%) delivered a healthy child. In only one case, delivery occurred after 37 weeks of gestation. Seven patients (50%) had a diagnosis of GTN. No patient had fatal evolution. Clinical events, such as vaginal bleeding, pre-eclampsia or hyperthyroidism, had no effect on the evolution to GTN. Continuation of the pregnancy did not increase the risk of GTN.In case of prenatal diagnosis of CHMCF, and even if delivery of a healthy child is possible, patients should be aware of a possibly higher risk of GTN than in CHM.

Summary Objective: In French national claims databases, claims are currently anonymous i.e. not linked to individual patients. In order to improve our estimate of the medical activity related to cancer in one French region, a statistical method was developed to use claims data to assess the number of cancer patients hospitalized in acute care. Methods: This method used the medical and administrative information available in the claims (i.e. age, primary site, length of stay) to predict an average number of stays per patient, followed by a number of patients. It was based on a two-phase study design using an internal dataset which contained personal identifiers to estimate the model parameters. Results: The predicted number of acute care patients hospitalized in one or several health care centers in one French region was 38,109 with a 95% predictive interval (37,990; 38,228) for the first six months of 2002. A prediction error of 24% was found. Conclusion: We provide a good estimate of the morbidity in acute care hospitals using claims data that is not linked to individual patients. This estimate reflects the medical activity and can be used to anticipate acute care needs.

Recently, to answer patients, caregivers and professionals needs, the "Plan Cancer" has been presented by the French Government. This plan is intended to improve quality of care in cancer patients and finally, patients' survival and quality of life. This planned strategy stresses the importance of organized interactions between hospitals and between the various health professionals. Measuring the number of patients with cancer and the activity related to cancer in large networks of multidisciplinary hospitals has became a real challenge in France for organizational, quality of care and economic reasons. Many University Hospitals in France have chosen to face this question by using the French DRG based information system called PMSI. It allows estimating the proportion of hospital stays concerned by cancers that are identified with algorithms based on ICD 10. However, French databases of hospital discharges do not allow patients identification. We collected data on hospital stays and patients in a subset of an organized network focused on cancer care and composed of 55 public or private hospitals in the Rhone-Alpes area. We used these data to estimate the number of patients who had been hospitalized within the network in 2000. Approximately 110,000 hospital stays were related with a diagnostic of cancer, corresponding to a number of patients within a range of 30345 to 35700. In absence of communicating files between hospitals, claims databases are an interesting source of information for cancer burden. The recent implementation of a procedure allowing the linkage of data concerning each patient should permit better estimates in the future. The main limitation will remain the possibility of a hospital to participate to more than one network.

The increasing costs of care make it important to identify those strategies of greatest value from both an effectiveness and cost perspective. Economic analysis is characterized by a simultaneous consideration of alternatives costs and outcomes, and can provide useful data for managerial decision making. In this paper, methods of economic evaluations in general and in cancer in particular is reviewed. In cancer treatment, preventive, curative or palliative strategies can be concerned. Economic evaluation have become increasingly important in oncology because of the proliferation of expensive new treatments. Furthermore, considering quality of life effects is particularly important in oncology, where many treatments obtain modest improvements in response or survival. Quality of life measurements are also reviewed.

In an era where health care expenditure control is a necessity, weighing a new treatment's cost against its added benefits is of crucial importance. These medico-economic analyses may be planned for the evaluation of new molecules in their daily use. Different methods may be used. The medico-economic evaluation of a drug can be performed with the use of clinical studies or modelization techniques. "Clinical studies" include the following methods: randomized trials, so-called "experimental", non-randomized studies, and observational studies. This classification follows a downward evolution of both the investigator's intervention power and the level of proof. Finally, modelization is becoming a commonly used tool. Randomized trials are the "gold standard" but the other, more pragmatic study types, providing a lesser degree of proof can complete the evaluation of a new molecule. One must find the best compromise between the study's objectives and the study type.

Objectives. – To describe the long-term effects of Hylan GF-20 viscosupplementation in patients with knee osteoarthritis and to identify factors predicting efficacy. Methods. – One hundred and fifty-five patients (80 women and 75 men; mean age, 69 years) with symptomatic knee osteoarthritis each received three intraarticular Hylan GF-20 injections. Effectiveness, safety, and satisfaction were evaluated 7–14 months later based on a physician’s examination and a five-item questionnaire. Radiological data (distribution and degree of joint space loss), size of the effusion (none, moderate, large), injection route (anterior, medial to the patella, or lateral to the patellar), and side effects were recorded. Factors predicting effectiveness were looked for by univariate analysis followed by multivariable analysis with adjustments on age, body mass index, gender, and time from treatment to questionnaire administration. Results. – Satisfaction was good in 78% and 58.9% of the patients according to the physician examination and questionnaire, respectively. Safety was considered excellent or good in 96.2% of the patients. Factors significantly (P < 0.05) associated with a good outcome were a moderate effusion, injection lateral to the patella, joint space loss in a single compartment, and radiological meniscal calcinosis. Conclusion. – The factors predictive of a good response to Hylan GF-20 in this study need to be confirmed, and their impact quantitated, in prospective studies.

Measuring the burden of cancer activity in big teaching multidisciplinary hospitals becomes a real challenge in France for organizational, quality of care and economic reasons. At the "Hospices Civils de Lyon" University Hospital in France, we have chosen to face this question by using the french DRG based information system called PMSI. It allows to identify hospital stays related to cancer care through the use of an algorithm based on selected ICD 10 codes for hospital stay. We then estimate the proportion of patients concerned by cancer and classify hospital stays and patients according to various epidemiological and clinical parameters. The results for the year 1999 taken as an example showed that 43,883 out of 293,827 (15%) of hospital stays were related with a diagnostic of cancer, corresponding to 12,777 different patients. The concordance study on 154 patients between the data from the electronic PMSI files and medical paper records showed a 97% concordance for cancer diagnosis and 93% for the precise type of tumor. In absence of hospital based cancer registries, the PMSI data base gives an accurate source of information for cancer burden and provides many potential applications in defining hospital policies for cancer management and resource allocations.

5099 Background: In low-risk GTN, MTX treatment is changed according to serum hCG levels. We previously showed that population modeling of hCG levels using kinetic equations provided parameters tha...

Objective The objective of the study was to describe women registered at the new French Trophoblastic Disease Reference Center and particularly the rates of gestational trophoblastic neoplasia (GTN) after molar pregnancies. Study design Epidemiological data from a prospective cohort of women registered between November 1999 and November 2004 were analyzed. Results Four hundred forty-eight women were registered. The referent pathologist reclassified 32% and 5% of assumed partial mole (PM) and complete mole (CM), respectively. GTN developed in 30 of 212 patients with singleton CM (14%) and in 5 of 108 with singleton PM (5%). Among 131 patients with GTN (35 women followed up after registration for a mole and 96 registered for a GTN), 115 (88%) were low-risk and 16 (12%) were high-risk patients according to 2000 International Federation of Gynecology and Obstetrics (FIGO) scoring system. Conclusion Creation of trophoblastic disease reference centers is desirable to improve treatment of patients. Our results will have to be compared with future publications based on the new 2000 FIGO oncology committee recommendations.