Urachal carcinoma: a large retrospective multicentric study from the French Genito-Urinary Tumor Group.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

[Chemotherapy in male external genital organs (testicular and penile cancer)]. / Chimiothérapie des organes génitaux externes chez l'homme (cancer du testicule et du pénis).

AIM: To describe drugs used in the chemotherapy of testis and penis neoplasms. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: Nowadays, the chemotherapy is perfectly codified in adjuvant treatment or in first-line treatment of metastatic testis cancer. A single dose of carboplatin for seminoma testicular (stage I) in adjuvant treatment situation is one of the latest advances. Concerning penis cancer, the optimal protocols validated by a high level of evidence are missing. CONCLUSION: The chemotherapy in testis and penis neoplasms knew few advances in recent years. So, it is necessary to include patients in clinical research protocols.

Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?

BACKGROUND: Sunitinib is a standard of care for metastatic renal cell carcinoma (mRCC). Hypothyroidism is frequently observed under sunitinib therapy. This study was conducted to prospectively determine the correlation between thyroid function and progression-free survival (PFS) in this population. PATIENTS AND METHODS: One hundred and eleven mRCC patients treated with sunitinib were evaluated for serum thyroid-stimulating hormone (TSH) and T4 levels before treatment and every 6 weeks during treatment. Survival was analysed according to a landmark method with a cut-off of 6 months, excluding early progressive or early-censored patients. RESULTS: Out of the 102 patients with normal baseline thyroid function, 53% developed thyroid dysfunction, including 95% hypothyroidisms out of which 90.9% received L-thyroxine replacement. Median time to TSH alteration was 5.4 months. Median PFS was 11.7 months for the entire population. Median PFS was not different between the groups with abnormal or normal thyroid function after 6 months of treatment (18.9 and 15.9 months, respectively, log-rank P = 0.94, hazard ratio = 1.02, 95% confidence interval = 0.54-1.93). There was no difference even after adjustment for Memorial Sloan-Kettering Cancer Centre classification and therapy line. CONCLUSIONS: Abnormal thyroid function with hormonal substitution did not increase survival in our population, independent of initial prognosis and previous treatments. Larger comparative studies are deserved to validate these conclusions.

[Chemotherapy in urologic oncology]. / Chimiothérapie en oncologie urologique.

Chemotherapy is an effective treatment in urologic cancers either for localized tumor or metastatic disease. In urologic cancers, chemotherapy always takes part in a multidisciplinary strategy including surgery, oncology and radiotherapy. Except for metastatic testicular germ cell cancers, chemotherapy is a palliative treatment in other metastatic urologic cancers such as bladder and castration-resistant prostate carcinomas. In metastatic clear cell renal carcinomas, it has not any indication and anti-angiogenic drugs are the only therapeutic options. Neoadjuvant chemotherapy in non-metastatic muscle-invasive bladder cancers must be considered as a standard treatment in fit patients.

A study of 28 flat bone osteosarcomas: prognostic factors and early and long-term outcome.

Limited information is available on clinical management of Flat Bone Osteosarcomas (FBOS). We retrospectively analysed prognostic factors and outcome. Twenty-eight patients were treated in our institution. Survival curves were obtained by the Kaplan-Meier method and compared with the log-rank test. The overall survival (OS) rates at 5 and 10 years were 52.4% and 45.8% respectively. The event-free survival (EFS) rates at 5 and 10 years were 41.5%. The factors influencing EFS in univariate analysis were location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and adequate local tumour control. Location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and local recurrence were statistically correlated with OS. Multivariate analysis retained metastatic disease at diagnosis as prognostic factors of EFS and OS. Our results suggest a more favourable outcome of FBOS as the use of a treatment scheme based on the protocols for long bone osteosarcomas. However, an adequate local treatment is essential to ensure a better outcome.

[Antiangionic drugs in soft tissue sarcoma]. / Antiangiogènes dans les sarcomes des tissus mous.

Angiogenesis is an essential prerequisite in the growth and dissemination of soft tissue sarcoma. The understanding of the VEGF and VEGFR pathway implication in the development of non GIST soft tissue sarcoma and the discovery of the antitumoral activity of drugs that inhibit this pathway in other solid tumors, led to the development of antiangiogenic drugs anti VEGF in soft tissue sarcoma, as monoclonal antibody (bevacuzimab) or as small molecules (tyrosine-kinase inhibitors anti VEGFR). This manuscript presents the results of the first clinical trials that have evaluated the efficacy and safety of some angiogenesis inhibitors in soft tissue sarcomas.

Resection of residual masses after chemotherapy for advanced non-seminomatous germ cell tumours, a monocentric analysis of pre-operative prognosticators.

Removal of residual masses after chemotherapy in non-seminomatous germ cell tumours (NSGCTs) remains the standard of care. We evaluated in a retrospective and monocentric study potential prognostic factors. Fifty-one patients underwent surgery after chemotherapy for NSGCT. We estimated event-free survival with Kaplan-Meier method and used Cox proportional hazards regression analysis to assess the prognostic significance of risk factors. Histology of residual masses revealed fibrosis in 25 (49%), mature teratoma in 18 (35%) and viable germ cells in 8 (16%). Alpha-fetoprotein mean level at diagnosis was higher in patients with residual masses showing mature teratoma and/or viable malignant cells (P = 0.036). In multivariate analysis, poor prognosis group according to International Germ Cell Cancer Collaborative Group was associated with worse outcome compared with good and intermediate prognosis groups (hazard ratio for events = 26.4; 95% confidence interval 2.46-283.9; P = 0.006) and primary testicular NSGCT was associated with better event-free survival than extragonadal NSGCTs (hazard ratio for events = 0.04; 95% confidence interval 0.004-0.48; P = 0.01). Resection of residual masses after chemotherapy in NSGCT results in favourable long-term survival in most patients. Our results compared favourably with those reported from higher volume centres.

Recurrence of neonatal haemochromatosis in half sibs born of unaffected mothers.

We report two families in which neonatal haemochromatosis was observed in half sibs. In the first family, two successive girls were born of different fathers. In the second family, an affected brother and sister were followed by an affected half brother born after donor insemination. These observations, as well as a previous abstract describing two affected half sisters, revive the debate over the inheritance of neonatal haemochromatosis. Incomplete penetrance or gonadal mosaicism for a dominant disorder, a maternal "environmental factor", or mitochondrial defect may be more suitable explanations than autosomal recessive inheritance in this condition. Alternative modes of fertilisation, such as donor insemination or in vitro fertilisation with donor eggs, should be considered with caution.

Clinical experience with a triphasic oral contraceptive ('Trinordiol') in young women.

Seven hundred and fifty cycles of treatment with a new triphasic oral contraceptive (WL-49(50). 'Trinordiol') containing the lowest quantity of steroids of all available preparations were evaluated in 75 healthy young women (mean age 19.6 years), 70% of whom had regular, normal cycles. Sixty-five percent had not used contraception before; the others had previously been on combined or progestagen-only oral contraceptives or had an IUD. The mean length of treatment with the triphasic preparation was 10 cycles. No pregnancy was recorded during the 750 cycles of treatment. Fifteen (20%) women dropped out of the study for medical reasons, essentially breast tenderness, weight increase, spotting and nausea, in decreasing order of frequency. Mastalgia was present in 21% of the women (8.9% of the cycles) during triphasic oral contraception, but this symptom disappeared in more than half of the cases within 3 months of continued use. Other side-effects were less frequent: vaginal discharge (4.4% of the cycles), nausea (3.7%), abdominal and leg cramps (2.8%), headaches (3.2%) and weight increase (3%). Spotting and breakthrough bleeding were reported during only 1.9% of the cycles, a remarkably low frequency. No absence of withdrawal bleeding was noted. Weight and blood pressure changes were minimal and never reached statistical significance. Hypertension developed during triphasic medication in 1 predisposed individual. Complaints of oestrogen-related symptoms such as breast tenderness and digestive disorders were probably due to the reduced progestagen content of the preparation compared with combined low fixed daily dose oral contraceptives. However, no increases in dysmenorrhoea and/or premenstrual tension were noted. It is concluded that the triphasic preparation provides effective contraception with excellent cycle control and minimal side-effects, which should help to increase the acceptability of low-dose combined oral contraceptives.

PIP: 750 cycles of treatment with a new triphasic oral contraceptive (OC), (WL-49(50), Trinordiol), containing the lowest quantity of steroids of all available preparations were evaluated in 75 healthy young women (mean age 19.6 years). 70% of all young women had normal, regular menstrual cycles. 65% had not used contraception previously, and the others had previously taken combined or progestogen only OCs or had an IUD. The mean length of treatment with the triphasic preparation was 10 cycles. Routine clinical evaluation, including gynecological examination, weight and blood pressure measurement, assessment of cycle events, and recording of spontaneously reported side effects, was performed every 3 months. Cycle control during triphasic OC use was very good. There was a statistically significant trend of the cycles toward more regularity than prior to this type of contraception, with an increased frequency of 28-day cycles. Duration of menses was significantly reduced and menstrual volume was more frequently rated by the women as normal. Spotting and breakthrough bleeding showed a very low frequency, the latter accounting for less than 10% of intermenstrual bleeding during triphasic OC medication. Frequency of side effects was 53.3% (40 women) during triphasic OC use. 20% of the population reported side effects among the reasons for stopping triphasic OC use. Breast tenderness was the most frequent side effect recorded in almost 9% of the total number of treatment cycles. It affected 21% of the women under study, a significantly more frequent occurrence than before triphasic OC use in these individuals. The tendency of this symptom to improve was observed in more than half of the cases within 3 months use of triphasic OC use. Other signs of estrogenic dominance such as gastrointestinal disturbances, vaginal discharge, pelvic congestion, and leg cramps were also present but much less prominent than breast tenderness. 16 (21.3%) patients presented with breast tenderness for 67 (8.9%) cycles. Nausea and vomiting were experienced by 6 (8%) patients for 28 (3.7%) cycles. Vaginal discharge was present in 10 (13.3%) patients for 33 (4.4% cycles). Spotting and breakthrough bleeding occurred in 6 (8%) women for 14 (1.9% cycles). Absence of change in weight was recorded in 1/3 of the women studied; another 1/3 experienced a weight reduction of 1-4 kg and the last 1/3 gained 1-4 kg. There were no statistically significant variations in either systolic or diastolic blood pressure values.

Serum concentrations of human chorionic gonadotrophin and its alpha and beta subunits. 1. During normal singleton and twin pregnancies.

Homologous radioimmunoassays have been developed for native hCG and its alpha and beta subunits. Their specificities were assessed by analysis of the inhibition ca and beta subunits. 1. During normal singleton and twin pregnancies.

Serum concentration of human chorionic gonadotropin and its alpha and beta subunits. 2. Trophoblastic tumours.

Using specific homologous radioimmunoassays of native hCG and its alpha and beta subunits, we determined the levels of these glycoproteins in unfiltered maternal blood serially obtained in five non-invasive hydatidiform moles before and after evacuation. Some of these samples were assayed after gel filtration chromatography on Sephadex G 100. Twelve samples, obtained in cases of invasive trophoblastic tumour after ablative surgery and chemotherapy, were also assessed for their hCG, hCG alpha and hCG beta content. In unaborted moles, mean circulating levels of native hCG and free hCG beta were considerably increased (seven and thirteen times, respectively) as compared to normal pregnancies of the same age, whereas levels of free hCG alpha were either normal or slightly elevated. Chromatographic analyses of molar sera confirmed the presence of free circulating subunits, and separated hCG beta in its monomeric form from its higher molecular weight form, the latter being in greater quantity than in normal pregnancy sera. In contrast, the elution profile of serum native hCG was comparable in cases of normal and molar pregnancy. Successful curettage was accompanied by a return to normal levels of the native hCG and its alpha and beta subunits in 40-90 days. Persistence of tumour tissue was indicated by a slight increase in levels of native hCG and the beta subunit. Determination of alpha subunit level was less useful for the detection of any relapse.

[Maternal serum levels of chorionic gonadotropin and its alpha and beta free subunits as a function of the fetal sex. Preliminary study]. / Taux sériques maternels de la choriogonadotrophine et de ses sous-unités libres alpha et bêta en fonction du sexe foetal. Etude préliminaire.

The maternal serum levels of hCG and its alpha or beta subunits were measured in 96 normal pregnancies and correlated with the fetal sex. During the first 20 weeks (69 cases), the maternal serum levels of hCG, of its alpha subunit and particularly of its beta subunit were higher in cases of female fetuses. However no statistically significant difference was observed between the levels of hCG or its subunits in serum of pregnancies with male or female fetuses. During the second half of pregnancy, the serum hCG levels were discretely higher in cases with female fetuses (no significant difference) and the serum levels of its alpha or beta subunits were identical in cases of male of female fetuses.