Incidence of pulmonary toxicity in bleomycin-containing regimens for testicular cancer with and without the use of growth factor.

INTRODUCTION: The concurrent use of bleomycin and granulocyte colony-stimulating factors (G-CSFs) has historically been debated as a risk factor for bleomycin-induced pulmonary toxicity in patients with both testicular cancer and Hodgkin's lymphoma. The purpose of this study is to evaluate the incidence of pulmonary toxicity in patients with testicular cancer who were treated with bleomycin and pegfilgrastim concurrently. METHODS: This is a retrospective study that includes male patients over the age of 18 years old diagnosed with testicular cancer who received bleomycin-containing chemotherapy regimens with and without the use of G-CSF agents. RESULTS: There were a total of 33 patients identified as receiving bleomycin, with 30 of those patients having received concurrent G-CSF therapy. Of the patients who received G-CSF therapy, 11 patients (36.6%) experienced pulmonary toxicity leading to discontinuation of bleomycin or changes in chemotherapy regimens altogether. CONCLUSION: There were no major differences in patient demographics or risk factors between those who received G-CSF and developed pulmonary toxicity and those who received G-CSF but did not develop pulmonary toxicity. Further studies are needed in order to fully assess the risk of pulmonary toxicity with this chemotherapy regimen.

Thirty-Year-Old Male Patient with Non-Seminoma and Coincidental Rectal Cancer.

We present the case of a 31-year-old male patient with non-seminoma (90% embryonal carcinoma, 10% teratoma) pT1b L1 V0 Pn0 R0 cN2 cM0, Clinical Stage IIb and "good prognosis group" according to IGCCCG of the left testis. According to EAU guidelines, he received three cycles of BEP. After the second cycle, he developed recurrent, clinically not significant rectal bleeding, which we associated with deep thrombocytopenia. Following chemotherapy, there was one lymph node in the CT scan left, with a diameter of 0.9 cm at the inferior mesenteric arteria and the rectal bleeding did not stop; so coloscopy and staging revealed rectal cancer (adenocarcinoma) with peritoneal carcinosis. The patient was scheduled for radio-chemotherapy. Next-generation sequencing of the adenocarcinoma showed two mutations in KRAS and TP53 genes. To our knowledge, this is the first case of non-seminoma and coincidental rectal cancer. Furthermore, this case underlines the significance of molecular biological studies for the development of individualized targeted therapies, especially in younger patients and in chemo- and/or platin-resistance.

Toxicity of benzyl paraben on aquatic as well as terrestrial life.

Parabens are derivatives of alkyl esters of p-hydroxybenzoic acid and come in different classes. These compounds are primarily used as antimicrobial preservative agents in many commercial products, including cosmetics and pharmaceuticals. Accordingly, Benzyl paraben (BeP) is known to be a potential endocrine disruptor. The aim of this study was to determine the toxicity of benzyl paraben (BeP) on aquatic and terrestrial organisms, specifically Scenedesmus sp., Moina macrocopa, and Eisenia fetida. All the organisms were treated with different concentrations of BeP (0.025 mg/L and 1000 mg/L), and LC25, LC50, and LC90 values were used to measure the toxicity levels. Results showed the LC values of BeP for M. macrocopa (3.3 mg/L, 4.7 mg/L, 7.3 mg/L) and E. fetida (173.2 mg/L, 479.8 mg/L, 1062 mg/L), respectively. Toxicity tests on green algae (Scenedesmus sp.) were conducted, the green algae were subjected to various BeP concentration. At 50 mg/L of BeP, cell viability was reduced to 56.2% and the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay indicated 35.4% viable cells. The chlorophyll value and the biochemical parameters of the algal cells were corroborative with the cell viability test. Lethal indices (LC50) for M. macrocopa and E. fetida were evaluated for their toxicity on biochemical properties and were found to be catalase (0.111 mg/L, 0.5 mg/L), lipid peroxidation (0.072 mg/L, 0.056 mg/L), and total protein (0.309 mg/L, 0.314 mg/L), respectively. Overall, this study demonstrated the toxic impact of BeP on non-target aquatic as well as terrestrial species.

Performance Analysis of Dual-Hop AF Relaying with Non-Linear/Linear Energy Harvesting.

Massive device-to-device communication nodes and Internet of Things (IoT) devices are expected to be crucial components in next-generation wireless networks. However, the energy constraint of these nodes presents a challenge since the energy of the batteries is limited. Motivated by this, radio frequency energy harvesting (EH) has been developed as an efficient strategy to overcome the energy constraint of IoT devices and sensor networks. In this paper, a wireless-powered dual-hop amplify-and-forward relaying system, in the absence of a direct link between the source (S) and the destination (D), is considered. It is assumed that a dedicated power beacon (PB) transmits an energy-bearing signal from which the power-constrained S and relay (R) harvest energy. Theoretical derivations of bit error probability, outage probability, and throughput expressions are performed for both linear and non-linear energy harvesting models. Moreover, the theoretical results provided for different system parameters are validated via Monte Carlo simulations. The obtained results reveal the difference between the realistic non-linear EH model and the conventional linear EH model, which overestimates the system performance at high levels of harvested energy. Thus, it leads to misunderstanding the real performance of the EH systems. However, at low levels of harvested energy, both models behave similarly and provide realistic results.

French AFU Cancer Committee Guidelines - Update 2022-2024: testicular germ cell cancer.

OBJECTIVE: Updated Recommendations for the management of testicular germ cell cancer. MATERIALS AND METHODS: Comprehensive review of the literature on PubMed since 2020 concerning the diagnosis, treatment and follow-up of testicular germ cell cancer (TGCT), and the safety of treatments. The level of evidence of the references was evaluated. RESULTS: The initial work-up for patients with testicular germ cell cancer is based on a clinical examination, biochemical (AFP, total hCG and LDH serum markers) and radiological assessment (scrotal ultrasound and thoracic-abdominal-pelvic [TAP] CT). Inguinal orchiectomy is the first therapeutic step whereby the histological diagnosis can be made, and the local stage and risk factors for stage I non-seminomatous germ cell tumours (NSGCT) can be determined. For patients with pure stage-I seminoma, the risk of progression is 15 to 20%. Therefore, surveillance in compliant patients is preferable; adjuvant chemotherapy with carboplatin AUC 7 is an option; and indications for para-aortic radiotherapy are limited. For patients with stage I NSGCT, there are various options between surveillance and a risk-adapted strategy (surveillance or 1 cycle of BEP [Bleomycin Etoposide Cisplatin] depending on the absence or presence of vascular emboli within the tumour). Retroperitoneal lymph node dissection for staging has a very limited role. The treatment for metastatic TGCT is BEP chemotherapy in the absence of any contraindication to bleomycin, for which the number of cycles is determined according to the prognostic risk group of the International Germ Cell Cancer Consortium Group (IGCCCG). Para-aortic radiotherapy is still a standard in stage IIA seminomatous germ cell tumours (SGCT). After chemotherapy, the size of residual masses should be assessed by TAP scan for NSGCT: retroperitoneal lymph node dissection is recommended for any residual mass of more than 1 cm, and all other metastatic sites should be excised. For SGCT, reassessment by 18F-FDG PET is required to specify the surgical indication for residual masses>3cm. Surgery is still rare in these situations. CONCLUSION: By adhering to TGCT management recommendations, excellent disease-specific survival rates are achieved; 99% for stage I and over 85% for metastatic stages.

Neutropenic sepsis rates in patients receiving bleomycin, etoposide and cisplatin chemotherapy using olanzapine and reduced doses of dexamethasone compared to a standard antiemetic regimen.

OBJECTIVE: To investigate whether the use of a steroid-sparing antiemetic protocol (substituting dexamethasone with olanzapine) affects the incidence of neutropenia and associated hospital admissions in patients receiving bleomycin, etoposide and cisplatin (BEP) chemotherapy. PATIENTS AND METHODS: Records from 108 patients who received BEP at St Bartholomew's Hospital, London were divided into two groups according to antiemetic regimen. Group 1 (treated 2008-2013) were treated with a steroid-containing antiemetic protocol and group 2 (treated 2014-2017) were treated according to a steroid-sparing protocol, i.e. using olanzapine. Outcomes included incidence of neutropenia at nadir blood count, severity of neutropenia, hospital admissions attributable to febrile neutropenia (FN) and baseline risk factors associated with FN. Statistical analyses were performed using two-sided chi-squared tests. RESULTS: The baseline characteristics of the two groups were balanced with regard to age, gender, histology, and proportion of patients with International Germ Cell Cancer Collaborative Group poor-risk disease. The incidence of neutropenia of any grade (group 1, 96.2%; group 2, 98.1%) was similar, although group 2 had more patients with severe neutropenia than group 2 (77.7% vs 88.8%). There was a significant difference in FN incidence (group 1, 22%; group 2 7.5%; P = 0.030). Most cases of FN occurred in cycle 1. Two baseline characteristics were over-represented in patients who developed FN: female sex and age ≥50 years. CONCLUSION: By comparing two cohorts who received prophylactic antibiotics, our audit suggests that rates of FN-related admissions were lower in the cohort of patients in whom we employed a steroid-sparing antiemetic protocol.

Regulatory mechanisms and therapeutic targeting of vasculogenic mimicry in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a typical hyper-vascular solid tumor; aberrantly rich in tumor vascular network contributes to its malignancy. Conventional anti-angiogenic therapies seem promising but transitory and incomplete efficacy on HCC. Vasculogenic mimicry (VM) is one of functional microcirculation patterns independent of endothelial vessels which describes the plasticity of highly aggressive tumor cells to form vasculogenic-like networks providing sufficient blood supply for tumor growth and metastasis. As a pivotal alternative mechanism for tumor vascularization when tumor cells undergo lack of oxygen and nutrients, VM has an association with the malignant phenotype and poor clinical outcome for HCC, and may challenge the classic anti-angiogenic treatment of HCC. Current studies have contributed numerous findings illustrating the underlying molecular mechanisms and signaling pathways supporting VM in HCC. In this review, we summarize the correlation between epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and VM, the role of hypoxia and extracellular matrix remodeling in VM, the involvement of adjacent non-cancerous cells, cytokines and growth factors in VM, as well as the regulatory influence of non-coding RNAs on VM in HCC. Moreover, we discuss the clinical significance of VM in practice and the potential therapeutic strategies targeting VM for HCC. A better understanding of the mechanism underlying VM formation in HCC may optimize anti-angiogenic treatment modalities for HCC.

Home consumption of two fortified balanced energy protein supplements by pregnant women in Burkina Faso.

Balanced energy protein (BEP) supplementation for pregnant and lactating women in low- and middle-income countries is a promising strategy to improve birth outcomes and child growth. The objective of this study was to assess and compare the acceptability of new formulations of two fortified BEP supplements, a lipid-based peanut paste and a vanilla biscuit, among 80 pregnant women in rural Burkina Faso, prior to an efficacy trial. A 10-week individually randomized cross-over study was designed, in which women received a weekly supply of each supplement for 4 weeks, and a daily choice between the supplements in the last 2 weeks. Questionnaires to assess daily consumption and supplement acceptability (n = 80) and home observations (n = 20) were combined with focus group discussions (n = 6) and in-depth interviews with women (n = 80) and stakeholders (n = 24). Results showed that the two supplements were well accepted. Quantitative findings indicated high compliance (>99.6%) and high overall appreciation (Likert score >6 out of 7) of both supplements. The assessment of preferred choice in Weeks 9 and 10 indicated a slight preference for the vanilla biscuit. Qualitative findings indicated that perceived health benefits, support from household members and educational messages from health professionals were important drivers for acceptance and compliance. Sharing was not often reported but was identified during interviews as a possible risk. We recommend that future studies use a combination of methods to identify appropriate food supplements and context-specific factors that influence acceptability, compliance and subsequent impact of nutritious food supplements.

Role of distinct type-IV-secretion systems and secreted effector sets in host adaptation by pathogenic Bartonella species.

The α-proteobacterial genus Bartonella comprises a large number of facultative intracellular pathogens that share a common lifestyle hallmarked by hemotrophic infection and arthropod transmission. Speciation in the four deep-branching lineages (L1-L4) occurred by host adaptation facilitating the establishment of long lasting bacteraemia in specific mammalian reservoir host(s). Two distinct type-IV-secretion systems (T4SSs) acquired horizontally by different Bartonella lineages mediate essential host interactions during infection and represent key innovations for host adaptation. The Trw-T4SS confined to the species-rich L4 mediates host-specific erythrocyte infection and likely has functionally replaced flagella as ancestral virulence factors implicated in erythrocyte colonisation by bartonellae of the other lineages. The VirB/VirD4-T4SS translocates Bartonella effector proteins (Bep) into various host cell types to modulate diverse cellular and innate immune functions involved in systemic spreading of bacteria following intradermal inoculation. Independent acquisition of the virB/virD4/bep locus by L1, L3, and L4 was likely driven by arthropod vectors associated with intradermal inoculation of bacteria rather than facilitating direct access to blood. Subsequently, adaptation to colonise specific niches in the new host has shaped the evolution of complex species-specific Bep repertoires. This diversification of the virulence factor repertoire of Bartonella spp. represents a remarkable example for parallel evolution of host adaptation.

Autonomous Power Decision for the Grant Free Access MUSA Scheme in the mMTC Scenario.

Non-orthogonal multiple access schemes with grant free access have been recently highlighted as a prominent solution to meet the stringent requirements of massive machine-type communications (mMTCs). In particular, the multi-user shared access (MUSA) scheme has shown great potential to grant free access to the available resources. For the sake of simplicity, MUSA is generally conducted with the successive interference cancellation (SIC) receiver, which offers a low decoding complexity. However, this family of receivers requires sufficiently diversified received user powers in order to ensure the best performance and avoid the error propagation phenomenon. The power allocation has been considered as a complicated issue especially for a decentralized decision with a minimum signaling overhead. In this paper, we propose a novel algorithm for an autonomous power decision with a minimal overhead based on a tight approximation of the bit error probability (BEP) while considering the error propagation phenomenon. We investigate the efficiency of multi-armed bandit (MAB) approaches for this problem in two different reward scenarios: (i) in Scenario 1, each user reward only informs about whether its own packet was successfully transmitted or not; (ii) in Scenario 2, each user reward may carry information about the other interfering user packets. The performances of the proposed algorithm and the MAB techniques are compared in terms of the successful transmission rate. The simulation results prove that the MAB algorithms show a better performance in the second scenario compared to the first one. However, in both scenarios, the proposed algorithm outperforms the MAB techniques with a lower complexity at user equipment.

[French ccAFU guidelines - update 2020-2022: testicular germ cell tumors]. / Recommandations françaises du Comité de cancérologie de l'AFU - actualisation 2020­2022: tumeurs germinales du testicule.

OBJECTIVE: - To update French guidelines concerning testicular germ cell cancer. MATERIALS AND METHODS: - Comprehensive Medline search between 2018 and 2020 upon diagnosis, treatment and follow-up of testicular germ cell cancer and treatments toxicities. Level of evidence was evaluated. RESULTS: - Testicular Germ cell tumor diagnosis is based on physical examination, biology tests (serum tumor markers AFP, hCGt, LDH) and radiological assessment (scrotal ultrasound and chest, abdomen and pelvis computerized tomography). Total inguinal orchiectomy is the first-line treatment allowing characterization of the histological type, local staging and identification of risk factors for micrometastases. In case of several therapeutic options, one must inform his patient balancing risks and benefits. Surveillance is usually chosen in stage I seminoma compliant patients as the evolution rate is low between 15 to 20%. Carboplatin AUC7 is an alternative option. Radiotherapy indication should be avoided. In stage I non seminomatous patients, either surveillance or risk-adapted strategy can be applied. Staging retroperitoneal lymphadenectomy has restricted indications. Metastatic germ cell tumors are usually treated by PEB chemotherapy according to IGCCCG prognostic classification. Lombo-aortic radiotherapy is still a standard treatment for stage IIA. Residual masses should be evaluated by biological and radiological assessment 3 to 4 weeks after the end of chemotherapy. Retroperitoneal lymphadenectomy is advocated for every non seminomatous residual mass more than one cm. 18FDG uptake should be evaluated for each seminoma residual mass more than 3 cm. CONCLUSIONS: - A rigorous use of classifications is mandatory to define staging since initial diagnosis. Applying treatments based on these classifications leads to excellent survival rates (99% in CSI, 85% in CSII+).

Feasibility of olanzapine, multi acting receptor targeted antipsychotic agent, for the prevention of emesis caused by continuous cisplatin- or ifosfamide-based chemotherapy.

Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing continuous five-day chemotherapy. Patients and methods This study was a prospective dose escalation study at a single center (UMIN ID: UMIN000015386). Patients received a combination of adriamycin and ifosfamide (AI) or a combination of bleomycin, etoposide, and cisplatin (BEP). On days 1-5, all patients received intravenous granisetron (1 mg) and intravenous dexamethasone sodium phosphate (24 mg). Olanzapine was administrated on day-1 to day5 at bedtime. The dose of olanzapine followed a dose-escalation scheme, with monitoring of safety and tolerability at each dose. A 3 + 3 cohort design was used, with three to six patients per cohort. Results Nine patients were enrolled (three for each cohort). No patients experienced dose-limiting toxicity (DLT). The most frequent adverse events were dry mouth and constipation. In each cohort, the maximum severity of nausea was Grade 2, and no patients experienced a vomiting episode. Conclusion A 2.5 mg/day dosage of olanzapine is sufficient to prevent from CINV in Japanese patients receiving continuous five-day chemotherapy. A dose of 10 mg/day, which is recommended by international CINV guidelines, is also tolerated. If CINV is not controlled by an initial dose of 2.5 mg/day of olanzapine, dosage escalation is encouraged. Future studies should compare olanzapine with aprepitant.

RETRACTED: Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : tumeurs germinales du testicule French ccAFU guidelines ­ Update 2018­2020: Testicular germ cell tumors / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020: tumeurs germinales du testicule.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: doi:10.1016/j.purol.2019.01.009. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the doi:10.1016/j.purol.2019.01.009. That newer version of the text should be used when citing the article.

[French ccAFU guidelines - Update 2018-2020: Testicular germ cell tumors]. / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : tumeurs germinales du testicule.

OBJECTIVE: To update French guidelines concerning testicular germ cell cancer. METHODS: Comprehensive Medline search between 2016 and 2018 upon diagnosis, treatment and follow-up of testicular germ cell cancer and treatments toxicities. Level of evidence was evaluated. RESULTS: Testicular Germ cell tumor diagnosis is based on physical examination, biology tests (serum tumor markers AFP, hCGt, LDH) and radiological assessment (scrotal ultrasound and chest, abdomen and pelvis computerized tomography). Total inguinal orchiectomy is the first- line treatment allowing characterization of the histological type, local staging and identification of risk factors for micrometastases. In case of several therapeutic options, one must inform his patient balancing risks and benefits. Surveillance is usually chosen in stage I seminoma compliant patients as the evolution rate is low between 15 to 20 %. Carboplatin AUC7 is an alternative option. Radiotherapy indication should be avoided. In stage I non-seminomatous patients, either surveillance or risk-adapted strategy can be applied. Staging retroperitoneal lymphadenectomy has restricted indications. Metastatic germ cell tumors are usually treated by PEB chemotherapy according to IGCCCG prognostic classification. Lombo-aortic radiotherapy is still a standard treatment for stage IIA. Residual masses should be evaluated by biological and radiological assessment 3 to 4 weeks after the end of chemotherapy. Retroperitoneal lymphadenectomy is advocated for every non-seminomatous residual mass more than one cm. 18FDG uptake should be evaluated for each seminoma residual mass more than 3cm. CONCLUSIONS: A rigorous use of classifications is mandatory to define staging since initial diagnosis. Applying treatments based on these classifications leads to excellent survival rates (99 % in CSI, 85 % in CSII+).

Hsp90ß promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma.

BACKGROUND: Vascular endothelial growth factor receptors (VEGFRs) are the major receptors involved in endothelial cell-dependent tumor angiogenesis. There are studies account for the effects of Hsp90 on angiogenesis, but the role and mechanism of Hsp90ß isoforms and NVP-BEP800, a specific inhibitor of Hsp90ß, in tumor angiogenesis is rarely mentioned. METHODS: Immunohistochemistry and statistical analysis was used to evaluate the correlation between Hsp90ß expression, CD31 endothelial cell-dependent vessel density, and VEGFRs expression in tissue samples of 96 HCCs. Kaplan-Meier survival analysis and COX proportional hazards analysis the relation of Hsp90ß and prognosis. HUVEC cells were transfected with Hsp90ß or treated with NVP-BEP800, and then cell proliferation, migration, invasion and tube formation were investigated. The VEGFR1 and VEGFR2 expression was determined by Western blot and immunofluorescence. The VEGFR1 and VEGFR2 promoter activities were detected by dual luciferase report system. In vivo, the angiogenesis promotion of Hsp90ß and anti-angiogenesis efficacy of NVP-BEP800 was tested in HCC xenograft models. Histological analysis was performed on tumor samples to evaluate Hsp90ß, VEGFRs expression and MVD. RESULTS: This study investigated the correlation between Hsp90ß expression and CD31+ endothelial cell-dependent vessel density. Hsp90ß promoted VEGFRs expression by increasing their promoter activities. The proliferation, migration, invasion, and tube formation activities of human endothelial cells significantly increased when Hsp90ß was overexpressed. NVP-BEP800 down-regulated VEGFRs expression to significantly reduce tubular differentiation, as well as endothelial cell proliferation, migration, and invasion. Furthermore, NVP-BEP800 decreased VEGFR1 and VEGFR2 promoter activities. In vivo, Hsp90ß promoted VEGFRs and CD31 expression in human hepatocellular carcinoma tumor xenografts and was associated with increased tumor microvessel density. After 18 days of treatment with 30 mg/kg/day NVP-BEP800, VEGFRs and CD31 expression significantly decreased. CONCLUSION: Hsp90ß induced endothelial cell-dependent tumor angiogenesis by activating VEGFRs transcription. NVP-BEP800 has potential as a therapeutic strategy for inhibiting tumor angiogenesis by decreasing endothelial cell progression and metastasis. It can help develop a therapeutic strategy for tumor treatment through the inhibition of endothelial cell progression and metastasis.

Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors.

BACKGROUND: The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. METHODS: This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. RESULTS: Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. CONCLUSIONS: An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. CONFLICT OF INTEREST STATEMENT: No conflict of interest.

[CCAFU french national guidelines 2016-2018 on testicular germ cell tumors]. / Recommandations en onco-urologie 2016-2018 du CCAFU : Tumeurs germinales testiculaires.

INTRODUCTION: The purpose of the oncologic comitee of the french association of urology was to establish guidelines proposed by the external genital organ group, for the diagnosis, treatment and follow-up of the germ cell tumours of the testis. MATERIAL AND METHODS: The multidisciplinary working group studied 2013 guidelines, exhaustively reviewed the literature, and evaluated references and their level of proof in order to attribute grades of recommandation. RESULTS: The initial workup of testicular cancer is based on clinical, laboratory (AFP, total hCG, LDH) and imaging assessment (scrotal ultrasound and chest, abdomen and pelvis computed tomography). Inguinal orchiectomy is the first line treatment allowing characterization of the histological type, local staging and identification of risk factors for micrometastases. The management of stage I tumors is based on surveillance or on a risk-adapted approach with explaining to the patient the benefits/disadvantages of active treatment or watchful waiting as a function of the risk of relapse. Treatment options for stage I seminomas comprise: surveillance, chemotherapy (1cycle of carboplatin) or para-aortic radiotherapy. Treatment options for stage I nonseminomatous germ cell tumours comprise: surveillance, chemotherapy (1cycle of BEP) or staging retroperitoneal lymphadenectomy. The management of metastatic tumors essentially comprises chemotherapy with 3, 4 cycles of BEP or dose-dense chemotherapy according to the IGCCCG. Radiotherapy may be indicated in seminomas with lymph node metastasis < 3cm. Review 3 to 4 weeks postchemotherapy is essentially based on tumor marker assays and chest, abdomen and pelvis computed tomography. Surgical retroperitoneal lymph node dissection is indicated for all residual NSGCT masses > 1cm and for persistent residual seminoma masses > 3cm with 18F- FDG PET- CT uptake. CONCLUSIONS: Good Germ cell tumors specific survival rates (99% CSI, 85% CSII, III) are based on precise initial staging, adapted and strictly defined treatment and close surveillance. © 2016 Elsevier Masson SAS. All rights reserved.

Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors.

BACKGROUND: The success of cisplatin-based (Platinol, Bristol-Myers Squibb Company, New York, NY, USA) chemotherapy for testicular cancer comes at the price of long-term and late effects related to healthy tissue damage. We assessed and modelled serum platinum (Pt) decay after chemotherapy and determined relationships between long-term circulating Pt levels and known late effects. PATIENTS AND METHODS: In 99 testicular cancer survivors, treated with cisplatin-based chemotherapy, serum and 24-h urine samples were collected during follow-up (1-13 years after treatment). To build a population pharmacokinetic model, measured Pt data were simultaneously analysed, together with cisplatin dose, age, weight and height using the NONMEM software. Based on this model, area under the curve between 1 and 3 years after treatment (Pt AUC1-3 years) was calculated for each patient. Predicted long-term Pt exposure was related to renal function and to late effects of treatment assessed median 9 (3-15) years after chemotherapy. RESULTS: Decay of Pt was best described by a two-compartment model. Mean terminal T1/2 was 3.7 (range 2.5-5.2) years. Pt AUC1-3 years correlated with cumulative cisplatin dose, and creatinine clearance before and 1 year after treatment. Patients with paraesthesia had higher Pt AUC1-3 years (30.9 versus 27.0 µg/l month) compared with those without paraesthesia (P = 0.021). Patients with hypogonadism, elevated LDL-cholesterol levels or hypertension also had higher Pt AUC1-3 years. CONCLUSIONS: Renal function before and after cisplatin treatment is an important determinant of long-term Pt exposure. Known long-term effects of testicular cancer treatment, such as paraesthesia, hypogonadism, hypercholesterolaemia and hypertension, are associated with long-term circulating Pt exposure.

Renal impairment and late toxicity in germ-cell cancer survivors.

BACKGROUND: Treatment with bleomycin-etoposide-cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ-cell cancer survivors. PATIENTS AND METHODS: BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. GFR were measured (51Cr-EDTA clearance) before and after treatment and at 1, 3 and 5-year follow-up. The influence of BEP on GFR was evaluated with a linear mixed model. Risk factors for late toxicity were identified by a landmark analysis adjusting for covariates. The cohort was compared with the background population with standardized hospitalization/mortality rates. RESULTS: GFR changed (ΔGFR) -11.3%, -15.4% and -25.9% after three, four and five+ cycles of BEP. For patients with impaired renal function before treatment the changes were 4.3%, 0.0% and -12.8%, respectively. During follow-up a significant rebound of GFR was documented. Compared with the background population, all patients, irrespective of renal function, had an increased risk of CVD and death. This risk depended on chronic kidney disease stage before treatment but not after treatment. ΔGFR had no influence on risk of late toxicity [death: hazard ratio (HR) 1.06, P = 0.50; CVD: HR 0.97, P = 0.61]. CONCLUSIONS: Renal function after BEP is closely related to number of cycles, but the changes in GFR are partly reversible and have no impact on risk of CVD or death.

Fertility-sparing approach to malignant ovarian germ cell tumors - Oncologic and obstetric outocome: A retrospective study.

OBJECTIVE: To evaluate oncologic (such as disease-free and overall survival) and obstetric outcomes in patients diagnosed with malignant ovarian germ cell tumors (MOGCTs). METHODS: Patients diagnosed with MOGCTs between March 2007 and February 2022 were evaluated and patients who underwent fertility sparing surgery were included in this retrospective study. The obstetric and oncologic outcomes were evaluated by collecting data up until the patient's last follow-up visit from the hospital records and patient files. The study was approved by Baskent University Institutional Review Board (KA23/124). RESULTS: Seventy FSS patients were included in this study. The median age of the patients was 22.5 years (range: 11-37). The median follow-up time was 92.0 months (10-189). Immature teratoma was the most common histological subtype (32.9%). Bilateral involvement was detected in only one patient with immature teratoma (1.4%). The 5-year DFS rates of immature teratoma, dysgerminoma, yolk sac, and mixed germ cell histologic types were 91.1%, 94.1%, 82.4%, and 88.9%, respectively (P: 0.716). The 5-year OS rates of the same histologic types were 95.7%, 100%, 88.2%, and 88.9%, respectively (P = 0.487). All patients (100%) had a regular menstrual cycle after the completion of adjuvant treatment. The mean time between the last chemotherapy and menstruation was 4.38 months. To date, a total of 34 patients tried to conceive after the completion of disease treatment. A total of 23 (67.6%) patients conceived, resulting in 27 live births in 22 (100%) patients. CONCLUSION: Fertility preservation should be the first treatment option in MOGCTs in young patients due to the unilateral involvement of the disease and its chemosensitive nature.