A 28-Year-Old Man With Mediastinal Seminoma Treated With BEP

Highlight:A 28-year-old male suffered chylothorax and mediastinal seminoma.The patient received bleomycin, etoposide and cisplatin chemotherapy for the management of mediastinal seminomas but he died beforeundergoing 5th cycle chemotherapy. Abstract:Seminoma is a type of germ cell tumor. In this case presentation, a rare primary germ cell tumor was reported in the form of mediastinal seminoma. A 28-year-old man with symptoms of shortness of breath, chest pain, swelling in the right upper extremity, enlarged lymph nodes in the colli region. Thoracic physical examination revealed signs of pleural fluid in the right hemithorax. After obtaining the results of radiological and pathological investigations, a mediastinal mass was obtained, then BEP chemotherapy was given. After 3 cycles of chemotherapy, a partial response was obtained. Patients with mediastinal seminoma treated with BEP base chemotherapy gave a partial response.

Unusual Cases of Pure Malignant Germ Cell Tumors of the Ovary: A Case Series on 10 Years Experience at a Tertiary Care Center

Background: Malignant ovarian germ cell tumors (MOGCTs) are rare female cancers, constituting up to 10% of ovarian cancers. Dysgerminoma is the most common histological variant. Surgical removal of the tumor with optimal debulking is the treatment of choice. Multidrug chemotherapy following surgery offers high remission rates. Considering the prevalence of these tumors in adolescent and young females, fertility-sparing treatment is of paramount importance. Methods: The data of all patients with ovarian malignancy admitted at a tertiary-care-teaching hospital from September 2009-March 2019 were analyzed. Ten patients of MOGCTs were treated in this period. The clinical features, radiological and biochemical findings, and management and treatment outcome were evaluated. Results: The median age of patients was 23 years. Histological subtypes included immature teratoma (n=3), endodermal sinus tumor (n=4), and dysgerminoma (n=3). Tumor markers namely AFP, βHCG, and LDH increased in all except the patients with immature teratoma. Two patients with dysgerminoma were in the second trimester of pregnancy. All patients except one underwent surgery followed by BEP chemotherapy. Two patients had developed metastasis within six months of treatment and died. In seven patients, no evidence of disease was reported till date. Conclusion: Management of antenatal patients with dysgerminoma by surgery followed by BEP chemotherapy has favorable prognosis. Fertility-sparing surgery with adjuvant chemotherapy offers great advantage in young girls. However, risk stratification based on prognostic factors should be implemented in order to individualize the treatment for achieving higher survival rates. The option for oocyte-cryopreser-vation prior to surgery must be discussed with patients desiring future fertlity.

P–061 Protective effect of melatonin against bleomycin, etoposide, and cisplatin (BEP) chemotherapy-induced testicular toxicity in Wistar rats: A biochemical, immunohistochemical and apoptotic genes based evidence

Study question Does exogenous melatonin (MLT) attenuate BEP-induced damage in testicular cells and spermatogenesis in a dose-dependent manner? Summary answer Melatonin protected the testes against BEP-induced testis damage through ameliorating nitro-oxidative stress, apoptosis, and inflammation. However, there was no significant difference between melatonin-treated groups. What is known already Recently, the prevalence of testicular cancer (TC), accounting for the most common cancer among young people of reproductive age (15–40 years), has risen internationally. BEP chemotherapy has increased the 5-year survival rate of TC patients at all stages of testicular germ cell tumors to 90–95%. However, BEP creates a high incidence of male infertility and even long-term genotoxic effects, which emerges as a critical health issue. Melatonin is a well-known potent antioxidant with widespread clinical applications that recently has been giving increasing attention to its role in male sub/infertility. Study design, size, duration 60 Adult male Wistar rats were randomly assigned to six groups (n = 10/group). Group 1, 3, and 4 were injected with vehicle, 10 and 20 mg/kg of melatonin, respectively. Other groups received one cycle of bleomycin, etoposide, and cisplatin for a total of 3 weeks with or without melatonin. Melatonin administration started daily one week before BEP initiation continued on days 2, 9, and 16; and one week after the completion of the BEP cycle. Participants/materials, setting, methods Bodyweight, testes weight, Sperm parameters (count, motility, viability, and morphology), testosterone hormone level, testicular histopathology, stereological parameters, testicular level of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), the expression of Bcl–2, Bax, Caspase–3, p53, and TNF-α (Real-time PCR and immunohistochemistry) were evaluated at the end of the study (day 35). Main results and the role of chance Our findings showed that melatonin restores the BEP-induced reduction in the body and testes weight (P<.05). the evaluation of quantitative analysis of the testes stereological procedures, QRT-PCR examination and immunohistochemical (IHC) staining revealed that melatonin reverses the BEP-induced impaired spermatogenesis (P<.05). Furthermore, melatonin rectifies BEP-induced disturbance on sperm count, motility, viability, and morphology. The testosterone level in the BEP-treated group was decreased significantly by comparison with the control group (P<.01). By contrast, co-administration of 10 and 20 mg/kg of melatonin could enhance the serum testosterone level significantly (P<.05). Moreover, melatonin enhanced the antioxidant status of the testis by elevating TAC and ameliorating MDA and NO levels. More notably, QRT-PCR examination indicated that melatonin therapy suppressed BEP-induced apoptosis by modulating apoptosis-associated genes such as Bcl–2, Bax, Caspase–3, p53 in the testis (P<.01). Besides, Co-administration of 10 and 20 mg/kg of melatonin with BEP regimen decreased significantly the population of p53 (54.21 ±6.18% and 51.83±8.45, respectively) and TNF-α positive cells (42.91±9.92% and 33.57±2.97, respectively) by comparison to the BEP group. Also, melatonin with low and high doses could enhance the expression of Bcl–2 protein in spermatogenic cells line (59.19±10.18%, 63.08±5.23, respectively) compared to the BEP-treated group. Limitations, reasons for caution Owing to limited laboratory facilities we were not able to perform further studies to verify the mechanism of melatonin in the specific targets by using transfection technique and transgenic. Wider implications of the findings: These findings can draw attention to the clinical application of melatonin and also suggest that melatonin may be an attractive agent for attenuating chemotherapy-associated male sub/infertility. This indolamine also may shorten the fertility recovery period in patients undergoing chemotherapy with the BEP regimen. Trial registration number N/A

Real-World Study of Cisplatin, Etoposide, and Bleomycin Chemotherapy Regimen in Gestational Trophoblastic Neoplasia

Objective. Little observational data exist regarding the use of cisplatin, etoposide, and bleomycin (BEP) chemotherapy regimen in patients with gestational trophoblastic neoplasia (GTN). Methods. This is a retrospective study of 95 patients with GTN in our center from June/2010 to June/2018. All patients received at least 2 cycles of BEP chemotherapy. The primary outcomes were the rate of complete remission (CR) and overall survival (OS). The secondary outcomes were disease-free survival (DFS), pregnancy rates after BEP exposure, drug resistance rate, and other adverse events. Results. Of the 95 patients included, 66 (69.5%) patients received BEP as primary treatment and 29 (30.5%) were Salvage chemotherapy. The median age at diagnosis was 37 years (range 29.75-46) and 34 years (range 27-40) in two groups, respectively. The median WHO prognostic scores were 6 (range 3.5-8), and 77.32% of patients were FIGO stage III-IV in the primary treatment group. The median WHO prognostic scores were 5 (range 3-9), and 66.55% of patients were FIGO stage III-IV in the salvage treatment group. Median cycles of BEP treatment were 4 (3, 5) and 3 (2, 4) in two groups, respectively. In the primary chemotherapy group, 18.2% received additional hysterectomy, 4.5% received UAE for vaginal bleeding, and 1.52% received whole-brain radiotherapy. In the salvage chemotherapy group, 20.7% received hysterectomy, 6.9% received lobectomy, 3.4% received hysteroscopic lesion resection, and 3.4% received whole-brain radiotherapy. CR rates to initial chemotherapy were 86.4%, including 87.9% in the primary chemotherapy group and 82.8% in the salvage chemotherapy group. No predictive factor of chemotherapy resistance was identified. The rate of 5 year-DFS was 96.52% (95% CI 86.78–99.12) in the primary chemotherapy group and 92.44% (95% CI 73.02-98.06) in the salvage chemotherapy group. The rate of 5 year-OS was 98.31% (95% CI 88.57–99.76) and 95.65% (95% CI 79.93-99.38) in the two groups, respectively. During the treatment, neutropenia, thrombocytopenia, anemia, and liver dysfunction occurred in 80.3%, 6.1%, 25.8%, and 50% primary chemotherapy patients and 82.8%, 31%, 10.3%, and 86.2% salvage chemotherapy patients. In patients with fertility requirements, live birth rates were 100% (10/10) in primary chemotherapy patients and 80% (4/5) in salvage chemotherapy patients. Conclusions. BEP regimen was effective in the treatment of GTINs. The treatment was well tolerated, with no safety concerns on patients’ fertility.

Myeloablative chemotherapy in testicular cancer patient

Chemotherapy is the standard treatment for metastatic testicular cancers. The autologous hematopoietic stem cell transplantation is a salvage option for relapsed patients. The paper presents a case of a 20-year-old patient with stage IIIC non-seminoma treated with BEP chemotherapy and autologous transplantation of stem cells, which allowed to achieve durable remission.

Sertoli-Leydig Cell Ovarian Tumors: Is Fertility or Endocrine-Sparing Surgery an Option upon Relapse?

Sertoli-Leydig cell ovarian tumors (SLCT) are rare ovarian tumors of the sex cord-stroma subset. Their incidence peaks in the second to third decade of life. Most SCLT are diagnosed at an early stage and have a good prognosis. Fertility-sparing surgery may thus be offered. Adjuvant chemotherapy may be indicated according to prognostic factors. However, outcome in relapsing SLCT is poor. There is no evidence supporting a best treatment option upon relapse, but most publications combine radical surgery, chemotherapy, and rarely radiotherapy. Two years after left adnexectomy for FIGO IA SLCT, a now 22-year-old patient presented with peritoneal recurrence without involvement of the remaining ovary and uterus. Since there is no evidence of a survival benefit in the literature of macroscopically healthy contralateral ovary ablation in relapse and hormonal replacement therapy is contraindicative, we consented to endocrine-sparing surgery with conservation of the contralateral ovary, followed by 3 cycles of BEP chemotherapy regimen. Our patient is disease-free 16 months after relapse diagnosis. Since recurrence of SLCT has a very poor prognosis and hormonal treatment is contraindicated, endocrine-sparing surgery for young patients with a normal contralateral ovary might be a legitimate option. This is one of the first reported cases of conservative surgery in SLCT recurrence, we therefore aimed to illustrate its management in a young patient with considerations of contraception, fertility- and then endocrine-sparing surgery, and quality of life.

Effect of Bleomycin, Etoposide, and Cisplatin Treatment on Spermatogonia Cell and Malondialdehyde Level in Male Rats

Co-administration of bleomycin, etoposide, and cisplatin (BEP) becomes standart chemotherapy for testicular cancer because it has brought a cure rate of more than 90%. Impact of the treatment to the outcome become a concern, particularly the adverse effect on a long-term reproductive health risk to cancer survivors. There is no evidence, when the damage to the testes began due to the administration of BEP chemotherapy, makes the indication of treatment still controversial. The aim of this study is to determine the effects of BEP on Spermatogonial cell and MDA levels outcome in an animal model. Male wistar rats (Rattus norvegicus) aged 13-15 weekswere treated daily with BEP for three cycles, 33 hours each. It was divided into one control group received 1cc of normal saline, and three groups received three cycles of 0.5 x dose-levels of BEP (Intraperitoneally; 0.75 mg/kg, 7.5 mg/kg, and 1.5 mg/kg). Cell number of Spermatogonia cells were calculated from HE-stained specimens and observed under light microscope (Olympus BX-51) using 400x magnification (high power field) Thiobarbituric acid (TBA) test method used to measure malondialdehyde (MDA) level by spectrophotometry. The result was a significant decrease in the average number of Spermatogonia cells (p = 0.003) between the control group and others. This is caused by excessive exposure to BEP chemotherapy, which cause atrophy of the seminiferous tubules and content of germ cells in the tubules has decreased, accompanied by the appearance of immature germ cells that enter the lumen. A significant increase in MDA levels (p = 0.001) occurred after the administration of the third cycle of BEP chemotherapy. In conclusion, BEP chemotherapy adversely affect the number of Spermatogonia cells and MDA level. The third cycle BEP chemotherapy significantly more destructive compared to the first and second cycle.

Ovarian Cancer Immature Teratoma Type in Pregnancy: Management and Feto-Maternal Outcomes

BACKGROUND: Immature teratoma is malignant ovarian germ cell tumours (MOGCTs). The case in pregnancy is very rare which less than 1% of all ovarian teratoma cases. The aim is to reach optimal and comprehensive management for immature ovarian teratoma in pregnancy to gain the healthiest maternal and fetal outcomes. CASE PRESENTATION: Thirty-one years old female G2P1A0, 8 weeks 1-day pregnancy, with left ovarian solid tumour 15 x 15 x 15 cm in size. At gestational age (GA) of 19 weeks 5 days, the size of the tumour was increasing rapidly to 30 x 30 x 30 cm. Alfa-fetoprotein raised to 699.9 IU/mL and LDH 579 U/L. The patient had gone primary conservative left oophorectomy, omentectomy, and ascites fluid cytology with histopathological conclusion grade II immature teratoma of left ovary containing the immature neuroepithelial and fat component: magnetic resonance imaging (MRI) at 25 weeks 3 days GA, no spreading. Amniocentesis performed at 27 weeks 2 days GA, the fetus had normal 46 chromosomes and sex XX without major structural abnormality. The patient had BEP chemotherapy start at 27 weeks 2 days GA. Patient in labour at 40 weeks 2 days GA. The female baby had spontaneous delivery with 2700 grams in body weight without congenital abnormality. Complete surgical staging performed at 58th days postpartum and histopathological result there was no malignant cell anymore, but post-chemotherapy ovarian atrophy feature had found on the contralateral ovary. The patient showed psychosocial problem including post-chemotherapy depression and premature ovarian failure (POF). Immunohistochemistry (IHC) ER and PR of teratoma tissue showed immature component had ER (-) and PR (+). Follow up of the baby was in good condition. CONCLUSION: BEP chemotherapy become regimen choice for this case with fetal outcomes was good, but there was a POF sign on the mother. Survival of patient on this case is 62%, free recurrence survival post-BEP 84% and progressivity post complete surgical staging 8% without delay the chemotherapy.