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1.
Zhonghua Fu Chan Ke Za Zhi ; 59(3): 210-214, 2024 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-38544450

RESUMEN

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 µg/L) were significantly higher than normal (<25 µg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.


Asunto(s)
Tumor del Seno Endodérmico , Neoplasias de Células Germinales y Embrionarias , Neoplasias Ováricas , Embarazo , Niño , Humanos , Femenino , Adulto Joven , Adulto , Adolescente , alfa-Fetoproteínas/uso terapéutico , Tumor del Seno Endodérmico/diagnóstico , Tumor del Seno Endodérmico/cirugía , Estudios Retrospectivos , Estadificación de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/cirugía , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/patología
2.
J Gynecol Oncol ; 35(2): e19, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37921603

RESUMEN

OBJECTIVE: To study clinical characters and outcomes in patients of malignant ovarian germ cell tumor (MOGCT) undergoing surgery following neoadjuvant chemotherapy (NACT). METHODS: Retrospective study of patients undergoing surgery following NACT for MOGCT at our institute. Platinum based chemotherapy was given in all patients in NACT. RESULTS: Between March 2013 and February 2023, 30 patients had surgery after NACT. Patient's median age was 22 years (range, 12 to 35 years) and median follow up 42months (range, 6 to 132 months). Majority had endodermal sinus tumor (n=12), dysgerminoma (n=9) and mixed GCT (n=7). All had either International Federation of Gynecology and Obstetrics (FIGO) stage 3 (n=19) or FIGO stage 4 disease (n=11). Complete response to NACT seen in 5 patients and 23 patients had partial response. Fertility sparing surgery in 18 patients and complete surgery in 12 patients. Suboptimal surgery was seen in 4 patients. Currently, 20 of 30 patients are alive and disease free, 3 lost for follow up and 7 patients had progression after adjuvant therapy. Five patients had mortality-4 with progression and 1 with bleomycin toxicity. Fifteen of 17 eligible patients have resumed menstruation and one had successful pregnancy. Prognostic factors noted in study are stage, optimal surgery and viable tumor in histopathology. Dysgerminoma had better outcome than other histology. CONCLUSION: NACT may be a reasonable option in patients with extensive unresectable disease or in whom fertility sparing is not possible or in the poor general condition. Fertility sparing surgery can be attempted post neoadjuvant chemotherapy without adversely affecting prognosis.


Asunto(s)
Disgerminoma , Neoplasias de Células Germinales y Embrionarias , Neoplasias Ováricas , Embarazo , Femenino , Humanos , Adulto Joven , Adulto , Terapia Neoadyuvante , Disgerminoma/tratamiento farmacológico , Disgerminoma/etiología , Disgerminoma/patología , Estudios Retrospectivos , Quimioterapia Adyuvante/efectos adversos , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/patología
3.
Cancer ; 129(24): 3952-3961, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37715631

RESUMEN

BACKGROUND: High-dose carboplatin is an essential part of curative high-dose chemotherapy (HDCT) for patients with previously treated germ cell tumors (GCTs). Although hearing loss (HL) is a known side effect of HDCT, data on its severity and characteristics are limited. METHODS: Eligible patients received HDCT for GCTs from 1993 to 2017 and had audiograms before and after HDCT. HL severity was classified by American Speech-Language-Hearing Association criteria, and mean change in hearing threshold at each frequency (0.25-8 kHz) was estimated from pre- to post-HDCT and between HDCT cycles. RESULTS: Of 115 patients (median age, 32 years), 102 (89%) received three cycles of HDCT. Of 106 patients with normal hearing to mild HL in the speech frequencies (0.5-4 kHz) before HDCT, 70 (66%) developed moderate to profound HL in the speech frequencies after HDCT. Twenty-five patients (22%) were recommended for hearing aids after HDCT. Patients with moderate to profound HL isolated to the higher frequencies (6-8 kHz) before HDCT were more likely to develop moderate to profound HL in the speech frequencies after HDCT (94% vs. 61%; p = .01) and to be recommended for hearing aids (39% vs. 18%; p = .05). CONCLUSIONS: HL was frequent after HDCT for GCTs, with most patients developing at least moderate HL in the speech frequencies and approximately one in five recommended for hearing aids. Moderate to profound HL isolated to high frequencies at baseline was predictive of more clinically significant hearing impairment after HDCT. PLAIN LANGUAGE SUMMARY: Some patients with germ cell tumors, the most common malignancy in adolescent and young adult men, are not cured with standard-dose chemotherapy and require high-dose chemotherapy (HDCT). Using detailed hearing assessments of patients receiving HDCT, we found that most patients developed significant hearing loss and that one in five needed hearing aids. Thus, strategies to reduce this side effect are urgently needed, and all patients receiving HDCT should have a hearing test after therapy.


Asunto(s)
Pérdida Auditiva , Neoplasias de Células Germinales y Embrionarias , Ototoxicidad , Masculino , Adolescente , Adulto Joven , Humanos , Adulto , Carboplatino/efectos adversos , Ototoxicidad/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/etiología , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/epidemiología
4.
Occup Environ Med ; 80(7): 407-417, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37230752

RESUMEN

OBJECTIVE: Testicular germ cell tumours (TGCT) are the most common cancer in men of working age and its incidence has increased notably over the past 40 years. Several occupations have been identified as potentially associated with TGCT risk. The aim of this study was to further explore the relationship between occupations, industries and TGCT risk in men aged 18-45 years. METHODS: The TESTIS study is a multicenter case-control study conducted between January 2015 and April 2018 in 20 of 23 university hospital centers in metropolitan France. A total of 454 TGCT cases and 670 controls were included. Full job histories were collected. Occupations were coded according to the International Standard Classification of Occupation 1968 version (ISCO-1968) and industry according to the 1999 version of Nomenclature d'Activités Française (NAF-1999). For each job held, ORs and 95% CIs were estimated using conditional logistic regression. RESULTS: A positive association was observed between TGCT and occupation as agricultural, animal husbandry worker (ISCO: 6-2; OR 1.71; 95% CI (1.02 to 2.82)), as well as salesman (ISCO: 4-51; OR 1.84; 95% CI (1.20 to 2.82)). An increased risk was further observed among electrical fitters and related, electrical and electronics workers employed for 2 years or more (ISCO: 8-5; OR≥2 years 1.83; 95% CI (1.01 to 3.32)). Analyses by industry supported these findings. CONCLUSIONS: Our findings suggest that agricultural, electrical and electronics workers, and salesmen workers experience an increased risk of TGCT. Further research is needed to identify the agents or chemicals in these high-risk occupations which are relevant in the TGCT development. TRIAL REGISTRATION NUMBER: NCT02109926.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Estudios de Casos y Controles , Ocupaciones , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/etiología , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/etiología , Factores de Riesgo
5.
Clin Adv Hematol Oncol ; 21(4): 179-188, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37039725

RESUMEN

Over the past half century, advancements in treatment have led to cures in an overwhelming majority of patients with testicular germ cell tumors. Astute clinical decision-making, informed by the abundant data from published clinical trials, is essential for achieving a cure whenever possible and minimizing the toxicity of treatment. Important remaining challenges include reducing the risk of secondary malignancies and other late effects of chemotherapy and radiation therapy, and developing curative treatments for patients with cancer that is refractory to current therapies. This article reviews the current treatment landscape and highlights recent discoveries in diagnosis and staging, emerging biomarkers for disease, and treatment for relapsed/refractory disease. Treatment algorithms for testis cancer are complex and clinicians should apply them carefully, not only to optimize shortterm, disease-related outcomes, but also to maximize long-term survival and quality of life.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Testiculares/patología , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/etiología
6.
Occup Environ Med ; 80(6): 312-318, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36972976

RESUMEN

OBJECTIVES: Testicular germ cell tumours (TGCTs) are the most commonly diagnosed malignancy among active duty US military servicemen. Occupational risk factors may play a role in TGCT aetiology, although the evidence is inconclusive. The objective of our study was to investigate associations between military occupations and TGCT risk among US Air Force (USAF) servicemen. METHODS: This nested case-control study among active duty USAF servicemen obtained information on military occupations for 530 histologically confirmed TGCT cases diagnosed during 1990-2018 and 530 individually matched controls. We determined military occupations using Air Force Specialty Codes ascertained at two time points: at case diagnosis and at a time point on average 6 years earlier. We computed adjusted ORs and 95% CIs from conditional logistic regression models to evaluate associations between occupations and TGCT risk. RESULTS: The mean age at TGCT diagnosis was 30 years. Increased TGCT risk was observed for pilots (OR=2.84, 95% CI: 1.20-6.74) and servicemen with aircraft maintenance jobs (OR=1.85, 95% CI: 1.03-3.31) who held those jobs at both time points. Fighter pilots (n=18) and servicemen with firefighting jobs (n=18) at the time of case diagnosis had suggestively elevated TGCT odds (OR=2.73, 95% CI: 0.96-7.72 and OR=1.94, 95% CI: 0.72-5.20, respectively). CONCLUSIONS: In this matched, nested case-control study of young active duty USAF servicemen, we found that pilots and men with aircraft maintenance jobs had elevated TGCT risk. Further research is needed to elucidate specific occupational exposures underlying these associations.


Asunto(s)
Personal Militar , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Adulto , Estudios de Casos y Controles , Ocupaciones , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/etiología , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/complicaciones , Factores de Riesgo
7.
Tumori ; 109(4): 379-386, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35915559

RESUMEN

INTRODUCTION: Patients with stage II germ-cell tumours (GCT) usually undergo radiotherapy (seminoma only) or chemotherapy. Both strategies display a recognised risk of long-term side effects. We evaluated retroperitoneal lymph node dissection (RPLND) as exclusive treatment in stage II GCT. METHODS: Between 2008 and 2019 included, 66 selected stage II GCT patients underwent primary open (O-) or laparoscopic (L-)RPLND. Type of procedure and extent of dissection, operative time, node rescue, hospital stay, complications (according to Clavien-Dindo), administration of chemotherapy, relapse and site of relapse were evaluated. RESULTS: Five patients had pure testicular seminoma. Nineteen (28.8%) had raised markers prior to RPLND; 48 (72.7%), 16 (24.2%) and two (3.0%) were stage IIA, IIB and IIC, respectively. O-RPLND and unilateral L-RPLND were 36 and 30 respectively. Six stage II A patients (12.5%) had negative nodes. Four patients underwent immediate adjuvant chemotherapy. One patient was lost at follow-up. After a median follow-up of 29 months, 48 (77.4%) of the 62 patients undergoing RPLND alone remained recurrence-free; one patient had an in-field recurrence following a bilateral dissection. According to procedure, number of rescued nodes (O-RPLND: 25. IQR 21-31; L-RPLND: 20, IQR 15-26; p: 0.001), hospital stay (L-RPLND: 3 days, IQR 3-4; O-RPLND: 6 days, IQR 5-8; p: .001) and grade ≥2 complications (L-RPLND 7%, O-RPLND 22%; p: 0.1) were the only significant differences. CONCLUSION: Primary RPLND is safe in stage II GCT, including seminoma, and may warrant a cure rate greater than 70%. When feasible, L-RPLND may be as effective as O-RPLND with better tolerability.


Asunto(s)
Laparoscopía , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Seminoma/patología , Neoplasias Testiculares/radioterapia , Neoplasias Testiculares/cirugía , Neoplasias Testiculares/tratamiento farmacológico , Resultado del Tratamiento , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Escisión del Ganglio Linfático/métodos , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/patología , Laparoscopía/efectos adversos , Laparoscopía/métodos , Espacio Retroperitoneal/patología , Espacio Retroperitoneal/cirugía , Estadificación de Neoplasias
8.
Pediatr Blood Cancer ; 69(9): e29697, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35373903

RESUMEN

PURPOSE: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT). METHODS AND MATERIALS: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children's Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40). RESULTS: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. CONCLUSIONS: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Terapia de Protones , Radioterapia de Intensidad Modulada , Niño , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/radioterapia , Órganos en Riesgo , Fotones/uso terapéutico , Terapia de Protones/métodos , Protones , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias Testiculares
9.
Int Arch Occup Environ Health ; 95(6): 1243-1253, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34853884

RESUMEN

OBJECTIVE: We assessed the association between parental prenatal exposures in wood-related jobs and risk of testicular germ cell tumours (TGCT) in offspring. METHODS: NORD-TEST, a registry-based case-control study in Sweden, Finland and Norway, included 8112 TGCT cases diagnosed at ages 14-49 years between 1978 and 2012 with no history of prior cancer, and up to four controls matched to each case on year and country of birth. Parents of cases and controls were identified via linkages with the population registries and their occupational information was retrieved from censuses. The Nordic Occupational Cancer Study Job-Exposure Matrix was used to assign occupational exposures to each parent. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Maternal wood-related job was not associated with the risk of TGCT in offspring (OR 1.08, CI 0.55-2.14), while paternal wood-related job was associated with a decreased risk of TGCT in offspring (OR 0.85, CI 0.75-0.96). None of the specific wood-related jobs, such as upholsterers, sawyers, or construction carpenters, were significantly associated with a risk of TGCT. Only exception was observed in a sensitivity analysis which showed an increased risk in the small group of sons of fathers working as 'cabinetmakers and joiners' the year before conception (OR of 2.06, CI 1.00-4.25). CONCLUSION: This large-scale NORD-TEST analysis provided no evidence of an association between parental prenatal exposures in wood-related jobs and TGCT in sons.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Exposición Profesional , Neoplasias Testiculares , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Finlandia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/etiología , Noruega/epidemiología , Exposición Profesional/efectos adversos , Embarazo , Sistema de Registros , Factores de Riesgo , Suecia/epidemiología , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/etiología , Madera , Adulto Joven
10.
Cancer ; 127(20): 3751-3760, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34260067

RESUMEN

BACKGROUND: High-dose chemotherapy (HDCT) plus peripheral blood stem cell transplantation (PBSCT) is effective salvage therapy for relapsed metastatic germ cell tumors (GCTs) but has potential toxicity. Historically, an age of ≥40 years has been associated with greater toxicity and worse outcomes. METHODS: This is a retrospective analysis of 445 consecutive patients with relapsed GCT treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen. Kaplan-Meier methods and log-rank tests were used for progression-free survival (PFS) and overall survival (OS) analysis. RESULTS: A total of 329 patients were <40 years of age, whereas 116 patients were ≥40 years of age; HDCT was used as second-line therapy in 85% and 79%, respectively. Median follow-up time was 42.5 months (range, 0.3-173.4 months). Grade ≥3 toxicities were similar between either group, except for greater pulmonary (P = .02) and renal toxicity (P = .01) in the ≥40-years-of-age group. Treatment-related mortality was similar between both age groups: 10 patients (3%) in the <40-years-of-age group and 4 patients (3.5%) in ≥40-years-of-age group died from complications of HDCT. Two-year PFS for <40 years of age versus ≥40 years of age was 58.7% versus 59.6% (P = .76) and 2-year OS was 63.9% versus 61.5% (P = .93). Factors predicting worse PFS included Eastern Cooperative Oncology Group performance status ≥1, platinum refractory disease, nonseminoma histology, and not completing 2 cycles of HDCT. Age was not an independent predictor of worse outcomes. CONCLUSIONS: HDCT plus PBSCT is effective salvage therapy in patients ≥40 years of age with relapsed metastatic GCT. Patients ≥40 years of age experience similar rates of toxicity and treatment-related mortality as those <40 years of age.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Trasplante de Células Madre de Sangre Periférica , Neoplasias Testiculares , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Etopósido , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/etiología , Estudios Retrospectivos , Terapia Recuperativa , Trasplante de Células Madre , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/etiología
11.
Clin Appl Thromb Hemost ; 27: 10760296211024756, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34121471

RESUMEN

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher (P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias Testiculares/etiología , Tromboembolia Venosa/complicaciones , Adolescente , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/patología , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Testiculares/patología , Adulto Joven
12.
Neoplasia ; 23(7): 731-742, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34153645

RESUMEN

Germ cell neoplasia in situ (GCNIS) is the noninvasive precursor of testicular germ cell tumors type II, the most common cancer in young men, which originates from embryonic germ cells blocked in their maturation. GCNIS is associated with impaired Sertoli cells (SCs) that express fetal keratin 18 (KRT18) and the pluripotency factor SRY-Box transcription factor 2 (SOX2). According to the current theory concerning the origin of GCNIS, these SCs are prepubertal cells arrested in their maturation due to (epi)genetic anomalies and/or environmental antiandrogens. Thus, they are unable to support the development of germ cells, which leads to their maturational block and further progresses into GCNIS. Alternatively, these SCs are hypothesized to be adult cells dedifferentiating secondarily under the influence of GCNIS. To examine whether tumor cells can dedifferentiate SCs, we established a coculture model of adult human SCs (FS1) and a seminoma cell line similar to GCNIS (TCam-2). After 2 wk of coculture, FS1 cells showed progressive expression of KRT18 and SOX2, mimicking the in vivo changes. TCam-2 cells showed SOX2 expression and upregulation of further pluripotency- and reprogramming-associated genes, suggesting a seminoma to embryonal carcinoma transition. Thus, our FS1/TCam-2 coculture model is a valuable tool for investigating interactions between SCs and seminoma cells. Our immunohistochemical and ultrastructural studies of human testicular biopsies with varying degrees of GCNIS compared to biopsies from fetuses, patients with androgen insensitivity syndrome, and patients showing normal spermatogenesis further suggest that GCNIS-associated SCs represent adult cells undergoing progressive dedifferentiation.


Asunto(s)
Carcinoma in Situ/etiología , Carcinoma in Situ/patología , Susceptibilidad a Enfermedades , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/patología , Biomarcadores de Tumor , Carcinoma in Situ/metabolismo , Comunicación Celular , Desdiferenciación Celular/genética , Línea Celular Tumoral , Transformación Celular Neoplásica , Regulación de la Expresión Génica , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/metabolismo , Seminoma/etiología , Seminoma/metabolismo , Seminoma/patología , Células de Sertoli/metabolismo , Células de Sertoli/patología , Células de Sertoli/ultraestructura
14.
Transplant Proc ; 53(4): 1345-1349, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33384179

RESUMEN

Transplantation of any organ has some inherent risk of disease transmission, such as infection and malignancy. The present study aims to describe 2 cases of choriocarcinoma transmission after kidney and liver transplantation originating from the same patient. The donor was a 17-year-old woman who died of cerebral hemorrhage. Both organ recipients died of metastatic choriocarcinoma few months after the transplantation, within days after starting chemotherapy. Retrospective hCG (human chorionic gonadotropin hormone) analysis in donor's blood stored at the time of donation had a result of 9324 mIU/mL. Despite its rarity, clinicians should be aware of the risk of transplant-related choriocarcinoma from female donors in childbearing age. In some cases, hCG dosage should be performed before donation.


Asunto(s)
Coriocarcinoma/diagnóstico , Trasplante de Riñón/efectos adversos , Neoplasias Hepáticas/diagnóstico , Trasplante de Hígado/efectos adversos , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Adolescente , Adulto , Anciano , Antineoplásicos/uso terapéutico , Hemorragia Cerebral/patología , Coriocarcinoma/tratamiento farmacológico , Coriocarcinoma/etiología , Gonadotropina Coriónica/sangre , Femenino , Humanos , Cirrosis Hepática/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Masculino , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/etiología , Insuficiencia Renal Crónica/cirugía , Donantes de Tejidos , Trasplante Homólogo
15.
Methods Mol Biol ; 2195: 147-165, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32852763

RESUMEN

Testicular germ cell tumors (TGCTs) are among the most curable solid cancers and are typically highly responsive to conventional DNA-damaging chemotherapies, even in patients with metastatic disease. It has therefore been of great interest to understand the basis for the unique chemosensitivity of these cancers, which is linked to the DNA damage sensitivity of their cancer stem cells. TGCTs have been difficult to study in the mouse, however, since most of the existing mouse models develop benign teratomas that are unlike the malignant TGCTs that afflict most testicular cancer patients. We describe here methods for generating a TGCT mouse model that closely resembles the malignant, metastatic disease observed in men with testicular cancer, and additionally include methods for analyzing the cancer stems cells and responses to chemotherapeutics in these murine TGCTs.


Asunto(s)
Modelos Animales de Enfermedad , Ratones Transgénicos , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Testiculares/etiología , Neoplasias Testiculares/patología , Alelos , Animales , Antineoplásicos/farmacología , Biomarcadores de Tumor , Cruzamiento , Línea Celular Tumoral , Ingeniería Genética , Genotipo , Humanos , Masculino , Ratones , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Methods Mol Biol ; 2195: 181-187, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32852765

RESUMEN

Somatic analysis of the molecular features of human tumors through numerous efforts including The Cancer Genome Atlas consortium has led to unprecedented insight into the biological basis of cancer behavior. Numerous genomewide sequencing techniques have been utilized in these studies to understand DNA mutations, epigenomic alterations, and ultimately differences in protein expression profiles across various cancers. Due to the dropping costs of next-generation sequencing as well as growing power and ease of use of computational resources, researchers are able to apply these techniques to more specific cancer contexts and/or rarer tumor types. In this chapter, we describe the rationale for and details of methods used in our group for exome analysis of germ cell tumors. The methods described should also be readily applicable to genomic analysis of other tumors.


Asunto(s)
Susceptibilidad a Enfermedades , Genómica , Neoplasias de Células Germinales y Embrionarias/etiología , Análisis de Datos , Bases de Datos Genéticas , Dosificación de Gen , Perfilación de la Expresión Génica , Biblioteca de Genes , Predisposición Genética a la Enfermedad , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de Células Germinales y Embrionarias/patología , Control de Calidad , Análisis de Secuencia de ADN , Transcriptoma
17.
Methods Mol Biol ; 2195: 245-261, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32852768

RESUMEN

While the majority of patients with advanced testicular germ cell tumors (GCT) achieve complete responses after chemotherapy and if indicated after postchemotherapy resection of residual lesions, about 20% of patients have incomplete responses or show relapses. Moreover, toxicity of chemotherapy is high, and severe adverse chronic effects have been described. Therefore, there is an urgent need for biomarkers that could help to improve tumor staging, and support decision-making, ideally including monitoring of therapy response and prediction of relapse. Besides the well-established serum markers lactate dehydrogenase, α-fetoprotein, and ß-subunit of human chorionic gonadotropin, during recent years new noninvasive liquid biopsy markers have been investigated in GCT, including cell-free nucleic acids like microRNAs, and circulating tumor cells (CTCs).Prognostic relevance has been demonstrated for circulating tumor cells (CTCs) in patients with different cancers. However, little is known in GCT patients. Histologically, GCT are a very heterogeneous group of tumors comprising pure seminomas (consisting of cells that remember primordial germ cells) and nonseminomas, which are either undifferentiated (embryonal carcinoma) or differentiated, exhibiting different degrees of embryonic (teratoma) or extraembryonic (yolk sac tumor and choriocarcinoma) differentiation. This heterogeneity hampers capture and detection of CTCs deriving from those tumors using a single method or a single antibody. To date, label-independent capture methods that enrich tumor cells according to the density of GCT cells, which is similar to that of mononuclear cells, have been successfully applied. Since testicular GCT might also express epithelial proteins, methods based on enrichment of CTCs using epithelial markers are promising to detect CTCs in certain subgroups of patients with GCTs as well.Here, we describe and discuss a combination of methods to capture and detect GCT cells with epithelial and germ cell characteristics in blood.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/etiología , Células Neoplásicas Circulantes/patología , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/etiología , Línea Celular Tumoral , Separación Celular/métodos , Células Cultivadas , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Biopsia Líquida , Masculino , Técnicas de Diagnóstico Molecular , Células Neoplásicas Circulantes/metabolismo , Pronóstico
18.
Methods Mol Biol ; 2195: 263-275, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32852769

RESUMEN

Germ cell tumors (GCTs) are a rare disease, but they account for 15% of all malignancies diagnosed during adolescence. The biological mechanisms underpinning their development are only starting to be explored. Current GCT treatment may be associated with significant toxicity. Therefore, there is an urgent need to understand the molecular basis of GCT and identify biomarkers to tailor the therapy for individual patients. However, this research is severely hamstrung by the rarity of GCTs in individual hospitals/institutes. A publicly available genomic data commons with GCT datasets compiled from different institutes/studies would be a valuable resource to facilitate such research. In this study, we first reviewed publicly available web portals containing GCT genomics data, focusing on comparing data availability, data access, and analysis tools, and the limitations of using these resources for GCT molecular studies. Next, we specifically designed a GCT data commons with a web portal, GCT Explorer, to assist the research community to store, manage, search, share, and analyze data. The goal of this work is to facilitate GCT molecular basis exploration and translational research.


Asunto(s)
Biología Computacional , Bases de Datos Genéticas , Susceptibilidad a Enfermedades , Neoplasias de Células Germinales y Embrionarias/etiología , Biología Computacional/métodos , Seguridad Computacional , Estudios de Asociación Genética/métodos , Genoma , Genómica/métodos , Humanos , Neoplasias de Células Germinales y Embrionarias/metabolismo , Neoplasias de Células Germinales y Embrionarias/patología , Fenotipo , Interfaz Usuario-Computador , Navegador Web
19.
Methods Mol Biol ; 2195: 13-29, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32852754

RESUMEN

Germ cell tumors (GCT) in men comprise of tumor subtypes with distinct histomorphologies, genetic and genomic alterations, and clinical behavior. Immunohistochemical (IHC) markers, including many newly described nuclear transcription factors, are often applied in challenging cases to arrive at a correct diagnosis and classification, and to establish germ cell origin for metastatic tumors. However, there is no established role for IHC markers in prognosis and therapy response prediction in GCTs. This chapter briefly reviews the clinical utility of IHC in diagnosis and classification of GCTs, including technical aspects of performing IHC and clinical applications of commonly used IHC markers in the workup of common and clinically relevant diagnostic scenarios.


Asunto(s)
Inmunohistoquímica , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Biomarcadores de Tumor , Toma de Decisiones Clínicas , Diagnóstico Diferencial , Manejo de la Enfermedad , Humanos , Inmunohistoquímica/métodos , Masculino , Neoplasias de Células Germinales y Embrionarias/etiología , Pronóstico , Factores Sexuales
20.
Methods Mol Biol ; 2195: 31-47, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32852755

RESUMEN

Testicular germ cell tumors are among the most common malignancies seen in children and young adults. Genomic studies have identified characteristic molecular profiles in testicular cancer, which are associated with histologic subtypes and may predict clinical behavior including treatment responses. Emerging molecular technologies analyzing tumor genomics, transcriptomics, and proteomics may now guide precision management of testicular tumors. Laser-assisted microdissection methods such as laser capture microdissection efficiently isolate selected tumor cells from routine pathology specimens, avoiding contamination from nontarget cell populations. Laser capture microdissection in combination with next generation sequencing makes precise high throughput genetic evaluation effective and efficient. The use of laser capture microdissection (LCM) for molecular testing may translate into great benefits for the clinical management of patients with testicular cancers. This review discusses application protocols for laser-assisted microdissection to investigate testicular germ cell tumors.


Asunto(s)
Biomarcadores de Tumor , Microdisección , Técnicas de Diagnóstico Molecular , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/etiología , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/etiología , Toma de Decisiones Clínicas , Diagnóstico Diferencial , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Inmunohistoquímica/instrumentación , Inmunohistoquímica/métodos , Masculino , Microdisección/instrumentación , Microdisección/métodos , Técnicas de Diagnóstico Molecular/métodos
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