Cisplatin­resistant germ cell tumor models: An exploration of the epithelial­mesenchymal transition regulator SLUG.

Germ cell tumors (GCTs) constitute diverse neoplasms arising in the gonads or extragonadal locations. Testicular GCTs (TGCTs) are the predominant solid tumors in adolescents and young men. Despite cisplatin serving as the primary therapeutic intervention for TGCTs, 10­20% of patients with advanced disease demonstrate resistance to cisplatin­based chemotherapy, and epithelial­mesenchymal transition (EMT) is a potential contributor to this resistance. EMT is regulated by various factors, including the snail family transcriptional repressor 2 (SLUG) transcriptional factor, and, to the best of our knowledge, remains unexplored within TGCTs. Therefore, the present study investigated the EMT transcription factor SLUG in TGCTs. In silico analyses were performed to investigate the expression of EMT markers in TGCTs. In addition, a cisplatin­resistant model for TGCTs was developed using the NTERA­2 cell line, and a mouse model was also established. Subsequently, EMT was assessed both in vitro and in vivo within the cisplatin­resistant models using quantitative PCR and western blot analyses. The results of the in silico analysis showed that the different histologies exhibited distinct expression profiles for EMT markers. Seminomas exhibited a lower expression of EMT markers, whereas embryonal carcinomas and mixed GCT demonstrated high expression. Notably, patients with lower SLUG expression had longer median progression­free survival (46.4 months vs. 28.0 months, P=0.022). In the in vitro analysis, EMT­associated genes [fibronectin; vimentin (VIM); actin, α2, smooth muscle; collagen type I α1; transforming growth factor­ß1; and SLUG] were upregulated in the cisplatin­resistant NTERA­2 (NTERA­2R) cell line after 72 h of cisplatin treatment. Consistent with this finding, the NTERA­2R mouse model demonstrated a significant upregulation in the expression levels of VIM and SLUG. In conclusion, the present findings suggested that SLUG may serve a crucial role in connecting EMT with the development of cisplatin resistance, and targeting SLUG may be a putative therapeutic strategy to mitigate cisplatin resistance.

Phosphokinases related to drug resistance in two cohorts from the cancer genome atlas (TCGA): uterine carcinoma and testicular cancer.

We aimed to find new therapeutic targets related to Cancer Stem Cell alterations in recurrent patients from two TCGA cohorts: Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC). Raw sequencing data were downloaded from the TCGA database. Datasets containing RNA expression and Methylation files were directly downloaded from cBioportal. Variant Call Format files (VCFs) were downloaded from the GDC portal. Gene enrichment analysis was performed using GSEA (Gene Set Enrichment Analysis) software. Transcriptome profiling, coexpression co-occurrence, networks, and survival analyses were performed using cBioportal tools, while mutational analysis of patients was processed using UNIX scripts. We found that cancer stem cell transcription factors were highly expressed in Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC) cohorts, compared to the other 29 cancer cohorts in TCGA. Patients presented a poorer diagnosis when the genes (POU5F1, NANOG, SOX2, SALL4, ABCB1, ABCC1, and ABCG2) were altered. In UCEC cohorts, recurrent patients showed the ABCG2 potentially phosphorylated by the PIM1 kinase. In the TGCT cohort, genes ABCB1 and ABCG2 only appeared in the phosphonetwork in recurrent patients potentially phosphorylated by the same kinase, PIM1, but also by PRKACA. Our data indicate that PRKACA and PIM1 may modulate POU5F1 phosphorylation.

Aging-related biomarkers in testicular cancer survivors after different oncologic treatments.

PURPOSE: Testicular cancer survivors (TCS) exposed to chemotherapy have an increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype associated with immunosenescence. We seek to define whether the immunosenescent phenotype is associated with chemotherapy. METHODS: Case-control study of TCS, disease-free ≥3 months and stratified by primary treatment modality into orchiectomy only, chemotherapy, or bone marrow transplant (BMT). Each group was compared with age-matched healthy controls (HC). We measured the relative proportions of lymphocyte subpopulations using flow cytometry, levels of C-reactive protein, and relative expression of CDKN2A/p16INK4a quantified by qPCR. RESULTS: We included 65 patients; 19 were treated with orchiectomy only, 35 received different doses of chemotherapy, and 11 underwent BMT. The chemotherapy and BMT groups had decreased naïve CD4 cells compared to HC. The chemotherapy group showed increased central and effector memory CD4 cells, as well as effector and terminally differentiated CD8 cells, compared to HC. Chemotherapy (chemotherapy 1.84 vs. HC 0.92; p < 0.01) and BMT (BMT 6.96 vs. HC 1.25; p < 0.005) groups had higher expression of CDKN2A/p16INK4a compared to HC. The orchiectomy group showed no significant difference with HC (orchiectomy 1.73 vs. HC 1.01; p = 0.17). CRP levels were higher in all groups when compared with HC; in the orchiectomy group, they were only marginally increased (chemotherapy 0.22 vs. HC 0.06; p < 0.01; BMT 0.26 vs. HC 0.06; p < 0.01; orchiectomy 0.09 vs. HC 0.07; p < 0.01). CONCLUSIONS: Among TCS, only patients exposed to cytotoxic agents developed an immunosenescent phenotype. This finding supports the attribution of this alteration to the cytotoxic treatment.

High Dose Chemotherapy With Autologous Stem Cell Transplant for Patients With Advanced Germ Cell Tumors: Real-World Evidence From a Tertiary Cancer Center in Brazil.

BACKGROUND: High-dose chemotherapy followed by stem cell transplant (HDCT) is potentially curative for patients with refractory germ cell tumors (rGCT). There is scarce real-world data supporting its implementation in low- and middle-income countries. We described the experience of our tertiary cancer center in Sao Paulo, Brazil. METHODS: We identified male patients ≥18 years-old with rGCT referred to HDCT after board discussion. Clinical data, including delays in HDCT protocol, were extracted from medical records, and survival outcomes were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazard were used to determine effects on overall survival (OS). RESULTS: From January 2013 to January 2023, 34 patients were referred and considered eligible to receive 2 cycles of HDCT. Most patients had primary testicular tumors (82%), nonseminomatous histology (88%), and poor International Germ Cell Collaborative Group (IGCCCG) (79%). Twenty-three patients received HDCT (1 cycle, n = 8; 2 cycles, n = 15). Main reasons for not receiving any HDCT were death due to progressive disease (n = 1), performance deterioration (n = 7), and failure of stem cell mobilization (n = 3). OS at 2 years was 36.7% for the eligible population, 56.1% for patients who underwent at least 1 HDCT, and 77.1% for those who had ≥2 cycles. The 2-year OS rate for patients not given HDCT was 0%. All patients had delays in protocol, and poor-risk patients had longer intervals from referral to protocol initiation (0.7 vs. 1.8 month, P < .01). CONCLUSION: Outcomes of patients who received ≥1 HDCT were encouraging; however, only 15 from 34 eligible patients were able to receive the planned 2 cycles of HDCT. Further strategies to minimize treatment delays in low- and middle-income countries are needed.

Prolonged survival after thoracic metastasectomy in patients with nonseminomatous testicular cancer.

INTRODUCTION: Almost 20 % of patients with Non-Seminomatous Germinative Cell Tumors (NSGCT) will require intrathoracic metastasectomy after chemotherapy. The authors aim to determine their long-term survival rates. METHODS: Retrospective study including patients with NSGCT and intrathoracic metastasis after systemic therapy from January 2011 to June 2022. Treatment outcomes and overall survival were analyzed with the Kaplan-Meier method. RESULTS: Thirty-seven male patients were included with a median age of 31.8 years. Six presented with synchronous mediastinum and lung metastasis, nine had only lung, and 22 had mediastinal metastasis. Over half had retroperitoneal lymph node metastasis. Twenty-two had dissimilar pathologies, with a discordance rate of 62 %. Teratoma and embryonal carcinoma were the prevalent primary tumor types, 40.5 % each, while teratoma was predominant (70.3 %) in the metastasis group. Thoracotomy was the main surgical approach (39.2 %) followed by VATS (37.2 %), cervico-sternotomy (9.8 %), sternotomy (5.8 %), and clamshell (3.9 %). Lung resection was performed in 40.5 % of cases. Overall, 10-year survival rates were 94.3 % with no surgical-related mortality. CONCLUSION: Multimodality treatment with systemic therapy followed by radical surgery offers a high cure rate to patients with intrathoracic metastatic testicular germ cell tumors.

Testicular yolk sac tumour metastasis to the L2 vertebra.

The role of surgery for metastases to the vertebra from yolk sac tumours has not been established. The main treatment for disseminated disease is chemotherapy. We present a man in his 30s with a left orchiectomy for a testicular mixed germ cell tumour with a prominent yolk sac component who, 12 months later, developed an asymptomatic metastasis to the L2 vertebra unresponsive to chemotherapy and radiotherapy. The patient underwent resection of the L2 vertebral body, leaving a small residual tumour anterior to the vertebra attached to the great vessels. Pathology confirmed the diagnosis of a metastatic testicular yolk sac tumour in the vertebra. The postoperative MRI 6 months later demonstrated significant expansion of the tumour at the soft tissues anterior to the expandable titanium cage encasing the great vessels and extending to the paraspinal areas. Additional salvage surgery was not recommended because of the advanced stage of the tumour.

Postchemotherapy retroperitoneal residual mass resection for germ cell testicular tumors: a single-center experience.

OBJECTIVE: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) plays an important role in the management of advanced germ cell testicular tumors. Bilateral template lymph node dissection is considered a standard treatment in postchemotherapy residual masses; however, modified unilateral templates have gained acceptance in patients with unilateral residual disease. In this study, we aimed to demonstrate the perioperative and oncological outcomes of the patients with advanced testicular cancer who underwent unilateral modified template PC-RPLND in our center. METHODS: This is a retrospective study in which patients who underwent PC-RPLND in a referred center between 2004 and 2021 were investigated. All patients had three or four cycles of chemotherapy and retroperitoneal residual masses. Data were retrospectively collected from medical, operative, radiology, and pathology records and analyzed. RESULTS: A total of 57 patients underwent PC-RPLND. The mean age was 32.7±8.1 years (19-50). According to the disease stage at presentation, there were 39 patients with stage 2 and 18 patients with stage 3. The average tumor size after chemotherapy was 57.6±2.7 mm (25-117). The overall complication rate was 35% (20/57 patients). No grade 4 and 5 complications were observed. Pathologic review demonstrated the presence of teratoma in 28 (49.1%) patients, fibrosis and/or necrosis in 15 (26.3%) patients, and viable germ cell tumor in 14 (24.5%) patients. The mean follow-up was 69.4 months (8-201). During follow-up after surgery, 14 (24.5%) deaths occurred due to advanced disease. CONCLUSION: PC-RPLND is a major component of the management of advanced testicular germ cell cancer. Our study demonstrated that modified unilateral template is an effective and safe procedure in the postchemotherapy setting for selected patients.

Oncological outcomes of retroperitoneal node dissection for residual masses after chemotherapy in germ cell tumor. Retrospective analysis of 15 years.

OBJECTIVE: To report experience in a hospital in Mexico regarding oncological results in overall survival (OS) and specific cancer survival (SCS), the presence of recurrence in the management of residual masses after chemotherapy with lymphadenectomy retroperitoneal for 15 years. METHOD: Between 2004 and 2019, a retrospective study was carried out in a single centre with patients with a germ cell tumor diagnosis who have received first or second line of chemotherapy and who present retroperitoneal residual mass were included have performed RPLND. Sociodemographic characteristics were analyzed, overall and histological survival. RESULTS: 346 patients had inclusion criteria, mean age was 27.6 years, the most affected testis was the left, the most frequent testicular histology was mixed germline. The most frequent retroperitoneal location was paraortic, the most frequent type of RPLND was standard, the most frequent histology was necrosis. Recurrence occurred in 24.2%, mean of 17.1 months, when analyzing individual factors, the most significant was the type of RPLND. The clinical stage, histology of the retroperitoneal tumor and type of RPLND influence mortality. Global follow up of 141 months, OS was 85.5% and SCS was 86.1%, mean of 139.9 months and 141 months respectively. CONCLUSIONS: RPLND is effective in survival and recurrence in advanced disease in patients who present postchemotherapy retroperitoneal tumor and although there is a clear benefit in the resection of retroperitoneal tumors in teratoma, there are conditioning factors that must be analyzed individually.

OBJETIVO: Reportar nuestra experiencia en supervivencia y recurrencia en el manejo de masas residuales posquimioterapia con linfadenectomía retroperitoneal durante 15 años. MÉTODO: Estudio retrospectivo de 2004 a 2019. Se incluyeron pacientes con diagnóstico de tumor de células germinales que habían recibido quimioterapia y presentaron una masa residual retroperitoneal en un solo centro y se les realizó linfadenectomía retroperitoneal. Se analizaron las características sociodemográficas, de supervivencia global e histológicas. RESULTADOS: Cumplían los criterios de inclusión 346 pacientes, con una media de edad de 27.6 años. El testículo más afectado fue el izquierdo, y la histología testicular más frecuente fue germinal mixto. La localización retroperitoneal más frecuente fue paraaórtica, el tipo de linfadenectomía más frecuente fue la estándar y la histología más frecuente fue la necrosis. Se presentó recurrencia en el 24.2% de los pacientes, en una media de 17.1 meses; al analizar los factores individuales, el más significativo fue el tipo de linfadenectomía. El estadio clínico, la histología del tumor retroperitoneal y el tipo de linfadenectomía influyen en la mortalidad. El seguimiento global fue de 141 meses, la supervivencia global fue del 85.5% y la supervivencia específica del cáncer fue del 86.1%, con media de 139.9 y 141 meses, respectivamente. CONCLUSIONES: La linfadenectomía retroperitoneal es efectiva en cuanto a supervivencia y recurrencia en la enfermedad avanzada en pacientes que presentan tumor retroperitoneal posquimioterapia, y aunque existe un claro beneficio en la resección de los tumores retroperitoneales en teratoma, existen factores condicionantes que deben ser analizados de manera individual.

Transcriptomic landscape of male and female reproductive cancers: Similar pathways and molecular signatures predicting response to endocrine therapy.

Reproductive cancers in both genders represent serious health problems, whose incidence has significantly risen over the past decades. Although considerable differences among reproductive cancers exist, we aimed to identify similar signaling pathways and key molecular oncomarkers shared among six human reproductive cancers that can advance the current knowledge of cancer biology to propose new strategies for more effective therapies. Using a computational analysis approach, here we uncover aberrant miRNAs-mRNAs networks shared in six reproductive tumor types, and identify common molecular mechanisms strictly associated with cancer promotion and aggressiveness. Based on the fact that estrogenic and androgenic signaling pathways were most active in prostate and breast cancers, we further demonstrated that both androgen and estrogen deprivation therapy are capable of regulating the expression of the same key molecular sensors associated with endoplasmic reticulum dysfunction and cell cycle in these cancers. Overall, our data reveal a potential mechanistic framework of cellular processes that are shared among reproductive cancers, and particularly, highlight the importance of hormonal deprivation in breast and prostate cancers and potentially new biomarkers of response to these therapeutic approaches.

Patterns of relapse and treatment outcome after active surveillance or adjuvant carboplatin for stage I seminoma: a retrospective study of the Spanish Germ Cell Cancer Group.

PURPOSE: Active surveillance (AS) and adjuvant chemotherapy (AC) with carboplatin are valid alternatives for managing stage I seminoma, and most relapses can be cured with cisplatin-based chemotherapy. However, some reports suggest that AC may modify the classical pattern of recurrences. METHODS: We analyzed all relapses observed in a series of 879 patients with stage I seminoma included in 4 consecutive studies of the Spanish Germ Cell Cancer Group. After a median follow-up of 67 months, recurrences were detected in 56/467 (12%) low-risk cases on AS and 13/412 (3%) high-risk cases after AC (p < 0.001). The objective was to describe clinical features, treatment and outcome. Univariate comparisons were performed between both groups. RESULTS: No significant differences were found between relapses on AS and those after AC in terms of time to relapse (13 vs 17 months), size (26 vs 27 mm), location (retroperitoneum in 88% vs 85%), and method of detection (computed tomography in 77% vs 69%). Treatment consisted of chemotherapy (etoposide + cisplatin ± bleomycin) in 89% and 92%, respectively. Late relapses (after > 3 years) were seen in 11% vs 7.7% (p = NS) and second or successive recurrences in 1.8 vs 23% (p < 0.05). With a median follow-up of 130 moths, two patients died of seminoma-unrelated causes (AS group) and the rest are alive and disease-free. CONCLUSION: In the setting of a risk-adapted treatment of stage I seminoma, the administration of two courses of AC in patients with tumor size > 4 cm and/or rete testis invasion is associated with a higher incidence of second recurrences but does not significantly modify the pattern of relapses or their outcome.

Surveillance of postchemotherapy subcentimeter residual retroperitoneal mass in metastatic nonseminomatous germ cell tumor: Does how you measure matter?

BACKGROUND: Approximately 70% to 80% of patients with metastatic nonseminomatous germ cell tumor (NSGCT) treated with cisplatin-based chemotherapy achieve a complete response, defined as normalization of serum tumor markers and either no residual retroperitoneal mass (RRM) or an RRM <1.0 cm. While there is universal agreement that patients with an RRM ≥1.0 cm should undergo retroperitoneal lymph node dissection (RPLND), many institutions including ours recommend surveillance for patients who achieve a complete response. However, studies have not defined which axis of the RRM should be considered when deciding between surveillance and RPLND. PATIENTS AND METHODS: Good-risk metastatic NSGCT patients treated with cisplatin-based chemotherapy who achieved a complete response and underwent surveillance were identified using our institution's electronic medical records. A post-hoc review was performed by a blinded radiologist. The RRM dimensions in the transaxial short axis (TSA), transaxial long axis (TLA), and craniocaudal axis (CCA) were recorded. Differences in the frequency of recurrence between groups with an RRM <1.0 cm and ≥1.0 cm in the TLA and CCA were assessed using the Fisher exact test. RESULTS: Thirty-nine patients who met study criteria were included. At a median follow-up of 63.8 months, 2 patients (5.1%) recurred. Both were successfully treated with salvage chemotherapy and RPLND. Thirteen (33%) and 27 (69%) patients had an RRM ≥1.0 cm in the TLA and CCA, respectively. There were no statistically significant differences in the risk of recurrence between patients with an RRM <1.0 cm and ≥1.0 cm in the TLA (P = 0.54) or CCA (P = 0.53). CONCLUSIONS: Surveillance is an effective strategy in good-risk NSGCT patients with a postchemotherapy RRM <1.0 cm in the TSA. Our study suggests referencing the TSA and not the TLA or CCA may avoid unnecessary postchemotherapy RPLNDs.

Mastocitoma de alto grau em bolsa testitular em cão / Mast cell tumor high grade in testicular bag in dog

Mast cell tumor is the most common skin tumor in dogs. Due to mast cell proliferation, the affected animals present clinical symptoms compatible with the release of excess histamine granules present inside these cells leading to changes in the gastrointestinal and vascular tracts with the possibility of causing anaphylactic shock. The diagnosis is made by cytopathological analysis and classified by means of histopathology. Treatment is based on staging, surgical exeresis with antineoplastic chemotherapy and drug treatment to inhibit the effects of histamine release. A dog of 14 years old of Boxer breed was attend complaining of nodulation in the testicular bag with a two month evolution. Animal was diagnosed with mast cell tumor. Treatment was instituted by surgical excision and due to the metastatic possibility in regional lymph node, antineoplastic and drug therapy was indicated, which was not successful due of the person responsible non-adherence to the treatment. Mast cell tumor classified as high grade after histopathological analysis. Animal survived for two months after diagnosis of the disease. Due to the high grade of neoplastic presentation and difficulty in treatment, the animal had low survival, corroborating with data described in the literature regarding the poor prognosis of this tumor type.(AU)

Mastocitoma de alto grau em bolsa testitular em cão / Mast cell tumor high grade in testicular bag in dog

Mast cell tumor is the most common skin tumor in dogs. Due to mast cell proliferation, the affected animals present clinical symptoms compatible with the release of excess histamine granules present inside these cells leading to changes in the gastrointestinal and vascular tracts with the possibility of causing anaphylactic shock. The diagnosis is made by cytopathological analysis and classified by means of histopathology. Treatment is based on staging, surgical exeresis with antineoplastic chemotherapy and drug treatment to inhibit the effects of histamine release. A dog of 14 years old of Boxer breed was attend complaining of nodulation in the testicular bag with a two month evolution. Animal was diagnosed with mast cell tumor. Treatment was instituted by surgical excision and due to the metastatic possibility in regional lymph node, antineoplastic and drug therapy was indicated, which was not successful due of the person responsible non-adherence to the treatment. Mast cell tumor classified as high grade after histopathological analysis. Animal survived for two months after diagnosis of the disease. Due to the high grade of neoplastic presentation and difficulty in treatment, the animal had low survival, corroborating with data described in the literature regarding the poor prognosis of this tumor type.

PET-CT for the management of testicular seminoma patients with post-chemotherapy residual masses. / PET-CT for the management of testicular seminoma patients with post-chemotherapy residual masses.

INTRODUCTION: The use of PET-CT could select a subgroup of advanced testicular seminoma patients that display post-chemotherapy residual masses measuring >3 cm and could be managed with surveillance, avoiding unnecessary surgical resection of unviable tumor masses. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews that included eleven primary studies; none of these were randomized trials. We concluded the assessment of postchemotherapy residual masses by PET-CT in testicular seminoma patients may prevent unnecessary surgeries, but the certainty of the evidence is low. Furthermore, PET-CT could also offer a favorable risk/benefit and cost/benefit ratio for the management of testicular seminoma patients. However, systematic reviews and primary studies assessing the direct diagnostic impact of PET-CT are required.

INTRODUCCIÓN: En pacientes con cáncer testicular avanzado tipo seminoma que tienen lesiones residuales post quimioterapia de más de 3 cm, el PET-CT podría seleccionar un subgrupo susceptible de ser manejado con seguimiento, evitando una resección quirúrgica innecesaria de tumor no viable. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos tres revisiones sistemáticas que en conjunto incluyeron 11 estudios primarios, de los cuales, ninguno es un ensayo aleatorizado. Concluimos que el uso de PET-CT en la evaluación de masas residuales post quimioterapia en pacientes con cáncer testicular tipo seminoma podría evitar un porcentaje importante de cirugías innecesarias (certeza de la evidencia baja). Además, el uso de PET-CT podría presentar balances riesgo/beneficio y costo/beneficio favorables en el manejo de pacientes con cáncer testicular tipo seminoma. Sin embargo, se requieren revisiones sistemáticas y estudios primarios que evalúen directamente el impacto diagnóstico del test.

Clinical Characteristics and Treatment Outcomes of Patients With Advanced Germ Cell Tumor Treated at a Tertiary Cancer Center in Brazil.

PURPOSE: Reported treatment outcomes for patients with advanced germ cell tumors (aGCT) are based mainly on series from developed nations. Data from low- and middle-income countries are underrepresented. MATERIAL AND METHODS: From 2000 to 2015, a retrospective analysis identified 300 patients with aGCT treated at our institution. Kaplan-Meier methods were used for analysis of progression-free survival (PFS) and overall survival (OS) according to the International Germ Cell Consensus Classification Group (IGCCCG). RESULTS: Patients' median age was 28 years. According to the IGCCCG, 57% had good-, 18.3% intermediate-, and 24.7% poor-risk disease. Median α-fetoprotein levels were 2.9, 243, and 3,998 ng/mL, and those of human chorionic gonadotropin were 0.4, 113, and 301.5 mUI/mL in IGCCCG good-, intermediate-, and poor-risk groups, respectively. At a median 46 months of follow-up, 93 PFS events and 45 deaths had occurred and estimated 5-year PFS and OS were 69% and 85%, respectively, including 83% and 95.3% in good-risk, 70.9% and 83.6% in intermediate-risk, and 35.1% and 62.2% in poor-risk patients, respectively. In multivariable analysis, Eastern Cooperative Oncology Group performance status ≥ 2 was a significant independent prognostic factor with a hazard ratio of 2.58 (95% CI, 1.55 to 4.29; P < .001) and 6.20 (95% CI, 2.97 to 12.92; P < .001) for PFS and OS, respectively. CONCLUSION: Brazilian patients with aGCT in this cohort had similar outcomes as patients in the IGCCCG database. In comparison with contemporary series, patients with intermediate- and poor-risk aGCT had slightly inferior PFS and OS, possibly due to a high percentage of patients with poor performance status and less use of high-dose chemotherapy.

Transformación de teratoma en rabdomiosarcoma / Transformation of teratoma in rabdomiosarcoma

Los teratomas son tumores germinales malignos compuestos por dos o más capas de tejido, que ocasionalmente se transforman en estirpes con crecimiento agresivo. Se presenta el caso de un paciente de 29 años con un tumor germinal gonadal localizado en testículo, cuya evolución fue desfavorable por presentar transformación en un fenotipo correspondiente a un rabdomiosarcoma. La patología aquí descripta deviene del crecimiento diferencial de un componente ya existente en el tumor original o la transformación en un linaje somático que se hace dominante. Los tumores transformados como el del caso descripto son raros y presentan características diferentes de la mayoría de las neoplasias germinales respecto del comportamiento, el pronóstico y la sensibilidad a los tratamientos establecidos.

Teratomas are malign germ cell tumors composed of two or more tissue layers. When there is specific organ differentiation they are called mature teratoma. They rarely grow aggressively. We report the case of a 29 year-old man with a diagnosis of gonadal germ cell tumor whose evolution was unfavorable owing to transformation into a different phenotype corresponding to a rhabdomyosarcoma. This phenomenon occurs through differential growth of a single histological component of the original tumor or transformation of a somatic lineage that becomes dominant. Transformed tumors such as the one herein described differ from most germ cell neoplasms regarding behavior, prognosis, and susceptibility to established treatments.

[Transformation of teratoma in rabdomiosarcoma]. / Transformación de teratoma en rabdomiosarcoma.

Teratomas are malign germ cell tumors composed of two or more tissue layers. When there is specific organ differentiation they are called mature teratoma. They rarely grow aggressively. We report the case of a 29 year-old man with a diagnosis of gonadal germ cell tumor whose evolution was unfavorable owing to transformation into a different phenotype corresponding to a rhabdomyosarcoma. This phenomenon occurs through differential growth of a single histological component of the original tumor or transformation of a somatic lineage that becomes dominant. Transformed tumors such as the one herein described differ from most germ cell neoplasms regarding behavior, prognosis, and susceptibility to established treatments.

PET-CT para el manejo de pacientes con cáncer testicular tipo seminoma con masa residual post quimioterapia / PET-CT for the management of testicular seminoma patients with post-chemotherapy residual masses

INTRODUCCIÓN En pacientes con cáncer testicular avanzado tipo seminoma que tienen lesiones residuales post quimioterapia de más de 3 cm, el PET-CT podría seleccionar un subgrupo susceptible de ser manejado con seguimiento, evitando una resección quirúrgica innecesaria de tumor no viable. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos tres revisiones sistemáticas que en conjunto incluyeron 11 estudios primarios, de los cuales, ninguno es un ensayo aleatorizado. Concluimos que el uso de PET-CT en la evaluación de masas residuales post quimioterapia en pacientes con cáncer testicular tipo seminoma podría evitar un porcentaje importante de cirugías innecesarias (certeza de la evidencia baja). Además, el uso de PET-CT podría presentar balances riesgo/beneficio y costo/beneficio favorables en el manejo de pacientes con cáncer testicular tipo seminoma. Sin embargo, se requieren revisiones sistemáticas y estudios primarios que evalúen directamente el impacto diagnóstico del test.

INTRODUCTION The use of PET-CT could select a subgroup of advanced testicular seminoma patients that display post-chemotherapy residual masses measuring >3 cm and could be managed with surveillance, avoiding unnecessary surgical resection of unviable tumor masses. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified three systematic reviews that included eleven primary studies; none of these were randomized trials. We concluded the assessment of postchemotherapy residual masses by PET-CT in testicular seminoma patients may prevent unnecessary surgeries, but the certainty of the evidence is low. Furthermore, PET-CT could also offer a favorable risk/benefit and cost/benefit ratio for the management of testicular seminoma patients. However, systematic reviews and primary studies assessing the direct diagnostic impact of PET-CT are required.