Low-dose carboplatin modifies the tumor microenvironment to augment CAR T cell efficacy in human prostate cancer models.

Chimeric antigen receptor (CAR) T cells have transformed the treatment landscape for hematological malignancies. However, CAR T cells are less efficient against solid tumors, largely due to poor infiltration resulting from the immunosuppressive nature of the tumor microenvironment (TME). Here, we assessed the efficacy of Lewis Y antigen (LeY)-specific CAR T cells in patient-derived xenograft (PDX) models of prostate cancer. In vitro, LeY CAR T cells directly killed organoids derived from androgen receptor (AR)-positive or AR-null PDXs. In vivo, although LeY CAR T cells alone did not reduce tumor growth, a single prior dose of carboplatin reduced tumor burden. Carboplatin had a pro-inflammatory effect on the TME that facilitated early and durable CAR T cell infiltration, including an altered cancer-associated fibroblast phenotype, enhanced extracellular matrix degradation and re-oriented M1 macrophage differentiation. In a PDX less sensitive to carboplatin, CAR T cell infiltration was dampened; however, a reduction in tumor burden was still observed with increased T cell activation. These findings indicate that carboplatin improves the efficacy of CAR T cell treatment, with the extent of the response dependent on changes induced within the TME.

Cancer-associated fibroblasts of the prostate promote a compliant and more invasive phenotype in benign prostate epithelial cells.

Reciprocal interactions between prostate epithelial cells and their adjacent stromal microenvironment not only are essential for tissue homeostasis but also play a key role in tumor development and progression. Malignant transformation is associated with the formation of a reactive stroma where cancer-associated fibroblasts (CAFs) induce matrix remodeling and thereby provide atypical biochemical and biomechanical signals to epithelial cells. Previous work has been focused on the cellular and molecular phenotype as well as on matrix stiffness and remodeling, providing potential targets for cancer therapeutics. So far, biomechanical changes in CAFs and adjacent epithelial cells of the prostate have not been explored. Here, we compared the mechanical properties of primary prostatic CAFs and patient-matched non-malignant prostate tissue fibroblasts (NPFs) using atomic force microscopy (AFM) and real-time deformability cytometry (RT-FDC). It was found that CAFs exhibit an increased apparent Young's modulus, coinciding with an altered architecture of the cytoskeleton compared with NPFs. In contrast, co-cultures of benign prostate epithelial (BPH-1) cells with CAFs resulted in a decreased stiffness of the epithelial cells, as well as an elongated morphological phenotype, when compared with co-cultures with NPFs. Moreover, the presence of CAFs increased proliferation and invasion of epithelial cells, features typically associated with tumor progression. Altogether, this study provides novel insights into the mechanical interactions between epithelial cells with the malignant prostate microenvironment, which could potentially be explored for new diagnostic approaches.

The clinical efficacy of PSMA PET/MRI in biochemically recurrent prostate cancer compared with standard of care imaging modalities and confirmatory histopathology: results of a single-centre, prospective clinical trial.

Prospective evidence for the clinical role and efficacy of prostate specific membrane antigen (PSMA) positron emission tomography (PET)/magnetic resonance imaging (MRI) combining MRI characterization and localization of lesions with PET avidity in comparison to conventional imaging is limited. In a prospective clinical trial, we aimed to evaluate the diagnostic yield and therapeutic impact of PSMA PET/MRI in men with biochemical recurrence (BCR) following curative therapy. A single-centre, prospective clinical trial at the Princess Alexandra Hospital recruited 30 patients with BCR. Patients underwent PSMA PET/MRI and concurrent conventional CT chest, abdomen, pelvis and whole-body bone scan. Biopsy was performed when safety possible for histological correlation of identified lesions. Clinical efficacy and impact of PSMA PET findings were evaluated. 30 patients with BCR were recruited (median PSA 0.69 ng/ml). PSMA avid lesions were present in 21 patients (70%). 23 patients were previously treated with definitive surgery, 6 patients received external beam radiotherapy and 1 patient had low dose rate brachytherapy. A total of 8 of 9 lesions biopsied were positive (88.9% histological correlation). PSMA PET/MRI detected local recurrence (p = 0.005) and pelvic lesions (p = 0.06) more accurately than conventional imaging. PSMA PET/MRI may be useful in staging men with biochemical recurrence, especially when PSA is low. Our data demonstrates a high detection rate, especially for locally recurrent disease, and highlights the role of this modality when PSA is low. This modality has the potential to significantly improve prostate cancer detection and may have implications for earlier salvage treatment, avoidance of futile local therapy and change patient management to lead to improved outcomes.

Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer.

PURPOSE: Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with (68)Ga-PSMA-HBED-CC has been shown to detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate. MATERIALS AND METHODS: In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis. RESULTS: A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value. CONCLUSIONS: A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy.

PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer.

The non-canonical Wnt pathway, a regulator of cellular motility and morphology, is increasingly implicated in cancer metastasis. In a quantitative PCR array analysis of 84 Wnt pathway associated genes, both non-canonical and canonical pathways were activated in primary and metastatic tumors relative to normal prostate. Expression of the Wnt target gene PITX2 in a prostate cancer (PCa) bone metastasis was strikingly elevated over normal prostate (over 2,000-fold) and primary prostate cancer (over 200-fold). The elevation of PITX2 protein was also evident on tissue microarrays, with strong PITX2 immunostaining in PCa skeletal and, to a lesser degree, soft tissue metastases. PITX2 is associated with cell migration during normal tissue morphogenesis. In our studies, overexpression of individual PITX2A/B/C isoforms stimulated PC-3 PCa cell motility, with the PITX2A isoform imparting a specific motility advantage in the presence of non-canonical Wnt5a stimulation. Furthermore, PITX2 specific shRNA inhibited PC-3 cell migration toward bone cell derived chemoattractant. These experimental results support a pivotal role of PITX2A and non-canonical Wnt signaling in enhancement of PCa cell motility, suggest PITX2 involvement in homing of PCa to the skeleton, and are consistent with a role for PITX2 in PCa metastasis to soft and bone tissues. Our findings, which significantly expand previous evidence that PITX2 is associated with risk of PCa biochemical recurrence, indicate that variation in PITX2 expression accompanies and may promote prostate tumor progression and metastasis.

Transplante renal de donante vivo: un análisis crítico de estrategias quirúrgicas basado en 40 años de experiencia / Renal transplantation with living donors. A critical analysis of surgical procedures based on 40 years of experience

Introducción: La prioridad inexcusable de un programa de trasplante renal de donante vivo (TRDV) es la seguridad vital del donante, seguida de la preservación del órgano, obtenido en las mejores condiciones anatómicas y funcionales. La reducción de la morbilidad del donante, inmediata y alargo término, debe ser otro objetivo. Tanto en el TRDV como en el trasplante de cadáver el implante del órgano debe realizarse con las mayores garantías técnicas. Analizamos nuestra mortalidad, morbilidad, incidencias, técnica de la nefrectomía y otros datos relevantes observados en nuestro programa de TRDV iniciado en 1968, con la intención de comparar nuestros resultados con los publicados utilizando técnicas laparoscópicas de nefrectomía, y en consecuencia decidir si nuestro programa debe modificar, o no, sus estrategias quirúrgicas actuales. Material y métodos: Nuestro programa de trasplante renal se inició en 1964, con riñón de cadáver, y en 1968 con riñón del donante vivo. Desde junio de 1968 hasta junio del 2008 hemos realizado 243 TRDV; un reducido número de trasplantes por año. La técnica de nefrectomía empleada desde 1968-1972 fue el abordaje supracostal propuesto por Turner-Warrick y desde 1972 una mini incisión subcostal, anterior extraperitoneal. La lumbotomía convencional con resección de la última costilla nunca ha sido practicada. El riñón derecho fue utilizado en el 78% y el implante en la fosa ilíaca derecha en el 85% La cirugía del donante y el receptor se realizan simultáneamente en dos quirófanos adyacentes, por dos equipos distintos, siendo un solo cirujano responsable de ambos procedimientos; la nefrectomía y el implante. Las complicaciones peroperatorias y postoperatorias, potencialmente relacionadas con la nefrectomía, o de otra naturaleza, han sido evaluadas por los equipos urológicos y nefrológicos. Resultados: No se han detectado en nuestra serie ningún caso de muerte del donante, pérdida del órgano o complicaciones mayores tales como neumotórax, hemorragias necesitando transfusión, infecciones graves, reintervenciones. Complicaciones menores tales como paresia intestinal, fiebre, infección de la herida operatoria, fueron más frecuentes con el abordaje supracostal que con el mini incisional. Igualmente, este abordaje ha reducido el dolor postoperatorio, consumo de analgésicos y tiempo de recuperación. En el seguimiento a largo plazo la incidencia de hernias incisionales, o paresia de la pared abdominal, no han sido detectadas. La responsabilidad personal de un cirujano en ambos procedimientos soslaya reclamaciones sobre la calidad anatómica y funcional del órgano, facilita la elección de vasos para la anastomosis y reduce el tiempo operatorio y de ocupación de quirófano. Conclusiones: El análisis de nuestros resultados cuestiona la conveniencia de sustituir nuestra estrategia quirúrgica actual por los potenciales beneficios e inconvenientes de la nefrectomía laparoscópica, especialmente en un programa de TRDV de reducido número anual. Nuestra técnica de nefrectomía ha ofrecido, a lo largo de una experiencia de 40 años, máximas garantías vitales para el donante y de calidad anatómica y funcional para el órgano, con morbilidad postoperatoria similar a la conseguida con la incisión final laparoscópica (AU)

Introduction: Absolute priority in an LDKT programme are donnor safety and kidney optimal anatomical and functional preservation. Reduced donnor morbidities, both at short and long term, are important objectives. Excellent technical grafting is a must as are the strategies employed for facilitatig it. We revised the incidences of our whole LDKT programme (40 years 243 donors) to confirm if these exigences have been acomplished or a change to new surgical procedures is recommended. Material and methods: Between 1968-2008 243 nephrectomies and grafting has been performed, a reduced number per year (A cadaver programme has been running simultaneously since 1964). For the nephrectomies a Turner-Warrick apprach was inititialy used and since 1973 a miniincisional, anterior, extraperitoneal approach of approximately 10 cm in length. The right kidney was removed in 75% of the cases and the right iliacarea for the implant in 85% In adjacent opperating rooms, one team performs the nephrectomy while the other prepares and dissects free the graftingvessels. Most of the time the same senior surgeon performed both operatios: the nephrectomy and the implant. Peroperative and postoperative complications were evaluated by urologists and nephrologists in charge. Results: No donors dead, organs lost or major complications in the donors have been documented Minor complications such as intestinal paresia, wound infection, persistent incisional pain were common. Miniincisional abdominal approach reduced postoperative pain and hospital stay (4days). At long term no incisional hernia or abdominal paresia have been documented. Simultaneous work reduces ischemia time (30-45 s warm: 30-45 min cold) and opperatig room occupation (patient preparation plus anesthesia plus operation) estimated in 90-120 min for the nephrectomy and 120-160 for the grafting. The responsibility of the senior surgeon in both procedures facilitates vessel selection for the grafting. Conclusions: No reasons have been found to reconvert our current nephrectomy procedure to laparoscpic or modify current surgical strategy. Superior safety of open surgery for donors and organs is confirmed. Pain and recovery time are reduced in laparoscopic surgery but not as much when compared with miniincisional approach. Open surgery permits optimal anatomical and functional organ extration facilitatig the quality of the implant. As numbers matter in laparoscopic surgery open nephrectomy is recommended for reduced LDKT programmes (AU)

[Experimental models for research and training in renal transplant]. / Modelos experimentales para la investigación y el entrenamiento en trasplante renal.

An update on aspects and use of different experimental models applied in kidney transplant research is presented . This paper includes qualities, as long as similarities between most frequently used animal models and human clinical standards. Contributions of those models based on microsurgical or laparoscopic techniques are revised. The physiological consequences (hemodynamic, immunologic) of surgical technique (laparoscopy), applied in experimental models as long as non-heart beating organ donor models and organ preservation methods are also reviewed. Finally, an update of those models applied in research in prothocols of either immunosupression or xenotransplant is done.

Modelos experimentales para la investigación y el entrenamiento en trasplante renal / Experimental models for research and training in renal transplant

Introducción y objetivos: Se presenta una revisión sobre las diferentes características y el uso de los distintos modelos experimentales utilizados para el trasplante renal (TR). Esta revisión incluye las cualidades, así como sus semejanzas a los humanos, de las especies más frecuentemente utilizadas. Se revisan las aportaciones de los diferentes modelos al entrenamiento de las diferentes técnicas quirúrgicas como la laparoscopia o la microcirugía. Se repasan sus contribuciones al estudio y la investigación en campos como los efectos hemodinámicos o inmunológicos del neumoperitoneo, las técnicas de donante a corazón parado o las diferentes formas de preservación de los injertos. Por último, se realiza una revisión de los diferentes modelos utilizados para la investigación de los distintos protocolos de inmunosupresión así como el xenotrasplante

Introduction and objetives: An update on aspects and use of different experimental models applied in kidney transplant research is presented . This paper includes qualities, as long as similarities between most frequently used animal models and human clinical standards. Contributions of those models based on microsurgical or laparoscopic techniques are revised. The physiological consequences (hemodynamic, immunologic) of surgical technique (laparoscopy), applied in experimental models as long as non-heart beating organ donor models and organ preservation methods are also reviewed. Finally, an update of those models applied in research in prothocols of either immunosupression or xenotransplant is done

[Renal transplantation with living donors. A critical analysis of surgical procedures based on 40 years of experience]. / Transplante renal de donante vivo: un análisis crítico de estrategias quirúrgicas basado en 40 años de experiencia.

INTRODUCTION: Absolute priority in an LDKT programme are donnor safety and kidney optimal anatomical and functional preservation. Reduced donnor morbidities, both at short and long term, are important objectives. Excellent technical grafting is a must as are the strategies employed for facilitatig it. We revised the incidences of our whole LDKT programme (40 years 243 donors) to confirm if these exigences have been acomplished or a change to new surgical procedures is recommended. MATERIAL AND METHODS: Between 1968-2008 243 nephrectomies and grafting has been performed, a reduced number per year (A cadaver programme has been running simultaneously since 1964). For the nephrectomies a Turner-Warrick apprach was inititialy used and since 1973 a miniincisional, anterior, extraperitoneal approach of approximately 10 cm in length. The right kidney was removed in 75% of the cases and the right iliac area for the implant in 85% In adjacent opperating rooms, one team performs the nephrectomy while the other prepares and dissects free the grafting vessels. Most of the time the same senior surgeon performed both operatios: the nephrectomy and the implant. Peroperative and postoperative complications were evaluated by urologists and nephrologists in charge. RESULTS: No donors dead, organs lost or major complications in the donors have been documented. Minor complications such as intestinal paresia, wound infection, persistent incisional pain were common. Miniincisional abdominal approach reduced postoperative pain and hospital stay (4 days). At long term no incisional hernia or abdominal paresia have been documented. Simultaneous work reduces ischemia time (30-45 s warm: 30-45 min cold) and opperatig room occupation(patient preparation plus anesthesia plus operation) estimated in 90-120 min for the nephrectomy and 120-160 for the grafting. The responsibility of the senior surgeon in both procedures facilitates vessel selection for the grafting. CONCLUSIONS: No reasons have been found to reconvert our current nephrectomy procedure to laparoscopic or modify current surgical strategy. Superior safety of open surgery for donors and organs is confirmed. Pain and recovery time are reduced in laparoscopic surgery but not as much when compared with miniincisional approach. Open surgery permits optimal anatomical and functional organ extration facilitatig the quality of the implant. As numbers matter in laparoscopic surgery open nephrectomy is recommended for reduced LDKT programmes.

Adecuación de las derivaciones desde Atención Primaria a un Servicio de Urología / Adequacy of referral from primary care to a department of urology

Objetivo: Valorar indirectamente el grado de adhesión de los médicos de Atención Primaria (AP) a un protocolo de derivación consensuado con Atención Especializada (AE) sobre diez motivos de consulta urológica. Material y métodos: Se analizaron todas las derivaciones al servicio de urología llevadas a cabo durante un período de 19 meses por 135 médicos adscritos a 10 centros de AP (CAP). El urólogo juzgó como 'confome' o 'no conforme al protocolo' la derivación. Se compararon los porcentajes de adecuación de las derivaciones desde cada CAP. Se exploraron las diferencias en la adecuación de las derivaciones procedentes de cada CAP en función del problema de salud. La relación entre el número de derivaciones y el número de canalizaciones adecuadas se exploró mediante un modelo de regresión lineal. Resultados: El análisis tuvo lugar sobre 2841 derivaciones. El 57,2% de esas derivaciones se ajustó al protocolo. No se detectaron diferencias significativas en los porcentajes de derivaciones ‘conforme al protocolo’ en relación a los CAP. Se detectaron diferencias significativas entre CAP en las derivaciones por cólico nefrítico e incontinencia urinaria. Se detectó una relación entre el número de pacientes remitidos y el número de remisiones 'no conforme al protocolo' (r2=0,86). Conclusiones: La adecuación al protocolo fue escasa. Algunos problemas de salud deberían de ser revisados a nivel local; la mayoría de los motivos de derivación (de modo particular la microhematuria) deberían de revisarse en todos los CAP

Objetive: To indirectly address the adequacy of referrals from general practitioners (GP) to specialized care taking into account a previously agreed protocol on ten urological topics. Materials & methods: The study analyzed all referrals to the Urology department originated in 10 primary care centres (135 GPs involved) throughout a 19-month period. Adequacy of 2841 referrals was checked. The urologist judged the referral as compliant (adequate) or not compliant (inadequate) with the terms of the protocol. Compliance per primary care centres was compared. Also referral adequacy corrected per centre and clinical topic was compared. The relationship between 'absolute number of referrals' and 'adequate referrals' was tested using a linear regression model. Results: 57.2% of the referrals were inadequate. Overall, no significant differences were detected between primary care centres. Nevertheless significant differences between centres were evident in terms of referrals due to renal colic and female urinary incontinence. 70% (94/135) of the GPs complied with the protocol in, at least, 50% of the cases. A strong association between 'absolute number of referrals' and 'adequate referrals' was evident (r2=0.86). Conclusions: Overall compliance with the protocol was modest. While no significant differences between centres were detected in terms of adequacy of referrals certain conditions have to be locally revisited; most of the topics (particularly microhematuria) have to be revisited in every center

[Adequacy of referral from primary care to a Department of Urology]. / Adecuación de las derivaciones desde Atención Primaria a un Servicio de Urología.

OBJECTIVE: [corrected] To indirectly address the adequacy of referrals from general practitioners (GP) to specialized care taking into account a previously agreed protocol on ten urological topics. MATERIALS & METHODS: The study analyzed all referrals to the Urology department originated in 10 primary care centres (135 GPs involved) throughout a 19-month period. Adequacy of 2841 referrals was checked. The urologist judged the referral as compliant (adequate) or not compliant (inadequate) with the terms of the protocol. Compliance per primary care centres was compared. Also referral adequacy corrected per centre and clinical topic was compared. The relationship between "absolute number of referrals" and "adequate referrals" was tested using a linear regression model. RESULTS: 57.2% of the referrals were inadequate. Overall, no significant differences were detected between primary care centres. Nevertheless significant differences between centres were evident in terms of referrals due to renal colic and female urinary incontinence. 70% (94/135) of the GPs complied with the protocol in, at least, 50% of the cases. A strong association between "absolute number of referrals" and "adequate referrals" was evident (r2=0.86). CONCLUSIONS: Overall compliance with the protocol was modest. While no significant differences between centres were detected in terms of adequacy of referrals certain conditions have to be locally revisited; most of the topics (particularly microhematuria) have to be revisited in every center.

[Adrenal pseudocyst. Report of a new case and review of the literature]. / Pseudoquiste adrenal. Aportación de un nuevo caso y revisión de la literatura.

Adrenal pseudocyst is the commonest type of benign lesions of adrenal gland althought is a very rare entity. Most of them are found as "incidentalomas" during imaging studies. A case of a patient with a left non-functioning and asymptomatic adrenal pseudocyst is reported. The diagnostic and therapeutic options are discussed and the literature is reviewed.

Pseudoquiste adrenal. Aportación de un nuevo caso y revisión de la literatura / Adrenal pseudocyst. Report of a new case and review of the literature

Los pseudoquistes adrenales son las lesiones quísticas mas frecuentes de la glándula suprarrenal, si bien constituyen una rara entidad. Se detectan cada vez con mas frecuencia en estudios radiológicos como incidentalomas. Se presenta el caso de una paciente con pseudoquiste adrenal izquierdo no funcionante y asintomático. Se realiza revisión de la literatura y se estudian las diferentes actitudes diagnósticas y terapéuticas

Adrenal pseudocyst is the commonest type of benign lesions of adrenal gland althought is a very rare entity. Most of them are found as “incidentalomas” during imaging studies. A case of a patient with a left non-functioning and asymptomatic adrenal pseudocyst is reported . The diagnostic and therapeutic options are discussed and the literature is reviewed

Cistitis crónica fibrótica telangectásica por ciclofosfamida / Fibrous chronic cystitis telangectasia for ciclofosfamide

Enfoque de estudio y manejo de pacientes pediátricos hematúricos, con antecedente de tratamiento previo con ciclofosfamida.Paciente femenino de 8 años, con antecedente de linfoma no Hodgkin diagnosticado a los 4 años, que es tratado durante un año en centro extranjero con quimioterapia que incluía ciclofosfamida, sin registro de protección vesical. Presenta también un síndrome atáxico de etiología desconocida. Tres años después consulta por disuria, hematuria recurrente micro y macroscópica con coágulos, presentando función renal normal. Estudio por imágenes (ecografía, pielografía y TAC), muestra imagen de defecto de llene de 4 cm a nivel del trígono vesical, sugerente de coágulo. Se descartan malformaciones vasculares y tumorales.Cistoscopía demostró una cistitis hemorrágica con telangectasias. Histología mostró cistitis crónicahemorrágica fibrosa G° III.Pacientes sometidos a terapias con ciclofosfamida o sus derivados deben recibir protección vesical con Ledoxina, para reducir al máximo este tipo de complicación. Este paciente es candidato a reemplazo vesical total, aún no operado por encontrarse en su centro de origen en el extranjero. Se discute la indicación quirúrgica y la técnica quirúrgica en este caso particular.

[Resolution with vascular endoprosthesis after first angioplasty failure in the treatment of post-transplant stenosis of the renal artery]. / Resolución con endoprótesis vascular tras primera angioplastia fallida en el tratamiento de la estenosis de la arteria renal post-trasplante.

We report a case of renal artery stenosis after a living transplant kidney, treated successfully with percutaneous transluminal angioplasty (PTA) and vascular endoprosthesis. PTA is the initial treatment of choice for most patients with high grade transplant renal artery stenosis. Surgical revascularization is indicated if PTA cannot be done or is unsuccessful.

[Diagnostic and therapeutic aspects in Klinefelter's syndrome. Our experience]. / Aspectos diagnósticos y terapéuticos en el síndrome de Klinefelter. Nuestra experiencia.

We present a retrospective study of 30 new cases of Klinefelter's syndrome and set forth our customary diagnostic and therapeutic schedule. We analyse the results obtained and single out the fact that 100% of the patients displayed high gonadotropins and 45% apparent plasmatic testosterone normality at the time of diagnosis. There is a relationship between lower semen fructose concentration, smaller volume of semen and higher degree of hypoandrogenism in Klinefelter's syndrome. Long duration hormonal treatment with testosterone esters is effective in improving the physical psychic and sexual state of patients. The interval between the last administration and the control hormone determination should be uniform for correct result evaluation.