Initial experience with brachytherapy treatment adjuvant to surgical resection of keloid scars in the pediatric population. / Experiencia inicial del tratamiento braquiterápico en coadyuvancia a la resección quirúrgica de cicatrices queloideas en población pediátrica.

OBJECTIVES: The treatment of keloid scars is based on multiple lines of therapy, with varying levels of efficacy(1), and there is currently no single treatment that guarantees cure and prevents recurrence. In the pediatric population, the treatments used are not standardized, and there is insufficient evidence to support efficacy and complications. The objective of this study was to analyze the patients who required brachytherapy as an adjuvant to surgical resection in recurrent keloid scars. MATERIALS AND METHODS: A retrospective analysis of patients diagnosed with keloids and undergoing adjuvant brachytherapy in our institution was carried out, while assessing efficacy and implementation in our treatment protocol for keloid scarring. RESULTS: After various therapeutic lines, 4 patients aged 9-17 years old with recurrent keloid scars around the ear and eligible for adjuvant brachytherapy - administered after surgical resection, in two sessions - were studied and followed up for up to 18-21 months. CONCLUSIONS: Despite our limited experience in the use of adjuvant brachytherapy, the results obtained to date support its efficacy, as reported in the literature. We therefore consider its inclusion in the treatment of keloid scars that have recurred after other treatments to be appropriate.

OBJETIVOS: El tratamiento de las cicatrices queloideas se basa en múltiples líneas terapéuticas, con diferentes niveles de eficacia(1), sin existir actualmente un tratamiento que garantice su curación y prevenga su recurrencia. En la población pediátrica los tratamientos empleados no están estandarizados y no hay evidencia suficiente que avale su eficacia y sus complicaciones. Este trabajo tiene como objetivo analizar los pacientes que han precisado braquiterapia coadyuvante a la resección quirúrgica en cicatrices queloideas recidivantes. MATERIAL Y METODOS: Análisis retrospectivo de los pacientes diagnosticados en nuestro centro de cicatriz queloidea, en los que se realizó braquiterapia coadyuvante, valorando su eficacia y su implementación en nuestro protocolo de tratamiento de la cicatriz queloidea. RESULTADOS: Se estudiaron 4 pacientes entre 9-17 años con cicatrices queloideas a nivel auricular, recidivantes a varias líneas terapéuticas, que fueron candidatos para el uso de braquiterapia coadyuvante, administrada posterior a la resección quirúrgica, en dos sesiones, se realizó seguimiento hasta 18-21 meses. CONCLUSIONES: A pesar de nuestra limitada experiencia en el uso de la braquiterapia coadyuvante, los resultados obtenidos hasta la fecha avalan su eficacia, de acuerdo con lo publicado en la literatura. Consideramos adecuada su inclusión en el tratamiento de cicatrices queloideas recidivantes a otros tratamientos.

Experiencia inicial del tratamiento braquiterápicoen coadyuvancia a la resección quirúrgica decicatrices queloideas en población pediátrica / Initial experience with brachytherapy treatment adjuvant to surgical resection of keloid scars in the pediatric population

Objetivos: El tratamiento de las cicatrices queloideas se basa enmúltiples líneas terapéuticas, con diferentes niveles de eficacia (1) , sinexistir actualmente un tratamiento que garantice su curación y prevengasu recurrencia. En la población pediátrica los tratamientos empleados noestán estandarizados y no hay evidencia suficiente que avale su eficaciay sus complicaciones. Este trabajo tiene como objetivo analizar lospacientes que han precisado braquiterapia coadyuvante a la resecciónquirúrgica en cicatrices queloideas recidivantes.Material y métodos: Análisis retrospectivo de los pacientesdiagnosticados en nuestro centro de cicatriz queloidea, en los quese realizó braquiterapia coadyuvante, valorando su eficacia y suimplementación en nuestro protocolo de tratamiento de la cicatrizqueloidea. Resultados: Se estudiaron 4 pacientes entre 9-17 años con cicatricesqueloideas a nivel auricular, recidivantes a varias líneas terapéuticas,que fueron candidatos para el uso de braquiterapia coadyuvante, admi-nistrada posterior a la resección quirúrgica, en dos sesiones, se realizóseguimiento hasta 18-21 meses.Conclusiones: A pesar de nuestra limitada experiencia en el usode la braquiterapia coadyuvante, los resultados obtenidos hasta la fechaavalan su eficacia, de acuerdo con lo publicado en la literatura. Conside-ramos adecuada su inclusión en el tratamiento de cicatrices queloideasrecidivantes a otros tratamientos.(AU)

Objectives: The treatment of keloid scars is based on multiple linesof therapy, with varying levels of efficacy (1) , and there is currently nosingle treatment that guarantees cure and prevents recurrence. In thepediatric population, the treatments used are not standardized, and thereis insufficient evidence to support efficacy and complications. The objective of this study was to analyze the patients who required brachytherapyas an adjuvant to surgical resection in recurrent keloid scars.Materials and methods. A retrospective analysis of patients diagnosed with keloids and undergoing adjuvant brachytherapy in ourinstitution was carried out, while assessing efficacy and implementationin our treatment protocol for keloid scarring.Results: After various therapeutic lines, 4 patients aged 9-17 yearsold with recurrent keloid scars around the ear and eligible for adjuvantbrachytherapy – administered after surgical resection, in two sessions– were studied and followed up for up to 18-21 months.Conclusions: Despite our limited experience in the use of adjuvant brachytherapy, the results obtained to date support its efficacy,as reported in the literature. We therefore consider its inclusion in thetreatment of keloid scars that have recurred after other treatments tobe appropriate.(AU)

A new and simple scoring system to predict overall survival after irradiation for metastatic spinal cord compression.

PURPOSE: To develop a model that predicts survival in patients irradiated for metastatic spinal cord compression (MSCC), hence assisting in the decision between a short and a long-course radiotherapy (RT) regimen. METHODS: 138 patients diagnosed with MSCC and treated with RT alone were included. Based on a multivariate analysis, a scoring system was developed. It included four prognostic variables: age, number of vertebrae, ECOG and histology. Total scores ranged between 14 and 24 points and patients were divided into two groups. RESULTS: The 6-month survival rate was 22% for patients with a score of 14-18 points; and 69% for patients with a score of 19-24 points (P < 0.001). The system exhibits a high specificity and positive predictive value and an appropriate discriminative ability. CONCLUSIONS: Patients with scores between 19 and 24 points were found to survive longer, thus a long-course RT appears to be more appropriate.

18F-FDG PET/CT in staging and delineation of radiotherapy volume for head and neck cancer. / 18F-FDG PET/TC para la estadificación y la delineación del volumen de radioterapia en el cáncer de cabeza y cuello.

PURPOSE: The aim is to investigate the use of 18F-FDG (fluorine-18 fluorodeoxyglucose) PET/CT in head and neck cancer (HNC) staging and its effect on the therapeutic strategy and radiotherapy (RT) planning. METHODS AND MATERIALS: One hundred patients with HNC were included. Primary tumor sites: 18% oral cavity, 20% oropharynx, 12% hypopharynx, 11% nasopharynx, 37% larynx, 2% paranasal sinuses. Patients were staged according to the American Joint Committee of Cancer 7th edition. Stage: 5% stage I, 7% stage II, 14% stage III, 61% stage IVA, 7% stage IVB and 6% stage IVC. A contrast-enhanced CT and a 18F-FDG PET/CT acquired under RT position were performed. Both exams were compared to analyze patients' staging reclassification. Changes in therapeutic strategy were analyzed. RESULTS: 18F-FDG PET/CT detected 6 distant metastases and treatment intention changed to palliative. Eight synchronous tumors were detected; one received palliative treatment. 18F-FDG PET/CT reclassified cTNM staging in 27patients. Tumor extension changed in 28 (14% up-staged; 14% down-staged), implying a change in GTV (Gross Tumor Volume) delineation. Nodal detection was reclassified in 47 patients: 8 patients down-staged (N2C to N2A/N2B/N1) and 2 were false positive. Nineteen patients were false negatives and 5 staged as N+(N1/N2A/N2B) turned out into N2C. These staging modifications imply adapting the nodal volume to be irradiated. CONCLUSIONS: 18F-FDG PET/CT reclassification was higher than 10% in almost all categories studied (cTNM, tumor extension and nodal disease) and detects more metastases and synchronous tumors than conventional studies, which has an impact on the therapeutic patient management and RT planning.

Consensus on treatment of endometrium carcinoma with brachytherapy.

Radiotherapy (RT) is commonly used as adjuvant treatment following hysterectomy and double oophorectomy in endometrial carcinoma. Prophylactic vaginal brachytherapy (BT) is the most common treatment in BT units. The PORTEC and GOG 99 studies have attempted to clarify the indications of BT and postoperative external RT, changing treatment standards. However, prophylactic BT regimens are very varied and there is currently no consensus on how to treat patients in terms of dose per fraction and number of fractions. Moreover, unoperated cases of endometrium are uncommon and there is limited experience in their treatment with BT. The 9th Consensus Meeting of the SEOR and SEFM Brachytherapy Group, held in Malaga on 11 March 2011, was therefore dedicated to "Brachytherapy in Endometrial Carcinoma". This article presents the consensus on treatment of endometrial carcinoma in operated (prophylactic vaginal BT) and unoperated (endouterine BT) patients.

Consensus on treatment of endometrium carcinoma with brachytherapy

Radiotherapy (RT) is commonly used as adjuvant treatment following hysterectomy and double oophorectomy in endometrial carcinoma. Prophylactic vaginal brachytherapy (BT) is the most common treatment in BT units. The PORTEC and GOG 99 studies have attempted to clarify the indications of BT and postoperative external RT, changing treatment standards. However, prophylactic BT regimens are very varied and there is currently no consensus on how to treat patients in terms of dose per fraction and number of fractions. Moreover, unoperated cases of endometrium are uncommon and there is limited experience in their treatment with BT. The 9th Consensus Meeting of the SEOR and SEFM Brachytherapy Group, held in Malaga on 11 March 2011, was therefore dedicated to "Brachytherapy in Endometrial Carcinoma". This article presents the consensus on treatment of endometrial carcinoma in operated (prophylactic vaginal BT) and unoperated (endouterine BT) patients (AU)

Valor de la biopsia gonadal en el diagnóstico de los desórdenes del desarrollo sexual / Diagnostic value of the gonadal biopsy in the disorders of sex development

La información proporcionada por la biopsia testicular en los estados intersexuales es primordial para la identificación, clasificación y detección precoz de neoplasias en estos pacientes. Antes de decidir una determinada opción terapéutica, los datos del estudio histológico de la biopsia gonadal deberán ser evaluados junto con los datos clínicos, genéticos, hormonales y moleculares. La diferenciación sexual es el resultado de complejos mecanismos genéticos y endocrinos, por ello, en el presente trabajo se revisan en primer lugar los acontecimientos que ocurren en el desarrollo embrionario de las gónadas, atendiendo a los mecanismos genéticos implicados en la determinación sexual y en la diferenciación testicular y del tracto urogenital. En segundo lugar se revisan los distintos tipos de gónadas observadas en los desórdenes del desarrollo sexual (síndromes de regresión testicular, cintilla fibrosa, disgenesia testicular, cintilla testículo, ovotestes, testículos microscópicamente normales y ovario), haciendo énfasis en los datos histológicos presentes en cada uno de ellos y en los datos diferenciales que permiten al patólogo distinguir unos desórdenes de otros, junto con la integración de los datos clínicos, genéticos hormonales y moleculares de cada una de estas situaciones. En tercer lugar se considera la incidencia de neoplasias, tanto en las diferentes situaciones clásicamente llamadas disgenesia gonadal, como de pseudohermafroditismos masculinos y hermafroditismo verdadero. Por último, se comentan las limitaciones de la biopsia gonadal que pueden impedir que el patólogo llegue a un diagnóstico preciso de un desórden del desarrollo sexual

The gonadal biopsy provides essential information for the identification, classification and early detection of neoplasias in patients with disorders of sex development. Histopathological findings in these cases must be analysed together with clinical, hormonal, genetic and molecular information before deciding a therapeutic option. Sexual differentiation is the result of multiple and complex genetic and endocrinal mechanisms; therefore, we first present the events taking place during gonadal embryonic development, focusing on the genetic mechanisms involved in sexual determination and the differentiation of the testis and the urogenital tract. In second place, we describe the different gonads in the intersexual states -in testicular regression syndrome, fibrous streak, testicular dysgenesis, streak testes, ovotestes and microscopically normal testes and ovaries-, highlighting the histological features and the differential findings that allow the pathologist to distinguish between these entities with the aid of clinical, genetic, hormonal and molecular information that are characteristic for each situation. In third place, we studied the incidence of neoplasias in gonadal dysgenesis, male pseudohermaphroditism and true hermaphroditism. Finally, we discuss the limitations of gonadal biopsy to achieve a correct diagnosis in the disorders of sex development

[Diagnostic value of the gonadal biopsy in the disorders of sex development]. / Valor de la biopsia gonadal en el diagnóstico de los desórdenes del desarrollo sexual.

The gonadal biopsy provides essential information for the identification, classification and early detection of neoplasias in patients with disorders of sex development. Histopathological findings in these cases must be analysed together with clinical, hormonal, genetic and molecular information before deciding a therapeutic option. Sexual differentiation is the result of multiple and complex genetic and endocrinal mechanisms; therefore, we first present the events taking place during gonadal embryonic development, focusing on the genetic mechanisms involved in sexual determination and the differentiation of the testis and the urogenital tract. In second place, we describe the different gonads in the intersexual states -in testicular regression syndrome, fibrous streak, testicular dysgenesis, streak testes, ovotestes and microscopically normal testes and ovaries-, highlighting the histological features and the differential findings that allow the pathologist to distinguish between these entities with the aid of clinical, genetic, hormonal and molecular information that are characteristic for each situation. In third place, we studied the incidence of neoplasias in gonadal dysgenesis, male pseudohermaphroditism and true hermaphroditism. Finally, we discuss the limitations of gonadal biopsy to achieve a correct diagnosis in the disorders of sex development.

Adenomatous hyperplasia of the rete testis. A review and report of new cases.

Adenomatous hyperplasia of the rete testis (AHRT) is an uncommon benign lesion that preferentially involves the septal rete testis and mediastinal rete testis. It is usually an incidental finding in surgical specimens from cryptorchidism and testicular tumour. It can be found in autopsy specimens from patients dying with different chronic diseases and newborns with kidney diseases. Since its first description many articles have been published communicating new cases and putting forward some hypotheses on its aetiology and pathogenic mechanisms. Some authors suggest a role for hormonal changes, tumour invasion and action of chemical agents. We think that AHRT should be categorised into two main aetiological categories: congenital and acquired. The cases associated with different kidney and spermatic duct diseases, most cases associated with cryptorchidic testis and some cases associated with testicular germ cell tumour should be included in the congenital group. The remaining cases associated with chemical agents, some hormonal changes (i.e. androgen blockade) and most of the germ cell tumour cases can be considered as acquired AHRT. Differential diagnosis must be established mainly with metastatic adenocarcinoma of prostate to testis and primary adenocarcinoma of the rete testis. Pseudohyperplasia of the rete testis must also be considered in atrophic testes. Here we review the papers published on this subject and report our recent cases.

Metástasis peritoneales en el cáncer de mama: un patrón típico de diseminación del carcinoma lobulillar infiltrante / Peritoneal metastasis in breast cancer: a typical dissemination pattern of infiltrative lobular carcinoma

- Propósito: Descripción del patrón característico de disemimación metastática peritoneal del carcinoma lobulillar infiltrante de mama.- Material y métodos: Describimos tres casos de carcinomatosis peritoneal secundaria a la diseminación metastática de carcinoma lobulillar infiltrante de mama. Dos de nuestras pacientes fueron diagnosticadas de carcinomatosis peritoneal como primera manifestación de un carcinoma lobulillar de mama, y la tercera diesiciete años después de su diagnóstico inicial. - Discusión: Las metástasis peritoneales en una paciente con un carcinoma de mama son poco frecuente, pero cuando aparecen suelen ser secundarias a un carcinoma lobulillar infiltrante de mama con receptores hormonales positivos. La inespecificidad de los síntomas junto a un intervalo normalmente largo, incluso de años después de un diagnóstico inicial del tumor, hace difícil diferenciar desde el punto de vista clínico entre un tumor primario de la cavidad peritoneal o la presencia de metástasis de un carcinoma de mama. Este diagnóstico se vuelve aún más complicado cuando la lesión metastática peritoneal es la primera manifestación del cáncer de mama, como ocurrió en dos de nuestras pacientes. Los estudios de inmunohistoquímica pueden ser útiles para lograr un diagnóstico correcto. Los marcadores más informativos son la proteína 15 del flujo de los quistes mamarios (GCDFP-15:gross cystic disease fluid protein-15), y los receptores de estrógeno y progesterona. La identificación de esta entidad es importante para el oncólogo, condiciona el pronóstico y la elección de modalidades terapéuticas adecuadas que difieren a la de otros tumores que también pueden cursar con carcinomatosis peritoneal en su evolución. La quimioterapia y sobre todo la hormonoterapia, tanto los antiestrógenos como los inhibidores de la enzima aromatasa, en tumores con receptores hormonales positivos, puede ser efectiva con remisiones parciales o completas del tumor, que en algunos casos son prolongadas en el tiempo (AU)

Antifungal activities of two new azasordarins, GW471552 and GW471558, in experimental models of oral and vulvovaginal candidiasis in immunosuppressed rats.

Sordarins constitute a new class of antifungal agents with a novel mechanism of action involving the selective inhibition of fungal protein synthesis. A further evolution of this class of antifungals has led to a new family of sordarin derivatives called azasordarins. The therapeutic efficacies of two new azasordarins, GW471552 and GW471558, were studied in experimental models of oral and vulvovaginal candidiasis in immunosuppressed rats. In all cases rats were immunosuppressed with dexamethasone in the drinking water. Oral candidiasis was established by inoculating 0.1 ml of a yeast suspension containing 5 x 10(8) cells of Candida albicans 4711E with a cotton swab on three alternate days. Vulvovaginal candidiasis was established in ovariectomized and estrus-induced rats by intravaginal inoculation of 10(7) CFU of C. albicans 4711E in 0.1 ml of saline. GW471552 and GW471558 were administered at 1, 5, and 10 mg/kg of body weight via the subcutaneous route. In oral candidiasis, azasordarins were administered each 8 h for 7 consecutive days, while in vaginal candidiasis the compounds were given each 4 h for 3 consecutive days. Antifungal activity of azasordarins was assessed by colony counts and by histological examination 1 day after treatment. In the oral infection model, GW471552 and GW471558 administered at 5 mg/kg significantly reduced (P < 0.05) the number of CFU of C. albicans compared with untreated controls. In addition, GW471552 and GW471558 given at 10 mg/kg eradicated C. albicans from the oral cavities of 100% of infected animals. Against vulvovaginal infection, both compounds showed significant therapeutic efficacy. GW471552 was able to eradicate the vaginal fungal burden at a dose of 10 mg/kg, and it significantly reduced the number of CFU of C. albicans in vaginas of rats treated with a dose of 5 mg/kg (P < 0.05). GW471558 showed greater efficacy, eradicating the fungal burden of 100% of infected rats at a dose of 5 mg/kg and significantly reducing (P < 0.05) the C. albicans vaginal counts even at a dose of 1 mg/kg. In both therapeutic efficacy studies, the histological findings confirmed the microbiological results. The experimental results presented show that the tested azasordarins are effective against oral and vulvovaginal candidiasis in immunosuppressed rats and could be promising antifungal agents for use in humans.

El papel de la radioterapia adyuvante en el cáncer de endometrio: a propósito de 290 casos, estadios I-II / The role of adjuvant radiotherapy in endometrial cancer: a report on 290 cases, stages I-II

Objetivo: Comunicar los resultados del tratamiento radioterápico adyuvante en enfermas con estadios clínicos precoces de cáncer de endometrio (estadios I-II (oculto)) e identificar factores pronósticos que se asocian a una peor evolución. Diseño: Se han seleccionado, los historiales médicos de 290 enfermas, que recibieron tratamiento radioterápico complementario en el Servicio de Oncología Radioterápica del Hospital Universitario 12 de Octubre, entre 1979 y 1996. Todas ellas, presentaban, estadios clínicos iniciales (I-II (oculto)) de cáncer de endometrio, siendo manejadas inicialmente con cirugía, bien histerectomía total y doble anexectomía (216 enfermas, 74.5 por ciento), o bien histerectomía total, doble anexectomía y muestreo ganglionar, con o sin lavado peritoneal (74 enfermas; 25.5 por ciento); todas ellas se seleccionaron porque tenían un estadio patológico comprendido entre IBIIIC que las hacía subsidiarias de recibir radioterapia postoperatoria, bien mediante radioterapia externa (36 enfermas), bien mediante radioterapia endocavitaria (18 enfermas) o bien mediante ambas (236 enfermas). El seguimiento medio libre de enfermedad (SLE, tiempo desde la finalización de la radioterapia hasta cualquier tipo de fracaso) de las pacientes ha sido de 71 meses (rango 2-210). Características de las pacientes: Edad media 62 años (rango 31-85); Agrupación por Estadios Patológicos: Estadio IB, 71 casos (24:5 por ciento), Estadio IC, 98 casos (33.8 por ciento), Estadio II, 56 casos (19.3 por ciento); Estadio III 65 casos; (22.4 por ciento); Infiltración miometrial: del 50 por ciento: 82 por ciento y 77.4 por ciento. Grado Histológico: G1: 91 por ciento y 89.5 por ciento, G2: 91 por ciento y 79 por ciento, G3: 67.7 por ciento y 54 por ciento. Estado de los bordes quirúrgicos: Libres: 89 por ciento y 84 por ciento, Infiltrados: 51 por ciento y 26 por ciento. La edad media del grupo de enfermas que fracasaron fue idéntica a las que no lo hicieron, 62 años En el análisis multivariante: los factores pronóstico que influyeron en el fracaso fueron el grado histológico G3 (Tasa de riesgo (TR) 3.67), la infiltración miometrial superior al 50 por ciento (TR 3.21), y el borde infiltrado (TR 3.2). El estadio patológico III pese a que se asoció a una mayor tasa de riesgo para la recidiva III (TR 3.37) y con tendencia a peor evolución, no alcanzó significación estadística. Conclusión: Las enfermas con estadios clínicos iniciales (I-II (oculto)) de cáncer de endometrio, tratadas con cirugía y RT postoperatoria, presentan un buen pronóstico; pero la presencia de bordes quirúrgicos infiltrados, infiltración miometrial superior al 50 por ciento, grado histológico G3 lo ensombrecen. Probablemente la cirugía extendida y los ensayos clínicos (pendientes de comunicación de resultados) ayuden a seleccionar, de forma más efectiva, la necesidad o no de radioterapia adyuvante, y la extensión de la misma. (AU)

Androgen receptor expression in sertoli cells as a function of seminiferous tubule maturation in the human cryptorchid testis.

Androgen receptor (AR) immunohistochemistry was performed in an archival collection of adult human cryptorchid testes to determine whether AR cellular distribution and intensity of immunostaining were functions of the severity of cellular dysgenesis. The seminiferous tubule histology of cryptorchid testes collected from adults is marked by three specific patterns. 1) Seminiferous tubules are characterized as maintaining focal areas of germinal cell differentiation (albeit incomplete) that are interspersed with 2) tubules composed of Sertoli cells only, these latter cells being principally of the adult type, although dysgenetic and immature Sertoli cells may also be detected. 3) In contrast, there is a class of tubule that is characterized as being composed exclusively of Sertoli cells that are extremely dysgenetic in appearance. The majority of adult-type Sertoli cells found in the first types of tubules exhibited either robust or moderate AR staining intensity. Peritubular cells of these tubules also expressed a similar AR staining intensity. In contrast, in the more dysgenetic and immature type Sertoli cells found in the second type of tubules, the intensity of AR staining was significantly less, if not missing altogether. Finally, in the most dysgenetic tubules, Sertoli cell AR staining was never detected. To our knowledge, this is the first report in the literature that addresses the intensity of AR immunostaining in Sertoli cells of cryptorchid testes. The results presented herein are consistent with the interpretation that the intensity of AR staining in Sertoli cells diminishes as a function of the severity to which the cells are afflicted within a cryptorchid testis and that focal absence of AR expression in Sertoli cells correlates with a lack of local spermatogenesis in the tubules.

Epididymal growth and differentiation are altered in human cryptorchidism.

Despite the knowledge and histological classification of testicular lesions, epididymal lesions associated with cryptorchidism are not well defined and only macroscopic alterations have been reported. We have evaluated the alterations in the growth of both the epithelium and muscular wall of efferent ducts and epididymis in human patients with cryptorchidism from infancy to adulthood. In addition, by cytokeratin immunostaining we have also evaluated the stage of differentiation of each segment along the human postnatal life in these patients. A decrease is shown in the size of efferent and epididymal ducts in cryptorchid children compared with normal, age-matched controls. The height of the epithelium, muscular wall, and lumen of the cryptorchid epididymis were reduced at every age studied. This decrease in all regions was seen even in the testicular quiescent period (1 to 4 years of age). In addition, the cryptorchid epididymis grows more slowly during the transition to the pubertal period. The smaller size of the cryptorchid epididymis in pubertal and adult men compared with that of normal men is due primarily to underdevelopment of the muscular wall and a reduction in epithelial height. The pattern of growth of cryptorchid efferent ducts and ductus epididymides parallels that in normal men, except that development of the lumen and muscular layer in the cauda epididymis region are delayed. Epithelial differentiation, monitored by cytokeratin expression, is minimal in efferent ducts and throughout the epididymis of the cryptorchid male, and this is already seen in children. In conclusion, our immunohistochemical and morphometric results show a reduced development of the human cryptorchid epididymis that is already evident in childhood. They indicate that cryptorchidism is a primary congenital illness of the testis and spermatic ducts, with evident lesions from the first years of life, and suggest that surgical descent would probably not be able to completely reverse these alterations.

Antifungal efficacy of GM237354, a sordarin derivative, in experimental oral candidiasis in immunosuppressed rats.

GM237354 is a novel sordarin derivative with a broad spectrum of potent activity against a wide range of fungi. The members of this new class of antifungal agents act as potent inhibitors of fungal protein synthesis. In this study, the therapeutic effects of GM237354 were investigated in a novel experimental oral Candida albicans infection model in immunosuppressed rats. The animals were immunosuppressed with dexamethasone in their drinking water and infected on three alternate days. GM237354 was given three times per day for seven consecutive days at 1.25, 2.5, 5, or 10 mg/kg of body weight per dose. In addition, to provide a preliminary idea of the correlation between regimen administration and therapeutic efficacy, GM237354 was administered to two additional groups of rats at 5 mg/kg once or twice a day for 7 days. The drug efficacy was assessed microbiologically, histologically, and by a morphometric study of lesions. Evident agreement was observed among results obtained by the different methods in all of the animals studied. Microbiologically, the efficacy of GM237354 was determined by measuring the number of C. albicans organisms in the oral cavities of rats in the middle (day 4) and at the end (day 7) of the treatment. GM237354 administered at 5, 7.5, 10, 15, or 30 mg/kg/day for 7 days significantly reduced the number of CFU in the oral cavities of treated rats compared with the number of CFU in the oral cavities of the untreated controls. A significant reduction was also observed when GM237354 was administered at 7.5, 10, 15, or 30 mg/kg/day for 4 days. Furthermore, C. albicans was not detected in oral swabs from any infected rats after 1 week of treatment when GM237354 was administered at 15 or 30 mg/kg/day or after 4 days of treatment at 30 mg/kg/day. Histologically, untreated control animals showed extensive colonization of the epithelium of the dorsal tongue by numerous hyphae. Animals treated with GM237354 at 7.5 mg/kg/day showed small areas with superficial hyphal penetration into the epithelium that produced intraepithelial microabscesses. However, animals treated with GM237354 at 15 mg/kg/day showed multiple regenerative areas of the covering epithelium, and only focalized zones of the tongue surface were occupied by hyphae. No hyphal colonization of the epithelium was seen in rats treated with GM237354 at 30 mg/kg/day and which showed extensive areas of epithelial regeneration of the tongue. The histopathology findings were confirmed by morphometry studies, and the percentage of epithelium occupied by C. albicans hyphae decreased from 17.5% in the control group to 4.8 and 0.1% in animals treated with GM237354 at 7.5 and 15 mg/kg/day, respectively. These results demonstrated that the sordarin derivative GM237354 was effective against experimental oral candidiasis in immunosuppressed rats, and further studies are needed to determine the potential of GM237354 for use in the treatment of this infection in humans.

Sustained gastrointestinal colonization and systemic dissemination by Candida albicans, Candida tropicalis and Candida parapsilosis in adult mice.

The ability of nine clinical isolates of Candida species (three C. albicans, three C. tropicalis and three C. parapsilosis) to colonize and invade the gastrointestinal (GI) tract of adult male CD-1 (ICR) mice was determined. The effect of dietary tetracycline plus glucose supplementation on colonization was evaluated. Strains were intragastrically inoculated. Tetracycline and glucose altered substantially aerobic flora, especially streptococci (average fall 1.1 +/-0.3 log(10) CFU/g, p<0.01 by the Student's t test). At two weeks after oral challenge, sustained and high colonization of GI tract by Candida (mean 5,28 +/- 0.18 log(10) CFU/g, p<0.01) was achieved in all mice receiving glucose-tetracycline supplementation, excepting in animals inoculated with one of C. tropicalis isolates. Histologic sections of the stomachs revealed multiple intraepithelial micro-abscesses associated with hyphae in the region of the cardial-atrium fold. Under immunosuppression, systemic spread of C. albicans and C. tropicalis was observed in 62% and 24% of animals receiving dietary supplementation respectively. Dissemination was not noted for C. parapsilosis isolates. We have developed a simple and inexpensive murine model of sustained colonization of GI tract. This model could be useful for analyzing prophylaxis, treatment and diagnosis of systemic Candida infections and for evaluating virulence of strains.

Carcinoma de recto de alto riesgo: factores pronóstico y resultados del tratamiento combinado postquirúrgico en el Hospital Universitario Doce de Octubre / High-risk rectal carcinoma: prognostic factors and postoperative adjuvant combined treatment results at Doce de Octubre University Hospital

Propósito: Análisis retrospectivo de los resultados del tratamiento adyuvante combinado postquirúrgico en el carcinoma de recto de alto riesgo en el H.U. Doce de Octubre (Madrid). Material y métodos: Entre 1992 y 1997, 186 pacientes diagnosticados de carcinoma de recto estadios II y III recibieron tratamiento postquirúrgico con radioterapia (50.4Gy) y quimioterapia (146 con 5 FU bolus o infusión continua y 40 con Tegafur oral). Resultados: La supervivencia global a 5 años es del 70 por ciento, la supervivencia libre de enfermedad del 65 por ciento, y el control loco-regional del 80 por ciento. Resultaron factores pronóstico significativos la afectación ganglionar, el estadio patológico, el grado histológico, el T y la prolongación del tratamiento radioterápico. Ni la localización del tumor en recto ni el esquema de quimioterapia empleado han influido significativamente en los resultados. Conclusiones: Los resultados obtenidos con el tratamiento adyuvante combinado postquirórgico en el carcinoma de recto son muy satisfactorios. El factor con mayor valor pronóstico es la afectación ganglionar. No existen diferencias significativas en función del régimen de quimioterapia administrado (AU)

Statistical considerations in the methodology of quantifying immunocompetent cells in tumors.

OBJECTIVE: To quantify immunocompetent cell (IC) density for different testicular tumors and antibodies and to verify if the results of the comparisons depend on the antibody used. STUDY DESIGN: T-lymphocytes were studied with CD3 and UCHL1 antibodies and macrophages with MAC387 and CD68 in 43 patients with seminomas, mature teratomas, immature teratomas and embryonal carcinomas of the testis. Counts were expressed as number of IC per square millimeter. RESULTS: Use of different antibodies produced significant differences in the IC cell number; moreover, in the case of macrophages, the tumor type sequence by increasing cell number was different according to the antibody used. CONCLUSION: These results suggest the existence of a statistical interaction between the type of tumor and antibody.