ADENOCARCINOMA PAPILAR DEL CUELLO UTERINO: COMUNICACIÓN DE UN CASO Y REVISIÓN DE LA LITERATURA

Se presenta el caso clínico de una paciente de 42 años con diagnóstico de adenocarcinoma seroso papilar del cuello uterino etapa Ib1 tratada mediante histerectomía radical más linfadenectomía pélvica bilateral. El estudio anatomopatológico demostró bordes quirúrgicos libres y ausencia de enfermedad metastásica ganglionar por lo que se consideró a la paciente tratada. Este es el primer caso de adenocarcinoma seroso papilar del cuello uterino reportado en el país. Hay que descartar el compromiso cervical secundario por tumores serosos de endometrio, ovario o trompa antes de plantear el origen primario de cuello uterino. No se conoce el real comportamiento, pronóstico y óptimo tratamiento en este tipo de tumores. La determinación de los niveles de CA-125 basal y seriados durante el seguimiento pudiese ser de utilidad en la evaluación del tratamiento realizado y en la sospecha de enfermedad persistente o reciPad

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

ADENOCARCINOMA PAPILAR DEL CUELLO UTERINO: COMUNICACIÓN DE UN CASO Y REVISIÓN DE LA LITERATURA

Se presenta el caso clínico de una paciente de 42 años con diagnóstico de adenocarcinoma seroso papilar del cuello uterino etapa Ib1 tratada mediante histerectomía radical más linfadenectomía pélvica bilateral. El estudio anatomopatológico demostró bordes quirúrgicos libres y ausencia de enfermedad metastásica ganglionar por lo que se consideró a la paciente tratada. Este es el primer caso de adenocarcinoma seroso papilar del cuello uterino reportado en el país. Hay que descartar el compromiso cervical secundario por tumores serosos de endometrio, ovario o trompa antes de plantear el origen primario de cuello uterino. No se conoce el real comportamiento, pronóstico y óptimo tratamiento en este tipo de tumores. La determinación de los niveles de CA-125 basal y seriados durante el seguimiento pudiese ser de utilidad en la evaluación del tratamiento realizado y en la sospecha de enfermedad persistente o reciPadaA 42 year old patient with a diagnosis of serous papillary adenocarcinoma of the cervix stage Ib1 treated by radical hysterectomy and bilateral lymphadenectomy is reported. The patient was considered treated because the pathology study did not demonstrate tumor outside the cervix or lymphatic nodes. The serous papillary adenocarcinoma of the uterine cervix is an extremely infrequent tumor and therefore compels to discard a secondary cervical involvement by serous tumors derived from the endometrium, ovary or tube. This is the first chilean case reported. The prognosis and optimum treatment of these tumors is still uncertain. Basal Ca-125 and then during the follow-up could help in evaluation of treatment as well as in the suspicion of persistent illness or reciPe

TUMOR DE CELULAS DE LA GRANULOSA DEL OVARIO

Se comunican 10 casos de tumor de células de la granulosa diagnósticados y/o tratados en nuestra Institución entre 1991 y 2002. Se revisa la forma de presentación, tipo cirugía, utilidad de la biopsia rápida, histología, distribución por etapas, el tipo de tratamiento y seguimiento posterior. El 70% de los casos se presentó en etapa I. En 4 de 5 casos en que se realizó biopsia contemporánea (80%), hubo concordancia con el informe definitivo. La modalidad terapéutica predominante en etapa temprana fue la cirugía (anexectomía en pacientes con deseo de paridad e histerectomia total más anexectomía bilateral en aquellas con paridad cumplida). En pacientes jóvenes diagnosticadas después de la cirugía inicial privilegiamos la reexploración para completar la etapificación. La mediana de seguimiento fue de 38 meses (12-140 meses). Solo hubo una recurrencia, en ganglios periaórticos, y fue tratada con bloqueo hormonal y quimioterapia. Concluimos que el tumor de la granulosa es una entidad poco frecuente, con diferentes formas de presentación clínica pero de buen pronóstico cuando se presenta en etapa temprana (etapa I) y se trata con cirugía sol

TUMOR DE CELULAS DE LA GRANULOSA DEL OVARIO

Se comunican 10 casos de tumor de células de la granulosa diagnósticados y/o tratados en nuestra Institución entre 1991 y 2002. Se revisa la forma de presentación, tipo cirugía, utilidad de la biopsia rápida, histología, distribución por etapas, el tipo de tratamiento y seguimiento posterior. El 70% de los casos se presentó en etapa I. En 4 de 5 casos en que se realizó biopsia contemporánea (80%), hubo concordancia con el informe definitivo. La modalidad terapéutica predominante en etapa temprana fue la cirugía (anexectomía en pacientes con deseo de paridad e histerectomia total más anexectomía bilateral en aquellas con paridad cumplida). En pacientes jóvenes diagnosticadas después de la cirugía inicial privilegiamos la reexploración para completar la etapificación. La mediana de seguimiento fue de 38 meses (12-140 meses). Solo hubo una recurrencia, en ganglios periaórticos, y fue tratada con bloqueo hormonal y quimioterapia. Concluimos que el tumor de la granulosa es una entidad poco frecuente, con diferentes formas de presentación clínica pero de buen pronóstico cuando se presenta en etapa temprana (etapa I) y se trata con cirugía solaWe report 10 patients with granulosa cell tumor of the ovary diagnosed and/or treated at our institution between 1991 and 2002. A review of the clinical presentation, the surgical approach, the utility of frozen-section biopsy, the histology and the stage of the disease, treatment modalities, and follow-up is done. Eighty percent of the patients were stage I. Four out of five patients whose frozen-section biopsies were done, the diagnosis was confirmed at the definitive report. At early stage, surgery was the main modality of treatment (unilateral salpingo-ophorectomy in patients who wanted to preserve fertility and bilateral salpingo-ophorectomy plus total abdominal hysterectomy who did not). Young patients who were diagnosed after initial surgery underwent complete surgical staging. The median follow-up was 38 months (range 12 to 140 months). Only one recurrence was diagnosed, at the periaortic lymph nodes, and treated with hormone therapy plus chemotherapy. We conclude that the granulosa cell tumor is an uncommon entity with different clinical presentations and with good prognosis when diagnosed at early stage (stage I) and treated with surgery alon

DISTRIBUCIÓN DE LA PATOLOGÍA QUIRÚRGICA DEL CUERPO UTERINO EN MUJERES CHILENAS SOMETIDAS A HISTERECTOMÍA EN UN HOSPITAL CLÍNICO UNIVERSITARIO

Antecedentes: La histerectomía es la cirugía ginecológica mundialmente más frecuente. Pocas series analizan la distribución de los hallazgos patológicos en histerectomizadas. Objetivos: Describir la distribución de la patología uterina originada en el endometrio, miometrio y estroma, en histerectomías efectuadas en un centro universitario. Determinar la frecuencia en que coexisten patologías, particularmente cáncer incidental en histerectomías por condiciones presuntamente benignas. Métodos: Estudio retrospectivo de todas las histerectomías efectuadas entre los años 1991 y 2005. Análisis descriptivo de la distribución de las enfermedades benignas y malignas originadas en el cuerpo uterino. Resultados: Se realizaron 5683 histerectomías. En 4275 úteros se diagnosticaron lesiones de origen no epitelial, principalmente leiomio-mas uterinos y adenomiosis. En las 2070 piezas con lesiones epiteliales (endometrio) los hallazgos más prevalentes fueron atrofia, pólipo endometrial e hiperplasia glandular del endometrio. Hubo coexistencia de patología miometrial y endometrial en 905 piezas quirúrgicas. En 240 casos no hubo lesiones en la biopsia (4,2%). En el 1% de las histerectomías se encontró como hallazgo un cáncer ginecológico, siendo los dos diagnósticos más frecuentes asociados con esta situación, la metrorragia disfuncional perimenopáusica y el pólipo endometrial. Conclusiones: La distribución de los diagnósticos de la patología uterina es similar a la descrita por series internacionales. El hallazgo más común es el leiomioma uterino, frecuentemente asociado con adenomiosis. Se destaca el hallazgo incidental de cáncer de endometrio en histerectomizadas por metrorragia y/o pólipo endometrial; esto nos hace recomendar el uso rutinario del estudio biópsico preoperatorio en pacientes con metrorragia y de la biopsia contemporánea en casos de pólipo endometrial.Background: Hysterectomy is the most frequently performed gynecologic procedure worldwide. Few studies have been done to analysis the distribution of pathological findings in hysterectomies. Objectives: To determine the distribution of epithelial and non-epithelial pathology in patients undergoing hysterectomy for uterine disease in an academic centre. To establish what is the percentage and the etiology of concurrent pathologies and the incidence of unexpected cancer within patients undergoing surgery for a presumably benign condition. Methods: A retrospective study was done of all the patients undergoing hysterectomy between 1991 and 2005. In addition a descriptive analysis of the distribution of benign and malignant conditions originated in the uterine corpus was done highlighting the occurrence of incidental cancer among different preoperative diagnosis. Results: During the period, 5683 hysterectomies were performed. In 4275 cases a non-epithelial pathology was found, mainly, fibroids and adenomyosis. In 2070 cases endometrial pathology was diagnosed: atrophy, polyps and hyperplasia as the most prevalent findings. In 905 cases myometrial and endometrial pathology of uterine corpus coexists. In 240 cases any pathology was found (4.2%). In 1% of hysterectomies an incidental gynecological cancer was found, and the two conditions more frequently associated were metrorrhagia and polyps. Conclusions: The distribution of etiologies for the uterine pathology, is similar to other international series. The most common finding is fibroid frequently associated to adenomyosis. It is important to highlight the incidental finding of endometrial cancer among patients operated on by metrorrhagia and/or polyps. Based on this, we recommend the routine use of preoperative biopsy in patients with metrorrhagia and frozen section biopsy in those with polyps