Transcriptomic Profiling of Primary Prostate Cancers and Nonlocalized Disease on Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.

PURPOSE: To characterize the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-based metastatic spread. MATERIALS AND METHODS: We identified patients from four institutions who underwent PSMA PET/CT scans pretreatment for primary staging or postradical prostatectomy (RP) for suspected recurrence and had Decipher transcriptomic data available from biopsy or RP specimens. PSMA PET/CT-based patterns of spread were classified as localized (miT + N0M0) or nonlocalized (miN1M0 or miM1a-c). We calculated the association between Decipher scores and the risk of nonlocalized disease on PSMA PET/CT using multivariable logistic regression for pretreatment patients and multivariable Cox regression for post-RP patients. We also compared select transcriptomic signatures between patients with localized and nonlocalized diseases. RESULTS: Five hundred eighty-six patients were included (pretreatment: n = 329; post-RP: n = 257). Higher Decipher scores were associated with nonlocalized disease on PSMA PET/CT both pretreatment (odds ratio, 1.18 [95% CI, 1.03 to 1.36] per 0.1 increase in Decipher score, P = .02) and post-RP (hazard ratio, 1.15 [95% CI, 1.05 to 1.27] per 0.1 increase in Decipher score, P = .003). In the pretreatment setting, nonlocalized disease was associated with higher rates of TP53 mutations and lower rates of PAM50 luminal A subtype compared with localized disease. In the post-RP setting, overexpression of signatures related to metabolism, DNA repair, and androgen receptor signaling were associated with higher rates of nonlocalized disease. CONCLUSION: Higher Decipher scores were associated with nonlocalized disease identified on PSMA PET/CT both pretreatment and post-RP. There were several transcriptomic differences between localized and nonlocalized diseases in both settings.

Response to RL-225Ac in prostate cancer: Effect of prior treatment with RL-177Lu: A systematic review of the literature.

BACKGROUND: Targeted radionuclide therapy with Actinium-225-labeled prostate-specific membrane antigen agents (225Ac-PSMA) is currently being studied in clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC). Compared to ß-emitting therapeutic radionuclides, alpha-emitters (e.g., 225Ac) have a significantly higher linear energy transfer and significantly shorter range. As a result, alpha emitters could be expected to improve efficacy and reduce bystander toxicity. This systematic literature review was conducted to evaluate the impact of sequencing of 177Lu-PSMA and 225Ac-PSMA targeted radionuclide therapy (TRT) in mCRPC. METHODS: The present systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The searches were made using relevant keywords in the PubMed, Scopus, and Web of Science databases, and articles up to August 22, 2022, were included. Publications were excluded if they were duplicate publications, wrong study or publication format, or discussing a topic out of scope. Data on efficacy, toxicity, and health-related quality of life were extracted from the individual articles. The I2 index was used to measure the extent of heterogeneity amongst studies. In the studies that reported subgroup outcomes according to the prior status on 177Lu-PSMA TRT, pooled estimates of the main outcomes were generated through descriptive analysis. Quality assessment was performed using the Newark-Ottawa-scale. RESULTS: The study included 12 articles; 1 series was performed prospectively. In total, data of 329 patients were analyzed. About 40.1% (n = 132) of the included men were pretreated with 177Lu-PSMA TRT. Seven studies, including data of 212 individuals, were eligible for quantitative analysis based on reporting outcomes of the subgroups according to their prior status on 177Lu-PSMA TRT. >25% PSA decline after 225Ac-PSMA TRT was lower in individuals who received prior 177Lu-PSMA TRT (pooled median 42.7%) compared to those who did not (pooled median 15.4%). The pooled medians of the reported median progression-free survival and overall survival for pretreated versus not pretreated individuals was 4.3 versus 14.3 months and 11.1 versus 9.2 months, respectively. However, the outcomes for each individual study were reported inconsistently (I2 = 99.9%). None of the included studies stratified the report of adverse events or changes in health-related quality of life for the subgroups. CONCLUSIONS: 225Ac-PSMA TRT is an experimental treatment for men with mCRPC. There is limited data available from high-quality trials but so far PSMA-targeted TRT has demonstrated a low morbidity profile. Our review revealed that there is a possible decrease in efficacy of targeted alpha-particle therapy if individuals previously were exposed to 177Lu-PSMA TRT. However, the level of evidence is low. The underlying mechanism by which 177Lu-PSMA TRT might trigger possible radioresistance as well as randomized controlled trials are required to establish the therapeutic efficacy and safety of 225-Ac-PSMA TRT in men refractory to 177Lu-PSMA TRT.

Características clínicas del espectro de la enfermedad asociada a los anticuerpos contra la glucoproteína del oligodendrocito asociada a la mielina / Clinical presentation of the spectrum of myelin oligodendocryte glycoprotein antibody disease

INTRODUCCIÓN: La enfermedad asociada a anticuerpos contra la glucoproteína del oligodendrocito asociado a la mielina (MOG) es una entidad infrecuente y prácticamente nueva en la medicina. En países en desarrollo, aún hay importantes limitaciones para la detección de los anticuerpos anti-MOG mediante ensayo basado en células, por lo que conocer las características clínicas de los diferentes fenotipos y sus diferencias con otras patologías desmielinizantes del sistema nervioso es fundamental, y con ello realizar un abordaje diagnóstico y terapéutico adecuado de los pacientes. OBJETIVO: Presentar una actualización en cuanto a las características clínicas del espectro de la enfermedad. Éste es el primer artículo en castellano que reúne los fenotipos más frecuentes y brinda una descripción clara de lo que se debe tener en cuenta en cada uno de ellos. DESARROLLO: Esta entidad se caracteriza por tener un curso monofásico o recurrente. La neuritis óptica es el fenotipo de presentación más frecuente en la población general, y la encefalomielitis aguda diseminada, la más frecuente en los niños. Otros fenotipos que se describen en la presente revisión son la mielitis transversa, la encefalitis cortical y los síndromes de tallo cerebral, así como los criterios propuestos para el diagnóstico de la enfermedad asociada a anticuerpos anti-MOG. CONCLUSIONES: En la actualidad no existen estudios que busquen caracterizar a la población hispanoparlante con esta enfermedad ni artículos de revisión en lengua castellana, por lo que es importante difundir conocimiento y desarrollar investigación en esta área

INTRODUCTION: Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a rare and practically new entity in medicine. In developing countries, there are still important limitations for the detection of anti-MOG antibodies by cell-based assay, so knowing the clinical characteristics of the different phenotypes and their differences with other demyelinating pathologies of the central nervous system is essential in order to make a proper diagnostic and therapeutic approach of the patients. AIM: To present an update regarding the clinical characteristics of the disease spectrum, being the first article in Spanish that gathers the most frequent phenotypes and provides a clear description of what should be considered to identify each of these phenotypes. DEVELOPMENT: This disease is characterized by having a monophasic or recurrent course, with optic neuritis being the most frequent presentation phenotype in general population and disseminated acute encephalomyelitis the most frequent in children. Other phenotypes described in this review are transverse myelitis, focal cortical encephalitis and cerebral stem syndromes, as well as the proposed criteria for the diagnosis of the disease associated with MOG antibody disease. CONCLUSION: Currently there are no studies that seek to characterize the Spanish-speaking population with this disease, or review articles in Spanish, so it is important to disseminate knowledge and develop research in this area

Reversible Cerebral Vasoconstriction Syndrome Associated with a Suprarenal Mass.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterised by severe thunderclap headaches (with or without the presence of acute neurological symptoms) and segmental vasoconstriction of cerebral arteries that resolves spontaneously in a period of three months. Cases have been described in the literature with producing and non-producing masses of metanephrines. Within these reports, associations with cavernous haemangioma, medulloblastoma, colon cancer, paraganglioma, pheochromocytoma, uterine fibroids, among others were found. However, no association with adrenal masses which do not produce metanephrines was found. In this context, we reported the case of a woman with this type of tumour associated with RCVS which provided a treatment challenge, as well as we reviewed the literature on cases of RCVS associated with masses.

Conservative management in a patient with cervical ectopic pregnancy in Nariño, Colombia: Case report and review of the literature / Manejo conservador en una paciente con embarazo ectópico cervical en nariño, colombia: reporte de caso y revisión de la literatura

RESUMEN Objetivos: reportar el caso de un embarazo cervical (EC) que recibió manejo conservador exitoso y realizar una revisión de la literatura sobre el tratamiento médico y quirúrgico conservador. Materiales y métodos: se presenta el caso de una paciente con embarazo cervical, quien recibió manejo farmacológico con metotrexate (MTX) y posterior legrado con evolución clínica satisfactoria. Se realizó una búsqueda de artículos en Medline vía PubMed, LILACS, SciElo y Google académico con los términos: "cervical ectopic pregnancy", "conservative treatment", "curettage", "methotrexate", "uterine artery embolization" "hysteroscopy". Se seleccionaron reportes y series de caso, pacientes con embarazo cervical diagnosticado por ultrasonido, de cualquier edad gestacional, sometidas tratamiento médico o quirúrgico conservador. Resultados: se incluyeron 22 estudios; se identificaron 95 pacientes con EC tratados con MTX, con tratamiento exitoso en 93. La complicación más frecuente fue la hemorragia en 12 %; el 26 % requirió tratamiento quirúrgico complementario. Cada vez más, la embolización de arterias uterinas (EAU) se realiza de manera preventiva (7 casos) antes del legrado o del tratamiento con MTX. La histeroscopia es otra alternativa reciente (20 casos). En 2 casos se requirió histerectomía abdominal, uno de los cuales fue un embarazo ístmico cervical. Conclusiones: el tratamiento con MTX sigue siendo el más frecuentemente utilizado. La dilatación y el curetaje con taponamiento endocervical puede ser una opción por considerar en el manejo de urgencia del EC en instituciones de atención primaria. En instituciones donde se dispone de tecnologías de alta complejidad, la embolización de arterias uterinas previa a los procedimientos quirúrgicos y la histeroscopia son opciones que se deben considerar. Dado que actualmente es posible el diagnóstico temprano del EC, se requieren estudios multicéntricos que comparen las diferentes alternativas de manejo para una mejor evaluación de su seguridad y efectividad. Conclusiones: el tratamiento con MTX sigue siendo el más frecuentemente utilizado. La dilatación y el curetaje con taponamiento endocervical puede ser una opción por considerar en el manejo de urgencia del EC en instituciones de atención primaria. En instituciones donde se dispone de tecnologías de alta complejidad, la embolización de arterias uterinas previa a los procedimientos quirúrgicos y la histeroscopia son opciones que se deben considerar. Dado que actualmente es posible el diagnóstico temprano del EC, se requieren estudios multicéntricos que comparen las diferentes alternativas de manejo para una mejor evaluación de su seguridad y efectividad

ABSTRACT Objectives: To report a case of cervical pregnancy (CP) treated successfully with a conservative approach, and to conduct a review of the literature regarding conservative medical and surgical treatment. Materials and Methods: Patient with cervical pregnancy treated pharmacologically with methotrexate (MTX) followed by dilation and curettage, with a satisfactory clinical course. A search of articles was conducted in Medline via PubMed, LILACS, SciElo and Google Scholar using the terms "cervical ectopic pregnancy," "conservative treatment," "curettage,¼ "methotrexate," "uterine artery embolization," "hysteroscopy." Reports and case series were selected of patients with cervical pregnancy diagnosed on ultrasound at any gestational age, subjected to conservative medical or surgical treatment. Results: A total of 22 studies were included; 95 patients with CP treated with MTX were identified, 93 of them successfully treated. The most frequent complication was bleeding in 12%; 26% required complementary surgical treatment. Increasingly, uterine artery embolization (UAE) is carried out preventatively (7 cases) before curettage or treatment with MTX. The hysteroscopy is another recent alternative (20 cases). Abdominal hysterectomy was required in two cases, one of which was a cervico-isthmic pregnancy. Conclusions: Treatment with MTX continues to be the most frequent strategy. Dilation and curettage with endocervical plugging may be an option to consider in the emergency management of EP in primary care institutions. In institutions equipped with high complexity technology, uterine artery embolization before the surgical procedure and histeroscopy are options to be considered. Considering that early diagnosis of EP is now possible, multi-center studies comparing different management options are needed for better assessment of their safety and effectiveness.

Síndrome de vasoconstricción cerebral reversible secundario a un paraganglioma yugular secretor de metanefrinas / Reversible cerebral vasoconstriction syndrome secondary to secreting jugular paraganglioma

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Síndrome de vasoconstricción cerebral reversible asociado a anastrozol: una causa inusual de alto impacto / Reversible cerebral vasoconstriction syndrome associated with anastrozole: an unusual cause of high impact

Introducción. El síndrome de vasoconstricción cerebral reversible (SVCR) es una entidad de baja incidencia, de etiología multifactorial y amplio espectro de presentación. El principal síntoma es la cefalea de tipo trueno. Puede estar acompañado de focalización neurológica y cursar con desenlaces clínicos variable que incluso pueden llevar a la muerte. El diagnóstico es clínico e imaginológico, y el tratamiento incluye adoptar medidas generales de monitorización, manejo sintomático, identificar la etiología y actuar sobre ella para evitar recurrencia. Caso clínico. Mujer de 71 años con antecedente de cáncer de seno, tratada inicialmente con tamoxifeno; por presentar urticaria, se escalonó tratamiento con anastrozol. Ingresó por cefalea de tipo trueno, afasia anterior y somnolencia. La paciente refirió un evento similar una semana antes del ingreso. En la resonancia magnética cerebral evidenció una hemorragia subaracnoidea (HSA) pequeña de la convexidad temporoparietal izquierda, y la panangiografía documentó vasoespasmo en la región parietal posterior, lo que confirmó el diagnóstico de SVCR más HSA. Durante el ingreso presentó tres eventos de iguales características, que requirieron monitorización intensiva y dos panangiografías terapéuticas con nimodipino intraarterial, con posterior resolución del vasoespasmo. Permanece asintomática seis meses después. Conclusión. El SVCR constituye un reto diagnóstico dada su presentación variable y su etiología multifactorial. En este caso, el SVCR más HSA está asociado al uso de anastrozol. Hasta el momento no hay casos descritos de inhibidores de la aromatasa asociados a esta patología, que debe comunicarse para su farmacovigilancia

Introduction. Reversible cerebral vasoconstriction syndrome (RCVS) is a low incidence disability with a multifactorial etiology and a wide array of symptoms. The main symptom is a thunderclap headache, accompanied sometimes with various neurological deficits that can lead to death. RCVS is usually diagnosed through radiological imaging technology. The treatment includes adopting general measures of monitoring, symptomatic management, identifying the etiology and acting on it to avoid recurrence. Case report. A 71-year-old woman with a history of breast cancer originally treated with tamoxifen. Due to urticaria, the anastrozole management was staggered. She was admitted for aphasia, drowsiness and a thunderclap headache. The patientreported a similar event two weeks prior admission. In rain resonance, there was evidence of small sub-arachnoidal haemorrhage (SAH) of the left parietal temporal convexity and cerebral angiography. As well as documented vasospasm in the posterior parietal region confirming the diagnosis of RCVS plus SAH. During the stay, she presented three events with the same characteristics, requiring intensive monitoring and two therapeutic panangiographies with intra-arterial nimodipine with subsequent resolution of the vessel spasm. The patient remains asymptomatic six months later. Conclusion. RCVS is difficult to diagnose given its wide array of symptoms and multifactorial etiology. In this case, RCVS plus SAH is associated with the use of anastrozole. So far there are no reported cases of aromatase inhibitors associated with this pathology and should be reported in the literature for pharmacovigilance

Conservative management in a patient with cervical ectopic pregnancy in Nariño, Colombia: Case report and review of the literature / Manejo conservador en una paciente con embarazo ectópico cervical en Nariño, Colombia: reporte de caso y revisión de la literatura

Objectives: To report a case of cervical pregnancy (CP) treated successfully with a conservative approach, and to conduct a review of the literature regarding conservative medical and surgical treatment. Materials and methods: Patient with cervical pregnancy treated pharmacologically with methotrexate (MTX) followed by dilation and curettage, with a satisfactory clinical course. A search of articles was conducted in Medline via PubMed, LILACS, SciElo and Google Scholar using the terms "cervical ectopic pregnancy," "conservative treatment," "curettage,¼ "methotrexate," "uterine artery embolization," "hysteroscopy." Reports and case series were selected of patients with cervical pregnancy diagnosed on ultrasound at any gestational age, subjected to conservative medical or surgical treatment. Results: A total of 22 studies were included; 95 patients with CP treated with MTX were identified, 93 of them successfully treated. The most frequent complication was bleeding in 12%; 26% required complementary surgical treatment. Increasingly, uterine artery embolization (UAE) is carried out preventatively (7 cases) before curettage or treatment with MTX. The hysteroscopy is another recent alternative (20 cases). Abdominal hysterectomy was required in two cases, one of which was a cervico-isthmic pregnancy. Conclusions: Treatment with MTX continues to be the most frequent strategy. Dilation and curettage with endocervical plugging may be an option to consider in the emergency management of EP in primary care institutions. In institutions equipped with high complexity technology, uterine artery embolization before the surgical procedure and histeroscopy are options to be considered. Considering that early diagnosis of EP is now possible, multi-center studies comparing different management options are needed for better assessment of their safety and effectiveness.

Objetivos: Reportar el caso de un embarazo cervical (EC) que recibió manejo conservador exitoso y realizar una revisión de la literatura sobre el tratamiento médico y quirúrgico conservador. Materiales y métodos: Se presenta el caso de una paciente con embarazo cervical, quien recibió manejo farmacológico con metotrexate (MTX) y posterior legrado con evolución clínica satisfactoria. Se realizó una búsqueda de artículos en Medline vía PubMed, LILACS, SciElo y Google académico con los términos: "cervical ectopic pregnancy", "conservative treatment", "curettage", "methotrexate", "uterine artery embolization" "hysteroscopy". Se seleccionaron reportes y series de caso, pacientes con embarazo cervical diagnosticado por ultra- sonido, de cualquier edad gestacional, sometidas tratamiento médico o quirúrgico conservador. Resultados: Se incluyeron 22 estudios; se identificaron 95 pacientes con EC tratados con MTX, con tratamiento exitoso en 93. La complicación más frecuente fue la hemorragia en 12 %; el 26 % requirió tratamiento quirúrgico complementario. Cada vez más, la embolización de arterias uterinas (EAU) se realiza de manera preventiva (7 casos) antes del legrado o del tratamiento con MTX. La histeroscopia es otra alternativa reciente (20 casos). En 2 casos se requirió histerectomía abdominal, uno de los cuales fue un embarazo ístmico cervical. Conclusiones: el tratamiento con MTX sigue siendo el más frecuentemente utilizado. La dilatación y el curetaje con taponamiento endocervical puede ser una opción por considerar en el manejo de urgencia del EC en instituciones de atención primaria. En instituciones donde se dispone de tecnologías de alta complejidad, la embolización de arterias uterinas previa a los procedimientos quirúrgicos y la histeroscopia son opciones que se deben considerar. Dado que actualmente es posible el diagnóstico temprano del EC, se requieren estudios multicéntricos que comparen las diferentes alternativas de manejo para una mejor evaluación de su seguridad y efectividad. Conclusiones: El tratamiento con MTX sigue siendo el más frecuentemente utilizado. La dilatación y el curetaje con taponamiento endocervical puede ser una opción por considerar en el manejo de urgencia del EC en instituciones de atención primaria. En instituciones donde se dispone de tecnologías de alta complejidad, la embolización de arterias uterinas previa a los procedimientos quirúrgicos y la histeroscopia son opciones que se deben considerar. Dado que actualmente es posible el diagnóstico temprano del EC, se requieren estudios multicéntricos que comparen las diferentes alternativas de manejo para una mejor evaluación de su seguridad y efectividad.

Lithopedion in a Geriatric Patient.

Lithopedion (lithos = rock and paidion = child) is a rare condition that only occurs in 1.5 to 1.8% of extrauterine pregnancies and in 0.00045% of all pregnancies. It consists of an ectopic pregnancy in which the fetus dies but cannot be reabsorbed by the mother's body, which then coats it in a calcium-rich substance. We present the case of a 77-year-old woman with an incidental diagnosis of a lithopedion, which had been retained in her left pelvis for presumably 40 years.