Acantosis nigricans maligna y carcinoma mamario. Presentación de un caso

Las manifestaciones cutáneas de los tumores malignos comprenden un grupo de dermatosis que pueden ser marcadores de la presencia de neoplasias ocultas y permiten su diagnóstico oportuno. El objetivo de este informe es presentar las características clínicas de una acantosis nigricans asociada a carcinoma de mamario. Para ello, se describe el caso clínico de una paciente de 50 años, color de piel negro, asistida en la consulta de Dermatología del Policlínico Universitario Raúl Sánchez, por tener una placa única eritematosa localizada en la mama izquierda, acompañada de dolor, aumento de la temperatura local y máculas hipercrómicas en las axilas; así como adenopatías axilares múltiples. Los exámenes complementarios mostraron la presencia de acantosis nigricans maligna asociada a un carcinoma inflamatorio de la mama izquierda. Fue intervenida quirúrgicamente, con la consiguiente desaparición de las lesiones cutáneas, pero con un pronóstico reservado. La mayoría de los síndromes paraneoplásicos son inespecíficos; existe una necesidad urgente de sospechar una correlación entre los cambios cutáneos y la posibilidad de una neoplasia interna, por lo que es de suma importancia derivar a estos pacientes para su identificación y el diagnóstico precoz de la enfermedad de base. Esto mejoraría el pronóstico y atenuaría en gran medida las consecuencias.

The skin manifestations of malignant tumors include a group of dermatoses that can be the sign of the occult neoplasms presence and allow their timely diagnosis. The objective of this report is to present the acanthosis nigricans' clinical characteristics associated with breast carcinoma. The clinical case of a 50-years-old black-skinned patient is described, assisted in the Dermatology consultation of the Raúl Sánchez University Polyclinic, for having a single erythematous plaque located in the left breast, accompanied by pain, increased local temperature and hyperchromic macules in the armpits; as well as multiple axillary lymphadenopathy. Complementary examinations showed the presence of malignant acanthosis nigricans associated with an inflammatory carcinoma of the left breast. She underwent surgery, with the consequent disappearance of the skin lesions, but with a reserved prognosis. Most paraneoplastic syndromes are nonspecific; there is an urgent need to suspect a correlation between skin changes and the possibility of an internal neoplasia, so it is of utmost importance to refer these patients for identification and early diagnosis of the underlying disease. This would improve the prognosis and greatly mitigate the consequences.

Tumor metastásico en tejido blando a nivel del sacro secundario a carcinoma de células claras de riñón. Reporte de caso / Metastatic tumor in soft tissue at the level of the sacrum secondary toclear cell carcinoma of the kidney. A case report

Introducción. El cáncer de riñón es la undécima neoplasia maligna más común en los Estados Unidos Mexicanos. El carcinoma de células claras de riñón (CCR) es considerado la estirpe más frecuente y representa el 2-3 % de todos los cánceres a nivel mundial. En el contexto de la enfermedad metastásica, por lo general se identifica un tumor renal primario y las metástasis se localizan en pulmón, hueso, hígado, cerebro y, raramente, en tejidos blandos. Los pacientes con metástasis a tejidos blandos no tienen síntomas en las etapas iniciales y generalmente se identifican sólo cuando las lesiones aumentan de tamaño o durante el estudio de la pieza de resección quirúrgica. Caso clínico. Se presenta el caso de una paciente en la séptima década de la vida, con una metástasis en tejidos blandos de la región sacra, de 10 años de evolución posterior a una nefrectomía secundario a CCR. Resultados. Hallazgos clínicos e imagenológicos de un tumor bien delimitado. Se realizó resección quirúrgica de la lesión, bajo anestesia regional, con extirpación completa. Conclusión. Se recomienda que los pacientes con un sitio metastásico resecable y solitario sean llevados a resección quirúrgica con márgenes libres, como fue el caso de nuestra paciente, por su fácil acceso y ser una lesión única. En el CCR, además de su tratamiento quirúrgico inicial, es indispensable una estrecha vigilancia con examen físico e imágenes transversales, para detectar la presencia de metástasis y con ello evitar tratamientos tardíos.

Introduction. Kidney cancer is the eleventh most common malignancy in the United States of Mexico. Carcinoma renal cell (CRC) is considered the most frequent type and represents 2-3% of all cancers worldwide. In the setting of metastatic disease, a primary renal tumor is usually identified, and metastases are located in the lung, bone, liver, brain, and rarely in soft tissue. Patients with soft tissue metastases do not have symptoms in the initial stages and are generally found only when the lesions increase in size or during the study of the surgical resection piece. Clinical case. In this case, we report a female patient in the seventh decade of life with a soft tissue metastasis located in the sacral region, 10 years after a nephrectomy secondary to CRC. Results. Clinical and radiological findings of a well-defined tumor. Surgical resection of the lesion is performed under regional anesthesia with complete excision. Conclusions. It is recommended that patients with a resectable and solitary metastatic site be candidates for surgical resection with free margins, as was the case with our patient due to its easy access and single lesion. In CRC, in addition to its initial surgical treatment, close surveillance with physical examination and cross-sectional images is essential to monitor the presence of metastases and thus avoid late treatments.

Bilateral choroidal metastasis of follicular thyroid carcinoma 7 years after total thyroidectomy: a case report

ABSTRACT Follicular thyroid cancers account for 15%-20% of all thyroid tumors. Choroidal metastases secondary to follicular thyroid cancer rarely occur. Herein, we report the case of an 85-year-old woman who presented choroidal metastasis from a follicular thyroid carcinoma in the right eye 7 years after total thyroidectomy and underwent enucleation. To confirm the diagnosis and primary tumor site, histopathological, and immunohistochemical examinations were performed. One year later, she presented metastasis in the contralateral eye. Few similar cases have been described in the literature.

Hepatic alveolar echinococcosis simulating metastatic malignancy

ABSTRACT Echinococcosis is a parasitic disease caused by infection with tiny tapeworms of the genus Echinococcus. Echinococcosis is classified as either cystic echinococcosis or alveolar echinococcosis. The common form is a zoonosis from goats and sheep that tends to cause liver lesions. The larval stage of Echinococcus multilocularis causes alveolar echinococcosis/alveolar hydatid disease. It is a zoonosis with field mice and tundra voles as intermediate and wild carnivores like foxes and wolves as definitive hosts. This zoonosis is highly uncommon compared to the other form known as cystic echinococcosis but poses a great human threat if untreated. We report the case of a young man who was working in the Kashmir Valley, North India, and presented with jaundice and right upper quadrant abdominal pain. Computed tomography revealed a large solid-cystic intrahepatic lesion measuring 125x118x123 mm, suggestive of a malignant tumor with central necrosis. A liver biopsy showed necrosis with PAS-positive membranes morphologically consistent with echinococcosis. Alveolar echinococcosis can present as a solid-cystic mass in the liver and can simulate metastatic malignancy.

Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Translation and Cross-cultural Adaptation of the SOSG-OQ 2.0 Questionnaire into Brazilian Portuguese / Tradução e adaptação transcultural do questionário SOSG-OQ 2.0 para o português brasileiro

Abstract Objective: To perform the cross-cultural adaptation and translation into Brazilian Portuguese of the Spine Oncology Study Group - Outcomes Questionnaire 2.0 (SOSG-OQ 2.0) to enable its application to Brazilian patients and to allow Brazilian researchers to use a questionnaire that is on trend in the scientific literature. Materials and Methods: The present is a basic, non-randomized, non-comparative study. The translation followed the proposal by Reichenheime and Moraes, mainly for the semantic equivalence and measurement equivalence sessions, as well as the recommendations by Coster and Mancini mainly in the translation stage. The stages were as follows: first - translation into Brazilian Portuguese; second - back-translation; third - semantic comparison; fourth - validation of the final construct. Results: The translations of the SOSG-OQ 2.0 made by three translators presented a high degree of similarity for most questions. The translators kept all question titles and subtitles, as well as their internal and external orders. Two sworn translators, with native proficiency in English, performed the back-translation of the amalgamated text. Both back-translations were quite similar, and any differences were solved through consensus between the main author and the sworn translators, and the translated text was considered the final version. Conclusion: The present study shows a translated version of the SOSG-OQ 2.0 with semantic validity with the original version published in English. As such, researchers can apply the questionnaire to the Brazilian population, adding another tool for spine surgeons to improve the monitoring of this complex group of patients.

Resumo Objetivo: Realizar a adaptação transcultural e a tradução para o português brasileiro da versão 2.0 do Questionário de Desfechos do Spine Oncology Study Group (Spine Oncology Study Group - Outcomes Questionnaire 2.0, SOSG-OQ 2.0, em inglês) para viabilizar sua aplicação em pacientes brasileiros e permitir a utilização deste questionário que está em voga na literatura científica por pesquisadores brasileiros. Materiais e Métodos: Trata-se de uma pesquisa básica, não randomizada, não comparativa. As etapas de tradução foram realizadas conforme propostas por Reichenheime e Moraes, principalmente as sessões de equivalência semântica e equivalência de mensuração, e também foram seguidas as recomendações de Coster e Mancini, principalmente na etapa de tradução. As etapas foram as seguintes: primeira - tradução do questionário para o português brasileiro; segunda - retroversão; terceira - comparação semântica; e quarta - validação final do constructo. Resultados: As traduções do SOSG-OQ 2.0 feitas por três tradutores apresentaram grande similaridade na maioria das questões. Todos os títulos e subtítulos de perguntas foram mantidos pelos tradutores, assim como as ordens interna e externa das perguntas. A retroversão da tradução conciliada foi realizada por dois tradutores juramentados, com fluência nativa na língua inglesa. Ambas as retroversões foram bastante similares, as divergências foram sanadas por consenso entre o autor principal e os tradutores juramentados, e a versão traduzida foi considerada a versão final. Conclusão: Neste estudo, apresenta-se uma versão traduzida do SOSG-OQ 2.0 que tem validade semântica com a versão original publicada em inglês, o que permite a sua aplicação na população brasileira, e acrescenta mais uma ferramenta para que os cirurgiões de coluna possam acompanhar de forma melhor este complexo grupo de pacientes.

La inmunoterapia en el manejo del cáncer renal metastásico: En tratamiento con inhibidores de checkpoint PD-L1 y/o anti-CTLA-4. A propósito de un caso / Case report about immunotherapy in management of metastatic renal cancer: Treatment with checkpoint PD-L1 and/or anti-CTLA-4 inhibitors

RESUMEN El carcinoma de células renales (CCR) aproximadamente el 15 por ciento se presentan como localmente avanzado o metastásico, donde la cirugía no es curativa. El pronóstico de los pacientes con CCR avanzado o metastásico puede variar desde unos meses hasta algunos años, según las características clínicas, patológicas, radiológicas de la enfermedad. El advenimiento del uso de anti monoclonales basado en la inmunoterapia como inhibidores de puntos de control en la terapia sistémica inicial para el CCR avanzado de células claras. Presentaremos un caso clínico donde la inmunoterapia juega un rol mediante el uso de anti monoclonales para el abordaje de un paciente varón con enfermedad renal metastásica que presenta respuesta clínica después del tratamiento quirúrgico e inmunoterapia por 2 años sin evidencia de enfermedad oncológica hasta la actualidad.

ABSTRACT Approximately 15 percent of renal cell carcinoma (RCC) present as locally advanced or metastatic, where surgery is not curative. The prognosis of patients with advanced or metastatic RCC can vary from a few months to a few years, depending on the clinical, pathological, and radiological characteristics of the disease. The advent of the use of anti-monoclonal-based immunotherapy as checkpoint inhibitors in initial systemic therapy for advanced clear cell RCC. We will present a clinical case where immunotherapy plays a role through the use of anti-monoclonal drugs to treat a male patient with metastatic kidney disease who presents a clinical response after surgical treatment and immunotherapy for 2 years without evidence of oncological disease to date.

Differential Diagnosis of Oral Metastases / Diagnóstico Diferencial de las Metástasis Orales

Metastatic lesions in the mouth can resemble common inflammatory lesions. Therefore, we set out to investigate oral metastases whose clinical and imaging characteristics mimicked those of harmless lesions, confusing and delaying the diagnosis. For this, a systematic review was carried out from case reports, case series, and cross-sectional studies in the PubMed/Medline, Scopus, Embase-via Elsevier, Virtual Health Library, Web of Science, and gray literature, using PICO strategy without period restriction. We assessed the quality of studies using the Joanna Briggs Institute assessment tool. A narrative synthesis of the data was carried out. Association analyses using chi-square and Fisher's exact tests were performed, with statistical significance at p<0.05. Most of the lesions came from the lung, breast, kidneys, liver, and thyroid. They affected mainly the mandibles of men, between the fifth and seventh decades of life, causing osteolysis. In soft tissue, there were firm swellings, associated with bleeding. Limitations regarding the heterogeneity of the included studies and the absence of clinic pathological descriptions of the tumors substantially reduced the chance of statistical analysis of the data. Knowing the different possibilities of clinical presentation of oral and maxillofacial metastases is important for the diagnost ic suspicion to occur and diagnostic errors to be avoided. Thus, treatment is instituted and survival can be extended. Protocol registration: PROSPERO CRD42020200696.

Las lesiones metastásicas en la cavidad oral pueden parecer similares a lesiones inflamatorias comunes. Por ello, nos propusimos investigar metástasis orales cuyas características clínicas e imagenológicas simularan las de lesiones inofensivas, confundiendo y retrasando el diagnóstico. Para ello, se realizó una revisión sistemática a partir de reportes de casos, series de casos y estudios transversales en PubMed/Medline, Scopus, Embase-vía Elsevier, Virtual Health Library, Web of Science y literatura gris, utilizando la estrategia PICO sin restricción de periodo. La calidad de los estudios se evaluó mediante la herramienta de evaluación del Instituto Joanna Briggs. Se realizó una síntesis narrativa de los datos. Se realizaron análisis de asociación mediante chi-cuadrado y prueba exacta de Fisher, con significancia estadística en p<0,05. La mayoría de las lesiones procedían de pulmón, mama, riñones, hígado y tiroides. Afectan principalmente a las mandíbulas de los hombres, entre la quinta y la séptima década de la vida, provocando osteólisis. En los tejidos blandos, había hinchazones firmes, asociadas con sangrado. Las limitaciones con respecto a la heterogeneidad de los estudios incluidos y la ausencia de descripciones clinicopatológicas de los tumores redujeron sustancialmente la posibilidad de realizar un análisis estadístico de los datos. Conocer las diferentes posibilidades de presentación clínica de las metástasis orales y maxilofaciales es importante para que se produzca la sospecha diagnóstica y se eviten errores diagnósticos. Por lo tanto, se instituye el tratamiento y se puede prolongar la supervivencia. Registro de protocolo: PROSPERO CRD42020200696.

Adequacy of surgical margins, re-excision, and evaluation of factors associated with recurrence: a retrospective study of 769 basal cell carcinomas

Abstract Background: Achieving adequate surgical margins and preventing recurrence are important in the treatment of basal cell carcinoma (BCC). Objectives: The objectives of this study were to evaluate the adequacy of surgical margins and the re-excision rates in patients with primary BCC who underwent standard surgical treatment using our proposed algorithm and to define the risk factors in patients with recurrent BCC. Methods: The medical records of patients who were histopathologically diagnosed with BCC were reviewed. An algorithm created based on previous literature was used to determine the distribution of optimal surgical margins adequacy and re-excision rates. Results: Statistically significant differences were observed between the cases with and without recurrence in age at diagnosis (p = 0.004), tumor size (p = 0.023), tumor location in the H zone of the face (p = 0.005), and aggressive histopathological subtype (p = 0.000). When the tumors were evaluated for adequacy of deep and lateral surgical margins and re-excision rates, higher rates of adequate excision (457 cases, 68.0%) and re-excision (43 cases, 33.9%) were noted for tumors in the H or M zone. Study limitations: Inadequate follow-up of newly diagnosed patients in terms of recurrence and metastasis and the retrospective application of our proposed algorithm are the limitations of the present study. Conclusions: Our results showed that if BCC was detected at an early age and at an early stage, recurrence was lower. The H and M zones were the regions with the highest rates of optimal surgical outcomes.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study / Estudo retrospectivo de vida-real, em centro único, para avaliação do comportamento da fosfatase alcalina total após terapia com rádio-223 no câncer de próstata resistente a castração

Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

El factor de transcripción nuclear NF-κB en cáncer

El factor nuclear κB (NF-κB) es una familia de factores de transcripción sumamente importantes que regulan una gran variedad de genes en diferentes procesos de las respuestas inmunitarias e inflamatorias. Esta familia está compuesta por cinco miembros relacionados estructuralmente, y pueden inducir la transcripción de genes diana al unirse a segmentos específicos de ácido desoxirribonucleico (ADN). Las proteínas NF-κB son usualmente secuestradas en el citoplasma por una familia de proteínas inhibidoras, sin embargo, diversas vías de señalización oncogénica pueden activarla y desencadenar fenotipos malignos en las células correspondientes. El objetivo principal de esta revisión es comprender los mecanismos de regulación del factor de transducción NF-κB, su patogénesis y sus posibles blancos terapéuticos en cáncer. Se consultaron diferentes bases de datos que incluyeron PubMed, Scopus y SciELO, desde el año 2000 hasta diciembre del año 2022; se buscaron las referencias bibliográficas en relación con las palabras clave asociadas al factor NF-κB y cáncer, para finalmente desarrollar la revisión. El factor nuclear de transcripción NF-κB es importante en muchas vías de señalización celular, participa en diversos procesos biológicos y sus alteraciones están asociadas a trastornos inmunitarios y cáncer, entre otras patologías. NF-κB se expresa en todos los tipos de células y tejidos, de tal forma que muchas mutaciones oncogénicas contribuyen a la activación de NF-κB en las células tumorales, y son nuevas rutas de investigación terapéuticas para el cáncer. Existen dos vías de señalización diferentes de NF-κB, denominadas vía canónica y la vía alternativa (no canónica), con distintos mecanismos de activación. Los mecanismos oncogénicos en las que participa el factor NF-κB incluyen inflamación crónica, proliferación, apoptosis, angiogénesis, acción sobre células madre del cáncer, metástasis, regulación metabólica y otros mecanismos asociados. En conclusión, existen aún muchas incógnitas sobre los mecanismos y funciones de NF-κB en el contexto celular; el bloqueo completo del factor NF-κB no parece ser una estrategia factible para el tratamiento del cáncer en el momento actual por la diversidad de acciones fisiológicas importantes que se alteran ante su bloqueo. Futuras investigaciones del factor nuclear NF-κB deberían centrarse en la inhibición de la actividad promotora del cáncer, evitando afectar sus funciones fisiológicas normales.

The nuclear factor kappa B (NF-κB) family of transcription factors, which regulates a large range of genes in various immunological and inflammatory response pathways, is of utmost importance. This family consists of five structurally similar members that can activate target genes by attaching to particular regions of deoxyribonucleic acid (DNA). A class of inhibitory proteins usually keep NF-κB proteins in the cytoplasm; however, different oncogenic signaling pathways can activate them and cause malignant phenotypes in the appropriate cells. The main goal of this review article is to understand the regulatory mechanisms of NF-κB transcription factor, its pathogenesis and its potential cancer therapies. From the year 2000 to December 2022, several databases, including PubMed, Scopus and SciELO, were consulted. Finally, the review was developed by searching bibliographic references looking for the keywords related to NF-κB and cancer. The NF-κB transcription factor plays a key role in numerous cell signaling pathways, is involved in a number of biological functions, and its mutations have been linked to cancer and immunological disorders, among other pathologies. Since NF-κB is expressed in all cell types and tissues, many oncogenic mutations can activate NF-κB in tumor cells, opening up new research possibilities for the treatment of cancer. The canonical pathway and the alternative (non-canonical) pathway are two distinct NF-κB signaling pathways with various activation methods. NF-κB is involved in a variety of oncogenic pathways, including chronic inflammation, proliferation, apoptosis, angiogenesis, effect on cancer stem cells, metastasis, metabolic control and other related mechanisms. In conclusion, there are still many unanswered questions regarding the mechanisms and functions of NF-κB in the cellular context. A complete blockade of NF-κB does not appear to be a feasible strategy for the treatment of cancer at this time due to the variety of significant physiological actions that are altered by its blockade. Future research on NF-κB should focus on preventing cancer promotion while preserving the body's natural physiological processes.

Prognostic effect of peritumoral vascular invasion of tumor thrombus in osteosarcomas / 中华骨科杂志

Objective:To analyze the value of peritumoral vascular invasion (PVI) on the prognosis of patients with osteosarcoma.Methods:A total of 232 patients with primary osteosarcoma from 2007 to 2016 were retrospectively analyzed, including 142 males and 90 females. The average age was 17.9±8.2 years (range, 3-39 years). There were 22 positive and 210 negative cases of PVI, 94 deaths and 138 survivals. Univariate survival analysis (Log-rank test and univariate Cox regression) was used to evaluate the effects of age, gender, PVI status, tumor location, surgical method, sensitivity to chemotherapy, and chemotherapy regimen on the prognosis of osteosarcoma. The indicators with statistically significant differences were included in the multivariate Cox regression model to finally determine the risk factors affecting the prognosis of osteosarcoma. The relationship between PVI status and 5-year survival and the incidence of recurrence or metastasis was evaluated using the Kaplan-Meier method.Results:All patients were followed up for 7.6±4.5 years (range, 0.1-15 years). The differences in sensitivity to chemotherapy (χ 2=9.52, P=0.002), choice of chemotherapy regimen (χ 2=8.87, P=0.012), choice of surgical modality (χ 2=13.50, P<0.001), tumor metastasis rate (χ 2=8.51, P=0.004) and mortality rate (χ 2=5.39, P= 0.020) of PVI positive group and PVI negative group had statistically significant differences. Univariate survival analysis was performed on 232 patients with osteosarcoma (gender, age, PVI status, site of tumor development, surgical modality, sensitivity to chemotherapy, and chemotherapy regimen). Indicators with statistically significant differences were included in a multifactorial Cox regression model. The results showed PVI positive [5-year survival rate: HR=2.02, 95% CI (1.61, 2.79), P=0.010; 5-year recurrence or metastasis rate: HR=2.25, 95% CI (1.55, 3.14), P<0.001], surgical procedure as amputation [5-year survival rate: HR=1.22, 95% CI (0.94, 1.78), P=0.037; 5-year recurrence or metastasis rate: HR=1.58, 95% CI (1.11, 2.23), P=0.026] and poor sensitivity to chemotherapy [5-year survival rate: HR=2.71, 95% CI (1.84, 3.98), P=0.001; 5-year recurrence or metastasis rate: HR=2.52, 95% CI (1.88, 3.45), P<0.001] was associated with poor prognosis. Kaplan-Meier curve showed that the 5-year survival rate of PVI positive group was 34%, which was lower than 68% of PVI negative group. The 5-year recurrence or metastasis rate was 72% in the PVI negative group, which was significantly higher than 38% in the PVI negative group ( P<0.05). Conclusion:The 5-year survival rate of PVI positive group was lower than that of PVI negative group, and the 5-year recurrence or metastasis rate was higher than that of PVI negative group. The presence of microvascular angiosarcoma plugs infiltrating the peritumoral tissue in surgical specimens of osteosarcoma after neoadjuvant chemotherapy is a useful indicator to assess the prognosis of patients with osteosarcoma.

Clinical outcome and prognosis of indeterminate pulmonary nodules in patients with osteosarcoma / 中华骨科杂志

Objective:To explore the incidence, clinical characteristics, imaging features, clinical outcome and prognosis of indeterminate pulmonary nodules (IPN) in patients with osteosarcoma.Methods:A total of 69 patients of osteosarcoma with IPN in lung treated in the Bone tumor Center of Eastern Theater General Hospital from January 2011 to January 2021 were collected retrospectively, there were 47 males and 22 females, with a median age of 19 years old (range 7-60 years old). The clinical characteristics including disease-free interval, the chemotherapy response, with recurrence/non-pulmonary, IPN presence before / during / after chemotherapy and imaging features of IPN including number of IPN, location of IPN, density of IPN, boundary clarity of IPN and outcome. The patients were divided into the metastasis pulmonary nodules group and the benign nodules group according to the final outcome of IPN. Further, χ 2 test was performed for comparison of the clinical and imaging characteristics between the two groups. The survival of patients was counted and the correlation between single factor and survival was compared by Kaplan-Meier test, and multivariate survival analyses were performed using Cox proportional hazards regression models. Results:Sixty-nine cases occurred IPN in 211 patients with osteosarcoma, with an incidence of 32.7%. Of the 69 patients, 45 patients (65.2%) with IPN were diagnosed as metastases, and 24 patients (34.8%) with IPN were diagnosed as benign nodules. Follow-up length ranged from 1 to 124 months, with the median follow up time 43 months. To the end of follow-up, 41 patients (59.4%) remained alive and 28 patients (40.6%) had died. The median survival time was 41.0 (20.0, 65.0) months and the median survival time after diagnosis of IPN was 25.0 (10.0, 43.0) months. There were significant differences in lung nodule density ( P<0.001), boundary ( P=0.002), history of recurrence/extra-pulmonary metastasis ( P=0.023) and chemotherapeutic effect ( P<0.001) between the metastasis pulmonary nodules group and the benign nodules group. Multivariate survival analysis showed that chemotherapeutic effect was an independent factor affecting the overall survival of patients [ HR=0.048, 95% CI (0.01, 0.26)]. Boundary definition [ HR=0.12, 95% CI (0.02, 0.93)] and chemotherapeutic effect [ HR=0.06, 95% CI (0.01, 0.29)] were independent factors influencing survival after diagnosis of IPN. Conclusion:Osteosarcoma patients with IPN have a poor prognosis. The poor effect of chemotherapy is an independent risk factor for the overall survival time of those patients and the survival time after diagnosis of IPN. The boundary definition of IPN is an independent risk factor for the survival time after diagnosis of IPN.

A meta-analysis of progressive pulmonary micro nodules in osteosarcoma / 中华骨科杂志

Objective:To identify the prevalence of pulmonary micro nodule (PMN) in osteosarcoma, investigate radiologic features of progressive PMN, and provide evidence for early diagnosis of pulmonary metastasis of osteosarcoma.Methods:Electronic articles published in PubMed, EMBASE, Web of Science and the Cochrane Library databases between January 1, 2000, and September 1, 2022, were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data on the prevalence of PMN in osteosarcoma and radiologic features of progressive PMN. Seven high quality studies were finally included in the meta-analysis with evidence level III.Results:The pooled prevalence of PMN in osteosarcoma was 36.0%, 95% CI (14.6%, 57.3%). The pooled progressive rate of PMN was 52.5%, 95% CI (37.7%, 67.2%). As for a specific PMN, it was more likely to progress which had a larger Dmax, HR=2.40, 95% CI (1.06, 5.42), P=0.035. No significant difference was found in number, component, and border. Conclusion:PMN is quite common in patients with osteosarcoma. About half of the patients suffered the progression of PMN, and it is related to several risk factors.

Application of MR-guided radiotherapy for brain metastases / 中华放射肿瘤学杂志

Radiotherapy (RT) is the primary local treatment modality for brain metastases, which are common secondary malignancies. Image-guidance system such as cone beam computed tomography (CBCT) may be not applicable to adaptive radiotherapy (ART), as well as hypofractionated RT in brain metastases, because it cannot clearly show the shrinkage and deformation of intracranial tumors, and the peritumoral edema changes in a real-time manner. Magnetic resonance (MR) image has high spatial resolution and soft tissue contrast and no radiation dose burden compared with CBCT. MR-guided adaptive radiotherapy (MR-gART) allows real-time tracking of deformation and position changes of the intracranial tumors, and enables online planning reconstruction during the treatment process. MR-gART could deliver high dose irradiation to the tumors while reducing the radiation dose of important organs at risk around, which contributes to achieving precision RT. In this work, the application of MR-gART in brain metastases was reviewed.

Recent advances in hippocampal sparing whole brain radiotherapy / 中华放射肿瘤学杂志

Whole brain radiotherapy (WBRT) is the standard radiotherapy regimen of preventive radiation for patients diagnosed with brain metastases and non-small cell lung cancer, which can improve intracranial control and prolong overall survival. However, neurocognitive functions (NCF) decline due to impaired hippocampal might occur thereafter. Recent studies have shown that hippocampal sparing WBRT (HS-WBRT) is capable of protecting neurocognitive function and improving quality of life (QOL). In this review, the authors described the methods and significance of hippocampal sparing, summarized the research progress on clinical trials related to HS-WBRT in combination with the development of radiotherapy technology and experimental drugs, and discussed the existing controversies and problems, aiming to provide reference for clinical work.

The value of radiomics for individualized prophylactic cranial irradiation in limited-stage small cell lung cancer / 中华放射肿瘤学杂志

Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.

Effects of primary location of colorectal cancer on surgical outcome of liver metastases / 中国基层医药

Objective:To analyze the effects of the primary location of colorectal cancer on the surgical outcome of liver metastases.Methods:A cross-sectional study was conducted on 178 patients with liver metastases from colorectal cancer admitted to Binzhou Central Hospital from January 2012 to January 2022. According to whether the patients had recurrence after surgery, they were divided into a recurrence group ( n = 88) and a control group ( n = 90). The general and clinical data were compared between the two groups. Logistic multivariate analysis of the factors with statistical significance was further performed to identify the risk factors of postoperative recurrence of liver metastases from colorectal cancer after surgery. The correlation between the primary location of colorectal cancer and each risk factor was analyzed. The recurrence of colorectal cancer was compared anong patients with different primary locations of colorectal cancer at 12 months after surgery. Results:Primary location at the right colon [55.68% (49/88), lymph node metastasis [92.05% (81/88)], D-dimer ≥ 180 μ g/L, albumin < 29 g/L, ineffective/no neoadjuvant chemotherapy [43.18% (33/38)], and high-risk clinical risk score [53.41% (47/88)] were risk factors for postoperative recurrence of liver metastases from colorectal cancer after surgery ( P = 0.024, 0.019, 0.001, 0.028, < 0.001, 0.001). The primary location of colorectal cancer was positively correlated with lymph node metastasis, D-dimer, and clinical risk score ( P = 0.043, 0.046, 0.030), and negatively correlated with albumin and the efficacy of neoadjuvant chemotherapy ( P = 0.004, 0.033). In 178 patients, the recurrence rate of liver metastases from colorectal cancer at 3 months [53.57% (15/70)], 6 months [55.17% (32/70)], and 12 months [55.68% (49/70)] was significantly higher in the right colon compared with the left colon [32.14% (9/40), 24.14% (14/40), 26.14% (23/40) and the rectum [14.29% (4/68), 20.69% (12/68), 18.18% (16/68)] ( χ2= 4.73, 7.85, 6.27, all P < 0.05). Conclusion:Right colon, lymph node metastasis, D-dimer, albumin, neoadjuvant chemotherapy efficacy, and clinical risk score are the risk factors for postoperative recurrence of liver metastases from colorectal cancer. Patients with the primary location at the right colon have a higher postoperative recurrence rate.

Analysis of misdiagnosed cases of neck, shoulder, waist and leg pain caused by bone metastases and early warning measures / 中国基层医药

Objective:To investigate the cause of misdiagnosis of neck, shoulder, waist, and leg pain caused by bone metastases and to improve the outpatient diagnosis rate.Methods:Five misdiagnosed cases of bone metastases who were admitted to the Traditional Chinese Medicine Department of Orthopedics and Traumatology, School of Traditional Chinese Medicine, Southern Medical University from January 2019 to July 2020 were included in this study. Their clinical manifestations, diagnosis results (outside hospital diagnosis and outpatient diagnosis), and imaging manifestations were retrospectively analyzed.Results:Five cases of bone metastases were misdiagnosed to have cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain. Accelerated red blood cell sedimentation rate and increased C-reactive protein level were found in all five cases. Bone metastases were confirmed by X-ray, CT, and MRI examination results. All of them had warning signs for bone metastasis: age > 50 years, history of a tumor, unexplained weight loss, general malaise, neck, shoulder, waist, and leg pain without an obvious cause, sudden worsening of pain, night pain, resting pain, pain on direct palpation, no obvious improvements in these symptoms after symptomatic treatment for 1 month, disease development not conforming to the general law of cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain, increases in red blood cell sedimentation rate, C-reactive protein, and alkaline phosphatase levels, which are not consistent with the symptoms of cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain, and slight external force leading to fractures.Conclusion:Further tests and imaging examinations should be performed according to warning signs. Clinical schemes of malignant bone tumors suitable for general practitioners can easily, economically, and effectively identify malignant bone tumors.

Study on LASSO regression prediction of lymph nodes around hepatic artery metastasis based on blood routine index in patients with distant gastric cancer / 中国医师进修杂志

Objective:To investigate the value of LASSO regression prediction of lymph nodes around hepatic artery metastasis based on blood routine index in patients with distant gastric cancer.Methods:The clinical data of 110 patients with distant gastric cancer from June 2018 to February 2022 in Jieshou People′s Hospital were retrospective analyzed. Among them, 43 patients had lymph nodes around hepatic artery metastases (metastasis group), and 67 patients have not lymph nodes around hepatic artery metastases (non-metastasis group). The basic clinical data were recorded; the routine blood test was detected, the indexes including white blood cell count, neutrophil percentage, lymphocyte count, platelet count, lymphocyte percentage, acidophil count, basophils count, hemoglobin, red blood cell distribution width (RDW), platelet distribution width (PDW) and neutrophil to lymphocyte ratio (NLR). The R language 4.1.0 software "grpreg" package was used to establish a Group LASSO Logistic regression analysis model to finally select the factors predicting lymph node around hepatic arterial metastasis in patients with distal gastric cancer. Nomogram were made using R language 3.5.3 software package and rms program package, calculated the consistency index (C-index), and the accuracy of the model was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.Results:The white blood cell count, neutrophil percentage, NLR and lymphocyte percentage in metastasis group were significantly higher than those in non-metastasis group: (12.16 ± 1.62) × 10 9/L vs. (9.38 ± 2.64) × 10 9/L, (73.36 ± 6.94)% vs. (52.21 ± 6.23)%, 3.23 ± 0.63 vs. 2.35 ± 0.13 and (48.62 ± 3.64)% vs. (31.02 ± 2.94)%, the acidophil count and basophils count were significantly lower than those in non-metastasis group: (0.31 ± 0.03) × 10 9/L vs. (0.36 ± 0.04) × 10 9/L and (0.08 ± 0.01) × 10 9/L vs. (0.09 ± 0.02) × 10 9/L, the degree of differentiation and TNM stage were also worse than those in non-metastasis group, and there were statistical differences ( P<0.01). The nomogram was constructed to predict lymph nodes around hepatic artery metastasis based on the degree of differentiation, TNM stage, white blood cell count, neutrophil percentage, NLR, lymphocyte percentage, acidophil count and basophils count in patients with distant gastric cancer, the scores of each indexes were 20.64, 26.42, 32.83, 25.78, 38.46, 35.65, 29.06 and 18.26 scores, the total score (227.10 scores) was the incidence of the nomogram model (29.82%). The validation result showed C-index of 0.819 and 0.806 (95% CI 0.785 to 0.864 and 0.779 to 0.816), and the correction curves for both sets were fitted well to the ideal curve with AUC of 0.801 and 0.810 (95% CI 0.784 to 0.826 and 0.795 to 0.852), and the decision curve showed high net benefit value with threshold probability from 1% to 9%. Conclusions:LASSO regression model combined with white blood cell count, neutrophil percentage, NLR, lymphocyte percentage, acidophil count and basophils count is ideal to predict lymph nodes around hepatic artery metastasis in patients with distant gastric cancer.