Resección de metástasis pancreáticas: análisis de resultados quirúrgicos y oncológicos. Estudio de cohorte retrospectiva / Pancreatic resections for metastases in the pancreas: analysis of surgical and oncologic outcomes. A retrospective cohort study

RESUMEN Antecedentes: las metástasis pancreáticas, si bien son poco frecuentes, representan una entidad clínica cuyo diagnóstico probablemente se incrementará en el futuro por el aumento de los programas de seguimiento oncológico. Objetivo: describir los resultados quirúrgicos y oncológicos de una serie de pacientes operados por metástasis pancreáticas. Materiales y métodos: se realizó un estudio de cohorte retrospectivo, descriptivo, multicéntrico, de los pacientes sometidos a resecciones pancreáticas por metástasis entre enero de 2016 y diciembre de 2022, en tres efectores de salud por el mismo grupo quirúrgico. Resultados: fueron operados 19 pacientes, con una media de edad de 59 años (45-79), 11 de sexo femenino, en buen estado general y sin otra evidencia de enfermedad oncológica. El origen de los tumores primarios fue 14 en riñón (7 diagnosticados durante el seguimiento), uno carcinoma mamario, uno melanoma, uno testicular, uno colorrectal y uno de cuello de útero. Las técnicas quirúrgicas empleada fueron: 7 esplenopancreatectomías (5 videolaparoscópicas y 2 convencionales), 4 enucleaciones (3 convencionales y 1 videolaparoscópica), 3 duodenopancreatectomías cefálicas convencionales, 2 duodenopancreatectomías totales convencionales, 2 pancreatectomías centrales convencionales, y una pancreatectomía corporocaudal con preservación del bazo. No se registró mortalidad operatoria (dentro de los 90 días posoperatorios), y presentaron una supervivencia global y libre de enfermedad de 58 y 53 meses, respectivamente. Conclusión: la resección de metástasis pancreáticas, en casos seleccionados, con un abordaje multidisciplinario, y en centros de alto volumen de patología hepatobiliopancreática, es segura y permite buenos resultados oncológicos y de supervivencia global.

ABSTRACT Background: Pancreatic metastases are rare but are likely to be diagnosed more frequently in the future due to the increase in oncology surveillance programs. Objective: The aim of this study was to describe the surgical and oncologic outcomes of a series of patients undergoing surgery for pancreatic metastases. Materials and methods: We conducted a retrospective, descriptive, and multicenter cohort study on patients who underwent pancreatic resections for metastases in the pancreas by the same surgical group between January 2016 and December 2022 in three healthcare providers. Results: A total of 19 patients were operated on, mean age was 59 years (45-79), and 11 were women with good performance status and no other evidence of oncologic disease. Clear cell renal cell carcinoma was the primary tumor in 14 cases (7 diagnosed during surveillance), and the remaining primary tumors were one case of breast ductal carcinoma, one testicular cancer, one colorectal cancer, one melanoma and one cervical cancer. The surgical techniques used were pancreatectomies and splenectomies in 7 patients (5 via laparoscopy and 2 conventional procedures), 4 enucleations (3 conventional procedures and 1 laparoscopic surgery), 3 conventional cephalic pancreaticoduodenectomies, 2 conventional central pancreatectomies and one spleen-preserving distal pancreatectomy. No deaths were reported within 90 days of surgery, and overall survival and disease-free survival were 58 and 53 months, respectively. Conclusion: Resection of pancreatic metastases is safe and provides good oncologic outcomes and overall survival when performed with a multidisciplinary approach in centers with a high volume of hepatobiliary and pancreatic surgeries and in selected cases.

ALPPS en cáncer colorrectal sincrónico en tiempos de COVID-19 / ALPPS in synchronous colorectal cancer in times of COVID-19

RESUMEN Durante la pandemia por SARS-CoV-2 evidenciamos un aumento de la morbimortalidad secundario a procedimientos quirúrgicos. Se estima una mortalidad a los 30 días del 19,1% en cirugías programadas y del 26% en procedimientos quirúrgicos de emergencia, y alrededor de la mitad de los pacientes que se someten a cirugía estando infectados con SARS-CoV-2 experimentan complicaciones pulmonares posoperatorias. Los tratamientos oncológicos sufrieron deficiencias en nuestro país debido a las limitantes secundarias a la emergencia sanitaria, en cuanto a capacidad de internación e implementación de los tratamientos quimioterápicos. Informamos la primera cirugía de ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) realizada en el nordeste argentino en una paciente con metástasis colorrectales múltiples en contexto de la pandemia por SARS-CoV-2, con buenos resultados.

ABSTRACT During the SARS-CoV-2 pandemic, we observed an increase in morbidity and mortality secondary to surgical procedures. The mortality rate for elective surgery is estimated at 19.1% and is 26% for emergency procedures. Additionally, approximately half of patients who undergo surgery while infected with SARS-CoV-2 experience postoperative pulmonary complications. Due to limitations caused by the health emergency, cancer treatments in our country have been affected in terms of hospitalization capabilities and implementation of chemotherapy treatments. We report the first ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) procedure performed in northeastern Argentina on a patient with multiple colorectal metastases during the SARS-CoV-2 pandemic, with successful outcomes.

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.

PKMYT1 Promotes Epithelial-Mesenchymal Transition Process in Triple-Negative Breast Cancer by Activating Notch Signaling

ABSTRACT Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that lacks receptors for targeted therapy. Deeper insight into the molecular mechanisms regulating TNBC metastasis is urgently needed. The epithelial-mesenchymal transition process facilitates the metastasis of neighboring epithelial tumor cells. Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, is upregulated in BC, and its high expression predicts poor prognosis in BC patients. Notch signaling activation is a pathognomonic feature of TNBC. PKMYT1 has been found to induce EMT in non-small cell lung cancer by activating Notch signaling. However, whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling remains unknown. Objectives: The objective of this study was to investigate whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling. Methods: Fifty cases of surgically resected BC samples (tumor and adjacent non-tumor tissue samples) were collected from patients diagnosed with BC. We measured the expression of PKMYT1 in clinical samples with real-time quantitative polymerase chain reaction (RT-qPCR). For in vitro analysis, RT-qPCR and Western blotting were conducted to evaluate PKMYT1 expression in TNBC cells. Then, the viability, migration, and invasion of TNBC cells were detected by cell counting kit-8 assays, wound healing assays, and Transwell assays. The EMT event was examined by evaluating the levels of EMT-associated proteins. For in vivo analysis, xenograft models in nude mice were established to explore PKMYT1 roles. E-cadherin and Ki67 expression in xenograft models were estimated by immunohistochemistry staining. Hematoxylin and eosin staining was performed to assess tumor metastasis. The underlying mechanisms by which PKMYT1 affected the malignant phenotypes of TNBC cells were explored by Western blotting measuring the pathway-associated proteins. Results: PKMYT1 was upregulated in BC tissues and cells, and its knockdown prevented cell proliferation, migration, invasion, and EMT event in TNBC. Mechanistically, Notch signaling was inactivated by PKMYT1 depletion, and Notch activation abolished the PKMYT1 silencing-induced inhibition in the malignant phenotypes of TNBC cells. For in vivo analysis, PKMYT1 knockdown inhibited tumorigenesis and metastasis of TNBC. Conclusion: PKMYT1 promotes EMT, proliferation, migration, and invasion of TNBC cells and facilitates tumor growth and metastasis by activating Notch signaling.

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.

Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells

Abstract The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma.

División ganglionar posquirúrgica y su efecto en el recuento ganglionar y la estadificación en pacientes con cáncer gástrico / Postoperative lymph node division and its effect on lymph node count and staging in patients with gastric cancer

Introducción. La gastrectomía y disección ganglionar es el estándar de manejo para los pacientes con cáncer gástrico. Factores como la identificación de ganglios por el patólogo, pueden tener un impacto negativo en la estadificación y el tratamiento. El objetivo de este estudio fue comparar el recuento ganglionar de un espécimen quirúrgico después de una gastrectomía completa (grupo A) y de un espécimen con un fraccionamiento por grupos ganglionares (grupo B). Métodos. Estudio de una base de datos retrospectiva de pacientes sometidos a gastrectomía D2 en el Servicio de Cirugía gastrointestinal de la Liga Contra el Cáncer seccional Risaralda, Pereira, Colombia. Se comparó el recuento ganglionar en especímenes quirúrgicos con y sin división ganglionar por regiones anatómicas previo a su envío a patología. Resultados. De los 94 pacientes intervenidos, 65 pertenecían al grupo A y 29 pacientes al grupo B. El promedio de ganglios fue de 24,4±8,6 y 32,4±14,4 respectivamente (p=0,004). El porcentaje de pacientes con más de 15 y de 25 ganglios fue menor en el grupo A que en el grupo B (27 vs 57, p=0,432 y 19 vs 24, p=0,014). El promedio de pacientes con una relación ganglionar menor 0,2 fue mayor en el grupo B (72,4 % vs 55,4 %, p=0,119). Conclusiones. Los resultados de nuestro estudio mostraron que una división por grupos ganglionares previo a la valoración del espécimen por el servicio de patología incrementa el recuento ganglionar y permite establecer de manera certera el pronóstico de los pacientes, teniendo un impacto positivo en su estadificación, para evitar el sobretratamiento

Introduction. A gastrectomy and lymph node dissection is the standard of management for patients with gastric cancer. Factors such as the identification of nodes by the pathologist can have a negative impact on staging and treatment. The objective of this study was to compare the lymph node count of a surgical specimen after a complete gastrectomy (group A) and of a specimen with lymph node by groups (group B). Methods. Study of a retrospective database of patients undergoing D2 gastrectomy in the Risaralda section of the Liga Contra el Cancer Gastrointestinal surgical service, Pereira, Colombia. The lymph node count was compared in surgical specimens with and without lymph node division by anatomical regions, prior to sending them to pathology. Results. Of the 94 patients who underwent surgery, 65 were from group A and 29 patients were from group B. The average number of nodes was 24.4±8.6 and 32.4±14.4, respectively (p=0.004). The percentage of patients with more than 15 and 25 nodes was lower in group A than in group B (27 vs 57, p=0.432 and 19 vs 24, p=0.014). The average number of patients with a nodal ratio less than 0.2 was higher in group B (72.4% vs 55.4%, p=0.119). Conclusions. The results of our study showed that a division by lymph node groups prior to the evaluation of the specimen by the pathology service increases the lymph node count and allows the prognosis of patients to be accurately established, having a positive impact on their staging, to avoid overtreatment.

Ultrasound-guided pericapsular nerve group and obturator nerve phenol neurolysis for refractory inpatient hip cancer metastasis pain: a case report

Abstract Introduction: Bone cancer metastasis may produce severe and refractory pain. It is often difficult to manage with systemic analgesics. Chemical neurolysis may be an effective alternative in terminally ill patients. Case report: Female terminally ill patient with hip metastasis of gastric cancer in severe pain. Neurolytic ultrasound-guided blocks of the pericapsular nerve group and obturator nerve were performed with 5% phenol. This led to satisfactory pain relief for 10 days, until the patient's death. Discussion: This approach may be effective and safe as an analgesic option for refractory hip pain due to metastasis or pathologic fracture in terminally ill patients.

The association of visceral pleural invasion with skip N2 metastasis on clinical stage IA NSCLC

Abstract Background Lung lymphatic drainage occurs mainly through a peribronchial path, but it is hypothesized that visceral pleural invasion could alter this path. This study aims to investigate the association between visceral pleural invasion, node upstaging, and N2 skip metastasis and the impact on survival in a population of patients with non-small cell lung cancer of 3 cm or smaller. Methods We retrospectively queried our institutional database of lung cancer resection for all patients with clinical stage IA NSCLC between June 2009 and June 2022. We collected baseline characteristics and clinical and pathological staging data. Patients were classified into two groups: The non-VPI group with negative visceral pleural invasion and the VPI group with positive. The primary results analyzed were the occurrence of nodal upstaging, skip N2 metastasis and recurrence. Results There were 320 patients analyzed. 61.3 % were women; the median age was 65.4 years. The pleural invasion occurred in 44 patients (13.7 %). VPI group had larger nodules (2.3 vs. 1.7 cm; p < 0.0001), higher 18F-FDG uptake (7.4 vs. 3.4; p < 0.0001), and lymph-vascular invasion (35.7 % vs. 13.5 %, p = 0.001). Also, the VPI group had more nodal disease (25.6 % vs. 8.7 %; p = 0.001) and skip N2 metastasis (9.3 % vs. 1.8 %; p = 0.006). VPI was a statistically independent factor for skip N2 metastasis. Recurrence occurred in 17.2 % of the population. 5-year disease-free and overall survival were worse in the VPI group. Conclusions The visceral pleural invasion was an independent factor associated with N2 skip metastasis and had worse disease-free and overall survival.

Identificación con azul patente de ganglio centinela en cáncer de mama / Patent blue for identification of sentinel nodes in breast cancer

Resumen OBJETIVO: Describir las características sociodemográficas, clínicas y patológicas y los resultados obtenidos con la técnica de ganglio centinela con azul patente en la cirugía de cáncer de mama temprano. Además, reportar la experiencia en la identificación del ganglio centinela en cáncer de mama temprano con la técnica con azul patente al 2.5%. MATERIALES Y MÉTODOS: Estudio retrospectivo y analítico consistente en la evaluación de los expedientes clínicos de pacientes diagnosticadas con cáncer de mama temprano, sin sospecha clínica o radiológica de afectación axilar, atendidas entre junio de 2022 y junio de 2023 en el servicio de Ginecología Oncológica de la UMAE Hospital de Ginecoobstetricia, Centro Médico Nacional de Occidente del IMSS. El sitio de inyección del colorante fue subdérmico periareolar, los ganglios identificados se estudiaron en el transoperatorio. Se analizaron el porcentaje de identificación, las tasas de falsos negativos y el valor predictivo negativo del método. RESULTADOS: Se analizaron 95 procedimientos de biopsia de ganglio centinela. Solo se practicó la linfadenectomía axilar en las pacientes con metástasis en el ganglio centinela comprobada en el estudio transoperatorio y en las que no se identificaron ganglios teñidos por no migración del colorante. La edad promedio de las pacientes fue de 57.1 años límites 25 y 78 años. El tamaño del tumor fue menor a 3 cm. A 64 67% pacientes se les hizo la mastectomía en comparación con 31 a quienes se efectuó cirugía conservadora de mama 33%. Se estadificaron como IA 57 de las 95 pacientes; el subtipo molecular más frecuente fue compatible con luminal A en 49%. CONCLUSIONES: La biopsia del ganglio centinela, con azul patente, es una técnica rápida, sencilla, precisa y de bajo costo para identificar daño axilar en etapas tempranas del cáncer de mama. Lo aquí reportado son resultados que corresponden a una primera evaluación de la técnica en nuestro servicio.

Abstract OBJECTIVE: To describe the sociodemographic, clinical and pathological characteristics and results of the patent blue sentinel lymph node technique in early breast cancer surgery. And to report the experience in identifying the sentinel lymph node in early breast cancer using the 2.5% patent blue technique. MATERIALS AND METHODS: Retrospective and analytical study consisting of the evaluation of the clinical records of patients diagnosed with early breast cancer, without clinical or radiological suspicion of axillary involvement, seen between June 2022 and June 2023 at the Oncological Gynaecology Service of the UMAE Hospital de Ginecoobstetricia, Centro Médico Nacional de Occidente of the IMSS. The dye injection site was subdermal periareolar, and the identified lumps were examined in the transoperative period. The percentage of identification, false negative rates and negative predictive value of the method were analysed. RESULTS: Ninety-five sentinel node biopsies were analysed. Axillary lymphadenectomy was performed only in patients with sentinel lymph node metastasis confirmed at surgery and in those in whom no stained nodes were identified due to non-migration of the dye. The mean age of the patients was 57.1 years range 25 to 78 years. The tumour size was less than 3 cm. Sixty-four patients 67% underwent mastectomy, compared with 31 who underwent breast-conserving surgery 33%. Fifty-seven of the 95 patients were staged as AI; the most common molecular subtype was compatible with luminal A in 49%. CONCLUSIONS: Sentinel lymph node biopsy with patent blue is a rapid, simple, accurate and inexpensive technique for identifying axillary disease in early breast cancer. The results reported here represent an initial evaluation of the technique in our service.

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.

Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities

BACKGROUND: Tumor-derived small extracellular vesicles (sEVs) can promote tumorigenic and metastatic capacities in less aggressive recipient cells mainly through the biomolecules in their cargo. However, despite recent advances, the specific molecules orchestrating these changes are not completely defined. Lactadherin is a secreted 0protein typically found in the milk fat globule membrane. Its overexpression has been associated with increased tumorigenesis and metastasis in breast cancer (BC) and other tumors. However, neither its presence in sEVs secreted by BC cells, nor its role in sEV-mediated intercellular communication have been described. The present study focused on the role of lactadherin-containing sEVs from metastatic MDA-MB-231 triple-negative BC (TNBC) cells (sEV-MDA231) in the promotion of pro-metastatic capacities in non-tumorigenic and non-metastatic recipient cells in vitro, as well as their pro-metastatic role in a murine model of peritoneal carcinomatosis. RESULTS: We show that lactadherin is present in sEVs secreted by BC cells and it is higher in sEV-MDA231 compared with the other BC cell-secreted sEVs measured through ELISA. Incubation of non-metastatic recipient cells with sEV- MDA231 increases their migration and, to some extent, their tumoroid formation capacity but not their anchorage-independent growth. Remarkably, lactadherin blockade in sEV-MDA231 results in a significant decrease of those sEV-mediated changes in vitro. Similarly, intraperitoneally treatment of mice with MDA-MB-231 BC cells and sEV-MDA231 greatly increase the formation of malignant ascites and tumor micronodules, effects that were significantly inhibited when lactadherin was previously blocked in those sEV-MDA231. CONCLUSIONS: As to our knowledge, our study provides the first evidence on the role of lactadherin in metastatic BC cell-secreted sEVs as promoter of: (i) metastatic capacities in less aggressive recipient cells, and ii) the formation of malignant ascites and metastatic tumor nodules. These results increase our understanding on the role of lactadherin in sEVs as promoter of metastatic capacities which can be used as a therapeutic option for BC and other malignancies.

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.

Elective parotidectomy and neck dissection are not beneficial in cutaneous squamous cell carcinoma of the head

Abstract Objective Cutaneous Squamous Cell Carcinoma (cSCC), a tumor with a significantly increasing incidence, is mostly diagnosed in the head region, where tumors have a worse prognosis and a higher risk of metastases. The presence of metastases reduces specific five-year survival from 99% to 50%. As the risk of occult metastases does not exceed 10%, elective dissection of the tributary parotid and neck lymph nodes is not recommended. Methods We retrospectively analyzed a group of 12 patients with cSCC of the head after elective dissections of regional (parotid and cervical) nodes by means of superficial parotidectomy and selective neck dissection. Results We diagnosed occult metastases neither in the cervical nor parotid nodes in any patient. None were diagnosed as a regional recurrence during the follow-up period. Conclucion Our negative opinion on elective parotidectomy and neck dissection in cSCC of the head is in agreement with the majority of published studies. These elective procedures are not indicated even for tumors showing the presence of known (clinical and histological) risk factors for lymphogenic spread, as their positive predictive value is too low. Elective parotidectomy is individually considered as safe deep surgical margin. If elective parotidectomy is planned it should include only the superficial lobe. Completion parotidectomy and elective neck dissection are done in rare cases of histologically confirmed parotid metastasis in the parotid specimen. Preoperatively diagnosed parotid metastases without neck involvement are sent for total parotidectomy and elective selective neck dissection. Cases of clinically evident neck metastasis with no parotid involvement, are referred for comprehensive neck dissection and elective superficial parotidectomy. The treatment of concurrent parotid and cervical metastases includes total conservative parotidectomy and comprehensive neck dissection. Level of evidence How common is the problem? Step 4 (Case-series) Is this diagnostic or monitoring test accurate? (Diagnosis) Step 4 (poor or non-independent reference standard) What will happen if we do not add a therapy? (Prognosis) Step 4 (Case-series) Does this intervention help? (Treatment Benefits) Step 4 (Case-series) What are the COMMON harms? (Treatment Harms) Step 4 (Case-series) What are the RARE harms? (Treatment Harms) Step 4 (Case-series) Is this (early detection) test worthwhile? (Screening) Step 4 (Case-series)

miR-186 regulates epithelial-mesenchymal transformation to promote nasopharyngeal carcinoma metastasis by targeting ZEB1

Abstract Objectives Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial-mesenchymal transformation (EMT) of NPC. Methods The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. Results The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. Conclusion miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC.

Prolonged survival after thoracic metastasectomy in patients with nonseminomatous testicular cancer

Abstract Introduction Almost 20 % of patients with Non-Seminomatous Germinative Cell Tumors (NSGCT) will require intrathoracic metastasectomy after chemotherapy. The authors aim to determine their long-term survival rates. Methods Retrospective study including patients with NSGCT and intrathoracic metastasis after systemic therapy from January 2011 to June 2022. Treatment outcomes and overall survival were analyzed with the Kaplan-Meier method. Results Thirty-seven male patients were included with a median age of 31.8 years. Six presented with synchronous mediastinum and lung metastasis, nine had only lung, and 22 had mediastinal metastasis. Over half had retroperitoneal lymph node metastasis. Twenty-two had dissimilar pathologies, with a discordance rate of 62 %. Teratoma and embryonal carcinoma were the prevalent primary tumor types, 40.5 % each, while teratoma was predominant (70.3 %) in the metastasis group. Thoracotomy was the main surgical approach (39.2 %) followed by VATS (37.2 %), cervico-sternotomy (9.8 %), sternotomy (5.8 %), and clamshell (3.9 %). Lung resection was performed in 40.5 % of cases. Overall, 10-year survival rates were 94.3 % with no surgical-related mortality. Conclusion Multimodality treatment with systemic therapy followed by radical surgery offers a high cure rate to patients with intrathoracic metastatic testicular germ cell tumors.

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.

Recent progress on the effects of structured lipids and fluidity of plasma membrane on tumor metastasis / 药学学报

The lipid composition of cell plasma membranes of aggressive tumors is significantly altered from normal, affecting the membrane fluidity and function. Plasma membrane fluidity involves multiple steps in tumor invasion and metastasis, including cell movement, adhesion, lateral diffusion of membrane molecules, signal transduction, material exchange and so on. This review highlights the difference in plasma membrane lipid composition and fluidity between normal and cancer cells, as well as the correlation with the invasion and metastasis potential of cancer. We also point out that the proliferation, invasion and metastasis of tumors can be inhibited by improving membrane fluidity or interfering with the membrane structured lipid composition, this focusing more on changing the biophysical properties of cancer cell membranes, and providing a novel strategy that works for treatment of tumor metastasis.

The characteristics of bone disseminated cells of 4T1 / 药学学报

Based on bone metastasis potential of mouse breast cancer 4T1 cells, the bone disseminated breast tumor cells 4T1 (B-4T1) were acquired through the screening of 6-mercaptopurine. The characteristics of B-4T1 were studied by morphological observation, proliferation assay, expression of epithelial and mesenchymal cell markers detection, transcriptome sequencing, and tumor formation experiments. The results showed that B-4T1 was round and spindle-shaped than primary 4T1 cells, and its proliferation rate was reduced, as well as epithelial cell adhesion molecule (EpCAM) and E-cadherin expression. The transcript level of N-cadherin was increased in the B-4T1, but not vimentin, indicating that B-4T1 had partial epithelial mesenchymal transition. Besides, B-4T1 had higher fatty acid metabolism and better tumor formation capacity. This study lays the experimental foundation for the basic study of metastasis in breast cancer. All animal experiments in this paper were conducted in accordance with the standards of the Animal Ethics Committee of China Pharmaceutical University.