Management and Clinical Outcomes of Breast Cancer in Women Diagnosed with Hereditary Cancer Syndromes in a Clinic-Based Sample from Colombia.

This study aimed to investigate prognosis and survival differences in 82 breast cancer patients with germline pathogenic/likely pathogenic variants (PVs) treated and followed at the Breast Unit of the Instituto Nacional de Cancerología, Colombia (INC-C) between 2018 and 2021. Median age at diagnosis was 46 years, with 62.2% presenting locally advanced tumors, 47.6% histological grade 3, and 35.4% with triple-negative breast cancer (TNBC) subtype. Most carriers, 74.4% (61/82), had PVs in known breast cancer susceptibility genes (i.e., "associated gene carriers" group, considered inherited breast cancer cases): BRCA2 (30), BRCA1 (14), BARD1 (4), RAD51D (3), TP53 (2), PALB2 (2), ATM (2), CHEK2 (1), RAD51C (1), NF1 (1), and PTEN (1). BRCA1-2 represented 53.7%, and homologous recombination DNA damage repair (HR-DDR) genes associated with breast cancer risk accounted for 15.9%. Patients with PVs in non-breast-cancer risk genes were combined in a different category (21/82; 25.6%) (i.e., "non-associated gene carriers" group, considered other breast cancer cases). Median follow-up was 38.1 months, and 24% experienced recurrence, with 90% being distant. The 5-year Disease-Free Survival (DFS) for inherited breast cancer cases was 66.5%, and for other breast cancer cases it was 88.2%. In particular, for carriers of PVs in the BRCA2 gene, it was 37.6%. The 5-year Overall Survival (OS) rates ranged from 68.8% for those with PVs in BRCA2 to 100% for those with PVs in other HR-DDR genes. Further studies are crucial for understanding tumor behavior and therapy response differences among Colombian breast cancer patients with germline PVs.

Prognostic Factors Associated with Tumor Recurrence and Overall Survival in Soft Tissue Sarcomas of the Extremities in a Colombian Reference Cancer Center.

Introduction: Soft tissue sarcomas (STS) are low-incidence tumors whose clinical and histopathological factors are associated with adverse oncological outcomes. This study evaluated prognostic factors (PF) associated with tumor recurrence and overall survival (OS) in patients diagnosed with STS of the extremities, treated at the Instituto Nacional de Cancerología (INC), Bogotá, Colombia. Materials and Methods: An analytical observational study of a historical cohort was carried out, including patients diagnosed with STS and managed surgically in the Functional Unit for Breast and Soft Tissue Tumors of the INC from January 2008 to December 2018. Results: A total of 227 patients were included; 74.5% had tumors greater than 5 cm. Most patients (29.1%) were in stage IIIB at diagnosis. Age was associated with higher mortality (HR = 1.01; CI95%: 1-1.02; p = 0.048). Tumor persistence at admission to the INC (HR = 2.34; CI95%: 1.25-4.35; p = 0.007) and histologic grade III (HR = 5.36; CI95%: 2.29-12.56; p = <0.001) showed statistical significance in the multivariate analysis for recurrence of any type, as did the PFs associated with a higher risk of local recurrence (HR = 2.85; CI95%: 1.23-6.57; p = 0.014 and HR = 6.09; CI95%: 2.03-18.2; p = 0.001), respectively. Tumor size (HR = 1.03; CI95%: 1-1.06; p = 0.015) and histologic grade III (HR = 4.53; CI95%: 1.42-14.49; p = 0.011) were associated with a higher risk of distant recurrence. Conclusions: This cohort showed that in addition to histologic grade and tumor size, tumor persistence at the time of admission has an impact on disease recurrence, so STS should be managed by a multidisciplinary team with experience in this pathology in high-volume reference centers.

g-NK cells from umbilical cord blood are phenotypically and functionally different than g-NK cells from peripheral blood.

FcRγ-deficient natural killer (NK) cells, designated as g-NK cells, exhibit enhanced antibody-dependent cellular cytotoxicity (ADCC) capacity and increased IFN-γ and TNF-α production, rendering them promising for antiviral and antitumor responses. g-NK cells from peripheral blood (PB) are often associated with prior human cytomegalovirus (HCMV) infection. However, the prevalence, phenotype, and function of g-NK cells in umbilical cord blood (UCB-g-NK) remain unclear. Here, we demonstrate significant phenotypical differences between UCB-g-NK and PB-g-NK cells. Unlike PB-g-NK cells, UCB-g-NK cells did not show heightened cytokine production upon CD16 engagement, in contrast to the conventional NK (c-NK) cell counterparts. Interestingly, following in vitro activation, UCB-g-NK cells also exhibited elevated levels of IFN-γ production, particularly when co-cultured with HCMV and plasma from g-NK+ adults. Furthermore, g-NK+ plasma from PB even facilitated the in vitro expansion of UCB-g-NK cells. These findings underscore the phenotypic and functional heterogeneity of g-NK cells based on their origin and demonstrate that components within g-NK+ plasma may directly contribute to the acquisition of an adult phenotype by the "immature" UCB-g-NK cells.

Morbidity and mortality of elderly patients with pancreaticobiliary disease according to age and comprehensive geriatric assessment: A prospective observational study.

BACKGROUND: This study was designed to analyze the influence of age and comprehensive geriatric evaluation on clinical results of pancreaticobiliary disease management in elderly patients. METHODS: A prospective observational study has been undertaken, including 140 elderly patients (over 75 years) with benign pancreaticobiliary disease. Patients were divided according to age in the following groups: group 1: 75-79 years old; group 2: 80-84 years old; group 3: 85 years and older. They underwent a comprehensive geriatric assessment with different scales: Barthel Index, Pfeiffer Index, Charlson Index, and Fragility scale, at admission and had been follow-up 90 days after hospital discharge to analyze its influence on morbidity and mortality. RESULTS: Overall, 140 patients have been included (group 1=51; group 2=43 and group 3=46). Most of them, 52 cases (37.8%), had acute cholecystitis, followed by 29 cases of acute cholangitis (20.2%) and acute pancreatitis with 25 cases (17.9%). Significant differences has been observed on complications in different age groups (p=0.033). Especially in patients with a Barthel Index result ≤60, which suggests that these less functional patients had more severe complications after their treatment (p=0.037). The mortality rate was 7.1% (10 patients). CONCLUSIONS: No significant differences were found between age, morbidity and mortality in elderly patients with pancreaticobiliary disease. Comprehensive geriatric scales showed some utility in their association with specific complications.

NK cells in peripheral blood carry trogocytosed tumor antigens from solid cancer cells.

The innate immune lymphocyte lineage natural killer (NK) cell infiltrates tumor environment where it can recognize and eliminate tumor cells. NK cell tumor infiltration is linked to patient prognosis. However, it is unknown if some of these antitumor NK cells leave the tumor environment. In blood-borne cancers, NK cells that have interacted with leukemic cells are recognized by the co-expression of two CD45 isoforms (CD45RARO cells) and/or the plasma membrane presence of tumor antigens (Ag), which NK cells acquire by trogocytosis. We evaluated solid tumor Ag uptake by trogocytosis on NK cells by performing co-cultures in vitro. We analyzed NK population subsets by unsupervised dimensional reduction techniques in blood samples from breast tumor (BC) patients and healthy donors (HD). We confirmed that NK cells perform trogocytosis from solid cancer cells in vitro. The extent of trogocytosis depends on the target cell and the antigen, but not on the amount of Ag expressed by the target cell or the sensitivity to NK cell killing. We identified by FlowSOM (Self-Organizing Maps) several NK cell clusters differentially abundant between BC patients and HD, including anti-tumor NK subsets with phenotype CD45RARO+CD107a+. These analyses showed that bona-fide NK cells that have degranulated were increased in patients and, additionally, these NK cells exhibit trogocytosis of solid tumor Ag on their surface. However, the frequency of NK cells that have trogocytosed is very low and much lower than that found in hematological cancer patients, suggesting that the number of NK cells that exit the tumor environment is scarce. To our knowledge, this is the first report describing the presence of solid tumor markers on circulating NK subsets from breast tumor patients. This NK cell immune profiling could lead to generate novel strategies to complement established therapies for BC patients or to the use of peripheral blood NK cells in the theranostic of solid cancer patients after treatment.

Direct Cell Death Induced by CD20 Monoclonal Antibodies on B Cell Lymphoma Cells Revealed by New Protocols of Analysis.

CD20 monoclonal antibodies (mAbs) eliminate B cells in several clinical contexts. At least two of these Abs, obinutuzumab (OBI) and rituximab (RTX), induce quick elimination of targets and put cancer patients at risk of tumor lysis syndrome (TLS) within 12-24 h of the first dose. The mechanisms of killing can require the recruiting of effector mechanisms from the patient's immune system, but they can induce direct killing as well. This can be more rapid than recruiting cellular effectors and/or complement. We showed here that OBI and RTX induce quick (<1 h) and high (up to 60% for OBI) killing of two different B cell lines. This was unveiled by using two different techniques that circumvent cell centrifugation steps: a Muse® Cell Analyzer-based approach and a direct examination of the cells' physical properties by using forward scatter (FS) area and side scatter (SS) area by flow cytometry. These results excluded the presence of aggregates and were also confirmed by developing a normalized survival ratio based on the co-incubation of RTX- and OBI-sensitive cells with MOLM-13, an insensitive cell line. Finally, this normalized survival ratio protocol confirmed the RTX- and OBI-direct killing on primary tumor B cells from B cell chronic lymphocytic leukemia (B-CLL) and Non-Hodgkin's lymphoma (NHL) patients. Moreover, we unveiled that direct killing is higher than previously expected and absent in patients' samples at relapse. We also observed that these mAbs, prior to increasing intracellular calcium levels, decrease calcium entry, although manipulating calcium levels did not affect their cytotoxicity. Altogether, our results show that direct killing is a major mechanism to induce cell death by RTX and OBI mAbs.

Perioperative Nursing Role in Robotic Surgery: An Integrative Review.

PURPOSE: Robotic surgery is an increasingly popular approach across surgical specialties in several countries. Nurses embedded in this highly technological environment, however, could excessively center their attention to the robot, deviating their focus from the patient. The Perioperative Patient Focused Model is proposed as a theoretical framework to guide nursing perioperative care toward a patient-centered approach based on 4 dimensions: Health System, Safety, Behavioral Responses and Physiological Responses. This review aimed to understand the role of perioperative nursing in robotic surgery according to the Perioperative Patient Focused Model. DESIGN: An integrative review. METHODS: The Whittemore and Knafl methodology guided this review. The following databases were searched: PubMed, Cochrane Library, ProQuest, Scielo, and LILACS. The keywords used were "Robotic Surgical Procedures" and "Nursing" and their equivalents in Spanish, Portuguese, and French, using the Boolean operator "AND," within the time frame of 2010-2021. FINDINGS: A total of 1,695 articles were retrieved, of which 26 were retained for the final analysis. The majority (n = 17) were written in English, with a level of evidence between 4 and 5. The main actions performed by nursing professionals were retrieved in the Health Systems, Safety, and Behavioral Responses dimensions, focusing on the intraoperative and postoperative period. However, most of the patient's responses were presented in the postoperative stage, even after discharge. Encompassing these findings, a theoretical framework is proposed. CONCLUSIONS: Nursing professional duties are diverse within the course of robotic surgery. It is necessary to expand the Perioperative Nursing specialty toward an extended care, encompassing even the community settings.

Seguimiento de la paciente con diagnóstico de cáncer de mama. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacionalde Cancerología - Colombia / Follow-up of the patient with breast cancer history. Review of the evidence and approach at the Instituto Nacional de Cancerología - Colombia

Los supervivientes de cáncer se definen como aquellos individuos que han completado su tratamiento inicial y no tienen evidencia de la enfermedad. Para el caso de las pacientes supervivientes de cáncer de mama, el seguimiento involucra no sólo la vigilancia de la recaída locorregional y a distancia, así como la tamización de segundos primarios mamarios, sino también la evaluación de los efectos relacionados con las terapias recibidas. Hoy en día, existe controversia sobre cuál debe ser el método, la frecuencia, la duración y tipo de personal de la salud que realice el seguimiento de estas pacientes. Las guías de las distintas sociedades científicas muestran una variabilidad importante en las recomendaciones a este respecto. Este documento pretende revisar la mejor evidencia disponible sobre los procedimientos para la detección de la recaída locorregional, de las metástasis a distancia, de un segundo cáncer de mama contralateral y de los eventos adversos relacionados con los tratamientos para el cáncer de mama. Adicionalmente, se examinan los porcentajes y sitios de recidiva tumoral con relación al estadio clínico y a la biología tumoral

Cancer survivors are defined as those individuals who have completed their initial treatment and have no evidence of disease. In the case of breast cancer survivors, follow-up involves not only surveillance of locoregional and distant relapse, as well as screening for second primary breast cancers, but also evaluation of the effects related to the therapies received. Nowadays, there is controversy about what should be the method, the frequency, the duration and the type of health personnel that carry out the follow-up of these patients. The guides of the different scientific societies show a significant variability in the recommendations in this regard. This document aims to review the best available evidence on procedures for the detection of locoregional relapse, distant metastases, contralateral second breast cancer, and adverse events related to breast cancer treatments. Additionally, the percentages and sites of tumor recurrence are examined in relation to clinical stage and tumor biology

Tratamiento sistémico para el cáncer de mama HER2 positivo avanzado. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Systemic treatment for advanced HER2 positive breast cancer. Review of the evidence and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

El cáncer de mama es la neoplasia más frecuente y de mayor mortalidad en las mujeres en todo el mundo. El receptor 2 del factor de crecimiento epidérmico humano (HER2) se sobreexpresa en aproximadamente el 20% de las pacientes con cáncer de mama y se asocia a mayor riesgo de recidiva tumoral y mortalidad. Antes del desarrollo de los anticuerpos monoclonales dirigidos contra HER2, el cáncer de mama HER2 positivo estaba asociado con un pronóstico desfavorable. El uso de las terapias dirigidas anti HER2 ha mejorado significativamente las tasas de supervivencia global tanto en el escenario adyuvante como en la enfermedad metastásica. En los últimos años han surgido nuevos medicamentos que bloquean esta vía de señalización, lo cual ha permitido establecer varias líneas de tratamiento con terapia anti HER2 en las pacientes con enfermedad metastásica. Por esta razón, las unidades funcionales de Oncología Clínica/Seno y Tejidos Blandos tomaron la decisión de realizar una revisión de la evidencia científica disponible a octubre de 2021, para establecer las recomendaciones en el abordaje terapéutico de las pacientes con cáncer de mama metastásico HER2 positivo en el Instituto Nacional de Cancerología (INC).

Breast cancer is the most common neoplasm and the one with the highest mortality in women worldwide. Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20% of breast cancer patients and is associated with an increased risk of tumor recurrence and mortality. Before the development of monoclonal antibodies directed against HER2, HER2-positive breast cancer was associated with a poor prognosis. The use of anti-HER2 targeted therapies has significantly improved overall survival rates both in the adjuvant setting and in metastatic disease. In recent years, new drugs have emerged that block this signaling pathway, which has made it possible to establish several lines of treatment with anti-HER2 therapy in patients with metastatic disease. For this reason, the clinical oncology/breast and soft tissue functional units made the decision to conduct a review of the available scientific evidence as of October 2021 to establish recommendations for the therapeutic approach to patients with HER2-positive metastatic breast cancer in the National Cancer Institute (INC).

Criterios para la identificación de síndromes de cáncer de mama hereditarios. Revisión de la literatura y recomendaciones para el Instituto Nacional de Cancerología - Colombia / Criteria for the identification of hereditary breast cancer syndromes. Review of the literature and recommendations for the Instituto Nacional de Cancerología - Colombia

Introducción. Los síndromes de cáncer de mama hereditario (SCMH) corresponden a un 5% a 10% de todos los casos de la enfermedad, en su mayoría explicados por mutaciones en los genes BRCA1 y BRCA2. Se han publicado múltiples guías y recomendaciones internacionales actualizadas, con el fin de dar lineamientos para seleccionar los casos con sospecha de un SCMH. Como antecedentes locales, el Instituto Nacional de Cancerología de Colombia cuenta con un "Programa institucional para la identificación y manejo de familias con sospecha de cáncer hereditario", con fines asistenciales, dentro del cual el cáncer de mama es la patología más remitida al servicio de genética (55%; 540/986). En el 21% de los casos con cáncer de mama que cumplieron criterios NCCN se diagnosticó un SCMH, la mayoría asociados a mutaciones en los genes BRCA1 y BRCA2 (12,3%) y en menor proporción a otros genes de susceptibilidad al cáncer de mama (8,6%).Objetivo. Identificar los criterios de selección más implementados para diagnosticar los casos de cáncer de mama hereditarios a través de una revisión de la literatura, y realizar un consenso Institucional sobre las indicaciones de remisión a consejería genética y solicitud de pruebas para fines diagnósticos y de tratamiento sistémico con iPARP. Materiales y métodos. Se realizó una revisión narrativa de la literatura científica publicada en los últimos 10 años, al 30 de agosto del 2021, sobre la prevalencia de mutaciones germinales en los genes BRCA1 y BRCA2, y en otros genes no BRCA, en pacientes con cáncer de mama, obteniéndose en total 146 y seleccionándose un total de 41 artículos. En el interior de las unidades funcionales de mama y tejidos blandos, genética y oncología clínica, se presentó la evidencia disponible, realizando una discusión amplia entre las tres unidades y finalmente se definieron las indicaciones para remisión a genética, para solicitar estudios genéticos y de tratamiento sistémico con iPARP.Resultados. Según lo reportado en la literatura, los principales criterios de sospecha de un SCMH deben incluir: el subtipo triple negativo, la presentación bilateral, la edad muy temprana de diagnóstico y los antecedentes familiares (AF) de cáncer de mama antes de los 50 años o cáncer de ovario a cualquier edad.Conclusiones. Se adoptan las recomendaciones de la NCCN para la remisión a consejería genética y solicitud de estudios genéticos para identificar cáncer de mama hereditario, y se establecen los criterios del estudio OlympiA para la solicitud de estudios genéticos con el fin de guiar el tratamiento sistémico con iPARP en el Instituto Nacional de Cancerología. Lo anterior permitirá que desde nuestra Institución se ofrezca adecuadamente este servicio a la población colombiana.

ntroduction: Hereditary breast and ovarian cancer syndromes (HBOC) represents 5% to 10% of all breast cancer cases, and BRCA1andBRCA2 explain most of these syndromes. Multiple guidelines and updated recommendations have been published to define which patients should be selected for genetic testing based on a clinical suspicion of a HBOC syndrome. For context, the Instituto Nacional de Cancerología from Colombia developed an "Institutional Program for the identification and management of families with suspected hereditary cancer" for healthcare purposes, within which breast cancer is the most referred pathology to the genetics service (55%; 540/986). Inherited cancer was diagnosed in 21% of the patients with breast cancer who met NCCN criteria; most of these were associated with BRCA1 and BRCA2 mutations (12.3%) and to a lesser extent to other breast cancer susceptibility genes (8.6%).Objective: To identify the most implemented selection criteria to diagnose inherited breast cancer cases, through a review of the literature, and to achieve an institutional consensus on the indications for referral to genetic counseling and genetic testing for diagnostic and systemic treatment with PARPi.Materials and methods: A narrative review of the scientific literature published in the last 10 years as of August 30, 2021 on the prevalence of germline mutations in the BRCA1 and BRCA2 genes, and in other non-BRCA genes, in patients with breast cancer was carried out. Overall, 146 articles were first identified but only 41 were selected. Within the functional units of breast and soft tissue, genetics and clinical oncology, the available evidence was presented and a broad discussion was carried out; finally the indications for referral to genetic counseling, for genetic testing and for systemic treatment with PARPi were defined.Results: As reported in the literature, clinical criteria for HBOC syndrome should include: triple negative subtype, bilateral presentation, very early age of diagnosis and family history (FH) of breast cancer before 50 years of age or ovarian cancer at any age. Conclusions: The NCCN recommendations for referral to genetic counseling and ordering genetic testing to diagnose HBOC cases are adopted at the Instituto Nacional de Cancerología from Colombia, as well as the OlympiA study criteria for ordering genetic testing to guide systemic PARPi therapy. This will allow our Institution to adequately offer this service to the Colombian population.

Indicaciones para el uso de pertuzumab en cáncer de mama HER2 positivono metastásico en los escenarios neoadyuvante y adyuvante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Indications for the use of pertuzumab in non-metastatic HER2-positive breast cancer in the neoadjuvant and adjuvant. Review of the literature and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La adición de la terapia dirigida a la quimioterapia citotóxica en pacientes con cáncer de mama ha mejorado significativamente los desenlaces oncológicos en las pacientes con tumores HER2 positivo. El uso de pertuzumab durante el manejo neoadyuvante incrementa significativamente la respuesta patológica completa y en la actualidad permite emplear regímenes libres de antraciclinas con una eficacia similar y menores efectos cardiovasculares (en especial sobre la fracción de eyección). El beneficio en supervivencia libre de enfermedad invasiva, de adicionar pertuzumab en el escenario adyuvante en las pacientes sin tratamiento anti HER2 previo, está limitado a aquellas con ganglios positivos. La implementación de esquemas con bloqueo dual anti HER2, durante el tratamiento inicial del cáncer de mama HER2 positivo, mejora significativamente el pronóstico oncológico en este grupo de pacientes.

The addition of targeted therapy to cytotoxic chemotherapy in patients with breast cancer has significantly improved oncologic outcomes in patients with HER2-positive tumors. The use of pertuzumab during neoadjuvant management significantly increases the complete pathological response and currently allows the use of anthracycline-free regimens with similar efficacy and fewer cardiovascular effects (especially on ejection fraction). The benefit of pertuzumab in disease-free survival in the adjuvant setting for patients without prior anti-HER2 treatment is limited to those with positive nodes. The implementation of schemes with dual anti-HER2 blockade during the initial treatment of HER2-positive breast cancer significantly improves the oncological outcomes in this group of patients.

Estudios de extensión para la estadificación del cáncer de mama infiltrante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Extension studies for the staging of infiltrating breast cancer. Review of evidence and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La estadificación del cáncer de mama tiene como objetivo determinar la extensión de la enfermedad, definir el tratamiento y el pronóstico de la misma. La American Joint Committee on Cancer(AJCC) ha asignado el estadio utilizando el tamaño del tumor (T), la presencia de compromiso ganglionar (N), y la presencia o ausencia de metástasis a distancia (M). Con el advenimiento de la biología molecular, se integra a la estadificación anatómica la información pronóstica con el grado histológico, el estado de los receptores hormonales y el resultado del receptor de HER2. En el Instituto Nacional de Cancerología (INC), la incorporación del TNM pronóstico trajo consigo un aumento de estadio en el 14,47% de los casos y una disminución en el 40,3%; este resultado se atribuyó en parte al mayor porcentaje de tumores localmente avanzados dentro de la institución. Por subtipo biológico, los tumores luminales presentan mayor riesgo de metástasis óseas, los tumores triple negativo a pulmón y sistema nervioso central; y los tumores HER2 a SNC, hígado y pulmón. Teniendo en cuenta este compromiso a distancia, los métodos de estadificación comúnmente utilizados son gammagrafía ósea (GO), radiografía de tórax (RxT), ecografía hepática (UH) y/o tomografía computarizada (TC). En el caso de identificar hallazgos sospechosos en estos exámenes o si el cuadro clínico del paciente lo sugiere, se realizan estudios adicionales como TC o resonancia magnética nuclear (RMN). Los cambios en la estadificación clínica y la biología del cáncer de mama motivaron a las Unidades de Seno y Tejidos Blandos y Oncología Clínica del Instituto Nacional de Cancerología a revisar la evidencia científica disponible para recomendar la pertinencia de los estudios de extensión.

The staging of breast cancer has the objective to determine the extent of the disease, define treatment and prognosis. The American Joint Committee on Cancer (AJCC) has assigned the stage using the size of the tumor (T), the presence of lymph node involvement (N), and the presence or absence of distant metastases (M). With the advent of molecular biology, prognostic information with histological grade, hormone receptor status, and HER2 receptor is integrated with anatomic staging. In the National Institute of Cancerology (INC) the incorporation of TNM brought with it an increase in stage in 14.47% of cases and a decrease in 40.3%; this result was attributed in part to the higher percentage of locally advanced tumors within the institution. By biological subtype, luminal tumors have a higher risk of bone metastases, triple negative tumors to the lung and central nervous system; and HER2 tumors to CNS, liver and lung. Taking this distant involvement into account, the commonly used staging methods are bone scan (BS), chest radiography (CXR), liver ultrasound (UH) and/or computed tomography (CT) scans. In the case of identifying suspicious findings in these tests or if the patient's clinical condition suggests it, additional studies such as CT or magnetic resonance imaging (MRI) are performed. Changes in the clinical staging and biology of breast cancer motivated the Breast and Clinical Oncology Functional Unit of the National Cancer Institute to review the available scientific evidence to recommend the relevance of extension studies.

Hallazgos incidentales en cirugía abdominal: masas y sarcomas retroperitoneales / Incidental findings in abdominal surgery: Retroperitoneal masses and sarcomas

Introducción. El retroperitoneo es una estructura que se extiende desde el diafragma hasta la pelvis, está delimitado adelante por el peritoneo parietal, atrás y a los lados por la fascia transversalis y se divide en 9 compartimientos. Se pueden encontrar lesiones primarias o secundarias, cuya evolución clínica varía desde un curso indolente hasta rápidamente progresivo, tanto local como a distancia. Su enfoque, desde el hallazgo hasta el tratamiento, es fundamental para el desenlace oncológico. Objetivo. Analizar la evaluación, el diagnóstico y el tratamiento de las masas retroperitoneales halladas incidentalmente y brindar un algoritmo de manejo. Métodos. Se hizo búsqueda en bases de datos como PubMed y MedicalKey de literatura referentes a tumores retroperitoneales, su diagnóstico y enfoque terapéutico, con el fin de presentar una revisión sobre el abordaje de las masas retroperitoneales y dar nuestras opiniones. Resultados. Se revisaron 43 referencias bibliográficas internacionales y nacionales, y se seleccionaron 20 de ellas, de donde se obtuvieron datos actualizados, recomendaciones de guías internacionales y experiencias nacionales, con lo cual se estructuró este manuscrito. Conclusiones. Las masas retroperitoneales abarcan un espectro de patologías que establecen un reto diagnóstico por su origen embriológico, localización y baja frecuencia. El diagnostico histológico es de vital importancia desde el inicio, para conocer la evolución natural de la enfermedad, y el manejo multidisciplinario en centros de referencia es fundamental para impactar en los desenlaces oncológicos. Existen variadas modalidades terapéuticas, como quimioterapia, radioterapia y resección quirúrgica con estándares oncológicos

Introduction. The retroperitoneum is an structure that extends from the diaphragm to the pelvis, bounded anteriorly by the parietal peritoneum, posteriorly and laterally by the transversalis fascia, and it is divided into 9 compartments. We can find primary or secondary lesions whose clinical evolution varies from an indolent course to a rapidly progressive one, both local and distant. Its approach from discovery to diagnosis and treatment is essential for the oncological outcomes. Objective. To analyze the evaluation, diagnosis and treatment of incidental retroperitoneal masses according to their origin and to provide a management algorithm. Methods. An updated literature search was carried out in databases such as PubMed and Medical Key on retroperitoneal tumors, therapeutic approach and diagnosis, obtaining national and international information to carry out a review article on the approach to retroperitoneal masses.Results. Forty-three international and national bibliographic references were reviewed, based on 20 updated data, recommendations from international guidelines and national experiences were obtained, with which a review and opinion manuscript was structured.Conclusions. Retroperitoneal masses cover a spectrum of pathologies that establish a diagnostic challenge due to their embryological origin, location and low frequency. Histological diagnosis is of vital importance from the beginning to know the natural evolution of the disease and multidisciplinary management in reference centers is essential to impact oncological outcomes. There are many therapeutic modalities from chemotherapy, radiotherapy and surgical resection with oncological standards

Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID.

T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitalized for SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to Intensive Care Units (ICUs) or non-ICU, and 29 age- and sex-matched healthy controls (HCs). Amounts of intracellular perforin and granzyme-B, as well as cell surface expression of the degranulation marker CD107A were determined by flow cytometry. The levels of 15 cytokines in plasma were measured by Luminex. The frequency of perforin-positive T4 cells and T8 cells was higher in patients than in HCs (9.9 ± 10.1% versus 4.6 ± 6.4%, p = 0.006 and 46.7 ± 20.6% vs 33.3 ± 18.8%, p = 0.004, respectively). Perforin expression was neither correlated with clinical and biological markers of disease severity nor predictive of death. By contrast, the percentage of perforin-positive T8 cells in the acute phase of the disease predicted the onset of long COVID one year later. A low T8 cytotoxicity in the first days of SARS-CoV-2 infection might favor virus replication and persistence, autoimmunity, and/or reactivation of other viruses such as Epstein-Barr virus or cytomegalovirus, paving the way for long COVID. Under this hypothesis, boosting T cell cytotoxicity during the acute phase of the infection could prevent delayed sequelae.

Estadificación laparoscópica en pacientes con carcinomatosis peritoneal. Un enfoque desde la cirugía citorreductiva / Laparoscopic staging in patients with peritoneal carcinomatosis. An approach from cytoreductive surgery

Introducción. Las metástasis peritoneales representan un estado avanzado de muchos cánceres intraabdominales y suelen dar un pronóstico ominoso a los pacientes que las desarrollan. Hasta hace poco la única opción terapéutica para este escenario era la quimioterapia paliativa. Sin embargo, la mayoría de los tumores metastásicos al peritoneo continúan siendo relativamente resistentes a las drogas citotóxicas y citostáticas administradas por vía endovenosa y, en general, a las terapias individuales. Métodos. Se realizó una búsqueda de la literatura en las bases de datos de PubMed, SciELO y Google Scholar utilizando las palabras claves: laparoscopia, carcinomatosis peritoneal, estadificación, citorreducción. Se incluyeron para la revisión los artículos con mayor relevancia publicados en inglés y español. Discusión. La cirugía citorreductiva asociada a técnicas de quimioterapia hipertérmica intraperitoneal se ofrece actualmente a pacientes con indicaciones precisas según el primario subyacente. Es aquí donde la laparoscopia de estadificación realizada de manera correcta y completa juega un papel determinante, puesto que ha demostrado ser un método fiable para realizar una aproximación del compromiso peritoneal. Conclusión. Todos los especialistas quirúrgicos, en especial los cirujanos generales, deben estar familiarizados en cómo realizar de forma completa una laparoscopia de estadificación, de manera que se pueda hacer una mejor aproximación al grado de compromiso peritoneal, contribuyendo en el manejo integral oncológico del paciente.

Introduction. Peritoneal metastases represent an advanced stage of many intra-abdominal neoplasms and often give an ominous prognosis. Recently, the only therapeutic option for this setting was palliative chemotherapy. However, most tumors metastatic to the peritoneum remain relatively resistant to intravenously administered cytotoxic and cytostatic drugs and, in general, to individual therapies. Methods. A literature search was performed in PubMed, SciELO and Google Scholar databases using the keywords: laparoscopy, peritoneal carcinomatosis, staging, cytoreduction. The most relevant articles published in English and Spanish were included in the review. Discussion. Cytoreductive surgery associated with intraperitoneal hyperthermic chemotherapy techniques is currently offered to patients with precise indications according to the underlying primary. It is here where staging laparoscopy performed in a complete and correct manner plays a determining role, since it has proven to be a reliable method for approximating peritoneal involvement. Conclusion. All surgical specialists, especially general surgeons, should be familiar with how to perform a complete staging laparoscopy, leading to a correct approach of the degree of peritoneal involvement and contributing to the integral oncologic management of the patient.

Clinical Outcomes of Adjuvant Hormone Therapy in a Cohort of Patients With Infiltrating Non-metastatic Breast Cancer in a Latin American Cancer Center.

INTRODUCTION: Breast cancer (BC) is the most commonly diagnosed cancer in women. This study evaluated the clinical outcomes and prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in a cohort of patients diagnosed with hormone receptor-positive non-metastatic BC managed with adjuvant hormone therapy. METHODS: An observational, analytical, historical cohort study was conducted. DFS and OS rates were estimated, Kaplan-Meier survival functions were calculated, and Cox models were developed to assess the association between time to event (all-cause mortality or relapse) and hormone therapy exposure with a set of established variables. RESULTS: Inclusion criteria were met by 685 patients; the mean age at diagnosis was 58 years (SD=11.9 years). The most commonly used drug was tamoxifen for five years in 241 (35.7%) patients; 470 (69.6%) patients received initial therapy, 112 (16.5%) underwent switch therapy, and 93 (13.8%) had extended therapy. The factors associated with better rates of DFS and OS were early clinical stage (p=0.00), luminal A and luminal B Her2-positive biological subtypes (p=0.00), and adherence to adjuvant hormone therapy (p=0.001). Mortality rate was 0.77 deaths per 100 patients/year (95% CI, 0.51-1.2). CONCLUSION: This cohort demonstrated that adjuvant hormone therapy improves DFS and OS rates in locally advanced tumors. The main factor for reducing disease progression in this cohort was adequate adherence to treatment.

Neuropilin-1 is present on Foxp3+ T regulatory cell-derived small extracellular vesicles and mediates immunity against skin transplantation.

Among the mechanisms of suppression that T regulatory (Treg) cells exert to control the immune responses, the secretion of small extracellular vesicles (sEV) has been recently proposed as a novel contact-independent immunomodulatory mechanism. Previous studies have demonstrated that Treg cells produce sEV, including exosomes, able to modulate the effector function of CD4+ T cells, and antigen presenting cells (APCs) such as dendritic cells (DCs) through the transfer of microRNA, cytokines, the production of adenosine, among others. Previously, we have demonstrated that Neuropilin-1 (Nrp1) is required for Tregs-mediated immunosuppression mainly by impacting on the phenotype and function of effector CD4+ T cells. Here, we show that Foxp3+ Treg cells secrete sEV, which bear Nrp1 in their membrane. These sEV modulate effector CD4+ T cell phenotype and proliferation in vitro in a Nrp1-dependent manner. Proteomic analysis indicated that sEV obtained from wild type (wt) and Nrp1KO Treg cells differed in proteins related to immune tolerance, finding less representation of CD73 and Granzyme B in sEV obtained from Nrp1KO Treg cells. Likewise, we show that Nrp1 is required in Treg cell-derived sEV for inducing skin transplantation tolerance, since a reduction in graft survival and an increase on M1/M2 ratio were found in animals treated with Nrp1KO Treg cell-derived sEV. Altogether, this study describes for the first time that Treg cells secrete sEV containing Nrp1 and that this protein, among others, is necessary to promote transplantation tolerance in vivo via sEV local administration.

Professional and Demographic Profile of Spanish-Speaking Child Neurologists in the United States.

>Objective: To ascertain the prevalence of culturally native Spanish-speaking child neurologists in the United States. Methods: Prevalence statistics regarding demographic and work profile were applied to data obtained from a cross-sectional electronic survey of Child Neurology Society (CNS) members. Results: Demographics of the 135 respondents were comparable to a similar CNS survey except for ethnicity as shown in Table 1. Fifty- three percent were male and 24% were over age 60. Approximately a quarter were represented each from East, South, Midwest, and Western US. 42% self-identified as Spanish, Hispanic, or Latino. 62% spoke English as their primary language and 39% spoke Spanish as their primary language. Two-thirds graduated from a US medical school, 51% practice general neurology, and epilepsy was the most common subspecialty (18%). Two-thirds of respondents practice at a major teaching hospital, and 93% hold university academic appointments. 79% are AAN members. 76% did not have medical student debt at the time of the survey. 29% report signs consistent with burnout. 87% would choose Child Neurology again and 96% would recommend Child Neurology to a medical student. Conclusion: 40% of survey respondents self-identified as Hispanic, Latino or Spanish and spoke Spanish as the primary language and the majority practice in Academic Medicine. Nearly a third of those in the current survey identify burnout symptoms. Consideration of distinctive language and cultural characteristics across the US may lead to provision of a more patient-centered and equitable care.

Factors Associated with Time to Progression and Overall Survival in Patients with De Novo Metastatic Breast Cancer: A Colombian Cohort.

PURPOSE: About 10% of breast cancer (BC) is diagnosed in stage IV. This study sought to identify factors associated with time to progression (TTP) and overall survival (OS) in a cohort of patients diagnosed with de novo metastatic breast cancer (MBC), from a single cancer center in Colombia, given that information on this aspect is limited. METHODOLOGY: An observational, analytical, and retrospective cohort study was carried out. Time to progression and OS rates were estimated using the Kaplan-Meier survival functions. Cox models were developed to assess association between time to progression and time to death, using a group of fixed variables. RESULTS: Overall, 175 patients were included in the study; 33.7% of patients had luminal B HER2-negative tumors, 49.7% had bone involvement, and 83.4% had multiple metastatic sites. Tumor biology and primary tumor surgery were the variables associated with TTP and OS. Patients with luminal A tumors had the lowest progression and mortality rates (10 per 100 patients/year (95% CI: 5.0-20.0) and 12.6 per 100 patients/year (95% CI: 6.9-22.7), respectively), and patients with triple-negative tumors had the highest progression and mortality rates (40 per 100 patients/year (95% CI: 23.2-68.8) and 44.1 per 100 patients/year (95% CI: 28.1-69.1), respectively). Across the cohort, the median TTP was 2.1 years (95% CI: 1.6; the upper limit cannot be reached) and the median OS was 2.4 years (95% CI: 2-4.3). CONCLUSIONS: In this cohort, patients with luminal A tumors and those who underwent tumor surgery given that they presented clinical benefit (CB) after initial systemic treatment, had the lowest progression and mortality rates. Overall, OS was inferior to other series due to high tumor burden and difficulties in accessing and continuing oncological treatments.

NK Cells Acquire CCR5 and CXCR4 by Trogocytosis in People Living with HIV-1.

NK cells play a major role in the antiviral immune response, including against HIV-1. HIV-1 patients have impaired NK cell activity with a decrease in CD56dim NK cells and an increase in the CD56-CD16+ subset, and recently it has been proposed that a population of CD56+NKG2C+KIR+CD57+ cells represents antiviral memory NK cells. Antiretroviral therapy (ART) partly restores the functional activity of this lymphocyte lineage. NK cells when interacting with their targets can gain antigens from them by the process of trogocytosis. Here we show that NK cells can obtain CCR5 and CXCR4, but barely CD4, from T cell lines by trogocytosis in vitro. By UMAP (Uniform Manifold Approximation and Projection), we show that aviremic HIV-1 patients have unique NK cell clusters that include cells expressing CCR5, NKG2C and KIRs, but lack CD57 expression. Viremic patients have a larger proportion of CXCR4+ and CCR5+ NK cells than healthy donors (HD) and this is largely increased in CD107+ cells, suggesting a link between degranulation and trogocytosis. In agreement, UMAP identified a specific NK cell cluster in viremic HIV-1 patients, which contains most of the CD107a+, CCR5+ and CXCR4+ cells. However, this cluster lacks NKG2C expression. Therefore, NK cells can gain CCR5 and CXCR4 by trogocytosis, which depends on degranulation.