The development of novel human epidermal growth factor receptor type-2 (HER2)-tar-geted therapies for HER2-positive breast cancer (HER2+ breast cancer (BC)) in recent decades has called fora reassessment of the benefit of including anthracyclines in neoadjuvant regimens, given their association with cardiotoxicity and secondary malignancies. Our study assessed the value of adding anthracyclines in a real-world cohort of early-stage HER2+ BC patients treated with trastuzumab with or without pertuzumab. We retrospectively evaluated 446 patients with early-stage HER2+ BC treated with neoadjuvant chemotherapy at two Chilean centers between 2010 and 2023. Patients received trastuzumab alone or trastuzumab plus pertuzumab, with anthracycline-containing or anthracycline-free regimens. Our primary endpoint was pathological complete response (pCR; ypT0/is ypN0). Secondary endpoints included invasive disease-free survival (iDFS) and overall survival (OS). Multivariate models assessed the predictive role of anthracyclines and pathological biomarkers (ER status, Ki67, HER2 amplification). Elevated Ki67, low ER expression and increased HER2 amplification were independent predictors of pCR. The addition of anthracyclines did not significantly improve pCR rates, even among patients treated with single HER2 targeted therapy (trastuzumab alone). With a median follow-up of 47 months, anthracyclines had no impact on iDFS (log-rank p = 0.19) or OS (p = 0.96). Subgroup and interaction analyses confirmed no benefit in other biomarkerdefined populations. Overall, anthracyclines did not improve response to treatment or survival in HER2+ BC, even without dual HER2 blockade. These findings support anthracycline-free regimens, even in health systems with limited access to dual HER2-blockade with pertuzumab.

Vasculogenic mimicry (VM) refers to the ability of non-endothelial cells to form fluid-conducting, vessel-like structures independently of endothelial cells. In cancer, VM is associated with tumor aggressiveness and poor prognosis, although similar structures may also be formed by non-cancerous cells. Here, we systematically screened more than 23 human and murine cell lines, including diverse cancer types, fibroblasts, and primary-tumor-derived cells, identifying cell types capable or incapable of VM formation. Using confocal microscopy and 3D reconstruction, we define in vitro VM as the formation of lumen-containing tubular structures by non-endothelial cells, distinguishing this phenomenon from simple cellular clustering or alignment. Importantly, cell types capable of confirmed VM in vitro corresponded closely with previous findings in mouse xenograft models. We further provide a practical protocol for screening VM capacity and demonstrate that cell density, glucose concentration, serum availability, and matrix stiffness are critical environmental determinants of VM formation.

Endometrial cancer incidence and mortality are rising globally, disproportionately affecting health systems facing diagnostic, therapeutic, and survivorship constraints. Rapid innovations-including the International Federation of Gynecology and Obstetrics (FIGO) 2023 staging, molecular classification, sentinel lymph node (SLN) mapping, evolving adjuvant strategies, immunotherapy, and digital tools-risk exacerbating inequities if implementation mismatches system readiness. This narrative review synthesizes key trials, international guidelines, and high-impact implementation studies published between 2010 and September 2025. We summarize contemporary evidence across staging, molecular pathology, imaging, surgery, radiotherapy, systemic therapy, survivorship, equity, and artificial intelligence (AI), translating this into a pragmatic, resource-stratified framework. A previously published principal-component-based structural-readiness clustering model encompassing 68 countries is applied-but not re-derived-to illustrate how health-system capacity shapes access to diagnostics, treatment, and innovation. Persistent gaps include limited availability of universal mismatch repair (MMR) and p53 immunohistochemistry, variable adoption of standardized SLN mapping, uneven radiotherapy access, restricted use of immunotherapy for mismatch-repair deficient (dMMR)/microsatellite instability high (MSI-H) tumors, and fragmented survivorship care. A minimum-core-optimal implementation ladder is proposed to guide diagnostic, surgical, radiotherapeutic, systemic-therapy, and survivorship priorities across varying resource levels. AI-supported quality assurance is discussed alongside essential requirements of local validation, bias mitigation, and robust governance. Rather than generating new empirical data, this review employs a cluster-informed, equity-oriented lens, applying previously validated system-level typologies to contextualize implementation gaps and support context-sensitive guideline adaptation.

Cancer vasculogenic mimicry (VM) is the formation of vasculature structures in the absence of endothelial cells. We previously established an in vitro model that facilitates the formation of a lumen-containing and fluid-conducting tubular structures after 4 days of cancer cell growth on Matrigel. Herein, we mechanistically characterize this model in breast and ovarian cancer cell lines demonstrating distinct phases of VM formation and the dependence of specific extracellular matrix proteins. We report that VM occurs in four distinct stages. Firstly, alignment, migration then clustering delineate the area of the future tubular structure. Secondly, contraction of aligned structures followed by loss of attachment of some cells and cellular blebbing. Thirdly, a phase of mass proliferation followed by the raising of specific areas of the cancer cell mass above the Matrigel (bridge). Finally, the formation of a cell monolayer closes the tubular structure, forms a glycoprotein-rich luminal lining, then elevates the structure. Only later stages of VM require AKT and FAK signaling, as confirmed by chemical inhibition and phosphorylation analysis. We demonstrate that the lining of the tubular lumen is rich in laminin. Furthermore, the presence of Laminin 111 (but not collagen I) is sufficient in the extracellular matrix (Matrigel) for VM to occur and we confirm that integrin β1, but not integrin β3, is required and this protein changes location during the formation process. RNASeq analysis suggests that VM formation principally occurs through post-transcriptional regulation. As VM is associated with poor patient survival VM, an understanding of the mechanism of VM may bring to light novel biomarkers and anticancer targets.

Abstract Introduction: Vasculogenic mimicry (VM) is a clinical phenomenon by which cancer cells can form vessel-like structures in an endothelial-free (CD31-) fashion. VM presence in tumors correlates to poor patient prognosis. In our laboratory we have established an in vitro model where cancer cells from either cell lines or primary culture form lumen-lined and fluid-conducting tubular structures when grown on laminin-rich Matrigel over a four-day period. Given the duration of formation and the complexity of these structures, we hypothesize that VM in vitro is a multistep process, where each stage requires spatio-temporal organization of adhesive proteins, stemness and EMT (suggesting the need for epithelial to mesenchymal transition) signaling. Methods: Using our in vitro models, we analyzed by siRNA, immunostaining and live cell imaging with Airyscan the distinct phases and the corresponding spatio-temporal organization of selected proteins. Results: We show that VM in vitro has three distinct phases that are characterized by (1) alignment and migration, (2) contraction, proliferation and bridge formation, and (3) tubular structure closure and lumen formation. These steps require spatio-temporal distribution of ZEB1 and E-cadherin (suggesting gain and loss of epithelial to mesenchymal transition), the presence of Integrin β1 and laminin 111, and the distinct localization of Laminin and CD44. Conclusion: A better characterization of VM may lead to the identification of a clinically useful marker to predict poor patient prognosis and shed light on a druggable pathway to treat this subgroup of aggressive cancer. Citation Format: Gareth I. Owen, Nicolle Santander, Gabriel Mingo, Pamela Gonzalez, Valentina George, Nicole Babbitt, Alejandra Espinioza, Isidora Vega, Cristobal Canales, Carolina Ibañez, Roger Gejman, Juan Carlos Roa, Francisco Nualart, Andrea Ravasio, Cristina Bertocchi. Vasculogenic mimicry: A three-step progress to form lumen-containing and fluid-conducting tubular structures in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5401.

Introducción: El leiomiosarcoma uterino es una causa poco común de sangrado uterino anormal (SUA) que debe sospecharse en la etapa de transición menopáusica. Inusualmente, se diagnostica de manera incidental en piezas de miomectomía/ histerectomía, hecho que angustia a la paciente y ensombrece el pronóstico. El mejor pronóstico involucra la eliminación quirúrgica completa del tumor confinado al útero. Caso clínico: Presentamos una recurrencia tardía de leiomiosarcoma originado desde un leiomioma donde el diagnóstico diferencial fue difícil desde un comienzo. La extirpación completa del tumor requirió de resección ureteral parcial (compromiso inadvertido preoperatoriamente) y reimplante en vejiga psoica. Conclusión: No todo SUA por tumor de músculo liso se origina en leiomioma. La incorporación y el análisis complementario (mediante renderización y reconstrucción 3D) de tomografía computarizada (TC), resonancia magnética o TC combinada con tomografía por emisión de positrones pueden ayudar a identificar entidades menos comunes, a la planificación preoperatoria y a anticipar el manejo de complicaciones potenciales. La caracterización patológica de las distintas formas de tumores originados en el músculo liso demanda de patólogos especialistas y de la incorporación del estudio molecular a la patología clásica, a fin tipificar de manera más precisa la entidad y de identificar nuevas alternativas terapéuticas, más allá de la cirugía.

El tumor de los cordones sexuales con estructuras túbulo anulares (TCSTA) es un tumor ovárico extremadamente infrecuente representando el 1%-2% de los tumores de los cordones sexuales. Cuando existe asociación con síndrome de Peutz-Jeghers (SPJ) el tumor generalmente tiene un comportamiento benigno, no así en la ausencia de esta asociación. Se presenta el caso de una paciente de 18 años con sus características clínicas e histopatológicas.

Los tumores cerebrales se caracterizan por su gran morbilidad y mortalidad. La gran mayoría corresponde a tumores secundarios (metástasis). Dentro de los tumores primarios del sistema nervioso central, los gliomas corresponden al 30% de éstos. En EEUU, entre el 2007-2011, se estima una incidencia aproximada de 21,4 casos por 100.000 habitantes. Los recientes avances en la comprensión molecular de la biología de estos tumores han permitido mejorar sustancialmente su clasificación, posibilitando realizar un mejor correlato con los desenlaces clínicos y el pronóstico. En esta línea, hoy en día es posible estratificar a los pacientes por riesgo y entregar tratamientos capaces de prolongar la sobrevida global entre 5-7 años, para los gliomas grado II y III. El presente consenso, elaborado por un panel multidisciplinario de expertos de diversas sociedades científicas chilenas y, por tanto, de todas las especialidades involucradas en el manejo médico-quirúrgico de las personas portadoras de gliomas cerebrales. A la luz de este nuevo conocimiento desarrollado al alero de la oncología molecular, esta propuesta ofrece un insumo de utilidad clínica real, que, articulado a una revisión actualizada en relación con el tratamiento y seguimiento de estos pacientes, permite entender la relevancia de estos biomarcadores en el manejo de precisión de la enfermedad. Cabe señalar que, este manuscrito emerge de la misma fuerza de trabajo, que elaboró el Protocolo Clínico de Gliomas del Adulto 2019, publicado por el Ministerio de Salud, y que ha diferencia de esta, que ofrece los detalles clínicos-operativos, como flujogramas y dosis, nuestra revisión intenta relevar los avances imagenológicos y moleculares y como estos impactan en el manejo actual de la enfermedad.

Neutral lipid storage disease with myopathy is an ultra-rare, inherited autosomal recessive neuromuscular metabolic disorder caused by pathogenic variants in PNPLA2. It typically presents in adults as a progressive myopathy and is associated with myocardiopathy, hepatic involvement, and high creatine kinase levels. Only three children and adolescents with neutral lipid storage disease with myopathy have been reported. We report a female infant with congenital hypotonia born to consanguineous parents, whose mother presented with polyhydramnios during pregnancy. She demonstrated delayed acquisition of motor milestones, hepatomegaly, and elevated creatine kinase levels. Homozygous pathogenic variants in PNPLA2 were identified. Lipid accumulation was observed within the muscle fibers and Jordans' anomaly was observed in a blood smear. This is the first report to describe an infant with mildly symptomatic neutral lipid storage disease with myopathy and demonstrate hepatic involvement in a pediatric patient. Despite her mild symptoms, her ancillary test results were markedly abnormal.

Ectopic thyrotropin-secreting pituitary adenomas are rare, with only 10 published cases. We report the case of a 52-year-old woman who was referred for primary hypothyroidism, who showed clinical signs of hyperthyroidism and had been under treatment with levothyroxine. Her exams revealed high levels of thyroid stimulating hormone (TSH), at odds with free thyroxin (FT4) and raised triiodothyronine (T3), which remained elevated after medication suspension, suggesting possible central hyperthyroidism. Sellar MRI showed normal pituitary gland, with a mass in the sphenoid sinus of 24 mm. A possible ectopic TSH secreting pituitary tumor of sphenoid sinus was hypothesized. After a intramuscularly (IM) single dose of a sustained-relase of a somatostatin analog (octreotide) 20 mg, plasma levels of thyroid hormones were normalized and a significant tumor reduction was demonstrated in MRI control at 7-weeks' follow-up. The tumor was removed by transsphenoidal endoscopy, and the biopsy confirmed an adenoma with positive immunostaining for TSH and GH. Hyperthyroidism recurrence was observed in hormonal controls 4 weeks after surgery. Treatment with sustained-release octreotide was reinitiated, every 60-days for two years, with normalization of the thyroid hormone profile, but with a residual lesion with the appearance of a tumor in the MRI. A second tumor resection was performed, achieving sustained hormonal cure and no residual tumor lesion at 2-years' follow-up. To our knowledge, this is the first report of an ectopic thyrotropin-secreting pituitary adenoma of the sphenoid sinus. Clinical and laboratory aspects relevant to this entity are reviewed, emphasizing the usefulness of octreotide in the management of the reported case.

La neuropatía ciática es una entidad infrecuente y de difícil diagnóstico en Pediatría. Su evolución a largo plazo no ha sido claramente definida.Objetivo: Analizar la presentación clínica y evolución de un grupo de niños con neuropatía ciática.Pacientes y Método: Análisis retrospectivo de las características clínicas de pacientes pediátricos con neuropatía ciática atendidos en 2 hospitales de Santiago, entre 2014-2018. Se evaluó examen motor, trofismo muscular, reflejos osteotendíneos, marcha, sensibilidad y dolor. Se estudió neuroconducción de nervio ciático, electromiografía (EMG) y en 3 pacientes, Resonancia Magnética (RM).Resultados: Se incluyeron 6 pacientes, edad promedio 11,8 años. Hubo 2 causas traumáticas, 2 compresivas, 1 vascular y 1 tumoral. Los 6 pacientes debutaron con pie caído e hiporreflexia/arreflexia aquiliana; 5 pacientes presentaron dolor neuropático severo. La EMG mostró en todos los casos compromiso en nervios y musculatura dependientes del nervio ciático. En 2 casos se realizó RM de cintura pélvica y extremidades inferiores, mostrando compromiso muscular selectivo en pierna en territorio ciático. En 1 caso, se realizó RM de plexo lumbosacro, y luego estudio histológico, que concluyeron un tumor neural benigno. En los 3 pacientes que tuvieron seguimiento mayor a un año, se observaron secuelas motoras, con marcha alterada.Conclusión: La neuropatía ciática en este grupo fue secundaria a diversas etiologías, predominando las traumático-compresivas. En los 3 casos que tuvieron seguimiento a largo plazo se observaron secuelas motoras significativas. En la mayoría la lesión se asoció a causas prevenibles como accidentes y posicionamiento en niños con compromiso de conciencia, lo que resulta fundamental en la prevención de una patología con alto grado de secuelas.

Tyrosine kinase inhibitors are the standard of care for epidermal growth factor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients. Studies suggest no significant benefit of immune checkpoint inhibitors (CPI) for these patients. We report an unusual clinical response to afatinib in a patient with advanced EGFR-mutant NSCLC, including rapid disease progression. Subsequent treatment with pembrolizumab (CPI) plus chemotherapy (pemetrexed and carboplatin) and concomitant stereotactic body radiotherapy triggered a complete and durable response. The combination of CPI plus stereotactic body radiotherapy, or CPI plus chemotherapy, could be an option for tyrosine kinase inhibitor-refractory EGFR-mutant NSCLC patients, or as a second-line treatment. (C) 2020 Elsevier Inc. All rights reserved.

INTRODUCTION:Sciatic neuropathy is rare and difficult to diagnose in pediatrics, and its long-term course has not been completely understood.OBJECTIVE:To analyze the clinical presentation and evolution of a group of pediatric patients with sciatic neuropathy.PATIENTS AND METHOD:Retrospective anal ysis of the clinical characteristics of pediatric patients with sciatic neuropathy treated in two hospitals of Santiago between 2014 and 2018. Locomotor examination, muscle trophism, deep tendon reflexes, gait, sensation, and pain were assessed. Sciatic nerve conduction study and electromyography (EMG) were performed, and magnetic resonance imaging (MRI) in three patients.RESULTS:Six patients were included with an average age of 11.8 years. The etiologies were traumatic (N = 2), by compression (N = 2), vascular (N = 1), and tumor (N = 1). All of the 6 patients presented foot drop and Achilles tendon hyporeflexia/areflexia, and 5 patients presented severe neuropathic pain. The EMG showed involvement of the sciatic nerve rami and dependent muscles. In two patients, a pelvic girdle and lower limbs MRI was performed, showing selective muscle involvement in sciatic territory. One patient underwent a lumbosacral plexus MRI, and subsequently histological study showing a benign neural tumor. Out of the three patients who were followed-up longer than one year presented motor sequelae and gait disorder.CONCLUSION:Sciatic neuropathy in the study group was secondary to different causes, predominantly traumatic and compressive etiologies. The three patients that were ina long-term follow-up presented significant motor sequelae. In most of the cases, neural injury wasassoci- ated with preventable causes, such as accidents and positioning in unconscious children, which is crucial in the prevention of a pathology with a high sequelae degree.

Introduction Lymphadenectomy is a common procedure in gynecologic oncology. Nonetheless, it is associated to important number of side effects. During the last decade there have been enormous efforts to develop different SLN techniques to reduce complications without affecting survival. Objective Evaluate the experience of SLN technique in a university setting. Methods Retrospective review of 58 cervical and endometrial cancers evaluated with SLN. Results Forty-one of the patients presented with uterine cervical cancer and 17 endometrial cancer. The method used for detection of the SLN was patent blue dye only in 42 patients (72%), technetium 99 in 2 (3.5%), both techniques was used in 10 (17%) and ICG in 4 (%) cases. 40 (69%) patients had laparoscopy. At least one pelvic SLN was detected in 53 (91.4%) 7 patients. Bilateral detection was achieved in 39 (67.2%). Most of the SLN were identified next to external iliac vessels and the obturator fossa. In 97% of the 92 samples identified as SLN had at least one lymph node detected. The mean of lymph-node count was 1.8 (1–7). Patients with uterine cervical cancer had neither SLN nor non-SLN positive. Four patients with endometrial cancer (23.52%) had metastasis on SLN. There were no false negative SLN on those patients who underwent lymphadenectomy. There were no surgical complications derived from de SLN technique. Conclusion SLN technique in cervical and endometrial cancer is technically feasible. Our results show that a good detection rate can be achieved for a proper diagnostic of lymph node status.

Background: Classification of growth hormone (GH) - secreting tumors by the granular pattern might predict their clinical behavior in acromegalic patients. There are several other prognostic factors. Aim: To compare the features at presentation and cure rates of patients with GH secreting tumors according to the granular pattern, and to define independent prognostic factors for surgical treatment in these patients. Material and Methods: A retrospective, observational study of 85 active acromegalic patients surgically treated in two medical centers. Results: Seventy-four patients (87%) were classified as having densely granulated (DG) and 11 (13%) as sparsely granulated (SG) tumors. The latter were less active biochemically, had a higher rate of macroadenoma and cavernous sinus invasion and had a lower rate of biochemical cure than the DG group. Several characteristics were associated with disease persistence but only age (Odds ratio (OR) = 0.93) and cavernous sinus invasion (OR = 21.7) were independently associated in the logistic regression model. Conclusions: The sparsely granulated pattern is associated with a more aggressive behavior, but the main determinants of prognosis are age and cavernous sinus invasion.

Postmenopausal hyperandrogenism constitutes a very rare condition of tumoral or non-tumoral origin primarily residing either in the ovary or in the adrenal glands. We present herein two cases with this condition; one with abnormal postmenopausal genital bleeding and mild increase in facial hair, and the second with slow-developing hirsutism and virilization. Both cases shared a notorious increase in libido.The laboratory tests showed high levels of testosterone (>100ng/ml). A normal value of dehydroepiandrosterone sulfateand a normal cortisol level at 9 am after 1mg of dexamethasone administered at midnight (Nugent test) made an adrenal etiology very unlikely. On the other hand, a high level of inhibine B oriented to an ovarian source. Transvaginal sonography failed to demonstrate an ovarian tumor, but an abdominal and pelvic computed tomography scan or magnetic resonance imaging detected an ovarian tumor and normal adrenal glands.A laparoscopic oophorectomy was performed, and the histological study demonstrated a steroidal cell tumor in the first case and a Leydig cell tumor in the second.

Background: Lung cancer (LC) is the second leading cause of cancer death in Chile, causing >3,000 deaths everyyear. Epidemiological LC data in Chile is scarce and scattered. Here, we aimed to quantify the prevalence of EpidermalGrowth Factor Receptor (EGFR) gene mutations in a Chilean cancer center. These data may identify individuals thatcould benefit from targeted therapies such as Tyrosine Kinase Inhibitors (TKIs). Methods: A total of 1,405 Biopsiesfrom 1,381 LC patients were retrospectively analyzed retrieving clinical data from EGFR mutants including age,gender, histological type, smoking habits and type of EGFR mutation. We also analyzed overall survival (OS) rates.Results: From all patients 21.7% had clinically relevant EGFR mutations, and a median age at diagnosis of 65 years.Most were female (64%), classified as adenocarcinomas (94.5%), and non-smokers/light smokers (93.1%). The mostprevalent mutation was exon-19 deletions (50.6%) followed by Leucine-to Arginine 858; OS was 15 months. Clinicalfollow-up information was available for 83 patients. The use of TKIs in these patients significantly improved OS.Conclusion: The prevalence of EGFR mutations in the studied population was 21.7%, comparable to other countriesin Latin America. The most frequent EGFR mutation was exon-19 deletion, OS in this group was 15 months, and TKIssignificantly improved OS.

Classification of growth hormone (GH) - secreting tumors by the granular pattern might predict their clinical behavior in acromegalic patients. There are several other prognostic factors.To compare the features at presentation and cure rates of patients with GH secreting tumors according to the granular pattern, and to define independent prognostic factors for surgical treatment in these patients.A retrospective, observational study of 85 active acromegalic patients surgically treated in two medical centers.Seventy-four patients (87%) were classified as having densely granulated (DG) and 11 (13%) as sparsely granulated (SG) tumors. The latter were less active biochemically, had a higher rate of macroadenoma and cavernous sinus invasion and had a lower rate of biochemical cure than the DG group. Several characteristics were associated with disease persistence but only age (Odds ratio (OR) = 0.93) and cavernous sinus invasion (OR = 21.7) were independently associated in the logistic regression model.The sparsely granulated pattern is associated with a more aggressive behavior, but the main determinants of prognosis are age and cavernous sinus invasion.

We report a 23 year old woman presenting with a nephrotic syndrome due to minimal change disease, central diabetes insipidus, primary hypothyroidism, vitiligo and universal alopecia. Eleven years later, she presented secondary amenorrhea due to hypogonadotropic hypogonadism, with mild hyperprolactinemia and central adrenal insufficiency. A magnetic resonance imaging of the sella turcica showed a pituitary mass with suprasellar extension that was resected using a transsphenoidal approach. Pathology confirmed the presence of a lymphoplasmacytic hypophysitis. She needed a second surgical resection due to mass growth and neuro-ophthalmologic impairment. One year later, systemic lupus erythematosus, arterial hypertension and type 2 diabetes mellitus were diagnosed. Two years later, due to back pain, constipation and renal failure, retroperitoneal fibrosis was found, satisfactorily treated with glucocorticoids and colchicine. Hence, this clinical vignette shows the coexistence of autoimmune polyglandular syndrome with retroperitoneal fibrosis and lymphoplasmacytic hypophysitis. Tissue analysis showed the presence of IgG4 producing plasma cells in the pituitary and retroperitoneum, which constitute a basis for the diagnosis of IgG4 related disease.