Saccular intracranial neonatal aneurysm.

INTRODUCTION: Neonatal cerebral aneurysms are very rare condition and distinct from those of the adults. CASE REPORT: We reported a 14-day-old male neonate who presented subarachnoid hemorrhage due to a ruptured anterior cerebral artery saccular aneurysm. In addition, we present a review of the relevant literature. CONCLUSION: Intracranial hemorrhage due to cerebral aneurysm rupture in a newborn is an uncommon diagnosis, but it must be unequivocally excluded.

Surgical Management of a Superior Orbital Fissure Cavernous Hemangioma.

Background: Cavernous sinus hemangiomas (CSHs) are intracranial extradural benign, well-demarcated neoplasms arising within dural sinuses. The orbital apex and superior orbital fissure (SOF) are common locations for these lesions. Because of the complex anatomy of this area and potential morbidity, SOF CSH surgical management is challenging. Objective: Describe a case of a SOF CSH and review of literature. Material and Methods: We present the case of a 44-year-old female with a 2-month history of right eye visual disturbances. A contrast-enhanced magnetic resonance imaging showed a right orbital apex nodular formation. A pterional craniotomy with a middle fossa mini peeling was performed. Results: Gross total resection was accomplished. No recurrences were observed 2 years after surgery. Conclusion: SOF CSH should be included in a differential diagnosis in cases of space-occupying orbital apex lesions with atypical features. Surgery is the gold standard treatment. Radiosurgery is a valid option for tumor remnants.

Terminal myelocystocele: Surgical management.

Background: The authors describe clinical and imaging findings, surgical technique, and outcomes in myelocystocele. Methods: We describe a surgical procedure performed in six patients, four males and two females, with myelocystocele treated at our hospital. We review the images obtained at the time of diagnosis and after surgery. The patients' age range was 12-56 months and had undergone surgery for terminal myelocystocele between 2015 and 2020. All patients had a large lumbar mass covered with healthy skin and presented spontaneous movements at birth. Two patients presented VACTERL syndrome. Results: A watertight closure of the soft tissues was performed in all cases. None of the patients presented postsurgical complications, such as cerebrospinal fluid leak or infection. All the patients had undergone excision of the meningocele sacs, the tethering bands were lysed, and the filum was detethered. The mean follow-up period was 34 (12-56) months. A motor deficit was seen in 2 patients (33.3%). Conclusion: Prenatal diagnosis and early corrective surgical intervention are recommended to prevent deterioration in neurological function. VACTERL association is a common condition and should be investigated.

Real Life Clinical Management and Survival in Advanced Cutaneous Melanoma: The Italian Clinical National Melanoma Registry Experience.

BACKGROUND: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR). METHODS: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. RESULTS: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62). CONCLUSIONS: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

Cavernoma Paraventricular / Paraventricular Cavernoma

Introducción: Los cavernomas representan el 5 al 13% de las malformaciones cerebrales y suelen tener una localización supratentorial. Clínicamente pueden permanecer asintomáticos o presentar síntomas neurológicos progresivos. Para estos últimos, así como los que presentan hemorragia recurrente, la resección quirúrgica es el tratamiento de elección. Sin embargo, para aquellos que presentan una localización profunda es menester estudiar la relación que existe entre la lesión y las estructuras cerebrales adyacentes. La tractografía (DTI) y las técnicas de navegación intraoperatoria son herramientas fundamentales para planificar y guiar el abordaje a la lesión y realizar un mapeo de las vías de proyección, asociación y comisurales, permitiendo un acceso seguro mediante corticotomías pequeñas y mínima retracción del parénquima cerebral. Objetivo: Describir la técnica quirúrgica guiada por neuronavegación para la resección de un cavernoma frontal derecho profundo yuxtaventricular a través de una pequeña corticotomía. Caso: Paciente de sexo masculino de 20 años de edad, deportista profesional, con parestesias miembro superior izquierdo y cefalea severa. Resonancia magnética evidencia lesión heterogénea en T1 y T2 y presencia de un halo de hemosiderina, compatible con cavernoma a nivel del techo del cuerpo en el ventrículo lateral derecho. Mide 28 mm x 31 mm x 28 mm en sus diámetros transversal, dorso-ventral y rostro-caudal. Tractografía evidencia lesión en íntima relación con el tracto corticoespinal en su recorrido por la corona radiada. Resultados: Exéresis completa de la lesión. El paciente evolucionó sin déficit neurológico y fue dado de alta a las 72 horas del postoperatorio. Conclusión: El uso de la tractografía y de la navegación intraoperatorio, permite abordar lesiones profundas, en contacto con áreas elocuentes, mediante corticotomías pequeñas con mínima retracción cerebral

Introduction: Cavernous malformation represents among 5 to 13% of brain vascular malformations, most of them have a supratentorial location. Clinically they can remain asymptomatic or present with neurological symptoms. In cavernomas with recurrent hemorrhage, located in safe areas, surgical resection is the treatment of choice. However, for those which have a deep yuxta-ventricular localization it is necessary to know the relationship between the lesion and eloquent cerebral structures. Fiber tractography and intraoperative navigation systems are essentials tools to plan and guide the surgical approach and make a mapping of the projection, association and commissural fibers in order to have a safe access to the lesion. Objective: To describe the surgical technique using neuronavigation for the resection of a right frontal yuxta-ventricular cavernous malformation through a minimal approach. Case: A 20-year-old man, professional athlete with left arm paresthesia and severe headache. Magnetic resonance shows a heterogeneous lesion in T1 and T2 with a hemosiderin in the roof of the right lateral ventricle, compatible with a cavernous malformation. Its size was 28 mm x 31mm x 28 mm in the transversal, dorsoventral and rostrocaudal diameter. The fiber tractography shows an intimate relationship with the corticospinal tract on its path through the corona radiata. Results: Complete resection of the lesion. The patient evolved without a neurological deficit and was discharged 72 hours later. Conclusion: The fiber tractography and the intraoperative navigation system allow the deep lesions approach, especially for those who have an intimal relationship with eloquent ́s areas, using minimally corticotomy with less parenchymal retraction.

Relationship between the posterior septal artery and the upper edge of the choana.

BACKGROUND: The pedicled nasoseptal flap has been a key element in advancing the endoscopic transnasal approach (ETA) for the treatment of skull base lesions from the anterior cranial fossa to the occipitocervical junction. To preserve vascular supply, an anatomical knowledge of the location of the posterior septal artery (PSA) is essential. The objective of this work is to establish the relationship between PSA and the superior edge of the choana to define a safety margin during the opening of the sphenoidal rostrum preserving PSA. METHODS: One hundred and eighty angiotomographies of the brain were assessed. The sphenopalatine artery (SPA) was evaluated in the pterygopalatine fossa and PSA at its entrance into the nasal cavity and on the sphenoidal rostrum. RESULTS: PSA was found in all 3 tomographic planes (axial, coronal and sagittal) in 100 patients (200 PSAs). Thirty-five were male and 65 were females. Average age was 62 years with a range of 19-90 years. Total average distance between PSA and the superior edge of the choana was 8.5 mm with a range of 2.5-18 (12.45 90th percentile). CONCLUSION: Although the distance between the choanal edge and PSA is 8.5 mm on average, due to its variability, a distance of at least 12.45 mm for the opening of the sphenoidal sinus in the ETA approach should be considered as a safety margin.

Surgical Indication Optimization of Brain Metastases Based on the Evolutionary Analysis of Karnofsky Performance Status.

BACKGROUND AND OBJECTIVE: Surgical resection of brain metastases (BM) offers the highest rates of local control and survival; however, it is reserved for patients with good functional status. In particular, the presence of BM tends to oversize the detriment of the overall functional status, causing neurologic deterioration, potentially reversible following symptomatic pharmacological treatment. Thus, a timely indication of surgical resection may be dismissed. We propose to identify and quantify these variations in the functional status of patients with symptomatic BM to optimize the indication of surgical resection. PATIENTS AND METHODS: Historic, retrospective cohort analysis of adult patients undergoing BM microsurgical resection, consecutively from January 2012 to May 2016, was conducted. The Karnofsky performance status (KPS) variation was recorded according to the symptomatic evolution of each patient at specific moments of the diagnostic-therapeutic algorithm. Finally, survival curves were delineated for the main identified factors. RESULTS: One hundred and nineteen resection surgeries were performed. The median overall survival was 243 days, while on average it was 305.7 (95% confidence interval [CI]: 250.6-360.9) days. The indication of surgical resection of 10% of the symptomatic patients in our series (7.5% of overall) could have been initially rejected due to pharmacologically reversible neurologic impairment. Survival curves showed statistically significant differences when KPS was stratified following pharmacological symptomatic treatment (p < 0.0001), unlike when they were estimated at the time of BM diagnosis (p = 0.1128). CONCLUSION: The preoperative determination of the functional status by KPS as an evolutive parameter after the nononcologic symptomatic pharmacological treatment allowed us to optimize the surgical indication of patients with symptomatic BM.

Neurocirugía en época de COVID-19. Protocolo de actuación / Neurosurgery in the time of COVID-19. Action protocol

El manejo de pacientes debido a la aparición del nuevo coronavirus 2019 (COVID-19) representa un desafío para los equipos médicos y quirúrgicos, ya que modificó el funcionamiento de los sistemas de salud en casi todo el mundo. Para contribuir a la re organización del sistema de salud, el Servicio de Neurocirugía del Hospital Italiano de Buenos Aires trabajó en adoptar distintas medidas en concordancia con las tomadas a nivel institucional y nacional; por lo que se analizó la bibliografia publicada, asi como las normas dictadas por el comité de crisis de nuestra institucion. A su vez realizamos una breve encuesta dirigida a neurocirujanos de america latina para conocer como se manejaban actualmente en relación a niveles de protección y realización de cirugias. La actual pandemia de COVID-19 es el mayor desafío que enfrentan los sistemas nacionales de salud en los últimos tiempos. Los neurocirujanos podemos contribuir a la reducción del riesgo de infección nosocomial de los trabajadores de la salud al adaptar distintos protocolos en pacientes con COVID-19.

Patient's management due to the appearance of new coronavirus 2019 (COVID-19) represents a challenge for medical and surgical departments, since it modified the running of health systems in almost all the world. In order to help in this new situation, the Neurosurgical Department of our institution has adopted different measures in accordance with those taken at institutional and national level. In order to do this, we made a literature review and we added to this, the norms dictated by the crisis committee of our hospital. We also carried out a brief survey among neurosurgeons from Latin America to find out how they managed protection levels in relation to surgery. COVID-19 pandemic is certainly one of the greatest challenge national health systems face in a century. Adapting different protocols in neurosurgical patients with COVID-19 can contribute in reducing the risk of nosocomial infection of health workers.

Craneofaringiomas: cirugía transnasal via endoscópica / Craniopharyngiomas: endoscopic transnasal surgery

Introducción: Debido a su ubicación anatómica, los craneofaringiomas son tumores complejos en su tratamiento. Una resección completa tiene riesgos elevados de morbimortalidad y si se opta por una resección parcial la tasa de recurrencia es alta. Según su extensión supraselar y su relación con el tallo hipofisario, pueden dividirse en preinfundibulares, transinfundibulares y retroinfundibulares. Objetivo: El objetivo de este video es describir la técnica vía endoscópica para la resección de un craneofaringioma preinfundibular. Materiales y Métodos: Se seleccionó un caso de un paciente con un craneofaringioma preinfundibular operado en el Servicio de Neurocirugía del Hospital Italiano de Buenos Aires, por vía endoscópica transnasal. Resultados: Se realizó una exéresis completa de la masa tumoral, sin evidenciar complicaciones tales como, diabetes insípida o fistula de líquido cefalorraquídeo y con recuperación completa del déficit campimétrico. Conclusión: El tratamiento quirúrgico de los craneofaringiomas requiere un conocimiento detallado de la anatomía de base de cráneo así como de las diferentes técnicas quirurgicas. El uso de la endoscopia ha permitido un mejor acceso a éste tipo de lesiones, disminuyendo las comorbilidades en el paciente y la estadía hospitalaria. Un resultado quirúrgico satisfactorio se obtiene con la resección completa y la menor morbilidad posible para el paciente

Introduction: Due to its anatomical location, craniopharyngiomas are difficult tumors to treat. Complete resection has high morbidity and mortality and if a partial resection is chosen, the recurrence is common. According to their suprasellar extension and its relationship with stalk, it can be classified into: preinfundibular, transinfundibular and retroinfundibular. Objetive: The aim of this video is to describe the surgical technique we use for preinfundibular craniopharyngioma. Methods: We review a preinfundibular craniopharyngioma operated on the Neurosurgery Department of the Hospital Italiano de Buenos Aires, through a transnasal endoscopic approach. Results: Total removal was achived, no acute complications were found such as diabetes insipidus or cerebrospinal fluid leak and improved their visual field. Conclusion: Craniopharyngioma surgery requires detailed knowledge of skull base anatomy and approaches. The use of endoscopy has allowed better access to this type of lesions, reducing comorbidities and patient hospital stay. Complete resection with low morbidity are the treatment of this tumors

Programa de Simulación Neuroquirúrgica / Neurosurgical Simulation Program

Objetivo: Describir un programa de entrenamiento básico para implementar en la residencia de Neurocirugía con una metodología estructurada, diferentes niveles de complejidad y elementos de fácil adquisición. Introducción: La simulación se define como el uso de modelos para imitar experiencias de la vida real. Debido a la complejidad del aprendizaje en Neurocirugía, el programa de la Residencia debería incluir entrenamiento básico mediante simulación que permita al residente entrenarse en habilidades básicas fuera del quirófano, o bien, desarrollar y complejizar las ya aprendidas. Materiales y Métodos: Se realizó un programa de entrenamiento básico a desarrollar en el Centro de Simulación Quirúrgica del Hospital italiano, dividido en tres niveles de complejidad quirúrgica. Se idearon distintos ejercicios con materiales accesibles, de bajo costo y replicables. El programa se diseñó para ser llevarse a cabo con una frecuencia de una vez por semana durante cinco horas. Discusión: Los modelos propuestos presentan fácil acceso y alta disponibilidad; y permitieron el desarrollo de habilidades microquirúrgicas desde etapas muy tempranas de la residencia, abarcando la utilización del instrumental microquirúrgico y la magnificación microscópica, y simulando distintas técnicas quirúrgicas en materiales biológicos y sintéticos realistas; enmarcado por un programa basado en objetivos sin límites de repeticiones. La evaluación con un neurocirujano Senior permitió brindar un espacio relajado de enseñanza y debate, sin ser influenciado por las presiones propias de la cirugía. El aprendizaje de técnicas quirúrgicas se basa en la repetición de maniobras específicas, por lo que el desarrollo de habilidades quirúrgicas en ámbitos académicos no asistenciales es fundamental en cualquier aprendizaje quirúrgico. Conclusión: La simulación en el entrenamiento neuroquirúrgico sigue siendo un campo de estudio que requiere mayor investigación y validación en su implementación. En nuestra experiencia resulta una herramienta sumamente favorable para su posterior aplicación en procedimientos quirúrgicos reales, que podría mejorar y homogeneizar la enseñanza en programas de formación quirúrgica

Objective: To describe a basic training program to implement at neurosurgery residency with a structured methodology, different complexity levels, and easily acquired elements. Introduction: Simulation is defined as use of models to imitate real life experiences. Due to complexity of neurosurgery learning, residency program should include simulation training that allows the resident learning basic skills outside the operating room and develop practices learned. Materials and methods: A training program was developed at Centro de Simulación Quirúrgica del Hospital Italiano, divided into three surgical complexity levels. Different exercises were designed with accessible, low cost and replicable materials. This program is carried out with a frequency of once a week, five hours each. Discussion: The proposed models have easy acquisition and high availability, allowing the development of microsurgical skills since early stages in residency, including the use of microsurgical instruments and microscopic magnification, surgical techniques in realistic biological and synthetic materials, based on a program with objectives without repetition limits. The evaluation with a senior neurosurgeon allowed providing a relaxed teaching space, without pressures of surgery. Learning of surgical techniques is based on repetition, so the development of surgical skills in non-assistance academic fields is fundamental in any surgical learning. Conclusion: Simulation in neurosurgical training remains a field that requires further investigation and validation in its implementation. In our experience, it is an extremely favorable tool because its subsequent application in real life procedures, which could improve and standardize surgical programs teaching

Relación entre la arteria septal posterior y el borde superior de la coana / Relationship between the posterior septal artery and the superior border of the choana

Introducción: El colgajo pediculado nasoseptal (CPNS) ha sido un elemento fundamental en el avance del abordaje transnasal endoscópico (TNE) para tratar lesiones de la base de cráneo desde la fosa anterior hasta el clivus y la unión occipitocervical. El CPNS provee un tejido viable, vascularizado, extenso y versátil el cual es capaz de adherirse al hueso y sellar el defecto dural disminuyendo así el riesgo de fístula de líquido cefalorraquídeo (LCR) en el postoperatorio, del más del 20% a menos del 5%. Tanto para el CPNS primario como para colgajo de rescate es necesario preservar el pedículo vascular por lo que es fundamental el conocimiento anatómico de la localización de la arteria septal posterior y sus ramas, así como los reparos anatómicos para reconocerla en el intraoperatorio. Objetivo: Establecer la relación entre la arteria septal posterior (ASP) y el borde superior de la coana para definir un margen de seguridad durante la apertura del rostro esfenoidal preservando la ASP y sus ramas. Material y métodos: Estudio observacional, descriptivo, retrospectivo de corte transversal. Angiotomografía cerebral (ATC) con contraste endovenoso realizadas en pacientes mayores a 18 años de ambos sexos para el estudio de lesiones vasculares intracraneales. Las ATC fueron realizadas en un tomógrafo Aquilion ONE 320 (Toshiba, Japan). Para la visualización y medición de las imágenes se utilizó el software Alma Workstation V4.2.0.2 (Alma IT Systems). Se documentaron las variaciones anatómicas y se realizaron mediciones entre el borde superior de la coana y la arteria septal posterior en ambas fosas nasales (Fig 2 a y b). Resultados: De los 98 pacientes estudiados, 32 eran varones y 66 mujeres. La edad media fue de 62,6 con un rango de 19 a 90 años (Tabla 1). Se realizaron mediciones en ambos lados (196 ASP). La distancia media entre la ASP y el borde superior de la coana fue de 14,8 mm del lado izquierdo y 14,7 mm del lado derecho. La distancia media total fue de 14,82 (Tabla 1, Fig 4). Discusión: El borde superior de la coana es un reparo confiable por su constancia en la práctica quirúrgica. Otros autores han medido la distancia entre la rama superior de la ASP y el ostium esfenoidal en 8.2 ± 0.5 mm con un rango de 6.6 a 12.2 mm. Sin embargo el ostium no es un reparo tan confiable por su variable localización en el rostro esfenoidal. La distancia entre la ASP o su rama inferior y el arco de la coana, está descrita a 6.72 ± 2.64 mm con un rango de 2.34­12.64. Sin especificar entre la ASP o su rama inferior. Conclusión: La ASP se encuentra en promedio a aproximadamente 15 mm cefálico al borde superior de la coana. Esta distancia puede ser considerada como un margen de seguridad para evitar lesionar el pedículo vascular durante la confección del CPNS o bien para preservarlo durante la apertura del rostro esfenoidal en caso de requerirse un CPNS de rescate.

Tratamiento endoscópico de quistes coloideos del tercer ventrículo / Third ventricle colloid cysts endoscopic approach

Introducción: los quistes coloideos (QC) son tumores benignos de crecimiento lento, que comprenden menos del 1% de los tumores intracraneales. Se presentan en adultos jóvenes y se ubican más frecuentemente en el techo del tercer ventrículo. El objetivo de este trabajo es presentar una serie de pacientes con QC del tercer ventrículo operados por vía endoscópica, analizar la técnica quirúrgica, ventajas y desventajas. Desarrollo: se realizó una búsqueda retrospectiva de pacientes operados por vía endoscópica, en el Servicio de Neurocirugía del Hospital Italiano de Buenos Aires, de tumores del tercer ventrículo en un período de 2 años (2013-2015), con diagnóstico de QC confirmado por anatomía patológica . Se identificaron cinco pacientes, tres mujeres y dos hombres, cuyo promedio de edad fue de 50 años. No hubo complicaciones perioperatorias y ninguno mostró recidiva en el lapso de observación. Conclusión: la vía endoscópica es una vía técnicamente simple y con muy baja morbilidad. Si bien no siempre puede realizarse una exéresis completa, los trabajos prospectivos permitirán definir si esto resulta suficiente para el control de la enfermedad. (AU)

Colloid cysts are benign, slow-growing tumors, comprising less than 1% of intracranial tumors. They occur in young adults and are more frequently located on the roof of the third ventricle. The objective of this study is to present a series of patients with Colloid cysts operated endoscopically and analyze advantages and disadvantages of this surgical technique. We performed a retrospective review of Colloid Cysts operated on endoscopically, at the Neurosurgical Department of Hospital Italiano de Buenos Aires in a period of 2 years (2013-2015). Five patients were identified, three women and two men whose average age was 50 years. No perioperative complications were observed, with no recurrences during the follow up period. Conclusion: the endoscopic approach is technically simple and has very low morbidity. Although a complete excision can not always be performed, prospective studies will allow us to define whether if is sufficient to control the disease. (AU)

[Relevance of Simpson's grades in the resection of grade I meningiomas]. / Relevancia de los grados de Simpson en la resección de meningiomas grado I.

OBJECTIVE: Compare the number of recurrences in patients with WHO Grade I meningiomas that underwent microsurgical resection. INTRODUCTION: In 1957 Simpson established five grades for surgical resection for intracranial meningiomas and recurrence rate. He thought that an aggressive removal of these tumors with dura and bone was necessary to cure them. Development of new diagnostic methods, advances in anatomopathology and microsurgical technique lead us to question if this scale has a value nowadays. METHODS: A retrospective analysis was performed. All patients operated from grade I meningiomas between February 2006 to December 2015 were included. Pre and postoperative MRI as well as histology were analyzed. A multivariate analysis was performed, a P < 0.05 was considered statistically significant. RESULTS: There was no statistical significant difference between patients undergoing Simpson Grade I, II, III or IV resection (P = 0,3117). This could be best stated for Simpson Grade I and II resection, where the number of patients included in the study was higher. When we analyze tumor location there was not significant difference in recurrence between groups (P = 0,2203). CONCLUSION: For grade I meningiomas there is no significant difference in the recurrence between patients with a Simpson Grade I or II resection, thus increasing morbidity of the surgery is not justified. A new resection scale should be designed taking into account the WHO classification.

Prolonged disease stability with trabectedin in two monorenal patients with retroperitoneal sarcoma.

Soft tissue sarcomas constitute a heterogeneous group of tumors of mesenchymal origin: at present, more than 50 separate histological subtypes of soft tissue sarcoma have been listed. Although there have been advances in the understanding of these tumors and their treatment over the past few years, there is still a lack of consensus on the standard of care, and new therapeutic options are eagerly awaited. Trabectedin has been approved for the treatment of patients with advanced soft tissue sarcomas after failure of anthracyclines and ifosfamide. However, the effectiveness and tolerability of this agent in retroperitoneal soft tissue sarcomas have been poorly characterized. Here we report the cases of two monorenal patients with a retroperitoneal sarcoma who achieved prolonged stabilization of disease with trabectedin. Trabectedin-associated toxicities were generally mild and were successfully managed by supportive care. Of note, the patients did not experience clinically relevant myelosuppression, which is currently considered the limiting toxicity of trabectedin.

Correlation of body mass index and leptin with tumor size and stage of disease in hormone-dependent postmenopausal breast cancer: preliminary results and therapeutic implications.

Obesity is considered the most important risk and prognostic factor for estrogen-dependent breast cancer in postmenopausal women. Adipokines, in particular leptin, are at the center of the etiopathogenetic mechanisms by which obesity and related metabolic disorders influence breast cancer risk and its prognosis. The present prospective observational study aims to investigate the relationship between body mass index (BMI), serum levels of leptin and proinflammatory cytokines, and breast cancer prognostic factors. In the study, 98 postmenopausal and 82 premenopausal patients with ER-positive breast cancer participated. During the same study period, 221 control subjects were simultaneously recruited. Women underwent baseline measurements pre-operatively, before any surgical and systemic treatments. Pathologic characteristics of tumors were abstracted from pathology reports. Leptin and proinflammatory cytokines were assayed in stored fasting blood specimens. In postmenopausal breast cancer patients, BMI, leptin, and interleukin-6 significantly correlated with pathological tumor classification (pT) and TNM stage. Multivariate regression analysis showed that BMI and leptin, but not interleukin-6, were independent predictive variables of pT and TNM stage. Our results seem to suggest a twofold role of leptin in the etiopathogenesis of postmenopausal estrogen-positive breast cancer. Indeed, leptin reflects the total amount of fat mass, which correlates to aromatase activity and subsequent estrogens levels. Further studies are warranted to clarify the role of leptin and interleukin-6 in breast carcinogenesis and identify new therapeutic options, beyond the use of aromatase inhibitors, acting selectively on adipokine-driven pathways.

Interleukin-6 and leptin as markers of energy metabolic changes in advanced ovarian cancer patients.

The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint.

Hemoglobin levels correlate with interleukin-6 levels in patients with advanced untreated epithelial ovarian cancer: role of inflammation in cancer-related anemia.

Anemia occurs in more than 30% of patients with epithelial ovarian cancer before any surgery. High levels of proinflammatory cytokines and increased oxidative stress may contribute to the development of cancer-related anemia. We assessed a population of previously untreated patients with advanced epithelial ovarian cancer to evaluate whether there was a correlation between hemoglobin (Hb) and parameters of inflammation and oxidative stress, stage of disease, and performance status (PS). In 91 patients with epithelial ovarian cancer and 95 healthy women matched for age, weight, and height, levels of Hb, C-reactive protein (CRP), fibrinogen (Fbg), proinflammatory cytokines, leptin, reactive oxygen species (ROS), and antioxidant enzymes were assessed at diagnosis before treatment. The correlations between Hb, parameters of inflammation and oxidative stress, stage, and PS were evaluated. Hb levels were lower in patients with advanced epithelial ovarian cancer than in control subjects and inversely related to stage and PS. Hb negatively correlated with CRP, Fbg, interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNFalpha), and ROS, and positively correlated with leptin and glutathione peroxidase (GPx). Multivariate regression analysis showed that stage and IL-6 were independent factors determining Hb values. This evidence suggests that anemia in epithelial ovarian cancer is common and its presence is related to stage of disease and markers of inflammation.