Predictive model of resection in endoscopic endonasal approach for pituitary adenomas based on anatomical limits.

INTRODUCTION: The aim of this project is to study several anatomical-radiological features of pituitary adenomas obtained from preoperative radiological images and to analyze their relationship with the extent of resection achieved through the endoscopic endonasal approach. The second objective was to create a prediction model of the extent of resection. MATERIAL AND METHODS: We retrospectively evaluated 105 patients. Tumor volume, Knosp grade, suprasellar-diaphragm coefficient and invasion of the posterior compartment have been analyzed. The extent of resection was assessed by analyzing the postoperative magnetic resonance. We created the predictive scale using statistically independent variables. RESULTS: When each of the variables has been studied individually, a statistically significant value of all of them is appreciated to obtain a complete resection. However, only the Knosp grade and the suprasellar-diaphragm coefficient had a statistically significant value as independent variables. The sum of the Odds Ratio obtained from the Knosp scale, and the suprasellar-diaphragm coefficient gives the probability of complete resection. A new set of cases was employed to validate the scale. CONCLUSIONS: The cavernous sinus invasion and the newly designed suprasellar diaphragm coefficient are directly related to the extent of resection in pituitary adenoma surgery performed by a transellar endoscopic approach. Moreover, based on both radiologic factors, a predictive scale may predict the probability of complete resection in a series of patients.

Utilidad de la neuromonitorización vagal continua en cirugía tiroidea: experiencia y resultados en un hospital de tercer nivel / The role of continuous vagal intraoperative nerve monitoring in thyroid surgery: experience and results in a third-level hospital

Resumen Objetivo: La lesión del nervio laríngeo recurrente es una grave complicación en cirugía tiroidea. El propósito del presente estudio es analizar la utilidad de la neuromonitorización vagal continua intraoperatoria en un hospital terciario. Materiales y Método: Estudio observacional, analítico y retrospectivo que recoge pacientes intervenidos de cirugía tiroidea con neuromonitorización en un período de 14 meses. La pérdida de señal se define como amplitud final nerviosa < 100 ^V, realizándose laringoscopia postquirúrgica ante la sospecha de lesión nerviosa. El análisis estadístico se realizó con el programa SPSS® V25,0, con p < 0,05. Resultados: Se incluyeron 120 pacientes intervenidos, registrándose en el 24,2% pérdida de señal. Factores de riesgo para lesión fueron bocio intratorácico (OR 5,31; IC 95% 1,56-17,99; p = 0,007), cirugía cervical previa (OR 5,76; IC 95% 0,64-51,97; p = 0,119) y patología maligna (OR 1,44; IC 95% 0,16-12,79; p = 0,743). Fue posible el cambio de estrategia quirúrgica en 7 casos. En el seguimiento posterior se cuantificó parálisis recurrencial transitoria en 27 pacientes y permanente en 4. Discusión: La neuromonitorización parece reducir la incidencia de parálisis laríngea porque aumenta la seguridad en la identificación del nervio recurrente y reduce su manipulación durante la cirugía. Conclusiones: La neuromonitorización intraoperatoria es útil para identificar el nervio laríngeo recurrente y advierte del riesgo potencial de lesión, permitiendo cambiar la estrategia quirúrgica para evitar la parálisis bilateral de cuerdas vocales.

Aim: Recurrent laryngeal nerve injury is a serious complication in thyroid surgery. The purpose of the present study is to analyze the use of intraoperative continuous vagal neuromonitoring in a tertiary hospital. Materials and Method: Observational, analytical and retrospective study that includes patients who underwent thyroid surgery with neuromonitoring in a period of 14 months. Loss of signal is defined as final nerve amplitude < 100 ^V, and postsurgical laryngoscopy is performed due to suspicion of nerve injury. Statistical analysis was performed with the SPSS® V25.0 program, with p < 0.05. Results: 120 operated patients were included, registering loss of signal in 24.2%. Risk factors for injury were intrathoracic goiter (OR 5.31; 95% CI 1.56-17.99; p = 0.007), previous cervical surgery (OR 5.76; 95% CI 0.64-51.97; p = 0.119) and malignant pathology (OR 1.44; 95% CI 0.16-12.79; p = 0.743). A change in surgical strategy was possible in 7 cases. In the subsequent follow-up, transient recurrent paralysis was quantified in 27 patients and permanent in 4. Discussion: Neuromonitoring seems to reduce the incidence of laryngeal paralysis because it increases the security in the identification of the recurrent nerve and reduces its manipulation during surgery. Conclusions: Intraoperative neuromonitoring is useful to identify the recurrent laryngeal nerve and warns of the potential risk of injury, allowing to change the surgical strategy to avoid bilateral vocal cord paralysis.

Impact of a clinical pathway on cardiovascular risk in patients with diabetes.

OBJECTIVES: Clinical pathways (CPs) are interventions that target the way clinical practice guidelines are applied. They can be implemented in different diseases, including diabetes. In this study we evaluated the impact of the implementation of a CP in the control of cardiovascular risk factors and the occurrence of new events in patients with type 2 diabetes. METHODS: A pre- and post-intervention population-based study in a Spanish region, conducted in 2014-2016. Variables before and after the intervention were: screening; good control of diabetes, dyslipidemia and hypertension; hypoglycemia and hyperglycemic decompensation; obesity; cardiovascular events; diabetic ketoacidosis; hyperglycemic and hypoglycemic coma. Proportional differences and parameters of clinical relevance (absolute and relative risk reduction, relative risk and number needed to treat) were calculated. RESULTS: The CP achieved an improvement in all outcomes, reducing events and increasing control of different cardiovascular parameters. The greatest improvement was in metabolic control (HbA1c) (37.1% in younger patients and 34.0% in older patients) and screening (5.4%). Indicators of clinical relevance showed that the CP was able to improve metabolic control of diabetes with little effort and great benefit. CONCLUSION: The CP was of considerable benefit to metabolic control as well as control of dyslipidemia and obesity. Screening for diabetes also benefitted. The CP decreased the incidence of events, especially of angina pectoris.

Proposal of a clinically relevant working classification of pituitary neuroendocrine tumors based on pituitary transcription factors.

The immunohistochemistry (IHC) characterization of pituitary transcription factors (PTFs) PIT1, TPIT, and SF1, which enable the identification of three different adenohypophyseal cell lines, has been incorporated into the latest classification system of the World Health Organization (WHO) for pituitary adenomas. This change overturns the concept of the adenoma as solely a hormone producer and classifies these tumors based on their cell lineage. The aim of the study was to provide a diagnostic algorithm, based on IHC expression of hypophyseal hormones with potential use in diagnostic practice, contributing to an improved classification of pituitary adenomas. Our sample included 146 pituitary adenomas previously classified based on hormonal subtypes by IHC (former 2004 WHO criteria) and re-evaluated after the IHC quantification of PIT1, TPIT, and SF1 expression, under WHO 2017 recommendations. We assessed the correlation between expression of PTFs and the classification as per hormonal IHC and correlated clinicopathological profiles based on PTFs. The IHC study of PTFs allowed reclassification of 82% of tumors that were negative for all pituitary hormones, with 21 positive cases for SF1 (reclassified as gonadotroph tumors), 1 positive case for TPIT (reclassified as a corticotroph tumor), and 4 positive cases for PIT1. Using SF1 enabled detection of a substantial portion of gonadotroph tumors, reducing the estimated prevalence of null cell tumors to less than 5%, and identification of plurihormonal pituitary neuroendocrine tumors with PIT1-SF1 coexpression and hormone-negative PIT1s, a group in which we did not observe differences in the clinical behavior compared with the rest of the tumors of the same cell lineage.Our results suggest that applying a diagnostic algorithm based on the study of PTFs could contribute to improving the classification of pituitary adenomas. By adding TPIT assessment, we propose a two-step algorithm, with hypophyseal hormones being used in a selective modality, depending on initial results.

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly / ACROSTART: Estudio retrospectivo del período de tiempo para lograr el control hormonal con lanreótida Autogel en pacientes con acromegalia en la práctica clínica española

Objectives: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline(R) Autogel(R)). Methods: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. Results: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. Conclusions: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals

Objetivos: El objetivo del estudio ACROSTART era determinar el período de tiempo para lograr la normalización hormonal (GH e IGF-I) en pacientes con acromegalia respondedores al tratamiento considerando los regímenes de lanreótida Autogel (Somatuline(R) Autogel(R)) utilizados en la práctica clínica. Métodos: Desde marzo de 2013 hasta octubre de 2013, en 17 hospitales españoles se analizaron los datos clínicos de 57 pacientes con acromegalia activa tratados con lanreótida durante ≥4 meses que lograron control hormonal (niveles de GH <2,5ng/ml y/o IGF-I normalizado en ≥2 evaluaciones). El objetivo principal fue determinar el período de tiempo desde el inicio del tratamiento con lanreótida hasta la normalización hormonal. Resultados: La mediana de edad de los pacientes fue 64 años, 21 pacientes eran hombres, 39 pacientes habían recibido cirugía, 14 pacientes habían recibido radioterapia. Los valores hormonales medianos al inicio del tratamiento con lanreótida fueron GH: 2,6ng/ml, IGF-I: 1,6×LSN. La dosis inicial más frecuente de lanreótida fue de 120mg (29 pacientes). Los principales regímenes iniciales fueron 60mg/4 semanas (n=13), 90mg/4 semanas (n=6), 120mg/4 semanas (n=13), 120mg/6 semanas (n=6), 120mg/8 semanas (n=9). Se administró un régimen de intervalo prolongado (≥6 semanas) en 25 pacientes. La duración media del tratamiento con lanreótida fue de 68 meses (7-205). El tiempo medio hasta lograr el control hormonal fue de 4,9 meses. Las inyecciones se manejaron sin asistencia médica en 13 pacientes. La mediana del número de visitas al endocrinólogo hasta el control hormonal fue 3. Cincuenta y un pacientes estaban "satisfechos"/"muy satisfechos" con el tratamiento y 49 pacientes no olvidaron ninguna dosis. Conclusiones: El tratamiento en la vida real con lanreótida Autogel condujo a un control hormonal temprano en pacientes que respondieron, con una alta adherencia al tratamiento y satisfacción con el tratamiento, a pesar de la disparidad de las dosis iniciales y los intervalos de dosificación

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly.

OBJECTIVES: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.

Cirugía endoscópica endonasal en adenomas hipofisarios: resultados quirúrgicos en una serie de 86 pacientes consecutivos / Endonasal endoscopic surgery in pituitary adenomas: Surgical results in a series of 86 consecutive patients

Introducción: El abordaje endoscópico endonasal se ha convertido en la técnica quirúrgica de elección para el tratamiento de los adenomas hipofisarios. Objetivos: El objetivo de este trabajo es presentar los resultados obtenidos en nuestro hospital en cirugía puramente endoscópica de los adenomas hipofisarios. Métodos: Hemos realizado un estudio prospectivo, recogiendo a los pacientes intervenidos de adenoma hipofisario mediante un abordaje endonasal puramente endoscópico, desde febrero de 2011 hasta agosto de 2016, obteniendo una muestra total de 86 pacientes. Todos los pacientes fueron intervenidos conjuntamente por un ORL y un neurocirujano con la técnica de four hands-two nostrils. El seguimiento medio postoperatorio fue de 32 meses. Todos los pacientes fueron evaluados según criterios clínicos, radiológicos y endocrinológicos. Resultados: En nuestra serie un 53% eran mujeres y un 47% hombres; el rango de edad variaba desde los 14 hasta los 84 años, siendo la media de 54 años. El síntoma inicial más habitual fue el déficit visual (42%), seguido por la hiperfunción hormonal (21%), siendo la acromegalia el síndrome clínico observado con más frecuencia. Los tumores más frecuentes fueron los no funcionantes (73%), y de entre los adenomas funcionantes el más frecuente fue el productor de GH (65%). En cuanto a tamaño tumoral, un 76% eran macroadenomas, un 11% microadenomas y un 13% gigantes. Un 63% presentaban extensión supraselar y un 37% invasión de seno cavernoso (grado de Knosp ≥3). Se consiguió una exéresis total en un 77% de los casos. Tras la intervención se consiguió en un 91% mejoría visual y hasta en un 73% remisión de la hiperfunción endocrina. En cuanto a las complicaciones, la más frecuente fue la insuficiencia de al menos un eje de la hipófisis anterior (9%), sin presentar casos de fístula de LCR posquirúrgica. Conclusiones: Nuestros resultados, en términos de calidad quirúrgica, se asemejan a las series publicadas y avalan la eficacia y seguridad del abordaje endoscópico endonasal como técnica de elección en el manejo quirúrgico de la glándula hipofisaria. Sin embargo, es necesario un estudio con mayor número de casos para obtener resultados con significación clínica

Introduction: The endoscopic endonasal approach has become the gold standard for the surgical treatment of pituitary adenomas. Objectives: The aim of this study is to present the results obtained in our hospital in purely endoscopic surgery of pituitary adenomas. Methods: From February 2011 to August 2016, we conducted a prospective study on a series of 86 patients with pituitary adenoma, all of whom underwent surgery with a purely endoscopic endonasal approach. The ‘four hands-two nostrils’ technique was performed in all cases by a surgical team composed of an ENT surgeon and a neurosurgeon. Mean follow-up was 32 months. All patients were evaluated according to clinical, radiological and endocrinological criteria. Results: In our series, 53% were women and 47% men. The age ranged from 14 to 84 years of age, with a mean of 54 years of age. The most common initial symptom was visual deficit (42%), followed by hormonal hyperfunction (21%), with acromegaly being the most common clinical syndrome. The most common tumours were non-functioning tumours (73%), while GH-secreting tumours (65%) were the most common functioning adenoma. Regarding tumour size, 76% were macroadenomas, 11% microadenomas and 13% giant adenomas. Approximately 63% of the adenomas exhibited suprasellar extension and 37% involved invasion of the cavernous sinus (Knosp grade ≥3). Total excision was achieved in 77% of the cases. After the intervention, visual improvement was achieved in 91% and remission of endocrine hyperfunction in up to a 73% of cases. The most common complication was anterior pituitary insufficiency of at least one axis (9%). There were no cases of postoperative cerebrospinal fluid fistula. Conclusions: In terms of surgical quality, our results are similar to those of published series, and demonstrate the efficacy and safety of the endoscopic endonasal approach as the surgical treatment of choice for pituitary adenomas. However, further studies with a higher sample size are necessary to obtain clinically significant results

[Endonasal endoscopic surgery in pituitary adenomas: Surgical results in a series of 86 consecutive patients]. / Cirugía endoscópica endonasal en adenomas hipofisarios: resultados quirúrgicos en una serie de 86 pacientes consecutivos.

INTRODUCTION: The endoscopic endonasal approach has become the gold standard for the surgical treatment of pituitary adenomas. OBJECTIVES: The aim of this study is to present the results obtained in our hospital in purely endoscopic surgery of pituitary adenomas. METHODS: From February 2011 to August 2016, we conducted a prospective study on a series of 86 patients with pituitary adenoma, all of whom underwent surgery with a purely endoscopic endonasal approach. The 'four hands-two nostrils' technique was performed in all cases by a surgical team composed of an ENT surgeon and a neurosurgeon. Mean follow-up was 32 months. All patients were evaluated according to clinical, radiological and endocrinological criteria. RESULTS: In our series, 53% were women and 47% men. The age ranged from 14 to 84 years of age, with a mean of 54 years of age. The most common initial symptom was visual deficit (42%), followed by hormonal hyperfunction (21%), with acromegaly being the most common clinical syndrome. The most common tumours were non-functioning tumours (73%), while GH-secreting tumours (65%) were the most common functioning adenoma. Regarding tumour size, 76% were macroadenomas, 11% microadenomas and 13% giant adenomas. Approximately 63% of the adenomas exhibited suprasellar extension and 37% involved invasion of the cavernous sinus (Knosp grade ≥3). Total excision was achieved in 77% of the cases. After the intervention, visual improvement was achieved in 91% and remission of endocrine hyperfunction in up to a 73% of cases. The most common complication was anterior pituitary insufficiency of at least one axis (9%). There were no cases of postoperative cerebrospinal fluid fistula. CONCLUSIONS: In terms of surgical quality, our results are similar to those of published series, and demonstrate the efficacy and safety of the endoscopic endonasal approach as the surgical treatment of choice for pituitary adenomas. However, further studies with a higher sample size are necessary to obtain clinically significant results.

Claves para avanzar hacia un rol más activo por parte del paciente con diabetes mellitus tipo 2 en España / Key aspects to moving towards a more active role for the patient with diabetes mellitus type 2 in Spain

OBJETIVOS: La diabetes mellitus tipo 2 (DM2) es un problema de salud pública de primer orden que preocupa a gestores, a profesionales sanitarios y a la sociedad en su conjunto. Contar con un paciente con DM2 más activo y responsable con su salud se perfila como una de las soluciones. Por ello la importancia de impulsar un debate multidisciplinar que aporte ideas y soluciones que contribuyan a conseguir un paciente con DM2 involucrado en su salud. En este artículo se presentan una serie de recomendaciones consensuadas por el Grupo Paciente Activo y Diabetes (PAyDInet). MATERIAL Y MÉTODOS: Se constituyó el grupo de trabajo PAyDInet, en el que participaron diferentes agentes del sistema. Siguiendo la técnica de grupo nominal, se identificaron y priorizaron las barreras, los elementos facilitadores así como iniciativas concretas que fomenten una actitud preventiva y de autocuidado en el paciente con DM2. RESULTADOS: El grupo llegó a un consenso sobre las 3 barreras, 3 elementos facilitadores y 3 iniciativas clave en la consecución de un paciente con DM2 más activo en el manejo de su enfermedad. La configuración actual del sistema sanitario, la necesidad de mejorar la coordinación interprofesional y el desarrollo de la educación diabetológica estructurada constituyen los puntos esenciales identificados por el grupo. CONCLUSIÓN: Es una necesidad ineludible seguir avanzando para situar al paciente como centro del sistema. Un paciente formado e informado en DM2 es una tarea compleja que solo se logrará con nuevas alianzas y la colaboración de todos los agentes. En cualquier caso, el debate y las recomendaciones del grupo PAyDInet aportan una buena aproximación al tema y un excelente punto de partida

OBJECTIVES: Diabetes mellitus type 2 (DM2) is a public health problem of the first order of concern to managers, health professionals and society as a whole. Having a more active and responsible patient with DM2 is emerging as one of the solutions. Hence the importance of promoting a multidisciplinary discussion that provides ideas and solutions that contribute to an active and involved patient with DM2. In this article some consensual recommendations are provided by the working group called Active Patient and Diabetes(PAyDInet by its Spanish initials). METHODS: PAyDInet team was established by gathering agents from different fields of the system. Following the nominal group technique, barriers, facilitators and specific initiatives to promote a preventive attitude and self-care in patients with DM2, were identified and prioritized. RESULTS: The team reached a final consensus on 3 key barriers, 3 enablers and 3 key initiatives to achieve patients with DM2 more active in managing their disease. The configuration of the healthcare system, the need to improve interprofessional coordination, and development of structured diabetes education, are the key points identified by the group. CONCLUSION: It is an inescapable need to move forward to put the patient at the centre of the system. Training and informing a patient on DM2 is a complex task that can only be achieved with new partnerships and collaboration of all stakeholders. In any case, the discussion and recommendations of the group PAyDInet give us a good approach to the subject and an excellent starting point

Pituitary tumor transforming gene and insulin-like growth factor 1receptor expression and immunohistochemical measurement ofKi-67 as potential prognostic markers of pituitary tumorsaggressiveness

Introducción y objetivo La capacidad de predecir recurrencia en los adenomas hipofisarios (AH) tras la cirugía puede ser útil para determinar la frecuencia de seguimiento y la necesidad de tratamientos adyuvantes. El objetivo del presente estudio fue valorar la capacidad pronóstica de gen transformador de tumores hipofisarios (pituitary tumor transforming gene [PTTG]), del receptor del factor de crecimiento insulinoide 1 (insulin-like growth factor 1 receptor [IGF1R]) y de Ki-67. Material y métodos En este estudio retrospectivo determinamos el número de copias normalizadas de ARNm (Cnn) de PTTG e IGF1R mediante RT-PCR y el índice Ki-67 mediante inmunohistoquímica en 46 muestras de AH. Los datos clínicos, el subtipo histológico y las características radiológicas se recogieron para determinar asociaciones entre las variables y el comportamiento tumoral. Además, estudiamos la progresión de los restos tumorales y su asociación con los marcadores en 14 pacientes sin tratamiento adyuvante posquirúrgico seguidos durante 46 ± 36 meses. Resultados Los tumores extraselares mostraron una expresión de PTTG menor que los intraselares (0,065 [1.er-3.er cuartil: 0,000-0,089] Cnn frente a 0,135 [0,105–0,159] Cnn, p = 0,04). La expresión de IGF1R varió en función del subtipo histológico (p = 0,014), siendo mayor en los tumores que presentaron crecimiento de los restos mayor del 20% durante el seguimiento (10,69 ± 3,84 Cnn frente a 5,44 ± 3,55 Cnn, p = 0,014). Conclusiones Nuestros resultados indican que IGF1R, en mayor medida que PTTG, es un marcador molecular útil en el manejo de los AH. Ki-67 no mostró asociación con el comportamiento tumoral. Sin embargo, el potencial de estos marcadores debe ser establecido en futuros estudios con una metodología estandarizada y una muestra mayor (AU)

Introduction and objective The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67. Materials and methods In this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46 ± 36 months. Results Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st–3rd quartile: 0.000–0.089] NCN vs. 0.135 [0.105–0.159] NCN, p = 0.04). IGF1R expression changed depending on histological subtype (p = 0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69 ± 3.84 NCN vs. 5.44 ± 3.55 NCN, p = 0.014). Conclusions Our results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples(AU)

Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence.

Some pituitary adenomas (PA) demonstrate aggressive behavior with local invasion and recurrences. Angiogenesis is regarded as an essential step in the formation of solid tumors. The aim of this study is to find out whether angiogenic factors may have information about the aggressiveness of PA that could be useful in determining the frequency of follow-up and whether adjuvant therapy is necessary. In this retrospective descriptive study, we evaluated vascular endothelial growth factors (VEGF) and VEGF receptor (KDR) mRNA expression by RT-PCR analysis on 46 human PA samples. Clinical data, histological subtype and radiologic characteristics were studied to determine the associations between the variables and the pre-operative behavior of the tumor. In addition, we monitored 12 patients without adjuvant post-operative therapies over 46 months after surgery, determining progression of tumor remnants and its association with these markers. VEGF expression correlates with KDR expression (r = 0.40, p = 0.006). VEGF demonstrates different expression between histological subtypes (p = 0.036). The extension at magnetic resonance imaging showed that VEGF expression was related to suprasellar extension (p = 0.007), being expressed more on tumors with extrasellar growth than intrasellar ones (p = 0.008). Our results demonstrate a 27.5 times increased risk of extrasellar growth when VEGF expression exceeds 0.222 normalized copy number (NCN) (p = 0.002). Likewise, tumors with KDR greater than 0.750 NCN had less recurrence-free survival time (p = 0.032). Our results suggest that the expression of VEGF and its receptor could be a marker for poor outcome after partial tumor resection. These data should be considered in future studies evaluating angiogenic factors as therapeutic targets in patients with PA.

[Rol of pituitary tumour-transforming gene (PTTG) in the pituitary adenomas]. / Papel de pituitary tumour-transforming gene (PTTG) en los adenomas hipofisarios.

The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours.

Papel de pituitary tumour-transforming gene (PTTG) en los adenomas hipofisarios / Rol of Pituitary Tumour-Transforming Gene (PTTG) in the pituitary adenomas

El pituitary transforming tumour gene (PTTG) está involucrado en una gran variedad de mecanismos fisiológicos. Se ha descrito sobreexpresión proteínica de PTTG en múltiples neoplasias, como los tumores hipofisarios, la cual favorece la aneuploidía, la inestabilidad genética, la proliferación celular y la angiogénesis, todos ellos procesos clave en la transformación neoplásica. Los estudios llevados a cabo en adenomas hipofisarios indican su asociación con un mayor grado de infiltración y de recidivas. Actualmente se plantea su función potencial como diana terapéutica (AU)

The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours (AU)

Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone: a comparison of two dosing regimens.

RATIONALE AND OBJECTIVE: The treatment of active moderate-severe Graves' ophthalmopathy (GO) is based on the administration of highdose intravenous glucocorticoids. The present study compares the efficacy and safety of 2 different intravenous methylprednisolone (MTPiv) dosing regimens. MATERIAL AND METHODS: We carry a retrospective descriptive study with sequential sampling of 24 patients (83% females) presenting moderatesevere GO (EUGOGO criteria) and receiving treatment in our center between January 2006 and June 2008. We use 2 dosing regimens: regimen A (12 weeks): 6 doses of 0.5g/week followed by 6 doses of 0.25 g/week, for a cumulative dose of 4.5 g of MTPiv (n=13); and regimen B (16 weeks): 4 cycles of 15 mg/kg, followed by 4 cycles of 7.5mg/kg, for a cumulative dose of 90 mg/kg (range, 4.9-7.4 g) (n=11). Comparisons were made for safety (fasting glucose, cytolysis-cholestasis enzymes, lipid profile) and efficacy data (clinical improvement and recurrence). RESULTS: Mild-moderate liver cytolysis was recorded in four patients, one with associated moderate cholestasis and another with hyperglycemia, leading to treatment suspension - with no differences between the 2 treatment regimens. Percentage clinical improvement with regimen A was 92% (CI, 65-94%) versus 100% with regimen B (CI, 74-100%). The recurrence rate was 43% with regimen A and 63% with regimen B (p>0.05). None of the variables examined in the univariate logistic regression study were associated to a lesser treatment response or increased risk of recurrence of GO. CONCLUSIONS: The treatment of GO with MTPiv is safe and effective, with a lower recurrence rate when using dosing regimen A.