Small cell lung cancer: an overview of the targets

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.

Carcinoma neuroendócrino de células pequeñas, como hallazgo incidental / Incidental Finding of Small Cell Neuroendocrine Carcinoma

Hombre de 45 años de edad, oriundo del Gran Buenos Aires, ocupación: administrativo, ex- tabaquista de 15 p/y. El paciente se realiza un examen preocupacional que incluía una radiografía de tórax (Figura 1). Se observa como hallazgo incidental una radiopacidad en región superior de campo pulmonar derecho de bordes netos El paciente no refería tos, disnea, descenso de peso o sudoración nocturna, así como tampoco otros síntomas. Consulta al médico de cabecera quien deriva a nuestra institución para diagnóstico y tratamiento. Se le realiza TACAR de tórax, donde se observa una masa sólida que abarca lóbulo superior derecho, sin plano de clivaje con el mediastino y que desplaza tráquea y esófago hacia la izquierda. La misma presenta realce heterogéneo tras la administración de contraste. Además, presenta bullas subpleurales en lóbulos superiores y adenopatías a nivel retrocavopretraqueal e infracarinal (Figura 2). Ante los diversos diagnósticos diferenciales, de masas mediastinales en un paciente joven (linfoma, tumores carcinoides atípicos, tumores mixtos), se decidió realizar un método diagnóstico mínimamente invasivo pero que aportara material suficiente para determinar el origen

Pancreatitis aguda en carcinoma de célula pequeña de pulmón (CPCP) resuelta con quimioterapia / Acute pancreatitis in small-cell lung carcinoma (SCLC) resolved with chemotherapy

Resumen El carcinoma de célula pequeña (CPCP) o microcítico de pulmón es un subtipo de cáncer de pulmón que típicamente se ha asociado al tabaquismo y que se caracteriza por su agresividad y mal pronóstico a corto plazo. Como entidad, puede metastatizar en cualquier órgano, siendo las metástasis pancreáticas raras y la mayoría de las veces asintomáticas. Por ello, la presencia de una pancreatitis neoplásica, como en el caso presentado, es excepcional, y aún más cuando presenta refractariedad al tratamiento médico convencional y responde al tratamiento citotóxico sistémico. Por todo ello, se expone esta experiencia clínica y se debate la presencia de esta rara entidad y su manejo.

Abstract Small-cell lung carcinoma is a subtype of neoplasm that has been typically associated with smoking; it is characterized by its aggressiveness and poor prognosis in the short term. As an entity, it can metastasize in any organ, but pancreatic metastases are rare and most of the time asymptomatic. Therefore, the presence of neoplastic pancreatitis as in our case is exceptional; even more when it presents refractoriness to conventional medical treatment, responding instead to systemic cytotoxic treatment. Therefore, we expose our clinical experience and discuss the presence of this rare entity and its management.

Análise comparativa do perfil imune no sangue de pacientes metastáticos e não metastáticos com câncer de pulmão de não pequenas células / Comparative analysis of the immune profile in blood of patients with non small cell lung cancer

Câncer de pulmão de não pequenas células (CPNPC) é o tipo mais frequente de câncer de pulmão, acometendo por volta de 85% à 90% de todos os cânceres de pulmão, sendo o tabagismo o fator de risco mais relevante para a doença. O sistema imune possui um papel importante na resposta antitumoral, porém, as células do tumor fazem uso de mecanismos para evadir da imunovigilância através de células imunossupressoras e produção de citocinas. A análise de células imunes e de citocinas pode auxiliar em um conhecimento mais abrangente do microambiente tumoral como um todo, permitindo um melhor entendimento da doença e a proposta de tratamentos que possam ser mais eficazes. Neste trabalho, foi avaliando o perfil imune sistêmico de pacientes com CPNPC, comparando pacientes não metastáticos (estágios I, II, III) e pacientes metastáticos (estágio IV). Nós avaliamos a frequência de células linfoides e mieloides por meio de citometria de fluxo, além das concentrações plasmáticas de citocinas por meio da análise multiplex a partir de amostras de sangue de pacientes coletadas antes do início do tratamento. Foram incluídos 39 pacientes com CPNPC, sendo 28 no grupo de metastáticos e 11 no grupo de não metastáticos. Foi possível verificar um aumento da frequência de monócitos inflamatórios no sangue de pacientes metastáticos, se comparados a pacientes não metastáticos, indicando um microambiente mais favorável ao desenvolvimento de metástase. Além disso, foram observados níveis mais elevados de monócitos não-clássicos, conhecidos como patrulhadores e das citocinas TRAIL E IL-1Ra em pacientes não metastáticos, indicando um microambiente mais protetor. Concluindo, este estudo propõe mecanismos imunológicos relacionados ao desenvolvimento de metástase para pacientes com CPNPC, sugerindo biomarcadores que podem auxiliar no prognóstico e acompanhamento desse grupo de pacientes

Non-small cell lung cancer (NSCLC) is the most common type of cancer among lung cancers, accounting for about 85% to 90% of cases, with smoking being the most relevant risk factor related to the disease. The immune system plays an important role in anti-tumoral response; however, tumor cells use mechanisms that allow escape from immune surveillance, such as the presence of immunosuppressive cells and production of inhibitory cytokines in the tumor microenvironment. Analyzing the immune cells and cytokines can be helpful to better understand the tumor microenvironment and diseases development allowing a more effective treatment. In this work it was determine the immune cells profile of patients with NSCLC, comparing non-metastatic (stages I, II and III) and metastatic (stage IV) patients. We evaluated the frequencies of lymphocytes and myeloid cells in patients using flow cytometry and plasmatic cytokines concentration cytokines using multiplex analysis in blood samples collected before treatment begins. It was including 39 NSCLC patients, of which 28 from the metastatic group and 11 from the non-metastatic group. There was an increase in inflammatory monocytes frequency in metastatic patients when compared to metastatic patients indicating a more favorable microenvironment for tumor metastasis. Moreover, it was found discovered a higher level of non-classic monocytes also known as patrolling monocytes, and TRAIL and IL-1Ra Cytokines in non-metastatic patients in compare with metastatic patients, indicating a more protective microenvironment. In conclusion, this study demonstrated immunological mechanisms related to metastasis in NSCLC patient suggesting helpful biomarker for prognosis and patient flow up

Bilateral metastases to the extraocular muscles from small cell lung carcinoma / Metástases bilaterais aos músculos extraoculares de um carcinoma de pequenas células do pulmão

ABSTRACT Bilateral orbital metastases restricted to the extraocular muscles (EOMs) are exceedingly rare. We report a case of bilateral extraocular muscle metastases from a small cell lung carcinoma and provide a review of the relevant literature. A 56-year-old smoker presented with proptosis, motility changes, and a relative afferent pupillary defect of the left eye, with a previous history of a small cell lung carcinoma. An orbital computerized tomography scan revealed a mass restricted to the left medial rectus. An incisional biopsy confirmed metastasis. Visual acuity of the left eye decreased rapidly, and right globe proptosis became evident. Orbital magnetic resonance imaging at two months follow-up showed marked left orbital mass enlargement and a new right lateral rectus mass. The patient was maintained on palliative care and died from metastatic disease-related complications.

RESUMO As metástases orbitárias bilaterais restritas aos mús­culos extraoculares são extremamente raras. Os autores apresentam um caso de metástases bilaterais, localizadas aos musculares extraoculares com base num carcinoma de pequenas células do pulmão e revisão da literatura relevante. Um homem, fumador, de 56 anos recorreu ao serviço de urgência por proptose, alterações de motilidade ocular extrínseca e um defeito pupilar aferente relativo do olho esquerdo, com história pessoal de carcinoma de pequenas células do pulmão. A tomografia computadorizada orbitária revelou uma massa restrita ao reto medial esquerdo. Uma biópsia incisional confirmou o diagnóstico de metástase. A acuidade visual do olho esquerdo diminuiu rapidamente e surgiu uma proptose do globo ocular direito. A ressonância magnética orbitária aos dois meses de seguimento revelou um aumento da massa orbitária esquerda e uma nova massa no reto lateral direito. O paciente foi mantido em cuidados paliativos e faleceu devido a complicações relacionadas com doença metastática.

Sudden onset acute liver failure in a patient with clinically occult small cell lung carcinoma: autopsy report and review of the medical literature

Liver metastases are commonly found in advanced cancer patients; however, acute liver failure secondary to diffuse liver infiltration is rare. Small cell lung carcinoma accounts for 15% of lung carcinomas. We describe the ninth case of small cell lung carcinoma massively metastatic to the liver, reported in the scientific literature, with sudden clinical onset and death after a few days. An autopsy was performed to understand the cause of death.

Small cell bladder cancer: should we consider prophylactic cranial irradiation?

ABSTRACT Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

Small cell lung cancer associated with multiple paraneoplastic syndromes / Cáncer de pulmón de células pequeñas asociado a múltiples síndromes paraneoplásicos

Abstracts We report the case of a patient presenting with multiple severe electrolyte disturbances who was subsequently found to have small cell lung cancer. Upon further evaluation, she demonstrated three distinct paraneoplastic processes, including the syndrome of inappropriate antidiuretic hormone, Fanconi syndrome, and an inappropriate elevation in fibroblast growth factor-23 (FGF23). The patient underwent one round of chemotherapy, but she was found to have progressive disease. After 36 days of hospitalization, the patient made the decision to enter hospice care and later she expired.

Resumen Se reporta el caso de una paciente que ingresó al hospital para evaluación de múltiples trastornos electrolíticos y, posteriormente, se le hizo el diagnóstico de cáncer de pulmón de células pequeñas. Tras la evaluación médica, se detectaron tres síndromes paraneoplásicos: síndrome de secreción inadecuada de hormona antidiurética, síndrome de Fanconi y elevación inapropiada del factor 23 de crecimiento de fibroblastos. Se le administró quimioterapia sin éxito, por lo cual se decidió darle tratamiento paliativo y, un tiempo después, falleció.

Pancreatitis aguda como primera manifestación de un carcinoma microcítico de pulmón / Metastasis-induced aAcute pancreatitis as the initial presentation of a small cell lung carcinoma

Las metástasis de cualquier origen son una causa muy infrecuente de pancreatitis aguda. Se presenta el caso de una paciente con un episodio de pancreatitis aguda como manifestación inicial de un carcinoma microcítico de pulmón metastásico. Es importante excluir la presencia de tumores malignos en aquellos casos de pancreatitis aguda sin agente etiológico claro para mejorar el pronóstico de estos pacientes. Se revisó la literatura al respecto.

Metastases of different any origin that induceare a rare cause of acute pancreatitis are not frequent. We report the case 5 of a patient with an acute pancreatitis episode as the initial manifestation of an extended small cell lung carcinoma. The exclusion of malignancy in cases of pancreatitis of unknown origin is clinically relevant to improve the prognosis of these patients. We review the A literature review on about this topic is also presented.

Cambios radiográficos después de radiocirugía/radioterapia estereotáctica corporal en cáncer de pulmón estadio I: reporte de caso / Radiographic changes after radiosurgery / stereotactic body radiotherapy in stage I lung cancer: case report

En la última década, la radioterapia estereotáctica corporal se ha implementado como tratamiento a pacientes con cáncer de pulmón estadio I, quienes son considerados inoperables o quienes rechazan el procedimiento quirúrgico. El artículo presenta el caso de uno de los primeros pacientes tratados con esta tecnología en un centro oncológico: un hombre de 72 años de edad con cáncer de pulmón estadio I, quien rechazó el manejo quirúrgico y se le realizó el tratamiento con radiocirugía, y con dos años de seguimiento, presentó cambios radiográficos, que inicialmente se interpretaron como progresión de la enfermedad. Además, se revisa la literatura relacionada con la interpretación de imágenes de seguimiento después del tratamiento.

Stereotactic radiotherapy body has been implemented in the last decade as a treatment for patients with stage I lung cancer, who are considered inoperable or who reject the surgical pro- cedure. For one of the first patients treated with this technology in our Cancer Center presented; 72 year old man with lung cancer stage I reject the surgical management and underwent radio- surgery treatment and for 2 years follow-up, presented radiographic changes, which were initially interpreted as disease progression. Additionally, a review of the literature related to image interpretation follow-up after treatment is done

Neuronopatía sensitiva: Su reconocimiento y tratamiento temprano / Sensory neuronopathy. Its recognition and early treatment

Las neuronopatías o ganglionopatías sensitivas, o enfermedades del ganglio dorsal, representan un subgrupo de enfermedades del sistema nervioso periférico, frecuentemente asociadas a trastornos disinmunes o paraneoplásicos, y a agentes tóxicos. Los pacientes típicamente presentan ataxia temprana, pérdida de los reflejos osteotendinosos y síntomas sensitivos positivos, presentes tanto en partes proximales como distales del cuerpo. Estudiamos retrospectivamente 10 casos con un diagnóstico final de neuronopatía sensitiva. El síntoma de presentación fue el de una neuropatía sensitiva de curso subagudo en todos los casos, con parestesias en el 100% de los casos. Otras manifestaciones fueron: hipoestesia (10/10), ataxia de la marcha (8/10), síntomas autonómicos (3/10) y parestesias periorales (3/10). La electrofisiología mostró un patrón de compromiso sensitivo axonal, con respuestas motoras normales. El diagnóstico final fue neuronopatía sensitiva adquirida en todos, asociada a síndrome de Sjögren en dos, a lupus eritematoso en uno, a artritis reumatoidea en uno, a cáncer en dos (paraneoplásica) e idiopática en cuatro. En los casos paraneoplásicos, los tumores fueron un carcinoma de pulmón de células pequeñas (con anticuerpos anti-Hu positivos) y un carcinoma epidermoide de pulmón. Ocho pacientes fueron tratados con inmunoterapia, con altas dosis de metilprednisolona endovenosa y/o con inmunoglobulina endovenosa; con pobre respuesta en cuatro casos, mejoría neurológica en cinco, y sin cambios en uno. El presente trabajo muestra el patrón clinico y electrofisiológico de las neuronopatías sensitivas subagudas, y la relevancia de un tratamiento temprano.

Sensory neuronopathies or ganglionopathies, or dorsal root ganglion disorders, represent a subgroup of peripheral nervous system diseases, frequently associated with dysinmune or neoplastic disorders and with toxic agents. A degeneration of both central and peripheral sensory proyections is present. Patients typically show early ataxia, loss of deep tendon reflexes and positive sensory symptoms present both in proximal and distal sites of the body. We retrospectively studied 10 cases with a final diagnosis of sensory neuronopathy. Sensory neuropathy was the presenting symptom and the course was subacute in all cases. Paresthesias in upper limbs were a predominant manifestation (100%). Other manifestations included: hypoesthesia (10/10), gait ataxia (8/10), autonomic symptoms (3/10) and perioral paresthesias (3/10). Electrophysiology showed sensory axonal neuronal pattern, with normal motor responses. Final diagnosis was acquired sensory neuronopathy in all patients, associated with Sjögren’s syndrome in 2, with lupus erythematosus in 1, with rheumatoid arthritis in 1, with a cancer in 2 (paraneoplastic) and idiopathic in 4. In paraneoplastic cases, the tumor was small cell lung cancer in 1 (with positive anti-Hu antibodies), and epidermoid lung cancer in the other. Eight patients were treated with immunotherapy, high dose intravenous methylprednisolone and/or intravenous immunoglobulin; with poor response in 4 cases, neurologic improvement in 5, and without any change in 1 patient. The present work shows the typical clinical and electrophysiological pattern of subacute sensory neuronopathy, and the relevance of early treatment.

Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; Pheterogeneity=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; Pheterogeneity=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; Pheterogeneity=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; Pheterogeneity=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer. .

Costo-efectividad de toracotomía versus videotoracoscopia en pacientes con cáncer de pulmón de célula no pequeña en estadio I / Cost-effective of thoracotomy versus videoassisted thoracoscopy in patients whith non-small-cell stage I carcinoma

Introducción. Los pacientes con cáncer de pulmón de célula no pequeña en estadio I, pueden someterse a videotoracoscopia o toracotomía. El objetivo de este estudio fue determinar la razón costo-efectividad de estas dos alternativas. Materiales y métodos. Se realizó un estudio de costo-efectividad mediante un modelo de árbol de decisiones extendido con un proceso de Markov desde la perspectiva del sistema de salud colombiano financiado públicamente, para comparar la videotoracoscopia con la toracotomía. Los resultados se midieron en años de vida ganados, obtenidos de revisiones sistemáticas de curvas de supervivencia. Se incluyeron costos médicos directos, obtenidos solamente de prestadores y aseguradores de tres ciudades principales de Colombia. El periodo de estudio fue de 10 años, con tasas de descuento de 3,5 % y 6 %. El modelo se evaluó usando la simulación de Montecarlo con 10.000 iteraciones. Resultados. Los costos totales medios esperados de la toracotomía y de la videotoracoscopia fueron de COP$ 22'831.299 (ICr95%: 22'773.228-22'889.370) y $ 16'955.369 (ICr95%: 16'920.215-16'990.523), respectivamente. Los años de vida ganados para toracotomía fueron 7,85 (ICr95%: 7,84-7,86) y para videotoracoscopia fueron 9,24 (ICr95%: 9,23-9,25). La toracotomía fue superada por la videotoracoscopia para disposiciones a pagar entre COP$ 15'000.000 y $ 45'000.000. Discusión. La videotoracoscopia superó a la toracotomía en el tratamiento de pacientes con cáncer de pulmón de célula no pequeña en estadio I, para diferentes disponibilidades por pagar en el sistema de salud colombiano.

Introduction: Patients with non-small cell lung cancer stage I may undergo VATS or open thoracotomy. The aim of this study was to determine the cost effectiveness of these two alternatives. Methods: A cost-effectiveness study was conducted by using a tree model with an extended Markov decision process. A perspective of public Colombian health system was adopted. The outcomes were measured in life-years saved, which were obtained from systematic reviews of survival analysis. The direct medical costs of providers and insurers of three cities in Colombia were included. The time horizon was 10 years with discount rates of 3.5% and 6%. The model was evaluated using Monte Carlo simulation with 10,000 iterations. Results: The expected average total costs of thoracotomy and thoracoscopy were COP $ 22.831.299 (95% ICr: 22.773.228-22.889.370) and $ 16.955.369 (95% ICr: 16.920.215-16.990.523) respectively. The number of saved life-years for thoracotomy were 7.85 saved LY (95% ICr: 7.84-7.86) and for VATS were 9.24 LYS (95% ICr: 9.23-9.25). The thoracotomy was dominated by VATS for willingness to pay between COP $ 15 million to $ 45 million. Discussion: The videothoracoscopy dominated open thoracotomy in the treatment of patients with non-small cell lung cancer stage I for different willingness to pay in the Colombian health system.

Biomarkers for screening of lung cancer and pre-neoplastic lesions in a high risk Chilean population

BACKGROUND: The mortality of lung cancer (LC), increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 µg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70) and Auto Fluorescence Bronchoscopy (AFB) might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL) and neoplastic lesions (NL). RESULTS: Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8%) and specificity (91.9%) than AQC. However, for PNL AQC showed a higher sensitivity (91.9%) than DR70 (27.3%), although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%). CONCLUSION: This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC. Supported by INNOVA-CORFO, Chile.

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer

OBJECTIVES: The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival. METHODS: We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxiainducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice. RESULTS: A significant difference (p=0.022) in hypoxia-inducible factor 1α expression was observed between nonsmall cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxiainducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p=0.001) when all types of lung cancer were examined, either collectively or separately. CONCLUSIONS: The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.

Dos casos de metástasis hipofisarias como forma de presentación de un carcinoma microcítico de pulmón / Two cases of pituitary metastases as initial presentation form of small cell lung cancer

Las metástasis en la silla turca son raras y se encuentran en muchas ocasiones incidentalmente o en necropsias. Solo un 7% de los casos son sintomáticos. Las manifestaciones clínicas más frecuentes son la diabetes insípida, la clínica compresiva y los síntomas derivados de déficit hormonales de la adenohipófisis. Se presentan los casos de 2 varones con un carcinoma microcítico de pulmón cuya manifestación clínica inicial correspondía a afectación metastásica de la silla turca. Un caso debutó con invasión del seno cavernoso y panhipopituitarismo, y el otro con una diabetes insípida. Ambos casos presentaron una rápida progresión de su enfermedad neoplásica, con escasa respuesta al tratamiento sistémico en uno de los casos y fueron éxitus a los pocos meses. Las metástasis hipofisarias se presentan con mayor frecuencia en mujeres con cáncer de mama y hombres con neoplasias de pulmón. La presencia de poliuria y polidipsia en un paciente oncológico debe hacer sospechar una diabetes insípida, siendo necesario un estudio de imagen de la silla turca. El tratamiento de estos tumores incluye la cirugía, la radioterapia, la quimioterapia y el tratamiento hormonal sustitutivo. A pesar que el tratamiento quirúrgico no se ha asociado a un aumento de la supervivencia, algunos pacientes pueden mejorar su calidad de vida.

Metastases in the sellar region are rare and are frequently found incidentally or in necropsies. Only 7% are reported to be symptomatic. Diabetes insipidus, anterior pituitary dysfunction, visual field defects, headache/pain and ophthalmoplegia are the most commonly reported symptoms. We present the cases of two male patients with a small-cell lung carcinoma whose first clinical symptoms were due to pituitary metastasis. One case presented with symptoms of cavernous sinus invasion and panhypopituitarism and the other case with diabetes insipidus. Both patients had a rapid progression of their disease despite chemotherapy and died after a few months. Pituitary metastases occur most commonly with breast cancer in women and lung cancer in men. The presence of polyuria and polydipsia in an oncologic patient should alert the physician for diabetes insipidus and, if confirmed, an imaging procedure of the pituitary gland is mandatory. Treatment for these tumors is often multimodal and includes surgery, radiation therapy, chemotherapy and hormone replacement. Although surgical series have not shown any significant survival benefits given by tumor resection, the patient’s quality of life may be improved.