Ovarian metastasis from colorectal adenocarcinoma / Metástase ovariana de adenocarcinoma colorretal

Introduction: Ovarian metastases of gastrointestinal origin, also called Krukenberg tumors, have a guarded prognosis. Physicians need to look for alternatives in diagnosis and treatment for this clinical condition in order to improve the outcome of the patients. Objectives: To report the experience of the authors in the treatment of these patients, and to perform a review of the literature on the epidemiology, clinical presentation, diagnosis, treatment, and prognosis for ovarian metastases from colorectal cancer. Methods: We collected clinical information regarding the patients treated for ovarian metastasis from colorectal adenocarcinoma at our coloproctology service, and performed a search on the PubMed database using the terms colorectal cancer, ovarian metastasis, Krukenberg tumor and surgery. Conclusion: Large abdominal tumors are the most frequent presentation of ovarian metastasis from colorectal cancer. The diagnosis is based on a histopathological analysis, levels of carcinoembryonic antigen (CEA) and cancer antigen 125 (CA-125), and immunohistochemical studies for the cytokeratin 20 (CK20), caudal-type homeobox 2 (CDX2) and vilina markers. Citoreductive surgical procedures are the most promising approach to treatment, with the highest impact on overall survival. The prognosis is negatively influenced by the extent of the metastasis, by citoreductive surgical procedures with persistence of macro- or microscopic foci of the disease, and by low scores on the general well-being index of the patient. (AU)

Introdução: As metástases ovarianas de tumores gastrointestinais, também chamadas de tumores de Krukenberg, são neoplasias de prognóstico reservado. Exigem conhecimento de alternativas diagnósticas e terapêuticas para garantir melhora da sobrevida das pacientes. Objetivos: Relatar a experiência dos autores no tratamento dessas pacientes, e fazer uma revisão da literatura sobre a epidemiologia, apresentação clínica, diagnóstico, tratamento e prognóstico das metástases ovarianas do câncer colorretal. Métodos: Foi realizada uma coleta de informações clínicas de pacientes tratados por metástases ovarianas de adenocarcinoma colorretal em nosso serviço de coloproctologia, em conjunto com uma pesquisa na base de dados PubMed com os termos colorectal cancer, ovarian metastasis, Krukenberg tumor, e surgery. Conclusão: Volumosas massas abdominais constituem a principal apresentação clínica da doença. As alternativas diagnósticas incluem a avaliação histopatológica, a identificação dos níveis de antígeno cárcino-embriônico (ACE) e de antígeno de câncer 125 (CA-125), e exame imunoistoquímico de espécimes cirúrgicos para os marcadores citoqueratina 20 (CK20), homeobox 2 do tipo caudal (CDX2), e vilina. O tratamento citorredutor completo demonstrou o maior impacto na sobrevida dos pacientes. O prognóstico é influenciado negativamente pela extensão da doença metastática, por cirurgia citorredutiva com persistência focos microscópicos ou macroscópicos da doença, e baixo escore de índice de bem-estar geral do paciente. (AU)

Immunhistochemical analysis of Nuclear Factor Kappa Beta expression in etiopathogenesis of ovarian tumors

Abstract Purpose: To investigate the place of the transcription factor nuclear kappa B (NF-kB), which is a marker of chronic inflammation, in the etiology of the ovarian carcinoma. Methods: NFkB analysis with the immunohistochemical method has been performed. To evaluate immunohistochemical NF-kB expression in the ovarian tissue, the H-score method. H-score = ∑ Pi (i+1), where ''Pi'' is the percentage of stained cells in each intensity category (0-100%) and ''i'' is the intensity indicating weak (i=1), moderate (i=2) or strong staining (i=3). Results: It has been seen that, the mean H score is statistically significantly higher in the patient group with serous and musinous adenocarcinoma diagnosis than the two other patient groups (p<0.005). Conclusions: Factor nuclear kappa B is an important mediator that acts in the chronic inflammation. The highest expression rates are determined by the immunohistochemical method in the ovarian cancer group.

Estruma ovárico asociado con enfermedad de graves / Struma ovarii associated with Graves' disease

El hipertiroidismo se define como la producción excesiva de hormonas tiroideas a partir de tejido tiroideo maduro eutópico o ectópico. La prevalencia general de hipertiroidismo es 1.2%, y la causa más frecuente es la enfermedad de Graves. El estruma ovárico representa el 1% de todos los tumores ováricos y es una causa infrecuente de hipertiroidismo ectópico. Su comportamiento es benigno en más del 90% de los casos; usualmente asintomáticos, sólo el 8% se presentan con tirotoxicosis, y es infrecuente su asociación con enfermedad de Graves. Se comunica el caso de una paciente con esta infrecuente asociación.

Hyperthyroidism is defined as an excessive production of thyroid hormones by eutopic or ectopic mature thyroid tissue. The overall prevalence of hyperthyroidism is 1.2% and the most common cause is Graves' disease. Struma ovarii represents 1% of all ovarian tumors and is an uncommon cause of ectopic hyperthyroidism. It is benign in >90% of the cases; usually asymptomatic, and only 8% are presented with thyrotoxicosis, being rare its association with Graves' disease. We report the case of a patient with this association.

Cáncer serosopélvico de alto grado: evidencia sobre su origen en la trompa de Falopio / High-grade serous pelvic cancer: evidence of its origin in the fallopian tube

Cáncer epitelial de ovario es una enfermedad altamente letal. Constituye la quinta causa de muerte por cáncer en mujeres a nivel mundial. El subtipo histológico más frecuente es el carcinoma seroso de alto grado. Este es el responsable de la alta letalidad de la enfermedad. Se presenta evidencia que respalda el origen tubario de este tipo histológico desde lesiones precursoras. A partir de estos datos se ha establecido que el cáncer tradicionalmente conocido como cáncer ovárico seroso de alto grado, el cáncer de trompa de Falopio y el carcinoma peritoneal primario, corresponden a una misma entidad nosológica: cáncer seroso pélvico de alto grado. Se revisa además la evidencia disponible para establecer que la salpingectomía podría constituir una medida de prevención para este tipo de cáncer.

Epithelial ovarian cancer is a highly lethal disease. It is the 5th cause of cancer death in women worldwide. The most common histologic subtype is the high-grade serous carcinoma. This is the responsible for the high lethality of the disease. Evidence supporting the tubal origin of this histological type from precursor lesions is presented. From these data it has been established that cancer traditionally known as serous high-grade ovarian cancer, cancer of the fallopian tube and primary peritoneal carcinoma, correspond to a single disease entity: pelvic serous high-grade cancer. We also check the available evidence to establish that the salpingectomy could be a preventive measure for this type of cancer.

Outcomes of carotid artery stenting at a high-volume Brazilian interventional neuroradiology center

OBJECTIVES: Carotid artery stenting is an emerging revascularization alternative to carotid endarterectomy. However, guidelines have recommended carotid artery stenting only if the rate of periprocedural stroke or death is < 6% among symptomatic patients and < 3% among asymptomatic patients. The aim of this study is to evaluate and compare clinical outcomes of symptomatic and asymptomatic patients who had undergone carotid artery stenting as a first-intention treatment. METHOD: A retrospective analysis of patients who underwent carotid artery stenting by our interventional neuroradiology team was conducted. Patients were divided into two groups: symptomatic and asymptomatic patients. The primary endpoints were ipsilateral ischemic stroke, ipsilateral parenchymal hemorrhage and major adverse cardiac and cerebrovascular events at 30 days. The secondary endpoints included ipsilateral ischemic stroke, ipsilateral parenchymal hemorrhage, ipsilateral transient ischemic attack and major adverse cardiac and cerebrovascular events between the 1- and 12-month follow-ups. RESULTS: A total of 200 consecutive patients were evaluated. The primary endpoints obtained in the symptomatic vs. asymptomatic groups were ipsilateral stroke (2.4% vs. 2.7%, p = 1.00), ipsilateral parenchymal hemorrhage (0.8% vs. 0.0%, p = 1.00) and major adverse cardiac and cerebrovascular events (4.7% vs. 2.7%, p = 0.71). The secondary endpoints obtained in the symptomatic vs. asymptomatic groups were ipsilateral ischemic stroke (0.0% vs. 0.0%), ipsilateral parenchymal hemorrhage (0.0% vs. 0.0%), ipsilateral TIA (0.0% vs. 0.0%, p = 1.00) and major adverse cardiac and cerebrovascular events (11.2% vs. 4.1%, p = 0.11). CONCLUSIONS: In this retrospective study, carotid artery stenting was similarly safe and effective when performed as a first-intention treatment in both symptomatic and asymptomatic patients. The ...

Asociación entre obesidad y cáncer de ovario / Association between obesity and ovarian cancer

Obesity is a risk factor for cancer. Epidemiological evidences associate ovarian cancer with obesity. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and accounts for a high rate of mortality. The association between ovarian cancer and obesity could be explained by molecular factors secreted by adipose tissue such as leptin. In EOC, leptin increases cell proliferation and inhibits apoptosis. Additionally, adipose tissue synthesizes endogenous estrogens, which increase cell proliferation of epithelial ovarian cells. Also, obesity associated hyperinsulinism could increase ovarian estrogen secretion.

A Huge Mucinous Cystadenoma Complicating Third Trimester of Pregnancy with Previous Two Caesarean Sections.

The incidence of ovarian tumor complicating caesarean section was about 1 in 200 caesarean births while ovarian tumors complicated termination of pregnancy in 1 of 594 procedures. Any type of Ovarian mass can be encountered during pregnancy, but the most common are cystic. Because pregnant women are usually young, malignant tumors are relatively uncommon. A patient third gravida with previous 2 caesarean sections presented in an emergency with complaints of persistent pain in abdomen for last 7 days with gestational age of 35 weeks and 3 days. Emergency Caesarean section was done to deliver an alive male baby of 2.25 Kg with good Apgar score. Intraoperative finding was suggestive of a huge multiloculated left ovarian mass of approximately. 40×30×15 cm weighing 20 Kg with straw coloured mucinous fluid. Up to 3 liters of fl uid aspirated before delivering the cyst out of the abdomen. Left salpingoopherectomy was done and specimen sent for histopathological examination that showed Mucinous cystadenoma of the ovary. Post operative period remain uneventful.

Correlación ultrasonográfica e histopatológica de los tumores de ovario / Ultrasonography and pathologic histology correlation of ovarian tumors

OBJETIVOS: demostrar el valor del ultrasonido en el diagnóstico de los tumores de ovario, describir desde el punto de vista sonográfico las características de las masas ováricas de acuerdo con su estructura y tamaño. Identificar su probable naturaleza benigna, maligna o dudosa, por la descripción sonográfica. Analizar cómo se comporta la frecuencia de las distintas variedades histopatológicas.MÉTODOS: se revisaron las historias clínicas del archivo del Hospital "Clínico Quirúrgico 10 de Octubre", en los últimos 5 años, de todas aquellas pacientes que habían sido operadas por tener un diagnóstico clínico-ultrasonográfico de una masa anexial y el resultado histopatológico fue un tumor de ovario. RESULTADOS: los tumores malignos se observaron con mayor frecuencia en edades por encima de 60 años. Hubo una alta correlación de pacientes con quistes simples y quistes con tabiques finos y ecos e informe anatomopatológico benigno.CONCLUSIONES: la presentación ultrasonográfica de los tumores malignos más frecuentemente encontrada fue la compleja a predominio ecolúcido y la compleja a predominio ecogénico. La mayoría de los tumores malignos tuvieron diámetro mayor de 10 cm. En la serie de los tumores benignos la variedad histológica más frecuente fue el cistoadenoma seroso y en la de los malignos el cistoadenocarcinoma seroso. El ultrasonido presentó una alta sensibilidad, especificidad y valor predictivo positivo

OBJECTIVE: to demonstrate the ultrasound (US) value in ovarian tumors diagnosis, to describe from the sonography point of view, the features of ovarian masses according to its structure and size, to identify its probable benign, malignant or doubtful origin by sonography description. To analyze how is the behavior of different pathologic histology varieties. METHODS: medical records from the "10 de Octubre" Clinical Surgical Hospital files over past 5 years of all patients operated on with a clinical-ultrasonography diagnosis of an adnexal mass where the histopathology results was a ovarian tumor. RESULTS: The malignant tumors were more frequent in ages over 60 years. There was a high correlation of patients presenting single cysts and thin septa and echoes and a benign anatomic-pathologic report. CONCLUSIONS: the more frequent ultrasonography presentation of malignant tumors was of complex type with echo-lucid predominance and the complex one with echogenic predominance. Most of malignant tumors had a diameter over 10 cm. In the benign tumor series the more frequent histological variety was the serous cystoadenoma and in that of malignant ones the serous cystoadenocarcinoma. Ultrasound had a high sensitivity, specificity and a positive predictive value

Edema maciço de ovário / Massive ovarian edema

O edema maciço de ovário é uma condição benigna rara caracterizada pelo aumento tumoral símile do ovário comprometido. As doenças ovarianas de importância cirúrgica da infância não são frequentes e podem ser divididas em lesões neoplásicas, em cistos não neoplásicos e em alterações inflamatórias. Os autores descrevem um caso de edema maciço de ovário em uma paciente de treze anos que referia dor abdominal associada a uma lesão sólido-cística do ovário direito, avaliada como neoplasia pela ultrassonografia. Ao exame macroscópico, o ovário era bocelado e estava aumentado de volume, medindo 9,5×6,0×5,0 cm e apresentando uma lesão sólida com áreas císticas à superfície de corte. O aspecto microscópico fundamental desse processo era a presença de edema acentuado e difuso do estroma, envolvendo folículos, e associado a uma camada cortical com espessamento fibroso superficial. O conhecimento dessa entidade é fundamental para auxiliar no diagnóstico durante a avaliação ultrassonográfica de tumores ovarianos e prevenir tratamentos incorretos.

Massive ovarian edema is a rare benign condition characterized by similar tumor growth of the affected ovary. The ovarian disorders of surgical importance of childhood are not frequent and can be divided into neoplastic lesions, non-neoplastic cysts, and inflammatory alterations. Here the authors describe the case of a massive ovarian edema in a 13-year-old female patient who reported abdominal pain associated with a solid-cystic lesion of the right ovary evaluated as a neoplasm by ultrasonography. The macroscopic examination showed ovary with increased volume, measuring 9.5×6.0×5.0 cm, and presenting a solid lesion with cystic areas at the cutting surface. The key microscopic feature of this process was the presence of pronounced diffuse edema of the stroma, involving follicles and associated with a cortical layer with superficial fibrous thickening. Knowledge of this entity is key in aiding the diagnosis during the ultrasonographic evaluation of ovarian tumors and preventing improper treatments.

Carcinogénesis de ovario, antecedentes endócrinos y reproductivos / Development of epithelial ovarian cancer

La etiología y los eventos precoces en el desarrollo y progresión del cáncer epielial del ovario se hallan enre los menos comprendidos de odos los tumores que afectan a la especie humana. Una de las razones para ello es que la mayoría de las veces se diagnosican en estadios avanzados, donde la posibilidad de estudiar su desarrollo se hace prácticamente imposible. El objetivo de este resumen es presentar algunos problemas especiales y las limitaciones que han impedido el proceso de comprensión de su carcinogénesis. Es por ello que en primer lugar se presentan los conocimientos epidemiológicos, y luego el estado actual de las investigaciones experimentales en cultivo de tejidos del epitelio superficial del ovario, origen de los mismos.

Turner syndrome: counseling prior to oocyte donation

Ovarian failure is a typical feature of Turner syndrome (TS). Patients are followed clinically with hormone replacement therapy (HRT) and inclusion in the oocyte donation program, if necessary. For patients with spontaneous puberty, genetic counseling regarding preimplantation genetic diagnosis and prenatal diagnosis is indicated. Patients with dysgenetic gonads and a Y chromosome are at increased risk of developing gonadoblastoma. Even though this is not an invasive tumor, its frequent association with other malignant forms justifies prophylactic gonadectomy. It is important to perform gonadectomy before HRT and pregnancy with oocyte donation. Among patients with TS stigmata and female genitalia, many have the Y chromosome in one of the cell lines. For this reason, all patients should undergo cytogenetic analysis. Nevertheless, in cases of structural chromosomal alterations or hidden mosaicism, the conventional cytogenetic techniques may be ineffective and molecular investigation is indicated. The author proposes a practical approach for investigating women with TS stigmata in whom identification of the X or Y chromosome is important for clinical management and follow-up.

A falência ovariana é um achado típico da síndrome de Turner (ST). As pacientes podem ser submetidas à terapia de reposição hormonal (TRH) e incluídas em programas de doação de oócito, quando necessário. Para as pacientes com puberdade espontânea, está indicado o aconselhamento genético para a futura descendência abordando os diagnósticos genéticos pré-natal e pré-implantação. Pacientes com gônadas disgenéticas e cromossomo Y apresentam risco aumentado para desenvolvimento de gonadoblastoma. Embora esse tumor não seja invasivo, sua associação freqüente com tumores malignos justificaria a gonadectomia profilática. Entre as pacientes com estigmas da ST e genitália feminina, muitas apresentam cromossomo Y em pelo menos uma linhagem celular. Por essa razão, todas as pacientes devem ser submetidas à análise citogenética, para a realização de cirurgia antes do início da TRH e da gravidez com doação de oócito. No entanto, em casos de alteração cromossômica estrutural ou mosaicismo críptico, as técnicas citogenéticas convencionais podem não ser efetivas, estando indicada a investigação molecular. Uma abordagem prática para o médico investigar as pacientes com ST é proposta neste artigo, devido à importância da identificação do cromossomo Y ou de um segundo cromossomo X para o manejo clínico e o acompanhamento das pacientes.

Repeatability of self-reported information for population-based studies of cancer.

PURPOSE: To measure the repeatability of a cancer risk factor questionnaire in a population-based case-control study. METHODS: Questionnaires were completed on two occasions by patients with cancer of the ovary (n=25) or esophagus (n=23) and by 37 controls without cancer. We assessed general cancer risk factors including height and weight (for calculating body mass index (BMI)), smoking and anti-inflammatory (NSAID) use. Risk factors specific for ovarian and esophageal cancers were also assessed. Agreement was measured by the correlation coefficient and weighted kappa statistic (kw) for continuous and categorical variables respectively. RESULTS: We observed very high levels of agreement for BMI (kw=0.84) and smoking history, including ages at initiation and quitting (Pearson correlation = 0.87 and 0.86 respectively). There was moderate to substantial agreement for use of anti-inflammatory drugs (aspirin kw =0.52, other NSAIDS kw =0.72). Agreement for lifetime prevalence of medical conditions varied from almost perfect (e.g. history of benign breast disease (k =0.86)) to moderate (e.g. heartburn (k =0.57)). Item repeatability was not materially altered by case-control status, age or sex of respondents or interval between completions. CONCLUSIONS: Self-reported cancer risk factor information demonstrates moderate to almost perfect levels of agreement, suggesting these items are suitable for risk estimation and epidemiologic inference.

Recurrent endocervical-like mucinous borderline tumor (ELMBT) arising in a case of long-standing endometriosis--a case report.

Endometriosis is a well-known precursor lesion of ovarian malignancies, particularly those of endometrioid and clear-cell types and rarely of serous or mucinous types. The association of endometriosis with mucinous borderline tumors also varies. This case is of a 60 year old female, who had a long history of more than thirty years of endometriosis and developed recurrent endocervical-like mucinous borderline tumor (ELMBT) in endometriotic foci. This case highlights challenges in the management of such complications associated with endometriosis and emphasizes the importance of long-term follow-up in cases of endometriosis.

Neoplasias associadas à síndrome dos ovários policísticos / Polycystic ovary syndrome associated neoplasms

A síndrome dos ovários policísticos (PCOS) é a endocrinopatia mais comum em mulheres em idade reprodutiva, caracterizada pela presença de anovulação, infertilidade e hiperandrogenismo, e freqüentemente associada à obesidade e resistência insulínica. Postula-se que, a longo prazo, estas pacientes possam apresentar maior risco de neoplasias do trato reprodutivo como carcinoma (CA) de endométrio, mama e ovário. Um risco aumentado de hiperplasia e CA endometrial nessas pacientes tem sido demonstrado em vários estudos, embora seja reconhecido que a variabilidade dos critérios de seleção para o diagnóstico de PCOS em alguns destes estudos limite o valor dos dados. Apesar das pacientes com PCOS apresentarem características clínicas associadas com um aumento de risco de CA de mama, até o momento não foi possível relacionar com certeza a presença da síndrome per se com maior prevalência desta neoplasia. Finalmente, quanto ao CA do ovário, considera-se que altas concentrações locais de hormônios esteróides e fatores de crescimento representam fatores de risco para esta neoplasia. Apesar destas alterações serem comumente observadas nas pacientes PCOS não tratadas ou em tratamento para infertilidade, ainda são poucos os estudos que avaliam uma possível relação entre PCOS e CA de ovário, mas seus resultados, embora conflitantes, sugerem ausência de associação.

Gonadal Tumors Developed from Consecutively Transplanted Spleens Bearing Gonad Implants

This study was conducted by consecutively transplanting spleens, which had gonads implanted previously. A total of 84 cases for infantile testicles and 106 cases for ovarian follicles were performed. In the case of ovarian implants, the results were determined by the total number of follicle implants. A modified spleen transplantation technique called double implantation of ovarian follicles was applied to increase the amount of the implants. In this technique, an extra spleen is implanted into the potential donor so that the ovarian follicles can be implanted to two different spleens, doubling the amount of implants. Through consecutive spleen transplantation, we observed the results beyond a typical rat's life span. In many of these cases, we found more aggressive forms of malignant tumor, seminoma and dysgerminoma. We present the results and discuss possible pathogenic mechanisms of tumor formation.

Old Abdominal Pregnancy Presenting as an Ovarian Neoplasm

Abdominal pregnancy is extremely rare, but even more unusual is the prolonged retention of an advanced abdominal pregnancy with lithopedion formation. The presentation of lithopedion as an ovarian tumor without a symptom has not been reported in Korea. A 63-yr-old, gravida 2, para 1, woman was referred to us with an abominal mass. Pelvic examination revealed normal postmenopaused uterus and a fetal head-sized movable hard mass in the lower abdomen. The computed tomographic scan showed a densely echogenic mass of 10-cm in diameter as an ovarian neoplasm. Laparotomy disclosed a lithopedion, of which the bones and cartilages were well preserved. There have been controversies on the treatment of lithopedion. Although some cases are stable for a long time, the morbidity increases when the operation is performed in an elderly patient. So we believe that the surgical intervention should be done as soon as possible after thorough consideration of the morbidity and the risk.

Tumor de senos endodérmicos del ovario con patrón hepatoide predominante y metástasis a hígado / Tumor of endodemic ovarian sinus with prevailing hepatoid pattern and liver metastasis

Se presenta el caso de una mujer de 16 años de edad, con tumor de senos endodérmicos del ovario derecho, macroscópicamente sólido y con patrón histológico de crecimiento predominantemente de tipo hepatoide. Este tumor cursó con metástasis masivas a hígado y ascitis, lo que planteó el diagnóstico diferencial de tumor de senos endodérmicos de tipo hepatoide con metástasis a hígado o carcinoma hepatocelular con metástasis a ovario, o bien un carcinoma hepatoide del ovario. Se considera que éste es el primer caso en los archivos de la Unidad de Patología del Hospital General, en el que un tumor de senos endodérmicos presenta un patrón hepatoide tan extenso.

Dermatomiosite - expressao paraneoplasica do cancer de ovario / Dermatomyositis - paraneoplastic expression of the ovarian cancer

Ha algumas afeccoes cutaneas que podem estar associadas com tumores viscerais. Sao as chamadas afeccoes paraneoplasicas. A dermatomiosite esta incluida neste grupo. E propria de adultos e associa-se mais frequentemente com carcinoma broncogenico, adenocarcinoma de mama, ou ovario, e em menor grau, com outros tumores, inclusive linfomas. O caso que relatamos corresponde a uma paciente de 68 anos sem antecedentes familiares, nem pessoais a destacar que, em progressiva, apenas 4 meses de evolucao, levando nos 2 ultimos a prostracao e disfagia, e com achados clinico-radiologicos sugestivos de neoplasia maligna de ovario em etapa avancada. Foi submetida a histerectomia total + anexectomia bilateral + linfadenectomia pelvica + omentectomia com diagnostico anatomopatologico de carcinoma indiferenciado de ovario

Resultado de la aplicación del protocolo de manejo de pacientes con cáncer de ovario en el Hospital Universitario del Valle en el período Enero 94 - Diciembre 97

Para asegurar el cumplimiento de los protocolos establecidos en el manejo de las pacientes oncológicas es indispensable una concienca colectiva de apoyo de todos los estamentos que directa o indirectamente rodean al paciente; permitiendo que se cumplan cada uno de los objetivos indispensables para poder llegar a un beneficio común el cual no es otro que la calida de vida del paciente