Enfermedad de Zuska: fístula crónica mamaria infrecuente / Zuska disease: An uncommon chronic fístula of the breast

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Portadoras de mutaciones en BRCA1 y 2 en familias de alto riesgo del área de Ciudad Real (España): prevalencia mutacional y características clínico-patológicas del cáncer de mama y ovario / Carriers of BRCA1 and 2 mutations in high-risk families from Ciudad Real (Spain): mutational prevalence and clinical-pathological characteristics of breast and ovarian cancer

Objetivo: Determinar la prevalencia mutacional en BRCA1 y 2 de mujeres afectas por cáncer de mama/ovario en el área de Ciudad Real y describir las características clinicopatológicas de dichas neoplasias. Pacientes y métodos: Estudio descriptivo. Se evaluaron 111 pacientes de familias de alto riesgo y se analizaron los antecedentes oncológicos, familiares y las mutaciones halladas en BRCA1 y 2. Resultados: La prevalencia de mutaciones patogénicas en BRCA fue del 21,6% (16 en BRCA2 y 8 en BRCA1). En las portadoras de mutaciones en BRCA1 predominó el cáncer de mama: 10 casos (90,9%), tipo ductal infiltrante: 8 (72,7%), estadioII: 6 (54,5%), luminalA: 4 (36,4%), triple negativo: 4 (36,4%) y grado histológico2: 3 (27,3%) y3: 3 (27,3%). Las portadoras de mutaciones en BRCA2 desarrollaron cáncer de mama en 16 casos (80%), tipo ductal infiltrante: 11 (55%), estadioII: 11 (55%), luminalA: 10 (50%) y grado histológico2: 5 (25%). Conclusiones: En nuestro análisis, la prevalencia de mutaciones en BRCA2 fue superior a la registrada en BRCA1, en correspondencia con algunos estudios previos nacionales. Las características clinicopatológicas de los cánceres de mama/ovario en las portadoras de estas mutaciones fueron similares al perfil descrito en la literatura

Objective: To determine the mutational prevalence in BRCA1 and 2 among women with breast/ovarian cancer in Ciudad Real and to describe the clinical-pathological characteristics of these neoplasms. Patients and methods: Descriptive study. A total of 111 patients from high-risk families were evaluated and the oncological history, family history, and BRCA1 and 2 mutations found were analysed. Results: The prevalence of pathogenic mutations in BRCA was 21.6% (16 in BRCA2 and 8 in BRCA1). In BRCA1 mutations, breast cancer was predominant: 10 cases (90.9%), infiltrating ductal type: 8 (72.7%), stageII: 6 (54.5%), luminalA: 4 (36.4%), triple negative: 4 (36.4%) and histological grade2: 3 (27.3%) and3: 3 (27.3%). Among BRCA2 mutation carriers, 16 (80%) developed breast cancer: infiltrating ductal type: 11 (55%), stageII: 11 (55%), luminalA: 50% (10) and histological grade2: 5 (25%). Conclusions: In our analysis, the prevalence of mutations was higher in BRCA2 than in BRCA1, in agreement with some previous national studies. The clinical-pathological characteristics of breast/ovarian cancer in the carriers of these mutations were similar to the profile described in the literature

Extended use of bemiparin as thromboprophylaxis during bariatric surgery: results of anti-factor Xa activity measurements.

BACKGROUND: The incidence of venous thromboembolism (VTE) in morbidly obese patients after obesity surgery is between .2% and 3.5%. Because there are a lack of prospective studies on the type of drug, the correct dosage, and the optimal duration, there are no specific recommendations found in the guidelines on thrombophylaxis. OBJECTIVES: To compare the incidence of VTE and hemorrhagic events in bariatric surgical patients receiving bemiparin thromboprophylaxis who have prophylactic and nonprophylactic Anti-factor Xa (AFXa) levels. SETTING: University General Hospital of Ciudad Real, Spain, public practice. METHODS: A cohort study of 122 morbidly obese patients who underwent bariatric surgery. The thromboprophylactic regimen consisted of bemiparin 5000 IU/24 hr for 30 days. AFXa levels were measured on the second and third day postoperation (prophylactic range: .3-.5 IU/mL). Body mass index, co-morbidities, prothrombotic risk factors, and thrombotic and hemorrhagic events were noted. RESULTS: The mean body mass index was 48.4 kg/m2. In 50 samples, the level of AFXa was within the prophylactic range; in 71, they were in the subprophylactic range. No VTEs were observed. Major hemorrhagic events were observed in 2.4%. We did not find a significant association between AFXa and thromboembolic and hemorrhagic events. There is a significant negative correlation between the level of AFXa and body mass index. CONCLUSION: A regimen of 5000 IU/24 hr of bemiparin for 30 days after obesity surgery appears to prevent VTE without increasing the risk of a major hemorrhage. The level of AFXa is not associated with postoperative thrombotic or hemorrhagic events occurring after bariatric surgery.

Tratamiento quirúrgico ambulatorio del cáncer de mama. Experiencia en el Hospital General de Ciudad Real / Breast cancer ambulatory surgery. Experience at General Hospital in Ciudad Real

Objetivo. Describir la casuística de pacientes con diagnóstico de cáncer de mama intervenidas en el Hospital General Universitario de Ciudad Real mediante un programa de cirugía mayor ambulatoria (CMA). Pacientes y método. Estudio descriptivo retrospectivo donde se presenta la serie de pacientes del Hospital General de Ciudad Real con diagnóstico de cáncer de mama e intervenidas quirúrgicamente en el periodo comprendido entre el 1 de enero de 2010 y el 1 de febrero de 2011. Resultados. Se intervinieron un total de 130 pacientes; de ellas, un 20% se consideraron larga estancia, un 32,3% corta estancia y un 47,7%, CMA. En el 69,4% de los casos, las técnicas quirúrgicas más asociadas a CMA fueron cirugías conservadoras. Conclusiones. La cirugía del cáncer de mama es factible en programas de cirugía mayor ambulatoria, con criterios establecidos de selección de pacientes. Las técnicas conservadoras fueron las más empleadas en nuestro programa (AU)

Objective. To describe the series of patients diagnosed with breast cancer that went to the operation room in the Ambulatory Surgery Program in the University General Hospital of Ciudad Real. Patients and methods. Retrospective descriptive study of patients diagnosed of breast cancer in University General Hospital of Ciudad Real and had been operated between 01-01-2010 to 01-02-2011. Results. 130 patients were analyzed. 20% were considered long stay more than 72 hours, 32,3% were short stay and 47,7% were ambulatory surgery. Conservative surgery were performed in 69,4% of all the cases included. Conclusion. Breast cancer surgery is feasible in ambulatory surgery programs with patients selection criteria. Conservative techniques were the most common surgery in our program (AU)

[Amyand's hernia: a report of two cases and review of the bibliography]. / Hernia de Amyand: presentación de dos casos y revisión de la bibliografía.

BACKGROUND: Presence of the vermiform appendix in an inguinal hernia sac is an uncommon finding (1%), exceptionally rare if it's inflamed (0.13%). Clinically simulating incarcerated inguinal hernia and proper preoperative diagnosis is exceptional. We present two unusual cases of Amyand's hernia, and review of the bibliography. CLINICAL CASES: 1. Male patient 78 year old with an incarcerated right inguinal hernia which was performed preoperatively the diagnosis of Amyand's hernia by abdominal Computed Tomography. Clinical case 2. Female patient 82 year old with symptoms of an incarcerated right femoral hernia that finally showed an Amyand's hernia through a right inguinal hernia. CONCLUSIONS: Amyand's hernia is a rare entity whose preoperative diagnosis is uncommon, that it should always be considered in the differential diagnosis in cases with clinical signs of incarcerated right inguinal hernia.

Antecedentes: encontrar el apéndice vermiforme en un saco herniario inguinal es un hallazgo infrecuente (1%), excepcionalmente raro si está inflamado (0.13%). Clínicamente simula una hernia inguinal incarcerada y el diagnóstico preoperatorio adecuado se establece en contadas excepciones. Se reportan dos casos excepcionales de hernias de Amyand y se revisa la bibliografía. Casos clínicos: 1. Paciente masculino de 78 años con una hernia inguinal derecha, incarcerada, en el que el diagnóstico de hernia de Amyand se estableció antes de la cirugía mediante tomografía computada abdominal. Caso clínico 2. Paciente femenina de 82 años de edad, con clínica de hernia crural derecha incarcerada con una hernia de Amyand a través de una hernia inguinal derecha. Conclusiones: la hernia de Amyand es una rara enfermedad cuyo diagnóstico preoperatorio es infrecuente y que siempre debe considerarse en el diagnóstico diferencial en los casos con signos clínicos de hernia inguinal derecha incarcerada.

Endometriosis de localización extraovárica. Nuestra casuística en 10 años / Extraovarian endometriosis. Our 10-year casuistics

Introducción. La endometriosis es una enfermedad ginecológica cuya prevalencia oscila alrededor del 5-10% de las mujeres. La localización es pélvica en la mayoría de los casos; sin embargo, en un pequeño grupo de pacientes, puede presentarse en regiones diferentes de esta. Material y métodos. Estudio descriptivo, observacional y retrospectivo de las historias clínicas de 26 pacientes intervenidas quirúrgicamente de endometriosis de localización extraovárica en el Hospital General Universitario de Ciudad Real en el período comprendido entre enero del 2003 y enero del 2013. Resultados. Nuestra serie consta de 26 pacientes intervenidas de endometriosis de localización extraovárica. Las localizaciones, por orden de frecuencia, fueron: pared abdominal, ombligo, vulva, apéndice, íleon, saco herniario y colon. Discusión. La localización extrapélvica de la endometriosis se presenta con muy baja frecuencia. El tratamiento quirúrgico es la elección, llevando a cabo una resección con márgenes suficientes que permitirá reducir las posibilidades de recidiva (AU)

Introduction. Endometriosis is a gynecological disease with a prevalence of about 5% to 10% of women. Localization is usually pelvic but in a small group of patients the disease can be localized elsewhere. Material and methods. We performed a descriptive, observational and retrospective study of the medical records of 26 patients treated surgically for extraovarian endometriosis at the University General Hospital of Ciudad Real between January 2003 and January 2013. Results. Our series included 26 patients who underwent surgery for extraovarian endometriosis. In order of frequency, the locations were the abdominal wall, umbilicus, vulva, appendix, ileum, hernia sac and colon. Discussion. The frequency of extrapelvic endometriosis is very low. The treatment of choice is surgery. Resection with adequate margins reduces the chances of recurrence (AU)

Determinación rápida intraoperatoria de la paratirina intacta en la cirugía del hiperparatiroidismo primario. La experiencia en nuestro centro / Rapid intraoperative determination of intact parathyroid hormone during surgery for primary hyperparathyroidism. Experience at our center

INTRODUCCIÓN: El hiperparatiroidismo primario (HPTP) se debe a un adenoma único en el 85-95% de las ocasiones, lográndose frecuentemente la curación con la extirpación del mismo. La determinación rápida intraoperatoria de la paratirina intacta (PTHio) puede constituir una herramienta para el control de la efectividad de la cirugía del HPTP. El objetivo principal de nuestro estudio fue evaluar la determinación de PTHio y objetivar si su implementación colaboraba en lograr la aplicación de una cirugía mínimamente invasiva (CMI) y en régimen de cirugía mayor ambulatoria (CMA) en el tratamiento del HPTP. MATERIAL Y MÉTODOS: Estudio retrospectivo de una serie consecutiva de pacientes diagnosticados e intervenidos quirúrgicamente de HPTP en el Hospital General Universitario de Ciudad Real entre enero de 2005 y enero de 2012. RESULTADOS: En el periodo estudiado, se intervinieron 91 pacientes. 39 (42,9%) fueron intervenidos bajo anestesia general y 52 (57,1%) fueron candidatos a anestesia locorregional mediante bloqueo cervical. Del total, 76 (83,5%) fueron subsidiarios de CMI con abordaje unilateral. En el resto se realizó cervicotomía clásica. En 75 pacientes se realizó la determinación de PTHio, de los cuales, en 68 se demostró curación en el mismo acto quirúrgico. El 70,3% (64) de los pacientes fueron intervenidos en régimen de CMA. CONCLUSIONES: La determinación de PTHio puede permitir modificar la estrategia quirúrgica del HPTP en nuestro servicio, colaborando en la realización de una CMI en un porcentaje importante de pacientes, de forma ambulatoria, con alguna mejora estética, probablemente menor dolor, menor ingreso y con menos complicaciones potenciales que en la exploración cervical bilateral

INTRODUCTION: Primary hyperparathyroidism (PHPT) is due to a single adenoma in 85%-95% of cases, and is often cured after adenoma removal. Intraoperative rapid determination of intact parathyroid hormone (PTHio) may be a tool for monitoring the effectiveness of PHPT surgery. The main objective of our study was to evaluate PTHio determination and to establish whether its successful implementation contributed to achieve minimally invasive surgery (MIS) and major ambulatory surgery (MAS) in the treatment of PHPT. MATERIAL AND METHODS: Retrospective study of a consecutive series of patients diagnosed and operated on for PHPT at the University General Hospital of Ciudad Real between January 2005 and January 2012.RESULTS: In the study period, 91 patients underwent surgery. 39 (42.9%) under general anesthesia, while 52 (57.1%) were candidates for regional anesthesia by cervical block. Seventy-six of all patients (83.5%) were amenable to MIS using a unilateral approach. Classical cervicotomy was performed in all other patients. PTHio determination was done in 75 patients, showing cure in the same surgery in 68 of them. MAS was performed in 70.3% (64) of patients. CONCLUSIONS: Determination of PTHio may allow for changing the surgical approach to PHPT at our department, allowing for performance of MIS on an outpatient basis in a significant proportion of patients with some cosmetic improvement, probably less pain, shorter hospital stay, and less potential complications than bilateral cervical exploration

Rapid intraoperative determination of intact parathyroid hormone during surgery for primary hyperparathyroidism. Experience at our center.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is due to a single adenoma in 85%-95% of cases, and is often cured after adenoma removal. Intraoperative rapid determination of intact parathyroid hormone (PTHio) may be a tool for monitoring the effectiveness of PHPT surgery. The main objective of our study was to evaluate PTHio determination and to establish whether its successful implementation contributed to achieve minimally invasive surgery (MIS) and major ambulatory surgery (MAS) in the treatment of PHPT. MATERIAL AND METHODS: Retrospective study of a consecutive series of patients diagnosed and operated on for PHPT at the University General Hospital of Ciudad Real between January 2005 and January 2012. RESULTS: In the study period, 91 patients underwent surgery. 39 (42.9%) under general anesthesia, while 52 (57.1%) were candidates for regional anesthesia by cervical block. Seventy-six of all patients (83.5%) were amenable to MIS using a unilateral approach. Classical cervicotomy was performed in all other patients. PTHio determination was done in 75 patients, showing cure in the same surgery in 68 of them. MAS was performed in 70.3% (64) of patients. CONCLUSIONS: Determination of PTHio may allow for changing the surgical approach to PHPT at our department, allowing for performance of MIS on an outpatient basis in a significant proportion of patients with some cosmetic improvement, probably less pain, shorter hospital stay, and less potential complications than bilateral cervical exploration.

Nesidioblastosis. A case of hyperplasia of the islets of Langerhans in the adult.

INTRODUCTION: Nesidioblastosis is a rare disease caused by hyperplasia of pancreatic islets, developing a state of hypoglycemia due to an increase in the insulin production. It is the leading cause of hyperinsulinic hypoglycemia in childhood, whereas in adults it only represents the 0.5-5% of cases. The pathogenesis is still unknown. We have studied several genetic mutations associated with dependent potassium channel of ATP present in the beta cells of the pancreas, as well as in patients underwent bariatric surgery because of the metabolic changes involved. REPORT: Woman (38 years old) attends consultation of General Surgery derived from Endocrinology before symptoms of persistent hypoglycemia. Factitious hypoglycemia and syndromes of neuroendocrine origin were ruled out. Imaging tests failed to identify space-occupying lesions. The medical treatment failed, persisting hypoglycemia symptoms. Before the given analytical and radiological findings obtained, and the persistence of symptoms affecting the quality of life of the patient, we opted for surgical treatment performing a pancreatectomy of the 80% of the gland. The final pathologic diagnosis was nesidioblastosis. DISCUSSION: Nesidioblastosis is a rare pathology, but it must be present in the differential diagnosis of hypoglycemia symptoms with endogenous hyperinsulinism in adults, once the intake of sulfonylureas and possible pancreatic neoformations have been ruled out.

Histiocitoma fibroso maligno. Un sarcoma excepcional en la glándula mamaria / Malignant fibrous histiocytoma. An exceptional sarcoma in the mammary gland

Introducción. El histiocitoma fibroso maligno constituye la neoplasia sarcomatosa más frecuente en los adultos, pero la mama es una localización excepcional. Presentamos el caso de una mujer que comenzó con una tumoración de crecimiento progresivo en la mama derecha. Caso clínico. Mujer de 68 años que consulta por autopalpación de un nódulo en la mama derecha que ha crecido de forma progresiva en los últimos meses. La mamografía y la ecografía muestran una imagen nodular con bordes bien definidos, situada en intercuadrantes superiores de mama derecha, sin adenopatías axilares. Se decidió intervención quirúrgica y el estudio histológico definitivo fue informado como neoformación mesenquimal fusocelular con patrón estoriforme. El estudio inmunohistoquímico fue compatible con un histiocitoma fibroso maligno. Conclusión. Es primordial el diagnóstico diferencial de esta entidad clínica debido a la variabilidad histológica de los tumores sarcomatosos. Sus características clínicas y radiológicas pueden hacerlo pasar desapercibido, pero su comportamiento agresivo hace necesario un diagnóstico precoz, lo cual permitirá un tratamiento adecuado para lograr el aumento en la supervivencia(AU)

Introduction. Malignant fibrous histiocytoma is the most common sarcomatous neoplasm in adults. Localization in the breast, however, is exceptional. We report the case of a woman who presented with progressive tumoral growth in the right breast. Case report. A 68-year-old woman consulted for a self-palpated nodule in the right breast that had grown steadily in the last few months. Mammography and ultrasound showed a nodule with well-defined borders, located in the upper inner quadrant of the right breast. There was no axillary lymphadenopathy. Surgery was performed and the histological examination gave a definitive diagnosis of mesenchymal spindle cell neoplasm with storiform pattern. Immunohistochemical analysis was compatible with a diagnosis of malignant fibrous histiocytoma. Conclusion. Due to the histological variability of sarcomatous tumors, differential diagnosis is paramount in malignant fibrous histiocytoma. Because of their clinical and radiological features, malignant fibrous histiocytoma can be overlooked. Because these tumors are aggressive, an early diagnosis is essential to allow appropriate treatment and to increase survival(AU)

[Fibromatosis breast in the male. Case study]. / Fibromatosis mamaria en el varón. A propósito de un caso.

BACKGROUND: mammary fibromatosis is a rare pathology. It constitutes 0.2% of breast cancers, and case in men are exceptional. The definitive diagnosis is histological. CLINICAL CASE: we report the case of a male of 52 years, diagnosed with breast fibromatosis after pathologic study of tumor in the right breast. Programmed surgery for excision with wide margins was done. We performed a mastectomy of the subcutaneous fibromatosis with a pathologic study with clear margins. The postoperative course was uncomplicated and did not require adjuvant therapy. At 6 months follow-up he remains free of disease. The treatment of choice is surgical excision with wide margins. Adjuvant treatment is controversial. CONCLUSIONS: the fibromatosis in the breast is very rare and an exceptional occurrence in men. Surgery is the definitive treatment; few results exist for adjuvant therapy.

Antecedentes: la fibromatosis mamaria es una enfermedad rara; sus casos son 0.2% de las neoplasias de mama, y en los varones es aún más rara. El diagnóstico definitivo es anatomopatológico. Caso clínico: se comunica el caso de un varón de 52 años, con diagnóstico anatomopatológico de fibromatosis mamaria posterior al estudio de un tumor en la mama derecha. Se le practicó exéresis con amplios márgenes, luego mastectomía subcutánea, con estudio histológico de fibromatosis con márgenes libres. El postoperatorio transcurrió sin complicaciones y no requirió tratamiento coadyuvante. En el seguimiento a seis meses continuaba libre de enfermedad. El tratamiento de elección es la escisión con amplios márgenes y el oncológico coadyuvante es motivo de controversia. Conclusiones: la fibromatosis en la mama es poco frecuente y su aparición en el varón excepcional. El tratamiento quirúrgico es el definitivo, no así la terapia oncológica neoadyuvante que sigue suscitando controversia.

Merkel cell carcinoma: case report and literature review.

BACKGROUND: Merkel cell carcinoma is an aggressive neuroendocrine cell carcinoma arising in the epidermis of patients aged >60 years. This lesion is found in sun-exposed areas and presents as a small violet raised nodule. It is usually painless and rapidly growing. Although its clinical presentation and characteristic histology are usually sufficient, immunohistochemical features are helpful in making an accurate diagnosis. CLINICAL CASE: We present the case of a 62-year-old male with epidermoid carcinoma of the lung who was treated with surgery and local radiation for 2 months. He presented a painless 8-cm subcutaneous mass of some weeks of evolution, without inflammatory signs. Computerized tomography demonstrated a mass of probable lymph node origin. Fine-needle aspiration biopsy (FNAB) reported malignant cells and excisional surgery of the mass was performed, revealing a subcutaneous Merkel cell carcinoma. CONCLUSIONS: Merkel cell carcinoma is a rare entity that develops in mature patients, often in sun-exposed areas, and presents cutaneous injury in intact skin. Definitive diagnosis is done using immunohistochemistry.

Angiosarcoma primario de mama y carcinoma papilar de tiroides sincrónico: presentación de un caso / Primary breast angiosarcoma and synchronous papillary carcinoma of thyroid: a case report

Presentamos el caso excepcional de paciente con angiosarcoma primario de mama y carcinoma papilar de tiroides sincrónicos. Mujer de 34 años con angiosarcoma primario en la mama derecha sometida a mastectomía simple. En el estudio de extensión se halló un incidentaloma tiroideo derecho compatible con carcinoma papilar que requirió tiroidectomía total y linfadenectomía del compartimento central en segundo tiempo. Los angiosarcomas primarios suponen menos del 0,05% de todos los tumores primarios malignos de la mama. El diagnóstico definitivo de estos tumores viene definido por el estudio anatomopatológico, que define tres grados: alto, bajo, intermedio, los cuales se relacionan de forma directa con la supervivencia. La prevalencia de los incidentalomas malignos tiroideos objetivados por PET varía del 14% - 30,9%. La planificación del tratamiento quirúrgico de las neoplasias incidentales tiroideas en pacientes con otro tumor primario debe analizarse de forma individualizada, según la supervivencia esperada del tumor primario

Present the exceptional case of a female patient with diagnostic of primary angiosarcoma of the breast and synchronous thyroid papillary carcinoma, we review the literature. Patient female 34 year old with diagnostic of primary angiosarcoma in the right breast, it was removed,in the extension study found an incidental thyroid papillary carcinoma that required total thyroidectomy and central lymphadenectomy in a second time. The primary angiosarcomas account for less than 0.05% of all primary malignant tumors of the breast. The definitive diagnosis is determined by the pathology study, which defines three grades: high, low and intermediate, which relate directlyto the survival. The prevalence of malignant thyroid incidentalomas was observed by PET varies from 14% to30,9%, according to different studies. Planning the surgical treatment of incidental thyroid malignancies in patients with other primary tumor should be analyzed individually,according the expected survival of the primary tumor

Proximal-type epithelioid sarcoma in pubis. Case report and review of the literature.

BACKGROUND: The "proximal-type" epithelioid sarcoma (PES) is a rare variant of conventional epithelioid sarcoma. It has been described in older patients in the proximal portion of the extremities with a predilection for the pelvis and perineum. It is clinically more aggressive, showing a higher incidence of recurrence, metastasis, resistance to chemotherapy and a higher mortality. We report the case of a patient with a PES of the pubic region and we review the previous literature. CLINICAL CASE: We report the case of a 57-year-old female with a painless, progressively growing mass in the region of the pubis. We performed surgical resection of the lesion with clear margins and histological and immunohistochemical study allowed the definitive diagnosis of PES. After 4 disease-free years, the patient had a tumor recurrence at the same location. We performed en bloc resection of the lesion and immunohistochemical study confirmed the recurrence of PES. The patient refused adjuvant therapy. Today, after 4 years of follow-up, the patient remains asymptomatic and without evidence of recurrence or distant disease. CONCLUSIONS: Diagnosis of PES is complex because histological findings may be confused with multiple tumors; therefore, immunohistochemical study is definitive. PES shows positivity for epithelial markers (cytokeratin and EMA), mesenchymal markers (vimentin) as well as CD34. According to what has been reported in the literature, surgical treatment with free margins is indicated, with adjuvant therapies when the risk of recurrence is high.