Cáncer colorrectal familiar y hereditario / Hereditary and familial colorectal cancer

Hasta un 5% de todos los casos de cáncer colorrectal se deben a un síndrome hereditario conocido. Estas formas hereditarias demandan en muchas ocasiones un alto grado de sospecha para su diagnóstico y requieren de un manejo específico y especializado. Además, el diagnóstico del cáncer colorrectal hereditario tiene importantes consecuencias no solo para el paciente, para el que existen medidas de prevención altamente efectivas, sino también para los familiares, que pueden ser portadores de la misma condición. Los avances más significativos en el campo del cáncer colorrectal hereditario se han producido en el diagnóstico y caracterización de estos síndromes

Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes

Clinical and mutation analysis of four Chinese families with von Hippel-Lindau disease

OBJECTIVE: von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome predisposed to the development of tumors in a variety of body organs. The major etiopathogenesis of VHL is a mutation of the VHL tumor-suppressor gene on the short arm of chromosome 3 (3p25-26). We report on the clinical and molecular features of four Chinese kindreds with VHL disease. MATERIALS AND METHODS: The VHL gene was screened for mutation using a direct DNA sequencing analysis and a multiplex ligation-dependent probe amplification (MLPA) for 44 volunteers from these four families. Any unaffected person, with germline VHL gene mutation, was required to undergo further examination, surveillance and treatment. RESULTS: The main lesions and the average diagnostic year of the 20 patients were central nervous system hemangioblastoma (60 %, 34.92 years), renal lesion (60 %, 39.08 years), pancreatic lesion (60 %, 37.67 years), adrenal pheochromocytoma (25 %, 37.8 years) and retinal hemangioblastoma (10 %, 25.5 years). Direct sequencing detected nucleotide substitutions or small deletions in three families and MLPA revealed exon 1 deletion in family A. The five asymptomatic patients were initially diagnosed by genetic analysis and verified radiologically or surgically. CONCLUSIONS: The spectrum of clinical manifestation of VHL in the mainland Chinese population is similar to the observation in Western kindreds. Genetic testing, which plays a crucial role in early diagnosis asymptomatic patients, is obviously superior to clinical informations when diagnosing VHL disease. The members of VHL disease family may benefit from pedigree study, genetic testing, periodic follow-up, early diagnosis and prompt treatment (AU)

Early surgical excision of giant congenital hemangiomas of the scalp in newborns: clinical indications and reconstructive aspects.

BACKGROUND: Infantile hemangioma is the most common vascular tumor in newborns, with an incidence from 12 to 23% among preterm infants with low weight at birth and a female to male ratio of 3:1. The head and neck is the most frequently affected area (60%), and the scalp is a typical site for such large lesions. OBJECTIVE: We describe some clinical and medical aspects in comparison with the surgical approach to giant infantile hemangioma of the scalp. METHODS: The indications to treatment are discussed. An outcome basis evaluation, by reviewing some clinical cases, is provided to help readers better understand when and how to undergo surgery safely. CONCLUSION: Early excision of huge infantile hemangioma of the scalp is the treatment of choice if feasible within 5 months of age.

Infantile hemangioma: treatment with short course systemic corticosteroid therapy as an alternative for propranolol.

Infantile hemangiomas (IHs) are increasingly being treated with propranolol or other beta-blockers, but before this therapeutic option was available, oral glucocorticosteroids (GCSs) were the criterion standard treatment and are still the alternative modality in problematic cases. Nevertheless, there is no standard treatment protocol for the dose and duration of GCSs. Long-term treatment with GCSs is associated with unwanted side effects such as growth suppression, behavioral changes, and reflux. Twenty-one children with troublesome IHs were treated according to an algorithm with 3 mg/kg/day of oral prednisolone divided three times per day with varying duration and number of GCS courses. Two blinded investigators independently interpreted therapy results using the Hemangioma Activity Score (HAS). Side effects were determined according to reports in patient charts and parental questionnaires. The median duration of a short course of GCSs was 2 weeks (range 1-6 weeks). The number of courses was 2 (range 1-5). The median cumulative dose was 91 mg/kg. Growth stabilized in all patients, with a good response (>50% reduction in HAS) in 62% and a favorable response (30-50% reduction is HAS) in 23%. Twelve of the 21 children (57%) had minor side effects. Persistent side effects did not occur. Intermittent short course, systemic, high-dose GCS therapy is an effective and safe treatment modality for IH, with a substantially lower cumulative dose of GCSs compared to prolonged therapy and no major side effects. This treatment is an alternative in cases in which propranolol fails or is contraindicated.

A prospective biological study in relation to a family with Li-Fraumeni syndrome

INTRODUCTION: The Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder associated with different tumor types in childhood and young adults. Approximately 70% of LFS cases contain germline mutations in the TP53 gene. We report a case of a family suspected of LFS. MATERIALS AND METHODS: The proband and four members of the family affected were diagnosed with cancer at an early age and they all died except the proband. Exons 5-9 from TP53 gene were analysed by direct amplification and sequencing in 7 family members. RESULTS: The analysis revealed a germline nonsense mutation in exon 8 at codon 306 of the codified region of the TP53 gene, causing a change of CGA to TGA (Arg→Stop) in the proband, her mother, her cousin and her maternal uncle. Proband's maternal grandmother and aunt do not have the mutation. CONCLUSIONS: The members of this family that were studied meet the criteria of classic LFS and the described mutation increases their susceptibility to develop cancer. The proband's maternal grandfather died of lung cancer in 1993, and we believe that he was the carrier of the mutation in this family (AU)

[Hereditary cutaneous leiomyomatosis]. / Hereditäre kutane Leiomyomatose.

The occurrence of multiple cutaneous leiomyomas can be indicative of hereditary cutaneous leiomyomatosis. This autosomal dominant disorder is due to germline mutations in the fumarate hydratase (FH) gene. Associations with uterine myomas and renal cell carcinomas have been described and are referred to as Multiple Cutaneous and Uterine Leiomyomas (MCUL) or Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), respectively. A 34-year-old man presented with multiple red-brown papules and nodules. After histopathologic confirmation of piloleiomyomas, we made the diagnosis of hereditary cutaneous leiomyomatosis. Taking into consideration the aforementioned complications, close interdisciplinary management of these patients and regular screening examinations within affected families are mandatory.