ABSTRACT
OBJECTIVE: Whether lymph-node dissection (LND) influences the lymph-node recurrence (LNR) risk in patients with papillary thyroid cancer remains controversial. The prognostic impact of macroscopic and microscopic lymph-node involvement at diagnosis is also an unresolved issue. A retrospective study was conducted to assess the influence of various LND procedures and to search for LNR risk factors. METHODS: Overall 545 patients without distant metastases prior to surgery and main tumour > or =10 mm were included. A total thyroidectomy was performed in all patients with either no LND (Group 1, n=161), bilateral LND of the central and lateral compartments (Group 2, n=181) or all other dissection modalities (Group 3, n=203). Post-operative radioiodine was given to 496 (91%) patients. The 10-year cumulative probability of LNR was assessed and a prognostic study using multivariate analysis was performed. RESULTS: Macroscopic lymph-node metastases were present in 118 patients, 57 diagnosed before surgery and 61 only at surgery (including 81% in the central compartment). Overall, the 10-year cumulative probability of LNR was 7%. Macroscopic lymph-node metastases (P=0.001), extra-thyroidal invasion (P=0.017) and male gender (P=0.05) were independent risk factors, while bilateral LND of the central and lateral compartments was protective (P=0.028). In patients with macroscopic lymph-node metastases, the 10-year probability was lower in Group 2 than in Group 3 (10% vs 30%, P<0.01). In patients without macroscopic lymph-node metastases (n=427), no significant differences were observed between the three LND groups. CONCLUSIONS: Patients with macroscopic, but not microscopic, lymph-node involvement have a major LNR risk and need an optimal LND at primary surgery.
Subject(s)
Carcinoma, Papillary/pathology , Neck Dissection , Neoplasm Recurrence, Local/diagnosis , Thyroid Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Papillary/diagnosis , Child , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neck Dissection/adverse effects , Neoplasm Recurrence, Local/etiology , Postoperative Complications/diagnosis , Prognosis , Retrospective Studies , Risk Factors , Thyroid Neoplasms/diagnosisABSTRACT
The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. Hypogonadotropic hypogonadism (HH) results from impaired secretion of GnRH. The patients display with delayed puberty, micropenis and cryptorchidism in the male reflecting gonadotropin insufficiency, and amenorrhea in the female. Kallmann's syndrome (KS) is defined by the association of HH and anosmia or hyposmia (absent smelling sense). Segregation analysis in familial cases has demonstrated diverse inheritance patterns, suggesting the existence of several genes regulating GnRH secretion. The X-linked form of the disease was associated with a genetic defect in the KALI gene located on the Xp22.3 region. KAL1 gene encodes an extracellular matrix glycoprotein anosmin-1, which facilitates neuronal growth and migration. Abnormalities in the migratory processes of the GnRH neurons with the olfactory neurons explain the association of HH with anosmia. Recently, mutations in the FGF recepteur 1 (FGFR1) gene were found in KS with autosomal dominant mode of inheritance. The role of FGFR1 in the function of reproduction requires further investigation. Besides HH with anosmia, there are isolated HH (IHH). No human GnRH mutations have been reported although hypogonadal mice due to a GnRH gene deletion exist. In patients with idiopathic HH and without anosmia an increasing number of GnRH receptor (GnRHR) mutations have been described which represent about 50% of familial cases. The clinical features are highly variable and there is a good relationship between genotype and phenotype. A complete loss of function is associated with the most severe phenotype with resistance to pulsatile GnRH treatment, absence of puberty and cryptorchidism in the male. In contrast, milder loss of function mutations causes incomplete failure of pubertal development. The preponderant role of GnRH in the secretion of LH by the gonadotrophs explains the difference of the phenotype between male and female with partial GnRH resistance. Affected females can have spontaneous telarche and normal breast development while affected males exhibit no pubertal development but normal testis volume, a feature described as "fertile-eunuch". High-dose pulsatile GnRH has been used to induce ovulation. Another gene, called GPR54, responsible for idiopathic HH has been recently described by segregation analysis in two different consanguineous families. The GPR54 gene is an orphan receptor, and its putative ligand is the product of the KISS-1 gene, called metastine. Their roles in the function of reproduction are still unknown.
