A Korean Family of Familial Medullary Thyroid Cancer with Cys618Ser RET Germline Mutation

Familial medullary thyroid carcinoma (FMTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. An identifiable RET mutation can be detected in about 85% of FMTC families. The majority of germline mutations in FMTC have been found in exons 10 and 11 of the RET proto-oncogene, specifically within the cysteine codons 609, 611, 618, 620, and 634. We screened members of a large Korean family that had a history of FMTC by genetic analyses, and propose a therapeutic approach for managing the disorder. We report a RET mutation in exon10, codon 618 that causes substitution of a cysteine by a serine in the cysteine-rich domain of the RET receptor in a three-generation FMTC family composed of 30 members with 11 carriers. Nine of the gene carriers were clinically affected. The FMTC with cysteine RET mutations found in the Korean population is consistent with the clinical pattern reported worldwide; to date there have been no ethnic differences identified for FMTC. Our results suggest that this genetic profile might be associated with usually aggressive clinical course with regional lymph node metastasis but late onset of MTC.

The Clinical Characteristics, Prognostic of Medullary Thyroid Cancer / 대한내분비외과학회지

PURPOSE: Medullary thyroid cancer (MTC) is a rare disease and the clinical course of MTC many vary. In this study, we analyzed the factors influencing the prognosis of MTC. METHODS: The study group consisted of 37 patients with MTC seen at KNUH between July 1985 and July 2003. We analyzed the medical records of MTC surgical cases in a retrospective study to analyze treatment results and utilized the Kaplan-Meier and chi-squred tests to determine the correlation of prognosis and recurrence. RESULTS: The median age of patients was 39 years and 7 patients had a family history and accompanying disease. No metastases were detected at the time of diagnosis. The majority of the sizes of tumors were under 4 cm in 22 cases and 24 cases (64.9%) showed unilateral tumor locations. Twenty cases (48.6%) showed lymph node metastasis, and invasion of the surrounding organs was seen in 5 cases (13.5%) of these cases. A total thyroidectomy and central neck dissection was performed in all cases. In 17 cases, a modified radical neck dissection was performed initially. Recurrence was detected in 13 out of 37 cases. The most common site of recurrence was the neck, followed by the lung and liver. We analyzed the factors that affected recurrence and it was found that lymph node metastasis and the TNM stage had a statistically significant relationship. No factor showed relevance to prognosis by multivariate analysis. The survival rates were 89.2% for 5 years and 83.8% for 10 years. CONCLUSION: We could not find any statistical significance for a factor relevant to the prognosis of the patients by multivariate analysis. However, as the 10 year-survival rate was 83.8%, we can expect improvement in the treatment of MTC with surgical management (total thyroidectomy and central neck dissection) and constant follow-up.

Prognostic Value of the Preoperative CEA, CA15-3 and TPS Serum Levels in Patients with Breast Cancer

PURPOSE: Tumor markers are often used to monitor the response to therapy and to detect recurrences in patients with resected breast cancer. Here we evaluated the prognostic value of the preoperative serum concentrations of tumor markers in patients with breast cancer. METHODS: The preoperative serum concentrations of tumor markers (CEA, CA15-3 and TPS) were measured in 670 patients who were treated via potentially curative surgical resection for breast cancer from 2001 to 2004. We investigated the association of the serum concentrations of tumor markers with the disease-free survival and overall survival at the time of the primary diagnosis in relation to the established prognostic factors such as tumor size, lymph node status, hormonal receptor status, age and menopausal status. RESULTS: The established prognostic factors and the elevated preoperative serum tumor marker values were correlated with disease-free survival (CEA: P=0.014, CA15-3: P=0.002 and TPS: P<0.001) and overall survival (CEA: P=0.045, CA15-3: P=0.002 and TPS: P<0.001) on univariate analysis. On multivariate analysis, tumor size, lymph node status, hormone receptor status and TPS (P=0.03) were independent prognostic factors for recurrence and the lymph node status, hormone receptor status and TPS serum level (P<0.001) were independent prognostic factors for overall survival. CONCLUSION: The preoperative serum concentrations of tumor makers (CEA, CA15-3 and TPS) are strong independent prognostic factors for recurrence and survival in patients with breast cancer. The tests for the preoperativeserum concentrations of tumor markers have convenient and reproducible advantages while the others require tumor tissue. Patients with elevated preoperative serum tumor marker values need appropriate adjuvant therapy, careful monitoring and detection of recurrences during the follow-up period.

Ultrasonographic Evaluation in Patients with Inguinal Hernia

Between March 1999 and January 2000, 82 boys with the diagnosis of inguinal hernias (12 bilateral and 70 unilateral hernias), underwent Ultrasound (US) examination of both sides of the groin, a total of 164 inguinal imaging prior to surgery. The patients ages ranged from 3 days to 12 years with a mean of 32.6 months. Ninty four examinations were on the clinically symptomatic side and 70 were on the asymptomatic side. The US criteria for the diagnosis of an inguinal hernia were as follows: 1) visceral hernia, the presence of bowel loops, or omentum in the inguinal canal, 2) communicating hydrocele, the presence of fluid in the processus vaginalis, 3) widening of patent processus vaginalis at the level of nternal inguinal ring. The width of patent processus vaginalis at the level of internal inguinal ring over 4 mm is onsidered an occult hernia. Among the 94 symptomatic groins, US findings showed 31 (33 %) visceral hernias, 18 (19 %) communicating hydroceles, and 38 (41 %) widening of the internal inguinal ring, and 7 (7 %) groins without abnormalities. In 70 asymptomatic groins, there were 4 (6 %) visceral hernias, 5 (7 %) communicating hydroceles, 11 (16 %) widening of the internal inguinal ring, and 50 (70 %) groins without abnormalities. Among the 70 asymptomatic groins there were US abnormalities in 20 (28 %). One hundred and seven groins with positive US findings were surgically explored. Among 107 operated sites, the operative findings were compatible with the US diagnosis in 104, a sensitivity for US of 97.2 %. In patients with US findings of widening of internal inguinal ring (>4 mm), there was patent processus vaginalis in 36 out of 38 symptomatic groins and 10 of 11 asymptomatic groins. The sensitivity of US to the operative findings in widening of internal inguinal ring was 93.8 %. For visceral hernia and communicating hydrocele, the sensitivity of positive US findings was 100 %. Ultrasonography for inguinal hernias appears to be a rapid, reliable, and noninvasive screening diagnostic tool with high positive specificity. Therefore, we recommend the use of US as a routine diagnostic tool in pediatric patients with inguinal hernias and hydroceles.