Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer

Background@#Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker. @*Methods@#LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results. @*Results@#LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages. @*Conclusion@#LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

Risk Factors of Postoperative Hypocalcemia after Total Thyroidectomy of Papillary Thyroid Carcinoma Patients / 대한내분비외과학회지

PURPOSE: Postoperative hypocalcemia is a common complication of thyroidectomy. This study evaluated the incidence and predisposing risk factors for postoperative permanent hypocalcemia after total thyroidectomy. METHODS: There were 1,247 consecutive patients undergoing total thyroidectomy and complete treatment and observation for differentiated thyroid cancer between January 2012 to December 2012 who were enrolled in this study. Patients were divided into two groups, those remaining normalcalcemic (Group I-824 pts) and those who had hypocalcemia requiring treatment (Groups II-423 pts). Group II was subdivided into a transient hypocalcemic group (Group IIA-409 pts) and a permanent hypocalcemic group (Group IIB-14 pts). RESULTS: Female gender, thyroiditis, preserved parathyroid number, lateral lymph node metastasis, RAI treatment, preoperative parathyroid hormone and preoperative vitamin D were significantly associated with the development of postoperative hypocalcemia by multivariate analysis. Comparing patients with transient versus permanent hypocalcemia, tumor size and multiplicity were significantly related to the development of permanent hypocalcemia by multivariate analysis. RAI treatment and parathyroid hormone level on the postoperative third day were significantly related to recovery from transient hypocalcemia to normo-calcemia. CONCLUSION: Risk factors of postoperative hypocalcemia were associated with preoperative patient factors and advanced thyroid cancer. Advanced thyroid cancer was a risk factor for permanent hypocalcemia. To prevent postoperative hypocalcemia, we should focus on patient condition and need to preserve parathyroid gland more carefully in thyroid surgery.

Is focused parathyroidectomy appropriate for patients with primary hyperparathyroidism?

PURPOSE: The aim of this study was to determine whether focused or complete parathyroidectomy was more appropriate and to compare follow-up data in primary hyperparathyroidism (PHPT). METHODS: We retrospectively analyzed 225 operations for PHPT at Yonsei University Health System between 2000 and 2012. After excluding 93 patients, the remaining 132 were divided into 2 groups: those who underwent focused parathyroidectomy (FP) and those who underwent conventional parathyroidectomy (CP). We compared clinicopathological features; preoperative calcium, parathyroid hormone (PTH), phosphorus, vitamin D, 24-hour urine calcium, and alkaline phosphatase levels; postoperative calcium and PTH levels; pathologic diagnosis; multiplicity; and results of a localization study between the 2 groups. RESULTS: There was no significant difference in the rates of development of postoperative persistent hyperparathyroidism (1/122 FP patients and 1/10 CP patients) between the 2 groups due to a technical reason (FP 0.8% vs. CP 10.0%, P = 0.146). Multiglandular disease (MGD) was uncommon in all cases (6 of 132, 4.5%). All MGD cases were diagnosed using a preoperative localization study. Sestamibi scan and ultrasonography sensitivity were 94.2% and 90.2%, respectively. CONCLUSION: We suggest that FP is appropriate in PHPT, except in cases of MGD if detected before the operation using preoperative imaging. Knowledge of hereditary PHPT and improved preoperative localization studies, such as high-resolution ultrasonography, contributed to the decision to perform FP rather than CP in all cases of unilateral results of the localizing study.

Is focused parathyroidectomy appropriate for patients with primary hyperparathyroidism?

PURPOSE: The aim of this study was to determine whether focused or complete parathyroidectomy was more appropriate and to compare follow-up data in primary hyperparathyroidism (PHPT). METHODS: We retrospectively analyzed 225 operations for PHPT at Yonsei University Health System between 2000 and 2012. After excluding 93 patients, the remaining 132 were divided into 2 groups: those who underwent focused parathyroidectomy (FP) and those who underwent conventional parathyroidectomy (CP). We compared clinicopathological features; preoperative calcium, parathyroid hormone (PTH), phosphorus, vitamin D, 24-hour urine calcium, and alkaline phosphatase levels; postoperative calcium and PTH levels; pathologic diagnosis; multiplicity; and results of a localization study between the 2 groups. RESULTS: There was no significant difference in the rates of development of postoperative persistent hyperparathyroidism (1/122 FP patients and 1/10 CP patients) between the 2 groups due to a technical reason (FP 0.8% vs. CP 10.0%, P = 0.146). Multiglandular disease (MGD) was uncommon in all cases (6 of 132, 4.5%). All MGD cases were diagnosed using a preoperative localization study. Sestamibi scan and ultrasonography sensitivity were 94.2% and 90.2%, respectively. CONCLUSION: We suggest that FP is appropriate in PHPT, except in cases of MGD if detected before the operation using preoperative imaging. Knowledge of hereditary PHPT and improved preoperative localization studies, such as high-resolution ultrasonography, contributed to the decision to perform FP rather than CP in all cases of unilateral results of the localizing study.

Surgical Outcomes of Adrenocortical Carcinoma; 20 Years of Experience in a Single Institution / 대한내분비외과학회지

PURPOSE: Adrenocortical carcinoma (ACC) is a rare malignant tumor. Early detection is difficult and prognosis is poor. We report on 20 years of ACC surgical experience at our institution. METHODS: This study included 32 ACC patients who underwent surgical resection at the Department of Surgery of the Yonsei University Health System in South Korea between January 1990 and February 2012. We reviewed these 32 patients and retrospectively analyzed long-term clinical outcomes and prognosis after radical surgery for ACC. RESULTS: The median age of the 32 patients at diagnosis was 42.25 years (range 3~81 years). There were 16 (50%) female and 16 (50%) male patients. Mean tumor size was 12.36 cm (range 1.8~20 cm). Twenty-five patients (78.12%) had nonfunctioning tumors while the other seven patients (21.87%) had functioning tumors. Seventeen patients (53.12%) were classified as stage II, two (6.25%) as stage III, and 13 (40.62%) as stage IV. Fourteen patients underwent radical surgical resection, while 14 patients received adjuvant chemotherapy, two received adjuvant radiotherapy, and two received adjuvant chemoradiation. Four patients were lost to follow-up. Among the remaining 28 patients, 15 patients survived. The 5- and 10-year overall survival was 60.6% and 37.8%, respectively (median survival=85+/-24.3 months). Seventeen patients (53%) experienced disease recurrence. Five- and 10-year recurrence-free survival was 41.5% and 29.7%, respectively (median survival=18+/-5.5 months). CONCLUSION: Early stage at diagnosis and surgical resection were the most important prognostic factors associated with prolonged survival. The role of additional therapy remains controversial and new agents should continually be evaluated for efficacy.

Surgical Outcomes of Robotic MRND versus Conventional Open MRND for Papillary Thyroid Carcinoma with Lateral Neck Node Metastasis: Comparative Analysis using Propensity Score Matching / 대한내분비외과학회지

PURPOSE: During the past decade, various endoscopic thyroid surgeries have been conducted, each with its own benefits. The incorporation of robotic systems to endoscopic thyroid surgery has improved the visualization and precision of endoscopic techniques. We previously reported our initial experience with robotic modified radical neck dissection (MRND) of papillary thyroid carcinoma (PTC) with lateral neck node metastasis (LNM). The aim of this study was to compare surgical outcomes of robotic vs. conventional open MRND of PTC with LNM using propensity score matching. METHODS: From January 2008 to February 2011, 515 patients with PTC with LNM were enrolled. One hundred patients underwent robotic MRND, and 415 patients underwent conventional open MRND. These two groups were retrospectively compared with respect to their clinicopathological characteristics, surgical outcomes, and surgical completeness. Furthermore, to avoid selection bias, propensity score matching analysis was used to compare surgical outcomes of each group without any compounding factors. RESULTS: The operative time for the robotic MRND was longer than for the open MRND (297.9±60.2 min vs. 212.1±55.6 min, P=0.089). However, the mean numbers of retrieved lymph nodes and mean hospital stay after surgery were similar in the two groups (36.0±12.9 vs. 40.8±13.3, P=0.235), (6.1±1.6 days vs. 6.1±2.1 days, P=0.577). The complication rates were similar between the two groups, and there was no statistical difference in postoperative thyroglobulin levels between groups (0.51±0.83 ng/ml vs. 0.89±2.46 ng/ml, P=0.593). CONCLUSION: According to our study, robotic MRND shows similar surgical outcomes to conventional open MRND after case-matched analyses. We suggest that robotic MRND is an acceptable alternative as an operative method for PTC with LNM, resulting in excellent cosmesis and patient satisfaction.

How Many Sentinel Lymph Nodes Are Enough for Accurate Axillary Staging in T1-2 Breast Cancer? / 한국유방암학회지

PURPOSE: During a sentinel lymph node biopsy (SLNB) for breast cancer, the appropriate number of sentinel lymph nodes (SLNs) to be removed for accurate axillary staging is still controversial. We hypothesized that there might be an optimal threshold number of SLNs. We investigated how many SLNs should be removed to achieve an acceptable accuracy and ensure minimal morbidity. METHODS: We reviewed data of 328 patients with invasive breast cancer who underwent SLNB followed by complete level I and II axillary dissection between January 2004 and December 2005. The false negative rate (FNR) and accuracy of SLNB according to the number of removed SLNs were evaluated. RESULTS: The mean number of SLNs removed was 3.0 (range, 1-14), and that of total retrieved axillary lymph nodes was 17.5 (range, 10-40). In total, 111 (33.8%) patients had positive nodes on the permanent pathological report. Among them, 12 patients had negative SLNs; thus, the overall FNR of SLNB was 10.8% (12/111) and the accuracy was 96.3% (316/328). The FNR was 26.6% for a single SLN, 8.0% for two, and 11.1% for three. In cases where four or more SLNs were removed, the FNR decreased to 0% and accuracy reached 100%. CONCLUSION: Our data suggest that a SLNB should not only remove one or two of the hottest node(s) when other hot nodes exist. We also suggest that four might be an optimal threshold number of SLNs to be removed and that removal of more than four SLNs does not improve axillary staging accuracy.