Silent pheochromocytoma in adrenal incidentaloma:unveiling clinical and radiological characteristics

Purpose@#Silent pheochromocytoma refers to tumors without signs and symptoms of catecholamine excess. This study aimed to clarify the clinical, radiological characteristics, and perioperative features of silent pheochromocytomas diagnosed after adrenalectomy for adrenal incidentaloma. @*Methods@#Medical records of patients who underwent adrenalectomy for adrenal incidentaloma and were subsequently diagnosed with silent pheochromocytoma between January 2000 and December 2020 were retrospectively reviewed for demographic, diagnostic, surgical, and pathological findings. @*Results@#Of the 130 patients who underwent adrenalectomy for incidentaloma, 8 (6.1%) were diagnosed with silent pheochromocytoma. Almost all patients had no hypertensive symptoms and their baseline hormonal levels remained within normal ranges. All patients exhibited tumor size >4 cm, precontrast Hounsfield unit >10, and absolute washout <60%. Intraoperative hypertensive events were noted in 2 patients (25.0%) in whom antiadrenergic medications were not administered. All patients in the intraoperative hypertensive event group exhibited atypical features on CT, whereas 83.3% of patients in the non-intraoperative hypertensive event group showed atypical features on CT imaging. @*Conclusion@#Silent pheochromocytomas share radiological traits with malignant adrenal tumors. Suspicious features on CT scans warrant surgical consideration for appropriate treatment. Administering alpha-blockers can enhance hemodynamic stability during adrenalectomy in suspected silent pheochromocytoma cases.

The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy

Background@#We aimed to evaluate the utility of repeat biopsy of thyroid nodules classified as atypia of undetermined significance with architectural atypia (IIIB) on core-needle biopsy (CNB). @*Methods@#This retrospective study evaluated patients with thyroid nodules categorized as IIIB on CNB between 2013 and 2015. Demographic characteristics, subsequent biopsy results, and ultrasound (US) images were evaluated. The malignancy rates of nodules according to number of CNBs and the number of IIIB diagnoses was compared. Demographic and US features were evaluated to determine factors predictive of malignancy. @*Results@#Of 1,003 IIIB nodules on CNB, the final diagnosis was determined for 328 (32.7%) nodules, with 121 of them confirmed as malignant, resulting in a malignancy rate of 36.9% (95% confidence interval, 31.7% to 42.1%). Repeat CNB was performed in 248 nodules (24.7%), with 75 (30.2%), 131 (52.8%), 13 (5.2%), 26 (10.5%), one (0.4%), and two (0.8%) reclassified into categories II, IIIB, IIIA, IV, V, and VI, respectively. Malignancy rates were not significantly affected by the number of CNBs (P=0.291) or the number of IIIB diagnoses (P=0.473). None of the nodules confirmed as category II on repeat CNB was malignant. US features significantly associated with malignancy (P<0.003) included solid composition, irregular margins, microcalcifications, and high suspicion on the US risk stratification system. @*Conclusion@#Repeat biopsy of nodules diagnosed with IIIB on CNB did not increase the detection of malignancy but can potentially reduce unnecessary surgery. Repeat biopsy should be performed selectively, with US features guiding the choice between repeat biopsy and diagnostic surgery.

Validation of CT-Based Risk Stratification System for Lymph Node Metastasis in Patients With Thyroid Cancer

Objective@#To evaluate the computed tomography (CT) features for diagnosing metastatic cervical lymph nodes (LNs) in patients with differentiated thyroid cancer (DTC) and validate the CT-based risk stratification system suggested by the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) guidelines. @*Materials and Methods@#A total of 463 LNs from 399 patients with DTC who underwent preoperative CT staging and ultrasound-guided fine-needle aspiration were included. The following CT features for each LN were evaluated: absence of hilum, cystic changes, calcification, strong enhancement, and heterogeneous enhancement. Multivariable logistic regression analysis was performed to identify independent CT features associated with metastatic LNs, and their diagnostic performances were evaluated. LNs were classified into probably benign, indeterminate, and suspicious categories according to the K-TIRADS and the modified LN classification proposed in our study. The diagnostic performance of both classification systems was compared using the exact McNemar and Kosinski tests. @*Results@#The absence of hilum (odds ratio [OR], 4.859; 95% confidence interval [CI], 1.593–14.823; P = 0.005), strong enhancement (OR, 28.755; 95% CI, 12.719–65.007; P < 0.001), and cystic changes (OR, 46.157; 95% CI, 5.07–420.234; P = 0.001) were independently associated with metastatic LNs. All LNs showing calcification were diagnosed as metastases. Heterogeneous enhancement did not show a significant independent association with metastatic LNs. Strong enhancement, calcification, and cystic changes showed moderate to high specificity (70.1%–100%) and positive predictive value (PPV) (91.8%–100%). The absence of the hilum showed high sensitivity (97.8%) but low specificity (34.0%). The modified LN classification, which excluded heterogeneous enhancement from the K-TIRADS, demonstrated higher specificity (70.1% vs. 62.9%, P = 0.016) and PPV (92.5% vs. 90.9%, P = 0.011) than the K-TIRADS. @*Conclusion@#Excluding heterogeneous enhancement as a suspicious feature resulted in a higher specificity and PPV for diagnosing metastatic LNs than the K-TIRADS. Our research results may provide a basis for revising the LN classification in future guidelines.

Diagnosis of parathyroid incidentaloma detected on thyroid ultrasonography: the role of fine-needle aspiration cytology and washout parathyroid hormone measurements

Purpose@#The aim of this study was to assess the diagnostic role of fine-needle aspiration cytology (FNAC) and analyze factors associated with false-negative FNAC results in patients with parathyroid incidentaloma who were referred for ultrasonography (US)-guided fine-needle aspiration (FNA) of thyroid nodules. @*Methods@#In this study, 121 patients with suspected parathyroid lesions were enrolled. The patients underwent US-guided FNAC with measurements of washout parathyroid hormone (PTH) between January 2015 and May 2020. The diagnostic performance of FNAC for the diagnosis of parathyroid lesions was assessed using surgical results and elevated washout PTH as a reference standard. The clinical and radiologic features associated with false-negative results on FNAC for the diagnosis of parathyroid lesions were evaluated. @*Results@#Among the 121 nodules assessed, 38 were parathyroid lesions (31.4%), and 83 were non-parathyroid lesions (68.6%). The diagnostic performance of FNAC for parathyroid incidentaloma showed a sensitivity of 31.6% (12/38), specificity of 100% (83/83), positive predictive values of 100% (12/12), negative predictive values of 76.1% (83/109), and accuracy of 78.5% (95/121). The FNAC results of non-parathyroid lesions included thyroid nodules, lymph nodes, neurogenic tumors, and fat tissue. True-positive results on FNAC were significantly associated with performing FNA twice (58.3% vs. 23.1%, P=0.043). @*Conclusion@#Considering the low sensitivity of FNAC, measuring washout PTH in addition to FNAC may help accurately diagnose parathyroid incidentaloma on thyroid US. Further, the falsenegative rate for FNAC can be reduced by obtaining two or more FNA samples.

Impact of Additional Preoperative Computed Tomography Imaging on Staging, Surgery, and Postsurgical Survival in Patients With Papillary Thyroid Carcinoma

Objective@#We investigated the impacts of computed tomography (CT) added to ultrasound (US) for preoperative evaluation of patients with papillary thyroid carcinoma (PTC) on staging, surgical extent, and postsurgical survival. @*Materials and Methods@#Consecutive patients who underwent surgery for PTC between January 2015 and December 2015 were retrospectively identified. Of them, 584 had undergone preoperative additional thyroid CT imaging (CT + US group), and 859 had not (US group). Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for 14 variables and balance the two groups. Changes in nodal staging and surgical extent caused by CT were recorded.The recurrence-free survival and distant metastasis-free survival after surgery were compared between the two groups. @*Results@#In the CT + US group, discordant nodal staging results between CT and US were observed in 94 of 584 patients (16.1%). Of them, CT accurately diagnosed nodal staging in 54 patients (57.4%), while the US provided incorrect nodal staging. Ten patients (1.7%) had a change in the extent of surgery based on CT findings. Postsurgical recurrence developed in 3.6% (31 of 859) of the CT + US group and 2.9% (17 of 584) of the US group during the median follow-up of 59 months. After adjustment using IPTW (580 vs. 861 patients), the CT + US group showed significantly higher recurrence-free survival rates than the US group (hazard ratio [HR], 0.52 [95% confidence interval {CI}, 0.29–0.96]; P = 0.037). PSM analysis (535 patients in each group) showed similar HR without statistical significance (HR, 0.60 [95% CI, 0.31–1.17]; P = 0.134). For distant metastasis-free survival, HRs after IPTW and PSM were 0.75 (95% CI, 0.17–3.36; P = 0.71) and 0.87 (95% CI, 0.20–3.80; P = 0.851), respectively. @*Conclusion@#The addition of CT imaging for preoperative evaluation changed nodal staging and surgical extent and might improve recurrence-free survival in patients with PTC.

Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism

Background@#Optimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision- making before engaging in AVS and surgery in clinical practice. @*Methods@#We conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression. @*Results@#We developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53). @*Conclusion@#We propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients.

Assessing the diagnostic performance of thyroid biopsy with recommendations for appropriate interpretation

Purpose@#The diagnostic performance of thyroid biopsy is influenced by several factors, including differences in the Bethesda categorization for malignancy, the inclusion or exclusion of non-diagnostic results, the definition used for the final diagnosis, and the definition of an inconclusive diagnosis. The purpose of this study was to provide an understanding of the factors influencing the diagnostic performance of thyroid biopsy. @*Methods@#We collected data retrospectively between January and December 2013 from a cohort of 6,762 thyroid nodules from 6,493 consecutive patients who underwent biopsy. In total, 4,822 nodules from 4,553 patients were included. We calculated the biopsy sensitivity according to the inclusion of different Bethesda categories in the numerator and the exclusion of non-diagnostic results, as well as the diagnostic accuracy according to different definitions of a benign diagnosis. We obtained the conclusive and inconclusive diagnosis rates. @*Results@#The sensitivity increased when more Bethesda categories were included in the numerator and when non-diagnostic results were excluded. When a benign thyroid nodule diagnosis was defined as benign findings on surgical resection, concordant benign results on at least two occasions, or an initial benign biopsy result and follow-up for more than 12 months, the accuracy was higher than when the diagnosis was based on surgical resection alone (68.7% vs. 91.1%). A higher conclusive diagnosis rate was obtained (78.3% vs. 72.8%, P<0.001) when Bethesda categories I and III were considered inconclusive. @*Conclusion@#Understanding the concepts presented herein is important in order to appropriately interpret the diagnostic performance of thyroid biopsy.

Computer-Aided Diagnosis System for the Evaluation of Thyroid Nodules on Ultrasonography: Prospective Non-Inferiority Study according to the Experience Level of Radiologists

OBJECTIVE: To determine whether a computer-aided diagnosis (CAD) system for the evaluation of thyroid nodules is non-inferior to radiologists with different levels of experience.MATERIALS AND METHODS: Patients with thyroid nodules with a decisive diagnosis of benign or malignant nodule were consecutively enrolled from November 2017 to September 2018. Three radiologists with different levels of experience (1 month, 4 years, and 7 years) in thyroid ultrasound (US) reviewed the thyroid US with and without using the CAD system. Statistical analyses included non-inferiority testing of the diagnostic accuracy for malignant thyroid nodules between the CAD system and the three radiologists with a non-inferiority margin of 10%, comparison of the diagnostic performance, and the added value of the CAD system to the radiologists.RESULTS: Altogether, 197 patients were included in the study cohort. The diagnostic accuracy of the CAD system (88.48%, 95% confidence interval [CI] = 82.65–92.53) was non-inferior to that of the radiologists with less experience (1 month and 4 year) of thyroid US (83.03%, 95% CI = 76.52–88.02; p < 0.001), whereas it was inferior to that of the experienced radiologist (7 years) (95.76%, 95% CI = 91.37–97.96; p = 0.138). The sensitivity and negative predictive value of the CAD system were significantly higher than those of the less-experienced radiologists were, whereas no significant difference was found with those of the experienced radiologist. A combination of US and the CAD system significantly improved sensitivity and negative predictive value, although the specificity and positive predictive value deteriorated for the less-experienced radiologists.CONCLUSION: The CAD system may offer support for decision-making in the diagnosis of malignant thyroid nodules for operators who have less experience with thyroid US.

Clinical Outcomes of N1b Papillary Thyroid Cancer Patients Treated with Two Different Doses of Radioiodine Ablation Therapy

Background@#The optimal dose of radioactive iodine (RAI) therapy for N1b papillary thyroid carcinoma (PTC) is controversial. We evaluated the clinical outcome of N1b PTC patients treated with either 100 or 150 mCi of RAI. @*Methods@#We retrospectively analyzed N1b PTC patients who underwent total thyroidectomy and postoperative RAI therapy at a tertiary referral center between 2012 and 2017. As the baseline characteristics differed between treatment groups, we performed exact matching for various pathological factors according to RAI dose. We evaluated the response to therapy and recurrence-free survival (RFS) in the matched patients. Structural recurrent/persistent disease was defined as new structural disease detected after initial therapy, which was confirmed by cytology or pathology. @*Results@#Of the total 436 patients, 37 (8.5%) received 100 mCi of RAI and 399 (91.5%) received 150 mCi of RAI. After an exact 1:3 matching, 34 patients in the 100 mCi group and 100 patients in the 150 mCi group remained. There was no significant difference in response to therapy between the groups in the matched population (P=0.63). An excellent response was achieved in 70.6% (n=24) of patients in the 100 mCi group and 76.0% (n=76) in the 150 mCi group. Two (5.9%) patients in the 100 mCi group and four (4.0%) in the 150 mCi group had recurrence and there was no significant difference in RFS between the groups in the matched population (P=0.351). @*Conclusion@#There were no differences in response to therapy and RFS in N1b PTC patients according to RAI dose.

Sonographic Assessment of the Extent of Extrathyroidal Extension in Thyroid Cancer

Objective@#This study aimed to determine the sonographic features suggestive of extrathyroidal extension (ETE) of thyroid cancers. @*Materials and Methods@#We retrospectively reviewed the sonographic images of 1656 consecutive patients who had undergone thyroidectomy in 2017. The diagnostic performance of sonographic features suggestive of ETE was evaluated using operation and histopathologic reports. Sonographic features for gross ETE to the strap muscle and minor ETE were assessed for thyroid cancer abutting the anterolateral thyroid capsule. Sonographic features for tracheal invasion were assessed according to whether the angle between the tumor and the trachea was an acute, right, or obtuse angle. Sonographic features for recurrent laryngeal nerve (RLN) invasion were assessed based on the association between the tumor and tracheoesophageal groove (TEG) as preserved normal tissue, abutting or protruding into the TEG. @*Results@#ETE was observed in 783 patients (47.3%), including 123 patients with gross ETE (7.4% [strap muscle, n = 97; RLN, n = 24; and trachea, n = 14]) and 660 patients with minor ETE (39.9%). Regarding the diagnosis of gross and minor ETE to the strap muscle, sonographic features of replacement of the strap muscle and capsular disruption showed the highest positive predictive value (75.9% and 58.5%, respectively). Thyroid cancer forming an obtuse angle with the trachea had the highest sensitivity for the diagnosis of tracheal invasion (85.7%), and thyroid cancer protrusion into the TEG showed the highest sensitivity for the diagnosis of RLN (83.3%). @*Conclusion@#Sonography is considered beneficial in the diagnosis of ETE to the strap muscle, trachea, and RLN. Assessment of ETE is important for the accurate staging of thyroid cancer, which in turn determines the extent of surgery or whether active surveillance is appropriate or not.

The Role of Core Needle Biopsy for the Evaluation of Thyroid Nodules with Suspicious Ultrasound Features

OBJECTIVE: Recent studies demonstrated that core needle biopsy (CNB) can effectively reduce the possibility of inconclusive results and prevent unnecessary diagnostic surgery. However, the effectiveness of CNB in patients with suspicious thyroid nodules has not been fully evaluated. This prospective study aimed to determine the potential of CNB to assess thyroid nodules with suspicious ultrasound (US) features. MATERIALS AND METHODS: Patients undergoing CNB for thyroid nodules with suspicious features on US were enrolled between May and August 2016. Diagnostic performance and the incidence of non-diagnostic results, inconclusive results, conclusive results, malignancy, unnecessary surgery, and complications were analyzed. Subgroup analysis according to nodule size was performed. The risk factors associated with inconclusive results were evaluated using multivariate logistic regression analysis. RESULTS: A total of 93 patients (102 thyroid nodules) were evaluated. All samples obtained from CNB were adequate for diagnosis. Inconclusive results were seen in 12.7% of cases. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for diagnosis of malignancy were 93.8%, 100%, 100%, 78.9%, and 95%, respectively. None of the patients underwent unnecessary surgery. The diagnostic performance was not significantly different according to nodule size. On multivariate logistic regression analysis, larger nodule size and shorter needle length were independent risk factors associated with inconclusive results. CONCLUSION: Samples obtained by CNB were sufficient for diagnosis in all cases and resulted in high diagnostic values and conclusive results in the evaluation of suspicious thyroid nodules. These findings indicated that CNB is a promising diagnostic tool for suspicious thyroid nodules.

Myxoid and Sarcomatoid Variants of Adrenocortical Carcinoma: Analysis of Rare Variants in Single Tertiary Care Center

The aim of this study is to describe rare variants of adrenocortical carcinoma (ACC) and to compare the prognosis with that of conventional ACC. We retrospectively reviewed 8 cases of myxoid variant, 1 sarcomatoid variant, and 14 cases of conventional ACC, who underwent surgical resection at the Asan Medical Center between 1996 and 2014. An analysis of the clinicopathological characteristics, including the Weiss score, Ki-67 labeling index, and reticulin framework assessment is presented. The mean age of patients with myxoid/sarcomatoid ACC was 45 years; 4 out of 9 patients were women. Mean primary tumor size was 12.9 cm and the mean weight was 702.4 g. Seven patients presented in an advanced stage (stage III/IV); 8 of these eventually developed distant metastasis. The mean Weiss score was 5.0 points and the Ki-67 labeling index was 15.6%. The extent of myxoid or sarcomatoid change on histological examination ranged from 10% to 75% of the examined tumor areas; reticulin framework alteration was observed in all cases. Four patients showed venous tumor thrombus. Most of the clinicopathological parameters were not significantly different from those of conventional ACC. However, myxoid or sarcomatoid variant (hazard ratios [HR], 3.59; 95% confidence intervals [CI], 1.13–11.38; P = 0.030) and Ki-67 labeling index (HR, 3.97; 95% CI, 1.18–13.41; P = 0.030) were independent predictors of overall survival after adjusting for age and sex. Myxoid or sarcomatoid histological features or an increased Ki-67 labeling index may be associated with poor overall survival in patients with ACC.

Outcomes of Laparoscopic Pyloromyotomy with Microscope and Stab Incision vs. Open Pyloromyotomy in Infantile Hypertrophic Pyloric Stenosis; Single Institution Experience

PURPOSE: We attempted to evaluate the outcomes of a newly inaugurated surgical technique of laparoscopic pyloromyotomy with microscope and stab incision (MS-LP) with right upper quadrant transverse open pyloromyotomy (RT-OP), which were performed in a single institution. METHODS: The outcome variables in terms of total anesthesia time, operative time, postoperative emesis, time to full-enteral feeding, postoperative hospital stay, cosmetic result score, medical cost, and postoperative wound complications were compared between the MS-LP and RT-OP groups. RESULTS: Fifty-one consecutive pyloromyotomy cases were enrolled; MS-LP (n=33) and RT-OP (n=18). There was no difference in age, pyloric thickness, and preoperative electrolyte levels between the two groups. The total anesthesia time and operative time of MS-LP were not significantly longer than that of RT-OP. Time to full-enteral feeding and postoperative hospital stay were shorter in MS-LP (20.0±18.3 vs. 35.3±14.8 hrs. and 2.4±1.3 vs. 3.4±1.2 days; p=0.047 and 0.050, respectively). The cosmetic result score and medical cost were significantly higher in MS-LP (9.1±1.0 vs. 7.3±1.2 in terms of scores and 3,501,950±1,093,147 vs. 2,522,474±68,605 in terms of KRW; p=0.001 and 0.021, respectively). No difference in postoperative wound complications was observed between the two groups. CONCLUSION: Laparoscopic pyloromyotomy with microscope and stab incision may suggest recovery benefits with a shorter time to full-enteral feeding and postoperative hospital stay, as well as better cosmetic results than RT-OP. However, MS-LP may induce higher costs.

Clinical Meaning of Neutrophil-to-Lymphocyte Ratio (NLR)in Papillary Thyroid Carcinoma / 대한내분비외과학회지

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammatory response, which is inexpensive, easily calculated, and known to show correlation with prognosis of cancer. The aim of this study was to evaluate the relationship between NLR and prognosis of papillary thyroid carcinoma. METHODS: A total of 1,142 patients who underwent total thyroidectomy for papillary thyroid carcinoma between 1995~2005 at Asan Medical Center were enrolled in this study. Patients were categorized according to two groups based on NLR and clinico-pathological variables and disease survival were compared between the two groups. RESULTS: Median age of patients was 45.4 years, and the median follow-up period was 48 months. The cut-off value of NLR for prediction of disease-free survival (DFS) was 2. Comparison of DFS between two groups stratified by NLR (NLR ≤2, NLR>2) showed little statistical difference (P=0.48). After adjusting for risk (N stage), there was no significant difference according to N stage (N0: P=0.86, N1a: P=0.4, N1b: P=0.12). CONCLUSION: NLR did not show correlation with disease free survival of papillary thyroid carcinoma.

Risk Factors for Distant Metastasis in Patients with Follicular Thyroid Carcinoma / 대한내분비외과학회지

PURPOSE: The major issue of follicular thyroid carcinoma (FTC) diagnosed after hemithyroidectomy is whether to undergo further treatments. The aim of this study is to examine the clinico-pathological characteristics of FTC and to evaluate the risk factors for distant metastasis. METHODS: From 1993 to 2010, 274 patients underwent initial thyroid surgery and were subsequently diagnosed as FTC. After review of the histological sections by an experienced pathologist, 211 patients were confirmed as FTC and were enrolled in this study. Clinicopathological features were compared based on the presence or absence of distant metastases, and the risk factors for distant metastases and distant metastases-free survival (DMFS) rates were analyzed. RESULTS: The patients included 39 males (18.5%) and 172 females (81.5%), with a mean age of 44.0±14.5 years. The median follow-up period was 99.5 months (range, 13.0~222.0). Distant metastases were detected in 23 patients (10.9%), including 15 synchronous distant metastases and 8 metachronous distant metastases. In multivariate analysis, age ≥45 years, widely invasive FTC, tumor size ≥4.3 cm, and vascular invasion were independent risk factors for distant metastasis. DMFS rates in patients with these risk factors were significantly poorer than those in patients without these risk factors. CONCLUSION: Older age, aggressive histological classification, larger tumor size, and vascular invasion were independent risk factors for distant metastasis. FTC patients with these risk factors may be candidates for further treatments after diagnostic thyroid hemithyroidectomy.

Innovative In Vitro Chemo-Hormonal Drug Therapy for Refractory Thyroid Carcinomas

More than 95% of the thyroid carcinomas are well differentiated types showing favorable prognosis. However, only a few therapeutic options are available to treat the patients with undifferentiated thyroid carcinomas, especially with refractory thyroid carcinomas that are not amenable to surgery or radioiodine ablation. We investigated the anticancer effects of 20 chemotherapy and hormonal therapy drugs on 8 thyroid carcinoma cell lines. In vitro chemosensitivity was tested using the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA). The tumor inhibition rate (TIR; or cell death rate) or half maximal inhibitory concentration (IC50) was analyzed to interpret the results. Of the 12 chemotherapy drugs, etoposide (178.9 index value in follicular carcinoma cell line) and vincristine (211.7 in Hurthle cell carcinoma cell line) were the most active drugs showing the highest chemosensitivity, and of the 8 additional drugs, trichostatin A (0.03 microg/mL IC50 in follicular carcinoma cell line) showed favorable outcome having the anticancer effect. In our study, the result of etoposide and vincristine show evidence as active anticancer drugs in thyroid carcinoma cell lines and trichostatin A seems be the next promising drug. These drugs may become an innovative therapy for refractory thyroid carcinomas in near future.

Recurred Parathyroid Carcinoma: A Case of Cervical Recurrence Presenting Discrepancy between Image Findings and Operative Findings / 대한내분비외과학회지

Parathyroid carcinoma is a rare malignancy presenting hyperparathyroidism. At times, diagnosis and localization are difficult. The optimum treatment for parathyroid carcinoma is en bloc resection when malignancy is highly suspicious or diagnosed. However, even after the adequate surgical treatment, persistent or recurrent disease is well encountered. Here we report a case with recurred parathyroid carcinoma presenting discrepancy between image findings and operative findings.

Expression of X-linked Inhibitor of Apoptosis Protein in Neoplastic Thyroid Disorder

X-linked inhibitor of apoptosis protein (XIAP) is associated with tumor genesis, growth, progression and metastasis, and acts by blocking caspase-mediated apoptosis. In the present study, we sought to evaluate the expression patterns of XIAP in various neoplastic thyroid disorders and determine the association between XIAP expression and clinicopathologic factors. Expression of XIAP was evaluated with immunohistochemical staining using monoclonal anti-XIAP in 164 specimens of conventional papillary thyroid carcinoma (PTC) and 53 specimens of other malignant or benign thyroid tumors. XIAP positivity was observed in 128 (78%) of the 164 conventional PTC specimens. Positive rates of XIAP expression in follicular variant PTC, follicular, medullary, poorly differentiated, and anaplastic thyroid carcinoma specimens were 20%, 25%, 38%, 67%, and 38%, respectively. Six nodular hyperplasia specimens were negative and 1 of 7 follicular adenomas (8%) was positive for XIAP. Lateral neck lymph node metastases were more frequent in patients negative for XIAP expression (P = 0.01). Immunohistochemical staining for XIAP as a novel molecular marker may thus be helpful in the differential diagnosis of thyroid cancer. Moreover, high XIAP expression in conventional PTC is strongly associated with reduced risk of lateral neck lymph node metastasis.

Surgical Treatment of Graves' Disease: Comparison between Total Thyroidectomy and Subtotal Thyroidectomy

PURPOSE: Subtotal thyroidectomy has been the standard operation for Graves' disease in achieving a favorable outcome in recovery of euthyroid state. However, the postoperative outcomes following subtotal thyroidectomy differ by surgeon and postoperative thyroid dysfunctions develop as time passes. Here, we have studied the validity of total thyroidectomy for Graves' disease patients, with a comparison to subtotal thyroidectomy. METHODS: A total of 299 patients with Graves' disease underwent thyroid operation consecutively in Asan Medical Center, Seoul, Korea from December 1995 to December 2005. Among them, 241 cases had subtotal thyroidectomy and 43 had total thyroidectomy. The subtotal thyroidectomy cases were divided into 3 groups according to estimated remnant thyroid; or =6 g. Also, according to postoperative thyroid function, the patients were divided into euthyroid, hypothyroidism and hyperthyroidism groups. The postoperative changes of thyroid function, postoperative complications and hospital days were analyzed. RESULTS: In subtotal thyroidectomy, postoperative thyroid function showed euthyroid in 25 (10.4%), hypothyroidism 206 (85.5%) and hyperthyroidism 10 (4.1%). However, total thyroidectomy showed no persistent hyperthyroidism or recurrence. The postoperative thyroid function state changed in 24 patients out of 148 who had more than 2 years postoperative follow-up. Hyper-functional changes developed with higher rates (Hypo-6 vs. hyper-18). The postoperative complication rate was higher in subtotal thyroidectomy including bleeding, hoarseness and hypocalcemia. CONCLUSION: In our study, the patients showing normal thyroid function after subtotal thyroidectomy were very limited and thyroid dysfunction developed continuously with time lapse, especially towards hyperthyroid state. Therefore, we suggest that total thyroidectomy should be considered as a treatment option in Graves' disease.

Medullary Thyroid Carcinoma: 25-year Experience and the Results of the RET Proto-oncogene Screening Test / 대한내분비외과학회지

PURPOSE: Medullary thyroid carcinoma (MTC) is a rare thyroid tumor and its clinical course is quite variable. The aim of this study was to retrospectively analyze our clinical and laboratory data for 25 years to review the clinicopathologic characteristics, the operation methods, the tumor recurrence and the prognosis of medullary thyroid carcinoma. We also reevaluate the limits of the previous diagnostic and treatment modalities. The positivity for and the location of the RET mutation are also evaluated. Finally, we want to contribute to a systemic approach for the diagnosis, treatment, patient management and clinical study of medullary thyroid carcinoma. METHODS: We conducted a retrospective review of the records of 77 patients with MTC that were seen at our hospital from 1982 to 2007. The medical records were reviewed for the demographic data, the laboratory data and the clinical course, the treatment, the long-term outcome and the RET proto-oncogene mutation. The mean follow-up period was 69.6 months (range: 6~201). RESULTS: There were 50 females and 27 males. The mean patient age was 44.2 years (range: 1~80). There were 16 cases of the sporadic form (79.2%) and 16 cases of the hereditary form. At diagnosis, 73 patients (94.8%) had local disease and 4 patients (5.2%) had distant metastasis. The patients with the hereditary form were younger than the patients with the sporadic form (P=0.004), and they had more muticentric (P=0.002) and bilateral tumor (P<0.001). The initial surgery consisted of total thyroidectomy in 74 patients (96.1%), and lateral neck dissection in 41 patients (53.2%) (therapeutic: 23, prophylactic: 18), except for 3 cases with less than total thyroidectomy. Forty-four patients (57.1%) achieved a long-term remission state, 13 patients (16.9%) had biochemical persistent disease, and 20 patients (26.0%) had metastasis. The 5- and 10-year survival rates were 86.5% and 74.1% respectively. On univariate analysis, tumor size (more than 2 cm), extracapsular invasion, involvement of the neck nodes and distant metastasis at the time of diagnosis were the significant prognostic factors of persistent or recurrence disease. CONCLUSION: Patients with MTC generally have a favorable outcome. The presence of distant metastasis at the time of diagnosis is predictive of persistent or recurrence disease by multivariate analysis. In order to achieve an early diagnosis and administer prompt treatment, we suggest that optimal RET oncogene screening and counseling should be performed for medullary patients and their relatives.