Determining the Factors Predicting the Response to Anti-HER2 Therapy in HER2-Positive Breast Cancer Patients.

PURPOSE: We aimed to identify the differently expressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant systemic therapy with trastuzumab in HER2-positive breast cancer patients. METHODS: This study was retrospectively analyzed from consecutively collected patient data. We recruited 64 women with breast cancer and categorized them into 3 groups: complete response (CR), partial response (PR), and drug resistance (DR). The final number of patients in the study was 20. RNA from 20 core needle biopsy paraffin-embedded tissues and 4 cultured cell lines (SKBR3 and BT474 breast cancer parent cells and cultured resistant cells) was extracted, reverse transcribed, and subjected to GeneChip array analysis. The obtained data were analyzed using Gene Ontology, Kyoto Gene and Genome Encyclopedia, Database for Annotation, Visualization and Integrated Discovery. RESULTS: In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines were identified. Among these, 3,224 were upregulated and 3,432 were downregulated. Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment in HER2-type breast cancer, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in the CR group. CONCLUSIONS: This multigene assay-based study provides insights into breast cancer signaling and possible predictions of therapeutic response to targeted therapies such as trastuzumab.

Survival benefit of postoperative radiotherapy for ductal carcinoma in situ after breast-conserving surgery: a Korean population-based cohort study.

PURPOSE: It has been accepted that radiation therapy (RT) for ductal carcinoma in situ (DCIS) has no survival benefit despite increasing local control. However, a recent large database study reported a small but significant benefit. Using a Korean population-based large database, we examined the survival benefit of RT for DCIS after breast-conserving surgery (BCS) and analyzed which subgroup might derive benefit from it. METHODS: Data from 6038 female DCIS patients who underwent BCS with or without RT between 1993 and 2012 were included in this study. We used propensity score analysis to control for differences in baseline characteristics. RESULTS: Before adjusting, patients who received RT were more likely to have a large-sized tumor, poor histologic grade, poor nuclear grade, and less hormone receptor positivity. Ten-year overall survival (OS) rates were 95.0% in the non-RT group and 97.1% in the RT group (p < 0.001). After adjusting, previously noted differences of characteristics were substantially reduced, and then ten-year OS rates were 94.3% in the non-RT group and 97.6% in the RT group (p = 0.001). When examining the benefit of RT according to proposed prognostic scores, patients with a score of 0 showed no difference in OS by adding RT after BCS, whereas those with high scores demonstrated a significant benefit. CONCLUSIONS: We demonstrated the significant OS benefit of postoperative RT after BCS based on a large database, and for the first time beyond the western population. The omission of RT for selected patients to prevent overtreatment needs to be more elaborately studied.

Radiation-related heart disease after breast cancer radiation therapy in Korean women.

PURPOSE: To study the late cardiac toxicity of breast radiation therapy (RT) in Asian women. METHODS: Female breast cancer patients in Korea who underwent breast conservation surgery followed by RT from 1990-2012 were identified from two large registries at institution and population levels. Cumulative incidences of acute coronary events (ACE) or cardiac mortality were estimated in relation to the laterality of breast cancer using a competing risks analysis. RESULTS: In an analysis of 2577 women from a single institution, 3.7% were obese (body mass index ≥30), and 3.4% were ever-smokers. Patients with a history of hypertension, diabetes, or coronary artery disease were 17.5, 5.7, and 2.8%, respectively. The mean heart doses were 6.2 and 1.5 Gy for left- and right-sided tumors, respectively. With a median follow-up of 7 (range 1-23) years, the overall and breast cancer-specific survivals at 10 years were 94.9 and 96.5%, respectively. The 10-year cumulative incidence of ACE was 2.96%. The mean time to ACE was 5.2 ± 3.9 years (range 1-17). There was no clinically relevant difference in rates of ACE between left-sided and right-sided patients, with an adjusted hazard ratio of 1.16 (CI 0.59-2.29). An analysis of 24,235 women in a nationwide registry validated these negative findings with respect to cardiac mortality, with an adjusted hazard ratio of 1.52 (CI 0.37-6.25). Increasing age, a higher body mass index, and a history of hypertension or ischemic heart disease were identified as risk factors. CONCLUSIONS: Our findings reassure that excess risk from breast RT may be small in healthy women, most of who not smoke, weigh less, and have fewer risk factors. A validation using a larger data set of National Health Insurance Corporation is ongoing.

Comparison of skin-sparing mastectomy using LigaSure™ Small Jaw and electrocautery.

BACKGROUND: Skin-sparing mastectomy (SSM) is increasingly used in patients with breast cancer. We compared the differences between use of electrocautery and LigaSure™ Small Jaw in patients with breast cancer who underwent SSM. METHODS: Between January 2012 and December 2015, 81 patients with breast cancer who underwent SSM were selected and were divided into the electrocautery group and the LigaSure™ Small Jaw group based on the devices that were used. Clinicopathological characteristics, body mass index, operative time, and weight of removed breast were obtained from medical records. Total amount and days of drain use, until removal, and postoperative skin necrosis, requiring debridement, were also analyzed. RESULTS: The study population consisted of 50 patients in the electrocautery group and 31 in the LigaSure™ Small Jaw group. The latter group has significantly shorter operative time (117.5 ± 16.9 vs. 104.0 ± 23.6 min, P = 0.004). The mean total volume of drainage was less (805 ± 278 vs. 694 ± 131 mL, P = 0.017) and mean duration of drainage was also significantly shorter in the LigaSure™ Small Jaw group (11.3 ± 2.5 vs. 10.1 ± 2.0 days, P = 0.029). CONCLUSIONS: The use of LigaSure™ Small Jaw during skin-sparing mastectomy shortened the operative time and duration of drainage and reduced the total volume of drainage.

Thermal injury of the recurrent laryngeal nerve by THUNDERBEAT during thyroid surgery: findings from continuous intraoperative neuromonitoring in a porcine model.

BACKGROUND: Recurrent laryngeal nerve (RLN) palsy is the most common and serious complication of thyroid surgery. The use of energy-based devices (EBDs) has replaced hand-tying methods in many institutions. However, EBD use proximal to the RLN presents risks related to lateral thermal spread and associated nerve damage. THUNDERBEAT (TB) is one of the most widely used EBDs. This study aimed to test the safety of TB during thyroidectomy. METHODS: Four piglets weighing 30-40 kg experienced thyroidectomy while continuous electrophysiologic monitoring (continuous intraoperative neuromonitoring) occurred, using an electromyography endotracheal tube and NIM 3.0 response system. TB was applied at various distances from the RLN, and we assessed the safety of the protocols. RESULTS: Adverse electromyography events did not occur at distances >3 mm from the RLN. Amplitude decreased at 2 mm from the RLN after 8 s. However, immediate loss of signal occurred at 1 mm from the RLN, likely due to immediate shrinkage of surrounding tissue after TB application. CONCLUSIONS: TB can be used safely at 3 mm from the RLN but must be used for <8 s at more proximal locations. This is the first report assessing the safety of TB, and findings indicate that TB should be used at least 1 mm from the RLN to avoid injury.

Pre-ablation stimulated thyroglobulin is a better predictor of recurrence in pathological N1a papillary thyroid carcinoma than the lymph node ratio.

BACKGROUND: Papillary thyroid carcinomas (PTC) with lymph node metastases have a high recurrence rate. We analyzed the potential of lymph node ratio (LNR) and the level of pre-ablation stimulated thyroglobulin (sTg) as risk factors predicting recurrence in patients with pathological N1a PTC. MATERIALS AND METHODS: This study involved 192 patients with pathologically confirmed PTC and central neck lymph node metastases who underwent total thyroidectomy with central lymph node dissection (CLND). The clinico-pathological characteristics, the pre-ablation sTg level and post-treatment recurrences were examined. Univariate and multivariate analyses were performed to identify factors associated with recurrence in these patients. RESULTS: During a median follow-up of 63 months, 17 patients had loco-regional recurrences. Receiver operating characteristic curve analysis showed that the appropriate cut-off values for LNR and the pre-ablation sTg level was 0.48 and 9.3 ng/mL, respectively. Patients with LNR values of ≥0.48 had a significantly worse disease-free survival (DFS) than those with LNR values of <0.48 (P = 0.015), and patients with pre-ablation sTg level values of ≥9.3 ng/mL had significantly worse DFS than those with pre-ablation sTg level values <9.3 ng/mL (P < 0.001). Relative to patients with LNR values of <0.48, those with LNR values of ≥0.48 had higher median pre-ablation sTg level values (0.55 vs. 4.20; P < 0.001). The correlation covariant between the LNR value and the pre-ablation sTg level value was r = 0.454 (P < 0.001). Multivariate analysis showed that a LNR value of ≥0.48 (P = 0.386) was not an independent risk factor for recurrence. To the contrary, a pre-ablation sTg level value of ≥9.3 ng/mL (P < 0.001) was an independent risk factor for recurrence. CONCLUSION: A high pre-ablation sTg level is a better predictor of recurrence in pathological N1a PTC than a high LNR value. Careful follow-up of patients with this risk factor is recommended.

Robotic thyroidectomy using bilateral axillo-breast approach: Comparison of surgical results with open conventional thyroidectomy.

BACKGROUND: The aim of the present study was to compare the surgical outcomes of robotic thyroidectomy using the bilateral axillo-breast approach (BABA) with open conventional thyroidectomy. METHODS: Database of patients who underwent thyroidectomy with cervical lymph node dissection after diagnosed as papillary thyroid carcinoma between July 2008 and February 2013 were examined. Clinicopathologic characteristics, surgical outcomes, and postoperative morbidities of robot group and open group were investigated. RESULTS: The dominant tumor size (P=0.974), body mass index (BMI) (P=0.426), and the mean number of metastatic lymph nodes in central compartment neck dissection (P=0.269) were comparable between the two groups. The mean number of retrieved central lymph nodes was higher in the open group than in the robot group (P=0.001). Postoperative complications were comparable: hypoparathyroidism in 2 weeks (P=0.296) and 3 months (P=0.446) after the surgery; vocal cord palsy in 2 weeks (P=0.363) and 3 months (P=0.312); hematoma (P=0.162); and wound infection (P=0.421). CONCLUSIONS: Robotic thyroidectomy using BABA may be a technically feasible and safe procedure comparable to conventional open surgery especially in node-negative patients.

Transoral periosteal thyroidectomy: cadaver to human.

BACKGROUND: Although endoscopic thyroid surgery is gaining wide acceptance, existing endoscopic methods for thyroidectomy are blamed for the increased frequency of flap dissections and longer surgical times. More recently, transoral endoscopic thyroidectomy has overcome the limitations of previous approaches. Herein, we present our initial experience with transoral periosteal thyroidectomy (TOPOT) in cadaver and porcine models. Using these models, the surgical view was improved and had greater freedom of motion; the technique was then performed in human subjects using robotic TOPOT, which has not previously been reported. METHOD: TOPOTs were performed in seven fresh human cadavers and ten live pigs. Total thyroidectomies were performed in all cadavers and pigs. After the cadaver and animal trials, four human patients underwent robotic TOPOT performed using the da Vinci® surgical system at Korea University Anam Hospital. Recurrent laryngeal nerve function, intra- and postoperative complications, and postoperative outcomes were assessed in all patients. RESULT: One left lobectomy for follicular adenoma, two right lobectomies for nodular hyperplasia, and one left lobectomy with a central neck dissection for papillary thyroid microcarcinoma were performed in the human subjects using a robotic transoral periosteal approach. In three cases, paresthesia occurred in the mental nerve, but this improved within 4 weeks in all cases. No local infections occurred at the incision site or anterior neck, and no recurrent laryngeal nerve cord palsies occurred postoperatively. CONCLUSION: TOPOT may be an effective and safe approach for robotic thyroid surgery.

Effect of Antiadhesion Barrier Solution and Fibrin on Capsular Formation After Silicone Implant Insertion in a White Rat Model.

INTRODUCTION: One of the most serious complications of breast reconstruction and augmentation using silicone implants is capsular contracture. Several preventive treatments, including vitamin E, steroids, antibiotics, and cysteinyl leukotriene inhibitors, have been studied, and their clinical effects have been reported. However, the problem of capsular contracture has not yet been completely resolved. This study was performed to compare anti-adhesion barrier solution (AABS) and fibrin in their ability to prevent fibrotic capsule formation and simultaneously evaluated their effect when used in combination by capsular thickness analysis and quantitative analysis of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and type I collagen within the fibrous capsule. MATERIALS AND METHODS: This study used female six-week-old Sprague-Dawley rats. Eighty rats were equally subdivided into the four following groups: AABS-treated, fibrin-treated, AABS and fibrin combined-treated, and untreated control groups. Each rat received two silicone chips under the panniculus carnosus muscle layer. The test materials were applied around the silicon chips. Four weeks later, the implantation sites including the skin and muscle were excised to avoid the risk of losing the fibrous capsule around the implants. The capsular thickness was analyzed by Masson's trichrome stain. Quantitative analysis of type I collagen, MMPs, and TIMPs was performed by real-time PCR, Western blot, and zymography. RESULTS: The mean capsular thickness was 668.10 ± 275.12 µm in the control group, 356.97 ± 112.11 µm in the AABS-treated group, 525.96 ± 130.97 µm in the fibrin-treated group, and 389.24 ± 130.51 µm in the AABS and fibrin combined-treated group. Capsular thickness was significantly decreased in all experimental groups (p < 0.05). Capsular thickness was greater in the fibrin-treated group than in the AABS-treated group (p < 0.05). There was no statistically significant difference in capsular thickness between the AABS and fibrin combined-treated group and the AABS- or fibrin-treated group (p > 0.05). Compared to the control group, the experimental groups had significantly lower expressions of type I collagen and MMP-1 (p < 0.05), but there was no statistically significant difference in expressions of type I collagen and MMP-1 between the AABS-, fibrin-, and AABS and fibrin combined-treated groups (p > 0.05). The expressions of MMP-2 and TIMP-2 were not significantly different between the control and the experimental groups (p > 0.05). CONCLUSION: AABS is more effective in reducing capsular thickness compared with fibrin treatment in a white rat model.

Prognosis according to the timing of recurrence in breast cancer.

Purpose: Clinically, breast cancer can be divided into 4 subtypes based on the presence of hormone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67. Because the pattern and time of recurrence vary according to the subtype, we evaluated whether there was a difference in overall survival (OS) among the subtypes according to the time and type of recurrence. Methods: A total of 2,730 patients who underwent breast cancer surgery were analyzed. Early and late recurrence were defined as recurrence within and after 5 years of diagnosis, respectively. Recurrence type was categorized as locoregional recurrence or systemic recurrence. Results: Hormone receptor-positive tumors were significantly more frequent in the late recurrence group than in the early recurrence group (estrogen receptor positive, 47.8% [early] vs. 78.7% [late]). However, there was no difference in the rate of HER2 overexpression (HER2+, 38.1% [early] vs.39.0% [late]). In subgroup analysis, early recurrence was a significant prognostic factor for OS in all subtypes. However, late recurrence was a significant prognostic factor for OS only in the luminal B subtype (hazard ratio of 4.30). In addition, the luminal B type had the highest proportion in late recurrence patients (63.2%). Conclusion: The luminal B subtype had a high rate of late recurrence, and late recurrence was a poor prognostic factor for OS only in this subgroup. Therefore, further targeted treatments for luminal B breast cancer are needed and patients with this subtype require close long-term surveillance.

Triple negative breast cancer in Korea-distinct biology with different impact of prognostic factors on survival.

We analyzed breast cancer subtypes using Korean Breast Cancer Society Registration Program data to compare clinical features and prognosis for triple-negative breast cancer (TNBC). A cohort of 26,767 breast cancer patients were divided in four groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+ HER2+), HER2+ (ER-, PR-, HER2+), and triple-negative (ER-, PR-, HER2-). Clinicopathologic factors were evaluated. The luminal A (14,437 patients, 53.9%) subtype was the largest in our study. Compared with luminal A subtype, TNBC correlated with younger age, more aggressive characteristics and poor overall survival and breast cancer-specific survival. The hazard rate showed a peak at 24 months for the TNBC subtype, but after 60 months, risk was similar to that of the luminal A subtype. Higher T, N stage and histologic grade, and lymphatic and vascular invasion showed poor prognosis in TNBC patients, but on multivariate analysis only histologic grade and ki-67 status were related. Young age was related to poor prognosis in the luminal A subtype, however, age was not related to prognosis in the TNBC subtype. Of the 5,586 TNBC patients, 282 patients (7.11%) expired within 3 years of diagnosis. T and N stage and grade were significantly associated with prognosis on multivariate analysis. TNBC subtype is characterized by younger age with poorer outcome. However, younger age is not related to prognosis, and mortality risk decreases to that of the luminal A subtype, which is known to have the best prognosis after a few years.

Differences in prognosis by p53 expression after neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: Our previous studies suggested that p53-positive triple-negative breast cancer (TNBC) should be more sensitive to chemotherapy than p53-negative TNBC. The aim of this study was to determine whether p53 expression in TNBC could predict response to neoadjuvant chemotherapy and the resulting prognosis. METHODS: From January 2009 to December 2017, TNBC patients who underwent neoadjuvant chemotherapy were reviewed, including a total of 31 TNBC patients who had clinical lymph node metastasis. The status of p53 expression in patients before and after chemotherapy was evaluated. RESULTS: Two patients (22.2%, 2 of 9) achieved pCR in p53(+) TNBC and 4 patients (50%, 5 of 10) achieved pCR in p53(-) TNBC. There was no correlation between pCR rate and p53 expression (P = 0.350). Based on prechemotherapy p53 expression, there was no significant difference in disease-free survival (DFS) between p53(+) TNBC and p53(-) TNBC (P = 0.335). However, after chemotherapy, p53(+) TNBC had shown higher DFS than p53(-) TBNC (P = 0.099). Based on prechemotherapy p53 expression, p53(+) TNBC had better overall survival (OS) than p53(-) TNBC, but the difference was not statistically significant (P = 0.082). After chemotherapy, p53(+) TNBC showed significantly better OS than p53(-) TNBC (P = 0.018). CONCLUSION: Immunohistochemically detected p53 expression in TNBC could not predict the response to neoadjuvant chemotherapy. However, p53(+) TNBC had a better OS than p53(-) TNBC in patients who underwent neoadjuvant chemotherapy.

HSP90 Inhibitor, 17-DMAG, Alone and in Combination with Lapatinib Attenuates Acquired Lapatinib-Resistance in ER-positive, HER2-Overexpressing Breast Cancer Cell Line.

Lapatinib, a Human Epidermal growth factor Receptor 2 (HER2)-targeting therapy in HER2-overexpressing breast cancer, has been widely used clinically, but the prognosis is still poor because most patients acquire resistance. Therefore, we investigated mechanisms related to lapatinib resistance to evaluate new therapeutic targets that may overcome resistance. Lapatinib-resistant cell lines were established using SKBR3 and BT474 cells. We evaluated cell viability and cell signal changes, gene expression and protein changes. In the xenograft mouse model, anti-tumor effects were evaluated using drugs. Analysis of the protein interaction network in two resistant cell lines with different lapatinib resistance mechanisms showed that HSP90 protein was commonly increased. When Heat Shock Protein 90 (HSP90) inhibitors were administered alone to both resistant cell lines, cell proliferation and protein expression were effectively inhibited. However, inhibition of cell proliferation and protein expression with a combination of lapatinib and HSP90 inhibitors showed a more synergistic effect in the LR-BT474 cell line than the LR-SKBR3 cell line, and the same result was exhibited with the xenograft model. These results suggest that HSP90 inhibitors in patients with lapatinib-resistant Estrogen Receptor (ER) (+) HER2 (+) breast cancer are promising therapeutics for future clinical trials.

A significant correlation between nuclear CXCR4 expression and axillary lymph node metastasis in hormonal receptor negative breast cancer.

BACKGROUND AND OBJECTIVES: In breast cancer, the expression pattern of CXCR4 may be correlated with the degree of axillary lymph node involvement. The aim of this study was to evaluate the contributing factors that contribute to the correlation between CXCR4 expression and axillary lymph node metastasis in breast cancer. METHODS: Between August 1997 and August 2002, sections of paraffin-embedded tissue were obtained from 107 patients who received optimal treatment for breast cancer. The expression of CXCR4 was evaluated by immunohistochemical staining. RESULTS: A significant correlation was found in the expression of nuclear CXCR4 and lymph node metastasis (P = 0.03). We found a significant correlation between a high nuclear expression of CXCR4 and axillary lymphatic metastasis in estrogen and progesterone receptor negative breast cancer (P = 0.01 and P = 0.01). There was a significant correlation between the high expression of nuclear CXCR4 and axillary lymphatic metastasis in comparisons between positive estrogen and/or progesterone receptor expression and negative expression (P = 0.02). CONCLUSIONS: Our results showed that high expression of nuclear CXCR4 was significantly correlated with lymph node metastasis in breast cancer. The high expression of nuclear CXCR4 in hormone receptor negative breast cancer was associated with a high possibility of lymph node metastasis.

Lymph node ratio as an alternative to pN staging for predicting prognosis after neoadjuvant chemotherapy in breast cancer.

Axillary nodal status is one of the most important prognostic factors in breast cancer. The lymph node ratio (LNR) has been suggested as an independent prognostic factor because the number of dissected and involved lymph nodes might differ across institutions. Neoadjuvant chemotherapy (NAC) has been the preferred treatment method for reducing tumor mass in the breast and axillary area. However, NAC can reduce total number of excised lymph nodes compared with upfront surgery. Therefore, an emerging question is whether axillary nodal status and LNR following NAC can accurately predict prognosis. We evaluated the prognostic value of axillary nodal status and LNR after NAC. A total of 236 patients were enrolled. Patients were divided into four groups according to the following cut-off values for LNR: 0 (n = 107), 0.01-0.20 (n = 68), 0.21-0.65 (n = 50) and >0.65 (n = 11). Pathologic complete responses were observed in 16.9% of the overall cohort. In univariate analysis, pathologic N stage was a significant prognostic factor of disease free survival (DFS, p = 0.013) and overall survival (OS, p = 0.004). However, in multivariate analysis, hormone receptor status (p = 0.043) and LNR (p = 0.028) were significantly associated with DFS and LNR (p = 0.017) showed statistical significance for OS; however, pathologic N stage was no longer significantly associated with DFS or OS. Traditional nodal staging has been accepted as an important prognostic factor; however, our result indicated that the nodal ratio could be an alternative to pN staging as a prognostic factor after NAC in breast cancer.

Overexpression of interleukin-10 in sentinel lymph node with breast cancer.

BACKGROUND: In breast carcinoma, identification of tumor cells in the sentinel lymph nodes is a predictor of the tumor's metastatic potential. Sentinel lymph node may be targeted not only by tumor cell metastasis but also by cytokines from the emergence of antitumor immune responses. METHODS: Between February 2003 and February 2004, the investigator evaluated 38 cases that underwent sentinel lymph node biopsy at the Samsung Medical Center. Eighty paraffin-embedded sections, 49 sentinel, and 31 nonsentinel lymph node, from breast carcinoma without lymphatic metastases were analyzed by real-time polymerase chain reaction to evaluate the cytokine profile (interferon-gamma, interleukin-2, interleukin-10 and interleukin-12) for the T cell response. RESULTS: A higher expression of interleukin-10 was observed in sentinel lymph node than in nonsentinel lymph node (P = 0.03). The expressions of interferon-gamma, interleukin-2, and interleukin-12 were similar between sentinel and nonsentinel lymph node. CONCLUSIONS: Theses results indicate that T cell response was downregulated by interleukin-10 overexpression in sentinel lymph node with breast cancer.

Extensive silicone lymphadenopathy after breast implant insertion mimicking malignant lymphadenopathy.

Silicone implants are widely used in aesthetic and reconstructive breast surgery. Silicone lymphadenopathy is a well-known rare complication of implant insertion. Silicone leakage from a rupture or silicone bleeding can accumulate in lymph nodes. Foreign body reactions in the affected lymph nodes may be misdiagnosed as metastasis or malignant lymphadeno pathy upon initial presentation if silicone lymphadenopathy is not considered in the initial diagnosis. We report a case of siliconoma with extensive involvement of multiple lymph nodes mimicking malignant features to emphasize that clinicians should carefully evaluate each patient's medical history and disease status during differential diagnosis.

Predictive factors for longer operative times for thyroidectomy.

BACKGROUND/OBJECTIVE: Conventional open thyroidectomy is considered as a safe surgery nowadays. However, surgeons sometimes encounter unexpected difficulty when performing thyroidectomies. The aim of this paper was to identify the predictors of a difficult thyroidectomy for the management of patients with papillary thyroid carcinoma. METHODS: A database of patients who underwent open conventional thyroidectomy with cervical lymph node dissection after diagnosed papillary thyroid carcinoma between July 2008 and June 2013 was examined. In addition, the patients were subgrouped by difficult thyroidectomy (DT) and nondifficult thyroidectomy to determine the predictors of DT according to operation time. Clinicopathologic characteristics, surgical outcomes, and postoperative morbidities were investigated. RESULTS: No between-group differences in clinicopathologic factors and postoperative complications, except for male sex (p < 0.001) and tumor size (p = 0.039), were noted. Male sex [odds ratio (OR) 4.158, 95% confidence interval (CI) 2.020-8.559, p = 0.043] and age < 45 years (OR 2.239, 95% CI 1.304-3.843, p = 0.003) were independent factors associated with DT in a multivariate logistic regression model. Elevated antithyroglobulin antibody (OR 1.004, 95% CI 1.000-1.008, p = 0.030) was a variable which is statistically significant, but not clinically significant. DISCUSSION: Young age and male sex might be regarded as predictors of DT. Expecting DT before surgery might help surgeons, especially beginners, prevent troublesome situations.

Significance of micrometastases in the calculation of the lymph node ratio for papillary thyroid cancer.

PURPOSE: The lymph node ratio (LNR) is an important prognostic factor in papillary thyroid carcinoma (PTC), but micrometastases in cervical lymph nodes (LNs) are not of great clinical importance. In this study, we analyzed the accuracy of prediction of the prognosis depending on whether micrometastases were included in the number of metastatic LNs when calculating LNR. METHODS: The study included 353 PTC patients who underwent total thyroidectomy with neck LN dissection, and calculated LNR by 2 methods according to whether micrometastases were included in the number of metastatic LNs: Method 1 did not and method 2 did include. To compare the predictive values of LNR by the 2 methods, correlation coefficients and receiver operating characteristic (ROC) curves were analyzed. RESULTS: Positive correlations were found between LNR and preablation stimulated thyroglobulin (sTg) levels in both methods, but the correlation between method 1 LNR and preablation sTg level was significantly stronger than that for method 2 (Fisher z = 1.7, P = 0.045). The areas under these 2 independent ROC curves were analyzed; the prognostic efficacy of method 1 LNR was more accurate than that of method 2 LNR, and the difference was statistically significant (P = 0.0001). CONCLUSION: Regional recurrence of PTC can be predicted more accurately by not including micrometastases in the number of metastatic LNs when calculating LNR.