Risk Factors for Non-sentinel Lymph Node Metastasis in HR+/HER2- Breast Cancer With cN0.

BACKGROUND/AIM: This study aimed to identify the risk factors associated with non-sentinel lymph node (non-SLN) metastasis in case of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with cN0 on preoperative exam, where the sentinel lymph node (SLN) is positive. PATIENTS AND METHODS: We conducted a retrospective review of medical records from the Chonnam National University Hwasun Hospital, spanning from January 2013 to January 2020, focusing on patients with HR+, HER2- breast cancer. Specifically, we collected the clinical and pathological data for those patients who underwent axillary lymph node dissection (ALND) due to positive SLN. RESULTS: Among the 166 patients who underwent ALND after positive SLNs, median patient age was 52 years. Univariate analyses demonstrated a significant association between non-SLN metastasis and the number of positive SLNs (p=0.039), SLN positive ratio (p<0.001), and primary tumor size (p=0.018). Multivariate analysis revealed that an SLN ratio >0.55 (p=0.004, HR=3.007, 95% CI=1.427-6.335) was independently associated with non-SLN metastasis. However, neither the number of positive SLN nor primary tumor size showed associations with non-SLN metastases. CONCLUSION: In patients with HR+, HER2- breast cancer who are cN0, completion of ALND should be considered when the positive SLN ratio is ≥0.55. This approach aims to provide the opportunity for survival benefit through additional adjuvant therapy or to contribute to de-escalation of unnecessary surgery.

Age and Post-Lobectomy Recurrence after Endoscopic or Robotic Thyroid Surgery: A Retrospective Cohort Study of 2348 Papillary Thyroid Carcinoma Patients.

The biology of papillary thyroid carcinoma (PTC) in young patients is poorly understood, and there are conflicting data regarding the recurrence for younger patients compared to older patients. We retrospectively analyzed 2348 clinically node-negative (cN0) PTC patients who underwent a thyroid lobectomy between 2008 and 2017. Young age was defined as less than 35 years old. The clinicopathological characteristics and oncologic outcomes of the young age group were compared to those of the older age group. The number of young age cN0 PTC patients accounted for 20.7% of the enrolled patients, and 24.2% were upstaged into pathologic N1a. The young age group had a significantly larger proportion of females, endoscopic/robotic thyroid lobectomies, stage N1a, and larger tumor sizes. Post-lobectomy recurrences were significantly higher in the young age group. In the Cox analysis, young age, large tumor size, and stage N1a were significant risk factors. The multivariate analysis reveals that young age and stage N1a are significant risk factors. Conversely, minimally invasive or robot-endoscopic thyroidectomies were not risk factors for post-lobectomy recurrence compared to conventional thyroidectomies. While young patients with a stage N1a had a significant risk factor for post-lobectomy recurrence, endoscopic/robotic thyroidectomy was as feasible and safe as conventional thyroidectomies in the median seven-year oncologic follow-up. Further high-quality studies are needed to elucidate the relationship between age and the risk of post-lobectomy recurrence.

Unilateral Multifocality Is Not a Risk Factor for Recurrence After Thyroid Lobectomy: A Study of 1,684 Patients With Differentiated Thyroid Cancer.

BACKGROUND/AIM: Many studies indicate that multifocality is associated with high-risk features of differentiated thyroid cancer (DTC). Herein, we evaluated the impact of the unilateral multifocality on post-lobectomy recurrence in patients with DTC. PATIENTS AND METHODS: We retrospectively analyzed 1,684 patients with DTC who underwent thyroid lobectomy from 2008 to 2015 using logistic regression models to calculate the relative risk on post-lobectomy recurrence. RESULTS: Tumor diameter increased from 4.9 mm to 8.1 mm and the proportion of extrathyroidal extension (ETE) and unilateral multifocality progressively increased from 2008 to 2015 (2.1% to 24.3% and 4.2% to 22.8%, respectively). During the 88.6-month follow-up period, 67 (3.98%) recurrences and 2 (0.12%) deaths were observed. There were 269 (16.0%) multifocal DTC cases. There was no significant difference between the multifocal and unifocal groups in terms of the proportion of recurrences (5.2% vs. 3.7%) and distant metastasis (0.4% vs. 0.1%). Logistic regression analysis revealed age <42.5 years (OR=1.83), tumor diameter greater than 7.5 mm (OR=1.89), and N1a (OR=2.04) were potent risk factors for post-lobectomy recurrence. Conversely, male sex (OR=0.77; p=0.407), ETE (OR=1.16; p=0.698) and multifocality (OR=1.23; p=0.526) were not risk factors for recurrence after thyroid lobectomy. A positive node ratio (PNR) ≥42.0%, N1a stage, a tumor diameter ≥7.5mm and age <42.5 years were significant risk factors for recurrence (Log-rank p=0.001, p=0.001, p=0.004 and p=0.009, respectively). Contrariwise, multifocality and ETE were proven to not be risk factors for DTC recurrence after thyroid lobectomy (Log-rank p=0.099 and p=0.126, respectively). CONCLUSION: Unilateral multifocality was not a risk factor for DTC recurrence after thyroid lobectomy and could not be considered an indication for immediate completion or total thyroidectomy.

Thyroglobulin Levels as a Predictor of Papillary Cancer Recurrence After Thyroid Lobectomy.

BACKGROUND/AIM: The effectiveness of using serum thyroglobulin (TG) to predict thyroid cancer recurrence after a thyroid lobectomy is unknown. This study aimed to evaluate the predictive nature of serum TG and TG trends after thyroid lobectomies. PATIENTS AND METHODS: We analyzed 514 papillary thyroid cancer (PTC) patients. The pre-, low-, high, and last-TG levels were reviewed and stratified into three groups. An ascending TG trend was defined if the last-TG level was more than 200% as high as the value of low-TG level. A descending trend was defined if the last-TG level decreased by more than 50% and a flat trend as between them. RESULTS: During a median follow-up period of 73.0 months, there were 21 (4.1%) recurrences. Most patients showed a descending (54.1%) or flat (35.6%) TG trend, but 10.3% of patients showed an ascending TG trend. Overall and lateral recurrences were significantly higher in the ascending TG group, indicating that an ascending TG trend was a good predictor for recurrence. Other factors such as positive node ratio (PNR), patient risk, age, and sex were not significant risk factors. In a Kaplan-Meier analysis, ascending TG trend was a good predictor of lateral recurrence. CONCLUSION: TG levels as a predictor of papillary cancer recurrence after thyroid lobectomy were found to be poor classifiers, and optimal cut-off values were not verified. An ascending TG trend was a good predictor of lateral recurrence. Further studies are warranted to investigate whether an ascending TG trend was due to an incomplete thyroid lobectomy or if the cancer had already metastasized to the lateral compartment.

Numerical and Experimental Investigation of Quasi-Static Crushing Behaviors of Steel Tubular Structures.

In this study, a numerical and experimental investigation of the quasi-static crushing behavior of steel tubular structures was conducted. As the crushing failure behavior involves a high level of nonlinearity for the numerical simulations, these were compared with previous experimental works, including crushing tests of steel square tubes to calibrate the numerical results. Six parameters for the numerical simulations, namely (1) loading boundary condition, (2) geometrical imperfection, (3) friction coefficient, (4) element size, (5) element type, and (6) material nonlinearity model, were examined using a series of finite element analyses. Through the sensitivity study for each parameter, the deformation and crushing load of the steel tube were investigated, and the value that best matched the experimental results was selected. The results of the numerical analysis for the determined model were compared with the experimental results. Finally, the authors provided recommendations that should be considered when performing nonlinear finite element simulations of crushing failure events.

Levothyroxine Cessation After Thyroid Lobectomy for Papillary Thyroid Cancer Can Be Achieved at the Same Rate as that for Benign Tumors Regardless of the Duration of Thyroid-stimulating Hormone Suppression.

BACKGROUND/AIM: Thyroid lobectomy may cause post-lobectomy hypothyroidism. We investigated the difference in levothyroxine (LT4) supplementation and cessation between patients with benign disease and those with papillary thyroid carcinoma (PTC) and found that the rate of LT4 cessation could be decreased after thyroid-stimulating hormone (TSH) suppression in PTC. PATIENTS AND METHODS: We retrospectively reviewed 88 patients with benign tumor and 463 patients with PTC and investigated the risk factors for LT4 supplementation after thyroid lobectomy. RESULTS: During the median follow-up of 73.0 months, 207 (37.6%) patients maintained the euthyroid state, while 344 (62.4%) patients continued LT4 supplementation for LT4 replacement or TSH suppression. In patients with benign tumors, only high pre-TSH level (>1.98 mIU/l) was a significant risk factor (odds ratio [OR]=10.09). However, in patients with PTC, pre-TSH level ≥1.98 mIU/l (OR=3.28), pregnancy planning (OR=2.97), and age ≥42.5 years (OR=1.94) were significant risk factors. Moreover, the most potent risk factor was tumor aggressiveness (OR=4.00), which was found to be more significant than high pre-TSH. The overall rate of LT4 cessation in all patients was 37.6%; however, in the 303 patients who underwent the LT4-Off trial, there was no difference in the rate in the benign tumor, low-risk PTC, and intermediate-risk PTC groups (66.2%, 68.8%, and 70.8%, respectively; p=0.886). CONCLUSION: When post-lobectomy TSH levels were adequate and the risk of recurrence was reduced, LT4 cessation in PTC could be achieved at the same rate as that in benign tumors, regardless of the duration of TSH suppression.

Wood transcriptome analysis of Pinus densiflora identifies genes critical for secondary cell wall formation and NAC transcription factors involved in tracheid formation.

Although conifers have significant ecological and economic value, information on transcriptional regulation of wood formation in conifers is still limited. Here, to gain insight into secondary cell wall (SCW) biosynthesis and tracheid formation in conifers, we performed wood tissue-specific transcriptome analyses of Pinus densiflora (Korean red pine) using RNA sequencing. In addition, to obtain full-length transcriptome information, PacBio single molecule real-time iso-sequencing was carried out using RNAs from 28 tissues of P. densiflora. Subsequent comparative tissue-specific transcriptome analysis successfully pinpointed critical genes encoding key proteins involved in biosynthesis of the major secondary wall components (cellulose, galactoglucomannan, xylan and lignin). Furthermore, we predicted a total of 62 NAC (NAM, ATAF1/2 and CUC2) family transcription factor members and identified seven PdeNAC genes preferentially expressed in developing xylem tissues in P. densiflora. Protoplast-based transcriptional activation analysis found that four PdeNAC genes, homologous to VND, NST and SND/ANAC075, upregulated GUS activity driven by an SCW-specific cellulose synthase promoter. Consistently, transient overexpression of the four PdeNACs induced xylem vessel cell-like SCW deposition in both tobacco (Nicotiana benthamiana) and Arabidopsis leaves. Taken together, our data provide a foundation for further research to unravel transcriptional regulation of wood formation in conifers, especially SCW formation and tracheid differentiation.

The clinical meaning of pre- and post-ablation thyroglobulin levels at first radioiodine therapy in patients with papillary thyroid cancer.

BACKGROUND/AIMS: This study was conducted to identify prognostic factors in patients with papillary thyroid cancer (PTC) at the time of first radioactive iodine (RAI) therapy, and to evaluate the clinical value of the thyroglobulin (Tg) increase after RAI. METHODS: Serum Tg was sampled prior to (pre-Tg) and 7 days after RAI (post-Tg) in 680 patients with PTC. Patients were classified into excellent response (ER), biochemical incomplete response (BCIR), structural incomplete response (SIR), and indeterminate response (IR) groups using dynamic risk stratification at 6 to 18 months after RAI therapy. RESULTS: After RAI therapy, 514 patients (75.6%) had an ER, 34 (5.0%) had a BCIR, 13 (2.0%) had an SIR, and 119 (17.5%) had an IR. Pre-Tg level was significantly different among the groups, with the highest level being in the SIR group, followed by the BCIR, IR, and ER groups. However, post-Tg levels were not different among the groups. Post-Tg level increased significantly after RAI therapy compared to the pre-Tg level (mean 13.8 ± 32.2 ng/mL vs. 2.5 ± 8.9 ng/mL). In 422 patients whose pre-Tg level was < 1 ng/mL, 205 had post-Tg levels < 1 ng/mL, while 167 had post-Tg levels of 1 to 10 ng/mL, and 50 had levels > 10 ng/mL. No difference was observed in the response to therapy. Differences in RAI dose and uptake pattern were observed among the three groups. CONCLUSION: Pre-Tg was useful as a prognostic factor in patients with PTC. In patients with low pre-Tg, increased post-Tg may reflect remnant tissue and does not help predict the prognosis.

Identifying risk factors of recurrence for clinically node negative papillary thyroid carcinoma with pathologic N1a.

BACKGROUND: Whether or not to perform prophylactic central lymph node dissection (CLND) in the case of clinically node-negative papillary thyroid cancer (PTC) is controversial. The purpose of this study was to investigate the risk factors for recurrence in clinically node-negative PTC patients who underwent total thyroidectomy plus bilateral central neck dissection and was verified pathologic N1a. METHODS: We retrospectively reviewed the medical records of 1082 PTC patients who underwent total thyroidectomy and prophylactic bilateral CLND between January 2004 and December 2012. We used Cox-proportional hazard regression analyses in order to explore potential predictive factors for recurrence. RESULTS: During a median follow-up (range) of 78 (12-158) months, recurrence occurred in 62 (5.7%) patients. Main tumor size more than 1 cm, gross extrathyroidal extension (ETE), positive lymph node (LN) more than 3, and LN ratio > 0.5 were all significantly associated with recurrence according to univariate analysis. In model I multivariate analysis (tumor size, gross ETE, LN ratio), LN ratio > 5 (hazards ratio [HR], 4.794; 95% confidence interval [CI], 2.674-8.595; p < 0.001) was found to be predictive of recurrence. Gross ETE (HR, 1.794; 95% CI, 1.024-3.143; p = 0.041) and positive LN more than 3 (HR, 2.505; 95% CI, 1.513-4.146; p < 0.001) were predictors for recurrence in model II multivariate analysis (tumor size, gross ETE, the number of positive LN). CONCLUSIONS: We recommend that surgeons try to focus completely on performing prophylactic CLND for patients with suspicious gross ETE during preoperative evaluation. Close monitoring and thorough management are needed for clinically node-negative PTC patients with LN ratio of more than 0.5 and more than 3 positive LN in the central compartment.

Combination of S100B and procalcitonin improves prognostic performance compared to either alone in patients with cardiac arrest: A prospective observational study.

This study aimed to determine whether the combination of procalcitonin (PCT) and S100B improves prognostic performance compared to either alone in cardiac arrest (CA) patients treated with targeted temperature management (TTM).We performed a prospective cohort study of CA patients treated with TTM. PCT and S100B levels were obtained at 0, 24, 48, and 72 hours after return of spontaneous circulation. The prognostic performance was analyzed using each marker and the combination of the 2 markers for predicting poor neurological outcome at 3 months and mortality at 14 days and 3 months.A total of 97 patients were enrolled, of which 67 (69.1%) had poor neurological outcome. S100B showed a better prognostic performance (area under the curve [AUC], 0.934; sensitivity, 77.6%; and specificity, 100%) than PCT (AUC, 0.861; sensitivity, 70.2%; and specificity, 83.3%) with the highest prognostic value at 24 hours. The combination of 24-hour PCT and S100B values (S100B ≥0.2 µg/L or PCT ≥6.6 ng/mL) improved sensitivity (85.07%) compared with S100B alone. In multivariate analysis, PCT was associated with mortality at 14 days (odds ratio [OR]: 1.064, 95% confidence interval [CI]: 1.014-1.118), whereas S100B was associated with neurological outcomes at 3 months (OR: 9.849, 95% CI: 2.089-46.431).The combination of PCT and S100B improved prognostic performance compared to the use of either biomarker alone in CA patient treated with TTM. Further studies that will identify the optimal cutoff values for these biomarkers must be conducted.

Identifying risk factors of lateral lymph node recurrence in clinically node-negative papillary thyroid cancer.

There is still debate regarding the role of routine central lymph node (LN) dissection in treating clinically node-negative papillary thyroid cancer (PTC). The aim of this study was to investigate the risk factors for lateral recurrence after total thyroidectomy and prophylactic bilateral central LN dissection in clinically node-negative PTC patients.We retrospectively collected the medical records of 1406 PTC patients who underwent total thyroidectomy and prophylactic bilateral central LN dissection between January 2004 and December 2008. We used Cox- proportional hazards regression analyses to inspect the predictive factors for recurrence.During a median follow-up of 107 months (range, 13-164 months), 68 (4.8%) and 37 (2.6%) patients experienced recurrence in any lesion and in lateral neck LN, respectively. Male, main tumor size >1 cm, nodal factors (pathologic N1a, positive delphian LN, and LN ratio >0.15), lymphovascular invasion, and extrathyroidal extension (ETE) were significantly associated with lateral neck LN recurrence in univariate analysis. Multivariate analysis showed that male (hazard ratio [HR], 2.217; 95% confidence interval [CI], 1.057-4.647; P = .035), main tumor size >1 cm (HR, 2.257; 95% CI, 1.138-4.476; P = .020), pathologic N1a (HR, 5.957; 95% CI, 2.573-13.789; P < .002), minor ETE (vs no ETE; HR, 3.027; 95% CI, 1.315-6.966; P = .009), and gross ETE (vs no ETE; HR, 4.058; 95% CI, 1.685-9.774; P = .002) were independent predictors for lateral neck LN recurrence.Among patients with pathologic N1a, those with LN ratio of more than 0.55 had worse lateral neck LN recurrence-free survival. Lateral neck LN recurrence in clinically node-negative PTC patients is predicted by the factors of male, main tumor size >1 cm, ETE, and pathologic N1a.

Identifying risk factors for recurrence of papillary thyroid cancer in patients who underwent modified radical neck dissection.

BACKGROUND: Papillary thyroid cancer (PTC) patients with ipsilateral neck metastatic lymph node (LN) and those with contralateral neck metastatic LN belong to N1b. Only a few studies have reported on comparisons with regard to laterality of metastatic lateral LN. The aim of this study was to evaluate predictive factors for contralateral neck LN metastasis and to determine prognostic factors for recurrence in PTC patients with N1b. METHODS: This retrospective study reviewed the medical records of 390 PTC patients who underwent total thyroidectomy and central LN dissection plus ipsilateral or bilateral modified radical neck dissection (MRND) between January 2004 and December 2012. RESULTS: During a median follow-up of 81 (range, 6-156) months, 84 patients had a recurrence in any lesion. Male gender, a main tumor of more than 2 cm, number of metastatic central LN, number of harvested and metastatic lateral LN, total LN ratio, multifocality, bilaterality, and gross ETE had significance in the patients who underwent bilateral MRND. In multivariate analysis according to recurrence, patients with LN ratio > 0.44 in the central compartment (hazard ratio [HR], 1.890; 95% confidence interval [CI], 1.124-3.178; p = 0.015), LN ratio > 0.29 in the lateral compartment (HR, 2.351; 95% CI, 1.477-3.743; p < 0.001), and multifocality (HR, 1.583; 95% CI, 1.030-2.431; p = 0.036) were associated with worse RFS. However, the type of MRND was statistically significant only in univariate analysis. CONCLUSIONS: Recurrence in N1b PTC patients is predicted by central neck LN ratio > 0.44, lateral neck LN ratio > 0.29, and multifocality of tumors. We suggest that patients with these factors should receive short-term follow-up using image modalities like ultrasonography and computed tomography.

Lymphovascular invasion can be better than pathologic complete response to predict prognosis in breast cancer treated with neoadjuvant chemotherapy.

Lymphovascular invasion (LVI) has been a predictor of worse survival outcomes in breast cancer. However, the role of LVI compared than pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) remains unclear. The aim of this study was to examine the association between LVI and survival outcomes and clinicopathological features in patients with breast cancer treated with NAC. We retrospectively analyzed 187 patients with breast cancer treated with NAC and surgery between 2005 and 2013 in our institution. Kaplan-Meier analyses were used to assess recurrence-free survival (RFS) and overall survival (OS). Median follow-up was 57.9 months. Mastectomy (vs breast conserving surgery [BCS]; hazard ratio [HR], 1.791; 95% confidence interval [CI], 1.022-3.139; P = .042), ypN1-3 stage (vs ypN0 stage; HR, 2.561; 95% CI, 1.247-5.261; P = .010), and LVI (vs no LVI; HR, 2.041; 95% CI, 1.170-3.562; P = .012) were associated with worse RFS. Mastectomy (vs BCS; HR, 2.768; 95% CI, 1.173-6.535; P = .020), LVI (vs no LVI; HR, 3.474; 95% CI, 1.646-7.332, P = .001), and human epidermal growth factor receptor 2 overexpression type (vs luminal A type; HR, 11.360; 95% CI, 1.501-85.972; P = .019) were associated with worse OS. Patients with LVI and hormone receptor-negative cancer had the worst RFS (P < .001) and OS (P < .001). LVI more than pCR in surgical breast cancer specimens obtained after NAC was a significant independent prognostic factor. Patients with hormonal receptor-negative cancer and LVI had unfavorable survival outcomes. We suggest that patients with hormone receptor-negative cancer and LVI should receive short-term follow-up and appropriate management.

Effects of ADAM10 and ADAM17 Inhibitors on Natural Killer Cell Expansion and Antibody-dependent Cellular Cytotoxicity Against Breast Cancer Cells In Vitro.

BACKGROUND/AIM: The inhibition of a disintegrin and metalloproteinase (ADAM) has the potential to become a novel approach for natural killer (NK) cell-based cancer immunotherapy. Thus, the aim of this study was to investigate the influence of ADAM10 and ADAM17 inhibitors on expanded NK cell to enhance antibody-dependent cellular cytotoxicity (ADCC) in breast cancer cell lines. MATERIALS AND METHODS: NK cells were expanded in medium supplemented with an ADAM10 or ADAM17 inhibitor to prevent the shedding of soluble CD16/FcγRIII. The expression level of CD16 and production of interferon-gamma (IFN-γ) was detected by flow cytometry using specific antibodies. ADCC activity of expanded NK cells was estimated in trastuzumab treated breast cancer cell lines such as MCF-7, MDA-MB-231, SKBR3, and BT-474 cells. RESULTS: The ADAM17 inhibitor increased the purity of expanded NK cells to 90% after 14 days at 5 and 10 µM in vitro (p=0.043). However, the expansion rate of NK cells was decreased at 10 µM of the ADAM 17 inhibitor (p=0.043). Inhibition of ADAM10 suppressed the expansion of NK cells, although the NK purity was increased at 1 µM of the inhibitor. The expression of CD16 was significantly increased at 1 and 5 µM of the ADAM17 inhibitor (p=0.046, 0.028, respectively) during the culturing period. Inhibition of ADAM10 reduced the expression of CD16 on NK cells. The cytotoxic activity of the ADAM17 inhibitor treated NK cells against MCF-7 (p=0.039) and BT-474 (p=0.027) cells was significantly elevated. The ADCC activity of NK cells treated with 5 µM of ADAM17 inhibitor was significantly increased against SKBR-3 and BT-474 (p=0.027). Inhibition of ADAM17 increased the production of IFN-γ in expanded NK cells. CONCLUSION: The inhibition of ADAM17 enhanced the purity of expanded NK cells and the ADCC activity of these cells against trastuzumab treated breast cancer cell lines.

Preparation for radioactive iodine therapy is not a risk factor for the development of hyponatremia in thyroid cancer patients.

The aim of this study was to evaluate whether the preparation for radioactive iodine (RAI) therapy by thyroid hormone withdrawal (THW) or a low-iodine diet (LID) can be risk factors for the development of hyponatremia in patients with differentiated thyroid cancer after thyroidectomy.We retrospectively reviewed the medical records and laboratory findings of 326 patients who underwent preparation for RAI therapy after thyroidectomy from 2012 to 2014. Demographic and clinical variables including the method of thyrotropin stimulation and duration of LID were assessed. Serum sodium was measured twice, before operation and before RAI therapy.Hyponatremia was detected in only 3 patients (0.9%) before operation, but in 15 patients (4.6%) before RAI therapy. None of the patients had severe hyponatremia after preparation for RAI therapy. Pre-RAI therapy serum sodium was correlated with the method of thyrotropin stimulation (TWH vs recombinant human thyroid stimulating hormone, P = 0.014) and duration of LID (r = -0.131, P = 0.018); however, the preparation of RAI therapy, THW and LID, did not affect the development of hyponatremia in logistic regression analysis. Preoperative serum sodium was a significant risk factor for hyponatremia during preparation for RAI therapy.Preparation for RAI therapy by THW or LID is not a risk factor for the development of hyponatremia in patients with thyroid cancer. The development of hyponatremia was neither frequent nor severe during preparation for RAI therapy. Physicians should not be greatly concerned about rare life-threatening hyponatremia during preparation for RAI therapy.

The neutrophil to lymphocyte ratio can discriminate anaplastic thyroid cancer against poorly or well differentiated cancer.

PURPOSE: We evaluated the capability of the neutrophil to lymphocyte ratio (NLR) as a diagnostic tool to discriminate between poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) from well differentiated thyroid cancer (WDTC). METHODS: The NLR of 3,870 patients with benign and malignant thyroid tumors were analyzed. There were 436 benign, 3,364 papillary, 15 medullary, 34 follicular or hurthle type, 14 PDTC, and 7 ATC type neoplasms. Patients were divided into two groups: a high NLR group and a low NLR group. RESULTS: The NLR of all 3,870 patients was a normal distribution, and the median value was 1.57. Advanced stage cancer, such as T3 or T4 was high (30.4% vs. 26.5%, P = 0.027), and cancer-specific deaths were also high (1.2% vs. 0.4%, P = 0.018) in the high NLR group. The proportion of PDTC (0.6% vs. 0.1%) and ATC (0.3% vs. 0.1%) was higher in the high NLR group. The NLR can discriminate between PTC, PDTC, and ATC (P = 0.035, P = 0.002, and P = 0.025, respectively), and the cutoff value was 3.8 between PDTC versus ATC. None of the NLR of PDTC exceeded the cutoff value of 3.8. CONCLUSION: NLR can play a relevant role as a discriminating tool and may be considered as a new diagnostic criterion in discriminating as well as in selecting therapeutic approaches to these aggressive forms of thyroid cancer.

Reduced MUC4 expression is a late event in breast carcinogenesis and is correlated with increased infiltration of immune cells as well as promoter hypermethylation in invasive breast carcinoma.

Altered expression of MUC4 is associated with tumor progression and immune surveillance, but the potential involvement of MUC4 in breast carcinogenesis has not been rigorously assessed. Immunohistochemical staining with anti-MUC4 antibody was performed in a total of 324 patients with 26 normal breasts, 25 usual ductal hyperplasia, 76 ductal carcinoma in situ, and 198 invasive breast carcinoma (IBC) using tissue microarray. Immunohistochemical staining for CD8, CD57, and CD1a and methylation-specific polymerase chain reaction were also performed in IBC. Reduced MUC4 expression in IBC was significantly higher than in usual ductal hyperplasia and ductal carcinoma in situ (P<0.001 and P<0.01, respectively). Reduced MUC4 expression in IBC was significantly correlated with promoter hypermethylation (P<0.05). No association between MUC4 expression and patient outcomes was identified. Intratumoral CD8 T cells and stromal CD57 natural killer cells were significantly increased in the reduced MUC4 expression group compared with those in the normal expression group (P<0.01 and P<0.05, respectively). Our results suggest that tumor progression in breast epithelium is accompanied by reduced MUC4 protein expression. Reduced MUC4 expression correlates with increased tumor-infiltrating CD8 T and NK cells as well as promoter hypermethylation in IBC.

Tumorigenesis of papillary thyroid cancer is not BRAF-dependent in patients with acromegaly.

INTRODUCTION: Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAFV600E mutation in PTC patients with and without acromegaly. MATERIALS AND METHODS: We conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US) and US-guided fine needle aspiration were performed on nodules with sonographic features of malignancy. We selected 16 patients with non-acromegalic PTC as a control group. The BRAFV600E mutation was analyzed in paraffin-embedded surgical specimens of PTC by real-time polymerase chain reaction, and tumor specimens from patients with PTC were stained immunohistochemically with an antibody against insulin-like growth factor-1 receptor ß (IGF-1Rß). RESULTS: Thyroid cancer was found in 15 (25.0%) patients. No differences in age, sex, initial growth hormone (GH) and IGF-1 percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC. Acromegaly was active in 12 of 15 patients at the time of PTC diagnosis; uncontrolled acromegaly had a significantly higher frequency in the PTC group (60%) than in the non-PTC group (28.9%) (p = 0.030). The BRAFV600E mutation was present in only 9.1% (1/11) of PTC patients with acromegaly, although 62.5% (10/16) of control patients with PTC had the mutation (p = 0.007). IGF-1Rß immunostaining showed moderate-to-strong staining in all malignant PTC cells in patients with and without acromegaly. Significantly less staining for IGF-1Rß was observed in normal adjacent thyroid tissues of PTC patients with acromegaly compared with those without (p = 0.014). CONCLUSION: The prevalence of PTC in acromegalic patients was high (25%). An uncontrolled hyperactive GH-IGF-1 axis may play a dominant role in the development of PTC rather than the BRAFV600E mutation in patients with acromegaly.

Comparison of epidemiology, emergency care, and outcomes of acute ischemic stroke between young adults and elderly in Korean population: a multicenter observational study.

Stroke in young adults has been known to show a lower incidence and a better prognosis. Only a few studies have examined the epidemiology and outcomes of ischemic stroke in young adults and compared them with the elderly in Korean population. All consecutive patients with ischemic stroke visiting 29 participating emergency departments were enrolled from November 2007 to October 2009. Patients with less than 15 yr of age and unknown information on age and confirmed diagnosis were excluded. We categorized the patients into young adults (15 to 45 yr) and elderly (46 yr and older) groups. Of 39,156 enrolled all stroke patients, 25,818 with ischemic stroke were included and analyzed (young adult; n=1,431, 5.5%). Young adult patients showed lower prevalence of most chronic diseases but significantly higher prevalence in exercise, current smoking, and alcohol consumption. Hospital mortality was significantly lower in young adults than elderly (1.1% vs. 3.1%, P<0.001). Higher number of patients in elderly group (68.1%) showed worsening change of modified Rankin Scale than young adults (65.2%). Young adults ischemic stroke showed favorable hospital outcomes than the elderly in Korean population.