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.

Nomogram for predicting the risk of central lymph node metastasis in papillary thyroid microcarcinoma: a combination of sonographic findings and clinical factors.

Background: A considerable controversy over performing thyroidectomy and central lymph node dissection in patients with papillary thyroid microcarcinoma (PTMC) remained. However, accurate prediction of central lymph node metastasis (CLNM) is crucial for surgical extent and proper management. The aim of this study was to develop and validate a practical nomogram for predicting CLNM in patients with PTMC. Methods: A total of 1,029 patients with PTMC who underwent thyroidectomy and central lymph node dissection at Tangdu Hospital (the Second Affiliated Hospital of Air Force Medical University) and Xijing Hospital (the First Affiliated Hospital of Air Force Medical University) were selected. Seven hundred and nine patients were assigned to the training set and 320 patients to the validation set. Data encompassing demographic characteristics, ultrasonography results, and biochemical indicators were obtained. Stepwise backward selection and multiple logistic regression were used to screen the variables and establish the nomogram. Concordance index (C-index), receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA) were employed to evaluate the nomogram's distinguishability, accuracy, and clinical utility. Results: Young age, multifocality, bigger tumor, presence of microcalcification, aspect ratio (height divided by width) ≥1, loss of fatty hilum, high free thyroxine (FT4), and lower anti-thyroid peroxidase antibody (TPOAb) were significantly associated with CLNM. The nomogram showed strong predictive capacity, with a C-index and accuracy of 0.784 and 0.713 in the training set and 0.779 and 0.703 in the external validation set, respectively. DCA indicated that the nomogram demonstrated strong clinical applicability. Conclusions: We established a reliable, cost-effective, reproducible, and noninvasive nomogram for predicting CLNM in patients with PTMC. This tool could be a valuable guidance for deciding on management in PTMC.

Differential diagnosis of thyroid nodules using heterogeneity quantification software on ultrasound images: correlation with the Bethesda system and surgical pathology.

Ultrasonography (US)-guided fine-needle aspiration cytology (FNAC) is the primary modality for evaluating thyroid nodules. However, in cases of atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), supplemental tests are necessary for a definitive diagnosis. Accordingly, we aimed to develop a non-invasive quantification software using the heterogeneity scores of thyroid nodules. This cross-sectional study retrospectively enrolled 188 patients who were categorized into four groups according to their diagnostic classification in the Bethesda system and surgical pathology [II-benign (B) (n = 24); III-B (n = 52); III-malignant (M) (n = 54); V/VI-M (n = 58)]. Heterogeneity scores were derived using an image pixel-based heterogeneity index, utilized as a coefficient of variation (CV) value, and analyzed across all US images. Differences in heterogeneity scores were compared using one-way analysis of variance with Tukey's test. Diagnostic accuracy was determined by calculating the area under the receiver operating characteristic (AUROC) curve. The results of this study indicated significant differences in mean heterogeneity scores between benign and malignant thyroid nodules, except in the comparison between III-M and V/VI-M nodules. Among malignant nodules, the Bethesda classification was not observed to be associated with mean heterogeneity scores. Moreover, there was a positive correlation between heterogeneity scores and the combined diagnostic category, which was based on the Bethesda system and surgical cytology grades (R = 0.639, p < 0.001). AUROC for heterogeneity scores showed the highest diagnostic performance (0.818; cut-off: 30.22% CV value) for differentiating the benign group (normal/II-B/III-B) from the malignant group (III-M/V&VI-M), with a diagnostic accuracy of 72.5% (161/122). Quantitative heterogeneity measurement of US images is a valuable non-invasive diagnostic tool for predicting the likelihood of malignancy in thyroid nodules, including AUS or FLUS.

Risk factors for sentinel lymph node metastasis in Korean acral and non-acral melanoma patients.

Breslow thickness, ulceration, and mitotic rate are well-known prognostic factors for sentinel lymph node (SLN) metastasis in cutaneous melanoma. We investigated risk factors, including especially the degree of pigmentation, for SLN metastasis in Korean melanoma patients. We enrolled 158, composed of Korean 107 acral and 51 non-acral melanoma patients who underwent SLN biopsy. Clinicopathologic features such as Breslow thickness, ulceration, mitotic rate, and the degree of pigmentation were evaluated. The recurrence-free survival (RFS) rate and date of recurrence were determined. Fifty-four patients (34.2%) had a positive SLN biopsy result. In a multivariate analysis, Breslow thickness (odds ratio [OR] 1.93; 95% confidence interval [CI], 1.12-3.47; p = .022) and heavy pigmentation (OR 13.14; 95% CI, 2.96-95.20, p = .002) were associated with SLN metastasis. Positive SLN patients had a higher rate of loco-regional and/or distant recurrence (hazard ratio 6.32; 95% CI, 3.39-11.79; p < .001). Heavy pigmentation was associated with poor RFS. Heavy pigmentation is an independent predictor of SLN metastasis in both acral and non-acral melanoma. Our results suggest the need for in-depth SLN evaluation of cutaneous melanoma patients with heavy pigmentation and provide clinicians with important information for determining patient prognosis.

Prediction of central lymph node metastasis in patients with papillary thyroid microcarcinoma by gradient-boosting decision tree model based on ultrasound radiomics and clinical features.

Background: In recent years, the study of radiomics in thyroid diseases has developed rapidly. This study aimed to establish a preoperative radiomics prediction model for central compartment lymph node metastases (CLNMs) in papillary thyroid microcarcinoma (PTMC) patients using gradient-boosting decision tree (GBDT) model and evaluate the performance of the model. Methods: A total of 274 patients with PTMC admitted for thyroid surgery at China-Japan Union Hospital of Jilin University from January 2020 to July 2022 were retrospectively analyzed. Patients were randomized into training and validation cohorts according to a ratio of 8:2. Radiomics features were extracted from the ultrasound (US) images of PTMC lesions. The open-source software Pyradiomics was used to extract radiomics features, and WEKA software was used to select CLNM-related radiomics features. Clinical risk factors for CLNM were screened by statistical methods. The GBDT model was constructed by combining radiomics features and clinical risk factors, and compared with the diagnostic efficacy of US-reported cervical lymph node status. Shapley Additive exPlanations (SHAP) was applied to visualize and analyze the GBDT model globally and locally. Results: A total of seven radiomics features were significantly correlated with central lymph node status in the training and validation cohorts. The predictors in the GBDT model included the radiomics features, sex, age, and body mass index (BMI). The area under the curve (AUC) values of the GBDT model in the training and validation cohorts were 0.946 [95% confidence interval (CI): 0.920-0.972] and 0.845 (95% CI: 0.714-0.976), respectively, compared with 0.583 (95% CI: 0.508-0.659) and 0.582 (95% CI: 0.430-0.736) for US-reported lymph node status alone. The Delong test showed a significant difference between AUS in the training and validation cohorts (P<0.001, respectively). SHAP visual analysis showed the effect of each parameter on the GBDT model globally and locally. Decision curve analysis demonstrated the clinical utility of the GBDT model. Conclusions: The prediction of CLNM by the GBDT model, based on US radiomics features and clinical factors, can be better than that by using US alone in patients with PTMC. Furthermore, the GBDT model may serve a guidance of clinical decision for patient's treatment strategy.

Prostate-specific membrane antigen expression predicts recurrence of papillary thyroid carcinoma after total thyroidectomy.

BACKGROUND: Prostate-specific membrane antigen (PSMA) overexpression has been observed in the endothelial neovasculature of several solid malignancies. This study aimed to identify PSMA expression in the primary tumor of classical papillary thyroid carcinoma (PTC) and assess the correlation between the degree of PSMA expression and recurrence. METHODS: We reviewed the electronic medical records of patients who underwent total thyroidectomy and central neck dissection, with or without lateral neck dissection, for classical PTC between 2009 and 2014 at our institution. Recurrence was defined as a structural disease based on histological confirmation on follow-up. Fifty-one patients with the recurrent structural disease were matched, using a propensity score matching method, to patients with no disease evidence during follow-up. Clinicopathological and follow-up data were collected for 102 patients. The monoclonal mouse anti-human PSMA/FOLH1/NAALADase I antibody was used for staining the primary tumor. The score of PSMA expression was classified as negative (< 5% positivity), weak (5-10 % positivity), moderate (11-49% positivity), and strong (more than 50% positivity). Clinicopathological factors were compared between patients with low and high PSMA expression. Moreover, whether the degree of PSMA expression and clinicopathological factors could predict recurrence was investigated. Cox proportional hazard regression models were used to evaluate the risk of recurrence. RESULTS: There was no significant difference in clinicopathological factors between low (negative or weak) and high (moderate or strong) PSMA expression. Gross extrathyroidal extension (ETE), absence of chronic lymphocytic thyroiditis, and high PSMA expression were all associated with lower recurrence-free survival (RFS) rate in a univariate analysis. In multivariate analysis, gross ETE (hazard ratio [HR], 2.279; 95% confidence interval [CI], 1.257-4.132; p = 0.007) and high PSMA expression (HR, 1.895; 95% CI, 1.073-3.348; p = 0.028) were associated with poor RFS. CONCLUSIONS: High PSMA expression in the primary tumor was a significant factor in predicting recurrence in classic PTC. PSMA could be a potential biomarker for personalized management for PTC.

Predictive Factors for Skip Lymph Node Metastasis and Their Implication on Recurrence in Papillary Thyroid Carcinoma.

Skip lymph node (LN) metastases in papillary thyroid carcinoma (PTC) belong to N1b classification in the absence of central neck LN involvement. This study aimed to evaluate the predictive factors of skip metastases and their impact on recurrence in PTC patients with pN1b. A total of 334 PTC patients who underwent total thyroidectomy with LN dissection (central and lateral neck compartment) followed by radioactive iodine ablation were included. Patients with skip metastases tended to have a small primary tumor (≤1 cm) and single lateral neck level involvement. Tumor size ≤ 1 cm was an important predictive factor for skip metastases. Univariate analysis for recurrence showed that patients with a central LN ratio > 0.68, lateral LN ratio > 0.21, and stimulated thyroglobulin (Tg) levels > 7.3 ng/mL had shorter RFS (recurrence-free survival). The stimulated Tg level was associated with shorter RFS on multivariate analysis (>7.3 vs. ≤7.3 ng/mL; hazard ratio, 4.226; 95% confidence interval, 2.226-8.022; p < 0.001). Although patients with skip metastases tended to have a small primary tumor and lower burden of lateral neck LN involvement, there was no association between skip metastases and RFS in PTC with pN1b. Stimulated Tg level was a strong predictor of recurrence.

A Novel 3D-Printed Head Holder for Guinea Pig Ear Surgery.

BACKGROUND: Otologic surgery in guinea pig requires head immobilization for microscopic manipulation. Existing commercially available stereotaxic frames are expensive and impede access to the ear as they rely on ear bars or mouthpieces to secure the head. METHOD: Prototype head holders were designed using the Solidworks 2019 software and 3D-printed using Formlabs Form 2 Printers with photopolymer resin. The head holder consists of a C-shaped brace with adjustable radial inserts of 1/4-20 UNC standard screws with cone point tips providing head fixation for animals of various sizes. The C-shaped brace is attached to a rod that can be secured to a commercially available micromanipulator. The head holder design was tested during in vivo guinea pig experiments where their head motion with (n = 22) and without the head holder (n = 2) was evaluated visually through a stereotaxic microscope at 24× magnification during surgery. RESULTS: The head holder design was easy to use and allowed for both nose cone administration of anesthesia and access to the ear for intraoperative auditory testing and manipulation. Functionally, the head holder successfully minimized head movement. Furthermore, harvested round window membranes evaluated at 72 hours following surgery showed precise perforations with the use of head holder. CONCLUSION: The novel 3D-printed head holder enables simultaneous access for nose cone administration of anesthesia and surgical manipulation of the ear and brain. Moreover, it provides a modular, intuitive, and economical alternative to commercial stereotaxic devices for minimizing head motion during small animal surgery.

A Stepwise Approach Using Metastatic Lymph Node Ratio-Combined Thyroglobulin for Customization of [18F]FDG-PET/CT Indication to Detect Persistent Disease in Patients with Papillary Thyroid Cancer.

We investigated whether an indication for [18F]FDG-PET/CT to detect FDG-avid persistent disease (PD) could be identified precisely using the extent of metastatic lymph nodes (MLNs) and serum thyroglobulin (Tg) in papillary thyroid cancer (PTC) patients. This retrospective study included 429 PTC patients who underwent surgery and radioactive iodine (RAI) therapy. [18F]FDG-PET/CT and serum Tg were evaluated just before RAI therapy. The MLN ratio (LNR) was defined as the ratio of the number of MLNs to the number of removed LNs. To derive the LNR-combined criteria, different Tg cut-off values for identifying the PET/CT-indicated group for PD detection were applied individually to subgroups initially classified based on LNR cut-off values. The cut-off values for serum Tg, the number of MLNs, and LNR for a PET/CT indication were 6.0 ng/mL, 5, and 0.51, respectively. Compared to a single parameter (serum Tg, total number of MLNs, and LNR), the LNR-combined criteria showed significantly superior diagnostic performance in detecting FDG-avid PD (p < 0.001). The diagnostic performance of PET/CT in detecting FDG-avid PD was significantly improved when the PET/CT-indicated group was identified through the LNR-combined criteria in a stepwise manner; this can contribute to a customized PET/CT indication in PTC patients.

Chronic lymphocytic thyroiditis protects against recurrence in patients with cN0 papillary thyroid cancer.

BACKGROUND: Chronic lymphocytic thyroiditis (CLT) frequently coexists with papillary thyroid carcinoma (PTC) that exhibits normal thyroid function. However, few studies have investigated the relationship between CLT and clinically lymph node (LN)-negative PTC. The aim of this study was to evaluate the relationship between subclinical central LN metastasis and CLT, and to assess the impact of CLT on the recurrence of clinically LN-negative PTC. METHODS: We investigated the medical records of 850 patients with PTC who underwent prophylactic bilateral central neck dissection as well as total thyroidectomy between 2004 and 2010; the median follow-up time was 95.5 months (range, 12-158 months). RESULTS: CLT was observed in 480 patients (56.5%). Female sex, a preoperative thyroid-stimulating hormone level >2.5 mU/L, a primary tumor ≤1 cm, no gross extrathyroidal extension, high number of harvested LNs, low number of metastatic LNs, and positive anti-thyroglobulin (Tg) antibody at 1 year post-initial treatment were significantly associated with the presence of CLT. Multivariate analysis revealed that patients with N1a stage (vs. N0 stage; hazard ratio [HR], 3.255; 95% confidence interval [CI], 1.290-8.213; p = 0.012) and positive anti-Tg antibody at 1 year post-initial treatment (vs. negative anti-Tg antibody; HR, 5.118; 95% CI, 2.130-12.296; p < 0.001) had poorer recurrence-free survival (RFS), while those with CLT (vs. no CLT; HR, 0.357; 95% CI, 0.157-0.812; p = 0.014) had favorable RFS outcomes. CONCLUSIONS: CLT is associated with less aggressive tumor characteristics and LN metastasis. Clinically LN-negative PTC patients with CLT experience longer RFS intervals than those without CLT.

Combined role of lymph node ratio and serum thyroglobulin levels in predicting prognosis of papillary thyroid carcinoma.

OBJECTIVES: The aim of this study was to evaluate a prognostic value of the extent of metastatic lymph node combined with TSH-stimulated serum thyroglobulin (sTg) measured just before radioactive iodine (RAI) therapy in patients with papillary thyroid cancer (PTC). METHODS: The retrospective study included 468 patients with PTC who underwent total thyroidectomy with neck dissection and postoperative RAI therapy. The extent of metastatic lymph node was evaluated with the lymph node ratio (LNR) which was defined as the number of metastatic lymph nodes out of the number of total removed lymph nodes. We investigated which factors could significantly predict persistent or recurrent disease (PRD). RESULTS: LNR ≥0.4 (P = 0.002) and sTg ≥6.0 ng/mL (P < 0.001) were associated with PRD in univariate analysis. In multivariate analysis, only male [hazard ratio: 2.35, 95% confidence interval (CI): 1.18-4.66, P = 0.014] and sTg (hazard ratio: 9.35, 95% CI: 4.44-19.67, P < 0.001) were associated with PRD prediction. When we divided patients into two groups (patients with sTg level < 6.0 ng/mL and those with sTg level ≥ 6.0 ng/mL), LNR (≥0.4) was a significant predictor of PRD in patients with sTg <6.0 ng/mL (hazard ratio: 4.38, 95% CI: 1.22-15.72, P = 0.024). CONCLUSIONS: LNR ≥0.4 was a significant predictor of PRD when the sTg level was <6.0 ng/mL. LNR should be used in combination with a relatively low level of serum sTg to predict the prognosis of patients with PTC.

Impact of prophylactic unilateral central neck dissection needed for patients with papillary thyroid microcarcinoma.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC), the increase in the diagnosis of which has led to an overall rise in the diagnostic rate of thyroid malignancies, is generally managed through a reduction in the surgical extent. Nevertheless, a considerable number of patients with PTMC experience subclinical central lymph node (LN) metastases following prophylactic central neck dissection (CND). This study aimed to investigate the impact of prophylactic CND on locoregional recurrence in PTMC patients who underwent hemithyroidectomy. METHODS: We reviewed the medical records of 1,071 patients with clinically LN-negative PTMC who underwent hemithyroidectomy between 2004 and 2012. Cox proportional hazards regression analysis was performed to investigate the predictive factors for recurrence. The median follow-up duration was 79 months (range, 12-176 months). RESULTS: Totally, 613 patients underwent hemithyroidectomy only, whereas 458 underwent hemithyroidectomy plus prophylactic unilateral CND. Recurrence was observed in 27 patients (eight and 19 patients in the prophylactic and non-prophylactic CND groups, respectively). Patients with a tumor size ≤6 mm (hazard ratio, 2.927; 95% confidence interval, 1.372-6.245; P=0.005) had favorable recurrence-free survival (RFS); however, there was no relationship between prophylactic unilateral CND and RFS. CONCLUSIONS: The incidence of locoregional recurrence was low in patients with PTMC who underwent hemithyroidectomy. In addition, prophylactic unilateral CND performance was not associated with RFS in PTMC. Accordingly, the use of prophylactic unilateral CND for clinically LN-negative PTMC should be avoided.

Optimization of Predictive Performance for the Therapeutic Response Using Iodine Scan-Corrected Serum Thyroglobulin in Patients with Differentiated Thyroid Carcinoma.

We investigated whether the performance of serum thyroglobulin (Tg) for response prediction could be improved based on the iodine uptake pattern on the post-therapeutic I-131 whole body scan (RxWBS) and the degree of thyroid tissue damage with radioactive iodine (RAI) therapy. A total of 319 patients with differentiated thyroid carcinoma who underwent total thyroidectomy and RAI therapy were included. Based on the presence/absence of focal uptake at the anterior midline of the neck above the thyroidectomy bed on RxWBS, patients were classified into positive and negative uptake groups. Serum Tg was measured immediately before (D0Tg) and 7 days after RAI therapy (D7Tg). Patients were further categorized into favorable and unfavorable Tg groups based on the prediction of excellent response (ER) using scan-corrected Tg developed through the stepwise combination of D0Tg with ratio Tg (D7Tg/D0Tg). We investigated whether the predictive performance for ER improved with the application of scan-corrected Tg compared to the single Tg cutoff. The combined approach using scan-corrected Tg showed better predictive performance for ER than the single cutoff of D0Tg alone (p < 0.001). Therefore, scan-corrected Tg can be a promising biomarker to predict the therapeutic responses after RAI therapy.

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.

Vaccinia-related kinase 2 plays a critical role in microglia-mediated synapse elimination during neurodevelopment.

During postnatal neurodevelopment, excessive synapses must be eliminated by microglia to complete the establishment of neural circuits in the brain. The lack of synaptic regulation by microglia has been implicated in neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. Here we suggest that vaccinia-related kinase 2 (VRK2), which is expressed in microglia, may stimulate synaptic elimination by microglia. In VRK2-deficient mice (VRK2KO ), reduced numbers of presynaptic puncta within microglia were observed. Moreover, the numbers of presynaptic puncta and synapses were abnormally increased in VRK2KO mice by the second postnatal week. These differences did not persist into adulthood. Even though an increase in the number of synapses was normalized, adult VRK2KO mice showed behavioral defects in social behaviors, contextual fear memory, and spatial memory.

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.