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Background: This study aimed to evaluate the association between soluble TGF‐β (sTGF‐β) and soluble PD‐L1 (sPDL1), the dynamics of sTGF‐β during treatment and its prognostic role in biliary tract cancer (BTC). Methods: The study population consisted of 90 BTC patients with first‐line chemotherapy (cohort 1) and 35 BTC patients with second‐ or third‐line chemotherapy (cohort 2). Plasma sTGF‐β and sPDL1 levels were measured using an enzyme‐linked immunosorbent assay. Results: In both groups, sTGF‐β was positive correlated with sPDL1 for baseline and change values after treatment. sTGF‐β was elevated at disease progression compared to baseline in cohort 1 (P <.001). Increased sTGF‐β after treatment revealed worse DFS and OS (P =.024, P =.028, respectively) in cohort 1 and significantly shorter OS (P =.020) in cohort 2. In multivariable analysis, this prognostic value of increased sTGF‐β for OS retained its significance in both cohorts (Hazard ratio (HR) = 1.8, 95% CI, 1.1‐3.0, P =.028, in cohort 1; HR = 4.7, 95% CI, 1.5‐14.6, P =.007, in cohort 2). Conclusions: In BTC, sTGF‐β was positively correlated with sPDL1 for baseline and changes after chemotherapy, and increased as tumour burden. sTGF‐β could be associated with survival; particularly, an elevated value after treatment suggests worse prognosis. [ABSTRACT FROM AUTHOR]

Objective: Some authors have found little or no diagnostic benefit from repeated biopsy of benign thyroid nodules. However, to our knowledge, integration of Thyroid Imaging Reporting and Data System (TIRADS) guidelines with one biopsy for sufficient benign thyroid nodule diagnosis has not been previously described. We investigated malignancy rate and probability by using various malignancy stratification systems in initially biopsy-proven benign nodules and sought to determine their clinical relevance in management of benign thyroid nodules.Methods: This retrospective study collected 6762 thyroid nodules from 6493 consecutive patients who underwent biopsy between January 2013 and December 2013. The initial biopsy with ≥1 year of follow-up was used as the gold standard for benign diagnosis. For our study purpose, we analyzed 2747 (57.0%, 2747 of 4822, 532 women, 2111 men; 229 malignant and 2518 benign) thyroid nodules diagnosed by initial biopsy with 28.2 ± 9.1 (range, 12-41) months of follow-up. We calculated the malignancy probability of thyroid nodules by using various malignancy risk stratification systems.Results: The overall calculated thyroid malignancy rate was 8.3% (229 of 2747). Initially biopsy-proven benign nodules exhibited a ≤3.0% malignancy probability when assessed as "low suspicion" by Korean-TIRADS (K-TIRADS), "low suspicion" by the ATA guideline, and "very probably benign" by the French TIRADS guideline and gave a score of ≤3 by the web-based TIRADS.Conclusion: When initially biopsy-proven benign nodules exhibit a "low suspicion" US pattern and low malignancy probability, as stratified by various TIRADS guidelines, imaging surveillance instead of second biopsy is warranted.Key Points: • One biopsy is sufficient for initially biopsy-proven benign nodules. • Repetitive biopsy is necessary for imaging-pathology mismatched nodules. • Scoring risk stratification permits personalized management. [ABSTRACT FROM AUTHOR]

Objectives Papillary thyroid microcarcinoma ( PTMC) has an excellent prognosis with an indolent disease course. However, some PTMCs have an aggressive course with lateral cervical lymph node ( LCLN) metastasis or distant metastasis. This study aimed to evaluate the pre-operative features of PTMC associated with LCLN metastasis. Design and Patients This retrospective cohort study with a nested, matched case-control design included 199 PTMC patients with LCLN metastasis at initial surgery (N1b group) and 196 PTMC patients without any LN metastasis or persistent disease (N0 NED group) as controls; primary tumour sizes were matched. Results Compared with the N0 NED group, the N1b group was younger (<50 years) and more likely to be male ( P = 0·002 and P = 0·003, respectively). On pre-operative neck ultrasonography ( US), N1b group PTMCs were more commonly associated with a location in the upper lobes of the thyroid, or in the subcapsular area and microcalcifications than N0 NED group PTMCs (all P < 0·001). An increase in the number of these features was significantly associated with a higher risk of LCLN metastasis ( P < 0·001). Evaluation of the clinical and pre-operative US characteristics of 26 patients with confirmed LCLN recurrence after initial treatment of clinical N0 PTMCs revealed that the distribution of the number of suspicious features in these patients was similar to that of the N1b group. Conclusions Papillary thyroid microcarcinomas in young (<50 years) or male patients, with an upper lobe or subcapsular location, and with microcalcification have a higher risk of LCLN metastasis. Individualized management according to the number of these suspicious features may be needed for small thyroid nodules. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-lymphocyte ratio (NLR) is associated with a poor prognosis in many cancers but the biological mechanisms involved are unknown. Since cytokines and angiogenic factors (CAFs) are reflected by various immune responses, we analyzed the association between the NLR and CAFs and their prognostic implications in gastric cancer (GC). Methods: Of 745 GC patients who were enrolled in NLR analysis, 70 underwent NLR and CAF association analyses. Pretreatment serum levels of 52 CAFs were measured by means of multiplex bead immunoassays and enzyme-linked immunosorbent assays. Linear regression analysis and survival analysis of the NLR with each CAF were performed. Results: Metastatic organ numbers and carbohydrate antigen 19-9 levels were significantly higher in patients with a high NLR [greater than 2.42 (median): P = 0.047 and P < 0.001 respectively]. The overall survival was significantly worse in the high NLR group (17.8 months vs 11.2 months, P < 0.001). In CAF analysis, osteopontin ( R = 0.337, P < 0.001) and interleukin-6 ( R = 0.141, P = 0.001) were significantly associated with the NLR. Stromal-cell-derived factor 1 (SDF-1) was a significant poor prognostic factor independently of the NLR. Consideration of both the NLR and SDF-1 divided patient groups with different overall survival (both low, 21.0 months; either high, 15.8 months; both high, 8.2 months). Conclusion: The NLR is a significant poor prognostic factor in advanced GC. The NLR is mainly associated with osteopontin and interleukin-6. Besides the NLR, SDF-1 is an independent poor prognostic factor in GC. Consideration of both the NLR and SDF-1 might give insights into antitumor immunity in GC. [ABSTRACT FROM AUTHOR]

Background: Little is known about cytokine and angiogenic factors (CAFs) in gastric cancer (GC) in terms of tumor classification and prognostic value. Here, we aimed to correlate CAF signature with overall survival (OS) in GC. Methods: We measured pretreatment serum levels of 52 kinds of CAFs in 68 GC patients who were treated with fluoropyrimidine and platinum combination chemotherapy using multiplex bead immunoassays and enzyme-linked immunosorbent assay. We evaluated correlations between CAF levels and pathological features and OS. Results: Three distinct patient groups were identified: one with high levels of proangiogenic factors, another with high levels of proinflammatory factors, and the other with high levels of both factors. Eleven CAFs [interleukin (IL)-2 receptor-alpha, growth-regulated alpha protein, hepatocyte growth factor, macrophage colony-stimulating factor, stromal cell-derived factor, IL-6, IL-8, IL-10, interferon-gamma, vascular endothelial growth factor, and osteopontin] were independently correlated with poor OS. Clustering analysis of these 11 CAFs revealed distinct high and low 11-CAF signature groups. High 11-CAF signature was associated with shorter OS (10.1 vs. 17.9 months, p = 0.026) along with poor performance status, and the presence of signet ring cell components in multivariate analysis of OS (HR 1.76, p = 0.029). The patients' traditional clinicopathological characteristics were not significantly different between the high and low 11-CAF signature groups. Conclusion: Serum CAF profiling differentiated GC patient groups. A high 11-CAF signature could identify GC patients with a poor prognosis when treated with standard chemotherapy who need urgent new treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Time to progression (TTP) is suggested as a reliable endpoint compared with the progression-free survival in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied.Methods: We searched PubMed and Embase data to obtain data source. Eligible studies were randomised controlled phase III trials, which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association of treatment effects as shown by the hazard ratio (HR) of TTP and OS in each trial was assessed by the Spearman rank correlation coefficient (rs) and linear regression analysis. The association between median TTP and OS was also investigated.Results: Nine studies with a total of 18 treatment arms and 6318 patients were included. Incremental benefit from the study treatment in TTP from each trial was correlated with incremental benefit in OS. The rs value and R2 value between log (HRTTP) and log (HROS) was 0.73 (95% confidence interval (CI) 0.12-0.94, P=0.024) and 0.57. The minimum TTP effect to predict a treatment effect on OS was 0.63. Median TTP was associated with median OS. The rs value between TTP and OS was 0.73 (95% CI 0.40-0.89, P<0.001) and the corresponding R2 was 0.42.Conclusions: Our study results suggest that TTP could be used as a surrogate marker for OS in the clinical trials of advanced HCC. However, the results suggest modest correlation between treatment effects on TTP and OS. [ABSTRACT FROM AUTHOR]

Objectives: To investigate usefulness of multiparametric fully integrated 18-FDG PET/MRI in predicting treatment response after chemotherapy for unresectable advanced gastric cancers (AGCs).Methods: Eleven patients with unresectable AGCs underwent multiparametric 18-FDG PET/MRI examinations prior to chemotherapy. Perfusion parameters obtained via dynamic contrast-enhanced MRI, apparent diffusion coefficient values from diffusion-weighted images, and maximum standardized uptake values (SUVmax) from 18-FDG PET were measured. For parameters obtained from 18-FDG PET/MRI data, interobserver agreement was obtained using intraclass correlation coefficients (ICC) and chemotherapy response relationship was evaluated using the Mann-Whitney test and receiver operating characteristic analysis.Results: After chemotherapy, six patients were classified into the responder group and five patients into the non-responder group. For all parameters, moderate to nearly perfect agreement was achieved (ICC = 0.452-0.911). K (trans) values (P = 0.018) and initial area under the curves (iAUCs) (P = 0.045) of gastric cancers were significantly higher in responder group than in non-responder group. The area under the curve was 0.917 for K (trans) and 0.867 for iAUC. However, SUVmax values were not significantly different between the two groups.Conclusion: Multiparametric approach using fully integrated 18-FDG PET/MRI was shown to be feasible for patients with unresectable gastric cancers. In addition, K (trans) and iAUC values can be used as early predictive markers for chemotherapy response.Key Points: • Multiparametric 18-FDG PET/MRI is feasible for patients with unresectable advanced gastric cancer • K (trans) and iAUC were significantly higher in the responder group of patients • K (trans) , iAUC can be utilized as early predictive markers for chemotherapeutic response. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NAC) is a standard treatment for stage II/III breast cancer patients, and response to NAC is a useful prognostic marker. Since its introduction, 6-8 cycles of NAC has become the standard regimen to improve the outcome of these patients. The purpose of this study is to evaluate the prognostic impact of the American Joint Committee on Cancer (AJCC) response criteria and this tool's usefulness in four different breast cancer subtypes.Methods: We conducted a retrospective cohort study of clinical stage II/III breast cancer patients who received NAC of more than 6 cycles. Response after NAC and the clinicopathological factors were reviewed. AJCC response criteria for NAC were adopted from the AJCC Manual, 7th edition: complete response (CR), partial response (PR), and no response (NR).Results: A total of 183 patients were enrolled; 22 (12.0 %), 123 (67.2 %), and 38 (20.8 %) patients showed CR, PR, and NR, respectively. The AJCC response was significantly associated with relapse-free survival (RFS) (P < 0.001), whereas pathologic CR (pCR), the current gold standard for response evaluation for NAC, was not (P = 0.140). AJCC response was a significant prognostic factor for RFS in all four breast cancer subtypes, namely luminal A (P = 0.006), luminal B (P = 0.001), HER-2 enriched (P = 0.039), and triple-negative breast cancer (P = 0.035).Conclusions: The AJCC response criteria represent a simple and easily reproducible tool for response evaluation of NAC patients and a useful clinical prognostic marker for RFS. These criteria also have a prognostic impact in all four breast cancer subtypes, including luminal A in which pCR has a limited role. [ABSTRACT FROM AUTHOR]

Background: The association between the CpG island methylator phenotype (CIMP) and clinical outcomes in metastatic colorectal cancer remains unclear. We investigated the prognostic impact of CIMP in patients with metastatic colorectal cancer treated with systemic chemotherapy.Methods: Eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, CDKN2A, CRABP1, and MLH1) were examined. The CIMP status was determined by the number of methylated promoters as high (⩾5), low (1-4), and negative (0).Results: A total of 153 patients were included (men/women, 103/50; median age, 61 years; range, 22-80 years). The CIMP status was negative/low/high in 77/ 69/7 patients, respectively. Overall survival (OS) was significantly different among the three CIMP groups, with median values of 35.7, 22.2, and 9.77 months for the negative, low, and high groups, respectively (P<0.001). For patients treated with fluoropyrimidine and oxaliplatin first-line chemotherapy (N=128), OS and progression-free survival (PFS) were significantly different among the three CIMP groups; the median OS was 37.9, 23.8, and 6.77 months for the negative, low, and high groups, respectively (P<0.001), while the median PFS was 9.97, 7.87, and 1.83 months, respectively (P=0.002). Response rates were marginally different among the three CIMP groups (53.4% vs 45.1% vs 16.7%, respectively; P=0.107). For patients treated with fluoropyrimidine and irinotecan second-line chemotherapy (N=86), only OS showed a difference according to the CIMP status, with median values of 20.4, 13.4, and 2.90 months for the negative, low, and high groups, respectively (P<0.001).Conclusions: The CIMP status is a negative prognostic factor for patients with metastatic colorectal cancer treated with chemotherapy. [ABSTRACT FROM AUTHOR]

As small bowel adenocarcinoma (SBA) is a rare cancer worldwide, prognostic factors have not been clearly defined. The purpose of this study is to assess the prognostic role of clinicopathologic features, including body mass index (BMI), in patients with advanced SBA. A total of 28 consecutive patients with advanced SBA treated with palliative chemotherapy were retrospectively enrolled and analyzed. Clinicopathologic features, progression-free survival (PFS), and overall survival (OS) were compared according to BMI level. Eighteen patients had BMI < 25 kg/m2(overweight/normal/underweight in Asian) and ten patients had BMI ≥ 25 kg/m2(obese in Asian). Baseline characteristics were similar regardless of patient's BMI. Compared to patients with BMI < 25 kg/m2, patients with BMI ≥ 25 kg/m2had higher response rate to chemotherapy (40.0% vs. 0%,P= 0.010), longer OS (11.2 vs. 7.0 months,P= 0.018) and a tendency toward prolonged PFS (2.1 vs. 1.9 months,P= 0.085). Multivariate analysis revealed that BMI ≥ 25 kg/m2is an independent positive prognostic factor of OS (adjusted hazard ratio 0.35,P= 0.024). In conclusion, baseline BMI ≥ 25 kg/m2has a positive prognostic role in patients with advanced SBA. [ABSTRACT FROM PUBLISHER]

Background: Although patients with minimally invasive follicular thyroid carcinoma (MIFTC) generally have an excellent prognosis, distant metastasis occurs in some patients. Risk factors for distant metastasis have been reported, none has been found to be conclusive. This study evaluated risk factors for distant metastasis, including protein markers, in patients with MIFTC. Methods: A review of patient records identified 259 patients who underwent surgery at Asan Medical Center from 1996 to 2010 and were subsequently diagnosed with MIFTC. After review of pathological slides, 120 patients with paraffin blocks suited for tissue microarrays (TMA) were included in this study. Immunohistochemical stain of TMA slides was performed by protein markers; β-catenin, C-MET, CK19, estrogen receptor (ER) α, ER β, HBME-1, MMP2, PPAR γ and progesterone receptor. Results: 120 patients included 28 males (23.3%) and 92 females (76.7%), of mean age 41.5±10.8 years (range, 13–74 years). Eight patients (6.7%) had distant metastases during follow-up. Univariate analysis showed that age (≥45 years), male sex, and extensive vascular invasion (≥4 foci) were associated with distant metastasis. Multivariate regression analysis showed that extensive vascular invasion was the only independent risk factor for distant metastasis (p = 0.012). Although no protein markers on TMA analysis were directly related to distant metastasis of MIFTC, CK19 expression was more frequent in patients with than without extensive vascular invasion (p = 0.036). Conclusion: Extensive vascular invasion was the only independent risk factor for distant metastasis of MIFTC. No proteins markers were directly related to distant metastasis, but CK19 was associated with extensive vascular invasion. [ABSTRACT FROM AUTHOR]

Background: Ampulla of Vater cancer (AoV Ca) is a rare tumor, and its adjuvant treatment has not been established. The purpose of this study was to find out prognostic factors including host immunity and role of adjuvant treatment in AoV Ca. Methods and Findings: We reviewed 227 AoV Ca patients with curative resection. Clinical characteristics, adjuvant treatment, disease-free survival (DFS) and overall survival (OS) were analyzed. Among all patients, 63.9, 36.1 and 33.9% had T1/T2, T3/T4 stage and lymph node-positive disease (LN+), respectively. OS of all patients was 90.9 months (95% CI: 52.9–129.0). OS was different according to neutrophil-to-lymphocyte ratio (HR 1.651, 95% CI: 1.11–2.47), platelet-to-lymphocyte ratio (HR 1.488, 95% CI: 1.00–2.21) and systemic inflammatory index (HR 1.669, 95% CI: 1.13–2.47). In multivariate analysis, adverse prognostic factors for OS included vascular invasion (HR 2.571, 95% CI: 1.20–5.53) and elevated CA 19–9 (HR 1.794, 95% CI: 1.07–3.05). A total of 104 patients (46.3%) received adjuvant treatment (25 out of 111of T1/T2 & LN (-), 79 out of 116 of T3/T4 or LN (+)). In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the longest OS (5-year OS rate: 47.0 vs. 41.4%). Conclusions: Vascular invasion and elevated CA 19–9 were adverse prognostic factors in resected AoV Ca. In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the best survival outcome. Adjuvant treatment should be further defined in AoV Ca, especially with poor prognostic factors. [ABSTRACT FROM AUTHOR]

Introduction: Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer. Methods: We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using ROC curve. Results: Among 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (P< 0.001) and decreased SMI (P = 0.001), the OS of female patients was influenced with overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI (P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002). Conclusions: Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background. In advanced biliary tract cancer (BTC), the metabolic landscape has not been evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) yet. Furthermore, reports of the clinical implications of these metabolic features are limited. We aimed to evaluate the metabolic features and their clinical relevance in advanced BTC using 18F-FDG PET. Patients and Methods. We consecutively enrolled patients with advanced BTC who underwent 18F-FDG PET prior to palliative chemotherapy between 2003 and 2013. We evaluated the findings of PET, such as SUVmax, the number of lesions and organs with FDG uptake, pathologic findings, and clinical outcomes. Results. A total of 106 patients were enrolled: (53 intrahepatic cholangiocarcinoma [ICC], 7 extrahepatic BTC, 30 gallbladder cancer [GB Ca], and 16 ampulla of Vater cancer [AoVCa]).The median SUVmax, differed according to the primary origin (ICC, 9.10; extrahepatic BTC, 5.90; GB Ca, 9.10; and AoV Ca, 6.37; p = .008) and histologic differentiation (well differentiated, 4.95; moderately differentiated, 6.60; poorly differentiated, 14.50; p = .004). Patients in the high metabolic group (SUVmax, of ≥7.5) had more poorly differentiated histology and more organs and lesions with FDG uptake than did those in the low metabolic group (SUVmax, of <7.5). The low metabolic group had a significantly longer OS (11.4 vs. 7.4 months, p = .007) and PFS (6.6 vs. 4.3 months, p 5 .024) than high metabolic group. In multivariate analysis, SUVmax, was a significant prognostic factor for overall survival (OS;p = .047) and progression-free survival (PFS; p = .039). Conclusion. Metabolic characteristics of advanced BTC differ according to primary origin and histology. These metabolic features could be prognostic factors for OS and PFS in advanced BTC. [ABSTRACT FROM AUTHOR]

The prognostic significance of ataxia-telangiectasia-mutated (ATM) expression in gastric cancer remains unclear. The functional loss of ATM gene exhibits a biologic correlation with microsatellite instability (MSI). In this study, we investigated the significance of ATM expression with MSI by evaluating gastric cancer patients who had underwent curative resection. ATM expression was classified into low ATM expression (−, ±, +) and high ATM expression (++, +++) using immunohistochemistry analysis. MSI status was classified as MSI-negative (MSS, MSI-low) and MSI-positive (MSI-high). Of 321 patients, 205 (63.9%) exhibited low ATM expression and 116 (36.1%) exhibited high ATM expression. Low ATM expression was more frequently identified in patients of older age, more advanced stage and with MSI-positive tumor ( p = 0.025, p = 0.001 and p = 0.014, respectively). The probability of 5-year disease-free survival (DFS) and overall survival (OS) was lower in low ATM expression group compared with the high ATM expression group (DFS: 62.5%, 76.4%, p = 0.017, OS: 65.9%, 78.5%, p = 0.027, respectively). According to MSI status, a subgroup of MSI-negative and low ATM expression cases exhibited the worst prognosis for DFS and OS; this subgroup also exhibited poorer DFS according to multivariable analysis (hazard radio = 1.8, 95% confidence interval, 1.2-2.8, p = 0.010), although prognostic value of ATM expression alone did not remain in the multivariable analysis. Taken together, these findings indicate that ATM expression with MSI status is an independent factor for gastric cancer prognosis in gastric cancer patients who received curative surgery. [ABSTRACT FROM AUTHOR]

Metastasis to the thyroid is uncommon, but the number of cases seems to have increased in recent years. This increase may be related to more frequent use of fine-needle aspiration biopsy (FNAB) in any suspected case.A retrospective review of patients with thyroid metastasis diagnosed by FNAB at the Asan Medical Centre.Twenty-two patients who were seen at the Asan Medical Centre between 1997 and 2003. Median age was 55 years with range between 34 and 74 years.Fourteen patients presented with a palpable thyroid nodule. Eight patients had an impalpable thyroid nodule that was found incidentally during the various imaging studies. The breast (five patients) was the most common primary site followed by the kidney (three), colon (three) and lung (three). FNAB confirmed metastatic disease in 19 patients and raised suspicion in three patients. The suspicion of metastasis to the thyroid was confirmed by Tru-cut needle core biopsy in one patient and surgery in two patients. Thyroid metastases were found during the initial work-up for primary tumour in eight patients. In the remaining 14 patients, the interval from diagnosis of primary tumour to the detection of thyroid metastasis varied from 8 months to 15 years, with a median of 54 months. Fifteen patients had metastatic disease elsewhere at the time of presentation. Ten patients received chemotherapy. Radiotherapy was used in two patients. Seven patients are still alive, with one patient disease free for 16 months following resection of the thyroid metastasis.Thyroid metastases are uncommon but can be detected more frequently with routine use of FNAB. Breast cancer is the most common tumour that metastasizes to the thyroid. They usually occur when there are metastases elsewhere, sometimes many years after the diagnosis of the original primary tumour and show poor prognosis in general. [ABSTRACT FROM AUTHOR]

Abstract Slits, representative axon guidance molecules, and their Roundabout (Robo) transmembrane receptors play roles in the progression of many cancers. We investigated the effects of Slit2 on the proliferation, migration, and invasion of thyroid cancer cells, and on the prognosis of papillary thyroid cancer (PTC). Slit2 overexpression inhibited the proliferation, migration and invasion of thyroid cancer cells by inhibiting transcriptional activity of beta-catenin and regulating Rho GTPase activity. Slit2 knockdown activated the migration and invasion of thyroid cancer cells and transcriptional activity of beta-catenin. Fragment Slit2 treatment inhibited thyroid cancer cell proliferation in a dose dependent manner, and also inhibited migration and invasion. When we evaluated the protein expression of Slit2 in PTCs, 24 of 160 PTCs (15%) were negative for Slit2 protein expression and these patients had significantly increased risk of cervical lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and recurrence of PTC (P < 0.001). Our findings suggest a role for Slit2 as a tumor suppressor, and also as a novel prognostic and potential therapeutic target for thyroid cancer. Highlights • Slit2 inhibits thyroid cancer cell proliferation, migration, and invasion. • The effect is caused by inhibiting transcriptional activity of beta-catenin and regulating Rho GTPase activity. • Loss of Slit2 protein expression is associated with metastasis and recurrence of papillary thyroid cancer. • These findings suggest Slit2 as novel prognostic and potential therapeutic target for thyroid cancer. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the proposed changes in the eighth edition of the tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in terms of pathologic subtypes, using a large multicenter thyroid cancer cohort.Materials and Methods: We retrospectively reviewed 7717 patients with papillary (PTC) and 273 with follicular thyroid carcinoma (FTC) who underwent thyroid surgery between 1996 and 2005. We assessed the proportion of variation explained (PVE) to compare the predictive accuracy of disease-specific survival (DSS).Results: During a median 11.3 years of follow-up, 169 (2%) disease-specific deaths were recorded. In patients with PTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 99.6%, 95.7%, 81.5%, and 54.8%, respectively; the corresponding rates in TNM-7 were 99.6%, 98.4%, 98.4%, and 90.1%, respectively. In patients with FTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 97.2%, 69.8%, 50.0%, and 45.5%, respectively; the corresponding rates in TNM-7 were 98.3%, 90.0%, 92.3%, and 42.1%, respectively. Comparing TNM-7 and TNM-8, the PVE values increased from 3.4% to 4.7% in the PTC group, whereas they decreased from 17.5% to 14.5% in the FTC group.Conclusion: Our study suggests that the changes in TNM-8 have improved the clinical usefulness of the TNM staging system in terms of predicting DSS in patients with PTC but not FTC. Further studies to establish a more predictable TNM staging system that focuses on patients with FTC are necessary. [ABSTRACT FROM AUTHOR]

Objectives: Based on the tumor-node-metastasis staging system, eighth edition (TNM-8), N1b is no longer used as a variable to determine final stage in papillary thyroid carcinoma (PTC). We aimed to evaluate the predictability of a simple modification of the TNM staging with N1b classification in a large multicenter thyroid cancer cohort.Materials and Methods: This study included 7717 patients with PTC who underwent thyroid surgery between 1996 and 2005 from six tertiary hospitals. We classified patients with stage II into stage IIA and IIB with modified-TNM: older patients with N1b disease were classified as stage IIB, while remaining patients were classified as stage IIA.Results: The mean age was 46.2 years, and 24% were aged ≥55 years. In older patients, the 10-year disease-specific survival (DSS) rate of N1b disease (86.3%) was approximately 10% lower than that of N1a disease, and patients with N1b had significantly poorer DSS than those with N1a (HR = 3.3, p < 0.001). When the modified-TNM was applied, DSS curves between stage groups significantly differed (p < 0.001), and the relative risk of DSS in stage IIB patients was 2.3 times higher than in stage IIA patients (p < 0.001). The proportion of variation explained value of the modified-TNM was 4.9% and that of the TNM-8 was 4.7%.Conclusion: This multicenter study reveals that the presence of lateral lymph node metastasis affects disease mortality in PTC, especially in older patients. The sub-classification of stage II in older patients improves DSS predictability. This simple modification of TNM-8 provides better prognostic information for patients with PTC. [ABSTRACT FROM AUTHOR]