Diagnostic Accuracy of MRI-Based Morphometric Parameters for Detecting Olfactory Nerve Dysfunction.

BACKGROUND AND PURPOSE: Although olfactory dysfunction is a common cranial nerve disorder, there are no simple objective morphometric criteria to assess olfactory dysfunction. The aim of this study was to evaluate the diagnostic performance of MR imaging morphometric parameters for detecting olfactory dysfunction. MATERIALS AND METHODS: This prospective study enrolled patients from those presenting with olfactory symptoms who underwent both an olfactory function test and MR imaging. Controls without olfactory dysfunction were recruited during the preoperative work-up for pituitary adenoma. Two independent neuroradiologists measured the olfactory bulb in 3D and assessed olfactory bulb concavity on MR imaging while blinded to the clinical data. Diagnostic performance was assessed using receiver operating characteristic curve analysis. RESULTS: Sixty-four patients and 34 controls were enrolled. The patients were significantly older than the controls (mean age, 57.8 ± 11.9 years versus 47.1 ± 12.1 years; P < .001). Before age adjustment, the olfactory bulb height was the only olfactory bulb parameter showing a significant difference between patients and controls (1.6 ± 0.3 mm versus 2.0 ± 0.3 mm, P < .001). After age adjustment, all parameters and olfactory bulb concavity showed significant intergroup differences, with the olfactory bulb height having the highest area under the curve (0.85). Olfactory bulb height was confirmed to be the only significant parameter showing a difference in the detection of olfactory dysfunction in 22 pairs after matching for age and sex (area under the curve = 0.87, P < .001). Intraclass correlation coefficients revealed moderate-to-excellent degrees of inter- and intrareader agreement. CONCLUSIONS: MR imaging morphometric analysis can differentiate patients with olfactory dysfunction, with the olfactory bulb height having the highest diagnostic performance for detecting olfactory dysfunction irrespective of age.

Diagnostic performance of MRI to detect metastatic cervical lymph nodes in patients with thyroid cancer: a systematic review and meta-analysis.

AIM: To evaluate the diagnostic performance of magnetic resonance imaging (MRI) in the diagnosis of metastatic cervical lymph nodes. MATERIALS AND METHODS: Ovid-MEDLINE and EMBASE databases were searched up until 12 June 2018. Eleven articles were included in the qualitative systematic review and nine of the 11 in the quantitative analysis. Two radiologists independently performed data extraction and methodological quality assessment using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A qualitative systematic review and quantitative analysis were performed, followed by a meta-regression analysis to determine factors causing heterogeneity. RESULTS: The pooled sensitivity and specificity in the diagnosis of metastatic cervical lymph nodes were 80% (95% confidence interval [CI]: 68-88%) and 85% (95% CI: 63-95%), respectively. The sensitivity and false-positive rate (correlation coefficient, 0.655) showed a positive correlation due to a threshold effect, which was responsible for heterogeneity across the studies, as indicated by a Q-test (p<0.01) and Higgins I2 statistic (sensitivity, I2=90.11%; specificity, I2=92.49%). In the meta-regression analysis, fat-suppressed imaging, and the analysis method were significant factors influencing the heterogeneity in diagnostic performance. CONCLUSIONS: MRI shows moderate diagnostic performance in the diagnosis of metastatic lymph nodes in patients with thyroid cancer in the neck. MRI may be an optional or complementary imaging method to ultrasound or computed tomography (CT) in thyroid cancer patients.

CT and MRI Findings of Glomangiopericytoma in the Head and Neck: Case Series Study and Systematic Review.

Glomangiopericytoma is a rare sinonasal mesenchymal tumor of borderline or low malignant potential. We reviewed the CT and MR imaging findings of head and neck glomangiopericytoma via a retrospective case series study and systematic review. Our study revealed that glomangiopericytoma is a well-defined lobulated avidly enhancing soft-tissue mass with erosive bony remodeling that is most commonly found in the sinonasal cavity. Typically, it is hyperintense on T2-weighted images with vascular signal voids, has a high mean ADC value, and a wash-in and washout pattern on dynamic contrast-enhanced MR imaging. Although the CT findings are nonspecific, typical MR imaging findings, including those on the ADC map and dynamic contrast-enhanced MR imaging, may be helpful for differentiating glomangiopericytomas from other hypervascular tumors in the head and neck.

Detection of Local Recurrence in Patients with Head and Neck Squamous Cell Carcinoma Using Voxel-Based Color Maps of Initial and Final Area under the Curve Values Derived from DCE-MRI.

BACKGROUND AND PURPOSE: Early detection of local recurrence is important to increase the chance of cure because local recurrence is the main cause of treatment failure in head and neck squamous cell carcinoma. We evaluated the added value of voxel-based color maps of dynamic contrast-enhanced MR imaging compared with conventional MR imaging alone for detecting local recurrence of head and neck squamous cell carcinoma. MATERIALS AND METHODS: We retrospectively enrolled 63 consecutive patients with head and neck squamous cell carcinoma after definitive treatment and posttreatment surveillance MR imaging studies that demonstrated focal enhancement at the primary site. Three independent readers assessed conventional MR imaging and a pair of color maps of initial and final 90-second time-signal intensity areas under the curve from dynamic contrast-enhanced MR imaging. The sensitivities, specificities, and accuracies of both conventional MR imaging alone and combined interpretation of conventional and dynamic contrast-enhanced MR imaging were assessed using the clinicopathologic diagnosis as the criterion standard. κ statistics were used to evaluate interreader agreement. RESULTS: There were 28 patients with subsequently documented local recurrence and 35 with posttreatment change. Adding dynamic contrast-enhanced MR imaging to conventional MR imaging significantly increased the diagnostic accuracies for detecting local recurrence (48%-54% versus 87%-91%; P < .05), with excellent interreader agreement (κ = 0.8; 95% CI, 0.67-0.92 to κ = 0.81; 95% CI, 0.69-0.93). By all 3 readers, the specificities were also significantly improved by adding dynamic contrast-enhanced MR imaging to conventional MR imaging (22%-43% versus 87%-91%; P < .001) without sacrificing the sensitivities (68%-82% versus 86%-89%; P > .05). CONCLUSIONS: Adding voxel-based color maps of initial and final 90-second time-signal intensity areas under the curve from dynamic contrast-enhanced MR imaging to conventional MR imaging increases the diagnostic accuracy to detect local recurrence in head and neck squamous cell carcinoma by improving the specificity without sacrificing the sensitivity.

Are patients with mild to moderate renal impairment on metformin or other oral anti-hyperglycaemic agents at increased risk of contrast-induced nephropathy and metabolic acidosis after radiocontrast exposure?

AIM: To investigate whether the use of metformin during computed tomography (CT) with radiocontrast agents increases the risk of contrast-induced nephropathy (CIN) and metabolic acidosis after CT in type 2 diabetes patients with mild to moderate renal failure. MATERIALS AND METHODS: Patient records from January 2015 to December 2017 were reviewed retrospectively. A total of 374 patients were included in the final analysis. Of them, 157 patients received metformin, and 217 patients were taking other oral hypoglycaemic agents (OHAs) during radiocontrast administration. RESULTS: No significant difference in CIN incidence was observed between the metformin use group and the other OHAs group (p=0.085). Metabolic acidosis after CT was seen in 91 (58%) patients who used metformin and 141 (65%) patients who were taking other OHAs. There was no relationship between metabolic acidosis after CT and the use of metformin (p=0.195). Metabolic acidosis after radiocontrast agent exposure was associated with malignant disease, low serum albumin level, and low serum total CO2 level at baseline. CONCLUSION: These data show that other factors, but not metformin use, are associated with metabolic acidosis after radiocontrast agent exposure in patients with reduced renal function. These data support current recommendations that there is no need to discontinue metformin before CT using radiocontrast agents in patients with mild to moderate renal failure.

A Scoring System for Prediction of Cervical Lymph Node Metastasis in Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: An accurate and comprehensive assessment of lymph node metastasis in patients with head and neck squamous cell cancer is crucial in daily practice. This study constructed a predictive model with a risk scoring system based on CT characteristics of lymph nodes and tumors for patients with head and neck squamous cell carcinoma to stratify the risk of lymph node metastasis. MATERIALS AND METHODS: Data included 476 cervical lymph nodes from 191 patients with head and neck squamous cell carcinoma from a historical cohort. We analyzed preoperative CT images of lymph nodes, including diameter, ratio of long-to-short axis diameter, necrosis, conglomeration, infiltration to adjacent soft tissue, laterality and T-stage of the primary tumor. The reference standard comprised pathologic results. Multivariable logistic regression analysis was performed to develop the risk scoring system. Internal validation was performed with 1000-iteration bootstrapping. RESULTS: Shortest axial diameter, ratio of long-to-short axis diameter, necrosis, and T-stage were used to develop a 9-point risk scoring system. The risk of malignancy ranged from 7.3% to 99.8%, which was positively associated with increased scores. Areas under the curve of the risk scoring systems were 0.886 (95% CI, 0.881-0.920) and 0.879 (95% CI, 0.845-0.914) in internal validation. The Hosmer-Lemeshow goodness-of-fit test indicated that the risk scoring system was well-calibrated (P = .160). CONCLUSIONS: We developed a comprehensive and simple risk scoring system using CT characteristics in patients with head and neck squamous cell carcinoma to stratify the risk of lymph node metastasis. It could facilitate decision-making in daily practice.

The Diagnostic Value of Diffusion-Weighted Imaging in Differentiating Metastatic Lymph Nodes of Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Accurate lymph node staging is crucial for proper treatment planning for metastasis in patients with head and neck squamous cell carcinoma. PURPOSE: Our aim was to evaluate the diagnostic performance of DWI for differentiating metastatic cervical lymph nodes from benign cervical lymph nodes in patients with head and neck squamous cell carcinoma and to identify optimal cutoff values for ADC. DATA SOURCES: A computerized literature search was performed to identify relevant original articles in Ovid MEDLINE and EMBASE. STUDY SELECTION: Studies evaluating the diagnostic performance of DWI for differentiating metastatic cervical lymph nodes from benign cervical lymph nodes were selected. DATA ANALYSIS: Diagnostic meta-analysis was conducted with a bivariate random-effects model, and a hierarchical summary receiver operating characteristic curve was obtained. Meta-regression was also performed. DATA SYNTHESIS: Nine studies with 337 patients were included. In all studies, ADC values derived from metastatic lymph nodes were significantly lower than ADC values derived from benign lymph nodes. The median ADC cutoff value was 0.965 × 10-3 mm2/s. The pooled sensitivity and specificity for the diagnostic performance of DWI in differentiating metastatic lymph nodes from benign lymph nodes were 90% (95% CI, 84%-94%) and 88% (95% CI, 80%-93%), respectively. In the meta-regression, sensitivity was significantly higher in the studies using a 3-mm slice thickness (93% [95% CI, 88%-98%]) than in studies using a slice thickness of >3 mm (86% [95% CI, 77%-95%], P < .01). LIMITATIONS: A small number of studies were included in our meta-analysis. CONCLUSIONS: DWI demonstrated high diagnostic performance for differentiating metastatic lymph nodes from benign lymph nodes in patients with head and neck squamous cell carcinoma, and the median ADC cutoff value was 0.965 × 10-3 mm2/s. A 3-mm DWI slice thickness can provide a slight improvement in sensitivity.

PIN1 is a new therapeutic target of craniosynostosis.

Gain-of-function mutations in fibroblast growth factor receptors (FGFRs) cause congenital skeletal anomalies, including craniosynostosis (CS), which is characterized by the premature closure of craniofacial sutures. Apert syndrome (AS) is one of the severest forms of CS, and the only treatment is surgical expansion of prematurely fused sutures in infants. Previously, we demonstrated that the prolyl isomerase peptidyl-prolyl cis-trans isomerase interacting 1 (PIN1) plays a critical role in mediating FGFR signaling and that Pin1+/- mice exhibit delayed closure of cranial sutures. In this study, using both genetic and pharmacological approaches, we tested whether PIN1 modulation could be used as a therapeutic regimen against AS. In the genetic approach, we crossbred Fgfr2S252W/+, a mouse model of AS, and Pin1+/- mice. Downregulation of Pin1 gene dosage attenuated premature cranial suture closure and other phenotypes of AS in Fgfr2S252W/+ mutant mice. In the pharmacological approach, we intraperitoneally administered juglone, a PIN1 enzyme inhibitor, to pregnant Fgfr2S252W/+ mutant mice and found that this treatment successfully interrupted fetal development of AS phenotypes. Primary cultured osteoblasts from Fgfr2S252W/+ mutant mice expressed high levels of FGFR2 downstream target genes, but this phenotype was attenuated by PIN1 inhibition. Post-translational stabilization and activation of Runt-related transcription factor 2 (RUNX2) in Fgfr2S252W/+ osteoblasts were also attenuated by PIN1 inhibition. Based on these observations, we conclude that PIN1 enzyme activity is important for FGFR2-induced RUNX2 activation and craniofacial suture morphogenesis. Moreover, these findings highlight that juglone or other PIN1 inhibitors represent viable alternatives to surgical intervention for treatment of CS and other hyperostotic diseases.

Effect of an Arm Traction Device on Image Quality and Radiation Exposure during Neck CT: A Prospective Study.

BACKGROUND AND PURPOSE: The image quality of neck CT is frequently disturbed by streak artifact from the shoulder girdles. Our aim was to determine the effects of an arm traction device on image quality and radiation exposure in neck CT. MATERIALS AND METHODS: Patients with lymphoma with complete remission who were scheduled to undergo 2 consecutive follow-up neck CT scans for surveillance within a 1-year interval were enrolled in this prospective study. They underwent 2 consecutive neck CT scans (intervention protocol: patients with an arm traction device; standard protocol: no positioning optimization) on the same CT system. The primary outcome measures were image noise in the lower neck and dose-length product. Secondary outcomes were streak artifacts in the supraclavicular fossa, volume CT dose index, and the extent of the biacromial line shift. RESULTS: Seventy-three patients were enrolled and underwent 2 consecutive CT scans with a mean interval of 155 days. In the intervention protocol, a mean noise reduction in the lower neck of 25.2%-28.5% (P < .001) was achieved, and a significant decrease in dose-length product (413 versus 397, P < .001) was observed. The intervention protocol significantly decreased streak artifacts (P < .001) and volume CT dose index (13.9 versus 13.4, P < .001) and could lower the biacromial line an average of 2.1 cm. CONCLUSIONS: An arm traction device can improve image quality and reduce radiation exposure during neck CT. The device can be simply applied in cooperative patients with suspected lower neck lesions, and the approach offers distinct advantages over the conventional imaging protocol.

Efficacy and Safety of Ethanol Ablation for Branchial Cleft Cysts.

BACKGROUND AND PURPOSE: Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst. MATERIALS AND METHODS: Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%-80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated. RESULTS: The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8-49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0-3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%-100.0%; P < .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic (P < .001) and cosmetic (P < .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient. CONCLUSIONS: Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation.

Ethanol Ablation of Ranulas: Short-Term Follow-Up Results and Clinicoradiologic Factors for Successful Outcome.

BACKGROUND AND PURPOSE: Surgical excision of an affected sublingual gland for treatment of a ranula can carry a potential of a nerve damage or postoperative complications. However, there have been little studies about effective minimally invasive therapeutic method, yet. Our aim was to evaluate the efficacy and safety of ethanol ablation of ranulas and the clinicoradiologic factors that can predict outcome. MATERIALS AND METHODS: This retrospective study evaluated 23 patients with ranulas treated by percutaneous ethanol ablation. Treatment outcome was assessed in 20 patients followed for at least 6 months. The duration of symptoms before ethanol ablation, pretreatment volume, and parapharyngeal extension on sonography and/or CT were correlated with the outcome. The Mann-Whitney U test and Fisher exact test were used for comparison of the factors according to the outcome. RESULTS: The study evaluated 14 males and 9 females with a median age of 26 years (range, 3-41 years). Among 20 patients who were followed for at least 6 months (median, 20 months; range, 6-73 months), 9 patients (45%) demonstrated complete disappearance of the ranulas and 11 (55%) showed an incomplete response. When the patients were divided according to the duration of symptoms before ethanol ablation, the complete response rate was significantly higher in patients with ≤12 months of symptoms (73%, 8/11) than that in others (11%, 1/9) (P = .010). Pretreatment volume and parapharyngeal extension were not significantly different between the 2 groups. CONCLUSIONS: Ethanol ablation is a safe and noninvasive treatment technique for ranulas with a significantly better outcome in patients with ≤12 months of symptoms. Therefore, it could be considered an alternative nonsurgical approach for ranulas with recent onset of symptoms.

Interobserver reproducibility of maximal axial diameter and tumour volume measurements from CT of patients with head and neck squamous cell carcinoma.

AIM: To evaluate the interobserver reproducibility of computed tomography (CT) measurements of maximum tumour diameter and tumour volume for head and neck squamous cell carcinoma. MATERIALS AND METHODS: Eighty consecutive patients who underwent neck CT for the initial evaluation of head and neck squamous cell carcinoma were included in this retrospective study. Two radiologists independently measured the maximal axial diameter and volume of tumours. The reproducibility between the two observers was assessed using 95% Bland-Altman limits of agreement, reproducibility coefficient, within-subject coefficient of variation, and intraclass correlation coefficient with subgroup analysis according to tumour location. Logistic regression analysis was performed to identify the risk factors for high variability in tumour volume. RESULTS: The 95% limits of agreement for maximal axial diameter and tumour volume were ±22.3% and ±42.8%, respectively. The within-subject coefficient of variation and reproducibility coefficient were 7.9% and 0.564 for maximal axial diameter and 22.9% and 5.069 for tumour volume. All intraclass correlation coefficients for maximal axial diameter and tumour volume demonstrated excellent agreement (all intraclass correlation coefficients >0.9). Peritumoural infiltration (odds ratio: 7.189; confidence interval: 1.815-28.469; p=0.005) was an independent risk factor for high interobserver variability. CONCLUSION: Changes in maximum axial diameter and tumour volume of <22.3% and 42.8%, respectively, were in the range of measurement error on CT. The presence of peritumoural infiltration on CT increases the error in tumour volume measurement.

The Role of Core Needle Biopsy for Thyroid Nodules with Initially Indeterminate Results on Previous Fine-Needle Aspiration: A Systematic Review and Meta-Analysis.

BACKGROUND: Sonography-guided fine-needle aspiration leads to relatively frequent cases of indeterminate cytology for the diagnosis of thyroid nodules. PURPOSE: Our aim was to evaluate the efficacy and safety of core needle biopsy for the examination of thyroid nodules with initially indeterminate results on fine-needle aspiration. DATA SOURCES: A computerized search of the MEDLINE and Embase databases was performed to identify relevant original articles. STUDY SELECTION: Studies investigating the use of core needle biopsy for thyroid nodules with initially indeterminate results on previous fine-needle aspiration were eligible for inclusion. DATA ANALYSIS: The pooled proportions for nondiagnostic results, inconclusive results, malignancy on core needle biopsy, the ability of core needle biopsy to diagnose malignancy, and the related complications of the procedure were analyzed. DATA SYNTHESIS: The meta-analytic pooling was based on a random-effects model. Nine eligible studies, involving 2240 patients with 2245 thyroid nodules, were included. The pooled proportion for nondiagnostic results was 1.8% (95% CI, 0.4%-3.2%), and the pooled proportion for inconclusive results was 25.1% (95% CI, 15.4%-34.9%). The pooled proportion for malignancy was 18.9% (95% CI, 8.4%-29.5%). With regard to the diagnostic performance for malignancy, the sensitivity of core needle biopsy varied, ranging from 44.7% to 85.0%, but the specificity was 100% in all cases. No major complications of core needle biopsy were observed. LIMITATIONS: The relatively small number of included studies and retrospective nature were limitations. CONCLUSIONS: Core needle biopsy has low nondiagnostic result rates and high specificity for the diagnosis of malignancy. It is a safe diagnostic technique with a higher diagnostic yield, especially when molecular testing is not available or fine-needle aspiration did not yield enough cells for molecular testing.

Improved Diagnostic Accuracy Using Arterial Phase CT for Lateral Cervical Lymph Node Metastasis from Papillary Thyroid Cancer.

BACKGROUND AND PURPOSE: Contrast-enhanced CT protocols for papillary thyroid cancer are yet to be optimized. Our aim was to compare the diagnostic accuracy of arterial phase CT and delayed-phase CT protocols for lateral cervical lymph node metastasis from papillary thyroid carcinoma by using the lymph node tissue attenuation. MATERIALS AND METHODS: This retrospective study included 327 lateral cervical lymph nodes (177 metastatic and 150 benign) from 131 patients with papillary thyroid carcinoma (107 initially diagnosed and 24 recurrences). Patients underwent CT by using 1 of 3 protocols: a 70-second (A) or a 35-second (B) delay with 100 mL of iodinated IV contrast or a 25-second delay with 75 mL of IV contrast (C). Two readers independently measured and compared lymph node tissue attenuation between metastatic and benign lymph nodes. An area under the receiver operating characteristic curve analysis was performed to differentiate metastatic and benign lymph nodes after multiple comparison correction for clustered data and was compared across the protocols. RESULTS: The difference in mean lymph node tissue attenuation between metastatic and benign lymph nodes was maximum in protocol C (P < .001 for both readers). Protocol C showed the highest diagnostic performance (area under the receiver operating characteristic curve, 0.88-0.92) compared with protocol A (area under the receiver operating characteristic curve, 0.73-0.74, P < .001 for both readers) and B (area under the receiver operating characteristic curve, .63-0.65, P < .01 for both readers). The sensitivity, specificity, positive predictive value, and negative predictive value of lymph node tissue attenuation by using a 99-HU cutoff value were 83%-87%, 93.7%-97.9%, 95.1%-97.3%, and 81.2%-87%. CONCLUSIONS: A combination of 25-second delay CT and 75 mL of iodinated IV contrast can improve the diagnostic accuracy for lateral lymph node metastasis from papillary thyroid carcinoma compared with a combination of a 35- or 70-second delay with 100-mL of iodinated IV contrast.

Risk of malignancy according to sub-classification of the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category in the Bethesda system for reporting thyroid cytopathology.

OBJECTIVE: According to the Bethesda System for Reporting Thyroid Cytopathology, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous category that includes cases with architectural and/or nuclear atypia insufficient to warrant classification as malignant neoplasms. The ambiguous and descriptive characteristics of the AUS/FLUS category mean that the impact of the present guidelines on repeat fine needle aspiration (FNA) is unclear. The present study reclassified AUS/FLUS cases into four sub-categories and then correlated them with histological or cytological follow-up data to clarify the risk of malignancy. METHODS: Ninety-four cases of AUS/FLUS with available follow-up data were reviewed and assigned to one of four sub-categories: (i) AUS-N (nuclear atypia); (ii) AUS-A (architectural atypia); (iii) AUS-O (predominant oncocytic changes); and (iv) AUS-N/A (both nuclear and architectural atypia). The four sub-categories were correlated with subsequent histological or cytological follow-up data, including core needle biopsy, resection, or repeat FNA. RESULTS: Malignancy was identified in 34 of 94 cases (36.2%). The upper limit estimate for malignancy was 43.6%, and the lower limit estimate was speculated as 9.8%. The malignancy rate was highest in cases within the AUS-N sub-category (65.8%, range 16.6%-78.1%). CONCLUSIONS: The present study suggests that cases in the AUS/FLUS category have a higher risk of malignancy than previously thought. Because of the heterogeneous nature of the AUS/FLUS category, further sub-classification might be more effective in achieving appropriate risk stratification and better clinical management.

Performance of CT in the Preoperative Diagnosis of Cervical Lymph Node Metastasis in Patients with Papillary Thyroid Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Ultrasound has become widely accepted as the first imaging technique used for the assessment of cervical lymph node metastasis in patients with papillary thyroid cancer. In this systematic review and meta-analysis, we evaluate the performance of CT for the preoperative diagnosis of cervical lymph node metastasis in patients with papillary thyroid cancer compared with ultrasound. MATERIALS AND METHODS: Ovid-MEDLINE and EMBASE data bases were searched for studies regarding the use of CT to diagnose cervical lymph node metastasis. The diagnostic performance of CT, ultrasound, and combined CT/ultrasound was assessed by using level-by-level and patient-based analyses. We also performed meta-analyses on the basis of the central and lateral neck levels. RESULTS: Nine eligible studies, including a total sample size of 1691 patients, were included. CT showed a summary sensitivity of 62% (95% CI, 52%-70%) and specificity of 87% (95% CI, 80%-92%) for diagnosing cervical lymph node metastasis when using level-by-level analysis. There was a positive correlation between the sensitivity and the false-positive rate (correlation coefficient, 0.807) because of the threshold effect. The summary sensitivity of combined CT/ultrasound (69%; 95% CI, 61%-77%) was significantly higher than ultrasound (51%; 95% CI, 42%-60%), though the summary specificity did not differ. CONCLUSIONS: The diagnostic performances of CT and ultrasound are similar, though CT and ultrasound combined are superior to ultrasound only. CT may be used as a complementary diagnostic method in addition to ultrasound for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer.

First-Line Use of Core Needle Biopsy for High-Yield Preliminary Diagnosis of Thyroid Nodules.

BACKGROUND AND PURPOSE: Although core needle biopsy was introduced as a diagnostic alternative to fine-needle aspiration, the utility and safety of core needle biopsy for thyroid nodules in a large population has yet to be studied comprehensively. We evaluate core needle biopsy yields on a large-scale basis to investigate its potential in the preliminary diagnosis of thyroid nodules. MATERIALS AND METHODS: Between March 2005 and December 2013, 2448 initially detected thyroid nodules from 2120 consecutive patients who underwent core needle biopsy were retrospectively evaluated. Of these, 72 thyroid nodules from 63 patients were excluded due to prior fine-needle aspiration attempts. The inconclusive and conclusive result rates, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and unnecessary surgery rate of core needle biopsy were evaluated. RESULTS: With core needle biopsy as the first-line method, the inconclusive result rate was 11.9% (283/2376) and the conclusive result rate was 88.1% (2093/2376). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of core needle biopsy for the diagnosis of malignancy were 96.7% (1160/1200), 89.7% (347/387), 100% (813/813), 100% (347/347), and 95.3% (813/853), respectively. There were no major complications and 12 minor complications. CONCLUSIONS: We have demonstrated that first-line use of core needle biopsy may well improve diagnostic accuracy in thyroid nodules, reducing inconclusive or false-negative results and unnecessary operations. Such benefits underscore the promising role of core needle biopsy in managing thyroid nodules and optimizing related surgical decision-making.

Interobserver reproducibility of cervical lymph node measurements at CT in patients with head and neck squamous cell carcinoma.

AIM: To determine the interobserver reproducibility of measuring cervical lymph nodes at computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to investigate the influence of finding extracapsular spread (ECS) at CT on measurement reliability. MATERIALS AND METHODS: The institutional review board approved the study protocol, and informed consent was obtained. A total of 146 patients with 224 suspicious lymph nodes underwent CT before treatment. Two observers independently measured the diameters (minimal axial, maximum axial, and maximum longitudinal diameter) and assessed the ECS using CT. The greatest diameter was defined as the largest among the three measured diameters. Interobserver variability was determined by the within-subject coefficient of variation, and interobserver agreement was determined by the intraclass correlation coefficient (ICC). RESULTS: The within-subject coefficients of variation were 7.8%, 7.6%, and 11.4% for the minimal axial, maximum axial, and greatest diameters, respectively. The ICC values for interobserver agreement were excellent for all diameter measurements (i.e., ICC >0.9). Minimum and maximum axial diameter measurements were statistically more reliable than the greatest diameter measurement (p=0.008 and p=0.0001, respectively). The presence of ECS on CT does not significantly affect the reliability of lymph node diameter measurements (p>0.05). CONCLUSION: Lymph node diameter measurement on CT is a highly reproducible and robust method. Additionally, imaging features of ECS do not affect reliability. Therefore, the measurement of lymph node diameter can be confidently performed in daily clinical practice or clinical trials.

Activation of nuclear PTEN by inhibition of Notch signaling induces G2/M cell cycle arrest in gastric cancer.

Mutation in PTEN has not yet been detected, but its function as a tumor suppressor is inactivated in many cancers. In this study we determined that, activated Notch signaling disables PTEN by phosphorylation and thereby contributes to gastric tumorigenesis. Notch inhibition by small interfering RNA or γ-secretase inhibitor (GSI) induced mitotic arrest and apoptosis in gastric cancer cells. Notch inhibition induced dephosphorylation in the C-terminal domain of PTEN, which led to PTEN nuclear localization. Overexpression of activated Notch1-induced phosphorylation of PTEN and reversed GSI-induced mitotic arrest. Dephosphorylated nuclear PTEN caused prometaphase arrest by interaction with the cyclin B1-CDK1 complex, resulting in their accumulation in the nucleus and subsequent apoptosis. We found a correlation between high expression levels of Notch1 and low survival rates and, similarly, between reduced nuclear PTEN expression and increasing the TNM classification of malignant tumours stages in malignant tissues from gastric cancer patients. The growth of Notch1-depleted gastric tumors was significantly retarded in xenografted mice, and in addition, PTEN deletion restored growth similar to control tumors. We also demonstrated that combination treatment with GSI and chemotherapeutic agents significantly reduced the orthotopically transplanted gastric tumors in mice without noticeable toxicity. Overall, our findings suggest that inhibition of Notch signaling can be employed as a PTEN activator, making it a potential target for gastric cancer therapy.