Radiomics in predicting mutation status for thyroid cancer: A preliminary study using radiomics features for predicting BRAFV600E mutations in papillary thyroid carcinoma

PURPOSE: To evaluate whether if ultrasonography (US)-based radiomics enables prediction of the presence of BRAFV600E mutations among patients diagnosed as papillary thyroid carcninoma (PTC). METHODS: From December 2015 to May 2017, 527 patients who had been treated surgically for PTC were included (training: 387, validation: 140). All patients had BRAFV600E mutation analysis performed on surgical specimen. Feature extraction was performed using preoperative US images of the 527 patients (mean size of PTC: 16.4mm±7.9, range, 10-85 mm). A Radiomics Score was generated by using the least absolute shrinkage and selection operator (LASSO) regression model. Univariable/multivariable logistic regression analysis was performed to evaluate the factors including Radiomics Score in predicting BRAFV600E mutation. Subgroup analysis including conventional PTC <20-mm (n = 389) was performed (training: 280, validation: 109). RESULTS: Of the 527 patients diagnosed with PTC, 428 (81.2%) were positive and 99 (18.8%) were negative for BRAFV600E mutation. In both total 527 cancers and 389 conventional PTC<20-mm, Radiomics Score was the single factor showing significant association to the presence of BRAFV600E mutation on multivariable analysis (all P<0.05). C-statistics for the validation set in the total cancers and the conventional PTCs<20-mm were lower than that of the training set: 0.629 (95% CI: 0.516-0.742) to 0.718 (95% CI: 0.650-0.786), and 0.567 (95% CI: 0.434-0.699) to 0.729 (95% CI: 0.632-0.826), respectively. CONCLUSION: Radiomics features extracted from US has limited value as a non-invasive biomarker for predicting the presence of BRAFV600E mutation status of PTC regardless of size.ope

Hemodynamic stability during adrenalectomy for pheochromocytoma: A case control study of posterior retroperitoneal vs lateral transperitoneal approaches

Hemodynamic stability is one of the most critical aspects of adrenal surgery for pheochromocytoma. Few articles have evaluated the hemodynamic status of patients undergoing posterior retroperitoneal adrenalectomy (PRA) for pheochromocytoma. The aim of this study is to compare the intraoperative hemodynamic parameters between lateral transperitoneal adrenalectomy (TPA) and PRA in this groups of patients.This report describes a retrospective study of 53 pheochromocytoma patients who underwent endoscopic adrenalectomy via transperitoneal (22 patients) or posterior retroperitoneal (31 patients) approaches from January 2008 to March 2015. Data from these patients were compared to investigate the differences in hemodynamic parameters between the 2 approaches.Clinical parameters at presentation were similar between the 2 groups, except for tumor size, which was larger in the TPA group. The PRA group is associated with reduced operative time, blood loss, and length of hospital stay compared to TPA even after adjusting for the tumor size. There was greater BP fluctuations and higher maximum systolic and diastolic blood pressure (BP) within the TPA group compared to PRA during univariate analysis. This was however not significant after adjusting for tumor size. There was no difference in the intraoperative inotropic support requirement between the 2 groups.PRA is associated with stable intraoperative hemodynamic status, as well as favorable perioperative outcomes compared to TPA in patients with small pheochromocytomas.ope

Integrative analysis of congenital muscular torticollis: from gene expression to clinical significance

BACKGROUND: Congenital muscular torticollis (CMT) is characterized by thickening and/or tightness of the unilateral sternocleidomastoid muscle (SCM), ending up with torticollis. Our aim was to identify differentially expressed genes (DEGs) and novel protein interaction network modules of CMT, and to discover the relationship between gene expressions and clinical severity of CMT. RESULTS: Twenty-eight sternocleidomastoid muscles (SCMs) from 23 subjects with CMT and 5 SCMs without CMT were allocated for microarray, MRI, or immunohistochemical studies. We first identified 269 genes as the DEGs in CMT. Gene ontology enrichment analysis revealed that the main function of the DEGs is for extracellular region part during developmental processes. Five CMT-related protein network modules were identified, which showed that the important pathway is fibrosis related with collagen and elastin fibrillogenesis with an evidence of DNA repair mechanism. Interestingly, the expression levels of the 8 DEGs called CMT signature genes whose mRNA expression was double-confirmed by quantitative real time PCR showed good correlation with the severity of CMT which was measured with the pre-operational MRI images (R2 ranging from 0.82 to 0.21). Moreover, the protein expressions of ELN, ASPN and CHD3 which were identified from the CMT-related protein network modules demonstrated the differential expression between the CMT and normal SCM. CONCLUSIONS: We here provided an integrative analysis of CMT from gene expression to clinical significance, which showed good correlation with clinical severity of CMT. Furthermore, the CMT-related protein network modules were identified, which provided more in-depth understanding of pathophysiology of CMT.ope

Simultaneous Expression of Long Non-Coding RNA FAL1 and Extracellular Matrix Protein 1 Defines Tumour Behaviour in Young Patients with Papillary Thyroid Cancer

We investigated the regulatory mechanism of FAL1 and unravelled the molecular biological features of FAL1 upregulation in papillary thyroid cancer (PTC). Correlation analyses of FAL1 and neighbouring genes adjacent to chromosome 1q21.3 were performed. Focal amplification was performed using data from copy number alterations in The Cancer Genome Atlas (TCGA) database. To identify putative transcriptional factors, PROMO and the Encyclopaedia of DNA Elements (ENCODE) were used. To validate c-JUN and JUND as master transcription factors for FAL1 and ECM1, gene set enrichment analysis was performed according to FAL1 and ECM1 expression. Statistical analyses of the molecular biological features of FAL1- and ECM1-upregulated PTCs were conducted. FAL1 expression significantly correlated with that of neighbouring genes. Focal amplification of chromosome 1q21.3 was observed in ovarian cancer but not in thyroid carcinoma. However, PROMO suggested 53 transcription factors as putative common transcriptional factors for FAL1 and ECM1 simultaneously. Among them, we selected c-JUN and JUND as the best candidates based on ENCODE results. The expression of target genes of JUND simultaneously increased in FAL1- and ECM1-upregulated PTCs, especially in young patients. The molecular biological features represented RAS-driven PTC and simultaneously enriched immune-related gene sets. FAL1 and ECM1 expression frequently increased simultaneously and could be operated by JUND. The simultaneous upregulation might be a potential diagnostic and therapeutic target for RAS-driven PTC.ope

The usefulness and accuracy of sentinel lymph node biopsy using single photon emission computed tomography/computed tomography with 99mTc phytate to detect locoregional lymph node metastases in patients with papillary thyroid carcinoma

PURPOSE: Regional lymph node (LN) metastases are detected in 57-85% of patients with papillary thyroid carcinoma (PTC) and are associated with increased tumor recurrence. However, the management of lymphatic disease in patients with PTC has been ongoing source of debate. We have prospectively assessed the usefulness and accuracy of sentinel LN (SLN) biopsy for the detection of LN metastases in patients with PTC on preoperative imaging using single photon emission computed tomography/computed tomography (SPECT/CT) and 99mTc phytate. METHODS: We prospectively assessed 39 patients with PTC who had risk factors for recurrence or with the necessity of intraoperative LN sampling for suspicious LN metastases on preoperative imaging from August 2010 to March 2011. The patients underwent preoperative lymphoscintigraphy and SPETC/CT and intraoperative SLN biopsy (SLNB). RESULTS: 99mTc lymphoscintigraphy and SPECT/CT localized SLN in 38 patients (97.4%), with the gamma probe identifying 2.15 mean SLNs in the lateral neck of the 39 patients. Skip metastasis was found in one patient, and lateral compartment LN metastasis in 17 (43.5%). The sensitivity, specificity, and accuracy of SLNB for lateral compartment LN metastasis were 88.2%, 100%, and 94.8%, respectively. SLNB was more accurate and useful for lateral than for central compartment LN metastasis. CONCLUSION: SPECT/CT improved SLN detection and anatomical localization compared with lymphoscintigraphy. SLNB in patients with risk factors for recurrence or the necessity of intraoperative LN sampling for suspected LN metastases on preoperative imaging was accurate in detecting LN metastases and may help in deciding whether to perform lateral compartment dissection in patients with PTC.ope

분화 갑상선암 환자에서 수술후 방사성 요오드 치료의 전처치 방법에 대한 비교: 기존의 갑상선 호르몬(LT4/T3) 중단요법 및 재조합 인간 갑상선 자극호르몬(rhTSH)주사법의 효과 및 삶의 질에 미치는 영향에 대한 비교

Dept. of Medicine/박사Purpose: Few reports have examined the use of recombinant human TSH(rhTSH) for ablation of postsurgical thyroid remnants after low dose RI (radioactive iodine) therapy, compared with conventional thyroid hormone withdrawal. The aim of the present study was to explore the effectiveness of each patient preparation method before RI ablation(30mCi) of the remnant thyroid in patients with differentiated thyroid carcinoma(DTC).Methods: This study included three groups of patients, enrolled consecutively. From February 2006 to March 2007, 291 patients were enrolled and randomized, after total thyroidectomy, to a 4-week LT4 withdrawal group(Group, I, n=89), a 2-week T3 withdrawal group(Group II, n=133), and a rhTSH administration group(Group III, n=69). Quality-of-life(QoL) was determined at the time of ablation.Results: Patients in the three groups did not differ significantly in baseline characteristics or TNM staging. In all study groups, serum TSH levels showed very good stimulation(mean, 82.24±18.21 mU/L), without significant between-group differences(p=0.5213). Follow-up examinations performed 12 months after ablation were satisfactory in all study patients, without significant between-preparation differences(p=0.2061). QoL was better preserved in Group III than in Groups I and II(p<0.0001). However, there was no QoL difference at the time of ablation between Groups I and II. Conclusion: Our study indicates that use of rhTSH preserves QoL in patients undergoing RI ablation, and affords an ablation success rate comparable to that seen after thyroid hormone withdrawal. However, ablation preparation using withdrawal of LT3 for 2 weeks did not prevent development of profound hypothyroidism, as also occurred when LT4 alone was withdrawn for 4 weeks.ope

Initial Experience Using Gasless Transaxillary Robotic Thyroidectomy by a Single Su

Purpose : Various endoscopic thyroidectomy procedures have been designed to minimize visible cervical scarring. However, endoscopic thyroidectomy is a technically challenging procedure that is performed by a limited surgeon. Robotic systems aida surgeon in performing minimally invasive head and neck surgery by offering superior visualization and dexterity. This study reports the initial experience of one surgeon with robotic thyroidectomy to assess the technical feasibility and safety of the approach. Methods : One hundred four thyroid cancer patients (97 females, 7 males; mean age of 39.8±8.1 years) underwent robotic thyroidectomy using gasless transaxillary approach between November 2008 and October 2009 in Ajou University Hospital. All the procedures were completed successfully using the da Vinci surgical system without open conversion. Patient characteristics, postoperative clinical results, complications, and pathologic details were assessed. Results : Total thyroidectomy was performed in 25 (24.0%) patients, subtotal thyroidectomy in 13 (12.5%) patients, and unilateral lobectomy in 66 (63.5%) patients. All patients underwent ipsilateral central compartment neck dissection, and two patients underwent selective lymph node (LN) dissection. The mean operation time was 134.5±47.2 min (range 61∼310 min), in which the actual time for the thyroidectomy with lymphadenectomy (console time) was 56.4 min. (range 31∼270). The mean number of LN resected was 3.9 (range 0∼28). There were no serious complications. The mean hospital stay was 2.9±0.9 days (range 2∼7). Conclusion : Robotic thyroidectomy is a feasible, safe, and cosmetically excellent procedure. The application of robotic technology for thyroid surgeries could be an alternative to endoscopic or conventional open thyroidectomy.ope

Long Non-Coding RNA-Based Functional Prediction Reveals Novel Targets in Notch-Upregulated Ovarian Cancer

Notch signaling is a druggable target in high-grade serous ovarian cancers; however, its complexity is not clearly understood. Recent revelations of the biological roles of lncRNAs have led to an increased interest in the oncogenic action of lncRNAs in various cancers. In this study, we performed in silico analyses using The Cancer Genome Atlas data to discover novel Notch-related lncRNAs and validated our transcriptome data via NOTCH1/3 silencing in serous ovarian cancer cells. The expression of novel Notch-related lncRNAs was down-regulated by a Notch inhibitor and was upregulated in high-grade serous ovarian cancers, compared to benign or borderline ovarian tumors. Functionally, Notch-related lncRNAs were tightly linked to Notch-related changes in diverse gene expressions. Notably, genes related to DNA repair and spermatogenesis showed specific correlations with Notch-related lncRNAs. Master transcription factors, including EGR1, CTCF, GABPα, and E2F4 might orchestrate the upregulation of Notch-related lncRNAs, along with the associated genes. The discovery of Notch-related lncRNAs significantly contributes to our understanding of the complex crosstalk of Notch signaling with other oncogenic pathways at the transcriptional level.ope

Association between Obesity and Tumor Size in Patients with Papillary Thyroid Cancer

Purpose: Many observational studies have reported a correlation between obesity and increased risk of thyroid malignancy. However, the relationship of obesity with aggressive features in papillary thyroid cancer (PTC) is controversial. We aimed to investigate whether the clinicopathological features of PTC are associated with obesity. Methods: We reviewed the medical records of 210 PTC patients who were followed up over a period of 10 years and examined body mass index (BMI) and other biochemical and clinicopathological parameters. The relationships between BMI and these parameters were assessed by logistic regression models based on BMI quartile (Q). The mean follow-up duration was 135.6±14.8 (range, 120–151) months. Results: BMI had a strong positive correlation with age (r=0.208; P=0.002) and tumor size (r=0.177; P=0.01). We also found that patients with a higher BMI tended to be older (P=0.011) and have elevated triglyceride concentration (P=0.006), fasting plasma glucose (P<0.001), and thyroid-stimulating hormone (P=0.035). According to pair-wise comparisons of BMI, tumor size was remarkably higher in patients in Q4 (overweight and obese) than in patients in Q2 (normal weight) (P=0.01). In a multivariable-adjusted model, higher BMI was consistently significantly associated with larger tumor size (odds ratio, 1.433; 95% confidence interval, 1.097–2.053; P=0.041). However, there was no significant difference in long-term disease status, such as recurrence, persistent disease, and disease-free status, by BMI (P=0.781). Conclusion: Higher BMI (>26.4 kg/m2) was significantly correlated with larger tumor size, but not long-term disease status, in patients with PTC.ope

Lymph node metastasis-dependent molecular classification in papillary thyroid carcinoma defines aggressive metastatic outgrowth

[No abstract available]ope