Precise Detection of Gene Mutations in Fine-Needle Aspiration Specimens of the Papillary Thyroid Microcarcinoma Using Next-Generation Sequencing.

PURPOSE: To assess the feasibility of next-generation sequencing (NGS) to detect mutations in BRAF, RAS, TERT promoter, and TP53 genes in ultrasound-guided fine-needle aspiration (FNA) biopsy samples of the papillary thyroid microcarcinoma (PTMC). METHODS: A total of 135 FNA samples out of 135 patients with suspected PTMC were submitted for mutation testing using NGS. NGS was successfully performed in 114 specimens, while the remaining 21 samples were excluded due to insufficient amount/poor quality of DNA and sequencing failure. Of those 114 samples, 72 who were confirmed as having PTMC by postoperative histopathology were enrolled in our study, and the other 42 who had a follow-up with ultrasound were excluded. Mutations of genes including BRAF, NRAS, HRAS, KRAS, TERT promoter, and TP53 were evaluated using NGS. The associations of gene mutations and clinicopathological characteristics of PTMC were analyzed. RESULTS: BRAF mutation was observed in 59 (81.94%) of 72 specimens. This mutation detected in BRAF was p.V600E (c.1799T>A) in exon 15 of all 59 specimens. NRAS mutation was identified in 1 (1.39%) specimen classified as Bethesda III and pathologically confirmed as a follicular variant PTMC. There were no mutations found in TERT promoter or TP53. The tumor with a maximum diameter (D max) larger than 5 mm was shown to be significantly correlated with the BRAF mutation in a multivariate analysis (OR 5.52, 95% CI 1.51-26.42, P = 0.033). But the BRAF mutation was not found to be significantly associated with the gender or age of patients with PTMC (P > 0.05). CONCLUSIONS: This study demonstrated that gene mutations in FNA specimens of PTMC could be successfully analyzed with a higher sensitivity using NGS compared to conventional methods for mutation detection. BRAF mutation of p.V600E was statistically associated with PTMC with a D max larger than 5 mm.

The value and limitations of contrast-enhanced transrectal ultrasonography for the detection of prostate cancer.

OBJECTIVES: To evaluate the role of contrast-enhanced transrectal ultrasonography (CE-TRUS) for detecting prostate carcinoma. METHODS: Sixty-five patients with elevated serum prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE) were assessed using transrectal ultrasound (TRUS) and CE-TRUS. In all the patients, CE-TRUS was performed with intravenous injection of contrast agent (SonoVue, 2.4 ml) before biopsy. The cancer detection rates of the two techniques were compared. False-positive and false-negative findings related to CE-TRUS were analyzed in comparison to the pathological results of biopsy or radical prostatectomy. The targeted biopsy to abnormal CE-TRUS areas was also compared to systematic biopsy. RESULTS: Prostate cancer was detected in 29 of the 65 patients. CE-TRUS showed rapid focal enhancement or asymmetric vessels of peripheral zones in 28 patients; 23 of them had prostate cancer. CE-TRUS had 79.3% sensitivity, compared to 65.5% of TRUS (P<0.05). There were five false-positive and six false-negative findings from CE-TRUS. Benign prostate hyperplasia, and acute and chronic prostatitis were important causes related to the false-positive results of CE-TRUS. Prostate cancer originating from the transition zone or peripheral zone with lower PSA levels, small-size foci, and moderately or well-differentiated tumor was missed by CE-TRUS. The cancer detection rate of targeted biopsy (75%, 33/44 cores) was significantly higher than one of systematic biopsy (48.2%, 162/336) in those 28 cases (P<0.05). In addition, no significant correlation was found between the cancer detection rate with CE-TRUS and serum PSA levels. CONCLUSION: CE-TRUS may improve the detection rate of prostate cancer through targeted biopsy of contrast-enhanced abnormalities. Our findings indicate that systematic biopsies should not be eliminated on the basis of false-positive and false-negative findings related to CE-TRUS.

Use of preoperative ultrasound in designing the true pectoralis major myocutaneous island flap.

BACKGROUND: Traditional techniques used for harvesting the pectoralis major myocutaneous (PMMC) flap have accompanying disadvantages, such as the necessity for an upper chest skin incision, the bulkiness of myocutaneous tissue at the pedicle of the flap, and the risk of total or partial necrosis of flap tissue. The aim of this study was to develop a safe and fast method for preparing PMMC island flaps using preoperative ultrasonography for vessel detection. METHODS: Forty-one PMMC island flaps were used for one-stage reconstruction of head and neck defects, including 21 cases in the treatment group and 20 cases in the control group. In the treatment group, ultrasonography was used to mark out the course of the thoracic branches of the thoracoacromial artery and the lower end of this artery perforating from the fascia into the muscles, as well as the largest perforating branch of the fourth or fifth internal mammary artery entering the PMMC flap. A line, from the lower end of the thoracic branch to the largest perforating branch of the fourth or fifth internal mammary artery, was drawn to determine the axis of the PMMC flap. In the control group, PMMC island flaps were designed according to conventional methods without using ultrasonography. RESULTS: According to the ultrasonic marks, the distance from lower end of thoracic branch to the midpoint of the margin of the inferior clavicular was (5.1 ± 1.2) cm. The time from designing to transferring the island flap was significantly shorter in the treatment group ((51.0 ± 10.5) minutes) compared with the control group ((78.0 ± 13.9) minutes, P < 0.01). The rate of partial necrosis was 4.7% (1/21) in the treatment group and 35.0% (7/20) in the control group. There was one case of flap failure in the control group due to vascular injury during vascular pedicle dissection. CONCLUSION: Preoperative vessel detection by ultrasonography facilitates easy and safe harvesting of the true PMMC island flap.

Sonographic assessment of hypopharyngeal carcinoma: preliminary study.

OBJECTIVES: This study investigated the ability of sonography for diagnosis of hypopharyngeal carcinoma. METHODS: Between November 2008 and January 2010, 34 consecutive patients with hypopharyngeal carcinoma (34 tumors) were examined by sonography. The visualization capability of sonography was evaluated by grading criteria of "excellent," "good," "moderate," and "poor" in comparison with computed tomography (CT). Localization of the primary tumor foci and intrahypopharyngeal and extrahypopharyngeal invasion were initially assessed by sonography and confirmed with surgical and pathologic findings. Laryngeal movement was observed on real-time sonography and compared with endoscopic findings. RESULTS: On sonography, 29 of the 34 lesions (85.3%) were graded excellent, similar to the shapes and dimensions of the tumors on CT. Localization was correctly undertaken in 26 of the 28 foci resected (92.9%), with excellent agreement between sonography and surgical and pathologic findings (κ = 0.823; P < .001). In evaluating intrahypopharyngeal and extrahypopharyngeal invasion with sonography, the sensitivity and specificity were 90.9% and 82.4%, respectively, for intrahypopharyngeal intersubsite spreading, 50.0% and 96.2% for diagnosis of thyroid cartilage destruction, both 100% for evaluation of cervical esophagus, neck soft tissue, and thyroid gland involvement, and 76.9% and 100% for assessment of hemilarynx fixation. CONCLUSIONS: Sonography has a similar role in visualization of hypopharyngeal carcinoma as CT and is satisfactory in localization of the primary focus and assessment of tumor extension inside and outside the hypopharynx.