Experience with the use of intraoperative continuous nerve monitoring in video-assisted neck surgery and external cervical incisions.

OBJECTIVES: Recurrent laryngeal nerve (RLN) injury is one of the severe complications in thyroid surgery. Therefore, intraoperative nerve monitoring (IONM) has been widely used to identify the RLN and confirm its integrity. Recently, the usefulness of continuous IONM (CIONM) with automatic, periodic stimulation to the vagus nerve during thyroid surgery was reported. This study aimed to report our experience with minimally invasive video-assisted endoscopic endocrine neck surgery (VANS), during which, CIONM was successfully applied for the first time. METHODS: Consecutive patients who underwent thyroid surgery with CIONM, performed in our department using either external neck incision surgery or VANS between July 2017 and June 2019, were retrospectively analyzed. RESULTS: A total of 22 patients who underwent thyroid surgery with neck incision (14 cases; 7 men and 7 women; age, 21-75 years [mean, 52 years]) or VANS (8 cases; 8 women, age, 20-61 years [mean, 41 years]) were enrolled in this study. The addition of CIONM in VANS prolonged the operation's duration by approximately 30 minutes as the endoscopic surgery was technically more difficult. No intra- and postoperative incidence of transient or permanent RLN palsy was observed in any patient, except for three patients who underwent external neck incision surgery in whom combined resection was unavoidable due to tumor invasion of the RLN. CONCLUSION: We reported the first successful application of CIONM during thyroidectomy using VANS. Future clinical trials should clarify the benefits of CIONM when compared to intermittent IONM in VANS. LEVEL OF EVIDENCE: 5.

The Utility of Ultrasonography in the Diagnosis of Cervical Lymph Nodes after Chemoradiotherapy for Head and Neck Squamous Cell Carcinoma.

Background and Objectives: There is evidence or consensus on the use of 18F-2-fluorodeoxyglucose-positron emission tomography with computed tomography (PET-CT) in evaluating the effects of treatment at 12 weeks after chemoradiotherapy for head and neck squamous cell carcinoma with cervical lymph node metastasis. However, the use of imaging to evaluate the effects of treatment within 12 weeks after chemoradiotherapy is controversial. The aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of lymph nodes metastasis after chemoradiotherapy according to the criteria of the "Evaluation of the effects of treatment on metastatic cervical lymph nodes using ultrasonography", which evaluated lymph nodes metastasis based on size change and presence of degeneration. Materials and methods: This prospective study included 34 head and neck squamous cell carcinoma patients with cervical lymph nodes metastasis. Thirty-two patients who completed treatment were analyzed. Ultrasonography was performed at 4 and 8 weeks after chemoradiotherapy and we judged whether a favorable prognosis could be expected or whether additional treatments should be considered. Ultrasonography and PET-CT were performed at 12 weeks after chemoradiotherapy. Neck dissection was performed if residual disease was suspected based on the PET-CT findings. Results: The accuracy and negative predictive value of ultrasonography were 81.3% and 96.3%, respectively. According to the Ultrasonography findings, the size of lymph nodes metastasis after chemoradiotherapy was significantly smaller than those before chemoradiotherapy (p < 0.05). The fluid and blood flow of lymph nodes metastasis showed a significantly reduced at 12 weeks after chemoradiotherapy (p < 0.05, p < 0.05, respectively). The echo density significantly changed from low to high echoic density after chemoradiotherapy (p < 0.05). Conclusions: Ultrasonography was useful for evaluating cervical lymph nodes metastasis after chemoradiotherapy for head and neck squamous cell carcinoma.

Third Epidemiological Analysis of Nasopharyngeal Carcinoma in the Central Region of Japan from 2006 to 2015.

The present study aimed to clarify the incidence and clinical outcomes of nasopharyngeal carcinoma (NPC) in the Chubu region of Japan from 2006 to 2015, compared with previous reports. A retrospective analysis was conducted based on medical records from 40 hospitals located in the Chubu region in the central Japanese main island, with a population of around 22.66 million individuals. This study was designed in line with to two previous clinical studies into NPC conducted in the same area of Japan. We recruited NPC patients diagnosed in hospitals across this area over a 10-year period (2006-2015) using a questionnaire about sex, age, primary site, clinical symptoms, pathology, Union for International Cancer Control (UICC) staging, serological exam, treatment, and survival. A total of 620 NPC patients were identified. The age-standardized incidence of NPC from 2006 to 2015 was 0.27 per 100,000 individuals per year. There were no significant differences between this study and the previous two studies conducted in the same area of Japan. The five-year overall survival rate for all patients was 75.9%, while those for patients with stages I, II, III, and IVA were 97%, 91%, 79%, and 68%, respectively. The age-standardized annual incidence of NPC in the present study was 0.27 per 100,000 individuals per year, which was relatively low and stable. The five-year overall survival rate for all NPC patients was significantly improved in this decade compared with previous studies. The smoking rates in male and female NPC patients were 64.5% and 18.8%, respectively, thereby suggesting the involvement of smoking in the incidence of NPC.

Detection of sentinel lymph node using contrast-enhanced agent, Sonazoid™, and evaluation of its metastasis with superb microvascular imaging in oral and oropharyngeal cancers: a preliminary clinical study.

BACKGROUND: In sentinel lymph node (SLN) biopsy for head and neck cancers, the radioisotope method has been the gold standard. However, this method has several problems, such as unavoidable radiation exposure and requirements of expensive equipment. AIMS/OBJECTIVES: To overcome these problems, we evaluated the contrast-enhanced ultrasonography (CEUS)-guided SLN-detection method, and predicted the SLN metastatic status using novel ultrasound technology, superb microvascular imaging (SMI). METHODS: Ten patients (6 with oral and 4 with oropharyngeal cancers) without neck lymph node metastasis were enrolled in this study. Ultrasound contrast agent, Sonazoid™, was infiltrated into the mucosa at the primary site to observe the lymphatic ducts and SLNs in the neck field. The detected SLNs were examined for blood flow using SMI to categorize the SLNs metastases-positive or negative. RESULTS: SLNs were successfully detected in 8 out of 10 cases. In 7 out of the 8 cases, in whom SLNs were successfully detected, the metastatic status of SLNs was correctly diagnosed with SMI. CONCLUSIONS AND SIGNIFICANCE: Although more clinical data are needed based on a larger cohort, establishing the CEUS-guided SLN-detection and criteria for the accurate diagnosis of SLN-metastases using SMI would be valuable as an alternative to radioisotope method, in oral and oropharyngeal cancers.

Diagnostic Performance of Adaptive 4D Volume Perfusion CT for Detecting Metastatic Cervical Lymph Nodes in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: The purpose of this study was to investigate the diagnostic performance of adaptive 4D volume perfusion CT covering the entire neck for detecting metastatic nodes in patients with head and neck squamous cell carcinoma. SUBJECTS AND METHODS: Thirty patients with histologically confirmed disease were enrolled. The relation between perfusion parameters and nodal size was analyzed, and perfusion parameters were compared between metastatic and benign nodes. The diagnostic capability for detecting metastatic nodes was evaluated. RESULTS: Significant inverse correlations with nodal size were found for blood flow (r = -0.40, p = 0.002), blood volume (r = -0.32, p = 0.02), and permeability surface product (r = -0.27, p = 0.04) of the metastatic nodes. All three parameters had significantly higher values in association with nodal maximum diameter < 10 mm compared with diameter ≥ 10 mm (blood flow, p = 0.004; blood volume, p = 0.01; permeability surface product, p = 0.02). Among the nodes with maximum diameter < 10 mm, blood flow of the metastatic nodes was significantly higher than that of the benign nodes (p = 0.02), whereas among the nodes ≥ 10 mm in diameter, the mean transit time of the metastatic nodes was significantly lower than that of the benign nodes (p = 0.04). In multivariate analysis, blood flow in nodes with maximum diameter < 10 mm had a significant association with the detection of metastatic nodes. The sensitivity and specificity of blood flow for differentiating metastatic from benign nodes were 73.3% and 70.8%. CONCLUSION: Findings from 4D volume perfusion CT covering the entire neck may be informative for characterization of cervical nodes. It is worthwhile to include the examination in nodal staging of head and neck squamous cell carcinoma.

Examination of Selective Low-pressure Fine Needle Aspiration Cytology Under Ultrasound Guidance.

Cytology by fine-needle cytology is indispensable for diagnosing head and neck tumor, especially for thyroid nodule. There are two methods of fine needle cytology; one of fine-needle aspiration cytology (FNAC and another of fine-needle non-aspiration cytology (FNNAC). These previous procedures has each disadvantage such as the mixing of blood or low yield of cells. We proposed a new technique: selective low-pressure fine needle aspiration cytology (SLOP-FNAC) to overcome the backwards of previous procedures. We used the scoring system by Mair et al. to evaluate smear quality of specimens obtained with FNNAC and SLOP-FNAC. SLOP-FNAC smears exhibited higher scores in amount of cellular material, degree of cellular degeneration and cell yield, and retention of appropriate architecture compared to FNNAC smears. The SLOP-FNAC smears scored significantly higher for amount of cellular material and retention of appropriate architecture evaluated (P = 0.0261 and P = 0.0024, Student's t-test). SLOP-FNAC may be a useful cell sampling technique that reduces blood contamination while securing a high cell yield with maintaining tissue structure.

The role of changes in maximum standardized uptake value of FDG PET-CT for post-treatment surveillance in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy: preliminary findings.

OBJECTIVE: No clear consensus exists regarding the optimal interval and frequency of follow-up positron emission tomography (PET)-CT in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemoradiotherapy (CRT). Here, we sought to clarify whether the changes in the maximum standardized uptake value (ΔSUVmax) may be a valid parameter to help decision-making for surveillance management after CRT. METHODS: 40 patients underwent PET-CT at pre-treatment and 3 months after CRT. Patients were followed by sequential PET-CT for 2 years after CRT. The ΔSUVmax of the primary tumour and the metastatic nodes were calculated between pre-treatment and 3 months after the CRT, and we evaluated the associations between ΔSUVmax and the manifestation of recurrence, time to recurrence and the patient survival. RESULTS: The ΔSUVmax of the primary tumour was significantly lower for the lesions with recurrence than that for those with non-recurrence for both the primary site and the nodal site (p = 0.007, 0.02). A significant correlation was found between the time to recurrence and the ΔSUVmax of the primary tumour (r = 0.63, p < 0.05). The threshold ΔSUVmax of the primary tumour of 1.04 revealed 76.9% sensitivity and 86.4% specificity for distinguishing recurrence from non-recurrence. The progression-free survival and overall survival of the two patient groups divided by the ΔSUVmax of the primary tumour at 1.04 showed a significant difference (p = 0.003, 0.02). The ΔSUVmax of the metastatic nodes did not show a significant association with recurrence or patient survival. CONCLUSION: The ΔSUVmax of the primary tumour showed a significant association with recurrence and patient survival. Advances in knowledge: The ΔSUVmax of the primary tumour may be a valid clinical parameter to help decision-making for the surveillance management of patients with HNSCC after CRT.

Lesion regression rate based on RECIST: prediction of treatment outcome in patients with head and neck cancer treated with chemoradiotherapy compared with FDG PET-CT.

The aim of this study was to evaluate whether the lesion regression rate (ΔLR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria could be used for the prediction of treatment outcome in head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiotherapy (CRT) compared with FDG PET-CT. A total of 33 patients underwent MRI and PET-CT at pretreatment and at 8 weeks after CRT. We assessed the treatment outcome by analyzing the following parameters: the RECIST criteria, ΔLR, the European Organization for Research and Treatment of Cancer (EORTC) criteria, and pretreatment SUVmax of the primary tumor and node. The correlation between the analysis of the parameters and the results of the long-term follow-up of the patients was determined. The RECIST did not significantly correlate with locoregional control (LRC) or survival. The ΔLR was significantly lower for the lesions with locoregional failure (LRF) than for those with LRC. A threshold ΔLR of 48% revealed a sensitivity of 72.7% and specificity of 77.3% for the prediction of LRF. Progression-free survival (PFS) of patients with ΔLR ≥ 48% was significantly better than that of patients with ΔLR < 48% (P = 0.001), but not overall survival. There was a significant correlation between LRC and the EORTC (P = 0.02). The patients who achieved a complete response by the EORTC criteria showed significantly better PFS and overall survival (P = 0.01 and 0.04, respectively). The ΔLR was inferior to FDG PET-CT with respect to the prediction of patient survival; however, it may be useful for selecting patients in need of more aggressive monitoring after CRT.

Thyroid adenomatous nodule with bizarre nuclei: a case report and mutation analysis of the p53 gene.

We present a rare case of adenomatous nodule with bizarre nuclei. The patient was incidentally found to have a nodule in the left lobe of the thyroid gland by ultrasonographic examination. Papillary thyroid carcinoma was suspected by fine needle aspiration cytology, and hemithyroidectomy was performed. The demarcated 1.5-cm nodule had a multinodular appearance with various features, including micro- and macrofollicular components, cystic degeneration, a hyalinized area, and a papillary structure. Hyperchromatic bizarre nuclei with cytoplasmic inclusions were restrictively observed in the microfollicular area. The bizarre nuclei demonstrated diffuse p53 protein immmunoreactivity, but no mutation in exons 5-9 of the p53 gene was detected. The bizarre nuclei were reactive for anti-5-methyl-2'-deoxycytidine antibody, indicating the enclosure of presumably inactive methylated DNA. The intranuclear cytoplasmic inclusions (ICIs) were proven to contain vimentin and beta-catenin by immunohistochemistry. In this case, a degenerative process is involved in the formation of bizarre nuclei because of the compression by surrounding micronodules, unidentifiable mitotic figures, and a quite low proliferative activity. This case suggests that bizarre nuclei and ICIs, which might be identical to those of papillary carcinomas, can be seen in benign thyroid lesions, and overdiagnosis should be avoided regardless of immunohistochemical overexpression of p53.

A phase I study of concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma.

OBJECTIVE: Chemoradiation based on S-1, a novel oral antitumor agent of fluorinated pyrimidines, is the treatment for T2N0 glottic carcinoma; however, the optimal scheduling and dosing have still not been established. A phase I study was conducted to determine the maximum tolerated dose of S-1 with radiotherapy of 2 Gy/day for 5 days a week to a total dose of 60 Gy. Endpoints of this study were to examine the toxicity profile of this regimen and to determine the recommended dose of S-1. METHODS: Concomitant administration with the above-mentioned radiotherapy of S-1 once a day for 2 weeks, beginning on the day therapy was started, followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60 mg/body (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day (level 3). RESULTS: Twenty-one patients were valid for safety. Eighteen patients were enrolled in the dose-escalation phase. In all patients, S-1 was administered. The maximum tolerated dose was determined to be 100 mg/body/day and the dose-limiting toxicity was indicated by the onset of grade 3 chemoradiation dermatitis. Therefore, the determined recommended dose of S-1 was 80 mg/body/day. Objective response according to Response Evaluation Criteria in Solid Tumors were observed in 20 of 21 patients who had measurable disease (95.2%). CONCLUSION: Concurrent S-1 and radiotherapy was feasible and well tolerated, and was suggested to produce a worthwhile response in T2N0 glottic carcinoma. These results warrant further investigation, and a phase II has already been started.