Ultrasound visualization of the vagus nerve for intraoperative neuromonitoring in thyroid surgery.

OBJECTIVE: Localization of the vagus nerve is required during intraoperative neuromonitoring (IONM) for thyroid surgery in order to electromyographically verify the functional integrity of inferior laryngeal nerve and aim to reduce the risk of postoperative vocal fold paralysis. Classically, the vagus nerve courses within the carotid sheath between the common carotid artery and internal jugular vein, but anatomic variations have been described. Our aim was to compare preoperative ultrasound (US) and intraoperative localization of vagus nerve and to document anatomic variations. PATIENTS AND METHODS: Retrospective study of patients undergoing thyroidectomy. The vagus nerve was identified 2 cm below the inferior border of the cricoid cartilage, on US performed 6 weeks prior to surgery; then, vagus nerve was identified surgically. RESULTS: For 82 patients, on preoperative US, the right vagus nerve was in between, superficial, or deep to the vessels in 94%, 2.4%, and 3.6%, and on the left in 72%, 24.4%, and 3.6%. Intraoperatively, the right vagus was in between, superficial, or deep in 90%, 4%, and 6%, and on the left in 67%, 27%, and 6%. US correlated with surgery on the right in 79/82 (96%) and on the left in 78/82 (95%). CONCLUSIONS: To our knowledge, this is the first study directly comparing US and intraoperative findings. The US and surgical findings were identical in 95% on the left and 96% on the right The vagus nerve was superficial in 27% of cases on the left and 4% on the right. Identifying this anatomic variation preoperatively may facilitate IONM. KEY POINTS: • Localization of the vagus nerve is necessary during thyroid surgery when using neuromonitoring for electromyographic testing of the inferior laryngeal nerve to reduce the risk of postoperative vocal fold paralysis. • The vagus nerve in the neck can be routinely visualized using ultrasound, and is generally in between the common carotid artery and the internal jugular vein. Its location on ultrasound corresponds very closely to that observed in vivo during surgery (95%). • At the level of the thyroid lobe, there is an anatomic variant with the vagus nerve superficial to the common carotid artery which is seen more often on the left than on the right.

Risk staging with prophylactic unilateral central neck dissection in low-risk papillary thyroid carcinoma.

OBJECTIVE: Current guidelines favor thyroid lobectomy for intrathyroidal cT1bT2cN0 papillary thyroid carcinoma. Prophylactic neck dissection (PND) is not recommended for these low-risk tumors due to the lack of high-level evidence on improvement in outcomes, but the information from PND may be used for staging. The aim of this study was to evaluate the rate of upstaging with ipsilateral PND. MATERIALS AND METHODS: Retrospective study of patients with intrathyroidal unifocal cT1bT2cN0 papillary thyroid carcinoma from 2008 to 2021. All patients underwent total thyroidectomy and PND. Tumors were classified as low or intermediate risk based on the information from pathological analysis of the primary tumor and then from adding the analysis of the lymph nodes. The difference between the tumor-only and the PND-added risk staging was evaluated. RESULTS: Three hundred three patients (241 women, median age 45, median tumor size 17 mm) were included. Microscopic extrathyroidal extension was found in 23.4%, aggressive histology in 6.6%, vascular invasion in 29.3%, and lymph node metastases in 37.3%. One hundred ten patients (36.3%) were intermediate-risk based on the primary tumor. An additional 26 (8.6%) were upstaged to intermediate-risk based on the ipsilateral PND and 2% based on the contralateral PND. Kaplan-Meier 10-year event-free survival in tumors upstaged with ipsilateral PND was not statistically different from intermediate-risk tumors based on the primary tumor characteristics (92% versus 90.9%, Log Rank p = 0.943). CONCLUSIONS: Ipsilateral PND upstaged low-risk cT1bT2cN0 patients to intermediate risk in only 8.6% of cases, and contralateral PND in an additional 2%. Routinely performing PND may not be warranted.

Quantitative functional imaging by dynamic contrast enhanced ultrasonography (DCE-US) in GIST patients treated with masatinib.

OBJECTIVES: To determine the quantitative parameters of DCE-US for predicting early functional response of patients with metastatic gastrointestinal stromal tumors (GIST). MATERIALS AND METHODS: Phase II multicentre clinical trial in patients with metastatic GIST treated with masatinib mesylate (7.5 mg/kg daily by oral route) Patients followed using three different imaging techniques: 1) DCE-US before treatment and on days 1, 7, 15 and after 1, 2, 4, 6 months and every 3 months. 2) CT assessments, using RECIST criteria, before treatment, after 2, 4, 6 months and then every 3 months. 3) FDG PET before treatment and after 1 month. RESULTS: Twenty patients included and followed-up for up to 36 months, with 269 DCE-US examinations performed. No significant changes in the 7 selected DCE-US variables on day 1 and 7 vs baseline. On day 15, significant reductions in all the variables related to blood volume recorded: area under the curve (AUC) (p = 0. 004), area under the wash-in (AUWI) (p = 0.002), area under the wash-out (AUWO) (p = 0.002) and Peak Intensity (p = 0.005). Also slope of wash-in changed significantly (p = 0.003). An important reduction in Standard Uptake Values (SUV) recorded in 7/11 patients (PFS >18 months). Decrease in DCE-US AUC, AUWI and AUWO values on day 7 were predictive of PET-CT results. CONCLUSIONS: AUC AUWI, AUWO are the DCE-US parameters related to blood volume that at D 15 can predict the response of GISTs to treatment with masatinib. Additional studies are ongoing.

Preoperative ultrasound mapping of the vagus nerve in thyroid surgery.

BACKGROUND: Intraoperative neuromonitoring (IONM) in thyroid surgery requires electric stimulation of the vagus nerve to verify correct electrode placement. Classically the nerve is found deep to or in-between the common carotid artery and internal jugular vein, but previous studies have shown that the nerve can sometimes be found superficial to the vessels. Our aim was to determine the incidence of a superficial vagus nerve using ultrasound (US) and study possible clinical factors associated with an anteriorly-located vagus nerve. METHODS: Retrospective study of patients undergoing thyroid surgery (lobectomy or total thyroidectomy) with intermittent IONM. Substernal goiters, locally invasive tumors or bulky lymph nodes were excluded. The vagus nerve was identified at the level of the mid-thyroid lobe on each side on preoperative US performed by two specialized radiologists, and its location according to 6 possible positions in relationship to the common carotid artery was recorded. The anatomic variability of the vagus nerve was analyzed in relationship to patient demographics and thyroid pathology. RESULTS: Five-hundred twenty-seven patients were included. The right vagus nerve (n=522) was in-between, superficial or deep to the vessels in 92.3%, 6.1% and 1.5% and of cases, respectively, and the left vagus (n=517) in 80.2%, 18.6% and 1.2% of cases, respectively, with a statistically significant difference between right and left vagus nerves (P<0.001). The type of pathology, size of the dominant nodule or the volume of the thyroid lobe were not correlated to finding a superficial vagus nerve. CONCLUSIONS: The vagus nerve was identified in all cases on US and found to be anterior to common carotid artery at the level of the thyroid lobe in 18.6% of cases on the left and 6.1% of cases on the right. Identifying this anatomic variant preoperatively may facilitate IONM and avoid inadvertent trauma to the vagus nerve during thyroid surgery.

Can preoperative ultrasound predict extrathyroidal extension of differentiated thyroid cancer?

OBJECTIVE: The presence of extrathyroidal extension (ETE) is generally considered as an indication for total thyroidectomy for differentiated thyroid cancer. The accuracy of neck ultrasound for the diagnosis of ETE is controversial. The aim of this study was to assess the diagnostic accuracy of preoperative ultrasound evaluation of ETE. METHODS: The retrospective and observational study of consecutive patients operated between 2016 and 2019 for cytologically suspicious or indeterminate thyroid nodules were analyzed. US images obtained preoperatively were retrospectively reviewed to identify signs of minimal or gross ETE. Histology was considered as the golden standard for diagnosis of ETE. The sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy of US were evaluated. RESULTS: A cohort of 305 patients (75% females, median age 48 years) with 378 nodules (median size 18 mm) was studied. Seventy-five percent of the nodules (n = 228) were malignant on histology and ETE was present in 106 cases (28%): 83 minimal ETE and 23 gross ETE. Suspicion of minimal ETE on preoperative ultrasound was found in 50 (13%) with a sensitivity of 30%, a specificity of 93%, a PPV of 62% and an NPV of 78%, with an accuracy of 76%. Gross ETE on ultrasound was found in 19 (5%) nodules with a sensitivity of 78%, a specificity of 99.7% a PPV of 94.7% an NPV of 98.6% and an accuracy of 98%. CONCLUSIONS: Preoperative US is very specific and accurate in diagnosing gross ETE which impacts the extent of initial surgery for thyroid cancers.

Risk-oriented concept of treatment for intrathyroid papillary thyroid cancer.

Adapting treatment and follow-up according to the risk of recurrence and/or death from thyroid cancer is a relatively recent concept of "personnalized" medicine, developed particularly to avoid overtreatment of low-risk thyroid cancer which represents the majority of thyroid cancers diagnosed in the world today. For low-risk thyroid cancer, this decrease in extent of treatment involves the extent of surgery-total thyroidectomy, lobectomy or no surgery with active surveillance-but also the indications, doses and methods of stimulation when or if administering radioactive iodine (RAI), the indication for suppressive thyroxin therapy and the extent and modalities for follow-up that should be adapted to the risk of recurrence. The aim is to optimize medical resources and quality of life, particularly for low-risk patients whose life expectancy is that of the general population.

F-18-Dopa Positron Emission Tomography/Computed Tomography Is More Sensitive Than Whole-Body Magnetic Resonance Imaging for the Localization of Persistent/Recurrent Disease of Medullary Thyroid Cancer Patients.

Background: Elevated postoperative serum calcitonin (Ctn) level indicates persistent/recurrent disease in patients with medullary thyroid carcinoma (MTC). Its location is a challenge. The aim of our study was to compare the disease detection rates of F-18-Dopa (fluoro dihydroxyphenylalanine) positron emission tomography (PET)/computed tomography (CT), whole-body (WB) magnetic resonance imaging (MRI), F-18-FDG (fluorodeoxyglucose) PET/CT, WB CT scanning, neck ultrasonography, and bone scintigraphy in MTC patients with increased Ctn levels and unknown localization of the source. Methods: We compared the independent reading of each imaging procedure with a reference assessment for structural disease defined by pathology or concordance between two imagings or with subsequent follow-up. The detection rate of each imaging modality was determined in per patient, per organ, and per lesion analysis. Results: Thirty-six consecutive patients (21 females, mean age: 57 years, sporadic MTC in 26 cases, median serum Ctn level: 760 pg/mL; range: 21-10,121) were analyzed. The reference assessment localized disease in 24 (64%) patients with 74 lesions detected in the thyroid bed (8), in neck lymph nodes (15), mediastinal lymph nodes (6), lungs (1), liver (2), bones (3), and other site (1). At the patient level, the detection rates were 64% (CI 0.48-0.80) for F-18-Dopa PET/CT with early acquisitions, 40% (CI 0.24-0.56) for F-18-FDG PET/CT, 40% (CI 0.24-0.56) for WB MRI, and 48% (CI 0.31-0.66) for WB CT scan. Conclusions: In MTC patients with increased Ctn and no known distant metastases, F-18-Dopa PET/CT is more sensitive to detect structural disease than any other imaging modality, including WB MRI.

Benefits of contrast-enhanced sonography for the detection of liver lesions: comparison with histologic findings.

OBJECTIVE: The objective of our study was to compare the usefulness of contrast-enhanced sonography with baseline sonography in detecting malignant liver lesions. SUBJECTS AND METHODS: This prospective study included 116 patients. All patients underwent a preoperative conventional sonography examination followed by sonography after injection of contrast agent combined with the use of perfusion software (vascular recognition imaging or pulse subtraction imaging). Histopathologic analysis was the reference standard used to compare the diagnostic value of baseline sonography versus contrast-enhanced sonography. RESULTS: Eighty-two patients underwent hepatic surgery, 31 did not because of disseminated lesions, and the remaining three patients did not meet inclusion criteria. Three hundred six surgically proven lesions were taken into account for comparison of the two techniques: 147 were detected on baseline sonography and 177 on contrast-enhanced sonography. Histopathologic analysis revealed 233 malignant and 73 benign lesions. Sensitivity and specificity were improved on contrast-enhanced sonography compared with baseline sonography for the detection of malignant lesions: 68.7% versus 58.8% and 67% versus 50.7%, respectively. Contrast-enhanced sonography detected 23 additional malignant lesions that had been seen as lacuna at the portal venous phase and characterized as 19 benign nodules, thus improving the performance of sonography in 13.7% of the cases. CONCLUSION: Contrast injection improved the sensitivity and specificity of baseline sonography and should be performed in routine practice if hepatic surgery is being considered for the management of liver lesions.

Study of Intrapatient Variability and Reproducibility of Quantitative Tumor Perfusion Parameters Evaluated With Dynamic Contrast-Enhanced Ultrasonography.

OBJECTIVES: Dynamic contrast-enhanced (DCE) ultrasonography (US) is a functional imaging technique enabling quantitative assessment of solid tumor perfusion in metastatic patients treated with antiangiogenic therapies.The objective of this prospective single-center study was to evaluate in real-life conditions (in routine clinical practice) the intrapatient variability and reproducibility of DCE-US parameters. MATERIALS AND METHODS: Each patient provided written informed consent and had 2 DCE-US examinations (preprandial and postprandial) at baseline, day 15, and 1 month after treatment initiation. Perfusion curves were recorded after Sonovue injections to determine 7 perfusion parameters. Dynamic contrast-enhanced US examinations were analyzed in pairs: preprandial and postprandial. Log transformed values were used to determine the variability of the pairs (within-subject coefficient of variation) and their reproducibility (Spearman correlation coefficient). RESULTS: We included 60 patients (23 colon cancers, 36 kidney cancers, and 1 breast cancer) treated with axitinib (26 patients), sunitinib (27 patients), and other antiangiogenic treatments (7 patients). The 60 patients included 38 men (63%) and 22 women (37%) with a median age of 62 (range, 25-82 years). Thirty patients had hepatic and 30 had extrahepatic target lesions. Data were analyzed for 128 pairs of DCE-US: 45 (baseline), 45 (day 15), and 38 (1 month). Preprandial and postprandial values were not significantly different. For area under the curve and area under the washout, the correlation coefficient between preprandial and postprandial values was 0.89; the associated within-subject coefficients of variation were 61% and 64%, respectively. However, the range of individual variations (postprandial value/preprandial value) was less than 2 logs for a range of parameter values of about 4 logs. Variability was independent of the metastatic site. CONCLUSIONS: This study showed that area under the curve and area under the washout are the 2 most reproducible DCE-US parameters.

Frequency and intensity of pain related to thyroid nodule fine-needle aspiration cytology.

BACKGROUND: Quality of life is an important issue in endocrine tumors because of the high prevalence of benign tumors and the indolent course of most malignant tumors. OBJECTIVE: To evaluate the frequency and the intensity of pain and anxiety in patients undergoing thyroid nodule fine-needle aspiration cytology (FNAC) and to identify factors associated with pain. METHODS: Single center prospective study in the setting of a one-stop outpatient diagnostic clinic for thyroid nodules. Pain was evaluated using a 100-mm visual analogue scale (VAS) immediately following (VAS1) and 30 minutes after (VAS2) FNAC and was considered significant if ≥ 30. Anxiety symptoms were assessed prior to FNAC using a self-report measure questionnaire: the state form of Spielberger State-Trait Anxiety Inventory (STAI, form Y-A). FNAC was performed with a 25-gauge needle and a moderate aspiration and two passes for each nodule. RESULTS: Two hundred eighteen consecutive patients (163 females, 55 males; mean age 53 years, range 12-84 years) undergoing FNAC of one to three nodules were included. VAS1 was ≥ 30 in 24% of the patients and VAS(2) was ≥ 30 in 13% of the patients. Independent significant factors correlated to a VAS1 of ≥ 30 were age under 25 years and the number of nodules being biopsied. Independent significant factors correlated to a VAS2 of ≥ 30 were VAS1 ≥ 30 and female sex. No correlation was found between pain and nodule size or nodule depth, nor the duration of application of the eutectic mixture of local anesthetics (EMLA) patch prior to FNAC. The mean STAI score for anxiety was 37 ± 12. The average STAI score was significantly higher in women (39) than in men (33; p = 0.01). There was no significant correlation between STAI score and age under 25 years, previous FNAC, number of nodules biopsied, or acetaminophen administration, but the STAI score was significantly correlated to VAS1 and VAS2. CONCLUSIONS: FNAC-related pain is frequent and correlates with the number of nodules biopsied, age under 25 years, female sex, and anxiety.

Dynamic contrast-enhanced ultrasonography (DCE-US) and anti-angiogenic treatments.

Dynamic contrast-enhanced ultrasonography (DCE-US) is a current functional imaging technique enabling a quantitative assessment of tumor perfusion using raw linear data. DCE-US allows calculating several parameters as slope of wash-in or area under the curve representing, respectively, blood flow or blood volume. Decrease of vascularization can easily be detected in responders after 1 or 2 weeks of anti-angiogenic treatment for gastrointestinal stromal tumors (GIST), renal cell carcinoma (RCC), and hepatocellular carcinoma (HCC) and is correlated with progression-free survival and overall survival in RCC or HCC. DCE-US is supported by the French National Cancer Institute (INCa), which is currently studying the technique in metastatic breast cancer, melanoma, colon cancer, gastrointestinal stromal tumors and renal cell carcinoma, as well as in primary hepatocellular carcinoma, to establish the optimal perfusion parameters and timing for quantitative anticancer efficacy assessments. Currently 479 patients are included in 19 centers and the preliminary results on 400 patients with 1096 DCE-US demonstrated that the area under the curve (AUC) quantified at 1 month could be a robust parameter to predict response at 6 months.

Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment.

Dynamic contrast-enhanced ultrasonography (DCE-US) is a new functional technique enabling a quantitative assessment of solid tumor perfusion using raw linear data. DCE-US allows the calculation of parameters as slope of wash-in or area under the curve (AUC) representing, respectively, blood flow or blood volume. Reduction in tumor vascularization can easily be detected in responders after 1 or 2 weeks and is correlated with progression-free survival and overall survival in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). DCE-US is supported by the French National Cancer Institute (INCa), which is currently studying the technique in metastatic breast cancer, melanoma, colon cancer, gastrointestinal stromal tumors and renal cell carcinoma, as well as in primary hepatocellular carcinoma, to establish the optimal perfusion parameters and timing for quantitative anticancer efficacy assessments. Currently 490 patients are included in 20 centers and the preliminary results on 400 patients with 1,096 DCE-US demonstrated that AUC could be a robust parameter to predict response.

[Interest of color Doppler ultrasonography to evaluate a new anti-angiogenic treatment with thalidomide in metastatic renal cell carcinoma]. / Intérêt de l'échographie-Doppler pour évaluer l'efficacité d'un traitement anti-angiogénique par thalidomide dans le cancer du rein métastatique.

PURPOSE: To assess the effectiveness of Doppler Ultrasonography (DUS) in evaluating the anti-angiogenic effect of thalidomide. MATERIALS AND METHODS: [corrected] Forty patients with metastases of cancer of the kidney were included in a phase II therapeutic trial. Twenty eight had tumor targets which could be evaluated by DUS. Before treatment, the volume was studied in 59 tumors and the vascularity in 54 tumors. During treatment, comparative DUS examinations were performed every 6 weeks. RESULTS: Before treatment, the mean tumor volume was 41 cm3, more than 10 vessels were visible in 57% of them. A correlation was noted between the size of the tumors and the degree of vascularity. A stabilisation of tumor volume correlated with a decrease in the number of vessels and an increase in vascularity preceding an increase in tumor volume were also observed. CONCLUSION: DUS is effective in assessing tumour size and vascularity.