The tracer mixture of ICG and Sonazoid did not induce an injection-related mucosal reaction.

<p><b>a.</b> Endoscopy revealed that there was no edema of the larynx in procedure 13, 120 minutes after injection of the tracer mixture. <b>b.</b> A low-power view of the H-E stained field revealed no edema or inflammatory cell infiltration in the mucosa of the hypopharynx in procedure 13. <b>c.</b> High-power field views showing a magnified view of the green boxed area in Fig 3b.</p

Sentinel node (SN) on the contrast-enhanced ultrasonography (CEUS) monitor.

<p>The left side of the monitor shows the contrast-enhanced mode and the right side shows the conventional B-mode view. <b>a.</b> View immediately after injection of the tracer mixture. The lymph node is not contrasted on the left side of the monitor. <b>b.</b> 20 minutes after injection of the tracer mixture, the lymph nodes were contrasted by Sonazoid. Note the high echogenicity of the SN due to the presence of contrast agent microbubbles on the left side. CEUS provided a clear image of the SN transcutaneously.</p

A SN was transcutaneously identified by CEUS.

<p>After the incision, the operation was guided by indocyanine green (ICG) fluorescence on the Hyper Eye Medical System (HEMS) monitor in the rabbit experiment. The brilliant white structure in the image is the lymph node that accumulated ICG.</p

Number of LNs identified by CEUS and HEMS.

<p>Operation time was measured from the first incision to extraction of the first lymph nodes that accumulated Sonazoid and ICG. CEUS, contrast-enhanced ultrasonography; HEMS, Hyper Eye Medical System; ICG, indocyanine green; LN, lymph node.</p><p>Number of LNs identified by CEUS and HEMS.</p

Time course of the number of LNs identified transcutaneously by HEMS and CEUS in the rabbit model.

<p>CEUS, contrast-enhanced ultrasonography; HEMS, Hyper Eye Medical System; LN, lymph node.</p><p>Time course of the number of LNs identified transcutaneously by HEMS and CEUS in the rabbit model.</p

Transmission electron microscopy (TEM) images.

<p><b>a.</b> Negative stain of Sonazoid. The particle size of Sonazoid was around 1 to 2 μm. <b>b.</b> Negative stain of the tracer mixture. ICG particles were extremely small compared to Sonazoid. Sonazoid and ICG were mixed well with no separation. <b>c.</b> There were many vacuoles in the macrophages in the rabbit experiment. The vacuoles contained Sonazoid. Almost all the vacuoles in the macrophages contained some small particles, which may have been ICG. The size of the vacuoles was variable. The bold arrow shows the biggest vacuole, which keep the size when injection, and the thin arrow indicates an intermediate-sized vacuole. <b>d.</b> Some of the vacuoles in the lymphocytes from the swine experiment contained ICG. The arrow shows a big vacuole containing ICG. <b>e.</b> There were no vacuoles in the macrophages in the untreated rabbit’s LN. We show this picture as a negative control. The LN was dissected from a rabbit that was not given the tracer.</p

Randomized Phase III Trial of Adjuvant Chemotherapy with S-1 after Curative Treatment in Patients with Squamous-Cell Carcinoma of the Head and Neck (ACTS-HNC)

<div><p>Background</p><p>We conducted a phase III study to evaluate S-1 as compared with UFT as control in patients after curative therapy for stage III, IVA, or IVB squamous-cell carcinoma of the head and neck (SCCHN).</p><p>Patients and Methods</p><p>Patients were randomly assigned to the UFT group (300 or 400 mg day^-1 for 1 year) or the S-1 group (80, 100, or 120 mg day^-1 for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were relapse-free survival, overall survival (OS), and safety.</p><p>Results</p><p>A total of 526 patients were enrolled, and 505 were eligible for analysis. The 3-year DFS rate was 60.0% in the UFT group and 64.1% in the S-1 group (HR, 0.87; 95%CI, 0.66-1.16; p = 0.34). The 3-year OS rate was 75.8% and 82.9%, respectively (HR, 0.64; 95% CI, 0.44-0.94; p = 0.022). Among grade 3 or higher adverse events, the incidences of leukopenia (5.2%), neutropenia (3.6%), thrombocytopenia (2.0%), and mucositis/stomatitis (2.4%) were significantly higher in the S-1 group.</p><p>Conclusions</p><p>Although DFS did not differ significantly between the groups, OS was significantly better in the S-1 group than in the UFT group. S-1 is considered a treatment option after curative therapy for stage III, IVA, IVB SCCHN.</p><p>Trial Registration</p><p><a href="http://ClinicalTrials.gov" target="_blank">ClinicalTrials.gov</a> NCT00336947 <a href="http://clinicaltrials.gov/show/NCT00336947" target="_blank">http://clinicaltrials.gov/show/NCT00336947</a></p></div

Comparison of clinical characteristics between the chemoradiotherapy group and the other therapy group.

<p>Comparison of clinical characteristics between the chemoradiotherapy group and the other therapy group.</p

Cumulative rates of locoregional recurrence (A) and distant metastasis (B).

<p>(A) One patient with secondary cancer before locoregional recurrence was censored. (B) One patient with secondary cancer before distant metastasis was censored.</p

Overall survival in the CRT group.

<p>(A) OS derived from Kaplan–Meier curves. (B) HR and corresponding CI were calculated using Cox proportional hazard model. <i>P</i> values were calculated based on stratified log-rank test. Abbreviations: CI, confidence interval. HR, hazard ratio. OS, overall survival.</p