Published papers

Background: Neuroendocrine carcinoma (NEC) arising from the esophagus (EsoNEC) is extreme rare, accounting for approximately 1% of esophageal cancer. Even for localized NEC, multidisciplinary approach including chemotherapy is recommended in treatment guidelines because of its high rates of systemic recurrence. However, it is controversial whether adding surgery or radiotherapy is appropriate local treatment for EsoNEC. There have been few reports regarding the clinical outcomes of definitive chemoradiotherapy (dCRT) for EsoNEC. The purpose of this study was to clarify the survival outcome of patients with locally advanced EsoNEC treated with dCRT. Methods: Clinical outcomes, feasibility, and prognostic factors of patients with locally advanced EsoNEC treated with radiotherapy (60 Gy/30 fraction) in combination with platinum plus etoposide (CE-RT) or cisplatin plus 5-fluorouracil (CF-RT) at the National Cancer Center Hospital from 2001 to 2017 were retrospectively analyzed. Results: A total of 22 patients were identified as the subjects of this study. The overall response rate and clinical complete remission rate in all patients were 86.4% and 77.3%, respectively. The median progression-free survival and median survival time in all patients were 12.7 and 37.5 months, associated with a 5-year survival rate of 45.4%. Patients treated with CE-RT experienced more hematological adverse events, especially in neutropenia (≥grade 3) and febrile neutropenia(≥grade 3), but achieved more long-term progression-free survival than with CF-RT. Conclusions: Definitive chemoradiotherapy can be considered as an important treatment option for locally advanced esophageal neuroendocrine carcinoma.

Chemosensitivity to cisplatin derivatives varies among individual patients with intractable malignancies including ovarian cancer, while how to unlock the resistance remain unknown. Ovarian cancer tissues were collected the debulking surgery in discovery- (n = 135) and validation- (n = 47) cohorts, to be analyzed with high-throughput automated immunohistochemistry which identified cystathionine γ-lyase (CSE) as an independent marker distinguishing non-responders from responders to post-operative platinum-based chemotherapy. We aimed to identify CSE-derived metabolites responsible for chemoresistant mechanisms: gold-nanoparticle (AuN)-based surface-enhanced Raman spectroscopy (SERS) was used to enhance electromagnetic fields which enabled to visualize multiple sulfur-containing metabolites through detecting scattering light from Au–S vibration two-dimensionally. Clear cell carcinoma (CCC) who turned out less sensitive to cisplatin than serous adenocarcinoma was classified into two groups by the intensities of SERS intensities at 480 cm ; patients with greater intensities displayed the shorter overall survival after the debulking surgery. The SERS signals were eliminated by topically applied monobromobimane that breaks sulfane-sulfur bonds of polysulfides to result in formation of sulfodibimane which was detected at 580 cm , manifesting the presence of polysulfides in cancer tissues. CCC-derived cancer cell lines in culture were resistant against cisplatin, but treatment with ambroxol, an expectorant degrading polysulfides, renders the cells CDDP-susceptible. Co-administration of ambroxol with cisplatin significantly suppressed growth of cancer xenografts in nude mice. Furthermore, polysulfides, but neither glutathione nor hypotaurine, attenuated cisplatin-induced disturbance of DNA supercoiling. Polysulfide detection by on-tissue SERS thus enables to predict prognosis of cisplatin-based chemotherapy. The current findings suggest polysulfide degradation as a stratagem unlocking cisplatin chemoresistance. −1 −1

Purpose: There is insufficient data to verify whether participation in clinical trials in itself can lead to better clinical outcomes. We have analyzed the characteristics and outcomes of patients who declined to participate in a randomized trial in comparison with those who participated in the trial. Patients and Methods: A randomized trial for naive advanced gastric cancer was offered to 286 patients. The trial investigated the superiority of irinotecan plus cisplatin and the noninferiority of S-1 compared with continuous fluorouracil infusion. We retrospectively reviewed the characteristics and outcomes for both participants and nonparticipants in this trial. Results: Of the 286 patients, 98 (34%) declined to participate in the trial. The rate of declining was significantly higher amongyounger patients (P = .003), and it varied significantly between attending physicians (range, 23% to 58%; P = .004). There were no other significant correlations between rate of declining and patient characteristics. No significant differences were observed in the clinical outcomes between the participants and nonparticipants, for whom the median survival times were 367 versus 347 days, respectively. The hazard ratio for overall survival, adjusted for other confounding variables, was 1.21 (95% CI, 0.91 to 1.60). No interaction was observed between participation and the various regimens. Conclusion: There was no difference in clinical outcomes between participants and nonparticipants. However, the patient's age and the doctor-patient relationship may have an effect on patient accrual to randomized trials. Copyright © 2011 by American Society of Clinical Oncology.

Objective: FOLFIRI is a standard chemotherapy regimen for the treatment of metastatic colorectal cancer. Although some studies have shown its efficacy in combination with bevacizumab as first-line chemotherapy, there are no data to support FOLFIRI plus bevacizumab as second-line chemotherapy in patients with this form of cancer. The aim of this study was to evaluate the efficacy and safety of FOLFIRI and bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer. Methods: Eligible patients were ≥20 years old, previously treated (except with irinotecan [CPT-11] and bevacizumab), with an Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and adequate organ function. Twenty-five eligible patients received FOLFIRI with bevacizumab at a dose of 10 mg/kg given intravenously on day 1. All therapy was administered every 2 weeks until disease progression. The primary endpoint was the response rate. Results: Twenty-five patients were enrolled between February 2008 and March 2009. The median age was 62 (range 38-73) years, the male/female distribution was 20/5, 16 patients had performance status 0 and 9 had performance status 1, and the proportion of patients who were oxaliplatin pretreated/untreated was 16/9. The overall response rate was 32% (90% confidence interval [CI]: 17.0-50.4%), with 8 patients showing partial responses, 15 with stable disease, and 2 with disease progression. Median progression-free survival was 11.6 months (95% CI: 6.9-16.4). Median overall survival was 21.4 months (95% CI: 12.0-30.8). The grade 3/4 adverse events with treatment were neutropenia (64%), leukopenia (16%), diarrhea (8%), anorexia (8%), and febrile neutropenia (8%). The bevacizumab-related grade 3/4 adverse event was hypertension, which was observed in 12% of patients. Conclusions: The FOLFIRI plus bevacizumab regimen is an active, well-tolerated second-line chemotherapy treatment for patients with metastatic colorectal cancer. © 2011 Japan Society of Clinical Oncology.

We recently demonstrated that overexpression of the nucleolar GTP-binding protein nucleostemin drives the fraction of genetically-defined tumor cells that exhibit markers and tumorigenic properties of tumor initiating cells. More specifically, cells that constitutively express elevated levels of nucleostemin exhibit increased TWIST expression; expression of genes that induced pluripotent stem cells; enhanced radioresistance; tumor formation, even when small numbers of cells are implanted; and an increased propensity to metastasize. An immunohistochemical analysis of cancer stem cell markers, such as nucleostemin and TWIST has not been conducted in surgically-resected esophageal squamous cell carcinomas after neoadjuvant chemotherapy. In the present study, we examined the expression of CD133, CD44, nucleostemin, guanine nucleotide-binding protein-like 3-like, and TWIST by immunohistochemistry in a series of 54 surgically-resected specimens of esophageal squamous cell carcinomas after neoadjuvant chemotherapy. We identified that high nucleostemin proportion, TWIST intensity, and advanced pathological N stage were significantly correlated with poor relapse-free survival. Together, these observations imply nucleostemin and TWIST as the predictive markers for postoperative recurrence. © 2011 Japanese Cancer Association.

Summary: Currently, no prospective data exists to support a stop-and-go modified FOLFOX6 regimen with bevacizumab in metastatic colorectal cancer (mCRC) patients. This study aimed to evaluate the efficacy and safety of this regimen in first-line mCRC patients. Eligible patients (age ≥20 years) had previously untreated mCRC; Eastern Cooperative Oncology Group performance status of 0-2; and adequate hematologic, hepatic, and renal function. The modified FOLFOX6 regimen and bevacizumab (5 mg/kg) was administered intravenously every 2 weeks. After 8 cycles, patients received maintenance therapy with simplified LV5FU2 and bevacizumab until completion of 8 cycles or disease progression. After maintenance therapy, patients received another 8 cycles of modified FOLFOX6 with bevacizumab until completion of 8 cycles or disease progression. We recruited 50 patients between August 2007 and January 2009. The overall response rate was 48% (80% confidence interval [CI]; 38.2-58) with outcomes as follows: complete response, n=1; partial response, n=23; stable disease, n=21; progression, n=1; and not evaluated, n=4. Median time to treatment failure was 7.7 months (80% CI: 6.2-8.0), and median progression-free survival was 12.8 months (80% CI: 10.8-14). Grade 3/4 toxicities included neutropenia (40%), nausea (4%), diarrhea (14%), thrombosis (4%), and hypertension (4%) et al. Grade 1, 2, or 3 peripheral neuropathy was reported in 38%, 40%, and 10% of patients, respectively. The stop-and-go modified FOLFOX6 and bevacizumab regimen is effective and well tolerated as first-line chemotherapy for mCRC patients. © 2011 Springer Science+Business Media, LLC.

Th17 cytokines IL-17A and IL-17F play a critical role in the activation and recruitment of neutrophils at airway inflammation mainly through the induction of CXC chemokines in the lungs. Vascular endothelial cells belong to the category of major CXC chemokine-producing cells. However, until now, the precise role of Th17 cytokines in CXC chemokine secretion in lung microvascular endothelial cells (LMVECs) has not been fully elucidated. In this study, we examined the biological effects of Th17 cytokines IL-17A and IL-17F on CXCL1, CXCL5, and CXCL8 release in LMVECs. Both IL-17 receptor A (IL-17RA) and IL-17RC are expressed on the surface of LMVECs. In contrast to IL-17F, IL-17A significantly upregulated CXCL1 mRNA expression and protein release, whereas both IL-17A and IL-17F did not have the ability to induce CXCL5 and CXCL8 secretion in LMVECs. IL-17A and IL-17F displayed positive regulatory effects on IL-1β- induced CXCL1, CXCL5, and CXCL8 secretion. On the other hand, IL-17A enhanced the upregulating effect of TNF-α on CXCL1, CXCL5, and CXCL8 release, whereas IL-17F had a negative regulatory effect on TNF-α-mediated secretion. Th2 cytokines IL-4 and IL-13 showed an inhibitory effect on IL-1β plus IL-17A-induced CXCL1, CXCL5, and CXCL8 secretion, but displayed a positive regulatory effect on TNF-α plus IL-17A-induced secretion. These results provide evidence that Th17 cytokines IL-17A and IL-17F have a distinct regulatory role in CXCL1, CXCL5, and CXCL8 expression in LMVECs stimulated either with IL-1β or with TNF-α. Our findings also suggest that CXC chemokine secretion in LMVECs may be complicatedly regulated by Th17 cytokines, Th2 cytokines, and macrophage-associated cytokines in pathological conditions such as bronchial asthma. © 2011 Springer Science+Business Media, LLC.

Background: Although bevacizumab-related hypertension has been reported as a predictive marker of therapy efficacy, an association between proteinuria and efficacy has not been reported. Patients and Methods: Eighty-two consecutive patients with metastatic colorectal cancer treated with bevacizumab as first-line treatment between July 2007 and April 2009 were examined. Results: Seventy-one patients were included in the analysis set. Proteinuria occurred in 29 patients: Grade 1 in 15 patients and grade 2 in 14 patients; no grade 3 or higher proteinuria was observed. The response rate did not increase with the severity of proteinuria (p=0.307). The median progressionfree survival was 17.8 months in cases with grade 2 proteinuria, 16.0 months in those with grade 1 proteinuria, and 10.4 months in those with grade 0 proteinuria (p=0.030). In multivariate analysis with a time-dependent adjustment, there was no correlation between severity of proteinuria and survival. Conclusion: Bevacizumab-related proteinuria was not a predictive marker for patients with colorectal cancer treated with first-line bevacizumab.

Objectives: In Japan, an annual health check-up and health promotion guidance programme was established in 2008 in accordance with the Act on Assurance of Medical Care for the Elderly. A self-reported questionnaire on medication use is a required item in this programme and has been used widely, but its validity has not been assessed. The aim of this study was to evaluate the validity of this questionnaire by comparing self-reported usage to pharmacy insurance claims. Setting: This is a population-based validation study. Self-reported medication use for hypertension, diabetes and dyslipidaemia is the evaluated measurement. Data on pharmacy insurance claims are used as a reference standard. Participants: Participants were 54 712 beneficiaries of the National Health Insurance of Chiba City. Primary and secondary outcome measures: Sensitivity, specificity and κ statistics of the self-reported medication-use questionnaire for predicting actual prescriptions during 1 month (that of the checkup) and 3 months (that of the check-up and the previous 2 months) were calculated. Results: Sensitivity and specificity scores of questionnaire data for predicting insurance claims covering 3 months were, respectively, 92.4% (95% CI 91.9 to 92.8) and 86.4% (95% CI 86.0 to 86.7) for hypertension, 82.6% (95% CI 81.1 to 84.0) and 98.5% (95% CI 98.4 to 98.6) for diabetes, and 86.2% (95% CI 85.5 to 86.8) and 91.0% (95% CI 90.8 to 91.3) for dyslipidaemia. Corresponding κ statistics were 70.9% (95% CI 70.1 to 71.7), 77.1% (95% CI 76.2 to 77.9) and 69.8% (95% CI 68.9 to 70.6). The specificity was significantly higher for questionnaire data covering 3 months compared with data covering 1 month for all 3 conditions. Conclusions: Self-reported questionnaire data on medication use had sufficiently high validity for further analyses. Item responses showed close agreement with actual prescriptions, particularly those covering 3 months.

Introduction: Kawasaki disease (KD) is an acute, selflimited vasculitis of unknown aetiology that predominantly affects infants and young children. We hypothesise that cyclosporin A (CsA) may be effective in treating KD by regulating the Ca2+/NFAT signalling pathway. This trial compares the current standard therapy of intravenous immunoglobulin (IVIG) and the combined IVIG+CsA therapy in paediatric patients with severe KD. Methods and analysis: This trial is a phase III, multicentre, randomised, open-label, blinded-end point trial that evaluates the efficacy and safety of IVIG+CsA therapy. Patients with severe KD who satisfy the eligibility criteria are randomised (1:1) to receive either CsA (5 mg/kg/day for 5 days; Neoral) plus high-dose IVIG (2 g/kg for 24 h and aspirin 30 mg/kg/day), or high-dose IVIG alone (2 g/kg for 24 h and aspirin 30 mg/kg/day). The primary end point is the frequency of occurrence of coronary artery abnormalities during the trial period. An independent end point review committee will be in charge of the trial assessment. Ethics and dissemination: The protocol was approved by the Institutional Review Board of each institution. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, in Japan. The trial is currently on-going and is scheduled to finish in April 2017. The findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number: JMA-IIA00174; Preresults.

Background/Objectives Recently, a body shape index (ABSI) was reported to predict all-cause mortality independently of body mass index (BMI) in Americans. This study aimed to evaluate whether ABSI is applicable to Japanese adults as a predictor for development of diabetes, hypertension, and dyslipidemia. Subjects/Methods We evaluated the predictive power of ABSI in a retrospective cohort study using annual health examination data from Chiba City Hall in Japan, for the period 2008 to 2012. Subjects included 37,581 without diabetes, 23,090 without hypertension, and 20,776 without dyslipidemia at baseline who were monitored for disease incidence for 4 years. We examined the associations of standardized ABSI, BMI, and waist circumference (WC) at baseline with disease incidence by logistic regression analyses. Furthermore, we conducted a casematched study using the propensity score matching method. Results Elevated BMI, WC, and ABSI increased the risks of diabetes and dyslipidemia [BMI-diabetes: odds ratio (OR) = 1.26, 95% confidence interval (95%CI) = 1.20-1.32; BMI-dyslipidemia: OR = 1.15, 95%CI = 1.12-1.19; WC-diabetes: OR = 1.24, 95%CI = 1.18-1.31; WC-dyslipidemia: OR = 1.15, 95%CI = 1.11-1.19; ABSI-diabetes: OR = 1.06, 95%CI = 1.01 -1.11; ABSI-dyslipidemia: OR = 1.04, 95%CI = 1.01-1.07]. Elevated BMI and WC, but not higher ABSI, also increased the risk of hypertension [BMI: OR = 1.32, 95%CI = 1.27-1.37; WC: OR = 1.22, 95%CI = 1.18-1.26; ABSI: OR = 1.00, 95%CI = 0.97-1.02]. Areas under the curve (AUCs) in regression models with ABSI were significantly smaller than in models with BMI or WC for all three diseases. In case-matched subgroups, the power of ABSI was weaker than that of BMI and WC for predicting the incidence of diabetes, hypertension, and dyslipidemia. Conclusions Compared with BMI or WC, ABSI was not a better predictor of diabetes, hypertension, and dyslipidemia in Japanese adults.

Aim: The present study investigated whether bevacizumab (BV) is associated with postoperative wound complications (PWCs). Patients and Methods: We retrospectively analyzed patients undergoing surgery for liver metastases of colorectal cancer at our Institution. Patients were divided into 3 groups according to the preoperative treatment: chemotherapy with BV (group A), chemotherapy without BV (group B) and no chemotherapy (group C). Results: Between February 2003 and September 2012, 297 patients underwent 373 surgeries. Groups A, B and C consisted of 23, 62 and 288 patients, respectively. PWCs occurred in 29 patients (7.8%). In multivariate analysis, there were no differences in PWCs among the groups (C vs. B:P=0.739; C vs. A: P=0.110). Conversely, lower serum albumin levels (<3.5g/dl vs. ≥3.5g/dl: p=0.030) and synchronous colorectal resection (no vs. yes; p<0.001) remained significant risk factors of developing PWCs. Conclusion: Chemotherapy with or without BV did not influence the risk of PWCs.

A randomized Phase II dose-finding trial comparing olanzapine 10 mg with olanzapine 5 mg for patients receiving highly emetogenic chemotherapy with cisplatin was started in June 2014. The purpose of the trial is to evaluate the efficacy and safety of the two olanzapine doses and to determine which is more promising as a test arm for comparison with the current standard antiemetic care (a combination of aprepitant, a 5-HT3 receptor antagonist and dexamethasone) in a subsequent Phase III trial. Patients receiving cisplatin-containing regimens will be randomized to the olanzapine 10 or 5 mg arm. A total of 150 patients will be accumulated from nine institutions over 2 years. The primary endpoint is complete response defined as no emetic episodes and no use of rescue medications in the delayed (24-120 h) phase. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000014214.

Objective: The utility of risk scores to predict the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogue (NA) remains to be elucidated. Methods: CU-HCC (The Chinese University of Hong Kong-HCC) and GAG-HCC (Guide with Age, Gender, HBV DNA, Core promoter mutations and Cirrhosis) scores of 225 Japanese patients treated with NAs for at least 2 years were calculated before and 2 years after the NA treatment. According to the cutoff values, the patients were categorized into high-score or low-score groups. Results: Sixteen of 225 patients developed HCC. Patients with a high score before the NA treatment showed a significantly higher HCC incidence than those with a low score using both score models (p < 0.001). Time-dependent receiver operating characteristic analyses based on scores before and 2 years after the NA treatment showed that both models exhibited moderate accuracy in predicting HCC development. The HCC incidence was significantly lower in the patients whose scores decreased below the cutoff values in response to the NA treatment than in those whose scores remained high using both models (p < 0.01). Conclusions: The predictive performance of the CU-HCC and GAG-HCC scores in the CHB patients treated with NAs is comparable to that in the NA-naive patients. The patients with sustained high scores after the NA treatment showed a higher incidence of HCC development.

Heptavalent pneumococcal conjugate vaccine (PCV7) was introduced to Japan in 2010. We investigated the impact of PCV7 on childhood community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP). Children aged <5 years living in Chiba city, Japan, who were admitted to hospitals were enrolled to estimate the incidence of CAP based on the mid-year population. PP was determined by the presence of Streptococcus pneumoniae in cultured blood and/or sputum samples of CAP patients. The incidence of CAP and S. pneumoniae isolated from PP patients was compared before (April 2008-March 2009) and after (April 2012-March 2013) the introduction of PCV7 immunization. The annual incidence of CAP was reduced [incidence rate ratio 0·81, 95% confidence interval (CI) 0·73-0·90]. When comparing post-vaccine with pre-vaccine periods, the odds ratio for PP incidence was 0·60 (95% CI 0·39-0·93, P = 0·024). PCV7-covered serotypes markedly decreased (66·6% in pre-vaccine vs. 15·6% in post-vaccine, P < 0·01), and serotypes 6C, 15A, 15C and 19A increased. Multidrug-resistant international clones in the pre-vaccine period (Spain -2/ST90, Taiwan -14/ST236) decreased, while Sweden -25/ST63 was the dominant clone in the post-vaccine period. A significant reduction in the incidence of both CAP hospitalizations and culture-confirmed PP of vaccine serotypes was observed at 2 years after PCV7 vaccination. 6B 19F 15A

Background Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare cause of demyelinating neuropathy, with multi-organ involvement characterised by plasma cell dyscrasia and VEGF overproduction. No treatments have been established for patients with POEMS syndrome who are not eligible for stem-cell transplantation. Thalidomide suppresses VEGF and plasma cell proliferation. We aimed to assess the safety and efficacy of thalidomide for the treatment of POEMS syndrome. Methods We did a randomised, double-blind, placebo-controlled, phase 2/3 trial at 12 hospitals in Japan. Adults (age ≥20 years) with POEMS syndrome who were ineligible for autotransplantation were randomly assigned (1:1) by a minimisation method to treatment with oral dexamethasone (12 mg/m per day on the first 4 days of every 28-day cycle) plus either oral thalidomide (200 mg daily) or placebo for six cycles. All study personnel and patients were masked to treatment allocation. The primary endpoint was the reduction rate of serum VEGF concentrations at 24 weeks. Analysis was by intention to treat. This study is registered with the UMIN Clinical Trials Registry, UMIN000004179. Findings Between Nov 11, 2010, and July 3, 2014, we randomly assigned 25 patients to receive either thalidomide (n=13) or placebo (n=12); one patient in the placebo group was excluded from analyses because of a protocol violation. The adjusted mean VEGF concentration reduction rate at 24 weeks was 0·39 (SD 0·34) in the thalidomide group compared with −0·02 (0·54) in the placebo group (adjusted mean difference 0·41, 95% CI 0·02–0·80; p=0·04). Mild sinus bradycardia was more frequent in the thalidomide group than in the placebo group (seven [54%] vs zero; p=0·006). Five patients had serious adverse events: three in the thalidomide group (transient cardiac arrest, heart failure, and dehydration) and two in the placebo group (ileus and fever). No deaths occurred during the randomised study. In the 48-week open-label study period (n=22), newly developed adverse events were sinus bradycardia (n=4), constipation (n=5), and mild sensory neuropathy (n=5). Two patients died in the open-label study; both patients were initially in the placebo group, and the cause of death was progression of the disease. Interpretation Thalidomide reduces serum VEGF concentrations and represents a new treatment for patients with POEMS syndrome who are not eligible for stem-cell transplantation. Thalidomide treatment poses a risk of bradycardia; however, the benefits are likely to exceed the risk. Funding Japanese Ministry of Health, Labour, and Welfare, and Fujimoto Pharmaceuticals. 2

Objectives-The purposes of this study were to measure intraobserver and interobserver repeatability of quantitative elastography using an acoustic coupler for the Achilles tendon, to compare elastographic values among different age groups, and to assess the correlation between quantitative and conventional qualitative measurements. Methods-One hundred asymptomatic Achilles tendons of 50 volunteers were examined. For quantitative elastography, the strain value of the tendon was divided by that of the acoustic coupler with a known Young modulus, and the strain ratio was calculated. B-mode image assessment and qualitative elastography were also performed. Intraobserver repeatability and interobserver repeatability of strain ratio measurements were calculated. The strain ratios were compared among age groups by the Kruskal-Wallis test. Additionally, strain ratios for each B-mode grade and qualitative elastographic grade were compared by the Wilcoxon signed rank test. Results-Intraobserver repeatability intraclass correlation coefficient (1, 3) values were 0.87 and 0.93, respectively. The correlation coefficient between the observers' measurements was 0.61. The strain ratio for the 30s age group was 0.27, which was significantly lower than the values for the other age groups (P < .001). Although 97 of 100 tendons were normal on B-mode evaluations, 36 of the 97 tendons were degenerated on qualitative elastography and also had higher strain ratio values than normal tendons. Conclusions-Quantitative elastography using an acoustic coupler is a reproducible technique for measuring the elasticity of the Achilles tendon. It may detect early tendon degeneration that is not depicted on B-mode imaging.