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Background: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. Methods: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. Results: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2–81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13–1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34–1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27–1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27–2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56–2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57–2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. Conclusion: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. Clinical trial registration: NCT02358031. [ABSTRACT FROM AUTHOR]

Background: Here, we report the results of the Japanese subgroup of the phase 3 KEYNOTE-048 study of pembrolizumab alone, pembrolizumab plus platinum and 5-fluorouracil (pembrolizumab–chemotherapy), or cetuximab plus platinum and 5-fluorouracil (EXTREME) in previously untreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Methods: Primary end points were overall survival (OS) and progression-free survival (PFS). Efficacy was evaluated in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1 and the total Japanese subgroup (n = 67). Results: At data cutoff (25 February 2019), pembrolizumab led to longer OS versus EXTREME in the PD-L1 CPS ≥ 20 subgroup (median, 28.2 vs. 13.3 months; HR, 0.29 [95% CI 0.09–0.89]) and to similar OS in the total Japanese (23.4 vs. 13.6 months; HR, 0.51 [95% CI 0.25–1.05]) and CPS ≥ 1 subgroups (22.6 vs. 15.8 months; HR, 0.66 [95% CI 0.31–1.41]). Pembrolizumab–chemotherapy led to similar OS versus EXTREME in the PD-L1 CPS ≥ 20 (median, 18.1 vs. 15.8 months; HR, 0.72 [95% CI 0.23–2.19]), CPS ≥ 1 (12.6 vs. 15.8 months; HR, 1.19 [95% CI 0.55–2.58]), and total Japanese subgroups (12.6 vs. 13.3 months; unadjusted HR, 1.10 [95% CI 0.55–2.22]). Median PFS was similar for pembrolizumab and pembrolizumab–chemotherapy versus EXTREME in all subgroups. Grades 3–5 treatment-related adverse events occurred in 5 (22%), 19 (76%), and 17 (89%) patients receiving pembrolizumab, pembrolizumab–chemotherapy, and EXTREME, respectively. One patient receiving pembrolizumab–chemotherapy died because of treatment-related pneumonitis. Conclusion: These results support the use of first-line pembrolizumab and pembrolizumab–chemotherapy for Japanese patients with R/M HNSCC. Clinical trial registry ClinicalTrials.gov, NCT02358031. [ABSTRACT FROM AUTHOR]

Intracranial germ cell tumors (IGCTs) are rare brain neoplasms that mainly occur in children and adolescents with a particularly high incidence in East Asian populations. Here, we conduct a genome-wide association study (GWAS) of 133 patients with IGCTs and 762 controls of Japanese ancestry. A common 4-bp deletion polymorphism in an enhancer adjacent to BAK1 is significantly associated with the disease risk (rs3831846; P = 2.4 × 10−9, odds ratio = 2.46 [95% CI: 1.83–3.31], minor allele frequency = 0.43). Rs3831846 is in strong linkage disequilibrium with a testicular GCTs susceptibility variant rs210138. In-vitro reporter assays reveal rs3831846 to be a functional variant attenuating the enhancer activity, suggesting its contribution to IGCTs predisposition through altering BAK1 expression. Risk alleles of testicular GCTs derived from the European GWAS show significant positive correlations in the effect sizes with the Japanese IGCTs GWAS (P = 1.3 × 10−4, Spearman's ρ = 0.48). These results suggest the shared genetic susceptibility of GCTs beyond ethnicity and primary sites. Intracranial germ cell tumors (IGCTs) are rare brain tumors mainly diagnosed in children and young adults. Here, the authors conduct a genome-wide association study for IGCTs, identify a risk locus at BAK1, and characterize its functional consequences. [ABSTRACT FROM AUTHOR]

Gastrointestinal involvement is a rare manifestation of systemic amyloidosis, and few reports have been published on localized amyloidosis of the colon. Only one case report has been published on the long-term prognosis of localized colorectal amyloidosis, and there are no previous reports on localized colorectal ATTR amyloidosis. Here, we report an 80-year-old male with localized colorectal wild-type ATTR amyloidosis who presented with edematous mucosa with vascular changes throughout the colon. He did not exhibit any symptoms or endoscopic exacerbation for 8 years after diagnosis. However, after 8 years, he developed early stage colorectal cancer and cytomegalovirus-associated ulcer. He was treated with endoscopic submucosal dissection, which was relatively challenging due to his hemorrhagic condition and poor elevation of the submucosa caused by amyloid deposits. Since the tumor was completely resected, he will undergo regular follow-up. Our review of 20 previous cases of localized colorectal amyloidosis revealed its clinical features and long-term prognosis. Specifically, ours is the second case of a diffuse pan-colon type of colorectal localized amyloidosis, which may lead to various complications, such as colorectal cancer, over a long period of time, and thus, regular follow-up is necessary. [ABSTRACT FROM AUTHOR]

Background: We have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy. Methods: In this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs). Results: Overall, 256 patients received a median of 6.0 doses (range: 1–52) of nivolumab over a median duration of 72.5 days (range: 1–736). Median OS was 9.5 months [95% confidence interval (CI) 8.2–12.0] and median PFS was 2.1 months (95% CI 1.8–2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9–11.9) and 3.5 months (95% CI 2.3–5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis. Conclusions: Results demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Leg length discrepancy (LLD) after total hip arthroplasty (THA) prevents functional recovery and reduces patient satisfaction. We investigated impact of changes in patient-perceived LLD on patient satisfaction and walking ability. Methods: one hundred and forty-nine patients with unilateral hip osteoarthritis undergoing THA from 2014 to 2017, (125 women, 24 men; average age, 68.5 years) with an objective LLD < 1 cm were included. Outcome measures included the patient-perceived LLD, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, 10-m walking speed, and affected leg loading rate, assessed preoperatively and at 3 weeks, 3 months, and 1 year postoperatively. Results: The absolute patient-perceived LLD (mean ± SD) (the number of patients with perceived LLD > 5 mm) were 6.4 ± 9.6 mm [88 patients (59%)] preoperatively; and 2.2 ± 4.0 mm [48 (32%); p < 0.001], 0.7 ± 2.3 mm [17 (11%); p < 0.001], and 0.4 ± 1.6 mm [10 (7%); p = 0.095] at 3 weeks, 3 months, and 1 year postoperatively, respectively. All outcome measures improved over time. One year postoperatively, a weak positive correlation between the patient-perceived LLD and WOMAC or 10-m walking speed (r = 0.24, 0.23, respectively) was found. The risk of patient-perceived LLD persisting > 1 year postoperatively was 5.5-fold higher in patients who exhibited it at 3 months and those with a WOMAC score > 10 at 3 months postoperatively, using multivariate logistic regression. Conclusion: Achieving a post-THA objective LLD < 1 cm significantly reduced the patient-perceived LLD up to 3 months postoperatively. The residual patient-perceived LLD at 1 year postoperatively was predicted from the WOMAC score or the presence of patient-perceived LLD at 3 months after THA. Level of evidence: Therapeutic level IV. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced oral or oropharyngeal cancer sometimes require surgery and adjuvant postoperative radiotherapy (PORT), which may cause dysphagia. However, the efficacy of rehabilitation treatment for PORT-induced dysphagia remains unclear. This study aimed to determine whether rehabilitation treatment during PORT after surgery is effective for dysphagia. Methods: We retrospectively studied 55 patients with oral or oropharyngeal cancer who received PORT. Of these, 25 received rehabilitation treatment for swallowing during PORT. The Functional Oral Intake Scale (FOIS) score at 6 months after treatment was used as the swallowing outcome. We performed multivariate linear regression and stratified analyses using the FOIS score (poor oral intake group: FOIS score <5, good oral intake group: FOIS score ≧5) before PORT. Results: The median (interquartile range) FOIS scores at 6 months post-PORT were 6 (5–6) and 6 (4–7) in the non-rehabilitation and rehabilitation groups, respectively. Multivariate linear regression revealed that rehabilitation treatment was a significant independent factor for a better FOIS score. Stratified analysis of the changes in the FOIS score from pre-PORT values to those obtained 6 months after treatment showed a significant difference in the good oral intake group between the rehabilitation and non-rehabilitation groups. There was no significant difference in the FOIS score from pre-PORT values to those obtained 6 months after treatment between the rehabilitation and non-rehabilitation groups in the poor oral intake group. Conclusion: Rehabilitation treatment during PORT may achieve better swallowing outcomes in patients with advanced oral or oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: To examine the effect of prior use of cetuximab and neck dissection on the effectiveness of nivolumab, we conducted a large-scale subgroup analysis in Japanese patients with recurrent/metastatic head and neck cancer. Methods: Data on the effectiveness of nivolumab were extracted from patient medical records. All patients were analyzed for effectiveness by prior cetuximab use. In the analyses for prior neck dissection, only patients with locally advanced disease were included. Results: Of 256 patients analyzed, 155 had received prior cetuximab. Nineteen of 50 patients with local recurrence underwent neck dissection. The objective response rate was 14.7 vs 17.2% (p = 0.6116), median progression-free survival was 2.0 vs 3.1 months (p = 0.0261), and median overall survival was 8.4 vs 12 months (p = 0.0548) with vs without prior cetuximab use, respectively. The objective response rate was 23.1 vs 25.9% (p = 0.8455), median progression-free survival was 1.8 vs 3.0 months (p = 0.6650), and median overall survival was 9.1 vs 9.9 months (p = 0.5289) with vs without neck dissection, respectively. Conclusions: These findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck dissection history. Trial registration number: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436) [ABSTRACT FROM AUTHOR]

Background: To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice. Methods: This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records. Results: Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1–27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2–12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141. Conclusions: The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141. Trial registration number: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436) [ABSTRACT FROM AUTHOR]

Background: Second cancers in patients with esophageal cancer (EC) are common and have a poor prognosis. We evaluated the incidence of second cancers at different sites by patients' ages when their index ECs were diagnosed.Methods: This study included patients who underwent endoscopic resection for superficial EC at our hospital between September 1994 and September 2011. Patients' data, including sex, age at diagnosis, sequence of cancer incidence, cancer histology, and cancer site, were extracted from the cancer registry.Results: Of 544 patients, 255 developed second cancers. Simultaneous head and neck cancers (HNCs) and other organ cancers (OCs) were, respectively, present in 15% (80/544) and 9.6% (52/544) of patients; and 30% (162/544) developed metachronous second cancers over a median follow-up period of 79.5 months (range 2-120), including 44 metachronous HNCs and 70 OCs. The cumulative incidence of metachronous HNCs was significantly higher in younger patients (< 60 years) than in older patients (≥ 60 years; P = 0.001), whereas the cumulative incidence of OCs was significantly higher in older patients than in younger patients (P = 0.03).Conclusions: The incidence of second HNC after index EC was higher in younger-onset patients than in older-onset patients. We suggest that younger patients with EC should be carefully monitored for early detection of second HNC. [ABSTRACT FROM AUTHOR]

Salivary duct carcinoma (SDC) is a high-grade carcinoma with poor prognosis, especially among various salivary carcinomas. In this study, we report a rare case of SDC of the parotid gland originating from an epithelial-myoepithelial carcinoma (EMC). A 71-year-old Japanese man presented with swelling of the right parotid region and a right facial nerve paralysis for 10 months. He underwent extended total parotidectomy and chemoradiotherapy after the surgery. Histologically, a major part of the tumor was an androgen receptor (AR)-positive, human epidermal growth factor receptor 2 (HER2)-positive, gross cystic disease fluid protein-15 (GCDFP-15)-positive SDC, with a focus of a typical EMC component at the periphery of the lesion. In the transitional area of the two components, inner ductal cells of double-layered ducts showed similar morphology and immunophenotype to SDC. These findings suggest that SDC originated from the inner ductal cells of EMC. Because the tumor included an EMC as a low-grade carcinoma and an SDC as a high-grade carcinoma, we can consider our case as a dedifferentiated carcinoma as well as a hybrid tumor. [ABSTRACT FROM AUTHOR]

Contraction of striated muscles is driven by cyclic interactions of myosin head projecting from the thick filament with actin filament and is regulated by Ca2+ released from sarcoplasmic reticulum. Muscle thin filament consists of actin, tropomyosin and troponin, and Ca2+ binding to troponin triggers conformational changes of troponin and tropomyosin to allow actin-myosin interactions. However, the structural changes involved in this regulatory mechanism remain unknown. Here we report the structures of human cardiac muscle thin filament in the absence and presence of Ca2+ by electron cryomicroscopy. Molecular models in the two states built based on available crystal structures reveal the structures of a C-terminal region of troponin I and an N-terminal region of troponin T in complex with the head-to-tail junction of tropomyosin together with the troponin core on actin filament. Structural changes of the thin filament upon Ca2+ binding now reveal the mechanism of Ca2+ regulation of muscle contraction. The contraction of cardiac and skeletal muscles is regulated by Ca2+ released from the sarcoplasmic reticulum in muscle cells. Here the authors provide molecular insights into Ca2+ regulation of muscle contraction by determining the cryo-EM structures of the human cardiac muscle thin filament in the absence and presence of Ca2+. [ABSTRACT FROM AUTHOR]

The appropriate stent platform for treating coronary bifurcation lesions (CBLs) remains controversial. Previous bench tests have demonstrated the superiority of a 2-link cell design to 3-link cell design for creating inter-strut dilation at the side branch ostium. This randomized multicenter prospective BEGIN trial compared the biodegradable polymer-based biolimus A9-eluting stent (2-link BES) with the durable polymer-based cobalt chromium everolimus-eluting stent (3-link EES) in 226 patients with de novo CBLs. Patients with true bifurcations, defined as > 50% stenosis in the main vessel and side branch (SB) and an SB diameter > 2.25 mm, were enrolled. Guide wire re-crossing to the distal cell (near the carina) in the jailed SB and final kissing inflation were recommended. The SB angiographic endpoint was < 50% stenosis diameter. Left-main CBLs (13.5% vs. 13.0%) and 2-stent technique (30.6% vs. 22.6%) rates were similar. The primary endpoints (minimum lumen diameter at the SB ostium measured at an independent core laboratory at the 8-month follow-up) were comparable (1.64 ± 0.50 mm vs. 1.63 ± 0.51 mm, p = 0.976). There was no significant difference in composite outcomes of cardiac death, myocardial infarction, or target vascular revascularization at 12 months (7.4% vs. 8.0%, p = 0.894). Two-link BES and 3-link EES showed similar 8-month angiographic and 1-year clinical outcomes for true CBLs. [ABSTRACT FROM AUTHOR]

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. Methods: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. Results: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. Conclusions: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer. Methods: This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates. Results: The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% ( P = 0.30), 68.9% and 68.0% ( P = 0.80), and 82.2% and 63.6% ( P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% ( P = 0.092), 56.5% and 41.3% ( P = 0.629), and 43.0% and 42.5% ( P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. Conclusions: The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer. [ABSTRACT FROM AUTHOR]

The aim of this study is to indicate differences of side branch jailing between the left main (LM)-left anterior descending artery (LAD) stenting and the LM-left circumflex artery (LCx) stenting. Thirty-one patients who underwent single-stenting using a two-link ten-crowns biolimus-eluting stent (Japanese design of BES, J-BES) and subsequent kissing balloon dilation (KBD) on an LM bifurcation with optical coherence tomography (OCT) were divided into two groups according to the stented vessel. Bifurcation angles were measured by three-dimensional (3D) quantitative coronary analysis. The jailing pattern on a side branch ostium was evaluated by stent-enhanced 3D-OCT. Incomplete stent apposition (ISA) after KBD was compared between the stented vessels. The to-be-stented angle of the LM-LCx stenting ( n = 11) was significantly steeper than that of the LM-LAD stenting ( n = 20) (132.6° ± 16.9° vs. 150.7° ± 10.6°, p < 0.01). The incidence of the free carina type, which has no stent links bridging from a carina, in the LM-LCx stenting was significantly higher than that in the LM-LAD stenting (90.9 vs. 45.0 %, p = 0.02). The percentage of ISA at the bifurcation segment in the LM-LCx stenting was significantly smaller than that in the LM-LAD stenting (4.4 ± 8.2 vs. 12.7 ± 9.2 %, p = 0.0003). This study showed, by higher incidence of the favorable configuration, that the LM-LCx stenting achieved a smaller percentage of ISA than the LM-LAD stenting. These insights may help guide LM bifurcation stenting with J-BES. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate definitive external-beam radiotherapy (EBRT) for patients with base of the tongue (BOT) cancers. Methods: We reviewed results for 26 patients with BOT cancers who were treated with EBRT. Clinical stages T1, T2, T3, and T4a were observed for 10, 7, 4, and 5 patients, respectively, and stages N0, N1, N2a, N2b, N2c, and N3 were observed for 4, 2, 5, 6, 8, and 1 patients, respectively. More than half of the patients ( n = 19) were stage IVA. Standard total delivered doses were 70 Gy to primary tumors and cervical lymph node (CLN) metastases and 40-46 Gy to elective nodal regions. Eleven patients with advanced loco-regional disease received concurrent or neoadjuvant chemotherapy. Four T3 patients and one T2 patient received 2 or 3 cycles of concurrent intra-arterial cisplatin with EBRT (RADPLAT). Results: Three-year overall survival was 69 % (95 % CI 47-83 %), with a median follow-up period of 33 months. Three-year local control was 100, 86, 100, and 20 % for T1, T2, T3, and T4 patients, respectively. Three-year regional control was 100 % for N0, N1, and N2a, 83 % for N2b, 75 % for N2c, and 0 % for N3 patients. Treatment failed for 7 patients. All 5 patients undergoing RADPLAT achieved complete responses and did not develop local recurrence. Conclusions: We achieved favorable outcomes for patients with T1-T3 BOT cancers by use of definitive EBRT with or without chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The present study examined the computed tomography (CT) findings after surgery and overnight drainage for chronic subdural hematoma (CSDH) to clear the significance of inner superficial subarachnoid CSF space and outer subdural hematoma cavity between the brain surface and the inner skull. Methods: A total of 73 sides in 60 patients were evaluated. Head CT was performed on the day after surgery and overnight drainage (1st CT), within 3 weeks of surgery (2nd CT), and more than 3 weeks after surgery (3rd CT). Subdural and subarachnoid spaces were identified to focus on density of fluid, shape of air collection, and location of silicone drainage tube, etc. Cases with subdural space larger than the subarachnoid CSF space were classified as Group SD between the brain and the skull. Cases with subarachnoid CSF space larger than the subdural space were classified as Group SA. Cases with extremely thin (<3 mm) spaces between the brain and the skull were classified as Group NS. Results: Group SA, SD, and NS accounted for 31.9, 55.6 and 12.5 % of cases on the 1st CT. No statistical differences were found between Groups SA, SD, and NS in any clinical factors, including recurrence. Group SA were found significantly more on 1st CT than on 2nd and 3rd CT. Conclusions: Subarachnoid CSF space sometimes expands between the brain and skull on CT after surgical overnight drainage. Expansion of the arachnoid space may be a passive phenomenon induced by overnight drainage and delayed re-expansion of the brain parenchyma. [ABSTRACT FROM AUTHOR]

The common single nucleotide polymorphism (SNP) rs1360780 (C/T) of the FK506 Binding Protein 5 (FKBP5) gene has been reported to be associated with an altered response of the hypothalamic-pituitary-adrenal (HPA) axis and the development of stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD). In the present study, we examined whether this SNP is associated with cognitive function in a non-clinical population. The full versions of the Wechsler Memory Scale-Revised and Wechsler Adult Intelligence Scale-Revised were administered to 742 and 627 Japanese individuals, respectively, followed by genotyping of rs1360780 by the TaqMan 5'-exonuclease allelic discrimination assay. For both cognitive tests, we found significantly poorer attention/concentration (working memory) in aged (>50 years old) individuals carrying the T allele compared with their counterparts. This finding accords with an altered HPA axis and vulnerability to stress-related psychiatric disorders. [ABSTRACT FROM AUTHOR]

The article Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real‑world clinical practice: a multicentre retrospective clinical study, written by. [ABSTRACT FROM AUTHOR]

Background: Previous studies on membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemic glomerulopathy (CG) were based upon case series that were performed before hepatitis C virus (HCV) infection was routinely investigated. Therefore, it remains unknown how far HCV contributes to MPGN or CG, and there have only been a few reports about HCV-negative idiopathic MPGN. Patients and methods: Thirty-five patients with MPGN diagnosed by renal biopsy who underwent examination for HCV infection at our institute between 1990 and 2008 were recruited for this study. Patients with HCV infection at presentation were included, but patients with complications such as underlying lymphoproliferative disorders, autoimmune diseases like lupus nephritis, infection, and liver disease due to hepatitis B virus or alcohol abuse were excluded. A total of 35 patients were enrolled and they were divided into two groups according to the presence/absence of circulating cryoglobulins (cryo). The 23 patients who had cryo-negative and HCV-negative idiopathic MPGN were divided into subgroups with type 1 and type 3 disease. Results: In the cryo-positive group ( n = 9), 7 patients were positive for HCV infection, while 2 patients were negative. In the cryo-negative group ( n = 26), 3 patients were positive for HCV infection, while 23 patients were negative (idiopathic MPGN). Compared with the cryo-negative group, the cryo-positive group had several characteristics such as more severe thrombocytopenia, higher serum immunoglobulin (Ig)G and IgM levels, lower levels of hemolytic complement (CH50) and complement component (C)4, predominant IgM staining, and type 1 histology. Patients with cryo-negative and HCV-negative 'idiopathic' MPGN showed predominant staining for IgG in both type 1 and type 3 cases, unlike the predominant staining for IgM in the cryo-positive group. Compared with type 3 cases, type 1 cases had a younger age, lower levels of CH50, C3 and C4, and less proteinuria. In the cryo-positive group, 4 patients (44.4 %) died, with death from B cell lymphoma and liver failure in 2 patients each, while 1 patient (8 %) developed end-stage renal failure requiring dialysis. In contrast, all patients in the cryo-negative group remained alive during follow-up, although 4 patients (2 type 1 cases and 2 type 3 cases) required dialysis. Conclusion: Cryo-positive MPGN shows a close relationship with HCV infection and IgM, resulting in a poor prognosis. Cryo-negative and HCV-negative idiopathic MPGN has a close relationship with IgG staining, and type 1 cases feature characteristics such as a younger age, more severe hypocomplementemia, and less proteinuria than in type 3 cases. [ABSTRACT FROM AUTHOR]

One of the major problems of a Fourier-domain optical coherence tomography (FD-OCT) is the guide wire (GW) shadow which disturbs precise coronary assessment. If two or more GWs are used in a bifurcation PCI, the GW shadow becomes larger. In FD-OCT, GWs were usually observed as a crescent shape, but GWs with the sparse spring coil were observed as either round or crescent shape. The measured angle making GW shadow of GW without the sparse spring coil was similar to its theoretical angle (30.4 ± 1.7° vs. 30.1 ± 0.7°, p = 0.21); however, the measured angle of GW with the sparse spring coil was significantly smaller than its theoretical angle (16.8 ± 4.8° vs. 28.7 ± 1.5°, p < 0.01). For standardization of shading-effect of GW, a virtual diameter of GW which was calculated from a measured angle, an actual diameter of GW, and a distance between an imaging catheter and GW was defined as the shading index. The shading index of GW with the sparse spring coil was significantly smaller than that of GW without the sparse spring coil (0.008 ± 0.002 vs. 0.014 ± 0.001, p < 0.01). Shading indices of GWs with the sparse spring coil were smaller than their actual diameters. The sparse spring coil structure could contribute to the reduction of the GW shadow in FD-OCT. Also, we proposed the new and useful shading index to indicate the shading-effect of GW. [ABSTRACT FROM AUTHOR]

In order to confirm the relation between stent struts and the jailed side branch (SB), the actual wire re-crossing position and the optimal wire re-crossing position during a bifurcation stenting, we developed the instant stent-accentuated three-dimensional optical coherence tomography (iSA 3D-OCT) system based on a novel algorithm. Stent struts in two-dimensional optical coherence tomography (2D-OCT) are represented as high-intensity line segments or spots in low-intensity background. Stent struts disappear and a vessel image is created by the mean filter followed by the minimum filter. A strut image is created by subtracting a vessel image from an original image, and accentuated. By adding a vessel image to a strut image, iSA 2D-OCT is created. It took only 3 s to accentuate stent struts of 100 frames by ImageJ with its macro program. By the iSA 3D-OCT system which consists of the console of OCT, the USB selector, USB cables, the USB flash drive, the computer, and three freeware programs, it took about 65 s from an export of the image data to an observation of iSA 3D-OCT semi-automatically. During a bifurcation stenting procedure, we could confirm the relation between stent struts and the jailed SB, the actual wire re-crossing position and the optimal wire re-crossing position. Using the iSA 3D-OCT system, a detailed process during a bifurcation PCI can be observed in very short waiting time, about 65 s. It is expected to improve the outcome of a complicated bifurcation PCI by the iSA 3D-OCT system. [ABSTRACT FROM AUTHOR]

Purpose: Standard treatment for patients with primary central nervous system (CNS) lymphoma involves combining high-dose methotrexate-based chemotherapy and radiation. However, chemotherapy is sometimes contraindicated, and radiotherapy alone becomes the only option. We retrospectively investigated the clinical outcomes of primary CNS lymphoma patients treated with radiotherapy alone. Materials and methods: Between 1983 and 2006, 35 patients (median age 69 years, range 37-89 years) with primary CNS lymphoma were treated with radiotherapy alone. Of these, 74 % had an Eastern Cooperative Oncology Group performance status (PS) of 2-4. Most patients (91 %) received whole-brain irradiation with or without irradiation boost to the tumor site (median dose 50 Gy, range 22-50 Gy); remaining patients received partial brain irradiation. Results: Median follow-up time was 20 (range 1-152) months, median survival time was 20 months, and the 1- and 2-year overall survival rates were 65 and 32 %, respectively. Median survival in patients aged <70 and ≥70 years was 26 and 10 months, respectively ( p = 0.01). Conclusion: Median survival with radiotherapy alone was 20 months. Patients aged <70 years have a better prognosis than those ≥70 years. [ABSTRACT FROM AUTHOR]

Myxofibrosarcoma (MFS) is a very rare fibroblast-derived sarcoma that occurs in the head and neck region. Here, we report the case of a 52-year-old man in whom MFS generated from the maxilla and whose beginning of treatment was considerably delayed because he was initially diagnosed as having a benign inflammatory lesion. Because a definite diagnosis was not obtained via 2 independent biopsies, total maxillectomy was used for both diagnosis and treatment. Histopathological and immunohistochemical analyses suggested that the tumor was a low-grade MFS. Because soft tissue tumors in the head and neck region are rare and a definite diagnosis is relatively difficult, surgical excision is indispensable if malignancy of the tumor is suspected. [ABSTRACT FROM AUTHOR]

In situ transmission electron microscopy (TEM) was carried out to investigate the dynamics of resistance switching in a solid electrolyte, Cu-Ge-S. By applying voltage to Pt-Ir/Cu-Ge-S/Pt-Ir, where Pt-Ir constituted the electrodes, a deposit containing conductive filaments composed mainly of Cu was formed around the cathode. As voltage continued to be applied, the deposit grew and finally narrow conductive filaments made contact with the anode. This corresponded to resistance switching from high- to low-resistance states (HRS and LRS). By alternating the voltage, the deposit contracted toward the cathode and detached from the anode. The resistance immediately changed from LRS to HRS. By applying voltage, the deposit containing Cu-based filaments grew and shrank, and resistance switching occurred at the electrolyte-anode interface. This conductive filament-formation model, which was recently reported, was experimentally confirmed with TEM through dynamic observations of the deposit-containing filaments. [ABSTRACT FROM PUBLISHER]

Altered neurotrophin functions have been implicated in major depressive disorder (MDD). Previously, we reported an association between MDD and a missense polymorphism (Ser205Leu: rs2072446) of the gene encoding the p75 neurotrophin receptor (p75NTR). However, contradictive negative results have also been reported. This study tried to replicate the association in an independent sample. Subjects were 668 patients with MDD and 1130 healthy controls. The proportion of individuals carrying the Leu205 allele was significantly decreased in the patients than in the controls (χ2=5.3, d.f.=1, P=0.021, odds ratio (OR) 0.74, 95% confidential interval (CI) 0.58-0.96). When allele frequencies were compared, the Leu205 allele was significantly reduced in the patients than in the controls (χ2=4.4, d.f.=1, P=0.037, OR 0.78, 95% CI 0.61-0.99). When men and women were examined separately, there was a significant difference in genotype and allele distributions in women (genotype: χ2=8.3, d.f.=1, P=0.0039, OR 0.60, 95% CI 0.43-0.85; allele: χ2=7.3, d.f.=1, P=0.0069, OR 0.64, 95% CI 0.47-0.89), but not in men. The present study provided support for the previously reported association between the Ser205Leu polymorphism of the p75NTR gene and MDD, indicating that the Leu205 allele has a protective effect against the development of MDD, particularly in women. [ABSTRACT FROM AUTHOR]

The article presents a study which focuses on the optical waveguide properties of ferroelectric LiTaO3 crystals. The study used laser pulses in crystal photoexcitation and conducted a refractive index profile calculation. The study shows that optical waveguide can be determined inside LiTaO3 crystals using focused femtosecond laser pulses. It also reveals the polarization-sensitivity of the waveguide.

F-actin is a helical assembly of actin, which is a component of muscle fibres essential for contraction and has a crucial role in numerous cellular processes, such as the formation of lamellipodia and filopodia, as the most abundant component and regulator of cytoskeletons by dynamic assembly and disassembly (from G-actin to F-actin and vice versa). Actin is a ubiquitous protein and is involved in important biological functions, but the definitive high-resolution structure of F-actin remains unknown. Although a recent atomic model well reproduced X-ray fibre diffraction intensity data from a highly oriented liquid-crystalline sol specimen, its refinement without experimental phase information has certain limitations. Direct visualization of the structure by electron cryomicroscopy, however, has been difficult because it is relatively thin and flexible. Here we report the F-actin structure at 6.6 Å resolution, made obtainable by recent advances in electron cryomicroscopy. The density map clearly resolves all the secondary structures of G-actin, such as α-helices, β-structures and loops, and makes unambiguous modelling and refinement possible. Complex domain motions that open the nucleotide-binding pocket on F-actin formation, specific D-loop and terminal conformations, and relatively tight axial but markedly loose interprotofilament interactions hydrophilic in nature are revealed in the F-actin model, and all seem to be important for dynamic functions of actin. [ABSTRACT FROM AUTHOR]

We performed a multicenter longitudinal study using our neck dissection questionnaire (NDQ) and arm abduction test (AAT) to assess the impact of rehabilitation and surgical modification on postoperative quality of life (QOL). Patients who had undergone neck dissection for the treatment of head and neck cancer answered the NDQ and completed the AAT 1, 3, 6, and 12 months after surgery. All patients enrolled in this study underwent a rehabilitation program designed for neck dissection. The obtained data were statistically analyzed according to the types of neck dissection and compared with the data of patients who had undergone neck dissection but not rehabilitation. A total of 224 patients were enrolled in this study. Our findings revealed that resection of the sternocleidomastoid muscle (SCM) and spinal accessory nerve (SAN) resulted in shoulder drop. Lowering the dissection level and preservation of the SAN and SCM significantly reduced various sensory symptoms of the neck, such as stiffness, pain, numbness, and constriction, and improved shoulder function. Postoperative rehabilitation had a significant effect on arm abduction ability, particularly when the SCM and SAN were resected. The study demonstrated that rehabilitation, in addition to modifications to radical neck dissection, contributed to the improvement of postoperative QOL after neck dissection. [ABSTRACT FROM AUTHOR]

The hydrothermal autoclave experiments were conducted to simulate the interactions in the scCO2/water/rock minerals (quartz, biotite and granite) reaction systems using a Hastelloy C reaction cell at 100 °C. The dissolution characteristics of rock minerals and their surface texture alternation after hydrothermal treatment were examined by ICP-AES and SEM/EDX investigation, respectively. The results suggested that the hydrolysis of plagioclase phase should be mainly responsible for the elements dissolved from the Iidate granite samples. The dissolution was encouraged by the introduction of CO2 in the water/granite system, and generated an unknown aluminosilicate. No distinct chemical alternations occurred in the water-free scCO2/granite system, which indicated that rock minerals should be chemically stable in the water-free scCO2 fluids under the current mild experimental conditions. Both the highest concentration of Ca existing in the scCO2/vapor/granite system and the SEM observation results of calcite deposit, suggested that a meaningful CO2 minerals trapping process should be potential in the CO2-rich field during a short physicochemical interaction period. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to investigate the value of preoperative thallium-201 (201Tl) SPECT as a predictor of outcome in malignant glioma.Methods: From January 1990 to September 2003, 109 patients with glioma were treated with postoperative radiotherapy. Of these, 36 patients with malignant gliomas who underwent preoperative 201Tl-SPECT were included in this study (grade 3: n=14, grade 4: n=22). On early (10 minutes) and delayed (2 hours) images after 111 MBq 201TlCl injection, we calculated radioactivity ratios of tumors to contralateral normal brain (T/N ratios) and retention indices (RIs). For early and delayed images, we compared outcome between a high T/N ratio group (T/N ratio equal or greater than the average) and a low T/N ratio group (T/N ratio less than the average). We also divided the patients into two groups on the basis of RI; a high RI group (RI equal or greater than the average) and a low RI group (RI less than the average), and similarly compared outcome between the two groups.Results: Median survival time was 12 months for both grade 3 and grade 4 tumors; however, two-year survival was 53% for grade 3 and 15% for grade 4. In both early and delayed images, outcome was significantly better for patients with low T/N ratios (early < 4.71, delayed < 3.96) than those with high T/N ratios (early: p = 0.030, delayed: p = 0.049). However, no significant survival difference was apparent between the low- (< -12.25) and high RI groups. In grade 3 glioma, patients with high T/N ratios demonstrated a tendency toward poorer outcome, although this trend was not significant (early: p = 0.079, delayed: p = 0.099). Overall outcome was poor for grade 4 glioma, and the difference in survival between low and high T/N ratio groups was not significant (early: p = 0.51, delayed: p = 0.53). However, long survival was seen only in patients with lower T/N ratios.Conclusions: Differences of 201Tl uptake in malignant gliomas could predict outcome. 201Tl-SPECT is potentially useful in the management of patients with malignant gliomas. [ABSTRACT FROM AUTHOR]

Objective: It has been reported that delayed scan of thallium-201 (201Tl) scintigraphy is useful for differentiating malignant tumors from benign lesions and for evaluating treatment response. However, physiological muscle uptake which usually increases in delayed scans, often makes it difficult to evaluate201T1 uptake and its washout in bone and soft-tissue tumors. The purpose of this study was to evaluate whether the delayed scan is necessary and whether a dynamic scan is useful in the evaluation of bone and soft-tissue tumors. Methods: We studied 175 cases of bone and soft-tissue tumors (malignant 45, benign 130). Dynamic scans were acquired every 5 seconds for 10 minutes after201T1 injection, and time activity curves (TACs) were generated by adaptive smoothing methods. Early and delayed scans were acquired at 10–15 minutes and 2 hours after injection.20lTl images were visually interpreted and the radioactivity count ratio (T/N) of tumors to normal tissues and washout rate [WR = (early T/N - delayed T/N)/early T/N] were denned. Results: When there were no201T1 uptake in dynamic (n = 67) and early scans (n = 68), no tumor uptake was also appreciated in delayed scans, and all but two cases of negative scans were benign. In 107 lesions, although there were significant differences in T/Ns between malignant and benign lesions both on early scans (2.84 ± 1.45 vs. 2.05 ± 1.13, p < 0.05) and delayed scans (2.17 ± 1.03 vs. 1.58 ± 0.64, p < 0.05), there was a substantial overlap. The T/Ns decreased in delayed scans (i.e., WR > 0) in 100 of 107 cases due to increase of surrounding muscle uptake, and there was no difference in WR between malignant tumors and benign lesions (0.21 ± 0.14 vs. 0.19 ± 0.14). Conclusions: For evaluating bone and soft-tissue tumors, delayed scan had little clinical usefulness and it may be time consuming. Dynamic scan would be useful for demonstrating the differences between tumor blood flow and201Tl uptake in tumors. [ABSTRACT FROM AUTHOR]

Controlling the friction between wheel and rail is direct and very effective measures to improve the curiving performances of railway trucks, because the curving performances depend much on friction characteristics Authors have proposed a method, “fnction control”, which utilizes friction modifier (KELTRACK™ HPF) with onboard spraying system With the method, not only friction coefficient, but also fuction characteristics can be controlled as expected In this study, MBD simulation is very valuable tool to foresee the effect of the control in advance of experiment with real car And the creep characteristics of wheel/rail contact with the fuction modifier takes very important role in the simulation In this paper, authors propose a theoretical model of wheel/rail contact condition considering the creep characterstics of friction modifier, which is derived the application of principle tribological theories [ABSTRACT FROM AUTHOR]

The article analyzes histopathological prognostic factors. One hundred and thirty patients with stage I-II uterine cervical cancer were treated with radical hysterectomy and postoperative radiotherapy at Ehime University Hospital between 1978 and 1997. All surgical specimens were reviewed, and the relationship between histopathological factors and the clinical outcome was analyzed. Significant differences in prognosis were observed for six factors: pT factor, venous infiltration, pelvic lymph node metastases, thickness of the residual muscular layer, tumor depth, and tumor growth pattern. The risk classification may make it possible to predict which patients are at risk of recurrence.

We describe a new case of isolated Langerhans cell histiocytosis (LCH) of the hypothalamus. A 53-year-old female patient presented with polydipsia, headache, anorexia, and fatigue. Neurological imaging revealed a mass projecting from the hypothalamus into the third ventricle. Gross total removal of the tumor was performed. Light microscopy showed LCH, and immunohistochemical studies revealed S-100 and CD1a immunoreactivity in the Langerhans cells. Although the most common CNS site for LCH is the hypothalamus, isolated hypothalamic LCH, confirmed by biopsy, is very rare. The residual mass appeared to remit spontaneously 3.5 years after surgery, with regrowth 3 years later. [ABSTRACT FROM AUTHOR]

We report a case of overdosage of tranexamic acid (TNA), which was suggested as the cause of visual impairment in a 56-year-old man. He had been undergoing chronic hemodialysis for 1 year, following 10 years of peritoneal dialysis. He had been hospitalized for an emergency operation for a bleeding ulcer of the stomach and duodenum. After the operation, he experienced a gradual loss of sight over about 1 week, although his general condition was good. He received intravenous injections of TNA as a hemostat during hospitalization for the operation. Two weeks after the operation he became blind. Retinography was flat and his visual field had become narrowed. On fluorescein angiography, microgranular hyperfluorescence, which indicated malfunction of the pigmented layer of the retina, was observed. No abnormality of the brain or the optic nerve was shown by magnetic resonance imaging. Concentrations of vitamins and trace minerals in the blood were within the normal ranges. Administration of vitamins A and B12 did not improve his sight. However, discontinuation of TNA rapidly restored his sight, within a few days. He had received TNA once before because of bleeding ulcer, and his sight had been impaired at that time. Based on the repeated episodes, it was strongly suggested that an overdose of TNA in this dialysis patient caused the sight disturbance. Because TNA is metabolized by the kidney, caution is necessary when prescribing TNA for patients with renal failure. [ABSTRACT FROM AUTHOR]

Background. The purpose was to estimate retrospectively the outcome of patients with musculoskeletal sarcoma or malignant lymphoma treated with intraoperative radiotherapy (IORT). Methods. Between 1988 and 1999, definitive IORT in combination with surgical excision was performed in 24 patients with musculoskeletal sarcoma (malignant fibrous histiocytoma, 10; osteosarcoma, 6; liposarcoma, 2; chondrosarcoma, 1; synovial sarcoma, 1; Ewing's sarcoma, 1; angiosarcoma, 1; epithelioid sarcoma, 1; malignant schwannoma, 1) and 3 patients with malignant lymphoma. The tumor was excised by marginal margin excision, intralesional margin excision, or wide margin excision; 15–45Gy electrons was then delivered to the affected sites. Results. In the 8 patients without distant metastases at the first visit, 4 patients are alive 6.5–11.5 years after IORT, and 4 patients died <4.5 years after IORT. The incidence of local recurrence was 13%. In the 19 patients with distant metastases at the first visit, 3 patients are alive 2.5–6.7 years after IORT, and 16 patients died 0.2–5.7 years after IORT. The incidence of local recurrence was 45%. Complications after IORT were found in 5 patients: neuropathy, 1 patient; skin necrosis, 1 patient; myelopathy, 1 patient; enteritis ileus, 1 patient; and edema, 1 patient. Conclusion. IORT with a radiation dose of 15–45Gy in combination with surgical excision appeared to be useful for local control and to be more effective in patients without distant metastases at the first visit than in patients with distant metastases. [ABSTRACT FROM AUTHOR]

Background. In order to slow the progression of chronic renal failure (CRF), a multimodal approach should be applied if the efficacy is proved. Although compelling evidence of a beneficial effect exists for the use of angiotensin-converting enzyme inhibitors (ACEIs) and low-protein diets, there is little evidence on whether carbon adsorbent has an effect on retardation of the progression of CRF. Methods. In experiment 1, we examined whether the oral carbon adsorbent, AST-120, conferred an additive effect with captopril and an 80% restriction diet on the survival rate of 3/4 nephrectomized rats (3/4 NX). The 3/4 NX rats were divided into three groups (C, control, n = 7; AD, captopril (an ACEI) +80% restriction diet (RD), n = 8; and ADK, ACEI + RD + AST-120, n = 8) and survival was observed for 72 weeks. In experiment 2, 3/4 NX rats were divided into four groups (C, control, n = 4; D, 80% restriction diet, n = 4; AD, temocapril + RD, n = 9; and ADK, temocapril + RD + AST-120, n = 9) for the examination of renal function, blood pressure, hematocrit (Ht), serum albumin, and proteinuria every month. We analyzed morphological changes in the kidney at 48 weeks. Results. In experiment 1, ADK did not improve the survival rate compared with AD, although ADK prolonged the survival significantly compared with C (C vs AD, P = 0.24; C vs ADK, P = 0.0007; AD vs ADK, P = 0.073). In experiment 2, renal function and proteinuria were significantly ameliorated in the ADK group compared with AD at 48 weeks. Concomitantly with the preservation of renal function, pathological indices, including the glomerular sclerosis index and the interstitial fibrosis index, were significantly improved in ADK compared with AD. In the ADK group, Ht and serum albumin did not change over the 48 weeks. Conclusions. Administration of AST-120 in addition to an ACEI and a restriction diet preserves renal function independently of blood pressure control, angiotensin II inhibition, and protein restriction in 3/4 NX rats at 48 weeks, but does not improve the survival significantly. [ABSTRACT FROM AUTHOR]