Sinc-collocation methods for weakly singular Fredholm integral equations of the second kind

AbstractIn this paper we propose new numerical methods for linear Fredholm integral equations of the second kind with weakly singular kernels. The methods are developed by means of the Sinc approximation with smoothing transformations, which is an effective technique against the singularities of the equations. Numerical examples show that the methods achieve exponential convergence, and in this sense the methods improve conventional results where only polynomial convergence have been reported so far

Reconsideration of Hormonal Therapy in the Era of Next‐ Generation Hormonal Therapy

Hormonal therapy is a major and effective tool in the treatment of prostate cancer patients. This is especially true for patients in the advanced stages of disease. Unfortunately, almost all prostate cancer cells will develop into castration‐resistant prostate cancer (CRPC) despite continued therapy and suppression of testosterone levels. Up until 5–6 years ago, there was little effective therapy for the treatment of CRPC patients. However, recently, a variety of methodologies and drugs such as cabazitaxel and sipuleucel‐T have been approved globally for the treatment of CRPC. Two novel drugs, abiraterone acetate and enzartamide, have also become available as potential treatment options. However, the anticancer effects of these two drugs are not always satisfactory in terms of prolonging survival. These drugs are also associated with adverse events and are expensive when compared with the costs of previously used anticancer drugs. In this section, we pay particular attention to hormonal therapies that do not include the use of abiraterone acetate or enzartamide. We believe that a detailed understanding of the range of currently available hormonal therapies, including their associated benefits and limitations, is important for supporting the prolongation of survival in patients with advanced prostate cancer. Therefore, this section offers a valuable discussion on the treatment strategies for prostate cancer including CRPC

The FTO genotype as a useful predictor of body weight maintenance: Initial data from a 5-year follow-up study

ObjectiveWe examined associations between the fat-mass and obesity-associated (FTO) gene (rs9939609) and any weight change over a 5-year period following a 14-week lifestyle intervention among middle-aged Japanese women.Materials/MethodsOne hundred twenty-eight Japanese women (BMI > 25 kg/m2) participated in a 14-week weight loss intervention between 2004 and 2006. Of the participants, 62 consented to the 5-year follow-up measurement session. Of these women, 47 women who achieved a weight loss of at least 10% from their baseline values during the 14-week intervention were included in the analysis. Body weight, body fat, abdominal fat assessed by CT scans, and metabolic risk factors (i.e., blood pressure, lipids, and glucose) were measured at baseline, post-intervention, and at the 5-year follow-up.ResultsDuring the 5-year non-intervention period, increases in body weight, fat mass, total abdominal fat, and subcutaneous abdominal fat were significantly greater in subjects with the homozygous minor allele (AA genotype, n = 4; 8.5%) than in those with the homozygous major allele (TT genotype, n = 31; 66.0%) or heterozygous allele (TA genotype, n = 12; 25.5%). In multiple regression analyses, the variation in rs9939609 was a significant and independent predictor (P < 0.001) for regaining weight during the 5-year follow-up.ConclusionsOur data suggest that Japanese women with the risk allele (AA) of rs9939609 may have more difficulty preventing fat gain from reoccurring after weight loss intervention than women with the other genotypes

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning

AbstractAllogeneic hematopoietic stem cell transplantation (allo-SCT) using post-transplant cyclophosphamide (PTCy) is increasingly performed. We conducted a multicenter phase II study to evaluate the safety and efficacy of PTCy-based HLA-haploidentical peripheral blood stem cell transplantation (PTCy-haploPBSCT) after busulfan-containing reduced-intensity conditioning. Thirty-one patients were enrolled; 61% patients were not in remission and 42% patients had a history of prior allo-SCT. Neutrophil engraftment was achieved in 87% patients with a median of 19 days. The cumulative incidence of grades II to IV and III to IV acute graft-versus-host disease (GVHD) and chronic GVHD at 1 year were 23%, 3%, and 15%, respectively. No patients developed severe chronic GVHD. Day 100 nonrelapse mortality (NRM) rate was 19.4%. Overall survival, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year. Subgroup analysis showed that patients who had a history of prior allo-SCT had lower engraftment, higher NRM, and lower overall survival than those not receiving a prior allo-SCT. Our results suggest that PTCy-haploPBSCT after busulfan-containing reduced-intensity conditioning achieved low incidences of acute and chronic GVHD and NRM and stable donor engraftment and low NRM, particularly in patients without a history of prior allo-SCT

A Pooled Analysis of Multicenter Cohort Studies of 123I-mIBG Imaging of Sympathetic Innervation for Assessment of Long-Term Prognosis in Heart Failure

ObjectivesThe study objectives were to create a cardiac metaiodobenzylguanidine (mIBG) database using multiple prospective cohort studies and to determine the quantitative iodine-123–labeled mIBG indices for identifying patients with chronic heart failure (HF) at greatest and lowest risk of lethal events.BackgroundAlthough the prognostic value of cardiac mIBG imaging in patients with HF has been shown, clinical use of this procedure has been limited. It is required to define universally accepted quantitative thresholds for high and low risk that could be used as an aid to therapeutic decision-making using a large cohort database.MethodsSix prospective HF cohort studies were updated, and the individual datasets were combined for the present patient-level analysis. The database consisted of 1,322 patients with HF followed up for a mean interval of 78 months. Heart-to-mediastinum ratio (HMR) and washout rate of cardiac mIBG activity were the primary cardiac innervation markers. The primary outcome analyzed was all-cause death.ResultsLethal events were observed in 326 patients, and the population mortality rate was 5.6%, 11.3%, and 19.7% at 1, 2, and 5 years, respectively. Multivariate Cox proportional hazard model analysis for all-cause mortality identified age (p < 0.0001), New York Heart Association (NYHA) functional class (p < 0.0001), late HMR of cardiac mIBG activity (p < 0.0001), and left ventricular ejection fraction (LVEF) (p = 0.0029) as significant independent predictors. Analysis of the 512-patient subpopulation with B-type natriuretic peptide (BNP) results showed BNP (p < 0.0001), greater NYHA functional class (p = 0.0002), and late HMR (p = 0.0011) as significant predictors, but LVEF was not. The receiver-operating characteristic–determined threshold of HMR (1.68) identified patients at significantly increased risk in any LVEF category. Survival rates decreased progressively with decreasing HMR, with 5-year all-cause mortality rates >7% annually for HMR <1.25, and <2% annually for HMR ≥1.95. Addition of HMR to clinical information resulted in a significant net reclassification improvement of 0.175 (p < 0.0001).ConclusionsPooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk

Expression of Standard CD44 in Advanced Gastric Cancer: Relationship with Metastasis to Lymph Nodes

Standard CD44 (CD44s) is reported to play an important role in determining the malignant potential of various carcinomas. The aim of the present study was to evaluate CD44s expression in T2-T3 gastric cancer (Japanese Classification of Gastric Cancer stages MP, SS, SE) and the relationship between CD44s expression and clinicopathological parameters. CD44s expression was measured using immunohistochemistry in tumors from 98 patients with primary gastric cancer. Cases were categorized into two groups based on CD44s staining; the CD44s positive group had > 10% positively stained tumor cells and the CD44s negative group had < 10%. CD44s positivity was demonstrated in 59.1% (58/98) of tumors. CD44s expression showed no significant relationship with patient age or gender, or tumor location, size or macroscopic/microscopic classification. However, CD44s expression showed a significantly negative relationship with metastasis to lymph nodes (p < 0.0001). Thus, in T2-T3 gastric cancer, loss of CD44s expression suggests that metastasis of the tumor to lymph nodes is likely

Three Cases of Noninvasive Carcinoma ex Pleomorphic Adenoma of the Parotid Gland and a Literature Survey Focusing on their Clinicopathologic Features

Only 30 cases of non-invasive carcinoma ex pleomorphic adenoma have been reported in the English language literature. Here, we report on three cases of non-invasive carcinoma ex pleomorphic adenoma. Only one of the 33 patients showed recurrence or metastasis after surgery most likely as a result of benign pleomorphic adenoma. Pleomorphic adenoma with focal areas showing malignant changes should be carefully assessed by serial sectioning. The prognosis and therapeutic appoach will depend on evidence of capsular invasion. HER-2/neu is a useful marker in the differential diagnosis of pleomorphic adenoma versus noninvasive carcinoma ex pleomorphic adenoma

Expression of HER2, EGFR, CD44, PPARγ and AR in Salivary Cancer-immunohistochemical Analysis Focusing on the Possibility of Specialized Molecular-targeted and Hormonal Therapy for Different Histological Subtypes

The aim of this study was to determine the expression of human epidermal growth factor receptor type 2 (HER2), epidermal growth factor receptor (EGFR), peroxisome proliferator-activated receptor γ (PPARγ), CD44 and androgen receptor (AR) in adenoid cystic carcinomas (ACC), carcinoma ex pleomorphic adenomas (CXPA) and mucoepidermoid carcinomas (MEC) of the salivary glands, to investigate their molecular difference and to estimate the availability of molecular-targeted and hormonal therapy in salivary-gland tumors. Forthy patients with a salivary gland tumor, diagnosed and treated at our hospital, were studied. On the basis of histopathology, 10, 19 and 11 patients were identified with ACC, CXPA and MEC, respectively. The associations between histological types were evaluated by the chi-square test. Differences were considered statistically significant at P < 0.05. HER2-positive expression was observed in 10% of ACC, 84% of CXPA and 18% of MEC. EGFR-positive expression was observed in 40% of ACC, 68% of CXPA and 91% of MEC. CD44-positive expression was observed in 40% of ACC, 47% of CXPA and 91% of MEC. PPARγ-positive expression was observed in 10% of ACC, 53% of CXPA and 18% of MEC. AR-positive expression was observed in 20% of ACC, 32% of CXPA and 9% of MEC. Compared with other histological types, CXPA demonstrated significant HER2 and PPARγ staining and MEC demonstrated significant EGFR and CD44 staining. The differences in expression of markers between histological types in our study suggests the possibility that HER2- and PPARγ-targeted therapy may be effective in CXPA, and that EGFR-target therapy may be effective in MEC of the salivary glands