Masatoshi Kida

University of Vermont, Burlington, Vermont, United States

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Publications (17)69.45 Total impact

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    ABSTRACT: Intraprostatic injection of ethanol has been previously tested in clinical trials as a potential treatment of BPH, with variable outcomes. As evident from animal studies, the inconsistency was owing to various degrees of ethanol backflow along the needle tract. In acute canine experiments, we previously documented that using convection enhanced delivery (CED) eliminates backflow and improves ethanol distribution. The goal of this study was to compare the diffusion pattern between a microporous hollow fiber catheter (MiHFC) and a standard needle in human prostates from organ donors. Prostates were harvested from cadaveric organ donors immediately after removal of organs for transplant. After trimming off excess fat and weighing, prostates were injected with absolute ethanol. The total injected volume was 25% of the calculated prostate volume. One lateral lobe was injected using a single lumen 21-gauge control needle. The contralateral lobe was injected with the same volume but using a MiHFC. Immediately after injection, prostates were fixed en bloc in 10% neutral-buffered formalin, and then sectioned. Three-dimensional reconstruction was performed to determine lesion volume based on hematoxylin- and eosin-stained cross-sections. Three fresh human prostates were harvested and injected. The time from harvest to intraprostatic injection was 15-35 min. The lesion created by the MiHFC was 1.14±0.52 cm3, whereas that from the control needle was 0.28±0.10 cm3 (P=0.038). No backflow was observed along the needle tract of the MiHFC. This study shows that freshly harvested human prostates can be used to evaluate new treatments using intraprostatic injection. Similar to in vivo canine experiments, the ethanol lesion sizes were significantly bigger with the use of a MiHFC when compared with a standard single lumen needle.Prostate Cancer and Prostatic Disease advance online publication, 26 May 2015; doi:10.1038/pcan.2015.24.
    No preview · Article · May 2015 · Prostate Cancer and Prostatic Diseases
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    Full-text · Dataset · Jan 2015
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    ABSTRACT: Objectives To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents.Methods Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry.ResultsMicrophotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent.Conclusions The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.
    No preview · Article · Jan 2015 · International Journal of Urology
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    ABSTRACT: A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (Ptrend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. Cancer Res; 74(20); 5808-18. ©2014 AACR.
    Full-text · Article · Oct 2014 · Cancer Research

  • No preview · Article · Oct 2013 · European Urology Supplements
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    Full-text · Dataset · Aug 2013
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    ABSTRACT: A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multivariable linear regression (P = 6.46×10−11; n = 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P = 3.10×10−5; n = 173) and T1 (P = 2.64×10−5; n = 60), and muscle-invasive tumors, stages T2 (P =.01; n = 23) and T3/4 (P =.03; n = 22). The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008. Future clinical studies will be needed to validate PSCA as a therapeutic target for bladder cancer.
    Full-text · Article · Dec 2012 · Journal of the National Cancer Institute
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    ABSTRACT: Cell-cycle proteins are important predictive markers in urothelial carcinoma but may also exhibit exposure-specific heterogeneity. Tumor tissue from 491 bladder cancer cases enrolled in the Maine and Vermont component of the New England Bladder Cancer Study was assembled as tissue microarrays and examined for aberrant expression of p53, p63, p16, cyclin D1, Rb, and Ki-67. The association between expression and histopathology, demographics, and cigarette smoking was examined using χ(2) tests, multivariable Poisson, and multinomial regression models. We found that overexpression of p53 and Ki-67 was associated with high-stage/grade tumors [relative risk (RR), 1.26; P(trend) = 0.003; and RR, 3.21; P(trend) < 0.0001, respectively], whereas expression of p63 and p16 was decreased in high-stage/grade tumors (RR, 0.52; P(trend) < 0.0001; and RR, 0.88; P(trend) = 0.04, respectively). No significant aberrations of cell-cycle proteins were identified using various smoking variables and multiple statistical models. The results of this population-based study of histologically confirmed urothelial carcinomas show significant aberration of cell-cycle proteins p53, p63, p16, and Ki-67, but not Rb or cyclin D1. p53 showed the most significant heterogeneity with respect to tumor stage and grade, especially when stratified for different staining intensities using novel digital image analysis techniques. Our findings do not support that smoking modifies expression of cell-cycle proteins. Impact: Our study shows significant heterogeneity in the expression of key cell-cycle proteins that are associated with disease progression in bladder cancer. Further studies may lead to the identification of biomarkers and their multiplexed interactions as useful prognostic and therapeutic targets. Cancer Epidemiol Biomarkers Prev; 21(9); 1555-64. ©2012 AACR.
    No preview · Article · Jul 2012 · Cancer Epidemiology Biomarkers & Prevention

  • No preview · Conference Paper · Jun 2012
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    ABSTRACT: Evidence suggests that global methylation levels in blood cell DNA may be a biomarker for cancer risk. To date, most studies have used genomic DNA isolated from blood or urine as a surrogate marker of global DNA methylation levels in bladder tumor tissue. A subset of 50 bladder cancer cases was selected from the New England Bladder Cancer Case-Control Study. Genomic DNA was isolated from buffy coat, buccal cells, serum, and formalin-fixed, paraffin-embedded tissue for each participant. DNA methylation at four CpG sites within the long interspersed nucleotide element (LINE-1) repetitive element was quantified using pyrosequencing and expressed as a mean methylation level across sites. Overall, the mean percent (%) LINE-1 5-methylcytosine (%5MeC) level was highest in serum (80.47% ± 1.44%) and lowest in bladder tumor DNA (61.36% ± 12.74%) and levels varied significantly across tissue types (P = 0.001). An inverse association between LINE-1 mean %5MeC and tumor stage (P = 0.001) and grade (P = 0.002) was observed. A moderate correlation between patient-matched serum and buffy coat DNA LINE-1 %5MeC levels was found (r = 0.32, P = 0.03) but levels were uncorrelated among other matched genomic DNA samples. The mean promoter LINE-1 %5MeC measurements were correlated between buffy coat and serum DNA samples. No correlation was observed between genomic DNA sources and tumor tissues; however a significant inverse association between tumor percent LINE-1 methylation and tumor stage/grade was found. LINE-1 methylation measured in case blood DNA did not reflect that observed in bladder tumor tissue but may represent other factors associated with carcinogenesis.
    Preview · Article · Apr 2012 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: We investigate the distribution of bladder tumor category and stage in Northern New England by geographic region, smoking status and over time. 1091 incident bladder cancer cases from the New England Bladder Cancer Study (NEBCS), a large population-based case-control study carried out in Maine, New Hampshire and Vermont (2001-2004), and 680 bladder cancer cases from previous case-control studies in New Hampshire (1994-2000) were used in the analysis. Of 1091 incident bladder cancer cases from the NEBCS, 26.7% of tumors were papillary urothelial neoplasms of low malignant potential (PUNLMP), 26.8% low-grade papillary urothelial carcinomas (PUC-LG), 31.3% high-grade papillary urothelial carcinomas (PUC-HG), 9.1% non-papillary urothelial carcinomas (non-PUC), and 4.3% carcinoma in situ (CIS). Approximately 70% of cases were non-invasive (Tis/Ta), and all PUNLMP cases were of the Ta category. By contrast, half of all PUC-HG carcinomas were invasive. Short-term time trend analysis within the NEBCS (2001-2004) indicated an increase in the percentage of PUNLMP (p-trend<0.0001) paralleled by a decrease in PUC-LG (p-trend=0.02), and for PUC-LG an increase in the percentage of non-invasive tumors (p-trend 0.04). Our findings suggest possible short-term trends with an increase in the percentage of PUNLMP and a change in the percentage of PUC-LG towards non-invasive disease.
    Preview · Article · Apr 2012
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    ABSTRACT: Transurethral intraprostatic ethanol chemoablation of the prostate has shown promising preliminary clinical results for benign prostatic hyperplasia with some variability in clinical outcome. This is likely due to the uneven prostate diffusion caused by varying resistance of the tissue type in which the tip of the needle is embedded. We examined whether the distribution of the injectable in the canine prostate could be improved using a microporous hollow fiber catheter (Twin Star Medical, Minneapolis, Minnesota). The prostate was exposed in 9 mongrel dogs. A single injection of 98% ethanol was delivered in each lobe using a microporous hollow fiber catheter and a standard needle. Prostates were harvested and fixed in 10% formalin. After injection 2.5 mm step sections were obtained and scanned. The ethanol induced tissue lesions were traced on hematoxylin and eosin sections. Three-dimensional reconstructions were created and the volume of each prostate lesion was calculated using stereology. Ethanol induced tissue changes were seen bilaterally in 8 of 9 ethanol injected prostates. In all cases the lesion created by microporous hollow fiber catheter injection was larger than that in the contralateral lobe injected with the control needle. When data were pooled, the hollow fiber catheter injection produced significantly greater tissue changes than the control needle injection (p = 0.03). Improved distribution and absent backflow were seen when using the microporous hollow fiber catheter, supporting its potential as a new method to treat prostate disease.
    No preview · Article · Mar 2012 · The Journal of urology
  • Karolyn B Bell · Masatoshi Kida · Kumarasen Cooper

    No preview · Article · Nov 2011 · Histopathology
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    ABSTRACT: Epithelioid angiomyolipomas (perivascular epithelioid cell tumors) of the kidney are defined as potentially malignant mesenchymal lesions that are closely related to classic angiomyolipoma. Although approximately 120 cases are published, mostly as case reports with variably used diagnostic criteria, the pathologic prognostic predictors of outcome are unknown. We analyzed the clinicopathologic parameters in a large series of 41 cases of pure epithelioid angiomyolipomas of the kidney, which we designate as pure (monotypic) epithelioid PEComas to contrast them from classic angiomyolipomas that are regarded by some as PEComas. We use the terminology “pure” to separate these cases from those that may have variable epithelioid components. The mean age of the patients was 40.7 years (range, 14 to 68 y). The male-to-female ratio was 1:1. Seventy-nine percent of patients were symptomatic at presentation with metastatic disease at onset in 12 cases. Follow-up and/or disease progression information were available for 33 of 41 cases (mean, 44.5 mo and median, 24.5 mo; range, 4 to 240); 9 patients had a history of associated tuberous sclerosis. Recurrence and metastasis were seen in 17% and 49% of patients; 33% of patients died of disease. Lymph node involvement was seen in 24% of patients; the liver (63%), lung (25%), and mesentery (18.8%) were the most common metastatic sites. Clinicopathologic parameters associated with disease progression (recurrence, metastasis, or death due to disease) in univariate analysis included associated tuberous sclerosis complex or concurrent angiomyolipoma (any metastasis, P=0.046), necrosis (metastasis at diagnosis, P=0.012), tumor size >7 cm (progression, P=0.021), extrarenal extension and/or renal vein involvement (progression, P=0.023), and carcinoma-like growth pattern (progression, P=0.040) (the 5 adverse prognostic parameters for pure epithelioid PEComas). Tumors with <2 adverse prognostic parameters (13 cases) were considered to be low risk for progression tumor, with 15% having disease progression. Tumors with 2 to 3 adverse prognostic parameters (14 cases) were considered to be “intermediate risk,” with 64% having disease progression. Tumors with more than 4 or more adverse prognostic parameters (6 cases) were considered to be high risk, with all patients having disease progression. Of tumors with 3 or more adverse prognostic parameters, 80% had disease progression. An exact logistic regression analytic model showed that only carcinoma-like growth pattern and extrarenal extension and/or renal vein involvement were significant predictors of outcome (P=0.009 and 0.033, respectively). Our data of a large series with uniform definitional criteria confirm the malignant potential for pure epithelioid PEComas and provide adverse prognostic parameters for risk stratification in these patients.
    Full-text · Article · Jan 2011 · American Journal of Surgical Pathology
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    ABSTRACT: Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case–control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the ‘null’ genotype) were 1.26 (0.85–1.88) and 1.54 (1.05–2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71–1.51), former (0.95; 0.75–1.20) or current smokers (1.33; 0.91–1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14–2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22–8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.
    Preview · Article · Oct 2010 · Carcinogenesis
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    Ryan Winters · Masatoshi Kida · Kumarasen Cooper

    Preview · Article · Nov 2007 · Journal of Clinical Pathology
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    ABSTRACT: To further assess the safety and feasibility of prostatic chemoablation with ethanol and to address previous concerns associated with transperineal injection using a canine model. The study included 25 dogs; normal saline or 98% dehydrated ethanol were injected into the prostate using both routes, at volumes of 25-50% of the total prostate volume. The prostate and adjacent structures were examined grossly and histopathologically after the dogs were killed humanely at 4 h, 7 days and 12 weeks after injection. Transperineal injection resulted in tissue necrosis in all prostates and significant extraprostatic necrosis in two of three animals treated. With transurethral injection, the control groups showed minimal change, whereas the group injected with ethanol resulted in lesions with variable necrosis and location. Intraprostatic chemoablation is possible with ethanol injection both transperineally and transurethrally. Transperineal ethanol injections were associated with more extraprostatic necrosis. Transurethral injections resulted in larger amounts of necrosis in the prostatic parenchyma with minimal extraprostatic effects. However, the extent of prostatic necrosis/ablation was inconsistent and further research is warranted.
    No preview · Article · Feb 2003 · BJU International

Publication Stats

203 Citations
69.45 Total Impact Points

Institutions

  • 2011-2015
    • University of Vermont
      • • Department of Surgery
      • • Department of Pathology
      Burlington, Vermont, United States
    • Charles University in Prague
      Praha, Praha, Czech Republic
  • 2007-2012
    • University of Vermont Medical Center
      Burlington, Vermont, United States