Kenji Zennami

Prostatic penetration of meropenem in humans, and dosage considerations for prostatitis based on a site-specific pharmacokinetic/pharmacodynamic evaluation

The aims of this study were to investigate the penetration of meropenem (MER) into human prostate tissue and to assess MER regimens for prostatitis by performing a site-specific pharmacokinetic/pharmacodynamic evaluation. Patients with prostatic hypertrophy (n=49) prophylactically received a 0.5-h infusion of MER (250 mg or 500 mg) before transurethral resection of the prostate. MER concentrations in plasma (0.5-5h) and prostate tissue (0.5-1.5h) were measured chromatographically. Concentration data were analysed pharmacokinetically with a three-compartment model and were used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (T>MIC, % of 24h) in prostate tissue, an indicator for antibacterial effects at the site of action. The prostate tissue/plasma ratio was 16.6% for the maximum drug concentration and 17.7% for the area under the drug concentration-time curve, irrespective of the dose. Against MIC distributions for clinical isolates of Escherichia coli, Klebsiella spp. and Proteus spp., 500 mg once daily achieved a >90% probability of attaining the bacteriostatic target (20% T>MIC) in prostate tissue, and 500 mg twice daily achieved a >90% probability of attaining the bactericidal target (40% T>MIC) in prostate tissue. However, against the Pseudomonas aeruginosa isolates, none of the tested regimens achieved a >90% probability of attaining the bacteriostatic or bactericidal targets.

Lactate dehydrogenase, Gleason score and HER-2 overexpression are significant prognostic factors for M1b prostate cancer

It has not been elucidated whether certain types of M1b prostate cancer (M1b PC) are associated with a poor outcome. The present study retrospectively identified predictive factors related to the outcome of M1b PC. The subjects were 104 patients who attended our hospital and received a diagnosis of M1b PC. The observation period ranged from 4 to 122 months (median, 43 months). The parameters investigated were: T classification, N classification, Gleason score (GS), pretreatment prostate-specific antigen (PSA) level, extent of disease (EOD) grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium, and hemoglobin (Hb) levels, platelet count, and the status of HER-2 overexpression as determined with a Hercep Test(TM) Kit using initial needle biopsy specimens for diagnosis. Log-rank test and Cox univariate analysis identified the following factors with statistically significant differences: pretreatment PSA ≥ 192, N1, GS ≥ 8, EOD grade 3+4, high LDH, high ALP, low Hb, and HER-2 overexpression. Multivariate Cox proportional hazard analysis identified the factors GS ≥ 8, high LDH, and HER-2 overexpression with significant differences. The hazard ratio was 5.962, 2.465, and 2.907, respectively, and the probability value was P=0.0218, P=0.0207 and P=0.0090, respectively. When the subjects with GS ≥ 8, high LDH, and HER-2 over-expression were classified as the high-risk group, the 5-year cause-specific survival rate was 51.2, 29.6, and 20.0%, respectively. The present study showed that M1b PC patients with GS ≥ 8, high LDH, and HER-2 overexpression have a very poor outcome and thus, should be treated as a high-risk group requiring close follow-up.

An immunohistochemical study of chromogranin A and human epidermal growth factor-2 expression using initial prostate biopsy specimens from patients with bone metastatic prostate cancer

To investigate, using prostate needle‐biopsy specimens at diagnosis from patients with bone metastatic prostate cancer, whether the relationship between neuroendocrine (NE) cell differentiation and human epidermal growth factor‐2 (HER‐2) expression is a prognostic factor for outcome.

Comparative investigation on clinical outcomes of robot-assisted radical prostatectomy between experienced open prostatic surgeons and novice open surgeons in a laparoscopically naïve center with a limited caseload

To compare perioperative, oncological and functional outcomes of robot‐assisted radical prostatectomy between experienced and novice open radical prostatectomy surgeons in a laparoscopically naïve center with a limited caseload.

Solitary brain metastasis from pT1, G3 bladder cancer

Abstract:u2003 Brain metastasis from bladder cancer occurs rarely. Particularly, solitary brain metastasis is very rare in patients who have never received systemic chemotherapy. We encountered a patient who underwent transurethral resection of bladder tumor and bacillus Calmette‐Guérin bladder instillation for pT1, G3 bladder cancer accompanied by carcinoma in situ, and subsequently revealed solitary brain metastasis after 34u2003months while neither cystoscopy nor urine cytology revealed abnormalities during this period. To our knowledge, our experience of solitary brain metastasis from pT1 bladder cancer is the second case in the world.

Determination of doripenem penetration into human prostate tissue and assessment of dosing regimens for prostatitis based on site-specific pharmacokinetic–pharmacodynamic evaluation

Abstract Prostatic hypertrophy patients prophylactically received a 0·5-hour infusion of doripenem (250 or 500 mg) before transurethral resection of the prostate. Doripenem concentrations in plasma and prostate tissue were measured chromatographically, and analysed pharmacokinetically using a three-compartment model. The approved doripenem regimens were assessed based on the time above the minimum inhibitory concentration for bacteria (T>MIC, % of 24 hours), an indicator for antibacterial effects, at the prostate. The prostate tissue/plasma ratios were 17·3% for the maximum drug concentration and 18·7% for the area under the drug concentration–time curve, and they were irrespective of the dose. Against Escherichia coli and Klebsiella species isolates, 500 mg once daily achieved a >90% probability of attaining the bacteriostatic target (20% T>MIC) in prostate tissue, and 500 mg twice daily achieved a >90% probability of attaining the bactericidal target (40% T>MIC) in prostate tissue.

Inflammatory pseudotumors of the kidney and the lung presenting as immunoglobulin G4-related disease: a case report

IntroductionIt has been reported that immunoglobulin G4-related systemic disease can spread to nearly every organ, and often presents as an inflammatory mass or masses at those sites. In the kidney, this disease is often diagnosed after a radical or partial nephrectomy following the discovery of an inflammatory mass which is often suspected to be a malignant tumor. Here, we present a rare case of inflammatory pseudotumors of the kidney and the lung presenting as immunoglobulin G4-related disease, which were diagnosed by computed tomography-guided biopsies.Case presentationA 54-year-old Japanese man was referred to our hospital with suspected bilateral renal cancer, multiple lung metastases and autoimmune pancreatitis. His serum immunoglobulin G4 level was high. We used computed tomography-guided biopsies and histopathological examinations of the biopsied specimens to diagnose the tumors as immunoglobulin G4-related bilateral renal and lung inflammatory pseudotumors. Our patient was treated with oral prednisolone, and after one month of treatment, contrast-enhanced computed tomography demonstrated a general improvement, as noted by a reduction in size of the masses.ConclusionRenal masses that are formed due to immunoglobulin G4-related disease require comprehensive diagnosis to prevent unnecessary surgical resections from being performed. Further consideration should be paid to immunoglobulin G4-related diseases in the future.

Penetration of piperacillin-tazobactam into human prostate tissue and dosing considerations for prostatitis based on site-specific pharmacokinetics and pharmacodynamics.

This study aimed to investigate the penetration of PIPC-TAZ into human prostate, and to assess effectiveness of PIPC-TAZ against prostatitis by evaluating site-specific PK-PD. Patients with prostatic hypertrophy (nxa0=xa047) prophylactically received a 0.5xa0h infusion of PIPC-TAZ (8:1.2-0.25xa0g or 4-0.5xa0g) before transurethral resection of the prostate. PIPC-TAZ concentrations in plasma (0.5-5xa0h) and prostate tissue (0.5-1.5xa0h) were analyzed with a three-compartment PK model. The estimated model parameters were, then used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (Txa0>xa0MIC, the PD indicator for antibacterial effects) in prostate tissue for six PIPC-TAZ regimens (2.25 or 4.5xa0g; once, twice, three times or four times daily; 0.5xa0h infusions). Prostate tissue/plasma ratio of PIPC was about 36% both for the maximum drug concentration (Cmax) and the area under the drug concentration-time curve (AUC). Against MIC distributions for isolates of Escherichia coli, Klebsiella species and Proteus species, regimens of 4.5xa0g twice daily and 2.25xa0g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% Txa0>xa0MIC) in prostate tissue; regimens of 4.5xa0g three times daily and 2.25xa0g four times daily achieved a >90% probability of attaining the bactericidal target for PIPC (50% Txa0>xa0MIC) in prostate tissue. However, against Pseudomonas aeruginosa isolates, none of the tested regimens achieved a >90% probability. PIPC-TAZ is appropriate for the treatment of prostatitis from the site-specific PK-PD perspective.

Significant prognostic factor of immunohistochemical HER-2 expression using initial prostate biopsy specimens with M1b prostate cancer.

We examined whether human epidermal growth factor‐2(HER‐2) overexpression could be a useful marker of outcome after hormone therapy in patients with M1b prostate cancer (PC).

A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system

Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16INK4a tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16INK4a functional peptide into 10 RCC lines, lacking expression of the p16INK4a molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96xa0h. Inxa0vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16INK4a peptide alone, however, inoculation of Wr-T and the p16INK4a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC.