ABSTRACT
This study aimed to develop a prostatic pharmacokinetic model of ceftazidime and suggest more effective dosing strategy for the bacterial prostatitis, based on a site-specific pharmacokinetic and pharmacodynamic perspective. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5-h infusion of 1.0 g or 2.0 g ceftazidime before transurethral resection of the prostate. Plasma and prostate samples were premeditatedly collected after the administration and the concentrations were measured by high-performance liquid chromatography. The prostate tissue/plasma ratio in area under the drug concentration-time curve was approximately 0.476. The prostatic population pharmacokinetic model incorporated creatinine clearance (CLcr) into ceftazidime clearance was developed, and adequately predicted prostate tissue concentrations by diagnostic scatter plots and visual predictive checks. Aiming for a bactericidal target of 70% of time above minimum inhibitory concentration (T > MIC) in prostate tissue, 2.0 g twice daily achieved ≥90% expected probability against main pathogens like Escherichia coli and Proteus species in patients regardless of renal function (CLcr = 60 and 90 mL/min). However, since the expected probability of attaining the bactericidal target of 0.5-h infusion dosing regimen did not achieve 90% against Pseudomonas aeruginosa in patients with CLcr = 60 and 90 mL/min, 4-h infusion dosing regimen of 2.0 g three times daily (6 g/day) might be required for empirical treatment. Based on site-specific simulations, the present study provides more effective dosing strategy for bacterial prostatitis.
ABSTRACT
BACKGROUND: Only 14 cases of leiomyoma with ureteral origin have been reported previously. Such primary leiomyomas often present as hydronephrosis, making the diagnosis difficult. Radical nephroureterectomy is often performed because of the possible diagnosis of a malignant tumor. We report the 15th case of primary leiomyoma with a ureteral origin. CASE PRESENTATION: A 51-year-old Japanese man presented with a chief complaint of asymptomatic gross hematuria with a history of hypertension. Enhanced computed tomography showed a tumor at the upper part of the right ureter that appeared to be the cause of hydronephrosis and contracted kidney; no retroperitoneal lymphadenopathy and distal metastasis were observed. A well-defined 20-mm (diameter) defect was identified at the upper of the right ureter on retrograde pyelogram with no bladder cancer on cystoscopy. Urine cytology and right divided renal urine cytology findings were negative. Laparoscopic nephroureterectomy was performed, and the extracted tumor measured 20 × 13 mm. Histopathological examination revealed primary leiomyoma with no recurrence 16 months after the operation. CONCLUSIONS: Preoperative examination with the latest available ureteroscopic technology can help preserve renal function in the case of benign tumors by enabling preoperative ureteroscopic biopsy or intraoperative rapid resection. Moreover, nephroureterectomy is recommended in the case of preoperative suspicion of ureteral malignant tumors.
Subject(s)
Leiomyoma , Ureter , Ureteral Neoplasms , Humans , Leiomyoma/diagnosis , Leiomyoma/diagnostic imaging , Male , Middle Aged , Neoplasm Recurrence, Local , Nephroureterectomy , Ureter/diagnostic imaging , Ureter/surgery , Ureteral Neoplasms/diagnostic imaging , Ureteral Neoplasms/surgeryABSTRACT
BACKGROUND: Extragonadal germ cell tumor (EGCT) is a relatively rare condition, reportedly representing 3-7% of all germ cell tumors. We report a patient who had metachronous testicular tumor with uncommon metastases 20 years after primary retroperitoneal EGCT treatment, along with a corresponding literature review. CASE PRESENTATION: A 49-year-old Japanese man visited our department in November 2017 with chief complaints of indolent right scrotum enlargement and a right inguinal mass. History showed that the patient visited our department of gastroenterology with chief complaints of blackish feces and ill complexion in February 1997. Computed tomography (CT) showed a right retroperitoneal tumor, which was removed in the same month. Histopathological examination showed a teratoma and yolk sac tumor. He was diagnosed with primary retroperitoneal EGCT and received three courses of chemotherapy (bleomycin/etoposide/cisplatin; BEP). Periodic imaging and the determination of tumor markers (alpha-fetoprotein [AFP], human chorionic gonadotropin [HCG], and lactate dehydrogenase [LDH]) showed no recurrence or metastasis during the 5 years postoperatively. Subsequently, he did not visit the outpatient ward. In August 1999, he underwent surgery of right hydrocele. Contrast-enhanced CT showed a 35-mm contrast effect with uneven content in the right testicle and enlarged nodes that raised suspicion for metastases in the right inguinal and right external iliac lymph nodes. All tumor markers were within normal ranges. He underwent right high orchiectomy and resection of the right inguinal lymph nodes in the same month. Histopathological findings revealed seminoma (pT1, pN2, M0, S0, and TNM stage IIB). He received postoperative chemotherapy, one course of BEP therapy, and three courses of etoposide and cisplatin therapy. Post-chemotherapy CT confirmed a complete clinical response at the right external iliac lymph nodes, and this response continued 12 months later. No recurrence or metastasis has been found so far. CONCLUSIONS: We report a patient in whom a testicular tumor with uncommon metastases occurred 20 years after primary retroperitoneal EGCT treatment. After EGCT treatment, testicular relapses tend to occur after relatively long-term follow-up. After EGCT treatment, such patients must be closely monitored for testicular recurrences and onset of testicular tumor.
Subject(s)
Neoplasms, Germ Cell and Embryonal , Seminoma , Testicular Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasms, Germ Cell and Embryonal/therapy , Orchiectomy , Testicular Neoplasms/drug therapy , Testicular Neoplasms/surgeryABSTRACT
This study aims to define the penetration of ampicillin and sulbactam into prostate tissue, develop a prostatic pharmacokinetic model of each drug, and assess the appropriateness of ampicillin-sulbactam regimens for the treatment of prostatitis and the prophylaxis of postoperative infection, based on a pharmacokinetic and pharmacodynamic simulation. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5-hour infusion of 1.5 g (1:0.5 g) or 3 g (2:1 g) ampicillin-sulbactam before transurethral resection of the prostate. Ampicillin and sulbactam concentrations in plasma and prostate tissue were measured. The prostate tissue/plasma ratios of both ampicillin and sulbactam were approximately 0.37 (area under the drug concentration-time curve), and penetration was similar. The prostatic population pharmacokinetic model, which included a covariate analysis, adequately predicted prostate tissue concentrations in our patient population. For therapeutic use, aiming for a bactericidal target of 50% of time above minimum inhibitory concentration (T > MIC) in prostate tissue, 3 g ampicillin-sulbactam 4 times daily achieved ≥90% expected probability against only Enterococcus faecalis in typical patients with a creatinine clearance (CLcr ) of 30 mL/min. For prophylactic use, aiming for a bacteriostatic target of 30% T > MIC, 3 g ampicillin-sulbactam 4 times daily achieved ≥90% expected probability of attaining the bacteriostatic target against E. faecalis and Proteus species when CLcr was 30 mL/min. Based on prostatic simulations, the present study provides helpful recommendations for the treatment of bacterial prostatitis and preoperative prophylaxis in prostatectomy.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis/methods , Prostatitis/drug therapy , Aged , Ampicillin/pharmacokinetics , Ampicillin/pharmacology , Ampicillin/therapeutic use , Anti-Bacterial Agents/pharmacology , Creatinine/blood , Dose-Response Relationship, Drug , Humans , Male , Microbial Sensitivity Tests , Models, Biological , Prospective Studies , Prostate/drug effects , Sulbactam/pharmacokinetics , Sulbactam/pharmacology , Sulbactam/therapeutic use , Transurethral Resection of Prostate/methodsABSTRACT
Background: Recently, two techniques of robot-assisted radical prostatectomy (RARP), which preserve dorsal vein complex (DVC), endopelvic fascia, and full neurovascular bundle (NVB), through anterior approach were reported. The techniques in a relatively large workspace seem less technically demanding than Retzius-sparing RARP. In this case report, we present a further modified technique of transperitoneal-anterior-antegrade approach with a division of the endopelvic fascia to reduce the technical demands. Case Presentation: In a routine evaluation, a 65-year-old man was shown to have a prostate-specific antigen level of 5.07 ng/mL. Prostatic biopsy revealed a Gleason score of 6 (3 + 3) adenocarcinoma in 2 of the 12 specimens, and the clinical stage was diagnosed as cT2aN0M0. RARP was performed including transperitoneal full NVB sparing, antegrade preservation of DVC, and division of endopelvic fascia to increase the prostate mobility and reduce technical demands. The patient completely gained continence on the day after removal of the catheter, and potency was recovered 30 days after surgery. Conclusion: Our DVC preservation technique in the transperitoneal-anterior-antegrade approach with a division of the endopelvic fascia during RARP may be safe, reduce technical demands, and facilitate early recovery of continence and sexual function after surgery.
ABSTRACT
A 49-year-old male visited our department of gastroenterology with chief complaints of blackish feces and ill complexion in February 1997. Computed tomography (CT) revealed a right retroperitoneal tumor, which was removed the same month. Histopathological examination showed teratoma and yolk sac tumor. He was diagnosed with primary retroperitoneal extragonadal germ cell tumor, and received three cycles of chemotherapy (bleomycin/etoposide/cisplatin ; BEP) starting in March 1997. Periodic imaging and determination of tumor markers (α fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) showed no recurrence or metastasis for five years after treatment. After his visit in April 2002 he stopped visiting our outpatient ward. In November 2017, the patient visited our department with chief complaints of indolent right scrotum enlargement and a right inguinal mass. Past history showed that he had undergone hydrocele of the right testicle in August 1999. Contrast enhanced CT showed a 35-mm contrast effect with uneven contents in the right testis, and enlarged nodes that were suspicious of metastases in the right inguinal and right external iliac lymph nodes. All tumor markers were within the normal ranges. He underwent right high orchiectomy and resection of the right inguinal lymph nodes in the same month. Histopathological findings revealed seminoma (pT1, pN2, M0, S0, and clinical Stage IIA). He received postoperative chemotherapy starting in January 2018 ; one cycle of BEP therapy and three cycles of etoposide and cisplatin (EP) therapy. Post-chemotherapeutic CT confirmed clinical complete response at the right external iliac lymph nodes, and this response was confirmed 12 months later. Neither recurrence nor metastasis has occurred so far.
Subject(s)
Neoplasms, Germ Cell and Embryonal , Retroperitoneal Neoplasms , Testicular Neoplasms/surgery , Antineoplastic Combined Chemotherapy Protocols , Bleomycin , Cisplatin/therapeutic use , Etoposide/therapeutic use , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , OrchiectomyABSTRACT
Flomoxef is used to treat bacterial prostatitis; however, its prostatic pharmacokinetics have not been fully clarified. Flomoxef (500 or 1000 mg) was administered to patients with benign prostatic hypertrophy (n = 54). After a 0.5-h infusion, venous blood samples were drawn at time points of 0.5-5 h, and prostate tissue samples were collected at time points of 0.5-1.5 h during transurethral resection of the prostate. The drug concentrations in plasma and prostate tissue were analyzed pharmacokinetically and used for a stochastic simulation to predict the probability of attaining pharmacodynamic target in prostate tissue. Showing dose linearity in the prostatic pharmacokinetics, flomoxef rapidly penetrated into prostate tissue, with a prostate/plasma ratio of 0.48-0.50 (maximum drug concentration) and 0.42-0.55 (area under the drug concentration-time curve). Against the tested populations of Escherichia coli, Klebsiella and Proteus species isolates, 0.5-h infusion of 1000 mg three times daily achieved a ≥90% expected probability of attaining the bactericidal target (70% of the time above the minimum inhibitory concentration [MIC]) in prostate tissue. The site-specific pharmacodynamic-based breakpoint (the highest MIC at which the target-attainment probability in prostate tissue was >90%) values were 0.25 mg/L (MIC for 90th percentile of E. coli and Klebsiella species) for 500 mg four times daily and 0.5 mg/L (MIC90 of Proteus species) for 1000 mg four times daily. These results help to fully characterize the prostatic pharmacokinetics of flomoxef, while also helping to rationalize and optimize the dosing regimens for prostatitis based on site-specific pharmacodynamic target attainment.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cephalosporins/pharmacokinetics , Prostatic Hyperplasia/drug therapy , Prostatitis/drug therapy , Aged , Anti-Bacterial Agents/administration & dosage , Cephalosporins/administration & dosage , Escherichia coli/drug effects , Humans , Klebsiella/drug effects , Male , Microbial Sensitivity Tests , Middle Aged , Prospective Studies , Prostate/microbiology , Prostate/surgery , Prostatic Hyperplasia/blood , Prostatic Hyperplasia/surgery , Prostatitis/blood , Prostatitis/microbiology , Prostatitis/surgery , Proteus/drug effects , Transurethral Resection of ProstateABSTRACT
Liposarcomas are most commonly found in the extremities, in the retroperitoneum and, less often, in the head and neck area. The spermatic cord is a rare site of origin, accounting for about 4-7% of all liposarcomas. We report a case of dedifferentiated liposarcoma of the spermatic cord. A 51-year-old man was referred to our hospital for a painless hard mass in the left inguinal region. Abdominal computed tomography showed a left spermatic cord mass measuring 70 mm in diameter. We performed left high orchiectomy with resection of the mass. Immunohistochemical analysis revealed positive for murine double minute 2 (MDM 2) and cyclin dependent kinase 4 (CDK 4). Therefore, this sarcoma was diagnosed to be dedifferentiated liposarcoma. Since the surgical margin was positive, an additional wide resection including the surrounding normal tissue was performed. Complete excision was achieved after re-resection. He was alive 12 months postoperatively without any signs of recurrence. Dedifferentiated liposarcoma of the spermatic cord is a rare neoplasm. To the best of our knowledge, the present case is the 14th reported case in Japan.
Subject(s)
Genital Neoplasms, Male , Liposarcoma , Spermatic Cord , Humans , Japan , Male , Middle Aged , Neoplasm Recurrence, LocalABSTRACT
BACKGROUND: Regulatory T cells (Tregs) play important roles in the suppression of immune responses, including antitumor immune responses. C-C chemokine receptor 4 (CCR4) is highly expressed on effector Tregs, and anti-CCR4 antibody is attracting attention as a novel immunotherapeutic agent for solid tumors. This study aimed to evaluate the expression of CCR4-positive Tregs (CCR4+Tregs) in prostate cancer and estimate the clinical potential of CCR4-targeting therapy for prostate cancer. METHODS: A total of 15 radical prostatectomy (RP) specimens and 60 biopsy specimens from individuals diagnosed with prostate cancer were analyzed to evaluate the infiltration of CCR4+Tregs in prostate cancer. The relationships between the number of CCR4+Tregs and clinical parameters were investigated in RP and biopsy specimens. Moreover, the total number of Tregs, CCR4+Tregs, and T cells and the ratio of CCR4+Tregs to Tregs and T cells in biopsy specimens were compared between patients with poor prognosis who progressed to castration-resistant prostate cancer (CRPC) within 12 months (n = 13) and those with good prognosis who were stable with hormone-sensitive prostate cancer over 12 months (n = 47). Furthermore, biopsy specimens were divided into two groups: low and high CCR4+Treg expression groups and the prognosis was compared between them. RESULTS: There was a higher expression of CCR4+Tregs in RP specimens with a higher (≥8) Gleason score than in those with a lower (<8) Gleason score (P = .041). In biopsy specimens, 65.9% Tregs were positive for CCR4. The number of CCR4+Tregs positively correlated with clinical stage (P < .001) and Gleason score (P = .006). The total number of Tregs and CCR4+Tregs significantly increased in the poor prognosis group compared with that in the good prognosis group (P = .024 and .01, respectively). Furthermore, patients with lower CCR4+Treg expression levels showed a significantly longer time to progression to CRPC (not reached vs 27.3 months; P < .001) and median survival time (not reached vs 69.0 months; P = .014) than those with higher expression levels. CONCLUSIONS: CCR4+Tregs are highly infiltrated in the prostate tissue of patients with poor prognosis with potential to progress to CRPC. Furthermore, the degree of infiltration of CCR4+Tregs is related to the prognosis of prostate cancer.
Subject(s)
Prostatic Neoplasms/pathology , Receptors, CCR4/analysis , T-Lymphocytes, Regulatory/chemistry , T-Lymphocytes, Regulatory/pathology , Aged , Biopsy , Humans , Immunotherapy , Male , Middle Aged , Neoplasm Grading , Prognosis , Prostatectomy , Prostatic Neoplasms/surgery , Prostatic Neoplasms, Castration-Resistant/pathology , T-Lymphocytes, Regulatory/immunologyABSTRACT
Docetaxel (DOC) is one of the most effective chemotherapeutic agents against castrationresistant prostate cancer (CRPC). Despite an impressive initial clinical response, the majority of patients eventually develop resistance to DOC. In tumor metabolism, where tumors preferentially utilize anaerobic metabolism, lactate dehydrogenase (LDH) serves an important role. LDH controls the conversion of pyruvate to lactate, with LDHA, one of the predominant isoforms of LDH, controlling this metabolic process. In the present study, the role of LDHA in drug resistance of human prostate cancer (PC) was examined by analyzing 4 PC cell lines, including castrationproviding strains PC3, DU145, LNCaP and LNCSS (which is a hormone refractory cell line established from LNCaP). Sodium oxamate (SO) was used as a specific LDHA inhibitor. Changes in the expression level of LDHA were analyzed by western blotting. Cell growth and survival were evaluated with a WST1 assay. Cell cycle progression and apoptotic inducibility were evaluated by flow cytometry using propidium iodide and Annexin V staining. LDH expression was strongly associated with DOC sensitivity in PC cells. SO inhibited growth of PC cells, which was considered to be caused by the inhibition of LDHA expression. Synergistic cytotoxicity was observed by combining DOC and SO in LNCSS cells, but not in LNCaP cells. This combination treatment induced additive cytotoxic effects in PC3 and DU145 cells, caused cell cycle arrest in G2M phase and increased the number of cells in the subG1 phase of cell cycle in LNCSS cells. SO promoted DOC induced apoptosis in LNCSS cells, which was partially caused by the inhibition of DOCinduced increase in LDHA expression. The results strongly indicated that LDHA serves an important role in DOC resistance in advanced PC cells and inhibition of LDHA expression promotes susceptibility to DOC, particularly in CRPC cells. The present study may provide valuable information for developing targeted therapies for CRPC in the future.
Subject(s)
Docetaxel/pharmacology , Enzyme Inhibitors/pharmacology , L-Lactate Dehydrogenase/antagonists & inhibitors , Oxamic Acid/pharmacology , Prostatic Neoplasms, Castration-Resistant/enzymology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Down-Regulation , Drug Resistance, Neoplasm/drug effects , Drug Synergism , Gene Expression Regulation, Neoplastic , Humans , Male , Prostatic Neoplasms, Castration-Resistant/drug therapyABSTRACT
OBJECTIVES: To evaluate the impact of a novel biopsy instrument that extends the length of the side-notch on the detection of prostate cancer in transrectal needle biopsy. METHODS: We collaborated with a biopsy needle manufacturer and developed a novel biopsy instrument (PRIMECUT II long-notch type) with a 25-mm side-notch length and 28-mm stroke length to take longer tissue cores. The sampled core length, cancer detection rate, pain and complications of 489 patients who underwent transrectal biopsy using the long-notch needle were compared with those of 469 patients who underwent biopsy using a normal instrument with a 19-mm side-notch length and 22-mm stroke length. RESULTS: The mean length of tissue taken by the long-notch needle was significantly longer than that of tissue taken by the normal-notch needle (16.3 vs 22.4 mm, P < 0.001). The overall cancer detection rate was 42.0% for the normal-notch needle and 51.1% for the long-notch needle (P = 0.005). In patients with a prostate volume of 20-40 mL, the cancer detection rate for the long-notch needle was especially higher than that for the normal-notch needle (74.2% vs 47.5%, P < 0.001). Multivariate analysis showed that the long-notch needle improved cancer detection significantly (odds ratio 1.702, P < 0.001). There were no differences of pain during biopsy and complication between the two groups. CONCLUSIONS: The novel biopsy instrument with a 25-mm side-notch can take longer tissue samples safely and has a significantly higher rate of prostate cancer detection in transrectal biopsy.
Subject(s)
Biopsy, Needle/instrumentation , Prostate/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , Aged , Biopsy, Needle/adverse effects , Equipment Design , Humans , Japan/epidemiology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Pain/etiology , Pain MeasurementABSTRACT
The present study examined the clinical pharmacokinetics of pazufloxacin in prostate tissue and estimated the probability of target attainment for tissue-specific pharmacodynamic goals related to treating prostatitis using various intravenous dosing regimens. Patients with prostatic hypertrophy received prophylactic infusions of pazufloxacin (500 mg, n = 23; 1000 mg, n = 25) for 0.5 h prior to transurethral prostate resection. Drug concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were measured by high-performance liquid chromatography and used for subsequent noncompartmental and three-compartmental analysis. Monte Carlo simulation was performed to evaluate the probability of target attainment of a specific minimum inhibitory concentration (MIC) in prostate tissue: the proportion that achieved both area under the drug concentration over time curve (AUC)/MIC = 100 and maximum concentration (Cmax)/MIC = 8. Prostatic penetration of pazufloxacin was good with mean Cmax ratios (prostate tissue/plasma) of 0.82-0.99 and for AUC, 0.80-0.98. The probability of reaching target MIC concentrations in prostate tissue was more than 90% for dosing schedules of 0.25 mg/L for 500 mg every 24 h (500 mg daily), 0.5 mg/L for 500 mg every 12 h (1000 mg daily), 1 mg/L for 1000 mg every 24 h (1000 mg daily), and 2 mg/L for 1000 mg every 12 h (2000 mg daily). Importantly, the 2000 mg daily regimen of pazufloxacin produced a profile sufficient to have an antibacterial effect in prostate tissue against clinical isolates of Escherichia coli and Klebsiella pneumonia with MIC values less than 2 mg/L.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Fluoroquinolones/pharmacology , Fluoroquinolones/pharmacokinetics , Oxazines/pharmacology , Oxazines/pharmacokinetics , Prostate/metabolism , Prostatitis/drug therapy , Surgical Wound Infection/prevention & control , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Escherichia coli/drug effects , Fluoroquinolones/administration & dosage , Fluoroquinolones/blood , Humans , Klebsiella pneumoniae/drug effects , Male , Microbial Sensitivity Tests , Monte Carlo Method , Oxazines/administration & dosage , Oxazines/blood , Prostate/microbiology , Prostatic Hyperplasia/surgery , Prostatitis/microbiology , Transurethral Resection of ProstateABSTRACT
A 61-year-old woman with metastatic renal carcinoma was treated with axitinib as a second-line tyrosine kinase inhibitor. Thirteen days after the treatment, the patient developed reversible posterior leukoencephalopathy syndrome (RPLS). Her symptoms and imaging findings resolved after withdrawal of axitinib, blood pressure control, and administration of glycerin and levetiracetam. RPLS should be kept in mind as a possible rare adverse event after axitinib administration.
ABSTRACT
OBJECTIVES: To compare various methods for measuring tumor extent in prostate biopsy specimens to identify small-volume prostate cancer. METHODS: A total of 100 radical prostatectomy specimens were retrospectively analyzed. Receiver operating characteristic analysis was used to compare the abilities of prostate-specific antigen density, and four measures of tumor extent in prostate biopsy specimens - positive core number, greatest percentage of cancer in a single core, greatest length of cancer in cores and total length of cancer in cores - to identify small volume prostate cancer. Four definitions of insignificant cancer volume were used in this analysis: index and total tumor volume <0.5 mL, index tumor volume <1.3 mL and total tumor volume <2.5 mL. Multivariate analysis was also used to evaluate variables for predicting small-volume prostate cancer. RESULTS: Total length of cancer in cores had the highest areas under the curve of all the measures defining small-volume prostate cancer: index tumor volume <0.5 mL (0.855), total tumor volume <0.5 mL (0.877), index tumor volume <1.3 mL (0.784) and total tumor volume <2.5 mL (0.818). On multivariate analysis total length of cancer in cores was an independent predictive factor for prostate cancers with index tumor volume <0.5 mL (P < 0.001), <1.3 mL (P < 0.001) and total tumor volume <0.5 mL (P < 0.001), respectively. CONCLUSION: Our data suggest that total length of cancer in cores is the optimal measure of tumor extent in prostate biopsy specimens for identifying small-volume prostate cancer.
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Prostatic Neoplasms/pathology , Tumor Burden , Aged , Area Under Curve , Humans , Male , Middle Aged , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , ROC CurveABSTRACT
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 (n = 47) prophylactically received a 0.5 h infusion of PIPC-TAZ (8:1.2-0.25 g or 4-0.5 g) before transurethral resection of the prostate. PIPC-TAZ concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) 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 (T > MIC, the PD indicator for antibacterial effects) in prostate tissue for six PIPC-TAZ regimens (2.25 or 4.5 g; once, twice, three times or four times daily; 0.5 h 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 4.5 g twice daily and 2.25 g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% T > MIC) in prostate tissue; regimens of 4.5 g three times daily and 2.25 g four times daily achieved a >90% probability of attaining the bactericidal target for PIPC (50% T > MIC) 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.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Penicillanic Acid/analogs & derivatives , Prostate/metabolism , Prostatitis/drug therapy , Aged , Anti-Bacterial Agents/blood , Area Under Curve , Escherichia coli/drug effects , Humans , Infusions, Intravenous , Klebsiella/drug effects , Male , Microbial Sensitivity Tests , Middle Aged , Monte Carlo Method , Penicillanic Acid/blood , Penicillanic Acid/pharmacokinetics , Penicillanic Acid/therapeutic use , Piperacillin/blood , Piperacillin/pharmacokinetics , Piperacillin/therapeutic use , Piperacillin, Tazobactam Drug Combination , Prostatic Hyperplasia/surgery , Prostatitis/metabolism , Proteus/drug effects , Pseudomonas aeruginosa/drug effects , Transurethral Resection of ProstateABSTRACT
We report a case of neuroendocrine carcinoma in a diverticulum of the bladder. A 65-year-old Japanese woman visited our hospital with the chief complaint of gross hematuria. Cystoscopy revealed a non-papillary broad-based tumor in a diverticulum of the posterior wall. She underwent transurethral resection of bladder tumor (TURBT) and subsequently total cystectomy with ileal conduit on the diagnosis of an invasive urothelial carcinoma. There was no residual tumor in the surgical specimen. Immunohistochemistry of TUR specimens showed positive synaptophysin, chromogranin A, CD56 and high ratio of positive Ki-67. Finally, it was diagnosed as a neuroendocrine carcinoma of the bladder. To our knowledge, this is the second case report of the neuroendocrine tumor or small cell carcinoma in a diverticulum of the urinary bladder in the Japanese literature.
Subject(s)
Carcinoma, Neuroendocrine , Diverticulum/pathology , Urinary Bladder Neoplasms/pathology , Aged , Carcinoma, Neuroendocrine/surgery , Cystectomy , Diverticulum/surgery , Female , Humans , Magnetic Resonance Imaging , Neoplasm Invasiveness , Urinary Bladder Neoplasms/surgeryABSTRACT
Patients with progressive renal cell carcinoma who undergo sunitinib treatment, experience many adverse events (AEs), including thrombopenia and hypertension. Dose reduction or treatment discontinuation due to AEs makes it difficult to control the clinical condition. Therefore, patients' understanding regarding the basics of blood pressure (BP) measurement and how to deal with each AE are particularly important. Here we report whether or not pharmacist instructions help in order to increase patients' awareness of early AE management results in an improvement of treatment outcomes. The present study included 15 patients who were administered sunitinib. From the start of sunitinib treatment, pharmacists continuously provided drug administration guidance to the patients and confirmed their awareness and knowledge regarding AEs, symptom management, and drug adherence. The relative dose intensity (RDI) of 15 patients from week 1 to 24 after sunitinib treatment was calculated. Pharmaceutical interventions significantly improved patients' understanding of BP measurements and reference values, etc. Although the RDI was 67.3%-78.7%, there were no cases of discontinuation of administration or reduction of the dose caused by e.g. hypertension, hand and foot syndrome (HFS) and stomatitis. Pharmaceutical interventions improved patients' awareness of the management of AEs and adherence to sunitinib therapy. As a result, a high RDI was maintained, which may lead to prolonged survival. Therefore, our results suggest that early AE management provided by pharmacists is particularly important to assure the safety and efficacy of sunitinib therapy.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Hypertension/prevention & control , Indoles/adverse effects , Kidney Neoplasms/drug therapy , Pyrroles/adverse effects , Aged , Blood Pressure Determination , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/secondary , Disease Management , Female , Follow-Up Studies , Humans , Hypertension/etiology , Kidney Neoplasms/complications , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Patient Compliance , Prognosis , SunitinibABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Prostate/chemistry , Prostatitis/drug therapy , Thienamycins/administration & dosage , Thienamycins/pharmacokinetics , Aged , Chromatography , Gram-Negative Bacteria/drug effects , Humans , Infusions, Intravenous , Male , Meropenem , Microbial Sensitivity Tests , Plasma/chemistryABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Carbapenems/pharmacology , Carbapenems/pharmacokinetics , Prostate/drug effects , Prostatitis/drug therapy , Aged , Anti-Bacterial Agents/administration & dosage , Carbapenems/administration & dosage , Computer Simulation , Doripenem , Humans , Male , Microbial Sensitivity Tests , Monte Carlo Method , Tissue DistributionABSTRACT
BACKGROUND: The aim was to retrospectively assess the results of treatment of upper urinary tract stones with the Sonolith vision manufactured by EDAP, and purchased in 2004. METHODS: The subjects were 226 Japanese patients who underwent extracorporeal shock wave lithotripsy (ESWL) alone as an initial treatment and could be followed up for at least 3 months, selected from 277 candidate patients who underwent this therapy between 2004 and 2006. Treatment effect was evaluated by kidney, ureter, and bladder X-ray or renal ultrasonography at 1 and 3 months after treatment. A stone-free status or status of stone fragmentation to 4 mm or smaller was considered to indicate effective treatment. RESULTS: At 3 months after treatment, the stone-free rate was 69.4% and the efficacy rate was 77.4% for renal stones, while these rates were 91.5 and 93.3%, respectively for ureteral stones. Assessment of treatment effect classified by the location of stones revealed a stone-free rate of 94.6% and an efficacy rate of 94.6% for lower ureteral stones (4.0 mm or smaller, 1 subject; 4.1-10.0 mm, 31 subjects; 10.1-20.0 mm, 5 subjects: number of treatment sessions, 1 or 2 sessions [mean: 1.03 sessions]). Complications of this therapy included renal subcapsular hematoma and pyelonephritis in 1 case each. CONCLUSIONS: ESWL with the Sonolith vision manufactured by EDAP produced a treatment effect equivalent to those achieved with other models of ESWL equipment. ESWL seems to be an effective first-line treatment also in patients who have lower ureteral stones 10 mm or larger but do not wish to undergo TUL, if measures such as suitable positioning of the patient during treatment are taken.