Clinical pharmacokinetics of flomoxef in prostate tissue and dosing considerations for prostatitis based on site-specific pharmacodynamic target attainment.

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.

[A Case of Metachronous Testicular Tumor Developing Twenty Years after Treatment of Retroperitoneal Extragonadal Germ Cell Tumor].

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.

Increased infiltration of CCR4-positive regulatory T cells in prostate cancer tissue is associated with a poor prognosis.

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.

[A Case of Dedifferentiated Liposarcoma of the Spermatic Cord].

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.

Impact of a novel biopsy instrument with a 25-mm side-notch needle on the detection of prostate cancer in transrectal biopsy.

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.

Clinical pharmacokinetics and pharmacodynamic target attainment of pazufloxacin in prostate tissue: Dosing considerations for prostatitis.

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.

Optimal method for measuring tumor extent in needle biopsy specimens to identify small-volume prostate cancer.

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.

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 (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.

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.

OBJECTIVES: 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. METHODS: Six surgeons carried out robot-assisted radical prostatectomy in 154 patients, which were divided into the following three groups: group 1 (n = 90), including patients operated on by a surgeon with experience in both open radical prostatectomy and robot-assisted radical prostatectomy; group 2 (n = 36), including patients operated on by two surgeons with experience in open radical prostatectomy only; and group 3 (n = 28), including patients operated on by three surgeons with limited experience in both open radical prostatectomy or robot-assisted radical prostatectomy. RESULTS: Groups 2 and 3 did not differ significantly in their median values of external blood loss (P = 0.165) or console time (P = 0.103). Positive surgical margin rates for pT2 patients were also similar in these two groups: 21.2% (7/33) in group 2 and 22.7% (5/22) in group 3 (P = 0.894). Kaplan-Meier analysis showed that 12 months after robot-assisted radical prostatectomy the prostate-specific antigen-free rate for pT2 patients was 96.0% in group 2 and 100% in group 3, but the pad-free continence rate was just 91.0% in group 1, 88.0% in group 2 and 75.5% in group 3 (group 1 vs group 3, P = 0.037; group 2 vs group 3, P = 0.239). The major complication rate after robot-assisted radical prostatectomy was 3.3% (3/90) in group 1, 11.1% (4/36) in group 2 and 17.9% (5/28) in group 3 (group 1 vs group 3, P = 0.008; group 2 vs group 3; P = 0.441). CONCLUSIONS: Robot-assisted radical prostatectomy offers satisfactory postoperative outcomes even when carried out by surgeons with limited experience in open radical prostatectomy.

[A case of neuroendocrine carcinoma in a diverticulum of the bladder].

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.

Imatinib mesylate inhibits androgen-independent PC-3 cell viability, proliferation, migration, and tumor growth by targeting platelet-derived growth factor receptor-α.

AIM: The abnormal expression of oncogenic tyrosine kinase receptors such as platelet-derived growth factor receptors (PDGFRs) has been reported in cancer progression. However, the role of PDGFRs in the human androgen-independent prostate cancer PC-3 cell line is not well understood. Thus, this study examined the role of PDGFRs in androgen-independent PC-3 cells. MAIN METHODS: PDGFR mRNA and protein expression was determined by quantitative real-time PCR and western blotting, respectively. The effects of the tyrosine kinase inhibitor imatinib (imatinib mesylate) and small interfering RNAs (siRNAs) were determined by a Cell Counting Kit-8 assay, bromodeoxyuridine assay, and Transwell migration assay. The in vivo effect of imatinib was analyzed using a tumor formation assay in nude mice. KEY FINDINGS: PDGFRα was upregulated in androgen-independent PC-3 cells compared with normal prostate epithelial cells. PDGF-BB induced the phosphorylation of PDGFRα and downstream signaling molecules, including Akt, in a dose-dependent manner. Imatinib reduced the phosphorylation of the PDGFRα/Akt axis. Imatinib also suppressed the viability, proliferation, migration, and tumor growth of PC-3 cells. PDGFRα knockdown by siRNA decreased the viability and migration of PC-3 cells. SIGNIFICANCE: These results demonstrated the distinct contribution of PDGFRα signaling to the proliferation and migration of PC-3 cells and suggested the potential for PDGFRα as a therapeutic target for metastatic and androgen-independent prostate cancer.

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

BACKGROUND: 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). SUBJECTS AND METHODS: The subjects were 102 patients who were diagnosed with M1b PC at Aichi Medical University Hospital. HER-2 expression was determined by immunohistochemical (IHC) staining using initial needle biopsy specimens for diagnosis. The results were classified into four grades (0, 1+, 2+, 3+), and scores of 1+ or greater were considered overexpression and defined as positive. RESULTS: The results showed a rating of 0 in 72 subjects, 1+ in 10, 2+ in 14, and 3+ in 6; 30 subjects (29.4%) were classified as HER-2 positive. Comparison of clinical data of HER-2 positive and negative subjects obtained at baseline revealed many of the subjects with high-grade tumors by Gleason score were HER-2 positive (P = 0.030). The prostate-specific antigen (PSA) relapse was observed in 76 subjects and cause-specific death occurred in 44. A significant difference was observed only in the item HER-2 (negative vs. positive) by multivariate Cox proportional hazard analysis. The 5-year PSA relapse-free rate was 0% in subjects with HER-2 positive (26/30), and 43.9% in subjects with HER-2 negative (50/72, P = 0.0192). The 5-year cause-specific survival rate was 40.9% in subjects with HER-2 positive (30/102), and 67.3% in subjects with HER-2 negative (72/102, P = 0.0301). CONCLUSION: HER-2 overexpression as determined by IHC staining using needle biopsy specimens for diagnosis with M1b PC is a significant prognostic factor for PSA relapse after hormone therapy and unfavorable outcome.

Treatment of upper urinary tract stones with extracorporeal shock wave lithotripsy (ESWL) Sonolith vision.

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.

MAZ51 Blocks the Tumor Growth of Prostate Cancer by Inhibiting Vascular Endothelial Growth Factor Receptor 3.

Vascular endothelial growth factor (VEGF) signaling plays a critical role in the carcinogenesis and tumor development of several cancer types. However, its pathological significance in prostate cancer, one of the most frequent and lethal malignancies in men, remains unclear. In the present study, we focused on a pathological role of the VEGF receptors (VEGFRs), and examined their expression and effects of MAZ51 (an inhibitor of the tyrosine kinase of VEGFR-3) on cell proliferation, migration, and tumor growth in human prostate cancer cells. The expression level of VEGFR-3 was higher in androgen-independent and highly metastatic prostate cancer PC-3 cells than in other prostate PrEC, LNCaP, and DU145 cells. In PC-3 cells, VEGFR-3 and Akt were phosphorylated following a stimulation with 50 ng/ml VEGF-C, and these phosphorylations were blocked by 3 µM MAZ51. Interestingly, PC-3 cells themselves secreted VEGF-C, which was markedly larger amount compared with PrEC, LNCaP, and DU145 cells. MAZ51 reduced the expression of VEGFR-3 but not VEGFR-1 and VEGFR-2. The proliferation of PC-3 cells was inhibited by MAZ51 (IC50 = 2.7 µM) and VEGFR-3 siRNA, and partly decreased by 100 nM GSK690693 (an Akt inhibitor) and 300 nM VEGFR2 Kinase Inhibitor I. MAZ51 and VEGFR-3 siRNA also attenuated the VEGF-C-induced migration of PC-3 cells. Moreover, MAZ51 blocked the tumor growth of PC-3 cells in a xenograft mouse model. These results suggest that VEGFR-3 signaling contributes to the cell proliferation, migration, and tumor growth of androgen-independent/highly metastatic prostate cancer. Therefore, the inhibition of VEGFR-3 has potential as a novel therapeutic target for the treatment for prostate cancer.

Prostatic Pharmacokinetic/Pharmacodynamic Evaluation of Ampicillin-Sulbactam for Bacterial Prostatitis and Preoperative Prophylaxis.

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.

Association between gefitinib and hemorrhagic cystitis and severely contracted bladder: a case report.

BACKGROUND: Gefitinib remains an excellent treatment option for patients with a variety of cancers, including non small cell lung cancer (NSCLC). However, clinicians must be aware of the potential of gefitinib to cause an inflammatory reaction in the skin, lungs and bladder. CASE PRESENTATION: We present a case on hemorrhagic cystitis and severely contracted bladder in a patient with NSCLC on gefitinib. CONCLUSIONS: Further studies are needed to substantiate the association of gefitinib therapy with hemorrhagic cystitis and contracted bladder.

A rare case of metastatic renal carcinoid.

BACKGROUND: Carcinoid is an endocrine cell tumor with low-grade atypia, which is generally a low-grade malignant cancer with a good prognosis. Metastatic renal carcinoid is even rarer than primary carcinoids. CASE PRESENTATION: We present our experience of a patient with metastatic renal carcinoid from the gastrointestinal tract. CONCLUSIONS: The carcinoid tumor of the kidney in our patient, who had a history of liver metastasis from rectal carcinoid, was considered metastatic based on the pathological findings.

Dorsal Vein Complex Preserving Technique During Robot-Assisted Radical Prostatectomy.

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.

Long-term results and management of ureteral transitional cell carcinoma using the holmium: YAG laser via rigid-ureteroscopy.

The standard operative procedure for ureteral transitional cell carcinoma is nephrouterectomy with partial cystectomy at the affected ureteral orifice. However, nephron-sparing surgery and endoscopic surgery and management have become common practice for low-grade and low-stage cases. We investigated the follow-up results of patients who underwent endoscopic surgery using the holmium:YAG laser, and evaluated its treatment effect. The patients were 4 men and 3 women aged from 68 to 87 years (mean: 74.7 years). Two were imperative cases and 5 were elective cases. The tumor size ranged from 8 to 25 mm (mean: 15.4 mm). Hydronephrosis was not found in any case, and urinary cytology was negative in all cases. Biopsy revealed 5 cases of grade 1, and 2 of grade 2. A Versa Pulse Select 80 laser generator, a 365-microm slim line laser fiber, and a rigid ureteroscope with 8F-point diameter were used. A 6F double J catheter was placed postoperatively for 3 weeks. Pulse energy was set at 0.5-1.0 J (mean: 0.8 J) with a frequency of 10 Hz. The total amount of energy was 0.9-11.22 KJ (mean: 2.89 KJ) and the operation time including ureteral stent placement was 20-97 min (mean: 66 min). Neither urinary tract perforation nor ureteral stricture associated with laser irradiation was observed. The postoperative follow-up period ranged from 23-88 months (mean: 67.8 months). Patients underwent urinary cytological examination once a month, and cystoscopy, retrograde pyelography and urethroscopy once every 3 months for 2 years, then once every 6 months thereafter. One patient developed tumor recurrence 23 months after surgery and received another laser treatment, but no recurrence has been observed in the other 6 patients (85.7%). Transurethral endoscopic surgery and management using the holmium:YAG laser is safe and effective nephron-sparing surgery for ureteral transitional cell carcinoma, and good long-term treatment results can be expected even in elective cases if the indications are carefully selected.