Vardenafil allows successful intercourse initiated rapidly after dosing in Japanese patients with diabetes mellitus and erectile dysfunction.

INTRODUCTION: Vardenafil is reported to improve success rates in the maintenance of an erection sufficient for completion of intercourse (SEP-3) compared with placebo in erectile dysfunction (ED) patients who attempted intercourse from as early as 15 minutes after dosing. However, these data were based on general ED patients, using time from administration to initiation of intercourse. It is unclear whether the results can be applied to difficult-to-treat ED patients, such as those with diabetes mellitus (DM), with the time between dosing and insertion into vagina. AIM: To determine whether early onset of activity with vardenafil is also achievable in ED patients with DM. METHODS: Data from a 12-week Phase III clinical trial (randomized, placebo-controlled, double-blind, parallel-group comparison) in Japanese men with ED and DM was used for analysis. In this study, patients received vardenafil 10 mg, 20 mg, or placebo, and were instructed to start sexual activity 1 hour after dosing. Mean per-patient SEP-3 success rates (intent-to-treat; ITT population), based on patient diary question, were calculated by the time between dosing and insertion. The least-squares means and nominal P values for differences versus placebo were derived by analysis of covariance with terms for baseline. MAIN OUTCOME MEASURES: SEP-3 success rates in each time interval. RESULTS: The majority of inserts occurred between 60-90 minutes after dosing, but 100 of inserts in 52 patients occurred in the first 30 minutes. SEP-3 success rates in patients who inserted in each interval from 0-15 minutes (P = 0.0268), 15-30 minutes (P = 0.0094) through > 120 minutes were all higher in vardenafil-treated patients than those in placebo. CONCLUSIONS: In this retrospective analysis, a rapid onset of activity was also demonstrated in difficult-to-treat ED patients. Vardenafil improved successful intercourse rates compared with placebo in Japanese DM patients who inserted from as early as 15 minutes to >120 minutes after dosing.

A pilot study of quality of life of patients with hormone-refractory prostate cancer after gene therapy.

BACKGROUND: The effects on quality of life (QOL) after a Phase I/II clinical trial of a combination of osteocalcin promoter-driven herpes simplex virus thymidine kinase (Ad-OC-TK) gene therapy and valacyclovir (VAL) were investigated for patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: The QOL of six patients was prospectively assessed after gene therapy on days 0, 14, and 28. A modified questionnaire was created based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire's prostate cancer-specific module (EORTC QLQ-PR25). RESULTS: The scores of all items significantly improved along with the total score. Further, bodily pain was significantly reduced on day 28. Moreover, the rate of change in the serum prostate-specific antigen levels from day 0 to day 28 was significantly correlated with the rate of change in bodily pain. CONCLUSION: In this clinical trial, Ad-OC-TK plus VAL treatment significantly improved the short-term QOL and bodily pain of patients with localized recurrence or bone metastases of HRPC.

Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer.

We evaluated the long-term safety and efficacy of Ad-OC-TK (recombinant adenoviral vector carrying an osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) gene therapy for hormone-refractory prostate cancer. Ad-OC-TK/VAL therapy is the first in vivo adenovirus-mediated gene therapy to be used to treat metastatic prostate cancer, including bone metastasis. Six patients were enrolled in this trial, and two doses of Ad-OC-TK (2.5 x 10(9) or 2.5 x 10(10) plaque-forming units) were injected into locally recurrent tumor or bone metastasis on day 1 and day 8. Patients were also given VAL (3 g/day) for 21 days. Safety and efficacy were evaluated for at least 8 months in each patient. All patients tolerated this therapy with no serious adverse events. One prostate-specific antigen (PSA) response (from 318.3 to 4.9 ng/ml) was observed with a time to PSA progression (TTP) of 12 months. Docetaxel (30 mg/m2 per week) and estramustine (560 mg/day) combination chemotherapy (DE) was given to three docetaxel-naive patients on PSA failure after gene therapy. All three patients had a PSA response to DE therapy with 21, 7, and 4 months of TTP. These results suggest that additional trials are warranted.

Usefulness and problems of the urinary tract infection criteria for evaluating drug efficacy for complicated urinary tract infections.

We aimed to reveal the usefulness of and problematic points with the Criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection (draft fourth edition) proposed by the UTI Subcommittee of the Clinical Evaluation Guidelines Committee, Japan Society of Chemotherapy, for evaluating antimicrobial agents for complicated urinary tract infections. We conducted a multicenter trial involving 159 patients with complicated urinary tract infections without indwelling urinary catheters. The antimicrobial agents used were cefcapene pivoxil and levofloxacin. "Early evaluation" took place the day after completion of 7 days of therapy; "late evaluation" took place 5-9 days after the end of treatment, and "follow-up evaluation" was done 4-6 weeks after treatment. In the early evaluation, overall clinical efficacy was judged as excellent in 52.9% of the patients, moderate in 26.1%, and poor in 21.0%, and the bacteriological response was judged as "eradicated" for 86.4% of the 198 bacterial strains isolated. Of 96 patients included in the "late evaluation" category in accordance with the draft fourth edition, the clinical outcome was judged as "cured" in 68.4% and the microbiological outcome was judged as "eradicated" in 59.4%. These rates may be low, because 25 patients in whom clinical efficacy was evaluated as "poor" at the end of treatment were separately classified as "failed" at the late evaluation. Of the 49 patients with an excellent clinical response at the end of treatment, symptoms were exacerbated in 18 at the follow-up evaluation. Overall, the draft fourth edition, with some modifications of the third edition criteria, such as the addition of a follow-up evaluation 7 days after the cessation of drug administration, has the potential to play a role in the international standards for evaluating antimicrobial drug efficacy for complicated urinary tract infections.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). III. Secular changes in susceptibility].

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of these bacteria to various antimicrobial agents were measured. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1995 and 2003. The drug sensitivity of S. aureus in this year was similar to those in up to the previous year and S. aureus showed the best susceptibility to vancomycin (VCM) and arbekacin (ABK). The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous year. The susceptibility of E. coli to cephems in this year was generally good and was similar to those in up to the previous year. MIC90 of cefozopran (CZOP) was the most stable and 0.125 microg/mL or less since 1995. The susceptibility of E. coli to cefpirome (CPR) and cefotiam (CTM) also was good but to cefaclor (CCL), cefixime (CFIX), and cefpodoxime (CPDX) was largely decreased in complicated UTI groups. The sensitivity of E. coli to carbapenems also was good but to carumonam (CRMN) tended to decrease. The susceptibility of E. coli to quinolones, however, has largely changed and has decreased since 2003 in uncomplicated UTIs and 2000 in complicated UTIs. That was suggested the development of the resistance to the drug. The susceptibility of Klebsiella spp. to cefazolin (CEZ), CTM, CCL, CPDX, and cefditoren (CDTR) decreased in the previous year and recovered to the year before the previous year in this year. The susceptibility of Klebsiella spp. to other cephems was stable since 1995, especially against CZOP, the highest sensitivity (MIC90: < or = 0.125 microg/mL) was maintained. The susceptibility of Klebsiella spp. to carbapenems and CRMN also was good. The susceptibility of Klebsiella spp. to aminoglycosides was lower than to CZOP but was stable since 1995. The susceptibility of P. aeruginosa was generally low and has largely changed against the majority of the agents since 1995. The susceptibility of P. aeruginosa isolated from uncomplicated UTIs has largely changed against ceftazidime (CAZ), cefsulodin (CFS), CZOP, imipenem (IPM), meropenem (MEPM), aztreonam (AZT), CRMN, gentamicin (GM), and tobramycin (TOB). The susceptibility of P. aeruginosa isolated from complicated UTIs has largely changed against CSF, CZOP, MEPM, GM, and ciprofloxacin (CPFX). The susceptibility of P. aeruginosa isolated from complicated UTIs has been stable against amikacin (AMK). For annual changes in MIC50, TOB and IPM had a relatively stable and high activity (MIC50: 0.5-2 microg/mL).

Efficacy and safety of tadalafil 5, 10, and 20 mg in Japanese men with erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVES: To investigate the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in Japanese men with erectile dysfunction (ED). METHODS: This multicenter, randomized, double-blind, placebo-controlled, 12-week study enrolled 343 Japanese men with ED. The men were stratified into those with mild, moderate, or severe ED and then randomly assigned 1:1:1:1 to placebo and 5 mg, 10 mg, and 20 mg tadalafil. Co-primary outcomes were the International Index of Erectile Function erectile function domain score, the percentage of "yes" responses to the Sexual Encounter Profile Diary Questions 2 and 3, and tolerability. Secondary outcomes included the International Index of Erectile Function intercourse satisfaction and overall satisfaction domain scores and the percentage of "yes" responses to a global assessment question. RESULTS: The least square mean change from baseline was 7.5, 9.1, and 9.4 for 5, 10, and 20 mg tadalafil versus 2.1 for placebo for the International Index of Erectile Function erectile function domain; 28.5, 36.0, and 36.5 for 5, 10, and 20 mg tadalafil versus 8.6 for placebo for Sexual Encounter Profile question 2; and 34.3, 47.3, and 50.8 for 5, 10, and 20 mg tadalafil versus 12.3 for placebo for Sexual Encounter Profile question 3, respectively (P <0.001 for all doses and all measures). Patients taking tadalafil had significantly greater changes from baseline for the intercourse satisfaction and overall satisfaction domains compared with patients taking placebo (P <0.001). Also, 76.5%, 81.4%, and 83.7% of patients taking 5, 10, and 20 mg tadalafil, respectively, reported improved erections (global assessment question) versus 31.4% of patients taking placebo (P <0.001). Most (98%) treatment-emergent adverse events were mild or moderate in severity. One patient (tadalafil 5 mg) discontinued because of an adverse event (ureteral calculus). Of the 343 patients, 302 (88%) completed the study. No deaths were reported. CONCLUSIONS: All doses of tadalafil studied were efficacious and well tolerated in Japanese men with ED.

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). I. Susceptibility distribution].

The bacterial strains isolated from 490 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of them to many kinds of antimicrobial agents were measured. Of them, 577 strains were estimated as causative bacteria and used for the measurement. The strains consisted of 156 gram-positive bacterial strains (27.0%) and 421 gram-negative bacterial strains (73.0%). Against Staphylococcus aureus, arbekacin (ABK), vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Enterococcus faecalis, ampicillin (ABPC) and VCM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially cefozopran (CZOP) and cefpirome (CPR) showed the strongest activity (MIC90: < or = 125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or = 4 microg/mL] was detected at frequency of 18.8%, which was higher than that in the last year. Against Klebsiella pneumoniae, CZOP, meropenem (MEPM), and carumonam (CRMN) showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. The antibacterial activity of the other cephems was relatively good, and decrease in their activity observed in the last year study was not recognized. Against Serratia marcescens, imipenem (IPM) and gentamicin (GM) had the strongest antibacterial activity. Against Proteus mirabilis, CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. MEPM prevented the growth of all strains with 0.25 microg/mL. Next, cefmenoxime (CMX), ceftazidime (CAZ), CZOP, cefixime (CFIX), cefpodoxime (CPDX), and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to > 128 microg/mL except IPM and MEPM having 16 microg/mL. The antibacterial activities of CZOP and CAZ were considered to be relatively good on MIC50 comparison (MIC50: 2 microg/mL).

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004) II. Background of patients].

Six hundred six bacterial strains isolated from 490 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The frequency of bacteria isolation stratified with patient clinical background was compared. The clinical background investigated included sex, age, type of infections, timing of antibiotics administration, and presence or absence of surgery affecting a decrease in defense against infection. The bacterial strains were stratified with the age and sex of the patients and the types of infections. In males, the number of patients aged less than 60 years was few and the complicated UTIs without indwelling catheter was observed most frequently. In females, the number of patients aged less than 60 years was comparatively more than in males. In all of ages except 0-19 and > or = 80 years, the ratio of the uncomplicated UTIs was high, accounting for 44.1-90.0% of all types of infections. In the present time, the bacteria most frequently isolated were Escherichia coli. Pseudomonas aeruginosa and Enterococcus faecalis also were relatively frequently isolated. E. coli most frequently isolated with the uncomplicated UTIs and P. aeruginosa and E. faecalis most frequently isolated with the complicated UTIs. With respect to the relation of these results to the age of the patients, in the uncomplicated UTIs, the isolation frequency of E. coli was the highest in all age groups except 0-19 years, accounting for 50% or higher. In the complicated UTIs without indwelling catheter, the isolation frequency of E. coli tended to be high in all age groups. In the complicated UTIs with indwelling catheter, P. aeruginosa were more frequently isolated. In comparison of causative bacteria in UTIs between before and after the administration of antibiotics, P. aeruginosa increased after the administration in any types of UTIs. In comparison of causative bacteria in UTIs with or without surgery, E. coli was more frequently isolated in the patients without surgery, while P. aeruginosa and E. faecalis were more frequently isolated in the patients with surgery in any UTIs.

Effect of sildenafil on arterial stiffness, as assessed by pulse wave velocity, in patients with erectile dysfunction.

BACKGROUND: The problems of patients with erectile dysfunction have been recognized, leading to the emergence of sildenafil, which has led to successful treatment in many cases. The purpose of this study is to examine the effect of sildenafil on the pulse wave velocity of patients with erectile dysfunction. METHODS: Fifteen patients with erectile dysfunction were enrolled for this study. The brachial/ankle pulse wave velocity was determined before dosing and at 30, 60, 120, and 180 min after dosing with 25 or 50 mg of sildenafil citrate. Concurrently, the changes in blood pressure, heart rate, and brachial/ankle pulse wave velocity were measured. For the consideration of revised brachial/ankle pulse wave velocity by blood pressure, the systolic blood pressure-derived brachial/ankle pulse wave was also investigated, and we classified and examined those results with and without risk factors for arteriosclerosis. RESULTS: The systolic blood pressure decreased significantly at 60 min after dosing compared with the placebo control. The heart rate decreased at 120 min after dosing compared with the placebo control but that decrease was not significant. The brachial/ankle pulse wave velocity transiently decreased at 30 or 60 min after dosing compared with the placebo control, but the decrease was not significant; however, the systolic blood pressure-derived brachial/ankle pulse wave velocity decreased significantly. In those patients with risk factors for arteriosclerosis, the pulse wave velocity decreased significantly. CONCLUSION: In patients with erectile dysfunction who were administered sildenafil, the pulse wave velocity, along with blood pressure, tended to decrease transiently after dosing. There is a possibility that sildenafil affects the improvement of erectile dysfunction via the decrease of pulse wave velocity, especially in patients with risk factors for arteriosclerosis.

Vardenafil 20-mg demonstrated superior efficacy to 10-mg in Japanese men with diabetes mellitus suffering from erectile dysfunction.

AIM: Vardenafil is a highly selective and potent phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction (ED). The efficacy of vardenafil has been demonstrated in a broad range of ED populations, but has not yet been assessed in Japanese patients with diabetes mellitus (DM), although DM is frequently associated with difficult-to-treat ED. This is the first study to investigate whether high-dose vardenafil (20 mg) can demonstrate superior efficacy to the usual dose (10 mg) in this subpopulation in Japan. METHODS: The study was a randomized, placebo-controlled, double-blind, multi-centre, parallel group comparison 12-week study. Following 4 weeks observation period, 778 patients aged 26-64 years old with ED and DM (HbA1c >12% at screening was excluded) both of more than 3 years duration were randomly allocated to one of the three groups, vardenafil 10 mg, 20 mg, or placebo (randomization ratio 3:3:1). Erectile function (EF) domain score of the International Index of Erectile Function was estimated as the primary efficacy parameter. RESULTS: Vardenafil 10 and 20 mg both significantly improved the EF domain score from 13.6 and 13.9 at baseline to 21.8 and 22.9 at last observation carried forward (LOCF), respectively, compared to placebo (13.7 at baseline to 16.3 at LOCF; p<0.0001). In addition, vardenafil 20 mg demonstrated superior efficacy to 10 mg (p<0.05), and the difference was more evident in severe ED patients (baseline EF domain score <11). The safety profile was comparable between these two doses (drug-related adverse events: 6.6, 22.0 and 24.2% in placebo, vardenafil 10 mg, and 20 mg arms, respectively). The most common adverse events were hot flush, headache and nasal congestion, which were mild in intensity and transient, and are known to be common to PDE5 inhibitors. CONCLUSION: In Japanese men with DM and ED, vardenafil 10 mg and 20 mg were effective in improving erectile function with comparable safety profiles. Vardenafil 20 mg demonstrated superior efficacy compared with 10 mg, suggesting incremental clinical benefit in using the higher dose in this difficult-to-treat population.

Progress report on phase I/II clinical trial of Ad-OC-TK plus VAL therapy for metastatic or locally recurrent prostate cancer: Initial experience at Kobe University.

There is no effective therapy for hormone-refractory prostate cancer and a novel therapeutic modality, such as a gene therapy, should be actively pursued. Previously, Gardner and Chung conducted a phase I clinical trial of Ad-OC-TK (recombinant adenoviral vector containing osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) for the treatment of hormone-refractory prostate cancer at the University of Virginia. We report on our ongoing phase I/II clinical trial of Ad-OC-TK plus VAL for the treatment of advanced prostate cancer at the Kobe University Hospital, Japan.

Hand-assisted laparoscopic radical nephrectomy using intraoperative ultrasonography for left renal cell carcinoma involving a level I renal vein tumor thrombus.

This report concerns two male patients, 65 (case 1) and 72 (case 2) years old, with a left renal tumor involving a level I renal vein tumor thrombus, who underwent hand-assisted laparoscopic radical nephrectomy using intraoperative ultrasonography. With the patient in the flank position, a midline supraumbilical hand port and two other ports were placed. Intraoperative ultrasonography identified the extent of the tumor thrombus. After hilar control, complete resection with intact removal was performed. Surgery lasted 305 min for case 1 and 237 min for case 2, with respective estimated blood loss of 410 mL and 572 mL. No postoperative complications occurred. Pathological examination showed a clear cell carcinoma with a level I tumor thrombus and negative surgical margins. Because the ultrasound probe can be easily inserted and the specimen can be extracted safely and intact, hand-assisted laparoscopic radical nephrectomy is practicable and effective for left renal cell carcinoma involving a level I renal vein tumor thrombus.

Antitumor effects of etodolac, a selective cyclooxygenase-II inhibitor, against human prostate cancer cell lines in vitro and in vivo.

OBJECTIVES: To investigate the effects of the selective cyclooxygenase-2 (COX-2) inhibitor etodolac on prostate cancer cell lines in vitro and in vivo and on E-cadherin expression in prostate cancer cells. METHODS: We evaluated the cytotoxicity of etodolac on the three prostate cancer cell lines LNCaP, C4-2, and PC-3. We also performed quantitative real-time polymerase chain reaction to measure the mRNA expression of COX-2, Bcl-2, and E-cadherin in these cell lines after etodolac treatment. In addition, we investigated the in vivo antitumor effects of etodolac on a human prostate cancer xenograft model. RESULTS: Etodolac exhibited significant antitumor effect in vivo and in vitro. The cytotoxicity of etodolac in LNCaP and C4-2 was markedly increased at a dose of 1000 nM in a time-dependent and dose-dependent manner. In the in vivo tumor growth study, the etodolac-treated mice exhibited more significant cytotoxicity than the phosphate-buffered saline-treated mice. Expression of E-cadherin after etodolac treatment tended to increase and that of Bcl-2 to decrease, but the expression of COX-2 had no definite tendency. CONCLUSIONS: The COX-2 inhibitor etodolac exhibited an antitumor effect on prostate cancer cell lines in vitro and in vivo, and it might be useful for the treatment of hormone-resistant prostate cancer.

Efficacy of 1-day prophylaxis medication with fluoroquinolone for prostate biopsy.

A prospective, randomized trial in which 236 patients received oral levofloxacin, either at 600 mg/day for 1 day (n = 124) or 300 mg/day for 3 days (n = 112). Urinalysis, plasma white blood cell count (WBC) (per mm3), and C reactive protein (CRP) (mg/dl) levels were checked before prostate biopsy (PBX), on the day after PBX, and on the seventh day after PBX. Two patients (1.61%) who received 600 mg for 1 day and 2 patients (1.79%) who received 300 mg for 3 days had febrile infectious complications. There was no statistically significant difference between levofloxacin at 600 mg for 1 day and levofloxacin at 300 mg for 3 days regarding the elevation of WBC and CRP. We can perform PBX safely with levofloxacin at 600 mg for 1 day as prophylaxis and recommend this method from the point of view of the decrease of antibiotic-resistant strains.

Clinical study of six cases showing late relapse of germ cell tumors.

Late relapse of germ cell tumors has been considered rare. We report six patients treated at our institution with relapses of germ cell tumors more than 2 years after first successful management. Median time to late relapse for pure seminomas and non-seminomatous germ cell tumors was 30.0 and 75.5 months, respectively. The sites of the late relapses in two cases of pure seminoma were located out of the fields of irradiation. After systematic chemotherapy, both these patients remain disease free. Two patients with non-seminomatous germ cell tumors received salvage chemotherapy at the time of late relapse, but tumor markers did not normalize in either case. A complete resection of relapsed masses was performed in three cases of non-seminomatous germ cell tumors. All three patients are without evidence of disease. The incidence of late relapse in patients with pure seminomas and non-seminomas was 2.4% and 3.3%, respectively, which suggests the necessity for long-term follow up.

[Is second course intravesical Bacillus Calmette-Guerin therapy for recurrent carcinoma in situ of the bladder useful?].

We evaluated the usefulness of second course intravesical bacillus Calmette-Guerin (BCG) therapy for carcinoma in situ (CIS) of the bladder that failed to respond to the initial BCG therapy. Between January 1995 and December 2000, 185 patients with CIS of the bladder underwent an initial 6- or 8-week course of intravesical BCG instillation with an average follow-up period of 40.9 months (range: 3.8 to 94.8 months). Of the 185 patients, 160 (86.5%) completely responded to an initial course of BCG therapy. During follow up, 49 (30.6%) of the complete responders had recurrent transitional cell carcinoma. Overall, 9 (36.0%) of the 25 patients who did not respond completely to the initial 6- or 8-week course of BCG therapy and 22 (44.9%) of the 49 who had recurrent tumor after initial complete response, a total of 31 patients received the second course intravesical BCG therapy. Of the 9 incomplete responders, 8 (88.9%) achieved a complete response after the second course BCG therapy. With an average follow-up period of 39.6 months (range: 2.8 to 62.2 months), 2 (22.2%) of the 8 had recurrence. On the other hand, 17 (77.3%) of the 22 with recurrent tumor after the initial complete response developed recurrence with an average follow-up period of 14.1 months (range: 2.8 to 55.2 months). Seven (31.8%) of the 17 patients had disease progression to muscle invasion. Subsequently, cystectomy was done in 10 (58.8%) and radiation in 1 (5.9%). Our results suggest that a selected group of incomplete responders with initial BCG therapy may benefit from continued second course BCG. However, in patients who had recurrence after initial BCG success, the benefits of second course BCG therapy are limited. Careful surveillance and aggressive therapy on optimal timing are mandatory.

Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model.

BACKGROUND: Previous studies demonstrated the antitumor effects of IL-2 and ADV/RSV-HSV-tk in bladder tumor models. In our study, we employed the intramuscular injection of recombinant IL-2 combined with ADV/RSV-HSV-tk gene therapy in the MBT-2 murine bladder tumor model. MATERIALS AND METHODS: In the in vitro study, after adenoviral gene transduction efficiency had been assessed, the cytotoxicity of ADV/RSV-HSV-tk/ACV was examined. In the in vivo study, ADV/RSV-HSV-tk was injected into MBT-2 subcutaneous tumors, ACV was injected intraperitoneally daily for 13 days and recombinant IL-2 was injected intramuscularly daily for 10 days. RESULTS: The X-gal staining of MBT-2 cells infected with 125 multiplicity of injection (MOI) indicated > 20% adenoviral gene transduction efficiency. The cell growth of MBT-2 infected with 125 MOI was significantly inhibited by 40 microM of ACV. In the in vivo study, the combination therapy significantly inhibited tumor growth in the MBT-2 tumor model. CONCLUSION: The systemic administration of recombinant IL-2 in combination with HSV-tk gene therapy exhibited an enhanced antitumor effect.

Granulocyte-colony stimulating factor producing urothelial carcinoma of renal pelvis.

We report a case of granulocyte-colony stimulating factor (G-CSF) producing urothelial carcinoma of the renal pelvis in a 39-year old man. The patient was admitted to Kobe University Hospital, Kobe, Japan, complaining of macrohematuria and a 6-month history of left abdominal swelling. Abdominal computed tomography showed a large mass in the left kidney and para-aortic lymph node enlargement. A remarkable degree of leukocytosis was detected without any acute infectious disease. Enzyme immunoassay of the serum demonstrated a remarkable high concentration of G-CSF. The patient underwent left nephroureterectomy and para-aortic lymphadenectomy. Histochemical examination revealed urothelial carcinoma. Immunohistochemical staining with an anti-G-CSF antibody demonstrated G-CSF secreting cells. The patient died 8 weeks after the surgical operation. To our knowledge, this is the second case of G-CSF producing urothelial carcinoma of renal pelvis reported in the English literature.