RESUMEN

AIM: We investigated the feasibility and safety of the early removal of urethral catheters 3 days after radical retropubic prostatectomy. METHODS: Seventy consecutive patients underwent radical retropubic prostatectomy with the intent of early catheter removal on postoperative day (POD) 3. Catheter removal was based on postoperative cystograms performed on POD 2. Patients were analyzed using a validated prostate cancer specific questionnaire (University of California, Los Angeles Prostate Cancer Symptom Index) to determine quality of life outcomes. Multiple logistic regression analysis was also used to evaluate if any of the preoperative or intraoperative parameters were able to predict the success of early catheter removal after radical retropubic prostatectomy. RESULTS: The catheter was removed on POD 3 in 67 of 70 patients (97%) excluding three patients with moderate or severe extravasation on postoperative cystograms. Of the 67 patients, 53 (76%) were successful in early catheter removal, but the remaining 14 (24%) patients experienced urinary retention within 48 h and were treated with simple catheter replacement for 1 or 2 days. Two patients developed anastomotic strictures 3 and 4 months postoperatively, which were managed by dilation alone. Multiple logistic regression analysis showed that no leak during an intraoperative leak test was the only independent predictor of success for early catheter removal (P = 0.0069; odds ratio, 6.667; 95% confidence interval, 1.682-26.428). CONCLUSION: The present study revealed that early catheter removal 3 days after radical retropubic prostatectomy is feasible in patients who show a negative intraoperative leak test. Postoperative monitoring of more patients is needed to determine if the early catheter removal is widely applicable.

Asunto(s)

RESUMEN

BACKGROUND: Additive antitumor effects could be achieved by combination of immunotherapy and cytotoxic agents with no or minimum suppression. METHODS: Thirteen patients positive for human leukocyte antigen (HLA)-A24 or -A2 with metastatic hormone refractory prostate cancer (HRPC) who had failed to respond to the prior-peptide vaccination were entered in the combined peptide vaccination and estramustine phosphate. Conducted immune monitoring on those 13 patients were mainly peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by IFN-gamma productions and peptide-reactive IgG by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Grade 3 arrhythmia or cerebral infarction was observed in two cases, and Grade 1 or 2 dermatologic reaction at the vaccination sites was observed in all 13 cases. Eleven patients who received more than one cycle of treatment were eligible for immunological and clinical evaluation. There was no significant immunosuppression in most cases when the peptide and a half dose (280 mg/day) of estramustine were administrated, whereas severe immunosuppression was observed in the first two patients who received both the peptide and a full dose (560 mg/day) estramustine. Augmentation of peptide-specific CTL precursors or peptide-specific IgG was observed in 6 of 11 or 10 of 11 cases, respectively. Ten of 11 patients showed serum prostate-specific antigen (PSA) level decrease from the baseline including 8 patients with a serum PSA level decrease of > or =50%. CONCLUSIONS: These results encouraged the further evaluation of the combination of peptide vaccination and low-dose estramustine phosphate for metastatic HRPC patients.

Asunto(s)

RESUMEN

To evaluate the safety and toxicity of peptide vaccination for patients with metastatic hormone-refractory prostate cancer (HRPC) based on pre-existing peptide-specific cytotoxic T-lymphocyte (CTL) precursors in the circulation, 10 patients positive for human leukocyte antigen (HLA)-A2 with metastatic HRPC were enrolled in a phase I study. Peptide-specific CTL-precursors reactive to 16 kinds of vaccine candidates in the pre-vaccination peripheral blood mononuclear cells (PBMCs) were measured, and patients were followed by vaccination with only positive peptides (up to 4 kinds of peptides). Serum prostate-specific antigen (PSA) levels were monitored regularly. The peptide vaccination was safe and well tolerated with no major adverse effects. The most common toxicities were dermatologic reactions at the injection site. Increased CTL response to peptides was observed in 4 of 10 patients. Anti-peptide IgG was also detected in post-vaccination sera of 7 of 10 patients. One patient showed the disappearance of a pelvic bone metastasis after five vaccinations. Three patients showed a decrease of serum PSA level from the baseline after the vaccination, but no patients showed a serum PSA level decrease of >/= 50%. The median survival duration of study patients was 22 months with follow-up from 3 to 27 months. We consider that the increase in cellular and humoral immune responses, and decrease in PSA level in some patients justify further development of peptide vaccination for metastatic HRPC patients.

Asunto(s)

RESUMEN

BACKGROUND: The present study was undertaken mainly to investigate whether chemohormonal therapy with estramustine phosphate plus luteinizing hormone-releasing hormone (LHRH) agonist has a more beneficial effect than the hormonal therapy with flutamide plus LHRH agonist for newly diagnosed patients with metastatic prostate cancer. METHODS: A total of 57 patients with metastatic prostate cancer aged 59-80 years (median 74 years) were entered in the study and were randomized to the treatment of estramustine phosphate (560 mg/day) plus LHRH agonist (estramustine group) or flutamide (375 mg/day) plus LHRH agonist (flutamide group) with stratification for the degree of performance status, histological differentiation and bone metastasis. RESULTS: Both of the treatment regimens were well tolerated with similar incidences of adverse drug reactions. The overall response rates (complete response plus partial response) at 12 weeks after treatment in the estramustine and flutamide groups were 76 and 55%, respectively. The median time to objective progression for the estramustine group (25.4 months) was longer than that of the flutamide group (14.6 months). The serum levels of follicle stimulating hormone and testosterone were significantly lower in the estramustine group. CONCLUSIONS: Chemohormonal therapy with estramustine phosphate plus LHRH agonist showed longer clinical progression-free survival than the hormonal therapy with flutamide plus LHRH agonist (P = 0.03), although there was no significant difference in the overall survival. A larger-scaled trial with more statistical power is required to clarify that the former regimen is more beneficial than the latter for newly diagnosed patients with advanced prostate cancer.

Asunto(s)

RESUMEN

We investigated whether a suspension technique of vesicourethral anastomosis with pubo-prostatic ligaments improved urinary continence following radical retropubic prostatectomy. The suspension of vesicourethral anastomosis was performed in 55 consecutive patients with clinically localized prostate cancer by placement of two stitches, which were anchored to pubo-prostatic ligaments preserving their anterior attachments to the pubic bone. Continence rates, positive rates of surgical margins, and complications in these patients after radical prostatectomy were compared with the results of 30 randomly selected patients in whom a suspension technique was not performed. There were no significant differences in the positive rates of either surgical margins or complications between these two groups. In contrast, continence rates in the suspension group at one and three months (75% and 89%) were significantly higher than those (13% [p<0.001] and 67% [p<0.01]) of the control group. The suspension technique appears to have an advantage in immediate recovery of urinary continence following radical retropubic prostatectomy.

Asunto(s)

RESUMEN

BACKGROUND: To assess the safety and immune response of a peptide-based immunotherapy for patients with hormone-refractory prostate cancer, a phase I clinical trial was conducted. METHODS: This study first investigated whether cytotoxic T-lymphocyte (CTL) precursors reacting to peptide with vaccine candidates (14 peptides for HLA-A24 positive patients) were detectable in the pre-vaccination peripheral blood mononuclear cells (PBMCs) of ten patients with hormone-refractory prostate cancer. Patients were then vaccinated subcutaneously with only those peptides to which pre-vaccination PBMCs reacted (CTL precursor-oriented peptide vaccine) for up to four kinds of peptides. RESULTS: Overall vaccinations were generally well tolerated, but most patients (nine of ten) developed grade 1 local redness and swelling at the injection site. Increased CTL response to both peptides and cancer cells were observed in four of ten patients. Anti-peptide IgG antibodies were also detected in post-vaccination sera of seven of ten patients. One patient achieved a partial response with an 89% decrease in PSA. Stable disease was demonstrated in five of ten patients (50%) for the median duration of 2 months (range, 2-5 months). There were no objective responses of measurable lesions. CONCLUSIONS: Increase in cellular and humoral immune responses, and decrease in PSA level in some patients support further development of peptide-based immunotherapy for hormone refractory prostate cancer.

Asunto(s)

RESUMEN

OBJECTIVES: To investigate the usefulness of bone turnover markers as a modality for monitoring bone metastasis in patients with prostate cancer with bone metastasis. METHODS: Serial measurements of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), carboxyterminal pro-peptide of type I procollagen (PICP), prostate-specific antigen (PSA), and the percentage of the positive area on the bone scan were prospectively performed before and after hormonal therapy in 84 patients with prostate cancer with bone metastasis for median follow-up of 29 months. RESULTS: Serial ICTP and PICP levels in 48 patients without progression of bone metastasis demonstrated a downward trend during treatment and were almost within the normal range by the end of follow-up. The remaining 36 patients, who had PSA failure with progression of bone metastasis, showed an upward trend for serial ICTP and PICP levels before the progression of bone metastasis. The rates of detecting bone progression using bone turnover markers were higher than those using PSA levels on the basis of the percentage of clinical effectiveness and receiver operating characteristic curves. CONCLUSIONS: Serial measurement of bone turnover markers is useful for monitoring the bone activity of prostate cancer and might detect early progression of bone metastasis in patients with PSA failure.

Asunto(s)

RESUMEN

BACKGROUND AND OBJECTIVES: The feasibility of treating upper urinary tract tumors with a holmium:YAG (Ho:YAG) laser in transurethral endoscopy was examined. STUDY DESIGN/MATERIALS AND METHODS: Thirty-three treatments were performed on 30 patients with renal pelvic and ureteral carcinomas. After vaporization and coagulation eliminated the tumors, the surrounding mucosa was fully coagulated. Postoperative follow-up consisted of urinary cytology once a month, cystoscopy every 3 months, excretory pyelography every 6 months, and uretero-pyeloscopy every 6-12 months. RESULTS: The recurrence rate after the first treatment was 86% in the imperative indication group. The tumor-free rate (median follow-up, 37 months) in the imperative indication group was 57%. In the elective indication group, those values were 20 and 95% (median follow-up, 33 months), respectively. CONCLUSIONS: Transurethral endoscopic treatment of upper urinary tract tumors using Ho:YAG laser can be a useful method on limited cases identified into specific treatments groups combined with a strict follow-up.

Asunto(s)

RESUMEN

Alterations in intracellular Ca2+ ([Ca2+]i) are generally associated with cellular distress. Oxalate-induced cell injury of the renal epithelium plays an important role in promoting CaOx nephrolithiasis. However, the degree of change in intracellular free calcium ions in renal epithelial cells during oxalate exposure remains unclear. The aim of this study is to determine whether acute short-term exposure to oxalate produces morphological changes in the cells, induces a change in cytosolic Ca2+ levels in renal tubular epithelial cells and whether the application of extracellular glycosaminoglycans (GAGs) prevents these changes. Cultured Mardin-Darby canine kidney cells were exposed to oxalate, and changes in cytosolic Ca2+ were determined under various conditions. The effect of heparin and heparan sulfate (HS) during oxalate exposure was examined. The change in the GAG contents of the culture medium was also determined. Transmission electron microscopy (TEM) was performed for morphological analysis. The degree of change in cytosolic Ca2+ strongly correlated with oxalate concentration. Cytosolic Ca2+ levels decreased in parallel with an increase in the concentration of oxalate. However, this decrease was strongly inhibited by pretreatment with heparin or HS. TEM revealed cytoplasmic vacuolization, the appearance of flocculent material and mitochondrial damage after oxalate exposure. On the other hand, pretreatment with heparin or HS completely blocked these morphological changes. The present data suggest that acute exposure to a high concentration of oxalate challenges the renal cells, diminishes their viability and induces changes in cytosolic Ca2+ levels. Heparin and HS, which are known as potent inhibitors of CaOx crystallization, may also prevent oxalate-induced cell changes by stabilizing the cytosolic Ca2+ level.

Asunto(s)

RESUMEN

A 36-year-old man was admitted to hospital due to right flank pain as a result of ureteral stones. He had been followed up for type 1 glycogen storage disease since the age of 11 years. He had four episodes of spontaneous stone birth during the previous 2 years, and each stone was composed mainly of calcium oxalate. Intravenous pyelography showed right hydronephrosis due to ureteral stones and bilateral multiple renal stones. We carried out transurethral ureterolithotripsy (TUL) on the right ureteral stones. The composition was a mixture of calcium oxalate and calcium phosphate. Laboratory evaluation demonstrated the association of distal renal tubular acidosis (RTA). These observations suggest that hypocitraturia and distal RTA are strongly correlated to recurrence of calcium nephrolithiasis. The patient's serum uric acid and urinary citrate excretion levels normalized after allopurinol and potassium citrate administration.

Asunto(s)

RESUMEN

Although open simple prostatectomy remains the reference standard for the treatment of excessively large or giant prostatic hyperplasia, advances in technology and techniques have facilitated safe transurethral management of select cases. We report a case undergoing removal over 200 g of prostatic adenoma by three transurethral electrovaporization (TVP) sessions and discuss its feasibility in clinical use.

Asunto(s)

RESUMEN

OBJECTIVES: To examine the possibility of antegrade incisions at varying stricture lengths. We have developed a new method of using a ureteroscope and holmium:yttrium-aluminum-garnet (YAG) laser to make an antegrade incision without using a guidewire. Endoscopic internal urethrotomy involves the use of a guidewire or ureteral catheter that is passed through the stricture as an indicator for retrograde incision. METHODS: An antegrade incision was performed in 31 procedures for 28 patients with urethral strictures. We used a semirigid ureteroscope with an outer diameter of 6F at the tip. The ureteroscope was inserted into the urethra and passed through the stricture into the bladder under direct vision. The ureteroscope was pulled distally while an incision was made using the holmium:YAG laser at the 10-o'clock and 2-o'clock positions to a diameter of 17F. The endoscope was then replaced by a 17F panendoscope and an antegrade incision was similarly made up to 21F to 22F. RESULTS: An antegrade incision without the use of a guidewire was possible in all cases. Of the 31 incisions, restenosis appeared in 11 (35%). Of the 11 cases, re-incision was performed in 4 cases, and urethral sounding was conducted in the other 7 cases. Of the 4 re-incision cases, restenosis recurred in only 1 case. Of the 31 incisions, 23 (74%) were eventually successful. CONCLUSIONS: Antegrade incision using the narrow-diameter ureteroscope and holmium:YAG laser is a safe and easy method. This method is especially effective in cases of long strictures.

Asunto(s)

RESUMEN

We reported that expression of both HSPG and of bikunin are increased in calcium oxalate (CaOx) nephrolithic rat kidneys (lida et al., J. Am. Soc. Nephrol. 1999, Urol. Res. 1997). However, these findings were obtained from separate experiments. The present study evaluates whether levels of HSPG and bikunin expression differ in the rat kidney during calcium oxalate nephrolithiasis. Twenty-four male Wistar rats weighing 200-250 g were assigned to one of four groups (n = 6 each group) and administered with 0.5% ethylene glycol daily and 0.5 microgram of 1 alpha-OH-D3 every other day to induce CaOx nephrolithiasis. Animals were sacrificed 1 or 2 weeks later and both kidneys were excised. The cortex was separated from the medulla and papillary tips in the right kidney, then stored in liquid nitrogen for quantitative competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR). The left kidney was fixed in 10% buffered formalin for histochemical studies. We assessed the variable gene expression of both HSPG and bikunin by QC-RT-PCR. Immunohistochemical analyses of left kidney tissue samples determined the localization of HSPG and bikunin. Normal rats serving as controls (n = 6 each) were also sacrificed and processed in the same manner as the experimental groups. QC-RT-PCR confirmed that HSPG and bikunin mRNA expression is significantly increased in nephrolithic kidneys (p < 0.05; Mann-Whitney test), and that medulla and papillary tips tended to express more mRNA of both. Immunohistochemical studies revealed that the production of HS and bikunin was increased in both the distal and proximal tubules of nephrolithic kidneys. These findings suggest that the increased expression of both HSPG and bikunin play an important role during calcium oxalate stone formation. In addition, this phenomenon might be associated with the progression of urothelial damage.

Asunto(s)

RESUMEN

To develop a gene therapy for osteopathies, this study was conducted to establish a method of transferring the BMP gene, a bone formation factor, to cells and administering the cells with BMP expression to patients with osteopathies. Although virus vectors are frequently used for gene transfer, there has been reported a death case of gene therapy using the adenovirus vector. Therefore, various efforts have been made to prevent such complications. In the present study, we used electroporation by which gene transfer can be efficiently performed without inducing severe complications after electric perforation of the cell membrane. Human bone tissues were initially collected intraoperatively, and BMP-2 and Smad4 genes were cloned and integrated into GFP and DsRed plasmid vectors. Using in vitro electroporation, these plasmid vectors were transferred to the cultured chondrocytes (KTN-1) derived from human herniated intervertebral disk. Confocal laser microscopy revealed that the BMP gene was successfully transferred to the nucleus of chondrocytes in the presence of Smad. Since electroporation facilitated human gene transfer to the target cells, gene therapy using electroporation may facilitate individualized treatment for patients.

Asunto(s)

Asunto(s)

RESUMEN

The role of neoadjuvant hormonal therapy (NHT) before radical prostatectomy for localized prostate cancer remains controversial because many argue that apparent downstaging results in difficulties with the pathological evaluation of the neoadjuvant treated prostatectomy specimen. Furthermore, the downstaging to pT0 (no residual tumor), as reported by several institutions, remains questionable and is not yet confirmed by clinical or experimental evidence. To examine this issue and to assess the influence of NHT on downstaging, we investigated the stage pT0 status in radical prostatectomy specimens after NHT. We retrospectively reviewed 31 patients with histologically confirmed clinical stage T1c, T2 or T3 prostate cancer. All patients had received NHT for a mean duration of 5.2 months (range 2-19). We compared the pretreatment parameters (PSA, clinical stage, biopsy Gleason grade, number of positive cores, total length of cancer on each sextant biopsy or duration of NHT) to the pathological findings in the specimen sectioned at 3-mm thick after NHT. Five (16%) of 31 patients had no residual cancer (pT0) after radical prostatectomy, 8 (26%) had organ-confined disease (stage pT2), 6 (19%) had specimen confined disease, 10 (33%) had non-specimen confined disease and only 2 (6%) had lymph node metastasis. The histologic changes, including glandular atrophy and cytoplasmic vacuolation were stronger in specimens with a long duration (4 or more months) of NHT than those of a short duration (3 or less months). Multiple logistic regression analysis showed that only a longer duration of NHT was an independent predictor of a stage pT0 status in radical prostatectomy specimens after NHT (p=0.04, Odds ratio; 1.92, 95% CI; 1.03-3.56). Downstaging to pT0 occurs after duration of NHT of longer than 3 months. Further investigation of the optimal duration of NHT for downstaging and for improving patients' survival should be accomplished in randomized trials.

Asunto(s)

RESUMEN

Since the emesis induced by cytotoxic drugs is intractable, and is a possible determinant of a patient's QOL during chemotherapy, the control of this adverse event is essential to complete a course of cancer chemotherapy. The anti-emetic effects of a 5-HT3 antagonist, ondansetron hydrochloride (OND), was evaluated during a course of CDDP-containing chemotherapy. Forty-eight patients with gynecologic carcinoma, respiratory malignancy, or urological cancer were followed throughout their treatment courses. For acute emesis, prophylactic OND was given intravenously before CDDP administration, and OND tablets were used for 4 days from the day following CDDP administration as a measure against delayed emesis. The efficacy of OND gradually decreased for the acute emesis (1st course: 73.8%, 2nd course: 62.8% and 3rd course: 56.7%). The efficacy, however, did not decrease against the delayed emesis. Of patients with a good response, "effective" or "highly effective", in the previous treatment course, over 80% could again obtain a good response in the next treatment course. Adverse events of this anti-emetic treatment were not observed except for mild leukocytosis in one case, and this unexplainable effect abated without any specific treatments. In conclusion, the anti-emetic effects of OND sufficiently prevented the emetogenic action of CDDP throughout the treatment course, with a special importance for successful control in the first treatment course. The additional use of corticosteroid might enhance the effects of OND for female patients.

Asunto(s)

RESUMEN

We have reported that heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG, syndecan-1) expression significantly increased in the rat kidney during calcium oxalate (CaOx) nephrolithiasis. Although the exact role of syndecan still remains unclear, HS/syndecan-1 is thought to have some important role in the CaOx crystal formation. Mardin-Darby canine kidney (MDCK) cells are most commonly used in kidney stone research. It was reported that MDCK cells do not express syndecan-1. In the present study, we established a novel MDCK cell line (KIC-synd-1) that expressed the human syndecan-1 gene. In this cell line, we confirmed stable expression of both sndecan-1 gene and core protein. Immunohistochemical study revealed positive staining of syndecan-1 monoclonal antibody in the basolateral and cytosolic area of the KIC-synd-1 cells. We also investigated the composition of glycosaminoglycans (GAGs) side chains in MDCK cells and KIC-synd-1 cells by using high-performance liquid chromatography (HPLC). Four types of HS chains were identified in both cells as follows; delta diHS-NS, delta diHS-6S, delta diHS-diS1, delta diHS-diS2. Increased production of delta diHS-NS and delta diHS-diS2 were shown in KIC-synd-1 cells compared with production in MDCK cells (p < 0.05). In contrast, only a small amount of delta diHS-6S and delta diHS-diS1 was contained in both cell lines. Total amount of HS was significantly increased in the KIC-synd-1 cells compare with that in the wild type MDCK cells (p < 0.05). Scanning electron microscopy revealed no significant difference between cell surface of wild type MDCK cells and that of KIC-synd-1 cells in normal conditions. However, calcium oxalate crystal attachment was apparently decreased in the KIC-synd-1 cells. These results suggested that cell surface HS/syndecan-1 has preventive role for calcium oxalate nephrolithiasis via creation of a charge barrier against COM crystal attachment.

Asunto(s)