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Biomedical subjects

Hideaki Miyake

Publications and source records attributed to Hideaki Miyake.

At least 91 records · Page 5Linked to original sources

Introduction of midkine gene into human bladder cancer cells enhances their malignant phenotype but increases their sensitivity to antiangiogenic therapy.

PURPOSE: Midkine (MK) is a member of a family of heparin-binding growth factors, which was reported to have an important role in angiogenesis. Although MK was reported to be associated with bladder cancer progression, the functional significance of MK expression in bladder cancer progression has not been elucidated. The objectives of this study were to determine whether overexpression of MK in bladder cancer cells enhances their malignant potential and to evaluate the inhibitory effect of the antiangiogenic agent TNP-470 on the growth of MK-overexpressing bladder cancer cells in vivo. EXPERIMENTAL DESIGN: We introduced the MK gene into human bladder cancer UM-UC-3 cells that do not secrete a detectable level of MK protein and generated the MK-overexpressing cell line UM-UC-3/MK. The biological activity of secreted MK was evaluated using a human umbilical vein endothelial cell proliferation assay. To investigate the in vivo effects of MK overexpression on tumor growth, each cell line was injected s.c. and orthotopically into nude mice. To evaluate the therapeutic effects of the antiangiogenic agent, mice were given TNP-470 after s.c. injection of each cell line. The microvessel density of tumors was quantitated by immunohistochemistry of CD31. RESULTS: The heparin affinity-purified conditioned media of UM-UC-3/MK cells significantly enhanced human umbilical vein endothelial cell proliferation. MK expression had no effect on in vitro growth but conferred a growth advantage on both s.c. and orthotopic tumors in vivo. Furthermore, enhanced tumor growth was closely associated with increased microvessel density. Significant inhibition of tumor growth by TNP-470 treatment was observed only in UM-UC-3/MK tumors and not in control tumors. CONCLUSIONS: We demonstrated that overexpression of the MK gene causes an increase in the angiogenic activity of cells through vascular endothelial cell growth, resulting in enhanced malignant potential of human bladder cancer cells. Moreover, the present findings suggest that TNP-470 could be used as a novel therapeutic adjunct to conventional agents for patients with advanced bladder cancer overexpressing MK.

Angiogenesis Inhibitors↗

Establishment of a prostatic small-cell carcinoma cell line (SO-MI).

BACKGROUND: Prostatic small-cell carcinoma is an extremely rare, highly aggressive disease. We established a cell line from this tumor. MATERIALS AND METHODS: Tumor tissue obtained from a 24-year-old Japanese man was used to establish the cell line. Cultured cells and tumors transplanted into nude mice were characterized by histologic, immunohistologic, immunocytologic, and molecular biologic methods. RESULTS: An immortal culture cell line (SO-MI) was successfully established. SO-MI cells adhered weakly to plastic surfaces in vitro, showing a 52- to 72-hr doubling time. SO-MI cells were heterotopically and orthotopically transplantable in nude mice. The cells were immunoreactive for NSE, chromogranin A, and NCAM, but not for ACTH, calcitonin, serotonin, gastrin, insulin, glucagons, LCA, EMA, PAP, PSA, androgen receptor, and p53. SO-MI cells secreted NSE in vitro and in vivo. SO-MI cells at passage 30 contained 50-59 chromosomes with a modal number of 55. PCR suggested that the p53 gene was deleted in SO-MI cells. RT-PCR detected no mRNA encoding androgen receptor in these cells. CONCLUSIONS: SO-MI cells retain the neuroendocrine nature of the original tumor, and should be useful in studying possible etiologies and new treatments.

Adult↗

Castration-induced increases in insulin-like growth factor-binding protein 2 promotes proliferation of androgen-independent human prostate LNCaP tumors.

Activation of alternative growth factor pathways after androgen withdrawal is one mechanism mediating androgen-independent (AI) progression in advanced prostate cancer. Insulin-like growth factor (IGF) I activation is modulated by a family of IGF binding proteins (IGFBPs). Although IGFBP-2 is one of the most commonly overexpressed genes in hormone refractory prostate cancer, the functional significance of changes in IGF-I signaling during AI progression remains poorly defined. In this article, we characterize changes in IGFBP-2 in the LNCaP tumor model after androgen withdrawal and evaluate its functional significance in AI progression using gain-of-function and loss-of-function analyses. IGFBP-2 mRNA and protein levels increase 2-3-fold after androgen withdrawal in LNCaP cells in vitro in LNCaP tumors during AI progression in vivo. Increased IGFBP-2 levels after castration were also identified using a human prostate tissue microarray of untreated and posthormone therapy-treated prostatectomy specimens. LNCaP cell transfectants that stably overexpressed IGFBP-2 progressed more rapidly after castration than control tumors. Antisense oligonucleotides (ASOs) targeting the translation initiation site of IGFBP-2 reduced IGFBP-2 mRNA and protein expression by >70% in a dose-dependent and sequence-specific manner. ASO-induced decreases in IGFBP-2-reduced LNCaP cell growth rates and increased apoptosis 3-fold. LNCaP tumor growth and serum prostate-specific antigen levels in mice treated with castration plus adjuvant IGFBP-2 ASOs were significantly reduced compared with mismatch control oligonucleotides. Increased IGFBP-2 levels after androgen ablation may represent an adaptive response that helps potentiate IGF-I-mediated survival and mitogenesis and promote androgen-independent tumor growth. Inhibiting IGFBP-2 expression using ASO technology may offer a treatment strategy to delay AI progression.

Androgens↗

Carcinoma in situ spread to mucosa of sigmoid colon neobladder.

This is the first case of carcinoma in situ (CIS) of a transitional cell carcinoma that had spread into a neobladder constructed using a bowel segment associated with local recurrence at the ureteral-neobladder anastomosis. Considering that the CIS lesion was found in macroscopically intact epithelium remote from the main tumor, this strongly suggests that CIS could arise from solid tumor by implantation. Although some studies have reported secondary malignancy occurring in the neobladder, most have been adenocarcinoma that arose from the replaced bowel segment. To our knowledge, the present case is the first of widespread CIS of transitional cell carcinoma in an orthotopic neobladder.

Aged↗

Prediction of the extent of prostate cancer by the combined use of systematic biopsy and serum level of cathepsin D.

BACKGROUND: The objective of this study was to assess the usefulness of combined systematic prostate biopsy with the serum level of cathepsin D, which has recently been shown to be a useful marker for prostate cancer, to predict the disease extension. METHODS: Seventy-two patients with clinically organ-confined disease who underwent radical prostatectomy were evaluated for serum prostate-specific antigen (PSA) and cathepsin D levels, systematic biopsy, and pathological stage. RESULTS: The incidence of extraprostatic disease in patients with more than half the biopsy cores positive or > or = 15 ng/mL cathepsin D was significantly higher than that in patients with less than half the biopsy cores positive or < 15 ng/mL cathepsin D, respectively; whereas cancer in bilateral lobes or > or = 10 ng/mL PSA could not be used as a predictor of extraprostatic disease. Furthermore, in patients with more than half the biopsy cores positive and > or = 15 ng/mL cathepsin D or those with more than half the biopsy cores positive and > or = 10 ng/mL PSA, extraprostatic disease was significantly more common than in those with less than half the biopsy cores positive and < 15 ng/mL cathepsin D or those with less than half the biopsy cores positive and < 10 ng/mL PSA, respectively. Furthermore, the prediction of the incidence of extraprostatic disease using these three variables was significantly more accurate than using two of the variables (percentage positive biopsy cores plus serum cathepsin D or PSA). CONCLUSION: Systematic biopsy together with serum cathepsin D and/or PSA was a useful predictor of the extent of prostate cancer. Patients with more than half the biopsy cores positive, > or = 15 ng/mL cathepsin D and/or > or = 10 ng/mL PSA could avoid prostatectomy because there is a significantly high probability that they already have extraprostatic disease.

Aged↗

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder.

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.

Adjuvants, Immunologic↗

Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy.

BACKGROUND: We analyzed the outcome of repeated transrectal ultrasound (TRUS)-guided systematic prostate biopsy in Japanese men whose clinical findings were suspected of prostate cancer after previous negative biopsies. METHODS: Between January 1993 and March 2002, 1045 patients underwent TRUS-guided prostate biopsy. Among them, 104 patients underwent repeat biopsy due to indications of persistent elevated serum prostate-specific antigen (PSA), abnormal digital rectal examination (DRE) or TRUS, increased PSA velocity, and/or previous suspicious biopsy findings. Several clinicopathological factors were evaluated for their ability to predict the detection of prostate cancer on repeat biopsy. RESULTS: Prostate cancer was detected in 22 of 104 patients (21.2%) who underwent repeat biopsies. PSA concentration and PSA density at both the initial and repeat biopsies, and PSA velocity in men with positive repeat biopsy were significantly greater than those in men with negative repeat biopsy. The incidence of abnormal findings in DRE and TRUS at initial biopsy in men with positive repeat biopsy was also significantly higher than that in men with negative repeat biopsy. However, neither the presence of prostatic intraepithelial neoplasia nor number of biopsy cores at initial biopsy had a significant association with the results of the repeat biopsy. Furthermore, multivariate analysis revealed that PSA and PSA density at both the initial and repeat biopsies, PSA velocity, and DRE and TRUS findings at initial biopsy were independent predictors of malignant disease on repeat biopsy. CONCLUSION: Despite an initial negative biopsy, repeat TRUS-guided biopsy should be carried out to exclude prostate cancer in cases of suspicious clinical findings, such as elevated PSA or PSA-related parameters, or abnormal findings of DRE or TRUS.

Adenocarcinoma↗

Pathological findings of radical prostatectomy specimens in Japanese men diagnosed on single core positive prostate biopsy in eight with a Gleason score less than 4.

BACKGROUND: The objective of the present study was to analyze the pathological findings of radical prostatectomy specimens diagnosed on single core positive prostate biopsy in eight systematic transrectal ultrasonography (TRUS)-guided biopsies with a Gleason score </= 4. METHODS: Between January 1993 and March 2001, 975 patients underwent TRUS-guided prostate biopsy, and 32 patients were diagnosed as having prostate cancer based only on one positive core with a Gleason score </= 4. In this study, 14 of the 32 patients who underwent radical prostatectomy without any neoadjuvant therapies were enrolled, and the pathological findings of their radical prostatectomy specimens were evaluated. RESULTS: The clinical stage of the 14 patients was T1c in 10 and T2 in four. Cancer was detected in the prostate apex in seven patients, the middle in two, the base of the peripheral zone (PZ) in three, the lateral horn of the PZ in one and the transitional zone (TZ) one. Pathological stage of the 14 patients was pT2a in four, pT2b in six, pT3a in three and pT3b one. Gleason score of the radical prostatectomy specimens in 11 patients was also </= 4. Of the 10 patients diagnosed with cT1c, extraprostatic disease was found in only one radical prostatectomy specimen. All three patients whose cancer was detected from the base of the PZ showed pT3 disease. During the median follow-up period of 47.5 months, all patients were alive with no evidence of disease. CONCLUSION: The prognosis of patients who were diagnosed with one core positive prostate biopsy with a Gleason score </= 4 is generally favorable; however, advanced disease tended to be observed in patients who were diagnosed with cT2a and/or whose cancer was detected from the base of PZ.

Aged↗

Comparison of quality of life following laparoscopic and open prostatectomy for prostate cancer.

PURPOSE: We compare the quality of life after laparoscopic prostatectomy to that after standard radical prostatectomy. MATERIAL AND METHODS: The quality of life of 52 and 54 patients who underwent laparoscopic and open radical prostatectomy, respectively, was analyzed using the European Organization for the Research and Treatment of Cancer Prostate Cancer quality of life questionnaire for general health related quality of life, International Index of Erectile Function 5 for screening erectile dysfunction and International Continence Society MaleSF questionnaire to evaluate urinary status. These questionnaires were given to patients before and 6 months after surgery. RESULTS: The general health related quality of life survey revealed no significant differences in health before and after laparoscopic and open prostatectomy. However, sexual quality of life was markedly lower after surgery (p <0.01). In addition, the International Index of Erectile Function score was markedly abrogated by surgery (p <0.05) and quality of life due to urinary incontinence was significantly disturbed by surgery (p <0.05). In contrast, quality of life due to voiding dysfunction was impaired before surgery and significantly improved by surgery (p <0.05). Patients were also asked if they would choose the same treatment if suffering from the same disease, with more patients treated laparoscopically choosing the same treatment than those treated with open surgery (p <0.05). CONCLUSIONS: While general health related quality of life was not impaired, sexual quality of life was diminished by surgery. Patients were generally satisfied with postoperative urinary status. Although patients who underwent laparoscopic prostatectomy expressed a more favorable attitude toward surgery, there was no significant difference in quality of life at 6 months after surgery between the 2 groups.

Activities of Daily Living↗

Over expression of clusterin is an independent prognostic factor for nonpapillary renal cell carcinoma.

PURPOSE: Recent studies have revealed the powerful anti-apoptotic activity of clusterin in several types of malignant tumors. However, the significance of clusterin expression in human renal cell carcinoma has not been well characterized. We determined whether the expression level of clusterin in nonpapillary renal cell carcinoma may be used as predictor of tumor progression and prognosis. MATERIALS AND METHODS: Total RNA was extracted from 93 nonpapillary renal cell carcinomas obtained at surgery and expression levels of clusterin messenger (m)RNA in these specimens were measured by Northern blot analysis. Findings were analyzed with respect to several clinicopathological factors. RESULTS: There were 48 cases (52%) with strong clusterin mRNA expression and 45 (48%) in which it was weak or nonexistent. The expression level of clusterin mRNA did not significantly correlate with patient gender, age, tumor grade or size, or histological cell type, whereas pathological stage and the incidence of tumor recurrence were closely associated with clusterin expression (p <0.005 and <0.01, respectively). The recurrence-free and overall survival rates in patients with strong clusterin expression were significantly lower than in those with weak or no expression (p <0.05). Furthermore, multivariate analyses revealed that strong expression of clusterin was an independent predictor of tumor recurrence and overall survival (p <0.05). CONCLUSIONS: These findings suggest that the over expression of clusterin may be a useful prognostic parameter in patients with nonpapillary renal cell carcinoma after radical nephrectomy.

Adult↗

Overexpression of clusterin in transitional cell carcinoma of the bladder is related to disease progression and recurrence.

OBJECTIVES: To determine whether the expression level of clusterin in transitional cell carcinoma (TCC) of the bladder could be used as a predictor of tumor recurrence and prognosis. METHODS: Total RNA samples were extracted from 89 specimens of TCC of the bladder, and the expression level of clusterin mRNA in these specimens was measured by Northern blot analysis. The results were evaluated with respect to several clinicopathologic factors. RESULTS: The mean level of clusterin mRNA expression in invasive TCC of the bladder was fourfold and fivefold higher than that in superficial TCC and normal urothelial tissue, respectively. The expression level of clusterin mRNA showed no significant correlation with sex, age, tumor size, or multiplicity, and the pathologic stage and tumor grade showed close associations with clusterin expression. The overall survival rate of patients with strong clusterin expression was significantly lower than that of patients with weak expression. Among the 43 patients with invasive TCC who underwent complete resection, the recurrence-free survival rate of patients with strong clusterin expression was significantly lower than that of patients with weak expression. Moreover, multivariate analyses indicated that among these 43 patients, strong expression of clusterin was an independent predictor of tumor recurrence. CONCLUSIONS. These findings indicate that clusterin mRNA is strongly expressed in invasive TCC of the bladder compared with the expression in superficial TCC and that strong clusterin expression could be used as a novel predictor of prognosis of patients with TCC of the bladder.

Adult↗

Increased serum carcinoembryonic antigen level in patients undergoing colon neobladder replacement compared with ileal neobladder replacement.

OBJECTIVES: To compare the serum and urinary carcinoembryonic antigen (CEA) levels for assessment of possible risk of malignant transformation in patients with orthotopic neobladder. METHODS: The serum and urinary levels of CEA, nutritional status, and acid-base and electrolyte balances were studied in 87 patients after radical cystectomy (22 with ileal neobladder, 28 with colon neobladder, and 37 with ileal conduit). The results of these groups were compared. RESULTS: The serum CEA level in patients with colon neobladder, ileal neobladder, and ileal conduit was 5.4 +/- 3.0, 3.7 +/- 1.6, and 3.1 +/- 1.5 ng/mL, respectively. The serum CEA level in the colon neobladder group was significantly higher than the levels in the remaining two groups (P <0.05); 16 patients (57%) with colon neobladder had elevated serum CEA values (ie, greater than 5 mg/mL). Elevated serum CEA was observed in only 5 (23%) and 3 (8%) patients with ileal neobladder or ileal conduit, respectively. The serum CEA value in these patients was associated with the urinary CEA value (P <0.001), but not the other factors examined. CONCLUSIONS: These findings suggest that colon bladder replacement caused significantly increased serum CEA values compared with ileal neobladder or ileal conduit; however, the elevated serum CEA level correlated with the urinary CEA level, irrespective of other clinical factors. Therefore, the elevated serum CEA in the colon neobladder group may have been due to reabsorption of CEA in urine rather than to an association with malignant changes in the bowel segments used for neobladder creation.

Acid-Base Equilibrium↗

Targeting anti-apoptotic genes upregulated by androgen withdrawal using antisense oligonucleotides to enhance androgen- and chemo-sensitivity in prostate cancer.

The main obstacle to improved survival of advanced prostate cancer is our failure to prevent its progression to its lethal and untreatable stage of androgen independence. New therapeutic strategies designed to prevent androgen-independent (AI) progression must be developed before significant impact on survival can be achieved. Characterization of changes in gene expression profiles after androgen ablation and during progression to androgen-independence suggest that the various therapies used to kill neoplastic cells may precipitate changes in gene expression that lead to the resistant phenotype. Castration-induced increases in antiapoptosis genes, Bcl-2 and clusterin, help create a resistant phenotype, while antisense oligonucleotides can inhibit these adaptive cell survival mechanisms and enhance both hormone and chemotherapy. Ongoing efforts are necessary to identify additional molecular pathways mediating AI progression and chemoresistance, since complexities of tumor heterogeneity and adaptability dictate that optimal control over tumor progression will require multi-target systemic therapies.

Adenocarcinoma↗

Neoadjuvant androgen withdrawal prior to external radiotherapy for locally advanced adenocarcinoma of the prostate.

BACKGROUND: It is unclear whether positive interactions between radiation and androgen withdrawal for patients with locally advanced prostate cancer is synergistic or additive. The present study aimed to clarify the significance of neoadjuvant androgen ablation prior to external radiotherapy in a human prostate LNCaP tumor model and in patients with locally advanced prostate cancer. METHODS: Comparisons were made between the effect of castration prior to radiation on the growth of subcutaneous LNCaP tumors implanted into male nude mice and their serum prostate-specific antigen (PSA) levels, and the results of castration or radiation alone. Twenty-nine patients with histologically proven and locally advanced adenocarcinoma of the prostate were treated with luteinizing hormone-releasing hormone analog at least 3 months before, during, and after external radiation therapy with a total dose of 70 Gy. The toxicity and response to this therapy were evaluated. RESULTS: Treatment combining castration and radiation resulted in synergistic inhibition of LNCaP tumor growth and a significant delay in the emergence of androgen-independent recurrence as opposed to either treatment alone. The external radiotherapy was completed in 28 patients (96.6%), resulting in a reduction of serum PSA levels in all 28 patients to below 1.0 ng/mL. All patients were alive after a mean follow-up period of 34 months (range 11-53) with a 3-year PSA relapse-free survival rate of 83.7%. Among several factors examined, only the Gleason score was significantly associated with PSA relapse-free survival in univariate analysis, but not in multivariate analysis. Thirteen of 28 patients (46%) and 7 of 28 (25%) also showed at least one form of gastrointestinal or genitourinary toxicity, respectively. Of these patients, 8 with gastrointestinal toxicities, and 1 with genitourinary toxicity, experienced acute complications higher than grade 3. CONCLUSION: The experimental findings objectively suggested the use of neoadjuvant androgen withdrawal prior to radiation therapy. Although our clinical experience is preliminary, combined androgen ablation and radiation therapy may also be effective in controlling locally advanced prostate cancer, with tolerable side-effects.

Adenocarcinoma↗

Comparison of surgical stress between laparoscopy and open surgery in the field of urology by measurement of humoral mediators.

BACKGROUND: Recently, laparoscopic procedures have become more common in urological surgery, and are suggested to be less stressful compared with open surgery; however, little data on objective evaluation of surgical stress after laparoscopic surgery are available. The objective of this study was to compare surgical stress between laparoscopic and open surgery in the field of urology by measurement of humoral mediators. METHODS: Blood samples were obtained from 25 patients who underwent laparoscopic surgery (laparoscopic radical prostatectomy, 10; retroperitoneoscopic nephrectomy or nephroureterectomy, seven; laparoscopic adrenalectomy, five; and hand-assisted laparoscopic radical nephrectomy, three) and 10 who underwent open surgery (retropubic radical prostatectomy, four; radical cystectomy, three; and radical nephrectomy, three), 48 h before surgery, during surgery, and 24, 48 and 96 h after surgery. Serum levels of interleukin (IL)-6, IL-10 and granulocytic elastase in these samples were measured, and the results were analyzed with respect to several clinical factors. RESULTS: In both groups, IL-6 and granulocytic elastase levels increased during surgery and reached maximum levels 24 h after surgery; the increase in granulocytic elastase tended to be prolonged compared with that of IL-6. Changes in IL-10 levels in the open surgery group were similar to those of IL-6 and granulocytic elastase levels, whereas IL-10 levels in the laparoscopic surgery group reached a maximum level during surgery and then decreased to the same level as at 48 h before surgery, on the first postoperative day. The maximum levels of these three mediators in the laparoscopic surgery group were significantly lower than those in the open surgery group. IL-6 was closely associated with the interval of fasting and duration of hospitalization after surgery. CONCLUSION: Although the present study was based on retrospective and non-randomized analysis, the findings suggest that serum levels of IL-6, IL-10 and granulocytic elastase are useful as objective markers of surgical stress, and that laparoscopic surgery is markedly less stressful than open surgery.

Female↗

D-xylose absorption after urinary orthotopic bladder replacement: colon neobladder compared with ileal neobladder.

BACKGROUND: To evaluate the digestive and absorptive status using the D-xylose test in patients who underwent radical cystectomy and orthotopic bladder replacement either by colon or ileal segment. METHODS: D-xylose serum levels after an oral load, nutritional status, plasma vitamin B12 levels, and acid-base and electrolyte balances were studied in 18 patients with colon neobladder and 12 patients with ileal neobladder. Mean follow-up period was 51 months. Results of both types of bladder replacement and a healthy control group were compared. RESULTS: Although no significant difference in the changes of plasma levels of D-xylose after oral load was observed between patients with colon neobladder and healthy controls, plasma levels of D-xylose 90 min after oral load in patients with ileal neobladder were significantly lower than those with colon neobladder. In contrast, there was no significant difference in nutritional status, plasma levels of vitamin B12, and acid-base and electrolyte balances between patients with colon and ileal neobladders. CONCLUSION: Despite acceptable nutritional status, intestinal malabsorption might be present in patients with ileal neobladder, as indicated by the plasma levels of D-xylose, while the colon neobladder group showed no significant differences compared with normal controls. Therefore, absorptive and metabolic status should be carefully monitored after ileal neobladder creation.

Administration, Oral↗

Feasibility and usefulness of laparoscopic radical prostatectomy: Kobe University experience.

OBJECTIVES: The objective of this study was to present the clinical outcomes of 26 patients who underwent laparoscopic radical prostatectomy at our institution. METHODS: We performed laparoscopic prostatectomy on patients who were clinical stage T1 or T2. The mean age was 70 years old (range: 52-76). The mean level of pre-treatment prostate-specific antigen (PSA) was 8.7 ng/mL (range: 3.3-45). The Gleason score of the needle biopsy was < 7 in 21 patients and > or = 7 in five patients. Clinical stage was T1c in 17 patients, T2a in 6 patients and T2b in 3 patients. Operative techniques followed those of the French groups. Five trocars were introduced into the peritoneal cavity. The vas deferens and seminal vesicles were dissected to reach the posterior wall of the prostate and the retroperitoneal space was dissected around the urinary bladder. Incision of endopelvic fascia and dorsal vein complex (DVC) ligation were performed. The bladder neck and prostate were divided, then the distal urethra was cut. The lateral pedicles of the prostate were cut and the entire prostate was removed. Vesico-urethral anastomosis was performed at eight points. RESULTS: Mean operation time was 7 h 30 min. Mean bleeding volume (including urine volume) was 850 mL (range: 32-3135). All patients underwent autologous blood transfusion. Only one patient required further blood transfusion. Gleason scores of resected specimens were < 7 in 10 patients, and > or = 7 in 16 patients. Pathological stage was T0 in 1 patient, T2a in 6 patients, T2b in 13 patients, T3a in 5 patients and T3b in 1 patient. The PSA value was undetectable in all patients one month after surgery. Ten patients who survived for 6 months after surgery had complete urinary continence without a pad. In 7 of the 12 patients who were potent before surgery, neurovascular bundles were preserved, and 5 of them (71%) achieved complete or incomplete erection 3 months after surgery. However, only one patient (14%) could have sexual intercourse. CONCLUSION: Although longer follow-up is necessary to evaluate this surgical technique, laparoscopic prostatectomy seems to be a reasonable option in the treatment of organ-confined prostate cancer.

Aged↗

Clinical outcome of bacillus Calmette-Guérin perfusion therapy for carcinoma in situ of the upper urinary tract.

BACKGROUND: The objective of this study was to evaluate the efficacy of intrarenal bacillus Calmette-Guérin (BCG) instillation for the treatment of carcinoma in situ (CIS) of the upper urinary tract. METHODS: Sixteen patients who were diagnosed as having CIS of the upper urinary tract were treated with intrarenal BCG instillation. BCG (80 mg) in normal saline was administered once weekly, 6 times in total as one course through a percutaneous nephrostomy tube in 5 patients, and a retrograde ureteric catheterization using a Single-J or Double-J stent in 2 and 9 patients, respectively. RESULTS: During the median follow-up period of 30 months (range: 9-90 months), no patients died, and 13 patients remained cytologically negative in urine collected from the upper urinary tract after BCG treatment was completed. However, one of these 13 patients had CIS in the bladder and prostatic urethra 34 months after the BCG therapy and had to undergo radical cystectomy. The remaining 3 patients experienced recurrence in the upper urinary tract 4, 8, and 11 months after treatment, despite a favorable response to the initial BCG instillation. Of these 3 patients, one patient received an additional course of BCG therapy, while the remaining 2 underwent nephroureterectomy. Bladder irritability or a fever higher than 38 degrees C was observed in 12 or 9 patients, respectively; however, such side-effects were not clinically significant, and no patient received antitubercular treatment. CONCLUSION: Intrarenal instillation of BCG appears to be effective and safe for treatment of CIS of the upper urinary tract; however, further experience and longer follow-up studies of this treatment are required.

Adjuvants, Immunologic↗