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Biomedical subjects

Shoji Hara

Publications and source records attributed to Shoji Hara.

At least 19 recordsLinked to original sources

Stereoselective generation of (E)- and (Z)-2-fluoroalkylidene-type carbenoids from (2-fluoro-1-alkenyl)iodonium salts and their application for stereoselective synthesis of fluoroalkenes.

Alkylidene-type carbenoids, generated from (Z)- or (E)-(2-fluoro-1-alkenyl)iodonium salts by treatment with LDA, reacted with trialkylboranes to give (E)- or (Z)-(fluoroalkenyl)boranes stereoselectively. The resulting (fluoroalkenyl)borane can be used for the selective synthesis of (E)- or (Z)-fluoroalkenes, (E)- or (Z)-fluoroiodoalkenes, and alpha-fluoroketones. [reaction: see text]

Journal Article↗

Clinical outcomes of laparoscopic adrenalectomy according to tumor size.

OBJECTIVES: In order to evaluate the indication and usefulness of laparoscopic adrenalectomy, clinical outcomes of laparoscopic adrenalectomy for patients with adrenal tumors were examined. Whether tumor size affects surgical outcome was analysed, along with the long-term clinical outcome for these patients. PATIENTS AND METHODS: A total of 63 patients with adrenal tumor underwent laparoscopic adrenalectomy in our institute between 1999 and 2003. A laparoscopic transperitoneal approach was used in all cases. Underlying pathologies comprised Cushing syndrome (n = 12), pheochromocytoma (n = 13), primary aldosteronism (n = 21), non-functioning adenoma (n = 12) and others (n = 5). RESULTS: No open conversion was performed. Mean operative duration was 239 min, and mean estimated blood loss was 134 mL. Tumor diameter was significantly smaller for primary aldosteronism than for Cushing syndrome, which in turn was significantly smaller than for adrenocorticotropic hormone-independent macronodular hyperplasia (AIMAH). No significant differences in surgical outcome and postoperative recovery were noted between large (>or=5 cm) and small (<5 cm) tumors. Long-term clinical outcome was better for patients with pheochromocytoma or primary aldosteronism than for patients with Cushing syndrome. CONCLUSIONS: Laparoscopic adrenalectomy for benign tumor offers excellent surgical outcomes and convalescence. This is true for both small and large tumors.

Adrenal Gland Neoplasms↗

Significance of renal function in changes in acid-base metabolism after orthotopic bladder replacement: colon neobladder compared with ileal neobladder.

BACKGROUND: The objective of this study was to determine whether renal function influences the acid-base metabolism in patients undergoing orthotopic bladder replacement using intestinal segment. METHODS: Acid-base balance, serum electrolytes and renal function were studied in 30 patients with colon neobladder and 18 patients with ileal neobladder. Mean follow up was 51 months. Effects of renal function on acid-base metabolism in both types of bladder replacement were compared. Therapeutic efficacy of the sodium bicarbonate administration was also evaluated in cases with hyperchloremic acidosis. RESULTS: No significant differences were observed in any of the variables examined between the colon and ileal neobladder groups, except for potassium concentration. Although metabolic acidosis was detected using the Siggard-Anderson acid-base nomogram in eight (26.7%) and seven (38.9%) patients in the colon and ileal neobladder groups, respectively, this difference was not significant. In both the colon and ileal neobladder groups, the serum creatinine concentrations in patients diagnosed with metabolic acidosis were significantly higher than in those diagnosed with a normal metabolic status. Furthermore, as a result of severe metabolic acidosis, three (10.0%) and three (16.7%) patients in the colon and ileal neobladder groups, respectively, were administered sodium bicarbonate and their metabolic status was fully normalized. CONCLUSIONS: Despite there being no statistical difference, patients with ileal neobladder may more easily develop metabolic acidosis compared with those with colon neobladder. In addition, a close association between the serum creatinine level and the degree of metabolic acidosis was observed in both groups. However, even if severe metabolic acidosis occurs, it is relatively easy to correct using sodium bicarbonate. These findings suggest that it might be safe to use a colon segment for orthotopic bladder reconstruction in patients with higher serum creatinine levels, despite no significant difference in acid-base metabolism and detection rates of metabolic acidosis between the colon and ileal neobladder groups.

Acid-Base Imbalance↗

Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model.

BACKGROUND: The objectives of this study were to evaluate the antitumor effects of the simultaneous introduction of interleukin 12 (IL-12) and IL-18 genes into a mouse bladder cancer cell line (MBT2). We intended to compare these with those of either gene alone and to investigate the mechanism of the effects induced by the transfer of IL-12 and/or IL-18 genes in this model system. METHODS: We transfected the IL-12 and/or IL-18 genes into MBT2 cells by the liposome-mediated gene transfer method. We confirmed the secretion of IL-12 and/or IL-18 by enzyme-linked immunosorbent assay. Parental (MBT2/P), IL-12-transfected (MBT2/IL-12), IL-18-transfected (MBT2/IL-18) or both IL-12- and IL-18-transfected (MBT2/Both) cells were subcutaneously or intravenously injected into syngeneic C3H mice. To analyze the mechanism of tumor rejection, these clones were subcutaneously injected into naive nude mice and those depleted with natural killer (NK) cells by antibody. RESULTS: MBT2/IL-12, MBT2/IL-18 and MBT2/Both were completely rejected when they were injected subcutaneously or intravenously into syngeneic mice. However, MBT2/IL-12, but not MBT2/IL-18, could grow in nude mice. Moreover, the antitumor effect of MBT2/IL-18 was partially abrogated when injected into nude mice of which NK cells were depleted by antibody treatment. MBT2/Both was completely rejected in both nude mice with and without NK cells. CONCLUSION: The results of the present study indicate that T cells and NK cells seem to play important roles in the antitumor effects by the secretion of IL-12 and IL-18, respectively, and MBT2/Both possesses both mechanisms.

Animals↗

Global analysis of gene expression profiles in ileum in a rat bladder augmentation model using cDNA microarrays.

BACKGROUND: The objective of the present study was to globally characterize the changes in the gene expression profile in the ileum after long-term urine exposure in a rat ileal augmented bladder model using cDNA microarrays. METHODS: Bladder augmentation using the ileum was performed in female 8-week-old rats. The ileal epithelia used for bladder augmentation were harvested 1 and 3 months postoperatively and changes in the gene expression in these tissues were compared with that of intact ileal epithelia from sham-operated rats using cDNA microarrays consisting of 1176 rat genes. RESULTS: Marked changes in gene expression in the ileum used for bladder augmentation were observed for 30 genes (16 up-regulated and 14 down-regulated genes). The differentially expressed genes include those associated with signal transduction, cell adhesion and stress response. Subsequent evaluation of changes in two randomly selected genes from the 30 differentially expressed genes by semiquantitative reverse transcription-polymerase chain reaction demonstrated the reliability of the present cDNA microarray analyses. CONCLUSION: The present experiments identified an extensive list of genes differentially expressed in the ileum after bladder augmentation, providing valuable information for the pathophysiological assessment of patients who undergo urinary reconstruction and representing a source of novel targets for treating complications after urinary diversion.

Animals↗

Stereoselective synthesis of (Z)-2-fluoro-1-alkenyl(phenyl)iodonium tetrafluoroborates.

[reaction: see text] (Z)-2-Fluoro-1-alkenyl(phenyl)iodonium salts were stereoselectively prepared by the reaction of alkynyl(phenyl)iodonium salts with aqueous HF in good yields. The method is applicable to the synthesis of fluoroalkenyliodonium salts having functional groups such as ketone, ester, and chloride. (Z)-2-Fluoro-1-alkene, (Z)-2-fluoro-2-alkenoate, and (Z)-beta-fluoroenyne could be stereoselectively prepared from the fluoroalkenyliodonium salt.

Journal Article↗

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↗

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↗

seco-Adianane-type triterpenoids from Dorstenia brasiliensis (Moraceae).

Two seco-adianane-type triterpenoids, dorstenic acid A and B, were isolated, along with a known isopimarane-type diterpenoid and six coumarins, from the roots of Dorstenia brasiliensis. Their structures were elucidated on the basis of their spectral data. The two triterpenoids showed moderate cytotoxicity against leukemia cells (L-1210 and HL-60).

Animals↗

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↗

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↗

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↗