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Biomedical subjects

Tomohiko Koyanagi

Publications and source records attributed to Tomohiko Koyanagi.

At least 19 recordsLinked to original sources

The long-term voiding function and sexual function after pelvic nerve-sparing radical surgery for rectal cancer.

BACKGROUND: The aim of the present study is to symptomatically analyze the extent to which pelvic nerve-sparing radical surgery for rectal cancer impacts on long-term voiding and male sexual function. METHODS: A self-administered questionnaire was mailed to 68 patients who underwent pelvic nerve-sparing radical surgery for invasive rectal cancer with 52 responses (28 men and 24 women; 27 complete and 25 incomplete preservation; response rate 76.5%). Each patient was asked to record if there had been any changes in lower urinary tract symptoms after surgery. Sexual function was also investigated in men. RESULTS: Of the 52 patients, 48 (92%) maintained voluntary voiding without catheterization in the long term. Clean intermittent self-catheterization was performed in only four patients with incomplete preservation because of persistent voiding dysfunction. Subjectively, approximately 60% of the patients remained unchanged in lower urinary tract symptoms after surgery. The satisfaction rate regarding the current voiding status was significantly higher in women than in men (83% versus 61%, P = 0.0294), but was not significantly different between those with complete (76%) and incomplete preservation (64%). Despite the acceptable urinary status, 88% of men had some deterioration in the erectile function, regardless of the types of surgical procedures. Overall, 64% of men were unsatisfied with the current sexual function. CONCLUSIONS: Pelvic nerve-sparing radical surgery for rectal cancer preserved the long-term voiding function in the majority of patients. In completely preserved patients and in women, symptomatic outcomes were more satisfactory. Postoperative erectile dysfunction was found to be a serious problem, even in complete nerve-sparing procedure.

Aged↗

Significance of COX-2 expression in human renal cell carcinoma cell lines.

Accumulating evidences indicate that cyclooxygenase (COX)-2 plays an important role in tumorigenesis in many human cancers. Yet the relationship between COX-2 and human renal cell carcinoma (RCC) remains unclear. The aim of our study was to evaluate COX-2 expression in human RCC cell lines and its role in tumorigenesis of human RCC. Among the human RCC cell lines (SMKT-R4, OS-RC-2, ACHN) and normal renal cell line RPTEC, COX-2 overexpression was found in OS-RC-2 cells both at mRNA and protein levels. COX-2 sense- and antisense-orientated vectors were constructed and transferred into RCC cells. Significant suppression of cellular proliferation was demonstrated in OS-RC-2 antisense transfectants, whereas promotion was found in SMKT-R4 sense transfectants by colony-forming assay despite the observation that COX-2 specific inhibitor NS398 exhibited similar IC50 among RCC cell lines by MTT assay. In comparison with parent cells and sense transfectants, significant suppression of COX-2 expression and PGE2 production and increase in butyrate-induced apoptosis were observed in OS-RC-2 antisense transfectants by Western blot, ELISA assay and FACS analysis, respectively. Furthermore, tumor growth and angiogenesis of OS-RC-2 antisense transfectants in nude mice was significantly suppressed and the survival time of these mice was significantly prolonged. Our study demonstrates that COX-2 is overexpressed in OS-RC-2 RCC cell line and plays an important role in tumorigenesis of the cells in vivo, which implies that COX-2 may be a therapeutic target for COX-2-expressing RCC, and that suppression of COX-2 expression by antisense-based strategy may have potential utility in treatment of COX-2-expressing RCC.

Animals↗

Difference of cancer core distribution between first and repeat biopsy: In patients diagnosed by extensive transperineal ultrasound guided template prostate biopsy.

BACKGROUND: We performed extensive transperineal ultrasound guided template prostate biopsy and evaluated cancer core distribution. METHODS: From August 2000 to May 2002, 113 men with prostate specific antigen levels between 4.0 and 10.0 ng/ml underwent template biopsy. Eighty-six had no previous biopsy (first group) and 27 had previous transrectal sextant biopsies (repeat group). A mean of 18.4 biopsy cores were taken. We defined the region over 2 cm from the rectal face of the prostate as the anterior region and the other as the posterior. RESULTS: Cancer was detected in 49 of 113 (43%) men. Forty-two were in the first group and seven in the repeat group. In the first group, the cancer core rate (cancer core number/biopsy core number) in the anterior region (7.0%) had no difference from that in the posterior region (8.6%) (P = 0.7111). But in the repeat group, the cancer core rate in the anterior region (4.6%) was higher than in the posterior (1.5%) (P < 0.0001). CONCLUSIONS: These results suggest that transrectal sextant biopsies miss more cancers in the anterior region than in the posterior. We believe template technique has an advantage to be able to detect cancer equally in the anterior and posterior.

Aged↗

Management of renal angiomyolipomas associated with tuberous sclerosis complex.

PURPOSE: Intensive management is generally recommended for angiomyolipomas associated with tuberous sclerosis complex (TSC), which are known to have a more aggressive nature than sporadic tumors. In this study we evaluated the management of these tumors. MATERIALS AND METHODS: The records of 6 men and 6 women with TSC and a mean age of 28.8 years) with angiomyolipomas treated from 1984 to 2000 were retrospectively analyzed. All patients had bilateral multiple tumors (mean size 6.6 cm). There were 10 lesions classified as small (less than 4 cm), 6 medium (4 to 10 cm) and 8 large lesions (10 cm or greater). Computerized tomography was repeated annually for followup observation and semiannually after embolization. RESULTS: Excluding from study 3 tumors treated prophylactically intervention was required in 20%, 50% and 100% of small, medium and large tumors, respectively. Among 14 tumors followed by observation, 8 grew and 4 required intervention. Uncontrollable hemorrhage did not develop in any patient. While some tumors showed remarkable growth in decade 3, growth did not exceed 1.5 cm per year. Embolization was performed in 11 tumors and tumors shrank in 10. Although 1 patient experienced renal atrophy, all patients but 1 are alive without renal failure with a mean followup of 60 months. CONCLUSIONS: Although asymptomatic angiomyolipomas associated with TSC grow gradually, severe hemorrhage is rare and most tumors can be managed conservatively with annual computerized tomography. Embolization is the first choice of intervention but should be reserved until symptoms develop.

Adolescent↗

Expression of vascular endothelial growth factor and its receptors Flk-1 and Flt-1 during the regeneration of autotransplanted adrenal cortex in the adrenalectomized rat.

PURPOSE: Autotransplantation of the adrenal cortex may be a therapeutic alternative in the future. For successful adrenal transplantation revascularization is necessary. It is possible that vascular endothelial growth factor (VEGF), which is a potent angiogenic peptide, may have some roles in adrenal transplantation through 2 its receptors, kinase insert domain-containing region (Flk-1) and fms-like tyrosine kinase (Flt-1). Therefore, we studied sequential changes in expression of VEGF, Flk-1 and Flt-1 in regenerated adrenal. MATERIALS AND METHODS: Eight to 9-week-old male Wistar rats underwent bilateral adrenalectomy and immediate adrenal capsular autotransplantation. The expression of VEGF, Flk-1 and Flt-1 was analyzed by immunohistochemistry and reverse-transcriptase-polymerase chain reaction. RESULTS: Angiogenesis was observed in the remodeling of adrenal sinusoidal endothelium during adrenal regeneration. Reverse transcriptase-polymerase chain reaction and immunohistochemistry showed that VEGF expression increased in grafted tissue with time after transplantation and its Flk-1 receptor, which localized to endothelial cells, increased transiently during the regeneration process. Immunostaining for Flt-1 receptor was identified in adrenocortical cells and its intensity gradually increased during adrenal regeneration. CONCLUSIONS: During adrenal gland regeneration VEGF and its receptors Flk-1 and Flt-1 are thought to be involved in neovascularization.

Adrenal Cortex↗

Peritoneal carcinomatosis in refractory seminoma.

Intraperitoneal metastasis from a testicular germ cell tumor is very rare. We report a case in a 33-year-old man who was referred to Hokkaido University Hospital, Hokkaido, Japan, for further therapy for refractory seminoma. Physical examination revealed abdominal distension as a result of ascites, and cytology of the ascites showed seminoma cells. Although the ascites completely disappeared after treatment with a novel regimen of irinotecan-based chemotherapy, the patient had a recurrence of ascites and died of progressive disease 5 months after the start of the therapy.

Adult↗

Multiple primary malignancies in Japanese patients with renal cell carcinoma.

AIM: To evaluate the incidence, nature and prognosis of multiple primary malignancies involving renal cell carcinoma (RCC) in Japan. METHODS: Between 1975 and 1998, 319 patients underwent an operation for RCC at Hokkaido University, Sapporo, Japan. The incidence of other primary malignancies was determined and classified as antecedent, synchronous or subsequent. Follow-up was obtained by thorough chart review or telephone interview, and ranged from 0 to 276 months (median 49.0 months). To analyze the influence of other primary malignancies on prognosis, overall and cause-specific survival rates of the patients with an antecedent or synchronous malignancy were compared to the remaining patients. RESULTS: Of the 319 patients there was at least one other malignancy in 38 patients (12%). Four patients had two other malignancies. The other malignancies were antecedent in 13, synchronous in 19 and subsequent in 10 patients. Twenty-two patients had gastrointestinal cancer. In cases of antecedent or synchronous diagnosis of other primary malignancies, RCC was commonly incidental, small or low-stage. Multivariate analysis using Cox's proportional hazards model showed that, for overall survival, the presence of other antecedent or synchronous malignancies was the second most significant prognostic factor, following the pathological stage of RCC. CONCLUSIONS: In Japanese patients with RCC, the incidence of other primary malignancies was not uncommon and these malignancies contributed to the prognosis of these patients. Therefore, the malignant potential of individual tumors should be paid careful attention in the management of these patients.

Age Factors↗

Medical management of recurrent aggressive angiomyxoma with gonadotropin-releasing hormone agonist.

Patients with aggressive angiomyxoma may experience local recurrences. We report a case of recurrent aggressive angiomyxoma medically treated successfully with a gonadotropin-releasing hormone agonist. A 34-year-old woman with a huge perineal tumor underwent an extensive resection of the abdominoperineal tumor combined with total pelvic exenteration. Histology showed aggressive angiomyxoma and the tumor cells were immunoreactive for estrogen and progesterone receptors. Although the patient had experienced no local recurrence for 12 months under adjuvant therapy with a gonadotropin-releasing hormone agonist, a recurrence occurred 3 months after the completion of adjuvant therapy. The patient underwent medical treatment with a gonadotropin-releasing hormone agonist and had a complete resolution of the recurrent tumor again. Hormonal treatment with a gonadotropin-releasing hormone agonist can be applied for small primary aggressive angiomyxomas in addition to adjuvant therapy for residual tumors.

Adult↗

Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancer.

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of adjuvant combination chemotherapy for locally advanced urothelial cancer. METHODS: Between 1987 and 1998, 56 patients with locally advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical nephroureterectomy and regional lymphadenectomy. Thirty-one patients had lymph node-positive disease and 25 patients did not. Twenty patients underwent adjuvant chemotherapy and 36 patients were observed after surgery. Cox proportional hazards models were used to determine the impact of numerous clinicopathological findings on survival. A subgroup analysis of patients with lymph node-positive disease was conducted to evaluate disease-free survival and overall survival rates. RESULTS: In this series, the median follow-up period was 39 months (range, 4-163) after surgery. Disease-free and overall survival rates of all 56 patients were 45% and 58%, respectively, at 3 years. Only lymph node status was significantly associated with disease-free and overall survival in the multivariate analyses. In a subgroup analysis of patients with lymph node-positive disease, 16 patients who underwent adjuvant chemotherapy had superior disease-free survival compared to 15 patients with no adjuvant chemotherapy (P = 0.0376). CONCLUSION: These findings show that the prognosis of advanced urothelial cancer is significantly associated with nodal status. Furthermore, adjuvant combination chemotherapy has a positive impact on survival in patients with lymph node-positive disease.

Adult↗

The estimated prevalence of hypospadias in Hokkaido, Japan.

BACKGROUND: Hypospadias is one of the most common congenital anomalies in the world. Recently, increases in the prevalence of hypospadias have been reported in various countries including Japan. In this study, we examined whether the prevalence of hypospadias in Hokkaido, Japan, increased or not, using standardized diagnostic criteria. We also investigated the degree of its severity. METHODS: We calculated prevalence of hypospadias using hospital records of hypospadias repair in Hokkaido. The prevalence from 1985 through 1997 by dividing the number of patients obtained from hospital records by the number of births. RESULTS: The average prevalence of hypospadias in Hokkaido was 3.9 per 10,000 births, and did not significantly change (p=0.7). The average proportions of distal, proximal and chordee alone were 56.7%, 39.6% and 3.7%, respectively. The decrease in the proportion of the proximal type was statistically significant (p=0.05) for the entire time period, whereas the proportion of the distal type did not have a significant upward trend for the observed 13 years (p=0.1). CONCLUSION: No significant changes in the prevalence of hypospadias existed in Hokkaido.

Child↗

[Paclitaxel, ifosfamide, nedaplatin (TIN) for patients with metastatic urothelial cancer].

TIN (ifosfamide 1.5 g/m2 daily for 3 days, paclitaxel 175 mg/m2, and nedaplatin 70 mg/m2 on day 1) was administered to patients with metastatic urothelial cancer previously treated by platinum-based chemotherapy and repeated every 4 weeks. Four patients received maintenance therapy, which consisted of 5'-DFUR 800 mg/day orally for 12 weeks and 1 subsequent course of TIN. This therapy regimen was repeated for 2 years from initiation of TIN. Eleven of 12 patients (91.6%) demonstrated a major response (3 complete responses, 8 partial responses), with durations of response ranging from 3 to 20 months. Progression-free survival time was from 0 to 20 months (median 8 months). One-year progression-free survival rate was 45.8%. Overall survival time was from 2 to 20 months (median 10.5 months). One-year overall survival rate was 53.5%. Grade 3/4 hematologic toxicity involved neutropenia in 100% and thrombocytopenia in 33.3%. Febrile neutropenia was observed in 5 patients (41.6%). Grade 3 nonhematologic toxicity involved malaise in 15.3%. No patient discontinued this therapy because of complications. TIN is a potent, well-tolerated regimen for previously treated patients with urothelial cancer.

Aged↗

Chemical bladder irritation provokes c-fos expression in the midbrain periaqueductal gray matter of the rat.

We investigated the topographical localization of c-fos expression in the midbrain periaqueductal gray matter (PAG) to detect nociception-induced neural activity in the PAG. In conscious female Wistar rats, c-fos expression was induced by continuous intravesical infusion of saline or 0.1% acetic acid. Number of c-fos protein (Fos)-positive cells was counted at each coronal section of the PAG as well as Barrington's nucleus. Fos-positive cells were also counted at L1 and L6 of the spinal cord, where most of the hypogastric and pelvic nerve afferent terminals project, respectively. Compared with saline infusion, acetic acid infusion provoked irritative bladder responses characterized by a marked increase in the frequency of bladder contractions, and induced a significant increase in the number of Fos-positive cells in both L1 and L6 of the spinal cord. Following acetic acid infusion, there was a significant increase in the number of Fos-positive cells in all coronal sections of the PAG compared with saline infusion, especially in the caudal part of the PAG. The increase in the number of Fos-positive cells was mainly observed in the ventrolateral and lateral parts of the caudal PAG, and in the dorsal part of the rostral PAG. However, there was no difference in the number of Fos-positive cells in Barrington's nucleus between saline and acetic acid infusion. In conclusion, nociception induced by chemical bladder irritation influences neural activity in the PAG. Implication of topographical difference in Fos expression in the PAG and its relevance to changes in bladder function remain to be elucidated.

Acetic Acid↗

Transient neonatal expression of NR2B/2D subunit mRNAs of the N-methyl-D-aspartate receptor in the parasympathetic preganglionic neurons in the rat spinal cord.

Physiological studies have shown that lower urinary tract function is regulated through glutamate receptors at the levels of spinal and supraspinal cord. Of the receptor family, N-methyl-D-aspartate (NMDA) receptors mediate activity-dependent changes of synaptic efficacy, underlying synaptic plasticity and synapse development. To know the ontogenic changes of NMDA receptor expression in the visceromotor system innervating pelvic organs, including the bladder, we employed double labeling technique of retrograde neuronal tracing and in situ hybridization for detecting NMDA subunit mRNAs in preganglionic neurons (PGNs) of the lumbosacral cord. Rats at postnatal day 7 (P7), 14 (P14), 21 (P21), and adult were used. In situ hybridization was conducted using 35S-labeled antisense oligonucleotides specific to mRNAs for NMDA receptor subunits. Hybridizing signals in PGNs were detected by a dark-field microscope equipped fluorescence detector. PGNs showed strong signals for NR1 subunit mRNA at each developmental stage examined. Moderate signals for the NR2B and NR2D subunit mRNAs were found in PGNs at P7. However, their expression levels decreased thereafter, reaching the minimal level in adults. No significant signals for NR2A and NR2C subunit mRNAs were detected at any stages. This temporal pattern of expression suggests a possible involvement of NMDA receptors in the development of micturitional neural circuit through activity-dependent mechanisms.

Aging↗

Effects of a selective metabotropic glutamate receptor agonist on the micturition reflex pathway in urethane-anesthetized rats.

AIMS: To determine a possible role of metabotropic glutamate receptors in the spinobulbospinal micturition reflex pathway in the rat. MATERIALS AND METHODS: A selective metabotropic glutamate receptor agonist, trans-(+/-)-1-amino1,3-cyclopentanedicarboxylic acid (trans-ACPD) was administered to the lumbosacral spinal cord via an intrathecal catheter in urethane anesthetized rats. Amplitude of reflex bladder contractions evoked by bladder distension under isovolumetric condition as well as amplitude of bladder contractions elicited by electrical stimulation of the pontine micturition center (PMC) were examined before and after administration of trans-ACPD. The effect of trans-ACPD on the urethral activity during isovolumetric bladder contractions was also examined by monitoring urethral perfusion pressure and electromyography of the external urethral sphincter (EUS-EMG). RESULTS: Trans-ACPD (3-10 microg) completely inhibited reflex bladder contractions evoked by bladder distension and the duration of inhibition was dose dependent (3 microg: 11.4 +/- 2.8 min, 5 microg: 13.2 +/- 1.3 min, 10 microg: 36.2 +/- 2.4 min). The mean amplitude of bladder contractions evoked by electrical stimulation of the PMC was reduced to 12.6 +/- 2.3% of control by 10 microg of trans-ACPD. In addition, bursting activity of EUS-EMG and corresponding high frequency oscillations of urethral pressure during isovolumetric bladder contractions were completely abolished by 10 microg of trans-ACPD. CONCLUSIONS: These results indicate that intrathecal administration of a selective metabotropic glutamate receptor agonist to the lumbosacral spinal cord has an inhibitory effect on the spinobulbospinal micturition reflex pathway in urethane-anesthetized rats. This pharmacological action is attributed at least to the inhibitory effect on the descending pathway from the PMC to the lumbosacral spinal cord.

Anesthesia, Intravenous↗

Laparoscopic antegrade continence enema procedure for fecal incontinence in a patient with spina bifida.

We report a laparoscopic procedure for antegrade continence enema (LACE) that was performed successfully in 39-year-old man patient with spina bifida suffering from severe fecal incontinence. The patient had been receiving regular follow-up at our clinic. He desired the antegrade continence enema procedure to improve his intractable fecal incontinence with a less invasive procedure. Following the placement of the first port at the umbilicus using an open access technique, two additional ports were introduced at the upper and lower abdomen in the midline. The appendix was laparoscopically mobilized to the right lower abdomen and brought out through another port. Next, an in situ appendicocutaneostomy was created. The patient began oral intake the day after surgery. Initial irrigation was performed on the second postoperative day. Convalescence was quick and there were no postoperative complications. Although a minor skin incision was required afterward for superficial stoma stenosis, the patient has been in a satisfactory condition with regular enemas. Laparoscopic appendicocutaneostomy can be a reasonable surgical alternative for antegrade continence stoma procedure. LACE has a clear advantage over conventional open procedures in view of its less invasive nature and better cosmetic results.

Abdomen↗

Urodynamic effects of alpha1-blocker tamsulosin on voiding dysfunction in patients with neurogenic bladder.

BACKGROUND: The therapeutic role of alpha-blockers in the treatment of voiding disorders due to benign prostatic hyperplasia has been extensively examined. To investigate a possible effect of alpha1-blocker on urodynamic voiding parameters in patients with neurogenic bladder, we conducted a clinical trial using tamsulosin. METHODS: Twenty-four patients (14 men and 10 women) ranging from 24 to 82 years of age (mean age 61 years) with neurogenic bladder were analyzed. Urodynamic studies were performed before and after treatment with 0.4 mg tamsulosin daily for 4 weeks. RESULTS: On uroflowmetry, the average flow rate (from 4.6 +/- 3.3 to 6.7 +/- 3.0 mL/s, P = 0.04), maximum flow rate (from 9.4 +/- 6.8 to 14.1 +/- 7.0 mL/s, P = 0.016) and residual urine rate (from 46 +/- 29 to 32 +/- 21%, P = 0.02) improved significantly. In patients with detrusor contraction during voiding, detrusor opening pressure and detrusor pressure at maximum flow decreased significantly from 69.0 +/- 36.2 to 49.2 +/- 26.4 cmH2O (P = 0.046) and from 66.7 +/- 34.6 to 53.6 +/- 26.5 cmH2O (P = 0.007), respectively. On the other hand, in patients with detrusor areflexia, vesical opening pressure (from 78.2 +/- 23.4 to 61.6 +/- 25.2 cmH2O), or vesical pressure at maximum flow (from 68.6 +/- 23.2 to 62.9 +/- 25.2 cmH2O) did not change significantly after treatment. CONCLUSION: Tamsulosin reduces functional urethral resistance during voiding and improves flow rate in patients with neurogenic bladder. It has more beneficial urodynamic effects in patients with detrusor contraction during voiding than in patients with detrusor areflexia.

Adrenergic alpha-Antagonists↗

Ureteral stricture developing after partial nephrectomy with a microwave tissue coagulator: case report.

A 32-year-old man with a 1.7-cm tumor in the left kidney underwent laparoscopy-assisted partial nephrectomy. Although his postoperative course was uneventful, a 6-month postoperative CT scan showed hydronephrosis secondary to a severe stricture at the ureteropelvic junction. Heat injury to the urinary tract was strongly suspected. The use of microwave tissue coagulator for the tumor close to the renal sinus and excessive coagulation should be avoided to prevent heat-related complications.

Adult↗