Gestational Outcomes and Birth Weight in Japanese Women at the Upper and Lower limits of the Normal BMI range.

To examine the outcome of gestational blood pressure and birth weight in women with normal pre-pregnancy BMI (18.5-25 kg/m2) who are at the lower and upper limits of this range, i.e., slightly underweight or slightly overweight. Overall, 2,038 Japanese women with low -risk who had delivered during January 2014-December 2016 were classified according to their pre-pregnancy BMI: underweight (< 18.5 kg/m2), slightly underweight (18.5≤BMI<21 kg/m2), normal (21≤BMI<23 kg/m2), slightly overweight (23≤BMI<25 kg/m2) and overweight (≤ 25 kg/m2). Their blood pressure during each trimester and birth weight was evaluated. The slightly overweight group showed a significantly higher blood pressure than the underweight and slightly underweight groups. Birth weight was lower in the slightly underweight than in the slightly overweight group (p<0.01). The incidence rate of "heavy for dates" (HFD) infants was significantly higher in the slightly overweight and overweight groups than in the other groups (p<0.05 and p<0.01, respectively). Weight gain of < 7 kg significantly increased the rate of "light for dates" (LFD) infants, while a weight gain of ≥13 kg significantly increased the rate of HFD infants (p<0.05 and p<0.01, respectively). Blood pressure during pregnancy was ssociated with pre-pregnancy BMI. The birth weight of infants of low-risk pregnant women is affected by both pre-pregnancy BMI and gestational weight gain.

Cine magnetic resonance imaging provides novel predictors of early continence recovery after radical prostatectomy: Assessment of the dynamics of pelvic floor muscles.

AIMS: Postprostatectomy incontinence is a major complication of prostatectomy. Although pelvic floor muscle training can successfully treat postprostatectomy incontinence, evidence for how muscle movement affects continence recovery is lacking. We evaluated dynamic factors of prostatectomy patients using cine magnetic resonance imaging to identify risk factors for postprostatectomy incontinence and reveal the contribution of pelvic floor muscles to continence recovery. METHODS: A total of 128 prostate cancer patients who underwent robot-assisted laparoscopic surgery were enrolled. Cine magnetic resonance imaging was performed preoperatively and 6 months after surgery. Continence was defined as pad-free or use of safety pads. We defined the bladder neck elevation distance during pelvic floor muscle training as the bladder elevation distance. Patients with continence recovery within 1 month comprised the continence group (n = 48); other patients comprised the incontinence group (n = 80). RESULTS: The preoperative bladder elevation distance was significantly longer in the continence group than in the incontinence group (10.4 vs. 8.2 mm; p < .001). The postoperative bladder elevation distance of the continence group tended to be longer (9.9 vs. 8.9 mm; p = .057). Multivariate analysis showed that the preoperative bladder elevation distance significantly contributed to continence recovery (p = .016). Patients with a longer preoperative bladder elevation distance (>8.5 mm) experienced continence recovery significantly faster than patients with a shorter distance (<8.5mm) (p = .038). CONCLUSIONS: Bladder elevation distance, a novel dynamic parameter, was strongly associated with early continence recovery. Cine magnetic resonance imaging can assess a patient's risk of postprostatectomy incontinence and guide pelvic floor muscle training.

[EVALUATING THE RELATIONSHIP BETWEEN LOWER URINARY TRACT SYMPTOMS AND ENDOTHELIAL FUNCTION USING FLOW-MEDIATED DILATION, AND THE EFFECTS OF TADALAFIL].

(Objective) Recently, lower urinary tract symptoms (LUTS) were reported to be associated with endothelial dysfunction. Endothelial function is non-invasively measured by flow-mediated dilation (FMD). As tadalafil has the potential to improve atherosclerosis, we evaluated the relationship between LUTS and endothelial function using FMD, and the effects of tadalafil. (Patients and methods) We conducted FMD examinations for a total of 122 males, and analyzed its association with IPSS, OABSS, and cardiovascular risks. Furthermore, 21 BPH patients received 5 mg of tadalafil per day for one year. We defined the Low FMD group as FMD < 3.9% and the Control group as other values, and compared the effects of tadalafil between groups. (Results) In the 122 male patients, FMD was negatively correlated with nocturia and OABSS. Patients with hypertension or coronary artery disease had a lower FMD than those without.In the tadalafil administration study, the Low FMD group achieved greater improvement of IPSS, OABSS and FMD than the Control group. (Conclusion) FMD examination revealed that endothelial dysfunction is closely associated with LUTS in males, and that tadalafil is effective for patients with endothelial dysfunction.

Efficacy of Testosterone Treatment in Hemodialysis Patients as Assessed by Aging Males' Symptoms Scores: A Pilot Study.

Numerous reports point to the beneficial effects of testosterone replacement therapy for patients with late-onset hypogonadism (LOH) syndrome. The aim of this study was to evaluate the effect of intramuscular injection of testosterone enantholactam acid ester on Aging Males' Symptoms (AMS) scores in hemodialysis patients with LOH. A total of 24 male patients with LOH (total AMS scores ≥27) were randomized into groups receiving intramuscular injections of either placebo or testosterone enantholactam acid ester at the dose of 250 mg for 6 months. In all, 13 and 11 participants from the active treatment and placebo groups, respectively, completed this study. An intramuscular injection of either placebo or testosterone enantholactam acid ester was given every 2 weeks. Self-administered AMS questionnaires were completed at the start, at Week 12 and at Week 24. The total AMS score was significantly more improved in the treatment group than in the placebo group ( p = .049) during the 24-week period. The change in the mean of total AMS score was +1% in the placebo group and -13.2% in the treatment group. The mean somato-vegetative domain scores decreased significantly only in the treatment group, and not in the placebo group (-1.21 vs. -2.43, p = .028). Although a large-scale study is needed, testosterone treatment may be effective in male patients with hemodialysis who have poor health-related quality of life resulting from LOH.

Endothelial dysfunction, abnormal vascular structure and lower urinary tract symptoms in men and women.

BACKGROUND: Lower urinary tract symptoms (LUTS) is not only common symptoms in elderly men and women but also risk of future cardiovascular events. The purpose of this study was to evaluate the relationships of vascular function and structure with LUTS in men and women. METHODS: We investigated flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as vascular function, brachial-ankle pulse wave velocity (baPWV) as vascular structure, and LUTS assessed by International Prostate Symptom Score (IPSS) in 287 men and 147 women. RESULTS: IPSS was significantly correlated with traditional cardiovascular risk factors, Framingham risk score, FMD, NID and baPWV. Moderate to severe LUTS was associated with the prevalence of coronary heart disease in men but not in women. In men, FMD and NID were significantly lower in the moderate to severe LUTS group than in the none to mild LUTS group (2.1 ±â€¯2.0% vs. 4.0 ±â€¯3.0% and 9.3 ±â€¯6.1% vs. 12.8 ±â€¯6.6%, P < 0.001, respectively). baPWV was significantly higher in the moderate to severe LUTS group than in the none to mild LUTS group (1722 ±â€¯386 cm/s vs. 1509 ±â€¯309 cm/s, P < 0.001). In multivariate analysis, FMD was independently associated with a decrease in the odds ratio of moderate to severe LUTS in men (OR: 0.83, 95% CI, 0.72-0.95; P = 0.008) but not in women. NID and baPWV were not independently associated with moderate to severe LUTS either in men or women. CONCLUSIONS: These findings suggest that endothelial dysfunction is associated with LUTS in men. LUTS in men may be useful for a predictor of cardiovascular events. CLINICAL TRIAL REGISTRATION INFORMATION: URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409.

[THE 10-YEAR OUTCOMES OF PVP (PHOTOSELECTIVE VAPORIZATION OF THE PROSTATE) FOR TREATING BPH (BENIGN PROSTATIC HYPERPLASIA)].

(Purpose) Photoselective vaporization of the prostate (PVP) was introduced in Japan about 10 years ago, and there has been few studies regarding long-term outcomes so far. Herein we report our 10-year follow up result of PVP. (Patients and methods) From January 2006 to June 2006, 31 patients with benign prostatic hyperplasia (BPH) underwent PVP and 20 patients were evaluable in 10 years after PVP. Patients were evaluated preoperatively, at 6 months and at 10 years after surgery by International Prostate Symptom Score (IPSS) and Quality of life score (QOL score). The surgery used 80 watt potassium-titanyl-phosphate laser that was an old model. (Results) The mean IPSS preoperatively, at 6 months and at 10 years was 21.1, 5.5 and 9.4, respectively. The mean QOL score preoperatively, at 6 months and at 10 years was 5.3, 2.2 and 2.5, respectively. Both IPSS and QOL score were significantly improved at 6 months and at 10 years compared with preoperatively. However, among 20 patients re-operation for residual adenoma was required in 4 patients (20%) during the follow-up period. (Conclusion) PVP is an effective method for BPH treatment, allowing sustained long-term improvement of the voiding function.

Sufficient Volume Ablation with Photoselective Vaporization of the Prostate Delivers 5-Year Durability and Improves Symptom Relief for Larger Prostates.

OBJECTIVES: To assess the long-term durability of photoselective vaporization of the prostate (PVP) for symptomatic benign prostatic enlargement (BPE) or benign prostatic obstruction (BPO) and treatment efficacy for large BPE. METHODS: Four hundred fifty-seven patients with symptomatic BPE underwent PVP between January 2006 and April 2009. Efficacy was evaluated with the International Prostate Symptoms Score (IPSS), Quality of Life (QOL) score, urinary peak flow (Qmax), postvoid residual volume (PVR), and prostate volume. Parameters were checked preoperatively, and at 1, 3, and 5 years postoperatively. One hundred fifty-three patients completed 5-year follow-up. To assess treatment effects, patients were divided into two groups according to the preoperative prostate volume: group A (<60 mL, n=104) and group B (>60 mL, n=49). RESULTS: Mean IPSS, QOL score, Qmax, and PVR improved significantly and were maintained for 5 years with no significant differences; at year 1, prostate volume had decreased significantly from 54.0 mL to 30.6 mL (43% of volume ablation) and remained at that level until year 5. Investigations according to prostate size demonstrate that IPSS and QOL scores in group B remained at significantly lower levels, and Qmax in group B improved more than in group A. 1.1% of patients needed transurethral resection of the prostate due to BPO recurrence. CONCLUSIONS: PVP is effective and provides durable results for 5 years, with sustained symptom relief and improved urinary flow rate, as well as a 43% volume reduction of prostate volume. Our data indicate PVP is more efficacious for larger prostates under sufficient volume ablation.

[MODIFICATIONS FOR CONTROLLING THE DORSAL VEIN COMPLEX IN ROBOTIC-ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY].

OBJECTIVE: To investigate a superior method for controlling the dorsal vein complex (DVC) in robotic-assisted laparoscopic radical prostatectomy at Nagakubo hospital. PATIENTS AND METHODS: DVC control was altered from suture ligation followed by DVC division (SL group, n = 115) to preceding division followed by suture (PD group, n = 62). Surgical margin status and functional outcomes were investigated. RESULTS: No notable surgical complications were found in the PD group. Operation time and estimated blood loss were significantly less in the PD group; however, changes to serum hemoglobin before and after surgery showed no significant difference. The rates of positive surgical margin were 26.1% and 11.3% in the SL and PD groups, respectively (p = 0.021). Apical margin positivity was 9.6% and 3.2% in the SL and PD groups, respectively (p = 0.12). Urinary continence outcomes of within one pad/day and pad free in the SL and PD groups until 6 mo after surgery were 93.6% and 89.1% (P = 0.21), and 67.3% and 67.5% (p = 0.96), respectively. Erection recovery within 6 mo was 43.6% and 41.7% in the SL and PD groups (p = 0.91). CONCLUSION: Preceding division followed by suture method decreased apical margin positivity and provided superior cancer control in comparison with suture ligation followed by DVC division, although, it was probably influenced by the learning curve. Functional outcomes were not significantly different with either method.

Safety and efficacy of teneligliptin: a novel DPP-4 inhibitor for hemodialysis patients with type 2 diabetes.

PURPOSE: Teneligliptin is a novel DPP-4 inhibitor in development for treating type 2 diabetes mellitus that does not require dose adjustment for diabetic patients with end-stage renal disease; however, it had not been known whether or not teneligliptin is safe or potent in dialysis patients. We conducted a prospective study to assess the utility of teneligliptin for diabetic patients undergoing hemodialysis. METHODS: Blood glucose, glycated albumin, and HbA1c were measured every 4 weeks, at 4, 12, 20, and 28 weeks, and every 8 weeks, respectively, for patients treated with teneligliptin (n = 14; 7 patients newly started and 7 that switched from other medications) and patients of a control group who continued ongoing antidiabetic therapy (n = 29). RESULTS: Blood glucose level showed a 36.7 mg/dl decrease from 4 weeks in the teneligliptin group (p < 0.05). The differences in glycated albumin (at 28 w) and HbA1c (at 24 w) between the teneligliptin group and the control group were -3.1 % (p < 0.05) and -0.57 % (p = 0.057), respectively. These parameters also decreased in patients who switched from voglibose 0.2 mg t.i.d. or vildagliptin 50 mg qd after teneligliptin administration. No case with hypoglycemia was identified. One patient had the dose of a laxative administered for constipation increased; however, no patient ceased teneligliptin due to side effects. CONCLUSION: Teneligliptin 20 mg is well tolerated, safe, and significantly improves glycemic control in diabetic patients with end-stage renal disease. Teneligliptin 20 mg once daily was considered to be more potent than voglibose 0.2 mg t.i.d. or vildagliptin 50 mg qd.

[Comparison of initial results with robotic-assisted laparoscopic radical prostatectomy and open retropubic radical prostatectomy].

OBJECTIVE: To investigate the superiority in 2 radical prostatectomies, we compared the initial results of robotic-assisted radical prostatectomy (RARP) to those of retropubic radical prostatectomy (RRP) performed during the same period at Nagakubo hospital. PATIENTS AND METHODS: The study was conducted on a total of 160 patients having undergone radical prostatectomy from April 2009 to March 2012 (92 patients with RARP and 68 with RRP). We investigated surgical stress, cancer control, functional outcomes and complications in both groups. RESULTS: Surgical stress; operation time was significantly shorter with RRP; however, blood loss and serum total protein loss were significantly less with RARP. White blood cell count at 2 days after surgery was significantly less with RARP. The rates of analgesic use and SIRS were similar. Although the date on which taking solid meals resumed did not differ, the duration of indwelling urethral catheter and admission period were significantly shorter with RARP. Cancer control; the rates of positive surgical margin were 27.2% and 19.1% with RARP and RRP, respectively (p = 0.24), and biochemical recurrence was seen in 12.0% and 19.1% with RARP and RRP, respectively (p = 0.73), which were not significantly different. Continence; urinary continence outcomes with RARP and RRP were 17% and 4% for urinary continence at discharge (p = 0.01), 1.8 and 3.3 months for no more than one pad per day (p < 0.01), and 4.3 and 6.2 months for pad free (p = 0.03), respectively. Sexual function; erection recovery within 6 mo was only observed with RARP; however, overall recovery rate of erection was 65% and 75% with RARP and RRP, respectively (p = 0.69). COMPLICATIONS: 1 case with a rectal injury was seen in both groups, but complication rates were 8.7% and 16.2% with RARP and RRP, respectively (p = 0.22). CONCLUSION: In spite of our initial experience of RARP, surgical stress and complications with RARP were considered to be superior to that with RRP. Cancer control and sexual function showed no significant difference between RARP and RRP, however, urinary continence outcome is significantly superior with RARP. Our data suggest that treatment outcome after initial experience with RARP is not inferior to that with RRP, and better results are expected by improving surgical techniques.

ß3-Adrenoceptor agonist mirabegron is effective for overactive bladder that is unresponsive to antimuscarinic treatment or is related to benign prostatic hyperplasia in men.

PURPOSE: To investigate the safety and efficacy of mirabegron for patients with overactive bladder (OAB) that is unresponsive to antimuscarinic agents or is related to benign prostatic hyperplasia (BPH). METHODS: Fifty-two newly diagnosed OAB patients (M group) and 45 patients with OAB that was unresponsive to antimuscarinics (S group) received mirabegron 50 mg once daily and were evaluated by OAB symptom score (OABSS), IPSS-QOL index, and IPSS at the time of baseline, 4 and 8 weeks. Newly diagnosed OAB patients treated with antimuscarinic agents were compared as controls. RESULTS: Mirabegron was effective for 85.2 % in M group. Significant improvements were seen in each domain of OABSS, and there was no significant difference with antimuscarinic therapy. Mirabegron was efficacious for 61.6 % of S group, and significant decreases of OABSS and IPSS-QOL index were observed. Significant improvements were also seen in voiding symptoms in men. Post-void residual urine volumes before and after treatment were 32.1 and 34.8 ml, and 26.2 and 31.3 ml in M and S group, respectively, and there was no significant difference. The incidence of adverse events was 8.4 %, although none were serious, and the patients recovered spontaneously after mirabegron was discontinued. CONCLUSION: The present study suggests mirabegron is as effective as antimuscarinics for OAB. It improves OAB symptoms in patients with OAB for which antimuscarinic agents are insufficient. This study revealed that mirabegron improves not only OAB symptoms related to BPH, but also voiding symptoms in men. Low and mild incidences of side effects support the safe utility of mirabegron.

Photoselective vaporization of the prostate: pursuing good indications based on the results of 400 Japanese patients.

OBJECTIVE: To investigate good indications of photoselective vaporization of the prostate (PVP) by retrospective evaluation of its efficacy in relation to prostate volume. PATIENTS AND METHODS: A cohort of 400 patients had International Prostate Symptoms Score (IPSS), Quality of Life (QoL) score, urinary peak flow (Q(max) ), and prostate volume (P(vol) ), assessed before and after surgery. Changes of outcome variables were compared among four groups classified according to preoperative prostate volume: <30 mL (group A), ≥30 and <50 mL (group B), ≥50 and <70 mL (group C), and >70 mL (group D). RESULTS: Operating times and amounts of energy applied were 44.2 min and 159 kJ, 67.7 min and 268 kJ, 111 min and 409 kJ, and 171 min and 604 kJ in groups A, B, C, and D, respectively. All variables improved significantly and immediately, and remained for more than 12 months. Investigation of groups classified by prostate size demonstrated that IPSS and QoL score decreased and improvement rate of Q(max) rose as prostate volume increased. Changes of P(vol) were from 24.5 mL to 13.2 mL (-46.1%), from 39.8 mL to 22.9 mL (-42.4%), from 58.4 mL to 32.8 mL (-43.8%), and from 92.1 mL to 53.8 mL (-41.5%) in groups A, B, C, and D, respectively. Overall the P(vol) reduction rate was 43.2%, and no significant differences were observed in reduction ratios among the groups. Complications were minimal, but bladder neck contracture arose in 16 cases with a smaller prostate. CONCLUSION: Whilst the percentage reduction in volume was similar across the groups, the larger absolute volume reduction in patients with larger prostates was associated with greater improvement in objective urinary function variables, and with symptom score reduction.

Transurethral resection in saline vaporization: evaluation of clinical efficacy and prostate volume.

OBJECTIVE: To assess the efficacy and safety of transurethral resection in saline vaporization for symptomatic bladder outlet obstruction and the change in prostate volume. METHODS: A total of 106 patients with symptomatic bladder outlet obstruction underwent transurethral resection in saline vaporization. The effectiveness of the treatment was evaluated using the International Prostate Symptom Score (IPSS), quality of life score, urinary peak flow, and prostate volume preoperatively and at 1, 3, 6, and 12 months postoperatively. To assess the treatment effect, the patients were divided into 3 groups according to the preoperative prostate volume: group 1 (<45 cm(3), n = 40), group 2 (≥ 45 but <65 cm(3), n = 34), and group 3 (≥ 65 cm(3), n = 32). RESULTS: The mean perioperative hemoglobin loss was 1.2 g/dL. The mean IPSS, quality of life score, and prostate volume decreased significantly from 24.3, 5.2, and 52.8 cm(3) to 11.1, 2.7, and 29.9 cm(3), respectively (P < .01) and the mean urinary peak flow had increased significantly from 7.3 to 15.1 (P < .01) at 1 month. Moreover, the IPSS, quality of life score, and prostate volume had significantly decreased to 8.8, 2.3, and 26.1 cm(3) at 3 months (P < .05). The investigation of groups classified by prostate size demonstrated that the IPSS in group 3 continued at a significantly lower level than that in groups 1 and 2. The prostate volume decreased gradually and resulted in 52.8% volume reduction for ≤ 12 months. No significant complications were seen; however, irritative symptoms occurred frequently (11.3%). CONCLUSION: Transurethral resection in saline vaporization was a safe and effective treatment option and was more efficacious for patients with a larger prostate. The bother scores and prostate volume gradually decreased for ≤ 12 months.

[Hemodialysis case in which RCC was identified after disappearance of perirenal hematoma following spontaneous renal rupture treated by transcatheter arterial embolization].

A 55-year-old man who had been undergoing hemodialysis for 9 years visited our institution after the sudden onset of severe left flank pain. He presented with hypotension and was admitted immediately because computed tomography (CT) revealed a massive perirenal hematoma. Renal arteriography showed contrast media leakage at the lower branch of the left renal artery, and spontaneous renal rupture was diagnosed. Five months after the bleeding was stopped by selective transcatheter embolization of the branch of renal artery, CT showed an enhanced mass at the upper pole of left kidney and renal cell carcinoma (RCC) was suspected. Radical nephrectomy was performed, the pathological diagnosis was clear cell carcinoma, and the man has not experienced recurrence within 36 months after the surgery. RCC did not appear to be the cause of the original hemorrhage because there was a small residual hematoma in the middle of the renal parenchyma that was separated from the RCC. In cases of spontaneous renal rupture, re-evaluation by imaging studies is mandatory after disappearance of perirenal hematoma because imaging studies at the time of the rupture sometimes do not reveal the cause of the hemorrhage.

[Photoselective vaporization of the prostate in severe heart disease or dementia patients who are not candidates for TUR-P].

OBJECTIVE: TUR-P for the treatment of BPH is not performed in cases with severe heart disease due to the risk of bleeding and hyponatremia etc. Besides, in cases with severe central nerve disease and dementia, TUR-P is not performed because patients cannot take postoperative rest. We report the efficacy and the safety of Photoselective Vaporization of the Prostate (PVP) using a high-power 80 W KTP (potassiumu-titayl-phosphate) in patients for whom TUR-P cannot be performed. PATIENTS AND METHODS: 312 patients underwent PVP in our hospital. Of these 312 patients, 8 patients with severe heart disease (American Society of Anesthesiology score of 3 or greater) and 4 patients with severe dementia (Performance status of 3 or greater) were evaluated. We assessed peak flow rate and post-void residual urine volume preoperatively and at 3 months postoperatively, safety of the procedure, and complication rates. The mean age was 81 years old (range 67 to 94) and the mean prostate volume was 63.8 ml (range 19 to 120). Urethral catheter was used in 8 patients because of chronic urinary retention. PVP was performed with GreenLightPV and a saline solution was used for irrigation. Upon completion of the procedure an 18Fr Foley catheter was inserted without continuous bladder irrigation and removed next morning, as a rule. RESULT: In all 12 patients, PVP was performed successfully without any intraoperative complications. Mean operating time was 101 minutes (range 28 to 184), mean total laser energy was 336,853 J (range 74,396 to 550,000), and mean irrigation volume was 21 L (range 8 to 36). The hemoglobin value changed from mean 13.1 mg/dl preoperatively to 12.2 mg/dl postoperatively. Blood transfusions were not required and hyponatremia was not observed. In 1 case, the urethral catheter was removed 3 hours following surgery. In the other cases, the urethral catheter was removed next morning. All patients could urinate after catheter removal and were discharged on the day following operation. Mean peak flow rate increased to 18 ml/s and mean post-void residual urine decreased to 46.9 ml at 3 months. No postoperative complications (urinary retention, hematuria, urinary tract infection, etc.) were observed. CONCLUSION: PVP is safe and effective in high-risk patients who are not candidates for TUR-P.

Array-based comparative genomic hybridization of circulating esophageal tumor cells.

Esophageal squamous cell carcinoma (ESCC) shows a high frequency of lymphatic and/or systemic metastasis, even when the tumor invades only the submucosa. To investigate the genetic alterations in circulating esophageal tumor cells, we performed array-based comparative genomic hybridization (CGH) analysis of 8 DNA samples of xenografts, which were previously established from the thoracic duct lymph of 13 ESCC patients. A total of 5 loci (or genes), 10q21.3 (EGR2), 11q13.3 (CCND1/CyclinD1, FGF4, and EMS1), 11q14 (PAK1), and 22qtel (ARSA) were found to be candidate amplified loci in the xenograft. In contrast, a total of 24 loci including 9p21 (p16 and MTAP) were found to be homozygously deleted candidates in the xenograft. Both p16 homozygous deletion and CCND1 amplification were detected in 6 (75%) and 5 (62.5%) of the 8 xenografts. Furthermore, by quantitative Southern blot analysis, we found p16 homozygous deletion in 30.8% (8/26) of the primary tumors and in 50% (4/8) of the metastasized lymph nodes. The frequency of CCND1 amplification and p16 homozygous deletion is suggested to be associated with ESCC progression. Matrigel invasion assays of p16-deleted ESCC cells showed that restoring wild-type p16 activity into the cells significantly inhibits tumor-cell invasion, suggesting that p16 inactivation could be involved in ESCC invasion. This is the first report showing the genetic alteration of concealed tumor cells in the thoracic duct lymph. The present gene list should be helpful for identifying new amplified and deleted genes in primary ESCCs as well as in metastasized lymph nodes.

[Effectiveness of taxanes-based chemotherapy against hormone-refractory prostate carcinoma].

We performed an investigative and clinical study of docetaxel, and evaluated its efficacy against hormone-refractory prostate carcinoma (HRPC). In an in vitro experiment, docetaxel suppressed the human prostate cell line proliferation not only in an androgen-dependent cell line, LNCaP, but also in androgen-independent cell line, PC-3, in a dose-dependent manner. In an in vivo experiment applying an SCID mouse xenograft model with PC-3, docetaxel administration suppressed the tumor growth more than 95%. In a clinical study, eight cases were enrolled to low-dose (20 mg/m2/wk) weekly regimen and an other eight to high-dose (60 mg/m2/wk) administration of docetaxel every three weeks. A prostate specific antigen (PSA) decline of more than 50% were observed in 4 (50%) in the low-dose group and 5 (63%) in the high-dose group. The median time to progression and overall survival were 8.5 and 13.2 months in the low-dose group and more than 5.5 and 8.5 months in the high-dose one, respectively. This regimen was well tolerated, and the incidence of adverse effect was relatively low and light. Grade 3 neutropenia or leukocytopenia without fever was seen in three patients (18.8%). Only one patient required administration of granulocyte-colony stimulating factor because of neutropenia. No other grade 3 or 4 toxicity was observed. In conclusion, docetaxel-based chemotherapy was well tolerated and an active treatment for HRPC cases.

[Rapid diagnosis of donor infection and renal allograft contamination using a polymerase chain reaction technique and rapid shaking culture].

Post transplant infection is one of the serious complications of the organ recipients. We detected the donor infections and allograft contaminations in a limited period of time by polymerase chain reaction (PCR) and rapid shaking culture (RSC). The pre-procurement blood from 86 possible renal donors as well as the preservation solution (PS) and renal pelvic urine (PU) from 158 grafts were examined in order to detect highly virulent organisms such as methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and fungi. The average age of donors was 48.8 years old. The average period between the admission and brain death was 4.9 days, and the average period between the brain death and cardiac arrest was 3.6 days. The inflammatory indices such as body temperature, white blood cell count and C-reactive protein increased to 37.9 +/- 1.1 degree C, 12,600 +/- 6300/microl, and 20.2 +/- 11.6 mg/dl, respectively. Following PCR and RSC, procurement operations of the three possible donors were cancelled because of systemic bacterial infections by MRSA or Bacteroides fragilis. Six out of 158 grafts were discarded due to the diagnoses of MRSA or Candida albicans in PS and/or PU. All the other 148 grafts were transplanted. Following transplant, no single infectious complication transmitted by the graft was noted. We conclude that PCR combined with RSC is very accurate and useful for detecting donor infections and allograft contaminations, which may cause severe complications in the recipients.

Alternative mechanisms of gene amplification in human cancers.

Gene amplification is a common phenomenon in cancer. Cytogenetic analyses have indicated that breakage-fusion-bridge (BFB) cycles drive intrachromosomal amplification of some oncogenes in a head-to-head manner in human cancers. However, the complex structures of an amplified sequence found in cancers are not always explained by the BFB model. At the 17q21 locus, which is not linked to common fragile sites, we discovered a recombination hot spot harboring amplicon repeats in tandem in a head-to-tail orientation, with the interamplicon junctions in each cancer cell being homogeneous. These findings clearly show the presence of alternative mechanisms other than BFB cycles in oncogene amplification.

Cloning of the conserved regulatory operon by its aerial mycelium-inducing activity in an amfR mutant of Streptomyces griseus.

We report cloning and characterization of a 2.8 kb DNA fragment that suppressed the aerial mycelium-deficient phenotype of an amfR mutant of Streptomyces griseus when it was introduced on a high-copy-number plasmid. Nucleotide sequencing revealed that the cloned DNA fragment contained a part of a regulatory operon homologous to one of the conserved operons identified in the genome of Streptomyces coelicolor A3(2). The operon appeared to consist of 5 CDSs (rarA-E; restoration of aerial mycelium formation in an amfR mutant): rarA encoded a membrane protein with weak similarity to the histidine kinase of the two-component regulatory system; rarB and rarC products did not show marked similarity to other proteins with known function; rarD encoded a G-protein carrying two GTP-binding consensus sequences conserved in the eukaryotic Ras-like proteins; rarE product showed end-to-end homology to cytochrome P450. The 2.8 kb fragment contained a 5'-end incomplete rarA and complete rarB-D in the downstream from the promoter region of mel operon of the vector plasmid. Subcloning showed that the region containing rarA only is sufficient for the aerial mycelium-inducing activity. The truncation of rarA at its 5' terminus was essential for the restoration activity, which implied that the mutated rarA product causes unusual signaling that directs the onset of morphogenesis without amfR function. Inactivation of both rarA in Streptomyces griseus and cvnD9, a rarD ortholog in S. coelicolor resulted in precocious and glucose-resistant formation of aerial mycelium and secondary metabolites, which suggested that the operon negatively regulates the onset of differentiation. S1 nuclease protection analysis showed that the transcriptional activity of the promoter preceding rarA is developmentally regulated in an amfR- and glucose-dependent manner.