Twelve Months Follow-up of Injection of OnabotulinumtoxinA into Vesical Submucosa for Refractory Non-neurogenic Overactive Bladder.

OBJECTIVE: The aim of the present study was to assess the effects of onabotulinumtoxinA injection for refractory non-neurogenic overactive bladder (OAB) for 12 months. METHODS: For patients with persistent urgency urinary incontinence (UUI) more than once a week despite taking anti-cholinergic agents or incapability to continue the agents because of adverse effects, 100 units of onabotulinumtoxinA was injected at 30 sites in the sub-epithelial bladder wall. Efficacy was assessed every month up to 12 months after injection, using a three-day frequency-volume chart (FVC) and postvoid residual urine (PVR), three questionnaires, and a simple score of Global Response Assessment (GRA). Failure was defined as when GRA was negative and additional treatment was administered. RESULTS: Nine men and eight women aged 67 ± 12 years were included. On FVC, frequencies of urgency, UUI and daytime urination significantly decreased up to the 11th month. PVR significantly increased at the first and second months but no patient required catheterization. The total scores of Overactive Bladder Symptom Score and International Consultation on Incontinence Questionnaire Short Form were significantly decreased for 10 and eight months, respectively. The score of GRA was significantly improved for eight months. The median time to failure was 11.0 months. CONCLUSION: This study suggests that onabotulinumtoxinA submucosal injection is promising for refractory non-neurogenic OAB. It is anticipated that the treatment is effective for eight to nine months and approximately 40% of the patients do not require anticholinergics at the 12th month postoperatively.

Influence of hospital surgical volume of radical prostatectomy on quality of perioperative care.

PURPOSE: We investigated the relationships between hospital surgical volume, surgical outcome, care plans indicated in critical pathways and actual perioperative care using data from a nationwide survey for radical prostatectomy. MATERIALS AND METHODS: In this study, urologists from 155 hospitals in Japan cooperated in submitting the data of 4,029 patients who underwent radical prostatectomy in 2007, and the perioperative care plan in critical pathways. Of these, we analyzed data of 3,499 patients undergoing open radical prostatectomy and minimum incision endoscopic radical prostatectomy. RESULTS: Increasing hospital volume was associated with decreased proportion of open radical prostatectomy (p < 0.001). As the hospital volume increased, surgical duration was significantly shorter (p < 0.001) and bleeding volume decreased (p < 0.004). Analyses of perioperative care suggested that low-volume hospitals (<15 patients annually) were likely to have longer care than medium-volume (15-29 patients per year) or high-volume (≥30 patients per year) hospitals, and the length of actual care was prolonged in the low-volume hospitals. Multivariate logistic regression analysis suggested that the occurrence of postoperative complications was significantly associated with surgeon's volume (p = 0.004), patient age (p = 0.001), preoperative anticoagulant therapy (p = 0.045), coexistent diabetes mellitus (p = 0.009), surgical duration (p = 0.002) and bleeding volume (p < 0.001), but not hospital volume. CONCLUSIONS: Urologists in high-volume hospitals appeared to attempt new types of surgery. Hospital surgical volume was strongly associated with the surgical duration, bleeding volume and planned and actual perioperative care; however, it was not associated with postoperative complications.

Changes in perioperative management of radical prostatectomy using clinical pathways according to a standardized care plan: a multi-institutional study.

OBJECTIVES: To improve the perioperative care for radical prostatectomy patients at a multi-institutional level and practice. METHODS: A prospective multi-institutional study involving 50 hospitals was carried out in cooperation with the Japanese Society of Endourology. As the first step, a consensus meeting was held to establish a standardized perioperative care plan. Second, the clinical pathways were individually developed and revised according to the standardized care plan in each of the participating hospitals. Patterns of perioperative care, including preoperative hospital stay, resuming meals and ambulation, removal of pelvic drain and urethral catheter, antimicrobial administration, and postoperative hospital stay, were compared before (2007) and after developing/revising pathways (2009). Furthermore, actual practice and complications before and after implementing the pathways were investigated. RESULTS: Except for resuming ambulation, all perioperative pathways were significantly shortened with the adoption of the newly defined clinical pathway (P < 0.001). Furthermore, all settings except for postoperative hospital stay significantly decreased in terms of variance (P < 0.002). In 2009, the overall complication rate significantly decreased (P < 0.001), and all of the outcomes except urethral catheter removal were also significantly shortened (P ≤ 0.008) and decreased in variance after implementation of the new pathways (P ≤ 0.006). In multivariate analyses, implementation of the refined clinical pathways was an important factor to improve perioperative care. CONCLUSIONS: When standardized goals in perioperative care are recommended to hospitals and care plans are developed/revised in individual hospitals, both settings and practice are significantly improved. It is to be investigated whether a similar intervention could be useful to achieve a standardization of surgical pathway for other diseases.

Botulinum toxin A submucosal injection for refractory non-neurogenic overactive bladder: early outcomes.

The objective of the present study was to assess the short-term effects of botulinum toxin A (BTX-A) injection for refractory non-neurogenic overactive bladder (OAB) in the setting of a prospective multicenter clinical trial. Refractory OAB was defined as persistent urgency urinary incontinence (UUI) ≥ once a week despite taking anticholinergic agents, or the incapability to continue the agents because of the adverse effects. A total of 100 U of BTX-A were reconstituted in 15 mL of normal saline and an aliquot of 0.5 mL was injected at 30 submucosal sites of the bladder wall. Nine men and eight women aged 67 ± 12 years were included. Subjective daytime frequency, urgency and UUI significantly decreased after treatment. On a 3-day frequency-volume chart, the daytime and night-time frequency of UUI significantly decreased from 5.5 and 0.5 pre-injection to 2.0 and 0.3 postinjection, respectively. Daytime urinary incontinence completely disappeared in six subjects. A urodynamic study showed the disappearance of detrusor overactivity in eight patients and a decrease in five patients. Maximum bladder capacity significantly increased from 179.9 to 267.3 mL. Difficulty on micturition or feeling of incomplete emptying was reported by 23.5% and 43.8% of patients at weeks 2 and 4, respectively. Postvoid residual urine increased to >100 mL in seven patients and >200 mL in one patient after injection; however, none of the patients required clean intermittent catheterization. These findings suggest promising efficacy of BTX-A in Japanese OAB patients.

Perioperative management of transurethral surgery for benign prostatic hyperplasia: a nationwide survey in Japan.

OBJECTIVES: Various types of minimally invasive surgical treatments, including transurethral resection of prostate (TURP), are being carried out in Japan for patients with benign prostatic hyperplasia (BPH). The aim of the present study was to elucidate the current status of perioperative care for these treatments by carrying out a nationwide survey. METHODS: Assisted by the Japanese Endourology and ESWL Association, perioperative data from 157 institutions participating in this survey were collected and analyzed. RESULTS: This survey included 3918 patients undergoing TURP, 242 TUR in saline (TURis), 638 holmium laser enucleation of the prostate (HoLEP), 90 holmium laser ablation (HoLAP) and 241 photoselective vaporization (PVP). Mean operative time was shorter in TURP (71 min) and longer in HoLEP (127). Although no transfusions were required in cases undergoing HoLAP or PVP, blood was frequently transfused in those undergoing TURis (25.6%), TURP (10.2%) and HoLEP (7.8%), and the difference was significant. During the hospital stay, the incidence of TUR-syndrome, postoperative bleeding requiring bladder irrigation, acute urinary retention/difficulty on micturition and pad use at discharge was highest in TURP (2.3%), TURis (7.9%), HoLAP (16.7%) and HoLEP (15.1%), respectively. Two patients undergoing TURP died (0.05%). The shortest mean postoperative hospital stay was for PVP (1.6 days, even if the readmission rate within 90 days was the highest in this same group; 6.2%). Perioperative care during hospital stay varied among the five types of procedures. CONCLUSIONS: This survey provides useful documentation on the current status of minimally invasive treatments for BPH in Japan. Complication rates for TURP are not significantly higher as compared with other procedures. Thus, TURP can still be considered as the gold standard for BPH treatment.

[Perioperative management of radical prostatectomy: a nationwide survey in Japan].

PURPOSE: Recently, various types of radical surgery have been performed in Japan. To elucidate the surgical consequences, morbidity and mortality, and perioperative care, we conducted a nationwide survey. MATERIALS AND METHODS: Assisted by the Japanese Society of Endourology, perioperative data from 156 hospitals participating in this survey in 2007 were analyzed. Using a spreadsheet database, data were collected from each institution. RESULTS: Open radical prostatectomy was performed in 3,138 patients at 143 hospitals, minimum incision endourological radical prostatectomy in 361 at 15 hospitals, laparoscopic radical prostatectomy via transperitoneal approach in 143 at 11 hospitals and laparoscopic radical prostatectomy via extraperitoneal approach in 337 at 13 hospitals. For open and minimum incision endourological radical prostatectomy, the surgical duration was shorter but the bleeding volume was greater than that in laparoscopic radical prostatectomy via both approaches. As a whole, perioperatvie mortality rate was 0.05% and morbidity rate was 23.4%. Rectal injury was similarly infrequent among the four types of surgery. Superficial surgical site infection was most frequent in open radical prostatectomy. Perioperative management significantly varied among the four types of surgery. In laparoscopic radical prostatectomy via extraperitoneal approach, urethral catheter was removed earlier but acute urinary retention frequently occurred. CONCLUSIONS: In Japan, open radical prostatectomy was the most frequently performed surgery for prostate cancer. Surgical volume per hospital was small, however, mortality was low and morbidity was acceptable. Comparisons of complications and outcomes among the types of currently performed surgery should be useful to promote standardization of the perioperative care.

[Multi-center study for standardisation of perioperative management of radical prostatectomy using clinical pathways].

PURPOSE: Our previous study indicated that there was a great variety in the perioperative management of radical prostatectomy among hospitals. Therefore we conducted a multiinstitutional study in order to standardize the perioperative management using clinical pathways. MATERIALS AND METHODS: The perioperative data on radical prostatectomy were collected between January and December 2004 (Period 1) from eight hospitals. These outcomes were discussed by researchers and the clinical pathway used at each hospital was constructed or revised. The outcomes using these pathways in Period 2 (January 2005 to March 2006) were compared with those in Period 1. RESULTS: Three hundred seventy-eight men in Period 1 and 360 in Period 2 were enrolled in this study. The settings of perioperative management using the new pathways were relatively similar among hospitals. A majority of perioperative management procedures in Period 2 were conducted as described in the new clinical pathways, judging from the median days. The day of initiating the resumption of fluid intake, meals and removing the epidural anesthetic catheter and drain changed from 1.2 +/- 0.7 to 1.3 +/- 1.4 postoperative day, 1.9 +/- 1.2 to 1.8 +/- 1.7, 2.4 +/- 0.7 to 2.5 +/- 0.6, 3.8 +/- 2.5 to 3.8 +/- 2.8, respectively, without a significant difference. The postoperative day of initiating the walking and discontinuing continuous drip infusion and intravenous antibiotics were shortened from 1.9 +/- 0.9 to 1.5 +/- 0.6, 3.7 +/- 2.1 to 3.1 +/- 2.2 and 3.6 +/- 2.0 to 2.5 +/- 2.2, respectively, which did show a significant difference. The day of removing the urethral catheter was changed 9.1 +/- 4.9 to 8.6 +/- 5.4 without significant difference. But the durations of preoperative hospitalization, hospitalization after removing the urethral catheter and postoperative hospitalization were significantly shortened from 3.4 +/- 2.1 to 2.5 +/- 1.0 days, 8.9 +/- 10.1 to 5.6 +/- 3.8, and 17.9 +/- 10.9 to 14.4 +/- 9.1, respectively. CONCLUSIONS: The clinical pathways established or revised at these hospitals after discussing the perioperative management in multiple hospitals were similar, and using such pathways advanced the standardization of peri-operative management after radical prostatectomy.

Psychometric analysis of international prostate symptom score for female lower urinary tract symptoms.

OBJECTIVES: Although the International Prostate Symptom Score (IPSS) has often been used for female lower urinary tract symptoms (FLUTS), the psychometric properties of IPSS for FLUTS have not been studied. We investigated the reliability and validity of IPSS for FLUTS. METHODS: Two samples were prepared. Sample A consisted of 227 women and 455 men who consulted a hospital doctor and sample B consisted of 519 women and 419 men who consulted a general practitioner. Eighty-nine percent of participants completed all IPSS items and quality of life index. Cronbach's alpha coefficients and Spearman's rho were calculated for reliability and validity assessment, respectively. A factor analysis was also conducted to explore the underlying structure. RESULTS: Significant differences were found in age and each IPSS item score between the 2 samples. Cronbach's alpha of IPSS in women was approximately 0.8 in both samples, comparable to that in men. The relatively high Spearman's rho among most of IPSS voiding items and among most storage items and low Spearman's rho among most of the different categories described indicated good convergent and discriminant validity. The factor analysis showed 2 components in IPSS for FLUTES. The first was consistently related to IPSS items 1, 3, 5, and 6 and the second was related to IPSS items 2, 4, and 7. In men, however, IPSS item 4 comprised different components between samples A and B. CONCLUSIONS: Although the subject background somewhat affects the psychometric properties, the IPSS can be relevant when used to examine women, as well as men.

Reliability and validity of the King's Health Questionnaire for lower urinary tract symptoms in both genders.

OBJECTIVE: To investigate the reliability and validity of the King's Health Questionnaire (KHQ) in both genders, which was originally developed as a health-related quality of life (HRQoL) questionnaire for female urinary incontinence for general lower urinary tract symptoms (LUTS). SUBJECTS AND METHODS: Data from the International Prostate Symptom Score (IPSS) and KHQ obtained from 179 men and 75 women consulting urologists (Sample A) were analysed. Cronbach's alpha coefficient and inter-domain correlation were calculated for reliability and validity assessment, respectively. Factor analysis was used to explore the underlying factor structure of the KHQ. KHQ scores of sample A were compared with those of 330 men and 418 women consulting general practitioners (Sample B). RESULTS: Internal consistency of KHQ was acceptable with a Crohnbach's alpha of 0.721-0.915 in the total population of sample A. Correlation analysis showed convergent validity among 'Physical Limitations', 'Role Limitation' and 'Social Limitations' and discriminant validity among 'Personal Relationship', 'Emotion's and 'Sleep/Energy'. Factor analysis showed three underlying components to explain convergent and discriminant validity. In both sample A and sample B, HRQoL was impaired in the eight domains according to IPSS severity. KHQ scores of domains other than 'General Health Perception' in sample B were lower than those in sample A. CONCLUSION: The KHQ can be used as a HRQoL questionnaire for LUTS in both genders. In the future, it is expected that the KHQ could be used in clinical studies for benign prostate hyperplasia and other conditions.

Diagnosis and treatment of lower urinary tract symptoms in the elderly by general practitioners.

AIM: We investigated the diagnosis and treatment of lower urinary tract symptoms (LUTS) by general practitioners (GPs) according to the Practical Manual for LUTS Evaluation and Treatment in the Elderly For GPs. METHODS: Using the manual, 14 GPs determined LUTS severity using the International Prostate Symptom Score, Quality of Life Index, post-void residual urine volume and the International Consultation on Incontinence Questionnaire-Short Form, then evaluated utilization of the frequency volume charts and other examinations to treat LUTS and assessed treatment effectiveness. RESULTS: This study included 52 men (aged 71 +/- 9 years) and 37 women (73 +/- 9). Voiding symptoms were more frequent in men but storage symptoms occurred similarly in both sexes. The overall severities of LUTS were similar between sexes. Of 36 men and 27 women who were treated, water restriction for polyuria and nocturnal polyuria was recommended for 17 men and 14 women, bladder training for six women, and pelvic floor exercise for three men and 16 women as behavioral therapy. Of 27 men and 25 women whose treatment effectiveness was assessed by GPs, effectiveness was judged as "fairly good" or greater in 20 men (74%) and 23 women (92%). Eleven men (40%) and 20 women (80%) were satisfied with their treatment. CONCLUSION: It is suggested that GPs can provide high-quality LUTS practice when they follow the manual and use the recommended tools for evaluation and monitoring.

[Continuous bladder irrigation following transurethral resection of the prostate (TURP)].

PURPOSE: We investigated whether continuous bladder irrigation after Transurethral Resection of the Prostate (TURP) would prevent catheter obstruction by the clot. MATERIALS AND METHODS: We analyzed data from 761 patients registered in "a multi-institutional study of TURP clinical pathway" sponsored by the Ministry of Health, Labor and Welfare between 2001 and 2003. The difference of clinical backgrounds of the cases, resected weight, operating time, risk of being feverish, risk of catheter obstruction and chance of postoperative Transurethral Fulguration (TUF) between each institution were investigated. The risk factor of catheter obstruction is characterized and the significance of continuous bladder irrigation is discussed. RESULTS: The incidence of catheter obstruction in the four institutions, in which 90% or more of patients underwent continuous bladder irrigation, was significantly lower than that in the three institutions, in which continuous bladder irrigation was performed in selected patients whose hematuria was severe (4.4% VS 12.9%, p<0.001). There was no difference in the frequency of either pyrexia or postoperative TUF. Logistic regression analysis showed that significant factors for catheter obstruction are continuous bladder irrigation, resected tissue weight and preoperative urinary infection. CONCLUSIONS: Routine continuous bladder irrigation achieved a lower incidence of catheter obstruction. However, we recommend that urologists should decide whether to perform routine continuous irrigation, considering the frequency of catheter obstruction, safety, labor and cost.

[Evolution of common clinical path for transurethral resection of prostate (TURP)].

OBJECTIVES: Improvement of perioperative management for transurethral resection of the prostate (TURP) by revising the common clinical path was investigated in multiple hospitals. METHODS: We discussed perioperative outcomes using the common path in 2002 and revised it for 2003. Changes in perioperative outcomes between 2002 and 2003 and differences among hospitals were compared. RESULTS: There were no statistically significant differences in age, proportion of patients with mildly impaired activity of daily living and/or impaired cognition, general anesthesia, operating duration, resected weight, incidence of intraoperative complications and blood transfusion between 2002 and 2003. Although there were no differences in preoperative hospital stay, re-hospitalization rate and charges for surgery and anesthesia, Foley catheter was removed significantly earlier from postoperative day 2.9 to 2.3 and total medical charge significantly decreased from 43,703 to 39,661 units (1 unit = 10 yen). The incidence of postoperative pyrexia increased from 2.4% to 11.2% in 2003, however, the incidences of epididymitis, postoperative bleeding and postoperative difficulty on micturition remained stable. The average and standard deviation of postoperative hospital stay and total medical charge at each hospital decreased, however, differences among hospitals found in 2002 remained in 2003. CONCLUSION: We found that standardization can be accomplished by discussing perioperative management using a common path in multiple hospitals and revising the path as needed. Common clinical path should be a valid method of advancing standardization in Japan.

[Questionnaire survey of peri-operative management of transurethral prostate resection in Japan].

OBJECTIVES: We investigated perioperative management for transurethral resection of the prostate (TURP) in Japan. METHODS: The questionnaire survey was conducted in 1,213 educational institutions for urology. RESULTS: The questionnaires were returned from 722 (60%) institutions. Admission to hospital was most frequently scheduled on preoperative day 1; termination of continuous drip infusion, starting meal intake and walking on postoperative day 1; intravenous antibiotics for three days; removal of Foley catheter on postoperative day 4; oral antibiotics for 7 days; and discharge from hospital on postoperative day 7. CONCLUSION: Although hospitalization was 14 days or less at most institutions, several procedures, especially the administration of prophylactic antibiotics, were fairly varied. Discussions from various perspectives might be needed to standardize the perioperative management of TURP in Japan.

[Questionnaire survey on lower urinary tract symptoms (LUTS) for patients attending general practice clinics].

OBJECTIVES: We investigated the incidence of lower urinary tract symptoms (LUTS) in people consulting a general practice (GP) clinics. MATERIALS AND METHODS: The questionnaire included 7 questions regarding LUTS and 1 question regarding QOL (QOL index) based on the International Prostate Symptom Score (I-PSS), 3 questions on the Overactive Bladder Symptom Score (OABSS) and 4 questions on the International Conference of Incontinence Questionnaire Short-form (ICIQ-SF) and the survey was conducted among 1,120 people aged 50 or older who consulted a GP clinic. RESULTS: Questionnaires were collected from 958 persons (86%) and the data from 822 (73%) who completed all the above questions were analyzed. There were 364 men (mean age: 67 year-old) and 458 women (68 year-old). Moderate or severe grades on I-PSS and OABSS were indicated in 99 (27%) and 43 (12%), respectively, for men, and 55 (12%) and 40 (9%) for women. Moderately or severely impaired QOL was indicated in 206 (57%) men and 193 (42%) women. Fifty-five (15%) men and 185 (40%) women indicated that they had some type of urinary incontinence. There were 138 (38%) men and 165 (36%) women showing both moderate or severe I-PSS and moderate or severe impairment of QOL, and/or with an ICIQ-SF score greater than 1. CONCLUSION: When I-PSS and QOL score were used for LUTS screening, 38% of men and 36% of women aged over 50, consulting a GP clinic, had some LUTS which should be assessed to determine whether they need treatment.

[Assessment criteria of lower urinary tract symptom severity for general practitioners].

OBJECTIVES: We conducted a preliminary study to examine the validity of assessment criteria of lower urinary tract symptoms (LUTS) severity for general practitioners (GPs). MATERIALS AND METHODS: This study included 194 patients with LUTS, who visited the urology clinics in three hospitals. In 177 who completed International Prostate Symptom Score (I-PSS), International Consultation on Incontinence Questionnaire : Short-Form (ICIQ-SF), frequency-volume chart, uroflowmetry and post-void residual urine measurement, three overall grades (mild, moderate and severe) of LUTS were determined using the newly-developed assessment criteria for GPs. The relationship between diagnoses and treatments by the urologists, and overall LUTS grades were examined. RESULTS: All of the 70 patients with "severe" grade and 68 (94%) of 72 with "moderate" grade were diagnosed as having urination problems. Sixty-eight (97%) with "severe" grade and 64 (89%) with "moderate" grade were treated with fluid restriction, behavioral therapy, and/or drug therapy. Of 35 with "mild" grade, 17 (49%) were diagnosed as having normal urination. In this grade, eight patients (23%) were treated with fluid restriction and 15 (43%) with drug therapy. CONCLUSIONS: This preliminary study revealed that our criteria of LUTS severity for GPs were useful to determine whether the elderly patients should be treated or not. It is necessary to examine the validity of the criteria in a model in which GPs participate.

[Endoscopic trigonoplasty II for primary vesico-ureteral reflux].

PURPOSE: We report a technique and outcome of endoscopic trigonoplasty II (ET II), anti-reflux surgery via a transvesicostomy transurethral approach and discuss its usefulness. MATERIALS AND METHODS: Fifteen female patients, aged 5 to 64, with 23 refluxing ureters (grade I : 5, II : 2, III : 14, IV : 2) underwent the ET II. The principle of this surgery is tightening the muscular backing and elongating the intramural ureter. The operation consists of three steps: 1) two 5 mm locking trocars are placed into the bladder, 2) irrigating with 3% D-sorbitol solution, the bladder wall is incised upward along each side of the ureter using a resectoscope, to make a 2 to 3 cm U-shaped bladder flap including the ureter, 3) under a pneumobladder, the incised wall is sutured to make a muscular bed with a needle-holder via the urethra and forceps via the abdominal trocar. The U-shaped flap is fixed with two distal anchor sutures and four additional mucosal sutures. Urethral catheter is indwelled and the operation is finished. In recent four cases, we closed the tracts endoscopically. RESULTS: The average operative time was 144 minutes per ureter. In one patient with unilateral reflux, we switched to open surgery because of bleeding. Of 22 refluxing ureters, the reflux disappeared in 18 ureters (82%) and improved grade III to I in 1 ureter (5%) after 3 months and disappeared in 19 ureters (86%) after 12 months postoperatively. Ureteral injury was occurred in 3 patients during the transurethral incision of the bladder. Though we repaired it by placing a double-J stent in the 2 patients, reflux recurred in 12 months postoperatively in one of them. In the other patient cystoscopy revealed a vesicoureteral fistula in the injured portion. She subsequently underwent successful open Politano-Leadbetter ureteroneocystostomy. The average duration of indwelling catheter was shortened from 4.3 to 3.0 days by closing the tracts endoscopically. CONCLUSIONS: The overall cessation rate of the ET II was inferior to those of open anti-reflux surgeries or laparoscopic extravesical ureteral reimplantation. We do not recommend ET II for vesicoureteral reflux.

[Prolonged complete remission of multiple organ metastases after radical nephrectomy induced by interferon-alpha therapy: a case report].

We experienced a case of advanced renal carcinoma that showed complete remission to interferon-alpha therapy. A 76-year-old male underwent radical nephrectomy for left renal cell carcinoma (pT3b pN0 M0, stage III). Two and a half months later, chest X-ray, computed tomographic (CT) scan and ultrasonography revealed multiple lung metastases and a hepatic metastasis simultaneously. We started the intramuscular administration of natural interferon-alpha (OIF, 5 MIU) combined with cimetidine everyday. It caused leukopenia, a possible side-effect of interferon-alpha. We reduced the dose to three times a week. The lung metastases and hepatic metastases disappeared after 5 and 12 months, respectively. After we reduced the dose to once a week, there was no evidence of disease for 21 months.

["Can high fluid intake prevent cerebral and myocardial infarction?" Systematic review].

OBJECTIVES: We performed a systematic review about whether high fluid intake can prevent cerebral and myocardial infarction. MATERIALS AND METHODS: Previously published papers were searched for in PubMed using the combined terms of dehydration, hydration, water intake, fluid intake, cerebral infarction, cerebrovascular disease, apoplexy, myocardial infarction, angina pectoris, ischemic heart disease, blood viscosity and hemorheology. RESULTS: Of 611 papers searched, twenty-two were selected. There was one prospective randomized study, four prospective non-randomized studies, eight epidemiologic (cohort or case-control) studies and nine retrospective descriptive studies, presenting the following points. Dehydration, which increases blood viscosity, is one of the causes of cerebral or myocardial infarction. Important factors other than dehydration can cause an increase in viscosity. Drinking water during the night can protect an increase in blood viscosity but there has been no evidence that drinking excessive amount of water prevents cerebral infarction. There was one report that the risk of myocardial infarction was lower in people drinking more than 5 glasses of water than those drinking less than 2. CONCLUSION: Since cerebral and myocardial infarction are primarily caused by atherosclerosis and atheroma plaque, it is essential to adjust life style for prophylaxis. There has been no direct evidence that decrease in viscosity due to high fluid intake can prevent cerebral infarction. Further studies regarding the relationship between fluid intake and ischemic diseases, and the appropriate fluid intake for the elderly to improve their QoL are needed.