Biomedical subjects

Haruo Ito

Publications and source records attributed to Haruo Ito.

At least 19 recordsLinked to original sources

PubMed2006

Serum immunosuppressive acidic protein doubling time as a prognostic factor for recurrent renal cell carcinoma after nephrectomy.

OBJECTIVES: To identify the prognostic factors in patients with recurrent renal cell carcinoma after nephrectomy, various factors were assessed, with special attention to serum immunosuppressive acidic protein (IAP) and its doubling time. METHODS: Age, sex, stage, grade, histopathologic type, primary tumor size, site and number of metastatic organs, time to recurrence, IAP levels before nephrectomy and at the diagnosis of recurrence, and IAP doubling time just before recurrence were analyzed in 125 patients with recurrent renal cell carcinoma after nephrectomy. RESULTS: Univariate analysis identified stage, grade, histopathologic type, primary tumor size, time to recurrence, IAP level at the diagnosis of recurrence, and IAP doubling time as significant prognostic factors. After exclusion of confounding factors, multivariate analysis showed that IAP doubling time was the most potent independent prognostic factor. Patient survival rates dichotomized according to IAP doubling time were compared at 100-day intervals from 100 to 700 days and 1000 and 2000 days. The maximal difference in survival rate was found when the cutoff level in the IAP doubling time was set at 200 days. CONCLUSIONS: The results of our study have shown that the IAP doubling time is a potent prognostic factor in patients with recurrent renal cell carcinoma. Periodic checkups with serum IAP level monitoring are recommended to predict prognosis after recurrence.

Adult↗

PubMed2006

High mechanical efficiency of left ventricular arrhythmic contractions during atrial fibrillation.

We analyzed the frequency distribution of the left ventricular (LV) mechanical efficiency of individual arrhythmic beats during electrically induced atrial fibrillation (AF) in normal canine hearts. This efficiency is the fraction of the external mechanical work (EW) in the total mechanical energy measured by the systolic pressure-volume area (PVA). The mean, median, and mode of this efficiency (EW/PVA) were as high as 78%, 80%, and 81%, respectively, on average in six hearts. These high efficiencies were comparable to that of the regular beats in these hearts. The frequency distribution of the EW/PVA during AF tended to skew to the higher side in all the hearts. Since the EW/PVA is directly related to both the ventriculo-arterial (or afterload) coupling ratio (E(a)/E(max); E(a) = effective arterial elastance, E(max) = end-systolic ventricular elastance) and the ejection fraction on a per-beat basis, we also analyzed their frequency distributions. We found them to skew enough to account for the rightward skewed frequency distribution of the EW/PVA during AF with the unexpectedly high mean EW/PVA. These results indicate that the LV arrhythmia during AF per se does not directly suppress the mean level of LV mechanical efficiency in normal canine hearts.

Animals↗

PubMed2006

[Effect of oral lactosucrose supplementation on human enteric oxalate-degrading bacteria].

A variety of oxalate-degrading bacteria including Oxalobacter formigenes and some species of Bifidobacterium are known to colonize the human intestinal tract. Oral lactosucrose supplementation promotes the growth of Bifidobacterium in the human intestine. Therefore, we investigated the effect of oral lactosucrose supplementation on enteric oxalate-degrading bacteria in twelve healthy men (age ranging from 25 to 39 years). Lactosucrose was orally administered 10 g daily for 2 weeks without restriction of dietary intake. The total number of oxalate-degrading bacteria in feces and the 24-hour urinary excretion of oxalate were examined before and after lactosucrose supplementation. The total number of oxalate degrading-bacteria was significantly increased by lactosucrose supplementation (9.20 +/- 0.44 versus 9.77 +/- 0.46, p<0.05), although there was no significant change in the urinary oxalate excretion. The oxalate degrading-bacteria isolated from feces was biochemically identified as Bifidobacterium adolescentis. In conclusion, oral supplementation of 10 g lactosucrose daily for 2 weeks was effective in multiplying oxalate-degrading bacteria, but not in reducing urinary oxalate excretion under free non-restricted dietary intake. In addition, it was suggested that various species of Bifidobacterium were related to degradation of oxalate in the human intestine.

Administration, Oral↗

PubMed2005

Variable Unstressed Volume Keeps Normal Distributions of Canine Left Ventricular Contractility and Total Mechanical Energy under Atrial Fibrillation.

We have reported that the contractility index (E(max)) and the total mechanical energy (PVA) of arrhythmic beats of the left ventricle (LV) distribute normally in canine hearts under electrically induced atrial fibrillation (AF). Here, E(max) is the ventricular elastance as the slope of the end-systolic (ES) pressure-volume (P-V) relation (ESPVR), and PVA is the systolic P-V area as the sum of the external mechanical work within the P-V loop and the elastic potential energy under the ESPVR. To obtain E(max) and PVA, we had to assume the systolic unstressed volume (V(o)) as the V-axis intercept of the ESPVR to be constant despite the varying E(max), since there was no method to obtain V(o) directly in each arrhythmic beat. However, we know that in regular stable beats V(o) decreases by approximately 7 ml/100 g LV with approximately 100 times the increases in E(max) from ~0.2 mmHg/(ml/100 g LV) of almost arresting weak beats to approximately 20 mmHg/(ml/100 g LV) of strong beats with a highly enhanced contractility. In the present study, we investigated whether E(max) and PVA under AF could still distribute normally, despite such E(max)-dependent V(o) changes. The present analyses showed that the E(max) changes were only approximately 3 times at most from the weakest to the strongest arrhythmic beat under AF. These changes were not large enough to affect V(o) enough to distort the frequency distributions of E(max) and PVA from normality. We conclude that one could practically ignore the slight E(max) and PVA changes with the Emax-dependent V(o) changes under AF.

Animals↗

PubMed2005

Predictability of O2 consumption from contractility and mechanical energy of absolute arrhythmic beats in canine heart.

Left ventricular (LV) O2 consumption (V(O2)) per minute is measurable for both regular and arrhythmic beats. LV V(O2) per beat can then be obtained as V(O2) per minute minute divided by heart rate per minute minute for regular beats, but not for arrhythmic beats. We have established that V(O2) of a regular stable beat is predictable by V(O2) = a PVA + b E(max) + c, where PVA is the systolic pressure-volume area as a measure of the total mechanical energy of an individual contraction and E(max) is the end-systolic maximum elastance as an index of ventricular contractility of the contraction. Furthermore, a is the O2 cost of PVA, b is the O2 cost of E(max), and c is the basal metabolic V(O2) per beat. We considered it theoretically reasonable to expect that the same formula could also predict LV V(O2) of individual arrhythmic beats from their respective PVA and E(max) with the same a, b, and c. We therefore applied this formula to the PVA - Emax data of individual arrhythmic beats under electrically induced atrial fibrillation (AF) in six canine in situ hearts. We found that the predicted V(O2) of individual arrhythmic beats highly correlated linearly with either their V(O2) (r = 0.96 +/- 0.01) or E(max) (0.97 +/- 0.03) while both also highly correlated linearly with each other (0.88 +/- 0.04). This suggests that the above formula may be used to predict LV Vo2 of absolute arrhythmic beats from their Emax and PVA under AF.

Animals↗

PubMed2005

Up-regulation of the interferon gamma (IFN-gamma)-inducible chemokines IFN-inducible T-cell alpha chemoattractant and monokine induced by IFN-gamma and of their receptor CXC receptor 3 in human renal cell carcinoma.

BACKGROUND: The antiangiogenic CXC chemokines interferon gamma (IFN-gamma)-inducible T-cell alpha chemoattractant (I-TAC) and monokine induced by IFN-gamma (Mig) are known as members of IFN-gamma-inducible antiangiogenic CXC chemokines. However, the expression of these chemokines in highly angiogenic tumors remains poorly understood. The authors examined expression of I-TAC, Mig, and their receptor, CXCR3, in tissue samples from patients with renal cell carcinoma (RCC). METHODS: Twenty-one samples of untreated RCC and corresponding normal renal tissues were obtained from surgical specimens. The expression levels of I-TAC, Mig, and CXCR3 were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, real-time RT-PCR analysis, and Western blot analysis. Immunohistochemistry was carried out to clarify the localization of both chemokines and of CXCR3. RESULTS: RT-PCR analysis showed strong expression levels of I-TAC, Mig, and CXCR3 in RCC tissues and very weak or undetectable expression in normal kidney tissues. Real-time RT-PCR analysis showed that expression levels of I-TAC, Mig, and CXCR3 in RCC tissues were 14.9 times greater, 30.3 times greater, and 9.9 times greater compared with the levels in the corresponding normal kidney tissues, respectively (P < 0.01). Western blot analysis showed up-regulation of I-TAC, Mig, and CXCR3 at the protein level. Immunofluorescence double stainings revealed that I-TAC coincided with pericytes and vascular smooth muscle cells (VSMCs) in tumor angiogenic vessels. Mig was detected in tumor endothelial cells (TECs) and in infiltrating leukocytes. In the corresponding normal kidney tissues, neither VSMCs nor endothelial cells showed positive stainings for these chemokines. CXCR3 was expressed in both tumor cells and infiltrating leukocytes. CONCLUSIONS: The results revealed special feature of vascular mural cells and TECs in RCC. The up-regulated I-TAC and Mig, produced by tumor vessels, may interact with CXCR3 expressed in tumor cells, with possible pathophysiologic significance in RCC progression.

Base Sequence↗

PubMed2005

Positive inotropic effect of nicorandil in adult rats in situ.

PURPOSE: Although the cardiac protective and negative inotropic effects of nicorandil via opening the sarcolemmal or mitochondrial K(ATP) channel and NO-like action are well known, positive inotropic effects of nicorandil in normal hearts have not been reported. The aim of the current study was to investigate how nicorandil affects left ventricular (LV) function of in situ adult rat hearts through the entire cardiovascular system. METHODS: We performed simultaneous and continuous measurements of LV pressure (P) by a catheter-tip micromanometer and LV volume (V) using a conductance catheter. We obtained steady-state LV P-V loops and intermittent curvilinear LV end-systolic pressure-volume relations (ESPVRs), LV end-systolic pressure (ESP(mLVV)), and systolic pressure-volume area (PVA(mLVV)) at midrange LVV (mLVV). We evaluated the effects of nicorandil on LV function by these mechanical indexes sensitively reflecting changes in LV contractility and work capability, preload (end-diastolic volume, EDV), and afterload (effective arterial elastance, Ea). RESULTS: Nicorandil (10 and 20 microg.kg(-1).min(-1)) (blood concentration: 0.53 +/- 0.14 and 1.48 +/- 0.21 microg/ml) largely shifted ESPVR upward and thus significantly increased ESP(0.06), PVA(0.06), stroke volume due to increase in EDV, and ejection fraction without significant changes in Ea and heart rate. In contrast, an NO donor, nitroglycerin (1 microg.kg(-1) . min(-1)), significantly decreased Ea but did not change ESP(0.06), PVA(0.06), and EDV. Furthermore, either a nonselective K(ATP) channel blocker, glybenclamide, or a mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, abolished these nicorandil-induced positive inotropic actions. CONCLUSION: These results suggest that nicorandil exhibited positive inotropic actions on LV function of in situ hearts in adult rats with resultant increased preload (EDV).

ATP-Binding Cassette Transporters↗

PubMed2005

Outcomes of shockwave lithotripsy for upper urinary-tract stones: a large-scale study at a single institution.

PURPOSE: We investigated the risk factors having an impact on the achievement of stone-free status and on the success rate, as well as on the likelihood of recurrence, in patients undergoing shockwave lithotripsy. PATIENTS AND METHODS: We evaluated the characteristics and outcomes of 3023 patients (3254 renal units) with upper urinary-tract stones who underwent SWL at the Funabashi Clinic over a 13-year period. We assessed the stone-free and success rates for 2844 patients (3061 renal units) 3 months post-SWL. We also determined the recurrence rate for the 1078 patients (1139 renal units) who had achieved stone-free status at that time. RESULTS: Overall, stone-free status was achieved in 65.1% of patients, and the success rate was 85.7%. There were significant differences in the stone-free rates depending on patient age, history of urolithiasis, and presence of pyuria before SWL, as well as the number, location, size, and composition of the stones. Stones recurred in 326 of 1139 renal units (28.6%) during a mean follow-up of 36 months. The recurrence rates were 7.5%, 24.1%, and 33.0% after 1, 3, 5 years, respectively. Multiple stones, a history of urolithiasis, and stones located in the kidney or both kidneys plus the ureter significantly influenced recurrence. Multivariate analysis demonstrated that multiple stones were most significantly related to recurrence. CONCLUSION: Treatment with SWL has a low morbidity and high effectiveness. The number and location of stones and a history of urolithiasis significantly influence recurrence. Further studies of prophylactic therapy are required, especially for patients with these factors.

Adolescent↗

PubMed2005

Efficacy and safety of laparoscopic surgery for pheochromocytoma.

OBJECTIVE: Laparoscopic surgery for primary aldosteronoma and Cushing's syndrome is well established. We report on our experiences with laparoscopic adrenalectomy for pheochromocytoma, and assess the efficacy and safety of the laparoscopic approach. METHODS: Between April 1998 and April 2003, a total of 23 patients underwent laparoscopic adrenalectomy for pheochromocytoma at Chiba University Hospital and Yokohama Rosai Hospital, Japan. We compared the surgical outcomes of these patients with those of 106 patients with adrenal tumors due to other pathologies who underwent laparoscopic adrenalectomy during the same period. RESULTS: The mean tumor size of pheochromocytoma was 4.96 cm. Mean operative time was 192.7 min, and mean estimated blood loss was 130 mL. Neither mean operative time nor mean estimated blood loss was greater for patients with pheochromocytoma. Intraoperative hypertension (systolic blood pressure > 180 mmHg) occurred in 39.1% (9/23) of patients with pheochromocytoma. During the follow-up period, there were no mortalities or recurrences of endocrinopathy. CONCLUSIONS: Laparoscopic adrenalectomy for pheochromocytoma is a safe and minimally invasive procedure.

Adrenal Gland Neoplasms↗

PubMed2005

Laparoscopic adrenalectomy in patients with large adrenal tumors.

OBJECTIVES: The maximum size of adrenal tumors that should be removed by laparoscopic adrenalectomy is controversial. We conducted a retrospective comparison of the results of laparoscopic adrenalectomy between patients with adrenal tumors > or =6 cm ('large tumors') and patients with adrenal tumors <6 cm ('small tumors'). METHODS: The participants in the study were 16 patients with large tumors and 111 patients with small tumors. The patients comprised 59 men and 68 women (mean age, 49.0 years; age range, 23-79) with varying diagnoses. Of the 16 patients with large tumors, five had Cushing's syndrome, four had pheochromocytomas, six had a non-functional tumor and one had malignant lymphoma. Adrenal tumors were confirmed by hormonal assays, biochemical tests and computed tomography. Of the 16 large tumors, five tumors were on the right and 11 were on the left. RESULTS: We found no significant differences in general demographic parameters between patients with large and small tumors. The mean duration of surgery was not significantly different between two groups. (large tumors, 210 min; small tumors,175 min). The mean volume of blood loss was 212 mL for large tumors and 30 mL for small tumors (P < 0.001, significant difference). There was no significant difference in time until walking, duration of hospitalization or number of using analgesics used. The time to first oral intake of group 1 (<6 cm) was significantly shorter than group 2 (> or =6 cm). Tumor size (> or =7.5 cm) was an independent predictor of a longer operation and greater blood loss in large tumors. CONCLUSIONS: Laparoscopic adrenalectomy for large tumors was safe and minimally invasive.

Adrenal Gland Neoplasms↗

PubMed2005

The prognostic value of p53, Ki-67 and matrix metalloproteinases MMP-2 and MMP-9 in transitional cell carcinoma of the renal pelvis and ureter.

AIM: To investigate the prognostic and predictive relevance of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract. METHODS: The expression of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki-67, MMP-2 and MMP-9 over-expression with conventional pathological parameters and patient survival was examined. RESULTS: p53 over-expression was significantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki-67 over-expression was significantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki-67 over-expression was a significant prognostic factor in the univariate analysis (P < 0.05), but it did not have a significant impact on survival in the multivariate analysis. Ki-67 labeling index was a significant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index. CONCLUSION: Ki-67 over-expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP-2 and MMP-9 are of limited value.

Adult↗

PubMed2005

[Androgen receptor].

Explore the source record for details and available documents.

Androgen-Insensitivity Syndrome↗

PubMed2004

Normal distribution of ventricular pressure-volume area of arrhythmic beats under atrial fibrillation in canine heart.

We previously found the frequency distribution of the left ventricular (LV) effective afterload elastance (E(a)) of arrhythmic beats to be nonnormal or non-Gaussian in contrast to the normal distribution of the LV end-systolic elastance (E(max)) in canine in situ LVs during electrically induced atrial fibrillation (AF). These two mechanical variables determine the total mechanical energy [systolic pressure-volume area (PVA)] generated by LV contraction when the LV end-diastolic volume is given on a per-beat basis. PVA and E(max) are the two key determinants of the LV O(2) consumption per beat. In the present study, we analyzed the frequency distribution of PVA during AF by its chi(2), significance level, skewness, and kurtosis and compared them with those of other major cardiodynamic variables including E(a) and E(max). We assumed the volume intercept (V(0)) of the end-systolic pressure-volume relation needed for E(max) determination to be stable during arrhythmia. We found that PVA distributed much more normally than E(a) and slightly more so than E(max) during AF. We compared the chi(2), significance level, skewness, and kurtosis of all the complex terms of the PVA formula. We found that the complexity of the PVA formula attenuated the effect of the considerably nonnormal distribution of E(a) on the distribution of PVA along the central limit theorem. We conclude that mean (SD) of PVA can reliably characterize the distribution of PVA of arrhythmic beats during AF, at least in canine hearts.

Animals↗

PubMed2004

In situ measurements of crossbridge dynamics and lattice spacing in rat hearts by x-ray diffraction: sensitivity to regional ischemia.

BACKGROUND: Synchrotron radiation has been used to analyze crossbridge dynamics in isolated papillary muscle and excised perfused hearts with the use of x-ray diffraction techniques. We showed that these techniques can detect regional changes in rat left ventricle contractility and myosin lattice spacing in in situ ejecting hearts in real time. Furthermore, we examined the sensitivity of these indexes to regional ischemia. METHODS AND RESULTS: The left ventricular free wall of spontaneously beating rat hearts (heart rate, 290 to 404 bpm) was directly exposed to brief high-flux, low-emittance x-ray beams provided at SPring-8. Myosin mass transfer to actin filaments was determined as the decrease in reflection intensity ratio (intensity of 1,0 plane over the 1,1 plane) between end-diastole and end-systole. The distance between 1,0 reflections was converted to a lattice spacing between myosin filaments. We found that mass transfer (mean, 1.71+/-0.09 SEM, n=13 hearts) preceded significant increases in lattice spacing (2 to 5 nm) during systole in nonischemic pericardium. Left coronary occlusion eliminated increases in lattice spacing and severely reduced mass transfer (P<0.01) in the ischemic region. CONCLUSIONS: Our results suggest that x-ray diffraction techniques permit real-time in situ analysis of regional crossbridge dynamics at molecular and fiber levels that might also facilitate investigations of ventricular output regulation by the Frank-Starling mechanism.

Actin Cytoskeleton↗

PubMed2004

Reversible effects of isoproterenol-induced hypertrophy on in situ left ventricular function in rat hearts.

The aim of the present study was to evaluate specifically left ventricular (LV) function in rat hearts as they transition from the normal to hypertrophic state and back to normal. Either isoproterenol (1.2 and 2.4 mg.kg(-1).day(-1) for 3 days; Iso group) or vehicle (saline 24 microl.day(-1) for 3 days; Sa group) was infused by subcutaneous implantation of an osmotic minipump. After verifying the development of cardiac hypertrophy, we recorded continuous LV pressure-volume (P-V) loops of in situ ejecting hypertrophied rat hearts. The curved LV end-systolic P-V relation (ESPVR) and systolic P-V area (PVA) were obtained from a series of LV P-V loops in the Sa and Iso groups 1 h or 2 days after the removal of the osmotic minipump. PVA at midrange LV volume (PVA(mLVV)) was taken as a good index for LV work capability (13, 15, 20, 21). However, in rat hearts during remodeling, whether PVA(mLVV) is a good index for LV work capability has not been determined yet. In the present study, in contrast to unchanged end-systolic pressure at midrange LV volume, PVA(mLVV) was significantly decreased by isoproterenol treatment relative to saline; however, these measurements were the same 2 days after pump removal. Simultaneous treatment with a beta(1)-blocker, metoprolol (24 mg.kg(-1).day(-1)), blocked the formation of cardiac hypertrophy and thus PVA(mLVV) did not decrease. The reversible changes in PVA(mLVV) reflect precisely the changes in LV work capability in isoproterenol-induced hypertrophied rat hearts mediated by beta(1)-receptors. These results indicate that the present approach may be an appropriate strategy for evaluating the effects of antihypertrophic and antifibrotic modalities.

Adrenergic beta-Agonists↗

PubMed2004

Phase I/II clinical trials of carbon ion therapy for prostate cancer.

BACKGROUND: Heavy ion beams possess high linear energy transfer components and a prominent Bragg peak in the human body, resulting in higher relative biological effectiveness and improved dose distribution. To establish heavy ion therapy techniques for the treatment of prostate cancer, phase I/II clinical trials were initiated. METHODS: For 96 patients with T1b-T3 prostate cancer, three carbon ion beams were used to irradiate the prostate and seminal vesicles (20 times/5 weeks) with or without endocrine therapy. Radiation dose was expressed in GyE which was initially thought to be equivalent to photon dose. Total dose was gradually increased from 54 to 72 GyE. RESULTS: Carbon ion therapy was completed in 20 cases of T1b/T1c/T2aN0M0 as monotherapy, in 8 cases of T2b/T3pN0M0 with neoadjuvant endocrine therapy, and in 68 cases of T2b/T3N0/pN1M0 with neoadjuvant and adjuvant endocrine therapy. Median observation period was 47 months. Grade 3 late radiation morbidity of rectum and/or bladder/urethra developed in one and five cases who received 66 and 72 GyE of radiation, respectively. After these adverse effects were observed, total dose was decreased to 66 GyE and the radiation field was coned down during the treatment course. At 5 years, overall, cause-specific, clinical recurrence-free, and biochemical recurrence-free survival rates were 87.7, 94.9, 90.0, and 82.6%, respectively. Local control was achieved in all patients except one patient who received 54 GyE of radiation. CONCLUSIONS: The therapeutic techniques of carbon ion therapy have been established for patients with prostate cancer. Carbon ion therapy may exert excellent effect to the tissues of prostate cancer.

Carbon↗

PubMed2004

Expression of regulator of G protein signalling protein 5 (RGS5) in the tumour vasculature of human renal cell carcinoma.

The gene expression profiles of tumour and normal vasculature are distinctively different. The altered expression of various angiogenesis-related genes in tumour-derived endothelial cells has been investigated intensively, but there may be as yet unidentified molecules that regulate tumour angiogenesis. In the present study, the distinctive expression of regulator of G protein signalling protein 5 (RGS5) in tumour vessels in human renal cell carcinoma (RCC) has been clarified. RGS5 is a member of the RGS superfamily and acts as a negative regulator of heterotrimeric G protein-mediated signalling through G protein-coupled receptors (GPCRs). RT-PCR showed strong expression of RGS5 in all RCCs examined, but expression was very weak or undetectable in normal kidneys. By real-time RT-PCR, the ratio of RGS5 mRNA in RCC to that in normal kidney was 6.6 : 1 (p = 0.0012). In situ hybridization showed strong expression of RGS5 in vessels within tumour cell nests. It was expressed neither in tumour cells nor in normal renal capillaries. Immunohistochemical staining using serial sections for endothelial cell markers (CD31 and CD34) and smooth muscle cell markers (alpha-SMA and desmin), as well as fluorescence double staining, strongly suggested that tumour endothelial cells were the main location of RGS5 in RCC. These findings suggest that RGS5 may be involved in G protein-mediated signalling in tumour vessels in human RCC.

Actins↗

PubMed2004

Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study.

OBJECTIVES: To clarify the effect of intermittent androgen suppression on the time to androgen-independent progression and changes in quality of life (QOL). METHODS: Patients with locally advanced or metastatic prostate cancer were treated with a combination of leuprolide acetate and flutamide for 36 weeks. When the serum prostate-specific antigen (PSA) levels at 24 and 32 weeks were less than 4.0 ng/mL, treatment was withheld until the PSA level reached 15 ng/mL or the pretreatment level. This cycle of on-treatment and off-treatment was repeated until PSA failure (three consecutive increases in PSA level greater than 4.0 ng/mL during the on-treatment period) or symptomatic progression was observed. Changes in QOL were assessed by a self-assessment questionnaire. RESULTS: Forty-nine patients (26 with T3N0M0, 8 with T2-T3N1M0, 2 with T4N0M0, and 13 with T2-T3N0M1) were enrolled. The mean follow-up period was 136.5 weeks. Thirty-one patients finished cycle 1, six finished cycle 2, and three finished cycle 3. The mean off-treatment duration in cycles 1, 2, and 3 was 46.1, 36.9, and 23.3 weeks, respectively. In the off-treatment period, statistically significant improvements in the QOL score were observed in the categories of potency (11.4 versus 2.4) and social/family well-being (20.3 versus 16.1) compared with those in the on-treatment period. PSA failure occurred in 6 patients (3 with T3N0M0 and 3 with T2-T3N1M0), and all patients were alive at last follow-up. CONCLUSIONS: Our interim analysis indicated that QOL is remarkably improved during the off-treatment period. Intermittent androgen suppression would be a viable option for treatment of advanced prostate cancer, although a randomized controlled study is required to determine whether intermittent androgen suppression prolongs the time to androgen-independent cancer. We will continue follow-up in this study to a minimum of 3 years.

Adenocarcinoma↗