Clinical utility of ursodeoxycholic acid in preventing flutamide-induced hepatopathy in patients with prostate cancer: A preliminary study

BACKGROUND: The present study was designed to ascertain retrospectively the validity of ursodeoxycholic acid (UDCA) in the treatment of prostate cancer in terms of prophylactic effects on the occurrence of flutamide-induced hepatopathy in a large number of patients surveyed in a multi-center cooperative study. METHODS: One hundred and eighty-one patients (74.1 +/- 4.9 years) with prostate cancer treated with flutamide with (n = 70) or without (n = 111) UDCA were retrospectively evaluated and the occurrence of hepatopathy was compared between these two patient groups. RESULTS: Between patients treated with UDCA and those without it, no significant differences were noted in age, clinical stage, grade, duration of flutamide administration and serum prostate-specific antigen (PSA) levels before treatment. However, there were significant differences in the presence or absence of previous treatments and treatments used together with flutamide. The incidence of hepatopathy was 11.4% (8/70) in patients with UDCA and 32.4% (36/111) in those without it, showing a statistically significant difference (P < 0.05). The hepatopathy-free rate obtained by the Kaplan-Meier method was also significantly higher in patients with UDCA (88.4% 1 year following flutamide administration) than that in those without it (59.6%) (P < 0.005). CONCLUSION: These results suggest that UDCA has a prophylactic effect against flutamide-induced hepatopathy in patients with prostate cancer.     

Binswanger's disease: clinical and computed tomography neuroradiological study of seven cases

Background: Binswanger's disease is a special type of vascular dementia, which requires further reappraisal and redefinition. In a geriatric psychiatry hospital (with 207 beds), we treated several patients who probably had this disease, and tried to establish a basis for making a clinical diagnosis. Methods: From 2001 to 2005, we treated seven inpatients with noteworthy symptoms, who had been under observation in hospital wards for between 4 and 19 months. Here, for these patients, we examine the history of the illness, the condition of the patients at admission, the clinical course, and serial computed tomography (CT) findings. Results: Characteristic features of the clinical courses and symptoms of these patients were: (i) onset occurred late in life (patients were aged in their 70s and 80s); (ii) vascular events were atypical and transient, leaving few permanent neurological sequelae; (iii) progression of dementia and other somatic or neurologic symptoms was continuous and fast in four patients, and rather gradual in three patients; (iv) there was an alternating or changing pattern in all patients’ state of consciousness, mood, behavior, or manner of respiration; symptoms such as mutism, lack of facial expression, and apparent indifference were counterbalanced with such behaviors as occasional unexpected smiles, pertinent verbal responses, and sincere gazes; (v) significant negative symptoms were a lack of dysarthria, lack of dysphagia, lack of involuntary movement, and occasional lack of muscle rigidity. The primary CT findings were: (i) moderate to severe generalized (involving whole of centrum semiovale), diffuse and homogeneous (except one patient) leukoaraiosis of the hemispheric white matter, including the temporal lobe (except one patient), all (except one patient) frontal and parietal dominant, with the corpus callosum involved in one case; (ii) diffuse and generalized atrophy of the pallium, most marked in the frontal and parietal lobes, restricted to the frontal and parietal lobes in three patients, and to the frontal, parietal and temporal lobes in four patients; (iii) atrophy of the medial temporal lobe was inconstant and, when present, ambiguous in degree; (iv) slight to moderate enlargement of the bilateral lateral and third ventricles; (v) a few small lacunae in the basal ganglia and thalamus in one patient, inhomogeneous macular changes of density in the basal ganglia and thalamus in two patients, and no such findings in the remaining four patients. Conclusion: We have described a group of patients with dementia characterized by a clinical course with episodes of rather transient vascular intervention, psychopathology characteristic of organic dementia, fluctuating psychotic symptoms in combination, and intensive extensive homogeneous leukoaraiosis of the hemispheric white matter on CT. These clinical and CT neuroradiological findings seem to warrant the clinical diagnosis of Binswanger's disease, which should be reconfirmed at autopsy. Early research on this disease by Binswanger, Alzheimer, Nissl and others is reviewed. Some points of differential diagnosis in serial neuroradiology are discussed in relation to multilacunar dementia.     

Long-term treatment outcome of tamsulosin for benign prostatic hyperplasia

BACKGROUND: The present study assessed the long-term efficacy (>12 months) of tamsulosin in 123 patients with lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH). METHODS: The patients received a starting dose of tamsulosin of 0.2 mg/day, with a further titration up to 0.4 mg/day until symptom relief. Subjective and objective clinical variables were assessed using the international prostate symptom score (IPSS), IPSS quality of life (QoL) score, BPH impact index score, peak urinary flow rate (Q(max)) and postvoid residual urine volume. RESULTS: Except for Q(max), all clinical variables showed significant sustained improvements from baseline throughout the study period (median follow up, 43 months). Thirty patients (24.4%) withdrew because of surgical interventions. The Cox proportional hazards model showed that a baseline IPSS total score >or=15 (HR [hazard ratio] 2.13; 95% CI 1.04-4.34) was predictive of failure for tamsulosin therapy. Furthermore, during the first 12 months, a lowest IPSS total score >or=13 (HR 2.34; 95% CI 1.12-4.89), a lowest IPSS QoL score >or=3 (HR 4.16; 95% CI 1.26-13.68), and a lowest BPH impact index score >or=4 (HR 3.54; 95% CI 1.62-7.75) were also predictive of failure for tamsulosin therapy. CONCLUSIONS: Tamsulosin treatment of BPH patients for more than 12 months showed a sustained, stable efficacy. Patients without short-term effects were prone to withdraw from tamsulosin therapy, but so did patients with a high baseline IPSS total score, even if therapy was effective for at least 12 months.     

Recurrence of renal cell carcinoma more than 5 years after nephrectomy

OBJECTIVES: We evaluated clinical features and predictive factors for the recurrence of renal cell carcinoma (RCC) developing more than 5 years after nephrectomy. METHODS: We retrospectively reviewed 239 patients with RCC who underwent surgery for the primary lesion. To identify factors that affected recurrence more than 5 years after nephrectomy (delayed recurrence) and its clinical outcomes, we performed a multivariate analysis using Cox's proportional hazards model and a survival study. RESULTS: Recurrence developing within 5 years after nephrectomy (early recurrence) was found in 57 patients and delayed recurrence in 11 patients. The multivariate analysis revealed no clinical and pathologic features influencing delayed recurrence in 114 patients who survived more than 5 years after nephrectomy without having early recurrence. The patients with delayed recurrence showed better clinical outcomes than those with early recurrence when the rate was determined from the time of recurrence. CONCLUSIONS: Although delayed recurrence is not a rare event for patients with RCC, no clinical and pathologic factors at the time of the initial treatment can predict the recurrence. Patients who are free of recurrence for more than 5 years after surgery for a primary lesion should be carefully followed up for delayed recurrence.     

Amino acids and peptides

The Gln-Val-Val-Ala-Gly sequence, which occurs frequently in several natural thiol proteinase inhibitors, and derivatives were synthesized by conventional solution methods and their effect on thiol proteinases were examined. The studies led us to the conclusion that certain of these peptides exhibited a weak inhibitory effect on the thiol proteinase, papain. One of them, Z-Gln-Val-Val-Ala-Gly-OMe, showed a protective effect on papain from natural thiol proteinase inhibitor-induced inactivation. The relationship between structure and activity of these derivatives was studied and certain conclusions were derived on possible mode of action of these inhibitors. From these studies, it was concluded that Z-Gln-Val-Val-OMe was the smallest peptide to exhibit some effect on papain.     

Long-term survivors after hepatectomy for hepatocellular carcinoma

Sixteen long-term (more than 5 years) survivors after hepatic resection performed for hepatocellular carcinoma (HCC) from 1970 to 1988, were reviewed. The mean age of the patients was 51 years. There were 11 males and 5 females. HBs antigen was positive in 9 patients. Liver cirrhosis was associated with 11 patients but its severity was designated as Child's A in all patients except one. The mean tumour diameter was 2.8 cm and was relatively small. At the first operation, limited procedures (i.e. partial hepatectomy and subsegmentectomy) were employed in 87.5% of patients. A large percentage of tumours were located in S5 and S6 segments. A recurrence of HCC occurred in 9 patients after the first resection. A second resection was carried out in 7 patients, in 2 of which a third resection was done. Transcatheter arterial embolization (TAE) was performed on 4 patients. These results show that, in addition to detection of small tumours and early resection, repeated operation or TAE for treatment of recurrent HCC was important in achieving long-term survival after HCC resection.     

Intraoperative electrical stimulation of cavernous nerves with monitoring of intracorporeal pressure to confirm nerve sparing during radical prostatectomy: Early clinical results

BACKGROUND: We performed intraoperative cavernous nerve stimulation with an intracavernous pressure (ICP) monitoring system to confirm nerve sparing during radical pelvic surgery and assessed the results. METHODS: Nineteen cases of radical prostatectomy and three of radical cystoprostatectomy were examined. Electrical stimulation of the site where the neurovascular bundle (NVB) was determined to run was performed and changes in ICP were measured before and after prostate removal. RESULTS: Of the 22 patients, bilateral NVBs were preserved in six patients while unilateral NVB was preserved in 16. Before dissection, all NVBs examined exhibited positive responses (ICP changes of>5 mmHg) to nerve stimulation. After removal of the prostate, positive responses were observed in 22 (79%) of 28 macroanatomically preserved NVBs. Of 16 sides on which the NVB was not preserved, there were positive responses in five (31%). In these patients, some nerve fibers were macroscopically observed lateral to the original site of NVB. Finally, bilateral or unilateral nerve sparing was confirmed electrophysiologically in 20 (91%) of the 22 patients. CONCLUSION: Intraoperative stimulation of the NVB while monitoring ICP changes is a simple and reliable method of accurately evaluating the preservation of cavernous nerves. This system may provide further insight into the mechanism of postoperative erectile dysfunction.     

The clinical features of Sjögren's syndrome in Japanese children

Sjögren's syndrome (SS) is thought to be uncommon in children. An epidemiological study to describe the clinical features distinguishing SS in Japanese children was performed by sending questionnaires to hospitals. A total of 61 cases of SS were reported from 1290 hospitals. The diagnosis of SS was based on histopathological changes and/or sialographic changes in the salivary glands. Forty-two cases had primary SS and 19 were secondary SS with other autoimmune disorders. Fourteen cases (65%) of secondary SS were associated with systemic lupus erythematosus. In primary SS, the initial symptoms were systemic manifestations (fever, exanthema, arthralgia, etc) except for sicca symptoms. In laboratory studies, antinuclear antibodies, elevated serum IgG, rheumatoid factor, anti-Ro/SS-A antibodies and anti-La/SS-B antibodies were frequently observed.