Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.     

ALCOHOL-RELATED SUDDEN DEATH WITH HEPATIC FATTY METAMORPHOSIS: A COMPREHENSIVE CLINICOPATHOLOGICAL INQUIRY INTO ITS PATHOGENESIS

To clarify the pathogenesis of the widely known but obscuresyndrome of sudden death with hepatic fatty metamorphosis observedin alcohol abusers, we have scrutinized both the clinical andpathological data of 11 subjects who died under such circumstancesbetween 1987 and 1993. Death followed several days of uninterrupteddrinking often with little dietary intake. The notable clinicalfeatures on arrival at the emergency room were disturbance ofconsciousness (11/11), hypotension (47/6), hypothermia (3/5),hypoglycaemia (8/11), metabolic acidosis (6/6), renal dysfunction(11/11), and hyperammonaemia (5/5). The common hepatic pathologywas the extensive appearance of numerous microvesicular fattydroplets in the hepatocytes together with varying degrees ofmacrovesicular fatty change; four subjects had an underlyingcirrhosis. Death undoubtedly results from a variety of metabolicdisturbances triggered by the combination of massive ethanolintake and starvation. The appearance of extensive microvesicularfatty change superimposed on macrovesicular fatty change wasconsidered to be an associated phenomenon     

The effect of indomethacin on cerebral blood flow and oxygen consumption in the rat at normal and increased carbon dioxide tensions

The effect of the fatty acid cyclo-oxygenase inhibitor indomethacin on cerebral blood flow (CBF) and the metabolic rate for oxygen (CMRO₂) was studied in paralyzed and artificially ventilated rats. In normocapnic animals, the drug (10 mg·kg^-1i. v.) reduced CBF to 50% of control without a measurable effect on CMRO₂. During hypercapnia (Pa_CO2 70–80 mmHg) the increase in CBF was reduced by about 80% but CMRO₂ remained unchanged. Autoradiographic evaluation of local CBF in 20 brain structures indicated that the reduction in CBF was relatively uniform throughout the brain. Dose response curves showed that an effect on CBF was evident already at an indomethacin dose of 1 mg·kg^-1 and maximal effects were obtained with 3–5 mg·kg^-1. Following i. v. injection of the drug reduction in CBF was observed already after 10 s and the full response occurred after 1–2 min. It is concluded that metabolites of arachidonic acid, possibly mainly prostacyclin, are powerful modulators of normal cerebrovascular tone, and help to mediate the CBF response to increased CO₂ tensions. However, since indomethacin does not modify the circulatory response in other conditions with increased CBF these substances do not qualify as general coupling factors controlling CBF in physiological or pathological states.     

Serum erythropoietin levels for predicting bone marrow recovery following chemotherapy in leukaemia

Summary To investigate whether serum erythropoietin (EPO) levels are influenced by the intensity of bone marrow erythroid activity, we used a radioimmunoassay (Nippon DPC Co., Japan) to study EPO levels in three acute leukaemia patients during treatment with intensive chemotherapy. We also measured the reticulocyte count and reticulocyte maturity using an automated reticulocyte analyser (Sysmex R-2000) to detect erythropoietic activity. From the day after the initiation of chemotherapy, EPO levels increased markedly without any change in Hb levels, suggesting that some other mechanism was regulating serum EPO. A decrease in EPO after chemotherapy was accompanied by an increase in high fluorescence ratio, an index of immature reticulocvtes, but the actual increase in the reticulocyte count was delayed for 3-4 days after this. These findings suggest that the decrease in serum EPO levels was closely related to the early stage of red cell production and that EPO levels may be a useful marker for the recovery of erythropoietic activity after chemotherapy.     

Sufficient prophylactic efficacy with minor adverse effects by intravesical instillation of low-dose bacillus Calmette-Guérin for superficial bladder cancer recurrence

BACKGROUND: Intravesical instillation of bacillus Calmette-Guérin (BCG) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence. Adverse effects of BCG are major obstacles, but the reduction of BCG dose could minimize these effects. The efficacy and adverse effects of half-dose (40 mg) BCG, Tokyo 172 strain, were prospectively evaluated. METHODS: A total of 93 patients with superficial bladder cancer (pTa or pT1) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection. BCG was administered weekly for 6 weeks postoperatively. Eighty patients observed longer than 12 months after BCG therapy (41, 40 mg group; 39, 80 mg group) were analyzed. RESULTS: BCG therapy course was completed in 71 patients. Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group. There was no significant difference in tumor recurrence rate between the two groups (P = 0.547). BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects. The morbidity of BCG-related toxicity was significantly higher in the 80 mg group. CONCLUSION: Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was significantly lower compared to the standard dose. Thus, half-dose of this strain might be suitable, at least for initial BCG therapy, for the prophylaxis of bladder cancer recurrence. Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients.     

Efficacy and morbidity of transrectal ultrasound-guided 12-core biopsy for detection of prostate cancer in Japanese men

BACKGROUND: The objectives of the present study were to determine whether an extensive biopsy scheme contributes to enhanced detection of prostate cancer in Japanese men and to assess the associated pain and morbidity. METHODS: A total of 147 patients were included in this analysis, with 12 biopsy cores being obtained from each patient. Standard systematic sextant biopsy at the apex, mid-prostate and base of the prostate gland was carried out under local anesthesia and this was followed by the acquisition of additional sextant cores at the same levels from the far lateral peripheral zone. Each patient answered a self-administered questionnaire on pain and morbidity during the 5 days following biopsy. RESULTS: Overall, 39 patients (26.5%) received a diagnosis of prostate cancer. Nine patients (23.1%) were positive only at the standard sextant sites, three patients (7.7%) were positive exclusively at the far lateral sites and the remaining 27 patients (69.2%) were positive at both sites. Cancer was found most frequently in cores obtained from the apex (P = 0.009), with this trend being more evident in patients with abnormal rectal findings, positive sonographic findings, gland volume < 40 cm(3) and prostate-specific antigen density > 0.15 ng/mL/cm(3) (P < 0.03). These findings were also true for those with a prostate-specific antigen range from 4.1 to 20.0 ng/mL. A gradual decrease in incidence and grade of pain, hematuria and rectal bleeding was observed during the first 5 days after biopsy (P < 0.0001). CONCLUSIONS: Using this 12-core biopsy scheme, we found cancer most frequently in cores taken at the level of the apex. While the extensive procedure only marginally enhanced overall detection of prostate cancer, it was well tolerated with gradually decreasing pain and morbidity over a brief postbiopsy period. Further efforts to optimize biopsy schemes are warranted.     

Proliferative activity and genetic changes in adrenal cortical tumors examined by flow cytometry, fluorescence in situ hybridization and immunohistochemistry

BACKGROUND: To determine differences in biological features among different adrenal tumors, we investigated the DNA ploidy, numerical chromosomal aberration and proliferative activity in human adrenal cortical neoplasms. METHODS: Our study included six adrenal cortical adenomas with Cushing syndrome, 12 adenomas with hyperaldosteronism, three non-functioning adenomas and three adrenal cortical carcinomas. Isolated nuclei from frozen samples were used for fluorescence in situ hybridization (FISH) analysis, and formalin-fixed, paraffin-embedded tissues from the same materials were analyzed using flow cytometry (FCM) for DNA ploidy. Sections from paraffin blocks were stained immunohistochemically with antibodies against Ki-67 and p53. For FISH analysis, we used an alpha-centromeric enumeration probe for chromosome 17. RESULTS: The mean Ki-67 labeling index (LI) of adrenal cortical carcinomas was markedly higher than that of adrenal cortical adenomas (209.4 vs 8.7). In functional adrenal cortical adenomas, the LI was significantly lower in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004), although FCM results indicated that tetraploid patterns were more frequently observed in the former type. Tumor size was significantly smaller in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004). Chromosome 17 showed disomy in all adrenal cortical adenomas, whereas chromosome 17 abnormalities were found in two of three adrenal cortical carcinomas. Only the latter two cases strongly expressed p53 protein. CONCLUSIONS: Our study characterized various biological features of benign and malignant adrenal cortical tumors. The use of a combination of markers might provide additional information to assist our understanding of the clinical behavior of an individual adrenal cortical tumor.     

Clinical significance of red blood cell distribution width in the elderly: a potential indicator of bone marrow stimulation by erythropoietin

Summary To investigate the clinical significance of red blood cell distribution width (RDW) and haemoglobin distribution width (HDW) in the elderly and their relationships with erythropoietin (EPO) secretion, we measured red cells parameters using a Technicon HI system and serum EPO using a radioimmunoassay in 247 elderly subjects (normal: n= 150; preanaemic iron deficiency: n= 24; iron deficiency anaemia: n= 8; senile anaemia: n= 65). RDW was slightly higher in the elderly subjects with preanaemic iron deficiency (14.1 ± 1.1%) than in the normal elderly subjects (13.5±0.7%). It was highest in iron deficiency anaemia (16.1 ± 1.3%), while the increase in senile anaemia was limited (13.9 ± 1.2%). The HDW increased only in iron deficiency anaemia. There was a strong positive relationship between EPO and RDW in iron deficiency anaemia (r= 0.817, P<0.01). Moreover, this correlation was also found in preanaemic iron deficiency (r= 0.456, P < 0.05), but not in senile anaemia, suggesting that bone marrow hypoactivity may partly play a role in the pathogenesis of senile anaemia. All the eight subjects with iron deficiency anaemia had a RDW ≥ 14.9% (mean + 2SD of normal subjects), while 55 (85%) of the 65 with senile anaemia had a RDW < 14.9%. Both the RDW and EPO levels of six anaemic subjects with high RDW values (≥ 14.9%) after oral iron therapy for 56–78 days decreased significantly. Our results suggest that RDW is useful to distinguish iron deficiency anaemia from senile anaemia, and may be a potential parameter of bone marrow stimulation by EPO.     

Haemophagocytic lymphohistiocytosis in association with granular lymphocyte proliferative disorders in early childhood: characteristic bone marrow morphology

Five paediatric cases of haemophagocytic lymphohistiocytosis (HLH) which showed proliferation of granular atypical lymphocytoid cells in bone marrow are reported. All cases were girls aged 8 months to 4 years who had marked hepatosplenomegaly. Marker analysis on peripheral blood mononuclear cells revealed an increase in the CD3⁺HLADR⁺ subset in three cases and the CD³⁻CD56⁺ subset in one case. An Epstein-Barr virus genome was detected in three cases, and monoclonality was confirmed in two cases. A characteristic morphology of large granular lymphocytes (LGL) was identified, with elongated bizarre features that resembled horsetail-, tadpole-, cucumber- or shooting star-type configurations on the bone marrow smear. Serum concentrations of soluble interleukin-2 receptor and interferon-gamma were elevated in all cases. All five cases required multi-agent chemotherapy which resulted in two complete remissions, two partial remissions and one no response. Refinement of treatment is required for these paediatric GLPD cases which probably comprise a specific high-risk subgroup among secondary HLH patients which had previously escaped notice.