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.     

Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.     

Multiple primary malignancies in Japanese patients with renal cell carcinoma

AIM: To evaluate the incidence, nature and prognosis of multiple primary malignancies involving renal cell carcinoma (RCC) in Japan. METHODS: Between 1975 and 1998, 319 patients underwent an operation for RCC at Hokkaido University, Sapporo, Japan. The incidence of other primary malignancies was determined and classified as antecedent, synchronous or subsequent. Follow-up was obtained by thorough chart review or telephone interview, and ranged from 0 to 276 months (median 49.0 months). To analyze the influence of other primary malignancies on prognosis, overall and cause-specific survival rates of the patients with an antecedent or synchronous malignancy were compared to the remaining patients. RESULTS: Of the 319 patients there was at least one other malignancy in 38 patients (12%). Four patients had two other malignancies. The other malignancies were antecedent in 13, synchronous in 19 and subsequent in 10 patients. Twenty-two patients had gastrointestinal cancer. In cases of antecedent or synchronous diagnosis of other primary malignancies, RCC was commonly incidental, small or low-stage. Multivariate analysis using Cox's proportional hazards model showed that, for overall survival, the presence of other antecedent or synchronous malignancies was the second most significant prognostic factor, following the pathological stage of RCC. CONCLUSIONS: In Japanese patients with RCC, the incidence of other primary malignancies was not uncommon and these malignancies contributed to the prognosis of these patients. Therefore, the malignant potential of individual tumors should be paid careful attention in the management of these patients.     

Colonoscopic classification of internal hemorrhoids: Usefulness in endoscopic band ligation

Background:  Bleeding is one of the main symptoms of internal hemorrhoids. However, the conventional Goligher's classification of internal hemorrhoids does not consider the severity of bleeding. We intended to establish a useful method for evaluating internal hemorrhoids using a colonoscope that reflected the severity of the symptoms.
Methods:  Using a colonoscope in the retroflexed and forward viewing position, 104 patients with symptomatic internal hemorrhoids were evaluated based on the criteria of range, form and red color signs (RCS). Range was determined by the circumferential distribution of internal hemorrhoids and scaled from 0 to 4. Form was determined by size and scaled from 0 to 2. The presence of RCS was also evaluated. Symptoms were determined by interview and scaled from 0 to 3. Patients were treated by endoscopic band ligation (EBL) and were examined endoscopically before and 4 weeks after the treatment.
Results:  Before the treatment, range, form and RCS were significantly correlated to bleeding ( P <  0.01), and form was significantly correlated to prolapse ( P <  0.05). The endoscopic classification scores at 4 weeks after EBL improved significantly (range from 3.25 ± 0.05–0.56 ± 0.08 [ P <  0.01] and form from 2.81 ± 0.04–0.56 ± 0.07 P <  0.01).
Conclusion:  The new endoscopic classification of internal hemorrhoids proved to be closely correlated to symptoms, particularly bleeding, and thus highly useful in evaluating the effectiveness of the treatment.     

Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy

Hypertrophic cardiomyopathy and dilated cardiomyopathy are two major clinical phenotypes of “idiopathic” cardiomyopathy. Recent molecular genetic analyses have now revealed that “idiopathic” cardiomyopathy is caused by mutations in genes for sarcomere components. We have recently reported several mutations in titin/connectin gene found in patients with hypertrophic cardiomyopathy or dilated cardiomyopathy. A hypertrophic cardiomyopathy-associated titin/connectin mutation (Arg740Leu) was found to increase the binding to actinin, while other dilated cardiomyopathy-associated titin/connectin mutations (Ala743Val and Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We also reported several other mutations in the N2-B region of titin/connectin found in hypertrophic cardiomyopathy and dilated cardiomyopathy. Since the N2-B region expresses only in the heart, it was speculated that functional alterations due to the mutations cause cardiomyopathies. In this study, we investigated the functional changes caused by the N2-B region mutations by using yeast-two-hybrid assays. It was revealed that a hypertrophic cardiomyopathy-associated mutation (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In addition, another TTN mutation (Arg25618Gln) at the is2 region was found in familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B and is2 regions of titin/connectin, these observations suggest that altered recruitment of metabolic enzymes to the sarcomere may play a role in the pathogenesis of cardiomyopathies.     

The Effect of Cimetidine on Natural Killer Activity of Peripheral Blood Lymphocytes of Patients with Ovarian Carcinoma

The effect of cimetidine on the natural killer (NK) activityof peripheral blood lymphocytes (PBL) of 32 patients with ovariancarcinoma was studied before and after surgery or chemotherapy.There was no significant difference in the NK activity betweennormal healthy women and patients who had been disease-freefor more than a year after initial surgery, while those in patientswith a large residual tumor after surgery were profoundly suppressed.Cimetidine stimulated the NK activity in the disease-free patientsin vivo or in Vitro. In addition, cimetidine augmented the responseto phytohemagglutinin of PBL from the disease-free patients.The NK activity of PBL of patients with a large residual tumorunder chemotherapy consisting of cisplatinum, adriamycin andcyclophosphamide, "CAP," was about half of that before initiationof chemotherapy. The inhibition of the NK activity by chemotherapywas abrogated by in vitro exposure of the PBL to cimetidine.     

DETECTION OF ANTIRIBOSOMAL P PROTEIN ANTIBODIES IN PATIENTS WITH SYSTEMIC SCLEROSIS

This study investigated the prevalence and clinical significanceof anti-ribosomal P protein (anti-P) antibodies in patientswith systemic sclerosis (SSc). Serum samples from 150 patientswith SSc were examined by indirect immunofluorescence, ELISAand immunoblotting. Anti-P antibodies were detected in four(3%) patients with SSc. Three of the four patients showed SSc/SLE(systemic lupus erythematosus) overlap syndrome, but psychiatricdisorders were not observed in these patients. By longitudinalimmunoblotting analysis one patient, who was initially diagnosedwith SSc, later developed anti-P antibodies along with clinicalmanifestations of SLE. Our data suggest that anti-P antibodiesare uncommon in SSc and that the presence of anti-P antibodiesin patients with SSc indicates an overlap with SLE. KEY WORDS: Anti-ribosomal P protein antibodies, Systemic sclerosis, Systemic lupus erythematosus