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     

Phagocytosis of heat‐killed Staphylococcus aureus by eosinophils: comparison with neutrophils

Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16‐coated immunomagnetic beads and centrifugation through a Ficoll‐Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti‐FcγRIIa mAb (CD32 mAb), anti‐FcγRIIIb mAb (CD16 mAb), anti‐CR3 (CD11b mAb), or anti‐CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat‐killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2′,7′‐dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat‐inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35).     

Intestinal Absorption of Stable Cyclic Glycylphenylalanine: Comparison with the Linear Form*

The absorption, especially the stability and transportability, of the cyclic peptide cyclic glycylphenylalanine (cyclo(Gly-Phe)) and the linear peptides glycylphenylalanine, glycyl-d -phenylalanine and phenylalanylglycine have been studied in rat small intestine. Linear peptides were degraded on the mucosal side and only glycyl-d -phenylalanine appeared on the serosal side. However, cyclo(Gly-Phe) was stable on the mucosal side and appeared on the serosal side. Furthermore, the absorption clearance of cyclo(Gly-Phe) was higher than that of glycyl-d -phenylalanine. In the presence of the peptidase inhibitor bestatin, the degradation of linear peptides was reduced and linear peptides appeared on the serosal side, but only phenylalanylglycine, which is transported by the oligopeptide transporter, was absorbed faster than cyclo(Gly-Phe). The absorption clearance of cyclo(Gly-Phe) was reduced as its concentration was increased from 125 μm to 500 μm . Furthermore, the absorption clearance of cyclo(Gly-Phe) at 125 μm was reduced at 4°C or in the presence of glycylsarcosine and cephalexin, which are transported by the oligopeptide transporter. These results indicated that cyclo(Gly-Phe) was stable enough to be absorbed and was transported in part by the oligopeptide transporter rather than completely by passive diffusion.     

Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model

BACKGROUND: The objectives of this study were to evaluate the antitumor effects of the simultaneous introduction of interleukin 12 (IL-12) and IL-18 genes into a mouse bladder cancer cell line (MBT2). We intended to compare these with those of either gene alone and to investigate the mechanism of the effects induced by the transfer of IL-12 and/or IL-18 genes in this model system. METHODS: We transfected the IL-12 and/or IL-18 genes into MBT2 cells by the liposome-mediated gene transfer method. We confirmed the secretion of IL-12 and/or IL-18 by enzyme-linked immunosorbent assay. Parental (MBT2/P), IL-12-transfected (MBT2/IL-12), IL-18-transfected (MBT2/IL-18) or both IL-12- and IL-18-transfected (MBT2/Both) cells were subcutaneously or intravenously injected into syngeneic C3H mice. To analyze the mechanism of tumor rejection, these clones were subcutaneously injected into naive nude mice and those depleted with natural killer (NK) cells by antibody. RESULTS: MBT2/IL-12, MBT2/IL-18 and MBT2/Both were completely rejected when they were injected subcutaneously or intravenously into syngeneic mice. However, MBT2/IL-12, but not MBT2/IL-18, could grow in nude mice. Moreover, the antitumor effect of MBT2/IL-18 was partially abrogated when injected into nude mice of which NK cells were depleted by antibody treatment. MBT2/Both was completely rejected in both nude mice with and without NK cells. CONCLUSION: The results of the present study indicate that T cells and NK cells seem to play important roles in the antitumor effects by the secretion of IL-12 and IL-18, respectively, and MBT2/Both possesses both mechanisms.     

Intestinal Absorption of Stable Cyclic Dipeptides by the Oligopeptide Transporter in Rat

Intestinal absorption of four cyclic dipeptides was studied in the everted small intestine of the rat. Cyclic seryltyrosine (cyclo(Ser-Tyr)) was stable enough to be transported whereas linear seryltyrosine was not. The absorption clearance of cyclo(Ser-Tyr) was concentration-dependent, and for cyclo(Ser-Tyr) at 125 μM decreased in the presence of glycylsarcosine (10 mM) or cephalexin (10 mM), which were reported to be absorbed by oligopeptide transporter. The absorption clearance was also reduced at 4°C and in the presence of 1 mM dinitrophenol. Kinetic analysis of cyclo(Ser-Tyr) absorption showed that K_m and V_max were 19.8 μM and 0.295 nmol min^?1 cm^?1, respectively. It was also suggested that cyclic aspartylphenylalanine and cyclic histidylphenylalanine were absorbed by oligopeptide transporters, but cyclic histidylproline was not. The absorption clearance of cyclo(Ser-Tyr) in the control was much higher than the value of the correlation line representing a plot of passive transport (which was obtained from the absorption clearance of cyclic peptides in the presence of glycylsarcosine (10 mM)) against hydrophobicity (oil-water partition coefficient). These results indicate that cyclo(Ser-Tyr) is absorbed by the oligopeptide transporter.     

Case of Spontaneous Gastrojejunal Fistula Due to Gastric Cancer

A rare case of gastrojejunul fistula secondary to gastric cancer is presented. Fluoroscopic examination visualized the passage of contrast medium from the stomach to the small intestine. Gastric fiberscopy revealed cancer on the greater curvature of the corpus perforation into the jejunum. The scope could be inserted readily into jejunum through this perforation. Laparotomy showed that the cancer infiltrated and perforated from the stomach to the jejunum at about 10 cm. from the ligament of Treitz. Distal gastrectomy and resection of 10 cm. of the perforated jejunum were performed. The resected specimen revealed a Borrmann III gastric cancer of the greater curvature perforating the jejunum.     

Serum Complement Levels in Uterine Cervical Cancer Patients and Their Relationship to Cell-Mediated Immunity

C3 and C4 concentrations in the serum of uterine cervical cancerpatients and healthy controls were determined and their relationshipto other immunological parameters was studied. Complement levelsin cancer patients were significantly higher than those in thehealthy controls. However, complement levels in cancer patientsin Stage IV were almost the same as those in the controls. Therewas a significant correlation between complement levels andlymphotoxin activity of the lymphocytes. Although lymphocyteresponse to phytohemagglutinin was depressed, elevated complementlevels were maintained in cancer patients in Stages I, II andIII.