Enhancing Effects of Estrogens on Endometrial Carcinogenesis Initiated by N-Methyl-N-nitrosourea in ICR Mice

The present study was undertaken to examine the effects of estrogens, such as estrone (E₁), 17β-estradiol (E₂) and estriol (E₃), on endometrial Carcinogenesis initiated by N-methyl-N-nitrosourea (MNU) in mice. A total of 120 female ICR mice received MNU solution (1 mg/100 g body wt.) and normal saline at 10 weeks of age into their left and right uterine corpora, respectively. One week later, they were divided into four groups and treated as follows: Group 1 (30 mice) was given 25 ppm E₁-containing diet; Group 2 (30 mice) was fed 5 ppm E₂-containing diet; Group 3 (30 mice) was given 25 ppm E₃-containing diet; and Group 4 (30 mice) was fed the basal diet alone. At the termination of the experiment (Week 30), all surviving animals were autopsied and histopathological examinations revealed that endometrial adenocarcinomas had developed in all groups. The incidence of adenocarcinomas in the MNU-treated uterine corpus in Group 1 (25 ppm E₁-feeding, 9/23, 39%) was significantly higher than that in Group 4 (basal diet, 3/26, 12%, P<0.05). Also, the incidences of adenocarcinomas in the MNU-treated uterine corpus in Groups 2 (5 ppm E₂-feeding, 8/24, 33%) and 3 (25 ppm E₃-feeding, 7/26, 28%) were higher than in Group 4, but the difference was not statistically significant. Feeding of diet containing E₁, E₂ and E₃ increased the incidences of the preneoplastic endometrial lesions (atypical, adenomatous or cystic glandular hyperplasia). In the uterine cervix, small numbers of squmous cell carcinomas, dysplasias or hyperplasias were occasionally found in all groups. These results indicate enhancing effects of the above three types of estrogens on the endometrial carcinogenesis induced by MNU in ICR mice.     

Clinical efficacy of cefpirome sulfate against Bacteroides species, Prevotella species and Porphyromonas species. Society of Anaerobic Bacterial Infections in the fields of obstetrics and gynecology in Gifu

The injectable cephalosporin cefpirome (CPR) was launched in Japan in 1993. It has widely been used in the various infectious diseases. We therefore studied the clinical and bacteriological efficacy of CPR against infections caused by Bacteroides species, Prevotella species and Porphyromonas species frequently isolated from the obstetric and gynecologic infections. Thirteen institutions were involved in this study which ran from March 1994 to January 1999. The administration dosage of CPR was 2 to 4 gram per day administered by drip infusion or intravenous infusion. The duration of treatment was from 3 to 15 days. The evaluations were performed before and after the treatment. CPR was administered to 194 patients with obstetric and gynecologic infections, and 146 of 194 cases were acceptable for the evaluation of drug efficacy. Bacteroides species were identified in 102 patients. Clinical efficacy in 146 cases was excellent in 12 patients, good in 110, fair in 9 and poor in 15 patients. The eradication rate for Bacteroides species could be in 37 cases out of 54 evaluable cases; Prevotella species in 38 out of 49; and Porphyromonas species in 5 out of 5. The overall assessment of bacteriological efficacy was "eradicated" in 91 cases out of 133 (68.4%). Adverse reactions including abnormal findings in laboratory tests were seen in 8 patients (4.76%). Based on these results, CPR promises efficacy and safety in the treatment of obstetric and gynecologic infections due to Bacteroides species.     

Sclerosing hepatic carcinoma: a report of a case treated with a transcatheter arterial embolization

Sclerosing hepatic carcinoma (SHC) is one of the variant primary liver carcinomas and is characterized by intense fibrosis which surrounds slender cords of neoplastic cells. We report on a 53-year-old male patient with SHC describing the radiological findings and clinical course after a transcatheter arterial embolization. To our knowledge, this was only the second reported case of SHC in Japan.     

Hypertrophy of the caudate lobe of the liver demonstrated with single photon emission CT

A case of hypertrophy of the caudate lobe of the liver is reported in which transmission CT scanning strongly suggested the presence of a liver tumor. However, single photon emission CT using Tc-99m phytate showed that there was only caudate lobe enlargement with no evidence of a space-occupying lesion. The usefulness of single photon emission CT in such situations is discussed.     

Gonadotropin-releasing hormone retards doxorubicin-induced apoptosis and serine/threonine phosphatase inhibition in ovarian cancer cells

We recently demonstrated serine/threonine phosphatase (protein phosphatase 2A, PP2A), a crucial enzyme in apoptosis control, within the plasma membrane as well as soluble fraction. This study aimed to determine whether gonadotropin-releasing hormone (GnRH) affects the membrane PP2A-associated apoptosis and the enzyme activity in ovarian cancer cells. PP2A activity was assessed by measuring the dephosphorylation of phosphopeptide highly selective for the PP2A in plasma membranes isolated from ovarian cancer SK-Ov-3 and Caov-3 cells. Apoptosis was quantified by nuclear morphology after staining with Hoechst 33342 and by loss of plasma membrane phospholipid asymmetry using Cy3-conjugated annexin-V. Treatment with doxorubicin (1 microM) for 48 h caused parallel increases in the percentage of cells undergoing apoptosis (71.3+/-5.5% vs. 2.2+/-0.8% for control, P<0.01) and decrease in the membrane-associated PP2A activity (to 38.5+/-8.2% of control, P<0.01). In cells simultaneously incubated with GnRH agonist leuprolide (1 microM) for 48 h, the maximum doxorubicine-induced apoptosis and membrane PP2A inhibition were reduced to 38.4+/-6.2% (P<0.01) and to 82.1+/-7.3% of control (P<0.01), respectively. The GnRH agonist alone caused apoptotic cell death accounting for only 6.8+/-2.1% (P<0.01) and had no effect on membrane PP2A activity. These findings demonstrate that PP2A inhibition is closely coupled to the onset of apoptosis in ovarian cancer cells exposed to doxorubicin. GnRH agonist may protect against the inhibition of membrane-associated PP2A activity and thus retard doxorubicin-induced apoptosis, suggesting an additional activity of GnRH to protect ovarian cancer cells from stimulated apoptotic cell death.     

Regenerating the fibula with beta-tricalcium phosphate minimizes morbidity after fibula resection

The aim of this study was to assess the radiologic and clinical outcome when beta-tricalcium phosphate is used as a bone graft substitute to backfill the fibular defect that is created by harvesting the fibula. Fourteen patients who had fibula resections to be used as bone grafts for bone tumor resections were assessed radiographically. Callus formation bridging the beta-tricalcium phosphate was seen in 12 of 14 patients at an average of 1.4 months after surgery. In these 12 patients the beta-tricalcium phosphate mostly was absorbed and replaced by newly formed bone at an average of 9.3 months after surgery. In all children, beta-tricalcium phosphate was replaced by newly formed bone at an average of 3.2 months after surgery. Only one adult patient had complete regeneration of the fibula. Few patients had continuity between the regenerated fibula and the native fibula. In one patient in whom free vascularized fibula was harvested, regeneration of the fibula was not observed. Clinical functional outcome was not correlated with successful fibula regeneration and union with the native fibula, as determined using radiographs. The results of the study suggest that, in children, regeneration of the fibula by implanting beta-tricalcium phosphate into a bone defect can reduce morbidity of the fibula harvest sites.     

Clinical and pathologic characteristics of dilated cardiomyopathy in hemodialysis patients

BACKGROUND: Some dialysis patients have impaired left ventricular (LV) function without coronary artery disease. The pathologic changes and prognoses of these patients have not been well described. METHODS: We performed LV endomyocardial biopsies on 40 hemodialysis patients with dilated cardiomyopathy (DCM; an ejection fraction <50% and a left ventricular end-diastolic volume index >90 mL/m(2) without coronary artery disease), and on 50 nondialysis patients with idiopathic DCM as the control group. Following LV biopsies, the patients were followed-up for a mean of 3.1 +/- 2.3 years. RESULTS: The pathologic characteristics of the dialysis group were severe myocyte hypertrophy (the mean myocyte diameter across the nucleus: 37.6 +/- 10.5 mum vs. 25.6 +/- 7.7 mum, P= 0.001), myocyte disarray (30%), and extensive fibrosis (the mean percent area of left ventricular fibrosis: 22.3 +/- 18.4% vs. 21.3 +/- 14.6%, P= NS). These pathologic characteristics resembled the dilated phase of hypertrophic cardiomyopathy. In the dialysis group, a high percent area of LV fibrosis was the only significant predictor of cardiac death by multivariate analysis (P= 0.02). The 3-year cumulative event-free survival rate for cardiac death in dialysis patients with severe fibrosis (more than 30%) was 42%, while that for patients without severe fibrosis was 82% (P= 0.03). CONCLUSION: The pathologic characteristics of the heart in dialysis patients with DCM are interstitial fibrosis and severe myocyte hypertrophy with occasional disarray. The extent of LV fibrosis is a strong predictor of cardiac death. Careful follow-up and treatment are necessary for dialysis patients with a high percent area of LV fibrosis.     

Parapapillary choledochoduodenal fistula associated with cholangiocarcinoma

Parapapillary choledochoduodenal fistula is a rare disorder. We herein report a case of parapapillary choledochoduodenal fistula associated with cholangiocarcinoma. A 61-year-old woman was admitted to our hospital for further examination of a liver tumor. She had no clinical symptoms, but computed tomography scans showed an irregularly contoured liver tumor which was histologically confirmed to be adenocarcinoma, by a needle biopsy examination. Duodenal fiberscopy revealed a fistula orifice 1.0cm proximal to the orifice of the papilla of Vater, and endoscopic retrograde cholangiography through the fistula showed a communication to the common bile duct. Hypotonic duodenography demonstrated reflux of contrast material into the choledochoduodenal fistula. The bile sample collected from the common bile duct showed extremely high levels of pancreatic enzymes, including amylase, phospholipase-A2, and elastase-I. Furthermore, Helicobacter DNA was detected in bile by polymerase chain reaction (PCR) analysis. This experience suggests to us that parapapillary choledochoduodenal fistula may be a risk factor for biliary tract carcinoma, and surgical management is the treatment of choice for this rare condition, even when the patient has no significant clinical symptoms.