Hormonal function after ovarian transposition to the abdominal subcutaneous fat tissue.

We previously reported a new technique for ovarian transposition to the abdominal subcutaneous fat tissue (OTAFT) following hysterectomy. The purpose of this study is to assess the hormonal function after OTAFT. From 1993 to 2000, OTAFT was performed in 27 patients (group A). Forty-two women underwent hysterectomy and retained ovaries without transposition (group B). In 19 cases, bilateral oophorectomy with hysterectomy was performed, and they received a hormone replacement therapy (HRT) (group C). Serum follicle-stimulating hormone (FSH) level of patients was monitored every 2-12 months, and the time of menopause (defined as FSH >40 mIU/mL two times consecutively) was determined in groups A and B. After a median follow-up of 65 months, cumulative ovarian survival did not show significant difference between group A and group B (HR = 0.52, 95% CI = 0.17-1.16; P= 0.10). In patients who were 40 years old or younger, ovarian function declined significantly in group A compared to group B (HR = 0.29, 95% CI = 0.02-0.91; P= 0.04). However, FSH level of postmenopausal patients in group A was not different from FSH level of patients in group C, but FSH level of postmenopausal patients in group B was significantly higher than FSH level of patients in group C (P= 0.002). Although the procedure of OTAFT may somewhat affect the ovarian function, the transposed ovary in postmenopausal women presumably still secrete a small amount of estrogen which is equivalent to an estrogen level by HRT.

Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study.

The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naïve or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status

Preliminary toxicity analysis of intraperitoneal carboplatin in combination with intravenous paclitaxel chemotherapy for patients with carcinoma of the ovary, peritoneum, or fallopian tube.

The objective of this study was to provide preliminary toxicity data of multiple-cycle combination chemotherapy with intraperitoneal (IP) carboplatin and intravenous (IV) paclitaxel for further clinical trials. The toxicity data of 42 patients with mullerian carcinoma who underwent IP carboplatin therapy in combination with IV paclitaxel were retrospectively analyzed. Chemotherapy was repeated through the Bard IP port placed at initial surgery using IV paclitaxel at 175 mg/m2 followed by IP carboplatin. The doses of carboplatin were either at area under the curve (AUC) = 5, 6, 6.5, 7, or 7.5. The toxicity data in a total of 237 cycles were analyzed. The median number of cycles for IP chemotherapy was 6 (range: 3-12). The incidences of maximal grade toxicities in all cycles were: grade (G)2/3 nausea/vomiting, 23.8%; G2/3 constipation, 42.9%; G2 abdominal pain, 28.6%; G2/3 sensory neuropathy, 14.3%; motor neuropathy, 4.8%; myalgia/arthralgia 33.4%; G3/4 neutrocytopenia, 85.4%; and G3/4 anemia, 35.4%. These were not related to the dose of carboplatin. The incidences of G3 thrombocytopenia in relation to the dose of carboplatin were AUC = 5, 0%; 6, 31.6%; 6.5, 44.4%; 7, 25.0%; and 7.5, 80%. G4 thrombocytopenia did not occur. A dose of carboplatin between AUC = 6 and 7 with IV paclitaxel at 175 mg/m2 is warranted for further evaluation.

Paclitaxel inhibits expression of heat shock protein 27 in ovarian and uterine cancer cells.

The purpose of the study was to determine whether paclitaxel inhibits the expression of heat shock protein 27 (HSP27) in two gynecologic cancer cell lines compared with other antineoplastic agents having different cytotoxic mechanisms. BG-1 ovarian cancer cells and HeLa uterine cancer cells were treated with a tubulin depolymerization inhibitor (paclitaxel), a topoisomerase-II inhibitor (etoposide), and two tubulin polymerization inhibitors (colcemid and vincristine). Cell kills were evaluated by counting the number of cells. Propidium iodide staining and flow cytometric analysis were applied for the determination of cell-cycle perturbation. HSP27 was stained by the indirect immunofluorescence technique and analyzed with a flow cytometer. In both BG-1 and HeLa cells, growth arrest and G2 / M accumulation were dependent on the dose of each cytotoxic agent. There were positive correlations between HSP27 overexpression and growth arrest and G2 / M accumulation when the cell lines were treated with etoposide, colcemid, or vincristine, but not with paclitaxel. Paclitaxel completely inhibited the expression of HSP27. The results of this study indicated that paclitaxel may possess unique mechanisms able to overcome drug resistance by inhibiting HSP27 expression.

Effect of simple omentoplasty and omentopexy in the prevention of complications after pelvic lymphadenectomy.

This multicenter collaborative study prospectively evaluated the effect of omentoplasty and omentopexy on the prevention of complications after pelvic lymphadenectomy. Sixty-four consecutive patients (42 cervical and 22 endometrial cancer) were enrolled and examined periodically for 12 months. All patients underwent simple, semiradical, or Okabayashi's radical hysterectomy and complete pelvic lymphadenectomy. The infracolic omentum was longitudinally divided in half and omentoplasty was performed so that bilateral omental flaps would reach the pelvic floor. The omental flaps were inserted into the retroperitoneal space and the edges of the flaps were sutured to the psoas muscle. The omental flap was then covered by the peritoneum. Incidence of lymphocele, lymphedema, and severe complications associated with lymphocele, such as infection or urinary stenosis, was evaluated at intervals for at least one year after surgery. Among the 64 patients, 12 patients received pelvic radiation because of occult lymph node metastasis. Planned omentoplasty was not possible in one patient because her omentum was too small; therefore, only unilateral omentopexy was performed. Asymptomatic lymphoceles only were detected by ultrasonogram in 12 patients (18.8%). Three patients (4.7%) had a symptomatic but pressure-only lymphocele. Hydronephrosis and bladder compression probably due to lymphocele were observed in one patient, respectively (3.1%), but resolved within 6 months. Lymphedema was observed in seven patients (10.9%) and persisted for more than 6 months in two patients (3.1%). We conclude that this simple technique of omentoplasty and omentopexy appeared to be effective in reducing the incidence of complications after pelvic lymphadenectomy.

Local radiation therapy for localized relapsed or refractory ovarian cancer patients with or without symptoms after chemotherapy.

The purpose of this paper is to prospectively evaluate the effects of local radiation therapy upon localized ovarian cancer following chemotherapy. Patients with objective relapses or refractory disease but with localized epithelial ovarian cancers and who had undergone at least one regimen of chemotherapy were enrolled in this study. External irradiation was performed on all patients. Twenty patients, with a mean age of 53.8 +/- 10.3 y, were enrolled in this study. The median number of previous chemotherapies was 2. The interval between previous chemotherapy and radiation therapy was 4.5 months. The maximum diameter of the lesions was 3.6 +/- 1.8 cm. The irradiation dose was 52.3 +/- 8.3 Gy. Neither hematologic nor intestinal toxicity >grade 3 was observed. Forty-four disease sites, including the lymph nodes, vaginal cuff, pelvis, abdomen, subcutaneous regions, and the brain were irradiated. Thirty of these sites were symptom-free before irradiation. In patients with symptoms, the symptomatic relief was obtained in approximately 50% of patients. Smaller lesions (P = 0.024) and lymph nodes (P = 0.042) demonstrated better responses than larger lesions or other sites, respectively. Regression rates correlated with longer survivals (P = 0.0195) after radiation therapy. Survival was significantly better when radiation therapy was given before patients had symptoms (P = 0.001). Survival was also better in patients with lymph node disease only (P = 0.0069). We conclude that local radiation therapy may be one of the treatment options for relapsed or refractory but localized ovarian cancer, particularly when the tumor is small and/or located in the lymph nodes, even when patients had no symptoms.

Successfully treated unstable angina pectoris in a young Japanese female.

A 25-year-old Japanese female complaining chest oppression and palpitation was admitted to hospital under the presumptive diagnosis of ischemic heart disease (IHD), although no obvious underlying disease associated with IHD was detected. Coronary angiography showed stenosis at the proximal site of left anterior descending artery (LAD), with dilatation and tortuosity at the bifurcation of the first and the second septal branches. Intravascular ultrasound imaging of the LAD showed intimal thickness without calcification at the site of stenosis. The stenosis was successfully and smoothly dilated by percutaneous transluminal angioplasty. Even with precise evaluation, the cause of the coronary artery disease in this young female patient was not clarified. Further careful follow-up is needed.

Expression of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase in early concepti.

Indoleamine 2,3-dioxygenase (IDO)-initiated tryptophan degradation in the placenta has been implicated in the prevention of the allogeneic fetus rejection [Munn, Zhou, Attwood, Bondarev, Conway, Marshall, Brown, and Mellor (1998) Science 281, 1191-1193]. To determine how IDO is associated with the development of the fetus and placenta, the time course of IDO expression (tryptophan-degrading activity, IDO protein and IDO mRNA) in the embryonic and extra-embryonic tissues as well as maternal tissues of mice was examined. A high tryptophan-degrading activity was detected in early concepti on days 6.5 and 7.5, whereas IDO protein and its mRNA were not expressed during early gestation, but appeared 2-3 days later, lasted for about 3 days and declined rapidly thereafter. The expression of IDO basically coincided with the formation of the placenta. On the contrary, the early tryptophan-degrading activity was due to gene expression of tryptophan 2,3-dioxygenase (TDO), as shown by Northern and Western analysis. These findings indicate that IDO is transiently expressed in the placenta but that the expression does not last until birth, and that the IDO expression is preceded by expression of another tryptophan-degrading enzyme, TDO, in the maternal and/or embryonic tissues in early concepti.

Florid endocervical glandular hyperplasia with pyloric gland metaplasia: a radiologic pitfall.

A case of florid endocervical glandular hyperplasia with pyloric gland metaplasia is described. MR images showed multiple and conjugated cysts in the uterine cervix, which suggested adenoma malignum. A postoperative examination revealed florid but definitely benign endocervical glandular hyperplasia. Hitherto described radiologic features considered suggestive of adenoma malignum are not necessarily specific and can be a diagnostic pitfall.

The platelet-sparing effect of paclitaxel is not related to changes in the pharmacokinetics of carboplatin.

PURPOSE: To determine whether the platelet-sparing effect of paclitaxel is related to changes in pharmacology of carboplatin. METHODS: A group of 32 patients with epithelial ovarian cancer were treated with intraperitoneal (i.p.) carboplatin-based chemotherapy with carboplatin alone or in combination with cyclophosphamide or paclitaxel, and the relationship between the pharmacology of serum platinum and thrombocytopenia was examined. The target AUC of i.p. carboplatin was 6.5 mg min/ml. Cyclophosphamide was administered intravenously at 400 mg/m2 after i.p. carboplatin and paclitaxel at 175 mg/m2 was given before i.p. carboplatin. RESULTS: Ten patients received i.p. carboplatin alone, 10 received cyclophosphamide and 12 received paclitaxel. The ages of the patients, body surface area, serum creatinine, platelet count before chemotherapy, and the total dose of carboplatin in each patient were similar in all groups. The measured AUC, Cmax, T 1/2, and MRT were similar in these groups. The nadir platelet counts were significantly higher (P = 0.0018) in patients treated with i.p. carboplatin with paclitaxel (12.1 +/- 4.3 x 10(4)/mm3) compared with carboplatin alone (5.2 +/- 3.3 x 10(4)/mm3) or with cyclophosphamide (5.2 +/- 4.8 x 10(4)/mm3). The percentage decrease in platelet counts was significantly lower (62.5 +/- 18.2%) in patients treated with paclitaxel than in the other two groups (81.5 +/- 12.6% carboplatin alone, 88.7 +/- 7.9% with cyclophosphamide). CONCLUSION: The addition of paclitaxel or cyclophosphamide to i.p. carboplatin did not alter the pharmacology of serum platinum. Thrombocytopenia was significantly less in patients treated with carboplatin in combination with paclitaxel. The platelet-sparing effect of paclitaxel is not related to changes in the pharmacology of carboplatin.

Negative MRI findings with invasive cervical biopsy may indicate stage IA cervical carcinoma.

OBJECTIVE: We attempted to prospectively determine the role of magnetic resonance imaging (MRI) in very early cervical cancer. STUDY DESIGN: T2-weighted and T1-dynamic enhanced images from patients with invasive or noninvasive lesions of the cervix were reviewed by two radiologists who had no clinical information on these patients. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. RESULTS: Seventy-nine cases were entered into the study and 75 were evaluable. Accuracy of T2 MR images for invasive and noninvasive disease by Radiologist 1 and Radiologist 2 was 0.8533 and 0.7733, respectively. Accuracy was greater (0.9867 and 0.9467, respectively) for the detection of noninvasive plus microinvasive lesions 5 mm. Dynamic technique provided only limited additional value in the detection of microinvasive cervical carcinoma. CONCLUSION: Simple T2 MRI is useful in differentiating noninvasive or microinvasive cervical lesions from invasive cervical carcinoma of the cervix >5 mm.

Pregnancy in a woman with a Y chromosome after removal of an ovarian dysgerminoma.

BACKGROUND: It appears to be a general belief that pregnancy might be impossible in women with the XY karyotype. Therefore, it is recommended that patients with dysgerminoma of the ovary associated with the XY karyotype should undergo a bilateral salpingo-oophorectomy. CASE: We report an extremely rare case of a true hermaphrodite with a 20% 46,XX/80% 46,XY karyotype who became pregnant after removal of an ovarian dysgerminoma. The patient had a completely normal female phenotype. A dysgerminoma with ovotestis was found in the right ovary. Two courses of chemotherapy following a right salpingo-oophorectomy were carried out. Nine months later she became pregnant and delivered a healthy male infant. CONCLUSION: A unilateral salpingo-oophorectomy followed by combination chemotherapy can be the treatment of choice for any woman who wishes to preserve her capacity for conception at the time of operation for dysgerminoma of the ovary.

Highly increased plasma concentrations of the nicked form of beta(2) glycoprotein I in patients with leukemia and with lupus anticoagulant: measurement with a monoclonal antibody specific for a nicked form of domain V.

beta(2)-Glycoprotein I (beta(2)GPI) consists of five tandem repeated domains (I, II, III, IV, and V). The nicked form of beta(2)GPI (N-beta(2)GPI ) which was cleaved by plasmin in vitro at Lys 317-Thr 318 in domain V, showed reduced affinity for the negatively charged phospholipids, especially cardiolipin (CL). Recently, the N-beta(2)GPI was detected in the plasma of patients with disseminated intravascular coagulation syndrome (DIC) by an immunological method. In the present study, we prepared monoclonal antibodies for the nicked form, and demonstrated that the concentrations of this form of beta(2)GPI, which were analyzed by a sandwich ELISA using two specially prepared monoclonal antibodies, were significantly increased in the plasma of patients with leukemia (n = 51, mean +/- SD: 162.0 +/- 118.3 ng/ml) and with lupus anticoagulant (LA) (n =40, mean +/- SD: 3,041.5 +/- 16,579.7 ng/ml), compared to the normals (n = 33, mean +/- SD: 1.04 +/- 1.54 ng/ml). We found a significant correlation between the concentrations of N-beta(2)GPI and those of typical molecular markers for a fibrinolytic state such as plasmin-alpha(2) plasmin inhibitor complex (PIC) and D-dimer in patients with leukemia, but not in patients with LA. These results suggested that the generation of N-beta(2)GPI was caused by plasmin in the patients with leukemia, and by unknown proteases in the patients with LA. In the patients with LA, the levels of N-beta(2)GPI tended to be higher in those without thrombosis than in those with thrombosis.

Improvement of exercise tolerance by single lead VDD pacemaker: evaluation using cardiopulmonary exercise test.

We used a cardiopulmonary test to assess the physiological benefit of single lead VDD pacing in ten patients (six men, four women; aged 32-84 years, mean 69 years) with atrioventricular block. Maximal symptom-limited treadmill exercise test using a ramp protocol was performed under VDD and VVIR or VVI pacing (VVI) in random sequence. The pacemaker was then programmed to the VDD mode, and Holter ECG was recorded in nine patients. Compared with findings during the VVI, the VDD mode had a greater chronotropic response (mean maximal heart rate, VDD 106 +/- 17 beats/min vs VVI 79 +/- 19 beats/min, P = 0.03), and was associated with prolongation of exercise duration (VDD 11.2 +/- 2.9 minute vs VVI 10.5 +/- 3.1 minute; P = 0.01), and the onset of anaerobic threshold at a higher oxygen uptake (VDD 12.4 +/- 3.4 mL/min per kilogram vs VVI 10.0 +/- 2.1 mL/min per kilogram; P < 0.01). Atrial sensing was recognized in almost all normal sinus P waves for all cases examined using Holter ECG. Thus, chronotropic response during exercise by VDD pacemaker improved exercise tolerance, indicating that a VDD pacemaker might be useful for patients requiring physical activity.

Cardiac arrhythmias and left ventricular hypertrophy in dipper and nondipper patients with essential hypertension.

To evaluate the behavior of cardiac arrhythmias in dipper and nondipper hypertensive patients, 48-h ambulatory blood pressure monitoring, 24-h Holter electrocardiogram recording and echocardiographic studies were performed in 56 untreated outpatients with essential hypertension. These patients were divided into 2 groups according to the presence (dipper, n=33) or absence (nondipper, n=23) of reduction of both systolic and diastolic blood pressure during nighttime by an average of more than 10% of daytime blood pressure. Mean 48-h systolic and diastolic blood pressures did not differ between the 2 groups. Nondipper patients had a significantly larger left atrial dimension (31.9+/-3.8 vs 35.6+/-3.7 mm; p<0.01), left ventricular mass index (114+/-26 vs 136+/-36 g/m2; p<0.05), as well as a larger number of total supraventricular (16+/-19 vs 89+/-197 beats; p<0.05) and ventricular ectopic beats (7+/-14 vs 47+/-96 beats; p<0.05) during daytime as compared with dippers. In conclusion, nondipper hypertensive patients are likely to experience supraventricular and ventricular arrhythmias more frequently than dippers. A blunted nocturnal blood pressure fall may be involved in the appearance of cardiac arrhythmias in patients with essential hypertension.

Hypertrophic cardiomyopathy complicated with cardiac amyloidosis.

The echocardiographic findings of hypertrophic cardiomyopathy (HCM) are very similar to those of cardiac amyloidosis. A 76-year-old Japanese man was admitted for treatment of early stage gastric cancer in July 1996. His electrocardiogram indicated left ventricular hypertrophy and echocardiography showed left ventricular hypertrophy with asymmetric septal hypertrophy. He was re-admitted complaining of dyspnea on effort and pretibial edema in October 1998. The amplitude of QRS complex on electrocardiogram was decreased. Echocardiogram showed left ventricular wall thickening with granular sparkling. He was diagnosed as HCM with cardiac amyloidosis.

Role of magnetic resonance imaging (MRI) in early cervical cancer.

The aim of this study was to prospectively determine if invasive carcinoma of the cervix can be ruled out by negative magnetic resonance image (MRI) findings. Eligible patients were those who were scheduled to undergo either hysterectomy or conization because of invasive or non-invasive lesions of the cervix. T2-weighted and T1-dynamic enhancement images were reviewed by two radiologists who had no information on these patients except for the preoperative diagnosis. Clinical information regarding location of the disease was not given. At least 12 longitudinal sections prepared from the surgically removed cervix were reviewed by a pathologist who was not provided with MRI information. The correlation between MRI and histological findings was analyzed in terms of depth of invasion. Seventy cases were entered and 66 were evaluable. Sensitivities of T2 and dynamic MRI for invasive and non-invasive disease by radiologist 1 were 0.8824 and 0.8235, respectively, and those by radiologist 2 were 0.6296 and 0.7647, respectively. Specificities were 0.8776 and 0.8571, respectively, for radiologist 1 and 0.8974 and 0.8367, respectively, for radiologist 2. When sensitivities and specificities were calculated for prediction of non-invasive plus microinvasive lesions < or = 5 mm vs. invasive lesions > 5 mm, specificities of T2 and dynamic MRI became 1.0000 for both radiologists. Negative findings on T2 and/or dynamic MRI indicated non-invasive or early invasive cervical diseases < or = 5 mm. The dynamic technique provided only limited additional value in the detection of early invasive cervical carcinoma.

Pathological findings of the isthmus between the inferior vena cava and tricuspid annulus ablated by radiofrequency application.

Anatomically guided radiofrequency ablation for the treatment of atrial flutter was performed in a 41-year-old man with interstitial pneumonia. He died of respiratory failure 2 months after ablation, and an autopsy was performed. The whole layer of the ablation site showed a transluminal fibrosis.