Feasibility and efficacy of intraperitoneal docetaxel administration as salvage chemotherapy for malignant gynaecological ascites.

Ovarian and endometrial cancers diagnosed at advanced stages are often associated with malignant ascites. This study aimed to determine the safety, feasibility and efficacy of intraperitoneal (IP) docetaxel (TXT) for the treatment of ascites. A phase I study, including nine patients, was undertaken to determine the maximum tolerable dose. Efficacy was retrospectively assessed in 18 patients treated with 40-70 mg/m(2) IP TXT between 2005 and 2012. In a phase I study, the dose was safely escalated to a maximum of 70 mg/m(2), at which level no patients had grade -3 haematological adverse events. In a retrospective study of 18 patients, seven had an Eastern Cooperative Oncology Group performance status of 3; 16 had prior paclitaxel administration and two, with doses of 40 and 70 mg/m(2), experienced a serological response and a decrease in paracentesis. Thus, palliative treatment of recurrent OC should be further studied with 40 mg/m(2) among more patients, and 70 mg/m(2) could be evaluated for first-line IP chemotherapy.

The 15-Country Collaborative Study of Cancer Risk Among Radiation Workers in the Nuclear Industry: design, epidemiological methods and descriptive results.

Radiation protection standards are based mainly on risk estimates from studies of atomic bomb survivors in Japan. The validity of extrapolations from the relatively high-dose acute exposures in this population to the low-dose, protracted or fractionated environmental and occupational exposures of primary public health concern has long been the subject of controversy. A collaborative retrospective cohort study was conducted to provide direct estimates of cancer risk after low-dose protracted exposures. The study included nearly 600,000 workers employed in 154 facilities in 15 countries. This paper describes the design, methods and results of descriptive analyses of the study. The main analyses included 407,391 nuclear industry workers employed for at least 1 year in a participating facility who were monitored individually for external radiation exposure and whose doses resulted predominantly from exposure to higher-energy photon radiation. The total duration of follow-up was 5,192,710 person-years. There were 24,158 deaths from all causes, including 6,734 deaths from cancer. The total collective dose was 7,892 Sv. The overall average cumulative recorded dose was 19.4 mSv. A strong healthy worker effect was observed in most countries. This study provides the largest body of direct evidence to date on the effects of low-dose protracted exposures to external photon radiation.

[Transapical aortic cannulation in the operation of acute type A aortic dissection].

From June 2003 to November 2006, transapical aortic cannulation was performed in 73 patients (41 men and 32 women, mean age 63 years, 64 hemiarch repair and 9 total arch replacement) with acute type A aortic dissection. A 1-cm incision was made in the apex of the left ventricle, and a 7-mm soft and flexible cannula was passed through the apex and across the aortic valve until positioned in the ascending aorta under guidance by transesophageal echocardiography. In all cases, cardiopulmonary bypass flow was sufficient. There were no malperfusion events. Our results showed that transapical aortic cannulation was secure and useful for repair of acute type A aortic dissection.

Increasing incidence of hepatocellular carcinoma possibly associated with non-A, non-B hepatitis in Japan, disclosed by hepatitis B virus DNA analysis of surgically resected cases.

At the National Cancer Center Hospital in Japan, the total number of surgically treated hepatocellular carcinomas (HCCs) has been increasing steadily and rapidly over the last 10 years, whereas the number of cases positive for hepatitis B surface antigen in sera (HBsAg) has remained almost stable. Thus, the relative percentage of HCC cases with serum HBsAg has shown a marked decrease. In order to examine whether this increased proportion of HBsAg-seronegative patients carries hepatitis B virus (HBV) DNA in the liver, we extracted DNA from the formalin-fixed and paraffin-embedded cancerous and noncancerous liver tissues of 79 patients with HCC. The HCCs examined included 49 specimens resected during a period from 1970 to 1980 and 30 resected in 1986 and 1987. We were able to detect reliably the presence of HBV DNA by dot-blot hybridization. The presence of HBV DNA in liver tissues showed a good correlation with positivity for serum HBsAg in both examined groups. In total, HBV DNA was detected in 81% (21 of 26) of HBsAg-seropositive cases and in only 8% (4 of 53) of HBsAg-seronegative cases, indicating that the increased number of HBsAg-seronegative cases had no HBV involvement. Among these HBsAg-seronegative HCC patients, 89.7% showed a histology of cirrhosis or chronic active hepatitis in the noncancerous liver and 29.1% had a history of blood transfusion. These results suggest an increasing incidence of non-A, non-B hepatitis-associated HCCs in Japan and the possible transmission of factors by means other than blood transfusion.

[Successful removal of aberrant needles in the pericardium and lung].

A 28-year-old woman who had been diagnosed as schizophrenia was admitted to our hospital, complaining of chest pain. Her chest X-ray demonstrated 9 foreign bodies in the pericardium, lung and others. Her chest computed tomography (CT) confirmed needle-like shadows in the pericardium and lung. They were diagnosed as aberrant needles, and surgically removed. The intrapulmonary aberrant needle was removed with video-assisted thoracoscopic surgery. Aberrant needle in pericardium or lung should be removed surgically, because it is very dangerous. Intraoperative chest X-ray is always necessary before closing the wound to avoid leaving the residual fragments.

[Lung cancer associated with bulla found during an operation of pneumothorax; report of a case].

A 50-year-old man was admitted to our hospital because of dyspnea. His chest X-ray and computed tomography (CT) showed right pneumothorax and multiple bullae. His pneumothorax was drained with a chest tube, however, because of a persistent air leak, bullectomy was performed 18 days after the occurrence of pneumothorax. Intraoperatively, we found a palpable tumor in the bulla approximately 10 mm in diameter and resected it with the bullae. Histologically, the tumor was diagnosed as a large cell carcinoma.

Daunorubicin attenuates tumor necrosis factor-alpha-induced biosynthesis of plasminogen activator inhibitor-1 in human umbilical vein endothelial cells.

The anthracycline antibiotic daunorubicin is reported to induce apoptosis in cells by triggering ceramide generation through de novo synthesis or sphingomyelin hydrolysis. Treatment of human umbilical vein endothelial cells (HUVEC) with daunorubicin markedly decreased the mRNA expression and protein release of plasminogen activator inhibitor-1 (PAI-1). This cellular event was accompanied by a significant increase in the total ceramide content in HUVEC. On the other hand, tumor necrosis factor (TNF)-alpha treatment of HUVEC led to an increase in both PAI-1 mRNA expression and protein release, and an enhancement of total ceramide content was also observed. The stimulating effect of TNF-alpha on PAI-1 synthesis was attenuated by the pretreatment of HUVEC with daunorubicin. Interestingly, the daunorubicin-induced increase in ceramide content was blocked by addition of the potent ceramide synthase inhibitor fumonisin B(1), while the TNF-alpha-induced ceramide increase was not affected by this drug. Fumonisin B(1) treatment restored the daunorubicin-induced decrease in PAI-1 release to approximately 70% of the control, but did not affect the TNF-alpha-induced increase in PAI-1 release. Thus, these data imply the possibility that the subcellular topology of ceramide production determines its lipid mediator function in the regulation of PAI-1 synthesis in HUVEC, because both TNF-alpha and daunorubicin could increase the ceramide levels.

Relation of saphenous vein graft obstruction to serum cholesterol levels.

OBJECTIVES: To determine the potential of lipid-lowering therapy to reduce saphenous vein graft obstruction, we retrospectively studied the association between graft obstruction and serum cholesterol levels. BACKGROUND: Atherosclerosis is the major cause of vein graft obstruction. Approximately 50% of grafts are occluded by 10 years after operation. It remains to be established whether lipid control affects long-term graft survival. METHODS: We carried out a retrospective review of all 284 patients who had undergone coronary artery bypass graft surgery at Juntendo University Hospital between 1976 and 1991 and met the following additional criteria: at least one saphenous vein graft, repeat coronary arteriography at some point after coronary artery bypass graft surgery and a serum cholesterol level > or = 200 mg/dl before operation. Saphenous vein graft obstruction rates were compared among three groups classified by serum cholesterol levels at follow-up arteriography: group I < 200 mg/dl; group II 200 to 239 mg/dl; group III > or = 240 mg/dl. A vein graft was considered obstructed if it was narrowed by > or = 70%. RESULTS: In group I, 88% of grafts were not obstructed 7 years after operation. The respective rates were 61% in group II and 57% in group III (p < 0.005). This relation was true for vein grafts to the left anterior descending and other coronary arteries. CONCLUSIONS: Lower serum cholesterol levels are associated with lower rates of vein graft obstruction for up to 7 years. This suggests that cholesterol-lowering therapy may improve long-term saphenous vein graft survival after coronary artery bypass surgery.

Effects of blood pressure changes on development and regression of electrocardiographic left ventricular hypertrophy: a 26 year longitudinal study.

At the Radiation Effects Research Foundation, medical examinations have been conducted biennially since 1958 on a fixed population of approximately 20,000 individuals. Blood pressure measurements and electrocardiographic (ECG) recordings are available for 6,569 individuals who were monitored for at least 11 of the 13 2 year intervals between 1958 and 1984. Data from 601 individuals who had satisfied the Foundation's ECG diagnostic criteria of left ventricular hypertrophy ("Kagan-Yano code") on at least one occasion were reviewed. Both the development and the regression of ECG left ventricular hypertrophy were ascertained in 61 subjects (17 men and 44 women). During the course of development of ECG left ventricular hypertrophy, hypertension (including borderline cases) was noted in 83.3% of the subjects. The most common pattern of ECG left ventricular hypertrophy development was high voltage, followed by ST-T changes. In about half of these cases, the condition of hypertrophy regression was associated with lowering of blood pressure, marked by the disappearance of high voltage ECG readings.

Plasma des-acyl and acyl ghrelin in patients with eating disorders.

A recently recognized peptide, ghrelin, increases appetite and energy retention in human. Previous reports have shown higher plasma level in eating disorder (ED) patients and correlations with body mass index (BMI). This study examined these findings by measuring active (N-RIA) and total (C-RIA) levels of plasma ghrelin. Multipurpose assessments of symptoms were conducted for 11 ED patients and 5 control females. Results revealed significant differences of C-RIA between the groups. The BMI did not correlate with ghrelin, but demonstrated reversal correlation with the ratio of N-RIA and C-RIA (NC ratio) according to the ED or control group. The NC ratio also tended to be associated with a self-rating score. The NC ratio might be related to specific characteristics of ghrelin secretion or clearance in ED patients. Further basic and clinical investigations are necessary.

Somatosensory conduction delay in central and peripheral nervous system of diabetic patients.

Fifty-four diabetic patients with or without clinical evidence of neuropathy and with no clinical evidence of CNS dysfunction were studied by somatosensory-evoked potentials after electrical stimulation of the median nerve at the wrist and recorded from the scalp electrode against a noncephalic reference. Peripheral conduction index, calculated as the distance from the wrist to the C7 spinous process divided by the P9 latency, was significantly decreased (P less than 0.01) in diabetic patients (69.81 +/- 6.47 m/s) compared with 28 age-matched nondiabetic subjects (76.85 +/- 5.65 m/s). The P11-P13 interpeak latency, representative of the transit time from the dorsal column at the level of the sensory input into the cervical cord to the brain stem along the somatosensory pathways (CCT1), and the P13-N19 interpeak latency, representative of the transit time from the brain stem to the somatosensory cortex (CCT2), were significantly increased in diabetic patients (CCT1, 2.51 +/- 0.63 ms; CCT2, 5.76 +/- 0.92 ms) compared with nondiabetic subjects (CCT1, 2.28 +/- 0.36 ms, P less than 0.05; CCT2, 5.18 +/- 0.51 ms, P less than 0.01). We conclude that, in diabetic patients, neurophysiological abnormalities may be present in two distinct parts of the CNS and the peripheral nervous system.

Role of 5-hydroxytryptamine in the progression of monocrotaline induced pulmonary hypertension in rats.

OBJECTIVE: The aim was to clarify the role of serotonin (5-hydroxytryptamine, 5-HT) in monocrotaline induced pulmonary hypertension. METHODS: Plasma 5-HT levels, pulmonary capillary platelet count, and vascular responsiveness to 5-HT were evaluated in the model. The effects of the selective 5-HT2 receptor antagonist, DV-7028, on the development of pulmonary hypertension were also investigated. RESULTS: Plasma 5-HT was raised 12 h to 3 d after monocrotaline administration (60 mg.kg-1), coinciding with accumulation of platelets in the pulmonary circulation. Isolated pulmonary arteries showed hyperreactivity to 5-HT at 14 and 21 d after monocrotaline. Administration of DV-7028 (20 mg.kg-1 x d-1) attenuated the increase in pulmonary arterial pressure, right ventricular hypertrophy, and medial thickening of the pulmonary arteries. CONCLUSIONS: The present study suggests that 5-HT released from platelets contributes to the initiation and progression of monocrotaline induced pulmonary hypertension.

A nation-wide study of atherosclerosis in infants, children and young adults in Japan.

This paper reports the results of a nation-wide cooperative study of atherosclerosis in young, first generation Japanese with ages ranging from 1 month to 39 years, who were autopsied between 1978 and 1982 in hospitals distributed over the entire archipelago of Japan. Atherosclerotic lesions in 2320 aortas, 1620 coronary arteries and 344 cerebral arteries were classified into fatty streaks, fibrous plaques and complicated lesions and were then quantificated with the point-counting method. Atherosclerosis of aortas, coronary arteries and cerebral arteries, determined by surface involvement (SI) of atherosclerotic lesions and atherosclerotic index (AI), increased with age; the severest were seen in aortas, and then, with decreasing severity, in the coronary and cerebral arteries. Fatty streaks preceded the other lesions and accounted for the largest portion of the lesions in aortas and coronary arteries. Fibrous plaques and complicated lesions developed in the later decades of life. The patients with collagen diseases had a greater severity of aortic atherosclerosis in the 2nd and 3rd decades of life, than those without such disorders. Correlation of antemortem clinical data with SI and AI of each artery were analyzed, using simple correlation analysis and multiple regression analysis. Age, serum cholesterol and blood pressure were significantly and positively correlated with SI and AI of aortas and coronary arteries. Serum cholesterol was more strongly correlated with the extent of fatty streaks than was mean blood pressure and vice versa with that of fibrous plaques. Atherosclerosis of cerebral arteries, however, showed a significant correlation only with the factor of mean blood pressure. Therefore the susceptibility to risk factors varies with the artery in cases of early lesions of atherosclerosis in young Japanese.

Phyllodes tumor of the breast containing the intracytoplasmic inclusion bodies identical with infantile digital fibromatosis.

This report illustrates a case of the phyllodes tumor of the breast with intracytoplasmic inclusion bodies that are diffusely distributed over the tumor. The inclusion bodies were identified as aggregated actin filaments by modified immunohistochemical and ultrastructural analyses. These structures are thought to be identical to those of the characteristic intracytoplasmic inclusion bodies observed in the case of infantile digital fibromatosis. To date, tumors with such intracytoplasmic inclusion bodies have been recognized exclusively as infantile digital fibromatosis. Although a few rare cases in which the infantile digital fibromatosis-like tumor occurred outside the digit or in adulthood, all these cases were in the category of fibromatosis or fibroma. This case is the first instance of the tumor containing intracytoplasmic inclusion bodies identical with the infantile digital fibromatosis other than fibromatosis or fibroma.

Papillary carcinoma of the thyroid. Tall-cell variant with extensive lymphocyte infiltration.

Thirteen cases of tall-cell variant of papillary thyroid carcinoma (PTC) showing extensive lymphocyte and plasma cell infiltration within the fibrous stalks of the papillary architecture were compared with age-, sex-, and tumor size-matched cases of ordinary tall-cell variant without extensive lymphocyte infiltration and also with cases of PTC of the conventional type. All cases of the tall-cell variant of PTC with extensive lymphocyte infiltration exhibited the histologic features of chronic thyroiditis. Dissemination of tumor cells with the thyroid was significantly less frequent than in control cases, but there was no difference between the incidences of lymph node metastasis. Immunohistochemically, the lymphocytes infiltrating the carcinoma focus were mainly CD20+, CD45+, and CD45RO+ cells, that is, basically the same as those found in foci of chronic thyroiditis. No tumor recurrence was observed during the mean follow-up period of 3 years 8 months. The results of this study suggest that the tall-cell variant of PTC with extensive lymphocyte infiltration has less aggressive characteristics and a more favorable prognosis.

Multicentric independent development of hepatocellular carcinoma revealed by analysis of hepatitis B virus integration pattern.

Two separate nodular lesions of hepatocellular carcinoma (HCC) were surgically removed from a patient with positive serum hepatitis B surface antigen. Southern blot analysis of DNA from the two separate HCC lesions showed different restriction patterns of integrated hepatitis B virus DNA, indicating their independent origins. The two lesions were composed mainly of poorly differentiated HCC; however, well-differentiated HCC was also observed in the periphery of the lesions. This histological finding is consistent with the multistep and independent development of HCC in each site of the liver.

CAM--a novel immunosuppressive agent.

This is an initial study of the immunosuppressive efficacy of CAM, a derivative of mycophenolic acid, in a rat heart allograft model when the major histocompatibility complex was fully incompatible, and its effect in improving heart allograft survival compared with mycophenolate mofetil (MMF, RS-61443). CAM or MMF was administered orally from day 1 following the allografting for 40 days. The median survival times (MST) were 6 days in rats with no immunosuppressive drug (control group; n = 6), 83 days with CAM 10 mg/kg (n = 6), and > 100 days with both 20 mg/kg (n = 7), and 30 mg/kg (n = 10). With MMF, in contrast, MST was 9, 17, 35, days with 10, 20, 30 mg/kg/day, respectively. All grafts in the CAM 30 mg/kg-treated group survived for more than 100 days after grafting, and, furthermore, CAM was also more effective than MMF in prolongation of the heart graft survival in rats at each dose. Rats with long-surviving cardiac allografts (30 mg/kg; CAM) accepted skin grafts from the donor-strain but rejected them from the third-party strain, suggesting that donor-specific tolerance was induced by CAM. In the tolerant rats, proliferative response against donor-type alloantigen was not impaired as compared with naive WKAH rats. In contrast, CML assay showed that T cells obtained from the rats bearing permanently accepted F344 heart grafts had less cytotoxic activity to the donor-type target, and the frequency of CTL precursor against donor-type alloantigen was also reduced.

Transplantation of infantile bladder in rats: an alternative procedure for bladder augmentation.

BACKGROUND: Our purpose was to evaluate whether bladder transplantation (BTx) can be used for bladder augmentation (BA). METHODS: Bladders from infantile Brown-Norway rats (less than 21 days old) were excised and each transplanted into a pouch created in the distal omentum of a 6-week-old Lewis rat (fully allogeneic BTx). No immunosuppressant was used in group I (n=12). Intramuscular FK506 was used daily from the day of BTx in group II (n=16; 0.2 mg/kg), group III (n=22; 0.6 mg/kg), and group IV (n=16; 1.2 mg/kg) until harvesting 3, 4, 5, or 6 weeks after BTx. FK506 was used for only 2 weeks in group V (n=12; 0.6 mg/kg/day) and group VI (n=12; 1.2 mg/kg/day). Syngeneic bladder transplants acted as controls (n=16). Hematoxylin and eosin staining was used to examine all grafts. In six rats from group III, BA was performed by anastomosing the graft to the recipient bladder 10 days after BTx. RESULTS: Each successfully transplanted graft appeared macroscopically as a thin-walled cyst. Rejection was seen in all grafts from groups I, II, V, and VI, and was minimal or absent in groups III and IV. On medium to long-term follow-up the only side effect of FK506 observed was reduced weight gain. Graft survival in the control group was 100%. BA was successful in all six cases, and the mucosa was normal throughout each augmented bladder. CONCLUSIONS: This is the first report of the successful transplantation of infantile tissue without vascular anastomosis. Because of the efficient, safe immunosuppression possible with FK506, our BTx technique could find clinical application for creating viable vesical tissue that could be used for BA.

Unilateral thickening of placental fetal veins.

Unilateral muscular thickening (ULT) was observed in the wall of the fetal veins on the placental surface beneath the amnion. The maternal facing wall of the fetal veins was thin, and protruded into the amniotic sac. The ratio of the thickness of the maternal facing to the fetal facing wall was 4:1 to 3:1 in the fetal veins. ULT was found to develop after 17 weeks of gestation and was not observed in the small veins less than 1.0 mm in diameter or in the veins located in the deep portion of the chorionic plate. The intimal thickening was not recognized and there was no lipid deposition in ULT. ULT was found in every one of 110 mature placentae and was assumed to be a normal histological finding.

Lightning injury as a blast injury of skull, brain, and visceral lesions: clinical and experimental evidences.

The present study attempts to better understand the mechanism of injuries associated with direct lightning strikes. We reviewed the records of 256 individuals struck by lightning between 1965 and 1999, including 56 people who were killed. Basal skull fracture, intracranial haemorrhage, pulmonary haemorrhage, or solid organ rupture was suspected in three men who died. Generally these lesions have been attributed to current flow or falling after being struck. However, examination of surface injuries sustained suggested that the true cause was concussion secondary to blast injury resulting from vaporization of water on the body surface by a surface flashover spark. To investigate this hypothesis, an experimental model of a lightning strike was created in the rat. Saline-soaked blotting paper was used to simulate wet clothing or skin, and an artificial lightning impulse was applied. The resultant lesions were consistent with our hypothesis that the blast was reinforced by the concussive effect of water vaporization. The concordance between the clinical and experimental evidence argues strongly for blast injury as an important source of morbidity and mortality in lightning strikes.