A primary retroperitoneal serous cystadenocarcinoma with clinically aggressive behavior

Case report We describe a 44-year-old woman with a primary retroperitoneal serous cystadenocarcinoma as the fourth report in the world literature. A contrast-enhanced computed tomographic scan of the abdomen demonstrated a mass with enhanced solid mural nodules and septa in the left retroperitoneum. Serum CA19–9 was elevated at 181 U/ml. The patient underwent a complete resection of the retroperitoneal tumor with a partial resection of the psoas major muscle and its fascia. Pathological examination showed a well-differentiated papillary serous cystadenocarcinoma of ovarian type and locoregional lymph node metastases. Seven months after surgery, the patient developed a pelvic recurrence, and underwent a total hysterectomy, a left salpingo-oophorectomy and a resection of the metastatic mesenteric mass. Two months after the second surgery, serum CA19–9 and CA125 increased to 1,114 U/ml and 218 U/ml, respectively. A solitary liver metastasis was confirmed on a computed tomographic scan. The patient is now being treated with weekly docetaxel and carboplatin.Conclusion The present case illustrates the clinically aggressive nature of a primary retroperitoneal serous cystadenocarcinoma.     

Dural arteriovenous fistulas of the cavernous sinus with onset of intracerebral haemorrhage mimicking hypertensive putaminal hemorrhage

Summary We describe a patient with dural arteriovenous fistulas of the cavernous sinus (CS-dAVFs) who developed an intracerebral haemorrhage (ICH) mimicking hypertensive putaminal haemorrhage. Drainage into the superior ophthalmic vein (SOV) and inferior petrosal sinus (IPS) was not demonstrated on cerebral angiography, and only cortical venous reflux into the Sylvian vein was observed. In cases of venous drainage concentrated on the Sylvian vein, CS-dAVFs could indicate ICH with radiological appearance resembling putaminal haemorrhage.     

Mature dendritic cells generated from patient-derived peripheral blood monocytes in one-step culture using streptococcal preparation OK-432 exert an enhanced antigen-presenting capacity

Dendritic cells (DCs) have been shown to be potent in inducing cytotoxic T cell (CTL) response leading to the efficient anti-tumor effect in active immunotherapy. Myeloid DCs are conventionally generated from human peripheral blood monocytes in the presence of interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Streptococcal preparation OK-432, which is known to be a multiple cytokine inducer, has been extensively studied as to its maturation effects on immature DCs using an in vitro culture system. The purpose of this study was to examine whether it could be possible to generate mature DCs directly from peripheral monocytes using OK-432. We specifically focused on the possibility that recombinant cytokines, which are considered to be essential for in vitro DC generation, could be substituted by OK-432. Human peripheral monocytes, which were obtained from patients with advanced cancer, were cultured with IL-4 and OK-432 for 7 days. Cultured cells were compared with DCs generated in the presence of IL-4 and GM-CSF with or without OK-432 with regard to the surface phenotype as well as the antigen-presenting capacity. As a result, the culture of monocytes in the presence of IL-4 followed by the addition of OK-432 on day 4 (IL-4/OK-DC) induced cells with a fully mature DC phenotype. Functional assays also demonstrated that IL-4/OK-DCs had a strong antigen-presenting capacity determined by their enhanced antigen-specific CTL response and exerted a Th1-type T cell response which is critical for the induction of anti-tumor response. In conclusion, human peripheral blood monocytes cultured in the presence of IL-4 and OK-432 without exogenous GM-CSF demonstrated a fully mature DC phenotype and strong antigen-presenting capacity. This one-step culture protocol allows us to generate fully mature DCs directly from monocytes in 7 days and thus, this protocol can be applicable for DC-based anti-tumor immunotherapy.     

A novel immunotherapeutic modality with direct hemoperfusion targeting transforming growth factor-beta prolongs the survival of tumor-bearing rats

Immune responses are frequently depressed in patients with cancer. One of the reasons for a poor immune response is the presence of increased levels of immunosuppressive substances associated with tumor growth. Transforming growth factor-beta (TGF-beta), a representative immunosuppressive cytokine, plays various roles in the progression of cancer. To remove immunosuppressive substances from tumor-bearing hosts, we developed an immunosuppressive substance adsorption (ISA) column for direct hemoperfusion (DHP) treatment. It is filled with extra-fine fibers that can adsorb TGF-beta. In this study, we investigated the effects of this DHP treatment on serum levels and activities of TGF-beta, cellular immune responses, and anti-tumor effects in KDH-8 (TGF-beta-producing hepatocellular carcinoma cell line)-bearing rats. We further studied the ability of ISA fibers to adsorb tumor-associated immunosuppressive cytokines [TGF-beta, interleukin (IL)-6 and vascular endothelial growth factor (VEGF)] in samples of body fluids obtained from patients with metastatic cancer. DHP treatment decreased serum levels and activities of TGF-beta in tumor-bearing rats and restored T lymphocyte response to mitogen. Tumor growth in rats treated by DHP was significantly slower than that in untreated rats. The survival time of treated rats was significantly longer than that of untreated rats. The concentrations of TGF-beta, IL-6, and VEGF in the samples of human body fluids were decreased markedly by in vitro treatment with ISA fibers. These results suggest that DHP treatment with an ISA column, which removes TGF-beta and other immunosuppressive substances from the sera of tumor-bearing hosts, is potentially a new immunotherapeutic strategy for cancer.     

Asian sand dust enhances ovalbumin-induced eosinophil recruitment in the alveoli and airway of mice

Asian sand dust (ASD) containing sulfate (SO4(2-)) reportedly causes adverse respiratory health effects but there is no experimental study showing the effect of ASD toward allergic respiratory diseases. The effects of ASD and ASD plus SO4(2-) toward allergic lung inflammation induced by ovalbumin (OVA) were investigated in this study. ICR mice were administered intratracheally with saline; ASD alone (sample from Shapotou desert); and ASD plus SO4(2-) (ASD-SO4); OVA+ASD; OVA+ASD-SO4. ASD or ASD-SO4 alone caused mild nutrophilic inflammation in the bronchi and alveoli. ASD and ASD-SO4 increased pro-inflammatory mediators, such as Keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-1 alpha, in bronchoalveolar lavage fluids (BALF). ASD and ASD-SO4 enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. However, a further increase of eosinophils by addition of SO4(2-) was not observed. The two sand dusts synergistically increased interleukin-5 (IL-5) and monocyte chemotactic protein-1 (MCP-1), which were associated with OVA, in BALF. However, the increased levels of IL-5 were lower in the OVA+ASD-SO4 group than in the OVA+ASD group. ASD caused the adjuvant effects to specific-IgG1 production by OVA, but not to specific-IgE. These results suggest that the enhancement of eosinophil recruitment in the lung is mediated by synergistically increased IL-5 and MCP-1. IgG1 antibodies may play an important role in the enhancement of allergic reaction caused by OVA and sand dust. However, extra sulfate may not contribute to an increase of eosinophils.     

Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study

Cerebral blood flow (CBF), oxygen metabolism (CMRO₂), and glucose metabolism (CMRGlc) were measure using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO₂ was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is imparied and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy.     

Comparison of Doppler velocimetry of the common carotid artery with cerebral blood flow measured by PET

The cervical carotid Doppler velocity is determined by the cardiovascular function, hemodynamic characteristics of proximal vascular beds, the carotid artery, and the distal vascular beds, i.e., cerebral circulation. If the former three factors remain constant, cervical carotid Doppler velocimetry reflects the cerebral circulation. The purpose of this report is to study whether the cervical carotid Doppler velocimetry reflects cerebral circulation or not. Parameters measured by the common carotid Doppler velocimetry were compared with cerebral blood flow (CBF) in the internal carotid arterial distribution measured by positron emission tomography (PET) in 50 patients, aged from 33 to 72 years old (mean: 56.5 +/- 8.6). These subjects were 14 with cerebral infarction, 12 with no abnormality (normal volunteers), 5 with brain tumor, 2 with normal pressure hydrocephalus, 3 with spinocerebellar degeneration, and so on. CBF was measured by the 15O-gas steady state method or H2(15)O autoradiographic method using a HEADTOME III scanner. Subsequently, pulsed Doppler flow velocimetry of the common carotid artery was performed using a RT-3600 scanner which employed a 5-MHz transducer, and systolic velocity (SV), diastolic velocity (DV), mean velocity (MV), and pulsatility index (PI) were measured. Cerebral angiography was performed in every patient except for normal volunteers, and it demonstrated no evidence of stenoocclusive lesions in the cervical carotid artery. X-ray computed tomogram (CT) was also performed in all patients. We compared CBF in the internal carotid arterial distribution with SV, DV, MV, and PI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of factors that influence the desire to use public health nursing visit and visiting nursing agencies' service

PURPOSE: The purpose of this study was to forecast the demand for public health nursing visit and visiting nursing agencies' service, and to obtain basic information on public policy after the Long-term Care Insurance Project Plan starts. METHOD: 8,940 randomly sampled subjects aged 65 and over, and 7,984 aged 64 and below, were selected for the surveys and mailed the questionnaire. A total of 5,775 aged 65 and over and 4,774 aged 64 and below responded to the questionnaire. RESULTS: 2,474 (42.8%) aged 65 and over and 1,643 (34.4%) aged 64 and below knew the name 'public health nursing visit', and the service provided, 1,635 (28.3%) aged 65 and over and 1,073 (22.5%) aged 64 and below, were aware of the visiting nursing agencies' service. The percentage of those who desired to use the service was significantly higher among the respondent aged 65 and over than among those aged 64 and below. It was also significantly higher among those who had already experienced the service previously. CONCLUSION: Awareness of the service and the number of those who use the visit will increase, as those aged 64 and below become more the elderly. We therefore can expect that service demand will increase in the future.     

Chemosensitization by STI571 targeting the platelet-derived growth factor/platelet-derived growth factor receptor-signaling pathway in the tumor progression and angiogenesis of gastric carcinoma

BACKGROUND: Autocrine and paracrine growth mediated by the platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR)-signaling pathway plays an important role in the progression of solid tumors. The authors assessed the effect of STI571 on the tumor growth of gastric carcinoma in combination with 5-fluorouracil (5-FU) or paclitaxel targeting the PDGF/PDGFR-signaling pathway. METHODS: In MKN-45 gastric carcinoma cells, the cytotoxic effect was evaluated by 3-(4,5 dimethiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and the in vivo antitumor effect was evaluated in a nude mouse xenograft. Both STI571 and an antitumor drug were administered intraperitoneally. Gene expression was assessed by Western blot analysis and immunohistochemical staining. Apoptotic cell death was evaluated by the terminal deoxyuridine triphosphate-biotin nick-end labeling assay, and tumor angiogenesis was evaluated by microvessel density analysis. RESULTS: Treatment with STI571 alone was not effective in vitro, as assessed by a 50% inhibitory concentration value of 24.3 microM. Combination treatment with STI571 and 5-FU or paclitaxel enhanced the cytotoxic effect somewhat when the concentration of STI571 was increased to 10 microM. Combination treatment with STI571 and 5-FU or paclitaxel enhanced the antitumor effect of the antitumor drug significantly in vivo. The enhanced antitumor effect was associated with increased apoptotic cell death and inhibition of tumor angiogenesis. Treatment with STI571 down-regulated the expression of PDGF-BB and PDGFR-beta in tumor cells and decreased the production of phosphorylated PDGFR-beta and phosphorylated Akt. Furthermore, treatment with STI571 inhibited the expression of PDGFR-beta in stromal cells. CONCLUSIONS: STI571 was an effective chemosensitizer of antitumor drugs, such as 5-FU and paclitaxel for gastric carcinoma, targeting the PDGF/PDGFR-signaling pathway of tumor cells and stromal cells in disease progression and angiogenesis.