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This retrospective study was conducted to review the complications of lung radiofrequency (RF) ablation and to clarify the effects of inflammation after lung RF ablation on mortality and morbidity. Complications were evaluated by reviewing medical records on an RF session basis. The C-reactive protein (CRP) value was used as an indicator of inflammation and was measured before and every 1-2 days during the hospital stay after RF ablation. The relationships between CRP values and patient baselines were evaluated to identify factors affecting lung inflammation. 130 patients who underwent 327 lung RF ablation sessions were enrolled in this study. The major complication rate was 18.3% (60/327). Inflammation-related complications such as interstitial pneumonia (n = 2) and aseptic pleuritis (n = 2) developed in four sessions (1.2%). Death occurred in two patients with interstitial pneumonia (0.6%). The mean CRP value increased significantly from 1.3+/-2.6 mg dl(-1) to 3.4+/-5.6 mg dl(-1) (p<0.01) after RF ablation. Large tumour size (>or=2 cm) and previous external-beam radiotherapy were significant factors associated with an increased CRP value in both univariate and multivariate analyses. In conclusion, although the incidence rate is low, fatal lung inflammation may develop after lung RF ablation. Large tumour size and previous external-beam radiotherapy are risk factors for severe lung inflammation.

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The objective of this study was to evaluate the clinical efficacy of brachytherapy combined with external-beam radiotherapy and repeated arterial infusion chemotherapy in improving stent patency and prognosis in patients with unresectable bile duct cancer as compared with brachytherapy alone. Seventeen patients were treated. Five patients received brachytherapy alone before stent placement. Twelve patients received brachytherapy combined with external-beam radiotherapy (n=5), repeated hepatic arterial infusion chemotherapy using an implanted catheter and port (n=1), or both (n=6). Mean survival was significantly improved in the group that received combined therapy as compared with the group that received brachytherapy alone (16.2 months vs. 4.6 months, p<0.01). Although stent occlusion rates were similar in the two groups (42% vs. 40%), there was a trend towards longer stent patency in the combined therapy group than in the brachytherapy group (22 months vs. 3.6 months, p<0.2). Radiation gastritis necessitating gastrectomy developed in 1 patient who received external-beam radiotherapy at more than 50 Gy. Brachytherapy combined with external-beam radiotherapy and repeated hepatic arterial infusion chemotherapy increases survival compared with brachytherapy alone in patients with unresectable bile duct cancer.

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This study was performed to evaluate the feasibility and clinical impact of intraluminal and endovascular high-dose-rate iridium-192 brachytherapy on the treatment of HCC lesions growing into biliary trees, portal veins and the inferior vena cava. HCCs involving biliary trees in 2 patients, the main and/or first-order portal veins in 3 patients, and the inferior vena cava in 2 patients. Brachytherapy was percutaneously performed with a 5F applicator, which was placed adjacent to the lesions. A mean total dose of 23 Gy (range, 5-7 Gy/fr) was irradiated (at a 5 mm radius) to the biliary or the portal venous tumors. A total dose of 10 Gy (5 Gy/fr) was given to the caval tumors. External-beam radiotherapy was combined in 2 patients with caval lesions, stent placement in 2 patients with biliary lesions and hepatic arterial infusion chemotherapy in 5 patients. There was no major complication except hemobilia, which ceased after placing a PTCD tube in the bile duct in one patient. All tumors were significantly reduced in size and remained controlled during the period of patients' survival. Complete tumor necrosis was histologically proved in 2 autopsy cases having biliary lesions. The median survival was 13 months. Intraluminal and endovascular high-dose-rate brachytherapy appears to be a feasible, and effective procedure to treat advanced HCCs invading biliary trees, portal veins and the vena cava.

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The effects of KF31327 (3-ethyl-8-[2-(4-hydroxymethylpiperidino)benzylamino]-2,3-dihydro-1H-imidazo[4,5-g]quinazoline-2-thione dihydrochloride) on phosphodiesterase 5 (cyclic GMP-specific phosphodiesterase) activity and platelet aggregation were investigated and compared with those of sildenafil, a well-known phosphodiesterase 5 inhibitor. KF31327 inhibited phosphodiesterase 5 from canine trachea (K(i)=0.16 nM) more potently than sildenafil (K(i)=7.2 nM). The kinetic analysis revealed that KF31327 was a non-competitive inhibitor. In the presence of nitroglycerin (nitric oxide generator), both compounds inhibited the collagen-induced aggregation of rabbit platelets at less than 0.1 microM, augmenting intracellular cyclic GMP level without affecting cyclic AMP. In contrast, in the absence of nitroglycerin, a higher concentration (10 microM) of KF31327 was required to inhibit platelet aggregation and increased both cyclic nucleotide levels. However, 10 microM sildenafil did not affect aggregation despite elevation of cyclic GMP comparable to that in the presence of nitroglycerin. These results indicate that in the presence of nitroglycerin, the inhibition of platelet aggregation by KF31327 is due to the elevation of cyclic GMP, whereas the mechanism underlying the inhibition without nitroglycerin might be related to a rise in intracellular cyclic AMP.

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The cytologic findings of the tumor cells characteristic of the stages of thymomas were investigated to assess the invasiveness of the tumors. Forty-six patients with thymoma who underwent extensive thymectomy without pre-operative corticosteroid therapy were included in this study. The histologic subtypes included 18 round/oval, 20 mixed, and 8 spindle type. The stages of thymoma classified according to Masaoka's clinicopathological classification included 16 stage I, 20 stage II, 6 stage III, 2 stage IVa, and 2 stage IVb, and myasthenia gravis was recognized in 5 patients. Cytologic findings were retrospectively analyzed in the Papanicolaou-stained stamp smears obtained from the cut surfaces of thymoma specimens. Morphometry of the epithelial tumor cells using Cosmozone-1A was performed to evaluate the validity of our cytologic categories. Compared with the cytologic findings of stage I or II thymomas, those of epithelial tumor cells in stage III or IV more frequently showed necrotic background (50.0%-stage III or IV vs 11.1%-stage I or II, p=0.006), large clusters of epithelial tumor cells (70.0% vs 36.1%, p=0.055), marked nuclear enlargement (90.0% vs 52.7%, p=0.033), marked anisokaryosis (100% vs 52.7%, p=0.006), marked nuclear polymorphism (40.0% vs 5.5%, p=0.004), hyperchromasia (50.0% vs 11.4%, p=0.007) and prominent nucleoli (50.0% vs 16.6%, p=0.028) whereas no significant correlation was observed between cytologic findings and tumor volume. Morphometric studies of thymoma tumor cells revealed that the nuclear size (mean values, 78.8 microm(3)-stage III or IV vs 58.2 microm(3)-stage I or II), the coefficient of variation of the nuclear size (0.326 vs 0.282), and the nuclear rotundity (0.849 vs 0.858) differed significantly between the two categories (p<0.05). Our findings demonstrated that there were significant differences between the cytologic findings of epithelial tumor cells of stage I or II thymomas and those of stage III or IV thymomas, and that the cytologic findings of thymoma tumor cells appear to be useful for distinguishing between non-invasive and invasive thymomas.

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Recently, radiation therapy has been reported to be effective in patients with low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) of the stomach. We describe changes in endoscopic ultrasonographic (EUS) findings after radiation therapy in a patient with low-grade gastric MALT lymphoma. Endoscopic ultrasonography initially showed enlargement of regional lymph nodes and diffuse thickening of the second and third mural layers in the gastric body. Two months after the end of radiation therapy, EUS showed hypoechoic changes in the third layer that corresponded to the ulcer scar but no wall thickening or lymph node enlargement. The hypoechoic changes were thought to reflect inflammatory change. We conclude that EUS is useful for assessing the response to radiation therapy in patients with low-grade gastric MALT lymphoma.

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Exaggerated or inappropriate signaling by the platelet-derived growth factor receptor (PDGFR) tyrosine kinase has been implicated in a wide variety of diseases. Thus, a series of piperazinyl quinazoline compounds were identified as potent antagonists of the PDGFR by screening chemical libraries. An optimized analog, CT52923, was shown to be an ATP-competitive inhibitor that exhibited remarkable specificity when tested against other kinases, including all members of the closely related PDGFR family. The PDGFRs and stem cell factor receptor were inhibited with an IC(50) of 100 to 200 nM, while 45- to >200-fold higher concentrations of CT52923 were required to inhibit fms-like tyrosine kinase-3 and colony-stimulating factor-1 receptor, respectively. Other receptor tyrosine kinases, cytoplasmic tyrosine kinases, serine/threonine kinases, or members of the mitogen-activated protein kinase pathway were not significantly inhibited at 100- to 1000-fold higher concentrations. In addition, this compound also demonstrated specificity for inhibition of cellular responses. Platelet-derived growth factor-induced smooth muscle cell migration or fibroblast proliferation was found to be blocked by CT52923 with an IC(50) of 64 and 280 nM, respectively, whereas 50- to 100-fold higher concentrations were required to inhibit these responses when induced with fibroblast growth factor. To investigate the effect of CT52923 on PDGFR signaling, in vivo studies demonstrated that CT52923 could significantly inhibit neointima formation following carotid artery injury by oral administration in the rat. Therefore, PDGFR antagonism by CT52923 could be a viable strategy for the prevention of clinical restenosis or the treatment of other human diseases involving PDGFR signaling.

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An applicator enabling simultaneous intraluminal radiotherapy and intraluminal hyperthermia delivery was developed to improve the treatment results for locally advanced oesophageal carcinoma. Eight inoperable cases were treated by this method. Six cases received 40 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (3 Gy and 4 Gy in three cases each) once weekly for 3 weeks; the remaining two cases received 50 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (4 Gy) once weekly for 2 weeks. Hyperthermia was delivered by a radiofrequency current thermotherapy instrument for 30 min at an output that raised the oesophageal mucosal surface temperature to 42-43 degrees C. Intraluminal radiotherapy was delivered with a microSelectron to a submucosal depth of 5 mm after the first 15 min of hyperthermia. Four cases achieved complete response, with all demonstrating local control. Partial response was obtained in four cases, and three of these patients died of local recurrence. There were no significant adverse side effects apart from fistula in one case. In conclusion, simultaneous intraluminal radiotherapy and hyperthermia may improve the current treatment results for locally advanced oesophageal carcinoma.

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OBJECTIVE: Nuclear factor kappa B (NFkappaB) participates in the regulation of a diverse range of genes involved in inflammation and acute phase responses. We investigated the expression of the activated form of NFkappaB and tumor necrosis factor alpha (TNFalpha), an inflammatory cytokine, in experimental brain injury. METHODS: We generated focal brain injury in mice using radiofrequency thermal ablation at the caudate putamen in mice. Intracerebral expression of TNFalpha and the p50 and p65 subunits of NFkappaB were studied using immunohistochemistry at 1, 4, and 8 hours and at 1, 2, 4, 8, 14, and 28 days postinjury. RESULTS: Coagulative necrosis approximately 2 mm in diameter was produced at the site of injury. No immunoreactivity for TNFalpha, NFkappaB p50, or NFkappaB p65 was detected in the injured area in the early phase postinjury. On posttrauma Day 2, however, weak expression of TNFalpha, NFkappaB p50, and NFkappaB p65 was detected in mononuclear cells that infiltrated edematous tissue surrounding the lesion. On posttrauma Days 4 to 8, the expression of TNFalpha, NFkappaB p50, and NFkappaB p65 was prominently increased in infiltrating and proliferating mononuclear cells (macrophages and microglia) and in proliferating reactive astrocytes surrounding the lesion. Nuclear subcellular localization of the expression of NFkappaB p50 and p65 was observed, which indicated that these subunits might be activated in these cells. On posttrauma Day 14, the expression of TNFalpha, NFkappaB p50, and NFkappaB p65 decreased and was limited to mononuclear cells, and it finally disappeared on Day 28. The temporal profiles of TNFalpha, NFkappaB p50, and NFkappaB p65 were closely associated with the occurrence of secondary insults and the tissue-remodeling process in wound healing. CONCLUSION: These results suggest that TNFalpha, NFkappaB p50, and NFkappaB p65 may play a central role in the injury-induced immune response that leads to secondary insults or wound healing after brain injury. Inappropriate and deregulated activation of NFkappaB in injured brain tissue may be implicated in the development of secondary brain damage.

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SUMMARY: We have recently developed a non-adhesive liquid embolic agent, hydroxyethylmethacrylate methylmethacrylate copolymer (HEMA-MMA), and used it for arteriovenous malformations (AVMs) in the central nervous system. To evaluate the toxicity and usefulness of this agent, we made a clinicopathological study of AVMs that were embolized with it and then excised surgically. This study includes ten cases: nine with pial AVM and one with scalp AVM. In a pathological study, special attention was paid to vascular and perivascular inflammation, angionecrosis, recanalization of the embolized vessels, and foreign body reactions. Inflammation was absent or very mild regardless of the interval between embolization and excision. There was no angionecrosis. Recanalization could be expected to occur in the partially occluded vessel. Foreign body reactions such as infiltration of monocytes or giant cells, and proliferation of fibroblasts or capillaries were also not seen in any case. It was concluded that HEMA-MMA is an excellent embolic material that is easy to handle, less vasotoxic than other agents, and highly histocompatible.

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Hemophilia A is a sex-linked recessive hereditary disease that is relatively rare and the number of patients with this disorder who undergo major surgery is limited. Although replenishing coagulation factors can allow hemophiliac patients to undergo similar surgery to that performed for patients without hemophilia, there have been few reports on major surgery and none on the resection of lung cancer in patients with hemophilia A. We recently performed completion pneumonectomy of the left lung in a 70-year-old man with hemophilia A, for squamous cell carcinoma in the residual left lung. The administration of a recombinant DNA coagulation factor VIII preparation allowed this operation to be successfully carried out. This case serves to demonstrate that the recombinant DNA coagulation factor VIII preparation described may enable us to safely perform major surgery on hemophiliac patients, since there is no risk of viral infection or any other adverse effects, such as deterioration of immunocompetence or hemolysis, which are occasionally encountered with human plasma-derived preparations.

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Palladium catalyzed cross coupling reactions of a vinyl triflate intermediate and various alkenyl stannanes afforded trisubstituted Z-olefins stereoselectively in high yields. These olefins were then converted to the corresponding 9Z-retinoic acids via Horner-Emmons reaction and subsequent basic hydrolysis in excellent yields.

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PURPOSE: The effects of morphine on natural killer (NK) cell activity were investigated in patients who underwent hysterectomy. METHODS: Forty patients were divided into four groups of ten. The groups received intrathecal 0.5 mg morphine (Group IT0.5), intrathecal 0.1 mg morphine (Group IT0.1) or 10 mg morphine i.v. (Group IV). The remaining ten patients served as controls and received inhalation anesthesia alone (Group C). Blood samples were withdrawn before and two hours after surgery and on postoperative days one and two to determine the blood NK cell activity using a chromium release assay with K562 cells as targets, plasma catecholamines and cortisol levels. The postoperative pain score and side effects were studied in the four groups. RESULTS: In Group IT0.5, the NK cell activity was lower on postoperative day 1 (23.9 +/- 8.4%) than the baseline level (45.7 +/- 13%) before surgery, and recovered on postoperative day 2. In Groups IT0.1, C and IV, the NK cell activities showed no significant changes. In all four groups, neither plasma adrenaline nor noradrenaline concentrations changed. In all four groups, the plasma cortisol levels increased after surgery, on postoperative days 1 and 2. The pain score was lower two hours after surgery and on postoperative day 1 in Group IT0.5 than in the other groups. CONCLUSION: These results suggest that long-lasting analgesic effects of intrathecal 0.5 mg morphine suppress the immune response following abdominal surgery.

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Our study was designed to determine whether supplementary information obtained with perfusion MRI can enhance accuracy. We used delayed perfusion, as represented by time to peak map on perfusion MRI, to classify strokes in 39 patients. Strokes were classified as hemodynamic if delayed perfusion extended to a whole territory of the occluded arterial trunk; as embolic if delayed perfusion was absent or restricted to infarcts; as arteriosclerotic if infarcts were small, multiple, and located mainly in the basal ganglias; or as unclassified if the pathophysiology was unclear. We compared these findings with vascular lesions on cerebral angiography, neurological signs, infarction on MRI, ischemia on xenon-enhanced CT (Xe/CT) and collateral pathway development. Delayed perfusion clearly indicated the area of arterial occlusion. Strokes were classified as hemodynamic in 13 patients, embolic in 14 patients, arteriosclerotic in 6 patients and unclassified in 6 patients. Hemodynamic infarcts were seen only in deep white-matter areas such as the centrum semiovale or corona radiata, whereas embolic infarcts were in the cortex, cortex and subjacent white matter, and lenticulo-striatum. Embolic and arteriosclerotic infarcts occurred even in hemo-dynamically compromised hemispheres. Our findings indicate that perfusion MRI, in association with a detailed analysis of T2-weighted MRI of cerebral infarcts in the axial and coronal planes, can accurately classify stroke as hemodynamic, embolic or arteriosclerotic.

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Nicotine produces profound behavioral effects in humans, but little is known about the sites of its action. There is a hypothesis that frontal lobe and limbic/cingulate cortical structures might be the sites. In this study, we examined the effects of cigarette smoking on feeling and cerebral blood flow (CBF) in human subjects. Young and healthy 9 cigarette smokers (all males, 24-33 years, average, 26.4) were included. After prohibiting them from smoking for 15 hours, CBF was measured using a Xenon CT-CBF system. Fifteen minutes later after allowing them to smoke two pieces of cigarette, the second CBF measurement was performed. Subtraction CBF map was created to display the changes after smoking. CT images were taken at three levels so as to include the cerebral lobes, basal ganglia, limbic system, brainstem and cerebellum. Arterial nicotine increased up to the levels 8 times higher than before smoking. The increases of blood pressure and pulse rate were minimal. Arterial carbon dioxide level and hematocrit did not change. Feeling after smoking was variable in individual subject. In 8 subjects with a relatively high feeling, CBF increased mainly in the frontal lobe, hippocampus, uncus, thalamus and caudate nucleus. CBF did not change in the parietal, temporal and occipital lobes, and in the putamen, insula, brainstem and cerebellum. In two subjects with uncomfortable feeling, CBF did reduce in the whole brain. The CBF increase in frontal lobe and limbic structures seems to be secondary to nicotine-induced neuronal activation in each structure. Mesocorticolimbic dopamine system, which is believed to influence learning, memory or emotional performance, appears to be a target for nicotine. The CBF reduction in the whole brain might be due to cerebral vasoconstriction or be secondary to a systemic hypotension.

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A 30-year-old woman was admitted to our hospital for investigation of an abnormal shadow in the right pulmonary hilus on a chest X-ray film. A percutaneous needle biopsy was performed, which revealed pulmonary blastoma. A right upper lobectomy was performed and the pathological stage was confirmed to be IIIa (T3N0M0). An analysis of preoperative cytological specimens showed that epithelial tumor cells with thin cytoplasm were either tubular or papillary, while some mesenchymal tumor cells with elliptic and spindle-shaped nuclei were also found in the necrotic background. Thus, pulmonary blastoma should be considered when a two-cell pattern consisting of both epithelial and mesenchymal components is observed. DNA analysis was performed on previously identified areas of the epithelial or sarcomatous components, using a microdissection method. An analysis of the p53 gene by the single-strand conformation polymorphysm method showed an abnormal band with shifted mobility of exon 8 in only the sarcomatous component.

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Sarcoidosis is a chronic inflammatory disease of unknown aetiology characterized by the formation of non-necrotizing granulomas. The course of disease is usually self-limiting with the spontaneous resolution of granuloma. In the immune system, Fas antigen (Fas) and Fas ligand (FasL) are involved in the down regulation of immune reactions by inducing apoptosis. Therefore, it was hypothesized that the Fas/FasL pathway and apoptosis may be associated with the course of granulomatous inflammation in sarcoidosis. Terminal deoxynucleotidyl transferase-mediated biotin nick end-labelling (TUNEL) was performed to assess deoxyribonucleic acid strand breakages as a characteristic of apoptosis. Immunohistochemistry was also performed to detect Fas and FasL protein, and reverse transcriptase polymerase chain reaction (RT-PCR) and RT in situ PCR to detect FasL messenger ribonucleic acid (mRNA). Positive signals for TUNEL were detected in epithelioid histiocytes and lymphocytes within granulomas and in bronchoalveolar lavage (BAL) lymphocytes from patients with sarcoidosis. Positive signals for Fas were also detected in these cells. FasL mRNA was expressed in BAL lymphocytes from 15 of 20 patients with sarcoidosis, but from only one of 10 patients with normal lung parenchyma. FasL protein was expressed in lymphocytes surrounding and within the granuloma. There was a significant correlation between the result of TUNEL and clinical course in patients with sarcoidosis. Apoptosis in epithelioid histiocytes and inflammatory cells seems to participate in the course of granulomatous inflammation. Further studies are needed to determine the role of Fas, FasL and other regulatory factors in apoptosis in the granulomatous inflammation in pulmonary sarcoidosis.

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CONTEXT: International differences in compliance of patients undergoing hemodialysis are poorly characterized and could contribute to international survival differences. OBJECTIVE: To compare international differences in patient compliance with hemodialysis treatments. DESIGN: A prospective observational study of patients undergoing hemodialysis in 1995 and a cross-sectional survey of health care professionals caring for hemodialyzed patients in 1996. SETTING AND PATIENTS: Four dialysis centers in the southeastern United States with 415 patients undergoing hemodialysis, 1 center in Sweden with 84 patients, and 4 centers in Japan with 194 patients participated in the prospective observational study. In the cross-sectional survey, nurses and nephrologists from the United States (n = 49), Japan (n = 21), and Sweden (n = 16) responded to questions regarding the compliance of their patients undergoing hemodialysis. MAIN OUTCOME MEASURES: Percentage of patients who miss a dialysis treatment and number of missed dialysis treatments. RESULTS: Of 415 US patients, 147 missed 699 treatments over a 6-month period (28.1 missed treatments per 100 patient-months or 2.3% of all prescribed treatments). During a 3-month period, there were 0 missed treatments per 100 patient-months for patients from Japan and 0 missed treatments per 100 patient-months for patients from Sweden (P<.001). In the cross-sectional survey, the mean (SD) estimated percentage of patients missing a treatment per month was 4% (3%) for the United States, 0% for Japan, and 0.1% (3%) for Sweden (P<.001). CONCLUSIONS: Noncompliance is much more common in US patients undergoing hemodialysis than Swedish and Japanese patients. The implications of these results for international differences in survival deserve further study.

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A 27-year-old male had experienced an episode of severe headache and nausea, sometimes accompanied by an inability to name objects. Magnetic resonance imaging showed a huge cyst within the left temporal lobe and a high degree of brain shift by it. A small round mass, which appeared to be a mural nodule, was located in the tip of left middle fossa. It was highly enhancing together with its attached dura mater, but the cyst wall was not enhanced. Sphenoid ridge meningioma with an associated intracerebral cyst or cystic glioma invading the dura mater was suspected. During surgery the small tumor was found to be arising from the sphenoid ridge and evaginating into the tip of the temporal lobe. The intracerebral cyst had a smooth surface and the tumor was visible outside the cyst through its wall. The tumor was totally removed, but the cyst wall was left without excision. Postoperatively he had no symptoms. Histological examination showed a microcystic meningioma. It is stressed that differentiations of cystic meningiomas from other cystic tumors and, of intratumoral from extratumoral cystic meningiomas using radiological, operative or histological findings are important.

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Fifty-two brain metastatic lesions occurring in 20 patients with small cell lung carcinoma (SCLC) were irradiated, and then the relationship between tumor size, dose and control was clinically and histopathologically studied. Lesions of 8 mm in diameter and those of 10 mm in diameter were determined to be controllable by irradiation at about 38 Gy and 42 Gy, respectively. According to size-dependent curative minimum doses, the lesions could be divided by the 10 Gy/ 5fr/wk method into controlled and non-controlled groups with the curve expressed as dose (Gy) = 15.27 log10 [tumor volume (mm3)] +0.6. Based on these results, tumors of 2 mm and 3 mm in diameter were estimated to be controllable at 14 and 20 Gy, respectively. Thus prophylactic cranial irradiation (PCI) in the treatment of SCLC was thought to be not always necessary if early treatment of small metastatic lesions, detected by Gd-DTPA-enhanced MRI could be achieved. The optimal interval between follow-up examinations was thought to be 1 month during the first two years after the diagnosis of SCLC, and then 3 months after that. In addition, the omission of PCI can save many patients who do not actually require PCI from suffering its adverse effects.

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