Management of soft tissue sarcomas (STS) in first isolated local recurrence: a retrospective study of 83 cases.

PURPOSE: To analyze the management and clinical outcome of patients treated for a first isolated local recurrence of soft tissue sarcomas (trunk or extremities) and to identify prognosis factors. METHODS AND MATERIAL: Between 1980 and 1999, 83 adult patients were included in the study. Mean age was 61 years. Mean tumor size was 6 cm. Most sarcomas were located in extremities (n=74), were deep (n=60), and proximal (n=53); 30 involved nerves or vessels. Histologic subtypes were mainly grade 2 (42%) or 3 (36%) histiocytofibrosarcomas (49%) and liposarcomas (20%). Surgical treatment of recurrences consisted in wide excision (29 cases), marginal resection (43 cases), 5 patients requiring amputation. Final results were R0 (n=33), R1 (n=47) or R2 (n=3) resection. Besides surgery, 6 patients received neo-adjuvant and 7 others adjuvant chemotherapy. Twenty three patients received post-operative external beam radiotherapy (EBRT) (mean dose 55 Gy) and 26 interstitial 192Ir low dose rate brachytherapy (BCT) (mean dose 45 Gy for BCT alone, 22 Gy when associated with EBRT), 19 patients being re-irradiated. RESULTS: Mean follow up was 13 years. Thirty-seven (45%) patients relapsed, 62% of whom presenting an isolated local recurrence. Nineteen patients developed distant metastases. Multivariate analysis showed only tumor depth (P=0.05) and re-resection for primary R1 resection (P=0.018) being independent prognosis factors for tumor control, radiotherapy (EBRT and/or BCT) being significant in univariate analysis (P=0.05). Overall survival rate was 73%, 54%, and 47% at, respectively, 3.5 and 10 years, and was 65%, 35% and 32% after a further local recurrence. Multivariate analysis showed trunk (P=0.0001) or inferior extremity locations (P=0.023), symptomatic (P=0.001), high grade (P=0.01), deep (P=0.01) tumors, and the occurrence of a further local failure (P=0.004) as unfavorable characteristics for overall survival. CONCLUSIONS: A first isolated local recurrence of STS increases mainly the risk of a subsequent local relapse. Quality of local treatment is decisive. When a conservative treatment is feasible, it should combine surgical resection and radiotherapy, BCT being the best suited in previously irradiated patients. Efforts have to be pursued to increase quality of the treatment of primary tumors, at best performed in centers that have expertise in this field.     

Nitric oxide and aneurysm formation in Kawasaki disease

The objective of this study is to show that nitric oxide plays a role in the development of coronary artery abnormalities in Kawasaki disease. We examined nitrite + nitrate, biopterin and neopterin in 316 urine samples of 34 patients with Kawasaki disease, those of 24 patients with other diseases, and those of 25 healthy children acting as a control group, because urinary nitrite + nitrate are reportedly useful as markers of nitric oxide generation in vivo , and pathways for neopterin-biopterin synthesis and nitric oxide generation are tightly coupled. In our study, the children with Kawasaki disease excreted more urinary nitrite + nitrate and neopterin than did the healthy control group children and excreted abnormally high quantities more often than did the patients with other diseases. Good relationships were found between the urinary nitrite + nitrate levels and the urinary biopterin levels, and between these biopterin levels and the urinary neopterin levels. Nitric oxide is therefore thought to be generated in abnormally high quantities, and to be closely related to the pathology of Kawasaki disease and to the development of coronary artery abnormalities. The role of nitric oxide in Kawasaki disease should be further studied to elucidate the pathophysiology of the disease and to aid in the development of new treatments.     

Subependymoma of the septum pellucidum: Characterization by PET

We report the evaluation of a subependymoma of the septum pellucidum by positron emission tomography (PET) with analysis of ₁₈F-fluorodeoxyglucose (FDG)kinetics. The tumor showed exceedingly low rates of glucose metabolism (rCMRG1) and kinetic constants (K1, K2, and K3). This hypometabolism indicates low cellular density and slow growth.     

Evaluation of syringomyelia with three-dimensional constructive interference in a steady state (CISS) sequence

The purpose of this study was to evaluate a three-dimensional (3D) constructive interference in steady state (CISS) sequence in the assessment of syringomyelia. Eleven patients with syringomyelia were prospectively studied with magnetic resonance imaging. All patients underwent sagittal imaging with T1- and T2-weighted spin-echo (SE), and 3D-CISS sequences. The SE and 3D-CISS images, as well as multiplanar reconstruction (MPR) images of the 3D-CISS sequence, were analyzed with regard to image quality, degree of artifacts, visualization of the extent and internal structure of the syringomyelia, and contrast-to-noise ratio (CNR) of the fluid within the syringomyelia. Contrast between the spinal cord and cerebrospinal fluid (CSF), as well as delineation was significantly poorer for the T1-weighted SE sequence than for the 3D-CISS sequence (P < 0.01), while there was no significant difference between the T2-weighted SE sequence and the 3D-CISS sequence. Artifacts induced by CSF flow were significantly more for the T2-weighted SE sequence than for the 3D-CISS sequence (P < 0.01). Although the extent of syringomyelia was delineated equally among the three sequences in 9 of 11 patients, it was better for the 3D-CISS sequence than for the SE sequences in the remaining two. Septation and communication between the cavities were best detected by the 3D-CISS MPR images. The CNR of the 3D-CISS sequence was significantly higher than that of the SE sequence (P < 0.01). The 3D-CISS sequence demonstrates the extent and internal structures of syringomyelia better than conventional SE sequences and should be added to SE sequences in the evaluation of syringomyelia.     

Primary transitional cell carcinoma of prostate: a case report

A 67-year-old male was admitted with a three-month history of voiding difficulty. Prostate specific antigen remained within the normal limit. Under the diagnosis of benign prostatic hypertrophy, transurethral resection of prostate was performed. Pathological examination of the resected specimens of the prostate revealed transitional cell carcinoma. Two courses of systemic M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) chemotherapy were performed, followed by cystoprostatourethrectomy, pelvic lymphadenectomy, and ileal conduit construction. Now one year has elapsed, with no clinical signs of recurrence.     

MN/CA IX antigen as a potential target for renal cell carcinoma

MN/CA IX is considered as a carbonic anhydrase isoenzyme expressed in the normal alimentary tract in a tissue-specific manner. This antigen is activated in the majority of renal cell carcinomas (RCC) but not in the normal kidney tissues. Our previous study revealed that increase of malignant potential is related to down-regulation of MN/CA9. To investigate the mechanism of MN activation in RCC, we examined the methylation status of this gene (MN/CA9) in RCC cell lines (SKRC-1, 6, 10, 12, 14, 44, 59). Moreover, we analyzed the circulating blood of patients for the presence of RCC cells by RT-PCR, to determine whether detection of circulating RCC cells could be useful as a biomarker. CpG methylation was investigated at 7 CpG sites in the MN/CA9 5' region. Clear mRNA signals were observed in 5 cell lines (SKRC-1, 6, 10, 44, 59), e.g., MN/CA9 positive. These 5 MN-positive cell lines showed hypomethylation in the 5' region. In contrast, all CpG sites were methylated in the remaining 2 lines and 3 normal kidney tissue samples. These results suggest that hypomethylation in the 5' region may play an important role in the expression of MN/CA9 in RCC. RT-PCR analysis of blood samples from RCC patients revealed the presence of circulating MN-positive cancer cells in the blood. Although a significant correlation with tumor stage and grade was not observed, the analysis of blood samples from patients with metastases resulted in a high detection rate of 82%. These findings suggest the usefulness of MN/CA IX as a potential diagnostic marker for detection of RCC.     

Application of PET-MRI registration techniques to cat brain imaging

In positron emission tomography (PET) studies of diseased animals, it is very useful to have accurate anatomical information as a reference. In human studies, anatomical information is usually obtained from magnetic resonance imaging (MRI) of the subject with retrospective registration of the subject's PET image to the MRI. A number of PET-MRI registration techniques are used for this purpose. However, the utility of these methods has not been tested for animals image registration. This paper studies the feasibility of applying two currently used human brain PET-MRI registration techniques to cat brain images. METHODS: Three cats were anesthetized with isoflurane gas, and PET images were acquired with H(2)(15)O, benzodiazepine receptor ligand 11C-flumazemil (FMZ), dopamine receptor ligand 11C-nemonapride (NEM) and fluorodeoxy glucose (18F-FDG). The four PET scans were acquired consecutively within the same day while the cat remained fixed in the scanner. We also obtained T1-weighted and T2-weighted MRI of the cats in a 4.7 T unit. The PET images were registered to MRI using two human brain registration techniques: a semi-automatic method (SAM), which is a two-step method based on the extraction of the midsagittal plane, and an automatic method (AMIR) method that minimizes PET pixel variance within spatially connected segments determined by MRI. RESULTS: T2-weighted MRI provided better structural information than T1 MRI. FMZ did, while FDG or H(2)O PET images did not, provide a structural outline of the brain. The FMZ PET image was registered to MRI satisfactorily using SAM. The striatum visualized in nemonapride PET image re-sliced with the same parameters matched the striatum identified in T2-weighted MRI. Registration by AMIR was successful by inspection for FMZ, FDG or H(2)O PET images in only one of the three cats. The registration error of SAM was estimated to be less than 2 mm or 2 degrees. CONCLUSION: A satisfactory registration of FMZ-PET to T2-weighted MRI of the cat brain was obtained by a two-step manual registration technique. This will enhance the usefulness of PET in the field of cerebral pathophysiology.     

Sevoflurane does not inhibit human platelet aggregation induced by thrombin

BACKGROUND: Sevoflurane reportedly inhibits adenosine diphosphate-induced platelet aggregation by suppressing thromboxane A2 formation. The increase in intracellular calcium concentration that fosters platelet aggregation, however, is also induced by other cell signaling pathways, such as activation of the production of inositol 1,4,5-triphosphate by thrombin. The current study aimed to clarify the net influence of sevoflurane on thrombin-induced platelet aggregation. METHODS: Washed platelets were stimulated by thrombin after incubation with 0.5, 1.0, or 1.5 mM sevoflurane, halothane, or isoflurane. Aggregation curves were measured by an aggregometer. Intracellular calcium concentration was measured fluorometrically using fura-2. Calcium mobilization via plasma membrane calcium channels and the dense tubular system was assessed differentially. Intracellular inositol 1,4,5-triphosphate was measured by radioimmunoassay. RESULTS: Halothane significantly suppressed aggregation ratios at 5 min compared with those in controls (89 +/- 7%) to 71 +/- 10% (1.0 mM) and 60 +/- 11% (1.5 mM) and the increase in intracellular calcium concentration (controls, 821 +/- 95 nM vs. 440 +/- 124 nM [1.0 mM] or 410 +/- 74 nM [1.5 mM]). Halothane also significantly inhibited release of calcium from the dense tubular system (controls, 220 +/- 48 nM vs. 142 +/- 31 nM [1.0 mM]). Neither sevoflurane nor isoflurane produced a net change in aggregation ratios, intracellular calcium concentration, or calcium mobilization. Halothane (1 mM) significantly suppressed inositol 1,4,5-triphosphate concentrations, whereas neither 1 mM isoflurane nor 1 mM sevoflurane had any effect. CONCLUSIONS: Although sevoflurane has been reported to inhibit human platelet aggregation induced by weak agonists such as adenosine diphosphate, it does not inhibit human platelet aggregation induced by strong agonists such as thrombin.     

Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells.

Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.     

Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy: A comparison of123I-MIBG scintigraphic and echocardiographic data

It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123I-MIBG scintigraphy. Both of these methods are associated with beta-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patients with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography: and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123 [123I] meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r = 0.682, p = 0.0146), wall motion after dobutamine stress (r = 0.758, p = 0.0043), the change in wall motion (r = 0.667, p = 0.0178), and with left ventricular diastolic diameter (r = 0.837, p = 0.0007). In addition, the 123I-MIBG washout rate correlated with baseline wall motion (r = 0.608, p = 0.0360), wall motion after dobutamine stress (r = 0.703, p = 0.0107), and with the change in wall motion (r = 0.664, p = 0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure.