Metabolic tumor volume of metastatic lymph nodes and survival after total laryngectomy in laryngeal and hypopharyngeal cancer.

OBJECTIVES: The prognostic value of metabolic tumor volume (MTV) in locally advanced laryngeal or hypopharyngeal cancer is established in the setting of chemoradiotherapy, while it remains unknown in the setting of upfront total laryngectomy. MATERIALS AND METHODS: We retrospectively analyzed 88 patients receiving total laryngectomy and neck dissection, using Cox regression models. RESULTS AND CONCLUSION: Variables related to metastatic lymph node were associated with overall survival, whereas those related to primary tumor were not. In multivariable models, MTV of metastatic lymph nodes (N-MTV) as a continuous variable (Akaike's information criterion (AIC), 277.5) was equivalent to pathological nodal status (AIC, 278.2; P = 0.40), and superior to pathological nodal classification as an ordinal variable (AIC, 281.4; P < 0.05) in ability of predicting death. The risk of death was increased by 1.2-fold (95% confidence interval (CI), 1.0-1.4; P = 0.03) every 10-ml increment of N-MTV, while patients with pN+ disease were at a higher risk of death by 2.9-fold (95% CI, 1.0-12.2; P < 0.05) compared with patients with pN0 disease. Using recursive partitioning analysis (RPA), we classified the patients as having a low, intermediate, or high risk of death on the basis of N-MTV and extranodal extension (ENE). This RPA classification system exhibited greater concordance with overall survival than the classification considering pathological nodal status and ENE (AIC, 275.8 versus 281.4; P = 0.02). In the setting of upfront total laryngectomy, N-MTV is a critical predictor of mortality. A staging system in which N-MTV is incorporated may better inform adjuvant treatment decisions.

Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas.

BACKGROUND AND PURPOSE: Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS: Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS: Grade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS: (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.

MR imaging-based correction for partial volume effect improves detectability of intractable epileptogenic foci on iodine 123 iomazenil brain SPECT images: an extended study with a larger sample size.

BACKGROUND AND PURPOSE: It has been suggested, on the basis of a previous pilot study conducted in a small number of patients, that MR imaging-based PVE correction in I-123 iomazenil brain SPECT improves the detectability of cortical epileptogenic foci. In the present study, we performed an investigation by using a larger sample size to establish the effectiveness of the PVE correction and to conduct a detailed evaluation based on the histologic classification of lesions. MATERIALS AND METHODS: Seventy-five patients (male/female, 37/38; age, 28 ± 12 years) with intractable epilepsy who had undergone surgical treatment were enrolled in this study. I-123 iomazenil SPECT and MR imaging examinations were performed before the operation in all patients. I-123 iomazenil SPECT images with and without MR imaging-based PVE correction were assessed visually and by semiquantitative analysis based on the AI(%) of the SPECT count in the resected lesions. RESULTS: The sensitivity, specificity, and accuracy of foci detection by visual assessment were significantly higher after PVE correction compared with the values obtained before the correction. The results of the semiquantitative analysis revealed that the asymmetry of the SPECT counts was significantly increased after the PVE correction in the surgically resected lesions in cases of mesial temporal sclerosis, tumor, and malformations of cortical development. CONCLUSIONS: The effectiveness of MR imaging-based PVE correction in I-123 iomazenil brain SPECT in improving the detection of cortical epileptogenic foci with abnormal histologic findings was established by our investigation conducted on a large sample size.

Unicentric and multicentric Castleman's disease.

Castleman's disease (CD) appears at ubiquitous lymph nodes. To date, detection of the lesion focus for CD has mainly been carried out by physical examination and radiological findings, such as X-ray analysis, CT and MRI. 18F-FDG PET visualizes the active focus of glucose metabolism and the clinical value has been investigated for many different tumours. Previous studies of 18F-FDG PET for CD have only reported four cases of unicentric CD and no cases of multicentric CD. In this paper, we report two cases of CD, one with unicentric CD and one with multicentric CD. We demonstrate that the use of 18F-FDG PET for the detection and monitoring of patients with CD, especially multicentric CD, would be effective.

Radionuclide imaging metabolic activity of brown adipose tissue in a patient with pheochromocytoma.

We describe a patient with extra-adrenal pheochromocytoma and high plasma norepinephrine levels. Radionuclide images of this patient obtained using (18)F-fluorodeoxyglucose and (123)I-metaiodobenzylguanidine revealed bilateral tracer accumulation in the shoulder and lower neck. The regions of radiotracer uptake corresponded to the location of human brown adipose tissue (BAT). Excessive sympathetic stimulation by high circulating catecholamine concentrations augmented the metabolic activity and tracer uptake in the BAT. This study showed that radionuclide imaging can noninvasively visualize human BAT in terms of metabolic and functional activity.

Chordoma with postoperative subcutaneous implantation and meningeal dissemination: MRI.

Chordomas are histologically benign tumours which are locally invasive. We present an unusual case of recurrent chordoma with subcutaneous implantation and widespread meningeal dissemination after surgery. Contrast-enhanced MRI was useful for determining the extent of the tumour.

Brain perfusion SPECT study with 99mTc-bicisate: clinical pitfalls and improved diagnostic accuracy with a combination of linearization and scatter-attenuation correction.

To evaluate the usefulness of a combination of linearization and scatter-attenuation correction on 99mTc-bicisate (ECD)-single photon emission tomographic (SPECT) images, both cerebral blood flow (CBF)-positron emission tomographic (PET) images and ECD-SPECT images from fifteen patients with chronic cerebral infarction were acquired. We measured radioactivity counts in regions of interest (ROIs) on all sets of both images and obtained a 2D scattered graph between ECD-SPECT and CBF-PET data. To evaluate diagnostic accuracy, the sensitivity, specificity and accuracy of ECD-SPECT images were calculated by means of discriminant analysis. The same analysis was also performed on the ECD-SPECT images corrected by a combination of linearization and scatter-attenuation correction. An overall nonlinear relationship was observed between ECD-SPECT and CBF-PET. The sensitivity, specificity, and accuracy of ECD-SPECT images were 69.6%, 91.4% and 73.0%, and those of ECD images corrected by the combination of linearization and scatter-attenuation correction were 79.5%, 95.7% and 82.0% respectively. The clinically diagnostic accuracy of ECD-SPECT images corrected by the combined method apparently increased. So that the linearization with the scatter-attenuation method is useful for improving the diagnostic accuracy of ECD-SPECT images.

Localization of endothelial nitric oxide synthase messenger ribonucleic acid by in situ hybridization in ectopic endometrial tissue in patients with adenomyosis.

This study was undertaken to determine the expression of endothelial nitric oxide synthase (NOS) mRNA in ectopic endometrium in adenomyosis. Endothelial NOS mRNA expression was investigated by in situ hybridization using a human endothelial NOS RNA probe. The subjects comprised six cases of adenomyosis, and 14 women with normal fecundity as controls. Specific expression of endothelial NOS mRNA was found in glandular and surface epithelial cells in eutopic endometrium throughout the menstrual cycle in all groups. It is noteworthy that the expression of endothelial NOS mRNA was moderately positive in ectopic endometrial tissues in three of the six cases of adenomyosis. In conclusion, the endothelial NOS mRNA expression seen in the ectopic endometrium suggests a possible relationship with the various pathologies associated with adenomyosis.

Blood flow and metabolism of oligodendrogliomas: a positron emission tomography study with kinetic analysis of 18F-fluorodeoxyglucose.

To accurately characterize the pathophysiology and proliferating activity of oligodendrogliomas, we studied cerebral blood flow and metabolism using positron emission tomography (PET) in five patients with this tumor. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and cerebral metabolic rates of oxygen (rCMRO2) and of glucose (rCMRGl) were quantitatively measured in tumor lesions and the contralateral gray matter, rCMRGl was analyzed based on both kinetic and autoradiographic methods. Tumor rCBF and rCBV were lower than in the contralateral gray matter in all preoperatively examined patients. Oxygen metabolism, determined by rCMRO2 and rOEF, was consistently reduced in the tumor (rCMRO2, P<0.05 vs. gray matter, determined by the Student's t-test). Tumor rCMRGl was significantly lower than the gray matter rCMRGl in both kinetic (P<0.01) and autoradiographic (P<0.05) analyses. Kinetic tumor rCMRGl varied between 1.22 and 4.13 mg/100 ml/min, but was lower than the gray matter value in all patients. Autoradiographic tumor rCMRGl, which ranged from 1.02 to 5.79 mg/100 ml/min, was also reduced in all tumors but one; the remaining tumor, which had a relatively high value of autoradiographic rCMRGl (comparable to gray matter rCMRGl), infiltrated the contralateral hemisphere through the corpus callosum, and was characterized by high cellular density. In one patient who suffered from tumor recurrence 8 years and 10 months after initial treatment, phosphorylation constant (K3) and kinetic rCMRGl of the recurring tumor were higher than those of the original tumor. No other tumors have regrown or recurred during the postoperative follow-up periods, which ranged from 22 to 130 months (median = 101 months). Circulation and metabolism measured by PET provide in vivo biological characteristics, including proliferating activity, in oligodendrogliomas.

Immunohistochemical assessment of superoxide dismutase expression in the endometrium in endometriosis and adenomyosis.

OBJECTIVE: To determine the expression of superoxide dismutase (SOD) in the endometrium during the menstrual cycle in endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of SOD in endometrial tissues using the monoclonal antibody. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): The subjects were divided into three groups: 36 patients with endometriosis, 38 patients with histologically proven adenomyosis, and 47 fertile control subjects. INTERVENTION(S): Endometrium was biopsied throughout the menstrual cycle. MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining (evaluation nomogram) score for endometrial cells. RESULT(S): The analyses revealed phase-dependent changes in the expression of SODs in the glandular and surface epithelia during the menstrual cycle in fertile controls. Specifically, the expression of copper, zinc SOD was weakest in the early and midproliferative phases, then gradually increased, and was most marked in the early and midsecretory phases. The expression of manganese SOD reached a peak in the late secretory phase. The expression of both SODs in endometriosis and adenomyosis was persistently higher than the control levels throughout the menstrual cycle. CONCLUSION(S): The exaggerated expression of both SODs in the endometrium throughout the menstrual cycle suggests that superoxide plays a key role in infertility in endometriosis and adenomyosis.

Development of a new method for simultaneously evaluating mucociliary clearance and pulmonary epithelial permeability in rabbit experiments by means of 18FDG, three-dimensional positron emission tomography and rectilinear scan.

We tried to simultaneously obtain the elimination constant of mucociliary clearance and the pulmonary epithelial permeability constant after inhalation of 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) solution by carrying out whole lung positron emission tomography and a rectilinear scan in rabbit experiments. The elimination constant of pulmonary epithelial permeability was obtained from the decrease in the amount of the radioactivity with time in the region of interest (ROI) confined to the lungs, trachea and tracheal cannula in the rectilinear scan. The total elimination constant of the radioactivity in the lungs was obtained from the ROI confined to the lungs in the tomography. The mucociliary clearance rate constant in the lungs was then obtained after subtracting the elimination constant of the pulmonary epithelial permeability from the total elimination constant of the 18FDG in the lungs. The mucociliary clearance constant in the trachea was calculated from the residual radioactivity in the trachea and the mucociliary clearance constant in the lungs. The mean pulmonary epithelial permeability constant was 0.0020% min(-1) obtained from the rectilinear scan. The mean mucociliary clearance constants of the lungs and the trachea were 0.0006 and 0.025% min(-1), respectively. These results indicated that the pulmonary epithelial permeability and mucociliary clearance could be evaluated simultaneously with 18FDG by using three-dimensional positron emission tomography and a rectilinear scan.

Is adenomyosis an immune disease?

Adenomyosis is characterized as ectopic endometrial tissues within the myometrium in the uterus. The only difference between adenomyosis and endometriosis is the site of endometriotic tissues: inside or outside of the uterus. It is well known that endometriosis is frequently associated with various autoimmune phenomena. This short review covers various aspects of the immune cascade found in adenomyosis. In adenomyosis, a series of immune responses is activated, including changes in both cellular and humoral immunity, i.e. a strong expression of cell surface antigens or adhesion molecules, an increased number of macrophages or immune cells, and deposition of immunoglobulins and complement components. Furthermore, the disease exhibited high frequency of autoantibodies in peripheral blood. Thus, an immunological 'vicious circle' is formed in the endometrium in adenomyosis. Endometrial cells seem to be under immunological stress, protecting themselves by exposing heat shock proteins. It is concluded that the endometrial environment in adenomyosis differs widely from that in normal fertile women. These abnormal immune responses might be involved in poor reproductive performance in adenomyosis.

Sarcoma botryoides of the uterine cervix: a case report.

Rhabdomyosarcoma of the uterine cervix is a very rare disease. We present a case of rhabdomyosarcoma (botryoide type) arising from the introitus of the uterine cervix, and make a discussion on the diagnosis, treatment and involving factors of prognosis.

Endothelial nitric oxide synthase in the endometrium during the menstrual cycle in patients with endometriosis and adenomyosis.

OBJECTIVE: To determine the expression of endothelial nitric oxide synthase in the endometrium during the menstrual cycle in endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of endothelial nitric oxide in endometrial tissues using the monoclonal antibody. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): The subjects were divided into three groups: 35 patients with endometriosis, 33 patients with adenomyosis proven histologically, and 46 fertile controls. MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining (evaluation nomogram) score in endometrial cells. RESULT(S): The analyses revealed phase-dependent changes in the expression of endothelial nitric oxide synthase in the surface and glandular epithelia during the menstrual cycle in the fertile controls. The expression was weakest in the early proliferative phase, gradually increased, was most marked in the midsecretory phase, and decreased thereafter. In contrast, stromal cells did not change throughout the cycle. Contrary to expectations, the expression of endothelial nitric oxide synthase in endometriosis and adenomyosis was persistently greater than the control levels throughout the menstrual cycle. CONCLUSION(S): This study has shown that endothelial nitric oxide synthase is changed in a phase-dependent manner during the menstrual cycle. The exaggerated expression of endothelial nitric oxide synthase in the endometrium throughout the cycle suggests some pathologic role in endometriosis and adenomyosis.

Parapharyngeal meningioma extending from the intracranial space evaluated by FDG PET.

We report a rare case of parapharyngeal meningioma extending from the intracranial space evaluated by PET with [18F]-2-fluorodeoxyglucose (FDG). Although the parapharyngeal meningioma had a high rate of glucose metabolism, it was proved to be pathohistologically benign. The high rate of glucose metabolism of the tumor reflected tumor aggressiveness well because the tumor grew in a relatively short time.

[Efficacy of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scans in diagnosis of pulmonary nodules].

To evaluate the value of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scans, we performed FDG-PET scans in 23 patients with indeterminate pulmonary nodules less than 3 cm in size and analyzed these scans qualitatively and semiquantitatively. Histologic specimens were obtained by thoracoscopic excisional biopsy in 16 patients, CT-guided needle aspiration cytology in three, and bronchoscopic brushing cytology in four. Pathological diagnoses were lung cancer in 16 patients, benign inflammation in six, and malignant lymphoma in one. Sensitivity, specificity and accuracy of the FDG-PET scans were 88% (15/17), 67% (4/6) and 83% (19/23), respectively. There were two false-positive cases (organizing pneumonia and cryptococcosis) and two false-negative ones (slow-growing adenocarcinoma and malignant lymphoma). Although a few false-positive cases of granulomatous disease were yielded, the FDG-PET scans were highly sensitive in the detection of lung cancer. We conclude that the FDG-PET scanning in a useful diagnostic imaging modailty in the management of indeterminate pulmonary nodules.

Intracarotid recombinant human tumor necrosis factor-alpha reduces cerebral blood flow and methionine uptake in rat brain tumors.

The aim of the present study is to understand the therapeutic effects of recombinant human tumor necrosis factor-alpha (rH-TNF) on hemocirculation and metabolism of brain tumors. Using double-label autoradiographic technique, we have monitored changes in regional cerebral blood flow (rCBF) and protein-bound fraction of (3H-methyl)-L-methionine, expressed as acid-insoluble fraction (AIF), in rat brain tumors following treatment with intracarotid rH-TNF. The central portion of tumors showed a significant decrease in rCBF and AIF at 4 hours after the injection (p < 0.01, p < 0.05, respectively, as compared with non-treated control rats), turned microscopically necrotic at 24 hours, and became more extensively necrotic at 72 hours. Tumor cells remained viable only in the peripheral portion of the tumors after the treatment. The peripheral portion also showed a moderate decrease in rCBF, but less change in AIF to 4 to 72 hours after the treatment. Neither ipsilateral nor contralateral non-involved cortex demonstrated appreciable changes in rCBF and AIF during the observed period. Intracarotid rH-TNF selectively reduces tumor rCBF and AIF, resulting in histological modification.

Distribution of heat shock proteins in eutopic and ectopic endometrium in endometriosis and adenomyosis.

OBJECTIVE: To evaluate the pathophysiologic role of heat shock proteins and to examine the effect of danazol on these proteins in patients with endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of human heat shock proteins 27, 60, and 70 in endometrial glandular cells identified using monoclonal antibodies. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): Subjects were 119 women with documented endometriosis or adenomyosis. The subjects were divided into three groups: fertile control (n = 38), with 14 in the proliferative phase and 24 in the secretory phase; endometriosis (n = 38); and adenomyosis (n = 43), including 33 who underwent hysterectomy and 10 treated with danazol. MAIN OUTCOME MEASURE(S): Staining of glandular cells by semiquantitative immunostaining (evaluation nomogram) score. RESULT(S): Significantly increased expression of heat shock protein 27 was noted in eutopic endometrium from patients with endometriosis and adenomyosis as compared with controls, regardless of the menstrual phase. The scores for heat shock protein 27 and heat shock protein 70 in the ectopic endometrium of patients with endometriosis were low compared with those in eutopic endometrium, whereas in adenomyosis, the scores were similar to those of eutopic endometrium. After treatment with danazol, the expression of heat shock proteins returned to control levels. CONCLUSION(S): We suggest that abnormally increased expression of heat shock proteins plays a role in the pathophysiology of endometriosis and adenomyosis.

Technetium-99m-ECD brain SPECT in misery perfusion.

UNLABELLED: Discordant findings of 99mTc-methyl cysteinate dimer (99mTc-ECD) brain distribution have been reported when brain tissue is supplied by excess blood flow. We evaluated changes in 99mTc-ECD brain activity in the opposing pathological state, in which cerebral blood flow (CBF) is more profoundly impaired than metabolism, and analyzed the relationship of 99mTc-ECD activity with CBF and metabolism to investigate the dominant regulating factor on 99mTc-ECD distribution. METHODS: Twelve patients with unilateral intracranial steno-occlusive diseases were evaluated using dynamic and static 99mTc-ECD SPECT. Relative 99mTc-ECD activities and the retention ratio of the affected and unaffected cortices were compared with CBF and oxygen metabolism obtained by PET. Change in the relationships until 1 hr after tracer injection were also analyzed. RESULTS: Relative 99mTc-ECD activity was significantly correlated with CBF, and the highest correlation was obtained for the first minute of imaging (r = 0.674, p < 0.0010. Fifteen minutes after injection, the correlation coefficient with CBF decreased, whereas higher correlation was observed with the parameter of oxygen metabolism (r = 0.758-0.815, p < 0.001). Changes in the retention ratio were dependent on changes in oxygen metabolism, and the retention ratio for the high oxygen extraction fraction (OEF) area was the same as that for the normal OEF area. CONCLUSION: In addition to CBF, brain distribution on 99mTc-ECD SPECT images is affected by brain metabolism, especially on delayed images after injection. The degree of discrepancy between CBF and metabolism should be considered when interpreting images of the misery perfusion state.