Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

¹8F-FP-(+)-DTBZ positron emission tomography detection of monoaminergic deficient network in patients with carbon monoxide related parkinsonism.

BACKGROUND AND PURPOSE: Although parkinsonism after carbon monoxide (CO) intoxication is well known, neurotransmitter deficient networks that are responsible for the severity of parkinsonism have rarely been systemically evaluated. METHODS: Eighteen patients with CO-related parkinsonism and nine age- and sex-matched controls were enrolled for detailed neurological examinations, three-dimensional T1-weighted images, diffusion tensor imaging and (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine ((18)F-FP-(+)-DTBZ) positron emission tomography (PET). The structural analysis included voxel-based morphometry to assess grey matter atrophy and tract-based spatial statistics related to white matter involvement. For presynaptic monoaminergic assessment, volume of interest analysis in six subcortical regions and non-parametric voxel-wise comparison were performed on PET images with estimation of registration parameters from magnetic resonance images. All the imaging modalities were compared between the patients and controls. For the patients, a regression model for correlation with cognitive behaviour and Unified Parkinson's Disease Rating Scale (UPDRS) score was used. RESULTS: In the patients, monoaminergic deficit networks were found in the caudate, anterior putamen, anterior insular, thalamus and anterior cingulate cortex. The UPDRS revealed significant correlations with the prefrontal white matter fractional anisotropy values and with the (18)F-FP-(+)-DTBZ uptake values in the caudate nucleus, insular, medial prefrontal and dorsomedial thalamus. The neuropsychiatric inventory score correlated with the (18)F-FP-(+)-DTBZ uptake values in the anterior cingulate cortex and dorsolateral prefrontal cortex. CONCLUSIONS: Our study demonstrated monoaminergic deficits and white matter damage networks in CO-related parkinsonism that determined the severity of parkinsonism or behaviour changes. As the substantia nigra was spared, the monoaminergic topography of involvement suggests a different pathophysiology in CO-related parkinsonism.

Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multicenter international pooled validation study.

PURPOSE: There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions. PATIENTS AND METHODS: We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions. RESULTS: In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I (2) statistic = 0). CONCLUSION: Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research.

BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research.

BACKGROUND: We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN-). METHODS: A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990-2011) had pN- disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan-Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis. RESULTS: A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN-. The 5-year OS and DSS of cN- patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates. CONCLUSIONS: Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN- nodes.

Phosphorylation of signal transducer and activator of transcription 1 reduces bortezomib-mediated apoptosis in cancer cells.

The potent and selective proteasome inhibitor bortezomib has shown remarkable antitumor activity and is now entering clinical trials for several cancers. However, the molecular mechanisms by which bortezomib induces cytotoxicity in ovarian cancer cells still remain unclear. In this study, we show that bortezomib induced apoptosis, which was demonstrated by the downregulation of antiapoptotic molecules (Bcl-2, Bcl-XL, p-Bad, and p-AKT) and the upregulation of proapoptotic proteins (p21, p27, and cleaved-Bid) in ovarian cancer cell lines. Moreover, bortezomib stimulates Janus kinase (JAK) phosphorylation and activates heat-shock transcription factor-1 (HSF-1) and heat-shock protein 70 (HSP70), ultimately leading to signal transducer and activator of transcription 1 (STAT1) phosphorylation. Phosphorylated STAT1 partially counteracted apoptosis induced by bortezomib in cancer cells. These findings suggest that the antitumor activity of bortezomib in ovarian cancer can be improved by inhibiting bortezomib-induced STAT1 phosphorylation. This effect can be achieved by STAT1 knockdown, HSP70 knockdown, JAK inhibition, or the addition of cisplatin, one of the most commonly used anticancer drugs. These results provide the first evidence that STAT1 phosphorylation can play a role in bortezomib resistance by exerting antiapoptotic effects. They also suggest the possibility to abolish or reduce bortezomib chemoresistance in ovarian cancer by the addition of cisplatin or JAK inhibitors.

Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: a preliminary study in swine.

BACKGROUND AND PURPOSE: FUS-induced BBB opening is a promising technique for noninvasive and local delivery of drugs into the brain. Here we propose the novel use of a neuronavigation system to guide the FUS-induced BBB opening procedure and investigate its feasibility in vivo in large animals. MATERIALS AND METHODS: We developed an interface between the neuronavigator and FUS to allow guidance of the focal energy produced by the FUS transducer. The system was tested in 29 swine by more than 40 sonication procedures and evaluated by MR imaging. Gd-DTPA concentration was quantitated in vivo by MR imaging R1 relaxometry and compared with ICP-OES assay. Brain histology after FUS exposure was investigated using H&E and TUNEL staining. RESULTS: Neuronavigation could successfully guide the focal beam, with precision comparable to neurosurgical stereotactic procedures (2.3 ± 0.9 mm). A FUS pressure of 0.43 MPa resulted in consistent BBB opening. Neuronavigation-guided BBB opening increased Gd-DTPA deposition by up to 1.83 mmol/L (a 140% increase). MR relaxometry demonstrated high correlation with ICP-OES measurements (r(2) = 0.822), suggesting that Gd-DTPA deposition can be directly measured by imaging. CONCLUSIONS: Neuronavigation provides sufficient precision for guiding FUS to temporally and locally open the BBB. Gd-DTPA deposition in the brain can be quantified by MR relaxometry, providing a potential tool for the in vivo quantification of therapeutic agents in CNS disease treatment.

Magnetic resonance imaging study of mouse islet allotransplantation.

Although only 10% of islet transplant recipients maintain insulin independence, 80% of them are C-peptide positive at 5 years. To better understand the fate of transplanted islets, a magnetic resonance imaging (MRI) technique has been used to detect superparamagnetic iron oxide (SPIO)-labeled transplanted islets. Recently, we successfully used a novel MRI contrast agent, chitosan-coated SPIO (CSPIO) nanoparticles, to monitor mouse islet isografts for 18 weeks after transplantation. In the present study, we tested whether CSPIO could be applied to monitor islet allografts, which are supposedly rejected without immune interventions. Male C57BL/6 and Balb/c mice were used as donors and recipients of islet transplantation, respectively. After overnight incubation with or without CSPIO (10 µg/mL), 300 C57BL/6 islets were transplanted under the left kidney capsule of each Balb/c mouse. Starting from day 10 after transplantation, 3.0-Tesla MRI of the recipients was performed weekly. Four mice were followed for ≥38 days. At 38 and 45 days, 1 islet graft was removed for insulin and Prussian blue staining, respectively. From days 10 to 45 after transplantation, CSPIO-labeled islet grafts were visualized on MRI scans as sustained distinct hypointense spots homogeneously located at the upper pole of left kidney, the site of transplantation. At days 38 and 45, the histology of CSPIO-labeled islet grafts revealed insulin and iron staining colocalized in the same areas. Our results in a mouse allotransplantation model indicated that CSPIO-labeled islets survived as long as 45 days with positive MRI.

Potential clinical role of 18F FDG-PET/CT in detecting hip prosthesis infection: a study in patients undergoing two-stage revision arthroplasty with an interim spacer.

AIM: We evaluated the potential role of [18F]fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) to identify latent infections at the site of an interim hip spacer after resection arthroplasty for hip prosthesis infection. METHODS: Twelve patients with an interim hip spacer following resection arthroplasty (Group A) were investigated. Twelve patients with painful primary hip prostheses served as controls (Group B). All underwent PET/CT before surgery. Both non-attenuation-corrected (NAC) and attenuation-corrected (AC) images were analyzed. Serum C-reactive protein (CRP) levels were measured in 22 patients. Elevated CRP level was defined as >/=10 mg/L. The diagnosis of infection was based on the results of intraoperative tissue cultures, intraoperative pathology, and clinical follow-up. RESULTS: FDG-PET/CT had 100% sensitivity and 100% negative predictive value for detection of latent infection in both groups. However, there were 4 and 3 false positive cases in Group A and Group B, respectively. Specificity improved from 50% to 62.5% in Group A, and from 62.5% to 87.5% in Group B when using NAC instead of AC. Seventeen patients had CRP values >/=10 mg/L, but only 8 were true positive for infection. FDG-PET/CT ruled out infection in 77.8% (7/9) of false-positive cases identified by CRP levels. CONCLUSION: FDG-PET/CT is highly sensitive to detect latent infections in prosthetic hips and in interim hip spacers. The high negative predictive value of PET/CT scans is useful to rule out infections in patients with persistently elevated CRP levels. PET/CT might serve as an auxiliary tool to exclude latent infections in patients posing a clinical diagnostic dilemma.

Magnetic resonance imaging of transplanted mouse islets labeled with chitosan-coated superparamagnetic iron oxide nanoparticles.

Although only 10% of islet recipients maintain insulin independence, 80% of them are C-peptide positive at 5 years after transplantation. To better understand the fate of transplanted islets, a magnetic resonance imaging (MRI) technique has been used to detect Feridex-labeled islet grafts in rodents. In this study, we used a novel MRI contrast agent, chitosan-coated superparamagnetic iron oxide (CSPIO) nanoparticles, to monitor mouse islet grafts. Male inbred C57BL/6 mice were used as donors and recipients of islet transplantation. The islet cytotoxicity was evaluated by fluorescein diacetate and propidium iodide staining for RAW cells incubated with CSPIO. After being incubated overnight with and without CSPIO (10 mg/mL), 300 islets were transplanted under the left kidney capsule of each mouse. After transplantation, 3.0-Tesla MRI of the recipients was performed biweekly until 19 weeks. At the end of study, the islet graft was removed for insulin and Prussian blue staining. The cell death rates in RAW cells did not increase with increasing CSPIO concentrations or incubation time. The grafts of CSPIO-labeled islets were visualized on MRI scans as distinct hypointense spots homogeneously located at the upper pole of left kidney. Their MRI signal was 30%-50% that of control islets and was maintained throughout the follow-up period. At 18 weeks, the histology of CSPIO-labeled islet graft revealed the insulin- and iron-stained areas to be almost identical. Our results indicate that isolated mouse islets labeled with CSPIO nanoparticles can be effectively and safely imaged by using MRI as long as 18 weeks after transplantation.

Peritoneal metastasis in primary cervical cancer: a case report.

PURPOSE OF INVESTIGATION: Peritoneal metastasis presenting at initial diagnosis of squamous carcinoma of the uterine cervix is extremely rare. However, one such case was treated successfully with curative treatment. CASE: A 43-year-old woman presented with FIGO Stage IVA cervical carcinoma and underwent concurrent chemoradiation (CCRT) with weekly cisplatin. During CCRT, she suffered from acute lower abdominal pain, high fever, and leukocytosis. Computed tomography (CT) favored a tubo-ovarian abscess, while [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) showed a lesion midway between the umbilicus and symphysis pubis. An exploration by laparoscopy, an omental metastasis adhering to the bladder dome was excised. This patient finished CCRT encompassing the disease extent including the trochar sites and no evidence of disease was noted 50 months after initial diagnosis. CONCLUSION: Though peritoneal metastasis above the pelvis seems ominous, curative treatment may still be viable in selected patients, even in surgical Stage IVB.

Supraclavicular lymph node metastases in cervical cancer.

PURPOSE OF INVESTIGATION: To evaluate the outcome and prognostic factors of patients with supraclavicular lymph node (SCLN) involvement at primary diagnosis. METHODS: We reviewed the medical records of cervical cancer patients primarily treated at Chang Gung Memorial Hospital between 1987 and 2005. Thirty-three patients with histologically confirmed SCLN metastasis at primary diagnosis were eligible for analysis. Clinical and pathological features were analyzed for association with outcome. RESULTS: The 3- and 5-year survival rates of patients with SCLN metastasis were 16.5% and 16.5%, respectively. Multivariate analysis showed the serum level of squamous cell carcinoma antigen (SCC-Ag) < 15 ng/ml at initial diagnosis (p = 0.021) and staging/restaging including [18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (p = 0.006) to be associated with a better prognosis. CONCLUSION: Primary SCLN metastasis in cervical cancer is not incurable. The benefit from PET findings might help in selecting appropriate patients for curative primary and/or salvage treatment.

Role of [18F]fluoro-2-deoxy-D-glucose positron emission tomography in re-recurrent cervical cancer.

Cervical cancer patients with histologically documented re-recurrence after curative salvage therapy or unexplained tumor marker elevation (negative computed tomography and/or magnetic resonance imaging [CT-MRI]) proven to be a re-recurrence when a further attempt for cure (or control of cancer) appeared feasible were enrolled. Lesion status was determined from pathology or clinical follow-up for at least 12 months. Management decisions were recorded with CT-MRI alone and incorporating [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), respectively. The benefits calculated were based on clinical impact because of the FDG-PET findings. Cox proportional hazards model was used to select independent prognostic covariates. Of the 26 patients who were eligible for analysis, 12 (46.2%) patients had positive impacts due to PET. Squamous cell carcinoma (SCC, P = 0.029), re-recurrence at distant metastasis only (P = 0.012), and level of SCC antigen < or = 4 ng/mL (P = 0.005) were significantly associated with better survival. A scoring system using these covariates defined three distinct prognostic groups (P = 0.0001). Patients with score 0 had a 36-month cumulative survival rate of 80%. Using this prognostic scoring system, FDG-PET may facilitate selecting appropriate management for the individual patient with re-recurrent cervical cancer.

Upper pole of a duplex kidney mimicking adrenal incidentaloma in 18F-fluoro-2-deoxy-D-glucose positron emission tomography: a pitfall in diagnosis.

18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has proved to be valuable in the diagnosis and management of a variety of malignancies, but is still limited in providing detailed anatomical information. According to the literature, an adrenal incidentaloma with high FDG uptake usually indicates malignancy and requires further investigation. However, accurate localization of the adrenal gland in FDG-PET is difficult without the presence of surrounding well-visualized organs, such as the kidney or liver. If these organs have a congenital anomaly or are altered due to a previous operation, misdiagnosis can occur. We present a case with right partial duplex kidney accompanied by abnormal urine retention in the upper pole, which was misinterpreted as an adrenal incidentaloma in FDG-PET. A subsequent CT scan revealed a normal right adrenal gland, but a right partial duplex kidney. Fusion of the PET and CT images showed that the right adrenal lesion seen in the PET image corresponded to the upper pole of the duplex kidney.

Multidetector computed tomography assessment on tumor size and nodal status in patients with locally advanced breast cancer before and after neoadjuvant chemotherapy.

AIMS: To evaluate the utility of multidetector computed tomography (MCT) in assessing tumor size and nodal status in patients with advanced breast cancers before and after the neoadjuvant chemotherapy. METHODS: Twenty-eight proven locally advanced breast cancer patients with 30 tumors were enrolled in this study. MCT was used to assess tumor size and axillary lymph nodes before and after the neoadjuvant chemotherapy. The correlation between tumor size on MCT and gross tumor size was tested. RESULTS: The MCT measurements documented complete response in 3, partial response in 18, non-response in 8 and progressed in 1. The mean tumor diameters on pathology and post-chemotherapy MCT were 3.6cm (S.D.=+/-2.9cm) and 3.1cm (S.D.=+/-2.6cm), respectively. The Pearson correlation coefficient was 0.76 (p<0.001). The sensitivity, specificity, positive predictive valve, negative predictive valve and accuracy of MCT in diagnosing the axillary lymph node metastases after pre-operative neoadjuvant chemotherapy were counted, respectively, to 72%, 40%, 85.7%, 22.2% and 66.7%. All the 5 downstaged axillary nodal statuses from node-positive to node-negative on MCT had micrometastases. CONCLUSION: MCT can be used to evaluate tumor size and nodal status in patients with advanced breast cancer. As there is a baseline MCT before chemotherapy for comparison, we are potentially aware of the possibility of false negative nodal micrometastases on the post-chemotherapy MCT.

An ovary in luteal phase mimicking common iliac lymph node metastasis from a primary cutaneous peripheral primitive neuroectodermal tumour as revealed by 18-fluoro-2-deoxyglucose positron emission tomography.

A 30-year-old female underwent surgical removal of a primary cutaneous peripheral primitive neuroectodermal tumour (PNET) of the left thigh. A subsequent 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) scan showed abnormal accumulation of FDG in the left upper pelvic region, consistent with metastasis to a left common iliac node. A series of follow-up imaging studies revealed that a cyst of the corpus luteum of ovary was responsible for the abnormal FDG accumulation.

False positive fluorine-18 fluorodeoxy-D-glucose positron emission tomography finding caused by osteoradionecrosis in a nasopharyngeal carcinoma patient.

Nasopharyngeal carcinoma (NPC) is treated by radiotherapy with or without chemotherapy. It is not uncommon to find the residual/recurrent lesion in the skull base area. For patients who had received radiotherapy, it is difficult to differentiate the skull base tumour from post-treatment change in the CT or MRI. (18)F-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) provides an alternative diagnostic choice in this situation for head and neck cancer including NPC especially when there is inconclusive CT/MRI finding. This report of an NPC patient who received radiotherapy 18 months previously, describes the misdiagnosis of tumour recurrence at the skull base found in both MRI and FDG PET scan. Histopathological studies showed osteoradionecrosis of the debrided tissue and follow-up PET showed complete regression of the skull base lesion. Therefore, a false positive result in FDG PET caused by osteoradionecrosis was confirmed. To the best of our knowledge, this is the first case report in the literature.

Biodistribution study of [99mTc] TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography.

A 99mTc labeled tropane derivative, [99mTc] TRODAT-1 (2beta-((N,N'-bis(2-mercaptoethyl) ethylene diamino)methyl), 3beta-(4-chlorophenyl) tropane), is a potential dopamine transporter (DAT) imaging agent for the central nervous system. To better understand the binding localization of [99mTc] TRODAT-1 both in the brain and the body, whole-body macroautoradiography (WBAR) was used in this study. The effect of DAT competing drugs, such as levadopa (L-DOPA), N-methyl-2beta-carbomethoxy-3beta-(4fluorophenyl)tropane (CFT, WIN 35,428) and methylphenidate, on the biodistribution of [99mTc] TRODAT-1 were also included in this study. Doses of 150 MBq [99mTc] TRODAT-1 were injected into normal male ICR mice through the caudal veins. For comparison, mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), L-DOPA, methylphenidate and CFT, respectively, were also investigated under the similar protocols. One and a half hours after [99mTc] TRODAT-1 injection, the mice were sacrificed. Whole-body autoradiography was performed immediately after sacrifice. Both frontal and sagittal sections showed that the liver and mucosa of stomach had the highest uptake of [99mTc] TRODAT-1. Other binding sites included the periphery of the spinal cord and the epithelium of the intestine. In the brain, autoradiographic imaging obtained from frontal sections showed symmetrical uptakes of [99mTc] TRODAT-1 in bilateral striata. Remaining binding sites include olfactory bulbs, thyroid gland, and salivary gland. The autoradiographic imaging obtained from sagittal sections showed a similar biodistribution. Mice treated with MPTP or L-DOPA showed no significant difference in the uptake of [99mTc] TRODAT-1 in bilateral striata, as compared to those of the control. In CFT or methylphenidate-treated mice, DAT binding sites were almost completely inhibited. These data showed that [99mTc] TRODAT-1 has potential clinical use for neurological investigation, such as Parkinson's and similar diseases.

Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanisms.

The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through alpha-adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser-Doppler flowmetry over sites following local administration of terazosin (alpha(1)-antagonist), yohimbine (alpha(2)-antagonist), phentolamine (non-selective alpha-antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 +/- 1 cm below the heart. The arm remained in this position for 2 min. Selective and non-selective alpha-adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering alpha-adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non-adrenergic, but neurally mediated, local mechanism.

Elevated F-18 FDG uptake in laryngeal muscles mimicking thyroid cancer metastases.

Fluorine-18 fluorodeoxyglucose (F-18 FDG) has been used to evaluate early-stage larynx cancer and metastases of thyroid cancer. However, elevated F-18 FDG uptake in laryngeal muscles may lead to misinterpretation. In this report, three patients with thyroid cancer are described who had thyroid surgery 2 months to 1 year before F-18 FDG positron emission tomographic imaging. Various degrees of moderate to intense uptake were observed in their laryngeal regions. In one patient, this was caused by laryngeal muscle uptake. To determine the origin of the increased muscle uptake in the other two patients, the authors analyzed the position and shape of the foci of high uptake in light of the patients' clinical histories and other imaging results.