Combined visual and semi-quantitative assessment of 123I-FP-CIT SPECT for the diagnosis of dopaminergic neurodegenerative diseases.

Visual and semi-quantitative assessments of 123I-FP-CIT single-photon emission computed tomography (SPECT) are useful for the diagnosis of dopaminergic neurodegenerative diseases (dNDD), including Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. However, the diagnostic value of combined visual and semi-quantitative assessment in dNDD remains unclear. Among 239 consecutive patients with a newly diagnosed possible parkinsonian syndrome who underwent 123I-FP-CIT SPECT in our medical center, 114 patients with a disease duration less than 7 years were diagnosed as dNDD with the established criteria or as non-dNDD according to clinical judgment. We retrospectively examined their clinical characteristics and visual and semi-quantitative assessments of 123I-FP-CIT SPECT. The striatal binding ratio (SBR) was used as a semi-quantitative measure of 123I-FP-CIT SPECT. We calculated the sensitivity and specificity of visual assessment alone, semi-quantitative assessment alone, and combined visual and semi-quantitative assessment for the diagnosis of dNDD. SBR was correlated with visual assessment. Some dNDD patients with a normal visual assessment had an abnormal SBR, and vice versa. There was no statistically significant difference between sensitivity of the diagnosis with visual assessment alone and semi-quantitative assessment alone (91.2 vs. 86.8%, respectively, p = 0.29). Combined visual and semi-quantitative assessment demonstrated superior sensitivity (96.7%) to visual assessment (p = 0.03) or semi-quantitative assessment (p = 0.003) alone with equal specificity. Visual and semi-quantitative assessments of 123I-FP-CIT SPECT are helpful for the diagnosis of dNDD, and combined visual and semi-quantitative assessment shows superior sensitivity with equal specificity.

Characteristics and prognosis of patients with thyroglobulin-positive and radioactive iodine whole-body scan-negative differentiated thyroid carcinoma.

OBJECTIVE: The prognosis of differentiated thyroid carcinoma is generally favorable. However, some patients have negative radioiodine whole-body scans and detectable serum thyroglobulin with biochemical radioiodine-refractory carcinoma and are candidates for treatment with a multikinase inhibitor, such as sorafenib. The purpose of this study is to investigate the characteristics and prognosis of differentiated thyroid carcinoma patients who are thyroglobulin positive and scan negative. METHODS: We retrospectively classified 153 patients treated for 15 years by serum thyroglobulin level and radioiodine scan results and examined the relationship between clinical characteristics and prognosis. RESULTS: Overall, 27% of the patients were classified as thyroglobulin positive/scan negative (positive/negative) while 61% were thyroglobulin negative/scan negative (double negative). Compared with double-negative patients, positive/negative patients were significantly older, predominantly male, had a higher pT and pN, stage, and had higher pre-operative thyroglobulin values. Positive/negative patients showed worse prognosis in terms of overall survival, disease-specific survival and disease-free survival than double-negative patients (10-year overall survival, 85 vs. 93%, P = 0.001; 10-year disease-specific survival, 94 vs. 100%, P = 0.03, 10-year disease-free survival, 77 vs. 93%, P < 0.001). Multivariate analysis revealed that positive/negative status was the only factor associated with disease-free survival, including age and TNM stage (hazard ratio: 6.37, 95% confidence interval: 1.22-33.3). However, the median duration of disease-free period for positive/negative patients was 14.2 years. CONCLUSIONS: Few patients among thyroglobulin-positive/scan-negative patients are candidates for sorafenib, despite the significant survival differences from double-negative patients.

A novel hook-shaped enhancement on contrast-enhanced sagittal magnetic resonance image in acute Sheehan's syndrome: a case report.

We report characteristic magnetic resonance (MR) image findings in a case of Sheehan's syndrome. A 37-year-old woman experienced complications of retained placenta and massive bleeding (3600 g) during delivery of a full-term baby. A pituitary function test demonstrated panhypopituitarism. MR image of the pituitary gland on postpartum day 10 revealed swelling of the anterior lobe. A hook-shaped enhancement was demonstrated on a sagittal image. The pituitary stalk, majority of the marginal zone of the anterior lobe, the anterior lobe just in front of the posterior lobe, and posterior lobe were well enhanced. In contrast, the central portion and the superior margin, just in front of the stalk insertion of the anterior lobe, were not enhanced. Anatomically, blood supply to these unenhanced portions of the anterior lobe was via the hypophyseal long portal vein and trabecular artery, which are tributaries of the superior hypophyseal artery that originate far from the internal carotid artery. Based on clinical history and MR image findings, the patient was diagnosed with Sheehan's syndrome and treated with hydrocortisone and levothyroxine. Follow-up MR image revealed marked atrophy of the anterior lobe. The characteristic hook-shaped enhancement in Sheehan's syndrome well reflected the vulnerability to massive bleeding based on the complex pituitary vasculature, which has not been reported previously. MR image with contrast enhancement is useful in the diagnosis of the acute phase of Sheehan's syndrome and in evaluating infarction of the anterior lobe.

Clinical Value of Fused PET/MRI for Surgical Planning in Patients With Oral/Oropharyngeal Carcinoma.

OBJECTIVES/HYPOTHESIS: To evaluate the usefulness of fused positron emission tomography (PET)/magnetic resonance (MR) images for surgical planning in patients with oral/oropharyngeal cancer and suspected mandibular invasion. STUDY DESIGN: Individual cohort study. METHODS: Eleven of 17 patients with suspected mandibular invasion of squamous cell carcinoma of the lower gingiva, oropharynx, and buccal mucosa who underwent 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) and contrast-enhanced MR imaging (MRI) and had fused PET/MR images were enrolled in this study. The area for surgical resection was determined based on the fused images. The usefulness of these images was confirmed by comparing them with the histopathologic findings in the resected tumors. RESULTS: Histopathologic evaluation of the surgical specimens revealed that nine of the 11 patients had invasion into the mandible and/or medial pterygoid muscle. All patients had a negative surgical margin. The sensitivity and specificity for detection of mandibular/medial pterygoid muscle invasion was 100%/40% and 83%/100% by fused PET/MRI, respectively, and 100%/20% and 100%/60% by PET/CT, respectively. Interobserver reproducibility between two radiologists/nuclear medicine physicians and two head and neck surgeons showed that the only statistically significant κ values were for PET/MRI. CONCLUSIONS: PET/MRI can be easily understood by head and neck surgeons, who are not diagnostic imaging professionals, and can be used when planning the area to be surgically resected in patients with oral/oropharyngeal cancer and clinically suspected mandibular invasion. Considering the expense of a hybrid PET/MRI system, creation of a fused PET/MR image would provide a reasonable and reliable tool for clinical use in these patients. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:367-374, 2020.

Evaluation of biliary abnormalities with 64-channel multidetector CT.

Precise preoperative assessment of the vascular and biliary anatomy is important in ensuring the safety of hepatobiliary surgical procedures, including laparoscopic cholecystectomy, living donor liver transplantation, and tumor resection of the liver. Endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography clearly depict the biliary anatomy but are considered invasive procedures. Magnetic resonance cholangiopancreatography is noninvasive but sometimes fails to depict the normal intrahepatic bile ducts. Multidetector computed tomography (CT) has contributed greatly to the evaluation of the normal anatomy, anatomic variants, and disease extent in this setting. With 64-channel multidetector CT, high-resolution three-dimensional images can be reconstructed from isotropic data with a 0.625-mm section thickness. Because of its capacity for thin-section scanning and multiplanar reformation, 64-channel multidetector CT cholangiography can clearly demonstrate the biliary anatomy, a variety of anatomic variants, and the extent of disease--information that is indispensable for successful hepatobiliary surgery.

Image quality and variability for routine diagnostic FDG-PET scans in a Japanese community hospital: current status and possibility of improvement.

PURPOSE: In Japan, commercially delivered FDG is manufactured in three batches per day at fixed constant activity and distributed in vials. Consequently, the amount of activity administered to the patient varies depending on the timing of injection. We evaluated a method for adjusting the scan time according to the body mass index (BMI) to obtain equivalent image quality for every patient. METHODS: We examined a total of 301 routine clinical oncology PET scans using commercially delivered FDG. The relation between the injected activity and the noise equivalent count per scan length (NECpatient) was evaluated as a marker of image quality; its association with BMI was also examined. RESULTS: The injected activity and NECpatient exhibited large variations (230.4 ± 55.8 MBq and 19.9 ± 2.9 Mcounts/m). There was a weak correlation between the injected activity and NECpatient (r ~ 0.3) for thin patients (BMI < 21 kg/m(2)), but no correlation for patients with higher BMIs. However, a significant correlation was found between BMI and NECpatient (p < 0.0001). CONCLUSION: In a community hospital using commercially delivered FDG, it is possible to reduce the variability of the NECpatient and obtain uniform image quality by changing the scan time as a function of patient BMI, even with uncontrollable injected activity.

Preoperative Diagnostic Strategy for Parotid Gland Tumors Using Diffusion-Weighted MRI and Technetium-99m Pertechnetate Scintigraphy: A Prospective Study.

OBJECTIVE: Fine needle aspiration cytology (FNAC) for diagnosis of a parotid gland tumor is widely used but its sensitivity is low and non-diagnostic rate is relatively high. In contrast, core needle biopsy (CNB) has a higher sensitivity and lower rate of sampling errors but has a higher risk of injury to adjacent organs such as facial nerve than FNAC. Screening of patients with parotid gland tumors to identify cases of pleomorphic adenoma (PA) and Warthin tumor (WT) may allow CNB to be confined to patients without PA and WT. We established an algorithm for preoperative diagnosis and management of parotid gland tumor using diffusion-weighted MRI and 99mTc pertechnetate scintigraphy. This algorithm was developed with the goal of maximal reduction of the number of patients in whom CNB is required. The purpose of the study is to validate our algorithm prospectively. METHODS: A prospective study was conducted in 71 cases who were newly diagnosed with parotid gland tumor and 53 cases were enrolled in the study. In the algorithm, PA (high apparent diffusion coefficient (ADC) mean≥1.5×10(-3) mm(2)/s) and non-PA (low ADCmean<1.5×10(-3) mm(2)/s) cases are first distinguished based on the ADCmean on diffusion-weighed MRI. Second, among suspected non-PA cases, WT and non-WT are distinguished using technetium-99m pertechnetate scintigraphy. CNB is then performed only in probable non-PA and non-WT cases. RESULTS: Although CNB was only required in 40% (21/53) of all cases, we made a preoperative histopathological diagnosis with an accuracy of 87% (46/53) and we correctly diagnosed whether a tumor was benign or malignant with an accuracy of 96% (51/53). Preoperative surgical planning had to be changed during surgery in only one case (2%). CONCLUSIONS: Our algorithm is valuable in terms of clinical practice with highly potential for preoperative diagnosis and with less risk of CNB procedure.

Detection of subclinical recurrence or second primary cancer using (18) F-FDG PET/CT in patients treated curatively for head and neck squamous cell carcinoma.

BACKGROUND: The efficacy of posttreatment surveillance (18) F-fluorodeoxyglucose positron emission tomography ((18) F-FDG PET)/CT was evaluated in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The subjects were 158 patients with HNSCC who underwent PET/CT after definitive treatment. PET/CT detection of subclinical recurrence or a second primary cancer and the effect of timing of PET/CT scans on survival were analyzed. RESULTS: Recurrence or a second primary cancer occurred in 70 patients, and 67% of these cases were detected by PET/CT. Detection rates were 17%, 9%, 5%, and 5% in the first, second, third, and fourth scans at 4, 9, 15, and 21 months, respectively. In multivariate analysis, patients who underwent early first scans had significantly better disease-specific (hazard ratio [HR] = 0.37; p = .031) and overall (HR = 0.45; p = .040) survival compared with those who underwent late first scans. CONCLUSION: Earlier detection of subclinical lesions by surveillance PET/CT within 4 months after treatment may improve survival in patients with HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E511-E518, 2016.

A Novel homozygous missense mutation of melanocortin-4 receptor (MC4R) in a Japanese woman with severe obesity.

The melanocortin-4 receptor (MC4R) is a member of the seven membrane-spanning G protein-coupled receptor superfamily and signals through the activation of adenylyl cyclase. The MC4R mutations are the most common known monogenic cause of human obesity. However, no such mutations have been found in Japanese obese subjects. Here we report a novel homozygous missense mutation of MC4R (G98R) in a nondiabetic Japanese woman with severe early-onset obesity, which is located in its second transmembrane domain. Her birth weight was 3,360 g, and she gained weight progressively from 10 months of age. At 40 years of age, her weight reached 160 kg and a BMI of 62 kg/m(2). Her parents, who are heterozygous for the mutation, have BMIs of 26 and 27 kg/m(2). In vitro transient transfection assays revealed no discernable agonist ligand binding and cAMP production in HEK293 cells expressing the mutant receptor, indicating a severe loss-of-function mutation. This study represents the first demonstration of a pathogenic mutation of MC4R in Japan and will provide further insight into the pathophysiologic role of the hypothalamic melanocortin system in human obesity.

Prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography/CT volume-based parameters in patients with oropharyngeal squamous cell carcinoma with known p16 and p53 status.

BACKGROUND: The purpose of this study was to determine whether pretreatment 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) volume-based parameters, such as metabolic tumor volume and total lesion glycolysis, add more prognostic information in patients with oropharyngeal squamous cell carcinoma (SCC). METHODS: The subjects were 47 patients with oropharyngeal SCC who underwent 18F-FDG PET/CT before any treatment and followed by definitive therapy. PET parameters (metabolic tumor volume and total lesion glycolysis) and tumor p16/p53 status were evaluated retrospectively. Univariate and multivariate analyses were performed for disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). RESULTS: All volume-based PET parameters were found to be significant prognostic factors for DFS, DSS, and OS in univariate analysis. In multivariate analysis, only metabolic tumor volume for total tumor lesions (cutoff 65) retained an independent association with DFS, DSS, and OS. CONCLUSION: Metabolic tumor volume for total tumor lesions may be a predictive marker for survival outcomes in patients with oropharyngeal SCC with known p16/p53 status.

Missense mutation of TRPS1 in a family of tricho-rhino-phalangeal syndrome type III.

We report a new Japanese family with tricho-rhino-phalangeal syndrome type III (TRPS III) who have a missense mutation (Arg908Gln) of theTRPS1 gene (TRPS1) in affected individuals of the family. This study supports the notion that TRPS III results from missense mutations in exon 6 of TRPS1.

[A case report of distant lymph nodes metastases from prostate cancer imaged with 201Tl and 99mTc-MIBI].

Prostate cancer most often metastases to regional lymph nodes and bones by hematogeneous or lymphatic spread. The authors present a rare case of metastatic prostate cancer to supradiaphragmatic lymph nodes that were detected on 201Tl and 99mTc-MIBI imaging and confirmed on a CT scan. An 81-yr-old man with bilateral painful cervical lymphadenopathies was referred to our hospital with suspected thyroid cancer. The US and thyroid scan indicated no abnormalities in his thyroid gland. Both 201Tl and 99mTc-MIBI scans showed multiple areas of abnormally increased radioactivity in both supraclavicular, anterior mediastinum, and bilateral hilar regions. A CT scan also revealed multiple lymphadenopatheis in the same regions as radionuclide scans. Prostate cancer was diagnosed from the results of immunohistochemical staining for PSA examination of a biopsy specimen of the mediastinal lymph node. The serum PSA concentration was markedly elevated at 490 ng/ml (normal, < 40 ng/ml). Both 99mTc-HMDP bone and 67Ga scans were normal. All supradiaphragmatic lymph nodes on CT images disappeared 2 months after subcapsular orchiectomy and endocrine treatment with Bicalutamide. Metastatic prostate cancer should be considered when metastatic adenocarcinoma is discovered in the supraclavicular lymph nodes of elder men.

Evaluation of a 1 step TRAb assay for the detection of high-affinity components to hTSHR: evidences indicating superiority of the assay in the lower TRAb range.

The aim of this study was to develop an assay to selectively detect high-affinity components among TRAb. Using an rhTSHR-coated tube system, a 1 step TRAb assay method was developed that included 1) co-incubation with (125)I-bTSH, 2) a 50 microl serum sample, 3) an increased incubation volume (450 microl), and 4) a 1 hour incubation time. Sixty-one TRAb positive Graves' sera were studied. When the regular TRAb assay (Reg) results were quantitatively compared to the 1 step assay (1 step) results, certain dispersions and overestimations using the latter were seen. Further, some 1 step positive results were observed in the low Reg range. Overestimations were considered mostly due to the differences between TRAb standard and patients' serum TRAb in the binding competition against co-incubated (125)I-bTSH, which was shown from a modified assay mimicking the 1 step conditions. Therefore, the 1 step results were decided to be expressed by % inhibition against (125)I-bTSH. As for data dispersions, TRAb absorptions during the regular 1st incubation were studied. Individually, the absorption rates varied from 11 to 69%, and higher absorptions were observed in lower Reg range, especially in those negative by the 1 step. Observed 1 step positive results in the low Reg range were of interest, and 1 step/Reg ratios were calculated. The ratios with 1 step negative samples were significantly lower than those of 1 step positive samples. In conclusion, the 1 step assay was proved to detect a particular and biologically active TRAb, especially in those with low TRAb. The clinical significance of the 1 step results should be of future interest.

Immeasurably low and non-TRH-stimulatable TSH associated with normal I-123 uptake in two goitrous euthyroid patients: possible existence of other thyroid-hormone regulated thyroid stimulators other than TSH.

We described two euthyroid patients with normally functioning goiters, but with persistently undetectable and non-stimulatable TSH levels. Subject 1 was a 64-year-old woman with a large diffuse goiter who has been clinically and biochemically euthyroid without any medication for at least 19 years. Subject 2 was a 31-year-old woman with a small diffuse goiter who has been euthyroid for 4 years. Both patients had persistently undetectable levels of serum TSH, TSH receptor antibodies (TRAb) and thyroid stimulating antibodies (TSAb). Their basal TSH levels were very low and their T3 responses to TRH were very diminished or absent. In contrast, the basal levels of the other pituitary hormones and their responses to LHRH, GRH and CRH stimulation were all within normal limits in both patients. MRI images of pituitary glands, 123I thyroid uptake, and thyroid scans were normal. Ectopic thyroids were not detected on (99m)TcO4- and 123I total body scans. Factors interfering with the measurement of TSH were excluded by recovery studies. In subject 1 a T3-suppression test was positive and a perchlorate discharge test was negative. In subject 2 a T3-suppression test was negative. Euthyroid Graves' disease, subclinical hyperthyroidism, destructive thyroiditis, thyrotoxicosis of extrathyroid origin, central hypothyroidism, and nonthyroidal illness were all ruled out by these observations. These results suggest that an unknown factor, such as thyrostimulin, but not TSH or TSAb, stimulates the thyroid and maintains euthyroidism, and may have a role in the regulation of the hypothalamus-pituitary-thyroid axis.

A case of TSH receptor antibody-positive hyperthyroidism with functioning metastases of thyroid carcinoma.

The presence of TSH receptor antibody (TRAb) is rarely responsible for hyperthyroidism due to metastatic lesions of thyroid carcinoma. A 70-year-old woman was incidentally found to be thyrotoxic around the time that external irradiation was performed for multiple bone metastases 9 years after subtotal thyroidectomy for follicular carcinoma. Hyperthyroidism persisted after oral administration of thiamazole. Relevant laboratory data were as follows: FT4 9.6 ng/L, FT3 7.3 ng/L, TSH <0.19 mU/L, TBII 70, TSAb 735, and Tg 32,000 microg/L. 131I-total body scan showed 131I accumulation in the occipital bone, cervical vertebra, thoracic vertebra, ilium, and residual thyroid gland. Since the ilium uptake (11.6) was markedly higher compared to the residual thyroid gland uptake (0.14), four subsequent 131I therapies were performed. The patient became hypothyroid, and TBII became negative. TSAb became negative after the first 131I-therapy but has increased again to 204 at present. Tg was 1,962 microg/L despite high TSH levels. 131I accumulation in the residual thyroid, cervical vertebra, and thoracic vertebra disappeared. Also 131I accumulation in the ilium has gradually decreased, but the image in the occipital bone has become markedly distinctive. This is a rare case characterized by TRAb-positive hyperthyroidism, by T3-predominant thyrotoxicosis, and by stronger accumulation of 131I in the metastatic tumor than in the residual thyroid gland. Thus, the response to TRAb and 131I-therapy is different among metastatic thyroid tissues.