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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. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1524–1531, 2015

Bifid tail of the pancreas is an extremely rare developmental anomaly, and its clinical importance is not well known. We report the case of a 28-year-old man with acute pancreatitis limited to one side of a bifid tail with no otherwise detectable parenchymal edema on magnetic resonance (MR) imaging. Neither was there evidence of other anatomical ductal abnormalities that could have contributed to the patient's pancreatitis. To the best of our knowledge, this is the first report to suggest that bifid tail of the pancreas might cause acute pancreatitis.

Although hepatic perfusion abnormalities have been reported in patients with acute pancreatitis, hepatic perfusion with severe acute pancreatitis (SAP) has not been quantitatively evaluated in humans. Therefore, we investigated hepatic perfusion in patients with SAP using perfusion CT.Hepatic perfusion CT was performed in 67 patients with SAP within 3 days after symptom onset. The patients were diagnosed as having SAP according to the Atlanta criteria. Fifteen cases were established as a control group. Perfusion CT was obtained for 54s beginning with a bolus injection of 40 ml of contrast agent (600-630 mgI/kg) at a flow rate of 4 ml/s. Perfusion data were analyzed by the dual-input maximum slope method to obtain hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP). Finally, we compared HAP and HPP in SAP patients with those in the control group, respectively.Average HAP was significantly higher in SAP patients than in the control group (75.1 ± 38.0 vs. 38.2 ± 9.0 ml/min/100ml; p0.001). There was no significant difference in average HPP between SAP patients and the control group (206.7 ± 54.9 vs. 204.4 ± 38.5 ml/min/100ml; p=0.92).Using quantitative analysis on perfusion CT, we first demonstrated an increase of HAP in the right hepatic lobe in SAP patients.

Dopamine is involved in multiple neural functions including motor control, reward and motivational processing, learning and reinforcement, and cognitive attention. Dopamine binds to two distinct classes of receptors, namely D1and D2, to exert these functions. Various endogenous substances regulate dopamine signaling, although their physiological functions are not fully understood. Here, we examined the role of prostaglandin E2(PGE2) and one of its receptors, EP1, in dopaminergic function in the striatum. EP1was expressed in both preprodynorphin-containing D1and preproenkephalin-containing D2neurons, and PGE2was produced in striatal slices in response to both D1and D2dopamine receptor stimulation. EP1-deficient mice exhibited significant suppression of hyperlocomotion induced by cocaine or SKF81297 (6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine hydrobromide), a D1agonist, and significant attenuation of catalepsy induced by raclopride, a D2antagonist. Despite these behavioral defects, the extracellular concentration of dopamine was not suppressed in the striatum of EP1-deficient mice, and the densities of D1and D2receptors in the striatum were not different between the two genotypes. Stimulation of the D1receptor induced phosphorylation of dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at Thr34 in striatal slices, and the addition of indomethacin, a PG synthesis inhibitor, attenuated the D1agonist-induced increase in DARPP-32–Thr34 phosphorylation. The further addition of an EP1agonist restored the indomethacin-attenuated phosphorylation. Furthermore, both D1- and D2-mediated changes in the DARPP-32–Thr34 phosphorylation were attenuated in EP1−/−slices. These results suggest that PGE2is formed in response to dopamine receptor stimulation in the striatum and amplifies both D1and D2receptor signaling via EP1.

Perfusion CT can diagnose pancreatic necrosis in early stage of severe acute pancreatitis, accurately. However, no study to date has examined whether early diagnosis of pancreatic necrosis is useful in predicting persistent organ failure (POF). We performed a multi-center prospective observational cohort study to investigate whether perfusion CT can predict the development of POF in the early stage of AP, based on early diagnosis of the development of pancreatic necrosis (PN). From 2009 to 2012, we examined patients showing potential early signs of severe AP (n = 78) on admission. Diagnoses for the development of PN were made prospectively by on-site physicians on the admission based on perfusion CT (diagnosis 1). Blinded retrospective reviews were performed by radiologists A and B, having 8 and 13 years of experience as radiologists (diagnosis 2 and 3), respectively. Positive diagnosis for the development of PN were assumed equivalent to positive predictions for the development of POF. We then calculated the area under the curve (AUC) of the receiver operating characteristic for POF predictions. Fourteen (17.9%) and 23 patients (29.5%) developed PN and POF, respectively. For diagnoses 1, 2, and 3, AUCs for POF predictions were 74, 68, and 73, respectively. Perfusion CT diagnoses pancreatic necrosis and on that basis predicts the development of POF; http://www.umin.ac.jp/ctr/index-j.htm,UMIN000001926 .

To determine the relationship between the fractional interstitial volume (Fis), as calculated at dynamic contrast material-enhanced (DCE) computed tomography (CT), and tumor-associated stroma and to analyze its spatial relationship with tumor hypoxia in several xenograft tumor models.All animal experiments were approved by the animal research committee. Mice with three different xenograft tumors (U251, CFPAC-1, and BxPC-3; n = 6, n = 8, and n = 6, respectively) underwent DCE CT then hypoxia imaging with fluorine 18 ((18)F) fluoromisonidazole (FMISO) positron emission tomography (PET) within 24 hours. Immunohistochemical analysis was performed in harvested tumors to detect hypoxia markers and to quantify microvascular and stromal density. Two DCE CT parameters (amount of interstitial space associated with the amount of stroma [Fis] and flow velocity [Fv]) were identified and quantitatively validated by using immunohistochemistry. FMISO uptake within the tumor was also assessed in relation to DCE CT parameters. Imaging and immunohistochemical parameters were assessed by using the Kruskal-Wallis test, Wilcoxon rank-sum test with Bonferroni correction, and Pearson correlation coefficient.Almost no α-smooth muscle actin-positive cells were found in the U251 xenograft, while abundant stroma was found in the entire BxPC-3 xenograft and in the periphery of the CFPAC-1 xenograft. Quantitative analysis showed a significant correlation (R = 0.83, P.0001) between Fis and stromal density. FMISO uptake had a negative correlation with Fis (R = -0.58, P.0001) and Fv (R = -0.53, P.0001).DCE CT can be used to quantify parameters associated with tumor-associated stroma. Tumor hypoxia was Complementarily localized in tumor-associated stroma in these models.

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 mm2/s) and non-PA (low ADCmean

ObjectivesTo assess the prognostic impact of the pretreatment mean apparent diffusion coefficient (ADCmean) values of tumors obtained by diffusion-weighted magnetic resonance imaging. We evaluated the prognostic value of the ADCmean for event-free survival (EFS) and overall survival (OS) among patients with uterine cervical cancer.Methods/MaterialsWe included 171 patients diagnosed as having International Federation of Gynecology and Obstetrics stage Ib to IIIb cervical cancer by pretreatment magnetic resonance imaging scans, regardless of therapeutic methods. In all patients and in patients with squamous cell carcinoma (SCC; n = 123), the optimal cutoff values of the tumor ADCmean for EFS and for OS were determined, respectively. The prognostic significance of the ADCmean was evaluated using univariate and multivariate Cox regression analyses.ResultsIn the univariate analyses, the ADCmean values were significantly associated with negative effects on EFS both in all patients and in patients with SCC, while not being significantly associated with OS in both groups. In the multivariate analysis, ADCmean was an independent biomarker for EFS (P < 0.05) in patients with SCC along with lymph node metastasis and definitive surgery, whereas ADCmean was not independently significant in EFS in all patients.ConclusionsThe pretreatment ADCmean value of the tumor was an independent prognostic factor for EFS in International Federation of Gynecology and Obstetrics stage Ib to III SCC of the uterine cervix.

Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is a rare familial focal epilepsy syndrome with auditory features1. The leucine-rich glioma inactivated 1 (LGI1) was identified as a causative gene. About 40 LGI1 mutations have been reported1-7. Disease mechanisms caused by LGI1 mutations haven't been fully clarified. Accumulation of case reports with detailed descriptions will contribute to elucidate the mechanisms. Here we describe a novel LGI1 mutation identified in the new Japanese family (Fig. 1A). This article is protected by copyright. All rights reserved.

Photoimmunotherapy (PIT) using the near-infrared-absorbing photosensitizing phthalocyanine dye, IRDye 700DX (IR-700), conjugated with a tumor-targeting antibody such as panitumumab (Pan) has shown efficacy in in vitro studies and several preclinical models in mice with promise for clinical translation. PIT results in rapid necrotic cell death in vitro and tumor shrinkage in vivo. Photochemical studies with the Pan-IR-700 conjugate showed that this agent can support generation of singlet oxygen and also generate reactive oxygen species after exposure to near-infrared (NIR) light. Moreover, in vitro studies using A431 cells, singlet oxygen scavengers abrogated the efficacy of PIT with Pan-IR-700, while oxygen depletion to undetectable levels in the exposure chamber almost completely inhibited the cellular cytotoxicity of PIT. Survival of tumor bearing mice was prolonged in PIT-treated animals but mice whose tumors were made transiently hypoxic prior to PIT had no benefit from the treatment. The results from this study support a central role for molecular oxygen-derived species in cell death caused by PIT.

OBJECTIVES: We herein report on development of a composite (synthetic and biological) tracheal scaffold with vascularized autologous connective tissue in the omentum, followed by in situ tissue engineering of the composite scaffold with the pedicled omentum. In this preliminary report, we focus on development and evaluation of the vascularized autologous connective tissue in the omentum. METHODS: In animal experiment 1, a polypropylene framework as a synthetic component was placed in the omental sac for 3 weeks and another was placed in the pouch of Douglas as a control in five beagle dogs. In animal experiment 2, a polypropylene framework placed in the omental sac for 3 weeks was compared with a polypropylene framework coated with porcine atelocollagen, which was also placed in the omental sac in another five dogs, to investigate whether the coating of porcine atelocollagen contributes to development of more vascularized connective tissue. Macroscopic, radiological and histological evaluations were performed for developed autologous connective tissue on the frameworks, with a focus on its thickness and capillary vessels. RESULTS: In animal experiment 1, the polypropylene framework in the omentum developed a composite tracheal scaffold with homogeneous and significantly thicker (2.6 ± 0.5 vs 1.2 ± 0.4 mm, P

The purpose of this study was to determine whether pretreatment quantitative and visual parameters seen on PET/CT using (18)F-FDG add prognostic information for clinical staging in patients with head and neck cancer.We enrolled 108 patients with histologically proven oral, oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinomas who underwent FDG PET/CT before treatment and, later, definitive therapy in our study. PET/CT parameters-maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and uptake pattern (sphere-shaped or ring-shaped)-were recorded. The prognostic value of these parameters was evaluated using univariate and multivariate Cox regression analyses.In the univariate analysis, all of the FDG PET/CT parameters--SUVmax (10 g/mL) of the primary tumor, MTV (20 cm(3)), TLG (70 g), and uptake pattern (ring-shaped)--were significantly associated with negative effects on disease-specific survival (DSS) and disease-free survival (DFS). In the multivariate analysis, the MTV and uptake pattern remained associated with DSS after corrections for the Union for International Cancer Control (UICC) stage and definitive therapy (p = 0.023 and0.001, respectively). Another multivariate model that included MTV as a continuous variable, uptake pattern, and UICC stage showed that the uptake pattern remained significantly associated with DSS, whereas the association between DSS and MTV was not significant (p0.001 and = 0.332, respectively).Our data indicate that the pretreatment PET/CT parameters had prognostic value. In particular, a qualitative factor, uptake pattern, provided better prognostic information to the clinical staging of head and neck squamous cell carcinomas than the other PET/CT parameters.

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).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).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.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.