This study was undertaken to address the effects of fetal mesencephalic tissue transplantation on the serotonin system in a rat model of Parkinson's disease (PD) while also investigating the usefulness of 4-[18 F]-ADAM (a serotonin transporter imaging agent) coupled with micro-PET for imaging serotonin transporters (SERTs). A PD model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of the nigrostriatal pathway, while cell transplantation was performed via intrastriatal injection of mesencephalic brain tissue dissected from embryonic (E14) rats. The 4-[18 F]-ADAM/micro-PET scanning was performed following both 6-OHDA lesioning and transplantation. Immunohistochemistry (IHC) studies were also performed following the final PET scan, and the results were compared to show a 17-43% decrease in the specific uptake ratio (SUR) and a 23-52% decrease in serotonin transporter immunoreactivity (SERT-ir) within various brain regions on the lesioned side. The number of methamphetamine-induced rotations also decreased significantly at the 4th week postgraft. In addition, striatal SUR and the SERT-ir levels were restored to 77% and 83% 5 weeks postgraft. These results suggest that Parkinson's disease also affects the serotonergic system, while both the dopaminergic and serotonergic systems can be partially restored in a rat model of PD after E14 mesencephalic tissue transplantation. In addition, we have also determined that 4-[ 18 F]-ADAM/micro-PET can be used to detect serotonergic neuron loss, monitor the progress of Parkinson's disease, and oversee the effectiveness of therapy.

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Recent studies revealed the risk of bullous pemphigoid (BP) in patients with diabetes mellitus (DM) taking dipeptidyl peptidase 4 (DPP‐4) inhibitors. To clarify the relationship between taking DPP‐4 inhibitors and the risk of BP among patients with DM, we conducted a cohort study by using the National Health Insurance Research Database of Taiwan from 1 January 2009 to 31 December 2015. We identified 6340 patients with DM taking DPP‐4 inhibitors and 25 360 DM patients who had not taken DPP‐4 inhibitors during the 7‐year follow‐up period. Compared with the non‐DPP‐4 inhibitor group, patients taking DDP‐4 inhibitors had a higher risk of BP (adjusted hazard ratio [aHR], 2.382; 95% confidence interval (CI), 1.163–4.883; P = 0.017]. Among the DPP‐4 inhibitors available in Taiwan, vildagliptin showed the highest risk of BP (aHR, 2.849; 95% CI, 1.893–4.215; P < 0.001), followed by saxagliptin (aHR, 2.657; 95% CI, 1.770–3.934; P < 0.001). Subgroup analysis revealed that the higher risk of BP was observed in patients older than 65 years (aHR, 2.403; 95% CI, 1.590–3.627; P < 0.001). This study revealed that treatment with DPP‐4 inhibitors, especially vildagliptin, was significantly associated with an increased risk of BP among DM patients.

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The pathology of Parkinson's disease (PD) results mainly from nigrostriatal pathway damage. Unfortunately, commonly used PD therapies do not repair the disconnected circuitry. It has been reported that using kainic acid (KA, an excitatory amino acid) in bridging transplantation may be useful to generate an artificial tract and reconstruct the nigrostriatal pathway in 6-hydroxydopamine (6-OHDA) lesioned rats. In this study, we used KA bridging and a co-graft of rat olfactory ensheathing cells (OECs) and rat E14 embryonic ventral mesencephalic (VM) tissue to restore the nigrostriatal pathway of the PD model rats. The methamphetamine-induced rotational behaviour, 4-[ F]-ADAM (a selectively serotonin transporter radioligand)/micro-PET imaging, and immunohistochemistry were used to assess the effects of the transplantation. At 9 weeks post-grafting in PD model rats, the results showed that the PD rats undergoing VM tissue and OECs co-grafts (VM-OECs) exhibited better motor recovery compared to the rats receiving VM tissue transplantation only. The striatal uptake of 4-[ F]-ADAM and tyrosine hydroxylase immunoreactivity (TH-ir) of the grafted area in the VM-OECs group were also more improved than those of the VM alone group. These results suggested that OECs may enhance the survival of the grafted VM tissue and facilitate the recovery of motor function after VM transplantation. Moreover, OECs possibly promote the elongation of dopaminergic and serotonergic axon in the bridging graft. Copyright © 2015 John Wiley & Sons, Ltd.

No abstract

Patients with pathological stage IA non-small cell lung cancer (NSCLC) may relapse despite complete surgical resection without lymphovascular invasion. A method of selecting a high-risk group for adjuvant therapy is necessary. The aim of this study was to assess the predictive value of 18F-fluorodeoxyglucose (FDG) uptake and the morphologic features of computed tomography (CT) for recurrence in pathological stage IA NSCLC.One hundred forty-five patients with pathological stage IA NSCLC who underwent pretreatment with FDG positron emission tomography and CT evaluations were retrospectively enrolled. The associations among tumor recurrence and patient characteristics, maximal standard uptake value (SUVmax) of primary tumors, and CT imaging features were investigated using univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors.Tumor recurrence developed in 21 (14.5%) of the 145 patients, and the 5-year recurrence-free survival rate was 77%. The univariate analysis demonstrated that SUVmax, the grade of histological differentiation, tumor size, and the presence of bronchovascular bundle thickening were significant predictive factors (P < 0.05). A higher SUVmax (≥2.5) (P = 0.021), a lower ground-glass opacity ratio (≤17%) (P = 0.014), and the presence of bronchovascular bundle thickening (P = 0.003) were independent predictive factors of tumor recurrence in the multivariate analysis. The use of this predictive model yielded a greater area under the ROC curve (0.877), which suggests good discrimination.The combined evaluation of FDG uptake and CT morphologic features may be helpful in the prediction of recurrence in patients with pathological stage IA NSCLC and in the stratification of a high-risk group for postoperative adjuvant therapy or prospective clinical trials.

KEY WORDS: gastrointestinal stromal tumor; esophagus; positron emission tomography/computed tomography.Although rare elsewhere in the gastrointestinal tract, leiomyoma (LM) is the most common esophageal mesenchymal neoplasm. As a comparison, gastrointestinal stromal tumor (GIST) predominates in the stomach and intestines, but esophageal GIST has been reported less frequently. In contrast to other esophageal mesenchymal tumors, GIST is typically immunoreactive for KIT protein (CD117) in more than 95% of cases and is frequently coexpressed with CD34 (60 to 70%) (1, 2). Mutation of the c-kit proto-oncogene is associated with increasing risk for malignant transformation (3). Positron emission tomography (PET) has recently been employed to monitor progression of GIST from gastrointestinal tracts other than the esophagus (4-6) but its role in the diagnosis of GIST remains unclear.Herein we present a case of GIST of the esophagus confirmed by immunohistochemical stain. Conventional radiological studies including barium meal and computed tomography (CT) were unable to differentiate reliably LM or leiomyosarama (LMS) from GIST of the esophagus. Fused PET/CT was performed in this patient and provided additional information preoperatively in terms of its metabolic activity and the likelihood of a submucosal tumor other than LM.A 36-year-old man presented with grade I dysphagia over 3 months before this admission. No remarkable past medical condition was noted. He denied any history of cigarette smoking or alcohol use, and the family history was also unremarkable. Laboratory results of a complete blood cell count as well as biochemical investigations of electrolytes and liver enzymes were normal. Prior to admission, an endoscopic ultrasonography barium swallowing study of the esophagus showed a segmental filling defect with intact mucosa, 6.5 cm long, over the lower third of the esophagus, which extended to the gastric cardia just beyond the esophagogastric junction ( Figure 1A). Consistent with barium swallowing, endoscopic ultrasonography (EUS) disclosed a hypoechoic submucosal tumor located predominantly in the lower esophagus, with extension to the cardia of the stomach ( Figure 1B). CT with contrast enhancement revealed a poorly enhanced submucosal tumor over the lower third of the esophagus without an apparent enlarged mediastinal lymph node. These studies suggested a submucosal tumor such as a LM or a GIST. As malignant tumor was considered because of the relatively large size of this lesion (<5 cm), endoscopic biopsy was performed to determine its nature but did not yield a conclusive result. PET/CT was therefore performed to obtain more information on the metabolic activity of this tumor and showed moderately increased glucose uptake by 18 F-FDG-PET ( Figure 1C), raising the suspicion of a submucosal tumor other than LM.The patient underwent an exploratory thoracotomy with complete resection by enucleation of the tumor mass followed by closure of the muscularis. Upon microscopic examination with hematoxylin and esoi...