Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson’s disease: A single-arm,open-label,prospective, multicenter study

Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A_2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A_2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.

Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.

Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.

Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.

Trial registration: UMIN-CTR (UMIN000020288).     

A sewing needle completely buried in the myocardium removed under extracorporeal circulation.

A 14-year-old boy had a needle accidentally inserted through his chest wall. Chest X-ray showed a needle-shaped metallic density localized in the cardiac silhouette. An echocardiography indicated the needle had passed through the interventricular septum, and its eye and point had reached the right and left ventricle, respectively. Surgical removal of the needle was performed. The needle could not be observed from the heart surface, and was recognized in a dent 5 mm on the right side from the left anterior descending branch (LAD). The needle was easily removed under extracorporeal circulation, and he was discharged ten days after the operation.     

Intrapulmonary metastasis developing eighteen years after complete resection of thymoma

We present a case of intrapulmonary metastasis developing 18 years after complete resection of thymoma. An 8 mm nodule in the lower lobe of the left lung was noted on chest X-ray in a 76-year-old woman who had undergone complete resection of Masaoka’s stage II thymoma 18 years earlier. Since the nodule grew to 17 mm during a 2-year follow-up, wedge resection was performed. The lesion was histologically diagnosed as an intrapulmonary metastasis from thymoma. Extremely late recurrence after complete resection of thymoma is discussed.     

Preoperative concurrent chemotherapy and radiation therapy followed by surgery for esophageal cancer.

Currently, the most promising strategy to improve the prognosis of advanced esophageal cancer is preoperative chemoradiation (CRT) followed by surgery. The superiority of CRT over radiation therapy alone has been demonstrated by several randomized studies. Many phase II studies of CRT followed by surgery have shown that the pathologic complete response (CR) rate ranges from 17 to 40%, and the median survival time (MST) is 12 to 31.3 months. Five randomized trials have compared preoperative CRT followed by surgery with surgery alone for resectable esophageal cancer, and four of them did not find any significant survival benefit for the combined treatment group. There are several issues in interpreting these findings, such as the quality of the surgery, the accuracy of the preoperative staging, the statistical power and design of the trials. Until comprehensive evaluation can be done, the standard therapy for resectable esophageal cancer should be considered to be surgery alone. The histological response in the resected specimen correlates well with the prognosis. Patients with pathologic CR display significantly better survival than those with microscopic residual cancer cells in the resected specimens. These findings suggest that more potent regimens leading to higher pathologic CR rates should improve the prognosis. Chemotherapy or radiation therapy sensitivity testing needs to be established. If accurate prediction of the response is possible prior to therapy, non-responders can be excluded. Cell cycle-related genes, apoptosis-related genes, and drug metabolizing genes have been investigated in many pilot studies and need to be evaluated by large-scale clinical studies. At present, pathologic CR can not be accurately diagnosed before surgery. Endoscopic biopsy is also unreliable for the diagnosis. In the future, new diagnostic tools such as positron emission tomography scanning, a sensitivity test or molecular markers may enable accurate diagnosis of pathologic CR to guide the choice of treatment strategies for individual patients.     

Immunohistochemical and ultrastructural study on effect of fibroblast growth factor on transformation of fibroblasts to regenerated mesothelial cells

To elucidate the effect of fibroblast growth factor on the phenotypical conversion of fibroblasts to mesothelial cells, both immunohistochemical and ultrastructural examinations were carried out on cultured spheroids that were composed of fibroblasts obtained from the parietal pleura of rats with and without addition of antifibroblast growth factor receptor antibody. In the present study, antifibroblast growth factor receptor antibody was employed to block the effect of the autocrine component of fibroblast growth factor in the culture medium. Phenotypical conversion from fibroblast to mesothelial cells was clearly blocked in the experimental group, to which culture medium had been added with antifibroblast growth factor receptor antibody, whereas the control group, cultured without addition of antifibroblast growth factor receptor antibody, showed phenotypical conversion of fibroblasts that was confirmed by the development of macula adherens, microvilli, and positive expression of cytokeratin. These results indicate the possibility that fibroblast growth factor plays a key role in the process of phenotypic conversion of fibroblasts to regenerated mesothelial cells.     

Recurrent mediastinal liposarcoma twenty years after the initial operation: case report

We report a case of mediastinal liposarcoma, recurrent after 20 years. A 58-year-old man who presented with dyspnea on exertion was found to have a large mediastinal tumor in chest computed tomography (CT), and he was referred to our hospital. He had undergone an extirpation of a mediastinal liposarcoma about 20 years earlier, and we suspected its recurrence. Because the tumor was very large, it was removed in two stages. Histologically it was diagnosed as a recurrence of the previous well-differentiated liposarcoma. Although liposarcoma is one of the most common soft-tissue sarcomas in adults, a mediastinal liposarcoma is rare. Because the recurrence rate is very high, it is necessary to follow up carefully over a long term.     

A minute small-cell lung cancer showing a latent phase early in growth.

A minute small-cell lung cancer measuring 8 x 5 mm was detected and serially imaged by computed tomography for about a year preceding resection. Although this solid nodule showed a short overall doubling time (76 days), the growth curve included an early phase without apparent growth prior to the phase of rapid growth. Accordingly, lung cancer cannot be ruled out when a small nodule (<10 mm) does not enlarge in the first several months of computed tomographic follow-up.