Two cases of stereotactic radiosurgical boost as an initial treatment for young nasopharyngeal cancer patients

Case 1: A 14-year-old boy with nasopharyngeal cancer (T4N0M0) was treated with stereotactic radiosurgery (SRS) as a boost therapy after conventional radiotherapy. Persistent residual tumor visible with MR remained after conventional radiotherapy comprising 59.6 Gy in total. We therefore performed SRS to add a further irradiation dose while causing minimal damage to adjacent normal tissue. SRS was performed using multiple non-coplanar arcs delivered to the residual tumor, which was defined to add 2 mm margins to the residual tumor. This was 30 cc as defined by CT and MR images. Twenty Gy were administered to the periphery of the planning target volume (PTV), corresponding to the 80% isodose line. No recurrences or late complications have been observed 4 years and 6 months after the SRS. Case 2: A 27-year-old man with nasopharyngeal cancer (T1N0M0) was treated with SRS as a boost therapy following conventional radiotherapy with 55 Gy. The SRS was performed using multiple non-coplanar arcs delivered to the PTV, which was 10 cc as defined by CT and MR images as in case 1. Sixteen Gy were administered to the periphery of the residual tumor, corresponding to the 80% isodose line. The tumor was not visible on follow-up MR images and no complications have been observed 4 years and 2 months after the SRS.     

Weekly paclitaxel and nedaplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer: a phase I/II study

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of nedaplatin and paclitaxel when given concurrently with radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC). METHODS: Nedaplatin was administered at a fixed dose of 20 mg/m(2), and paclitaxel was administered at a starting dose of 30 mg/m(2) with an incremental increase of 5 mg/m(2) until dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered once a week for 6 weeks. The RT was given at a single daily dose of 2 Gy for 5 days per week. The pharmacokinetics of nedaplatin and paclitaxel were investigated. RESULTS: Overall, 20 patients were recruited and assigned to three different treatment groups: group 1 (paclitaxel 30 mg/m(2)), group 2 (paclitaxel 35 mg/m(2)) and group 3 (paclitaxel 40 mg/m(2)). Pulmonary toxicity was the main toxicity which occurred in 16 of 20 patients. In group 3, grades 3 and 4 pulmonary toxicity occurred in two of six patients and grade 3 esophagitis in one patient. The maximum tolerated dose of paclitaxel in this study was 40 mg/m(2) and the recommended dose of paclitaxel was therefore 35 mg/m(2). Four complete and 11 partial responses were observed, resulting in a 75% overall response rate. The area under the concentration-time curve of paclitaxel in group 3 was significantly higher than that in group 1. CONCLUSION: Nedaplatin 20 mg/m(2) and paclitaxel 35 mg/m(2) could be safely administered for NSCLC with concurrent thoracic RT, and this regimen was effective. The most important DLT was pulmonary toxicity.     

Oral cancer

This paper reviews the Japanese literature regarding sentinel lymph node localization in head and neck surgery and relevant domestic and foreign articles from other fields of medicine, and reports our results. Even though we have less experience with it in Japan, we believe the sentinel node concept for the head and neck region will be established. Further investigation and practical application in clinical settings are anticipated in the future.     

Pancreatic Cancer Registry in Japan: 20 years of experience

The prognosis of pancreatic cancer is defined by the histology and extent of disease. Preoperative histologic diagnosis and diagnostic imaging are fundamentals in managing the disease, but it is not rare to find unexpected peritoneal dissemination or liver metastasis at the time of operation. The overall resectability rate of pancreatic cancer is 40% in Japan. Resecting the portal vein and peripancreatic plexus were performed on 40% of the patients who underwent pancreatectomy for invasive cancer in the head of the pancreas. Long-term survival was only found in patients who underwent pancreatectomy. Radical lymph node dissection, or combined resection of the large vessels, did not seem to improve survival further than the standard resection. Multidisciplinary treatments combined with surgery were performed, and various effects of postoperative chemotherapy after pancreatectomy, intraoperative- and postoperative-radiation therapy, or postoperative chemotherapy for unresectable tumor, were shown. Development of unconventional therapies and refinement of the conventional therapy should be promoted on a randomized prospective trial basis. To promote this effort, which requires the international comparisons and cooperation, JPS developed a computerized JPS registration system downloadable from the JPS website (http://www.kojin.or.jp/suizou/index.html).     

Primary seminoma in the middle mediastinum

Primary mediastinal seminoma is a relatively rare tumor usually located in the anterior mediastinum. We report here an extremely rare case of a 66-year-old man with primary seminoma in the middle mediastinum. A physical examination showed lymphadenopathy in the right supraclavicular area. A chest CT confirmed the presence of a tumor occupying the retrotracheal space. A histological examination demonstrated metastatic seminoma from the open biopsy of the lymph node. Abdominal, pelvis, and cerebral CT scan and testicular ultrasound were negative. Thus, primary mediastinal seminoma in the middle mediastinum with supraclavicular lymph node metastasis was diagnosed.     

Novel autoantibody to Cu/Zn superoxide dismutase in patients with localized scleroderma

Abnormal production of reactive oxygen species (ROS) induces tissue damage and superoxide dismutase (SOD) that converts superoxide radicals to hydrogen peroxide functions as defense against ROS. Cu/Zn SOD administration has been shown to be effective for various fibrotic conditions by inhibiting the fibrogenic effects of ROS. We hypothesized that autoimmune background in localized scleroderma induced anti-Cu/Zn SOD autoantibodies that inhibited SOD activity and thereby contributed to fibrosis by increasing ROS. ELISA using human purified Cu/Zn SOD revealed that IgG or IgM anti-Cu/Zn SOD Ab was detected in the serum of 89% of localized scleroderma patients, especially 100% of patients with generalized morphea, the severest form of localized scleroderma, but was positive only in the serum of less than 15% of patients with other autoimmune disorders, including systemic sclerosis, systemic lupus erythematosus, dermatomyositis, and autoimmune bullous disorders. The immunoblotting analysis confirmed the presence of IgG anti-Cu/Zn SOD Ab in sera from localized scleroderma patients. Remarkably, anti-Cu/Zn SOD autoantibody could inhibit Cu/Zn SOD enzymatic activity. Collectively, these results indicate that anti-Cu/Zn SOD Ab is a novel, major autoantibody in localized scleroderma, and also suggest that the autoantibody may play a role in the development of fibrosis by directly inhibiting SOD activity.     

Activated natural killer cells adhere to cultured hippocampal neurons and affect the dendritic morphology

To examine the manner of interactions between immune cells and central nervous system (CNS) neurons, mouse hippocampal neurons were co-cultured with lymphokine (IL-2)-activated killer (LAK) cells. Immunocytochemical and time-lapse observations indicated that LAK cells migrated along neuronal processes and made adhesive contacts with them. In addition to the direct physical effects, LAK cells released glutamate, induced the formation of beads-like structure in the dendrites of about 14% of hippocampal neurons and caused the reduction of dendritic protrusions. These results suggest that infiltrating immune cells can form direct adhesive connections with CNS neurons and affect their dendritic morphology.     

Learned audio-visual cross-modal associations in observed piano playing activate the left planum temporale. An fMRI study

Lip reading is known to activate the planum temporale (PT), a brain region which may integrate visual and auditory information. To find out whether other types of learned audio-visual integration occur in the PT, we investigated "key-touch reading" using functional magnetic resonance imaging (fMRI). As well-trained pianists are able to identify pieces of music by watching the key-touching movements of the hands, we hypothesised that the visual information of observed sequential finger movements is transformed into the auditory modality during "key-touch reading" as is the case during lip reading. We therefore predicted activation of the PT during key-touch reading. Twenty-six healthy right-handed volunteers were recruited for fMRI. Of these, 7 subjects had never experienced piano training (na?ve group), 10 had a little experience of piano playing (less trained group), and the remaining 9 had been trained for more than 8 years (well trained group). During task periods, subjects were required to view the bimanual hand movements of a piano player making key presses. During control periods, subjects viewed the same hands sliding from side to side without tapping movements of the fingers. No sound was provided. Sequences of key presses during task periods consisted of pieces of familiar music, unfamiliar music, or random sequences. Well-trained subjects were able to identify the familiar music, whereas less-trained subjects were not. The left PT of the well-trained subjects was equally activated by observation of familiar music, unfamiliar music, and random sequences. The na?ve and less trained groups did not show activation of the left PT during any of the tasks. These results suggest that PT activation reflects a learned process. As the activation was elicited by viewing key pressing actions regardless of whether they constituted a piece of music, the PT may be involved in processes that occur prior to the identification of a piece of music, that is, mapping the complex sequence structure of hand movements onto the sequence of sounds.     

Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain

Abnormal phosphorylation of tau is a feature of Alzheimer's disease (AD), which develops prematurely in Down syndrome (DS) patients. Cognitive impairment is also recognized as a clinical characteristic of schizophrenia, which does not appear to be associated with tau-aggregate formation. Several kinases can phosphorylate tau in cell-free assays. Here we show increased activity of mitogen-activated protein kinases (MAPKs) (including ERK1/2, SAPKs and p38) in post mortem AD and DS brains, which could not be accounted for by expression changes. In contrast, glycogen synthase kinase-3 activity (GSK-3 alpha beta) was reduced significantly. Examination of tau in AD and DS using antibodies selective for MAPK phosphorylation sites showed increased immunoreactivity. In addition, phosphorylation of S(199), reportedly a selective substrate for cyclin-dependent kinase-5 (cdk5) or GSK-3 alpha beta was only observed in AD samples, which showed a concomitant increase in the expression of p25, the enhancing cofactor for cdk5 activity. However, in schizophrenia brain, MAPK-phosphorylated tau was unchanged compared to matched controls, despite similar expression levels to those in AD. The activities of the MAPKs and GSK-3 alpha beta were also unchanged. These data demonstrate that in AD and DS, enhanced MAPK activity, which has an established role in regulating neuronal plasticity and survival, can account for irregular tau phosphorylation, and that the molecular processes involved in these neurodegenerative disorders are distinct from those in schizophrenia. These data also question the significance of GSK-3 alpha beta, as much previous work carried out in vitro has placed this kinase as a favoured candidate for involvement in the pathological phosphorylation of tau.