[Efficacy and safety of TS-1 monotherapy for advanced/metastatic breast cancer - an observational study by the Kumamoto Breast Cancer Cooperative Group(KBCCG)].

TS-1, an oral fluoropyrimidine, is known to be effective for the treatment of various carcinomas including advanced/metastatic breast cancer.The Kumamoto Breast Cancer Cooperative Group(KBCCG)conducted an observational study, wherein, the efficacy and safety of TS-1 monotherapy was analyzed in 35 patients with recurrent or metastatic breast cancer.The median time to cancer progression was 3.7 months, overall response rate was 12%, and clinical benefit rate was 32%. Adverse events were observed in 27 patients(77%), and adverse events of Grade >3 were observed in 7 patients(20%). The rate of treatment-related Grade 3 and 4 adverse events increased, and was associated with poor levels of creatinine clearance(Ccr)ie <60mL/min.This study suggests that TS-1 monotherapy can potentially be used as a salvage treatment for advanced/metastatic breast cancer owing to its safety and efficacy.Measuring the level of Ccr before TS-1 therapy should be considered to avoid severe adverse events.

Psychologic management of brace therapy for patients with idiopathic scoliosis.

STUDY DESIGN: A trial of brace therapy modified by a measured personality pattern of patients with idiopathic scoliosis was performed. OBJECTIVE: To evaluate the effectiveness of performing personality tests for patients with idiopathic scoliosis who undergo brace therapy. SUMMARY OF BACKGROUND DATA: Brace therapy has often been used for the treatment of scoliosis. However, emotional distress can result from this therapy. Few attempts have been made to reduce such stress. METHODS: A test using the Maudsley Personality Inventory was performed on 145 adolescent females with idiopathic scoliosis, treated with brace therapy alone, before the start of brace therapy and 1 month after the start of brace therapy. On the basis of test results, the patients were rated as normal type and four abnormal types. Brace therapy was continued considering the personality pattern of patients. For all patients, changes in psychologic test results, compliance with braces wearing instructions, and correction of scoliosis were analyzed. RESULT: Of the 134 patients rated as normal before the start of therapy, 108 patients were rated as abnormal pattern when tested 1 month after the start of therapy. After performing autogenic training for patients with E-N+ and E-N- personalities, and giving advice to school teachers to decrease the emotional stress for patients with E+N+ personality, 47 patients were finally rated as abnormal pattern. In total, 12 (8%) of the 145 patients dropped out. In dropouts, the average pretreatment deformity of 29 degrees (range: 21 degrees -37 degrees ) had increased to an average of 37 degrees (range, 31 degrees -48 degrees ). CONCLUSION: Psychologic tests may be useful and provide a means of modifying brace therapy tailored to the psychologic conditions of individual patients.

Occupational recovery after open-door type laminoplasty for patients with ossification of the posterior longitudinal ligament.

STUDY DESIGN: A cross-sectional survey of occupational recovery after surgery with patients who had ossification of the posterior longitudinal ligament. OBJECTIVES: To evaluate occupational recovery after open-door type laminoplasty for patients with ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: The literature contains numerous reports on the surgical results of laminoplasty for ossification of the posterior longitudinal ligament, but very few reports are available on postoperative quality of life, and even fewer on occupational recovery after laminoplasty. METHODS: A cross-sectional survey was conducted of 301 patients with ossification of the posterior longitudinal ligament in the cervical spine who were employed before open-door type laminoplasty. Presurgical occupations were classified into three categories: light sedentary labor, light standing labor, and heavy labor. High-rise workers and professional drivers were analyzed separately. The subjects were rated by occupational category for determining the occupational recovery ratio. Factors analyzed for impact on recovery were pre- and postsurgery severity of myelopathy, duration of myelopathy, age at surgery, gender, and type of ossification of the posterior longitudinal ligament. RESULTS: Of the 301 patients studied, 160 (53%) returned to work. Poor recovery rates were observed for heavy labor, high-rise workers, and professional drivers. The period required for return to work did not significantly differ among occupational categories. Occupation, presurgery severity of myelopathy, and postsurgery severity of myelopathy were significantly correlated with occupational recovery. CONCLUSION: Patients' occupations should be carefully considered when designing postsurgery occupational rehabilitation programs, and patients should receive postoperative advice regarding the suitability of occupation.

Prognosis of patients with upper cervical lesions caused by rheumatoid arthritis: comparison of occipitocervical fusion between c1 laminectomy and nonsurgical management.

STUDY DESIGN: A matched controlled comparative study of patients with upper cervical lesions caused by rheumatoid arthritis was performed at two different hospitals to evaluate occipitocervical fusion associated with C1 laminectomy and nonsurgical treatment. OBJECTIVES: To evaluate the long-term results and advantages of occipitocervical fusion associated with C1 laminectomy, and to compare these results with those of nonsurgical management of patients with myelopathy related to rheumatoid arthritis. SUMMARY OF BACKGROUND DATA: Few studies have reported the prognosis of patients with rheumatoid arthritis managed by occipitocervical fusion associated with C1 laminectomy. METHODS: In this study, 40 patients with rheumatoid arthritis and myelopathy caused by irreducible atlantoaxial dislocation with or without upward migration of the odontoid process were studied. Of these 40 patients, 19 were treated by occipitocervical fusion using a rectangular rod associated with C1 laminectomy at one hospital, whereas 21 matched patients were treated conservatively at another hospital. The patients were observed by the same protocol to assess the radiologic and clinical results, including functional recovery and survival rate. All the patients were followed until their death. RESULTS: The atlantodental interval was reduced immediately after surgery, and this result had been well maintained at the final follow-up assessment. Redlund-Johnell values did not vary significantly throughout the course of the study. As for neural assessment with the Ranawat classification system, improvement was found in 13 (68%) of the 19 patients who underwent surgery. The survival rate was 84% 5 years after surgery, and 37% in the first 10 years. In the patients who did not undergo surgical treatment, atlantodental interval and Redlund- Johnell values were aggravated. These patients showed no neural improvement, and aggravation was found in 16 (76%) of the 21 cases during the follow-up period. All the patients were bedridden within 3 years after the onset of myelopathy. The survival rate was 0% in the first 8 years. CONCLUSIONS: The findings lead to the conclusion that occipitocervical fusion associated with C1 laminectomy for patients with rheumatoid arthritis is useful for decreasing nuchal pain, reducing myelopathy, and improving prognosis.

Membranous lipodystrophy (Nasu-Hakola disease) presenting an unusually benign clinical course.

Membranous lipodystrophy is known as Nasu-Hakola disease. The main symptoms of membranous lipodystrophy are those of a progressive presenile dementia due to sclerosing leukoencephalopathy with skeletal polycystic lesions. There is no report detailing long-term follow-up of patients with membranous lipodystrophy. We present a 56-year-old woman with this disease who has not manifested any typical neuropsychiatric symptoms during the 16-year follow-up, and thus has had an unusually benign clinical course. The patient underwent curettage and bone grafts. Periodic examinations have been continued for 16 years from discharge. No recurrence of lesions or occurrence of new cystic lesions has been noted. Computerized tomography and magnetic resonance imaging of the brain revealed none of the abnormal change which are reported in this disease. Our findings suggest that some patients with this disease may be fortunate enough to follow a relatively benign clinical course.

Pathogenesis of myelopathy in patients with ossification of the posterior longitudinal ligament.

OBJECT: The goal of this study was to clarify the pathogenesis of myelopathy in patients with ossification of the posterior longitudinal ligament (OPLL) based on the relationship between static compression factors and dynamic factors. METHODS: There was a total of 247 patients, including 167 patients who were conservatively followed for a mean of 11 years and 2 months and 80 patients who had myelopathy at initial consultation and underwent surgery. The changes in clinical symptoms associated with OPLL in the cervical spine were examined periodically. During the natural course of OPLL in the cervical spine, 37 (22%) of 167 patients developed or suffered aggravated spinal symptoms. All of the patients with a space available for the spinal cord (SAC) less than 6 mm suffered myelopathy, whereas the patients with an SAC diameter of 14 mm or greater did not. No correlation was found between the presence or absence of myelopathy in patients whose SAC diameter ranged from 6 mm to less than 14 mm. In patients with myelopathy whose minimal SAC diameter ranged from 6 mm to less than 14 mm, the range of motion of the cervical spine was significantly greater. CONCLUSIONS: These results indicate that pathological compression by the ossified ligament above a certain critical point may be the most significant factor in inducing myelopathy, whereas below that point dynamic factors may be largely involved in inducing myelopathy.

Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization.

Osteoblasts and adipocytes are derived from a common precursor in bone marrow, the mesenchymal stem cell (MSC). Factors driving human MSCs (hMSCs) to differentiate down the two lineages play important roles in determining bone density because it has been shown that bone volume loss associated with osteoporosis and aging is accompanied by reduced osteoblastic bone formation and increased marrow adipose tissue. The genes upregulated in hMSCs during osteogenic differentiation were screened using cDNA microarrays and were semi-quantitated by real-time RT-PCR. One of the genes identified was sortilin, which was upregulated one day after osteogenic induction and remained upregulated for a week. The overexpression of sortilin in hMSCs using an adenovirus vector resulted in the acceleration of mineralization during osteogenic differentiation without affecting alkaline phosphatase activity. Lipoprotein lipase (LPL), produced by adipocytes, is bound by sortilin, which may mediate its endocytosis. By adding LPL to osteogenic induction medium, osteoblastic mineralization was inhibited in a dose-dependent manner. Interestingly, sortilin overexpression abolished the LPL-mediated suppression of osteogenic differentiation. hMSCs exist in marrow where LPL-producing adipose cells are abundant and where osteogenesis is negatively regulated by LPL. Sortilin has a counter effect of promoting osteogenesis by acting as a scavenger of LPL.

Trauma-induced myelopathy in patients with ossification of the posterior longitudinal ligament.

OBJECT: In these prospective and retrospective studies the authors evaluated trauma-induced myelopathy in patients with ossification of the posterior longitudinal ligament (OPLL) to determine the effectiveness of preventive surgery for this disease. METHODS: The authors studied 552 patients with cervical OPLL, including 184 with myelopathy at the time of initial consultation and 368 patients without myelopathy at that time. In the former group of 184 patients retrospective analysis was performed using an interview survey to ascertain the relationship between onset of myelopathy and trauma. In the latter group of 368 patients prospective examination was conducted by assessing radiographic findings and noting changes in clinical symptoms apparent during regular physical examination. The follow-up period ranged from 10 to 32 years (mean 19.6 years). In the retrospective investigation, 24 patients (13%) identified cervical trauma as the trigger of their myelopathy. In the prospective investigation, 70% of patients did not develop myelopathy over a follow-up period greater than 20 years (determined using the Kaplan-Meier method). Of the 368 patients without myelopathy at the time of initial consultation, only six patients (2%) subsequently developed trauma-induced myelopathy. Types of ossification in patients who developed trauma-induced myelopathy were primarily a mixed type. All patients in whom stenosis affected 60% or greater of the spinal canal developed myelopathy regardless of a history of trauma. CONCLUSIONS: Preventive surgery prior to onset of myelopathy is unnecessary in most patients with OPLL.