Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial

We have previously demonstrated the efficacy of therapeutic exercise for osteoarthritis (OA) of the knee. This study was performed to examine the additive effects of glucosamine or risedronate on the exercise therapy. In this study, 142 female patients with moderate OA of the knee, who had been recommended to undergo home exercise at the first visit to the hospital, were randomly given glucosamine hydrochloride, risedronate, or no additive. Although improvement after 18 months was observed in all groups using individual scales for evaluation of pain and function of the knee, no significant differences were observed between the groups regarding any of the scales, indicating no significant additive effect of glucosamine or risedronate. One reason for the lack of effect of glucosamine or risedronate on OA of the knee may be that the effect of these agents was occluded by the effect of therapeutic exercise to improve pain and function of the knee. This finding means that even if glucosamine and risedronate were to have an effect on OA of the knee, the effect would not be greater than the effect of knee exercise to improve the symptoms.     

Novel interventional treatment technique for intractable pancreatic fistula due to dehiscence of pancreatico-jejunal anastomosis following pancreaticoduodenectomy

Despite recent technological advances in the treatment of hepatobiliary pancreatic disease, intractable external pancreatic fistula is still a major critical complication after pancreaticoduodenectomy, and the treatment strategy is not well defined. We report here a case that was successfully treated by our novel interventional internal drainage technique. A 62-year-old woman underwent pylorus-preserving pancreaticoduodenectomy for carcinoma of the papilla of Vater, with reconstruction by a modified Child's procedure. One year later, she was readmitted to our hospital because of external pancreatic fistula. Both computed tomography and fistulography demonstrated a pancreatic fistula derived from dehiscence of the pancreatico-jejunal anastomosis. The pancreatic fistula persisted for 1 week with conservative management. Therefore, we performed repeated fistulography and cannulation, using two comparatively stiff guidewires introduced into the main pancreatic duct and stenotic anastomosed jejunal lumen, respectively, and we placed an endoprosthesis, using bilateral guidewires to connect the two lumens. Consequently, the pancreatic fistula was successfully closed within a few days. Our novel technique is simple, rapid, and not costly. Therefore, it should be considered an effective treatment strategy for persistent pancreatic fistula following pancreaticoduodenectomy that fails to respond to initial conservative management and an endoscopic approach. Also, this technique is applicable to other intractable fistulous situations.     

Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is widely expressed in the brain, and plays key roles in various cellular processes in response to both extracellular and intracellular stimuli. Here, we explored the role of FAK in cerebellar development. In the mouse cerebellum, FAK was found to be distributed as tiny cytoplasmic aggregates in various neuronal and glial elements, including Purkinje cells (PCs), Bergmann glia (BG), parallel fiber (PF)-terminals and climbing fiber (CF)-terminals. The neuron/glia-specific ablation of FAK impaired cerebellar foliation, such as variable decreases in foliation sizes and the lack of intercrural and precentral fissures. Some of the BG cells became situated ectopically in the molecular layer. Furthermore, the FAK ablation altered the innervation territories of CFs and PFs on PCs. CF innervation regressed to the basal portion of proximal dendrites and somata, whereas ectopic spines protruded from proximal dendrites and PFs expanded their territory by innervating the ectopic spines. Furthermore, the persistence of surplus CFs innervating PC somata caused multiple innervation. When FAK was selectively ablated in PCs, diminished dendritic innervation and persistent somatic innervation by CFs were observed, whereas cerebellar foliation and cell positioning of BG were normally retained. These results suggest that FAK in various neuronal and glial elements is required for the formation of normal histoarchitecture and cytoarchitecture in the cerebellum, and for the construction of proper innervation territory and synaptic wiring in PCs.     

Non-opsonising aggregates of IgG and complement in haemoglobin C erythrocytes

Haemoglobin C (HbC) differs from normal HbA by a lysine for glutamate substitution at position 6 of beta-globin. Heterozygous AC and homozygous CC phenotypes are associated with shortened erythrocyte life spans and mild anaemia. AC and CC erythrocytes contain elevated amounts of membrane-associated haemichromes, band 3 clusters, and immunoglobulin G (IgG) in vivo. These findings led us to investigate whether AC and CC erythrocytes might expose elevated levels of IgG and complement, two opsonins that have been implicated in the phagocytic clearance of senescent and sickle erythrocytes. Surprisingly, we found IgG, complement, and other plasma proteins co-localised in aggregates beneath the membrane of circulating AC and CC erythrocytes. These observations, and our finding of similar aggregates in erythrocytes heterozygous or homozygous for haemoglobin S (sickle-cell haemoglobin), suggest that the vast majority of membrane-associated IgG and complement detected in these abnormal erythrocytes is intracellular and does not contribute to the eventual opsonic clearance of these cells. Phagocytosis studies with macrophages provide evidence in support of this suggestion. Studies of erythrocyte clearance that involve the detection of membrane-associated IgG and complement as putative opsonins should investigate the possibility that these plasma proteins reside in the erythrocyte interior, and not on the cell surface.     

A pilot study of docetaxel-carboplatin versus paclitaxel-carboplatin in Japanese patients with epithelial ovarian cancer

Background It has been reported that a docetaxel-carboplatin combination as first-line chemotherapy for ovarian cancer showed a level of progression-free survival similar to that of paclitaxel-carboplatin while reducing neurotoxicity and improving quality of life. We investigated the recommended doses of docetaxel-carboplatin in Japanese patients with ovarian cancer and conducted a comparative study of docetaxel-carboplatin versus paclitaxel-carboplatin. Methods Thirty-nine patients with ovarian cancer were enrolled in this study and 38 patients were evaluated. We conducted a dose-escalation study using a docetaxel dose of 70 mg/m² and carboplatin AUC 5 and 6. In the comparative study, patients received either docetaxel 70 mg/m² and carboplatin AUC 5 or paclitaxel 175 mg/m² and carboplatin AUC 5. Progression-free survival, survival rate at 2 years, response rate, toxicity, and quality of life were investigated. Results In the dose-finding study, we determined the recommended doses as docetaxel 70 mg/m² and carboplatin AUC 5. In the comparative study, the two arms showed similar progression-free survival. Grade 4 neutropenia occurred more frequently in the docetaxel-carboplatin group (84.6%) than in the paclitaxel-carboplatin group (43.8%), while sensory neurotoxicity was less frequent in the docetaxel-carboplatin group (53.8%) than in the paclitaxel-carboplatin (68.8%) group. There were significant differences in the quality-of-life data in favor of docetaxel-carboplatin. Conclusion We determined the recommended doses of docetaxel-carboplatin for Japanese patients with ovarian cancer to be docetaxel 70 mg/m² and carboplatin AUC 5. In the comparative study, we suggest that the docetaxel-carboplatin combination is effective and well tolerated as first-line chemotherapy for Japanese patients with ovarian cancer.     

Glucose transporter type 1 expression are associated with poor prognosis in patients with salivary gland tumors

The objective of this study was to investigate the expression of Glucose transporter type 1 (GLUT1) and its relation to clinicopathologic parameters in patients with salivary gland tumors. Tissue samples were 49 cases of malignant tumors, 38 cases of benign tumors, mainly pleomorphic adenoma and 10 cases of normal salivary glands. Immunohistochemically, GLUT1 Labeling Index of malignant tumor was significantly higher than benign tumor. In RT-PCR assay, GLUT1 mRNA level in malignant tumor were higher than that of normal tissue. In malignant tumors, expression of GLUT1 correlated significantly with tumor size (p=0.002) and distant metastasis (p=0.007). Cumulative survival rate of high expression group was significantly lower than that of low (p<0.001). In multivariable analysis, overall survival significantly correlated with lymph node metastasis (p=0.042) and GLUT1 expression (p=0.022). These results suggest that GLUT1 expression may provide useful prognostic information in patients with salivary gland carcinoma.     

A case of recurrent GIST of the esophagus which completely responded to imatinib mesilate

Middle and lower esophagectomy was performed in a 68-year-old man in 1997 for the local recurrence of esophageal submucosal tumor after enucleation of the tumor. We subsequently performed partial hepatectomy for multiple liver metastases in 2001. The tumor was first diagnosed as GIST in the histological examinations of the liver metastases. However, 12 months after the hepatectomy, further recurrent lesions were found in multiple lymph nodes, in the remnant liver, and in the pancreas, as well as in the subcutaneous tissue. The lesions were initially considered unresectable, and we thus started an internal use of Glivec (400 mg/day) since July 2004. Within 2 months,all detected recurrent lesions changed into liquid forms,and the size of the subcutaneous tumor was also remarkably reduced. Accumulation of FDG was not seen on FDG-PET examination, suggesting the complete response of the tumor to Glivec. We still continue internal use of Glivec, and new recurrent lesions have not been detected up to now. Furthermore, the sizes of the liquid-regenerated lesions are gradually reducing.     

Acral myxoinflammatory fibroblastic sarcoma of the foot

We report a rare case of acral myxoinflammatory fibroblastic sarcoma (AMFS) in a 68-year-old woman. Tumor excision of a mass between the 1st and 2nd toe of the left foot was performed after a diagnosis of ganglion in February 2003. Examination of the surgical specimen confirmed AMFS. No recurrence or metastasis occurred during the follow-up period of 4 years. Clinical characteristics such as recurrence rate, metastasis rate and period of metastasis are unclear for AMFS. Long-term clinical follow-up is thus required.     

The effect of neoadjuvant chemotherapy on lymph node micrometastases in squamous cell carcinomas of the thoracic esophagus

BACKGROUND: Neoadjuvant chemotherapy (NACT) has been postulated but not yet proven to eradicate micrometastases and improve the prognosis of patients with advanced esophageal squamous cell carcinomas (ESCC). Cytokeratin immunohistochemistry of the lymph nodes of ESCC revealed immunohistochemical micrometastases (IHM) and cytokeratin deposits (CD), which are hyalinized denucleated particles considered to be cadavers of carcinoma cells. Successful chemotherapy should convert cancer cells from IHM to CD and improve the status of ESCC patients from systemic disease to regional disease. METHODS: Cytokeratin immunostaining of surgically removed lymph nodes was performed for 107 patients with node-positive ESCC, including 32 patients without preoperative treatment (Surgery group) and 75 patients undergoing NACT using CDDP, doxorubicin hydrochroride, and 5-fluorouracil (NACT group). Cytokeratin-positive staining was done for serial hematoxylin-eosin-stained sections and classified as pathologic metastasis, IHM, or CD. RESULTS: CD was observed less frequently in the Surgery group than in the NACT group (6% vs 43%, P < .0001), whereas IHM was more frequent in the former (47% vs 24%, P = .019). IHM was a poor prognostic factor in both groups, whereas CD was a favorable one in the NACT group. The effect of chemotherapy on IHM was classified as eradicated, IHM(-)/CD(+); persistent, IHM(+)/CD(+); no effect, IHM(+)/CD(-); or not informative, IHM(-)/CD(-). This classification correlated well with the clinical response of the primary neoplasm, number of pathologic metastases, and postoperative survival (3-year survival rates: 78%, 18%, 0%, and 38%). IHM/CD was found to be an independent prognostic factor together with the number of pathologic metastases in the multivariate analysis. CONCLUSIONS: Disappearance of IHM and the emergence of CD suggest the eradication of micrometastases by NACT. The clinical benefit of NACT was apparent for IHM(-)/CD(+) patients with node-positive ESCC.