[Efficacy of in travenous cyclophosphamide therapy on rheumatic diseases].
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Antirheumatic Agents↗
Biomedical subjects
Eiichi Tanaka
Publications and source records attributed to Eiichi Tanaka.
Expression of hepatocyte growth factor and its receptor (c-met) in skin fibroblasts from patients with systemic sclerosis.
OBJECTIVE: To determine the effect of excessive induction of hepatocyte growth factor (HGF)/c-met signaling in fibroblasts derived from patients with systemic sclerosis (SSc). METHODS: Fibroblasts were obtained from skin of patients with SSc and healthy controls. The 2.4 kb interleukin 1alpha (IL-1alpha) cDNA was subcloned into pcDNA3 expression vector, which was stably transfected into normal fibroblasts by lipofection. HGF production in cultured fibroblasts was measured by ELISA. C-met protein (a receptor for HGF) in cultured fibroblasts was evaluated by immunocytochemistry using polyclonal anti-c-met antibody. Production of procollagen type I was estimated by an ELISA system using antibodies against procollagen type I C-peptide. RESULTS: Cultured skin fibroblasts expressed mRNA and protein of HGF constitutively in both SSc and control cultures. However, HGF production in SSc fibroblasts was significantly higher than in normal fibroblasts. In both SSc and normal fibroblasts, HGF production was dose dependently increased by the addition of recombinant IL-1alpha. Immunocytochemical staining revealed that c-met was spontaneously expressed in SSc fibroblasts, whereas no expression of c-met was detected in normal fibroblasts. C-met mRNA was expressed in normal fibroblasts transfected with the IL-1alpha gene. Addition of recombinant HGF (100 ng/ml) to cultured SSc fibroblasts significantly decreased procollagen type I production. CONCLUSION: High concentration of HGF inhibited collagen production in cultured fibroblasts derived from patients with SSc. Overexpression of HGF/c-met appears to be a biological feedback response to the fibrotic process of SSc, suggesting that the antifibrotic effect of HGF might be used as a novel strategy for treatment of SSc.
Adult↗
Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene.
OBJECTIVE: N-acetyltransferase 2 (NAT2) is a key enzyme for the acetylation of sulfasalazine (SSZ). We examine whether there was a correlation between diplotype configurations (combinations of 2 haplotypes for a subject) at the NAT2 gene and the adverse effects of SSZ used for the treatment of rheumatoid arthritis (RA). METHODS: The findings from 144 patients with RA who had been treated with SSZ were collected from our outpatient department and used for a retrospective study. Haplotype analysis was performed by the maximum-likelihood estimation based on the EM algorithm using the obtained polymorphism data. RESULTS: Sixteen patients (11.1%) had experienced adverse effects from SSZ, the most common being allergic reactions including rash and fever. The slow acetylators who had no NAT2*4 haplotype had experienced adverse effects more frequently (62.5%) than the fast acetylators who had at least one NAT2*4 haplotype (8.1%) (p < 0.001, OR 7.73, 95% CI 3.54-16.86). In 25% of the slow acetylators, the adverse effects were so severe that they were hospitalized. CONCLUSION: Genotyping the NAT2 gene followed by estimation of diplotype configuration before administration of SSZ is likely to reduce the frequency of adverse effects in Japanese patients with RA.
Acetylation↗
[Pharmacogenetics of disease modifying anti-rheumatic drugs].
There are large differences in the effectiveness of disease modifying anti-rheumatic drugs(DMARD) from one person to the next. Adverse drug reactions caused by DMARD can also occur to some patients, but do not occur to others. One possible cause of the differences in the effectiveness and adverse drug reactions is genetic variation in how individuals metabolize drugs. The Human Genome Project heralds new opportunities for using information about genetic variation to predict responses to drug therapies, called pharmacogenetics. Based on pharmacogenetics, tailor-made drug therapy is going to be realized. Our recent studies revealed the relationship between genetic polymorphisms of drug metabolizing enzymes and the efficacy of methotrexate or sulfasalazine in patients with rheumatoid arthritis, suggesting pharmacogenetics is applicable to the treatment of rheumatoid arthritis.
Antirheumatic Agents↗
Changes in natural killer cell activity by external radiotherapy and/or brachytherapy.
Our purpose in this study was to determine the influence of radiotherapy, especially brachytherapy, on the activity of natural killer cells (NK). We examined changes in NK activity before and after radiotherapy in 27 patients who underwent radiotherapy with or without brachytherapy, comprising of 16 cases of cervical cancer (three recurrences), 5 of prostate cancer, 4 of esophageal cancer and 2 of tongue cancer. Fourteen intracavitary procedures (for 13 cervical cancers and 1 esophageal cancer) and 10 interstitial brachytherapy (for 3 cases of recurrent cervical cancer, 5 of prostate cancer and 2 of tongue cancer) were performed with Ir-192 microSelectron HDR and Selectron Cs-137. External radiotherapy consisted of 10 MV X-ray administration for 13 cases of cervical cancer and 4 of esophageal cancer. The number of white blood cell was reduced by radiotherapy from 5065 +/- 2002 count/ml to 4281 +/- 1392 count/ml (p=0.02), that of lymphocytes from 1518 +/- 817 to 762 +/- 409 /ml (p<0.0001), and that of CD 16+ cells from 274 +/- 197 to 14 +/- 96 (p=0.03). No significant change was observed in the number of CD 56+ cells (274 +/- 166 to 211 +/- 153 /ml). Overall NK activity was reduced by radiotherapy from 37 +/- 19% to 30 +/- 19% (p=0.001). External radiotherapy with or without brachytherapy reduced NK activity from 33 +/- 18% to 23 +/- 16% (p=0.004). However interstitial brachytherapy produced little change in NK activity from 42 +/- 18 to 39 +/- 19%). Radiotherapy reduced the number of white blood cell, lymphocyte and CD 16+ cells. Although external radiotherapy suppressed NK activity, only brachytherapy showed little influence on NK activity alteration.
Adult↗
High dose rate endovascular brachytherapy in aorto-iliac lesion for the prevention of restenosis.
This study examined the applicability of endovascular brachytherapy to larger del arteries such as the abdominal aorta and iliac artery. Endovascular brachytherapy using an Ir-192 HDR source was administered 11 times to nine patients who had undergone percutaneous transluminal angioplasty (PTA) between 1995 and 1999. The follow-up lasted 13 to 55 months after treatment (median, 24 months). Eight of the 11 lesions have been controlled so far. Although one case developed thrombus inside the stent five months later, recanalization was achieved by means of retreatment. One patient who underwent low-dose irradiation (6 Gy) without stent implantation showed restenosis five months after treatment. We used a centering catheter that did not block the blood stream for exact centering of the radiation source in larger vessels such as the abdominal aorta. Although endovascular brachytherapy is a promising and safe procedure, careful follow-up is needed to detect untoward reactions such as thrombosis.
Aged↗
CyberKnife stereotactic irradiation for metastatic brain tumors.
BACKGROUND: The CyberKnife provides a new technique for performing frameless stereotactic irradiation. So far, few reports have been published on clinical outcomes obtained with the CyberKnife. This report summarizes our clinical experience with CyberKnife irradiation for metastatic brain tumors. MATERIALS AND METHODS: Seventy-seven lesions (48 patients) were evaluated and analyzed, and 66 lesions in 41 patients were treated with stereotactic radiosurgery (SRS). The prescribed dose was 9 to 30 Gy. RESULTS: Freedom from progression of the tumors was more likely with a prescribed dose of at least 24 Gy than with one of less than 20 Gy (p=0.0244; log-rank test). The CR (complete response) rate was significantly higher when D99 was at least 24 Gy (p=0.0045). There were no severe side effects. CONCLUSION: Stereotactic irradiation with the CyberKnife for metastatic brain tumors is effective and safe. D99 should be at least 24 Gy for CyberKnife SRS treatment.
Brain Neoplasms↗
Middle colic artery-gastroepiploic artery bypass for compromised collateral flow in distal pancreatectomy with celiac artery resection.
BACKGROUND/AIMS: Radical distal pancreatectomy with en-bloc resection of the common hepatic, celiac, and left gastric arteries for pancreatic body cancer that involves these arteries does not routinely require arterial reconstruction because the collateral pathways via the pancreatoduodenal arcades from the superior mesenteric artery are recruited immediately. However, accidental injury to the pancreatoduodenal artery compromises collateral blood flow and may lead to fatal complications. This article describes the middle colic artery-gastroepiploic artery bypass as an emergent salvage procedure for restoring collateral flow. METHODOLOGY: The inferior pancreatoduodenal artery was accidentally injured in 2 of 9 patients who underwent the radical procedure between 1997 and 2001. Microvascular anastomosis between the left branch of the middle colic artery and the gastroepiploic artery in an end-to-side fashion was employed. RESULTS: The pulsation of the gastroepiploic artery and the color of the stomach recovered immediately after completion of the middle colic artery-gastroepiploic artery bypass. No ischemia-related complication developed postoperatively. Postoperative angiography showed the middle colic artery-gastroepiploic artery bypass supplying arterial flow to the liver, stomach, duodenum, and pancreas. CONCLUSIONS: The middle colic artery-gastroepiploic artery bypass is an excellent alternative restoring compromised collateral flow via the pancreatoduodenal arcades when microsurgical technique is available.
Celiac Artery↗
Venous-drainage-guided selective hepatectomy: a novel approach to liver surgery.
Selective hepatectomy under the guidance of hepatic venous drainage has not yet been developed because hepatic venous occlusion alone produces no visible congested area. Now that this area can be identified by simultaneous occlusion of the hepatic vein and artery, venous-drainage-guided selective hepatectomy is considered feasible. Because the congested area becomes dysfunctional or atrophic due to the absence of portal blood supply, it can be regarded as a first candidate for preventive resection in livers that may bear latent tumors. We report here a novel approach to selective hepatectomy. Segment 4 hepatectomy and ventral hemisectorectomy of segments 5+8, with middle hepatic vein resection, was undertaken in a patient with hepatocellular carcinoma. After hepatic dissection between segments 2+3 and 4, the root of the middle hepatic vein was isolated. Test clamping of the middle hepatic vein and proper hepatic artery demonstrated a discolored area. Hepatic dissection was performed along the discolored border towards the hepatic hilum, exposing the right anterior portal pedicle with division of the ventral branches. The middle hepatic vein was finally divided. Selective hepatectomy was successfully performed without transfusion or complications. Venous-drainage-guided selective hepatectomy is feasible with acceptable perioperative results.
Aged↗
Treatment results of radiotherapy with or without surgery for posterior pharyngeal wall cancer of oropharynx and hypopharynx: prognostic value of tumor extension.
PURPOSE: We have been treating posterior pharyngeal wall cancer of the oropharynx and hypopharynx with external radiotherapy according to our policy reported in the 1970s. MATERIALS AND METHODS: Between 1968 and 1995, 51 patients were treated. Treatment policy was decided on the basis of the treatment response after 40 Gy of radiotherapy. Thirty-six good responders were treated with radical radiotherapy, eight poor responders received radical surgery, and the other seven patients could not receive radical treatment because of tumor or patient factors. RESULTS: The 5-year local control and cause-specific survival rates were 56% and 48% for all 51 patients. The 5-year local control rate was 52% for radical radiotherapy. Tumors limited to the posterior wall showed better treatment results (76% for both local control and cause-specific survival) than tumors involving the postcricoid area (0% and 10%). CONCLUSION: Radiotherapy for carefully selected patients dependent on response after 40 Gy of radiotherapy is a useful policy. Tumor extension is an important prognostic factor.
Adult↗
Quantitative evaluation of changes in irradiated lung fields after stereotactic irradiation by the Polygon Method.
PURPOSE: To evaluate areas of change in lung after thoracic stereotactic irradiation (STI). MATERIALS AND METHODS: We developed a method of evaluation named the Polygon Method, to measure the irradiated lung fields of 12 lung tumors treated by STI. Before treatment, each targeted field was divided into several circular zones of 2 cm in width centered at the tumor on high resolution computed tomography, and the areas of each zone before and after treatment were compared. RESULTS: Six months after treatment, the areas of the zone within 2 cm from the tumor decreased, and the mean ratio of areas after and before STI was 0.849 (range, 0.515 to 1.052, p=0.0254). By contrast, the areas of zones located at 4 to 6, 6 to 8, 8 to 10, and more than 10 cm from the tumor tended to increase, with mean ratios of 1.059, 1.058, 1.089 (p=0.0374), and 1.084, respectively. CONCLUSION: After thoracic STI, volume loss in the lung is limited to the field in close proximity to the tumor, while compensatory expansion of the lung occurs in fields distant from the tumor.
Adenocarcinoma↗
Pancreas-preserving biliary amputation with pancreatic diversion: a new surgical technique for complete resection of the intrapancreatic biliary system.
Pancreatoduodenectomy is not optimal for organ preservation in patients with mucosal carcinoma of the choledochus. When the lesion spreads near the papilla of Vater, pancreas-preserving biliary amputation may be indicated to achieve complete resection of the biliary system. The first successful case is reported here with technical considerations. First, the pancreatic neck was divided and a tube was inserted into the main pancreatic duct beyond the papilla. The choledochus was dissected downward with division of the posterior pancreatoduodenal vessels. The main pancreatic duct was isolated with the aid of palpation of the tube, and was then ligated and divided. Subsequent dissection was performed to the level of the duodenal mucosa, which was incised circularly. The duodenal defect was then closed. The elevated jejunum was interposed between the pancreatic stumps and bilateral pancreaticojejunostomies were created. The procedure was successfully performed in a patient with superficially spreading cholangiocarcinoma. Postoperative bile leak and pancreatic fistula were controlled with medical management. The patient is currently well without tumor recurrence 19 months after surgery. Her glucose tolerance, which was moderately impaired preoperatively, has been maintained. Pancreas-preserving biliary amputation has been developed as an organ-preserving procedure alternative to pancreatoduodenectomy. Indications, methods of pancreatic reconstruction, and long-term results require further study.
Aged↗
Appraisal of DSRS with SPGD for esophagogastric varices: a retrospective comparative study according to the underlying liver diseases.
BACKGROUND/AIMS: The differences in long-term results of distal splenorenal shunt with splenopancreatic and gastric disconnection (DSRS with SPGD) for portal hypertension of different etiologies including non-cirrhotic portal hypertension have yet to be reported. The data are important to determine the indications and contraindications for this procedure. METHODOLOGY: Records of 54 patients of esophagogastric varices who survived 3 years or longer after DSRS with SPGD operation were reviewed. Patients were divided into three groups based on underlying liver disease; posthepatitic cirrhosis (HC) group, alcoholic cirrhosis (AC) group, and idiopathic portal hypertension (IPH) group. RESULTS: The only serious long-term complication of DSRS with SPGD was portal thrombosis in two patients in the IPH group. Postoperative bleeding occurred in two cases of each group; one in IPH group was the only variceal bleeding and others were bleeding from portal hypertensive gastropathy. Hepatocellular carcinoma (HCC) was developed in 28.6% patients in both the HC group and AC group. In all the cases, treatment for HCC was accomplished without aggravation of the varices. The cumulative survival rate was similar in the three groups, and no patient died of gastrointestinal bleeding. CONCLUSIONS: A favorable outcome was achieved by DSRS with SPGD operation both in the patients with cirrhosis or IPH. Underlying liver disease is not a factor when considering DSRS with SPGD for portal hypertension.
Dissection↗
High-dose-rate interstitial brachytherapy for mobile tongue cancer: influence of the non-irradiated period.
BACKGROUND: It has been demonstrated that the outcome of primary radiotherapy in squamous cell carcinomas of the head and neck is strongly influenced by overall treatment time. The purpose of this study was to evaluate the results of high-dose-rate (HDR) interstitial brachytherapy (ISBT) for early mobile tongue cancer and to examine whether the non-irradiated period affected treatment results. MATERIALS AND METHODS: Seventy-one patients with early mobile tongue cancer (T1-T2N0M0) were treated with HDR ISBT alone. The total dose was 54-60 Gy/9-10 fractions/5-9 days. All patients were classified into 4 groups: R0, maximum non-irradiated period (NIP) was less than 24 h (n=16); R1, maximum NIP was from 24 to 48 h (n=24); R2, maximum NIP was from 48 to 72 h (n=26); R3, maximum NIP was from 72 to 96 h (n=5). RESULTS: The 3-year local control rate was 94% in R0, 83% in R1, 85% in R2 and 100% in R3. The 3-year overall survival rate was 84% in R0, 92% in R1, 71% in R2 and 80% in R3. There was no significant difference in the local control rate, overall survival rate, or complications among the 4 groups. CONCLUSION: In HDR ISBT for early mobile tongue cancer, the non-irradiated period did not affect the treatment results or complications.
Adult↗