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Keiichi Kubota

Publications and source records attributed to Keiichi Kubota.

At least 37 records · Page 2Linked to original sources
PubMed2005

Prognostic significance of CD83 positive, mature dendritic cells in the gallbladder carcinoma.

Dendritic cells (DCs) are very potent antigen-presenting cells that play an essential role in the primary immune response to carcinoma. Tumor-infiltrating DCs have been found to be clinically significant in many human malignancies such as colon, stomach, lung, breast and hepatic carcinoma. However, clinical significance of activated and/or immature DCs in gallbladder carcinoma has not been reported yet. Thus, we immunohistochemically evaluated CD83+ DCs and CD1a+ DCs of cancerous and peritumoral area in 29 cases of resected gallbladder. In the results, CD83(+) DCs were significantly fewer in cancerous area than that in peritumoral area (1.55/hpf vs. 4.26/hpf, p=0.0047), but the numbers of CD1a(+) DCs did not differ (p=0.075). In addition, we defined a CD83 index as CD83(+) DCs/(CD83(+) DCs plus CD1a(+) DCs), and analyzed the relationship between CD83 index and clinicopathological factors. The group with a higher CD83 index (index >0.316) showed significantly better prognosis than the group with a lower CD83 index (index < or =0.316) in cancerous and peritumoral areas. In conclusion, we suggest the importance of tumor-infiltrating CD83(+) DCs as a useful prognostic factor for patients with gallbladder carcinoma.

Antigens, CD↗
PubMed2005

[Experience with capecitabine in patients with anthracycline and/or taxane-resistant recurrent breast cancer].

We evaluated the safety and efficacy of capecitabine in 12 patients with anthracycline and/or taxane-resistant metastatic breast cancer on an outpatient basis. Their mean age was 57 years, and they previously received chemotherapy consisting of anthracycline in 7 cases, taxane in 12 and doxifluridine in 8. Their mean disease-free interval was 28.5 months, HER 2/neu and ER and/or PgR-positive was shown in 2 and 8 cases, respectively. The recurrent sites were lymph node in 9 cases, lung in 6, skin in 5, pleural effusion in 4, liver, bone and pleura in 3, brain and CBS in 2, and thyroid, ascites and pericardial effusion in one, respectively. The administration dose was 2,400 mg/day in 11 cases and 3,000 mg/day in one. Capecitabine was administered orally for 21 consecutive days followed by a one-week rest. The mean follow-up period was 6.5 months. The overall response rate was 18.2% in 11 cases, including 2 partial responses, 4 stable diseases and 5 progressive diseases. Clinical benefit was 36.4% including two long stable diseases. The mean time to treatment failure was 6.5 months. Adverse events included Hand-Foot Syndrome in 5 cases, nausea in 3, diarrhea, appetite loss and high fever in one, respectively. In two of them administration was discontinued due to adverse events. Capecitabine had satisfactory effects with tolerable adverse events for anthracycline- and/or taxane-resistant metastatic breast cancer.

Administration, Oral↗
PubMed2005

[Capsule endoscopy].

Wireless capsule endoscopy is a new diagnostic tool in which a disposable video capsule is swallowed by the patient. This examination enables visualization of the small intestine that is not within the reach of conventional upper and lower endoscopy. The best indications include an obscure source of gastrointestinal bleeding, Crohn's disease, and small intestinal tumors. The disadvantage that biopsy cannot be performed is compensated for by employing double-balloon endoscopy. In particular, this examination can identify the origin of bleeding and diagnose the underlying disease, leading to prompt surgical treatment with better results. In future, capsule endoscopy will become a necessary examination for diagnosing digestive tract disease.

Endoscopes, Gastrointestinal↗
PubMed2004

Immunization by blood-type antigen in human immunoglobulin products before ABO-incompatible kidney transplantation.

A 29-year-old man wanted to receive an ABO-incompatible kidney transplant. His blood type was O, and the donor, his father, was A1. After endoscopic splenectomy performed before kidney transplantation, the recipient developed a high fever and leukocytosis, and he was treated with antibiotics and 5 g of human immunoglobulin products by intravenous infusion for 3 d. Soon after the infusions, his anti-blood type A antibody titer (anti-A titer) rose, and several sessions of plasma-exchange (PEX) and double-filtration plasmapheresis (DFPP) failed to lower it. Three courses of anti-CD20 monoclonal antibody were administered to suppress the antibody production more specifically, and the rituximab infusions and repeated PEX and DFPP session lowered the anti-A titer and enabled kidney transplantation. Mild humoral rejection was observed 16 d after transplantation, but the recipient's serum creatinine was 1.5 mg/dL when discharged from the hospital. The increased anti-A titer may have been due to immunization by blood-type A antigen, with the human immunoglobulin products given to the patient being the source of the antigen. Administration of human immunoglobulin products to recipients of ABO-incompatible kidney transplants should be avoided, because it may cause an unexpected increase in anti-blood-type antibody titer.

ABO Blood-Group System↗
PubMed2004

Long-term complications of laparoscopic ventral and incisional hernia repair.

To date, there have been no long-term follow-up studies of the results of laparoscopic ventral and incisional hernia repair. We evaluated the long-term complications of these repairs over a mean follow-up period of 64 months. Between March 1993 and April 2000, we retrospectively evaluated 9 patients who underwent ventral or incisional hernia repair with prosthetic material and one patient who received laparoscopic primary closure of a hernia defect. The prosthetic material polypropylene was used in one patient and an expanded-polytetrafluoroethylene patch was used in the other 8. In one patient, the hernia was closed directly. In 7 patients, the prosthesis was fixed by stapling or tacking with no transfacial suture fixation and a 2-cm prosthesis overlap. In 2 later patients, we modified our technique by fixing the prosthesis by stapling or tacking with transfacial suture fixation and using prosthesis overlap of more than 3 cm. There were 2 episodes of hernia recurrence (20%), one of which required reoperation. Both occurred in patients in whom we used the unmodified repair technique. One of the patients in whom we used the unmodified technique developed a seroma which resolved spontaneously without antibiotic therapy. One patient in whom we used the modified technique developed infection (10%) requiring removal of the prosthetic material. The 2 episodes of hernia recurrence occurred 40 months after laparoscopic treatment, and the case of infection occurred 11 months after treatment. There were no episodes of recurrence in patients who received the unmodified surgery and had hernia defects less than 42 cm2. To perform safe and effective laparoscopic repair of ventral or incisional hernias, it is necessary to use a prosthetic overlap of more than 3 cm from the edge of the hernia gate and to use transfacial suture fixation with nonabsorbable sutures. In addition, patients who undergo laparoscopic ventral or incisional hernia repair should be observed for more than 5 years.

Aged↗
PubMed2004

Laparoscopic removal of an intragastric foreign body with endoscopic assistance.

We report the successful laparoscopic removal of an intragastric foreign body. A 57-year-old woman who had accidentally swallowed her own partial denture was referred to our hospital for its removal. Laparoscopic removal of the foreign body was urgently performed with the assistance of oral endoscope, following an earlier failed endoscopic removal associated with subcutaneous and mediastinal emphysema. The foreign body was removed from the stomach through a gastrotomy. There were no perioperative complications. The patient was uneventfully discharged on the ninth postoperative day. Laparoscopic removal of an intragastric foreign body is a feasible and safe treatment, and can be an alternative choice following failed endoscopic removal.

Adult↗
PubMed2004

Preconditioning regimen consisting of anti-CD20 monoclonal antibody infusions, splenectomy and DFPP-enabled non-responders to undergo ABO-incompatible kidney transplantation.

Patients undergoing ABO-incompatible kidney transplantation must have their anti-donor blood-type antibody titer (ADBT) reduced to below 1:16 by using either plasma-exchange (PEX) or double filtration plasma exchange (DFPP) before they can safely undergo a transplantation. The ADBT can be reduced to under 1:16 in most cases; however, some cases (non-responders) do not respond to PEX or DFPP treatment. To enable kidney transplantations to be performed in non-responders, we developed a new preconditioning regimen consisting of anti-CD20 monoclonal antibody (rituximab) infusions, a splenectomy, and DFPP. Four non-responders were infused with rituximab at a dose of 375 mg/m(2) weekly for 3-4 wk and splenectomized 1 or 2 wk before transplantation. Four to five DFPP-sessions were then performed after the splenectomy. Using this preconditioning regimen, the ADBT was reduced to below 1:16, enabling kidney transplantations to be successfully performed in all patients. After the kidney transplantation, no episodes of humoral rejection were observed, and only one episode of cellular rejection was encountered. The cellular rejection was associated with a reduction in immunosuppressant administration because of CMV infection that occurred 80 d after the kidney transplantation. The renal allografts were functioning well in all patients after a mean follow-up period of 390 d. No serious complications or side effects were encountered. We have developed a new preconditioning regimen that enables PEX and DFPP non-responders to undergo ABO-incompatible kidney transplantations.

ABO Blood-Group System↗
PubMed2004

beta6 integrin is up-regulated in chronic renal allograft dysfunction.

Up-regulation of beta6 integrin, which is indispensable to the activation of transforming growth factor-beta1 (TGF-beta1), was investigated in chronic renal allograft dysfunction (CAD). A total of 103 renal biopsy samples (normal, 10; acute rejection, 30; CAD, 63) were immunohistochemically evaluated for expression of TGF-beta1 and beta6 integrin. No TGF-beta1 or -beta6 integrin was detected in normal kidney, but both TGF-beta1 and -beta6 integrin reactivity were observed in the distal tubules in acute rejection, and even greater reactivity was observed in the distal tubules in the CAD samples. Semiquantitative analysis revealed that the reactivity of TGF-beta1 and -beta6 integrin was significantly greater in the CAD kidney than in the normal kidney and the kidney in acute rejection. The results suggest that beta6 integrin as well as TGF-beta1 is up-regulated in CAD and that it may serve as an alternative target for the treatment for CAD.

Acute Disease↗
PubMed2004

Dysfunction of p53 pathway in human colorectal cancer: analysis of p53 gene mutation and the expression of the p53-associated factors p14ARF, p33ING1, p21WAF1 and MDM2.

Mutations of p53 tumor suppressor gene increase with tumor progression in colorectal cancers. In this study, we examined the expressions of p33ING1, p14ARF, MDM2 and p21WAF1 mRNA in 25 advanced colorectal cancers by quantitative RT-PCR method, and compared the expression levels of p33ING1, p14ARF, p21WAF1 and MDM2 in relation to p53 status in the tumors. Fifteen of 25 colorectal cancers (60%) showed abnormal accumulation of p53 protein in the nucleus, and the remaining 10 colorectal cancers (40%) were negative for p53 immunostaining. We found a G --> T transition (nonsense mutation) at the first nucleotide of codon 298 (exon 8) in one p53-negative case, and a frame shift mutation on exon 7 in another p53-negative case. In remaining eight p53-negative cases, there was no mutation in the entire open reading frame of p53 cDNA. Interestingly, in eight cases with p53 wild-type gene, 6 cases (75%) showed a marked down-regulation of p14ARF mRNA, and three cases (37.5%) over-expressed MDM2 mRNA. Only one case with wild-type p53 gene showed normal level expression of p53 regulatory-factors (p33ING1, p14ARF, and MDM2). Thus, p53 tumor suppressor pathway was disrupted in 24 of 25 colorectal cancers (96%).

Aged↗
PubMed2004

[Docetaxel (TXT), epirubicin (EPI) and doxifluridine (5'-DFUR) combination neoadjuvant chemotherapy for outpatients with locally advanced breast cancer].

We evaluated the safety and efficacy of neoadjuvant chemotherapy with docetaxel (TXT), epirubicin (EPI) and doxifluridine (5'-DFUR) in 5 patients with locally advanced breast cancer on an outpatient basis. Their mean age was 49.6 years, and preoperative stages were IIa: one case, IIb: two; and IlIb: two; respectively. The regimen consisted of 5'-DFUR (800 mg/day) orally for 14 consecutive days, and TXT (60 or 70 mg/m2) and EPI (50 or 60 mg/m2) intravenously on day 8. It was repeated 4 times every 3 weeks. Although the results revealed leucopenia and neutropenia of more than grade 3 in 4/5 patients, no other adverse events were observed. The use of G-CSF was necessary to maintain this regimen, and the patients could be treated on an outpatient basis. Breast conserving therapy was performed in two patients. Pathological findings revealed Grade 2 and 3 cytological degeneration in two and one patients, respectively, and parasternal lymph node metastasis in one, but no axillary lymph node metastasis. These findings suggested satisfactory effects of this neoadjuvant chemotherapy regimen. This combination chemotherapy without severe adverse events would be an alternative choice of neoadjuvant chemotherapy on an outpatient basis.

Adenocarcinoma, Scirrhous↗
PubMed2003

Heterozygous disruption of the alpha1,3-galactosyltransferase gene in cattle.

BACKGROUND: Animal cloning techniques have enabled gene disruption in several species. Here, we report the first successful disruption of the alpha1,3-galactosyltransferase (alpha1,3-GT) gene in cattle. METHODS: The alpha1,3-GT gene of the Japanese Black cow (JBC) was used to construct pGT-6, a targeting vector for the bovine alpha1,3-GT gene, and pGT-6 was introduced into the fetal fibroblast cell line JBC906 by the lipofection method. Four polymerase chain reaction (PCR)-positive colonies were obtained from 797 G418-resistant colonies, and Southern blot analysis revealed successful homologous recombination at the alpha1,3-GT locus in one of the four colonies. Nuclear transfer was performed, and the four embryos were transferred to a heifer. RESULTS: To establish fetal fibroblasts that were heterozygously disrupted at the alpha1,3-GT locus, one of the fetuses was recovered at 5 weeks of pregnancy, and PCR and Southern blot analysis of the fetal fibroblasts established from it showed definite homologous recombination of the alpha1,3-GT gene. CONCLUSIONS: Heterozygous knockout of the alpha1,3-GT gene was performed in JBC, and production of a homozygous alpha1,3-GT knockout JBC by a second round of targeting 906htGT is currently in progress. The technique described here can be applied to disruption of other genes in cattle.

Active Transport, Cell Nucleus↗
PubMed2003

Unusual onset of chronic graft-versus-host disease after adult living-related liver transplantation from a homozygous donor.

Graft-versus-host disease (GVHD) is a rare complication that occurs after living-related liver transplantation (LRLT). This condition usually occurs early after transplantation and is fatal. Although one-way matching between a human leukocyte antigen (HLA)-homozygous donor and a haploidentical recipient has been shown to be a significant risk factor for the development of acute GVHD, chronic GVHD has not been clarified. A 50-year-old woman underwent LRLT for primary biliary cirrhosis with her 32-year-old HLA-homozygous son as the donor. The patient developed chronic GVHD 114 days posttransplant, presenting with a skin rash only. Her atypical onset included neither fever nor gastrointestinal symptoms. The patient responded to corticosteroid therapy and is now doing well at home. Careful donor selection and HLA matching before LRLT should be performed to prevent GVHD. However, the risks associated with grafts from homozygous donors may be unavoidable at present because of the shortage of cadaveric donors in Japan.

Administration, Oral↗
PubMed2003

Evaluation of cell proliferation and apoptosis in Helicobacter pylori gastritis using an image analysis processor.

BACKGROUND: Infection of the gastric mucosa by helicobacter pylori is primarily responsible for gastritis, gastric ulcer, adenocarcinoma, and lymphoproliferative disorders. H. pylori appears to accelerate apoptosis and the proliferation of the gastric epithelium directly or indirectly. To precisely assess the proliferative and apoptotic profile of .H pylori-infected gastric mucosa, a quantitative imaging system is now required. METHODS: Fifty-two patients with H. pylori gastritis were the subjects of the study. Biopsy materials were taken from at least two sites (usually three to five sites) including the antrum and corpus. The grade of gastritis was evaluated by the updated Sydney System. The proliferative and apoptotic profile was examined by Ki-67 immunohistochemistry and by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling method. In addition, Ki-67-positive cells were quantitated by an image processor for analytical pathology (IPAP) system. RESULTS: H. pylori density and polymorphonuclear neutrophil activity were significantly decreased after H. pylori eradication ( P< 0.0001). Chronic inflammation (P< 0.0001) and lymphoid follicle numbers ( P < 0.0005) were also significantly decreased after the eradication. Glandular atrophy and intestinal metaplasia were slightly decreased after eradication, but the decrease did not reach the significant level. the Ki-67 labeling index was significantly decreased after the eradication P< 0.0001). The apoptosis index was also decreased after the eradication, but this decrease did not reach the significant level ( P = 0.06). CONCLUSION: our data suggest that the activation of proliferative cells and induction of apoptosis in the gastric mucosa is a response to H. pylori-induced mucosal damage. Moreover, IPAP may be a useful technology for evaluating the results of immunohistochemistry, and it could provide quantitative and reliable data for studying H. pylori gastritis.

Adult↗
PubMed2003

Long-term results of laparoscopic unroofing of symptomatic solitary nonparasitic hepatic cysts.

The long-term results of laparoscopic unroofing for symptomatic solitary nonparasitic hepatic cysts have not been well demonstrated. During the last 8 years, five patients with symptomatic solitary nonparasitic hepatic cysts underwent laparoscopic unroofing. Their symptoms were right-upper-quadrant pain (in three patients) and epigastric pain (in two). Accompanying the hepatic cysts were acute cholecystitis in one case and adenomyomatosis of the gallbladder in another. Perioperative data, including operation time, estimated blood loss, complications, hospital stay, and mortality rate, were evaluated. There were no conversions to open laparotomy. Cysts were located in segments 4 and 5 in three patients, segment 3 in one, and segment 8 in another, and the mean size of the cysts was 10.4 cm in diameter (range: 7-18 cm). In four cases cholecystectomy was performed simultaneously. Mean operation time, estimated blood loss, and postoperative hospital stay were 182 minutes (range: 72-270), 168 mL (range: minimal to 800 mL), and 9.4 days (range: 7-12), respectively. There were no deaths or instances of major morbidity. During a mean follow-up period of 66 months (range: 35-102), one patient had a recurrent lesion requiring reoperation. Laparoscopic unroofing is a feasible and safe procedure for patients with symptomatic solitary nonparasitic hepatic cysts. Strict patient selection, accurate location of the cyst within the liver, and a sufficiently wide unroofing technique are needed for the outcome to be successful.

Adult↗
PubMed2003

Long-term outcome of extended hemihepatectomy for hilar bile duct cancer with no mortality and high survival rate.

OBJECTIVE: To demonstrate our strategy for hilar bile duct cancer and to elucidate prognostic factors and the surgeon's role in long-term survival. SUMMARY BACKGROUND DATA: Extended hemihepatectomy is recognized as a curative treatment of hilar bile duct cancer but is not always safe because of the risk of postoperative liver failure. A safe and beneficial strategy is required. METHODS: Fifty-eight consecutive major hepatectomies for hilar bile duct cancer were reviewed retrospectively. Appropriate preoperative treatments, biliary drainage, and portal embolization were performed before major hepatectomies. The short- and long-term results of our strategy are presented and analyzed. RESULTS: Biliary drainage and portal embolization were performed in 39 patients (67.2%) and 31 patients (53.4%), respectively. Major hepatectomies comprised 27 extended right and 22 extended left hemihepatectomies and 9 hepatoduodenopancreatectomies. Operative morbidity and mortality rates were 43% and 0%, respectively. There was no postoperative liver failure. The overall 5-year survival rate was 40%. Univariate analysis showed that residual tumor status, lymph node involvement, and perineural invasion were associated with patients' long-term survival. A surgical margin over 5 mm resulted in better long-term survival. The delay resulting from preoperative treatment was not detrimental to long-term survival. Multivariate analysis showed that lymph node involvement was the only prognostic factor. CONCLUSIONS: Our strategy, which includes preoperative biliary drainage and portal embolization, led to a reduction in the risks associated with major hepatectomy for hilar bile duct cancer, and resulted in zero mortality. Surgeons should aim at complete clearance of the tumor with an adequate surgical margin to ensure optimal long-term survival.

Adult↗
PubMed2003

Identification of genes differentially expressed in a newly isolated human metastasizing esophageal cancer cell line, T.Tn-AT1, by cDNA microarray.

We isolated a metastasizing human esophageal squamous cell carcinoma (SCC) cell line, T.Tn-AT1, from a parental non-metastasizing cell line, T.Tn, by in vitro selection and by use of a nude mouse orthotopic inoculation model. Then, we compared the expression profiles of 9206 genes in T.Tn-AT1 and T.Tn by cDNA microarray analysis. The gene expression profiles of T.Tn and T.Tn-AT1 were very similar, and only 34 genes showed more than 3-fold differential expression. Among the 34 genes, 29 genes were down-regulated and only 5 genes were up-regulated in T.Tn-AT1 cells. Subsequently, we confirmed the expression levels of 14 of the 34 genes in T.Tn and T.Tn-AT1 cells by means of reverse transcription-polymerase chain reaction. The expression of 8 genes (KAL1, HPGD, NDN, REG1A, CXCR4, SPOCK, DIAPH2 and AIF1) was down-regulated and that of one gene (VNN2) was up-regulated in T.Tn-AT1 cells. These 9 genes encoded proteins associated with metastatic processes, such as adhesion, migration, inflammation, proliferation, and differentiation. Thus, these genes might regulate the metastasis of esophageal SCC, and could be predictive markers for lymph node metastasis of esophageal SCC.

Carcinoma, Squamous Cell↗
PubMed2003

Effect of apolipoprotein E polymorphism on bile lipid composition and the formation of cholesterol gallstone.

OBJECTIVE: It remains a matter of controversy whether possession of the apolipoprotein E4 (apoE4) allele is a genetic risk factor for the formation of cholesterol gallstones. The aim of the present study was to test this hypothesis by investigating the effect of apoE4 on bile lipid composition in normal subjects and in patients with cholesterol gallstones and to evaluate the distributions of apoE alleles in these two groups. METHODS: The study population consisted of 79 patients who underwent open or laparoscopic cholecystectomy for symptomatic cholesterol gallstone disease. The control group (n = 53) included 11 patients with benign gallbladder polyps and 42 normal subjects acting as donors in living donor liver transplantation. The apoE genotypes were assessed by dot blot hybridization with digoxigenin-labeled probes. Bile lipid composition was determined by enzymatic assays and high performance liquid chromatography. RESULTS: Bile lipid composition and cholesterol saturation index (CSI) were similar in the control subjects harboring the apoE4 allele and those without apoE4 (mean CSI, 85.9% and 72.2%, respectively, p = 0.69). Likewise, in the cholesterol gallstone patients, bile lipid composition and CSI were similar in the patients with and without apoE4 allele (mean CSI, 134.9% vs 152.2%, p = 0.6). Furthermore, the prevalence of the apoE4 allele was similar in the patients with cholesterol gallstones and in the control group (8.5% vs 7.6%, p = 0.46, OR = 0.88; 95% CI = 0.64-1.22). CONCLUSIONS: The apoE4 allele is not a contributory factor to cholesterol gallstone formation, at least in the Japanese population.

Adult↗