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Keiichi Kubota

Publications and source records attributed to Keiichi Kubota.

At least 19 recordsLinked to original sources
PubMed2007

Rectal angiolipoma diagnosed after surgical resection: a case report.

Angiolipoma is a common benign tumor with a characteristic vascular component that usually occurs in subcutaneous tissue. Although lipomas are frequently encountered at colonoscopy as submucosal tumors, angiolipomas are rarely found in the gastrointestinal tract including the large intestine. Here we report a 77-year old Japanese man who underwent transanal resection of a tumor that was diagnosed tentatively as a leiomyoma. Histologically, the tumor consisted of mature fat cells and blood vessels. Immunohistochemically, the tumor cells were negative for c-kit and HMB-45, which are consistently expressed in tumors such as gastrointestinal stromal tumor and angiomyolipoma. The tumor was therefore diagnosed as an angiolipoma. This is thought to be the first case report of a surgically resected angiolipoma of the rectum.

Aged↗
PubMed2006

Autoimmune pancreatitis diagnosed on the basis of immunohistology alone. A case report.

CONTEXT: The differential diagnosis between autoimmune pancreatitis and pancreatic cancer is sometimes difficult, especially for those patients in whom laboratory and radiological criteria are lacking. CASE REPORT: A 72-year-old woman was found to have a tumor in the head of the pancreas. Laboratory data showed no abnormal values, including gammaglobulins or autoantibodies. Endoscopic retrograde cholangiopancreatography showed extrinsic stenosis of the main pancreatic and lower common bile ducts. Computed tomography showed a lesion in the head of the pancreas. With a tentative diagnosis of head of the pancreas cancer, the patient underwent pancreaticoduodenectomy. Macroscopically, a tumor 2 cm in diameter not having clear margins was evident in the head of the pancreas. Histological examination showed the infiltration of lymphocytes, plasma cells, and eosinophils with lymphoid follicles around the main pancreatic duct. Immunohistological examination demonstrated that the main pancreatic duct was surrounded by abundant IgG4-positive plasma cells. CONCLUSIONS: The patient was diagnosed as having autoimmune pancreatitis on the basis of the immunohistological findings alone, without any well-defined criteria such as high serum level of IgG4 and presence of autoantibodies before or after surgery.

Aged↗
PubMed2006

Deferoxamine enhances anti-proliferative effect of interferon-gamma against hepatocellular carcinoma cells.

BACKGROUND: Interferon-gamma (IFN-gamma) is a multifunctional cytokine, whose anti-proliferative effect is expected to be of therapeutic value against human cancer. However, hepatocellular carcinoma (HCC) shows resistance to the anti-proliferative effect of IFN-gamma, due mainly to down-regulation of IFN-gamma receptor chain 2 (IFN-gammaR2), even though IFN-gamma receptor chain 1 (IFN-gammaR1), the domain that includes the binding site of IFN-gamma, is stably expressed. The aims of this study were to investigate whether iron chelation, blocking of the human insulin-like growth factor-1 receptor (hIGF1R), or both could upregulate IFN-gammaR2 and enhance the anti-proliferative effect of IFN-gamma. METHODS: Two HCC cell lines, HuH7 and SNU449, were treated with the iron-chelating agent deferoxamine (DFO), IFN-gamma, and/or anti-hIGF1R blocking antibody. The expression of IFN-gammaR1 and IFN-gammaR2 was then evaluated by flow cytometry and Western blotting. The anti-proliferative effect of IFN-gamma was investigated by MTT assay, and the pro-apoptotic effect was investigated by annexin-V flow cytometry. RESULTS: DFO and blocking with anti-hIGF1R antibody increased the expression of IFN-gammaR2, but the effect on IFN-gammaR1 expression was less marked. DFO, anti-hIGF1R blocking antibody, or both directly enhanced the anti-proliferative effect of IFN-gamma through increased pro-apoptotic activity. CONCLUSION: The present results indicate that IFN-gamma reinforced by iron modulation could be a promising new therapeutic approach for HCC.

Apoptosis↗
PubMed2006

alpha1,3-Galactosyltransferase-gene knockout in cattle using a single targeting vector with loxP sequences and cre-expressing adenovirus.

BACKGROUND: Gene targeting in large animals has the potential to be useful in medicine as well as in agriculture. Previously, we reported the first successful targeting of the bovine alpha1,3-galactosyltransferase (alpha1,3GT) gene and establishment of a heterozygous knockout cell line. In this report, we generated both heterozygous and homozygous knockout bovine cell lines, and alpha1,3GT-gene knockout cattle. METHODS: alpha1,3GT gene-disruption was accomplished using primary fetal fibroblasts with a single targeting vector, a promoter-less positive selection vector containing IRES (internal ribosome entry site)-antibiotic-resistance gene (neo) cassette and loxP sequences. At each step in establishing heterozygous and homozygous knockout cell lines, the antibiotic-resistance gene cassette in the targeted allele was removed by a Cre-loxP recombination system that utilizes an adenovirus with transient Cre recombinase expression. A nuclear transfer was performed using alpha1,3GT fetal fibroblasts, and one alpha1,3GT knockout calf was generated but died shortly after birth (day 287). RESULTS: Necropsy revealed normal morphology in all organs. The calf weighed 22.3 kg at birth and this value is within the normal range. CONCLUSION: The alpha1,3GT knockout- and antibiotic-resistance gene free (alpha1,3GT(-/-)neo-) cells could be cloned normally. Thus, cloned cattle from alpha1,3GT(-/-) neo- cells are potentially safer for human use. Additionally, our strategy is faster and more economical than backcrossing to produce homozygous knockouts. This method should be useful for future production of knockouts of multiple genes in livestock.

Adenoviridae↗
PubMed2006

Total colectomy improves altered distribution of regulatory T cells in patients with ulcerative colitis.

BACKGROUND: It is now generally believed that regulatory T cells (Tregs) play an important role in peripheral tolerance, and a defect in Tregs is considered one of the most important factors in the induction of various kinds of autoimmune disease including ulcerative colitis (UC). Here, we examined the change in frequency of Tregs phenotype in five patients with UC whose condition had not been controllable by conventional conservative therapy and who were scheduled for total colectomy. AIMS: The aim of this study was to elucidate the role of Tregs in the pathogenesis of UC in a clinical setting. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from five patients with UC, and the change in frequency of Tregs was analyzed by flow cytometry before total colectomy and on postoperative days 1, 7, and 20. Tregs were defined as CD4+ CD25+ CD45RA+ T cells, and data (%) were expressed as frequency of Tregs/CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) from healthy blood donors (n = 5) and from patients undergoing other types of major surgery (n = 5) were used as controls. RESULTS: Comparison with normal subjects showed that generation of Tregs was suppressed in UC patients before they underwent total colectomy (0.95 versus 5.06; P = 0.009). The frequency of Tregs increased shortly after total colectomy. The frequency at postoperative days 1, 7, and 20 was 3.81%, 8.13%, and 3.76%, respectively. There were significant differences in the change in frequency in the period before surgery and postoperative day 1, between postoperative days 1 and 7, and between days 7 and 20. CONCLUSIONS: Elimination of targeted antigens residing in the colorectal mucosa by total colectomy improved the suppressed distribution of Tregs in UC patients. The present study provides the first direct clinical evidence that Tregs play a pivotal role in the pathogenesis of UC.

Adult↗
PubMed2006

Intraoperative assessment of reconstructed vessels in living-donor liver transplantation, using a novel fluorescence imaging technique.

BACKGROUND/PURPOSE: In living-donor liver transplantation (LDLT), hepatic arterial thrombosis and portal venous thrombosis are critical problems that can result in graft loss. Only intraoperative Doppler ultrasound (IDUS) is able to evaluate blood flow in the reconstructed vessels. The aim of this study was to evaluate the utility of a newly developed fluorescence imaging technique using indocyanine green (ICG) for visualizing reconstructed vessels. METHODS: In three patients who had undergone LDLT, IDUS was performed after reconstruction of the portal vein and hepatic artery. Fluorescence images were then recorded, using a SPY system (Novadeq Technologies), which employs ICG as a fluorescent imaging medium activated by light. The ICG (3.75 mg) was injected intravenously, then, 10 s later, the images were recorded for 30 s (first photographic recording). Two minutes later, the same procedure was repeated (second photographic recording), and 40 min later, images were obtained without injection of ICG (third photographic recording). RESULTS: After portal venous reconstruction, IDUS demonstrated a nonphasic and continuous waveform, with a mean velocity of 52.1 cm/s and a mean portal blood flow volume of 69.5 ml/s per kg. After hepatic arterial reconstruction, a pulsatile waveform with a mean peak systolic velocity of 52.4 cm/s and a mean resistance index of 0.76 was obtained. The first photographic recording clearly visualized the blood flow in the reconstructed hepatic artery, without kinking or stenosis, in all three patients. The second photographic recording visualized the flow in the portal vein without stenosis, kinking, or stagnation. The third photographic recording demonstrated the excretion of ICG into bile, thus confirming bile production by the grafts. CONCLUSIONS: Fluorescence imaging can clearly visualize the reconstructed hepatic artery and portal vein and demonstrate the production of bile by a transplanted liver graft. A combination of IDUS and the new system can guarantee the patency of the reconstructed vessels.

Blood Flow Velocity↗
PubMed2006

Hepatectomy in patients with nonuremic minimal renal failure.

In this study, the perioperative management and short-term outcome of hepatectomy were evaluated in patients with nonuremic minimal renal failure to assess the safety of hepatectomy in such patients. Ninety-one patients who underwent hepatectomy were retrospectively divided into two groups based on their creatinine clearance (Ccr) values: a group with Ccr values >or=50 but <100 ml/min (group 1; n = 77) and a group with Ccr values of >or=20 to <50 ml/min (group 2; n = 14). Preoperative patient characteristics, intraoperative parameters (including operation time and blood loss), and postoperative management and complications were evaluated. The preoperative evaluation showed no differences in liver function between the two groups, and there were no statistically significant differences between the two groups in intraoperative blood loss (522 ml in group 1 and 806 ml in group 2) or intraoperative urine volume (1.01 ml/kg per hour in group 1 and 0.75 ml/kg per hour in group 2). The difference between the two groups in postoperative complications was not statistically significant. None of the patients in group 2 required dialysis therapy, and no patients died as a result of hepatectomy or hepatectomy-related causes. Adequate indications, appropriate operative procedures, and perioperative management can enable hepatectomy to be performed safely in patients with nonuremic minimal renal failure.

Aged↗
PubMed2006

[Pilot study of primary systemic chemotherapy with docetaxel (DOC), epirubicin (EPI) and capecitabine (Xeloda) in patients with advanced breast cancer].

We evaluated the safety and efficacy of primary systemic chemotherapy (PSC) with docetaxel (DOC), epirubicin (EPI) and capecitabine (Xeloda:XLD) in 10 patients with advanced breast cancer. Their mean age was 54.7 years,and preoperative stages were IIB, seven cases; IIIA, two; and IV, one,respectively. The regimen consisted of XLD (2,400 or 3,000 mg/day) orally for 14 consecutive days, and DOC (60 or 70 mg/m2) and EPI (50 or 60 mg/m2) intravenously on day 8. This was repeated 4 times every 3 weeks. One patient discontinued this regimen after one course at her own request. Although the results revealed leucopenia and neutropenia of more than grade 3 in 8 and 10 patients,they could be treated on an outpatient basis with the use of G-CSF to maintain this regimen. Alopecia of grade 2 was found in all patients,neutropenic fever of more than 38.5 degrees C in 5,and hand-foot syndrome in 3. Downstaging after PSC was demonstrated in 7 cases (Stage IIB to I, three cases; IIB to IIA, three; and III A to I, one), with a response rate of 77.8%. Breast conserving therapy was performed in 8/10 patients. Pathological findings on cytological degeneration showed grade 0, one; grade 1a,seven; grade 2, one; and grade 3, one, respectively. Axillary lymph node metastasis was revealed in 7 cases. This regimen would be an alternative to PSC on an outpatient basis while taking great care of myelosuppression and hand-foot syndrome.

Adult↗
PubMed2005

Loss of E-cadherin mRNA and gain of osteopontin mRNA are useful markers for detecting early recurrence of HCV-related hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: We investigated whether expression of E-cadherin (E-cad) and osteopontin (OPN) mRNAs could predict the early recurrence of HCV-associated hepatocellular carcinoma (HCV-HCC) after curative surgery. METHODS: Forty-four HCV-HCC patients who underwent curative hepatectomy were divided into three categories: category 1--recurrence (3 mR+: n = 6) or non-recurrence (3 mR-: n = 38) within 3 months; category 2--recurrence (6 mR+: n = 4) or non-recurrence (6 mR-: n = 34) between 3-6 months; category 3--recurrence (1 yR+: n = 4) or non-recurrence (1 yR-: n = 30) between 6-12 months. Levels of expression of E-cad and OPN mRNAs were analyzed quantitatively by real-time PCR and calculated using the formula: t = (copy of E-cad or OPN/copy of GAPDH) x 1,000. RESULTS: The t-value for E-cad was significantly lower in 3 mR+ than in 3 mR- (0.4 and 28.1, P < 0.05), in 6 mR+ than in 6 mR- (4.0 and 30.6, P < 0.05), and in 1 yR+ than in 1 yR- (9.2 and 32.9, respectively, P < 0.05). The t-value for OPN was higher in 3 mR+ than in 3 mR- (92.6 and 65.7, P = 0.57), in 6 mR+ than in 6 mR- (457.1 and 58.15, respectively, P = 0.24), and in 1 yR+ than in 1 yR- (221.8 and 53.5, respectively, P = 0.06). CONCLUSIONS: Low expression of E-cad mRNA and high expression of OPN mRNA are associated with a higher likelihood of early recurrence of HCV-HCC.

Aged↗
PubMed2005

Disposal of replaced common hepatic artery coursing within the pancreas during pancreatoduodenectomy: report of a case.

A replaced common hepatic artery (RCHA) originating from the superior mesenteric artery (SMA) is a rare anomaly. We herein report such a case in a 62-year-old man who was scheduled to undergo a pancreatoduodenectomy for lower bile duct cancer. Computed tomography (CT) showed the RCHA to run along the ventral side of the pancreas. Abdominal angiography showed an RCHA originating from the SMA, which communicated with an aberrant left hepatic artery from the left gastric artery. No gastroduodenal artery was observed, but instead a direct ramification of a right gastroepiploic artery was seen. Similar cases from the English literature were reviewed. The RCHA was confirmed to course first along the ventral side of, and then within, the pancreas. Clamping of the RCHA did not influence the arterial flow in the liver, and the RCHA was subsequently divided without reconstruction. In three of the five reviewed cases in which the RCHA coursed either within or along the ventral side of the pancreas, no gastroduodenal artery was found, but instead a direct ramification of a right gastroepiploic artery was observed. A combination of CT and angiographic findings can help in both the diagnosis of an anomalous RCHA coursing either within or along the ventral side of the pancreas as well as in selecting optimal operative procedures. Pancreatoduodenectomy was performed with a curative resection according to our usual practice except for the fact that we preserved the aberrant left hepatic artery.

Bile Duct Neoplasms↗
PubMed2005

Gastric cancer developing in the stomach after pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy: case report and review of the literature.

A 59-year-old woman underwent surgery for uterine corpus cancer in March 1998. She also underwent pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy for common bile duct cancer in November 1998. She was followed up at our outpatient clinic after pylorus-preserving pancreaticoduodenectomy. In November 2002, her carcinoembryonic antigen level became elevated and abdominal ultrasound revealed a huge tumor. Gastroscopy showed a Borrmann type 3 tumor at the anastomosis of the pancreaticogastrostomy, and a biopsy revealed adenocarcinoma. With a diagnosis of advanced gastric cancer, she underwent total gastrectomy, splenectomy, and residual pancreatectomy in January 2003. The pathologic findings revealed that the gastric cancer was separated from the pancreas, suggesting that the cancer had developed from the stomach. The present report describes a rare case of gastric cancer that had developed at the anastomosis of a pancreaticogastrostomy.

Adenocarcinoma↗
PubMed2005

Malignant stromal tumor, so called "gastrointestinal stromal tumor", with rhabdomyomatous differentiation occurring in the gallbladder.

Gastrointestinal stromal tumors (GISTs) constitute the largest category of primary nonepithelial neoplasms of the gastrointestinal tract. It is extremely rare that this tumor occurs in the bile tract, and only a few cases have been reported. Immunohistochemically, the tumor cells revealed a phenotype similar to Cajal cells, occasionally with differentiation to smooth muscle cells or neural cells. We present a case of malignant stromal tumor similar to GISTs with rhabdomyomatous differentiation of the gallbladder in a 68-year-old woman. The resected tumor was predominantly composed of spindle cells with rhabdomyomatous differentiation. Immunohistochemical study revealed diffuse staining of tumor cells using vimentin despite negative staining for desmin or S-100. This indicated a mesenchymal origin of the cells without smooth muscle or neuronal differentiation. Myoglobin-positive cells, in which phosphotungstic acid hematoxylin staining revealed cross striations of the cytoplasm, suggested rhabdomyomatous differentiation. Diffuse positivity for KIT in the cells suggested that the pathogenesis of this tumor may resemble that of GIST. The tumor may have derived from a mesenchymal stem cell that had undergone partial rhabdomyomatous differentiation.

Aged↗
PubMed2005

Huge mucinous cystadenoma of the pancreas developing during pregnancy: a case report.

A 33-year-old woman, gravida 2, para 1, was found to have a huge intra-abdominal cyst (2619 ml) in the 15th week. The cyst increased in volume to 3660 ml during the next 31 days. A tentative diagnosis of ovarian or pancreatic mucinous cystadenoma was made. Since the cyst was considered to cause fetal intra-uterine growth restriction, the patient underwent surgery in the 23rd week of pregnancy. The cyst was found to originate from the pancreas, and distal pancreatectomy with splenectomy was performed. The specimen weighed 5500 gm, which is the largest so far reported. Her postoperative course was uneventful, and she had a healthy full-term infant. Histological diagnosis was a benign mucinous cystadenoma. Up to the present, there have been three reported cases of pancreatic mucinous cystadenoma, including our case, and two cases of pancreatic mucinous cystadenocarcinoma, in association with pregnancy. Our case is the third reported of successful resection of the tumor during pregnancy resulting in a healthy infant.

Adult↗
PubMed2005

Simultaneous laparoscopic treatment for diseases of the gallbladder, stomach, and colon.

We describe a successful simultaneous laparoscopic treatment of a gallstone and gastric and colonic neoplasms. The patient was a 72-year-old man with epigastric discomfort. Abdominal ultrasound revealed a gallstone 2 cm in diameter. Gastroscopy revealed a 3-cm protruding submucosal tumor in the gastric fundus and colonoscopy revealed a 2-cm sessile lesion in the sigmoid colon. He underwent simultaneous laparoscopic treatment of the 3 organs because of the high risk of perforation or bleeding after gastric or colonic resection. This required the use of 5 ports, and a 3.5-cm incision was made in the left lower quadrant to access the 3 organs. The laparoscopic procedures consisted of cholecystectomy, partial stapled resection of the gastric fundus, and partial resection of the sigmoid colon. The histopathologic diagnoses were chronic cholecystitis, leiomyoma of the stomach, and tubulovillous adenoma with severe dysplasia of the colon. The operation took 183 minutes and blood loss was minimal. The patient started oral intake from the second postoperative day and was discharged uneventfully. He had from no postoperative complications or abdominal symptoms during a 15-month follow-up period. To our knowledge, this is a first successful clinical report of simultaneous laparoscopic treatment of 3 organ disorders.

Adenoma, Villous↗
PubMed2005

Lobular damage caused by cellular and humoral immunity in liver allograft rejection.

BACKGROUND: Diagnosis of acute liver allograft rejection (ALAR) is usually performed by the estimation of changes in portal areas. In this study, changes in the hepatic lobules were investigated retrospectively by immunohistochemistry, and compared with changes in the portal areas. Humoral immunity in ALAR was also studied by C4d-staining. MATERIALS AND METHODS: In total, 35 biopsy specimens from 20 patients who had undergone living-related liver transplantation were included. Specimens had been graded as mild, moderate-to-severe acute rejection based on the Banff Schema. Changes in hepatic lobules were investigated by hematoxylin-eosin (H & E) staining, an immunohistochemical study using anti-CD3 (T cells), anti-GMP-17 (cytotoxic cells), anti-CD68 (macrophages) and C4d, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) method. RESULTS: Changes in hepatic lobules consisted of the infiltration of mononuclear cells, swelling and necrosis of hepatocytes, and hemorrhages. The degree of these changes increased with the severity of ALAR. Immunohistochemical analysis revealed that infiltrating cells included CD3+ T cells, GMP-17+ cytotoxic cells and CD68+ macrophages. The number of infiltrating cells increased with the severity of the ALAR. The TUNEL assay demonstrated apoptotic cells in ALAR and the number of apoptotic cells increased with the severity of the ALAR. In moderate-to-severe rejection, C4d depositions were observed in the hepatic sinusoids as well as the portal veins and hepatic arteries. CONCLUSIONS: Changes in the hepatic lobules were observed in ALAR and the severity increased with the severity of ALAR. Apoptosis was involved in the mechanism of cell death and humoral immunity plays a role in the mechanism of ALAR.

Adolescent↗
PubMed2005

Injury and progressive loss of peritubular capillaries in the development of chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) remains the most important cause of late renal graft loss. However, the mechanism for graft dysfunction and the process of the development of CAN are not well understood. This study examined the role of microvascular injury in the development of CAN. METHODS: We studied renal biopsies obtained from grafts with CAN (N= 79) and pretransplant control kidneys (N= 20). Microvascular injury was examined morphologically, and was correlated with interstitial fibrosis, glomerular sclerosis, graft function, and the severity of CAN. The humoral and cellular immunity involved in CAN were examined by C4d, CD3, and TIA-1 staining. RESULTS: In all the cases of CAN, microvascular injury was evident with or without CD3-positive T cells, TIA-1-positive cytotoxic cells, and/or C4d+ complement deposition. Irrespective of chronic rejection (N= 14), C4d+ chronic humoral rejection (N= 6), or other CAN, the development process of CAN was characterized by injury and progressive loss of identifiable peritubular capillaries (PTCs) accompanied with the development of interstitial fibrosis. Injured PTCs were characterized morphologically by the process of angioregression with the presence of apoptotic cells, lamination of the basement membrane, and loss of PTCs. The low number of PTCs correlated significantly with the severity of CAN (r=-0.74, P < 0.001), the development of interstitial fibrosis (r=-0.75, P < 0.001), graft dysfunction (r=-0.69, P < 0.001), and also correlated weakly with proteinuria (r=-0.45, P < 0.05). In the glomeruli, capillary loss significantly correlated with the degree of glomerular sclerosis (r=-0.66, P < 0.001) and proteinuria (r=-0.65, P < 0.001), but did not correlate with the severity of CAN (r=-0.24, P > 0.05) or graft dysfunction (r=-0.32, P > 0.05). CONCLUSION: CAN was characterized by progressive injury to the renal microvasculature and the development of renal scarring. In particular, injury, angioregression and progressive loss of the PTC network strongly contributed to the development of interstitial fibrosis and graft dysfunction in CAN, and might play a crucial role in the development of CAN.

Adult↗