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K Fukao

Publications and source records attributed to K Fukao.

192 records · Page 11Linked to original sources
PubMedDate not supplied

Clonogenic colony-forming ability of flow cytometrically isolated hepatic progenitor cells in the murine fetal liver.

Stem cells are defined as cells having multilineage differentiation potential and self-renewal capability. Hepatic stem cells have aroused considerable interest not only because of their developmental importance but also for their therapeutic potential. However, their presence in the liver has not yet been demonstrated. With the use of a fluorescence-activated cell sorter (FACS) and monoclonal antibodies, we attempted to ascertain whether hepatic stem cells are present in the murine fetal liver. For this purpose, we optimized a cell isolation technique for FACS sorting of fetal liver cells. When isolated CD45 TER119 cells (the non-blood cell fraction in the fetal liver) were tested for their clonogenic colony-forming ability, mechanical dissociation (pipetting) was the most suitable cell isolation technique for FACS sorting. We confirmed that these colonies contained not only cells expressing hepatocyte markers but also cells expressing cholangiocyte markers. To identify hepatic stem cells, studies must focus on CD45TER119- cells in the murine fetal liver.

Animals↗
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Over-expression of vascular endothelial growth factor after preoperative radiation therapy for rectal cancer.

Vascular endothelial growth factor expression before and after preoperative radiation therapy was examined in 16 stage III rectal carcinoma patients. The biopsied tissues before preoperative radiation therapy and the tissues at operation were immunohistochemically stained. Four cases were negative for VEGF expression before radiation, but the other 12 cases were positive, with 4 cases showing strong immunoreactivity. After radiation, all except 1 case showed VEGF positive patterns, in which 14 cases demonstrated strong staining. In 12 cases, VEGF expression became higher after radiation therapy than before, as compared to the only 1 case that showed lower expression than before.

Adult↗
PubMedDate not supplied

Benefits of combining radiotherapy with aggressive resection for stage IV gallbladder cancer.

BACKGROUND/AIMS: The efficacy of combining resection and radiation in the management of advanced gallbladder cancer has not yet been defined. In this study, effects of combining radiation therapy on survival, local control and the pattern of recurrences were analyzed as a retrospective review. METHODOLOGY: From October 1976 to May 1996, 85 patients with stage IV (pTNM) gallbladder cancer underwent various aggressive resection modalities in our institute, including 34 liver resections, 30 hepatopancreaticoduodenectomies. Intra-operative, external or intracavitary radiation therapy was supplemented to resection in 47 patients. RESULTS: The 30-day operative mortality rate was 5.9% and the overall 5-year survival rate of stage IV disease patients was 6.3%; 3 patients are living well more than 6 years after surgery. Adjuvant radiotherapy yielded a significantly (p=0.0023) higher 5-year survival rate (8.9%) than resection alone (2.9%). The local control rate was significantly (p=0.0467) higher in the adjuvant radiation group than in the resection alone group (59.1% vs. 36.1%). However, there was no statistical difference in the frequency of distant metastasis between the two groups. Significant improvement (p=0.0028) of long-term survival was exhibited when radiation was used appropriately on patients with microscopic residues only. Those with macroscopic or without microscopic residues failed to improve. The 5-year survival rate and median survival time of patients receiving adjuvant radiation therapy for microscopic residues were 17.2% and 463 days, respectively. CONCLUSIONS: Adjuvant radiation therapy following aggressive resection, in certain circumstances, improves prognosis with acceptable operative mortality for stage IV gallbladder cancer.

Adenocarcinoma↗
PubMedDate not supplied

Outcomes of aggressive treatment of stage IV gallbladder cancer and predictors of survival.

BACKGROUND/AIMS: Stage IV gallbladder carcinoma patients are rarely considered treatable by resection. They resign themselves to palliation because there is no long-term survival data available on the risks of morbidity and mortality following aggressive treatment. The aim of this study was to evaluate predictors of survival following aggressive resection surgery for stage IV gallbladder carcinoma. METHODOLOGY: In this retrospective study, we examined 93 patients with stage IV gallbladder carcinoma who had undergone resections. Of the 93 patients, 69 had undergone liver resection to various extents together with hepaticocholedochus resection (HCR); 2 had undergone pancreaticoduodenectomy (PD) both with and without HCR; 31 had undergone hepatopancreaticoduodenectomy (HPD); 7 had undergone cholecystectomy together with HCR; 12 had undergone cholecystectomy; and 3 had undergone extended cholecystectomy. Fifty of the 93 patients had also undergone adjuvant radiotherapy. Using univariate and multivariate analyses, 13 clinicopathologic risk factors were analyzed to predict survival. RESULTS: Operative morbidity and mortality rates were 17.2% and 5.4%, respectively. Overall, the 5-year survival rate and median survival time were 9.8% and 243 days, respectively. The 5-year survival rate was significantly higher in stage IVA (n = 17) than in stage IVB (n = 76), at 42.8% and 4.9%, respectively. Multivariate analysis revealed that sex, histopathologic type, lymph node involvement (N), subgroup of stage IV, post-resection residual tumors, and adjuvant radiotherapy were significant predictors of survival. CONCLUSIONS: Long-term survival, with acceptable mortality and morbidity, can be expected in female patients who have stage IVA gallbladder cancer consisting of well-differentiated adenocarcinoma and who undergo either complete microscopic resection or grossly complete resection followed by adjuvant radiotherapy.

Adenocarcinoma↗
PubMedDate not supplied

Hepatic functional reserve in patients with biliary malignancies: an assessment by technetium 99m galactosyl human serum albumin hepatic scintigraphy.

PROBLEM: Technetium 99m galactosyl human serum albumin (99mTc-GSA) is a hepatic scintigraphy agent that binds to the asialoglycoprotein receptors. We evaluated the clinical use of the scintigraphy for the pre-operative assessment of biliary malignancies. PATIENTS AND METHODS: Scintigraphy was performed before operation in 56 patients with biliary malignancies. A hepatic uptake ratio of 99mTc-GSA (LHL15; the count ratio of the liver to the sum of the heart and liver 15 min after injection of 99mTc-GSA) was calculated. RESULTS: LHL15 was significantly associated with bilirubin half-life in patients treated before operation with percutaneous transhepatic biliary drainage (P = 0.007). After operation, 4 of 18 patients with LHL15 < 0.925 died within 30 days. The postoperative mortality was significantly greater in patients with LHL15 < 0.925 than in patients with LHL15 > or = 0.925 (P = 0.033). CONCLUSION: 99mTc-GSA scintigraphy is useful in evaluating the hepatic functional reserve in patients with biliary malignancies.

Adult↗
PubMedDate not supplied

Amputation neuroma mimics common hepatic duct carcinoma.

Most amputation neuromas of the biliary tract occur in the cystic duct stump after cholecystectomy and are asymptomatic. However, when they arise in the main hepatic duct and are associated with obstructive jaundice, it is difficult to distinguish them from carcinoma. We describe a case in which preoperative differential diagnosis was difficult. A 60-year-old man was admitted to the Institute of Clinical Medicine, University of Tsukuba, with a chief complaint of jaundice. Cholangiography showed an irregularly elevated nodular lesion on the lateral wall of the common hepatic duct and multiple floating stones in the choledochus. Ultrasonography and computed tomography revealed one-sided regional thickening of the common hepatic duct associated with dilatation of the intrahepatic and extrahepatic bile ducts. Carbohydrate antigen 19-9 level was markedly elevated to 11,200 IU/mL in the bile juice, but was only 38 IU/mL in the serum, below the limit of abnormality. Cholangioscopy showed papillary tumor with coarse granular surface mimicking papillary carcinoma, but biopsy revealed no malignancy. The patient underwent hepaticocholedochus resection. Although the macroscopic finding from the surgical specimens was papillary carcinoma of the common hepatic duct penetrating to the hepatoduodenal ligament, histopathological examination revealed an amputation neuroma consisting of hypertrophic nerve tissues and giant cells containing foreign bodies, probably as a consequence of a previous cholecystectomy. The postoperative course was uneventful and the patient has been living well for the 5 years since the resection.

Aged↗
PubMedDate not supplied

Hepatic resection for metastatic tumors from noncolorectal carcinoma.

BACKGROUND/AIMS: The role of liver resection for hepatic metastases from noncolorectal carcinomas has yet to be clarified. The present study examines a single institutional experience of hepatic resection for noncolorectal metastases. METHODOLOGY: From January 1987 to March 1999, 14 patients underwent curative resection for liver metastases from noncolorectal carcinomas. Records of these patients were reviewed. RESULTS: Resections were performed for liver metastases from gastric cancers (n = 8), pancreatic cancers (n = 2), and cancers of bile duct, the papilla of Vater, kidney, and breast (n = 1, each). Six patients (5 with gastric cancers and 1 with pancreas cancer) presented with synchronous disease and 8 with metachronous disease. In the gastric cancer patients, there are 2 disease-free survivors (26 and 53 months) in the metachronous group, though all of the 5 patients with synchronous disease died within 29 months. All of the 4 patients with pancreatobiliary carcinomas died within 2 years. One case of breast cancer and another of renal cell cancer are alive without disease at 49 and 9 months, respectively. CONCLUSIONS: For metastases from gastric cancers, better survival after hepatic resection is expected in metachronous cases than in synchronous cases. Hepatic resection may afford little benefit for patients with liver metastases from pancretobiliary cancers.

Aged↗
PubMedDate not supplied

Retroperitoneal multiple lymphangioma with differential cyst contents causing hydronephrosis and biliary dilatation.

We report a 40-year-old woman with retroperitoneal multiple cystic lymphangioma. Multiple cystic lesions were found on both sides of the aorta in the retroperitoneal and right pelvic spaces. These thin-walled cysts gradually increased in size leading to left hydronephrosis and dilatation of the common bile duct with cholecystitis, requiring resection. Analysis of cystic contents revealed differences between the cysts. The right cyst contained high concentrations of amylase, 3429 U/L, while the left cyst contained high concentrations of triglyceride, 470 mg/dL. No reports of patients with idiopathic retroperitoneal cystic lymphangioma have described differences in cystic contents. Differences in cystic contents according to tumor location strongly suggest that the cause of retroperitoneal lymphangioma is a developmental malformation in which lymphangiectasia follows the failure of developing lymphatic tissue to establish normal communication with the remainder of the lymphatic system.

Adult↗
PubMedDate not supplied

Utility of serum CA 19-9 monitoring in preoperative radiotherapy for pancreatic cancer.

BACKGROUND/AIMS: Pancreatic cancer is extremely refractory even to aggressive treatments including surgery, resulting in early metastasis and/or local recurrence. We investigated changes in serum tumor marker CA 19-9 levels during preoperative radiotherapy in conjunction with initial treatment failure. METHODOLOGY: Twenty-three patients presenting with localized disease and an increased serum CA 19-9 level, who were slated to undergo pancreatectomy and/or intraoperative radiotherapy following preoperative radiotherapy were reviewed. CA 19-9 response, the ratio of post-radiotherapy level before laparotomy to pre-radiotherapy level, was analyzed in relation to disease-control time and survival. RESULTS: Eleven patients revealed metastasis at restaging or laparotomy; 12 patients (52%) completed aggressive treatments. Initial failure was identified at the liver (52%), peritoneum (52%), or local site (26%) with a median disease-control time of 91 days; 7 patients showed combined failure. All but 1 patient died of cancer with a median survival time of 264 days. CA 19-9 response (range: 0-1185%) did not correlate with disease-control time or survival; 8 progressive-disease patients (> 140% response), however, showed significantly shorter disease-control time than 15 nonprogressive-disease patients (< or = 140% response). CONCLUSIONS: CA 19-9 monitoring is useful in preoperative radiotherapy for identifying patients who will not benefit by succeeding aggressive treatments by predicting early metastasis.

Adult↗
PubMedDate not supplied

Treatment of advanced colorectal adenocarcinoma with weekly high-dose l-leucovorin and 5-fluorouracil.

We report the results of 5-fluorouracil (5-FU) combined with high-dose l-folinic acid (leucovorin) therapy for patients with advanced colorectal carcinoma. In each treatment course, the patients weekly received both 5-FU (600 mg/m2 by intravenous 15 min infusion) and l-folinic acid (250 mg/m2 by intravenous infusion over a period of 2 h). A total of six treatments were administered with a 14-day interval to the next course of six treatments. Forty-eight patients were evaluated for toxicity and 32 for response. The combined complete and partial response rate was 25% in 32 patients. Toxicity was within acceptable limits without grade 4 toxicity. Although the response rate was slightly lower than those reported in phase II trials in Japan, the result was satisfactory. This therapy can be the standard chemotherapy for colorectal cancer patients, even in Japan.

Adenocarcinoma↗
PubMedDate not supplied

Protecting the viability of hepatic allografts procured from non-heart-beating donors by blockade of endothelin and platelet activating factor in porcine liver transplantation.

PROBLEM: The function of hepatic allograft from non-heartbeating donors (NHBD) is significantly affected by warm ischemic injury before harvesting. MATERIALS AND METHODS: The effects of the endothelin (ET) antagonist TAK-044 and the platelet activating factor (PAF) antagonist E5880 on the function of grafts from NHBD were evaluated in a porcine orthotopic liver transplantation. The liver grafts were subjected to 90 min of warm ischemia and 4 hours cold preservation. Group 1 (n = 4; n is the number of donor/recipient pairs) was used as a control (untreated). In group 2 (n = 4), donors and recipients were treated with TAK-044 (3 mg/kg). In group 3 (n = 4), pigs were treated with E5880 (0.3 mg/kg). In group 4 (n = 4), pigs were treated with TAK-044 and E5880. RESULTS: The 7 day survival rate of the recipients in groups 1, 2, 3 and 4 was 0, 25, 25 and 100%, respectively (p<0.05, group 1 versus 4). The increases of the serum concentrations of aspartate transaminase, lactate dehydrogenase and arterial lactate 1-4 hours after transplantation were significantly inhibited in the treated groups. CONCLUSION: The blockade of ET and PAF has protective effects on the function of hepatic grafts from NHBD.

Animals↗