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Biomedical subjects

K Kunieda

Publications and source records attributed to K Kunieda.

At least 37 records · Page 2Linked to original sources

A case of liver metastasis from colon cancer masquerading as focal sparing in a fatty liver.

Focal sparing in diffusely fatty liver is a well recognized entity. However, it occasionally creates some problems in the diagnosis of hepatic mass lesions. We recently experienced a case of liver metastasis from colon cancer which appeared as a wedge-shaped hyperdense area on non-enhanced CT (computed tomography). Other imaging techniques also demonstrated a wedge-shaped area which was difficult to distinguish from mere focal sparing in the fatty liver. CT arteriography and dynamic magnetic resonance images were useful for diagnosing this metastatic tumor. CT during arterial portography showed a wedge-shaped ischemic area in the anterior segment caused by intrahepatic portal vein blockade. The histological findings eventually revealed that the tumor, an adenocarcinoma, was surrounded by fibrotic tissue that mimicked focal sparing. We present the radiological features of this case and discuss how to arrive at a correct diagnosis.

Adenocarcinoma↗

[Significance in gene expression of matrix metalloproteinase-9, urokinase-type plasminogen activator and tissue inhibitor of metalloproteinase for metastases of gastric and/or colo-rectal cancer].

In order to clarify the role of matrix metalloproteinase-9 (MMP-9), urokinase-type plasminogen activator (uPA) and tissue inhibitor of metalloproteinase (TIMP) in metastases of gastroenterological cancer, their gene expression in the primary lesions on 47 gastric or 48 colorectal cancer patients was examined by RT-PCR method. 1) The expression of MMP-9, uPA, and TIMP was observed in 55.3%, 66.0% and 87.2% of gastric cancer and in 54.2%, 70.8%, and 89.6% of colorectal cancer, respectively. 2) In the cases with either peritoneal dissemination or lymph node metastases, the incidence of gene expression of MMP-9 was significantly higher in comparison to the cases without those metastases. The same result was observed as for uPA. 3) In the cases with liver metastases, the incidence of gene expression of MMP-9 was significantly higher in comparison to the cases without liver metastasis. The same result was observed as for uPA. The above results indicate that MMP-9 and uPA might play important roles in the peritoneal and lymph node metastases in gastric cancer and in liver metastasis in colorectal cancer. Therefore the investigation of their gene expression in the primary lesions of cancer could be one of the useful methods for the prediction of metastasis, leading to the best decision as to the treatment.

Aged↗

Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts.

Liposomes containing polyethylene glycol-derivatized phospholipids are able to evade the reticuloendothelial system and thereby remain in circulation for prolonged periods. We report here that doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) suppresses the growth of established human lung tumor xenografts in severe combined immunodeficient (SCID) mice and inhibits the spontaneous metastases of these tumors. The enhanced therapeutic efficacy of S-DOX compared to free doxorubicin was demonstrated in two independent human/mouse models. In the first model, S-DOX inhibited the growth of a human non-small cell lung tumor xenograft established orthotopically in the lungs of SCID mice. Treatment of these mice with S-DOX, but not with free drug, suppressed the growth of the tumor in the lung, prevented metastasis from the lung, and enhanced survival percentage. In another model, the human lung tumor is engrafted into gonadal fat pad of SCID mice. Human tumor xenografts grow floridly in this site of engraftment, and the tumor spreads from this primary site into the peritoneal cavity and subsequently reaches the liver and lung. In this model, free drug suppressed the growth of the primary tumor but had no effect upon the subsequent spread of the tumor into the peritoneal cavity, liver, and lung. In contrast, treatment of the tumor-bearing mice with S-DOX (but not with doxorubicin in conventional liposomes) suppressed the tumor spread to the peritoneal cavity, completely arrested metastasis to the liver and lung, and suppressed the growth of the primary tumor xenograft. This report provides the first evidence that antitumor drugs delivered by sterically stabilized liposomes can arrest the metastasis of human tumor xenografts.

Animals↗

Palliative therapy using polyurethane-covered self-expandable metallic stents for malignant esophageal strictures: experiences in six patients.

To evaluate the utility and limitations of palliative stenting with polyurethane-covered self-expandable metallic stents, 6 patients (3 males and 3 females ranging in age from 58-85 [mean 72.1] years) with malignant esophageal strictures were treated with these stents between April 1993 and October 1995. Three had esophageal carcinoma, two had gastric carcinoma and one had lung carcinoma. Song-type self-expandable metallic stents were inserted by intubation under local laryngeal anesthesia. A retriever was attached in 4 stents and an anti-reflux mechanism was attached in 2 stents placed over the esophagocardiac strictures. The stents were placed successfully in all patients, and no major complication related to intubation was encountered. All the stents fully expanded within 3 days after insertion. The grade of dysphagia was improved in 5 (83%) of the 6 patients. One stent was extracted using a retriever in one patient with no improvement. No reflux symptoms were observed in 2 patients whom received stents with an anti-reflux mechanism. No blockage of the stent due to food impaction or secondary stricture occurred in any patient during the observation period. One stent migrated into the stomach in one patient 27 days after insertion. Esophageal stenting with polyurethane-covered self-expandable metallic stents is a relatively safe and effective palliation for malignant esophageal strictures.

Aged↗

[Locoregional therapy for liver metastases of colorectal cancer].

The role of biological response modifiers (BRM) in locoregional therapy for liver metastases of colorectal cancer was studied clinically and experimentally. Seven patients with numerous metastases to both lobes of liver were given intraarterial administration of BRM in combination with anticancer drugs. A partial response was observed in 1 patient. The response rate was 14.3%. Alternatively, intraarterial administration of both OK-432 and IL-2 into the rabbit with liver metastases of VX-2 tumors could bring about the infiltration of cytotoxic T lymphocytes around the tumors, followed by a significant decrease of the metastatic nodules. In addition, the same anti-tumor effect was observed when PSK was administered intraperitoneally into the BALB/c mouse with liver metastases of colon 26 tumors. Moreover, the therapeutic effect of water in oil type emulsion encapsulating both OK-432 and IL-2 was greater than that of the solution of BRM in BALB/c mouse with liver metastases of colon 26 tumors. These results indicated that BRM could be one of the promising agents in locoregional therapy against liver metastases of colorectal cancer.

Adult↗

[A new modality of locoregional chemotherapy based on biochemical double modulation of 5-fluorouracil with both leucovorin and cisplatin against liver metastases of colorectal cancer].

A new modality of locoregional chemotherapy based on biochemical double modulation of 5-fluorouracil (FU) with both leucovorin (LV) and cisplatin (CDDP) against liver metastases of colorectal cancer was devised. The schedule for the locoregional therapy was as follows; bolus infusion of LV (6 mg/body) followed by 30-minute infusion of CDDP (10 mg/body) and 30-minute infusion of 5-FU (250 mg/body). Four colorectal cancer patients with numerous metastases to both lobes of liver were given intraarterial administration of above anticancer drugs every 1-2 weeks after resection of primary lesions. On the one hand, 3 colorectal cancer patients, who developed a few metastases to both lobes of liver, were treated preventively by the same schedule every 2-3 weeks after the resection of metastatic tumors. As for the clinical (radiographic) response, complete response and partial response were observed in 1 and 2 of 4 patients, respectively. The response rate was 75%. No new lesions appeared for over 1 year by the preventive treatment in 2 of 3 patients, whereas new lesions appeared in one patient at 3 months after discontinuation of treatment because of mild toxicity. The toxicity, however, was within acceptable limits. These results indicated that biochemical double modulation of 5-FU with both LV and CDDP is a very promising locoregional chemotherapy against liver metastases of colorectal cancer.

Aged↗

[A study on the relationship between clinicopathological findings of gastric cancer and its biological behavior such as DNA ploidy pattern and immunohistochemical staining of PCNA, laminin, p53 and nm 23].

UNLABELLED: The quantity of DNA ploidy and the expression of PCNA, laminin, p53 and nm23 by immunohistochemical stain were investigated using paraffin-embedded specimens obtained from 135 gastric cancer patients, and were compared with clinicopathological findings. RESULTS: (1) The incidence of DNA high ploidy (HP) was significantly higher in such a case with infiltrating type (INF) and positive lymph node metastasis (p+) compared with that of negative cases. (2) The high level of PCNA labeling index (HLI), negative expression of laminin (NEL) and nm23 (NE23) were more frequently observed in INF; large tumor size, deep invasion and p+, while positive p 53 was noted only in p+ cases. (3) The survival curve of HP, HLI, NEL, and NE 23 was significantly lower than that of the cases showing the reverse findings. As a conclusion, it is suggested that the investigation of the DNA ploidy, PCNA, laminin, p53 and nm23 might be useful as a parameter of biological behavior for gastric cancer and the prognosis of gastrectomized patients.

DNA, Neoplasm↗

Ultrasonically guided percutaneous microwave coagulation therapy for small hepatocellular carcinoma.

BACKGROUND: The authors have used percutaneous microwave coagulation therapy (PMCT) as a new percutaneous local treatment for single unresectable hepatocellular carcinoma (HCC) measuring 2 cm or less in greatest dimension (small HCC). PMCT was used to attempt a cure of the disease. In this study, the efficacy of this treatment was assessed. METHODS: PMCT was performed on 18 patients with single small HCC. A microwave electrode (custom-made, 30-cm long by 1.6-mm thick) was inserted percutaneously into the tumor area under ultrasonic guidance. Microwaves at 60 W for 120 seconds were used to irradiate the tumor and surrounding area. RESULTS: After PMCT was administered, various image findings were correlated with tissue necrosis. At the tumor and surrounding area, ultrasonography showed echogenic change, contrast enhancement disappeared on contrast enhanced computed tomography, and magnetic resonance imaging (T2-weighted image) showed decreased intensity in all cases after treatment. Complete necrosis of the tumor area in a specimen obtained from one patient who underwent hepatectomy after PMCT also was confirmed. The treatment reduced levels of the tumor marker, alpha-fetoprotein, which had been high in some patients. Although the follow-up period was short (11-33 months), 17 patients remain alive. Local recurrence in the treated area has not been detected, and no serious side effects or complications have been encountered. CONCLUSIONS: PMCT may be an effective and safe treatment for small HCCs.

Adult↗

[Studies on adjuvant chemotherapy using subserosal or submucosal administration of neocarzinostatin for gastric cancer and colorectal cancer].

The significance and effectiveness of adjuvant intraoperative chemotherapy using subserosal or submucosal administration of Neocarzinostatin (NCS) and CH 40 for gastric cancer and colorectal cancer were studied. Tissue NCS concentration of proximal lymph nodes were higher than for distant lymph nodes, while the immunocompetency of distant lymph nodes (lower NCS concentration) showed slightly higher activity than that of proximal lymph nodes. From these results, it is suggested that loco-regional administration of NCS might be effective for chemical lymph node cleaning of the cancer.

Carbon↗

Biliary endoprosthesis in bile duct obstruction secondary to hepatocellular carcinoma.

The effect of biliary endoprosthesis was evaluated in 13 patients with major bile duct obstruction secondary to invasion by hepatocellular carcinoma. In 12 patients major portal vein branches were also invaded by the tumors. After several days' instillation of nasobiliary or percutaneous drainage tubes to flush the bile ducts, biliary endoprosthesis was performed either endoscopically (N = 9) or percutaneously (N = 4). Significant decrease (less than 50% of initial values) of alkaline phosphatase and bilirubin levels was observed in eight and two patients on day 20, respectively. Twelve patients died of hepatic failure at 27-132 days (mean 60 days). One patient without portal vein involvement is currently alive at 300 days. Biliary endoprosthesis has a limited role in the palliation of bile duct obstruction secondary to hepatocellular carcinoma, and the prognosis may be influenced mainly by the underlying hepatic function.

Adult↗

Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer.

We performed an experimental study on slow releasing anticancer drug implantation treatment as a new therapy for hepatocellular carcinoma. Hydroxyapatite (HAP) was chosen for the carrier material and doxorubicin hydrochloride (DOX) for anticancer agent. DOX-HAP was produced by adsorbing DOX to porous HAP particles of 1375 +/- 125 microns diameter using the freeze drying method. In vitro experiments showed slow release of the drug resulting in the steady release of DOX from HAP for 1 month duration. In healthy white rabbits with DOX-HAP implantation in the liver, serum DOX was not detectable, and DOX release rate was stable at the implanted region after 7, 14, and 21 days. When DOX-HAP (DOX; 100 mg kg-1) was administered to mice with sarcoma 180, an improved survival rate was observed without acute toxicity. We also found that VX2 liver tumour growth on white rabbit was inhibited by implantation of DOX-HAP, without acute toxicity. We hope that DOX-HAP implantation therapy will open up new avenues for the treatment of hepatoma.

Animals↗

[Immunological effects of locoregional immunochemotherapy for liver metastases of gastric cancer].

Nine gastric cancer patients with simultaneous liver metastases were given intermittent transarterial administration of chemotherapeutics (adriamycin, mitomycin C or 5-fluorouracil) and biological response modifiers (BRM; OK-432 and interleukin (IL) -2) after gastrectomy. In terms of direct antitumor effect on liver metastases, a partial response was observed in 4 of 9 cases (44%). In addition, the concentration of 3 kinds of cytokines such as IL-6, tumor necrosis factor (TNF) -alpha and interferon (IFN) -gamma in the peripheral blood sera was measured immediately before and after transarterial administration of agents. While the concentration of IL-6 increased by BRM, chemotherapeutics could not alter the level of IL-6. As for TNF-alpha and IFN-gamma, no particular changing pattern was observed after transarterial administration. Furthermore, natural killer (NK) activity of peripheral blood mononuclear cells was measured. Administration of either BRM or BRM in combination with chemotherapeutics caused a decrease in NK activity, whereas chemotherapeutics did not. Flow cytometric analysis using 3 kinds of monoclonal antibodies (Anti-CD16, CD56 and CD57) revealed that the proportion of subset of both highly activated NK cells (CD16+.CD56+.CD57-) and moderately activated NK cells (CD16+.CD56+.CD57+) reduced after administration of BRM.

Antineoplastic Combined Chemotherapy Protocols↗

[Fundamental study on hyperthermic chemotherapy using adriamycin-loaded hydroxyapatite].

We developed a porous hydroxyapatite ceramic (HAP) incorporating adriamycin (ADM), that is, ADM-HAP as a new delivery system (DDS) to release ADM gradually. We also researched the possibility of hyperthermic chemotherapy using ADM-HAP by in vitro and in vivo experiments. As for in vitro experiments, we implanted HAPs into uniform Agar-Phantom, and observed thermal distribution generated by Thermotron-RF 8 using thermography. Then we found the hot spot that the edge temperature of HAPs always at the range of 0.5-0.7 degrees C than in the other regions. On the other hand, slow constant release (1%) of ADM from ADM-HAP in PBS was recognized for 24 hrs up to 30 days. When the incubating temperature was shifted up to 42.5 degrees C or 44 degrees C from 37 degrees C, the quantity released over 24 hrs increased about 1.1-fold or 1.3-1.4-fold of the cases at 37 degrees C, respectively. In the in vivo experiment, we inoculated Sarcoma 180 cells in the leg of ddY-mice, and measured the tumor growing times by the treatment of hyperthermia+ADM (whole body), hyperthermia+ADM (tumor region) or hyperthermia+ADM-HAP (tumor region). Then we found that the effect of hyperthermia with ADM-HAP inhibited synergistically the tumor growth as compared with hyperthermia with ADM. Consequently, we succeeded in tumor growth inhibition by increasing the temperature and by limiting ADM release to only a target region using hyperthermia with ADM-HAP.

Animals↗

[A long-term survival case of advanced gastric cancer undergoing radical gastrectomy by second-look operation after successful chemotherapy (CDDP, MMC, 5-FU)].

A 55-year-old woman with gastric cancer underwent laparotomy and was found to have an unresectable tumor characterized by S3 (invasion of the pancreas), N3, P0 and H0. She was then treated by combined administration of cisplatinum, mitomycin C and 5-fluorouracil. A remarkable response (CR) was confirmed by upper gastrointestinal roentgenography and endoscopy. Upon reoperation about 8 weeks after chemotherapy, a successful radical total gastrectomy with R2 (partially R3) lymphnode dissection was performed. Histological examination of the specimens, including the stomach and lymphnodes, revealed no cancer cells in any region (pCR). She had been given UFT and PSK for 4 years 4 months after reoperation. She has lived for 5 years 2 months after reoperation without any signs of recurrence or metastases.

Adenocarcinoma↗