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Biomedical subjects

Yuji Nimura

Publications and source records attributed to Yuji Nimura.

At least 37 records · Page 2Linked to original sources
PubMed2006

Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary cancer: surgical outcome and long-term follow-up.

OBJECTIVE: To assess clinical benefit of portal vein embolization (PVE) before extended, complex hepatectomy for biliary cancer. SUMMARY BACKGROUND DATA: Many investigators have addressed clinical utility of PVE before simple hepatectomy for metastatic liver cancer or hepatocellular carcinoma, but few have reported PVE before hepatectomy for biliary cancer due to the limited number of surgical cases. METHODS: This study involved 240 consecutive patients with biliary cancer (150 cholangiocarcinomas and 90 gallbladder cancers) who underwent PVE before an extended hepatectomy (right or left trisectionectomy or right hepatectomy). All PVEs were performed by the "ipsilateral approach" 2 to 3 weeks before surgery. Hepatic volume and function changes after PVE were analyzed, and the outcome also was reviewed. RESULTS: There were no procedure-related complications requiring blood transfusion or interventions. Of the 240 patients, 47 (19.6%) did not undergo subsequent hepatectomy. The incidence of unresectability was higher in gallbladder cancer than in cholangiocarcinoma (32.2% versus 12.0%, P < 0.005). The remaining 193 patients (132 cholangiocarcinomas and 61 gallbladder cancers) underwent hepatectomy with resection of the caudate lobe and extrahepatic bile duct (n = 187), pancreatoduodenectomy (n = 42), and/or portal vein resection (n = 63). Seventeen (8.8%) patients died of postoperative complications: mortality was higher in gallbladder cancer than in cholangiocarcinoma (18.0% versus 4.5%, P < 0.05); and it was also higher in patients whose indocyanine green clearance (KICG) of the future liver remnant after PVE was <0.05 than those whose index was >or=0.05 (28.6% versus 5.5%, P < 0.001). The 3- and 5-year survival after hepatectomy was 41.7% and 26.8% in cholangiocarcinoma and 25.3% and 17.1% in gallbladder cancer, respectively (P = 0.011). In 136 other patients with cholangiocarcinoma who underwent a less than 50% resection of the liver without PVE, a mortality of 3.7% and a 5-year survival of 27.6% were observed, which was similar to the 132 patients with cholangiocarcinoma who underwent extended hepatectomy after PVE. CONCLUSIONS: PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

Adult↗
PubMed2006

Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with gallbladder carcinoma.

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors). SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma. METHODS: A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors. CONCLUSIONS: Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.

Adult↗
PubMed2006

Perioperative synbiotic treatment to prevent postoperative infectious complications in biliary cancer surgery: a randomized controlled trial.

SUMMARY BACKGROUND DATA: Use of synbiotics has been reported to benefit human health, but clinical value in surgical patients remains unclear. OBJECTIVE: To investigate the effect of perioperative oral administration of synbiotics upon intestinal barrier function, immune responses, systemic inflammatory responses, microflora, and surgical outcome in patients undergoing high-risk hepatobiliary resection. METHODS: Patients with biliary cancer involving the hepatic hilus (n = 101) were randomized before hepatectomy, into a group receiving postoperative enteral feeding with synbiotics (group A); or another receiving preoperative plus postoperative synbiotics (group B). Lactulose-mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, natural killer (NK) cell activity, interleukin-6 (IL-6), fecal microflora, and fecal organic acid concentrations were determined before and after hepatectomy. Postoperative infectious complications were recorded. RESULTS: Of 101 patients, 81 completed the trial. Preoperative and postoperative changes in L/M ratio and DAO activity were similar between groups. Preoperatively in group B, NK activity, and lymphocyte counts increased, while IL-6 decreased significantly (P < 0.05). Postoperative serum IL-6, white blood cell counts, and C-reactive protein in group B were significantly lower than in group A (P < 0.05). During the preoperative period, numbers of Bifidobacterium colonies cultured from and total organic acid concentrations measured in feces increased significantly in group B (P < 0.05). Postoperative concentrations of total organic acids and acetic acid in feces were significantly higher in group B than in group A (P < 0.05). Incidence of postoperative infectious complications was 30.0% (12 of 40) in group A and 12.1% (5 of 41) in group B (P < 0.05). CONCLUSIONS: Preoperative oral administration of synbiotics can enhance immune responses, attenuate systemic postoperative inflammatory responses, and improve intestinal microbial environment. These beneficial effects likely reduce postoperative infectious complications after hepatobiliary resection for biliary tract cancer.

Amine Oxidase (Copper-Containing)↗
PubMed2006

Local balance of transforming growth factor-beta1 secreted from cholangiocarcinoma cells and stromal-derived factor-1 secreted from stromal fibroblasts is a factor involved in invasion of cholangiocarcinoma.

Tumor-stromal interactions are important for the progression of malignant tumors. The purpose of the present study was to examine interactions of cholangiocarcinoma (CC) cells and stromal fibroblasts with respect to stromal-derived factor-1 (SDF-1) and transforming growth factor (TGF)-beta1. Two cell lines of CC (HuCCT-1 and CCKS-1) and WI-38 fibroblast cell line were used for cell culture, and 12 CC tissue specimens for immunohistochemical studies. Invasion of CC cells was increased significantly by the supernatant from fibroblast cultures, but not by the supernatant from fibroblasts cocultured with CC cells. Expression of SDF-1 in cultured fibroblasts was downregulated by TGF-beta1 treatment, and coculture with CC cells and anti-TGF-beta1 neutralizing antibody restored the decreased SDF-1 expression, suggesting that TGF-beta1 secreted from CC cells might have reduced the expression of SDF-1 by fibroblasts and might have reduced the increased invasion of CC cells induced by the supernatant from fibroblasts. Immunohistochemical expression of TGF-beta1 in CC cells was focal or negative and that of SDF-1 was evident in stromal fibroblasts at the invasive front of CC. In conclusion, local mutual influence of TGF-beta1 secreted from carcinoma cells and SDF-1 expressed by stromal fibroblasts may be involved in invasion of CC cells.

Aged↗
PubMed2006

Non-palpable and non-invasive ductal carcinoma with bloody nipple discharge successfully resected after cancer spread was accurately diagnosed with three-dimensional computed tomography and galactography.

A case of ductal carcinoma in situ (DCIS) that was treated by partial mastectomy is reported. The operation was performed after accurate estimation of cancer spread by three-dimensional computed tomography (3D-CT). The patient was a 39-year-old woman without a palpable lump who had a bloody nipple discharge. Ultrasonography showed distended mammary ducts with intraductal components. Fine needle aspiration cytology revealed ductal carcinoma. Galactography showed two subsegmental ducts and peripheral branches in the upper-inner quadrant of the right breast. 3D-CT depicted a well enhanced segmental-clumped lesion including two subsegments of a duct lobular system shown in galactograms. DCIS was diagnosed and partial mastectomy following the video assisted thoracoscopic surgery (VATS) marker insertion was performed, after cancer spread was accurately diagnosed by 3D-CT guidance. DCIS resected by minimally sufficient partial mastectomy with negative surgical margins was diagnosed histopathologically.

Adult↗
PubMed2006

Possible regulation of migration of intrahepatic cholangiocarcinoma cells by interaction of CXCR4 expressed in carcinoma cells with tumor necrosis factor-alpha and stromal-derived factor-1 released in stroma.

Intrahepatic cholangiocarcinoma (ICC) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. We examined roles of CXCR4 and its ligand, stromal cell-derived factor (SDF)-1, in migration of ICC with respect to tumor-stromal interaction by using two ICC cell lines, a fibroblast cell line (WI-38), and 28 human ICC tissues. The two ICC cell lines expressed CXCR4 mRNA and protein, and WI-38 fibroblasts expressed SDF-1 mRNA and protein. Migration of cultured ICC cells in Matrigel was induced by co-culture with WI-38 fibroblasts and by incubation with SDF-1. Anti-SDF-1 antibody suppressed migration, demonstrating that SDF-1 released from WI-38 fibroblasts was responsible for this migration. Tumor necrosis factor (TNF)-alpha pretreatment of ICC cells up-regulated CXCR4 mRNA and protein expression in a concentration-dependent manner. Administration of SDF-1 and TNF-alpha increased synergistically ICC cell migration, which was suppressed by the CXCR4 antagonist AMD3100. In ICC tissue, TNF-alpha was mainly expressed in infiltrated macrophages, CXCR4 in ICC cells, and SDF-1 in stromal fibroblasts. In conclusion, the interaction of SDF-1 released from fibroblasts and CXCR4 expressed on ICC cells may be actively involved in ICC migration, and TNF-alpha may enhance ICC cell migration by increasing CXCR4 expression. CXCR4 could be a therapeutic target to prevent ICC invasion.

Aged↗
PubMed2006

[Dose "extended" surgery for pancreatic head adenocarcinoma have survival impact?].

Adenocarcinoma of the pancreas is the most difficult to treat, and the prognosis, even if curative resection is possible, is dismal. Improving survival in this intractable disease is a challenging issue. Most Japanese surgeons have stressed that resection with extended lymphadenectomy and autonomic nerve dissection (extended surgery) can offer a better chance of long-term survival. On the other hand, surgeons in Western countries are skeptical about extended surgery and have preferred resection without extended lymphadenectomy (standard surgery). Two randomized controlled trials (RCTs) on "standard vs. extended surgery for pancreatic head adenocarcinoma" were reported in 1998 from Italy and in 2002 from USA. Those two RCTs demonstrated that extended surgery did not improve patient survival; however, they had little impact on Japanese surgeons because the extended surgery used in those RCTs were not "true" extended surgery. Thereafter, one RCT was conducted in Japan in which extensive lymphadenectomy including paraaortic node and complete resection of autonomic nerves around the common hepatic and the superior mesenteric arteries were performed in extended surgery. Unexpectedly, the results showed that the survival rates were similar between extended and standard surgeries, compatible with the results of the Western RCTs. We should therefore conclude that extended surgery does not improve survival for patients with pancreas head adenocarcinoma.

Adenocarcinoma↗
PubMed2005

Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct--an immunohistochemical study of 110 cases of hepatolithiasis.

BACKGROUND/AIMS: Two types of neoplastic lesions preceding invasive intrahepatic cholangiocarcinoma (ICC) are identified: a flat-type neoplastic lesion called 'biliary intraepithelial neoplasia (BilIN)' and an intraductal papillary neoplasm of the bile duct (IPN-B). Multi-step carcinogenesis has been suggested in both lesions, although phenotypic changes during this process remain unclarified. METHODS: We immunohistochemically examined expression patterns of MUC1, MUC2, MUC5AC, cytokeratin 7 (CK7), and CK20 in BilIN, IPN-B, and ICC in 110 cases of hepatolithiasis. RESULTS: Thirty-seven cases of ICC in hepatolithiasis were divided into 18 tubular adenocarcinomas with BilIN, 10 tubular adenocarcinomas with IPN-B and nine colloid carcinomas with IPN-B. Carcinogenesis via BilIN was characterized by MUC2-/CK7+/CK20-with increasing MUC1 expression. IPN-B was characterized by the intestinal phenotype (MUC2+/CK20+), and carcinogenesis leading to tubular adenocarcinoma was associated with increasing MUC1 expression and that to colloid carcinoma with MUC1-negativity. Pathological stages of tubular adenocarcinoma of ICC with BilIN or IPN-B were more advanced than those of colloid carcinoma with IPN-B. CONCLUSIONS: Immunophenotypes of MUCs and cytokeratins might characterize three cholangiocarcinogenetic pathways in hepatolithiasis. Increased expression of MUC1 in BilIN and also IPN-B is associated with tubular adenocarcinoma, while colloid carcinoma in IPN-B is characterized by MUC1-negativity and less advanced pathologic stages.

Adenocarcinoma, Papillary↗
PubMed2005

TNM classification for perihilar cholangiocarcinoma: comparison between 5th and 6th editions of the AJCC/UICC staging system.

BACKGROUND: A few investigators have evaluated the TNM classification for perihilar cholangiocarcinoma. The new sixth edition of the American Joint Committee on Cancer (AJCC)/Internal Union Against Cancer (UICC) staging system focuses on vascular invasion and regional lymph node metastasis. METHODS: For 166 patients with perihilar cholangiocarcinoma undergoing R0 resection, survival curves stratified according to TNM classifications were compared between fifth and sixth editions. RESULTS: The previous T3 now is divided into T3 and T4. Most new pT4 patients had invasion of the portal bifurcation; their survival was poorer than that for new pT3 patients. The 5-, 10-, and 15-year survival rates were worse in the previous stage III than in the previous stage IVA, although the difference fell short of significance. The previous stage IVA (T3 Any NM0) is divided into new stages: IIA (T3N0M0), IIB (T1-3N1M0), and III (T4 Any NM0). All patients in stage III had invasion of the portal bifurcation. Survival was similar between stages IA, IB, and IIA, while patients with T4N0M0 tumors survived longer than those with T4N1M0 tumors and similarly to those with stage IIB tumors. CONCLUSIONS: The sixth edition provided improved prediction of survival in patients with perihilar cholangiocarcinoma; for still better prediction, cancer invasion of the portal bifurcation and regional lymph node metastasis should be weighted equally.

Adult↗
PubMed2005

Impaired expression of hepatic multidrug resistance protein 2 is associated with posthepatectomy hyperbilirubinemia in patients with biliary cancer.

BACKGROUND AND AIMS: Hyperbilirubinemia is a critical complication following hepatectomy for biliary cancer. Hepatic multidrug resistance protein 2 (MRP2), a bilirubin transporter, is shown to be down-regulated by acute biliary obstruction in rats. However, little is known about the effect of chronic obstruction by malignancy on the MRP2 expression in patients or the association of MRP2 expression with posthepatectomy hyperbilirubinemia. MATERIALS AND METHODS: The MRP2 expression before hepatectomy was determined by immunostaining and Western blotting in patients with biliary cancer. To directly determine the effect of chronic bile duct obstruction on the MRP2 expression, the expression levels were compared between the cholestatic and noncholestatic lobes in each of seven patients. In another 39 patients, the correlation of the MRP2 expression of the anticipated remnant liver with the posthepatectomy severe hyperbilirubinemia, defined as a serum total bilirubin concentration>or=200 micromol/l, was evaluated. RESULTS: The MRP2 staining in the cholestatic lobes was weak and not restricted to the canalicular membrane, unlike the noncholestatic lobes. The expression levels in the cholestatic lobes were 45% of those in the noncholestatic lobes. Postoperative maximum bilirubin levels were significantly correlated with MRP2 expression of the anticipated remnant liver. The MRP2 expression had been already impaired before hepatectomy in all patients who eventually developed severe hyperbilirubinemia. CONCLUSIONS: Decreased MRP2 expression, caused by biliary obstruction due to cancer, is a possible risk factor for posthepatectomy severe hyperbilirubinemia.

Adult↗
PubMed2005

Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2.

We studied the effect of TNF-alpha stimulation on a cholangiocarcinoma cell line, CCKS1. CCKS1 expressed only one type TNF receptor, TNFR2. Treatment of CCKS1 with TNF-alpha substantially activated NFkappaB, MAPK and Akt signalings which in turn activated matrix metalloproteinase-9 (MMP-9) secretion and in vitro invasiveness of CCKS1. Pretreatment of cells with anti-TNFR2 neutralizing antibody inhibited the TNF-alpha-dependent signaling and MMP-9 secretion and subsequently blocked invasion in vitro. Moreover, an inhibitor for matrix metalloproteinase, Galardin, suppressed the invasion in a dose-dependent manner. Similarly, pharmacological inhibition of signaling clearly suppressed the TNF-alpha dependent MMP-9 secretion. These results strongly suggest that TNF-alpha-TNFR2 signaling plays an important role to convert the cholangiocarcinoma cells to be more aggressive one.

Cholangiocarcinoma↗
PubMed2005

Synbiotics reduce postoperative infectious complications: a randomized controlled trial in biliary cancer patients undergoing hepatectomy.

BACKGROUND AND AIMS: The clinical value of synbiotics in surgical patients remains unclear. The aim of this study was to investigate the effect of synbiotics on intestinal integrity and microflora, as well as on surgical outcome, in patients undergoing high-risk hepatectomy. METHODS: Fifty-four patients with biliary cancer were randomly allocated to two groups before hepatectomy. One group received postoperative enteral feeding that included synbiotics; the other received enteral feeding only. Lactulose/mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, and fecal microflora and organic acid concentrations were determined. Postoperative infectious complications were recorded. RESULTS: Of the 54 patients, 44 completed the trial (21 receiving synbiotics and 23 others as controls). Postoperative changes in L/M ratios and serum DAO activities were identical between the two groups. Numbers of beneficial bacteria increased in the synbiotics group after surgery but decreased in controls. Numbers of harmful microorganisms decreased in the synbiotics group but increased in controls. Total organic acid concentrations increased in the synbiotics group but decreased in controls. Incidence of infectious complications was 19% (4/21) in the synbiotics group and 52% (12/23) in controls (P<0.05). All study patients tolerated surgery (mortality 0%). CONCLUSIONS: Synbiotics, combined with early enteral nutrition, can reduce postoperative infections. This beneficial effect presumably involves correction of an intestinal microbial imbalance induced by surgical stress.

Aged↗
PubMed2005

Role of thromboxane in producing hepatic injury during hepatic stress.

Hepatic injury after hepatic stress is caused by several mechanisms, including inflammatory reaction and microcirculatory disturbance. Levels of thromboxane, a vasoconstrictive eicosanoid, have been shown to increase in systemic circulation after different types of hepatic stress such as endotoxemia, hepatic ischemia-reperfusion, hepatectomy, liver transplantation, hemorrhagic shock and resuscitation, hepatic cirrhosis, and alcoholic liver injury. The production of thromboxane from the liver is also enhanced under these stresses, which may act on the liver in an autocrine or a paracrine fashion. Kupffer cells, resident hepatic macrophages, may be a major source of stress-induced thromboxane, although other cell types in the liver such as sinusoidal endothelial cells and hepatocytes may also produce this eicosanoid. Thromboxane induces hepatic damage through vasoconstriction, platelet aggregation, induction of leukocyte adhesion, up-regulation of proinflammatory cytokines, and induction of other vasoconstrictor release. In this regard, administration of cyclooxygenase inhibitor, specific thromboxane synthase inhibitor, and specific thromboxane receptor antagonists has been shown to protect from severe hepatic injury elicited by these hepatic stresses. Furthermore, blockade of Kupffer cell function by administration of gadolinium chloride showed salutary effects in preventing hepatic damage in bile duct ligation models. This review article summarizes the recent knowledge of the role of thromboxane in various types of hepatic stress and the effects of thromboxane inhibitors in these models.

Animals↗
PubMed2005

Dutch surgery in Japan.

An isolation policy was adopted in feudal Japan from 1639 to 1853 owing to the fear of foreign influence. During those 200 years of isolation, all foreigners were withheld from the country with the exception of the Dutch, who were permitted to establish a trading post on a small island in the Bay of Nagasaki, called Decima. Western culture and science reached the Japanese exclusively through the Dutch on Decima. Health care on Decima was provided by Dutch barber-surgeons, who introduced Western surgical practice in Japan. Official interpreters were the only Japanese allowed on Decima. It was from among these interpreters that the first Japanese surgeons arose who, having mastered the Dutch language, translated several Dutch anatomic and surgical texts. Genpaku Sugita translated a Dutch anatomy textbook into Japanese, which was completed in 1774. This book, entitled Kaitai Shinsho [New Book on Anatomy], was the first Western scientific monograph to be translated entirely into Japanese. Several Dutch surgical schools were founded through which Dutch surgery, known in Japan as "surgery of the red-haired" was propagated. According to the custom of the surgical guilds in Holland, certificates were granted to Japanese apprentices who had completed their training in Dutch surgery. About 60 Dutch surgeons had served on Decima up to 1850, providing the basis for surgery to develop in Japan. Among them, Philipp Franz von Siebold was an exceptional scholar who also had a great impact in making Japanese culture known to the Western world.

Anatomy↗