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Atsushi Kudo,
Kaoru Mogushi,
Tadatoshi Takayama,
Satoshi Matsumura, Daisuke Ban,
Takumi Irie,
Takanori Ochiai,
Noriaki Nakamura,
Hiroshi Tanaka,
Naohiko Anzai,
Michiie Sakamoto,
Shinji Tanaka,
Shigeki Arii
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ABSTRACT: BACKGROUND: Recurrence determines the postoperative prognosis with hepatocellular carcinoma (HCC). It is unknown how the liver dysfunction involving organic anion transporter failure causes the occurrence of HCCs. This study was designed to elucidate the link between liver dysfunction and multicentric occurrence (MO) after radical hepatectomy. METHODS: Forty-nine samples of noncancerous liver tissue from HCC patients within the Milan criteria who were treated at our institution between January 2004 and August 2008 were examined as a training set by using genome-wide gene expression analysis. Using the independent 2-institutional cohort of 134 patients between September 2008 and December 2009, we performed a validation study using tissue microarray analysis. Cox proportional hazard regression analyses for MFS were performed to estimate the risk factors. RESULTS: In the Gene Ontology database (GO:0015711), SLC22A7 expression was the best predictor of MO-free survival [MFS] (Fold, 0.726; P = 0.001). High SLC22A7 gene expression prevented the occurrence of HCC after hepatectomy (odds ratio [OR], 0.2; P = 0.004). Multivariate analyses identified SLC22A7 expression as an independent risk factor (OR, 0.3; P = 0.043). In the validation study, multivariate analyses of MFS identified SLC22A7 expression as an independent risk factor (OR, 0.5; P = 0.012). As judged by gene set enrichment analysis, SLC22A7 down regulation was associated with mitochondrion (P = 0.008) and oxidoreductase activity (P = 0.006). Sirtuin 3 as a regulator of mitochondrial metabolism also determined MFS (P = 0.018). CONCLUSIONS: The mitochondrial pathways may affect SLC 22A7 function to promote the occurrence of HCC. (Word count: 246).
Journal of Gastroenterology 03/2013; · 4.16 Impact Factor
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Shunsuke Muramatsu,
Shinji Tanaka,
Kaoru Mogushi,
Rama Adikrisna,
Arihiro Aihara, Daisuke Ban,
Takanori Ochiai,
Takumi Irie,
Atsushi Kudo,
Noriaki Nakamura,
Koh Nakayama,
Hiroshi Tanaka,
Shoji Yamaoka,
Shigeki Arii
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ABSTRACT: Background:Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies because of recurrence and/or metastasis even after curative resection. Emerging evidence suggests that tumor metastasis and recurrence might be driven by a small subpopulation of stemness cells, so-called cancer stem cells (CSCs). Previous investigations have revealed that glioma and breast CSCs exhibit intrinsically low proteasome activity and that breast CSCs also reportedly contain a lower reactive oxygen species (ROS) level than corresponding non-tumorigenic cells. Aims: Here, we visualized 2 stem cell features, low proteasome activity and low intracellular ROS, in HCC cells using 2-color fluorescence activated cell sorting to isolate cells with stem cell features. These cells were then analyzed for their division behavior in normoxia and hypoxia, expression of stem cell markers, tumorigenicity, metastatic potential, specific gene expression signatures, and their clinical implications. Results: A visualized small subpopulation of HCC cells demonstrated asymmetric divisions. Their remarkable tumorigenicity in nonobese diabetic/severe combined immunodeficient mice suggested the cancer initiation potential of these HCC CSCs. Comprehensive gene expression analysis revealed that chemokine-related genes were upregulated in the CSCs subpopulation. Our identified HCC CSCs facilitated the migration of macrophages in vitro and demonstrated metastatic potentials via recruitment of macrophages in vivo. In patients who undergo curative operation for HCC, the CSC-specific gene signature in the liver microenvironment significantly correlates with recurrence. Conclusions: Based on these findings, the stem cell feature monitoring system proposed here is a promising tool to analyze the in vivo significance of CSC microenvironments in human HCCs. (HEPATOLOGY 2013.).
Hepatology 02/2013; · 11.66 Impact Factor
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Kota Sato,
Shinji Tanaka,
Yusuke Mitsunori,
Kaoru Mogushi,
Mahmut Yasen,
Arihiro Aihara, Daisuke Ban,
Takanori Ochiai,
Takumi Irie,
Atsushi Kudo,
Noriaki Nakamura,
Hiroshi Tanaka,
Shigeki Arii
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ABSTRACT: BACKGROUND & AIMS: The abnormal tumor vascularity is one of the typical features of hepatocellular carcinoma (HCC). In this study, the significance of contrast-enhanced intraoperative ultrasonography (CEIOUS) images on the HCC vasculatures was evaluated by clinicopathological and gene expression analyses. METHODS: We enrolled 82 patients who underwent curative hepatic resection for HCC with CEIOUS. According to the CEIOUS vasculature patterns, the clinicopathological and gene expression analyses were performed. RESULTS: The CEIOUS images of HCC vasculatures were classified into reticular type or thunderbolt type. The thunderbolt type HCC was significantly correlated with higher alpha-fetoprotein levels, tumor size, histological differentiation, portal vein invasion, and TNM stage, and these patients demonstrated a significantly poorer prognosis for both recurrence-free survival (P=0.0193) and overall survival (P=0.0362) than the patients with the reticular type HCC. Gene expression analysis revealed that a re-replication inhibitor geminin was significantly overexpressed in thunderbolt type HCCs (P=0.00326). In vitro knockdown of geminin gene reduced significantly the proliferation of human HCC cells. Immunohistochemical analysis confirmed the overexpression geminin protein in the thunderbolt type HCC (P < 0.0001). Multivariate analysis revealed geminin expression as one of the independent factors to predict poor survivals of the HCC patients (P=0.0170). CONCLUSION: The CEIOUS vascular patterns were distinctly identifiable by gene expression profiling associated with the cellular proliferation of HCC, and significantly related to HCC progression and poor prognosis, as well. These findings of CEIOUS might be clinically useful for one of the determinant factors of the postoperative treatment of HCC. (HEPATOLOGY 2012.).
Hepatology 11/2012; · 11.66 Impact Factor
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ABSTRACT: BACKGROUND: Severe macrosteatotic liver has been regarded as a donor contraindication for liver transplantation. However, it has not yet been determined whether hepatocytes lose function before cold ischemia. This study was designed to elucidate certain pathophysiological alterations and how to ameliorate such hepatic dysfunctions. MATERIALS AND METHODS: Wistar rats were fed with a choline-deficient diet (CD) for up to 6 wk, and their livers were then perfused with Krebs-Henseleit buffer to examine bile output and biliary constituents. Organic anion transport from hepatocellular canalicular membranes through Mrp2 was examined by kinetic analyses for biliary exclusion of 5-carboxyfluorescein (CF), a fluoroprobe excreted through Mrp2. RESULTS: Macrovesicular fatty deposits exceeded 60% and serum aspartate aminotransferase (AST) increased on 6-wk CD (CD6w), but not 3-wk CD (CD3w). Mrp2-deficient rat livers (Eisai hyperbilirubinemia) with 3-wk CD were more vulnerable than CD3w livers. In CD6w rats, bile flow rate and biliary glutathione significantly decreased. These declines coincided with the intracellular localization of Mrp2. Moreover, kinetic analyses for biliary CF revealed significant delay in 6-wk CD-fed rat livers. Pioglitazone, a ligand of PPARγ activating protein kinase A (PKA), significantly attenuated this delay by sorting Mrp2 into bile canalicular membranes. However, a PKA inhibitor blunted the increase in CF exclusion, re-localizing Mrp2 into the hepatocellular cytoplasm. A thromboxane A2 synthase inhibitor also ameliorated the CF exclusion delay. CONCLUSION: Pioglitazone activated PKA, increasing Mrp2 transports to detoxify xenobiotics. Pioglitazone may allow the donor indications for liver transplantation to be expanded to include severe macrovesicular fatty livers.
Journal of Surgical Research 05/2012; · 2.25 Impact Factor
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ABSTRACT: Background/Aims: In gastroenteropancreatic neuroendocrine tumors (GEP-NETs), primary lesions cannot be resected when the patients have highly advanced disease or when the primary sites are undefined. Such GEP-NETs cannot be evaluated with Ki-67 or the mitotic index. The aim of this study was to examine the prognosis of GEP-NETs that were ungraded by WHO G1-3 grading (U-NET group). Methodology: Between 2000 and 2011, 75 patients with sporadic GEP-NETs were treated at our institution. The prognosis of patients graded as new WHO grading (G-NET group) was compared with that of the U-NET group. Cox proportional hazard regression analyses were performed to estimate the risk factors for overall survival (OS). Results: Overall 1-, 3- and 5-year survival rates were 90.7%, 79.9% and 74.9%, respectively. The odds ratio (OR) of patients with synchronous liver metastasis and U-NET was 1.73 (p=0.01) and 5.84 (p=0.002), respectively. Multivariate analyses of OS according to baseline characteristics revealed the only independent risk factor to be U-NET (OR, 3.95; p=0.02). Conclusions: The malignant potential of U-NET may be no less than that of G-NET, while WHO-G3 patients have the worst prognoses in the G-NET group.
Hepato-gastroenterology 05/2012; 59(118):1682-6. · 0.66 Impact Factor
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ABSTRACT: Background/Aims: The WHO 2010 grading system for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is used to evaluate the malignant potential without clinicopathological information. This study was conducted to examine whether the new index is superior to the previous WHO 2004 classification, e.g. for well-differentiated endocrine carcinoma (WEC), involving clinical information. Methodology: Between 2000 and 2011, 77 patients with sporadic GEP-NETs were treated at our institution and statistically estimated risk factors for overall survival (OS) were evaluated. Cox proportional hazards regression analyses were performed to estimate risk factors for OS. Results: Overall 1-, 3- and 5-year survival rates were 92.8%, 78.4% and 76.0%, respectively. Median OS was 551 days in WEC-patients (odds ratio (OR) for OS=13.1, 95% confidence interval (CI)=2.90-59.5; p=0.001). The median OS was 813 days in G3-patients as compared with 1885 days in G1/G2-patients (OR for OS= 2.64, p=0.002). Multivariate analyses according to baseline characteristics revealed WEC as independent risk factor (OR=9.06, p=0.01). WEC was the only predictor of prognosis with an area under the receiver operating characteristic curves of 0.78 (p=0.001). Conclusions: Clinical information was the best predictor for the prognosis of NETs.
Hepato-gastroenterology 05/2012; 59(120). · 0.66 Impact Factor
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Rama Adikrisna,
Shinji Tanaka,
Shunsuke Muramatsu,
Arihiro Aihara, Daisuke Ban,
Takanori Ochiai,
Takumi Irie,
Atsushi Kudo,
Noriaki Nakamura,
Shoji Yamaoka,
Shigeki Arii
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ABSTRACT: Identification and purification of cancer stem cells (CSCs) could lead to new therapeutic targets, but their heterogeneous expansion is an obstacle to their study. We investigated whether it is possible to monitor pancreatic CSCs in real time, based on their intrinsic low level of proteasome activity.
We engineered human pancreatic adenocarcinoma cells (PANC1, MIAPaCa2, BxPC3, and KLM1) to express a green fluorescent molecule fused to the degron of ornithine decarboxylase (Gdeg) from a retroviral vector; the fluorescent Gdeg accumulates in CSCs as a result of low activity of the 26S proteasome. Cells with high and low levels of fluorescence (Gdeg(high) and Gdeg(low)) were isolated by flow cytometry; tumor growth was analyzed in immunocompromised mice. We performed a screen for agents that were specifically toxic to pancreatic CSCs, in a synthetic lethal manner.
Gdeg(high) cells, but not Gdeg(low) cells, formed spheres and underwent asymmetric division-features of CSCs. Injection of as few as 10 Gdeg(high) cells led to tumor formation in mice. Gemcitabine was toxic to cultured Gdeg(low) cells, whereas Gdeg(high) cells were resistant. We observed that quercetin was toxic to Gdeg(high) cells in culture and in pre-established tumors grown from these cells in mice. Nuclear accumulation of β-catenin was detected in Gdeg(high), but not Gdeg(low), and lost after exposure to quercetin.
We used a fluorescence marker system for level of proteasome activity to identify pancreatic cancer cells with features of cancer stem cells. We identified quercetin as a compound that is specifically toxic to pancreatic CSCs.
Gastroenterology 04/2012; 143(1):234-45.e7. · 11.68 Impact Factor
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ABSTRACT: BACKGROUND: Postoperative early recurrence is a crucial issue in the treatment of hepatocellular carcinoma (HCC) patients. Some early recurrences seem to occur from minute tumors which were overlooked during both preoperative and intraoperative investigations. Therefore, it is urgently necessary to increase detectability of minute HCCs during operation. If they could be detected and resected during surgery, the prognosis should be improved. The purpose of this study is to investigate the usefulness of contrast-enhanced intraoperative ultrasound (CEIOUS) for the diagnosis and treatment of HCC. METHODS: Institutional ethics committee approval and informed consent were obtained. Fifty-two patients (mean age 65 years; 38 males and 14 females) who underwent liver resection with either preoperative computed tomography during angiography (CTA) or CEIOUS with Sonazoid (perflubutane microbubble contrast agent) were studied. We determined the presence of HCC on the basis of the histopathological findings of resected specimens. RESULTS: The sensitivity of CEIOUS [97.6% (95% CI 91.8-99.4)] was higher than that of CTA [89.4% (95% CI 81.1-94.3)]. The positive predictive values of CEIOUS [91.2% (95% CI 83.6-95.5) and CTA [91.6% (95% CI 83.6-95.9)] were similar. Eight new HCCs from 7 patients, which accounted for 9.4% (8/85) of the total HCCs, were correctly detected and diagnosed by CEIOUS, and we performed an additional partial hepatectomy in 3 of these 7 patients. CONCLUSIONS: CEIOUS with Sonazoid provided increased sensitivity of detection of small HCCs compared with preoperative CTA, thereby leading to a more appropriate surgical procedure and contributing to complete tumor removal.
Journal of hepato-biliary-pancreatic sciences. 03/2012;
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ABSTRACT: The clinical impact of the distal pancreatectomy with en-bloc celiac axis resection for locally advanced pancreatic body cancer remains unclear.
We reviewed the records of 13 patients who underwent distal pancreatectomy-celiac axis resection between 1991 and 2009, 58 patients who underwent distal pancreatectomy for pancreatic body cancer involving major vessels, the extrapancreatic neural plexus or other organs (T4 according to the Japanese stage classification) between 1991 and 2009, and 24 patients with unresectable locally advanced pancreatic cancer without distant metastases (unresectable group) between 2001 and 2009. The clinicopathologic factors and overall survival among the 3 groups were compared.
The distal pancreatectomy-celiac axis resection group was associated with a significantly higher incidence of morbidity (92% vs 60%, P = .03) and positive surgical margins (69% vs 26%, P = .003) than the distal pancreatectomy group; however, no survival difference was found between the 2 groups. No survivor has lived more than 3 years after operation in the distal pancreatectomy-celiac axis resection group. The distal pancreatectomy-celiac axis resection group had a significantly better prognosis than the unresectable group (median survival time, 20.8 vs 9.8 months; P = .01).
Aggressive resection for T4 pancreatic body cancer by distal pancreatectomy-celiac axis resection can be justified for otherwise unresectable tumors. The surgical indication should be evaluated carefully because of the higher incidence of morbidity and lower incidence of curability compared with distal pancreatectomy, as well as because there have been no long-term survivors so far.
Surgery 11/2011; 151(1):61-9. · 3.10 Impact Factor
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Shinji Tanaka,
Kaoru Mogushi,
Mahmut Yasen, Daisuke Ban,
Norio Noguchi,
Takumi Irie,
Atsushi Kudo,
Noriaki Nakamura,
Hiroshi Tanaka,
Masakazu Yamamoto,
Norihiro Kokudo,
Tadatoshi Takayama,
Seiji Kawasaki,
Michiie Sakamoto,
Shigeki Arii
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ABSTRACT: The prediction of cancer recurrence holds the key to improvement of the postoperative prognosis of patients. In this study, the recurrence of early-stage hepatocellular carcinoma (HCC) after curative hepatectomy was analyzed by the genome-wide gene-expression profiling on cancer tissue and the noncancerous liver tissue. Using the training set of 78 cases, the cytochrome P450 1A2 (CYP1A2) gene in noncancerous liver tissue was identified as the predictive candidate for postoperative recurrence (hazard ratio [HR], 0.447; 95% confidence interval [CI], 0.249-0.808; P = 0.010). Multivariate analysis revealed the statistically significant advantage of CYP1A2 down-regulation to predict recurrence (odds ratio, 0.534; 95% CI, 0.276-0.916; P = 0.036), and the expression of CYP1A2 protein was confirmed immunohistochemically. An independently multi-institutional cohort of 211 patients, using tissue microarrays, validated that loss of expression of CYP1A2 in noncancerous liver tissue as the only predictive factor of recurrence after curative hepatectomy for early-stage HCC (HR, 0.480; 95% CI, 0.256-0.902; P = 0.038). Gene set-enrichment analysis revealed close association of CYP1A2 down-regulation with oxidative stress pathways in liver tissue (P < 0.001, false discovery rate [FDR] = 0.042; P = 0.006, FDR = 0.035). Our results indicate these pathways as the molecular targets to prevent recurrence, as well as the potential prediction of the super high-risk population of HCC using liver tissue.
Hepatology 10/2011; 54(4):1273-81. · 11.66 Impact Factor
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Kenichiro Yoshitake,
Shinji Tanaka,
Kaoru Mogushi,
Arihiro Aihara,
Ayano Murakata,
Satoshi Matsumura,
Yusuke Mitsunori,
Mahmut Yasen, Daisuke Ban,
Norio Noguchi,
Takumi Irie,
Atsushi Kudo,
Noriaki Nakamura,
Hiroshi Tanaka,
Shigeki Arii
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ABSTRACT: Perturbations in the nuclear microenvironment, including transport systems, play a critical role in malignant progression, but the nuclear import abnormalities remain unclear in hepatocarcinogenesis. We analyzed the role of importin in hepatocellular carcinoma (HCC).
Gene expression profiling of the importin family was performed in HCC tissues. The significance of importin protein expression was analyzed in vitro as well as clinicopathologically.
According to the microarray profiles, the importin-α1 was dominantly overexpressed in HCC tissues as compared to the adjacent noncancerous tissues. By means of human HCC cell lines, a knockdown of importin-α1 by its siRNA greatly reduced cellular proliferation by 15.2-26.6% (P < 0.005). Immunohistochemical analysis on tissue samples demonstrated cancer-specific overexpression in 36.3% of HCCs. The overexpression of importin-α1 was correlated statistically with high levels of alfa-fetoprotein ( P = 0.0017), the tumor number (P = 0.0116), histological dedifferentiation (P = 0.0054), tumor morphology (P = 0.0433), portal vein invasion (P = 0.0007), hepatic vein invasion (P = 0.0081), Fc (P = 0.0367), Fc-inf (P = 0.0122), and the tumor, node, metastasis stage (P = 0.0026); this resulted in a significantly poorer prognosis in both overall survival (P = 0.0164) and recurrence-free survival (P = 0.0101). Multivariate analysis of recurrence-free survival revealed importin-α1 expression to be a statistically significant factor (P = 0.0361). In addition, early recurrence after curative resection was observed more frequently in the importin-α1-positive group as compared to the negative group (P = 0.0023). The multivariate analysis identified importin-α1 as the only independent predictor of early recurrence after HCC resection (odds ratio = 5.291, P = 0.0191).
Because importin-α1 might be closely associated with HCC progression, further analysis should be pursued to evaluate it as a novel prognostic target.
Annals of Surgical Oncology 02/2011; 18(7):2093-103. · 4.17 Impact Factor
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ABSTRACT: Acinar cell carcinoma (ACC) of the pancreas is very rare, which usually grows expansively. Recently, a variant of ACC with predominant growth in the pancreatic ducts has been proposed, and is speculated to have potentially less aggressive behavior. The aim of this study was to investigate how the pancreatic duct system is related to the growth and extension of ACC. We reviewed the detailed gross and histologic features of 13 cases of ACC, of which 7 (54%) showed intraductal polypoid growth (IPG) of the tumor in the large pancreatic ducts with a mean IPG length of 24.8 mm. Tumors with IPG were found to spread characteristically along the pancreatic ducts as extending polypoid projections, filling the ducts and destroying the duct walls, although tumors did not tend to extend beyond the pancreatic parenchyma. Comparison of the clinicopathologic characteristics showed that ACC with IPG had less infiltrative features including lymphatic, venous, and neural invasion, formation of tumor thrombus in the portal vein, nodal metastasis, and invasion beyond the pancreas to the surrounding organs; death in only 1 case (14%) of ACC with IPG was the result of ACC itself. In contrast, ACC without IPG frequently showed more infiltrative growth, and was the cause of death in 50% of patients with this type of tumor. Intraductal dissemination of ACC in pancreatic ducts was proven in 1 case of ACC with IPG. These findings suggest that a significant proportion of ACC shows IPG, which is potentially linked to less aggressive clinicopathologic characteristics.
The American journal of surgical pathology 07/2010; 34(7):1025-36. · 4.06 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) with major portal tumor thrombus has been considered to be a fatal disease. A thrombectomy remains the only therapeutic option that offer a chance of complete tumor removal avoiding acute portal vein obstruction. However, the efficacy of tumor thrombectomy in addition to hepatectomy has not been well evaluated.
Of 979 patients who consecutively underwent initial HCC resection, 45 (4.6%) HCC patients with tumor invasion of the first branch of the portal vein (vp3) and tumor in the main portal trunk or the opposite-side portal branch (vp4) were retrospectively analyzed to evaluate the efficacy of hepatectomy and tumor thrombectomy.
Alpha-fetoprotein, serosal invasion, and intrahepatic metastases were independently significant prognostic factors in all the 45 patients with vp3 or vp4 HCC. The 3- and 5-year survival rates in vp3 and vp4 group were 35.3% and 41.8%, and 21.2% and 20.9%, respectively. There were longer operative times and more intraoperative bleeding in patients with vp4, but no significant difference in mortality, morbidity, and survival between patients with vp3 and vp4.
Hepatectomy and thrombectomy for vp4 could not only avoid acute portal occlusion due to tumor thrombus but provide a comparable survival benefit with hepatectomy for vp3.
Journal of Gastrointestinal Surgery 10/2009; 13(11):1921-8. · 2.83 Impact Factor
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International Journal of Colorectal Disease 09/2009; 25(3):405. · 2.38 Impact Factor
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ABSTRACT: Surgical resection for pancreatic and hepatic cancer sometimes involves combined resection and reconstruction of the major veins using venous grafts. Autologous venous grafts made from the bilateral gonadal veins (BGVs) have never been utilized or discussed.
We reconstructed the portal vein (PV), superior mesenteric vein (SMV), and middle hepatic vein (MHV) using cylindrical or patch grafts customized from the BGVs in two female patients and in one male patient. In order to assess the sexual difference in the availability of the cylindrical graft to replace these major veins, we measured the diameters of the BGVs, PV, SMV, and MHV on computed tomography in 50 male and 50 female patients, and estimated the diameter-ratios (DRs) of the cylindrical graft made from BGVs/PV, SMV, and MHV. We assumed that the cutoff value of the DR would be 0.8, for replacing of major veins using cylindrical grafts.
The reconstructed PV, SMV, and MHV presented sufficient patency, and the postoperative courses were uneventful. The DRs of BGVs graft/PV, graft/SMV, and graft/MHV were significantly larger in female patients than those in male patients (0.82 vs. 0.54, p < 0.01, 0.96 vs. 0.61, p < 0.01, 1.39 vs. 0.95; p < 0.01) and were larger than 0.8 in 50%, 70%, and 92% in female patients, respectively, and 0%, 8%, and 68% in male patients, respectively.
The present newly customized cylindrical and patch grafts made from the BGVs showed sufficient feasibility. A cylindrical graft made from the BGVs would be better utilized in female patients than in male patients.
Langenbeck s Archives of Surgery 05/2009; 394(6):1115-21. · 1.81 Impact Factor
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ABSTRACT: Intrahepatic cholangiocellular carcinoma (ICC) presenting intraductal growth (IG) has distinct clinicopathological features with a favorable prognosis. The mass-forming (MF) plus IG type of ICC has not been previously investigated.
One hundred forty-four patients with ICC underwent surgical resections and were classified according to the macroscopic type. The clinicopathological features of the IG type (n = 7) and MF plus IG type (n = 14) were retrospectively analyzed. The clinicopathological differences between the MF plus IG type and MF plus periductal infiltrating (PI) type (n = 37) were compared.
All of the patients with the IG type had no sign of recurrence and survived. The 5-year overall survival rates was significantly better in the MF plus IG type than in the MF plus PI type (41.3% vs. 13.3%, P = 0.034). Significant differences were recognized between the MF plus IG type and MF plus PI type, in terms of vascular resection (P = 0.030), mucosal extension (P = 0.006), and postoperative recurrence (P = 0.004).
The MF plus IG type had significantly better prognosis than the MF plus PI type. The IG type and MF plus IG type should be distinguished from other types even if hepatic hilar confluence is involved, because of the favorable outcome after surgery.
Journal of Surgical Oncology 01/2009; 99(3):161-5. · 2.10 Impact Factor
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ABSTRACT: A preoperative inferior vena cava (IVC) filter is reported to be effective in surgical cases with proximal deep venous thrombosis (DVT) or in which pulmonary embolism (PE) has already developed, and considered to be at high risk of developing secondary fatal PE during or after surgery. However, guidelines for using an IVC filter have yet to be established. The patient in the present report had two huge tumors, ascending colon cancer and renal angiomyolipoma, which occupied the entire right half of the abdomen, coexisting PE, DVT and tumor thrombus in the right renal vein. Secondary PE is fatal in the perioperative period, therefore, the vena cava filters were preoperatively inserted into the supra- and the infrarenal IVC. We successfully removed the tumors without complications. The patient is alive without tumor recurrence and PE or recurrent DVT 1 year and 6 months after surgery. The coexistence of two huge abdominal tumors as potential causes of PE and DVT is extremely rare, and we could have safely undergone the operation, using two vena cava filters in the supra- and infrarenal IVC.
Japanese Journal of Clinical Oncology 11/2008; 38(10):710-4. · 1.78 Impact Factor
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Japanese Journal of Clinical Oncology 07/2008; 38(6):455. · 1.78 Impact Factor
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ABSTRACT: The link between microcirculatory disturbance and hepatocellular dysfunction remains unknown. The present study was designed to examine the key event of warm ischemia reperfusion (WIR) injury with subsequent cholestasis.
A left lobar 70% ischemia and reperfusion rat model was used in this study. The portal vein and hepatic artery to the left lateral lobe of the liver were subjected to 20 min of warm ischemia followed by 60 min of reperfusion to collect bile and to measure its constituents.
The hepatocellular injury was increased significantly in livers exposed to WIR, as judged by serum alanine aminotransferase. This event coincided with decreased bile production and biliary concentration of glutathione (GSH), suggesting impaired bile salts-independent bile flow, while biliary phospholipids and bile salts were not decreased. Additionally, hepatic adenosine triphosphate and GSH were not decreased after WIR. Since the biliary GSH, which is a major driving force for bile salts-independent bile flow, is excreted from hepatocytes into the bile via multidrug resistance protein 2 (Mrp2), we examined whether intracellular localization of Mrp2 occurred. Immunohistochemical analyses revealed hepatocellular Mrp2 was retrieved from bile canalicular membrane into the pericanalicular cytoplasm in the post-warm ischemic livers. Microcirculatory disturbance in livers exposed to 20 min of warm ischemia improved to levels comparable to controls.
Mrp2 internalization, observed in this study, may play an important determinant of cholestasis in the post-warm ischemic livers.
Journal of Surgical Research 04/2008; 153(2):310-6. · 2.25 Impact Factor
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ABSTRACT: We report a rare case of a curative resection performed on a carcinoma developing in the remnant pancreas at 3 years 7 months after a pancreaticoduodenectomy for pancreatic cancer. A 63-year-old man underwent a pancreaticoduodenectomy for pancreatic cancer on November 1999. Because the celiac trunk was occluded by atherosclerosis, an aortohepatic bypass with a saphenous vein graft was performed simultaneously. In May 2003, tumor marker levels increased, and a tumor was detected in the remnant pancreas on computed tomography. There were no findings such as invasion into the surrounding tissue or distant metastasis, and therefore we removed the remnant pancreas in July 2003. Histopathologically, the tumor consisted of a well-differentiated tubular adenocarcinoma and was limited to the pancreas. Moreover, the anastomotic site of the pancreaticojejunostomy was negative for cancer, and some foci of papillary hyperplasia and goblet cell metaplasia of the pancreatic ductal epithelium, which was thought to be the precursor of the pancreatic cancer, were seen. These findings suggested that the tumor was a second primary cancer developing in the remnant pancreas. This case provided suggestive evidence for the development of pancreatic cancer, and the surgical procedure for a pancreaticoduodenectomy with occlusion of the celiac trunk is discussed.
Journal of Gastrointestinal Surgery 03/2005; 9(2):263-9. · 2.83 Impact Factor
