[A Case of Hepatocellular Carcinoma with Erythrocytosis].

Hepatocellular carcinoma is associated with a relatively high rate of paraneoplastic syndrome, but the frequency of erythrocytosis is low. We report a case of hepatocellular carcinoma with preoperative erythrocytosis and hypererythropoietinemia. The case is a 50-year-old man who has been cured by interferon treatment for hepatitis C 20 years ago(SVR). He visited our hospital with the complaint of right hypochondrial pain, and was diagnosed with hepatocellular carcinoma, which occupied S8/5/7 of the liver, and showed erythrocytosis and high erythropoietin(Epo)as tumor-related symptoms. A right hepatic lobectomy was performed, and the patient was discharged 13 days after the operation. The red blood cell count and Epo were normalized immediately after the operation. One year and 2 months after the operation, multiple lung metastases recurred, and chemotherapy is currently underway. Hepatocellular carcinoma with erythrocytosis and hypererythropoietinemia has been reported to have a poor prognosis, and multimodal treatment and strict surveillance are considered necessary.

[A Case of Curative Resection of Advanced Rectal Cancer with Multiple Liver Metastases and Cancerous Ascites after Preoperative Chemotherapy].

The patient was a 59-year-old man who was hospitalized with diarrhea and general malaise. Massive ascites and systemic edema were observed upon initial physical examination. Blood test findings showed anemia, hepatic dysfunction, and increased tumor marker levels. Imaging examination revealed the presence of a primary tumor associated with stenosis, extending from the rectosigmoid junction to the upper rectum, multiple liver metastases, and massive ascites. Pathological examination indicated well-differentiated adenocarcinoma. A treatment strategy comprising colostomy and chemotherapy was implemented. Administration of 6 courses of mFOLFOX6 plus panitumumab(Pmab)and 4 courses of FOLFIRI plus Pmab led to marked shrinkage of the primary tumor and liver metastases and disappearance of the ascites. Chemotherapy was discontinued at the request of the patient. The patient developed melena after 2 years. Colonoscopy revealed enlargement of the rectal cancer, and surgical intervention was indicated. We adopted a treatment policy of 2-stage resection, and low anterior resection was performed. The liver was partially resected 3 months later. Hepatic recurrence was observed 9 months after the liver resection, and repeated resection of the liver was performed. An aggressive treatment approach can lead to improved prognosis even in cases involving multiple liver metastases and cancerous ascites.

[Effect of tolvaptan on ascites due to malignancy].

Ascites accompanying a malignancy is often refractory to conventional treatment with saline diuretics, making it difficult to control. We administered a new diuretic, Tolvaptan, to 10 individuals with malignancy and heart failure accompanied by ascites, which was refractory to saline diuretics, and assessed its efficacy and adverse events. We observed a significant reduction in abdominal distension following 2 weeks of Tolvaptan administration. However, we also observed significant increases in serum potassium, urea nitrogen, and creatinine levels, but no serious adverse events. This suggests that Tolvaptan may also be effective as treatment for ascites.

[Two Cases of Curative Resection of Locally Advanced Rectal Cancer after Preoperative Chemotherapy].

Reports of conversion in cases of locally advanced colorectal cancer have been increasing. Here, we present 2 cases in which curative resection of locally advanced rectal cancer accompanied by intestinal obstruction was achieved after establishing a stoma and administering chemotherapy. The first case was of a 46-year-old male patient diagnosed with upper rectal cancer and intestinal obstruction. Because of a high level of retroperitoneal invasion, after establishing a sigmoid colostomy, 13 courses of mFOLFOX6 plus Pmab were administered. Around 6 months after the initial surgery, low anterior resection for rectal cancer and surgery to close the stoma were performed. Fourteen days after curative resection, the patient was discharged from the hospital. The second case was of a 66-year-old male patient with a circumferential tumor extending from Rs to R, accompanied by right ureter infiltration and sub-intestinal obstruction. After establishing a sigmoid colostomy, 11 courses of mFOLFOX6 plus Pmab were administered. Five months after the initial surgery, anterior resection of the rectum and surgery to close the stoma were performed. Twenty days after curative resection, the patient was released from the hospital. No recurrences have been detected in either case.

Gene transfer of heme oxygenase-1 using an adeno-associated virus serotype 6 vector prolongs cardiac allograft survival.

Introduction. Allograft survival can be prolonged by overexpression of cytoprotective genes such as heme oxygenase-1 (HO-1). Modifications in vector design and delivery have provided new opportunities to safely and effectively administer HO-1 into the heart prior to transplantation to improve long-term graft outcome. Methods. HO-1 was delivered to the donor heart using an adeno-associated virus vector (AAV) with a pseudotype 6 capsid and vascular endothelial growth factor (VEGF) to enhance myocardial tropism and microvascular permeability. Survival of mouse cardiac allografts, fully or partially mismatched at the MHC, was determined with and without cyclosporine A. Intragraft cytokine gene expression was examined by PCR. Results. The use of AAV6 to deliver HO-1 to the donor heart, combined with immunosuppression, prolonged allograft survival by 55.3% when donor and recipient were completely mismatched at the MHC and by 94.6% if partially mismatched. The combination of gene therapy and immunosuppression was more beneficial than treatment with either AAV6-HO-1 or CsA alone. IL-17a, b, e and f were induced in the heart at rejection. Conclusions. Pretreatment of cardiac allografts with AAV6-HO-1 plus cyclosporine A prolonged graft survival. HO-1 gene therapy represents a beneficial adjunct to immunosuppressive therapy in cardiac transplantation.

Intrahepatic cholangiojejunostomy (Longmire procedure) for recurrent bilioenteric anastomotic stricture with hepatolithiasis.

Interventional procedure via percutaneous transhepatic route is often performed, as an initial treatment, in patients with benign bilioenteric anastomotic stricture. However, surgical management is required in most cases in which radiological intervention is unsuccessful. In this report, we describe a case of a 67-year-old woman with recurrent bilioenteric anastomotic stricture, accompanying bilateral hepatolitiasis after several times of transhepatic interventions. The patient underwent intrahepatic cholangiojejunostomy (Longmire procedure) and cholangioscopic lithotomy after resection of an atrophic left lateral segment resulting from hepatolithiasis. Although the damaged hilar bile duct had to be isolated and divided from the corresponding vasculature for re-anastomosis, it was quite impossible due to severe inflammatory change at the hepatic hilus. We, therefore, anastomosed the intact biliary stump on the cut surface of the left lateral segment to the jejunal loop with a stent tube. The patient's postoperative course was uneventful and she exhibited no evidence of cholangitis during follow-up period of 1 year after surgery. At present, the indications for intrahepatic cholangiojejunostomy for biliary obstruction, are quite limited, but biliary surgeons should keep this procedure in mind at the time of biliary reconstruction for benign proximal bile duct stricture, particularly in cases of multiply operated hilum.

Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma.

BACKGROUND: Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. FGF19, a member of the FGF family, has unique specificity for its receptor FGFR4. This study aimed to clarify the involvement of FGF19 in the development of HCC. METHODS: We investigated human FGF19 and FGFR4 expression in 40 hepatocellular carcinoma specimens using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Moreover, we examined the expression and the distribution of FGF19 and FGFR4 in 5 hepatocellular carcinoma cell lines (HepG2, HuH7, HLE, HLF, and JHH7) using RT-PCR and immunohistochemistry. To test the role of the FGF19/FGFR4 system in tumor progression, we used recombinant FGF19 protein and small interfering RNA (siRNA) of FGF19 and FGFR4 to regulate their concentrations. RESULTS: We found that FGF19 was significantly overexpressed in HCCs as compared with corresponding noncancerous liver tissue (P < 0.05). Univariate and multivariate analyses revealed that the tumor FGF19 mRNA expression was an independent prognostic factor for overall and disease-free survival. Moreover, we found that the FGF19 recombinant protein could increase the proliferation (P < 0.01, n = 12) and invasion (P < 0.01, n = 6) capabilities of human hepatocellular carcinoma cell lines and inhibited their apoptosis (P < 0.01, n = 12). Inversely, decreasing FGF19 and FGFR4 expression by siRNA significantly inhibited proliferation and increased apoptosis in JHH7 cells (P < 0.01, n = 12). The postoperative serum FGF19 levels in HCC patients was significantly lower than the preoperative levels (P < 0.01, n = 29). CONCLUSIONS: FGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC.

Endothelin-1 aggravates hepatic ischemia/reperfusion injury during obstructive cholestasis in bile duct ligated mice.

BACKGROUND: Cholestasis of the liver is known to be an important risk factor for surgical morbidity and mortality after major hepatectomy. However, the mechanism of liver injury in cholestatic liver is not fully understood. The goal of this study was to investigate the process of liver injury due to hepatic ischemia/reperfusion in obstructive cholestasis. MATERIALS AND METHODS: Male C57BL/6 mice underwent common bile duct ligation and subsequently developed obstructive cholestasis. The mice were subjected to 90 min of partial hepatic ischemia followed by reperfusion. RESULTS: The survival rate of the mice with cholestatic livers after hepatic ischemia/reperfusion was lower than that of the mice with normal livers. Biochemical and histological analyses showed that the cholestatic mice had a much higher degree of hepatocellular injury after reperfusion than the normal mice. Neutrophil accumulation after reperfusion was significantly decreased in the cholestatic livers; however, considerable microcirculatory disturbances were observed in cholestatic livers after reperfusion. Hepatic stellate cell activation and hepatic expression of endothelin-1 were evaluated by immunohistochemical staining in cholestatic livers after reperfusion. These observations were also associated with increased serum levels of endothelin-1. CONCLUSIONS: Hepatic stellate cell activation and increased endothelin-1 production play a crucial role in hepatic ischemia/reperfusion injury in cholestatic liver.

Surgical strategy for mucin-producing bile duct tumor.

Tumors with copious mucin production within the intra- or extrahepatic bile ducts have been reported as mucin-producing bile duct tumors (MPBTs). Because mucin produced by these tumors causes recurrent cholangitis and obstructive jaundice, surgical resection should be indicated even if these tumors are regarded as benign. In order to choose the appropriate surgical procedure, exact preoperative assessment of tumor location and cancer extension is important, especially evaluation of the extent of superficial spreading through cholangioscopic observation and biopsy. In principle, MPBTs should be resected in a manner similar to that employed for other types of bile duct carcinomas. That is, major hepatectomy with or without extrahepatic bile duct resection or pancreaticoduodenectomy should be chosen as the surgical procedure, and intraoperative frozen section at the stumps of the bile duct is essential. On the other hand, when precise diagnosis is completed preoperatively and the lesion is diagnosed as adenoma or carcinoma with invasion confined to the ductal wall and limited superficial spreading, limited resections preserving organ functions as much as possible can be considered as a choice among surgical procedures. All ten patients with MPBT resected at our institution according to these strategies are still alive without tumor recurrence, with a median survival of 48.0 months.

Surgical management of occluded biliary expandable metallic stent for benign stricture of bilioenteric anastomosis: usefulness of anterior transhepatic procedure.

The occluded biliary expandable metallic stent (EMS) placed for postoperative stricture of bilioentero-anastomosis can be treated with percutaneous interventional procedures, but most EMSs eventually re-occlude after a certain period of time with sludge/stone or epithelial hyperplasia. The complete removal of EMS is, therefore required for a good long-term outcome. Surgical procedures with EMS removal, and re-bilioenteric anastomosis after resection of damaged bile ducts, are usually complex and difficult, especially when the proximal end of the EMS is located at the second or more proximal biliary branch. In such cases, we have devised a new technique for complete EMS removal and more proximal hepatic duct resection by separating the liver parenchyma along the interlobar plane (anterior transhepatic hepatic approach). Liver transection is performed along the left side of the middle hepatic vein until good exposure of the hilar plate is obtained. The EMS is then extracted, together with resection of the dense/damaged intrahepatic ducts for re-biliary reconstruction. The anterior transhepatic approach may be a very useful procedure for approach to the second or more proximal biliary ducts without hepatic resection.

Preoperative GATA3 mRNA expression in peripheral blood mononuclear cells is up-regulated in patients with postoperative infection following hepatobiliary pancreatic surgery.

BACKGROUND: Aggressive hepatobiliary pancreatic surgery has been associated with high complication rates. Correlations of Th1/Th2 balance and toll-like receptor (TLR) 2/4 expression with postoperative infection following surgery were prospectively evaluated. METHODS: Plasma concentrations of interleukin (IL)-6, IL-10, soluble lymphocyte activation gene (sLAG)-3, and soluble CD30 were determined by enzyme-linked immunosorbent assay, and expression levels of T-bet, GATA-3, TLR2, and TLR4 mRNA in peripheral blood mononuclear cells were assayed by reverse transcription-polymerase chain reaction perioperatively in 56 consecutive patients who underwent hepatobiliary pancreatic surgery. RESULTS: Of the 56 patients, 30 patients had postoperative infection. Postoperative plasma levels of IL-6 and IL-10 were significantly higher in patients with postoperative infection than in those without infection (P < 0.05). Plasma soluble CD30 level and GATA-3 mRNA expression level were significantly higher preoperatively, and remained higher by postoperative d 7 in patients with postoperative infection (P < 0.05). Soluble lymphocyte activation gene levels were not significantly different between the two groups. T-bet mRNA expression level was significantly higher on postoperative d 3, 7, and 14 in patients with postoperative infection (P < 0.05). Preoperative expression levels of GATA-3 mRNA correlated significantly with those of TLR2 and TLR4 mRNA (P < 0.05). CONCLUSIONS: These results suggest that in patients with postoperative infection, Th1/Th2 balance shifts toward Th2 dominance preoperatively.

Induction of antitumor response by in vivo allogeneic major histocompatibility complex gene transfer using electroporation.

BACKGROUND: Most malignancies lack tumor-associated antigens, which are recognized by T-lymphocytes through major histocompatibility complex (MHC) molecules, and seem to evade host immunological defense. In this study, we investigated whether allogeneic MHC gene transfer into the low-antigenic tumor might induce cell-mediated immunity, and provide an immunotherapeutic effect in vivo. MATERIALS AND METHODS: Mammary adenocarcinoma cells (MAT B III) originated from an F344 rat (RT1A(l)) were transfected with a plasmid DNA encoding RT1A(a) (pcMRT1A) in vitro. Cytolytic T-cell response was then evaluated using F344 splenocytes. Furthermore, pcMRT1A-liposome complex was injected into the MAT B III tumors grown in F344 rats, followed by a series of eight electrical pulses with a electroporator, every other d for total of four times. The tumor size and survival of animals were evaluated thereafter. RESULTS: The expression of RT1A(a) on the tumor cells induced cytolytic T-cell response in vitro. Intratumor injection of pcMRT1A-liposome complex followed by in vivo electroporation markedly generated biological response, including increased interferon-gamma (IFN-gamma) expression and a large number of infiltrated cells in the tumor. Inhibited tumor growth, even complete tumor regression, was observed, resulting in prolonged survival time. CONCLUSIONS: Direct transfer of allogeneic MHC gene into the tumor by in vivo electroporation could induce a cell-mediated immune response against the introduced antigens, resulting in local IFN-gamma production. This initial response may bring about the subsequent immunological response even to the unmodified tumor cells through cytokines such as IFN-gamma, resulting in the marked tumor regression.

Usefulness of intraoperative fluorescence imaging to evaluate local anatomy in hepatobiliary surgery.

BACKGROUND/PURPOSE: One of the major complications encountered in hepatobiliary surgery is the incidence of bile duct and blood vessel injuries. It is sometimes difficult during surgery to evaluate the local anatomy corresponding to hepatic arteries and bile ducts. We investigated the potential utility of an infrared camera system as a tool for evaluating local anatomy during hepatobiliary surgery. METHODS: An infrared camera system was used to detect indocyanine green fluorescence in vitro. We also employed this system for the intraoperative fluorescence imaging of the arteries and biliary system in a pig. Further, we evaluated blood flow in the hepatic artery, portal vein, and liver parenchyma during a human liver transplant and we investigated local anatomy in patients undergoing cholecystectomy. RESULTS: Fluorescence confirmed that indocyanine green was distributed in serum and bile. In the pig study, we confirmed the fluorescence of the biliary system for more than 1 h. In the liver transplant recipient, blood flow in the hepatic artery and portal vein was confirmed around the anastomosis. In most of the patients undergoing cholecystectomy, fluorescence was observed in the gallbladder, cystic and common bile ducts, and hepatic and cystic arteries. CONCLUSIONS: Intraoperative fluorescence imaging in hepatobiliary surgery facilitates better understanding of the anatomy of arteries, the portal vein, and bile ducts.

Clinical implications of unusual NeuroD and mASH1 expression in a patient with primary large-cell neuroendocrine carcinoma of the duodenum: report of a case.

A 69-year-old woman was referred to our hospital for investigation of tarry stools. Abdominal computed tomography (CT) showed a slightly enhanced heterogeneous mass in the first to second part of the duodenum, adjacent to the gallbladder and head of the pancreas. Endoscopy showed a huge protruding tumor with ulceration in the first part of the duodenum. The preoperative histopathological diagnosis was neuroendocrine carcinoma with expression of synaptophysin. Thus, we performed pancreaticoduodenectomy with gallbladder bed resection. Histopathologically, the tumor was a large-cell neuroendocrine carcinoma (LCNEC) of the duodenum. To our knowledge, this is the first report of duodenal LCNEC arising outside the ampulla of Vater. The patient has been disease-free for 24 months since her operation, without additional therapy. Immunohistochemically, the tumor cells revealed positive expression to NeuroD and faint expression to mASH1 (hASH1): both essential transcriptional factors for normal neural development. The expression patterns of NeuroD and mASH1 suggest a favorable prognosis.

Clinical significance of alpha-fetoprotein: involvement in proliferation, angiogenesis, and apoptosis of hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma is one of the most common cancers. alpha-Fetoprotein is strongly expressed in most patients with hepatocellular carcinoma, and high levels of alpha-fetoprotein expression have been reported as an independent prognostic factor. However, there have been few reports on the reasons for poor prognosis. METHODS: We analyzed the correlation between serum alpha-fetoprotein levels and clinicopathological findings in 37 hepatocellular carcinoma patients undergoing curative surgery. alpha-Fetoprotein mRNA expression in tissue samples was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR), while protein expression was assessed by immunohistochemistry. To assess the mechanistic correlations between alpha-fetoprotein and tumor progression, we further analyzed cell proliferation (Ki-67), angiogenesis (CD34), and apoptosis (TdT-mediated dUTP-biotin nick end labeling [TUNEL] assay). RESULTS: Post-operative serum alpha-fetoprotein levels were correlated with disease-free and overall survival, and were an independent prognostic factor for survival. alpha-Fetoprotein expression, as assessed by immunohistochemistry, was strong and heterogeneous in hepatocellular carcinoma. Control livers did not express alpha-fetoprotein and there was weak expression of alpha-fetoprotein in adjacent regions in hepatocellular carcinoma patients. The Ki-67 labeling index in the high serum alpha-fetoprotein cases was significantly higher than in alpha-fetoprotein-negative cases (P = 0.042). The alpha-fetoprotein-positive cases also showed a significantly higher microvessel density than alpha-fetoprotein-negative cases (P = 0.035), whereas hepatocellular carcinoma without alpha-fetoprotein overexpression had a higher apoptotic index when compared to hepatocellular carcinoma with alpha-fetoprotein overexpression (P = 0.033). CONCLUSION: These results indicate that the poor prognosis associated with high alpha-fetoprotein is due to high cell proliferation, high angiogenesis, and low apoptosis.

Interval period tumor progression: does delayed hepatectomy detect occult metastases in synchronous colorectal liver metastases?

BACKGROUND: Rapid remnant liver recurrence in patients with synchronous colorectal liver metastases (CRLM) is occasionally experienced after simultaneous colorectal and liver resection. We evaluated the tumor progression during interval periods to determine whether delayed hepatic resection detects occult metastases. METHODS: One hundred thirty-seven patients underwent hepatectomy for synchronous CRLM. Up to 2003, 116 patients underwent simultaneous colorectal and hepatic resection. From 2004 onward, we identified 21 patients undergoing delayed hepatectomy for synchronous CRLM. The tumor progression during interval was determined by a dynamic computed tomography scan. RESULTS: Median/mean interval between the two evaluations prior to the first and second surgery was 2/2.4 months. The median/mean number of metastases detected at each evaluation was 2/3.3 and 3/4.6, respectively. Nine of the 21 (43%) patients had new detectable metastatic lesions after reevaluation. For 11 of the 21 patients, it was necessary to reconsider planned surgical procedure which was determined prior to colorectal surgery. Hepatic disease-free survival was significantly different between patients undergoing delayed and simultaneous hepatectomy. Multivariate analysis showed that the delayed hepatectomy was a significant independent prognostic factor in hepatic disease-free survival. CONCLUSION: Tumor progression was recognized and occult metastases were detected after the interval reevaluation. Delayed hepatectomy may be a useful approach to reduce rapid remnant liver recurrence in synchronous CRLM.

Angiopoietin-2 levels in the hepatic vein as a useful predictor of tumor invasiveness and prognosis in human hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is characteristically a hypervascular tumor and its progression is known to be closely related to angiogenesis. In this study, we investigated angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) levels in the hepatic vein draining from HCC, as well as in the peripheral vein, to evaluate their relation to clinicopathological features and prognosis. METHODS: To obtain hepatic venous blood samples, a catheter was placed into the main branch of the hepatic vein draining from HCC in 21 patients. The Ang-2 and VEGF levels in both the hepatic and peripheral veins were investigated. Furthermore, Ang-2 mRNA expression in surgically resected HCC was evaluated by quantitative reverse-transcription polymerase chain reaction (RT-PCR), as well as microvessel density (MVD) by CD34 immunostaining. RESULTS: Ang-2 levels in the hepatic vein significantly correlated with Ang-2 mRNA expression in HCC, but Ang-2 levels in the peripheral vein did not correlate. Furthermore, a significant correlation was found between hepatic venous Ang-2 and MVD levels, whereas there was no significant correlation with hepatic venous VEGF levels. When hepatic venous Ang-2 levels were compared with clinicopathological features, a significant relationship was found between high Ang-2 levels and portal vein invasion. The survival for patients in the high hepatic venous Ang-2 group was significantly poorer when compared with the low group. CONCLUSION: Preoperative hepatic venous Ang-2 levels may be a good predictor for portal vein invasion and also prognosis in patients with HCC.

Excessive inflammation but decreased immunological response renders liver susceptible to infection in bile duct ligated mice.

BACKGROUND/AIMS: Obstructive jaundice (OJ) is associated with increased surgical morbidity and infectious complication. The aim of the current study was to clarify the mechanism of excessive inflammation and susceptibility to infection in OJ. METHODS: C57/BL6 mice were subjected to bile duct ligation (BDL) or sham surgery. Expression tumor necrosis factor-alpha, macrophage inflammatory protein-2, monocyte chemoattractant protein-1, inducible protein-10, and interleukin (IL)-10, activation of nuclear factor kappa B, fluorescence activated cell sorter analysis, serum alanine aminotransferase levels, and histology were examined. Survival after lipopolysaccharide (LPS) administration or cecal ligation and puncture 3 or 14 d after surgery was determined. IL-1beta and interferon-gamma expression was examined after LPS administration. RESULTS: OJ induced nuclear factor kappa B activation and increased expression of macrophage inflammatory protein-2, which caused significant increases in neutrophil recruitment. Serum alanine aminotransferase levels increased consistent with histological observations in OJ. Mononuclear cells were recruited in the liver after BDL associated with monocyte chemoattractant protein-1 up-regulation. The recruitment of NK and T cells was varied, consistent with IP-10 expression during the time course of OJ. IL-10 expression was significantly up-regulated 14 d after BDL. After LPS administration, the mice at 3 d after BDL and at 3 and 14 d after sham surgery were all still alive, but all mice at 14 d after BDL died. After LPS administration, IL-1beta significantly increased in the mice at 14 d after BDL. CONCLUSIONS: Immune response such as expression of pro- and anti-inflammatory mediators and recruitment of immune cells may thus differ over the time course of OJ. Prolonged OJ may cause excessive inflammation, thus result in susceptibility to infection.

Recent advance in the treatment of hilar cholangiocarcinoma: hepatectomy with vascular resection.

Radical surgical resection has been revealed to be the only hope of cure for the patient with hilar cholangiocarcinoma. Therefore, major efforts have been made to increase the resection rate by surgeons employing combined hepatic resection and vascular resection of the portal vein and the hepatic artery. Especially, the technical feasibility and surgical safety of hepatic resection with combined portal vein resection have recently been reported by several authors. On the other hand, there have been few reports of combined hepatic artery resection in hilar cholangiocarcinoma. There are fears that combined vascular resection with extended hepatectomy for hilar cholangiocarcinoma may lead to high surgical morbidity and mortality. Herein, we describe the results of aggressive surgical approaches in our series, and we also review the outcomes of hepatic resection with combined vascular resection in the previously reported literature.