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Intrahepatic cholangiocarcinoma (ICC) is resistant to most chemotherapeutic agents. Yes-associated protein (YAP) is related to tumor progression; however, its role in ICC remains unknown. We investigated the mechanism underlying YAP-mediated cancer progression by focusing on the property of cancer stem cells (CSCs) in ICC. Immunohistochemistry results revealed the positive YAP expression in 37 of 52 resected ICC cases. Those with positive YAP expression showed poor prognosis in Kaplan-Meier analysis (P = 0.023). YAP expression was associated with vimentin and the putative CSC marker, hepatic oval cell marker 6 (OV-6). The knockdown of YAP expression using specific siRNAs in ICC cells decreased octamer-binding transcription factor 4 (OCT4) expression in Western blot analyses and OV-6 and CD133 expression in flow cytometry analysis. Verteporfin, a YAP inhibitor, decreased N-cadherin and OCT4 expression in Western blot analyses. In vitro sphere formation and anoikis resistance assays revealed the impairment in CSC property and anoikis resistance in response to the decrease in YAP expression. Verteporfin treatment activated the protein kinase B/mechanistic target of rapamycin signaling pathway and dramatically impaired IL-6-stimulated STAT3 phosphorylation in ICC cells. The combination of verteporfin and rapamycin, an inhibitor of mechanistic target of rapamycin phosphorylation, inhibited cell proliferation and tumor growth. In conclusion, verteporfin regulates multiple signaling pathways and, in combination with rapamycin, might be a promising therapeutic strategy for ICC treatment., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Left trisectionectomy (LT) extending to the segment I with bile duct resection for perihilar cholangiocarcinoma (PHC) is a technically demanding procedure with high morbidity. Liver transection during LT is generally conducted to expose the right hepatic vein (RHV) on the remnant side. In clinical practice, we have often encountered a discrepancy between the theoretical RHV-oriented plane and the actual right intersectional plane., Methods: To enable anatomical LT safely, the three-dimensional right intersectional transection plane based on portal inflow was investigated using multidetector-row computed tomography, and it was compared to the theoretical RHV-oriented plane in 100 patients with hepatobiliary disease., Results: The posterior portion of RHV just below the diaphragm was supplied by the dorsal portal branches of segment VIII in 85 cases of 100 (85.0%). The median volume of this portion was 82 mL (25-169 mL). On the other hand, the anterior region of the peripheral RHV was supplied by a few small ventral portal branches of segment VI in 24 of 90 cases (26.7%). The median volume of this portion was 53 mL (20-104 mL). In ten cases with a large inferior RHV, the RHV trunk was relatively short and did not reach the caudal part of the liver., Conclusions: The portal inflow-oriented right intersectional plane does not coincide with the RHV-oriented plane in most cases. The cranial part of the actual transection plane becomes hollow, whereas the caudal part is protruded in relation to the RHV. Hepatobiliary surgeons should recognize this complicated transection plane to avoid postoperative complications when performing LT for PHC.

Background: Right hepatectomy (RH) is the standard surgical procedure for perihilar cholangiocarcinoma (PHC) with right-sided predominance in many centers. Although left trisectionectomy (LT) is aggressively performed for PHC with left-sided predominance in high-volume centers, the surgical and survival outcomes of LT are unclear. Therefore, this study aimed to compare the outcomes of LT and RH for PHC., Methods: Consecutive patients who underwent surgical resection for PHC at Chiba University Hospital from 2008 to 2016 were retrospectively reviewed. The outcomes of patients with PHC who underwent LT were compared with those who underwent RH following one-to-one propensity score matching., Results: Of 171 consecutive PHC resection patients, 111 were eligible for the study; 41 (37%) underwent LT, and 70 (63%) underwent RH. In a matched cohort (LT: n = 27, RH: n = 27), major complication rates (67% vs. 52%; p = 0.42), 90-day mortality rates (15% vs. 0%; p = 0.11) and R0 resection rates (56% vs. 44%; p = 0.58) were similar in both groups. The 3-year recurrence-free survival rates (27% vs. 47%; p = 0.27) and overall survival rates (45% vs. 60%; p = 0.17) were also similar in both groups., Conclusions: In patients with PHC, LT could achieve similar surgical and survival outcomes as RH., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Although multidetector-row computed tomography (MDCT) before biliary drainage is useful for the assessment of the resectability of perihilar cholangiocarcinoma (PHC), the impact of biliary drainage on MDCT images before surgical resection for PHC has been poorly studied, and its possible consequences for R0 resection of PHC remain unclear. This study was performed to compare the surgical outcomes of patients with PHC who underwent MDCT before versus after biliary drainage., Methods: All consecutive patients who underwent major hepatectomy extending to segment 1 with extrahepatic bile duct resection for PHC from 2009 to 2016 were retrospectively evaluated. R0 resection was defined as no residual cancer at all surgical margins. Patients with pathological stage IV PHC were excluded., Results: Of 142 patients who underwent major hepatectomy, 108 were eligible for this study. Of these 108 patients, 64 (59%) and 44 (41%) underwent MDCT before and after biliary drainage, respectively. The total bilirubin concentration at presentation was lower in patients who underwent MDCT before than after biliary drainage (4.1 ± 5.9 vs. 8.0 ± 7.1 mg/ml, respectively; p = 0.002). Although there were no significant differences in the surgical characteristics or pathological stages between the two groups, R0 resection was more frequently achieved in patients who underwent MDCT before than after biliary drainage [46/64 (72%) vs. 22/44 (50%), respectively; p = 0.03]. On multivariate analysis, MDCT before biliary drainage was independently associated with R0 resection of PHC (risk ratio: 2.38, 95% CI 1.05-5.41; p = 0.04)., Conclusions: In selected patients, MDCT should be performed before biliary drainage to achieve R0 resection of PHC.

Background: Although several studies have reported the effects of immunonutrition on clinical outcomes, detailed mechanisms of immunonutrition after an operation are still unclear. It was recently reported that resolvin E1, a novel lipid mediator generated from eicosapentaenoic acid (EPA), activates factors that reduce inflammation. This randomized clinical trial was designed to investigate not only the effect of immunonutrition on postoperative complications but also the participation of resolvin E1 on anti-inflammatory effects of immunonutrition in patients undergoing major hepatobiliary resection., Methods: Forty patients who underwent major hepatobiliary resection were divided into 2 groups. Twenty patients received oral supplementation enriched with EPA, arginine, and nucleotides before the operation (group IN). Twenty patients (control group) received no artificial nutrition before the operation (group C)., Results: The rate of infectious complications and severity of complications in group IN was significantly lower than in group C (P < .05). Immediately after the operation, plasma resolvin E1 levels were significantly higher in group IN than in group C (P < .05), and plasma interleukin-6 levels were significantly lower in group IN than in group C (P < .05). Preoperative serum EPA levels correlated with plasma resolvin E1 levels immediately after the operation. Plasma resolvin E1 levels correlated with plasma interleukin-6 levels immediately after the operation., Conclusion: Preoperative immunonutrition reduced inflammatory responses and protected against the aggravation of postoperative complications in patients undergoing major hepatobiliary resection. Resolvin E1 may play a key role in the resolution of acute inflammation when immunonutrition is supplemented with EPA. (ClinicalTrials.gov Identifier: NCT01256047.)., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

We report the case of a 77-year-old woman with mediastinal lymph node metastasis of combined hepatocellular and cholangiocarcinoma who was successfully treated with S8 segmentectomy and lymphadenectomy. A hepatic nodule was detected in segment 8 during follow-up computed tomography (CT) after left iliac arterial aneurysm repair. The patient was diagnosed with a hepatocellular carcinoma (HCC), and transcatheter arterial chemoembolization (TACE) was selected for HCC because of the patient's condition. The levels of tumor markers did not change after TACE was performed twice. Therefore, TACE treatment was considered to be ineffective for HCC, and the patient was admitted to our hospital for surgical resection. In addition to the primary lesion, a lymph node with a diameter of 20 mm was detected in the anterior mediastinum using CT and magnetic resonance imaging(MRI). We did not find any other metastases, and therefore, S8 segmentectomy and lymphadenectomy in the anterior mediastinum were performed. Recovery was uneventful, and the patient was discharged from the hospital on postoperative day 12. Based on histopathologic findings, combined hepatocellular and cholangiocarcinoma with mediastinal lymph node metastasis was confirmed. Levels of tumor markers normalized, and the patient survived without recurrence for 6 months.

Background: Full understanding of the hilar anatomy is crucial for successful surgical resection of perihilar cholangiocarcinoma (PHC)., Methods: The three-dimensional positional relationship between the left hepatic artery (LHA) and the umbilical portion of the left portal vein (UP) was evaluated using multidetector-row computed tomography (CT) in 58 consecutive patients who underwent right-sided hepatectomy for Bismuth-Corlette IIIa or IV tumors. The positional relationship of the LHA related to UP was classified into the following three types: L-UP type, LHA runs into the left lateral section (LLS) from the left caudal side of the UP; R-UP type, LHA runs into the LLS from the right cranial side of the UP; and combined type, one branch of the LHA runs into the LLS from the right cranial side of the UP, and the other from the left caudal side of the UP., Results: L-UP-type LHA was observed in 53 cases (91.4 %), R-UP type in three cases (5.2 %), and combined type in two cases (3.4 %). No cancer involvement of the LHA was seen in any cases with L-UP type. In one case with R-UP type (one of three; 33.3 %) and one case with combined type (one of two, 50 %), cancer invasion to the LHA was observed at the right side of the UP, requiring combined resection of the involved LHA., Conclusions: R-UP-type LHA running just along the left hepatic duct may be easily involved by right-side predominant PHC when extending to the left hepatic duct. Hepatobiliary surgeons should recognize this anatomical variant and carefully evaluate the running courses of LHA to successfully perform R0 resection in right-sided hepatectomy for PHC.

A 61-year-old woman was referred to our hospital because of jaundice and general itching. Computed tomography (CT) scan demonstrated that the tumor was located in the caudate lobe of the liver with hilar invasion and involved the hepatic inferior vena cava (IVC) and the right renal artery and vein. The patient was diagnosed with locally advanced intrahepatic cholangiocarcinoma, for which she underwent right hemihepatectomy with right caudate lobectomy, portal vein resection, hepatic IVC resection, extrahepatic bile duct resection, and right nephrectomy. IVC was reconstructed using vascular prosthesis by expanded polytetrafluoroethylene (ePTFE)-ringed graft. The patient's postoperative course was uneventful. The patient was treated with gemcitabine for postoperative chemotherapy, and 3 years after the operation, she died due to recurrence resulting from peritoneal dissemination. Although the thrombosis-related vascular prosthesis obstruction had occurred 2 years after the operation, no clinical symptom were noted, such as lower leg edema or renal dysfunction, during the postoperative course. Hepatic IVC prosthesis reconstruction for locally advanced cancer with extensive IVC invasion can be a useful surgical procedure for improving the resection rate and maintaining quality of life (QOL) in such cases.

This case report describes an 83-year-old man with intrahepatic cholangiocarcinoma who was referred by a local hospital. Abdominal computed tomography (CT) showed a large tumor in hepatic segments 4, 5, and 8 involving the right hepatic vein and inferior vena cava, which is normally indicative of an unresectable locally advanced tumor. After systemic chemotherapy with gemcitabine and cisplatin, the observed decrease in the level of tumor marker suggested that the cancer was responding to treatment, while radiological findings showed the main tumor shrunk without the presence of distant metastases. Thus, hepatic left trisectionectomy with bile duct resection was performed after portal vein embolization. Pathological examination revealed negative margins (R0). Eighteen months after surgery, the patient is free of disease and shows no signs of recurrence. An initially unresectable, locally advanced biliary tract cancer may be down sized by chemotherapy, which makes radical resection possible, at least in a proportion of patients. This approach provides longer survival and may have a potential for disease eradication as a new multidisciplinary approach for patients with unresectable locally advanced biliary tract cancer.

A 70-year-old man was diagnosed with local recurrence 1 and half years after pancreatoduodenectomy for extrahepatic cholangiocarcinoma. Progression of the recurrent tumor involved the portal vein, even though the patient had received chemotherapy (gemcitabine). Although no clinical symptoms caused by portal venous stenosis were found at the time, we performed percutaneous transhepatic portal vein stenting to avoid interrupting chemotherapy. Eighteen months after this procedure, the patency of the portal vein stent was well maintained, and the patient was treated with S-1 chemotherapy continuously without any symptoms related to portal venous stenosis reported. Prophylactic portal vein stenting without clinical symptoms of portal vein stenosis is a useful procedure, not only for palliative care but for improving the prognosis of patients with cholangiocarcinoma by continuous chemotherapy.

Objective: To evaluate recent surgical strategy for hilar cholangiocarcinoma (HC) of the left-side predominance., Background: When employing left hemihepatectomy (LH) for HC, vasculobiliary anatomy of the right liver often makes it difficult to achieve a tumor-free margin of the right posterior sectional bile duct (RPSBD). Because left trisectionectomy (LTS) can produce a longer resection margin for the RPSBD, we have expanded the indications for LTS over the last 5 years., Methods: Sixty-one consecutive patients underwent left-sided hepatectomy for HC, divided into 2 groups according to the operative periods: period 1 (2001-2007; n = 29) and period 2 (2008-2012; n = 32). Clinicopathological outcomes of the groups were compared. The difference in the length of the resectable RPSBD between LH and LTS was radiologically investigated using multidetector-row computed tomography., Results: The proportion of LTS increased from 10.3% (3/29) in period 1 to 46.9% (15/32) in period 2. R0 resection rates were also improved in period 2. The most common margin positive site in period 1 was the stump of the proximal bile duct; high rates of positive RPSBD stump were noted after LH. The positive proximal ductal margin ratio decreased significantly in period 2. The difference in the length of resectable RPSBD between LH and LTS was 9.0 ± 1.3 mm. There was no mortality in period 2, even after LTS., Conclusions: LTS for HC of the left-side predominance improved R0 resection rates without affecting postoperative mortality. LTS should be aggressively performed in patients with appropriate hepatic function, even if tumors are possibly resectable by LH.

Background: Surgical resection is the only method for curative treatment of biliary tract cancer (BTC). Recently, an improved efficacy has been revealed in patients with initially unresectable locally advanced BTC to improve the prognosis by the advent of useful cancer chemotherapy. The aim of this study was to evaluate the effect of downsizing chemotherapy in patients with initially unresectable locally advanced BTC., Methods: Initially unresectable locally advanced cases were defined as those in which therapeutic resection could not be achieved even by proactive surgical resection. Gemcitabine was administered intravenously once a week for 3 weeks followed by 1 week's respite. Patients whose disease responded to chemotherapy were reevaluated to determine whether their tumor was resectable., Results: Chemotherapy with gemcitabine was provided to 22 patients with initially unresectable locally advanced BTC. Tumor was significantly downsized in nine patients, and surgical resection was performed in 8 (36.4%) of 22 patients. Surgical resection resulted in R0 resection in four patients and R1 resection in four patients. Patients who underwent surgical resection had a significantly longer survival compared with those unable to undergo surgery., Conclusions: Preoperative chemotherapy enables the downsizing of initially unresectable locally advanced BTC, with radical resection made possible in a certain proportion of patients. Downsizing chemotherapy should be proactively carried out as a multidisciplinary treatment strategy for patients with initially unresectable locally advanced BTC with the aim of expanding the surgical indication.

Intraductal papillary neoplasms of the bile duct (IPNB) have been recently proposed as the biliary counterpart of intraductal papillary mucinous neoplasms of the pancreas (IPMN-P). However, in contrast to IPMN-P, IPNB include a considerable number of the tumors without macroscopically visible mucin secretion. Here we report the similarities and differences between IPNB with and without macroscopically visible mucin secretion (IPNB-M and IPNB-NM). Surgically resected 27 consecutive cases with IPNB were divided into IPNB-M (n=10) and IPNB-NM (n=17), and their clinicopathologic features were examined. Clinically, both tumors were similar. Pathologically, the most frequent histopathologic types were pancreatobiliary in IPNB-NM and intestinal in IPNB-M. Various degrees of cytoarchitectural atypia within the same tumor were exhibited in 8 IPNB-M, but only 3 in IPNB-NM. Although the tumor size was similar, 9 IPNB-NM were invasive carcinoma, whereas all but 1 IPNB-M with carcinoma were in situ or minimally invasive. Immunohistochemically, positive MUC2 expression was significantly more frequent in IPNB-M than in IPNB-NM, whereas MUC1 tended to be more frequently expressed in IPNB-NM compared with IPNB-M. Among IPNB-NM with positive MUC1 expression, 3 had negative MUC2 and MUC5AC expressions. These tumors showed a tubulopapillary growth with uniform degree of cytoarchitectural atypia. All IPNB-M were negative for p53, and the frequency of positive p53 protein in IPNB-NM was at the middle level of that in IPNB-M and nonpapillary cholangiocarcinoma. In conclusion, IPNB-M showed striking similarities to IPMN-P, but IPNB-NM contained heterogeneous disease groups.

A 62-year-old woman underwent an extended left hepatectomy with a combined resection of portal vein and extrahepatic bile duct for intrahepatic cholangiocarcinoma (ICC). After 7 years, she presented with repeated tarry black stool and severe anemia. The source of bleeding was not identified on upper and lower gastrointestinal endoscopy. Computed tomography (CT) revealed a small hypodence lesion at portal hepatis, by which portal vein (PV) stenosis was induced in the absence of sufficient development of portal venous collateral. Positron emission tomography revealed an accumulation of fluorodeoxy glucose around PV obstruction. Based on these findings, we diagnosed that the local recurrence of ICC, which resulted in mesenteric hypertension and small bowel varices. Therefore, portal stent placement was carried out under percutaneous transhepatic portgraphy to maintain portal blood flow. An uncovered expandable metallic stent was inserted into the stenotic region. Portgraphy after the stent replacement showed a relief of the PV stenosis and disappearance of the collateral pathways. After this procedure, the patient had no additional episode of gastrointestinal hemorrhage. Our experience suggests that stent placement for postoperative PV stenosis is recommended as a useful treatment for gastrointestinal bleeding caused by portal hypertension that is less invasive.

The patient was a 61-year-old man. He was underwent pancreaticoduodenectomy for common bile duct cancer. The preoperative dynamic CT revealed that hepatic artery was branched from the superior mesenteric artery, run through pancreatic surface caudal to cranial and flowed into liver. And this vessel had several branches into pancreas. In operation, to ensure blood flow to the liver, hepatic artery was detached from pancreas by cutting off branches into pancreas. In addition, intestinal malrotation was also confirmed (Treitz ligament was not formed and small intestine was present in the right side of abdominal space, while colon was present in the other side). Performing a pancreatoduodenectomy for malignant tumors, it is very important to recognize the variation of hepatic artery, because of the necessity for the consideration of blood flow to the liver. In this case, we indicated a preservation of hepatic artery with adequate lymph node dissection.

Many authors at high-volume centers all over the world have reported improved outcomes of hilar cholangiocarcinoma by several aggressive surgical approaches such as extended hepatic resection, combined vascular resection, and hepatopancreaticoduodenectomy in recent years. There has been great progress in the surgical treatment of hilar cholangiocarcinoma with these previous efforts by aggressive hepatobiliary surgeons. In particular, surgical techniques, diagnostic modalities, and perioperative management have been remarkably improved as compared with before. Herein we report the surgical outcome for both hilar cholangiocarcinoma of Bismuth types II, III, and IV and intrahepatic cholangiocarcinoma involving the hepatic duct confluence during the recent 8-year period between 2001 and 2008 at our institution, the Department of General Surgery at Chiba University. From our recent experienced results, it can be concluded that the surgical strategy for hilar cholangiocarcinoma has been improved remarkably, and major surgical hepatectomy can be done with relative safety, and these aggressive surgical approaches, including combined vascular resection, may be warranted for the surgical treatment of hilar cholangiocarcinoma. However, the adoption of new innovative therapeutic approaches might be required for further improvement of surgical outcome of hilar cholangiocarcinoma.

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.

Objectives: To evaluate the clinicopathologic outcomes in patients with hilar cholangiocarcinoma (HC) after left-sided hepatectomy (L-H)., Summary Background Data: L-H is indicated as radical surgery for HC, predominantly involving left hepatic duct. However, several reports have demonstrated that L-H often results in tumor-positive margin and unfavorable prognosis compared with right-sided hepatectomy (R-H)., Methods: A total of 224 patients with HC underwent surgical resection with curative intent at our institution: L-H for Bismuth-Corlette (B-C) type IIIb tumors in 88 patients (39.3%) including 75 left hemihepatectomies and 13 left trisectionectomies, and R-H mainly for B-C type IIIa and IV tumors in 84 patients (37.5%). In this study, clinicopathologic outcomes and perioperative morbidity and mortality rates after L-H were investigated and compared with those after R-H., Results: Histologically negative margin (R0) resection was achieved in 56 cases (63.6%) with L-H, similar to the results for R-H (58/84, 69.1%). However, the R0 resection rate in L-H cases with portal vein (PV) resection was lower (11/25, 44.0%), and various types of PV reconstruction were required. Proximal ductal stumps and excisional surface at periductal structures were the most common sites of positive margins. However, when curative resection was achieved, 5-year survival was comparable to that in R-H cases. Furthermore, lower mortality was noted in L-H cases, even with left trisectionectomy. Multivariate analysis indicated curability and hepatic artery resection as independent prognostic factors., Conclusions: Since L-H is a safe procedure and represents the only curative resectional option for type IIIb tumor, aggressive surgical resection should be performed even in cases with PV involvement, if R0 resection is possible.

Background/aims: Management of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following surgical resection is difficult, and surgical resection is rarely indicated. We retrospectively reviewed patients with recurrent intrahepatic cholangiocarcinoma., Methodology: Between April 1998 and March 2007, 57 consecutive patients with ICC underwent surgical resection. Mode of recurrence and treatment of recurrent tumors, especially surgical resection for these tumors, in patients with cancer recurrence were evaluated., Results: 37 (65%) patients experienced tumor recurrence. Out of these patients, 24 underwent some type of cancer-directed therapy, including 9 patients (24%) for whom surgical resection was attempted: the latter included 4 hepatic resections, 2 pulmonary resections, 2 tumor resections, and 1 gastric resection. For 6 patients with recurrent tumor in the liver or the lung, microscopic complete resection was achieved, while incomplete resection was resulted in the remaining 3 patients. No postoperative mortality was encountered. Among patients with complete resection, 3 are alive without disease 32, 39 and 77 months after the second operation, one has lived with disease for 13 months, and 2 died of disease after 22 and 26 months. No significant difference in overall survival was observed between patients undergoing primary and second surgical resections, calculated from the primary and the second operations, respectively., Conclusions: Repeated surgical resection for recurrent ICC can be performed with acceptable morbidity, and affords selected patients a chance for long-term survival.

Background: It is still not clear how combined vascular resection affects the outcome of patients with hilar cholangiocarcinoma. Our aim was to evaluate implications of combined vascular resection in patients with hilar cholangiocarcinoma by analyzing the outcomes of all patients who underwent operative resection., Methods: A total of 161 of 228 consecutive patients with hilar cholangiocarcinoma underwent bile duct resection with various types of hepatectomy (88%) and pancreaticoduodenectomy (4%). Combined vascular resection was carried out in 43 patients. Thirty-four patients had portal vein resection alone, 7 patients had both portal vein and hepatic artery resection, and 2 patients had right hepatic artery resection only. The outcomes were compared between the 3 groups: the portal vein resection alone (34), hepatic artery resection (9), and non-vascular resection (118)., Results: Histologically-positive tumor invasion to the portal vein beyond the adventitia was present in 80% of 44 patients undergoing combined portal vein resection. Operative mortality occurred in 11 (7%) patients. The survival rates of the non-vascular resection group were better than that of the portal vein resection alone and the hepatic artery resection groups: 1, 3, and 5 years after curative resection, 72%, 52%, and 41% versus 47%, 31%, and 25% (P < .05), and 17%, 0%, and 0% (P < .0001), respectively. Multivariate analysis showed 4 independent prognostic factors of adverse effect on survival after operation; operative curability, lymph node metastases, portal vein resection, and hepatic artery resection., Conclusions: Although both portal vein and hepatic artery resection are independent poor prognostic factors after curative operative resection of locally advanced hilar cholangiocarcinoma, portal vein resection is acceptable from an operative risk perspective and might improve the prognosis in the selected patients, however, combined hepatic artery resection can not be justified.

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.

The patient was a 73-year-old man diagnosed with bile duct cancer. He underwent hepato-pancreatoduodenectomy and a combined resection of portal vein in July 2002. The post operative course was uneventful. In December 2003 he had a loss of consciousness, and was admitted to our hospital as an emergency patient. Abdominal CT scan and angiography revealed the presence of portal vein stenosis due to local recurrence of bile duct cancer resulting in portal hypertension. Thus, a metallic stent was placed in the portal vein to maintain portal blood flow. A non-covered metallic stent, 10 mm in diameter and 80 mm in length (SMART stent, Cordis Endovascular), was deployed through the stenotic portal vein. Portography after the stent placement showed a relief of the portal vein stenosis. Intravenous heparin administration was performed at a dose of 5,000 IU per day for 5 days after the stent placement, and this was followed by oral warfarin potassium administration. The clinical course was uneventful and the patient was discharged 21 days after portal stent placement. Portal stenting successfully improved portal hypertension due to stenosis of the portal vein without any complication. Our experience suggests that the portal vein stenting using the SMART stent is useful palliative therapy for portal vein stenosis.

Surgical resection has been reported to be only hope for cure for the patients with hilar cholangiocarcinoma. Therefore, first of all, radical surgical resection should be considered to be a therapeutic option for hilar cholangiocarcinoma as much as possible. In preoperative staging for hilar cholangiocarcinoma, various extensive patterns of cancer such as the involvements of bile duct, portal vein, hepatic artery and lymph node etc, should be evaluated in each patient. As most patients are associated with obstructive jaundice at presentation, liver function has to be evaluated by appropriate tests for deciding the suitable surgical procedure. When the future remnant liver volume is less than 40% or severe liver functional damage exists or greater surgical stress is expected, preoperative portal vein embolization might have to be selected. On the other hand, if hilar cholangiocarcinoma involves limited region of the hilar bile duct confluence, parenchyma preserving hepatectomy such as S1 resection and S1 + S4 resection should be selected for avoiding the occurrence of liver failure. Combined portal vein resection should be done for the case of the cancer involvement of the portal vein without hesitation to improve the prognosis. However, hepatic artery resection and reconstruction in the involved case should be carefully performed only in severely selected cases. By using several useful pre-operative and intra-operative therapeutic modalities, hilar cholangiocarcinoma should be surgically resected with curative intent and without increasing surgical morbidity and mortality rates.