Curative Resection Of Hilar Cholangiocarcinoma Research Articles

Postoperative morbidity adversely impacts oncological prognosis after curative resection for hilar cholangiocarcinoma.

BACKGROUNDPostoperative morbidity after curative resection for hilar cholangiocarcinoma (HCCA) is common; however, whether it has an impact on oncological prognosis is unknown.AIMTo evaluate the influence of postoperative morbidity on tumor recurrence and mortality after curative resection for HCCA.METHODSPatients with recently diagnosed HCCA who had undergone curative resection between January 2010 and December 2017 at The First Affiliated Hospital of Army Medical University in China were enrolled. The independent risk factors for morbidity in the 30 d after surgery were investigated, and links between postoperative morbidity and patient characteristics and outcomes were assessed. Postoperative morbidities were divided into five grades based on the Clavien-Dindo classification, and major morbidities were defined as Clavien-Dindo ≥ 3. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence-free survival (RFS) and overall survival (OS).RESULTSPostoperative morbidity occurred in 146 out of 239 patients (61.1%). Multivariate logistic regression revealed that cirrhosis, intraoperative blood loss > 500 mL, diabetes mellitus, and obesity were independent risk factors. Postoperative morbidity was associated with decreased OS and RFS (OS: 18.0 mo vs 31.0 mo, respectively, P = 0.003; RFS: 16.0 mo vs 26.0 mo, respectively, P = 0.002). Multivariate Cox regression analysis indicated that postoperative morbidity was independently associated with decreased OS [hazard ratios (HR): 1.557, 95% confidence interval (CI): 1.119-2.167, P = 0.009] and RFS (HR: 1.535, 95%CI: 1.117-2.108, P = 0.008). Moreover, major morbidity was independently associated with decreased OS (HR: 2.175; 95%CI: 1.470-3.216, P < 0.001) and RFS (HR: 2.054; 95%CI: 1.400-3.014, P < 0.001) after curative resection for HCCA.CONCLUSIONPostoperative morbidity (especially major morbidity) may be an independent risk factor for unfavorable prognosis in HCCA patients following curative resection.

The impact of portal vein resection on outcome of hilar cholangiocarcinoma.

Backgrounds/AimsPortal vein resection (PVR) with major hepatic resection can increase the rate of curative resection for hilar cholangiocarcinoma (HC). However, the oncologic role and safety of PVR is still debatable. This study aims to analyze PVR in terms of safety and therapeutic effectiveness.MethodsWe retrospectively analyzed 235 patients who had undergone major hepatic resection for HC with curative intent, including patients with PVR (PVR, n=35) consisting of PV invasion (PVR-A, n=9), No PV invasion (PVR-B, n=26); and patients without PVR (No PVR, n=200).ResultsThere was no significant difference in the 30-day mortality or postoperative morbidity between PVR and No PVR (2.9% vs. 1.0%; p=0.394 and 34.3% vs. 35.0%; p=0.875). The rate of advanced HC (T3: 40% vs. 12%; p<0.001 and nodal metastasis: 60% vs. 28%; p<0.001) was higher in PVR compared to No PVR. There was no significant difference in the 5-year overall survival rates and disease-free survival between PVR-A vs. PVR-B vs. No PVR. In multivariate analysis, estimated blood loss >600 ml (p=0.010), T3 diseases (p=0.001), nodal metastasis (p=0.001) and poor differentiation (p=0.002) were identified as independent risk factors for survival.ConclusionsPVR does not increase postoperative mortality or morbidity. It showed a similar oncologic outcome, despite a more advanced disease state in patients with HC. Given these findings, PVR should be actively performed if necessary, after careful patient selection.

Minimally invasive surgery for hilar cholangiocarcinoma: a multicenter retrospective analysis of 158 patients.

Curative resection of hilar cholangiocarcinoma (HC) is typically carried out using open surgery. In the present study, we examined the safety (postoperative complication) and effectiveness (resection margin status and patient survival) of minimally invasive surgery (MIS) for HC. This retrospective analysis included 158 patients receiving MIS for HC at 10 participating centers between December 2013 and November 2019. Patient demographics, surgical outcomes, and oncological outcomes were retrospectively analyzed. Clinical information obtained from 10 different clinical centers did not show any evident cohort-bias clustering. One hundred and twenty-six (79.7%) patients underwent LRHC, 12 (7.6%) patients underwent RARHC, conversion to an open procedure occurred in 20 (12.7%) patients. The operation time and estimated blood loss were 410.8 ± 128.9min and 477.8 ± 706.3mL, respectively. The surgical radicality of the 158 patients was R0, 129 (81.6%); R1, 20 (18.4%) and R2, 9 (5.7%). Grades I-II complications was occurred in 68 (43.0%) patients. Severe morbidity (grade III-V) occurred in 14 (8.7%) patients. The median overall survival in whole cohort was 25.4months. The overall survival rate was 67.6% at year 1, 28.8% at year 3, and 19.2% at year 5. Comparing the first half of MISHC performed by each center with the following cases, the operation time and postoperative hospital stay does not decrease with the increasing cases. On literature review, MISHC is non-inferior to open surgery at least in perioperative period. In this Chinese MIS for HC multicenter study, the largest to date, long-term overall survival rates after MIS appear comparable to those reported in current open series. Further randomized controlled trials are necessary to assess the global impact of MISHC.

Vascular resection and reconstruction in hilar cholangiocarcinoma.

The aggressive approach of vascular resection plus reconstruction in curative resection of hilar cholangiocarcinoma (HC) remains controversial. This retrospective study investigated its short- and long-term outcomes. Data of HC patients from 1989 to 2016 were reviewed. Operated patients were divided into two groups (with and without vascular resection) and compared in terms of perioperative results. Patients who had unresectable HC were also compared with patients who had been operated. Ninety patients underwent curative HC resection. They were divided into group A (without aggressive approach, n = 68) and group B (with aggressive approach, n = 22). The groups were comparable in all parameters including rates of overall and major complication and in-hospital, 30-day and 90-day mortality except that group B had more patients with more advanced disease (P = 0.008), more patients with tumour invasion of the vasculature (40.9% versus 7.4%, P = 0.001), and fewer patients with blood transfusion (27.3% versus 52.9%, P = 0.036). The groups had similar disease-free survival (group A: median, 17.9 months, 5 years, 27.4%; group B: median, 11.7 months, 5 years, 14.3%; P = 0.427) and overall survival (group A: median, 22.0 months, 5 years, 26.5%; group B: median, 26.5 months, 5 years, 14.7%; P = 0.90). Two hundred patients with unresectable HC were compared with patients who had received operation and found to have worse survival outcomes (P < 0.001). Vascular resection plus reconstruction in HC resection was feasible and safe and might improve the long-term survival of patients with advanced HC. This aggressive approach should be adopted if the expertise is available and the patient's condition allows.

Treatment of resectable hilar cholangiocarcinoma: a choice of right- or left-side hepatectomy

Introduction: Radical resection is the only curative treatment for patients with hilar cholangiocarcinoma. Some have argued that left-side hepatectomy has worse prognosis regarding its contiguous anatomical relationship between hepatic inflow and biliary confluence, otherwise right-side hepatectomy has worse surgical morbidity and mortality. This study aimed to compare the surgical morbidity and long-term outcome between right- and left-side hepatectomy to help the decision of which side to be resected in the surgical treatment of hilar cholangiocarcinoma. Method: A total of 83 patients attempting curative resection for hilar cholangiocarcinoma at the Korea University Medical Center between 2010 and 2017 were considered for this study. After excluding patients who did not undergo curative-intent surgery or hepatectomy, 57 patients undergoing right- or left-side hepatectomy were finally enrolled for analysis. Prospectively collected clinicopathologic characteristics, perioperative outcomes, and survival were evaluated. Result: Right-side hepatectomy (RH) and left-side hepatectomy (LH) were performed for 33 and 24 patients, respectively. The proportion of R0 resection was comparable between both groups (75.8% for RH group and 75.0% for LH group, p=0.948). Posthepatectomy liver failure was significantly more prevalent in the RH group than the LH group (75.7% vs. 12.5%, p<0.001). 90-day mortality did not differ between both groups (9.1% vs. 4.2%, p=0.631). The 5-year overall survival rate was 37.7% for the RH group; and 41.9% for the LH group (p=0.500). The 5-year recurrence-free survival rate was 26.3% for the RH group; and 33.9% for the LH group (p=0.580). Conclusion: Posthepatectomy liver failure was more prevalent in the RH group than the LH group, but it did not affect the 90-day mortality. It is recommended to perform surgical resection only according to the possibility to achieve radical resection, regardless of right- or left-side hepatectomy.

Post-hepatectomy liver failure is associated with tumor recurrence in patients with hilar cholangiocarcinoma

Purpose: For curative resection of hilar cholangiocarcinoma (HCCA), major hepatectomy with a high risk of hepatic insufficiency is often performed in combination with extrahepatic bile duct resection. However, the association between post-hepatectomy liver failure (PHLF) and oncologic outcomes in HCCA patients has not been described. Materials and methods: Between October 2001 and December 2013, 105 patients who underwent radical extrahepatic bile duct resection and major hepatectomy for HCCA were included in this study. Clinically relevant PHLF was defined as liver failure corresponding to grade B or C of the International Study Group of Liver Surgery (ISGLS) criteria. Results: The rates of 1-, 3-, and 5-year recurrence-free survival (RFS) were 49.8%, 19.5%, and 19.5%, respectively, for patients with PHLF (n = 47) and 73.9%, 47.3%, and 41.9%, respectively, for those without PHLF (n = 58) (P = 0.001). In addition, there was significant difference in overall survival (OS) between the two groups (P < 0.001). In multivariate analysis, PHLF was a significant prognostic factor for RFS (hazard ratio [HR] 2.320, 95% confidence interval [CI] 1.341 - 4.012; P = 0.003) and OS (HR 2.000, 95% CI 1.181 - 3.379; P = 0.010). Patients with PHLF had a higher cumulative incidence at all recurrence sites, with intrahepatic recurrence showing statistical significance (P = 0.039). Conclusion: PHLF is an independent prognostic factor for recurrence and survival after curative resection in HCCA patients. In particular, PHLF is strongly associated with intrahepatic recurrence.

Meta-analysis of prognostic factors for overall survival in patients with resected hilar cholangiocarcinoma.

Hilar cholangiocarcinoma is staged using the AJCC staging system. Numerous other prognostically important histopathological and demographic characteristics have been reported. The objective of this meta-analysis was to assess statistically the effect of postresectional tumour characteristics on overall survival of patients undergoing attempted radical curative resection for hilar cholangiocarcinoma. Relevant studies were identified by searching the Ovid MEDLINE and PubMed databases. The search was limited to studies published between 2009 and 2017. Papers referring to intrahepatic or distal cholangiocarcinoma were excluded from review. Data extraction used standard Parmar modifications to determine pooled univariable hazard ratios (HRs). Twenty-four articles, containing 4599 patients, were assessed quantitatively. In pooled analyses, age (HR 1·16, 95 per cent c.i. 1·04 to 1·28), T category (HR 1·49, 1·30 to 1·70), lymph node involvement (HR 1·78, 1·65 to 1·93), microvascular invasion (HR 1·49, 1·34 to 1·68), perineural invasion (HR 1·54, 1·40 to 1·68) and tumour differentiation (HR 1·54, 1·38 to 1·72) were significant prognostic factors, with low heterogeneity. Portal vein resection (HR 1·54, 1·15 to 1·70) and resection margin status (HR 1·77, 1·57 to 1·99) had significant effects, but with high heterogeneity. Sex, tumour size and preoperative carbohydrate antigen 19-9 levels did not have a statistically significant effect on postoperative prognosis. Several tumour biological variables not included in the seventh edition of the AJCC classification affect overall survival. These require incorporation into prognostic models to ensure a personalized approach to prognostication and treatment.

Curative Resection for Hilar Cholangiocarcinoma: Single-Center Experience with Long-Term Follow-Up

Curative Resection for Hilar Cholangiocarcinoma: Single-Center Experience with Long-Term Follow-Up

Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the U.S. extrahepatic biliary malignancy consortium.

Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection. We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis. A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded. AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.

Outcomes after vascular resection during curative resection for hilar cholangiocarcinoma: a multi-institution analysis from the US extrahepatic biliary malignancy consortium

Outcomes after vascular resection during curative resection for hilar cholangiocarcinoma: a multi-institution analysis from the US extrahepatic biliary malignancy consortium

Curative resection for hilar cholangiocarcinoma: Does adjuvant therapy impact overall survival? A multi-institution analysis from the U.S. Extrahepatic Biliary Malignancy Consortium.

388 Background: Surgical resection is the cornerstone of curative therapy for localized hilar cholangiocarcinoma. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall survival (OS) in those patients undergoing curative resection for hilar cholangiocarcinoma. Methods: We reviewed 294 patients who underwent curative resections for hilar cholangiocarcinoma between 1998 and 2015 from ten institutions participating in the U.S Extrahepatic Biliary Malignancy consortium. We analyzed the impact of AT on the primary outcome of OS. Probability of OS was calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis. Statistical significance was set at p≤0.05. Results: Mean age was 65 years. OS at 5 years was 16%. A total of 146 patients (50%) received AT. Of these patients, 44 patients underwent solely chemotherapy, 5 underwent only radiation therapy (XRT), and 97 underwent combined therapy. On univariate analysis, patients who received AT and those who did not had similar demographic and preoperative features, with the major difference being in the rate of lymph node (LN) positive disease (50% AT group vs. 19% no AT group, p&lt;0.01). In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.578, p&lt;0.01, 95% CI 0.38-0.86), even when adjusting for age, tumor size, R0 resection status, ASA classification, and LN positivity (Table). Conclusions: AT is associated with improved OS in resected hilar cholangiocarcinoma. This association remains even after adjusting for poor prognostic features. We acknowledge that there is an inherent selection bias when looking at those who underwent AT, and thus future prospective randomized trials are needed. [Table: see text]

Use of an autologous liver round ligament flap zeros postoperative bile leak after curative resection of hilar cholangiocarcinoma.

BackgroundPostoperative bile leak is a major surgical morbidity after curative resection with hepaticojejunostomy for hilar cholangiocarcinoma, especially in Bismuth-Corlette types III and IV. This retrospective study assessed the effectiveness and safety of an autologous hepatic round ligament flap (AHRLF) for reducing bile leak after hilar hepaticojejunostomy.MethodsNine type III and IV hilar cholangiocarcinoma patients were consecutively hospitalized for elective perihilar partial hepatectomy with hilar hepaticojejunostomy using an AHRLF between October 2009 and September 2013. The AHRLF was harvested to reinforce the perihilar hepaticojejunostomy. Main outcome measures included operative time, blood loss, postoperative recovery times, morbidity, bile leak, R0 resection rate, and overall survival.ResultsAll patients underwent uneventful R0 resection with hilar hepaticojejunostomy. No patient experienced postoperative bile leak.ConclusionsThe AHRLF was associated with lack of bile leak after curative perihilar hepatectomy with hepaticojejunostomy for hilar cholangiocarcinoma, without compromising oncologic safety, and is recommended in selected patients.

Curative resection of hilar cholangiocarcinoma in a 25-year-old woman: report of a case

A 25-year-old woman was referred to our hospital with persistent upper abdominal pain. Preoperative imaging studies revealed a hilar bile duct stricture with portal venous encasement, and the patient underwent curative resection involving extended left hepatectomy and segmental portal vein resection. The pathological findings demonstrated a well-differentiated tubular adenocarcinoma of the bile duct with regional lymph node metastasis (stage IIIB according to the UICC TNM classification), as well as the overexpression of p53 proteins and the K-ras gene mutation in tumor cells. The patient has shown no evidence of recurrence in the 10 months since the operation. Although there are several reports of relatively young adults with cholangiocarcinoma, the majority of such patients demonstrate either an anomalous arrangement of the pancreaticobiliary duct system or primary sclerosing cholangitis. The absence of any morphological abnormalities in this patient's biliary system implicates de novo carcinogenesis as the most likely cause of the cholangiocarcinoma.

Impact of three-dimensional analysis of multidetector row computed tomography cholangioportography in operative planning for hilar cholangiocarcinoma

Background A detailed evaluation of portal triad structures, especially the biliary anatomy at the hepatic hilus, is essential to ensure curative resection for hilar cholangiocarcinoma. Methods Patients underwent 3-dimensional analysis using multidetector row computed tomography cholangioportography preoperatively. The number of bile duct orifices in the cut end of the hilar plate was estimated and compared with the actual number of bile ducts. Furthermore, the estimated length of the surgical margin and its relationship to the pathological margin status was evaluated. Results The number of bile duct orifices was correctly estimated in 14 of 19 patients. Of 18 hepatic ducts in which the estimated length of the hepatic side surgical margin was calculated 17 hepatic ducts (94.4%) were diagnosed pathologically as margin negative. Conclusions This investigatory technique has the advantages of precise visualization of anatomic structures and multidirectional assessment of biliary branches and vessels, allowing improved operative planning for the treatment of hilar cholangiocarcinoma.

Microvessel density correlates with lymph node metastases and prognosis in hilar cholangiocarcinoma

Neovascularization was shown to be critically involved in the progression of multiple cancers, and treatment approaches targeting tumor-associated neovascularization provide convincing results in recent years in some tumor entities. However, little is known about the tumor-associated neovascularization in hilar cholangiocarcinoma. The present study was conducted to analyze tumor-associated neovascularization in hilar cholangiocarcinoma and to determine its influence on tumor growth, metastasis, recurrence, and prognosis. We analyzed tissue specimens of hilar cholangiocarcinoma (n = 60) by immunohistochemistry using the endothelial-specific antibody CD31 and subsequently quantified the microvessel density (MVD). The MVD was correlated with clinicopathological characteristics and recurrence pattern of the tumors as well as survival of patients. Hilar cholangiocarcinoma revealed a high degree of vascularization, with a calculated mean MVD of 28.1 +/- 14.5 vessels. Tumors with a high MVD had a significant higher incidence of lymph node involvement (P = 0.009) and local recurrence (P < 0.001). Furthermore, a high MVD was identified to be a significant overall survival disadvantage (3-year, 28% vs. 93%; 5-year, 8% vs. 78%; P < 0.001) as well as disease-free survival disadvantage (3-year, 7% vs. 88%, 5-year, 7% vs. 72%; P < 0.001), with MVD representing an independent prognostic factor for survival. Neovascularization is associated with nodal spread as well as local recurrence and serves as an independent prognostic factor for survival after curative resection of hilar cholangiocarcinoma. Therefore, tumor-associated neovascularization seems to be critically involved in the progression of this tumor entity. In addition, neovascularization may represent a potential target in he development of new therapeutic approaches in hilar cholangiocarcinoma.

Portal Vein Interposition Using Homologous Iliac Vein Graft during Extensive Resection for Hilar Bile Duct Cancer

Although autologous vein grafts have been used for portal vein (PV) reconstruction after long-segment portal vein resection during surgery for hilar bile duct cancer, their procurement prolongs operation time and increases morbidity. Less is known regarding the use of homologous vein grafts. The feasibility of homografts for PV reconstruction was preliminarily evaluated in two patients who underwent curative resection for hilar cholangiocarcinoma. Both patients underwent left lobectomy, caudate lobectomy, bile duct resection, and segmental PV resection and interposition vein graft reconstruction. The iliac vein homografts were obtained from deceased organ donors and stored for 1–2 days in cold preservation solution without freezing. Neither immunosuppression nor anticoagulation was attempted. One patient has shown good PV patency for 27 months. The second patient, who had received adjuvant chemoradiotherapy, showed an asymptomatic waisting at the proximal PV anastomosis site after 4 months, which was relieved by percutaneous balloon dilatation, and has been doing well for 12 months. In conclusion, our preliminary experience with these two patients suggests that cold-stored iliac vein homografts can be considered as PV substitutes after long PV segment resection during extensive hepatobiliary surgery.

Solitary recurrence of hilar cholangiocarcinoma in a mediastinal lymph node two years after curative resection

We recently encountered an unusual case of hilar cholangiocarcinoma in which a solitary recurrence in a mediastinal lymph node occurred two years after curative resection of the primary tumor. A 64-year old woman was admitted to our hospital with a complaint of right hypochondrial discomfort. After imaging studies demonstrated a hilar cholangiocarcinoma in the left hepatic duct, a curative resection of the tumor was performed, consisting of a left hepatic lobectomy along with caudate lobectomy, regional lymph node dissection, and resection of the extrahepatic bile duct. No nodal metastasis was observed histologically. Two years after surgery, the patient was found to have a nodule in the posterior mediastinum, which was thoracoscopically resected. No other swollen lymph nodes, local recurrence, or distant metastasis were noted. Histologically, the nodule proved to be a metastatic lymph node, and adjuvant chemoradiation therapy was initiated. The patient remained well for the four years following her first operation and had no evidence of disease recurrence 28 mo after her second operation. To our knowledge, this case is the first report of solitary recurrence in a mediastinal lymph node after curative resection of hilar cholangiocarcinoma.

Extended right hepatectomy for hilar cholangiocarcinoma with resection of the left hepatic duct prior to hepatic resection

Extended hepatectomy for hilar cholangiocarcinoma results in high operative or in-hospital mortality rates despite of the recent progress in perioperative management. As a new procedure to prevent postoperative hepatic failure in hilar cholangiocarcinoma infiltrating predominantly the right hepatic duct, we devised a combination of extended right lobectomy plus caudal lobectomy with resection of the left hepatic duct prior to hepatic resection by utilizing intraoperative cholangiography, and applied the procedure to a 70-year-old patient. He had a favorable postoperative course and remains recurrence-free at 4 years after operation. This is a procedure for confining the extent of hepatectomy to the minimum necessary, aiming at curative resection of hilar cholangiocarcinoma.

Hilar cholangiocarcinoma—surgical anatomy and curative resection

We have studied the surgical anatomy of the intrahepatic bile duct, hepatic hilus, and caudate lobe based on intraoperative findings and selective cholangiography of surgical patients and resected specimens, and have established the cholangiographic anatomy of the intrahepatic subsegmental bile duct. Thorough knowledge of the three-dimensional anatomy of the subsegmental bile duct, hepatic hilus, and caudate lobe is indispensable for curative surgery of hilar cholangiocarcinoma. We designed and actually performed 15 kinds of hepatic segmentectomies with caudate lobectomy and extrahepatic bile buct resection in 100 consecutive patients, with curative resection being possible in 82 patients. Postoperative survival after curative resection of hilar cholangiocarcinoma was better than expected, and the 5-year survival rates for all 82 patients with curative resection and for 55 patients with curative surgery without portal vein resection were 31% and 43%, respectively. Hepatic segmentectomy with caudate lobectomy and extrahepatic bile duct resection should be designed not only in accordance with the preoperative diagnosis of tumor extension into the intrahepatic bile ducts but also so that curative surgery for advanced hilar cholangiocarcinoma can be performed.