Surgical Management Of Intrahepatic Cholangiocarcinoma Research Articles

New Insights into Surgical Management of Intrahepatic Cholangiocarcinoma in the Era of “Transplant Oncology”

Intrahepatic cholangiocarcinoma (iCCA) represents the second most frequent type of primary liver neoplasm. The diagnosis and treatment of patients with iCCA involves many challenges. To date, surgical resection with negative margins is the main curative option, achieving an acceptable long-term survival. Despite enabling a considerable improvement in the outcome, iCCA recurrence after surgery is still common. Tumor extension and the histological subtype, as well as vascular and lymph node involvements, are key factors used to define the prognosis. In this narrative review, we aimed to discuss the potential benefits of using different surgical strategies in the field of iCCA, including vascular resection, the mini-invasive approach, liver transplantation, the mechanism used to enable future liver remnant augmentation, and lymph node dissection. We also discussed the new protocols developed in the field of systemic treatment, including immunotherapy and molecular targeted therapy. Recent advancements in the diagnosis, surgical treatment, and understanding of tumor biology have changed the landscape in terms of treatment options. Creating a multidisciplinary tumor board is essential to achieving the best patient outcomes. Further investigational trials are required with the intent of tailoring the treatments and establishing the right patient population who would benefit from the use of new therapeutics algorithms.

Surgical management of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICCA) is a rare tumor with a poor prognosis that arises from the intrahepatic biliary tract. Patients who present with locally advanced or metastatic ICCA are generally treated with first-line gemcitabine/cisplatin and/or liver-directed therapy with the hope of downstaging/downsizing the disease. Patients who present with resectable ICCA may be treated with upfront surgery and postoperative adjuvant capecitabine. Staging laparoscopy should be considered to evaluate for occult metastatic disease and laparoscopic ultrasound can be used to better evaluate the liver parenchyma. Resection with the goal of achieving an R0 margin, along with lymphadenectomy to adequately stage patients, should be the standard operative approach. Unfortunately, the surgical technique cannot overcome poor tumor biology, and ICCA has a high incidence of recurrence, with many patients developing metastatic disease. Targeted therapy with IDH and FGFR inhibitors has had promising results in early clinical trials. Future endeavors should strive to identify more effective systemic and targeted therapies, which will hopefully improve survival for patients with ICCA.

Surgical management of intrahepatic cholangiocarcinoma: a narrative review

Surgical management of intrahepatic cholangiocarcinoma: a narrative review

Surgical management of intrahepatic cholangiocarcinoma: The mayo experience

Surgical management of intrahepatic cholangiocarcinoma: The mayo experience

Surgical Management of Intrahepatic Cholangiocarcinoma in Patients with Cirrhosis: Impact of Lymphadenectomy on Peri‐Operative Outcomes

The consequences of lymphadenectomy (LND) on cirrhotic patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) have not been investigated. We sought to analyze the impact of LND on morbidity among patients undergoing resection for ICC. A total of 1005 patients who underwent hepatectomy for ICC at one of the 14 participating institutions between 1990 and 2015 were identified. A propensity score match analysis was performed to reduce confounding biases between cirrhosis and non-cirrhosis groups. Cirrhosis was diagnosed in 118 (11.7%) patients. Among non-cirrhotic patients, 63% underwent major liver resection versus only 20% among patients with cirrhosis (p<0.001). LND was also less common among cirrhotic versus non-cirrhotic patients (19 vs. 50%, p<0.001). The incidence of complications was 41 and 30% among patients who did not and did have cirrhosis, respectively (p=0.022). The propensity-matched cohort included 150 patients. The incidence of complications was 71% among patients who underwent lymphadenectomy versus 23% among patients who did not undergo lymphadenectomy (OR 8.39) (p<0.001). In the propensity-matched analysis, the median HLN was comparable among patients independent of cirrhosis status (median HLN: non-cirrhosis, 2.5 vs. cirrhosis, 2) (p=0.95). While lymphadenectomy was associated with a higher risk of infections (non-cirrhosis, 0% vs. cirrhosis, 21%, p<0.001) among patients with cirrhosis, infections were not associated with lymphadenectomy among non-cirrhotic patients (p=0.19). Lymphadenectomy was associated with an increased risk of complications among patients with cirrhosis undergoing surgery for ICC. The benefit of lymphadenectomy in cirrhotic patients should be considered in light of the higher risk of postoperative complications compared with non-cirrhotic patients.

Surgical management of intrahepatic cholangiocarcinoma in the modern era: advances and challenges.

Intrahepatic cholangiocarcinoma (ICC) is one of the few gastrointestinal cancers with increasing incidence and mortality worldwide. Unlike hepatocellular carcinoma (HCC) which arises usually in a cirrhotic environment ICC frequently arises in the context of normal hepatic parenchyma. Surgical resection represents the mainstay of curative treatment, with minimally invasive approaches being increasingly utilized. Despite good surgical outcomes, most patients suffer from disease recurrence and eventually succumb to their disease. Effective adjuvant treatments are therefore needed. For unresectable disease hepatic artery utilization techniques are becoming more widely used. New treatments for non metastatic disease such as proton beam therapy (PBT) are also emerging. Systemic chemotherapy is also changing and targeted biologic agents are being added to conventional chemotherapeutic agents.

Epidemiology and surgical management of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary malignancy arising from the epithelial cells of the intrahepatic bile ducts. The increased incidence of ICC worldwide may reflect both a true increase and the earlier detection of the disease. Despite the advances in modern surgical care, the curative chance for ICC remained suboptimal: tumor-free margins are hard to achieve due to tumor locations, and technical challenges and recurrence, either local or distant, may hamper the resectability in a large number of patients. Lymph node involvement and vascular invasions are considered negative predictive factors for survival of ICC patients. This review discusses the epidemiology, risk factors and surgical management of ICCs, and mainly focuses on outcomes and factors associated with surgical treatment.

Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma

Data on outcomes following surgical management of intrahepatic cholangiocarcinoma (ICC) are limited. The incidence of ICC is increasing and it has a poor prognosis. No consensus has been reached regarding the optimal treatment modalities. To systematically review and synthesize the available evidence regarding treatment and prognosis in patients with ICC. The PubMed database was searched for relevant articles published between January 1, 2000, and April 1, 2013. Only studies assessing predictors of survival or recurrence in patients undergoing curative-intent surgical treatment of ICC were included. Small series, studies reporting on mixed types of cholangiocarcinoma, or exclusively on hepatolithiasis-associated cholangiocarcinoma, and those published in a language other than English, French, German, Italian, or Greek, were excluded. Fifty-seven of 960 articles were therefore analyzed. Data on preoperative, intraoperative, and postoperative variables were extracted by 3 independent reviewers. Multiple studies reporting on the same population were excluded. Data were pooled using a random-effects model. We hypothesized that preoperative variables and tumor characteristics affect patient survival. The outcomes of the study were overall survival and recurrence-free survival. The hypothesis was formulated before data collection. Fifty-seven studies (4756 patients) were included in the review. Median patient age ranged from 49 to 67 years, and 57% were male. Most patients had a solitary (69%), large (median size, 4.5-8.0 cm) tumor of the mass-forming type (86%). Approximately one-third of the patients had lymph node metastasis (34%) or vascular (38%), perineural (29%), or biliary invasion (29%). Most underwent a major hepatectomy (82%), often accompanied by lymphadenectomy (67%) and sometimes by extrahepatic bile duct resection (23%). Median and 5-year overall survival (OS) generally were approximately 28 months (range, 9-53 months) and 30% (range, 5%-56%), respectively; factors predicting shorter OS included large tumor size, multiple tumors, lymph node metastasis, and vascular invasion. Adjuvant chemotherapy or radiotherapy did not appear to be beneficial. Seven studies (2132 patients) provided data for the meta-analysis. Factors associated with shorter OS included older age (pooled hazard ratio, 1.10; 95% CI, 1.03-1.17), larger tumor size (1.09; 1.02-1.16), presence of multiple tumors (1.70; 1.43-2.02), lymph node metastasis (2.09; 1.80-2.43), vascular invasion (1.87; 1.44-2.42), and poor tumor differentiation (1.41; 1.17-1.71). The prognosis of ICC is dictated mainly by tumor factors. Future research could focus on the usefulness of adjuvant treatment as well as other multidisciplinary treatment modalities.

Intrahepatic Cholangiocarcinoma: An International Multi-Institutional Analysis of Prognostic Factors and Lymph Node Assessment

To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival. From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20; P < .001), multiple lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P < .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0; P < .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34). Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.

Intrahepatic cholangiocarcinoma: An international, multi-institutional analysis of prognostic factors and lymph node assessment.

162 Background: Intrahepatic cholangiocarcinoma (ICC) is a rare and poorly understood primary liver cancer. The role of routine lymphadenectomy at the time of surgical resection remains poorly defined. We sought to identify factors associated with outcome following surgical management of ICC and examine the impact of lymph node (LN) assessment on survival. Methods: 411 patients who underwent curative intent surgery for ICC between 1973-2010 were identified from an international multi-institutional database. Clinical and pathologic data were evaluated using uni- and multivariate analyses. Results: Median tumor size was 6.5 cm. Most patients had a solitary tumor (55%) and no evidence of vascular invasion (64%). Resection involved ≥hemi-hepatectomy (74%) and margin status was R0 (82%). Overall median survival was 28 months and 5-year survival was 32%. Factors associated with adverse prognosis included positive margin status (HR=3.11; p&lt;0.001), multiple lesions (HR=2.16; p=0.007) and vascular invasion (HR=2.13; p=0.01). Tumor size was not a prognostic factor (HR=1.05; p=0.08). Lymphadenectomy was performed in 233 (57%) patients; 87 (37%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0 39 months vs. N1 21 months; p=0.02). Preoperative factors such as tumor size, number, and morphologic subtype did not predict presence of LN metastasis (all p&gt;0.05); however, vascular invasion did (OR=2.24; p=0.003). Conclusions: While tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. Presence of LN metastasis cannot be predicted using preoperative tumor features. Lymphadenectomy should be routinely performed for ICC as up to one-quarter of patients will have LN metastasis. No significant financial relationships to disclose.

Fifteen-year, single-center experience with the surgical management of intrahepatic cholangiocarcinoma: Operative results and long-term outcome

Limited data exist regarding the role of extended liver resection for the management of intrahepatic cholangiocarcinoma (ICC), most of which derive from small single-center or larger multicenter series. In the current report, we present our experience with the surgical management of ICC, analyze operative results, and investigate prognostic factors in resected patients. A total of 72 patients underwent operative exploration for ICC between 1991 and 2005; 54 patients were resected, and 18 patients were deemed unresectable based on intraoperative findings. Demographics, pathology, anatomic characteristics, operative results, and survival were analyzed. The resectability rate was 71%, with negative margins achieved in 78% of the resected patients. Extended liver resections were performed in 24 (44%) of the 72 patients. Perioperative mortality after resection was 7%, with 11% morbidity. The 1-, 3- and 5-year survival rates after resection were 80%, 49% and 25%, respectively, and were significantly greater than for patients with unresectable disease (P < .001). R1 liver resections conferred increased 5-year survival compared with patients deemed unresectable (P = .03). None of the factors evaluated proved to be independent prognostic factors on multivariate analysis. R0 resection of ICC provides the best chance for prolonged survival, whereas R1 resection appears to be superior to nonoperative treatment. Declining operative mortality as a result of improved intraoperative and perioperative care justifies the performance of extended liver resections in these patients, although benefit has to be evaluated with respect to nodal involvement.

Surgical Management of Intrahepatic Cholangiocarcinoma - A Population-Based Study

Cholangiocarcinoma (CCA) is associated with poor survival and therapeutic nihilism. To date, there has not been an examination of the surgical management of CCA at a population level. Using the Surveillance, Epidemiology and End Results (SEER) database, we identified all patients with intrahepatic CCA diagnosed between 1988 and 2003. Tumors categorized as a single, unilobar lesion with no evidence of vascular invasion were defined as localized. It was then determined whether patients received cancer directed surgery (CDS). Multivariable logistic regression was used to evaluate factors associated with CDS in patients with localized disease. The influence of CDS on overall survival (OS) was evaluated using Kaplan-Meier curves and Cox proportional hazards modeling. Only 446 (12%) of 3,756 patients with intrahepatic CCA underwent CDS. On multivariable analysis, non-Klatskin tumor (p < 0.01) and younger age (p = 0.02) was associated with CDS. Localized disease was strongly associated with CDS (p < 0.01); however, only 91 (37%) of these 248 patients underwent CDS. Of patients with localized disease, those who had CDS had significantly better survival than those who did not (p < 0.01), with median overall survival (OS) of 44 months versus 8 months, and five-year OS of 42% versus 4%, respectively. Patients with localized CCA who are selected for CDS are strongly associated with improved survival, with rates approaching that found in single institution studies. However, many patients with localized tumors do not receive potentially curative cancer-directed surgery. Further study is warranted to address the barriers to the delivery of appropriate care to these patients.

Surgical management of intrahepatic cholangiocarcinoma: a 31-year experience.

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant primary tumor of the liver. It is, though, a rare tumor and little is known regarding its natural history, clinicopathologic characteristics, or the outcomes of surgical therapy. We reviewed the experience of 61 patients with ICC seen by the surgical service at the Mayo Clinic over a 31-year period. Patient demographic and clinical data were recorded, as were survival statistics. Pathologic data were also obtained and patients stratified according to the TNM classification. Twenty-eight patients were resected for cure. Overall, 45 patients died of ICC. Of the patients resected for cure, survival at 3 years was 60%. No pathologic condition was found to be associated with the development of ICC. Overall survival correlated with stage of the tumor. Among patients resected for cure, stage did not correlate with survival. Prognosis for patients with ICC remains poor; resection, though, appears to prolong survival.