Surgery For Intrahepatic Cholangiocarcinoma Research Articles

Probability of lymph node metastases in patients undergoing adequate lymphadenectomy during surgery for intrahepatic cholangiocarcinoma: a retrospective multicenter study

Probability of lymph node metastases in patients undergoing adequate lymphadenectomy during surgery for intrahepatic cholangiocarcinoma: a retrospective multicenter study

Surgical strategy for incidental intrahepatic cholangiocarcinoma in terms of lymph node dissection

BackgroundAlthough many guidelines recommend performing lymph node dissection (LND) during surgery for intrahepatic cholangiocarcinoma (ICC), there is no evidence for patients with incidentally detected ICC who did not undergo LND. This study aimed to identify the role of LND in patients with incidental ICC. MethodsThe data from 284 patients who had undergone radical surgery for ICC from 2000 to 2020 were retrospectively reviewed. The enrolled patients were divided into 3 groups according to their T stage (T1 vs T2 vs T3 + 4). Moreover, the patients of each T group were divided into 3 groups according to their nodal status (N0 vs N1 vs Nx) and their survival outcomes were compared. ResultsSurvival outcomes of Nx group were statistically similar to that of N0 group in T1 stage (Nx vs N0: disease-free survival [DFS] [months], 129.0 [75.6–182.4] vs 125.0 [65.7–184.3], P = .948; overall survival [OS] [months], 175.0 [153.9–196.1] vs 173.0 [109.0–237.0], P = .443). In contrast, survival outcomes of Nx group in the other T stage (T2 and T3 + 4) were poorer than that of N0 group and were better than that of N1 group. In addition, in the Nx subgroup analysis according to T stage, T1 group showed significantly better survival outcomes than the other groups (T1 vs T2 vs T3 + 4: DFS [months], 129.0 [75.9–182.1] vs 16.0 [9.8–22.2] vs 13.0 [0.3–25.7], P < .001; OS [months], 175.0 [153.9–196.1] vs 53.0 [30.8–75.2] vs 37.0 [17.6–56.4], P < .001). ConclusionPatients with ICC incidentally diagnosed as having T2 or above T stage may consider additional LND.

ASO Visual Abstract: Minimally Invasive Approach Provides Oncological Benefit in Patients with High Risk of Very Early Recurrence (VER) After Surgery for Intrahepatic Cholangiocarcinoma (iCCA).

ASO Visual Abstract: Minimally Invasive Approach Provides Oncological Benefit in Patients with High Risk of Very Early Recurrence (VER) After Surgery for Intrahepatic Cholangiocarcinoma (iCCA).

Analysis of Preoperative Risk Factors for Early Recurrence in Patients After Hepatic Resection for Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis even after curative-intent hepatic resection due to a high recurrence rate. The aim of this study was to investigate preoperative risk factors for early recurrence after surgery for ICC, which may help to identify patients who need preoperative chemotherapy. We retrospectively analyzed 51 patients who had undergone primary surgery for ICC. We investigated the association of preoperative clinical variables with recurrence within 1year after resection for ICC. We then created a high-risk ICC score using the identified preoperative factors and investigated the association of the score with disease-free and overall survival. Recurrence within 1year after surgery for ICC was significantly associated with poor overall survival (P < .01). In the multivariate analysis, preoperative tumor size > 5cm (P = .03) and elevated C-reactive protein-to-albumin ratio (CAR) (P = .04) were significantly associated with recurrence within 1year after surgery. A high-risk ICC score of 2 was associated with poor disease-free survival (P < .01) and overall survival (P = .02) compared with a score of 0 or 1. Our high-risk ICC score, combining preoperative tumor size and CAR, can be an indicator of early recurrence and poor survival in patients after hepatic resection for ICC. Our findings may provide better preoperative risk stratification of patients with ICC, and the high-risk ICC patients may benefit from preoperative therapy.

Minimally Invasive Approach Provides Oncological Benefit in Patients with High Risk of Very Early Recurrence (VER) After Surgery for Intrahepatic Cholangiocarcinoma (iCCA).

Surgery for intrahepatic cholangiocarcinoma (iCCA) is jeopardized by significant risk of early recurrence (≤ 6 months). The aim of the present study is to analyze the oncological benefit provided by laparoscopic over open approach for iCCA in patients with high risk of very early recurrence (VER). A total of 532 liver resections (LR) were performed for iCCA [265 by minimally invasive surgery (MIS) and 267 with open approach, matched through a 1:1 propensity score] and stratified using the postoperative prediction model of VER. Outcomes were compared between open and laparoscopic approaches, specifically evaluating oncological benefit. The percentage of patients with high risk of VER was similar (32.7% in the laparoscopic group and 35.3% in the open group, pNS). The number of retrieved nodes as well as the rate and depth of negative resection margins were comparable between laparoscopic and open. The surgery-adjuvant treatment interval was shorter in laparoscopic patients in the overall series, as well in the subgroup of high risk of VER. The rate of patients starting adjuvant treatments within 2 months from surgery was higher in laparoscopic group compared with open group. In VER high-risk group both disease-free survival (DFS) and overall survival (OS) were significantly improved in MIS compared with open group (p = 0.032 and p = 0.026, respectively). In patients with high risk of VER, laparoscopy translates into an advantage in terms of recurrence-free survival, likely related to lower biological impact of surgery, together with a shorter interval between surgery and start of adjuvant treatments, even allowing for a higher number of patients to start adjuvant therapies within 2 months from resection.

Minimally invasive approach provides oncological benefit in patients with high risk of very early recurrence (VER) after surgery for intrahepatic cholangiocarcinoma (iCCA): a propensity-score based, matched analysis

Minimally invasive approach provides oncological benefit in patients with high risk of very early recurrence (VER) after surgery for intrahepatic cholangiocarcinoma (iCCA): a propensity-score based, matched analysis

Body composition is associated with disease aetiology and prognosis in patients undergoing resection of intrahepatic cholangiocarcinoma.

Body composition alterations are frequent in patients with cancer or chronic liver disease, but their prognostic value remains unclear in many cancer entities. We investigated the impact of disease aetiology and body composition after surgery for intrahepatic cholangiocarcinoma (iCCA), a rare and understudied cancer entity in European and North American cohorts. Computer tomography-based assessment of body composition at the level of the third lumbar vertebra was performed in 173 patients undergoing curative-intent liver resection for iCCA at the Department of Surgery, Charité - Universitätsmedizin Berlin. Muscle mass and -composition as well as subcutaneous and visceral adipose tissue quantity were determined semi-automatically. (Secondary) sarcopenia, sarcopenic obesity, myosteatosis, visceral and subcutaneous obesity were correlated to clinicopathological data. Sarcopenia was associated with post-operative morbidity (intraoperative transfusions [p = 0.027], Clavien-Dindo ≥ IIIb complications [p = 0.030], post-operative comprehensive complication index, CCI [p < 0.001]). Inferior overall survival was noted in patients with myosteatosis (33 vs. 23 months, p = 0.020). Fifty-eight patients (34%) had metabolic (dysfunction)-associated fatty liver disease (MAFLD) and had a significantly higher incidence of sarcopenic (p = 0.006), visceral (p < 0.001) and subcutaneous obesity (p < 0.001). Patients with MAFLD had longer time-to-recurrence(median: 38 vs. 12 months, p = 0.025, log-rank test). Multivariable cox regression analysis confirmed only clinical, and not body, composition parameters (age > 65, fresh frozen plasma transfusions) as independently prognostic for overall survival. This study evidenced a high prevalence of MAFLD in iCCA, suggesting its potential contribution to disease aetiology. Alterations of muscle mass and adipose tissue were more frequent in patients with MAFLD.

Biomarkers for predicting the prognosis of intrahepatic cholangiocarcinoma: A retrospective single-center study.

The aim of this retrospective study was to investigate the association between preoperative serological and clinical indicators and postoperative recovery in patients who had undergone resection of intrahepatic cholangiocarcinoma (ICC). We collected data form the medical records of patients who underwent operations for the treatment of ICC at Qingdao University Affiliated Hospital from 2015 to 2021. We analyzed the data to explore the independent predictors of disease prognosis after surgery for ICC. By univariate analysis, we found that the following factors were significantly associated with overall survival and tumor-free survival in patients with ICC: TNM stage; degree of vascular invasion; levels of hemoglobin, carcinoembryonic antigen, carbohydrate antigen 125, direct bilirubin, alkaline phosphatase, and albumin; prothrombin time; neutrophil to lymphocyte ratio; prothrombin time to albumin ratio; albumin to alkaline phosphatase ratio; albumin to gamma-glutamyl transferase ratio; prognostic nutrition Index, and incisional margin. However, only carbohydrate antigen 24-2 and glutamyl transpeptidase were correlated with overall survival in patients with ICC. However, only a positive history of biliary surgery was significantly associated with tumor-free survival in patients with ICC. Preoperative prothrombin time, vascular invasion, N-stage, incisal edge, and carcinoembryonic antigen levels may be simple predictors of disease progression in ICC after hepatectomy.

Minimally Invasive Approach Provides an Oncological Benefit in Patients with High Risk of Very Early Recurrence after Surgery for Intrahepatic Cholangiocarcinoma

Minimally Invasive Approach Provides an Oncological Benefit in Patients with High Risk of Very Early Recurrence after Surgery for Intrahepatic Cholangiocarcinoma

Patterns of Regional Lymph Node Recurrence after Surgery for Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma: A Retrospective Analysis in a Single Institution

<h3>Purpose/Objective(s)</h3> The overall incidence of cholangiocarcinoma (CCA) has increased progressively worldwide over decades. CCAs are highly aggressive, which renders a dismal prognosis with high recurrence rates after dissection and disappointing 5-year survival rate (7%-20%). Surgical resection remains the mainstay of potentially curative therapy for intrahepatic CCA (iCCA) or combined hepatocellular carcinoma (HCC)-CCA. Most patients develop recurrent disease after surgery and extrahepatic recurrence was found in 40% patients. Postoperative radiotherapy (RT) has been considered an adjuvant treatment modality. However, no consensus has been reached regarding to the clinical target volume (CTV) of RT. We aim to investigate the patterns of regional recurrence after surgery for iCCA and combined HCC-CCA to give insights on CTV delineation. <h3>Materials/Methods</h3> Medical records of iCCA and combined HCC-CCA patients who underwent surgery at Cancer Hospital of Chinese Academy of Medical Sciences between 2010 to 2019 were retrospectively reviewed. Patients were included in this study if they 1) had been pathologically diagnosed with iCCA or combined HCC-CCA; 2) underwent surgical resection; and 3) had been diagnosed with first recurrent event in regional LNs. Patients were excluded if they had adjuvant radiotherapy. All available follow-up imaging studies were thoroughly reviewed. Patterns of recurrence were categorized as local (intrahepatic), regional (regional LNs) and distant failure. Regional failures as first site of recurrence were further evaluated. <h3>Results</h3> A total of 53 patients were included in analysis, 42 of which had iCCA and 11 had combined HCC-CCA. The median age was 59 years (35-70) for all patients. The proportion of patients with history of hepatitis B and elevated AFP was higher in combined HCC-CCA group than in iCCA group. 67.9% patients underwent R0 resection and the median number of dissected LNs is 5 (0-31). Hepatic hilar is the most common recurrent region for both groups followed by portal vein-vena cava (high risk stations). Recurrence rates at left gastric, paracardial, diaphragmatic, common hepatic, celiac trunk and superior mesenteric artery are similar and moderate (medium risk stations). There is much less recurrence at other LN regions with likelihood less than 10% (low risk stations). A total of 20.8% patients had skip metastases. 13.2% patients had recurrence at medium risk stations without recurrence at high-risk stations and 7.6% patients had recurrence at high and low risk stations without recurrence at medium risk stations. A figure of 3-dimentional distribution of recurrent LNs was created. A standard patient was selected and all recurrent LNs were contoured on her CT images according to relationship between LNs and vessels. <h3>Conclusion</h3> This study created a LN recurrence map of surgically resected iCCA and combined HCC-CCA patients, which might be helpful for radiation oncologists in CT-guided delineation of postoperative CTV.

Application of Hazard Function to Investigate Recurrence of Intrahepatic Cholangiocarcinoma After Curative-Intent Liver Resection: A Novel Approach to Characterize Recurrence.

To investigate recurrence patterns after surgery for intrahepatic cholangiocarcinoma (ICC) relative to lymph node status, tumor extension, tumor burden score (TBS), and adjuvant chemotherapy. Patients who underwent curative-intent resection for ICC from 1990 to 2020 were enrolled from a multi-institutional database. The hazard function was applied to plot the hazard rates over time, with further stratification by T and N AJCC 8th edition categories, TBS, and adjuvant chemotherapy. A total of 1192 patients underwent curative-intent resection for ICC and 59.9% experienced recurrence. Overall, the peak of recurrence occurred at 6.6 months. Among patients with negative lymph nodes, the T4-category had a higher peak rate of recurrence (0.1199 at 10.2 months) compared with other T-categories, while high TBS had an earlier peak of recurrence (4.2 months) compared with lower TBS. Among patients with N1 disease, T2-T4 categories had multipeak patterns of recurrence with higher hazard rates during the first 3 years after surgery in comparison with T1-category, while patients with high TBS had an earlier (4.0 months) and higher hazard peak rate compared with lower TBS groups. The administration of adjuvant chemotherapy was associated with delayed hazard rates of recurrence for N1 (4 months) and NX (6 months) categories. The novel application of the hazard function to assess hazard rates and timing patterns of recurrence following resection for ICC demonstrated that recurrence varied based on T- and N-categories, as well as TBS. Hazard function-based recurrence data may be helpful to tailor counseling, surveillance, and adjuvant therapy recommendations.

The Effect of Lymph Node Dissection According to the Tumor Size in Surgery for Intrahepatic Cholangiocarcinoma

Introduction: Although surgical resection is considered as the treatment of choice for intrahepatic cholangiocarcinoma (IHCC), the role of lymph node dissection during hepatectomy is still under debate. The aim of this study was to evaluate the effect of lymph node dissection (LND) according to the size of the tumor. Method: The medical records of patients who underwent hepatectomy for IHCC between Aug 2004 to Dec 2020 were retrospectively reviewed. Excluding patients who underwent R1/R2 resection, 119 patients were enrolled in this study. Based on the maximal tumor size, patients were divided into two groups: small tumor group < 5cm (Group S, n=83) and large tumor group ≥ 5cm (Group L, n=36). The association of LND and survival rates was investigated in each group. Results: Eighty patients (67.2%) were male, and the others were female. Laparoscopic hepatectomy was done in 38 patients (31.9%). Although LND did not improve patient and disease-free survivals in Group L (p=0.356 and 0.217, respectively), it tended to improve disease-free survivals in Group S, which was statistically insignificant (5-year disease-free survival rates: 41.0% with LND, 27.8% without LND, p=0.091). Moreover, its effect was more definite in laparoscopic subgroup of Group S (5-year disease-free survival rates: 61.2% with LND, 20.3% without LND, p=0.049). However, the difference of patient survival rate did not achieve statistical significancy even in laparoscopic subgroup (p=0.199). Conclusions: LND might not be helpful on surgery for large IHCC. However, it should be positively considered in surgery for small IHCC < 5cm to decrease tumor recurrence.

Compelling Long-Term Results for Liver Resection in Early Cholangiocarcinoma.

Surgery for intrahepatic cholangiocarcinoma (iCCA) is associated with a high rate of recurrence even after complete resection. To achieve acceptable results, preoperative patient selection is crucial. Hence, we aimed to identify preoperative characteristics with prognostic value focusing on certain radiological features. Patients who underwent hepatectomy for iCCA between 2010 and 2020 at University Hospital, RWTH Aachen were included. Kaplan–Meier and Cox regressions were applied for survival analysis and associations of overall survival (OS) and recurrence-free survival (RFS) with clinical/radiological characteristics, respectively. Based on radiological features patients were stratified into three groups: single nodule ≤ 3 cm, single nodule > 3 cm, and ≥2 nodules. Analysis of 139 patients revealed a mean OS of 142 months for those with a single nodule ≤3 cm, median OS of 28 months with a single nodule >3 cm, and 19 months with ≥2 nodules, respectively. Multivariable analyses based on preoperative characteristics showed the radiological stratification to be independently associated with OS (HR (hazard ratio) = 4.25 (1 nodule, >3 cm), HR = 5.97 (≥2 nodules), p = 0.011), RFS (HR = 4.18 (1 nodule, >3 cm), and HR = 11.07 (≥2 nodules), p = 0.001). In conclusion, patients with single iCCA ≤3 cm show compelling OS and RFS. Basic radiological features (e.g., nodule size, number) are prognostic for patients undergoing surgery and useful in preoperative patient selection.

Can the Presence of Previous Malignant Disease Have Influence on Patients with Surgery for Intrahepatic Cholangiocarcinoma?

Can the Presence of Previous Malignant Disease Have Influence on Patients with Surgery for Intrahepatic Cholangiocarcinoma?

Performance of prognostic scores and staging systems in predicting long-term survival outcomes after surgery for intrahepatic cholangiocarcinoma.

We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center patient cohort. The overall (OS) and disease free survival (DFS) prognostic discriminatory ability of various commonly used models were assessed in a large retrospective cohort. Harrell's concordance index (c-index) was used to determine accuracy of model prediction. Among 1054 ICC patients, median OS was 37.7 months and 1-, 3-, and 5-year survival, were 78.8%, 51.5%, and 39.3%, respectively. Recurrence of disease occurred in 454 (43.0%) patients with a median DFS of 29.6 months. One-, 3- and 5- year DFS were 64.6%, 46.5 % and 44.4%, respectively. The prognostic models associated with the best OS prediction were the Wang nomogram (c-index 0.668) and the Nathan staging system (c-index 0.639). No model was proficient in predicting DFS. Only the Wang nomogram exceeded a c-index of 0.6 for DFS (c-index 0.602). The c-index for the AJCC staging system was 0.637 for OS and 0.582 for DFS. While the Wang nomogram had the best discriminatory ability relative to OS and DFS, no ICC staging system or nomogram demonstrated excellent prognostic discrimination. The AJCC staging for ICC performed reasonably, although its overall discrimination was only modest-to-good.

1025 - Surgery for Intrahepatic Cholangiocarcinoma with Multiples Nodules: Comparison of Single Tumor, Single Tumor with Satellites and Multifocal Tumors

1025 - Surgery for Intrahepatic Cholangiocarcinoma with Multiples Nodules: Comparison of Single Tumor, Single Tumor with Satellites and Multifocal Tumors

A Novel Biomarker-Based Preoperative Prognostic Grading System for Predicting Survival After Surgery for Intrahepatic Cholangiocarcinoma.

Although treatment strategies for intrahepatic cholangiocarcinoma (ICC) are shifting towards multidisciplinary approaches, preoperative radiographic methods for identifying patients requiring further therapy are unclear. This study was designed to establish a prognostic grading system using preoperatively available objective biomarkers. A novel preoperative prognostic grading system for predicting survival after surgery for ICC was developed from multivariate analysis of 134 ICC patients who underwent surgery between 1996 and 2015 using preoperatively available biomarkers. The median overall survival time and 3- and 5year survival rates were 33.3months, 48, and 38%, respectively. Of the preoperative biomarkers, the neutrophil-to-lymphocyte ratio (≥5), and C-reactive protein (≥5mg/L) and carbohydrate antigen 19-9 (≥500IU/mL) levels were independently associated with poor overall survival. Based on the presence of these factors, the preoperative prognostic grades were defined as follows: grade 1, no factor; grade 2, one factor; and grade 3, two or three factors. The median overall survival time and 3- and 5year survival rates of patients with grade 1 (70.3months, 66, and 53%, respectively) were higher than those of patients with grade 2 (23.4months, 37, and 30%, respectively; P=0.004) and grade 3 (8.8months, 5% both; 2 vs. 3, P<0.001). Multivariable analysis revealed that the preoperative prognostic grading system independently predicted survival after adjusting for known prognostic factors. A novel biomarker-based preoperative prognostic grading system for ICC significantly stratifies survival after surgery and may identify patients requiring further treatment.

Surgical treatment for intrahepatic cholangiocarcinoma.

Despite surgical treatment for intrahepatic cholangiocarcinoma (ICC) becoming more widely available, the prognosis after hepatic resection for ICC remains poor. Because ICC is relatively rare, the TNM staging system for ICC was finally established in the 2000s. Resection margin status and lymph node metastases are important prognostic factors after surgery for ICC; however, the true impact of wide resection margins or lymph node dissection on postoperative survival is unclear. Although adjuvant chemotherapy can improve the postoperative prognosis of patients with various types of cancer, no standard regimen has been developed for ICC. Over 50 % of patients suffer postoperative recurrence, even after curative resection, and no effective treatment for recurrent ICC has been established. Therefore, despite advances in imaging studies and hepatobiliary surgery, significant challenges remain in improving the prognosis of patients with ICC.

Intestinal obstruction caused by colonic metastasis from intrahepatic cholangiocarcinoma 6 years after removal of the primary tumor: report of a case

We report a case of intestinal obstruction caused by metastasis that manifested 6 years after surgery for intrahepatic cholangiocarcinoma (ICC). The patient, a 57-year-old man, had undergone resection of the hepatic left lobe, Spiegel lobe, and extrahepatic bile duct, following which histopathological examination had confirmed the diagnosis of ICC and that the resection margins were free from disease. There had been no signs of recurrence until an increase in the CA19-9 level was detected 6 years later. Colonoscopy revealed an ulcer-like lesion and stenosis at the level of the hepatic flexure. The patient was subsequently admitted to our hospital with abdominal pain and underwent right hemicolectomy with partial resection of hepatic segment V. Based on the immunohistological finding that the expression pattern of cytokeratins and mucins was consistent with ICC origin rather than colon cancer origin, we diagnosed colon metastasis from ICC.

Chirurgie radicale des cholangiocarcinomes périphériques

The aim of this retrospective study was to evaluate the results of surgical treatment of intrahepatic cholangiocarcinoma treated by the same team. Between 1988 and 2005, 75 patients underwent surgery for intrahepatic cholangiocarcinoma. There were 53 resections including three additional interventions for recurrence. Twenty-seven exploratory laparotomies showed non resectable tumors and two were followed by a liver transplantation at the beginning of the study. Major hepatectomy was performed in 85% of resections while hepatectic resection was extended to an adjacent organ in 40%. A lymphadenectomy was performed in 32 cases. Mortality was 7.8% (two massive pulmonary embolisms, one mutiple organ failure after transplantation and one post-operative peritonitis). Global morbidity was 47%. Resectability was 66%. In case of surgical resection, the median survival rate was 18 months versus 4 months without resection (p<0.001). Actuarial survival rates at 1 year, 3 years and 5 years were 69, 31 and 27% respectively. Positive nodes decreased the survival rate (13 months versus 20 months, p=0.01). A positive margin (R1 or R2 resection) did not significantly decrease the survival rate (18 months versus 15 months). In conclusion, intrahepatic cholangiocarcinoma is a tumor that often requires a major or an extended hepatectomy. Complete resection is an acceptable and reasonable goal, whatever the patient's age. This radical surgical approach can prolong survival. Palliative surgery is not an option if incomplete resection is predicted.