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.     

Characteristics of intrahepatic cholangiocarcinoma in patients with hepatitis B virus infection: clinicopathologic study of resected tumours

Recent efforts suggest an aetiological role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC). The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcomes of patients with HBV‐associated ICC. All patients with chronic HBV infection were identified from a database of patients with ICC that underwent surgical resection between 1 January 2005 and 31 December 2006. Their clinicopathologic and survival characteristics were compared with ICC patients without chronic HBV infection. The age of the HBV‐associated ICC patients tend to be younger than that of ICC patients without chronic HBV infection. HBV‐associated ICC patients tend to have higher abnormal α‐fetoprotein levels and lower abnormal serum carbohydrate antigen19‐9 (CA19‐9), r‐glutamyltransferase (r‐GT) and alkaline phosphatase levels. The pathologic features of the resected specimens revealed that HBV‐associated ICC patients tended to be of the mass‐forming type have a lower prevalence of lymphatic involvement and poorer tumour differentiation, and a higher prevalence of capsule formation and liver cirrhosis. Patients with HBV‐associated ICC had a significantly better survival than patients without chronic HBV infection. The clinicopathological features of HBV‐associated ICC patients showed significant differences from ICC patients without HBV infection. These tumours are characterized by the mass‐forming growth pattern and appeared to have a more favourable prognosis.     

Analysis of metastasis and survival between extrahepatic and intrahepatic cholangiocarcinoma: A large population-based study

To date, extrahepatic cholangiocarcinoma (ECCA) and intrahepatic cholangiocarcinoma (ICCA) have rarely been compared; therefore, we attempted to learn more about the rates of metastasis and survival in both ICCA and ECCA.Data of patients in the SEER database diagnosed with ICCA or ECCA were extracted to analyse the rate of metastasis and survival. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for metastasis. Propensity score matching (PSM) was used to compare survival rates between ECCA and ICCA.Data from a total of 15,751 patients diagnosed with ICCA or ECCA were extracted to analyse the rate of metastasis. Metastasis was more common in ECCA than ICCA (42.62% vs. 31.46%, P < .05), while ICCA in the T1 stage had a lower rate of metastasis (25.35% vs. 30.61%, P < .05). Age, pathology grade, tumour size, lymph node metastasis and T stage were independent risk factors for metastasis in both ECCA and ICCA. There was an inverse correlation between age and metastasis in both ICCA and ECCA. Moreover, PSM demonstrated that patients with ECCA had a better prognosis than patients with ICCA. Patients with ICCA in the T1 stage had better survival than those with ECCA in the T1 stage.Our study was the first to compare the rates of metastasis and survival between ECCA and ICCA. We observed an inverse association between age and metastasis, that patients with ECCA had a better prognosis than patients with ICCA, and that patients with ECCA in the T1 stage had worse survival than patients with ICCA in the T1 stage.     

Conditional recurrence analysis of intrahepatic cholangiocarcinoma: Changes in recurrence rate and survival after recurrence resection by disease-free interval

Aim

The prognosis of patients with resected intrahepatic cholangiocarcinoma (ICC) is still unsatisfactory, with a high recurrence rate. We aimed to evaluate risks of recurrence changing over time and the survival benefit of resection for recurrent ICC.

Methods

This study included patients who underwent hepatectomy for ICC during 1995–2020. Risk factors for recurrence-free survival (RFS) in patients undergoing initial resection and overall survival (OS) in patients who developed recurrence after initial resection were analyzed. Conditional cumulative incidence of recurrence was assessed.

Results

A total of 169 patients were included in the study and 114 patients (67.5%) developed recurrence. Cumulative analyses showed that the 5-year recurrence rate was 69.3% at the time of initial resection but decreased to 24.8% in patients free from recurrence at 2 years after initial resection and 2.6% in patients free from recurrence at 4 years. Re-resection was carried out in 26 (22.8%) of 114 patients who developed recurrence. Multivariable Cox proportional hazards model analysis indicated re-resection (hazard ratio [HR] 0.19; 95% confidence interval [CI] 0.11–0.40, p < 0.001), microvascular invasion (MVI) (HR 2.39; 95% CI 1.05–5.40, p = 0.037), and disease-free interval (months) (HR 0.97; 95% CI 0.95–1.00, p = 0.067) were significantly associated with longer OS after recurrence.

Conclusions

Although the rate of recurrence remains high, conditional cumulative recurrence rate analysis showed that the rate of recurrence decreased by disease-free interval. Resection of recurrent ICC was associated with improved OS, particularly among patients with longer disease-free interval and absence of MVI after initial hepatectomy.     

Resection of intrahepatic cholangiocarcinoma: a Western experience

We analyzed the results of an aggressive surgical approach to intrahepatic cholangiocarcinoma. Between 1990 and 1997, 30 of 42 patients with intrahepatic cholangiocarcinoma underwent resection with curative intent. Mean tumor size was 10 ± 5 cm, and the tumors were classified as TNM type III, IVa, and IVb in 63%, 34%, and 3% of the patients, respectively. All patients underwent hepaticoduodenal lymphadenectomy. Fifteen patients received adjuvant radio- and chemotherapy. The overall survival rates at 1, 2, and 3 years were 86%, 63%, and 22%, respectively, and the median survival time was 28 months. Tumor recurrence was the main cause of death. Three patients survived for more than 5 years, including 2 patients with no evidence of recurrence. Factors influencing survival were: presence of satellite nodules (P = 0.007) and lymph node invasion (P = 0.05). The width of the resection margin and the use of an adjuvant therapy had no impact on survival. Complete surgical resection may offer a chance for long-term survival in selected patients and may improve the quality of life of patients with more advanced disease.     

Recurrent intrahepatic cholangiocarcinoma: single-center experience using repeated hepatectomy and radiofrequency ablation

Background

Intrahepatic cholangiocarcinoma (IHC) is a rare liver malignancy with a rising incidence worldwide. Since no standard treatment has been established so far, the aim of this study was to assess the safety and efficacy of repeated liver resection and/or radiofrequency ablation (RFA) in selected cases with recurrent IHC.

Patients and methods

The outcome of 13 patients who had been treated at least once for recurrent IHC by repeated liver resection and/or RFA was retrospectively analyzed. A total of 12 repeated liver resections and 8 radiofrequency ablations were performed in these patients between 2002 and 2008.

Results

After a median follow-up period of 28 months after primary liver resection (12–69 months), seven patients (54%) are still alive and three of these patients (23% of the entire cohort) are regarded as disease-free. The median survival for all patients was 51 months (12–69 months). One- and three-year survival after primary surgery was 92 and 52%, respectively, with an overall complication rate of 7.6%.

Conclusion

According to the present data, repeated liver resection and radiofrequency ablation are feasible in select patients with recurrent IHC. Both procedures can be regarded as safe and might lead to a prolongation of patient survival.     

Extended resection for intrahepatic cholangiocarcinoma in Japan

To elucidate surgical outcome after extended sugery for intrahepatic cholangiocarcinoma (ICC), we retrospectively allocated 83 patients who had undergone resection to a standard surgery group (n = 56), in which the patients had undergone hepatectomy alone or hepatectomy with bile duct resection, and an extended surgery group (n = 27), in which the patients had undergone the standard operation combined with vessel resection and/or pancreatectomy. The incidence of mass-forming plus periductal-infiltrating type lesions (P = 0.0129), lymph node metastasis (P = 0.0005), noncurative resection (P < 0.0001), mortality within 30 days and within 1 year after surgery (P = 0.0392,P = 0.0010), local recurrence (P = 0.0439), and peritoneal disseminated recurrence (P = 0.0241) was significantly higher in the extended surgery group than in the standard surgery group. The 5-year survival rate was significantly higher in the standard surgery group (30%) than in the extended surgery group (10%;P = 0.0061). The mortality rate within 1 year after extended surgery was significantly higher in the patients with infiltrating-spread type tumors than in the patients with non-infiltrating spread type tumors (P = 0.0032), and long-term (5-year) survival in the extended surgery group was significantly lower in the patients with infiltrating-spread type tumors than in the patients with non-infiltrating spread type tumors (P = 0.0253). We conclude that extended surgery does not improve the curative resection rate or the surgical outcome of ICC, and that extended surgery is not indicated for patients with infiltrating-spread type tumors.     

Extended hepatic resection and outcomes in intrahepatic cholangiocarcinoma

Background/Purpose. The aim of this report was to assess the outcome of aggressive surgical treatment for intrahepatic cholangiocarcinoma. Methods. From 1984 to 2001, we encountered 64 patients with intrahepatic cholangiocarcinoma. Of the 64 patients, 50 patients who underwent surgical resection with macroscopically curative objectives (78%) were reviewed for surgical procedures and outcomes. Results. Hemi- or more extensive hepatectomy was required for surgical resection in 40 patients (80%). Overall hospital morbidity and mortality rates were 50% and 8%, respectively. Curative resection with pathological free margins was achieved in 34 patients (68%). The 1-, 3-, and 5-year patient survival and tumor-free survival rates were 61.6%, 37.6%, and 22.5%; and 55%, 11%, and 11%, respectively. Among the macroscopic types, all 9 patients with intraductal growth type are alive 11–75 months after surgery. Survival rates among patients who had undergone curative resection were significantly better than those in patients who had undergone noncurative resection, even when patients with the intraductal growth type were excluded. Nodal status did not affect patient survival. Conclusions. Although the overall survival rate after surgical resection remains unsatisfactory, long-term survival is possible through extended surgical resection with pathological free margins. Patients with the intraductal growth type of intrahepatic cholangiocarcinoma might have the best chance of being cured by surgical treatment.     

Long-term survival and prognostic factors in the surgical treatment for intrahepatic cholangiocarcinoma

Background/Purpose. We retrospectively investigated the clinicopathologic features and outcome of 51 patients who underwent hepatectomy for intrahepatic cholangiocellular carcinoma (ICC) between 1991 and 2000, and we also analyzed the potential prognostic factors for long-term survival. Methods. There were 27 men and 24 women, with a mean age of 63.7 years. The surgical procedures were extended right or left hepatectomy (15 cases), right or left hepatectomy (19 cases), bisegmentectomy (3 cases), segmentectomy (7 cases), and subsegmentectomy (7 cases). The macroscopic findings of the excised tumor showed the mass-forming (MF) type (31 cases), the periductal-infiltrating (PI) type (13 cases), and the intraductal growth (IG) type (7 cases). Results. The patients with the MF type had a significantly higher incidence of lymph node metastasis (44.8%), as compared to those with the PI or IG type (15.0%). Two patients who died of hepatic failure during their hospital stay were excluded from this survival study. The cumulative 1-, 3-, and 5-year survival rates in 49 patients who underwent liver resection were 68.2%, 44.1%, and 32.4%, respectively. The patients with the IG type had the best outcome, followed by those with the PI type and MF type. The survival rates with or without lymph node metastasis were 9.0% and 60.6% at 3 years, and 9.0% and 42.9% at 5 years, respectively (P ? 0.05). The 1-, 2-, and 3-year survival rates in the MF-type patients with lymph node metastasis were 25.4%, 16.9%, and 0%, respectively. Eight patients (15.7%) survived for more than 5 years after operation. The gross appearance of these tumors was the PI type in 5 patients, the IG type in 2, and the IG + MF type in 1. Except for one case with the PI-type tumor, lymph node metastasis was not observed. All of the 5-year survivors underwent curative resection and none of them had any positive surgical margin. Conclusion. Analysis of the clinicopathologic factors influencing the survival after surgical treatment showed that the macroscopic type, surgical curability, lymph node metastasis, tumor size, and cancer-free margin were the most predictive.     

Extended right hepatic lobectomy with resection of inferior vena cava and portal vein for intrahepatic cholangiocarcinoma

We report a case of intrahepatic cholangiocarcinoma treated by extended right lobectomy and resection of the inferior vena cava (IVC) and portal vein. A 53-year-old man was referred with elevated serum alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GTP) levels on April 23, 1999. He was not jaundiced and did not have any symptoms. Endoscopic retrograde cholangiopancreatography (ERCP) revealed irregular strictures in both the anterior and posterior segmental ducts. Contrast-enhanced computed tomography (CT) scan demonstrated a low-density tumor with an unclear margin in the right lobe of the liver. The patient underwent extended right hepatic lobectomy and total caudate lobectomy. Partial resection of the IVC (6 cm) was performed under total hepatic vascular exclusion. The main portal trunk and left portal vein were resected and reconstructed with an end-to-end anastomosis. Macroscopically, a 5.0 × 5.0 × 4.5-cm periductal infiltrating-type tumor occupied the right hepatic parenchyma along the posterior and anterior segmental ducts. Histological examination revealed moderately differentiated tubular adenocarcinoma with marked perineural invasion. Lymph node metastasis was observed in the hepatoduodenal ligament and posterior surface of the pancreatic head. The resected margins of the common bile duct and left hepatic duct were free of tumor. The patient's postoperative course was uneventful, and he was discharged from hospital on the 28th postoperative day. Nine months after the operation, he suddenly developed obstructive jaundice, and died with recurrent disease. This is the first reported case of intrahepatic cholangiocarcinoma treated with major hepatectomy and resection of the IVC and portal vein except ex situ procedure. This aggressive surgical approach may offer hope for patients with intrahepatic cholangiocarcinoma involving the IVC.     

Patient with advanced intrahepatic cholangiocarcinoma with long-term survival successfully treated with a combination of surgery and chemotherapy

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare malignancy arising from the biliary epithelium. Prognosis is typically poor. Currently, aggressive surgical resection is the only treatment modality that offers patients any chance of long-term survival. Here, we present the case of a 57-year-old woman in whom we diagnosed ICC, with the tumor occupying the entire left and caudate hepatic lobes and daughter nodules in the right lobe. She underwent hepatectomy of segments I to VI, combined with intraoperative microwave coagulation therapy for nodules in the residual liver. Three months after the surgical resection, she had recurrence of the disease. The patient subsequently received weekly intraarterial chemotherapy with irinotecan (CPT-11), and a partial response was observed which persisted for 18 months. Subsequent computed tomography revealed the regrowth of three tumors, and she therefore underwent a repeat resection 24 months after the first surgical operation. In postoperative-month (POM) 32, she received systemic chemotherapy with tegatur/gimeracil/oteracil potassium (S-1)/cisplatin for multiple small nodules in her lung. Following three cycles of chemotherapy with a stable disease response, partial resections of the lung were performed. Third and fourth hepatectomies were performed in POMs 46 and 59, respectively. Five years and 5 months after the first hepatectomy, she is alive with small lesions in her lung. This multimodal approach may be effective for ICC.     

Liver transplantation in patients with incidental hepatocellular carcinoma/cholangiocarcinoma and intrahepatic cholangiocarcinoma:a single-center experience

BACKGROUND: Reports of liver transplantation (LT) in pa-tients with mixed hepatocellular carcinoma/cholangiocarci-noma (HCC/CC) and intrahepatic cholangiocarcinoma (ICC) are modest and have been mostly retrospective after patho-logical categorization in the setting of presumed HCC. Some studies suggest that patients undergoing LT with small and unifocal ICC or mixed HCC/CC can achieve about 40%-60%5-year post-transplant survival. The study aimed to report our experience in patients undergoing LT with explant pathology revealing HCC/CC and ICC.METHODS: From a prospectively maintained database, we performed cohort analysis. We identified 13 patients who un-derwent LT with explant pathology revealing HCC/CC or ICC. RESULTS: The observed recurrence rate post-LT was 31%(4/13) and overall survival was 85%, 51%, and 51% at 1, 3 and 5 years, respectively. Disease-free survival was 68%, 51%, and 41% at 1, 3 and 5 years, respectively. In our cohort, four pa-tients would have qualified for exception points based on up-dated HCC Organ Procurement and Transplantation Network imaging guidelines.CONCLUSIONS: Lesions which lack complete imaging char-acteristics of HCC may warrant pre-LT biopsy to fully eluci-date their pathology. Identified patients with early HCC/CC or ICC may benefit from LT if unresectable. Additionally, incor-porating adjunctive perioperative therapies such as in the case of patients undergoing LT with hilar cholangiocarcinoma may improve outcomes but this warrants further investigation.     

Risk factors of intrahepatic cholangiocarcinoma in patients with hepatolithiasis:a case-control study

BACKGROUND:Why 3.3% to 10% of all patients with hepatolithiasis develop intrahepatic cholangiocarcinoma (ICC) remains unknown.We carried out a hospital-based case-control study to identify risk factors for the development of ICC in patients with hepatolithiasis in China.METHODS:Eighty-seven patients with pathologically diagnosed hepatolithiasis associated with ICC and 228 with hepatolithiasis alone matched by sex,age (±2 years),hospital admittance and place of residence were interviewed during the period of...     

Photodynamic therapy is associated with an improvement in survival in patients with irresectable hilar cholangiocarcinoma

Background:

The majority of patients with hilar cholangiocarcinoma have irresectable disease and require palliation with biliary stenting to alleviate symptoms and prevent biliary sepsis. Chemotherapy and radiotherapy have proved ineffective, but recent studies suggest photodynamic therapy (PDT) may improve the outlook for these patients. This prospective clinical cohort study has evaluated the efficacy of radical curative surgery, standard palliative therapy (stent ± chemotherapy) and a novel palliative therapy (stent ± Photofrin-PDT) in 50 consecutive patients treated for hilar cholangiocarcinoma over a 5-year period.

Methods:

Between January 2002 and December 2006, 50 patients with hilar cholangiocarcinoma were evaluated for treatment. Ten patients were considered suitable for curative resection (Cohort 1). Forty patients with irresectable disease were stratified into Cohort 2 – Stent ± chemotherapy (n= 17); and Cohort 3 – Stent ± PDT (n= 23). Prospective follow-up in all patients and data collected for morbidity, mortality and overall patient survival.

Results:

The median age was 68 years [range 44–83]. Positive cytology/histology was obtained in 28/50 (56%). One death in Cohort 1 occurred at 145 days after surgical resection. No treatment related-deaths occurred in Cohort 2 or 3, chemotherapy-induced morbidity in three patients in cohort 2, PDT-induced morbidity in 11 patients in cohort 3. Actual 1-year survival was 80%, 12% and 75% in Cohorts 1, 2 and 3, respectively. Mean survival after resection was 1278 days (median survival not reached). Mean and median survival was 173 and 169 days, respectively, in Cohort 2; and 512 and 425 days in Cohort 3. Patient survival was significantly longer in cohorts 1 and 3 (P < 0.0001; Log rank test).

Conclusion:

This prospective clinical cohort study has demonstrated that radical surgery and palliative Photofrin-PDT are associated with an increased survival in patients with hilar cholangiocarcinoma.     

Surgical treatment of intrahepatic cholangiocarcinoma: outcomes and predictive factors

Background

Intrahepatic cholangiocarcinoma (ICC) remains a rare tumour, although its incidence is increasing. Surgical resection is the mainstay of treatment. Published data regarding prognostic factors and optimal patient selection for resection are scant. We sought to determine the clinicopathologic characteristics of resectable ICC and outcomes following surgical treatment.

Methods

We reviewed prospectively collected clinical data including patient, pathologic and operative details. Survival and recurrence outcomes were analysed using Cox hazard models and the Kaplan–Meier method.

Results

We identified 31 surgically treated patients. Their 3-year overall survival rate (OS) was 40.1%; median follow-up was 16.2 months (range: 0.2–86.9 months). R0 resection was associated with significantly improved OS compared with R1/R2 resection (3-year OS was 68.6% in R0 vs. 24.0% in R1/R2; P = 0.042). The postoperative complication rate was 58.1%. Two patients died of postoperative liver failure within 30 days. Preoperative hypoalbuminaemia was significantly associated with worse survival.

Conclusions

Surgical therapy for ICC is associated with longterm survival in the subset of nutritionally replete patients in whom an R0 resection can be achieved. Surgical mortality is significant in patients undergoing extended resection. The margin involvement rate is high and surgeons should consider the infiltrative nature of the disease in operative planning.     

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case–control study in China

Background/Aims: The risk factors for cholangiocarcinoma are incompletely defined in China, especially for intrahepatic cholangiocarcinoma (ICC). We evaluated the risk factors for both ICC and extrahepatic cholangiocarcinoma (ECC). Methods: A case–control study in which cases were cholangiocarcinoma patients referred to Peking Union Medical College Hospital (PUMCH) between 1998 and 2008 and controls were healthy individuals. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on liver disease, family history, diabetes, smoking and drinking were collected by a retrospective review of the patients' records and health examination reports or by interview. Results: A total of 190 patients (61 ICC; 129 ECC) and 380 age‐ and sex‐matched controls were enrolled. HBsAg (P<0.001) and anti‐HBc without HBsAg (P=0.001) were significantly related to ICC. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were 18.1 (95% CI: 7.5–44.0) and 3.6 (95% CI: 1.7–7.6) respectively. Diabetes mellitus (P=0.007), cholecystolithiasis (P=0.004) and previous cholecystectomy (P<0.001) were significantly associated with ECC. The prevalence of cirrhosis was higher in ICC than that in ECC (P<0.001). Furthermore, on excluding the ICC patients with cirrhosis, ICC patients showed significant independent associations with HBsAg (OR: 7.3; 95% CI: 3.1–17.2) and anti‐HBc without HBsAg (OR: 2.4; 95% CI: 1.1–5.2). Conclusion: Cirrhosis and chronic hepatitis B virus infection are risk factors for ICC, while cholecystolithiasis, diabetes and previous cholecystectomy are risk factors for ECC.     

腹腔镜与开腹肝切除术治疗肝内胆管细胞癌患者疗效与安全性研究

目的 比较腹腔镜肝切除术(LLR)与开腹肝切除术(OLR)治疗肝内胆管细胞癌(ICC)患者的疗效与安全性。方法 2015年1月～2018年6月我院诊治的ICC患者74例,其中32例接受LLR手术,另42例接受OLR手术。随访3年。结果 两组年龄、性别、腹部手术史、血清CA19-9和CEA水平、神经侵犯、微血管侵犯、肿瘤低分化、肿瘤直径和淋巴结肿大等差异无统计学意义(P>0.05);LLR组术中失血量、手术切口长度、肝门阻断、术后住院日、输血和胃肠道功能恢复时间分别为325(250,475)ml、5(3.5,6.5)cm、9例(28.1%)、7(5,12)d、2例(6.2%)和2(2,4)d,与OLR组【分别为500(375,750)ml、20.5(17.0,25.0)cm、31例(73.8%)、10(7,15)d、7例(16.7%)和4(3,6)d】比,差异具有统计学意义(P<0.05),而两组1 a生存率(81.2%对76.2%)和3 a生存率(46.8%对33.3%)无显著性差异(P>0.05);术后,两组均未发生严重并发症。结论 在当前情况下,采取OLR或LLR...