Professor Chen Minshan
[Cite This Article] Chen Minshan, Fu Yizhen. Local Treatment and Evaluation of Intrahepatic Cholangiocarcinoma[J]. Chinese Practical Surgery Magazine, 2020, 40(6):684-688.
Local Treatment and Evaluation of Intrahepatic Cholangiocarcinoma
Chen Minshan, Fu Yizhen
Chinese Practical Surgery Magazine, 2020, 40(6):684-688
Intrahepatic cholangiocarcinoma (ICC) is a rare and highly aggressive primary liver malignancy. Treatment options for ICC are limited, with surgical treatment being the only curative approach. Recent advancements in local treatment techniques, including ablation therapy, interventional therapy, and radiotherapy, have made significant progress. Local treatment can be integrated throughout the treatment process of ICC. For early-stage ICC patients who are not suitable for surgery, local treatment may offer a potential cure; for patients with advanced ICC, local treatment can reduce tumor burden, alleviate symptoms, extend survival, and even provide opportunities for surgical intervention. Additionally, adjuvant interventional or radiotherapy can reduce the risk of recurrence in patients undergoing curative surgery. Thus, local treatment is a crucial component of the multidisciplinary comprehensive treatment of ICC, benefiting patients.
Funding Project: National Key Research and Development Program (No.2018ZX10723204)
Author Affiliation: Department of Hepatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China
Corresponding Author: Chen Minshan, E-mail: [email protected]
ICC treatment options are limited, with surgical resection considered the only curative approach. However, many patients are diagnosed at locally advanced stages or with lymph node metastasis, with only 30%-40% of patients having the opportunity for surgical treatment [2-4]. Furthermore, postoperative recurrence and survival rates are not optimistic. Reports indicate that the recurrence rate after ICC surgery can be as high as 40%-80%, with a median disease-free survival time of only 26 months; ≤1/3 of patients survive >5 years after curative surgery [2-5]. Therefore, for patients who are not suitable for surgical resection or have lost the opportunity for surgery, it is particularly important to reduce tumor burden, alleviate symptoms, and extend survival through local treatment. Currently, the local treatment methods recommended by the European Association for the Study of the Liver mainly include ablation, interventional therapy, and radiotherapy [3].
1. Ablation Therapy for ICC
Radiofrequency ablation (RFA) operates on the principle of generating high temperatures around the ablation electrode through high-frequency currents, leading to coagulative necrosis of the tumor. RFA plays an important role as one of the curative methods for HCC, but research and reports on RFA for ICC are relatively rare. Kim et al. [7] reported the long-term follow-up outcomes of RFA treatment for 13 patients with newly diagnosed ICC, involving a total of 17 lesions. The results showed that 15 lesions with a diameter <5 cm achieved complete necrosis after a single ablation, with a median progression-free survival (PFS) of 32.2 months. The overall survival rates at 1, 3, and 5 years were 85%, 51%, and 15%, respectively, suggesting that RFA can achieve favorable treatment effects in early-stage ICC. A team from Peking University Cancer Hospital reported in 2012 the results of RFA treatment for 17 ICC patients (26 lesions), with a median PFS of 17 months and a 5-year overall survival rate of 28.9%. Further analysis showed that overall survival (OS) was related to tumor pathological grading, while PFS was associated with lymph node metastasis, tumor pathological differentiation, and the number of tumors [8]. A retrospective study in 2019 included 84 early to mid-stage ICC patients, making it the largest study of its kind. This study compared the efficacy of RFA and chemoradiotherapy in early-stage ICC patients who had tumor diameters <5 cm, AJCC stage I and II, and had not undergone surgery or interventional treatment. The results showed that the 5-year survival rate in the RFA treatment group was 17.6%, significantly better than the 3.8% in the chemoradiotherapy group. Subgroup analysis indicated that the survival benefit from RFA was only present in patients with AJCC stage I; there was no statistically significant difference in the 5-year survival rates between the two treatment modalities in patients with AJCC stage II, further highlighting the effectiveness of RFA in treating early-stage ICC [9].
In the case of recurrent ICC, a study by Kim et al. [10] reported on RFA treatment for 20 patients with recurrent ICC after curative resection, with an average tumor diameter of 1.9 cm (0.7-4.4 cm). The local tumor control rate at 1 year post-RFA was 93%, with overall survival rates at 1 year, 2 years, and 4 years being 70%, 60%, and 20%, respectively. However, one patient developed a liver abscess and another had biliary stricture post-RFA. A team from the Eastern Hepatobiliary Surgery Hospital compared the effects of thermal ablation and re-resection for recurrent ICC. The two groups were comparable in terms of age, liver function, tumor differentiation, size, and number. The results showed that the median PFS in the ablation group was 6.8 months, while in the re-resection group it was 9.1 months; median OS was 21.3 months and 20.3 months, respectively, with no statistically significant difference. However, subgroup analysis revealed that in patients with tumor diameters >3 cm, re-resection had better OS than ablation (P=0.037). In terms of adverse reactions, 46.9% of patients in the re-resection group experienced severe adverse reactions, compared to only 3.9% in the ablation group [11].
In addition to RFA, another ablation method, microwave ablation (MWA), has also been reported for use in ICC. Overall, its indications, efficacy, and adverse reactions are similar to those of RFA [12-13]. Currently, most reports on ablation therapy for ICC are single-center, retrospective studies, and there is significant bias among studies. Nonetheless, it can be observed that for early-stage ICC, especially those <3 cm, ablation therapy can achieve favorable local control rates and overall survival rates without significant adverse reactions, making it a potential alternative treatment for early-stage ICC patients who are unsuitable for surgery. However, due to the technical characteristics of ablation, its effectiveness is poor for tumors >5 cm or those near blood vessels, bile ducts, and liver capsules. Many ICC patients already have a significant tumor burden or vascular invasion at the time of diagnosis, which limits the large-scale application of ablation therapies like RFA in ICC, emphasizing the importance of early diagnosis and treatment of ICC. On the other hand, ICC cannot rely on imaging for clinical diagnosis; confirmation can only be achieved through histopathology. Performing a puncture biopsy on early-stage ICC patients before ablation increases the risk of bleeding and needle tract seeding. Conversely, if a biopsy is not performed, a definitive diagnosis cannot be made, creating a dilemma. Therefore, currently, RFA or MWA is only empirically applied to early-stage ICC patients who are unsuitable for surgical treatment based on their efficacy in HCC, and their exact efficacy and comparison with surgical resection need to be validated through large-scale clinical trials.
2. Interventional Therapy for ICC
Interventional therapies (IATs) mainly include transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and hepatic arterial infusion chemotherapy (HAIC). IATs are widely used in mid to late-stage unresectable HCC patients, based on the principle that HCC lesions are primarily supplied by the hepatic artery and have abundant blood supply, while ICC often presents a relatively poor blood supply state, leading to weaker control of ICC lesions compared to HCC [3]. Park et al. [14] reported on the efficacy of TACE treatment in 72 mid to late-stage unresectable ICC patients, using iodized oil embolization and injecting the drug cisplatin. The results showed that 23% of patients achieved partial response (PR) after TACE treatment, with a median OS of 12.2 months, significantly higher than the 3.3 months for patients receiving supportive therapy, indicating the efficacy and safety of TACE for mid to late-stage ICC. Interventional therapy also has certain advantages over systemic intravenous chemotherapy. According to a report by Li Wanci et al. [15], among 51 patients receiving interventional therapy, 11 achieved PR, and 4 patients achieved complete remission (CR) after sequential RFA treatment, with a median OS of 12.1 months in the interventional therapy group; while the median OS for patients receiving gemcitabine combined with oxaliplatin or mitomycin systemic chemotherapy was only 5.5 months (P<0.05). The main adverse reactions of interventional therapy include post-embolization syndrome (30%), liver function impairment (20%), and bone marrow suppression (10%). However, the reliability of this study’s conclusions is questionable, as the authors did not provide baseline data comparisons between the two groups. Wright et al. [16] further compared the effects of interventional and surgical resection treatments for multifocal ICC. Despite the interventional treatment group having a greater tumor burden, the median OS was 16 months, while the surgical resection group had a median survival time of 20 months, with no statistically significant difference (P=0.627). Further studies have indicated that HAIC is superior to TACE or surgical resection in terms of both tumor recurrence and overall survival, suggesting that in multifocal ICC patients with intrahepatic metastasis, interventional treatment, especially HAIC, may be a better option. TARE treatment for mid to late-stage ICC has also been studied, with median OS around 12 months [17-19], consistent with reports on TACE. Notably, a phase II clinical trial using intravenous chemotherapy combined with TARE for locally advanced ICC patients showed that among 41 patients receiving cisplatin combined with gemcitabine chemotherapy along with yttrium-90 microsphere embolization treatment, 17 achieved CR or PR, with a median PFS of 14 months and median OS of 22 months. Additionally, 9 patients had a reduced tumor burden and underwent R0 resection after treatment, with 2 patients undergoing liver transplantation. This offers new possibilities for the treatment of locally advanced ICC [20].
Interventional therapy can also be used as adjuvant treatment for high-risk patients post-surgery. The Eastern Hepatobiliary Hospital in China was the first to report the experience of using TACE for adjuvant treatment in ICC patients post-curative surgery. In this study, 53 patients received postoperative adjuvant TACE treatment, among whom 43.4% had microscopic vascular invasion (MVI), while only 20.8% of the 72 patients who did not receive adjuvant TACE had MVI. The results showed no significant difference in recurrence-free survival rates between the two groups, but adjuvant TACE treatment significantly extended the OS of patients with early recurrence (within 3 months) (P<0.01). The authors believed this was because iodized oil and chemotherapy drugs could not prevent tumor recurrence but could control tumor growth after recurrence [21]. The team later reported a similar study with a larger sample size [22]. After matching a series of confounding factors, it was found that postoperative adjuvant TACE treatment did not improve overall patient recurrence and survival outcomes. The authors further stratified all patients by risk level, with high-risk patient characteristics including larger tumor diameter, more tumors, higher rates of vascular invasion, and lymph node metastasis. In this group, the 1-year and 3-year postoperative recurrence rates for the TACE group were 45.2% and 85.7%, while the rates for the non-TACE group were 69.3% and 92.5%; the 1-year and 3-year survival rates for the TACE group were 61.3% and 28.3%, while the non-TACE group had 33.8% and 7.0%. In high-risk patients, adjuvant TACE treatment can significantly reduce the risk of recurrence and extend survival.
Thus, interventional therapy plays a significant role in the treatment of mid to late-stage ICC, demonstrating a notable advantage over supportive treatment or systemic chemotherapy without causing significant liver function deterioration or severe adverse reactions such as bone marrow suppression. Its role should be affirmed. For mid to late-stage ICC patients who have lost surgical opportunities, those carefully assessed and selected can benefit from interventional therapy. Due to the insidious nature and high invasiveness of ICC, most patients have already lost surgical opportunities by the time of diagnosis, so the treatment focus for mid to late-stage ICC is more on alleviating tumor burden and extending survival, in which interventional therapy can play an important role. Numerous clinical trials related to interventional therapy are currently underway, but due to limited case numbers, the enrollment periods for these trials are long, making it challenging to obtain higher-level evidence to confirm the effectiveness of interventional therapy in the short term. Furthermore, combination treatments centered around interventional therapy are also a direction for future exploration. For example, the combination of interventional and ablation therapies is still in the exploratory stage, and their exact efficacy has yet to be determined. Whether adjuvant interventional therapy post-curative surgery can genuinely benefit patients also requires more data support. Moreover, whether neoadjuvant interventional therapy can convert unresectable ICC into resectable ICC remains to be studied in depth.
3. Radiotherapy for ICC
Previous studies have considered ICC to belong to the adenocarcinoma type, which is relatively insensitive to radiotherapy; therefore, simple radiotherapy for unresectable tumors can only serve a palliative purpose [23]. However, in recent years, with the development of technologies such as stereotactic body radiotherapy (SBRT), radiotherapy is increasingly being used in the treatment of ICC. Unlike HCC, ICC patients often present with lymph node metastasis, so during radiotherapy, the radiation field must consider not only intrahepatic lesions but also the lymphatic drainage areas, making radiotherapy more challenging than in HCC. Additionally, because ICC patients often suffer from obstructive jaundice and abdominal pain, the application of radiotherapy in ICC mainly aims to alleviate tumor burden and relieve tumor-related symptoms. In 2007, Zeng Zhao-chong [23] reported on a group of ICC patients receiving radiotherapy. Before treatment, 24 patients experienced abdominal pain, and 18 patients had obstructive jaundice. After radiotherapy, 15 patients had complete relief from abdominal pain, 6 had partial relief, and 15 patients had significant alleviation of jaundice, greatly improving the quality of life. The team later reported on the survival of 35 mid to late-stage ICC patients receiving radiotherapy. The study indicated that after receiving an average dose of 50 Gy of conventional radiotherapy, 3 patients achieved CR, 10 patients achieved PR, with an objective response rate of 37.1%, and the median OS was 9.5 months. Moreover, 68.4% of patients had their jaundice relieved, with only 4 cases of grade 3 or higher adverse reactions, demonstrating good disease control and safety [24]. Another retrospective study included 79 ICC patients, of whom 73% had stage III or IV tumors, with a median tumor diameter of 7.9 cm, and 46 patients had regional lymph node metastasis. Patients received a median dose of 58 Gy of radiotherapy, with 63% and 47% of patients receiving concurrent chemotherapy or chemoradiotherapy afterward. The results showed local tumor control rates at 1 year, 2 years, and 3 years were 81%, 45%, and 27%, respectively; overall survival rates at 1 year, 2 years, and 3 years were 87%, 61%, and 44%, with a median OS of 30 months. The total radiation dose significantly affected patient survival, with higher doses correlating with better prognosis, indicating a significant dose-response relationship. In terms of safety, no radiation-induced liver disease (RILD), biliary obstruction, or cholangitis occurred during radiotherapy. Despite most patients in this study being mid to late-stage ICC, the median survival time still reached 30 months, far exceeding other treatment methods such as interventional, ablation, or chemotherapy, and even approaching the effects of surgical resection. This suggests that high-dose radiotherapy has good safety and tolerance, effectively controlling tumors and translating into survival benefits [25]. The observed relationship between survival time and radiation dose has also been confirmed by other reports [26-28], indicating that when general condition and liver function permit, appropriately increasing the radiation dose can better eliminate tumors, greatly expanding the application of radiotherapy in the field of ICC. Furthermore, more than half of the patients in this study received concurrent chemoradiotherapy, and related studies support the use of concurrent chemoradiotherapy for advanced ICC [29].
In terms of adjuvant therapy, due to the high invasiveness of ICC, postoperative pathological examinations often indicate positive margins or lymph node metastasis, making it difficult to achieve R0 resection. Therefore, postoperative adjuvant radiotherapy becomes particularly important. An analysis of the SEER database indicated that postoperative adjuvant radiotherapy significantly extended the median OS compared to surgery alone (11 months vs. 6 months, P=0.014), but due to the SEER database’s lack of detailed baseline patient data, this conclusion can only serve as preliminary reference [30]. A domestic team compared survival differences among patients with narrow margins (<1 cm) receiving postoperative radiotherapy, those not receiving radiotherapy, and those with wide margins (≥1 cm). The 3-year overall survival rate for narrow-margin patients receiving postoperative radiotherapy was 55%, superior to the 20% for those not receiving radiotherapy, and the difference was not statistically significant compared to the 65% for wide-margin patients. Patients receiving postoperative adjuvant radiotherapy had lower risks of intrahepatic or extrahepatic recurrence than those not receiving adjuvant radiotherapy [31]. Additionally, for patients with lymph node metastasis, postoperative radiotherapy to regional lymph nodes can improve overall survival without causing significant adverse reactions [32]. However, some studies have reached negative conclusions, suggesting that postoperative adjuvant radiotherapy does not improve prognosis [23].
Given the lack of prospective, large-scale literature reports on the value of radiotherapy in ICC, its role remains unclear. For mid to late-stage liver cancer, radiotherapy is superior to palliative treatment and is safe and reliable; the benefits of adjuvant radiotherapy post-curative surgery for recurrence and survival still require more data support; and issues such as concurrent chemoradiotherapy, neoadjuvant radiotherapy, and comparisons between radiotherapy and interventional therapy remain to be conclusively answered.
4. Conclusion
Due to the unique nature of ICC, surgical resection is the preferred treatment method. However, most ICC patients often do not have the opportunity for surgical treatment, and local treatment can bring hope to this group. For early-stage ICC patients who are unsuitable for surgery, ablation therapy may offer a potential cure; for mid to late-stage ICC patients, local treatment can primarily reduce tumor burden, alleviate symptoms, and improve quality of life. Moreover, through interventional therapy, radiotherapy, or combined local and systemic treatments, tumors can be controlled, survival time significantly extended, and even opportunities for surgical intervention may arise through local treatment. For patients undergoing surgical treatment, adjuvant interventional therapy or radiotherapy can also reduce the risk of recurrence. Therefore, local treatment can be integrated throughout the treatment process of ICC and is an indispensable part of the multidisciplinary comprehensive treatment of ICC patients. However, due to the lower number of ICC cases compared to HCC, research on local treatment for ICC is mostly single-center, retrospective data analysis, leading to significant bias, resulting in conclusions that lack persuasion and difficulty in forming systematic consensus and standardized treatment protocols. In recent years, the increasing incidence of ICC has brought greater diagnostic and treatment pressures to clinicians while also providing more opportunities for in-depth research into the characteristics of ICC and the exploration of feasible treatment options. Numerous clinical trials on ICC are underway, and the results of these trials are expected to bring benefits to patients.
References
(Swipe to browse)
[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018[J]. CA Cancer J Clin, 2018, 68(1): 7-30.
[2] Sirica AE, Gores GJ, Groopman JD, et al. Intrahepatic cholangiocarcinoma: continuing challenges and translational advances[J]. Hepatology, 2019, 69(4): 1803-1815.
[3] Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma[J]. J Hepatol, 2014, 60(6): 1268-1289.
[4] Chen Yajin, Shang Changzhen. Treatment strategies for intrahepatic cholangiocarcinoma[J]. Chinese Practical Surgery Magazine, 2015, 35(1): 43-45.
[5] Pan Qi, Wang Lu. Surgical scope and difficulties of intrahepatic cholangiocarcinoma[J]. Chinese Practical Surgery Magazine, 2016, 36(6): 706-708.
[6] European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma[J]. J Hepatol, 2018, 69(1): 182-236.
[7] Kim JH, Won HJ, Shin YM, et al. Radiofrequency ablation for the treatment of primary intrahepatic cholangiocarcinoma[J]. Am J Roentgenol, 2011, 196(2): W205-209.
[8] Fu Ying, Yang Wei, Chen Minhua. Current status of radiofrequency ablation in the treatment of intrahepatic cholangiocarcinoma[J]. Chinese Journal of Clinical Physicians (Electronic Edition), 2012, 6(4): 969-971.
[9] Wu L, Tsilimigras DI, Farooq A, et al. Potential survival benefit of radiofrequency ablation for small solitary intrahepatic cholangiocarcinoma in nonsurgically managed patients: A population-based analysis[J]. J Surg Oncol, 2019, 120(8): 1358-1364.
[10] Kim JH, Won HJ, Shin YM, et al. Radiofrequency ablation for recurrent intrahepatic cholangiocarcinoma after curative resection[J]. Eur J Radiol, 2011, 80(3): e221-225.
[11] Zhang SJ, Hu P, Wang N, et al. Thermal ablation versus repeated hepatic resection for recurrent intrahepatic cholangiocarcinoma[J]. Ann Surg Oncol, 2013, 20(11): 3596-3602.
[12] Zhang K, Yu J, Yu X, et al. Clinical and survival outcomes of percutaneous microwave ablation for intrahepatic cholangiocarcinoma[J]. Int J Hyperthermia, 2018, 34(3): 292-297.
[13] Xu C, Li L, Xu W, et al. Ultrasound-guided percutaneous microwave ablation versus surgical resection for recurrent intrahepatic cholangiocarcinoma: intermediate-term results[J]. Int J Hyperthermia, 2019, 36(1): 351-358.
[14] Park SY, Kim JH, Yoon HJ, et al. Transarterial chemoembolization versus supportive therapy in the palliative treatment of unresectable intrahepatic cholangiocarcinoma[J]. Clin Radiol, 2011, 66(4): 322-328.
[15] Li Wanci, Zhu Xiaoli, Wang Wansheng, et al. Clinical efficacy analysis of interventional therapy for mid to late-stage intrahepatic cholangiocarcinoma[J]. Journal of Interventional Radiology, 2016, 25(9): 813-817.
[16] Wright GP, Perkins S, Jones H, et al. Surgical resection does not improve survival in multifocal intrahepatic cholangiocarcinoma: a comparison of surgical resection with intra-arterial therapies[J]. Ann Surg Oncol, 2018, 25(1): 83-90.
[17] Zhen Y, Liu B, Chang Z, et al. A pooled analysis of transarterial radioembolization with yttrium-90 microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma[J]. Onco Targets Ther, 2019, 12: 4489-4498.
[18] White J, Carolan-Rees G, Dale M, et al. Yttrium-90 transarterial radioembolization for chemotherapy-refractory intrahepatic cholangiocarcinoma: a prospective, observational study[J]. J Vasc Interv Radiol, 2019, 30(8): 1185-1192.
[19] Kohler M, Harders F, Lohofer F, et al. Prognostic factors for overall survival in advanced intrahepatic cholangiocarcinoma treated with yttrium-90 radioembolization[J]. J Clin Med, 2019, 9(1): E56.
[20] Edeline J, Touchefeu Y, Guiu B, et al. Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial[J]. JAMA Oncol, 2020, 6(1): 51-59.
[21] Shen WF, Zhong W, Liu Q, et al. Adjuvant transcatheter arterial chemoembolization for intrahepatic cholangiocarcinoma after curative surgery: retrospective control study[J]. World J Surg, 2011, 35(9): 2083-2091.
[22] Li J, Wang Q, Lei Z, et al. Adjuvant transarterial chemoembolization following liver resection for intrahepatic cholangiocarcinoma based on survival risk stratification[J]. Oncologist, 2015, 20(6): 640-647.
[23] Zeng Zhao-chong. Radiotherapy for intrahepatic cholangiocarcinoma[J]. Practical Oncology, 2007, 22(5): 385-387.
[24] Chen YX, Zeng ZC, Tang ZY, et al. Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients[J]. BMC Cancer, 2010, 10: 492.
[25] Tao R, Krishnan S, Bhosale PR, et al. Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis[J]. J Clin Oncol, 2016, 34(3): 219-226.
[26] Ben-Josef E, Normolle D, Ensminger WD, et al. Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies[J]. J Clin Oncol, 2005, 23(34): 8739-8747.
[27] Dawson LA, McGinn CJ, Normolle D, et al. Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies[J]. J Clin Oncol, 2000, 18(11): 2210-2218.
[28] Tse RV, Hawkins M, Lockwood G, et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma[J]. J Clin Oncol, 2008, 26(4): 657-664.
[29] Chang WW, Hsiao PK, Qin L, et al. Treatment outcomes for unresectable intrahepatic cholangiocarcinoma: Nationwide, population-based, cohort study based on propensity score matching with the Mahalanobis metric[J]. Radiother Oncol, 2018, 129(2): 284-292.
[30] Shinohara ET, Mitra N, Guo M, et al. Radiation therapy is associated with improved survival in the adjuvant and definitive treatment of intrahepatic cholangiocarcinoma[J]. Int J Radiat Oncol Biol Phys, 2008, 72(5): 1495-1501.
[31] Zheng X, Chen B, Wu JX, et al. Benefit of adjuvant radiotherapy following narrow-margin hepatectomy in patients with intrahepatic cholangiocarcinoma that adhere to major vessels[J]. Cancer Manag Res, 2018, 10: 3973-3981.
[32] Jiang W, Zeng ZC, Tang ZY, et al. Benefit of radiotherapy for 90 patients with resected intrahepatic cholangiocarcinoma and concurrent lymph node metastases[J]. J Cancer Res Clin Oncol, 2010, 136(9): 1323-1331.
(Received on 2020-05-07)
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