Cancer Stem Cells in Intrahepatic Cholangiocarcinoma; Their Molecular Basis, and Therapeutic Implications

Cancer tissue consists of heterogenous cell types, and cancer stem cells (CSCs) are a subpopulation of the tissue which possess therapy resistance, tumor reconstruction capability, and are responsible for metastasis. Intrahepatic cholangiocarcinoma (iCCA) is one of the most common type of liver cancer that is highly aggressive with poor prognosis. Since no target therapy is efficient in improving patient outcomes, new therapeutic approaches need to be developed. CSC is thought to be a promising therapeutic target because of its resistance to therapy. Accumulating evidences suggests that there are many factors (surface marker, stemness-related genes, etc.) and mechanisms (epithelial-mesenchymal transition, mitochondria activity, etc.) which are linked to CSC-like phenotypes. Nevertheless, limited studies are reported about the application of therapy using these mechanisms, suggesting that more precise understandings are still needed. In this review, we overview the molecular mechanisms which modulate CSC-like phenotypes, and discuss the future perspective for targeting CSC in iCCA.

Treatment of Intrahepatic Cholangiocarcinoma—A Multidisciplinary Approach

Intrahepatic cholangiocarcinoma (iCC) is distinguished as an entity from perihilar and distal cholangiocarcinoma and gallbladder carcinoma. Recently, molecular profiling and histopathological features have allowed further classification. Due to the frequent delay in diagnosis, the prognosis for iCC remains poor despite major technical advances and multimodal therapeutic approaches. Liver resection represents the therapeutic backbone and only curative treatment option, with the functional residual capacity of the liver and oncologic radicality being deciding factors for postoperative and long-term oncological outcome. Furthermore, in selected cases and depending on national guidelines, liver transplantation may be a therapeutic option. Given the often advanced tumor stage at diagnosis or the potential for postoperative recurrence, locoregional therapies have become increasingly important. These strategies range from radiofrequency ablation to transarterial chemoembolization to selective internal radiation therapy and can be used in combination with liver resection. In addition, adjuvant and neoadjuvant chemotherapies as well as targeted therapies and immunotherapies based on molecular profiles can be applied. This review discusses multimodal treatment strategies for iCC and their differential use.

Laparoscopic Versus Open Surgery for Early-Stage Intrahepatic Cholangiocarcinoma After Mastering the Learning Curve: A Multicenter Data-Based Matched Study

BackgroundSurgical resection is the only widely accepted curative method for intrahepatic cholangiocarcinoma (ICC). However, little is known about the efficacy of laparoscopic liver resection for ICC, especially in patients with early-stage disease. The aim of this study was to compare the short-term and long-term effects of laparoscopy and open surgery for the treatment of ICC.MethodsData from 1,084 patients treated at three hospitals from January 2011 to December 2018 were selected and analyzed. Propensity score matching was performed to compare the long-term outcomes (overall survival and recurrence-free survival) and short-term outcomes (perioperative outcomes) of all-stage and early-stage patients.ResultsAfter matching, 244 patients (122 vs. 122) in the all-stage group and 65 patients (27 vs. 38) in the early-stage group were included. The baseline of the two groups was balanced, and no significant differences were found in sex or age. The short-term results of the laparoscopic group were better than those of the open group, including less blood loss [blood loss ≥400 ml 27 (22.1%) vs. 6 (4.92%), p<0.001 for all-stage, 12 (31.6%) vs. 2 (7.41%), p=0.042 for early stage), shorter surgery [200 (141; 249) min vs. 125 (115; 222) min, p=0.025 for early stage] and shorter hospital stay [11.0 (9.00; 16.0) days vs. 9.00 (7.00; 12.0) days, p=0.001 for all stage, 11.0 (8.50; 17.8) days vs. 9.00 (6.50; 11.0) days, p=0.011 for early stage]. Regarding long-term outcomes, no significant differences were found for all-stage patients, while there were significant differences observed for the early-stage group (p=0.013 for OS, p=0.014 for RFS). For the early-stage patients, the 1-, 3-, and 5-year OS rates of the OLR group were 84.2, 65.8, and 41.1%, respectively, and those of the LLR group were 100, 90.9, and 90.9%, respectively. The RFS rates of the OLR group were 84.2, 66.7, and 41.7%, respectively, and those of the LLR group were and 92.3, 92.3, and 92.3%, respectively.ConclusionPatients treated with laparoscopy seemed to have better short-term outcomes, such as less blood loss, shorter operation duration, and shorter hospital stay, than patients undergoing open surgery. Based on the long-term results, laparoscopic treatment for early ICC may have certain advantages.