Intrahepatic cholangiocarcinoma has high malignancy, poor prognosis and few long-term survivors. The prognosis of patients without operation is very poor, and the 3-year survival rate was only 40% − 50% after the operation (5). Compared with other liver malignancies, ICC means shorter survival time, lower resection rate and cure rate (6). In addition, the gross classification of ICC is related to the prognosis of tumor. The prognosis of peritubular infiltration type is the worst, followed by mass type, and intratubular growth type is the best. At present, tumor markers lack sensitivity and specificity in the diagnosis of ICC. CA19-9 has a certain significance in the diagnosis of tumor, evaluation of tumor resection and prognosis, while CEA, AFP and CA-125 have little significance in the diagnosis of ICC(7). The definite diagnosis depends on the combination of imaging and pathological examination (8).
Intrahepatic cholangiocarcinoma is more likely to recur than hepatocellular carcinoma(9).The survival of patients with ICC is affected by the number of tumors, the extent of liver resection, the degree of tumor differentiation and the type of tumor cells. According to NCCN guidelines, preoperative biopsy is not necessary, especially in surgical resectable cases. Imaging suspicious nodules should be treated as malignant, and diagnostic laparoscopic exploration is recommended to exclude unresectable disseminated lesions (10).
Exploration and evaluation should include: multiple intrahepatic cancer, lymph node metastasis and distant metastasis. Lymph node metastasis and distant metastasis outside the porta hepatis should be considered as surgical contraindications. It is recommended that hilar lymph node dissection should be performed routinely to provide staging and prognosis information. According to NCCN guidelines, radical surgery (plus lymph node dissection) is the only cure treatment (11). Surgical indications and neoadjuvant therapy are still the focus of clinical justice (12). Literature reports showed that two patients with stage Ⅲ B ICC received 13 m and 16 m CR after chemotherapy with PD-1 monoclonal antibody(13). This case of intrahepatic cholangiocarcinoma with hilar lymph node metastasis, abdominal aortic lymph node metastasis is suspected, belongs to AJCC stage Ⅲb. After multidisciplinary discussion, it is suggested that patients should implement neoadjuvant therapy and surgical resection and lymph node dissection and postoperative adjuvant therapy, in addition, neoadjuvant therapy includes chemotherapy and immunotherapy.
After immunotherapy with PD-1 and chemotherapy with GP regimen, re evaluation showed that the tumor was shrunk and necrotic, and the oncology evaluation reached PR. According to the NCCN guidelines, the patients continued to receive immunotherapy and chemotherapy after tumor resection. So far, no recurrence has been found. Lymph node dissection is another focus of clinical debate. The existing research data show that extended dissection does not improve the prognosis, however, both NCCN and ESMO guidelines recommend routine hilar lymph node dissection. NCCN guidelines consider that positive extrahepatic lymph node metastasis is a surgical contraindication, and neoadjuvant therapy is recommended, followed by surgery at a lower stage. So the independent risk factors for the prognosis of the patients included: the distance between the cutting edge and the tumor was less than 1cm; the diameter of the tumor was more than 5cm; the number of tumors was multiple; microvascular invasion and positive pathological lymph node metastasis (12, 14).
A literature confirmed that lymph node dissection cannot improve the prognosis of patients with intrahepatic cholangiocarcinoma(15). Postoperative pathology confirmed that positive lymph node metastasis is an independent risk factor affecting the prognosis of patients with intrahepatic cholangiocarcinoma, which confirmed the clinical value of lymph node dissection, and also showed that the current lymph node dissection are still many problems(15).Lymph node dissection is still routine (lymph node metastasis rate is 25–50%), CSCO biliary system tumor diagnosis and treatment expert consensus 2019 recommend active surgical resection and lymph node dissection, so there is no consensus on the scope of regional lymph node dissection (14). We should carefully choose extended hepatectomy, the improvement of chemotherapy, the emergence of immunotherapy and radiotherapy With the development of surgery, adjuvant therapy has become an important means to improve the prognosis of intrahepatic cholangiocarcinoma (16, 17).
Another point of contention about ICC is there is no RCT study on preoperative neoadjuvant therapy for ICC. A multicenter study contain 62 cases of ICC with neoadjuvant chemotherapy had a median OS of 47m after resection, 74 cases of unresectable ICC had a median OS of 24m after 6 cycles of chemotherapy(18). At present, preoperative neoadjuvant therapy was regarded as the “TEST”, and there is no report about immunotherapy as neoadjuvant therapy or transformation therapy.
Immunotherapy as a research hotspot at present. PD1 inhibitors are effective for solid tumors, but currently only melanoma and lung cancer are the clinical indications for immunotherapy. At present, the objective remission rate of ICC in the treatment of advanced HCC patients is about 20%, showing a certain efficacy, and more phase III clinical trials are needed to verify. The development of more sensitive and efficient predictive methods will help ICC therapy more accurately benefit potential patients with advanced HCC and benefit patients who are suitable for ICC therapy. This will hopefully open up a new prospect of immunotherapy for liver tumors (19). Immunotherapy may provide an attemptable treatment option for hepatic ICC, but it needs to be confirmed by a larger sample of cases (20); and as part of preoperative neoadjuvant therapy for intrahepatic cholangiocarcinoma is still a hot topic in clinical trials (21).Overall, the value of neoadjuvant therapy, the time of operation after neoadjuvant therapy, the necessity of lymph node dissection, the means of adjuvant therapy, and the treatment plan after recurrence are still the hot topics of current research.