Patients with intrahepatic cholangiocarcinoma (ICC) who have perineural invasion have a poor prognosis after surgery. However, these patients have a good response to adjuvant chemotherapy, found a new study published in the journal Hepatology International.

“Our study deciphered the genomic features and the immune suppressive metastasis-prone niche in ICC with [perineural invasion],” the study authors wrote.

To confirm the contribution of perineural invasion as an unfavorable prognostic factor in ICC, a team of researchers from China analyzed 2 groups of patients. The first group included 255 patients for whom RNA-seq and genomic data was available, while the second group included 309 patients who underwent curative resection for their disease.

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The researchers compared these patients to 186 patients with genomic data, perineural invasion, and clinical information from the Memorial Sloan-Kettering (MSK) Cancer Center.

They reported that 30.6% of patients in the MSK group and 20.7% of patients who underwent curative resection had a perineural invasion.

Patients with perineural invasion had malignant phenotypes, which included high carbohydrate antigen 19-9 levels, the large bile duct type, lymph node invasion, and shortened overall and relapse-free survival.

They also had high mutation frequency in the KRAS gene, decreased natural killer cells, increased neutrophils, and elevated expression of PD-L1, CD80, and CD86. 

Finally, these patients had extended overall survival following adjuvant chemotherapy with tegafur, gimeracil, and oteracil potassium capsules, gemcitabine plus oxaliplatin, or capecitabine.

ICC is a subtype of cholangiocarcinoma located inside the hepatic parenchyma, which can occur at any location in the intrahepatic biliary tree.

Perineural invasion is defined as the appearance of tumor cells along the nerves and/or within the neuronal sheath surrounding at least a third of the nerve. It is associated with metastasis and poor prognosis in many malignancies.


Meng XL, Lu JC, Zeng HY, et al. The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion. Hepatol Int. Published online November 22, 2022. doi:10.1007/s12072-022-10445-1