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BACKGROUND: Cholangiocarcinoma (CCA), which consists of intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), is an aggressive malignancy worldwide. PCCA and dCCA are often classified as extrahepatic CCA (exCCA). However, the differences in mutational characteristics between pCCA and dCCA remain unclear. METHODS: Deep sequencing targeting of 450 cancer genes was performed for genomic alteration detection. The tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was conducted using Fisher’s exact test. RESULTS: FGFR2 and ERBB2 mutations mainly occurred in iCCA and exCCA, respectively. In exCCA, the frequencies of PIK3CA, FAT4, KDM6A, MDM2, and TCF7L2 mutations were significantly higher in pCCA compared to dCCA, while the frequencies of TP53 and KRAS mutations were markedly lower in pCCA than those in dCCA. The prognosis-related mutations were different among the CCA subtypes. NF1 mutation was associated with short disease-free survival (DFS) and overall survival (OS), and ERBB2 mutation was associated with short DFS in dCCA patients. Meanwhile, MAP2K4 mutation was associated with long DFS and OS, and TERT mutation was associated with short DFS in pCCA. A series of mutations in genes, including ARID1A, ARID2, SMAD4, TERT, TP53, and KRAS, were found to be associated with the TMB. CONCLUSIONS: In this study, we investigated the comprehensive genomic characterizations of CCA patients, identified the significant alterations in each subtype, and identified potential biomarkers for prognosis prediction. These results provide molecular evidence for the heterogeneity of CCA subtypes and evidence for further precision targeted therapy of CCA patients.

The incidence of multiple lung cancer has been steadily increasing worldwide. Although cases of patients with lung cancers in the right upper and lower lobe have also become more frequently reported in clinical work, simultaneous right upper and lower lobectomy reports with the middle lobe preservation are still quite rare. A total of three patients with lung cancers in the right upper and lower lobe were included in the study. The patients underwent simultaneous right upper and lower lobectomy, whereas the remaining middle lobe was sutured and fixed to the intercostal muscle of the incision to prevent postoperative lobe torsion. There was no procedure to reduce residual space，such as phrenic nerve crush or thoracoplasty. All patients were discharged from the hospital 7 days after the operation. The chest tube was removed 5 days after the operation in two patients. One patient was discharged with the tube because of slight pulmonary leakage, and the tube was removed 2 weeks after the operation. Six months after the operation, the chest computer tomography showed that the middle lobe expanded well and no obvious cavity or pleural effusion was found. The suture of the remaining middle lobe and intercostal muscle of the incision is a simple and effective method that can be used to successfully avoid middle lobe torsion. This strategy is safe and can be used as the first choice for eligible patients., The patients with lung cancers in right upper and lower lobe have been found in clinical work. Right pneumonectomy has a higher risk of mortality than lobectomy. We found a new simple and effective method to fix the middle lobe after right upper and lower bilobectomy, and the method can be preferred as the first choice of surgical procedure for eligible patients in clinical work.