Neoadjuvant therapy leads to objective response in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA. METHODS: iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas. RESULTS: 47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first. DISCUSSION: In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm.

WITHDRAWN: Neoadjuvant therapy leads to objective response in intrahepatic cholangiocarcinoma.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.hpb.2024.04.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Gene fusions in gastrointestinal tract cancers.

Fusion genes have been identified in a wide array of human neoplasms including hematologic and solid tumors, including gastrointestinal tract neoplasia. A fusion gene is the product of parts of two genes that are joined together following a deletion, translocation, or chromosomal inversion. Together with single nucleotide variants, insertions, deletions, and amplification, fusion genes represent one of the key genomic mechanisms for tumor development. Detecting fusions in the clinic is accomplished by a variety of techniques including break-apart fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and next-generation sequencing. Some recurrent gene fusions have been successfully targeted by small molecule or monoclonal antibody therapies (ie targeted therapies), while others are used as biomarkers for diagnostic and prognostic purposes. The purpose of this review article is to discuss the clinical utility of detection of gene fusions in carcinomas and neoplasms arising primarily in the digestive system.

Mismatch repair deficiency: The what, how and why it is important.

The mismatch repair system is a major pathway that functions in the maintenance of genomic integrity. It is involved in mitotic and meiotic recombination, apoptosis, immunoglobulin gene rearrangement, somatic hypermutation, and other processes. Deficiencies in mismatch repair give rise to hypermutability and the phenomenon called microsatellite instability. Detection of deficient mismatch repair function or microsatellite instability is used diagnostically, predictively, and prognostically. Specifically, deficient mismatch repair function is used for screening of Lynch syndrome, determining patients who are likely to respond to immune checkpoint inhibition, and to contributes to an understanding of which cancer patients may pursue a more aggressive clinical course. Microsatellite instability can be evaluated directly by polymerase chain reaction (PCR) or indirectly by assessment of mismatch repair protein expression using immunohistochemistry (IHC), and mismatch repair function using next-generation sequencing assays which evaluates homopolymer indels. In this article, we provide a concise practical review on mismatch repair deficiency (MMR-d)/microsatellite instability (MSI), focusing on clinical testing, different testing methods, interpretation of findings, the predictive, and prognostic utility of MSI.