TP53 Mutation Predicts Worse Survival and Earlier Local Progression in Patients with Hepatocellular Carcinoma Treated with Transarterial Embolization.

The aim of this study was to evaluate associations between TP53 status and outcomes after transarterial embolization (TAE) for the treatment of patients with hepatocellular carcinoma (HCC). This single-institution study included patients from 1/2014 to 6/2022 who underwent TAE of HCC and genomic analysis of tumoral tissue. The primary outcome was overall survival (OS) with relation to TP53 status, and the secondary outcome was the time to progression.

Evaluation of the Ki-67 labeling index on immediate pre-ablation biopsies as a predictive biomarker of local recurrence of colorectal cancer liver metastases.

The aim of this study was to evaluate if the Ki-67 labeling index (LI) on immediate pre-ablation biopsies of colorectal liver metastases (CLM) is associated with the presence of viable tumor cells in subsequent ablation zone biopsies and/or local tumor progression-free survival (LTPFS). Biopsies of CLM were performed before and after microwave ablation (MWA), as part of a prospective clinical trial between October 2013 and May 2019. Pre-ablation biopsy slides were examined for the Ki-67 LI using light microscopy.

Engineered extrachromosomal oncogene amplifications promote tumorigenesis.

Focal gene amplifications are among the most common cancer-associated mutations but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs) in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures.

Extraction and classification of structured data from unstructured hepatobiliary pathology reports using large language models: a feasibility study compared with rules-based natural language processing.

Aims: Structured reporting in pathology is not universally adopted and extracting elements essential to research often requires expensive and time-intensive manual curation. The accuracy and feasibility of using large language models (LLMs) to extract essential pathology elements, for cancer research is examined here.

Methods: Retrospective study of patients who underwent pathology sampling for suspected hepatocellular carcinoma and underwent Ytrrium-90 embolisation.

Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer.

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches.

A Novel Approach to Quantify Heterogeneity of Intrahepatic Cholangiocarcinoma: The Hidden-Genome Classifier.

Purpose: Intrahepatic cholangiocarcinoma (IHC) is a heterogeneous tumor. The hidden-genome classifier, a supervised machine learning-based algorithm, was used to quantify tumor heterogeneity and improve classification.

Experimental Design: A retrospective review of 1,370 patients with IHC, extrahepatic cholangiocarcinoma (EHC), gallbladder cancer (GBC), hepatocellular carcinoma (HCC), or biphenotypic tumors was conducted.

Concordance in Oncogenic Alterations Between the Primary Tumor and Advanced Disease: Insights Into the Heterogeneity of Intrahepatic Cholangiocarcinoma.

Purpose: Intrahepatic cholangiocarcinoma (ICCA) is characterized by significant phenotypic and clinical heterogeneities and poor response to systemic therapy, potentially related to underlying heterogeneity in oncogenic alterations. We aimed to characterize the genomic heterogeneity between primary tumors and advanced disease in patients with ICCA.

Methods: Biopsy-proven CCA specimens (primary tumor and paired advanced disease [metastatic disease, progressive disease on systemic therapy, or postoperative recurrence]) from two institutions were subjected to targeted next-generation sequencing.

Cytopathologic features of epithelioid hemangioendothelioma including touch imprints for rapid on-site evaluation.

Objectives: Epithelioid hemangioendothelioma (EHE) is a vascular tumor of intermediate malignant potential, which presents as infiltrative lesions involving multiple organs. We reviewed our institutional experience with the cytologic diagnosis of this neoplasm including the performance of rapid on-site evaluation (ROSE).

Material And Methods: From our institutional database, we identified 29 cytology specimens, obtained between 2012 and 2020, from 21 patients with biopsy confirmation of EHE.

The World Health Organization classification of pancreaticobiliary cytopathology stratifies risk of malignancy and outcome for endoscopic ultrasound-guided fine-needle aspiration of the pancreas.

Background: The World Health Organization (WHO) has recently published a classification for reporting pancreaticobiliary cytopathology with differences compared to the Papanicolaou Society of Cytopathology (PSC) classification.

Methods: Retrospective data were collected from pancreatic endoscopic ultrasound-guided fine-needle aspirations from 2014 to 2017 at a pancreatic cancer center. Absolute risk of malignancy (AROM), relative risk (to benign), performance characteristics, and overall survival were calculated for the entire cohort with comparison of cysts and solid lesions.

Prognostic value of circumferential radial margin involvement in esophagectomy for esophageal cancer: a case series.

Background: Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection.

Materials And Methods: We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019.

Comparison of Stage I Non-Small-Cell Lung Cancer Treatments for Patients Living With HIV: A Simulation Study.

Introduction: Non-small-cell lung cancer (NSCLC) is a leading cause of death for people living with HIV (PWH). Nevertheless, there are no clinical trial data regarding the management of early-stage lung cancer in PWH. Using data from large HIV and cancer cohorts we parameterized a simulation model to compare treatments for stage I NSCLC according to patient characteristics.

Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival.

Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression.

Phase 1 Dose Escalation Study of SBRT Using 3 Fractions for Locally Advanced Pancreatic Cancer.

Purpose: The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC.

Diagnostic features of low- and high-grade mucinous neoplasms in pancreatic cyst FNA cytology.

Background: Pancreatic cyst cytology evaluates for neoplastic mucin and epithelial grade. This study describes cytological features of low- and high-grade mucinous neoplasms (MNs) using gastrointestinal contaminants for comparison.

Methods: Histologically confirmed pancreatic cystic neoplasms were reviewed by a panel of cytopathologists to identify which, among 26 selected cytologic features, correlate significantly with low- and high-grade MN.

Intraductal papillary neoplasm of the bile duct: Cytomorphologic and molecular features.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare premalignant neoplasm that can progress to invasive adenocarcinoma. In this retrospective study, cases of IPNB were reviewed to examine cytomorphologic and molecular features.

Methods: IPNB cytology cases with histopathologic confirmation were retrieved from the pathology archives.

Prognostic Impact of Tumor Budding in Intrahepatic Cholangiocellular Carcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) represents an aggressive carcinoma with a dismal prognosis. For resection specimens, histopathological prognosticators are limited to standard AJCC parameters. Tumor budding (TB), a quantitative leviable parameter for tumor cell separation and infiltration is a promising prognostic factor for several cancers.

Ketohexokinase-mediated fructose metabolism is lost in hepatocellular carcinoma and can be leveraged for metabolic imaging.

The ability to break down fructose is dependent on ketohexokinase (KHK) that phosphorylates fructose to fructose-1-phosphate (F1P). We show that KHK expression is tightly controlled and limited to a small number of organs and is down-regulated in liver and intestinal cancer cells. Loss of fructose metabolism is also apparent in hepatocellular adenoma and carcinoma (HCC) patient samples.

Biopsy and Margins Optimize Outcomes after Thermal Ablation of Colorectal Liver Metastases.

Background: Thermal ablation is a definitive local treatment for selected colorectal liver metastases (CLM) that can be ablated with adequate margins. A critical limitation has been local tumor progression (LTP).

Methods: This prospective, single-group, phase 2 study enrolled patients with CLM < 5 cm in maximum diameter, at a tertiary cancer center between November 2009 and February 2019.

Genome-Derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care.

Purpose: The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management.

Experimental Design: The hidden-genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile-duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA-sequencing data from ampullary adenocarcinomas.

Integrated digital pathology at scale: A solution for clinical diagnostics and cancer research at a large academic medical center.

Objective: Broad adoption of digital pathology (DP) is still lacking, and examples for DP connecting diagnostic, research, and educational use cases are missing. We blueprint a holistic DP solution at a large academic medical center ubiquitously integrated into clinical workflows; researchapplications including molecular, genetic, and tissue databases; and educational processes.

Materials And Methods: We built a vendor-agnostic, integrated viewer for reviewing, annotating, sharing, and quality assurance of digital slides in a clinical or research context.

Intrahepatic Cholangiocarcinoma with Lymph Node Metastasis: Treatment-Related Outcomes and the Role of Tumor Genomics in Patient Selection.

Purpose: Lymph node metastasis (LNM) drastically reduces survival after resection of intrahepatic cholangiocarcinoma (IHC). Optimal treatment is ill defined, and it is unclear whether tumor mutational profiling can support treatment decisions.

Experimental Design: Patients with liver-limited IHC with or without LNM treated with resection ( = 237), hepatic arterial infusion chemotherapy (HAIC; = 196), or systemic chemotherapy alone (SYS; = 140) at our institution between 2000 and 2018 were included.

Adrenocortical Carcinoma: A Case of Missed Diagnosis.

Incidentalomas are commonly encountered adrenal lesions. However, adrenocortical carcinoma (ACC) represents a rare etiology of adrenal incidentalomas (AI). The diagnosis of AI is generally based on laboratory data and imaging results, Fine needle aspiration (FNA) is not usually indicated in the workup of incidentaloma.