Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

Identification of IGF2 as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma.

Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays.

Safety Attitude of Operating Room Personnel Associated With Accurate Completion of a Surgical Checklist: A Cross-sectional Observational Study.

Objective: How the checklist is executed in routine practice may reflect the teamwork and safety climate in the operating room (OR). This cross-sectional study aimed to identify whether the presence of a fully completed checklist in medical records was associated with teams' safety attitudes.

Methods: Data from 29 French hospitals, including 5677 operated patients and 834 OR professionals, were prospectively collected.

Cabozantinib Enhances Anti-PD1 Activity and Elicits a Neutrophil-Based Immune Response in Hepatocellular Carcinoma.

Purpose: Immune checkpoint inhibitors combined with antiangiogenic agents produce benefits in the treatment of advanced hepatocellular carcinoma (HCC). We investigated the efficacy and immunomodulatory activity of cabozantinib alone and combined with anti-PD1 in experimental models of HCC, and explored the potential target population that might benefit from this combination.

Experimental Design: C57BL/6J mice bearing subcutaneous Hepa1-6 or Hep53.

Long-Term Outcome of Lobectomy for Thyroid Cancer.

Introduction: Recent guidelines of the American Thyroid Association (ATA) suggest that a lobectomy may be sufficient to treat low- to intermediate-risk patients with thyroid tumors ≤40 mm, without extrathyroidal extension or lymph node metastases. The present study aimed to evaluate long-term recurrence after lobectomy for differentiated thyroid cancer and to analyze factors associated with recurrence.

Methods: In this retrospective cohort study, patients who underwent a lobectomy for thyroid cancer in a tertiary center between 1970 and 2010 were included.

Immunomodulatory Effects of Lenvatinib Plus Anti-Programmed Cell Death Protein 1 in Mice and Rationale for Patient Enrichment in Hepatocellular Carcinoma.

Background And Aims: Lenvatinib is an effective drug in advanced HCC. Its combination with the anti-PD1 (programmed cell death protein 1) immune checkpoint inhibitor, pembrolizumab, has generated encouraging results in phase Ib and is currently being tested in phase III trials. Here, we aimed to explore the molecular and immunomodulatory effects of lenvatinib alone or in combination with anti-PD1.

Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis.

Background And Aims: Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies.

Methods: We collected 80 NASH-HCC and 125 NASH samples from 5 institutions.

DNA Methylation Profiling of Human Hepatocarcinogenesis.

Background And Aims: Mutations in TERT (telomerase reverse transcriptase) promoter are established gatekeepers in early hepatocarcinogenesis, but little is known about other molecular alterations driving this process. Epigenetic deregulation is a critical event in early malignancies. Thus, we aimed to (1) analyze DNA methylation changes during the transition from preneoplastic lesions to early HCC (eHCC) and identify candidate epigenetic gatekeepers, and to (2) assess the prognostic potential of methylation changes in cirrhotic tissue.

Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma.

Background & Aims: Cholangiocarcinoma (CCA), a deadly malignancy of the bile ducts, can be classified based on its anatomical location into either intrahepatic (iCCA) or extrahepatic (eCCA), each with different pathogenesis and clinical management. There is limited understanding of the molecular landscape of eCCA and no targeted therapy with clinical efficacy has been approved. We aimed to provide a molecular classification of eCCA and identify potential targets for molecular therapies.

An Immune Gene Expression Signature Associated With Development of Human Hepatocellular Carcinoma Identifies Mice That Respond to Chemopreventive Agents.

Background & Aims: Cirrhosis and chronic inflammation precede development of hepatocellular carcinoma (HCC) in approximately 80% of cases. We investigated immune-related gene expression patterns in liver tissues surrounding early-stage HCCs and chemopreventive agents that might alter these patterns to prevent liver tumorigenesis.

Methods: We analyzed gene expression profiles of nontumor liver tissues from 392 patients with early-stage HCC (training set, N = 167 and validation set, N = 225) and liver tissue from patients with cirrhosis without HCC (N = 216, controls) to identify changes in expression of genes that regulate the immune response that could contribute to hepatocarcinogenesis.

Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials.

The clinical utility of serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC) is widely recognised. However, a clear understanding of the mechanisms of AFP overexpression and the molecular traits of patients with AFP-high tumours are not known. We assessed transcriptome data, whole-exome sequencing data and DNA methylome profiling of 520 HCC patients from two independent cohorts to identify distinct molecular traits of patients with AFP-high tumours (serum concentration > 400 ng/ml), which represents an accepted prognostic cut-off and a predictor of response to ramucirumab.

Correction to: Does Surgery Without Lugol's Solution Pretreatment for Graves' Disease Increase Surgical Morbidity?

In the original article, Mathieu Bonal's last name was spelled incorrectly. It is correct as reflected here. The original article has also been updated.

Predictive factors of outcome in poorly differentiated thyroid carcinomas.

Background: The prognosis of poorly differentiated thyroid carcinomas (PDTC) is heterogeneous though generally poor. The objectives of this study were to identify clinical and molecular factors of poor prognosis.

Methods: One hundred four consecutive patients treated for a PDTC between 01/01/2000 and 31/12/2010 were included in this study.

Predicting thyroid nodule malignancy at several prevalence values with a combined Bethesda-molecular test.

Investigation of thyroid nodules using fine-needle aspiration cytology (FNAC) gives indeterminate results in up to 30% of samples using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We present a combined Bethesda-molecular predictor of nodule malignancy to improve the accuracy of the preoperative diagnosis of thyroid nodules. To detect a molecular signature of thyroid nodule malignancy, a molecular test was performed on FNACs from 128 thyroid nodules from prospectively included patients, collected in a tertiary center.

Determinants of operative time in thyroid surgery: A prospective multicenter study of 3454 thyroidectomies.

Objective: To identify the determinants of operative time for thyroidectomy and quantify the relative influence of preoperative and intra-operative factors.

Background: Anticipation of operative time is key to avoid both waste of hospital resources and dissatisfaction of the surgical staff. Having an accurate and anticipated planning would allow a rationalized operating room use and may improve patient flow and staffing level.

Can we consider immediate complications after thyroidectomy as a quality metric of operation?

Background: Permanent recurrent laryngeal nerve palsy and hypoparathyroidism are 2 major complications after thyroid operation. Assuming that the rate of immediate complications can predict the permanent complication rate, some authors consider these complications as a valid metric for assessing the performance of individual surgeons. This study aimed to determine the correlation between rates of immediate and permanent complications after thyroidectomy at the surgeon level.

Aldosterone-Producing Adenoma With a Somatic KCNJ5 Mutation Revealing APC-Dependent Familial Adenomatous Polyposis.

Context: Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 have been identified in aldosterone-producing adenomas (APAs). The question as to whether they are responsible for both nodulation and aldosterone production is not solved.

Case Description: We describe the case of a young patient who was diagnosed with severe arterial hypertension due to primary aldosteronism at age 26 years, followed by hemorrhagic stroke 4 years later.

Cluster randomized trial to evaluate the impact of team training on surgical outcomes.

Background: The application of safety principles from the aviation industry to the operating room has offered hope in reducing surgical complications. This study aimed to assess the impact on major surgical complications of adding an aviation-based team training programme after checklist implementation.

Methods: A prospective parallel-group cluster trial was undertaken between September 2011 and March 2013.

Is it possible to limit the risks of thyroid surgery?

Objective: Inferior laryngeal nerve (ILN) palsy and hypocalcemia remain the two most frequent major complications after thyroid surgery. Their occurrences may be explained by the influence of factors related to the patient, the surgical procedure, thyroid pathology, or the surgeon's technique. This study aims To assess whether systematically following a rigorous surgical technique during thyroidectomy affects postoperative complications and long-term patient recovery.

Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma.

Objective: Sorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterise the role of tumour-initiating cells (T-ICs) and signalling pathways involved in sorafenib resistance.

Does Molecular Genotype Provide Useful Information in the Management of Radioiodine Refractory Thyroid Cancers? Results of a Retrospective Study.

Introduction: Whether mutation status should be used to guide therapy is an important issue in many cancers. We correlated mutation profile in radioiodine-refractory (RAIR) metastatic thyroid cancers (TCs) with patient outcome and response to tyrosine kinase inhibitors (TKIs), and discussed the results with other published data.

Materials And Methods: Outcome in 82 consecutive patients with metastatic RAIR thyroid carcinoma prospectively tested for BRAF, RAS and PI3KCA mutations was retrospectively analyzed, including 55 patients treated with multikinase inhibitors.