Emergence of multi-targeted kinase inhibitors (MTIs) and immune checkpoint inhibitors (ICI) have changed the landscape of management in hepatocellular carcinoma (HCC). Combination therapy involving ICI has superseded sorafenib as the first-line treatment option for advanced HCC due to their superior response rates and survival benefits based on recently published phase III trials. However, the role of first-line lenvatinib remains uncertain as no prospective trials have compared its efficacy with ICI in advanced HCC. Several retrospective studies have shown that first-line lenvatinib may not be inferior to ICI combination. Indeed, a growing body of evidence suggests that ICI treatment is associated with inferior treatment outcome in non-viral HCC patients, questioning the supremacy of ICI treatment in all patients and rendering first-line lenvatinib as a potential preferred treatment option. Furthermore, in high-burden intermediate-stage HCC, accumulating evidence supports first-line lenvatinib, or in combination with transarterial chemoembolization (TACE), as a preferred treatment option over TACE alone. In this Review, we describe the latest evidence surrounding the evolving role of first-line lenvatinib in HCC.

INTRODUCTIONThe objective of this case report was to illustrate the diagnostic and intervention approach of anomalous right coronary artery (RCA).

CLINICAL PICTUREA 60-year-old man presented with acute inferior myocardial infarction. Cardiac catheterisation revealed an anomalous RCA arising from the posterior coronary sinus as the infarct-related artery.

TREATMENTAd hoc percutaneous coronary intervention with stent implantation was performed using a few technical modifications.

OUTCOMEGood angiographic result was achieved within 90 minutes, with 260 mL of contrast used.

CONCLUSIONA high index of suspicion and logical diagnostic and intervention approach are required for the proper management of anomalous RCA.

Angioplasty, Balloon, Coronary ; Cardiac Catheterization ; methods ; Coronary Angiography ; Coronary Vessel Anomalies ; complications ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; complications ; surgery

BACKGROUNDSotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity. Haploinsufficiency of the NSD1 gene has been implicated as the major cause of Sotos syndrome, with a predominance of microdeletions reported in Japanese patients. This study was conducted to investigate into the spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome.

METHODSThirty-six Chinese patients with Sotos syndrome and two patients with Weaver syndrome were subject to molecular testing.

RESULTSNSD1 gene mutations were detected in 26 (72%) Sotos patients. Microdeletion was found in only 3 patients, while the other 23 had point mutations (6 frameshift, 8 nonsense, 2 spice site, and 7 missense). Of these, 19 mutations were never reported. NSD1 gene mutations were not found in the two patients with Weaver syndrome.

CONCLUSIONSMost cases of Sotos syndrome are caused by NSD1 gene defects, but the spectrum of mutations is different from that of Japanese patients. Genotype-phenotype correlation showed that patients with microdeletions might be more prone to congenital heart disease but less likely to have somatic overgrowth. The two patients with Weaver syndrome were not found to have NSD1 gene mutations, but the number was too small for any conclusion to be drawn.

Abnormalities, Multiple ; genetics ; Brain ; abnormalities ; Child, Preschool ; Craniofacial Abnormalities ; genetics ; Developmental Disabilities ; genetics ; Gene Deletion ; Growth Disorders ; genetics ; Humans ; Infant ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Nuclear Proteins ; genetics ; Syndrome

There have been many clinical trials conducted to evaluate novel systemic regimens for unresectable pancreatic cancer. However, most of the trial results were negative, and gemcitabine monotherapy has remained the standard systemic treatment for years. A number of molecular targeted agents, including those against epidermal growth factor receptor and vascular endothelial growth factor receptors, have also been tested. In recent years, there have been some breakthroughs in the deadlock: three regimens, namely gemcitabine-erlotinib, FOLFIRINOX, and gemcitabine-nab-paclitaxel, have been shown to prolong the overall survival of patients when compared with gemcitabine monotherapy. In addition, emerging data suggested that the membrane protein human equilibrative nucleotide transporter 1 is a potential biomarker with which to predict the efficacy of gemcitabine. Here we review the literature on the development of systemic agents for pancreatic cancer, discuss the current choices of treatment, and provide future directions on the development of novel agents.
Adenocarcinoma ; drug therapy ; Albumins ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Camptothecin ; analogs & derivatives ; Deoxycytidine ; analogs & derivatives ; Equilibrative Nucleoside Transporter 1 ; Erlotinib Hydrochloride ; Fluorouracil ; Humans ; Leucovorin ; Organoplatinum Compounds ; Paclitaxel ; Pancreatic Neoplasms ; drug therapy ; Quinazolines ; Receptor, Epidermal Growth Factor ; Receptors, Vascular Endothelial Growth Factor

The outcome of hepatocellular carcinoma (HCC) patients significantly differs between western and eastern population centers. Our group previously developed and validated the Chinese University Prognostic Index (CUPI) for the prognostication of HCC among the Asian HCC patient population. In the current study, we aimed to validate the CUPI using an international cohort of patients with HCC and to compare the CUPI to two widely used staging systems, the Barcelona Clinic Liver Cancer (BCLC) classification and the Cancer of the Liver Italian Program (CLIP). To accomplish this goal, two cohorts of patients were enrolled in the United Kingdom (UK; n = 567; 2006-2011) and Hong Kong (HK; n = 517; 2007-2012). The baseline clinical data were recorded. The performances of the CUPI, BCLC, and CLIP were compared in terms of a concordance index (C-index) and were evaluated in subgroups of patients according to treatment intent. The results revealed that the median follow-up durations of the UK and HK cohorts were 27.9 and 29.8 months, respectively. The median overall survival of the UK and HK cohorts were 22.9 and 8.6 months, respectively. The CUPI stratified the patients in both cohorts into three risk subgroups corresponding to distinct outcomes. The median overall survival of the CUPI low-, intermediate-, and high-risk subgroups were 3.15, 1.24, and 0.29 years, respectively, in the UK cohort and were 2.07, 0.32, and 0.10 years, respectively, in the HK cohort. For the patients who underwent curative treatment, the prognostic performance did not differ between the three staging systems, and all were suboptimal. For those who underwent palliative treatment, the CUPI displayed the highest C-index, indicating that this staging system was the most informative for both cohorts. In conclusion, the CUPI is applicable to both western and eastern HCC patient populations. The performances of the three staging systems differed according to treatment intent, and the CUPI was demonstrated to be optimal for those undergoing palliative treatment. A more precise staging system for early-stage disease patients is required.
Carcinoma, Hepatocellular ; Hong Kong ; Humans ; Liver Neoplasms ; Neoplasm Staging ; Prognosis ; United Kingdom