Liver cancer international最新文献

{"title":"Endoscopic considerations for the management of cholangiocarcinoma","authors":"Joe Geraghty","doi":"10.1002/lci2.40","DOIUrl":"10.1002/lci2.40","url":null,"abstract":"<p>Cholangiocarcinoma (CCA) is a rare malignancy of the biliary tract. The goals of endoscopy in CCA are to (a) provide an accurate diagnosis (tissue acquisition) and staging of disease and (b) relieve biliary obstruction and associated symptoms such as pruritis (stent placement). This then facilitates optimal treatment to occur; be this surgical resection, uninterrupted chemotherapy or improvement in symptoms. Endoscopy can involve endoscopic retrograde cholangiopancreatography with or without cholangioscopy, or endoscopic ultrasound with fine-needle aspiration to support these goals of making surgery safer and chemotherapy possible while avoiding endoscopy compilations such as pancreatitis and sepsis.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 3","pages":"96-101"},"PeriodicalIF":0.0,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.40","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42205867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatotoxicity of systemic therapies for unresectable hepatocellular carcinoma","authors":"Ciro Celsa,&nbsp;Paolo Giuffrida,&nbsp;Carmelo Marco Giacchetto,&nbsp;Caterina Stornello,&nbsp;Gabriele Rancatore,&nbsp;Mauro Grova,&nbsp;Maria Rita Ricciardi,&nbsp;Sergio Rizzo,&nbsp;Calogero Cammà,&nbsp;Giuseppe Cabibbo","doi":"10.1002/lci2.38","DOIUrl":"10.1002/lci2.38","url":null,"abstract":"<p>The number of effective systemic therapies for the treatment of unresectable hepatocellular carcinoma (uHCC) is rapidly increasing and the advent of immunotherapy changed the treatment paradigm for these patients, leading to a significant improvement in survival outcomes. While sorafenib, a tyrosine-kinase inhibitor monotherapy, remained the only effective treatment for almost a decade, the combination of atezolizumab, an immune checkpoint inhibitor (ICI) targeting programmed death-ligand 1, plus bevacizumab, an antiangiogenic agent targeting vascular endothelial growth factor, now represents the new standard of care for patients with uHCC. Moreover, several further clinical trials are ongoing to evaluate novel combinations between ICIs with other drugs, belonging to the same class or to other classes. As HCC occurs in most cases in the setting of cirrhosis, the evaluation of the risk/benefit ratio of systemic treatments represents a critical point. The underlying liver disease significantly influences the safety and the effectiveness of current and future systemic treatments for uHCC. For this reason, the hepatotoxicity profile and impact on liver function of these molecules should be carefully assessed in both clinical trials and in the real-world setting. Here, we review hepatotoxicity data on systemic treatments for uHCC and offer suggestions on monitoring and managing liver-related adverse events occurring during the treatment.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 3","pages":"82-95"},"PeriodicalIF":0.0,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.38","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47458286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicentre external validation of the GES score for predicting HCC risk in Japanese HCV patients who achieved SVR following DAAs","authors":"Kazumichi Abe,&nbsp;Masashi Fujita,&nbsp;Manabu Hayashi,&nbsp;Atsushi Takahashi,&nbsp;Hiromasa Ohira,&nbsp;Nabiel Mikhail,&nbsp;Reham Soliman,&nbsp;Gamal Shiha","doi":"10.1002/lci2.41","DOIUrl":"10.1002/lci2.41","url":null,"abstract":"<p>A simple score combining clinical and biochemical parameters (general evaluation score (GES)) has shown value in predicting hepatocellular carcinoma (HCC) risk after hepatitis C virus (HCV) eradication in Egyptian patients with HCV genotype 4. We aimed to apply the GES to predict HCC risk in Japanese HCV patients who achieved sustained virological response (SVR) following direct-acting antivirals (DAAs). This multicentre retrospective cohort study included 187 HCV patients without a history of HCC treatment who achieved SVR. The GES was calculated using pre- and post-treatment data. The median age of the patients was 66 years; 49% were male, 89% had cirrhosis and 69% had HCV genotype 1. During the mean 36-month follow-up, 19 (10.2%) developed HCC. Regarding the pretreatment scores, 75 (40.1%), 58 (31.0%) and 54 (28.9%) patients had low-, intermediate- and high-risk scores, respectively. The 4-year cumulative incidence (CumI) was 1.64% in the low-risk group, 2.82% in the intermediate-risk group and 6.88% in the high-risk group (log-rank <i>P</i> = .029). In patients with cirrhosis, 60 (36.1%), 57 (34.3%) and 49 (29.5%) had low-, intermediate- and high-risk scores respectively. The 4-year CumI was 0.98% in the low-risk group, 2.86% in the intermediate-risk group and 6.67% in the high-risk group (log-rank <i>P</i> = .02). The GES calculated with pretreatment data was more useful than that calculated with post-treatment data (Harrell's C statistic: 0.670 vs 0.587). This tool incorporates changes over time to estimate variations in HCC risk and could help identify low-risk patients for whom HCC surveillance can be discontinued.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 3","pages":"102-109"},"PeriodicalIF":0.0,"publicationDate":"2021-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.41","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47816677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unmet needs in basic and translational research in Cholangiocarcinoma","authors":"M. Cadamuro, R. Macías, A. Strain, M. Strazzabosco, P. Simioni, J. Marin, L. Fabris","doi":"10.1002/lci2.39","DOIUrl":"https://doi.org/10.1002/lci2.39","url":null,"abstract":"Despite the impact of cutting‐edge technologies in providing deep molecular phenotyping of many tumours, management of cholangiocarcinoma (CCA), a rare and insufficiently studied cancer with marked heterogeneity (including intrahepatic and extrahepatic variants), has remained limited and it has poor prognosis. Renewed interest in this enigmatic disease has been fostered in the last decade. Here, we will give an overview of the most important gaps in knowledge of the basic and translational research of CCA that must be prioritized to improve the CCA management in the future.","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 1","pages":"16 - 5"},"PeriodicalIF":0.0,"publicationDate":"2021-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42920941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of sitagliptin in treatment of hepatocellular carcinoma in chronic liver disease patients","authors":"Clémence Hollande,&nbsp;Jeremy Boussier,&nbsp;Estelle Mottez,&nbsp;Vincent Bondet,&nbsp;Tan Phuc Buivan,&nbsp;Bruno Charbit,&nbsp;Alba Llibre,&nbsp;Frédéric Charlotte,&nbsp;Eric Savier,&nbsp;Olivier Scatton,&nbsp;Darragh Duffy,&nbsp;Matthew Albert,&nbsp;Vincent Mallet,&nbsp;Stanislas Pol","doi":"10.1002/lci2.36","DOIUrl":"10.1002/lci2.36","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <h3> Background &amp; Aims</h3> \u0000 <p>Systemic therapies for hepatocellular carcinoma (HCC) treatment have limited efficacy and poor safety. Dipeptidyl peptidase-4 inhibitors were initially developed and approved as treatment for type 2 diabetes, yet oral administration of sitagliptin has recently been shown to improve naturally occurring tumour immunity in animal models of HCC.</p> </section>\u0000 \u0000 <section>\u0000 <h3> Methods</h3> \u0000 <p>We conducted a phase Ib clinical trial to evaluate the impact of a pre-operative 3-week DPP4 inhibitor (sitagliptin) treatment in HCC patients undergoing liver resection. The primary objective was to evaluate the safety of a sitagliptin treatment in each of the three groups of patients, according to an escalating dosage of sitagliptin (100, 200 and 600 mg/d). Secondary objectives included the assessment of DPP4 activity, cytokine expression in plasma samples and circulating immune populations.</p> </section>\u0000 \u0000 <section>\u0000 <h3> Results</h3> \u0000 <p>Fourteen patients were included and analysed. In all three dose groups, no severe adverse event related to sitagliptin was reported. A significant inhibition of DPP4 activity was observed upon sitagliptin treatment, which prevented the N-terminal truncation of CXCL10, leading to a mobilization of circulating CD8+ T cells and eosinophils. Immunochemistry analysis showed a lymphoid infiltration in all tumour samples with the presence of a population of CXCR3+ T cells in all but one of the tumours. Positivity for CXCL10 (IP10) and CCR3 in tumour and/or stroma cells was found in all resection pieces.</p> </section>\u0000 \u0000 <section>\u0000 <h3> Conclusion</h3> \u0000 <p>In summary, sitagliptin can be used safely in patients with chronic liver disease and HCC, and could be tested in phase 2 trial, as an adjuvant in combination with others drugs, for the treatment of HCC patients.</p> </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 3","pages":"73-81"},"PeriodicalIF":0.0,"publicationDate":"2021-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43110344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treating patients with advanced hepatocellular carcinoma and impaired liver function: Broadening the reach of anti-cancer therapy","authors":"Antonio D'Alessio,&nbsp;Claudia Angela Maria Fulgenzi","doi":"10.1002/lci2.37","DOIUrl":"10.1002/lci2.37","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) usually arises on the background of liver cirrhosis, which carries an intrinsic risk of death because of liver failure and poses a major treatment challenge. Patient stratification is therefore important to avoid unnecessary treatment for those who are more likely to die from underlying liver disease rather than from cancer. In clinical practice, the severity of liver disfunction is commonly graded with the Child–Pugh (CP) score, which divides patients into three categories (A–B–C), with worsening liver function according to clinical and laboratory criteria.<span>¹</span> For CP-C patients, exclusive supportive care is recommended. CP-B patients, which represent a high percentage of HCC cases, are a heterogeneous category including patients presenting with both mild and moderate–severe liver function. Treatment options for these patients are limited, and they are usually excluded from clinical trials as their impaired liver function is thought to act as a strong confounder and a competitive cause of death.</p><p>According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients with very early (BCLC-0) and early (BCLC-A) disease can undergo a potentially curative approach, such as surgical resection, local ablative therapies and orthotopic liver transplantation (OLT), which is the only curative approach for both HCC and liver cirrhosis. In particular, according to the EASL and the AASLD guidelines, surgical resection is indicated only in patients with good liver function (CP-A) because of the risk of post-surgical liver failure.<span>^{2, 3}</span> Concerning local ablative strategies (radiofrequency ablation, microwave ablation and percutaneous ethanol injection), the treatment choice should be personalised, since there is no a priori contraindication for CP-B patients, but these patients often suffer from ascites and coagulation disorders, which are known contraindications for local ablation.<span>⁴</span> In cases of BCLC B HCC, the recommended treatment is trans-arterial chemoembolization. AASLD guidelines restrict this approach to CP-A patients and only limited CP-B patients,<span>³</span> whereas EASL guidelines include also asymptomatic patients with CP B7, with particular precautions because of the risk of post-treatment liver failure and ischaemic necrosis.<span>²</span></p><p>Systemic therapies are the treatment of choice for patients with advanced (BCLC-C) or intermediate stage (BCLC-B) liver cancer not amenable for loco-regional therapies. While any systemic agent would be contraindicated for CP-C patients, there is a subgroup of CP-B patients which could still be potential candidates for systemic therapy. Data from clinical trials are scattered in this subgroup and most of the evidence comes from real-life experiences and is therefore limited for newly approved drugs. In particular, the only positive large phase III study enrolling patie","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 2","pages":"31-32"},"PeriodicalIF":0.0,"publicationDate":"2021-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.37","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44403645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutations in circulating cell-free tumour DNA: Predictors of survival in hepatocellular carcinoma","authors":"Jessica Howell,&nbsp;Stephen R. Atkinson,&nbsp;David J. Pinato,&nbsp;Shahid A Khan,&nbsp;Rosalba Minisini,&nbsp;Michela E. Burlone,&nbsp;Monica Leutner,&nbsp;Mario Pirisi,&nbsp;Reinhard Büttner,&nbsp;Margarete Odenthal,&nbsp;Rohini Sharma","doi":"10.1002/lci2.34","DOIUrl":"10.1002/lci2.34","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) incidence is increasing worldwide and prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Circulating cell-free DNA of tumour origin (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer. We determined the utility of ctDNA as a prognostic biomarker of survival in HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma cell-free DNA and matched germline DNA were isolated from patients with HCC (n = 51) and cirrhosis (n = 10). Targeted, multiplex PCR ultra-deep sequencing was performed using a liver cancer-specific primer panel for genes <i>ALB, AMPH, APC, ARID1A, ARID2, ATM, AXIN1, BAZ2B, BRAF, CSMD3, CTNNB1, DSE, ERBB2, HNF1A, IGFR2, IGSF10, KEAP1, MET, TP53, UBR3, USP25, ZIC3</i> and <i>ZNF226</i>. Associations between mutations in ctDNA and overall survival were analysed using Cox proportional hazards modelling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>114 putative mutations (70 unique) in were detected in plasma ctDNA in 35 of 51 patients with HCC (69%). On univariable analysis, <i>CSMD3</i> gene mutations were associated with shorter overall survival (Logrank HR 3.18, 95% CI 1.14-8.86, <i>P</i> = .027). The median survival time was 15.5 months (IQR 7.77-16.5 months) in patients with <i>CSMD3</i> mutations compared with the median survival of 26.5 months (IQR 16.93-46.07 months) in patients without <i>CSMD3</i> mutations. Other factors associated with overall survival were advanced BCLC stage (HR 16.52, 95% CI 2.22-122.94, <i>P</i> = .006) and Child-Pugh Class (CPC HR 7.98, 95% CI 2.31-27.61, <i>P</i> = .001). Cox proportional hazards modelling showed mutations in <i>CSMD3</i> remained a significant independent risk for shorter overall survival in HCC when adjusted for age, BCLC stage and Child-Pugh class (HR 4.91, 95% CI 1.60-15.02, <i>P</i> = .005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Detection of <i>CSMD3</i> mutations in plasma ctDNA is associated with reduced overall survival in HCC patients, adjusted for potential confounding factors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 2","pages":"54-62"},"PeriodicalIF":0.0,"publicationDate":"2021-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46629562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focal nodular hyperplasia after systemic chemotherapy: Pathological features of a series of 15 cases","authors":"Anaïs Brunet,&nbsp;Aurélie Beaufrère,&nbsp;François Cauchy,&nbsp;Valérie Paradis","doi":"10.1002/lci2.32","DOIUrl":"10.1002/lci2.32","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Chemotherapy, particularly oxaliplatin, has been associated with the development of focal nodular hyperplasia (FNH). Imaging diagnosis of FNH is well standardized, but it can be misdiagnosed as liver metastasis. The aim of this study was to describe the pathological features of FNH occurring after systemic chemotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>From our pathological files for 1990-2021, we retrieved 15 cases of resected newly developed FNH in adults with liver metastasis treated with systemic chemotherapy. Pathological features of FNH nodules and non-tumoral liver samples were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 11/15 (73%) cases, FNH developed after an oxaliplatin-based regimen. The median interval from the beginning of chemotherapy to the FNH diagnosis was 15 months. FNH was unique in 11 (73%) cases, and the median size of nodules was 1.1 cm [range 0.5-2.5]. Histologically, 9 (60%), 11 (73%) and 11 (73%) cases exhibited fibrous central scar, dystrophic vessels and ductular proliferation, respectively, with all three criteria present in five (33%) cases. Eight (53%) cases showed intralesional steatosis and nine (60%) cases showed a glutamine synthetase immunostaining map-like pattern. In non-tumoral liver, eight (53%) cases exhibited sinusoidal obstruction syndrome and four (27%) nodular regenerative hyperplasia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The occurrence of FNH after systemic chemotherapy is an emerging condition challenging the imaging diagnosis because typical morphological features are frequently missing. The presence of sinusoidal changes, including regenerative hyperplasia, in non-tumoral liver supports the potential role of chemotherapy in the pathogenesis of FNH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 3","pages":"67-72"},"PeriodicalIF":0.0,"publicationDate":"2021-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44290027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recalibrating survival prediction among patients receiving trans-arterial chemoembolization for hepatocellular carcinoma","authors":"Alessandro Cucchetti,&nbsp;Edoardo G. Giannini,&nbsp;Cristina Mosconi,&nbsp;Maria Corina Plaz Torres,&nbsp;Giulia Pieri,&nbsp;Fabio Farinati,&nbsp;Gian Ludovico Rapaccini,&nbsp;Maria Di Marco,&nbsp;Eugenio Caturelli,&nbsp;Rodolfo Sacco,&nbsp;Giuseppe Cabibbo,&nbsp;Claudia Campani,&nbsp;Andrea Mega,&nbsp;Maria Guarino,&nbsp;Antonio Gasbarrini,&nbsp;Gianluca Svegliati-Baroni,&nbsp;Francesco Giuseppe Foschi,&nbsp;Gabriele Missale,&nbsp;Alberto Masotto,&nbsp;Gerardo Nardone,&nbsp;Giovanni Raimondo,&nbsp;Gianpaolo Vidili,&nbsp;Maurizia Rossana Brunetto,&nbsp;Vito Sansone,&nbsp;Marco Zoli,&nbsp;Francesco Azzaroli,&nbsp;Franco Trevisani,&nbsp;the ITA.LI.CA Study Group","doi":"10.1002/lci2.33","DOIUrl":"10.1002/lci2.33","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The four risk-categories identified by the Pre-TACE-Predict model had gradient monotonicity, with median survivals of 52.0, 36.2, 29.9, and 14.1 months respectively. However, predicted survivals systematically underestimated observed survivals (<i>R</i>²: 0.667). A recalibration was adopted maintaining fixed the prognostic index and modifying the baseline survival function. This resulted in an almost perfect calibration (<i>R</i>²: 0.995) in all the four risk categories. Cox regressions showed that aetiology and macrovascular invasion, included in the Pre-TACE-Predict model, had no prognostic impact in the present study population, and that coefficients for tumour size and multiplicity were overestimated. The <i>c</i>-index was similar to that of the m-HAP-III, but higher than those of HAP, m-HAP-II and the six-and-twelve models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The recalibration of Pre-TACE-Predict model improved the estimation of survival probabilities of HCC patients treated with TACE. The highest discriminatory ability of the Pre-TACE-model in comparison to other available models, together with risk stratification and recalibration, makes it the best prognostic tool currently available for these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 2","pages":"45-53"},"PeriodicalIF":0.0,"publicationDate":"2021-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45475488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary metabolites are promising non-invasive biomarkers of hepatocellular carcinoma and chronic liver disease","authors":"Courtney E. Hershberger,&nbsp;Alejandro I. Rodarte,&nbsp;Shirin Siddiqi,&nbsp;Amika Moro,&nbsp;Lou-Anne Acevedo-Moreno,&nbsp;J. Mark Brown,&nbsp;Daniela S. Allende,&nbsp;Federico Aucejo,&nbsp;Daniel M. Rotroff","doi":"10.1002/lci2.25","DOIUrl":"10.1002/lci2.25","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Improved tools are needed for detecting HCC so that treatment can begin as early as possible. Current diagnostic approaches and existing biomarkers, such as alpha-fetoprotein (AFP) lack sensitivity, resulting in too many false negative diagnoses. Machine learning may be able to identify combinations of biomarkers that provide more robust predictions and improve sensitivity for detecting HCC. We sought to evaluate whether metabolites in patient saliva could distinguish those with HCC, cirrhosis, and those with no documented liver disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We tested 125 salivary metabolites from 110 individuals (43 healthy, 37 HCC, 30 cirrhosis) and identified four metabolites that displayed significantly different abundance between groups (FDR <i>P</i> &lt; .2). We also developed four tree-based, machine-learning models, optimized to include different numbers of metabolites, that were trained using cross-validation on 99 patients and validated on a withheld test set of 11 patients. A model using 12 metabolites –octadecanol, acetophenone, lauric acid, 1-monopalmitin, dodecanol, salicylaldehyde, glycyl-proline, 1-monostearin, creatinine, glutamine, serine and 4-hydroxybutyric acid – had a cross-validated sensitivity of 84.8%, specificity of 92.4% and correctly classified 90% of the HCC patients in the test cohort. This model outperformed previously reported sensitivities and specificities for AFP (20-100 ng/mL) (61%, 86%) and AFP plus ultrasound (62%, 88%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Impact</h3>\u0000 \u0000 <p>Metabolites detectable in saliva may represent products of disease pathology or a breakdown in liver function. Notably, combinations of salivary metabolites derived from machine learning may serve as promising non-invasive biomarkers for the detection of HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"2 2","pages":"33-44"},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/lci2.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39433907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}