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The Lancet. Oncology Apr 2022The clinical presentation and outcomes of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma are unclear when compared with hepatocellular... (Meta-Analysis)
Meta-Analysis
Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis.
BACKGROUND
The clinical presentation and outcomes of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma are unclear when compared with hepatocellular carcinoma due to other causes. We aimed to establish the prevalence, clinical features, surveillance rates, treatment allocation, and outcomes of NAFLD-related hepatocellular carcinoma.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE and Embase from inception until Jan 17, 2022, for articles in English that compared clinical features, and outcomes of NAFLD-related hepatocellular carcinoma versus hepatocellular carcinoma due to other causes. We included cross-sectional and longitudinal observational studies and excluded paediatric studies. Study-level data were extracted from the published reports. The primary outcomes were (1) the proportion of hepatocellular carcinoma secondary to NAFLD, (2) comparison of patient and tumour characteristics of NAFLD-related hepatocellular carcinoma versus other causes, and (3) comparison of surveillance, treatment allocation, and overall and disease-free survival outcomes of NAFLD-related versus non-NAFLD-related hepatocellular carcinoma. We analysed proportional data using a generalised linear mixed model. Pairwise meta-analysis was done to obtain odds ratio (OR) or mean difference, comparing NAFLD-related with non-NAFLD-related hepatocellular carcinoma. We evaluated survival outcomes using pooled analysis of hazard ratios.
FINDINGS
Of 3631 records identified, 61 studies (done between January, 1980, and May, 2021; 94 636 patients) met inclusion criteria. Overall, the proportion of hepatocellular carcinoma cases secondary to NAFLD was 15·1% (95% CI 11·9-18·9). Patients with NAFLD-related hepatocellular carcinoma were older (p<0·0001), had higher BMI (p<0·0001), and were more likely to present with metabolic comorbidities (diabetes [p<0·0001], hypertension [p<0·0001], and hyperlipidaemia [p<0·0001]) or cardiovascular disease at presentation (p=0·0055) than patients with hepatocellular carcinoma due to other causes. They were also more likely to be non-cirrhotic (38·5%, 27·9-50·2 vs 14·6%, 8·7-23·4 for hepatocellular carcinoma due to other causes; p<0·0001). Patients with NAFLD-related hepatocellular carcinoma had larger tumour diameters (p=0·0087), were more likely to have uninodular lesions (p=0·0003), and had similar odds of Barcelona Clinic Liver Cancer stages, TNM stages, alpha fetoprotein concentration, and Eastern Cooperative Oncology Group (ECOG) performance status to patients with non-NAFLD-related hepatocellular carcinoma. A lower proportion of patients with NAFLD-related hepatocellular carcinoma underwent surveillance (32·8%, 12·0-63·7) than did patients with hepatocellular carcinoma due to other causes (55·7%, 24·0-83·3; p<0·0001). There were no significant differences in treatment allocation (curative therapy, palliative therapy, and best supportive care) between patients with NAFLD-related hepatocellular carcinoma and those with hepatocellular carcinoma due to other causes. Overall survival did not differ between the two groups (hazard ratio 1·05, 95% CI 0·92-1·20, p=0·43), but disease-free survival was longer for patients with NAFLD-related hepatocellular carcinoma (0·79, 0·63-0·99; p=0·044). There was substantial heterogeneity in most analyses (I>75%), and all articles had low-to-moderate risk of bias.
INTERPRETATION
NAFLD-related hepatocellular carcinoma is associated with a higher proportion of patients without cirrhosis and lower surveillance rates than hepatocellular carcinoma due to other causes. Surveillance strategies should be developed for patients with NAFLD without cirrhosis who are at high risk of developing hepatocellular carcinoma.
FUNDING
None.
Topics: Carcinoma, Hepatocellular; Child; Cross-Sectional Studies; Humans; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease
PubMed: 35255263
DOI: 10.1016/S1470-2045(22)00078-X -
Frontiers in Immunology 2021Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations...
Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype with an increased risk of cancer. Variant AT patients present with milder phenotype or atypical form of classical symptoms causing under- or mis- diagnosis. Although missense mutations are more frequent, an atypical presentation can be associated with deleterious mutations due to unknown modifying factors.
Topics: Adolescent; Adult; Ataxia; Ataxia Telangiectasia; Child; Child, Preschool; Female; Humans; Iran; Male; Mutation, Missense; Phenotype; T-Lymphocytes, Regulatory; Young Adult; alpha-Fetoproteins
PubMed: 35095854
DOI: 10.3389/fimmu.2021.779502 -
Rambam Maimonides Medical Journal Jan 2022Congenital nasopharyngeal masses (CNMs) are rare. Presenting symptoms vary, and the differential diagnoses cover a wide spectrum of possibilities. As it is uncommon,... (Review)
Review
OBJECTIVE
Congenital nasopharyngeal masses (CNMs) are rare. Presenting symptoms vary, and the differential diagnoses cover a wide spectrum of possibilities. As it is uncommon, most examples discussed in literature are described as case reports or series. Guidelines on CNM patient management do not exist. In this study, we present two (2) cases of neonates with CNMs that were encountered at our tertiary center. Additionally, to best elaborate a comprehensive, case-based approach to CNM management, we offer an up-to-date, diagnosis-to-treatment review of current literature.
METHODS
Case series and systematic literature review.
RESULTS
Twenty-eight (28) studies are included since January 2000 to October 2021, with a total of 41 cases. Most common diagnosis was teratoma (78%). Female-to-male ratio was 2.5:1. Twenty percent of cases presented prenatally with polyhydramnios or elevated alpha-fetoprotein. Postnatally, the presenting symptoms most frequently encountered were respiratory distress (78%), oral mass (52%), and feeding difficulties (29%). Seventy-five percent of affected newborns showed symptoms within the first 24 hours of life. Forty percent of cases had comorbidities, especially in the head and neck region.
CONCLUSIONS
Congenital nasopharyngeal masses can be detected antenatally, or symptomatically immediately after birth. Airway protection is a cornerstone in the management. Selecting the right imaging modality and convening a multidisciplinary team meeting are important toward the planning of next steps/therapeutic approach. Typically, a transnasal or transoral surgical approach will be deemed sufficient to address the problem, with a good overall prognosis.
PubMed: 35089125
DOI: 10.5041/RMMJ.10463 -
Frontiers in Surgery 2021This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection....
This study aims to comprehensively analyze the influence of spontaneous tumor rupture on the prognosis of hepatocellular carcinoma patients following hepatic resection. We systematically searched four online electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, for eligible studies published from inception to March 2021. The main endpoints were overall survival (OS) and disease-free survival (DFS). This meta-analysis included 21 observational articles with 57,241 cases. The results revealed that spontaneous tumor rupture was associated with worse OS (hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.33-2.05) and DFS (HR, 1.42; 95% CI, 1.12-1.80) in resectable hepatocellular carcinoma patients. This phenomenon was observed in most subgroups, which were classified by recorded survival time, age, country, alpha-fetoprotein (AFP) concentration, liver cirrhosis, and microvascular invasion. However, in subgroups of macrovascular invasion positive, spontaneous tumor rupture was not a risk factor for OS (HR, 1.55; 95% CI, 0.99-2.42) and DFS (HR, 1.23; 95% CI, 0.91-1.65) in hepatocellular carcinoma patients after hepatectomy. For macrovascular invasion negative, compared with non-ruptured hepatocellular carcinoma patients, ruptured hepatocellular carcinoma patients exhibited worse prognosis for OS (HR, 1.55; 95% CI, 0.99-2.42) and DFS (HR, 1.23; 95% CI, 0.91-1.65) following hepatectomy. Spontaneous tumor rupture was a prognostic risk factor for hepatocellular carcinoma patients after hepatic resection. However, in macrovascular invasion patients, spontaneous tumor rupture was not a prognostic risk factor.
PubMed: 34869566
DOI: 10.3389/fsurg.2021.769233 -
Frontiers in Genetics 2021The lack of an accurate biomarker in hepatocellular carcinoma (HCC) has hindered early detection, diagnosis, and treatment. Circular RNAs (circRNAs), which can be used...
The lack of an accurate biomarker in hepatocellular carcinoma (HCC) has hindered early detection, diagnosis, and treatment. Circular RNAs (circRNAs), which can be used as novel biomarkers in liquid biopsies, have been brought to light as a result of the advances in research on molecular biomarkers and the progression of genomic medicine. We conducted a meta-analysis of the diagnostic accuracy of serum/plasma circRNAs or the combination of circRNAs and α-fetoprotein (AFP) in HCC. We identified eight studies that met the inclusion/exclusion criteria from PubMed, Web of Science, EMBASE, and Cochrane Library databases. The data were pooled, and the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) with 95% confidence intervals (CIs) were calculated. The areas under the summary receiver operator characteristic (SROC) curves (AUCs) were also calculated. The sensitivity of circRNAs was 0.82 (95% CI: 0.78-0.85), and the specificity was 0.82 (95% CI: 0.78-0.86). The sensitivity of AFP was 0.65 (95% CI: 0.61-0.68), and the specificity was 0.90 (95% CI: 0.85-0.93). The AUC was 0.89 (95% CI: 0.86-0.91) for circRNAs and 0.77 (95% CI: 0.74-0.81) for AFP. The sensitivity of the combination of circRNAs and AFP was 0.88 (95% CI: 0.84-0.92), specificity was 0.86 (95% CI: 0.80-0.91), and AUC was 0.94 (95% CI: 0.91-0.96). Additionally, a subgroup analysis was conducted based on the control groups used; the diagnostic accuracy was particularly high in the comparison of HCC vs. healthy controls. In summary, serum/plasma circRNAs are accurate biomarkers suitable for clinical use for detecting HCC, and the combination of circRNAs and AFP improved the diagnostic accuracy.
PubMed: 34659344
DOI: 10.3389/fgene.2021.722208 -
European Journal of Surgical Oncology :... Mar 2022Many prognostic models for Hepatocellular Carcinoma (HCC) have been developed to inform patients and doctors about individual prognosis. Previous reviews of these models... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many prognostic models for Hepatocellular Carcinoma (HCC) have been developed to inform patients and doctors about individual prognosis. Previous reviews of these models were qualitative and did not assess performance at external validation. We assessed the performance of prognostic models for HCC and set a benchmark for biomarker studies.
METHODS
All externally validated models predicting survival for patients with resected HCC were systematically reviewed. After selection, we extracted descriptive statistics and aggregated c-indices using meta-analysis.
RESULTS
Thirty-eight validated prognostic models were included. Models used on average 7 (IQR:4-9) prognostic factors. Tumor size, tumor number, and vascular invasion were almost always included. Alpha-fetoprotein (AFP) was commonly incorporated since 2007. Recently, the more subjective items ascites and encephalopathy have been dropped. Eight established models performed poor to moderate at external validation, with a pooled C-index below 0.7; including the Barcelona Clinic Liver Cancer (BCLC) system, the American Joint Committee on Cancer (AJCC) 7th edition, the Cancer of the Liver Italian (CLIP) Program, and the Japan Integrated Staging (JIS) score. Out of 24 prognostic models predicting OS, only 6 (25%) had good performance at external validation with pooled C-indices above 0.7; the Li-post (0.77), Li-OS (0.74), Yang-pre (0.74), Yang-post (0.76), Shanghai-score (0.70), and Wang-nomogram (0.71). Models improved over time, but overall performance and study quality remained low.
CONCLUSIONS
Six validated prognostic models demonstrated good performance for predicting survival after resection of HCC. These models can guide patients and doctors and are a benchmark for future models incorporating novel biomarkers.
Topics: Biomarkers; Carcinoma, Hepatocellular; China; Humans; Liver Neoplasms; Neoplasm Staging; Prognosis
PubMed: 34602315
DOI: 10.1016/j.ejso.2021.09.012 -
Medicine Sep 2021The present network meta-analysis was conducted to perform an indirect comparison among ramucirumab, regorafenib, and cabozantinib in patients with advanced... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety for second-line treatment with ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma progressed on sorafenib treatment: A network meta-analysis.
BACKGROUND
The present network meta-analysis was conducted to perform an indirect comparison among ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma (HCC) progressed on sorafenib treatment.
METHODS
A systematic review through Medline, Embase, and Cochrane library was developed, with eligible randomized clinical trials been included. Hazard ratios (HRs) including progression-free survival (PFS), overall survival (OS), odds ratios of disease control rate (DCR), objective response rate (ORR), and adverse events were compared indirectly with network meta-analysis using random model in software STATA version 13.0.
RESULTS
A total of 4 randomized clinical trials including 2137 patients met the eligibility criteria and enrolled. Indirect comparisons showed that there was no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among agents of regorafenib, cabozantinib, and ramucirumab in advanced HCC patients with elevated α-fetoprotein (AFP) (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib was the only agent associated with significant superiority in OS, compared with placebo (hazard ratio 0.67, 95% CI, 0.50-0.90).
CONCLUSIONS
The present network meta-analysis revealed that there might be no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among regorafenib, cabozantinib, or ramucirumab in advanced HCC patients with elevated AFP (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib might be associated with significant superiority in OS, compared to placebo, which need further investigation in clinical practice.
Topics: Anilides; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Drug Administration Schedule; Humans; Liver Neoplasms; Neoplasm Metastasis; Phenylurea Compounds; Pyridines; Randomized Controlled Trials as Topic; Sorafenib; Ramucirumab
PubMed: 34559096
DOI: 10.1097/MD.0000000000027013 -
Journal of Clinical Medicine Aug 2021We aimed to systematically evaluate the incidence of inadequate US in hepatocellular carcinoma (HCC) surveillance and determine the risk factors. Original studies...
We aimed to systematically evaluate the incidence of inadequate US in hepatocellular carcinoma (HCC) surveillance and determine the risk factors. Original studies reporting the incidence or risk factors for inadequate US were identified in MEDLINE, EMBASE, and the Cochrane database. The pooled incidence of inadequate US was calculated using a random effects model, and subgroup analyses were performed. The pooled odds ratio (OR) was calculated for each risk factor for inadequate US. Six eligible articles were identified from 756 screened articles (4250 patients). The pooled incidence of inadequate US was 21.5%. Significantly higher rates of inadequate US were noted in studies including patients with and without hepatic observations compared with those evaluating only patients with hepatic observations (23.2% vs. 18.8%), studies using US alone compared with US plus alpha-fetoprotein (28.0% vs. 20.8%), and those using pathology and imaging as a reference standard compared with imaging only (23.2% vs. 17.9%). Nonalcoholic steatohepatitis (OR = 2.3 (1.07-4.84)), Child-Pugh B cirrhosis (OR = 2.2 (1.10-4.37)), and high body mass index (OR = 2.2 (1.12-4.24)) were significant risk factors for inadequate US ( ≤ 0.04). In patients at risk of HCC, 21.5% of US surveillance was inadequate. An alternative surveillance modality might be considered in patients with risk factors.
PubMed: 34441831
DOI: 10.3390/jcm10163535 -
Frontiers in Oncology 2021We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study...
OBJECTIVES
We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment.
METHODS
We report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.
RESULTS
A total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% ( = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients ( = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis ( = 0.82, = 0.96, = 0.25).
CONCLUSIONS
HAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.
PubMed: 34422656
DOI: 10.3389/fonc.2021.702216 -
Cancers Jul 2021This systematic review and meta-analysis was performed to explore overall survival (OS) and event free survival (EFS) rates internationally over the past two decades and... (Review)
Review
OBJECTIVE
This systematic review and meta-analysis was performed to explore overall survival (OS) and event free survival (EFS) rates internationally over the past two decades and to define specific subgroups with inferior outcomes which may demand different treatment strategies.
METHODS
The search focused on malignant extracranial germ cell tumours (GCTs) in the paediatric population. The initial database search identified 12,556 articles; 32 articles were finally included in this review, comprising a total of 5095 patients.
RESULTS
The studies were heterogeneous, varying from single institution reports to large prospective trials. Older studies, describing eras where non-platinum-based chemotherapy regimens were used, showed clearly worse outcomes. Survival for stage I-II gonadal disease is excellent. On the other hand, patients with an initial alpha-fetoprotein (AFP) > 10,000 ng/mL or kU/L, age > 11 years and stage IV disease confer a survival disadvantage. For testicular disease in particular, lymphovascular invasion and certain histopathological subtypes, such as embryonal carcinoma (EC) and mixed malignant GCTs, survival is poorer. Survival data for sacrococcygeal and mediastinal GCTs show a heterogeneous distribution across studies in this review, independent of year of publication. Patients > 12 years presenting with a mediastinal GCT pose a subpopulation which fares worse than GCTs in other locations or age groups. This is independent of AFP levels, stage of disease or treatment protocol, and these patients may demand a different treatment strategy.
CONCLUSIONS
This review describes the heterogeneous nature of GCTs in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, in line with the current developmental biology-based classification system, subpopulations can be defined which have an inferior EFS and OS and where future research and more individualised treatment would help to improve survival.
PubMed: 34298776
DOI: 10.3390/cancers13143561