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Journal of Pediatric Surgery Sep 2020The incidence of children developing recurrent sacrococcygeal teratoma (SCT) is 2-35%. Serum alpha-fetoprotein (AFP) is often used as a tumor marker for (malignant)...
BACKGROUND
The incidence of children developing recurrent sacrococcygeal teratoma (SCT) is 2-35%. Serum alpha-fetoprotein (AFP) is often used as a tumor marker for (malignant) recurrences of SCT and could potentially be used during routine follow-up after SCT resection. However, the diagnostic accuracy of serum AFP levels during follow-up has not been well established. Therefore, we aimed to systematically review the diagnostic accuracy of serum AFP levels in recurrent SCT.
METHODS
We queried Search Premier, COCHRANE Library, EMCARE, EMBASE, PubMed, ScienceDirect and Web of Science databases to identify studies regarding patients with SCT with follow-up using serum AFP levels postoperative. We estimated sensitivity and specificity of serum AFP levels.
RESULTS
Fifteen studies (613 patients, 121 recurrences) were included and these mainly described serum AFP levels in patients with recurrent SCT (n = 111); 83 (75%) patients with recurrent SCT had elevated serum AFP levels. A subgroup analysis of articles that measured serum AFP levels in all patients (n = 6, 136 patients, 14 recurrences) showed a sensitivity and specificity of 79% and 95%, respectively. The sensitivity of AFP levels to detect malignant recurrence was 96%.
CONCLUSION
Diagnostic accuracy of serum AFP levels to detect recurrent SCT seems promising, though sensitivity could be overestimated since serum AFP levels are mainly described in patients with elevated AFP levels or at recurrent SCT. Furthermore, serum AFP levels could be helpful to detect malignant recurrences.
TYPE OF STUDY
Systematic review of level 2-4 studies.
LEVEL OF EVIDENCE
Level 2-4 (mostly level 2).
Topics: Biomarkers, Tumor; Child; Humans; Neoplasm Recurrence, Local; Pelvic Neoplasms; Sacrococcygeal Region; Sensitivity and Specificity; Spinal Neoplasms; Teratoma; alpha-Fetoproteins
PubMed: 32376010
DOI: 10.1016/j.jpedsurg.2020.03.014 -
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 -
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 -
Liver Transplantation : Official... Dec 2022Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing...
Clinical outcomes of patients with Liver Imaging Reporting and Data System 3 or Liver Imaging Reporting and Data System 4 observations in patients with cirrhosis: A systematic review.
Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing hepatocellular carcinoma (HCC), but risk estimates remain imprecise. We conducted a systematic review of Ovid MEDLINE, EMBASE, and Cochrane databases from inception to December 2021 to identify cohort studies examining HCC incidence among patients with LR-3 or LR-4 observations on computed tomography (CT) or magnetic resonance imaging (MRI). Predictors of HCC were abstracted from each study, when available. Of 13 total studies, nine conducted LR-3 observation-level analyses, with the proportions of incident HCC ranging from 1.2% to 12.5% at 12 months and 4.2% to 44.4% during longer study follow-up. Among three studies with patient-level analyses, 8%-22.2% of patients with LR-3 lesions developed LR-4 observations and 11.1%-24.5% developed HCC. Among nine studies conducting LR-4 observation-level analyses, incident HCC ranged from 30.8% to 44.0% at 12 months and 30.9% to 71.0% during study follow-up; conversely, 6%-42% of observations were downgraded to LR-3 or lower. Patient-level factors associated with HCC included older age, male sex, higher alpha-fetoprotein levels, viral etiology, and prior history of HCC; observation-level factors included maximum diameter, threshold growth, T2 hyperintensity, and visibility on ultrasound. Studies were limited by small sample sizes, inclusion of patients with prior HCC, short follow-up duration, and failure to account for clustering of observations in patients or competing risks of transplantation and death. LR-3 and LR-4 observations have elevated but variable risks of HCC. Higher quality studies are necessary to identify high-risk patients who warrant close CT or MRI-based follow-up.
Topics: Humans; Male; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Liver Transplantation; Liver Cirrhosis; Magnetic Resonance Imaging; Contrast Media; Sensitivity and Specificity
PubMed: 35980600
DOI: 10.1002/lt.26562 -
Clinical and Experimental Medicine Feb 2022A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option.
METHODS
Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels.
RESULTS
Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50-0.79), cabozantinib (HR = 0.76, 95% CI = 0.63-0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70-0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36-0.52), regorafenib (HR = 0.46, 95% CI = 0.37-0.56), ramucirumab (HR = 0.54, 95% CI = 0.43-0.68), brivanib (HR = 0.56, 95% CI = 0.42-0.76), S-1 (HR = 0.60, 95% CI = 0.46-0.77), axitinib (HR = 0.62, 95% CI = 0.44-0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57-0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients' stratification.
CONCLUSIONS
The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC.
Topics: Bayes Theorem; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Network Meta-Analysis; Sorafenib
PubMed: 34146196
DOI: 10.1007/s10238-021-00727-7 -
World Journal of Gastroenterology Sep 2020Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging...
BACKGROUND
Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM
To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS
A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS
There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival ( = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival ( = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant ( = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION
NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
Topics: Albumins; Bilirubin; Carcinoma, Hepatocellular; Child; Humans; Liver Neoplasms; Lymphocytes; Neutrophils; Prognosis; Retrospective Studies
PubMed: 32952347
DOI: 10.3748/wjg.v26.i33.5022 -
Medicine Aug 2019Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not consistent. This meta-analysis aimed to explore the relationship between AFP response and clinical outcomes of HCC.
METHODS
PubMed, Embase, Medline and Cochrane library were searched for relevant articles published before March 20, 2019. The data were analyzed using RevMan5.3 software.
RESULTS
Twenty-nine articles with 4726 HCC patients were finally included for analysis. The pooled results showed that post-treatment AFP response was significantly associated with overall survival (OS) (hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.35-0.47, P <.001), progression free survival (PFS) (HR = 0.46, 95% CI: 0.39-0.54, P <.001) and recurrence free survival (RFS) (HR = 0.41, 95% CI: 0.29-0.56, P <.001) of HCC patients.
CONCLUSION
post-treatment AFP response might be a useful prognostic marker for HCC patients.
Topics: Humans; Liver Neoplasms; Prognosis; alpha-Fetoproteins
PubMed: 31374020
DOI: 10.1097/MD.0000000000016557 -
The Turkish Journal of Gastroenterology... Mar 2020Previous study has shown a positive relationship between the hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and cholangiocarcinoma (CCA); however, their... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Previous study has shown a positive relationship between the hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and cholangiocarcinoma (CCA); however, their correlation with different anatomical sites of CCA (i.e. ICC and ECC) has not been revealed. This study aims to evaluate the association of HBV or HCV infection with CCA, including the intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), and to determine the roles of α-1 fetoprotein (AFP), CA19-9, and lymph node involvement in CCA with HBV infection.
MATERIALS AND METHODS
Relevant studies published between 2004 and 2016 were systematically searched and retrieved from PubMed, SpringerLink, and Science Direct using key terms such as "cholangiocarcinoma", "bile duct cancer", "extrahepatic cholangiocarcinoma", and "intrahepatic cholangiocarcinoma". The demographic, clinical, and laboratory data were extracted from the included studies, and the meta-analysis was performed using RevMan and STATA 11.0 software.
RESULTS
A total of 13 studies with CCA matched the inclusion criteria in this meta-analysis, including 7,113 CCA patients and 24,763 controls. This meta-analysis showed that the HBV or HCV infections can significantly increase the risk of CCA, including ICC and ECC. In addition, the higher levels of AFP, lower levels of CA19-9, and lymph node involvement were detected in the CCA patients with HBV infection as compared to those without.
CONCLUSION
The HBV and HCV infections significantly increased the risk of CCA, as well as ICC and ECC. The involvement of AFP, CA19-9, and lymph nodes may play an important role in the diagnosis of CCA.
Topics: Adult; Aged; Antigens, Tumor-Associated, Carbohydrate; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Female; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Lymph Nodes; Male; Middle Aged; Risk Factors; alpha-Fetoproteins
PubMed: 32343237
DOI: 10.5152/tjg.2020.19056 -
Therapeutic Advances in Gastroenterology 2024Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to...
BACKGROUND
Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials.
OBJECTIVES
The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES AND METHODS
PubMed, Embase, ClinicalTrials.gov, and international conference databases have been searched from 1 January 2010 to 1 December 2023.
RESULTS
After screening, 17 phase III trials encompassing 18 treatments were included. In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93-1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva. In the context of progression-free survival, Atezo + Beva seemed to outperform Tre + Du (HR: 0.66 CI: 0.49-0.87), while the effects are comparable to Sint + Beva, Camre + Rivo, and Lenva + Pemb. Upon comparison between Asia-Pacific and non-Asia-Pacific cohorts, as well as between hepatitis B virus (HBV)-infected and non-HBV-infected populations, immune checkpoint inhibitor (ICI)-based treatments seemed to exhibit heightened efficacy in the Asia-Pacific group and among individuals with HBV infection. However, combined ICI-based therapies did not show more effectiveness than molecular-targeted drugs in patients without macrovascular invasion and/or extrahepatic spread. As for grades 3-5 adverse events, combined therapies showed comparable safety to sorafenib and lenvatinib.
CONCLUSION
Compared with sorafenib and lenvatinib, combination therapies based on ICIs significantly improved the prognosis of advanced HCC and demonstrated similar safety. At the same time, the optimal treatment approach should be tailored to individual patient characteristics, such as etiology, tumor staging, and serum alpha-fetoprotein levels. With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies.
TRIAL REGISTRATION
PROSPERO, CRD42022288172.
PubMed: 38645513
DOI: 10.1177/17562848241237631 -
Medicine Aug 2019To verify the accuracy of serum dickkopf-1 protein (DKK-1) in the diagnosis of hepatocellular carcinoma (HCC) by an updated meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To verify the accuracy of serum dickkopf-1 protein (DKK-1) in the diagnosis of hepatocellular carcinoma (HCC) by an updated meta-analysis.
METHODS
We searched potential eligible studies in PubMed and Embase before July 8, 2018. Sensitivity (SN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), summary receiver operating characteristics curve (sROC), and diagnostic odds ratio (DOR) were pooled with their 95% confidence intervals CIs) using a bivariate random-effects model.
RESULTS
A total of 8 articles contained 10 studies on diagnosis of HCC with DKK-1 alone,7 articles contained 9 studies on diagnosis of HCC with a-fetoprotein (AFP) alone and 5 articles contained 7 studies on diagnosis of HCC with DKK-1 + AFP were identified. The pooled SN, SP, PLR, NLR, and DOR of DKK-1 alone, AFP alone and DKK-1 + AFP were 0.72 (95% CI: 0.70-0.75), 0.62 (95% CI:0.59-0.64) and 0.80 (95% CI:0.78-0.83), 0.86 (95% CI: 0.84-0.87), 0.82 (95% CI:0.80-0.84) and 0.87 (95% CI: 0.85-0.88), 4.91 (95% CI: 2.73-8.83), 3.60 (95% CI:2.01-6.44) and 6.18 (95% CI: 4.68-8.16), 0.32 (95% CI: 0.22-0.47), 0.49 (95% CI:0.40-0.60) and 0.20 (95% CI: 0.15-0.26), and 17.21 (95% CI: 9.10-32.57), 7.45 (95% CI:3.69-15.01) and 31.39 (95% CI: 23.59-43.20), respectively. The area under the sROC was 0.88, 0.70, and 0.92 for the 3 diagnostic methods.
CONCLUSIONS
Serum DKK-1 + AFP showed a high accuracy for diagnosis of HCC, and serum DKK-1 alone had moderate accuracy as compared to a previous meta-analysis, while AFP alone owned an unsatisfied diagnostic behavior for HCC. Due to the limitations of the current analysis, further well-designed studies are needed to confirm the diagnostic value of DKK-1 and DKK-1 + AFP in HCC diagnosis.
Topics: Carcinoma, Hepatocellular; Humans; Intercellular Signaling Peptides and Proteins; Liver Neoplasms; Predictive Value of Tests; alpha-Fetoproteins
PubMed: 31393380
DOI: 10.1097/MD.0000000000016725