UNASSIGNED: Primary liver tumors constitute one of the most common tumors. These are aggressive tumors with poor survival. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), most commonly used functional imaging, shows limited tracer retention and poor tumor to background ratios (TBR). Novel 68Ga-fibroblast-activation-protein inhibitor (FAPI) PET/CT has shown better tracer uptake and detection efficacy in liver tumors. However, most of the available literature is limited to single center studies with limited number of patients. So, we tried to review and analyze the head-to-head comparison of 18F-FDG PET/CT and 68Ga-FAPI PET/CT in evaluation of liver tumors.
UNASSIGNED: Literature available on head to head comparison of diagnostic accuracy of 18F-FDG PET/CT and 68Ga-FAPI PET/CT was searched in databases like PubMed, SCOPUS, EMBASE and Google Scholar for published original studies till April 2023. The relevant studies were selected and assessed using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. A random-effect model was used for calculating pooled sensitivity and specificity. They were represented with 95% confidence intervals (95% CI) and demonstrated in Forest plots. I-square statistic was used to assess heterogeneity in the studies.
UNASSIGNED: Pooled sensitivity and specificity of FAPI PET/CT and 18F-FDG PET/CT for detection of primary liver tumors was 94.3% (95% CI: 90.6-96.8%); 89.3% (95% CI: 71.8-97.7%) and 56.1% (95% CI: 49.7-62.5%); 96.4% (95% CI: 81.7-99.9%) respectively. Pooled sensitivity for detection of extrahepatic metastatic disease was 92.2% (range: 88.1-100%; 95% CI: 87.8-95.4%) and 72.4% (range: 69.8-76.5; 95% CI: 65.9-78.2%) respectively. Also, the maximum standardized uptake value (SUVmax) and TBR were higher for FAPI PET/CT than 18F-FDG PET/CT in the included studies.
UNASSIGNED: Overall, FAPI PET/CT showed higher sensitivity for detection of liver tumors with better SUVmax and TBR than 18F-FDG PET/CT.
UNASSIGNED: Primer karaciğer tümörleri en sık görülen tümörlerdendir. Bunlar hayatta kalma oranı düşük olan agresif tümörlerdir. En sık kullanılan fonksiyonel görüntüleme olan florodeoksiglukoz (FDG) pozitron emisyon tomografisi/bilgisayarlı tomografi (PET/BT), sınırlı radyofarmasötik tutulumu ve zayıf tümör/arka plan oranları (TBR) gösterir. Yeni 68Ga-fibroblast aktivasyon protein inhibitörü (FAPI) PET/BT, karaciğer tümörlerinde daha iyi radyofarmasötik tutulumu ve tespit etkinliği göstermiştir. Ancak mevcut literatürün çoğu, sınırlı hasta sayısıyla yapılan tek merkezli çalışmalarla sınırlıdır. Bu nedenle, karaciğer tümörlerinin değerlendirilmesinde 18F-FDG PET/BT ve 68Ga-FAPI PET/BT’nin birebir karşılaştırmasını gözden geçirip analiz etmeye çalıştık.
UNASSIGNED: 18F-FDG PET/BT ve 68Ga-FAPI PET/BT’nin tanısal doğruluğunun birebir karşılaştırılması konusunda mevcut literatür, Nisan 2023’e kadar yayınlanmış araştırma makaleleri için PubMed, SCOPUS, EMBASE ve Google Scholar gibi veritabanlarında tarandı. İlgili çalışmalar Tanısal Doğruluk Çalışmalarının Kalite Değerlendirmesi için Gözden Geçirilmiş Araç-2 kontrol listesi kullanılarak seçilmiş ve değerlendirilmiştir. Birleştirilmiş duyarlılığı ve özgüllüğü hesaplamak için rastgele etki modeli kullanıldı. Bunlar %95 güven aralıklarıyla (%95 GA) temsil edildi ve Orman grafiklerinde gösterildi. Çalışmalardaki heterojenliği değerlendirmek için I-kare istatistiği kullanıldı.
UNASSIGNED: Primer karaciğer tümörlerinin tespiti için FAPI PET/BT’nin havuzlanmış duyarlılığı ve özgüllüğü sırasıyla %94,3 (%95 GA: %90,6-96,8) ve %89,3 (%95 GA: %71,8-97,7); 18F-FDG PET/BT’nin havuzlanmış duyarlılığı ve özgüllüğü sırasıyla %56,1 (%95 GA: %49,7-62,5) ve %96,4 (%95 GA: %81,7-99,9) idi. Ekstrahepatik metastatik hastalığın saptanması için havuzlanmış duyarlılık FAPI PET/BT ve 18F-FDG PET/BT için sırasıyla %92,2 (aralık: %88,1-100; %95 GA: %87,8-95,4) ve %72,4 (aralık: 69,8-76,5; %95 GA: %65,9-78,2) idi. Ayrıca, dahil edilen çalışmalarda FAPI PET/BT için maksimum standardize tutulum değeri (SUVmaks) ve TBR, 18F-FDG PET/BT’den daha yüksekti.
UNASSIGNED: Genel olarak, FAPI PET/BT, karaciğer tümörlerinin tespitinde 18F-FDG PET/BT’ye göre daha iyi SUVmaks ve TBR ile daha yüksek duyarlılık gösterdi.

Globally, hepatic cancer ranks fourth in terms of cancer-related mortality and is the sixth most frequent kind of cancer. Around 80% of liver cancers are hepatocellular carcinomas (HCC), which are the leading cause of cancer death. It is well known that HCC may develop resistance to the available chemotherapy treatments very fast. One of the biggest obstacles in providing cancer patients with appropriate care is drug resistance. According to reports, more than 90% of cancer-specific fatalities are caused by treatment resistance. By binding to the 3\'-untranslated region of target messenger RNAs (mRNAs), microRNAs (miRNAs), a group of noncoding RNAs which are around 17 to 25 nucleotides long, regulate target gene expression. Moreover, they play role in the control of signaling pathways, cell proliferation, and cell death. As a result, miRNAs play an important role in the microenvironment of HCC by changing immune phenotypes, hypoxic conditions, and acidification, as well as angiogenesis and extracellular matrix components. Moreover, changes in miRNA levels in HCC can effectively resist cancer cells to chemotherapy by affecting various cellular processes such as autophagy, apoptosis, and membrane transporter activity. In the current work, we narratively reviewed the role of miRNAs in HCC, with a special focus on tumor microenvironment and drug resistance.

Cancer is characterized by the abnormal and uncontrollable division and growth of cells that can infiltrate tissues and alter normal physiological function, which will become crucial and life-threatening if left untreated. Cancer can be a result of genetics, such as mutations or environmental causes, including smoking, lack of physical activity, as well as nutritional imbalance in the body. Vitamin D is one of the foremost nutrients that play a crucial role in a variety of biochemical pathways, and it is an important key factor in several diseases. Vitamin D is an essential nutrient for preventing malignancies and a complementary treatment for cancer through direct and indirect biochemical pathways. In this article, we summarized the correlation between vitamin D and various cancers using an extensive search on PubMed, Google Scholar, and Scopus. This paper reviews the role of vitamin D in different types of cancer.

BACKGROUND: Hepatobiliary cancers are notoriously difficult to detect, frequently leading to diagnosis in later stages of disease when curative treatment is not an option. The currently used biomarkers such as AFP (alpha-fetoprotein) and CA19.9 lack sensitivity and specificity. Hence, there is an unmet need for an alternative biomarker.
OBJECTIVE: To evaluate the diagnostic accuracy of volatile organic compounds (VOCs) for the detection of hepatobiliary and pancreatic cancers.
METHODS: A systematic review of VOCs\' use in the detection of hepatobiliary and pancreatic cancers was performed. A meta-analysis was performed using the software R. Heterogeneity was explored through meta-regression analysis.
RESULTS: A total of 18 studies looking at 2296 patients were evaluated. Pooled sensitivity and specificity of VOCs for the detection of hepatobiliary and pancreatic cancer were 0.79 (95% CI, 0.72-0.85) and 0.81 (97.5% CI, 0.76-0.85), respectively. The area under the curve was 0.86. Meta-regression analysis showed that the sample media used contributed to heterogeneity. Bile-based VOCs showed the highest precision values, although urine and breath are preferred for their feasibility.
CONCLUSIONS: Volatile organic compounds have the potential to be used as an adjunct tool to aid in the early diagnosis of hepatobiliary cancers.

BACKGROUND: Prediction of survival after the treatment of hepatocellular carcinoma (HCC) has been widely investigated, yet remains inadequate. The application of artificial intelligence (AI) is emerging as a valid adjunct to traditional statistics due to the ability to process vast amounts of data and find hidden interconnections between variables. AI and deep learning are increasingly employed in several topics of liver cancer research, including diagnosis, pathology, and prognosis.
OBJECTIVE: To assess the role of AI in the prediction of survival following HCC treatment.
METHODS: A web-based literature search was performed according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis guidelines using the keywords \"artificial intelligence\", \"deep learning\" and \"hepatocellular carcinoma\" (and synonyms). The specific research question was formulated following the patient (patients with HCC), intervention (evaluation of HCC treatment using AI), comparison (evaluation without using AI), and outcome (patient death and/or tumor recurrence) structure. English language articles were retrieved, screened, and reviewed by the authors. The quality of the papers was assessed using the Risk of Bias In Non-randomized Studies of Interventions tool. Data were extracted and collected in a database.
RESULTS: Among the 598 articles screened, nine papers met the inclusion criteria, six of which had low-risk rates of bias. Eight articles were published in the last decade; all came from eastern countries. Patient sample size was extremely heterogenous (n = 11-22926). AI methodologies employed included artificial neural networks (ANN) in six studies, as well as support vector machine, artificial plant optimization, and peritumoral radiomics in the remaining three studies. All the studies testing the role of ANN compared the performance of ANN with traditional statistics. Training cohorts were used to train the neural networks that were then applied to validation cohorts. In all cases, the AI models demonstrated superior predictive performance compared with traditional statistics with significantly improved areas under the curve.
CONCLUSIONS: AI applied to survival prediction after HCC treatment provided enhanced accuracy compared with conventional linear systems of analysis. Improved transferability and reproducibility will facilitate the widespread use of AI methodologies.

MiRNA polymorphisms had potential to be biomarkers for hepatocellular cancer (HCC) susceptibility. Recently, miRNA single nucleotide polymorphisms (SNPs) were reported to be associated with HCC risk, but the results were inconsistent. We performed a systematic review with a meta-analysis for the association of miRNA SNPs with HCC risk. Thirty-seven studies were included with a total of 11821 HCC patients and 15359 controls in this meta-analysis. We found hsa-mir-146a rs2910164 was associated with a decreased HCC risk in the recessive model (P=0.017, OR = 0.90, 95% confidence interval (CI) = 0.83-0.98). While hsa-mir-34b/c rs4938723 was related with an increased HCC risk in the co-dominant model (P=0.016, odds ratio (OR) = 1.19, 95%CI = 1.03-1.37). When analyzing the Hepatitis B virus (HBV)-related HCC risk, hsa-mir-196a-2 rs11614913 was associated with a decreased HBV-related HCC risk in the co-dominant and allelic models. And hsa-mir-149 rs2292832 was found to be associated with a decreased HBV-related HCC risk in the dominant and recessive models. In conclusion, hsa-mir-146a rs2910164 and hsa-mir-34b/c rs4938723 could be biomarkers for the HCC risk while hsa-mir-196a-2 rs11614913 and hsa-mir-149 rs2292832 had potential to be biomarkers for HBV-related HCC risk.

OBJECTIVE: To perform a systematic review and meta-analysis on platelet-to-lymphocyte ratio (PLR) as a risk factor for post-transplant hepatocellular cancer (HCC) recurrence.
METHODS: A systematic literature search was performed using PubMed. Participants of any age and sex, who underwent liver transplantation for HCC were considered following these criteria: (1) studies comparing pre-transplant low vs high PLR values; (2) studies reporting post-transplant recurrence rates; and (3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measure was set for HCC recurrence after transplantation.
RESULTS: A total of 5 articles, published between 2014 and 2017, fulfilled the selection criteria. As for the quality of the reported studies, all the investigated articles presented an overall high quality. A total of 899 cases were investigated: 718 cases (80.0%) were males. Three studies coming from European countries and one from Japan presented HCV as the main cause of cirrhosis. On the opposite, one Chinese study presented a greater incidence of HBV-related cirrhotic cases. In all the studies apart one, the PLR cut-off value of 150 was reported. At meta-analysis, high PLR value was associated with a significant increase in recurrence after transplantation (OR = 3.33; 95%CI: 1.78-6.25; P < 0.001). A moderate heterogeneity was observed among the identified studies according to the Higgins I2 statistic value.
CONCLUSIONS: Pre-transplant high PLR values are connected with an increased risk of post-operative recurrence of hepatocellular cancer. More studies are needed for better clarify the biological mechanisms of this results.

Recently, many reports showed that the pretransplant neutrophil-lymphocyte ratio (NLR) may be correlated with the prognosis of patients undergoing liver transplantation (LT) for hepatocellular cancer (HCC). However, their results still remained controversial. Thus we performed a meta-analysis of 13 studies to estimate the prognostic value of pretransplant NLR.
Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to September 2017. Hazard ratio (HR) or odds ratio (OR) with its 95% CI was used to evaluate the association between elevated NLR and the prognosis or clinical features of liver cancer patients.
A total of 13 studies including 1936 patients were included in this meta-analysis. Elevated pretransplant NLR had a close association with the overall survival (HR: 2.22; 95% CI: 1.34-3.68), recurrence-free survival (HR: 3.77; 95% CI: 2.01-7.06) and disease-free survival (HR: 2.51; 95% CI: 1.22-5.15) of patients undergoing LT for HCC, respectively. In addition, elevated NLR was associated with the presence of vascular invasion (OR: 2.39; 95% CI: 1.20-4.77) and Milan criteria (OR: 0.26; 95% CI: 0.17-0.40).
The results of this meta-analysis showed that elevated pretransplant NLR may be used as a new prognostic predictor after LT for HCC.

Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-γ and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, and chemokines attracting these cells are particularly important in disease progression. Among C-X-C chemokines, the non-ELR group [as IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ (MIG) and IFN-inducible T-cell-alpha chemoattractant (I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3). IP-10 has uniquely been shown to have prognostic utility as a marker of treatment outcome. IFN- γ-induced chemokines, as MIG and IP-10, may promote lymphocyte recruitment to HCC playing important roles in cancer immunology. The production of CXC chemokines by HCC cell lines has been shown. It has been identified immune-gene signature that predicts patient survival including the chemokine gene IP-10. Inflammatory cytokines (tumour necrosis factor-α, IFN-γ) and Toll-like receptor 3 ligands stimulate intratumoral production of these chemokines which drive T and Natural Killer cells tumor infiltration, leading to enhanced cancer cell death. Furthermore selective recruitment of CXCR3(+) B-cells that bridges proinflammatory IL-17 response and protumorigenic macrophage polarization in HCC has been shown, suggesting that blocking CXCR3(+) B-cell migration or function may help defeat HCC. It has been also shown that the overexpression of IP-10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway in HCC; IP-10 neutralizing antibody could be a potential adjuvant therapy to sensitize HCC-cisplatin treatment.

Hepatocellular cancer (HCC) is increasing dramatically in incidence in Europe and the United States due mainly to the hepatitis C epidemic and, to a lesser extent, increased body mass index of the population. In the fairly recent past, HCC was largely considered as untreatable due to detection mainly at late stages and lack of effective drugs for treatment. Several advances have led to changes in the prognosis of HCC. Screening of high-risk populations has allowed for earlier detection in some studies. If found at an early stage, liver transplantation not only cures the usual underlying cirrhosis but has cure rates for HCC in the range of 60% in recent series. Larger lesions can sometimes be cured by partial hepatic resection assuming the remaining liver is not too damaged to sustain liver functions after surgery. Vaccination for hepatitis B has led to reduction in the incidence of HCC. Significant improvements in antiviral treatments for both hepatitis B and hepatitis C may be having an impact on the incidence of HCC as well. It is still generally held that a finding of metastases precludes cure of HCC. We here report the case of a patient who presented with a large HCC in the context of occult hepatitis C infection. The primary tumor was resected. Over a year later, he developed a lung metastasis that was resected as well. He has not shown recurrence for 6 years since the metastasectomy. We review the recent literature on resection of lung metastases from HCC.