Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.

Role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: A systemic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients.

BACKGROUND AND AIMS: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.

Auxin plays a role in the adaptation of rice to anaerobic germination and seedling establishment.

Auxin is well known to stimulate coleoptile elongation and rapid seedling growth in the air. However, its role in regulating rice germination and seedling establishment under submergence is largely unknown. Previous studies revealed that excessive levels of indole-3-acetic acid(IAA) frequently cause the inhibition of plant growth and development. In this study, the high-level accumulation of endogenous IAA is observed under dark submergence, stimulating rice coleoptile elongation but limiting the root and primary leaf growth during anaerobic germination (AG). We found that oxygen and light can reduce IAA levels, promote the seedling establishment and enhance rice AG tolerance. miRNA microarray profiling and RNA gel blot analysis results show that the expression of miR167 is negatively regulated by submergence; it subsequently modulates the accumulation of free IAA through the miR167-ARF-GH3 pathway. The OsGH3-8 encodes an IAA-amido synthetase that functions to prevent free IAA accumulation. Reduced miR167 levels or overexpressing OsGH3-8 increase auxin metabolism, reduce endogenous levels of free IAA and enhance rice AG tolerance. Our studies reveal that poor seed germination and seedling growth inhibition resulting from excessive IAA accumulation would cause intolerance to submergence in rice, suggesting that a certain threshold level of auxin is essential for rice AG tolerance.

MALAT1/ mir-1-3p mediated BRF2 expression promotes HCC progression via inhibiting the LKB1/AMPK signaling pathway.

BACKGROUND: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. METHODS: The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. RESULTS: We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B­related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. CONCLUSIONS: Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.

The role of MSCs and CAR-MSCs in cellular immunotherapy.

Chimeric antigen receptors (CARs) are widely used by T cells (CAR-T cells), natural killer cells dendritic cells and macrophages, and they are of great importance in cellular immunotherapy. However, the use of CAR-related products faces several challenges, including the poor persistence of cells carrying CARs, cell dysfunction or exhaustion, relapse of disease, immune effector cell-associated neurotoxicity syndrome, cytokine release syndrome, low efficacy against solid tumors and immunosuppression by the tumor microenvironment. Another important cell therapy regimen involves mesenchymal stem cells (MSCs). Recent studies have shown that MSCs can improve the anticancer functions of CAR-related products. CAR-MSCs can overcome the flaws of cellular immunotherapy. Thus, MSCs can be used as a biological vehicle for CARs. In this review, we first discuss the characteristics and immunomodulatory functions of MSCs. Then, the role of MSCs as a source of exosomes, including the characteristics of MSC-derived exosomes and their immunomodulatory functions, is discussed. The role of MSCs in CAR-related products, CAR-related product-derived exosomes and the effect of MSCs on CAR-related products are reviewed. Finally, the use of MSCs as CAR vehicles is discussed. Video Abstract.

The Association of Glycemic Index, Glycemic Load, and Daily Carbohydrates Intake with the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Glycemic index (GI), glycemic load (GL) and daily carbohydrates intake have been associated with a variety of cancers, but their implications in hepatocellular carcinoma (HCC) remain controversial. The purpose of our study is to investigate the association of GI, GL and daily carbohydrates intake with the risk of HCC. Methods: Systematic searches were conducted in PubMed, Embase and Web of Science until November 2020. According to the degree of heterogeneity, random effect model or fixed effect model was chosen to obtain the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results: Four cohort studies and three case-control studies were eventually included. The pooled results showed no significant association of GI (RR = 1.11, 95% CI = 0.80-1.53), GL (RR = 1.09, 95% CI = 0.76-1.55), and daily carbohydrates intake (RR = 1.09, 95% CI = 0.84-1.32) with the risk of HCC in the general population. Subgroup analysis revealed that in hepatitis B virus (HBV) or/and hepatitis C virus (HCV)-positive group, GI was irrelevant to the risk of HCC (RR = 0.65, 95% CI = 0.32-1.32), while a high GL diet was associated with a higher risk of HCC (RR = 1.52, 95% CI = 1.04-2.23). In contrast, in HBV and HCV-negative group, both GI (RR = 1.23, 95% CI = 0.88-1.70) and GL (RR = 1.17, 95% CI = 0.83-1.64) were not associated with the risk of HCC. Conclusion: A high GL diet increases the risk of HCC in those with viral hepatitis. A low GL diet is recommended for them to reduce the risk of HCC.

Comparison of BACTEC versus conventional enrichment medium for peritoneal dialysate fluid culture.

BACKGROUND: Bacterial peritonitis remains a significant cause of mortality in patients on peritoneal dialysis (PD). Early detection of causative organisms and targeted antimicrobial treatment allow for better clinical outcomes. This study compares bacterial growth results from peritoneal dialysate in the BACTEC blood culture system vs. conventional culture. MATERIALS AND METHODS: We conducted a prospective study on 46 patients with 63 consecutive episodes of suspected PD peritonitis between August 2020 and August 2021. PD dialysate was simultaneously sent to the laboratory in both BACTEC and sterile bottles. BACTEC bottles were incubated in the BD BACTEC FX system for 5 days. PD effluent transported from the sterile bottles was centrifuged at 3,000 rpm for 15 minutes; the supernatant was inoculated into cooked-meat broth for enrichment. Both incubation methods were extended to 14 days if microorganisms were seen on the Gram-stained smear. Recovery of isolated micro-organisms and time to detection (TTD) were compared. RESULTS: 26 episodes of suspected PD peritonitis based on clinical criteria were identified during the study period. The sensitivity of the BACTEC and the conventional culture methods was 50% and 42.3%, respectively (p = 0.45). Seven samples had partial concordance or discordant results. McNemar's χ2-test revealed no statistical difference between either method (p = 0.45). TTD was 18.9 ± 24.4 hours via the BACTEC method vs. 37 ± 16.5 hours in conventional cultures (p = 0.014). CONCLUSION: The comparable sensitivities and similar yield in identifying pathogens could be due to the enrichment medium and prolonged incubation period. The shorter TTD for the BACTEC method could facilitate earlier confirmation of bacteriological diagnosis and subsequent treatment strategies.

Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Preliminary studies have suggested that soluble programmed death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) have prognostic implications in many malignant tumors. However, the correlation between sPD-1/sPD-L1 level and prognosis of hepatocellular carcinoma (HCC) is still unclear. METHODS: We searched several electronic databases from database inception to October 7, 2021. Meta-analyses were performed separately for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), time to progression (TTP), and tumor-free survival (TFS). Random effects were introduced to this meta-analysis. The correlation between sPD-1/sPD-L1 level and prognosis was evaluated using hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS: A total of 11 studies (1291 patients) were incorporated into this meta-analysis, including seven on sPD-L1, two on sPD-1, and two about both factors. The pooled results showed that high sPD-L1 level was associated with worse OS (HR = 2.46, 95%CI 1.74-3.49, P < 0.001; I2 = 31.4, P = 0.177) and poorer DFS/RFS/TTP/TFS of patients with HCC (HR = 2.22, 95%CI 1.47-3.35, P < 0.001; I2 = 66.1, P = 0.011), irrespective of method of detection, study type, treatment, cut-off value and follow-up time. In contrast, the level of sPD-1 was not correlated to the OS (HR = 1.19, 95%CI 0.55-2.56, P = 0.657) and DFS/TFS of patients with HCC (HR = 0.94, 95%CI 0.36-2.49, P = 0.906). CONCLUSION: sPD-L1 rather than sPD-1 could be a good predictor for recurrence and survival after treatment for HCC. More high-quality prospective studies are warranted to assess the prognostic value of sPD-1 or sPD-L1 for HCC.

Microsphere-assisted Fabry-Perot interferometry: proof of concept.

We propose a microsphere-assisted Fabry-Perot interferometry (MAFPI) for microstructure measurement. We stretch the single-mode fiber and combine it with microspheres of different sizes and refractive indices, which can form super-focused spots with different characteristics, that is, a photonic nanojet phenomenon. As a proof of principle, we performed scanning imaging of optical discs and holographic gratings by MAFPI. The optical disc image obtained by MAFPI is consistent with the result obtained by a scanning electron microscope, and the obtained grating image is consistent with the actual result.

Automated lung ultrasound image assessment using artificial intelligence to identify fluid overload in dialysis patients.

BACKGROUND: Fluid assessment is challenging, and fluid overload poses a significant problem among dialysis patients, with pulmonary oedema being the most serious consequence. Our study aims to develop a simple objective fluid assessment strategy using lung ultrasound (LUS) and artificial intelligence (AI) to assess the fluid status of dialysis patients. METHODS: This was a single-centre study of 76 hemodialysis and peritoneal dialysis patients carried out between July 2020 to May 2022. The fluid status of dialysis patients was assessed via a simplified 8-point LUS method using a portable handheld ultrasound device (HHUSD), clinical examination and bioimpedance analysis (BIA). The primary outcome was the performance of 8-point LUS using a portable HHUSD in diagnosing fluid overload compared to physical examination and BIA. The secondary outcome was to develop and validate a novel AI software program to quantify B-line count and assess the fluid status of dialysis patients. RESULTS: Our study showed a moderate correlation between LUS B-line count and fluid overload assessed by clinical examination (r = 0.475, p < 0.001) and BIA (r = 0.356. p < 0.001). The use of AI to detect B-lines on LUS in our study for dialysis patients was shown to have good agreement with LUS B lines observed by physicians; (r = 0.825, p < 0.001) for the training dataset and (r = 0.844, p < 0.001) for the validation dataset. CONCLUSION: Our study confirms that 8-point LUS using HHUSD, with AI-based detection of B lines, can provide clinically useful information on the assessment of hydration status and diagnosis of fluid overload for dialysis patients in a user-friendly and time-efficient way.

TMPRSS4 Drives Angiogenesis in Hepatocellular Carcinoma by Promoting HB-EGF Expression and Proteolytic Cleavage.

BACKGROUND AND AIMS: Heparin-binding epidermal growth factor (HB-EGF), a member of the epidermal growth factor family, plays a pivotal role in the progression of several malignancies, but its role and regulatory mechanisms in hepatocellular carcinoma (HCC) remain obscure. Here, we report that transmembrane protease serine 4 (TMPRSS4) significantly enhanced the expression and proteolytic cleavage of HB-EGF to promote angiogenesis and HCC progression. APPROACH AND RESULTS: A mechanistic analysis revealed that TMPRSS4 not only increased the transcriptional and translational levels of HB-EGF precursor, but also promoted its proteolytic cleavage by enhancing matrix metallopeptidase 9 expression through the EGF receptor/Akt/mammalian target of rapamycin/ hypoxia-inducible factor 1 α signaling pathway. In addition, HB-EGF promoted HCC proliferation and invasion by the EGF receptor/phosphoinositide 3-kinase/Akt signaling pathway. The level of HB-EGF in clinical samples of serum or HCC tissues from patients with HCC was positively correlated with the expression of TMPRSS4 and the microvessel density, and was identified as a prognostic factor for overall survival and recurrence-free survival, which suggests that HB-EGF can serve as a potential therapeutic target for HCC. More importantly, we provide a demonstration that treatment with the HB-EGF inhibitor cross-reacting material 197 alone or in combination with sorafenib can significantly suppress angiogenesis and HCC progression. CONCLUSIONS: HB-EGF can be regulated by TMPRSS4 to promote HCC proliferation, invasion, and angiogenesis, and the combination of the HB-EGF inhibitor cross-reacting material 197 with sorafenib might be used for individualized treatment of HCC.

Down-regulation of EGFL8 regulates migration, invasion and apoptosis of hepatocellular carcinoma through activating Notch signaling pathway.

BACKGROUND: Our previous studies have reported the down-regulation of EGFL8 correlates to the development and prognosis of colorectal and gastric cancer. The present study is carried out to explore the expression pattern and role of EGFL8 in hepatocellular carcinoma (HCC). METHODS AND MATERIALS: EGFL8 expression in 102 cases of HCC tissues matched with adjacent non-tumorous liver tissues, a normal liver cell line and three liver cancer cell lines with different metastatic capacity was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Moreover, the clinicopathological features and prognosis of HCC patients were correlated with expression of EGFL8. Subsequently, the gain-and loss-of-function experiments were carried out to investigate the biological function of EGFL8 in HCC. We also used N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-(S)- phenylglycine t-butyl ester (DAPT), an inhibitor for Notch signaling pathway, in these experiments to verify the involvement of Notch signaling pathway in the effects of EGFL8. Additionally, a mouse model was established to investigate the effect of EGFL8 on metastasis of HCC cells. The expression of Notch signaling pathway in HCC cells and xenograft mouse tumors were detected by Western blot and immunohistochemistory. RESULTS: The expression of EGFL8 was significantly decreased in HCC tissues and cell lines and EGFL8 down-regulation correlated to multiple nodules, vein invasion, high TNM stage and poor prognosis of HCC. Interestingly, the expression levels of EGFL8 in three liver cancer cell lines were negatively associated with their metastatic capacity. In vitro and in vivo experiments indicated that EGFL8 obviously suppressed metastasis and invasion of HCC cells but slightly promoted apoptosis. Meanwhile, the expression of Notch signaling pathway was obviously suppressed in EGFL8 overexpressed HCCLM3 cells and xenograft mouse tumors generated from these cells but markedly elevated in EGFL8 depleted Hep3B cells. Furthermore, the up-regulated expression of Notch signaling pathway and effects induced by EGFL8 knockdown in Hep3B cells could be counteracted by DAPT treatment. CONCLUSION: The down-regulation of EGFL8 was correlated to progression and poor prognosis of HCC and regulates HCC cell migration, invasion and apoptosis through activating the Notch signaling pathway, suggesting EGFL8 as a novel therapeutic target and a potential prognostic marker for HCC.

Effects of hypoxia-inducible factor-1α and hypoxia-inducible factor-2α overexpression on hepatocellular carcinoma survival: A systematic review with meta-analysis.

BACKGROUND AND AIM: The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF-1α and HIF-2α overexpression with the prognosis and clinicopathological features of HCC. METHODS: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model. RESULTS: Twenty-two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF-1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53-2.00)] and DFS [HR = 1.64 (95% CI: 1.34-2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36-2.48)], tumor size [OR = 1.36 (95% CI: 1.12-1.66)], and tumor number [1.74 (95% CI: 1.34-2.25)]. In contrast, HIF-2α overexpression was not associated with the prognosis and clinicopathological features of HCC. CONCLUSION: Our data provided compelling evidence of a worse prognosis of HCC in HIF-1α overexpression patients but not HIF-2α overexpression ones.

Correction to: Hepatic metastatic paraganglioma 12 years after retroperitoneal paraganglioma resection: a case report.

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Hepatic metastatic paraganglioma 12 years after retroperitoneal paraganglioma resection: a case report.

BACKGROUND: Paragangliomas, also known as chemodectomas, are rare tumors arise from chemoreceptor tissue, and most commonly locate at the bifurcation of the common carotid, the jugular foramen, aortic arch, and retroperitoneum. Paragangliomas generally are considered to be benign tumors, and rarely produce local or distant metastases. Metastasis to liver is extremely rare. CASE PRESENTATION: We report the case of a 39-year-old woman, who had undergone resection of a retroperitoneal paraganglioma at her local hospital for 12 years. She was referred to our hospital for further evaluation of a hepatic mass, which was misdignosed as hepatocellular carcinoma (HCC) and was treated by transarterial chemoembolization (TACE) in the local hospital 6 years ago. At admission, CT scan revealed a huge hypervascular mass with many feeding arteries, almost the same size as 5 years ago. Ultrasound-guided biopsy of the liver tumor was performed and immunohistochemical examination confirmed the diagnosis of hepatic metastatic paraganglioma. Though liver metastasis failed to achieve complete response or partial response to TACE treatment, it remained stable without progression during the 7-year follow-up. CONCLUSION: Paragangliomas are slow growing tumors and metastasis may develop decades after resection of the primary lesion. Long-term follow-up is necessary, and curative or palliative treatment should be considered to control symptoms, improve life quality, reduce complications and prolong survival.

Effects of Regulated Deficit Irrigation on Amino Acid Profiles and Their Derived Volatile Compounds in Cabernet Sauvignon (Vitis vinifera L.) Grapes and Wines.

Amino acid contents and their derived volatile compositions in Cabernet Sauvignon grapes and wines after regulated deficit irrigation (RDI) were investigated during the 2015 and 2016 growing seasons in Yinchuan (NingXia, China). High-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) were used for amino acid and volatile compound analyses. Three RDI strategies were tested: 60% (RDI-1), 70% (RDI-2), and 80% (RDI-3) of grapevine estimated evapotranspiration (ETc), and 100% ETc was used as the control group (CK). RDI-treated vines had lower yields and berry weights with higher total soluble solids than the control treatment. RDI-1 increased proline levels in berries and wines. RDI-2 enhanced tyrosine and asparagine levels in wines. RDI-3 enhanced arginine, alanine, valine, leucine, and isoleucine levels in berries and wines. RDI-2 and RDI-3 increased the concentrations of 2-methyl-1-butyl acetate, benzaldehyde, 3-methyl-1-pentanol, and 3-methyl-1-butanol in wines. The accumulation of volatile compounds was closely related to the amino acid concentrations-especially isoleucine, valine, and leucine-in grapes. Our results showed that RDI treatments altered amino acid concentrations and their derived volatile compositions in wines.