Diagnostic and economic value of carcinoembryonic antigen,carbohydrate antigen 19-9,and carbohydrate antigen 72-4 in gastrointestinal cancers

BACKGROUND The diagnostic and economic value of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale.AIM To reassess the diagnostic and economic value of the three tumor biomarkers.METHODS A retrospective analysis of all 32857 subjects who underwent CEA,CA19-9,CA72-4,gastroscopy and colonoscopy from October 2006 to May 2018 was conducted.Then,we assessed the discrimination and clinical usefulness.Total cost,cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes(gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive).RESULTS The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer(CRC),while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers(GICs).Regarding early diagnosis,only CEA could be used for early CRC.The combination of biomarkers didn’t greatly increase the area under the curve.The economic indicators of CEA were superior to those of CA19-9,CA72-4 and any combination.At the threshold of 1.8μg/L to 10.4μg/L,all four indicators of CEA were lower than those in the scheme that conducted gastrointestinal endoscopy only.Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable.CONCLUSION CEA had qualified diagnostic value for CRC and superior economic value for GICs,especially for elderly health checkup subjects.CA72-4 was not suitable as a diagnostic biomarker.

A case-control study of the relationship between hepatitis B virus DNA level and risk of hepatocellular carcinoma in Qidong,China

AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS:One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS:In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels ≥ 104 to < 105; ≥ 105 to < 106; ≥ 106 to < 107; ≥ 107 copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.CONCLUSION:The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 104-107 range.

Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice

AIM: To prepare chitosan-polyaspartic acid-5-fluorouracil (CTS-Pasp-5Fu) nanoparticles and investigate its anti-carcinoma effect and toxicity. METHODS: CTS-Pasp-5Fu nanoparticles were synthesized by ionic gelatification. Male BABL/c nude mice were injected with SGC-7901 gastric carcinoma cell line mass to establish a human gastric carcinoma model. They were randomly allocated into 4 groups: CTS-Pasp-5Fu (containing 5-Fu 1.25 mg/kg), 5-Fu (1.25 mg/kg), CTS-Pasp and normal saline groups. Tumor weight was measured and assay of colony forming unit-granulocyte and macrophage (CFU-GM) was performed. The structural change of cells and tissues was observed and the Bax and Bcl-2 genes were detected. RESULTS: Compared with normal saline, the inhibition rates of tumor growth for the CTS-Pasp, 5-Fu and CTS-Pasp-5Fu groups were 5.58%, 58.69% and 70.82%, respectively. The tumor inhibition rates for the CTS-Pasp, 5-Fu and CTS-Pasp-5Fu groups were 5.09%, 65.3% and 72.79%, respectively. There was a significant decrease in the number of CFU-GMformation and increase of total bilirubin, and alanine aminotransferase in the 5-Fu group, but no change in those of the other three groups. There was no change in white blood cell count and creatinine among the four groups. Pathological section of liver and nephridial tissues showed that the damage in the 5-Fu group was more severe than that in the CTS-Pasp-5Fu group. 5-Fu and CTS-Pasp-5Fu groups could both down-regulate the Bcl-2 expression and up-regulate the Bax expression to different extent, and the accommodate effect of CTS-Pasp-5Fu was more obvious than 5-Fu. CONCLUSION: The tumor inhibition rate of CTS-Pasp-5Fu nanoparticles is much higher than that of 5-Fu alone.

Novel mutation in a Chinese patient with progressive familial intrahepatic cholestasis type 3

Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.

Portal hypertension induced by congenital hepatic arterioportal fistula:Report of four clinical cases and review of the literature

Intrahepatic arterioportal fistula(IAPF)can be caused by many secondary factors.We report four cases of portal hypertension that were eventually determined to be caused by congenital hepatic arterioportal fistula.The clinical manifestations included ascites,variceal hemorrhage and hepatic encephalopathy.Computed tomography scans from all of the patients revealed the early enhancement of the portal branches in the hepatic arterial phase.All patients were diagnosed using digital subtraction angiography(DSA).DSA before embolization revealed an arteriovenous fistula with immediate filling of the portal venous radicles.All four patients were treated with interventional embolization.The four patients remained in good condition throughout follow-up and at the time of publication.IAPF is frequently misdiagnosed due to its rarity;therefore,clinicians should consider IAPF as a potential cause of non-cirrhotic portal hypertension.

Auphen and dibutyryl cAMP suppress growth of hepatocellular carcinoma by regulating expression of aquaporins 3 and 9 in vivo

AIM: To investigate whether the regulation of aquaporin 3(AQP3) and AQP9 induced by Auphen and dibutyryl c AMP(dbc AMP) inhibits hepatic tumorigenesis. METHODS: Expression of AQP3 and AQP9 was detected by Western blot, immunohistochemistry(IHC), and RT-PCR in HCC samples and paired non-cancerous liver tissue samples from 30 hepatocellular carcinoma(HCC) patients. A xenograft tumor model was used in vivo. Nine nude mice were divided into control, Auphen-treated, and dbc AMP-treated groups(n = 3 for each group). AQP3 and AQP9 protein expression after induction of xenograft tumors was detected by IHC and m RNA by RT-PCR analysis. The terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling assay and histological evaluation were used to detect apoptosis of tumor cells, and the concentration of serum α-fetoprotein(AFP) was measured using RTPCR and an ELISA kit.RESULTS: The volumes and weights of tumors decreased significantly in the Auphen- and dbc AMP-treated mice compared with the control mice(P < 0.01). The levels of AQP3 were significantly lower in the Auphen treatment group, and levels of AQP9 were significantly higher in thedbc AMP treatment mice than in the control mice(P < 0.01). The reduction of AQP3 by Auphen and increase of AQP9 by dbc AMP in nude mice suppressed tumor growth of HCC, which resulted in reduced AFP levels in serum and tissues, and apoptosis of tumor cells in the Auphen- and dbc AMP-treated mice, when compared with control mice(P < 0.01). Compared with para-carcinoma tissues, AQP3 expression increased in tumor tissues whereas the expression of AQP9 decreased. By correlating clinicopathological and expression levels, we demonstrated that the expression of AQP3 and AQP9 was correlated with clinical progression of HCC and disease outcomes. CONCLUSION: AQP3 increases in HCC while AQP9 decreases. Regulation of AQP3 and AQP9 expression by Auphen and dbc AMP inhibits the development and growth of HCC.

Effect of interferon-γ and tumor necrosis factor-α on hepatitis B virus following lamivudine treatment

AIM:To evaluate anti-hepatitis B virus (HBV) activity and cytotoxicity of interferon (IFN-γ) and tumor necrosis factor (TNF-α) following lamivudine treatment of HepG2.2.15 cells.METHODS:HepG2.2.15 cells were treated with 2 mol/L lamivudine for 16 d (lamivudine group),cultured for 10 d,followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (cytokine group),or treated with 2 mol/L lamivudine for 10 d followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (sequential group),or cultured without additions for 16 d (control group).Intracellular DNA was extracted from 3 × 105 HepG2.2.15 cells from each group.The extracted DNA was further purified with mung bean nuclease to remove HBV relaxed circular DNA that may have remained.Both HBV covalently closed circular DNA (cccDNA) and HBV DNA were examined with real-time polymerase chain reaction.The titers of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were quantified with enzyme-linked immunosorbent assay.Cell viability was measured with the cell counting kit-8 assay.RESULTS:Compared to lamivudine alone (22.63% ± 0.12%),both sequential (51.50% ± 0.17%,P = 0.034) and cytokine treatment (49.66% ± 0.06%,P = 0.041) showed a stronger inhibition of HBV cccDNA;the difference between the sequential and cytokine groups was not statistically significant (51.50% ± 0.17% vs 49.66% ± 0.06%,P = 0.88).The sequential group showed less inhibition of HBV DNA replication than the lamivudine group (67.47% ± 0.02% vs 82.48% ± 0.05%,P = 0.014);the difference between the sequential and cytokine groups was not statistically significant (67.47% ± 0.02% vs 57.45% ± 0.07%,P = 0.071).The levels of HBsAg and HBeAg were significantly decreased in the sequential treatment group compared to the other groups [HBsAg:3.48 ± 0.04 (control),3.09 ± 0.08 (lamivudine),2.55 ± 0.13 (cytokine),2.32 ± 0.08 (sequential),P = 0.042 for each between-group comparison;HBeAg:3.48 ± 0.01 (control),3.08 ± 0.08 (lamivudine),2.57 ± 0.15 (cytokine),2.34 ± 0.12 (sequential),P = 0.048 for each between-group comparison].Cell viability in the cytokine group was reduced to 58.03% ± 8.03% compared with control cells (58.03% ± 8.03% vs 100%,P = 0.000).Lamivudine pretreatment significantly reduced IFN-γ + TNF-α-mediated toxicity of HepG2.2.15 cells [85.82% ± 5.43% (sequential) vs 58.03% ± 8.03% (cytokine),P = 0.002].CONCLUSION:Sequential treatment overcame the lower ability of lamivudine alone to inhibit cccDNA and precluded the aggressive cytotoxicity involving IFN-γ and TNF-α by decreasing the viral load.

Application of deep learning in image recognition and diagnosis of gastric cancer

In recent years,artificial intelligence has been extensively applied in the diagnosis of gastric cancer based on medical imaging.In particular,using deep learning as one of the mainstream approaches in image processing has made remarkable progress.In this paper,we also provide a comprehensive literature survey using four electronic databases,PubMed,EMBASE,Web of Science,and Cochrane.The literature search is performed until November 2020.This article provides a summary of the existing algorithm of image recognition,reviews the available datasets used in gastric cancer diagnosis and the current trends in applications of deep learning theory in image recognition of gastric cancer.covers the theory of deep learning on endoscopic image recognition.We further evaluate the advantages and disadvantages of the current algorithms and summarize the characteristics of the existing image datasets,then combined with the latest progress in deep learning theory,and propose suggestions on the applications of optimization algorithms.Based on the existing research and application,the label,quantity,size,resolutions,and other aspects of the image dataset are also discussed.The future developments of this field are analyzed from two perspectives including algorithm optimization and data support,aiming to improve the diagnosis accuracy and reduce the risk of misdiagnosis.

Early diagnosis and therapeutic choice of Klebsiella pneumoniae liver abscess

Nowadays,pyogenic liver abscess(PLA)is still a common and severe intra-abdominal infection,and Klebsiella pneumoniae had emerged as the most common pathogenic bacteria worldwide in the past ten years.Our study aims to achieve an early pathogenic diagnosis and rational therapy modality for Klebsiella pneumoniae liver abscess(KLA)through clinical data analysis.A total of 197 inpatients in Zhongshan Hospital,Shanghai,diagnosed as having liver abscess between March 2001 and September 2009 were enrolled.Patients with monomicrobial infection were divided into two groups:patients with K.pneumoniae liver abscess(KLA group,n=106)and those with non-Klebsiella pneumoniae liver abscess(NKLA group,n=56).A retrospective analysis was made between these two groups on the aspects of underlying diseases,clinical characteristics,laboratory data,culture results,and imaging findings.To evaluate the effects of different medical interventions,monomicrobial KLA patients were further divided into four subgroups(percutaneous liver aspiration,aspiration plus antibiotics flushing,aspiration plus retained catheter,and aspiration plus antibiotics flushing and retained catheter),and corresponding therapeutic effects were analyzed.KLA was more likely to occur in patients with coexisting diseases such as diabetes mellitus(53.77%vs 25.00%,P=0.001)and hepatic adipose infiltration(16.04%vs 5.36%,P=0.029).Compared to NKLA group,clinical characteristics including abdominal pain(40.57%vs 57.14%,P=0.044),hypodynamia(19.81%vs 46.43%,P=0.001),and hepatomegaly(4.72%vs 14.29%,P=0.033)were much milder,but with a higher fasting blood glucose level(7.84±0.36 vs 5.76±0.30,P=0.001)on admission in KLA group.In addition,KLA abscess often appeared singly in the right lobe of the liver with gas forming nature(32.88%vs 13.51%,P=0.039),unsmooth rim(71.23%vs 40.54%,P=0.002),and dynamic septum enhancement(41.10%vs 16.22%,P=0.009).Compared to mono aspiration subgroup,additional antibiotic flushing could not further improve clinical outcomes of KLA patients(P>0.05);however,the retained catheter showed obvious advantage in reducing abscess diameter(34.38±3.25 mm vs 22.67±2.37 mm,P=0.017).It can be concluded that the strong association with diabetes,milder clinical symptoms,and gas-forming nature in CT images makes early pathogenic diagnosis of KLA possible.Comparatively,ultrasonography-guided percutaneous liver aspiration with retained catheter may be the most rational intervention modality of KLA.