Clinical diagnosis and treatment of alpha-fetoprotein-negative small hepatic lesions

Objective： We examined 103 cases over the last five years and discussed diagnosis and treatment of alpha- fetoprotein （AFP）-negative small hepatic lesions. Background： Small hepatic lesions （less than 2 cm in diameter） usually have no typical imaging characteristics and therefore are difficult to diagnose, especially when AFP tests provide a negative result. Methods： A total of 103 patients with AFP-negative small hepatic lesions from January 2003 to December 2008 were retrospectively reviewed. Differential diagnosis was performed by digital subtraction angiography （DSA）, dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）, contrast-enhanced ultrasound （CEUS）, or positron emission tomography-computed tomography （PET-CT） based on the multiplicity of lesions. Ninety-four patients with suspected cancers underwent partial hepatectomy. Clinical data were collected from hospital records and follow-up questionnaires. Results： Hepatocellular carcinoma （HCC） diagnostic sensitivity of DSA, DCE-MRI, CEUS and PET-CT was 88.2%, 93.9%, 88.9% and 88.9%, respectively. The surgery-related complication rate was 6.4%. Prognosis was good, with 1- and 3-year survival rates of 98.8% and 76.1%, respectively. Conclusions： DSA, DCE-MRI, CEUS and PET-CT are valuable for diagnosis of small hepatic lesions. Partial hepatectomy is a preferred surgical procedure. Surgery for small liver cancers usually has little risk and good prognosis, therefore it can be actively applied in suspected HCC cases.

Hairy cell leukemia presenting as multiple discrete hepatic lesions

The involvement of hairy cell leukemia in the liver is in the form of portal and sinusoidal cellular infiltration. Here we describe the first case of hepatic hairy cell leukemia presenting as multiple discrete lesions,which was treated successfully.We suggest that in the inves- tigation of discrete hepatic lesions in cases of cancer of unknown primary,hairy cell leukemia should be consid- ered.The excellent response of hairy cell leukemia to therapy highlights the need for such a consideration.

Quantitative evaluation of diffusion-weighted magnetic resonance imaging of focal hepatic lesions

AIM: To explore the quantitative analysis of diffusionweighted magnetic resonance imaging (DWMRI) in differential diagnosis of focal hepatic lesions.METHODS: DWMRI was performed in 149 hepatic lesions, including hepatocellular carcinoma (34 cases),hepatic metastases (37 cases), cavernous hemangioma (42 cases), hepatic cyst (36 cases). Apparent diffusion coefficient (ADC) values were evaluated using four different b values in different sequences. The ratio of ADC values of lesion/liver in hepatocellular carcinoma and hepatic metastases was also calculated.RESULTS: The mean ADC values of hepatic lesions were as follows: hepatocellular carcinoma (0.95 ± 0.11) × 10-3 mm2/s, hepatic metastasis (1.13 ± 0.21)× 10-3 mm2/s, cavernous hemangioma (1.86±0.36)×10-3 mm2/s,hepatic cyst(3.14±0.31)×10-3 mm2/s. The ratio of ADC values in lesion/liver in hepatocellular carcinoma was 0.91 ±0.11, being significantly different from that in hepatic metastasis (1.21 ± 0.18, P＜ 0.05).CONCLUSION: ADC values and quantitative analysis of focal hepatic lesions are of significant values in differential diagnosis of focal hepatic lesions.

Liver resection for benign hepatic lesions:A retrospective analysis of 827 consecutive cases

AIM:To analyze the operative and perioperative factors associated with hepatectomy of benign hepatic lesions.METHODS:A total of 827 condecutive cases of benign hepatic lesion undergoing hepatectomy from January 1986 to December 2005 in the Chinese PLA General Hospital were investigated retrospectively according to their medical documentation.RESULTS:The effect of operative and perioperative factors on the outcome of patients were analyzed.Of the 827 cases undergoing hepatectomy for more than 3 liver segments accounted for 22.1%,316(38.21%) required transfusion of blood products during operation.The average operating time was 220.59 ± 109.13 min,the average hospital stay after operation was 13.55 ± 9.38 d.Child-Pugh A accounted for 98.13%.The postoperative complication rate was 13.54% and the in-hospital mortality rate was 0.24%.Multivariate analysis showed that operating time(P = 0.004,OR = 1.003) and albumin value(P = 0.040,OR = 0.938) were the independent predictors of morbidity and indicated that operating time,blood transfusion,complication rate,and LOS had a trend to decrease.CONCLUSION:Hepatectomy for benign hepatic lesions can be performed safely with a low morbidity and mortality,provided that it is carried out with optimized perioperative management and an innovative surgical technique.

Relatively Increased Number of Liver Foxp3^+ Regulatory T Cells against Hepatic Lesions in Murine Lupus

Systemic lupus erythematosus（SLE） is a multiple organ autoimmune disorder,including the liver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcription factor Foxp3＋ regulatory T cells（Tregs） and several other immune molecules [programmed cell death 1 and its ligand（PD1 and PD-L1）,and interleukin 10（IL-10） and transform growth factor β（TGF-β）] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry,real-time quantitative reverse transcription PCR,and enzyme-linked immunosorbent assay.Results showed that both frequency and number of Foxp3＋ Tregs were dramatically reduced in the thymus,spleen and kidney of the BXSB mice（P0.05）,but those in the liver were kept in nearly normal range,when compared to negative control C57BL/6 mice.In comparison to control mice,the mRNA levels of Foxp3,PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice（P0.05）,but there was no significant difference in the livers of the BXSB mice（P0.05）.Protein levels of IL-10 and TGF-β in serum showed no significant difference between BXSB and C57BL/6 mice,but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice（P0.05）.These results suggest that reduced Foxp3＋ Tregs are involved in the pathogenesis of SLE in BXSB mice,and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice,which may provide insights into development of new therapeutic approaches in SLE patients.

Complementary comments on metastatic liver lesions with exceptional and rare cases

Liver metastases can appear in different forms in magnetic resonance imaging.Contrary to popular belief,while radiologists report hypovascular or hypervascular metastatic lesions,exceptional examples may be detected in various tumors.The aim of this article is to improve this review by presenting rare and atypical examples of liver metastasis,as well as cases that might potentially be misdiagnosed as metastases during the process of differential diagnosis.

Role of endoscopic ultrasound and endoscopic ultrasound-guided tissue acquisition in diagnosing hepatic focal lesions

BACKGROUND Endoscopic ultrasonography(EUS)has become an established method in diagnostic and therapeutic procedures in gastroenterology;however,it has recently gained a growing role in hepatology.AIM To evaluate the role of EUS features,strain elastography(SE),and EUS-tissue acquisition in diagnosing hepatic focal lesions(HFLs)that could affect further management.METHODS This cross-sectional study included 215 patients with pancreatic,biliary,or gastrointestinal malignancies referred for EUS examination.HFLs were identified in 43 patients(20%),and EUSguided tissue acquisition was performed from these lesions.RESULTS EUS features were highly sensitive(100%)but much less specific(57%)in diagnosing HFLs;the overall accuracy was 94%.Real-time elastography was also very sensitive(97%)but less specific(67%)in diagnosing HFLs;however,the overall accuracy was 92%.EUS tissue acquisition was extremely sensitive(100%)and specific(100%),with a 100%overall diagnostic accuracy.CONCLUSION The diagnostic utility of EUS-guided tissue acquisition was extremely accurate in diagnosing HFLs.EUS characteristics and real-time SE accurately predicted the histological diagnosis of both benign and malignant HFLs.

Value of a virtual hepatic segment model in assisting in the ultrasonic localization of intrahepatic lesions

Background During scanning of the right hypochondrium and right intercostal regions with an ultrasonic transducer,several ultrasonic images of oblique sections are obtained.It is still a challenge for ultrasonography to divide these nonconventional sections into an accurate hepatic segmentation pattern.The aim of this research was to investigate the value of the virtual hepatic segment model （VHSM） in assisting the ultrasonic localization of space-occupying hepatic lesions.Methods VHSM was constructed via 3D reconstruction according to the first Chinese visible human dataset.Preoperative ultrasonography,contrast-enhanced CT scan and VHSM techniques were performed in 100 patients with spaceoccupying focal lesions in the liver parenchyma for segmental localization.The results of these three techniques were compared with the operative findings.Results VHSM was successfully detected on 2D sectional images by 3D reconstruction through surface rendering and volume rendering.The model could simulate ultrasonic directions to conduct a virtual dissection on any section plane,and fine liver segmentation could be displayed in any virtual plane.In 100 patients,there were 112 liver space-occupying focal lesions distributed in 148 liver segmentations.Regarding the positioning accuracies for lesions of different sizes and the lesion segmental distribution accuracies estimated using the three methods mentioned above,ultrasonography exhibited a significantly lower accuracy than VHSM for the segmental localization of lesions （P ＜0.05）,and contrast-enhanced CT was not significantly different from ultrasonography plus VHSM （P ＞0.05）.Conclusion VHSM increased the accuracy of ultrasonic localization of space-occupying hepatic lesions,particularly in hepatic hypovascular regions.

Promotive action of 2-acetylaminofluorene on hepatic precancerous lesions initiated by diethylnitrosamine in rats:Molecular study

BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.

Hepatic focal nodular hyperplasia in children:Imaging features on multi-slice computed tomography

AIM:To retrospectively analyze the imaging features of hepatic focal nodular hyperplasia(FNH) in children on dynamic contrast-enhanced multi-slice computed tomography(MSCT) and computed tomography angiography(CTA) images.METHODS:From September 1999 to April 2012,a total of 218 cases of hepatic FNH were confirmed by either surgical resection or biopsy in the Sun Yat-sen Memorial Hospital of Sun Yat-sen University and the Cancer center of Sun Yat-sen University,including 12 cases(5.5%) of FNH in children(age ≤ 18 years old).All the 12 pediatric patients underwent MSCT.We retrospectively analyzed the imaging features of FNH lesions,including the number,location,size,margin,density of FNH demonstrated on pre-contrast and contrastenhanced computed tomography(CT) scanning,central scar,fibrous septa,pseudocapsule,the morphology of the feeding arteries and the presence of draining vessels(portal vein or hepatic vein).RESULTS:All the 12 pediatric cases of FNH had solitary lesion.The maximum diameter of the lesions was 4.0-12.9 cm,with an average diameter of 5.5 ± 2.5 cm.The majority of the FNH lesions(10/12,83.3%) had well-defined margins.Central scar(10/12,83.3%) and fibrous septa(11/12,91.7%) were commonly found in children with FNH.Central scar was either isodense(n = 7) or hypodense(n = 3) on pre-contrast CT images and showed progressive enhancement in 8 cases in the equilibrium phase.Fibrous septa were linear hypodense areas in the arterial phase and isodense in the portal and equilibrium phases.Pseudocapsule was very rare(1/12,8.3%) in pediatric FNH.With the exception of central scars and fibrous septa within the lesions,all 12 cases of pediatric FNH were homogenously enhanced on the contrast-enhanced CT images,significantly hyperdense in the arterial phase(12/12,100.0%),and isodense in the portal venous phase(7/12,58.3%) and equilibrium phase(11/12,91.7%).Central feeding arteries inside the tumors were observed on CTA images for all 12 cases of FNH,whereas no neovascularization of malignant tumors was noted.In 9 cases(75.0%),there was a spoke-wheel shaped centrifugal blood supply inside the tumors.The draining hepatic vein was detected in 8 cases of pediatric FNH.However,the draining vessels in the other 4 cases could not be detected.No associated hepatic adenoma or hemangioma was observed in the livers of the 12 pediatric cases.CONCLUSION:The characteristic imaging appearances of MSCT and CTA may reflect the pathological and hemodynamic features of pediatric FNH.Dynamic multi-phase MSCT and CTA imaging is an effective method for diagnosing FNH in children.

Value of shear wave elastography with maximal elasticity in differentiating benign and malignant solid focal liver lesions

BACKGROUND It is important to differentiate benign and malignant focal liver lesions(FLLs)accurately.Despite the wide use and acceptance of shear wave elastography(SWE),its value for assessing the elasticity of FLLs and differentiating benign and malignant FLLs is still investigational.Previous studies of SWE for FLLs used mean elasticity as the parameter to reflect the stiffness of FLLs.Considering the inhomogeneity of tumor stiffness,maximal elasticity(Emax)might be the suitable parameter to reflect the stiffness of FLLs and to differentiate malignant FLLs from benign ones.AIM To explore the value of SWE with Emax in differential diagnosis of solid FLLs.METHODS We included 104 solid FLLs in 95 patients and 50 healthy volunteers.All the subjects were examined using conventional ultrasound(US)and virtual touch tissue quantification(VTQ)imaging.A diagnosis of benign or malignant FLL was made using conventional US.Ten VTQ values were acquired after 10 consecutive measurements for each FLL and each normal liver,and the largest value was recorded as Emax.RESULTS There were 56 cases of malignant FLLs and 48 cases of benign FLLs in this study.Emax of malignant FLLs(3.29±0.88 m/s)was significantly higher than that of benign FLLs(1.30±0.46 m/s,P<0.01)and that of livers in healthy volunteers(1.15±0.17 m/s,P<0.01).The cut-off point of Emax was 1.945,and the area under the curve was 0.978.The sensitivity and specificity of Emax were 92.9%and 91.7%,respectively,higher(but not significantly)than those of conventional US(80.4%for sensitivity and 81.3%for specificity).Combined diagnosis of conventional US and Emax using parallel testing improved the sensitivity to 100%with specificity of 75%.CONCLUSION SWE is a convenient and easy method to obtain accurate stiffness information of solid FLLs.Emax is useful for differential diagnosis of FLLs,especially in combination with conventional US.

Evaluation in vinyl chloride monomer-exposed workers and the relationship between liver lesions and gene polymorphisms of metabolic enzymes

AIM： To analyze occupational health hazards exposure to doses lower than the Chinese occupational health standard in a selected VC polymerization plant in China, and also to elucidate the relationship between genetic polymorphisms and genetic susceptibility on liver lesions of workers exposed to vinyl chloride monomer （VCM）. METHODS： In order to explore the mechanism of VCM- related health effects, we used a case-control design to investigate the association between the genetic polymorphisms of metabolic enzymes and liver lesions in workers occupationally exposed to VCM. Genotypes of CYP2E1, GSTT1, GSTM1, ALDH2 and ADH2 were identified using PCR and PCR-RFLP. RESULTS： Even when the concentration of VCM was lower than the current Chinese occupational health standard, neurasthenia, pharyngeal irritation, liver ultrasonography abnormalities and hemoglobin disorders were significantly higher in exposure subjects compared to non-exposure subjects, and the relative risks （RRand 95% C1） were 1.74 （1.06-2.85）, 1.97 （1.56-2.48）, 10.69 （4.38-26.12）, and 2.07 （1.20-3.57）. CYP2E1 c1c2/c2c2 genotype was significantly associated with liver damages （OR 3.29, 95% CI 1.51-7.20, P〈0.01）. CONCLUSION： The incidences of neurasthenia and liver ultrasonography abnormalities significantly increase when the cumulative exposure dose increases. The genotypes of metabolic enzymes （CYP2E1 c1c2/c2c2, null GSTT1 and ADH2 1-1） play important roles in VCM metabolism. Polymorphisms of CYP 2E1, GSTT1 and ADH2 may be a major reason of genetic susceptibility in VCM-induced hepatic damage.

^(18)F-fluorodeoxyglucose PET/CT findings of a solitary primary hepatic lymphoma:A case report

Primary hepatic lymphoma is extremely rare,and only a few cases have been described on positron emission tomography(PET) or PET/computed tomography(PET/CT) imaging in the English literature.We report a case of a 55-year-old woman who presented with low-grade fever and weight loss of three months.On CT scanning,a mass was identified which appeared to be a hypoattenuating lesion,on ultrasonographic imaging,the mass was hypoechoic,therefore,liver abscess or hepatic metastasis from a gastrointestinal primary was initially suspected.Tumor markers such as alpha-fetoprotein,carcinoembryonic antigen and carbohydrate antigen 19-9 were within normal limits.PET/CT demonstrated a large abnormal ring-like hypermetabolic focus in the right liver lobe.The lesion was resected and the histo-pathological findings were consistent with lymphoma.The patient was discharged two weeks after surgery and did not receive any further treatment.After 25 mo follow-up,she is in good health.18F-fluorodeoxyglucose PET/CT is useful in confirming the diagnosis of primary hepatic lymphoma by demonstrating no other foci with high uptake in other parts of the body.

Expression of Redox Factor-1 in Early Injury Period after Liver Transplantation in Rat Model

The aims of this study were to observe the relationship between injury of graft and expression of redox factor-1 （Ref-1） in early period （24 h） after liver transplantation in rat model One hundred and fifty adult male Wister rats were randomly divided into three groups including liver transplant group, sham surgery group and untreated control group. After liver transplantation, animals were sacrificed at different time points, and the changes and significance of the expression of Ref-1 were then explored by immunohistochemistry, serology and histopathology. As compared with sham surgery group and untreated control group, the expression of Ref-1 protein in transplant group was stronger in early period after liver transplantation. With pathology analysis, lots of infiltrating inflammation cells were found around the portal veins. Hepatic tissues were injury. However, the injury in sham surgery and untreated control group were comparatively slight. The serum ALT and AST levels reached the peak at 6-12 h, and decreased significantly after 12 h. These data suggested that the degree of liver injury in earlier period after transplantation peaked at 6 h and then decreased. And Ref-1 protein induced by hepatic ischemic reperfusion injury might play critical role in repairing the injury.