Hepatic Alveolar Echinococcosis Lesions Research Articles

Evaluation of the Metabolic Activity of the Infiltration and Proliferation Areas of Hepatic Alveolar Echinococcosis in Rats Using Contrast-Enhanced Ultrasound.

This study evaluated the value of contrast-enhanced ultrasound (CEUS) in assessing the metabolic activity of infiltration and proliferation areas of hepatic alveolar echinococcosis (HAE) in rats. CEUS was performed on Wistar rats with HAE. The average grayscale value of the HAE lesion in peripheral infiltration and proliferation areas (PIPAs) and the adjacent normal liver tissue was analyzed quantitatively. Contrast imaging was classified as highly increased enhancement, moderately increased enhancement, and equal or decreased enhancement. Microvessel density (MVD) in the PIPAs was classified as strongly positive, moderately positive, and weakly positive. The metabolic activity of HAE in the PIPAs was classified as high activity, moderate activity, and low activity according to the MVD classification results. The kappa test was combined with the metabolic activity level of the PIPAs to analyze the consistency of CEUS intensity and MVD. CEUS can score the metabolic activity of the infiltration and proliferation areas around HAE lesions, and provides a basis for clinical treatment and follow-up visits. CEUS could be used as a more economical and effective imaging option for evaluating the metabolic activity of HAE lesions.

Effectiveness and safety of ultrasound-guided percutaneous microwave ablation for hepatic alveolar echinococcosis

BackgroundMicrowave ablation (MWA) is a popular therapy for liver malignant tumor in recent years. Few studies have been conducted on its use in the treatment of hepatic alveolar echinococcosis (HAE). The study aims to evaluate the efficacy and safety of MWA in the treatment of HAE.MethodsThis study analyzed the data of 45 patients (mean age, 38 ± 2 years; 24 males) diagnosed with HAE and underwent MWA treatment between June 2014 to December 2019. The patients after MWA were examined by CT or MRI [follow-up: 32 months (IQR 23–48.5)] to determine whether the lesions were relapsed and to evaluate the therapeutic effect of MWA. The safety of MWA was evaluated by monitoring postoperative complications. Clinical data, such as patient demographics, imaging features of the lesions, relevant findings of laboratory tests before and after ablation, and information related to ablation, were collected and analyzed. Paired-sample t tests and paired-sample Wilcoxon signed-rank tests were used to compare relevant laboratory indicators before and after MWA.ResultsMWA was applied to 57 HAE lesions in 45 patients. The median size of lesions was 3.42 cm (IQR2.85–4.41). The rate of complete ablation was 100% (57/57). The median follow-up time was 32 months (IQR 23–48.5). The recurrence rate was 13% (6/45), and the median time of recurrence was 22 months. The rate of minor complications was 11.1% (5/45), and there were no major complications and deaths. Compared to preoperative, ALB, RBC, HBG, and PLT were decreased (p < 0.001); ALT, TB, DB, and WBC were increased (p < 0.001); and no statistically difference in PT, APTT, and INR (p > 0.05).ConclusionsMWA might be a safe and effective way to cure HAE. Meanwhile, it provides a new option and a new way of thinking about treatment for patients with HAE.

Long-term experience with debulking surgery in extensive hepatic alveolar echinococcosis: A case series and literature review

Objective: To assess the role of debulking surgery in extensive hepatic alveolar echinococcosis (HAE).Methods: Five cases of extensive HAE undergoing debulking surgery with their long-term follow-ups were reported. Additionally, a systematic review was carried out.Results: The average age of patients in the study was (50.8±17.1) years (range 36 to 77 years). Three cases were female. The median follow-up period was 61 months (range 12 to 84 months). Left liver resections were performed in 2 cases and right hemihepatectomies were undertaken in 2 cases. Two patients (cases 2 and 4) developed early surgical complications, while one of them (case 4) who suffered from the recurrent sub-hepatic abscess died at 12 months postoperatively.Conclusions: This study highlights the importance of debulking surgery for the management of complex symptomatic HAE lesions in patients with no curative option available.

Long-term follow-up of liver alveolar echinococcosis using echinococcosis multilocularis ultrasound classification.

BACKGROUNDWhen Echinococcus multilocularis infects humans as a false intermediate host, alveolar echinococcosis (AE) usually manifests primarily intrahepatically and is initially asymptomatic. If the disease remains undiagnosed and untreated, progressive growth occurs, reminiscent of malignant tumours. The only curative therapy is complete resection, which is limited to localised stages, and palliative drug therapy is used otherwise. Consequently, early diagnosis and reliable detection of AE lesions are important. For this reason, abdominal ultrasonography, as the most common primary imaging for AE, relies on classification systems.AIMTo investigate how hepatic AE lesion sonomorphology changes over time in the Echinococcosis Multilocularis Ulm Classification (EMUC)-ultrasound (US) classification.METHODSBased on data from Germany’s national echinococcosis database, we evaluated clinical and US imaging data for 59 patients according to the AE case definition in our preliminary retrospective longitudinal study. There had to be at least two liver sonographies ≥ 6 mo apart, ≥ 1 hepatic AE lesion, and complete documentation in all US examinations. The minimum interval between two separately evaluated US examinations was 4 wk. The AE reference lesion was the largest hepatic AE lesion at the time of the first US examination. To classify the sonomorphologic pattern, we used EMUC-US. In addition to classifying the findings of the original US examiner, all reference lesions at each examination time point were assigned EMUC-US patterns in a blinded fashion by two investigators experienced in US diagnosis. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, United Stated). P values < 0.05 were considered statistically significant.RESULTSThe preliminary study included 59 patients, 38 (64.5%) women and 21 (35.6%) men. The mean age at initial diagnosis was 59.9 ± 16.9 years. At the time of initial ultrasonography, a hailstorm pattern was present in 42.4% (25/59) of cases, a hemangioma-like pattern in 16.9% (10/59), a pseudocystic pattern in 15.3% (9/59), and a metastasis-like pattern in 25.4% (15/59). For the hailstorm pattern, the average lesion size was 67.4 ± 26.3 mm. The average lesion size was 113.7 ± 40.8 mm with the pseudocystic pattern and 83.5 ± 27.3 mm with the hemangioma-like pattern. An average lesion size of 21.7 ± 11.0 mm was determined for the metastasis-like pattern. Although the sonomorphologic pattern remained unchanged in 84.7% (50/59) of AE reference lesions, 15.3% (9/59) showed a change over time. A change in pattern was seen exclusively for AE lesions initially classified as hemangioma-like or pseudocystic. A total of 70% (7/10) of AE lesions initially classified as hemangioma-like showed a relevant change in pattern over time, and 85.7% (6/7) of these were secondarily classified as having a hailstorm pattern, with the remainder (1/7; 14.3%) classified as having a pseudocystic pattern. A total of 22.2% (2/9) of AE lesions initially classified as pseudocystic showed a relevant change in pattern over time and were classified as having a hailstorm pattern. For AE lesions initially classified as having a hailstorm or metastatic pattern, no pattern change was evident. All patients with pattern change were on continuous drug therapy with albendazole.CONCLUSIONThe sonomorphology of hepatic AE lesions may change over time. The hemangioma-like and pseudocystic patterns are affected.

Expression and significance of TGF-β1, p38MAPK and BMP-7 protein in liver specimens of patients with alveolar hepatic echinococcosis

To detect the expression of transforming growth factor-β1 (TGF-β1), p38MAPK and bone morphogenetic protein-7 (BMP-7) protein in the liver specimens of patients with hepatic alveolar echinococcosis, and to investigate the potential role of TGF-β1, p38MAPK and BMP-7 protein in hepatic fibrosis caused by hepatic alveolar echinococcosis. A total of 20 patients with hepatic alveolar echinococcosis were enrolled as study subjects, and hepatic specimens were sampled from the sites within 0.5 cm (Group A) and 0.5 to 1.5 cm from hepatic alveolar echinococcosis lesions (Group B), while normal liver specimens sampled from the sites 2 cm and greater from hepatic alveolar echinococcosis lesions served as controls (Group C). The fibrosis of liver specimens was pathological examined using HE and Masson staining, and the expression of TGF-β1, p38MAPK and BMP-7 protein was quantified in liver tissues using Western blotting. The associations of TGF-β1, p38MAPK and BMP-7 protein expression with hepatic fibrosis were assessed. HE staining showed the malaligned structure of hepatocytes and destruction of the structure of hepatic lobules at various degrees in liver specimens in groups A and B, with hepatocyte degeneration, atrophy and necrosis, hyperplasia of fibrous tissues and eosinophilic granulocyte infiltration seen, while no abnormal pathological alterations of liver tissues, normal hepatocyte structure and morphology and uniform size, no malaligned structure of hepatocytes, clear structure of hepatic lobules, no or mild hepatocyte degeneration or necrosis, and no eosinophilic granulocyte infiltration were seen in Group C. Masson staining showed that there was hyperplasia of multiple fibrous connective tissues in the liver portal areas in groups A and B, with fibrosis seen in hepatic lobules, while no obvious pathological changes were seen in Group C. There were significant differences seen in TGF-β1 (P < 0.001), p38MAPK (P < 0.01) and BMP-7 protein (P < 0.05) expression in liver tissues in groups A, B and C, and higher TGF-β1, p38MAPK and BMP-7 protein expression was quantified in groups A and B than in Group C (all P values < 0.05), while greater TGF-β1, p38MAPK and BMP-7 protein expression was detected in Group B than in Group C (all P values < 0.05). The expression of TGF-β1, p38MAPK and BMP-7 protein correlated positively with the severity of hepatic fibrosis (r = 0.866, 0.702 and 0.801, all P values < 0.05), and there were significant differences in TGF-β1 (F = 72.580, P < 0.01), p38MAPK (χ2 = 31.705, P < 0.01) and BMP-7 protein expression (χ2 = 48.388, P < 0.01) among liver tissues with different degrees of fibrosis. The TGF-β1 protein expression correlated positively with p38MAPK and BMP-7 protein expression (r = 0.607 and 0.702, both P values < 0.001), and the BMP-7 protein expression also correlated positively with p38MAPK protein expression (r = 0.456, P < 0.001). The interaction among TGF-β1, p38MAPK and BMP-7 jointly participates in the development of hepatic fibrosis induced hepatic alveolar echinococcosis.

Impact of Albendazole on Cytokine and Chemokine Response Profiles in Echinococcus multilocularis-Inoculated Mice.

Objective Alveolar echinococcosis (AE) is a zoonosis caused by the larval stage of the metacestode Echinococcosis multilocularis with a tumor-like behavior in the targeted organ, especially in the liver. Surgery with albendazole is first-line modality for AE. Drug discontinuation is usually based upon the parasitic viability shown by the positron emission tomography (PET) scan. However, as a demanding and expensive method, it is not widely practiced in majority of the endemic regions. Further understanding on the cytokine and chemokine response profiles in AE patients may provide an interesting insight for potential markers in viability assessment. Methods Mice were inoculated with Echinococcus multilocularis intrahepatically to develop the hepatic AE murine model. Oral albendazole administration was then applied for three months after the first inoculation, and peripheral and regional immune cells including type 1 T helper cells (Th), Th2, Th17, regulatory T (Treg) cells, related cytokines, and chemokines were examined. Results The hepatic AE lesion was confirmed by ultrasound examination resulting in a successful rate of 70%. Among the 17 cytokines and chemokines detected, plasma levels of IL-23 were significantly higher in E. multilocularis-infected mice when compared to the control group; furthermore, more obvious increasing levels were found after albendazole treatment (p < 0.05). All chemokine levels other than eotaxin and MCP-3 were slightly higher in E. multilocularis-infected mice compared to the control group (p > 0.05). Eotaxin levels were significantly decreased in mice with E. multilocularis infection followed by albendazole treatment (p < 0.05). Both IL-17A and IL-23 expressions in hepatic AE lesions were significantly higher and related with disease activity. Conclusion Albendazole administration influenced the balance of immune response and promotes the secretion of proinflammatory factors which is beneficial to parasite clearance. IL-23 seems to be associated with the successful albendazole treatment in mice with E. multilocularis infection; such a change could be translated into clinical application in the near future.

Differential diagnosis between hepatic alveolar echinococcosis and intrahepatic cholangiocarcinoma with conventional ultrasound and contrast-enhanced ultrasound

BackgroundMisclassifications of hepatic alveolar echinococcosis (HAE) as intrahepatic cholangiocarcinoma (ICC) may lead to inappropriate treatment strategies. The aim of this study was to explore the differential diagnosis with conventional ultrasound and contrast-enhanced ultrasound (CEUS).MethodsSixty HAE lesions with 60 propensity score-matched ICC lesions were retrospectively collected. The 120 lesions were randomly divided into a training set (n = 80) and a testing set (n = 40). In the training set, the most useful independent conventional ultrasound and CEUS features was selected for differentiating between HAE and ICC. Then, a simplified US scoring system for diagnosing HAE was constructed based on selected features with weighted coefficients. The constructed US score for HAE was validated in both the training set and the testing set, and diagnostic performance was evaluated.ResultsCompared with ICC lesions, HAE lesions were mostly located in the right lobe and had mixed echogenicity, a pseudocystic appearance and foci calcifications on conventional ultrasound. On CEUS, HAE lesions showed more regular rim-like enhancement than ICC lesions and had late washout with a long enhancement duration. The simplified US score consisted of echogenicity, pseudocystic/calcification, bile duct dilatation, enhancement pattern, enhancement duration, and marked washout. In the testing set, the sensitivity, specificity, LR+, LR- and the area under the ROC curve for the score to differentiate HAE from ICC were 80.0, 81.3%, 4.27, 0.25 and 0.905, respectively.ConclusionsThe US score based on typical features from both conventional ultrasound and CEUS could accurately differentiate HAE from ICC.

Intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis: a multicenter cohort study.

The main endemic areas of alveolar echinococcosis (AE) are in central Europe and western China. The infiltration of intrahepatic vascular and bile ducts as well as extrahepatic disease can lead to complications and may increase morbidity in AE. To evaluate the vascular/biliary involvement of hepatic alveolar echinococcosis (HAE) and distant extrahepatic disease at each of four locations in Germany, France, and China. Contrast-enhanced abdominal magnetic resonance imaging (MRI) scans of patients with HAE, 200 in total, were evaluated by five examiners. AE liver lesions were classified according to Kodama's classification. Furthermore, distant extrahepatic manifestations were documented with additionally performed imaging modalities. Vascular/biliary involvement of hepatic manifestations as well as the presence of extrahepatic manifestations were correlated with the respective Kodama type of the liver lesion. Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (12/100 vs. 3/100; Fisher's exact test: P=0.0286). A significant relationship exists between presence of distant extrahepatic disease manifestation and size of the AE liver lesion (132.53 ± 48.65 vs. 92.49 ± 50.06; P = 0.0030). Vascular/biliary involvement is significantly more frequent in China than in Europe (86/100 vs. 65/100; χ2 = 11.92; P = 0.0006). Vascular/biliary involvement depends on lesion size (111.10 ± 47.44 vs. 47.36 ± 24.36; P<0.0001). Different types of AE liver lesions are associated with differences in vascular/biliary involvement and extrahepatic manifestations. Vascular/biliary involvement and presence of distant extrahepatic manifestations depend on size of the HAE lesions and are more frequently detected in China. Different MRI morphological patterns influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.

Evaluation of intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis.

BACKGROUNDThe main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE.AIMTo evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.METHODSConsecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations (n = 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography–CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States).RESULTSDistant extrahepatic AE manifestations were significantly more frequent in China than in Europe (P = 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size (P = 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe (P < 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III (P < 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I–III were found to varying degrees, with a maximum of 22% for type III.CONCLUSIONDifferent CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation.

Magnetic resonance imaging evaluation of characteristics of vascular invasion in intermediate and advanced hepatic alveolar echinococcosis.

The objective of the present study was to provide a basis for the personalized treatment of intermediate and advanced hepatic alveolar echinococcosis (HAE) by elucidating the characteristics of vascular invasion and lesion growth. A total of 160 patients with intermediate and advanced HAE who were subjected to plain as well as contrast-enhanced 3.0-T magnetic resonance imaging prior to surgery were analyzed. Pathological and intra-operative observations of the subjects were also considered. The size and location of HAE lesions, vascular invasion characteristics and growth patterns were assessed. A total of 78 patients (48.75%) had lesions involving the S5-8 segment/partial right liver lobe, 21 (13.13%) had involvement in the S2-4 segment/partial left liver lobe and 61 (38.13%) had lesions that transcended the left and right liver lobes. Pathological examination revealed that the vascular invasion rates of the hepatic portal veins, intrahepatic veins (left, central and right vein, and inferior vena cava) and hepatic arteries were 51.88, 43.28 and 26.87%, respectively. Liver hilum invasion was observed in 128 patients (80.00%), 71 of which (44.38%) presented with invasion of the primary porta hepatis, 11 (6.88%) with invasion of the secondary porta hepatis and 46 (28.75%) with invasion of the primary as well as the secondary porta hepatis. In conclusion, the growth pattern of intermediate and advanced HAE is determined by the site, blood supply and activity of the lesion. The current study demonstrated that lesions tend to invade the intrahepatic venous system and porta hepatis, and to target veins rather than arteries.

The role of contrast-enhanced ultrasound in the diagnosis of hepatic alveolar echinococcosis.

To evaluate the value of contrast-enhanced ultrasound (CEUS) compared with ultrasound (US) in the diagnosis of hepatic alveolar echinococcosis (AE).Thirty-one patients with 43 hepatic AE lesions between January 2010 and September 2017 were included in the study. All lesions which were histopathologically proven to be hepatic AE were retrospectively reviewed. Features of the lesions by CEUS were retrospectively studied.All lesions were detected by US and CEUS in the 31 patients (17 males and 14 females) with a mean age of 38.5 ± 10.6 years (range: 16–58 years). The size of the lesions ranged from 1.5 × 0.7 cm to 15 × 18 cm. By US, 3 lesions (7%, 3/43) were hypoechoic nodules, 21 (48.8%, 21/43) were hyperechoic, and 19 lesions (44.2%, 19/43) were of mixed echogenicity type (solid-cystic). 27 lesions (62.8%, 27/43) had calcifications. Only 1 lesion was detected blood-flow signals. With CEUS, 23 lesions (53.5%, 23/43) displayed no enhancement in the arterial phase, portal phase and delayed phase on CEUS. 11 lesions (25.6%, 11/43) displayed a slight ring-like hyper-enhancement in the arterial phase and displayed hypo-enhancement in the portal and delayed phase. 6 lesions (14%, 6/43) displayed hyper-enhancement in the arterial phase and hypo-enhancement in the portal and delayed phase. 2 lesions (4.7%, 2/43) showed iso-enhancement in the arterial, portal, and delayed phase. 1 lesion (2.3%, 1/43) showed slight hypo-enhancement in the arterial, portal, and delayed phase.CEUS is a more valid technique for diagnosing AE than US. It could be a reliable tool in the diagnosis of hepatic AE.

Simple liver cysts and cystoid lesions in hepatic alveolar echinococcosis: a retrospective cohort study with Hounsfield analysis.

Background. Alveolar echinococcosis (AE) is a rare zoonosis caused by the larval stage of the tapeworm Echinococcus multilocularis. AE lesions affect the liver in more than 98% of cases. AE lesions have various morphological characteristics that are described in the Echinococcus multilocularis Ulm classification for computed tomography (EMUC-CT). One of these characteristics is a cystoid portion. The aim of the study was to compare the density of simple hepatic cysts with cystoid portions of AE lesions classified on the basis of the EMUC-CT. Results. Hounsfield Unit (HU) measurements of the cystoid portions of all EMUC-CT type I–IV AE lesions (n = 155) gave a mean of 21.8 ± 17.6, which was significantly different from that of 2.9 ± 4.5 for the simple hepatic cysts (p < 0.0001). The difference between each of the individual AE types and simple hepatic cysts was also significant. In addition, the HU values of the cystoid portions in types I, II and IIIa/b and simple cysts were each significantly different from type IV (p < 0.0001). The HU measurements in type IV presented by far the highest mean. Conclusions. The significantly higher density measured in the cystoid portions of hepatic AE lesions offers a good means of differentiation from simple hepatic cysts.

Quantitative characterization and diagnosis via hard X-ray phase-contrast microtomography.

Nondestructive three-dimensional (3D) micromorphological imaging technique is essential for hepatic alveolar echinococcosis (HAE) disease to determine its damage level and early diagnosis, assess relative drug therapy and optimize treatment strategies. However, the existing morphological researches of HAE mainly depend on the conventional CT, MRI, or ultrasound in hospitals, unfortunately confronting with the common limit of imaging resolution and sensitivity, especially for tiny or early HAE lesions. Now we presented a phase-retrieval-based synchrotron X-ray phase computed tomography (PR-XPCT) with striking contrast-to-noise ratio and high-density resolution to visualize the HAE nondestructive 3D structures and quantitatively segment different pathological characteristics of HAE lesions without staining process at the micrometer scale. Our experimental results of the HAE rat models at early and developed pathological stages and albendazole liposome (L-ABZ) therapeutic feeding models successfully exhibited the different HAE pathological 3D morphological and microstructural characteristics with excellent contrast and high resolution, demonstrating its availability and superiority. Moreover, we achieved the quantitative statistics and analysis of the pathological changes of HAE lesions at different stages and L-ABZ therapeutic evaluation, helpful to understanding the development and drug treatment of HAE disease. The PR-XPCT-based quantitative segmentation and characterization has a great potential in detection and analysis of soft tissue pathological changes, such as different tumors.

Diffusion-Weighted MRI for the Initial Viability Evaluation of Parasites in Hepatic Alveolar Echinococcosis: Comparison with Positron Emission Tomography.

ObjectiveMore than 70% of hepatic alveolar echinococcosis (HAE) are inoperable. Thus, long-term, or even life-long, pharmacological treatment with benzimidazoles is necessary. For effective treatment, it is of great importance to employ imaging techniques to detect and monitor the non-resectable parasitic viability. Therefore, this study aimed to evaluate diffusion-weighted imaging (DWI) in assessing the viability of HAE in comparison to 18-fluoro-deoxyglucose (18F-FDG) positron emission tomography, combined with computed tomography (PET/CT).Materials and MethodsPositron emission tomography, computed tomography and DWI (b-values: 0, 800 s/mm2) were retrospectively analysed in eight patients with clinically-verified HAE to, generate the apparent diffusion coefficient (ADC) map. The activity of HAE lesions in both techniques were determined independently by two radiologists according to the following standard: (+), marked focally or perilesionally increased FDG uptake/high signal intensity; (−), a hepatic defect without FDG uptake/no high signal intensity. Every lesion's maximum standardized uptake value (SUVmax) on the PET/CT images and mean ADC values on the parametric ADC maps were measured respectively. Results of PET/CT and DWI were compared on a per-lesion-basis. Pearson's correlation coefficient was assessed for statistical analysis.ResultsA total of 14 HAE lesions were detected. Eight lesions (diameter 3–15 cm) showed perilesional hyper-signal intensity on DWI. This was visualised on PET/CT as increased FDG uptake. They mainly existed in the lesion's border with normal liver parenchyma. Five lesions (diameter < 2 cm) were detected as nodular hyperintensity on DWI and a ‘hot spot’ on PET/CT in the same distribution. One patient, who had received oral drug therapy for three years showed significantly decreased perilesional hyperintensity on the DWI and a hepatic defect without any FDG uptake on PET/CT. Pearson's correlation coefficient indicated a significant inverse correlation of the ADC and the SUVmax (r = −0.67, p < 0.001).ConclusionDiffusion-weighted imaging is capable of offering information on visually detecting the HAE lesions' viability and may be useful for routine application in the initial diagnosis of HAE.

Differentiation between hepatic alveolar echinococcosis and primary hepatic malignancy with diffusion-weighted magnetic resonance imaging.

To determine the value of diffusion-weighted magnetic resonance imaging (DW-MRI) in discriminating between hepatic alveolar echinococcosis (AE) and hepatocellular carcinoma and intrahepatic cholangiocarcinoma. We included 49 patients (27 men, 22 women; mean age: 52.02±9.76 [SD] years; range: 25-72years) with 57 histopathologically confirmed hepatic AE lesions. Fifty patients (18 men, 32 women; mean age: 58.93±8.42 [SD] years; range: 42-71years) with 61 histopathologically confirmed hepatocellular carcinoma and 50 patients (24 men, 26 women; mean age: 50.11±7.70 [SD] years; range: 38-69years) with 54 histopathologically confirmed intrahepatic cholangiocarcinoma lesions were used as control groups. All patients had MRI examination of the liver that included conventional MRI sequences and DW-MRI using b values of 50, 400 and 800s/mm2. Two radiologists evaluated conventional MRI and DW-MRI images and calculated ADC values of hepatic lesions. The mean ADC value of solid components of hepatic AE lesions was 1.34±0.41×10-3mm2/s (range: 0.9-1.59×10-3mm2/s) and was significantly higher than that of the solid components of hepatocellular carcinoma lesions (mean ADC value, 0.99±0.29×10-3mm2/s; range: 0.7-1.15×10-3mm2/s) and of intrahepatic cholangiocarcinoma lesions (mean ADC value, 1.05±0.22×10-3mm2/s; range: 0.86-1.18×10-3mm2/s) (P<0.001). In general ADC values can help discriminate between AE and hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, the use of ADC values cannot help differentiating Type 4 AE from hepatocellular carcinoma or intrahepatic cholangiocarcinoma.

Albendazole increases the inflammatory response and the amount of Em2-positive small particles of Echinococcus multilocularis (spems) in human hepatic alveolar echinococcosis lesions.

BackgroundAlveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. The inflammatory response to this infection is influenced by the interaction of the parasite with the host. We aimed to analyze human liver lesions infected with Echinococcus multilocularis and the changes of the cellular infiltrates during albendazole (ABZ) treatment.Methodology/Principal findingsWe analyzed liver tissue samples from 8 untreated patients, 5 patients treated with two daily doses of 400 mg ABZ for up to two months and 7 patients treated for more than two months with the same ABZ therapy. A broad panel of monoclonal antibodies was used to characterize the lesion by immunohistochemistry. A change in the cellular infiltrate was observed between the different chemotherapy times. During the initial phases of treatment an increase in CD15+ granulocytes and CD68+ histocytes as well as in small particles of Echinococcus multilocularis (spems) was observed in the tissue surrounding the metacestode. Furthermore, we observed an increase in CD4+ T cells, CD20+ B cells and CD38+ plasma cells during a longer duration of treatment.Conclusions/SignificanceABZ treatment of AE leads to morphological changes characterized by an initial, predominantly acute, inflammatory response which is gradually replaced by a response of the adaptive immune system.

Expression of Hypoxia-Inducible Factor-1α in the Infiltrative Belt Surrounding Hepatic Alveolar Echinococcosis in Rats.

Our main aims were to investigate hypoxia inducible factor-1α (HIF-1α) expression in the surrounding invasion range of hepatic alveolar echinococcosis (HAE) lesions and determine the pathological basis of angiogenesis. In total, 23 Wistar rats with hepatic echinococcus multilocularis infection were killed and their livers, which contained 27 HAE lesions, obtained. Specimen segments were generated from 119 paraffin blocks. Comparative analysis of the tissue samples containing HAE nodules and hepatic parenchyma of the surrounding region was performed with the immunohistochemical SP method in this animal experiment. Expression patterns of HIF-1α in the surrounding invasion range and the hepatic parenchyma were compared. The HIF-1α positive expression rate was 97.5% (116/119 samples). Expression of HIF-1α in the actively multiplying infiltrative region of the HAE lesions was significantly higher than that in hepatic parenchyma (P < 0.05). Overexpression of HIF-1α in the actively multiplying infiltrative region of HAE lesions in rats is closely related to angiogenesis and microvasculature. The sensitivity of HIF-1α facilitates its application as a representative maker of HAE. Our data indicate that the invasion range of HAE lesions is based on extrusion and compression, and induces anoxia and ischemia in hepatic tissue. Thus, HIF-1α provides a valuable index for evaluating HAE activity, and induces anoxia and ischemia in hepatic tissue.

Value of MR diffusion weighted imaging in assessing the viability of hepatic alveolar echinococcosis

Objective To evaluate DWI in the assessment of viability of hepatic alveolar echinococcosis (HAE) by comparing DWI with PET-CT results. Methods 18-fluorodeoxy glucose(18F-FDG) PET-CT and DWI(b values=0, 800 s/mm2) were retrospectively analyzed in 8 patients with clinically verified HAE. The metabolic activity of HAE lesions in both techniques were determined by two independent radiologists respectively. Kappa test was assessed between the results of two observers. Results Sixteen lesions (composed of 14 HAE and 2 cystic echinococcosis, CE) were detected.(1)Eight lesions (≥2 cm) showed perilesional hyper-signal intensity on DWI, mainly around the lesion bounding by normal liver parenchyma. One patient (≥2 cm) had oral drug therapy for three years, and the lesion showed discontinuous perilesional hyper-signal intensity on DWI after the therapy. Five lesions (<2 cm) were depicted as nodular high signal on DWI.(2)Eight lesions (≥2 cm) showed perilesional increased FDG uptake on PET-CT, while 5 lesions (<2 cm) displayed ashot pot. One patient (leison≥2 cm) who had oral drug therapy for three years showed hepatic defect without any FDG uptake in post-treatment PET-CT. Two CE lesions showed negative results on both DWI and PET-CT. The Kappa value of 0.880 indicated a good coincidence between DWI and PET-CT in depicting the metabolic activity of HAE (P=0.006). Conclusions This preliminary study showed the value of DWI in assessing HAE viability. DWI should be routinely used as one of the techniques in the evaluation of HAE. Key words: Echinococcosis, hepatic; Magnetic resonance imaging; Tomography, X-ray computed

Proposal of an ultrasonographic classification for hepatic alveolar echinococcosis: Echinococcosis multilocularis Ulm classification-ultrasound.

To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis (AE). Clinical data and ultrasonography (US) findings of 185 patients (100 males; 85 females; mean age at diagnosis: 51.4 ± 17.6 years; mean age at time of US examination: 58.7 ± 18.2 years) were retrospectively reviewed with respect to the US morphology of hepatic AE lesions. The sonomorphological findings were grouped according to a five-part classification scheme. Application of the new classification resulted in the following distribution of sonomorphological patterns among the patients examined: hailstorm (54.1%); pseudocystic (13.5%); ossification (13.0%); hemangioma-like (8.1%); and metastasis-like (6.5%). Only 4.9% of lesions could not be assigned to a sonomorphological pattern. The sonomorphological classification proposed in the present study facilitates the diagnosis, interpretation and comparison of hepatic alveolar echinococcosis in routine practice and in the context of scientific studies.

Acoustic structure quantification (ASQ): a new tool in sonographic examination of liver lesions in hepatic alveolar echinococcosis.

Qualitative and quantitative acoustic structure quantification (ASQ) is a new, noninvasive sonographic imaging method based on B-mode. This prospective clinical pilot study aims to answer the question whether delineation and measurement of liver lesions in hepatic alveolar echinococcosis (HAE) can be improved by ASQ. Furthermore, this is the first pilot study to explore how ASQ parameters in HAE lesions develop. A total of 24 patients (male=13/female=11, mean age=52years (16-85), mean disease duration=68months (1-334)) with HAE were examined with ASQ using a Toshiba Aplio 500 unit. ASQ parameters were measured in HAE liver lesions and in adjacent non-tumor parenchyma. Quantitative analysis was performed offline using ASQ quantification software. Subjectively parasitic tumors in HAE appear more prominent in color-coded ASQ imaging, but the size of lesions measured in ASQ mode does not differ from size measurements in B-mode. Median focal disturbance ratio (FD ratio) in lesions was 3 (0.1-3), compared with 0.5 (0.1-1.8) in surrounding liver parenchyma (p<0.0001). Statistical comparison of other ASQ parameters (mode, average, standard deviation) shows results that are similarly significant with p values between p<0.0001 and p<0.0018. ASQ is a promising sonographic method for examination and quantification of structural changes of liver parenchyma in HAE lesions.