Alveolar Echinococcosis Lesions Research Articles

Complete mitochondrial exploration of Echinococcus multilocularis from French alveolar echinococcosis patients

Alveolar echinococcosis (AE) is a parasitosis that is expanding worldwide, including in Europe. The development of genotypic markers is essential to follow its spatiotemporal evolution. Sequencing of the commonly used mitochondrial genes cob, cox1, and nad2 shows low discriminatory power, and analysis of the microsatellite marker EmsB does not allow nucleotide sequence analysis. We aimed to develop a new method for the genotyping of Echinococcus multilocularis based on whole mitochondrial genome (mitogenome) sequencing, to determine the genetic diversity among 30 human visceral samples from French patients, and compare this method with those currently in use. Sequencing of the whole mitochondrial genome was carried out after amplification by PCR, using one uniplex and two multiplex reactions to cover the 13,738 bp of the mitogenome, combined with Illumina technology. Thirty complete mitogenome sequences were obtained from AE lesions. One showed strong identity with Asian genotypes (99.98% identity) in a patient who had travelled to China. The other 29 mitogenomes could be differentiated into 13 haplotypes, showing higher haplotype and nucleotide diversity than when using the cob, cox1, and nad2 gene sequences alone. The mitochondrial genotyping data and EmsB profiles did not overlap, probably because one method uses the mitochondrial genome and the other the nuclear genome. The pairwise fixation index (Fst) value between individuals living inside and those living outside the endemic area was high (Fst = 0.222, P = 0.002). This is consistent with the hypothesis of an expansion from historical endemic areas to peripheral regions.

Metabolomic profiling of early inactive hepatic alveolar and cystic echinococcosis

Hepatic alveolar echinococcosis (AE) and cystic echinococcosis (CE) are severe helminthic zoonoses and leading causes of parasitic liver damage. They pose a high mortality risk due to invisible clinical signs, especially at the early inactive stage. However, the specific metabolic profiles induced by inactive AE and CE lesions remain largely unclear. Therefore, we used gas chromatography-mass spectrometry-based metabolomic profiling to identify the global metabolic variations in AE and CE patient sera to differentiate between the two diseases and reveal the mechanisms underlying their pathogenesis. In addition, specific serum biomarkers of inactive hepatic AE and CE were screened using receiver operating curves, which can contribute to the clinical diagnosis of both diseases, especially in the earlier phase. These differential metabolites are involved in glycine, serine, tyrosine, and phenylalanine metabolism. Further analysis of key metabolic pathways showed that inactive AE lesions strongly alter amino acid metabolism in the host. CE lesions have an altered metabolism of oxidative stress response. These changes suggest these metabolite-associated pathways can serve as biomarkers to distinguish individuals with inactive AE and CE from healthy populations. This study also investigated the differences in serum metabolic profiles in patients with CE and AE. The biomarkers identified belonged to different metabolic pathways, including lipid, carnitine, androgen, and bile acid metabolism. Taken together, by investigating the different phenotypes of CE and AE with metabolomic profiling, serum biomarkers facilitating early diagnosis were identified.

Investigating intermediate hosts of Echinococcus multilocularis throughout Turkey: Focus on voles.

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis, is one of the most important zoonotic diseases. The parasite has a heterogeneous life cycle; more than 40 small mammal species have been determined to be potential intermediate hosts worldwide. Turkey is one of the highest endemic countries for AE, but only limited information is available concerning the transmission biology of E.multilocularis. The study aimed to provide data on potential intermediate host species (focus on genus Microtus) across Turkey involved in E.multilocularis transmission to foxes, which is a risk for public health. Trapping sites have been specially selected considering field voles' habitats and ecological requirements. In total, 843 rodents were collected from 141 locations. The metacestodes and lesions of AE were identified as macroscopy and microscopy and confirmed by PCR and DNA sequencing. Seventeen (2.0%) small mammals from 13 (9.2%) locations were found infected with E.multilocularis. Infected individuals were identified as Microtus irani, Microtus mystacinus, Microtus hartingi, Microtus guentheri, Cricetulus migratorius and Mus macedonicus. M.hartingi and M.macedonicus are documented for the first time as intermediate hosts of E.multilocularis. In conclusion, 15 of 17 infected small mammals were found in the Microtus genus. Therefore, the genus Microtus, which inhabits fields near villages and is potential prey for foxes, could be considered an important intermediate host for E.multilocularis across Turkey.

Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability.

Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally, which is the only effective first-line anti-AE drug. Unfortunately, in most cases, complete resection of AE lesions is impossible, requiring ABZ administration for even longer periods. Only one-third of patients experienced complete remission or cure with such treatments, primarily due to ABZ's low solubility and low bioavailability. To improve ABZ bioavailability, albendazole bile acid derivative (ABZ-BA) has been designed and synthesized. Its structure was identified by mass spectrometry and nuclear magnetic resonance. Its physicochemical properties were evaluated by wide-angle X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and polarizing microscopy; it was compared with ABZ to assess its solubilization mechanism at the molecular level. To avoid the effects of bile acid on the efficacy of albendazole, the inhibitory effect of ABZ-BA on protoscolex (PSCs)s was observed in vitro. The inhibitory effect of ABZ-BA on PSCs was evaluated by survival rate, ultrastructural changes, and the expression of key cytokines during PSC apoptosis. The results showed that ABZ-BA with 4-amino-1-butanol as a linker was successfully prepared. Physicochemical characterization demonstrated that the molecular arrangement of ABZ-BA presents a short-range disordered amorphous state, which changes the drug morphology compared with crystalline ABZ. The equilibrium solubility of ABZ-BA was 4-fold higher than ABZ in vitro. ABZ-BA relative bioavailability (Frel) in Sprague-Dawley (SD) rats was 26-fold higher than ABZ in vivo. The inhibitory effect of ABZ-BA on PSCs was identical to that of ABZ, indicating that adding bile acid did not affect the efficacy of anti-echinococcosis. In the pharmacodynamics study, it was found that the ABZ-BA group had 2.7-fold greater than that of Albenda after 1 month of oral administration. The relative bioavailability of ABZ-BA is significantly better than ABZ due to the transformation of the physical state from a crystalline state to an amorphous state. Furthermore, sodium-dependent bile acid transporter (ASBT) expressed in the apical small intestine has a synergistic effect through the effective transport of bile acids. Therefore, we concluded that the NC formulation could potentially be developed to improve anti-AE drug therapy.

Real-time multiplex PCR for human echinococcosis and differential diagnosis

Molecular identification of rare human infectious pathogens appears to be one of the most relevant current methods for rapid diagnosis and management of patients. PCR techniques, in particular real-time quantitative PCR, are best suited for the detection of DNA from the pathogens, even at low concentrations. Echinococcosis infections are due to helminths of the Echinococcus genus, with closely related species involved in parasitic lesions affecting animals and, accidentally, humans. We developed a multiplex qPCR (MLX qPCR) assay allowing for the detection of four Echinococcus species involved in Europe in alveolar echinococcosis (AE) and cystic echinococcosis (CE) (Echinococcus multilocularis, E. granulosus sensu stricto, E. ortleppi, and E. canadensis), based on short mitochondrial targets. A collection of 81 fresh and formalin-fixed paraffin-embedded tissues (FFPE) of AE and CE lesions was assembled. The qPCR assays were performed in triplex for Echinococcus spp. detection, associated with a qPCR inhibitor control. A duplex qPCR was also designed to enable diagnosis of two other dead-end helminthiases (cysticercosis (Taenia solium), and toxocariasis (Toxocara cati and T. canis)). The sensitivity of the qPCR was assessed and ranged from 1 to 5×10-4ng/μL (seven PCR assays positive), corresponding to 37-42 cycles for quantifiable DNA. The specificity was 100% for all the targets. This multiplex qPCR, adapted to low amounts of DNA can be implemented in the laboratory for the rapid molecular diagnosis of Echinococcosis species.

A rare disease: a single-center experience of cerebral alveolar echinococcosis in 12 operated patients.

In this study, we have evaluated 12 patients with cerebral alveolar echinococcosis (AE). All patients underwent surgery for cerebral AE. We aimed to demonstrate the relationship between the demographic properties of patients and surgical outcomes as well as surgical suggestions about surgical approaches. Patients were analyzed according to demographic properties, hepatic/ pulmonary AE lesion existence, symptoms, neurological and radiological examination, histopathological findings, and outcome after treatment. Preoperative diagnosis based on the history of the patient, neurological examination, serological tests, and radiology. When enhanced radiological imaging like MR-Tractography and intraoperative neuromonitoring is combined with precision surgical methods cerebral AE is treatable. Ten of twelve cerebral AE patients had favorable outcomes after surgery. AE of the brain is a rare but life-threatening parasitic disease. Wherever the primary focus is, surgery for cerebral involvement of AE is challenging but safe with appropriate surgical techniques and the help of radiological examination.

Research progress on infiltrating zone and microvascular invasion of hepatic alveolar echinococcosis

Hepatic alveolar echinococcosis (AE) is a parasitic disease with biological characteristics similar to malignant tumor. It has no obvious clinical symptoms in the early stage. Most patients have complications such as jaundice, ascites and gastrointestinal bleeding when they see a doctor. At this time, the course of disease is at an advanced stage. In addition, the incomplete resection of the AE lesion(s) leads to a high postoperative recurrence rate, which has a serious impact on the physical and mental health of patients. Based on the summary of the latest research at home and abroad and the analysis of blood supply, microvascular invasion and vascular growth factor expression in the "infiltrating zone" adjacent to the lesions of hepatic AE, this article has a deep understanding of the occurrence and development process of hepatic AE, aiming to better guide clinical practice and improve the quality of life of patients.

Approaches to reconstruction of inferior vena cava by ex vivo liver resection and autotransplantation in 114 patients with hepatic alveolar echinococcosis

BACKGROUNDHepatic alveolar echinococcosis (AE) is most commonly found in retrohepatic inferior vena cava (RHIVC). Ex vivo liver resection and autotransplantation (ELRA) can better realize the radical resection of end-stage hepatic AE with severely compromised hepatocaval confluences, and reconstruction of the affected vessels. Currently, there is a scarcity of information regarding RHIVC reconstruction in ELRA.AIMTo propose reasonable RHICV reconstruction strategies for ex vivo liver resection and autotransplantation.METHODSWe retrospectively summarized the clinical data of 114 patients diagnosed with hepatic AE who treated by ELRA in our department. A total of 114 patients were divided into three groups according to the different reconstruction methods of RHIVC: Group A with original RHIVC being repaired and reconstructed (n = 64), group B with RHIVC being replaced (n = 43), and group C with RHIVC being resected without reconstruction (n = 7). The clinical data of patients, including the operation time, anhepatic phase, intraoperative blood loss, complications and postoperative hospital stay, were analyzed and the patients were routinely followed up. The normally distributed continuous variables were expressed as means ± SD, whereas the abnormally distributed ones were expressed as median and analyzed by analysis of variance. Survival curve was plotted by the Kaplan-Meier method.RESULTSAll patients were routinely followed up for a median duration of 52 (range, 12-125) mo. The 30 d mortality rate was 7.0% (8/114) and 7 patients died within 90 d. Among all subjects, the inferior vena cava (IVC)-related complication rates were 17.5% (11/63) in group A and 16.3% (7/43) in group B. IVC stenosis was found in 12 patients (10.5%), whereas thrombus was formed in 6 patients (5.3%). Twenty-two patients had grade III or higher complications, with the complication rates being 17.2%, 16.3%, and 57.1% in the three groups. The average postoperative hospital stay in the three groups was 32.3 ± 19.8, 26.7 ± 18.2, and 51.3 ± 29.4 d (P = 0.03), respectively.CONCLUSIONELRA can be considered a safe and feasible option for end-stage hepatic AE patients with RHIVC infiltration. The RHIVC reconstruction methods should be selected appropriately depending on the defect degree of AE lesions in IVC lumen. The RHIVC resection without any reconstruction method should be considered with caution.

Differentiation of hepatic alveolar echinococcosis with a hemangioma-like pattern compared to typical liver hemangioma using contrast-enhanced ultrasound: a pilot study

PurposeEchinococcus multilocularis infects humans as a false intermediate host, primarily with intrahepatic manifestation. Incorrect diagnostic interpretation of these liver tumors, especially the hemangioma-like pattern, can lead to progressive disease. The aim of the study was to investigate the differentiation of typical hemangioma and a hemangioma-like pattern of E. multilocularis using contrast-enhanced ultrasound (CEUS).MethodsThis prospective clinical pilot study comprised patients with hemangioma (n = 14) and patients with alveolar echinococcosis (AE) and hemangioma-like pattern (n = 7). Inclusion criteria were the detection of a liver lesion according to a hemangioma-like pattern on E. multilocularis Ulm classification—ultrasound (EMUC-US) and “confirmed” or “probable” AE according to WHO case definition. The comparison group had hepatic hemangioma with typical B-scan sonographic morphology. All participants underwent conventional and contrast-enhanced ultrasonography.ResultsThe patient group comprised five men (71.4%) and two women (28.6%) with a mean average age of 64.1 ± 11.2 years. The patient group with hemangioma comprised nine female subjects (64.3%) and five male subjects (35.7%) with a mean average age of 56.1 ± 12.0 years. Early arterial bulbous ring enhancement (p < 0.0001) and iris diaphragm phenomenon could only be visualized in the patients with hemangioma (p < 0.0001). Furthermore, the patients with hemangioma exhibited hyperenhancement in the late phase (p = 0.0003). In contrast, the patients exhibited typical early arterial rim enhancement (p < 0.0001) and, in the portal venous and late phase, complete or incomplete non-enhancement (black hole sign; p = 0.0004).ConslusionThe behavior of hemangioma-like AE lesions and typical liver hemangiomas is significantly different on CEUS. AE should be considered as a possible differential diagnosis, especially in high-endemic areas.

Initial Risk Assessment in Patients with Alveolar Echinococcosis-Results from a Retrospective Cohort Study.

Background: Alveolar echinococcosis (AE) is a potentially lethal parasitosis with a broad spectrum of disease dynamics in affected patients. To guide clinical management, we assessed initial prognostic factors for both progressive and controlled AE based on initial staging. Methods: A retrospective cohort study was conducted, examining 279 patients assigned to different clinical groups: cured, stable with and without the need for benzimidazole treatment, and progressive disease. Univariate analysis compared demographic and clinical variables. Significant variables were subsequently entered into two separate logistic regression models for progressive and controlled disease. Results: Based on the multivariate analysis, a large AE lesion (OR = 1.02 per millimetre in size; 95%CI 1.004–1.029), PNM staging (OR = 2.86; 95%CI 1.384–5.911) and especially the involvement of neighbouring organs (OR = 3.70; 95%CI 1.173–11.653) remained significant risk factors for progressive disease. A negative Em2+ IgG (OR = 0.25; 95%CI 0.072–0.835) and a small AE lesion (OR = 0.97; 95%CI 0.949–0.996) were significant protective factors. Conclusions: Patients with large lesions and advanced stages should be monitored closely and most likely require long-term treatment with benzimidazoles if curative resection is not feasible. Patients with small lesions and negative Em2+ IgG seem able to control the disease to a certain extent and a less strict treatment regimen might suffice.

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.

Quantitative evaluation of range and metabolic activity of hepatic alveolar echinococcosis lesion microenvironment using PET/CT and multi-site sampling method

BackgroundAlveolar echinococcosis (AE) lesion microenvironment (LME) is crucial site where parasite-host interactions happen and of great significance during surgery and obtaining liver samples for basic research. However, little is known about quantification of LME range and its’ metabolic activity regarding different lesion characteristics.MethodsA prospective and retrospective analysis of LME from surgical AE patients was performed. Patients (n = 75) received abdominal computed tomography (CT) and position emission tomography/computed tomography using 18F-fluodeoxyglucose (18F-FDG-PET/CT) within 1 week prior to surgery. Semiquantitatively, calcification was clustered with 0%, < 50% and ≥ 50% degrees at lesion periphery; liquefaction was clustered with 0%, < 50%, 50 ~ 75%, ≥75% degrees at lesion center using volumetric ratio. Tumor to background ratio (TBR) of 18F-FDG standard uptake value (SUV, n = 75) was calculated, and range of 18F-FDG uptake area was measured; Multi-site sampling method (MSS, n = 35) was introduced to obtain histological slides to evaluate immune cell infiltrative ranges.ResultsAltogether six major lesion groups have been identified (A: 0% calcified, 0% liquefied; B: ≥50% calcified, 0% liquefied; C: < 50% calcified, < 50% liquefied; D: ≥50% calcified, < 50% liquefied; E: < 50% calcified, 50 ~ 75% liquefied; F: ≥50% calcified, ≥75% liquefied). Statistically, TBR values respectively were 5.1 ± 1.9, 2.7 ± 1.2, 4.2 ± 1.2, 2.7 ± 0.7, 4.6 ± 1.2, 2.9 ± 1.1 in groups A ~ F, and comparisons showed A > B, A > D, A > F, E > B, E > D, E > F, C > B, C > D, C > F (P < 0.05); LME ranges indicated by PET/CT respectively were 14.9 ± 3.9, 10.6 ± 1.5, 12.3 ± 1.1, 7.8 ± 1.6, 11.1 ± 2.3, 7.0 ± 0.4 mm in groups A ~ F, and comparisons showed A > B, A > D, A > F, A > E, C > B, C > D, C > F, E > D, E > F, B > D, B > F (P < 0.05); LME ranges indicated by MSS respectively were 17.9 ± 4.9, 13.0 ± 2.7, 11.9 ± 2.6, 6.0 ± 2.2, 11.0 ± 4.1, 6.0 ± 2.2 mm in groups A ~ F, and comparisons showed A > C, A > D, A > F, B > D, B > F, C > D, C > F (P < 0.05). Generally, less calcifications indicated higher TBR values and wider LME ranges; and, severer liquefactions indicated smaller LME ranges. Additionally, patients with previous medication history had lower TBR values.ConclusionsPET/CT and MSS method showed distinct TBRs and LME ranges for different calcifications and liquefactions. This study would be able to provide references for both surgical resections of lesions and more accurate sample acquisitions for basic research targeted to immunology.

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.

Clinical Features, Radiological Characteristics, and Outcomes of Patients With Intracranial Alveolar Echinococcosis: A Case Series From Tibetan Areas of Sichuan Province, China.

Objectives: Intracranial alveolar echinococcosis (IAE), a zoonotic disease, is a critical health problem in the Tibetan region. We aimed to describe the clinical and radiological characteristics and outcomes among patients with IAE.Methods: We screened patients diagnosed with IAE between March 2015 and May 2019 at the Ganzi Tibetan Autonomous Prefecture People's Hospital. Detailed demographics, clinical characteristics, neuroimaging features, and outcomes were recorded.Results: A total of 21 patients with an average age of 44.1 ± 12.7 years were included. Thirteen (61.9%) patients were male. The most common chief neurological complaint was headache (n = 17, 81.0%), followed by dizziness, seizure, visual disturbances, hemiparesis, disturbed consciousness, and dysphasia. All the patients had coexisting liver localizations. The typical neuroimaging features of IAE on cerebral magnetic resonance imaging scans showed obvious low-signal shadow with multiple small vesicles inside the lesions on T2-weighted images and FLAIR images. The pathological HE staining demonstrates vesicular lesions with several internal sacs. For hepatic alveolar echinococcosis (AE), the hepatic portal was invaded in six (28.6%) patients, and the portal vein (n = 5, 23.8%) was the mostly commonly involved vessel. As for treatment, 11 patients (52.4%) had poor compliance with albendazole. The duration of patients taken albendazole ranged from 2 months to 3 years. Cerebral AE surgery was performed in 11 patients, five of them underwent partial resection of AE lesions, and six patients received total resection. One patient with primary IAE underwent radical surgery. Ten patients (47.6%) died during the follow-up for a mean of 21.7 ± 11.9 (3–46) months. In total, 28.9% of the patients died within 5 years, and 71.6% died within 10 years. The median interval between the date of diagnosis as AE and death was 84 (19–144) months.Conclusion: Despite substantial advances in diagnostic and therapeutic methods, the treatment of IAE remains difficult and results in unsatisfactory outcomes. The major critical issue is surgical treatment of IAE although the disease is disseminated. Besides, lifelong albendazole would be indicated, but most patients had poor medication compliance. It is important to educate patients about the necessity of medical treatment.

Kodama-XUUB: an informative classification for alveolar echinococcosis hepatic lesions on magnetic resonance imaging.

Objective: To propose a modification of the Kodama classification to classify type III lesions of alveolar echinococcosis (AE) that do not have microcysts. Materials and Methods: 200 magnetic resonance imaging (MRI) images of AE liver lesions from four endemic regions of the world were classified according to Kodama, distinguishing within type III those with microcysts from those without. Each center included 50 MRIs of patients with unoperated AA liver lesions. The first 50 cases were classified by a first reader in the presence of four second-line readers from each region. Then each second-line reader classified his or her 50 cases. Results: In all centers, type III lesions were predominant: 58% of the total lesions and 23% of them were without microcysts. The average age of the patients was 47 years. In China, the patients were on average younger and the lesions larger. German patients had more lesions within the liver. Type I and II lesions, synonymous with earlier diagnosis, were more common in Europe. Conclusion: The Kodama classification needed to be modified because of the existence of a significant proportion of unclassifiable lesions. This is especially true since the presence of microcysts is an informative element of parasite activity. Therefore, this study proposes a Kodama-XUUB classification with type IIIa lesions having microcysts and type IIIb lesions not having microcysts.

Simultaneous combined radical surgery for hepatic and renal alveolar echinococcosis: an analysis of 10 clinical cases

Objective: To examine the feasibility, safety and efficacy of simultaneous combined radical surgery for hepatic and renal alveolar echinococcosis (AE). Methods: Clinical dates of consecutive 10 hepatic and renal AE patients who accepted surgical treatment in the First Affiliated Hospital of Xinjiang Medical University during April 2013 to September 2019 were analyzed retrospectively. There were 8 males and 2 females, aged (42.5±10.3) years (range: 27 to 52 years). Seven of them had previously palliative surgical treatment with poor compliance to post-operative medication. All of the patients had hepatic-renal combined AE lesions, and two of them had left lateral and left renal lesions for each, which sized for (726.4±576.1)cm3 (range: 117.0 to 1 998.0 cm3). Extra-hepatic or renal lesions infiltrated to right diaphragm, inferior vena cava, right adrenal gland, abdominal wall, right psoas muscle, duodenum wall and right pulmonary lobe (respectively were 7, 7, 6, 2, 1, 1, 2 cases). Surgery were performed mainly with simultaneous combined surgery and vascular reconstruction techniques for this series. Hemi-hepatectomy or extended right lobectomy was applied in 8 patients, while 2 other patients received ex vivo liver resection and autotransplantation, additionally, one patient had partial hepatectomy for left lateral lobular lesion. Total right nephrectomy, partial right nephrectomy and partial left nephrectomy were respectively performed on 7, 3 and 1 patient(s). Additionally, extra-hepatic or renal lesions were eradicated followed by relevant repairments or reconstructions. Results: Surgeries went well and there was no intra-or post-operative liver or renal dysfunction occurred. During recovery period, 3 cases experienced with hydrothorax and managed well after drainage and supportive treatment, and one patient developed peri-renal urinary leakage and cured by "J" catheter. The subjects were followed-up for 6 to 81 months (median: 21 months), no death, organ dysfunction, chronic or acute kidney diseases occurred. One case encountered with abdominal hernia at post-operative 7th month and was successfully managed with laparoscopic repair with artificial mesh. No disease recurrence in all patients, which reached clinical cure at last. Conclusion: When complied strictly to indications, simultaneous combined radical surgery could be a feasible, safe and efficient approach for patients with hepatic and renal AE, which is primary or relapsed from previous hepatic AE surgery or interventional therapies as well as neighboring organ AE invasions.

Feasibility of Retrohepatic Inferior Vena Cava Resection Without Reconstruction for Hepatic Alveolar Echinococcosis.

This study evaluates the feasibility of retrohepatic inferior vena cava (RHIVC) resection without reconstruction in patients with end-stage hepatic alveolar echinococcosis (AE). Four hundred and fifty-seven patients diagnosed with hepatic AE and who underwent surgical resections between January 2010 and October 2018 were retrospectively analyzed. Nine patients receiving RHIVC resection without reconstruction were included in this study. Among the patients, 5 were male and 4 female. Mean follow-up time was 64.4 months (18-95). In this series, adequate collateral circulation was formed before operation in all patients, and 7 cases underwent ex vivo liver resection and autotransplantation (ELRA) and 2 cases underwent extended right hemi-hepatectomy. Average standard liver volume, graft volume, surgical time, and anhepatic phase in ELRA group patients was 1144 ± 127 cm3, 740 ± 235 cm3, 16.8 ± 4.1 hours, and 337.4 ± 108.65 minutes respectively. Average hospital stay time for all patients was 45 ± 36.4 days. There were no intraoperative deaths. The 30-day mortality rate was 11.1%, and total mortality rate was 22.2%. Postoperative complications occurred in 4 patients. During follow-up, no relapsed AE lesions were found. RHIVC resection without reconstruction is a feasible way for hepatic AE patients with adequate collateral circulation. Careful protection of collateral venous is the key factor for successful operation.

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.

The importance of uninterrupted albendazole treatment in patients with unresectable alveolar echinococcosis undergoing liver transplantation.

This study focused on the monitoring of patients who had undergone liver transplantation (LT) because of unresectable alveolar echinococcosis (AE). The role of long-term administration of albendazole (ABZ) in patients with residual/recurrent AE lesions and without AE lesions was evaluated. Albendazole therapy was prescribed to patients diagnosed with AE 4-6weeks after LT on the background of continuous suppressive therapy while following the protocol for managing patients after LT. Clinical data (general condition, blood counts, and level of hepatic transaminases), ultrasound scans (USs), magnetic resonance imaging (MRI) or multispiral computed tomography (MSCT), and serological data were collected from four patients with residual/recurrent AE lesions and without AE lesions. The results of the USs, MRI, and MSCT examinations at diagnosis and at the end of follow-up were retrospectively reviewed for all patients. Observation of patients over a long period (up to 10years) showed that the continuous (without interruption) use of ABZ restrained the development of metacestodes. Interruptions in taking the drug, associated with the manifestation of hepatotoxicity in some patients, led to the development of lesions in other organs in which the parasite had not previously been detected. No new foci were found in the transplanted livers of the patients. Liver transplantation, together with continuous anti-relapse chemotherapy, prolongs the patient's life, both in the absence and in the presence of metastases in other organs.