RESUMO
BACKGROUND: Hepatic alveolar echinococcosis (AE) is a severe zoonotic parasitic disease, and accurate preoperative prediction of lymph node (LN) metastasis in AE patients is crucial for disease management, but it remains an unresolved challenge. The aim of this study was to establish a radiomics model for the preoperative prediction of LN metastasis in hepatic AE patients. METHODS: A total of 100 hepatic AE patients who underwent hepatectomy and hepatoduodenal ligament LN dissection at Qinghai Provincial People's Hospital between January 2016 and August 2023 were included in the study. The patients were randomly divided into a training set and a validation set at an 8:2 ratio. Radiomic features were extracted from three-dimensional images of the hepatoduodenal ligament LNs delineated on arterial phase computed tomography (CT) scans of hepatic AE patients. Least absolute shrinkage and selection operator (LASSO) regression was applied for data dimensionality reduction and feature selection. Multivariate logistic regression analysis was performed to develop a prediction model, and the predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 7 radiomics features associated with LN status were selected using LASSO regression. The classification performances of the training set and validation set were consistent, with area under the operating characteristic curve (AUC) values of 0.928 and 0.890, respectively. The model also demonstrated good stability in subsequent validation. CONCLUSION: In this study, we established and evaluated a radiomics-based prediction model for LN metastasis in patients with hepatic AE using CT imaging. Our findings may provide a valuable reference for clinicians to determine the occurrence of LN metastasis in hepatic AE patients preoperatively, and help guide the implementation of individualized surgical plans to improve patient prognosis.
Assuntos
Equinococose Hepática , Excisão de Linfonodo , Linfonodos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equinococose Hepática/cirurgia , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Hepatectomia/métodos , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/parasitologia , Linfonodos/patologia , Linfonodos/cirurgia , Radiômica , Estudos Retrospectivos , Curva ROC , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis (AE). Currently, there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial. Radical hepatectomy combined with regional lymph node dissection is a better treatment. AIM: To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy. METHODS: A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed. Fifty-five patients with combined lymph node metastasis were analysed for their clinical data, diagnosis and treatment methods, follow-up efficacy, and characteristics of lymph node metastasis. Finally, we comparatively analysed the lymph node metastasis rates at different sites. Categorical variables are expressed as frequencies and percentages, and the analysis of difference was performed using the χ 2 test. The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables. RESULTS: A lymph node metastasis rate of 8.8% (55/623) was reported in patients with hepatic AE, with a female predilection (69.1%) and a statistically significant sex difference (χ 2 = 8.018, P = 0.005). Of the 55 patients with lymph node metastasis, 72.7% had a parasite lesion, neighbouring organ invasion, and metastasis stage of P3N1M0 and above, of which 67.3%, 78.2%, and 34.5% of hepatic AE lesions invaded the bile ducts, blood vessels, and distant metastases, respectively. Detection rates of lymph node metastasis of 16.4%, 21.7%, and 34.2% were reported for a preoperative abdominal ultrasound, magnetic resonance imaging, and computed tomography examinations. All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection. After surgery, a routine pathological examination was conducted on the resected lymph nodes. A total of 106 positive lymph nodes were detected in six groups at various sites, including 51 single-group metastasis cases and four multi-group metastasis cases. When the metastasis rates at different sites were statistically analysed, we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites (χ 2 = 128.089, P = 0.000 < 0.05). No statistical difference was observed in the metastasis rate between the five other groups. Clavien-Dindo grade IIIa complication occurred in 14 cases, which improved after administering symptomatic treatment. Additionally, lymph node dissection-related complications were not observed. Recurrence after 2 years was observed in one patient. CONCLUSION: Lymph node metastasis is a rare form of metastasis in hepatic AE, which is more frequent in women. Para-hepatoduodenal ligament lymph nodes are commonly observed. Radical hepatectomy combined with regional lymph node dissection is a safe, effective, and feasible treatment for liver AE combined with lymph node metastasis.
Assuntos
Equinococose Hepática , Hepatectomia , Excisão de Linfonodo , Linfonodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Equinococose Hepática/complicações , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Equinococose Hepática/cirurgia , Hepatectomia/métodos , Excisão de Linfonodo/métodos , Linfonodos/parasitologia , Linfonodos/patologia , Linfonodos/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Alveolar echinococcosis (AE) is caused by Echinococcus multilocularis, affecting dogs as accidental intermediate hosts. CT is increasingly used for abdominal imaging in small animals, providing valuable information, particularly for large masses and limited ultrasound accessibility. This study describes CT findings of hepatic lesions in 13 dogs with AE. All cases displayed well-defined cavitary lesions in the liver. Lesions showed minimal to no contrast uptake in the periphery, no uptake centrally, irregular internal walls, and soft tissue septa. Eight of 13 cases exhibited large cavitary masses (mean diameter 18.7 cm) with thick walls and feathery mineralization. Three of 13 cases had multiple smaller cavitary lesions with thin walls and without mineralization (mean diameter 8.4 cm). Two of 13 cases presented with both lesion types. These findings suggest two typical CT appearances correlated with AE: large thick-walled- and smaller thin-walled lesions. These groups may represent different stages of AE, with smaller lesions merging and progressing into larger ones. In conclusion, CT provides valuable information in evaluating hepatic lesions in dogs with AE. Large cavitary, thick-walled liver lesions with feathery wall mineralization, irregular inner margination, septation, and no central contrast uptake strongly indicate hepatic AE in dogs, differentiating it from other masses.
Assuntos
Doenças do Cão , Equinococose Hepática , Equinococose , Cães , Animais , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/veterinária , Equinococose Hepática/patologia , Estudos Retrospectivos , Equinococose/veterinária , Tomografia Computadorizada por Raios X/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologiaRESUMO
BACKGROUND: Hepatic alveolar echinococcosis (HAE), as a benign parasitic disease with malignant infiltrative activity, grows slowly in the liver, allowing sufficient time for collateral vessels to emerge in the process of vascular occlusion. METHODS: The portal vein (PV), hepatic vein and hepatic artery were observed by enhanced CT and the inferior vena cava (IVC) by angiography, respectively. Analysis of the anatomical characteristics of the collateral vessels helped to look into the pattern and characteristics of vascular collateralization caused by this specific etiology. RESULTS: 33, 5, 12 and 1 patients were included in the formation of collateral vessels in PV, hepatic vein, IVC and hepatic artery, respectively. PV collateral vessels were divided into two categories according to different pathways: type I: portal -portal venous pathway (13 cases) and type II: type I incorporates a portal-systemic circulation pathway (20 cases). Hepatic vein (HV) collateral vessels fell into short hepatic veins. The patients with IVC collateral presented with both vertebral and lumbar venous varices. Hepatic artery collateral vessels emanating from the celiac trunk maintains blood supply to the healthy side of the liver. CONCLUSIONS: Due to its special biological nature, HAE exhibited unique collateral vessels that were rarely seen in other diseases. An in-depth study would be of great help to improve our understanding related to the process of collateral vessel formation due to intrahepatic lesions and its comorbidity, in addition to providing new ideas for the surgical treatment of end-stage HAE.
Assuntos
Equinococose Hepática , Humanos , Equinococose Hepática/complicações , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Circulação Colateral , Veia Porta/patologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologiaRESUMO
BACKGROUND: Alveolar echinococcosis (AE) is an endemic parasitic zoonosis in Germany. In most cases, the liver is the primary organ affected. CASE PRESENTATION: A 59-year old female patient presented with increasing exertional dyspnea and unintentional weight loss. A computed tomography (CT) scan showed a left-sided chylous pleural effusion and multiple intrahepatic masses with infiltration of the diaphragm and the pleura. The findings were initially misinterpreted as hepatocellular carcinoma (HCC) with infiltrating growth. Liver biopsy of one of the masses showed no evidence of malignancy, but an amorphous necrosis of unclear origin. HCC was further ruled out by magnetic resonance imaging (MRI). However, MRI findings were highly suspicious for hepatothoracic dissemination and complications due to AE. Typical histologic findings in a repeated and more specific examination of the liver tissue and a positive serology for echinococcosis confirmed the diagnosis of AE. As the hepatic and pulmonary manifestations were considered inoperable in a curative matter, an anti-parasitic treatment with albendazole was initiated. A video-assisted thoracoscopic surgery (VATS) with removal of the chylous effusion as well as a talc pleurodesis was performed to relieve the patient from dyspnea. Two months later, the patient was asymptomatic and a positron emission tomography (PET)-CT-scan with [18 F] fluoro-2-deoxy-d-glucose (FDG) showed a remarkable diminution of the hepatic manifestation. CONCLUSIONS: This case demonstrates a rare presentation of alveolar echinococcosis with a focus on pulmonary symptoms, emphasizing the importance of evaluation for pulmonary involvement in patients with AE and respiratory symptoms.
Assuntos
Carcinoma Hepatocelular , Quilotórax , Equinococose Hepática , Neoplasias Hepáticas , Feminino , Humanos , Pessoa de Meia-Idade , Equinococose Hepática/complicações , Equinococose Hepática/diagnóstico , Equinococose Hepática/patologia , Diafragma/patologia , Pleura/patologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , DispneiaRESUMO
PURPOSE: Echinococcus 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). METHODS: This 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. RESULTS: The 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). CONSLUSION: The 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.
Assuntos
Equinococose Hepática , Hemangioma , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Projetos Piloto , Estudos Prospectivos , Meios de Contraste , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia , Hemangioma/diagnóstico por imagem , Hemangioma/patologiaRESUMO
PURPOSE: Hepatic alveolar echinococcosis (HAE) of the metastasis-like pattern, according to the Echinococcus Ulm classification, is usually discovered as an incidental finding, and the diagnostic differentiation from "true metastases" is difficult. The aim of this study was to investigate whether lesions of the "metastasis-like pattern" in HAE show a typical contrast behavior that can be used for differentiation from metastasis in malignancies. METHODS: This prospective clinical study included 11 patients with histologically confirmed HAE of the metastasis-like pattern (7 female and 4 male; mean age, 57.1 years; mean disease duration, 59.5 months), who had been examined by B-scan sonography and CEUS, from the National Echinococcosis Registry Germany. RESULTS: On contrast-enhanced sonography, 11/11 reference lesions showed annular rim enhancement in the arterial and portal venous phases. Throughout the entire 4-min study period, none of the reference lesions showed central contrast enhancement-i.e., all exhibited a complete "black hole sign". A small central scar was seen in 81.8% of cases. CONCLUSION: In clinically unremarkable patients with incidentally detected metastasis-like lesions of the liver, contrast-enhanced sonographic detection of rim enhancement without central contrast uptake (black hole sign) should be considered evidence supporting a diagnosis of hepatic alveolar echinococcosis with a rare metastasis-like pattern. This can help to differentiate HAE from metastases, especially in high-endemic areas.
Assuntos
Equinococose Hepática , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Estudos de Coortes , Meios de Contraste , Estudos Prospectivos , Ultrassonografia , Neoplasias Hepáticas/diagnóstico por imagem , Estudos RetrospectivosRESUMO
BACKGROUND: Alveolar echinococcosis (AE) results of an infection with the larval stage of Echinococcus multilocularis. It has been increasingly described in individuals with impaired immune responsiveness. OBJECTIVES: This narrative review aims at describing the presentation of AE according to the type of immune impairment, based on retrospective cohorts and case reports. Implications for patient management and future research are proposed accordingly. SOURCES: Targeted search was conducted in PubMed using ((alveolar echinococcosis) OR (multilocularis)) AND ((immunosuppressive) OR (immunodeficiency) OR (AIDS) OR (solid organ transplant) OR (autoimmunity) OR (immune deficiency)). Only publications in English were considered. CONTENT: Seventeen publications were found, including 13 reports of 55 AE in immunocompromised patients (AE/IS) and 4 retrospective studies of 755 AE immunocompetent patients and 115 AE/IS (13%). The cohorts included 9 (1%) solid organ transplantation (SOT) recipients, 2 (0.2%) HIV patients, 41 (4.7%) with chronic inflammatory/autoimmune diseases (I/AID) and 72 (8.3%) with malignancies. SOT, I/AID and malignancies, but not HIV infection, were significantly associated with AE (odds ratios of 10.8, 1.6, 5.9, and 1.3, respectively). Compared to AE immunocompetent patients, AE/IS was associated with earlier diagnosis (PNM stages I-II: 49/85 (58%) vs. 137/348 (39%), p < 0.001), high rate of atypical imaging (24/50 (48%) vs. 106/375 (28%), p < 0.01), and low sensitivity of serology (19/77 (25%) vs. 265/329 (81%), p < 0.001). Unusually extensive or disseminated infections were described in SOT and I/AID patients. IMPLICATIONS: Patients who live in endemic areas should benefit from serology before onset of a long-term immunosuppressive therapy, even if the cost-benefit ratio has to be evaluated. Physicians should explain AE to immunocompromised patients and think about AE when finding a liver lesion. Further research should address gaps in knowledge of AE/IS. Especially, extensive and accurate records of AE cases have to be collected by multinational registries.
Assuntos
Equinococose Hepática , Infecções por HIV , Humanos , Equinococose Hepática/epidemiologia , Equinococose Hepática/diagnóstico , Equinococose Hepática/patologia , Estudos Retrospectivos , Hospedeiro ImunocomprometidoRESUMO
OBJECTIVES: 7T small animal magnetic resonance imaging (MRI) was used to analyze the growth characteristics of hepatic alveolar echinococcosis (HAE). METHODS: A mouse model of HAE was established by intraperitoneal injection of alveolar Echinococcus tissue suspension. Ten mouse models successfully inoculated by ultrasound screening were selected. The mouse model was scanned with T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) sequence by 7T small animal MRI. Size, morphology, boundary, signal, and relationship with surrounding tissues of the lesions were recorded as characteristic alterations. Mice were killed at the end of the experiment, and the pathological specimens were taken for routine hematoxylin and eosin staining. RESULTS: Lesions were mainly located in the right lobe of the liver. The multivesicular structure is the characteristic manifestation of this disease. In the liver, lesions invaded the portal vein and were mainly distributed at the hepatic hilum. The left branch of the portal vein was mainly invaded. The mean diameter of the lesions in the left lobe of the liver was larger than in other parts of the liver. The mean diameter of the cystic solid lesions was greater than the multilocular cystic lesions. HAE showed hypointense on T1WI, hyperintense on T2WI, and hypointense on DWI; the marginal zone of the lesion showed hyperintensity on DWI and grew toward the hilum. The MRI features of intraperitoneal lesions were similar to those of intrahepatic lesions. Intraperitoneal lesions increased faster than intrahepatic lesions in the same period. CONCLUSION: Polyvesicular structure is a characteristic manifestation of hepatic alveolar echinococcosis in mice. The noninvasive monitoring of liver HAE in mice by 7T small animal MRI provides a visual basis for the diagnosis and treatment integration of HAE.
Assuntos
Equinococose Hepática , Humanos , Animais , Camundongos , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
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.
Assuntos
Equinococose Hepática , Humanos , Equinococose Hepática/diagnóstico , Equinococose Hepática/patologia , Equinococose Hepática/cirurgia , Qualidade de Vida , Exame FísicoRESUMO
Objective: To analyze the impact of high or low levels of anatomical risk of hepatic alveolar echinococcosis (HAE) on complications after radical resection. Methods: The baseline, surgical, and complication data were retrospectively collected from hepatic alveolar echinococcosis patients who underwent radical resection at the Ganzi Branch Hospital, West China Hospital, Sichuan University from 2015 to 2022. The patients were divided into anatomical low-risk (ALR) and anatomical high-risk (AHR) groups based on the PNM staging system designed by the World Health Organization (WHO-PNM). Complications were analyzed according to the Clavien-Dindo classification. Univariate and multivariate logistic regression analyses were performed to assess the effect of high and low risks of lesion anatomy on complications. Results: Radical surgery was performed in 216 HAE patients and 102 of whom were in the AHR group. The median operative time was 230 (175, 300) min, the median intraoperative blood loss was 600 mL, and 129 (59.7%) patients developed complications. The complication rate was 73.5% (75/102) in the AHR group and 47.4% (54/114) in the ALR group, demonstrating statistically significant difference ( P<0.05). The incidence of serious complications was 36.3% (37/102) in the AHR group and 13.2% (15/114) in the ALR group, demonstrating statistically significant difference ( P<0.05). There was significant difference in the proportions of patients having postoperative complications of bile leak, anemia, fever, pleural effusion and ascites between the AHR group and the ALR group ( P<0.05). Multivariate logistic regression analysis suggested that AHR was the only independent risk factor for complications, including bile leak, anemia, fever, and pleural effusion, and severe complications. Conclusion: The anatomical risk of hepatic alveolar echinococcosis is independently associated with the development of multiple postoperative complications, and physicians should choose surgical procedures cautiously according to the actual situation when dealing with patients defined as AHR according to WHO-PNM.
Assuntos
Equinococose Hepática , Derrame Pleural , Equinococose Hepática/complicações , Equinococose Hepática/patologia , Equinococose Hepática/cirurgia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Derrame Pleural/complicações , Derrame Pleural/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Alveolar echinococcosis (AE) is one of the most dangerous human parasitoses. The main site of disease manifestation is the liver (about 98â%). The Echinococcus Multilocularis Ulm Classification for Computed Tomography (EMUC-CT), presented in 2016, was the first compilation of CT morphological criteria of hepatic AE. Studies based on EMUC-CT made it possible to draw conclusions about the development of the lesions in the course of disease beyond purely diagnostic typing. Among the most important findings of these precursor studies was that EMUC-CT type IV presented as an initial lesion, whereas EMUC-CT type III lesions were mostly associated with an advanced disease constellation. An intermodal view of image morphological criteria provides further multi-layered indications for lesion evolution. METHOD: With the "Alveolar Echinococcosis Ulm Classification" (AEUC), a revision of the previous EMUC-CT was carried out with stage-oriented reorganization of the primary morphologies. Furthermore, an intermodal classification scheme for the evolution of hepatic AE lesions based on AEUC, MRI Kodama classification, and aspects of ultrasound could be outlined. RESULTS: The first stage-oriented CT classification of hepatic AE "AEUC" is based with respect to its lesion characterization on the separate consideration of two classification pillars, the five "primary morphologies", AEUC I-V (AEUC II-IV with subcriteria) and the five "patterns of calcification". In addition, an intermodal classification scheme presents five stages of lesion evolution: "initial stage", "progressive stage", "advanced stage", "transitional stage" and "regressive stage". CONCLUSION: The imaging modalities differ with respect to their visualization of lesion criteria. This underlines the need for unimodal classification systems. Staging of an AE lesion can be done more accurately by evaluating different modalities. KEY POINTS: · The AEUC provides a stage-oriented CT classification for hepatic AE.. · Aspects of different modalities allow a more multi-layered view of lesion evolution.. · More accurate staging can be achieved by combining different modalities.. CITATION FORMAT: · Graeter T, Schmidberger J. Stage-Oriented CT Classification and Intermodal Evolution Model in Hepatic Alveolar Echinococcosis. Fortschr Röntgenstr 2022; 194: 532â-â544.
Assuntos
Equinococose Hepática , Equinococose , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Humanos , Tomografia Computadorizada por Raios XRESUMO
To investigate the effect of cystic echinococcosis (CE) on liver damage, we developed a secondary experimental echinococcosis in Swiss mice by intraperitoneal inoculation of viable protoscoleces. Mice were randomly allocated into three groups: Ctrl group, PBS group, and CE group. Mice were euthanized and associated indications were investigated to evaluate inflammatory and fibrotic responses in liver. Hepatic damage and fibrotic reaction were histologically analyzed. The hepatic expression of iNOS, TNF-α, NF-κß, vimentin, Bcl-2 and CD68 was evaluated by Immunohistochemical examinations. Interestingly, a significant iNOS, TNF-α, NF-κß, vimentin, Bcl-2 and CD68 increase levels was observed in liver tissue and pericystic layer of hepatic hydatid cyst and correlate with the abundance of collagen and reticulin fibers. These observations could promote a potential target for the treatment of CE-associated hepatic injury.
Assuntos
Equinococose Hepática , Equinococose , Animais , Equinococose/complicações , Equinococose/tratamento farmacológico , Equinococose/patologia , Equinococose Hepática/complicações , Equinococose Hepática/tratamento farmacológico , Equinococose Hepática/patologia , Fibrose , Inflamação , Fígado/patologia , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Alveolar echinococcosis (AE) is a zoonotic disease caused by the larval stage of Echinococcus multilocularis parasitizing in the human liver, causing local pathological changes in the liver and manifesting as hyperplasia, liver fibrosis, atrophy, degeneration, and necrosis. Here, we report a method that can simultaneously isolate hepatocytes and hepatic stellate cells (HSCs) from mice infected with Echinococcus multilocularis. METHODS: A mouse model of AE was established. Hepatocytes and HSCs were isolated from mouse liver using a two-step method combining in situ collagenase perfusion and gradient centrifugation. Expressions of Alb, Desmin, and α-SMA were detected with immunofluorescence to identify the isolated hepatocytes and HSCs. RESULTS: The viability and purity of hepatocytes and HSCs both reached 90% or above. For hepatocytes, clear cell boundaries were observed, and the nuclei were round or oval, with clear nucleoli. There was a homogeneous distribution of the hepatocyte marker Alb in the cytoplasm of hepatocytes. Lipid droplets and Desmin expression were observed in the cytoplasm of freshly isolated HSCs. During the activation of HSCs, the lipid droplets gradually decreased and disappeared with a high expression of α-SMA. CONCLUSION: Hepatocytes and HSCs are simultaneously isolated. This may provide a research tool to investigate the interaction between hepatocytes and HSCs and to investigate the mechanism of Echinococcus multilocularis infection-induced liver pathological changes.
Assuntos
Separação Celular/métodos , Equinococose Hepática/patologia , Células Estreladas do Fígado , Hepatócitos , Fígado/patologia , Actinas/metabolismo , Animais , Biomarcadores/metabolismo , Técnicas de Cultura de Células , Sobrevivência Celular , Desmina/metabolismo , Modelos Animais de Doenças , Equinococose/patologia , Echinococcus multilocularis/patogenicidade , Feminino , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/parasitologia , Hepatócitos/metabolismo , Hepatócitos/parasitologia , Fígado/parasitologia , Camundongos Endogâmicos BALB CRESUMO
Autologous liver transplantation (ALT) to cure end-stage hepatic alveolar echinococcosis (HAE) requires that hepatobiliary surgeons understand the invasion of intrahepatic structure and adjacent tissues or organs. Triphase contrast-enhanced CT of the liver has been widely used for diagnosis and preoperative evaluation of HAE. Three-dimensional (3D) reconstruction allows for accurate measurement of remnant liver volume (RLV). The objective of the study was to evaluate value of triphase contrast-enhanced CT together with 3D reconstruction in preoperative evaluation of indications for ALT in patients with end-stage HAE. This cohort include twenty-one consecutive patients with end-stage HAE, who preoperatively underwent triphase enhanced CT together with 3D reconstruction for ALT. To depict the indications, the 2D image data were reviewed statistically focusing on porta hepatis invasion, retrohepatic vena cava (RHVC) involvement and degrees of intrahepatic vessel invasion, and the 3D reconstruction was performed to obtain ratio of RLV to standard liver volume (SLV). The results showed that 95.24% patients (20/21) had porta hepatis invasion. When lesions located in right liver lobe, porta hepatis invasion occurred most commonly in the second and third porta hepatis (7/10), whereas the first, second and third porta hepatis were most commonly invaded by lesions in the right and caudate / left medial liver lobes (7/11) (P < 0.05). The mean value of longitudinal invasion of RHVC was 8.0 cm, and 95.2% (20/21) of patients had RHVC invasion with ≥ 180° circumferential invasion. As for the important vascular events, moderate and severe invasion occurred most commonly in the right hepatic vein, right branch of portal vein and RHVC each in 95.2% (20/21) patients (P < 0.05). We also found that preoperative CT had a good agreement with intraoperative findings in assessing intrahepatic vascular involvement by HAE (kappa index = 0.77). The estimated average ratio of RLV to SLV was 0.95 (range, 0.43-1.62). In conclusion, the 2D contrast-enhanced CT could well depict anatomic location and size of HAE, and invasion of porta hepatis and vascular by this disease, and involvement of other adjacent organs and tissues. Above all, 3D reconstruction could accurately measure RLV in patients with end-stage HAE for ALT.
Assuntos
Equinococose Hepática/patologia , Equinococose Hepática/cirurgia , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Tomografia Computadorizada por Raios X/métodos , Abdome/patologia , Abdome/cirurgia , Adolescente , Adulto , Criança , Feminino , Hepatectomia/métodos , Veias Hepáticas/patologia , Humanos , Fígado/patologia , Fígado/cirurgia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Transplante Autólogo/métodos , Adulto JovemRESUMO
OBJECTIVE: To detect the expression of transforming growth factor-ß1 (TGF-ß1), 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-ß1, p38MAPK and BMP-7 protein in hepatic fibrosis caused by hepatic alveolar echinococcosis. METHODS: 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-ß1, p38MAPK and BMP-7 protein was quantified in liver tissues using Western blotting. The associations of TGF-ß1, p38MAPK and BMP-7 protein expression with hepatic fibrosis were assessed. RESULTS: 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-ß1 (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-ß1, 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-ß1, p38MAPK and BMP-7 protein expression was detected in Group B than in Group C (all P values < 0.05). The expression of TGF-ß1, 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-ß1 (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-ß1 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). CONCLUSIONS: The interaction among TGF-ß1, p38MAPK and BMP-7 jointly participates in the development of hepatic fibrosis induced hepatic alveolar echinococcosis.
Assuntos
Equinococose Hepática , Fator de Crescimento Transformador beta1 , Proteína Morfogenética Óssea 7/genética , Equinococose Hepática/patologia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Human cystic echinococcosis, caused by the larval stage of Echinococcus granulosus sensu lato, has been reported a near-cosmopolitan zoonotic disease. Various infiltrating immune cells gather around the lesion and produce a lesion microenvironment; however, cellular composition and heterogeneity in hepatic cystic echinococcosis lesion microenvironments are incompletely understood. Here, 81,865 immune cells isolated from peripheral blood, perilesion liver tissue, and adjacent normal liver tissue from four cystic echinococcosis patients were profiled using single-cell RNA sequencing. We identified 23 discrete cell populations and found distinct differences in infiltrating immune cells between tissue environments. Despite the significant similarity between perilesion and adjacent normal liver tissue-resident immune cells, the cellular proportions of type 2 innate lymphoid cells (ILC2s) and plasmacytoid dendritic cells (pDCs) were higher in perilesion liver tissue. Interestingly, the immunosuppressive gene NFKBIA was upregulated in these cells. Seven subsets of CD4+ T cell populations were found, and there were more regulatory-CD4+ T cells (Treg-CD4+) and Th2-CD4+ T cells in perilesion tissue than in adjacent normal tissue. There was close contact between CD4+ T cells and ILC2s and pDCs, which caused upregulation of genes related to positive immune activity in adjacent normal liver tissue. However, expression of genes related to immunosuppression, especially the immune inhibitory checkpoint gene NKG2A/HLA-E, was obviously higher in perilesion tissue, suggesting that cellular interaction resulted in an inhibitory microenvironment in the cystic echinococcosis (CE) lesion. This work offers new insights into the transcriptional heterogeneity of infiltrating immune cells in hepatic cystic echinococcosis lesion microenvironments at a single-cell level and provides potential target signatures for diagnosis and immunotherapies.
Assuntos
Microambiente Celular , Suscetibilidade a Doenças , Equinococose Hepática/etiologia , Equinococose Hepática/patologia , Interações Hospedeiro-Parasita , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Microambiente Celular/imunologia , Células Dendríticas , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Humanos , Imunidade Inata , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/patologia , Análise de Célula ÚnicaRESUMO
BACKGROUND: Alveolar 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. METHODS: A 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. RESULTS: Altogether 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. CONCLUSIONS: PET/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.
Assuntos
Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Adulto , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Estudos Retrospectivos , Microambiente TumoralRESUMO
BACKGROUND: To evaluate the role of radiomics based on magnetic resonance imaging (MRI) in the biological activity of hepatic alveolar echinococcosis (HAE). METHODS: In this study, 90 active and 46 inactive cases of HAE patients were analyzed retrospectively. All the subjects underwent MRI and positron emission tomography computed tomography (PET-CT) before surgery. A total of 1409 three-dimensional radiomics features were extracted from the T2-weighted MR images (T2WI). The inactive group in the training cohort was balanced via the synthetic minority oversampling technique (SMOTE) method. The least absolute shrinkage and selection operator (LASSO) regression method was used for feature selection. The machine learning (ML) classifiers were logistic regression (LR), multilayer perceptron (MLP), and support vector machine (SVM). We used a fivefold cross-validation strategy in the training cohorts. The classification performance of the radiomics signature was evaluated using receiver operating characteristic curve (ROC) analysis in the training and test cohorts. RESULTS: The radiomics features were significantly associated with the biological activity, and 10 features were selected to construct the radiomics model. The best performance of the radiomics model for the biological activity prediction was obtained by MLP (AUC = 0.830 ± 0.053; accuracy = 0.817; sensitivity = 0.822; specificity = 0.811). CONCLUSIONS: We developed and validated a radiomics model as an adjunct tool to predict the HAE biological activity by combining T2WI images, which achieved results nearly equal to the PET-CT findings.