Primary pelvic Echinococcus granulosus infection: A case report.

BACKGROUND: Primary pelvic Echinococcus granulosus infection is clinically rare. The reported cases of pelvic Echinococcus granulosus infection are considered to be secondary to cystic echinococcosis in other organs. Single Echinococcus granulosus infection is very rare. CASE SUMMARY: In this report, we presented a case of primary pelvic Echinococcus granulosus infection admitted to the First Affiliated Hospital of Xinjiang Medical University. We described the key diagnostic points and surgical treatment of this case. We also summarized the epidemiological characteristics and pathogenesis of the disease. CONCLUSION: Our case may provide clinical data for the diagnosis and treatment of primary pelvic Echinococcus granulosus infection.

Collateral circulation caused by end-stage hepatic alveolar echinococcosis.

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.

Study on the characteristics of 18F-flurodeoxyglucose uptake in the microenvironment of hepatic alveolar echinococcosis / 中华肝胆外科杂志

Objective:To investigate characteristics of the 18F-flurodeoxyglucose ( 18F-FDG) uptake intensity and ranges in distinct hepatic alveolar echinococcosis lesions. Methods:The clinical data of 39 patients with position emission tomography during Jan 2017 to Dec 2019 in the First Affiliated Hospital of Xinjiang Medical University were enrolled. Among them, there were 17 males and 22 females, aging from 15 to 65 years (median 34 years). Lesions were classified into six groups based on heterogenic scales of calcification and liquefaction: A. non-calcified and non-liquefied ( n=7); B. obvious calcified and non-liquefied ( n=7); C. partial calcified and partial liquefied( n=10); D. obvious calcified and partial liquefied ( n=5); E. partial calcified and subtotal liquefied ( n=5); F. obvious calcified and subtotal liquefied ( n=5). Tumor to background ratio (TBR) and width (W) of lesion infiltrative boundary were measured and calculated. Statistical comparison using Mann-Whitney U test as well as correlation analysis was performed. Results:TBR values [ M( Q1, Q3)] for each group were 4.40(3.66, 7.03), 2.55(1.69, 3.60), 3.73(3.37, 5.21), 2.90(2.75, 3.60), 3.80(3.49, 6.36), 2.49(2.21, 3.97), among which A>B, A>D, A>F, C>B, E>B ( U=3.0, 4.0, 4.5, 11.0, 5.0, all P<0.05); From the perspective of the calcification in each group, it was found that the lighter the calcification was, the greater the TBR value was. W values [ M( Q1, Q3)] for each group were [12.5(10.0, 19.5), 11.2(10.5, 12.5), 12.2(10.9, 13.2), 7.8(7.3, 9.3), 10.0(7.3, 13.4), 7.3(6.8, 7.6)] mm, among which A>D, A>F, B>D, B>F, C>D, C>F (all U=0, all P<0.05); According to the degree of calcification and liquefaction of lesions in each group, the lighter the calcification was, the greater the W value was; The heavier the liquefaction was, the smaller the W value was. A mild strength linear correlation has been observed between the TBR value and W value ( r=0.4136, P<0.05). Conclusions:Less calcification and liquefaction implicated higher 18F-FDG uptake intensity and wider range. Radical resection margins and tissue sampling should be individualized based on different lesion features in surgical treatment.

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

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.

Double versus single T-tube drainage for frank cysto-biliary communication in patients with hepatic cystic echinococcosis: a retrospective cohort study with median 11 years follow-up.

BACKGROUND: Partial peri-cystectomy (PPC) is one of the major surgical approaches for hepatic cystic echinococcosis (CE) and has been practiced in most centers worldwide. Cysto-biliary communication (fistula, leakage, rupture) is a problematic issue in CE patients. T-tube is a useful technique in situations where an exploration and decompression are needed for common bile duct (CBD). However, postoperative biliary complications for cystic cavity still remains to be studied in depth. METHODS: A retrospective cohort analysis of CE cases in our single center database from 2007 March to 2012 December was performed. Patients (n = 51) were divided into two cohorts: double T-tube drainage (one at CBD for decompression and one at the fistula for sustaining in cystic cavity, n = 23) group and single T-tube drainage cohort (only one at CBD for decompression, n = 28). Short-/long-term postoperative complications focusing on biliary system was recorded in detail and they were followed-up for median 11 years. RESULTS: Overall biliary complication rates for double and single T-tube drainages were 17.4% vs. 39.3% (P > 0.05). Short-term complications ranged from minor to major leakages, cavity infection and abscess formation, and prevalence was 17.4% vs. 21.4% (P > 0.05) respectively for double and single T-tube groups; most importantly, double T-tube drainage group had obvious advantages regarding long-term complications (P < 0.05), which was biliary stricture needing surgery and it was observed only in single T-tube drainage group. CONCLUSIONS: Double T-tube drainage had better outcomes without procedure-specific postoperative biliary complications than single T-tube drainage. Meanwhile, we recommend long-term follow-up when comparing residual cavity related biliary complications in CE patients as it could happen lately.

Multiple recurrent cystic echinococcosis with abdominal aortic involvement: A case report.

BACKGROUND: Recurrent cystic echinococcosis (CE) with vital organ involvement is a challenge for clinicians. Herein, we report a case of aortic involvement in recurrent retroperitoneal CE lesions following primary splenic CE resection. CASE SUMMARY: A 60-year-old male was admitted due to progressive abdominal pain and poor appetite. He was diagnosed with multiple recurrent CE with abdominal aortic involvement according to preoperative evaluation. During surgical resection, major aortic bleeding accidentally occurred while dissecting the cyst, which was firmly attached to the abdominal aortic wall. Hemostasis attempts were conducted to deal with this emergency situation and maintain circulation. Post-interventional recovery was uneventful, and 2-year follow-up showed no sign of recurrence or any other complications. CONCLUSION: Radical resection of recurrent complicated CE with aortic involvement should be carefully planned and performed to prevent possible severe adverse complications, thereby improving the postoperative outcome.

Dual Role of Hepatic Macrophages in the Establishment of the Echinococcus multilocularis Metacestode in Mice.

Echinococcus multilocularis larvae, predominantly located in the liver, cause a tumor-like parasitic disease, alveolar echinococcosis (AE), that is characterized by increased infiltration of various immune cells, including macrophages, around the lesion that produces an "immunosuppressive" microenvironment, favoring its persistent infection. However, the role of hepatic macrophages in the host defense against E. multilocularis infection remains poorly defined. Using human liver tissues from patients with AE and a hepatic experimental mouse model of E. multilocularis, we investigated the phenotype and function of hepatic macrophages during the parasite infection. In the present study, we found that a large number of CD68+ macrophages accumulated around the metacestode lesion in the liver of human AE samples and that both S100A9+ proinflammatory (M1 phenotype) and CD163+ anti-inflammatory (M2 phenotype) macrophages were significantly higher in close liver tissue (CLT) than in distant liver tissue (DLT), whereas M2 macrophages represent the dominant macrophage population. Furthermore, E. multilocularis-infected mice exhibited a massive increase in macrophage (F4/80+) infiltration in the liver as early as day 5, and the infiltrated macrophages were mainly monocyte-derived macrophages (CD11bhi F4/80int MoMFs) that preferentially differentiated into the M1 phenotype (iNOS+) at the early stage of E. multilocularis infection and then polarized to anti-inflammatory macrophages of the M2 phenotype (CD206+) at the chronic stage of infection. We further showed that elimination of macrophages by treatment of mice with clodronate-liposomes before E. multilocularis infection impaired worm expulsion and was accompanied by a reduction in liver fibrosis, yielding a high parasite burden. These results suggest that hepatic macrophages may play a dual role in the establishment and development of E. multilocularis metacestodes in which early larvae clearance is promoted by M1 macrophages while persistent metacestode infection is favored by M2 macrophages.

Immune Exhaustion of T Cells in Alveolar Echinococcosis Patients and Its Reversal by Blocking Checkpoint Receptor TIGIT in a Murine Model.

BACKGROUND AND AIMS: The cestode Echinococcus multilocularis infection, a serious health problem worldwide, causes alveolar echinococcosis (AE), a tumor-like disease predominantly located in the liver and able to spread to any organs. Until now, there have been few studies that explore how T-cell exhaustion contributes to the parasite's escape from immune attack and how it might be reversed. APPROACH AND RESULTS: In this study, we found that liver T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was significantly enhanced and positively correlated with lesion activity in AE patients. High TIGIT expression in both liver-infiltrating and blood T cells was associated with their functional exhaustion, and its ligand CD155 was highly expressed by hepatocytes surrounding the infiltrating lymphocytes. In co-culture experiments using human blood T cells and hepatic cell line HL-7702, CD155 induced functional impairment of TIGIT+ T cells, and in vitro blockade with TIGIT antibody restored the function of AE patients' T cells. Similar TIGIT-related functional exhaustion of hepatic T cells and an abundant CD155 expression on hepatocytes were observed in E. multilocularis-infected mice. Importantly, in vivo blocking TIGIT prevented T-cell exhaustion and inhibited disease progression in E. multilocularis-infected mice. Mechanistically, CD4+ T cells were totally and CD8+ T cells partially required for anti-TIGIT-induced regression of parasite growth in mice. CONCLUSIONS: This study demonstrates that E. multilocularis can induce T-cell exhaustion through inhibitory receptor TIGIT, and that blocking this checkpoint may reverse the functional impairment of T cells and represent a possible approach to immunotherapy against AE.

The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model.

The local immune mechanisms responsible for the establishment and development of Echinococcus granulosus sensu stricto infection in the liver, have been little explored. We developed a suitable experimental model that mimics naturally infected livers using portal injection of protoscoleces. Opposite to Echinococcus multilocularis infection which is dose-dependent, fully mature hydatid cysts can be established in the liver whatever the injection dose; although most of the infection sites were seen at the establishment phase as inflammatory granulomas associated with fibrosis, they never matured into cysts. At the establishment phase, a strong immune response was composed of T and B cells, with T1-type, T2-type cells and cytokines and IL-10-secreting CD8+ T cells in the liver. At the established phase, results suggested a local production of antibodies by B cells, and an involvement of NK and NKT cells. Infection outcome and local immune response in the liver, were different in the mouse models of Echinococcus granulosus sensu stricto and Echinococcus multilocularis respectively; however, only early specificities at the microenvironment level might explain the major differences found between the lesions induced by the two species. Our quantitative experimental model appears fully appropriate to further study this microenvironment and its relationship with each cestode species.

Echinococcus multilocularis inoculation induces NK cell functional decrease through high expression of NKG2A in C57BL/6 mice.

BACKGROUND: Alveolar echinococcosis (AE) is caused by the larval stage of Echinococcus multilocularis (E. multilocularis), and considered as public health issue. Parasite-host immune interaction is pivotal during infection. As a subset of innate lymphoid cells, NK cells are known to play an important role during virus, bacteria, intra/extracellular parasitic infections and tumor progression. However, the possible role of NK cells in E. multilocularis infection in both human and murine is little known. Herein, the functional alteration of hepatic NK cells and their related molecules in E. multilocularis infected mice were studied. METHODS: 2000 protoscoleces (PSCs) were injected to C57BL/6 mice via the portal vein to establish secondary E. multilocularis infection. NK cells population and their related molecules (CD69, Ly49D, Ly49G2, Ly49H, Ly49I, NKG2A, NKG2D, granzyme B, IFN-γ, TNF-α) were assessed by using fluorescence-activated cell sorter (FACS) techniques and qRT-PCR. NK cell depletion was performed for further understanding the possible function of NK cells during infection. RESULTS: The total frequencies of NK cells and NK-derived IFN-γ production were significantly reduced at designated time points (2, 4, 12 weeks). The liver resident (CD49a+DX5-) NK cells are decreased at 4 weeks after inoculation and which is significantly lower than in control mice. Moreover, in vivo antibody-mediated NK cell depletion increased parasitic load and decreased peri-parasitic fibrosis. Expression of the inhibitory receptor NKG2A was negatively related to NK- derived IFN-γ secretion. CONCLUSIONS: Our study showed down regulates of NK cells and upper regulates of NKG2A expression on NK cells during E. multilocularis infection. Reduction of NK cell frequencies and increased NKG2A might result in low cytotoxic activity through decreased IFN-γ secretion in E. multilocularis infection. This result might be helpful to restore NK cell related immunity against E. multilocularis infection to treat alveolar echinococcosis.

Differentiation between hepatic cystic echinococcosis types 1 and simple hepatic cysts: A retrospective analysis.

This study aims to evaluate the clinic value of ultrasound, computed tomography (CT) and serological testing in the differentiation between hepatic Cystic Echinococcosis (CE) types 1 and simple hepatic cysts.Totally 50 patients with CE Types 1 and 50 patients with simple hepatic cysts were included. All patients examined by ultrasound, CT and serological testing respectively. The receiver operating characteristic (ROC) curve of diagnosis methods was drawn and their sensitivity, specificity, Youden index, positive likelihood ratio, negative likelihood ratio, positive predictive value and negative predictive value were compared. Pathology result was used as golden standard.The area under ROC curve of ultrasound was 0.97 and of CT and serological testing was 0.79 and 0.71 respectively. The sensitivity of ultrasound in the diagnosis of CE Types 1 was 96.00%, specificity was 98.00%, the positive likelihood ratio was 48.00, and negative likelihood ratio was 0.04. Disease prevalence was 50%, positive predictive value was 97.96%, and negative predictive value was 96.08%. The sensitivity of CT was 80.00%, specificity was 62.00%, positive likelihood ratio was 2.11, and negative likelihood ratio was 0.32. Disease prevalence was 50%, positive predictive value was 67.80%, and negative predictive value was 75.61%. The sensitivity of immunological test was 86.00%, specificity was 72.00%, positive likelihood ratio was 3.07, and negative likelihood ratio was 0.19. Disease prevalence was 50%, positive predictive value was 75.44%, and negative predictive value was 83.72%. Combined ultrasound and immunological test, the sensitivity and the specificity was 82% and 100% respectively. Combined CT and immunological test, the sensitivity the specificity was 70% and 82% respectively.In the differentiate diagnosis of CE Types 1 and simple hepatic cyst, ultrasound is better than CT with high sensitivity and specificity, therefore recommended. Immunological examination is an important complement to the imaging examination.

Sequence analysis of mitochondrial cytochrome c oxidase 1 and cytochrome b genes of echinococcus multilocularis from human patients.

Echinococcus multilocularis (E. multilocularis) is the cause of alveolar echinococcosis (AE) in humans. Differences in gene sequence may exist among strains of E. multilocularis that are isolated from different patients in different areas of Xinjiang Uyghur Autonomous Region of China. Other studies have shown that genetic variation and biomolecular classification of E. multilocularis exists. A total of 47 AE samples were collected from AE patients for sequence analysis of mitochondrial cytochrome c oxidase 1 (cox1) and cytochrome b (cytb) genes using PCR. We compared the obtained sequences with the GenBank database to identify the parasite and 5 haplotypes were detected among the geographical isolates from cox1 and cytb, respectively. Nearly all of the samples originated from Northern Xinjiang. Homology comparison of gene haplotypes in GenBank showed that 3 cox1 haplotypes and one cytb haplotype had 100% homology with sequences in GenBank. Two cox1 haplotypes and 4 cytb haplotypes had no homology with previous deposits in GenBank and thus were considered as newly discovered gene haplotypes. This present study demonstrates that comparatively conservative intraspecific genetic variations of E. multilocularis exist in Xinjiang Uyghur Autonomous Region and the main epidemic haplotypes in Xinjiang are H1 (cox1) and H1 (cytb). Cox1 haplotypes H4, H5, and cytb haplotypes H2, H3, H4, and H5 are considered newly discovered gene haplotype sequences.

Advances in multidisciplinary individualized treatment of refractory hepatic alveolar echinococcosis / 临床肝胆病杂志

Hepatic alveolar echinococcosis (HAE)is a zoonotic parasitic disease that seriously threatens the population in western China and compromises patients′quality of life.With the continuous improvement in radical resection rate in recent years,late-stage HAE pa-tients that were incurable in the past now have the opportunity for radical resection.However,patients who are not suitable candidates for radical resection still suffer from various complications and poor quality of life.Therefore,HAE is still considered a refractory and complex disease.The simple empirical treatment model provided by traditional professional discussion is unable to satisfy the treatment of advanced refractory HAE as it is unable to integrate specialized,standardized clinical skills for diagnosis and treatment.Multidisciplinary individual-ized treatment (MDT)organically integrates the advantages of the available treatment into a reasonable individualized comprehensive treat-ment regimen.This review summarizes the advances in MDT for HAE as the best option to increase long-term survival,and suggests MDT as the first-line treatment for late-stage refractory hepatic alveolar echinococcosis.

Multidisciplinary team approach in individualized treatment for refractory hepatic alveolar echinococcosis / 中华肝胆外科杂志

Objective To analyze the use of multidisciplinary team approach (MDT) for advanced and refractory hepatic alveolar echinococcosis in individualized treatment.Methods A retrospective study was conducted on the use of multidisciplinary team approach in individualized diagnosis and treatment for 137 patients with advanced and refractory hepatic alveolar echinococcosis (with invasion of major blood vessels and bile ducts,and/or with lung and brain metastasis) in our hospital from January 2005 to December 2013.The patients were divided into two groups:The MDT group (n =49) and the non-MDT group (n =88).The MDT group was further divided into two subgroups:subgroup A was the surgical treatment group (n =26),and subgroup B was the non-surgical treatment group (n =26).In the subgroup B,13 patients underwent late radical surgery.The non-MDT group was also further divided into two subgroups:subgroup a was the surgical treatment group (n =61),and subgroup b was the non-surgical treatment group (n =27).In subgroup b,5 patients underwent late radical surgery.The time taken to confirm the diagnosis,perioperative hospital stay,operation time,blood loss,postoperative drainage time,postoperative hospital stay,early postoperative complications (pleural and peritoneal effusions,bile leak,anastomotic leak),late postoperative complications (jaundice,anastomotic stenosis,recurrence),and rates of radical surgery were compared between subgroup A and subgroup a.The rates of late radical resection were compared between subgroup B with subgroup b.All data were analyzed using the Mann-Whitney rank sum test or the Chi-square test.Results Subgroup A had significantly shorter perioperative hospital stay,postoperative hospital stay,and total length of hospital stay than subgroup a (P ＜ 0.05).The incidence of late postoperative complications (jaundice,anastomotic stenosis,recurrence) was also significantly less than subgroup a (P ＜ 0.05),and the radical surgery rate was significantly higher than subgroup a (P ＜ 0.05).There was no significant difference in the time taken to confirm the diagnosis,operation time,blood loss,postoperative drainage time,early postoperative complications (pleural and peritoneal effusions,bile leak,anastomotic leak) (P ＜ 0.05) between subgroup A and subgroup a.The ratio of subgroup B receiving chemotherapy alone or drainage + chemotherapy,and the rate of late implement of radical resection were significantly higher than subgroup b (P ＜0.05).Conclusions A multidisciplinary team approach in individualized treatment comprehensively combined the advantages of the effects of drugs,intervention,surgery and systemic nutritional support.The best individualized treatment plan could be used which improved the rates of radical surgery in advanced and refractory hepatic alveolar echinococcosis,reduced postoperative complications,improved quality of life,and offered chances of radical resection in the patients who had lost the opportunities for surgery.