Macrophages induce natural killer cell dysfunction via KIR2DL1 during Echinococcus multilocularis infection

Purpose: To investigate the mechanism by which natural killer (NK) cells are compromised by infection with Echinococcus multilocularis in patients with alveolar echinococcosis (AE). Methods: NK cells from AE patients and healthy individuals were measured by flow cytometry and quantitative real-time polymerase chain reaction (PCR) to identify the frequency of different types of NK cells and assess their function. E. multilocularis cyst fluid (EMF) was applied to human monocytic leukaemia cells (THP-1 cells) to assess its effect on their differentiation. In a co-culture system with NK and EMF-THP-1 cells, the function of NK cells were analyzed by enzyme-linked immunosorbent assay (ELISA) with or without antibody against KIR2DL1. Results: Blood from AE patients had fewer CD56low NK cells (p < 0.01) with decreased production of IFN-γ and granzyme B due to the elevated expression of KIR2DL1 (p < 0.001). Treatment of THP-1 cells with EMF induced a tolerogenic phenotype upon activation. Incubation of these EMF-THP-1 cells with NK cells isolated from AE patients significantly impaired the cytotoxic function of NK cells, but this effect was largely blocked by an anti-KIR2DL1 antibody (p < 0.001). Conclusion: E. multilocularis modulates infection macrophages to induce NK cell dysfunction via interaction with KIR2DL1. These results provide a new insight into the mechanisms of parasitic infection-induced dysfunction of NK cells, and may be helpful for the development of therapeutic strategies for the treatment of alveolar echinococcosis

Diagnosis and treatment modalities of hilar biliary duct stricture in hepatic cystic echinococcosis after endocystectomy

Aim: Hilar biliary duct stricture may occur in hepatic cystic echinococcosis (CE) patients after endocystectomy. This study aimed to explore diagnosis and treatment modalities. Methods: Clinical data of 26 hepatic CE patients undergoing endocystectomy who developed postoperative hilar biliary duct stricture were retrospectively analyzed and were classified into three types: type A, type B, and type C. Postoperative complications and survival time were successfully followed up. Results: Imaging showed biliary duct stenosis, atrophy of ipsilateral hepatic lobe, reactive hyperplasia, hepatic hilum calcification, and dilation or discontinuity of intrahepatic biliary duct. All patients received partial hepatectomy to resect residual cyst cavity and atrophic liver tissue, and anastomosis of hepatic duct with jejunum or common bile duct exploration was applied to handle hilar biliary duct stricture. Twenty-five patients were successfully followed up. Among type A patients, one patient died of organ failure, and upper gastrointestinal bleeding and liver abscess occurred in one patient. Moreover, calculus of intrahepatic duct was found in one type B and type C patient. Conclusion: Long-term biliary fistula, infection of residual cavity or obstructive jaundice in hepatic CE patients after endocystectomy are possible indicators of hilar bile duct stricture. Individualized and comprehensive treatment measures, especially effective treatment of residual cavity and biliary fistula, are optimal to avoid serious hilar bile duct stricture

Research advances in surgical treatment of hepatic alveolar echinococcosis

Hepatic alveolar echinococcosis (HAE) is a parasitic disease characterized by invasive growth. Major treatment methods include pharmacotherapy and surgical treatment, and surgical treatment mainly includes radical hepatectomy and palliative surgery. Radical hepatectomy is the first choice, and palliative surgery is mainly used to alleviate disease conditions and complications. Pharmacotherapy also plays an important role in the delay and control of HAE. In recent years, autologous liver transplantation has been used in the treatment of HAE and has become an effective therapy for end-stage HAE patients who cannot be cured by routine surgery. This article introduces the indications and advantages/disadvantages of radical hepatectomy and palliative surgery, as well as the experience in the application of multidisciplinary treatment, the concept of fast-track surgery, and autologous liver transplantation in the treatment of HAE patients, in order to provide a reference for the treatment of HAE

Phenotype and function of MAIT cells in patients with alveolar echinococcosis

Mucosal-associated invariant T (MAIT) cells are a subpopulation of unconventional T cells widely involved in chronic liver diseases. However, the potential role and regulating factors of MAIT cells in alveolar echinococcosis (AE), a zoonotic parasitic disease by Echinococcus multilocularis (E. multilocularis) larvae chronically parasitizing liver organs, has not yet been studied. Blood samples (n=29) and liver specimens (n=10) from AE patients were enrolled. The frequency, phenotype, and function of MAIT cells in peripheral blood and liver tissues of AE patients were detected by flow cytometry. The morphology and fibrosis of liver tissue were examined by histopathology and immunohistochemistry. The correlation between peripheral MAIT cell frequency and serologic markers was assessed by collecting clinicopathologic characteristics of AE patients. And the effect of in vitro stimulation with E. multilocularis antigen (Emp) on MAIT cells. In this study, MAIT cells are decreased in peripheral blood and increased in the close-to-lesion liver tissues, especially in areas of fibrosis. Circulating MAIT exhibited activation and exhaustion phenotypes, and intrahepatic MAIT cells showed increased activation phenotypes with increased IFN-γ and IL-17A, and high expression of CXCR5 chemokine receptor. Furthermore, the frequency of circulating MAIT cells was correlated with the size of the lesions and liver function in patients with AE. After excision of the lesion site, circulating MAIT cells returned to normal levels, and the serum cytokines IL-8, IL-12, and IL-18, associated with MAIT cell activation and apoptosis, were altered. Our results demonstrate the status of MAIT cell distribution, functional phenotype, and migration in peripheral blood and tissues of AE patients, highlighting their potential as biomarkers and therapeutic targets

Laparoscopic hepatectomy for the treatment of hepatic alveolar echinococcosis

Background: At present, laparoscopy is relatively mature as a minimally invasive technique, but there are few reports on this approach for the radical treatment of hepatic alveolar echinococcosis (AE). In this study, we aimed to evaluate the safety and feasibility of laparoscopic hepatectomy (LH) for AE treatment. Results: A retrospective review of medical records obtained from 13 patients diagnosed with AE between January 2018 and December 2019 and treated with laparoscopic hepatectomy was conducted at the First Affiliated Hospital of Xinjiang Medical University. All patients (n = 13) underwent hepatic resection using laparoscopy and none were transferred to open surgery. The average duration of surgery was 285 min (145–580 min). Intraoperative bleeding was 305 mL (20–2000 mL). The mean duration of postoperative catheterization was 6.9 days (3–21 days), and postoperative hospital stay was 7.2 days (4–14 days). No complication of Clavien-Dindo grade III or above occurred, except for the second patient with acute liver failure post-surgically. No recurrences or deaths were observed at 9–30 months of follow-up. Conclusions: Laparoscopic hepatectomy appears to be safe and effective in selected AE patients. The advantages of this technique for AE treatment need to be further compared with the classical open approach

Laparoscopic approach for total cystectomy in treating hepatic cystic echinococcosis

Background: The laparoscopic approach has been proposed for treating hepatic cystic echinococcosis (HCE) and has already been used in clinical practice, mostly for non-radical operations. In this study, we aimed to evaluate the feasibility of total cystectomy of HCE under laparoscopy (LS). Results: A retrospective review of the medical records obtained from 22 patients diagnosed with HCE between June 2009 and June 2013 and treated with an LS approach was conducted in the First Affiliated Hospital of Xinjiang Medical University. A total of 15 patients underwent total cystectomy of HCE using LS. The average time of surgery was 174 min (160–210 min). Intraoperative bleeding was 103 mL (80–200 mL). The mean duration of hospitalization was 7 days (6–15 days). Seven patients were transferred to open surgery (OS). For these patients, the average duration of surgery was 177 min (150–230 min). Intraoperative bleeding was 237 mL (160–350 mL), and the mean duration of hospitalization was 10 days (8–15 days). The most frequent postoperative complications were hydrops in the surgical area (two cases in LS and three cases in OS), and temporary bile leakage (one patient in the LS group). Recurrence was not seen in any cases in either group with a follow-up of 6–12 months. Conclusions: Total cystectomy of HCE appears to be safe and effective in selected patients with unique, small-sized, superficially located cysts. To establish precise recommendations about the technique and its indications, prospective studies are necessary

Laparoscopic approach for total cystectomy in treating hepatic cystic echinococcosis

Background: The laparoscopic approach has been proposed for treating hepatic cystic echinococcosis (HCE) and has already been used in clinical practice, mostly for non-radical operations. In this study, we aimed to evaluate the feasibility of total cystectomy of HCE under laparoscopy (LS). Results: A retrospective review of the medical records obtained from 22 patients diagnosed with HCE between June 2009 and June 2013 and treated with an LS approach was conducted in the First Affiliated Hospital of Xinjiang Medical University. A total of 15 patients underwent total cystectomy of HCE using LS. The average time of surgery was 174 min (160–210 min). Intraoperative bleeding was 103 mL (80–200 mL). The mean duration of hospitalization was 7 days (6–15 days). Seven patients were transferred to open surgery (OS). For these patients, the average duration of surgery was 177 min (150–230 min). Intraoperative bleeding was 237 mL (160–350 mL), and the mean duration of hospitalization was 10 days (8–15 days). The most frequent postoperative complications were hydrops in the surgical area (two cases in LS and three cases in OS), and temporary bile leakage (one patient in the LS group). Recurrence was not seen in any cases in either group with a follow-up of 6–12 months. Conclusions: Total cystectomy of HCE appears to be safe and effective in selected patients with unique, small-sized, superficially located cysts. To establish precise recommendations about the technique and its indications, prospective studies are necessary

Diagnosis and treatment modalities of hilar biliary duct stricture in hepatic cystic echinococcosis after endocystectomy

Aim: Hilar biliary duct stricture may occur in hepatic cystic echinococcosis (CE) patients after endocystectomy. This study aimed to explore diagnosis and treatment modalities. Methods: Clinical data of 26 hepatic CE patients undergoing endocystectomy who developed postoperative hilar biliary duct stricture were retrospectively analyzed and were classified into three types: type A, type B, and type C. Postoperative complications and survival time were successfully followed up. Results: Imaging showed biliary duct stenosis, atrophy of ipsilateral hepatic lobe, reactive hyperplasia, hepatic hilum calcification, and dilation or discontinuity of intrahepatic biliary duct. All patients received partial hepatectomy to resect residual cyst cavity and atrophic liver tissue, and anastomosis of hepatic duct with jejunum or common bile duct exploration was applied to handle hilar biliary duct stricture. Twenty-five patients were successfully followed up. Among type A patients, one patient died of organ failure, and upper gastrointestinal bleeding and liver abscess occurred in one patient. Moreover, calculus of intrahepatic duct was found in one type B and type C patient. Conclusion: Long-term biliary fistula, infection of residual cavity or obstructive jaundice in hepatic CE patients after endocystectomy are possible indicators of hilar bile duct stricture. Individualized and comprehensive treatment measures, especially effective treatment of residual cavity and biliary fistula, are optimal to avoid serious hilar bile duct stricture

Comparative Analysis of Immunoactivation by Nanosecond Pulsed Electric Fields and PD-1 Blockade in Murine Hepatocellular Carcinoma

Nanosecond pulsed electric field (NsPEF) ablation effectively eliminates early-stage hepatocellular carcinoma (HCC) by local ablation and advanced HCC by inducing a remarkable and sustained host immune response. However, this approach is not sufficient to prevent cancer progression, and complementary approaches are necessary for effective immunotherapy. In this study, we evaluated the immunoactivating effects and mechanisms of action of nsPEF ablation and PD-1 blockade on an HCC orthotopic xenograft mouse model. Briefly, 24 C57BL-6J tumor-bearing mice were randomly assigned to three groups: nsPEF ablation group, anti-PD-1 administration group, and untreated control group. Tumor-infiltrating T, B, and NK cell levels and plasma concentrations of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-5, IL-6, and IL-10), Th9 (IL-9), and Th17 (IL-17A, IL-17F, IL-21, and IL-22) cytokines were evaluated. Both nsPEF ablation and anti-PD-1 treatment induced immune cell infiltration in local tumors and modulated cytokine levels in the peripheral blood, with distinct changes in the two treatment groups. Based on these findings, both nsPEF ablation and PD-1 antibody administration can trigger a local and systemic immune response in a partially complementary manner, and nsPEF ablation should be considered along with PD-1 blockade for the treatment of HCC

Treatment of hepatic cystic echinococcosis patients with clear cell renal carcinoma: a case report

Human cystic echinococcosis is a zoonosis caused by the larval cestode Echinococcus granulosus. Clear cell renal carcinoma is the most common pathological type of renal cell carcinoma. Echinococcosis complicated with carcinoma is rarely reported. Here, we reported a female patient with echinococcal cyst of the liver accompanied with clear cell renal carcinoma. This 27-year-old woman was admitted for abdominal pain. The serological testing of hydatid cyst was positive and levels of tumor markers were within the normal range. The computed tomography and histological findings confirmed hepatic echinococcal cyst complicated with renal carcinoma of kidney. Preoperative liver function was grade A. The patient underwent pericystectomy of liver hydatid cyst and partial nephrectomy. No recurrence was found at 1 year of follow-up. Liver hydatid complicated with renal cell carcinoma is rare, which should be differentiated from liver metastasis of renal cancer. Surgical resection is the optimal treatment. This case may provide insight for the diagnosis and research on the co-occurrence of tumor and hydatid cyst