MiR-942-3p Promotes the Proliferation and Invasion of Hepatocellular Carcinoma Cells by Targeting MBL2.

MicroRNAs (miRNAs), a subgroup of small noncoding RNAs, play critical roles in tumor growth and metastasis. Accumulating evidence shows that the dysregulation of miRNAs is associated with the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism by which miR-942-3p contributes to HCC remains undocumented. The association between miR-942-3p expression and the clinicopathological characteristics in HCC patients was analyzed by The Cancer Genome Atlas data set. The targets of miR-942-3p were identified by bioinformatic analysis and dual luciferase report assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays were performed to assess the functional role of miR-942-3p in HCC cells. Consequently, we found that miR-942-3p expression level was elevated in HCC tissues and cell lines as compared with the normal tissues and was associated with the pathological stage and tumor node metastasis (TNM) stage, acting as an independent prognostic factor of poor survival in patients with HCC. Ectopic expression of miR-942-3p enhanced the proliferation and invasive potential of HCC cells, but inhibition of miR-942-3p expression had the opposite effects. Mannose-binding lectin 2 (MBL2) was further identified as a direct target of miR-942-3p and possessed a negative correlation with miR-942-3p expression and unfavorable survival in patients with HCC. Restoration of MBL2 inhibited the progression of HCC cells and attenuated the tumor-promoting effects induced by miR-942-3p. In conclusion, miR-942-3p may act as an oncogenic factor in HCC cells by targeting MBL2 and provide a potential marker for patients with HCC.

Excessive intraoperative blood loss independently predicts recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Several studies have investigated the effect of intraoperative blood loss (IBL) on recurrence of tumors. However, the independent effect of IBL on oncological outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC) is unclear. METHODS: A total of 479 patients who underwent LT for HCC from January 2001 to December 2012 at our institution were enrolled in this retrospective study. Kaplan-Meier and Cox regression methods were used to assess the recurrence rate, as well as its risk factors. Stratified analysis was performed to further examine the effect of IBL on HCC recurrence according to different characteristics of tumors. We also investigated the independent risk factors for excessive IBL using logistic regression analysis. RESULTS: The median follow-up was 28 months (range, 1-131 months). Kaplan-Meier analysis with the log-rank test according to IBL at per liter intervals showed that IBL > 4 L was significantly associated with a higher recurrence rate (P < 0.001). Multivariate analysis identified that IBL > 4 L (P < 0.001; hazard ratio [HR] = 2.32, 95 % confidence interval [CI] = 1.60-3.36) was an independent risk factor for post-LT HCC recurrence, as well as age < 60 years, exceeding Milan criteria, α-fetoprotein levels > 400 ng/mL, and micro- and macrovascular invasion. IBL > 4 L (P < 0.001; HR = 2.45, 95 % CI = 1.64-3.66) was also independently associated with early (within 1 year) recurrence after LT. Furthermore, a significant correlation between IBL > 4 L and vascular invasion (P = 0.019) was found. IBL > 4 L was independently associated with HCC recurrence for patients with vascular invasion, but not for patients without vascular invasion. Finally, we found that the presence of ascites, model for end-stage liver disease score, and operation time were independent risk factors for IBL > 4 L. CONCLUSIONS: Excessive IBL is an independent predictor of HCC recurrence after LT, especially in patients with vascular invasion.

Dichotomous roles of ADAR1 in liver hepatocellular carcinoma and kidney renal cell carcinoma: Unraveling the complex tumor microenvironment and prognostic significance.

BACKGROUND: Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA-editing enzyme that significantly impacts cancer progression and various biological processes. The expression of ADAR1 mRNA has been examined in multiple cancer types using The Cancer Genome Atlas (TCGA) dataset, revealing distinct patterns in kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and liver hepatocellular carcinoma (LIHC) compared to normal controls. However, the reasons for these differential expressions remain unclear. METHODS: In this study, we performed RT-PCR and western blotting (WB) to validate ADAR1 expression patterns in clinical tissue samples. Survival analysis and immune microenvironment analysis (including immune score and stromal score) were conducted using TCGA data to determine the specific cell types associated with ADAR1, as well as the key genes in those cell types. The relationship between ADAR1 and specific cell types' key genes was verified by immunohistochemistry (IHC), using clinical liver and kidney cancer samples. RESULTS: Our validation analysis revealed that ADAR1 expression was downregulated in KICH, KIRC, and KIRP, while upregulated in LIHC compared to normal tissues. Notably, a significant correlation was found between ADAR1 mRNA expression and patient prognosis, particularly in KIRC, KIRP, and LIHC. Interestingly, we observed a positive correlation between ADAR1 expression and stromal scores in KIRC, whereas a negative correlation was observed in LIHC. Cell type analysis highlighted distinct relationships between ADAR1 expression and the two stromal cell types, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), and further determined the signature gene claudin-5 (CLDN5), in KIRC and LIHC. Moreover, ADAR1 was inversely related with CLDN5 in KIRC (n = 26) and LIHC (n = 30) samples, verified via IHC. CONCLUSIONS: ADAR1 plays contrasting roles in LIHC and KIRC, associated with the enrichment of BECs and LECs within tumors. This study sheds light on the significant roles of stromal cells within the complex tumor microenvironment (TME) and provides new insights for future research in tumor immunotherapy and precision medicine.

Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons.

Liver transplantation (LT) has emerged as a curative strategy for hepatocellular carcinoma (HCC), but contributes to a higher predisposition to HCC recurrence in the immunosuppression context, especially for tumors beyond the Milan criteria. Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors, including HCC, it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection. Nevertheless, accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC, from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting. Generally, immunotherapy mainly includes immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and vaccine therapy. ICIs, followed by ACT, have been most investigated in LT, with some promising results. Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy, it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients. In addition, the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT. In this review, we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC. Moreover, we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.

A cellular senescence-related classifier based on a tumorigenesis- and immune infiltration-guided strategy can predict prognosis, immunotherapy response, and candidate drugs in hepatocellular carcinoma.

Background: Cellular senescence plays an irreplaceable role in tumorigenesis, progression, and tumor microenvironment (TME) remodeling. However, to date, there is limited research delineating the landscape of cellular senescence in hepatocellular carcinoma (HCC), and an improved understanding on the interaction of tumor-associated cellular senescence with HCC prognosis, TME, and response to immunotherapy is warrant. Methods: Tumorigenic and immune infiltration-associated senescence genes were determined by weighted gene co-expression network analysis (WGCNA) and the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm, and subsequently, a prognostic scoring model (named TIS) was constructed using multiple survival analysis algorithms to classify the senescence-related subtypes of HCC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were conducted to identify the distinct hallmark pathways between high- and low-risk subtypes. Additionally, we carried out correlation analyses for TIS and clinical traits, senescence-associated secretory phenotype (SASP), immune infiltration and evasion, immune checkpoint factors, drug response, and immunotherapeutic efficacy. External experimental validation was conducted to delineate the association of CPEP3 (a TIS gene) with HCC phenotypes through assays of proliferation, colony formation, and invasion. Results: A five-gene TIS, composed of NET1, ATP6V0B, MMP1, GTDC1, and CPEB3, was constructed and validated using TCGA and ICGC datasets, respectively, and showed a highly robust and plausible signature for overall survival (OS) prediction of HCC in both training and validation cohorts. Patients in the TIS-high group were accompanied by worse OS, activation of carcinogenetic pathways, infiltration of immunosuppressive cells, exclusion of effector killing cells, overexpression of immunomodulatory genes and SASP, and unsatisfied response to immunotherapy. In response to anticancer drugs, patients in the TIS-high group exhibited enhanced susceptibility to several conventional chemotherapeutic agents (5-fluorouracil, docetaxel, doxorubicin, gemcitabine, and etoposide), as well as several inhibitors of pathways involved in cellular senescence (cell-cycle inhibitors, bromodomain and extraterminal domain family (BET) inhibitors, PI3K-AKT pathway inhibitors, and multikinase inhibitors). Additionally, four putative drugs (palbociclib, JAK3 inhibitor VI, floxuridine, and lestaurtinib) were identified as potential compounds for patients in the TIS-high group. Notably, in vitro functional validation showed that CPEB3 knockdown boosted the phenotypes of proliferation, clonogenicity, and invasion in HCC cells, whereas CPEB3 overexpression attenuated these phenotypes. Conclusions: Our study provides comprehensive clues demonstrating the role of novel TIS in predicting HCC prognosis, immunotherapeutic response, and candidate drugs. This work highlights the significance of tumorigenesis- and immune infiltration-related cellular senescence in cancer therapy.

The relationship between adenosine triphosphate within CD4(+) T lymphocytes and acute rejection after liver transplantation.

BACKGROUND: There have been increasing interests in the relationship between CD4(+) T lymphocytes and acute rejection (AR) in transplantation. In this study, we explore the role of CD4(+) T lymphocytes after liver transplantation. METHODS: From February to October 2009, 87 patients underwent liver transplantation. They were divided into the AR group and non-acute rejection (NAR) group, with 56 healthy individuals in the control group. Blood specimens were collected preoperatively and at one, two, and four wk postoperatively for all groups and also on the day when AR occurred and one wk after intravenous glucocorticoid therapy for the AR group. Adenosine triphosphate (ATP) levels were measured using the ImmuKnow™ test kits for immune cell functions. RESULTS: After transplantation, the ATP levels within CD4(+) T lymphocytes were significantly elevated in the two groups when compared with the preoperative levels. It peaked in the AR group and was significantly higher than that of the NAR group (p < 0.05). By ROC curve analysis, the obvious elevation of the ATP value one wk after transplantation had better sensitivity and specificity in diagnosing the AR. The ATP sensitivity rate for early AR was 85.7% and specificity rate 80.9% when the cutoff value was 407 µg/L. The ATP value collected on the day of AR occurrence has apparently positive correlation with the rejection acting index (RAI) (p < 0.01). After the intravenous glucocorticoid therapy, all the ARs were reversed and the ATP value declined significantly compared with the control group and that on the day when AR occurred (p < 0.01). CONCLUSIONS: During the early postoperative period (especially at first week after liver transplantation), the elevation of ATP levels within CD4(+) T lymphocytes has good sensitivity and specificity in diagnosing the AR at early stage. And the degree of AR has positive relationship with ATP value. After the intravenous glucocorticoid therapy, the obvious declination of AR might be used in evaluating the effectiveness of anti-rejection treatment.

Reconstruction of the middle hepatic vein tributary in adult right lobe living donor liver transplantation.

BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 °C University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. METHODS: From June 2007 to January 2008, 11 adult LDLT patients received modified right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 °C UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation. RESULTS: MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outflow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent. CONCLUSION: The cadaveric venous allograft preserved in 4 °C UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outflow of the MHV.

Merged hepatopulmonary features in hepatoid adenocarcinoma of the lung: a systematic review.

This study aimed to provide diagnostic clues for patients with elevated serum alpha-fetoprotein (AFP) in the absence of liver tumors and rectify some previously confused concepts about hepatoid carcinoma of the lung through a systematic review on hepatoid adenocarcinoma of the lung (HAL). A thorough search for original articles on HAL published prior to November 2020 was performed using the PubMed, EBSCOhost, Embase, WanFang Data, and China National Knowledge Infrastructure (CNKI) databases. Ninety-four patients from 88 studies met the eligibility criteria. HAL was rare and mainly occurred among male Asian smokers in their 60 s, presenting with cough, hemoptysis, chest pain, dyspnea and/or weight loss, as well as elevated serum AFP with a mass usually in the right upper lung lobe but no liver masses. Hepatoid differentiation regions, acinar or papillary structures in tumor tissues, and positive immunohistochemical expression of AFP, HepPar-1, and CK8/18 were crucial indicators for the diagnosis of HAL. Surgery-based strategies were recommended for stage I-III patients, while stage IV patients were mainly treated with chemotherapy-based strategy. The 1-, 3-, and 5-year overall survival rates were 40%, 35%, and 19%, respectively. The 1-year relapse-free survival rate was 58%. The postoperative monitoring of AFP contributed to the early detection of tumor recurrence, with a positive rate of 71.43%. In conclusion, patients with elevated serum AFP levels without any detectable hepatic lesions should be evaluated for the possibility of HAL.

A single-center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) was advocated as a salvage treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). This study was designed to assess the eligibility of LT criteria for patients with HCC and to analyze the factors influencing the recurrence of HCC following LT, aiming to further improve the efficacy of LT for patients with HCC. METHODS: Clinical data of 255 patients with HCC who underwent LT between December 2001 and December 2007 at Shanghai Changzheng Hospital, China were retrospectively analyzed. RESULTS: Among these cases, 75 patients were within the Milan criteria and 180 were beyond it; 110 patients were within the University of California, San Francisco (UCSF) criteria, while 145 were beyond it. The difference in overall survival rates was not only significant between the patients within and beyond the Milan criteria but also between patients within and beyond the UCSF criteria. Tumor-node-metastasis (TNM) staging, portal vein tumor thrombus (PVTT), and the pre-operative alpha-fetoprotein (AFP) level were independent risk factors affecting the overall survival and post-operative recurrence-free survival rates of patients with HCC. Pathological staging and pre-operative local treatment of HCC had no obvious correlation with the post-operative recurrence-free survival rate. CONCLUSION: LT is an effective treatment modality for HCC. The UCSF criteria did not show better effectiveness than the Milan criteria. TNM staging, PVTT, and the pre-operative AFP level are closely related to the recurrence of HCC following LT.

[Effects of astilbin on maturation and immunologic function of mouse bone marrow-derived dendritic cells].

OBJECTIVE: To explore the effects of astilbin on the maturation and immunologic function of mouse bone marrow-derived dendritic cells (DCs). METHODS: Mouse bone marrow cells were cultured with recombinant mouse granulocyte-macrophage colony-stimulating factor and interleukin-4 (IL-4) for 5 days to get immature DCs (imDCs), then the imDCs was cultured in the presence of 1 microg/mL lipopolysaccharide (LPS) or LPS (1 microg/mL) plus astilbin (25, 50, 100 microg/mL) for 48 h. Then, the cells were harvested, and the apoptosis, immunophenotypes and antigen phagocytosis capability of imDCs in LPS, and low-, medium- and high-dose astilbin groups were analyzed by flow cytometry. Contents of p40 subunit of interleukin-12 (IL-12p40) in the supernatants were detected with enzyme-linked immunosorbent assay (ELISA). The stimulatory activity of the harvested cells on allogeneic T cells in mixed lymphocyte reactions (MLR) was tested by incorporation of 3H-thymidine, and the contents of IL-2, IL-4, IL-10 and interferon-gamma (INF-gamma) in the supernatants of MLR were examined by ELISA. RESULTS: At the concentrations of 25 to 100 microg/mL, astilbin exhibited no toxicity on co-cultured DCs. Compared with the lipopolysaccharide, low-, medium- and high-dose astilbin could decrease the expression levels of major histocompatibility complex-Ia (MHC-Ia), CD40, CD80 and CD86 molecules in DCs. DCs in the low-, medium- and high-dose astilbin groups exhibited weaker capabilities for antigen phagocytosis and less contents of IL-12p40 in the supernatants than in the LPS group. Furthermore, low-, medium- and high-dose astilbin showed weak activities in stimulating the proliferation of allogeneic T cells as compared with the LPS (P<0.05). Compared with the LPS, low-, medium- and high-dose astilbin could decrease IL-2 and INF-mu secretion from T cells in MLR but had no effect on IL-10 secretion. CONCLUSION: Astilbin can inhibit maturation of mouse bone marrow-derived DCs with dose-dependent effect and exert negative effects on immunologic function of the DCs.

Acute rejection after liver transplantation is less common, but predicts better prognosis in HBV-related hepatocellular carcinoma patients.

BACKGROUND: With a novel finding of significantly lower incidence of acute rejection (AR) in patients with hepatocellular carcinoma (HCC) after liver transplantation, compared with those with benign end-stage liver disease (BESLD), in a large national cohort, we analyzed the correlations among the perioperative immuno-inflammation status, postoperative AR, and prognosis in HCC and BESLD patients with same etiology of hepatitis B virus (HBV), who underwent liver transplantation. METHODS: Patients who underwent liver transplantation due to HBV-related HCC or BESLD and experienced AR between September 2008 and April 2017 were analyzed retrospectively and followed up until April 2018. HCC patients with AR were matched with those without AR according to tumor stage and immunosuppressant concentration, at a 1:3 ratio. Preoperative immuno-inflammation status and prognosis of patients in both groups were compared. RESULTS: The overall incidences of AR in patients with HCC and BESLD were 8.60% and 10.61%, respectively. The postoperative 28-day incidence of AR was significantly lower in HCC compared with BESLD patients (3.23% vs 7.08%, p = 0.031). Compared with BESLD patients, the rejection activity index and perioperative CD4/CD8 ratio were significantly lower (p = 0.047 and p < 0.001, respectively), while platelet/lymphocyte ratio was significantly higher in HCC patients (p = 0.041). Later tumor stage in HCC patients was associated with higher systemic immuno-inflammation index, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, platelet/lymphocyte ratio, aspartate aminotransferase/lymphocyte ratio, C-reactive protein/albumin ratio and fibrinogen level, and lower CD4/CD8 ratio before transplantation. In HCC patients with AR, the percentage of regulatory T cells (CD4+/CD25+) and the level of IL-10 significantly decreased (p = 0.0023, < 0.0001, respectively), while Th1/Th2 ratio, levels of IFN-γ and IL-2 markedly increased before transplantation (p = 0.0018, 0.0059, 0.0416, respectively). Preoperative monocyte/lymphocyte ratio was an independent risk factor for overall and recurrence-free survival after liver transplantation in HCC patients (p = 0.025, < 0.001, respectively). The 1-, 3-, and 5-year survival rates were 76%, 71% and 53% in the AR group, and 67%, 37% and 25% in the non-AR group (p = 0.042). CONCLUSION: Preoperative tumor-related immunosuppression may persist after liver transplantation in HCC patients, and reduce the incidence of AR. AR after liver transplantation may indicate a better prognosis in HCC patients.

Bruton's Tyrosine Kinase Inhibitor Attenuates Warm Hepatic Ischemia/Reperfusion Injury via Modulation of the NLR Family Pyrin Domain Containing 3 Inflammasome.

The NLR family pyrin domain containing 3 (NLRP3) inflammasome is a widely studied inflammasome that plays a critical role in inflammatory responses. Many triggers, including microbial pathogens (ie, bacteria and viruses) and other signals (ie, reactive oxygen species, adenosine triphosphate, urate, silicon, and asbestos), can stimulate the NLRP3 inflammasome. Liver ischemia/reperfusion (I/R) injury is a common pathologic process during liver surgery and shock and can induce severe liver damage. Although its pathogenesis is still unclear, oxidative stress and overproduction of the inflammatory response are likely to contribute to I/R injury. The NLRP3 inflammasome is activated during the I/R process, resulting in further recruitment and activation of caspase-1. Activated caspase-1 cleaves the pro-forms of interleukin-1ß and interleukin-18 and results in their maturation, triggering a proinflammatory cytokine cascade and causing liver damage. Bruton's tyrosine kinase is a critical molecule involved in diverse cellular pathways, such as proliferation, apoptosis, inflammation, and angiogenesis. Intrahepatic Bruton's tyrosine kinase is mainly expressed on Kupffer cells and sinusoidal endothelial cells, and the inflammasome is activated in Kupffer cells. Our study found that inhibition of Bruton's tyrosine kinase effectively attenuated liver I/R injury by suppressing activation of the NLRP3 inflammasome in Kupffer cells.

Prediction of survival after liver transplantation for chronic severe hepatitis B based on preoperative prognostic scores: a single center's experience in China.

BACKGROUND: The aim of this study was to estimate the utility of a preoperative model of end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score in predicting the prognosis after othotopic liver transplantation (OLT) for chronic severe hepatitis B (CSHB) and explore the prognostic factors. METHODS: The outcome of 137 patients who underwent OLT using donors after cardiac death (DCDs) for CSHB in our center was reviewed retrospectively. Survival analysis was performed using the Kaplan-Meier method; the log-rank test was used for univariate analysis; and the Cox proportional hazards regression model was used for prognostic factors screening. RESULTS: The overall mortality rate was 33.6% (46/137); and 1-month, 6-month, 1-year, and 5-year patient survival rates were 75.8, 72.0, 71.0, and 60.1%, respectively. Most patients (33/46) died during the first month after OLT. The area under the curve values generated by the receiver operating characteristics curves were 0.82 [95% confidence interval (CI) 0.72-0.92] and 0.68 (95% CI 0.58-0.79), respectively (P < 0.01), for the MELD and CTP models in predicting 1-month mortality after OLT. Patients with a preoperative MELD score <33.8 or a CTP score <12.5 had significantly better prognosis than those with higher scores (P < 0.05). Other mortality predictors include hepatic encephalopathy, preoperative infection, serum creatinine > or = 1.5 mg/dl. CONCLUSIONS: The MELD score was more efficient than the CTP score for evaluating the short-term prognosis in patients with CSHB undergoing OLT using DCDs, which should be taken into consideration during graft allocation.

Liver transplant recipients with portal vein thrombosis: a single center retrospective study.

BACKGROUND: Portal vein thrombosis (PVT) used to be a contraindication for liver transplantation (LT). This obstacle has been delt with following the improvement of LT-related techniques and therapeutic approaches to thrombosis. But the effect of PVT on LT outcomes is still controversial. We reviewed retrospectively the outcome of LT patients with PVT as well as risk factors and surgical management according to PVT grades. METHODS: A total of 465 adult LTs were performed from December 2002 through December 2006. Operative findings and the result of preoperative ultrasonography and imaging were reviewed for PVT grading (Yerdel grading). Comparison of risk factors, variables associated with perioperative period and prognosis between recipients with and without PVT is based on the grades. RESULTS: In the 465 LTs, 42 were operatively confirmed to have PVT (9.0%) (19 recipients with grade 1, 14 with grade 2, 7 with grade 3, and 2 with grade 4). Increased age and treatment of portal hypertension were associated with PVT. Grade 1 or 2 PVT was treated by direct anastomosis or single thrombectomy. In grade 3 PVT patients, the donor PV was directly anastomosed to the dilated branch of the recipient portal venous system or to the distal open superior mesenteric vein through an interposition vein graft if needed. Grade 4 PVT was managed by our modified cavoportal hemitransposition technique. The comparison between PVT patients and controls showed no significant difference in operative duration and blood transfusion (P>0.05). The flow rate of the PV was lower in the PVT patients (48.881+/-12.788 cm/s) than in the controls (57.172+/-21.715 cm/s, P<0.05). The PVT patients had such postoperative complications as renal failure and PV rethrombosis (P<0.05). The 1-year survival rates in PVT and non-PVT patients were 78.6% and 76.4% respectively (P>0.05); the 3-year survival rates were 58.8% and 56.4% respectively (P>0.05). CONCLUSIONS: PVT is not contraindicated for LT if it is graded. PVT recipients may have post-transplantation complications like renal failure and PV rethrombosis, and operative difficulty and patient survival are similar to those in recipients without PVT. Development of therapeutic approaches and accumulation of experience in dealing with PVT further improve the outcomes of LT in PVT recipients.

Two case reports and literature review for hepatic epithelioid angiomyolipoma: Pitfall of misdiagnosis.

BACKGROUND: Hepatic epithelioid angiomyolipoma (HEAML) is a rare liver disease and is easily misdiagnosed. Enhanced recognition of HEAML is beneficial to the differential diagnosis of rare liver diseases. CASE SUMMARY: We presented two cases of HEAML in Changzheng Hospital, Naval Medical University, and then collected and analyzed all reports about HEAML recorded in PubMed, MEDLINE, China Science Periodical Database, and VIP database from January 2000 to March 2018. A total of 409 cases of HEAML in 97 reports were collected, with a ratio of men to women of 1:4.84 and an age range from 12 years to 80 years (median 44 years). Among the patients with clinical symptoms mentioned, 61.93% (205/331) were asymptomatic, 34.74% (115/331) showed upper or right upper quadrant abdomen discomfort, while a few of them showed abdominal mass, gastrointestinal symptoms, low fever, or weight loss. The misdiagnosis rate of HEAML was as high as 40.34% (165/409) due to its nonspecific imaging findings. Most of the tumors were solitary and round in morphology, with clear boundaries. Ultrasound scan indicated low echo with internal nonuniformity and rich blood supply in most cases. Computer tomography/magnetic resonance imaging enhanced scan showed varied characteristics. The ratio of fast wash-in and fast wash-out, fast wash-in and slow wash-out, and delayed enhancement was roughly 4:5:1. A definite diagnosis of HEAML depended on the pathological findings of the epithelioid cells in lesions and the expression of human melanoma black 45, smooth muscle actin, melanoma antigen, and actin by immunohistochemical staining. HEAML had a relatively low malignant rate of 3.91%. However, surgical resection was the main treatment for HEAML, due to the difficulty diagnosing before operation. CONCLUSION: HEAML is a rare and easily misdiagnosed disease, and it should be diagnosed carefully, taking into account clinical course, imaging, pathological ,and immunohistochemical findings.