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In August 2023， the European Society for Organ Transplantation （ESOT） published the ESOT Consensus Statement on Biomarkers in Liver Transplantation online. The consensus statement focuses on biomarkers in liver transplantation， clinical applicability， and future needs and explores the role of new biomarkers in predicting liver transplantation outcomes by reviewing the literature on primary disease recurrence， development of chronic kidney disease （CKD）， and safe weaning of immunosuppression. This consensus statement conducts studies from the four aspects of recurrent liver disease after liver transplantation， recurrent hepatocellular carcinoma， weaning of immunosuppression， and CKD progression， emphasizes the importance of biomarkers in predicting or detecting disease recurrence， and proposes that large-scale prospective studies are still needed to improve the quality of evidence. The author’s team gives an excerpt of the consensus statement and systematically introduces the four aspects of the consensus statement and related discussions and conclusions， in order to provide more evidence-based medical evidence for identifying and exploring new biomarkers for liver transplantation.
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Objective:To explore the feasibility and safety of robotic-assisted living donor left lateral segmentectomy (LDLLS) in a large pediatric liver transplant program.Methods:Retrospective analysis was performed for clinical data of 45 LDLLS donors and recipients from June 2021 to September 2022.Traditional open donor liver resection (n=30) and robotic-assisted segmentectomy (n=15) were performed.Two groups were compared with regards to operative duration, intraoperative hemorrhage, postoperative healing and postoperative complications.SPSS 21.0 was utilized for statistical analysis.Independent sample T, paired sample T, Wilcoxon rank sum and Chi-square tests were performed for examining the inter-group differences.Results:Operative duration of robot-assisted surgery group was substantially longer than that of traditional open surgery group ( P<0.001). Intraoperative blood loss was less in robot-assisted surgery group was less than that in traditional open surgery group[(106.0±39.8) vs.(251.0±144.8) ml, P=0.001]. Postoperative hospital stay of robot-assisted surgery group was shorter than that of traditional open surgery group[6.0(6.0, 6.0) vs.7.0(6.0, 9.0), P<0.05]. Two cases of postoperative biliary leakage were observed in donor of traditional open surgery group.Among 2 cases of abdominal infection, one was due to biliary leakage from liver section and secondary surgery was then performed.One case of incisional infection and another case of thrombosis occurred in donor of traditional open surgery group.In robot-assisted surgery group, only one donor had amylase elevation.In traditional open surgery group, there were one case of local thrombosis in middle hepatic vein and one case of bile duct stricture.No long-term complications occurred in robot-assisted surgery group during a follow-up period of over 6 months.Finally recipient data analysis indicated that no significant inter-group differences existed in operative duration, intraoperative blood loss, postoperative hospital stay or postoperative abdominal infection ( P=0.634, P=0.180, P=0.86 and P=0.153). Conclusions:Robotic-assisted LDLLS proves to be be a safe and reliable option for living donor segmentectomy.It is superior to conventional LDLLS in terms of shorter hospital stay, less intraoperative blood loss and fewer postoperative complications.
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Objective:To ulteriorly explore the differences of psychotic symptoms and neurocognitive between patients with first-episode deficit subtype of schizophrenia (FDS) and patients with first-episode nondeficit subtype of schizophrenia (FNDS).Methods:From January 2021 to September 2021, a total of 88 first-episode treatment-naive schizophrenia were recruited from the Mental Health Center of West China Hospital and divided into FDS group( n=44) and FNDS group( n=44) according to the schedule for the deficit syndrome (SDS), and 44 healthy subjects were included as healthy control group (HC group, n=44). Positive and negative syndrome scale (PANSS) was used to assess psychotic symptoms of patients and Wechsler adult intelligence scale, trail making test and logic memory test were used to evaluate intelligence quotient and neurocognitive function of all subjects.SPSS 22.0 was used for statistical analysis, and independent samples t-test and one-way analysis of variance (ANOVA) were used to compare variables that met normal distribution, while the Mann-Whitney U test and Kruskal-Wallis H test were used to compare variables that did not meet normal distribution. Results:(1) There were significant differences in psychotic symptoms between the FDS group and the FNDS group.Compared with the FNDS group, the FDS group had higher total score of PANSS ((95.95±16.82) vs (88.39±16.29)), negative symptoms ((27.57±7.52) vs (16.57±5.76)) and anergastic reaction ((13.43±3.82) vs (7.00(5.00, 9.00)), and lower positive symptoms scores ((21.95±6.88) vs (25.41±6.07)), activation ((8.00(5.00, 9.00) vs (9.27±3.47)), depression ((5.50(4.00, 9.00) vs (8.00(6.00, 12.00)) and supplementary item ((13.60±4.17) vs (17.30±5.39))(all P<0.05). (2) There were differences in neurocognitive functions between FDS group and FNDS group, and which in FDS and FNDS group were worse than that in HC group.Spatial memory (block design test: (23.70±11.05) vs (31.72±11.49)) and information processing speed (digit symbol test: (38.38±15.85) vs (47.97±14.99)) of FDS group were significantly lower than those of FNDS group(both P<0.05). Intelligence quotient, information processing speed and spatial memory of FDS group and FNDS group were lower than those of HC group(all P<0.05). Conclusion:FDS patients has more severe negative symptoms and anergastic reaction, and exit worse information processing speed and spatial memory dysfunction than FNDS patients.This unique pattern of impairment suggests that information processing speed and spatial memory may be important classification indicators for differentiating the deficit subtype of schizophrenia in the early stage.
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Cholangiocarcinoma (CCA) is a highly malignant biliary tumor with strong invasion and poor prognosis and is insensitive to radiotherapy and chemotherapy. Tumor-associated macrophage (TAM) is an important component of the tumor microenvironment. CCA cells recruit TAM into tumor tissue by releasing cytokines and polarize them into M2 TAM, which promotes the progression of CCA through various mechanisms such as assisting immune escape, promoting tumor cell proliferation, regulating angiogenesis, promoting tumor metastasis, and mediating immune resistance. As an emerging target of tumor immunotherapy, TAM provides new ideas for targeted therapy for CCA. This article reviews the mechanisms of TAM in promoting the progression of CCA and immunotherapy targeting TAM in recent years.
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Objective To establish a scoring system based on the preoperative serum levels of alpha-fetoprotein (AFP) and alkaline phosphatase (ALP), and to investigate its value in predicting the prognosis of patients with resectable hepatocellular carcinoma (HCC). Methods A retrospective analysis was performed for 154 HCC patients who underwent hepatectomy as the initial treatment in Tianjin First Central Hospital from January 2016 to August 2019. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values of serum AFP and ALP; the Kaplan-Meier curve and the log-rank test were used for survival analysis to evaluate the relationship between the AFP-ALP score and disease-free survival (DFS); univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors for HCC patients. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results The ROC curve analysis showed that serum AFP had an optimal cut-off value of 250.0 ng/mL and an area under the ROC curve (AUC) of 0.674 (95% confidence interval [ CI ]: 0.580-0.767) in predicting DFS, while serum ALP had an optimal cut-off value of 95.5 U/L and an AUC of 0.745 (95% CI : 0.652-0.838). The survival analysis showed that high preoperative serum levels of AFP (≥250.0 ng/mL) and ALP (≥95.5 U/L) were significantly associated with the poor prognosis of HCC patients ( P < 0.001). Based on the AFP-ALP score, all HCC patients were further divided into 0-point group (AFP < 250.0 ng/mL and ALP < 95.5 U/L), 1-point group (AFP≥250.0 ng/mL, ALP < 95.5 U/L; or AFP < 250.0 ng/mL, ALP ≥95.5 U/L), and 2-point group (AFP≥250.0 ng/mL and ALP≥95.5 U/L). The survival curves showed that the 0-, 1-, and 2-point groups had a median DFS of 60.0 (56.7-67.3) months, 20.0 (1.4-36.6) months, and 13.0(7.9-18.0) months, respectively, and there were significant survival differences between the three groups ( P < 0.05). Serum AFP-ALP score (1 point vs 0 point: hazard ratio [ HR ]=4.060, 95% confidence interval [ CI ]: 2.050-8.039, P < 0.001; 2 points vs 0 point: HR =4.583, 95% CI : 2.385-8.805, P < 0.001) was an independent prognostic factor for HCC patients. Conclusion The scoring system based on the serum levels of AFP and ALP can effectively identify HCC patients with poor prognosis, and therefore, it might be used as a simple and reliable tool for prognostic assessment in the clinical treatment of HCC.
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Objective:To investigate the protective effect of IL-22 on rat liver ischemia reperfusion injury (IRI) and the potential mechanisms.Methods:Eighteen male specific pathogen free SD rats (7-8 weeks, about 250g) were randomly divided into three groups: Sham group (Sham), hepatic ischemia reperfusion (IRI) and IL-22 preconditioning group (IL-22+ IRI), respectively. The liver IRI model of 70% rats was established. The IL-22+ IRI group was intraperitoneally injected with rcIL-22 (50 mg/kg) 1 hour before surgery, and the Sham group and IRI group were injected with the same dose of normal saline 1 hour before surgery. After 1 h ischemia and 6 h reperfusion, blood was collected from the abdominal aorta, then liver tissue, serum aspartate transaminase (AST) and alanine aminotransfease (ALT) levels were measured. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissue were detected. The expression of signal transducer and activator of transcription 3 (STAT3), p-STAT3, nuclear factor erythorid-2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by Western blot. Results:Compared with Sham group, serum AST [(1 923.50±92.63) U/L, (1 004.25±65.05) U/L)] and ALT [(1 172.51±180.31) U/L, (583.50±164.75) U/L] levels were increased in IRI group and IL-22+ IRI group (AST: F=293.62; ALT: F=30.33, P<0.05). The levels of MDA in IRI group and IL-22+ IRI group [(1.72±0.12) μmol/mg, (0.98±0.05) μmol/mg] in liver tissue were higher than those in Sham group (0.58±0.14) μmol/mg protein ( F=186.73, P<0.05), and the expression of p-STAT3, Nrf2 and HO-1 was increased. SOD level in IRI group (28.51±3.85) U/mg was lower than that in Sham group (70.25±5.64) U/mg protein ( F=203.41, P<0.05). Compared with IRI group, serum AST and ALT levels in IL-22+ IRI group were decreased, SOD activity in liver tissue was increased, MDA level was decreased, and p-STAT3, Nrf2 and HO-1 expression was increased (all P<0.05). Conclusion:IL-22 could alleviate liver IRI in rats, and the mechanism may be related to the activation of STAT3 and Nrf2/HO-1 signaling pathway and anti-oxidative stress.
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Liver transplantation is the most effective way to treat end-stage liver disease, but biliary stenosis after liver transplantation, and tumor recurrence after liver transplantation impairs patients’ life quality and long-term survival. This article discussed the current status of treatment of biliary stenosis after liver transplantation and tumor recurrence after liver transplantation which based on the latest domestic and international researches and the authors’ clinical experience.
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Hepatic ischemia-reperfusion injury(HIRI) is a kind of liver injury caused by reperfusion after ischemic injury, which is clinically manifested by a series of deterioration phenomena such as liver function impairment, jaundice and even multi-organ failure after restoration of blood supply to the liver. HIRI seriously affects the patient's regression and prognosis. The essence of HIRI is a sterile inflammatory response. High mobility histone 1 (HMGB1) is an important intermediate mediator of HIRI and is a multiple cell type effector involved in HIRI. The receptor for glycosylated end products(RAGE) signaling axis of HMGB1 plays a key role in HIRI, but its mechanism is unclear. In this paper, the recent studies related to the pro-inflammatory mechanism of HMGB1-RAGE signaling axis in HIRI were summarized, and the relationship between HMGB1-RAGE signaling pathway and HIRI was discussed. The research progress of preventing and treating HIRI with surgical operation, ischemic preconditioning, drug and gene therapy using HMGB1-RAGE signaling axis as the target was reviewed.
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Objective:To explore the pathogenesis and prognostic factors of brain metastasis of hepatocellular carcinoma(HCC)after liver transplantation(LT).Methods:Retrospective review was performed for 17 HCC cases with brain metastasis after liver transplantation from 2000 to 2020.All cases were diagnosed as hepatitis B cirrhosis complicated with HCC.All of them were beyond the Milan Criteria.The immunosuppressive regimen consisted of baliximab + mycophenolate mofetil + calcineurin inhibitors(CNIs)+ corticosteroids in early postoperative period with a gradual tapering of corticosteroids and mycophenolate mofetil.Three patients received sirolimus immunotherapy after tumor recurrence and withdrew CNIs.One of three cases received sorafenib.Results:Other organ involvements included lung metastasis( n=16, 94.1%), bone metastasis( n=5, 29.4%)and liver metastasis( n=6, 35.3%). The median survival time after brain metastasis was 7 months and the 1-year cumulative survival rate 29.4%.The median survival time post-LT was 14 months and the 1-year cumulative survival rate 64.7%.Among 7 patients with a resection of brain metastasis, two deaths at Month 1 post-operation were due to cerebral hemorrhage.The longest survival time was 214 months and the median survival time 9 months. Conclusions:The prognosis of brain metastasis post-LT remains poor.However, early detection and reasonable treatment can prolong patient survival time and even achieve long-term survival.Most brain metastases are accompanied by lung metastases.And the finding of lung metastatic tumor hints at a presence of intracranial lesions.
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Objective:To establish the patient derived xenograft (PDX) model of liver malignant tumor, analyze the related factors affecting the carcinogenesis of PDX model, and analyze the differences of biological characteristics between the primary tumor and PDX model.Methods:Fresh liver malignant tumor tissue samples were collected from the patients who received the surgery from the Tianjin First Central Hospital and the samples were inoculated subcutaneously into BALB/c-nu mice. The correlations between clinicopathological information and tumor formation rate were analyzed, and the pathological morphology and specific protein expression of PDX model and primary tumor were compared.Results:Thirty-three PDX models were successfully established from 63 cases of liver malignant tumors. The overall tumor formation rate was 52.4% (33/63), including 46.3% (25/54) of primary liver cancer and 88.9% (8/9) of liver metastasis. The main factors affecting the tumor formation rate were tumor pathological type, distant metastasis and TNM stage (all P<0.05). The pathological morphology and specific protein expression of PDX model and primary tumor were similar. Conclusion:The PDX model of liver malignant tumor was successfully constructed, and the tumor formation rate was high, and can maintain the biological characteristics of the primary tumor.
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In recent years, chimeric antigen receptor-modified T-cell (CAR-T) immunotherapy, as a new idea of tumor immunotherapy, has been proved to be effective in hematological diseases. More and more studies have been focusing on this field. At present, some progress have been made in the treatment of hepatocellular carcinoma with CAR-T, but some problems such as solid tumor inherent barrier, tumor microenvironment, immune escape and specific tumor associated antigens still need to be further figure out. Nevertheless, CAR-T immunotherapy will provide a more cutting-edge treatment for hepatocellular carcinoma immunotherapy. In addition, the combination of CAR-T and other methods may also be the direction to be explored in the next step.
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World Society of Emergency Surgery (WSES), in conjunction with Surgical Infection Society Europe (SIS-E), World Surgical Infection Society (WSIS), American Association for the Surgery of Trauma (AAST), and Global Alliance for Infection in Surgery (GAIS) developed guideline about the management of acute abdomen in immunocompromised patients, which was published in the World Journal of Emergency Surgery (WJES) on August 9, 2021. The guidelines elaborate on the definition, classification, diagnosis and treatment of immunocompromised patients. In addition, based on evidence-based medicine, it provides guidance and suggestion on the management of specific acute abdominal infections in immunocompromised patients, common acute abdominal infections in transplanted patients, patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), as well as perioperative steroid management. An interpretation of the guideline was performed to accomplish a better understanding the current status and recommendations for the management of acute abdominal conditions in immunocompromised patients, and to make forward suggestions on its limitations.
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Objective:To explore the clinical efficacy ofendoscopic retrograde cholangiopancreatography (ERCP) plus percutaneous transhepatic cholangiodrainage (PTCD) of biliary reunion in the treatment of biliary occlusion after liver transplantation.Methods:From May 2018 to August 2019, clinical data were retrospectively analyzed for 9 patients with biliary tract occlusion after an initial liver transplantation. All of them underwent biliary reunion. An endoscopist performed ERCP while an interventional physician completed PTCD with bilateral guide wire under the same anesthetic period so that bilateral guide wire completed a reunion at biliary occlusion for re-opening biliary tract or establishing a new bile duct outflow path. Postoperative follow-ups were performed for observing the treatment outcomes and various factors of biliary stricture factors analyzed.Results:All of them received PTCD or T-tube sinus angiography and interventional treatment. The diagnosis of complete biliary occlusion was definite. After treatment, 7 cases of biliary tract reunion were successful. During operation, three reunion types of guide wire biliary, intestinal cavity and intra-abdominal cavity were employed. Two failed cases received continuous PTCD drainage after operation. The influencing factors of biliary tract stenosis were retrospectively analyzed after operation. Among them, there were non-anastomotic stenosis ( n=2), biliary leakage ( n=2) and anastomotic stenosis and long tortuous biliary tract ( n=5). Conclusions:Rapid, mini-invasive and safe, ERCP plus PTCD biliary tract reunion may be employed as a first choice for biliary occlusion after liver transplantation.
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Objective:To Eveluate the safty and clinical efficacy of combined laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation in the treatment of solid pseudopapillary neoplasm.Methods:A 22 years old solid pseudopapillary neoplasm female patient who underwent distal pancreatectomy and an autologous islet transplantation at Tianjin First Central Hospital, clinical date for 6 months follow up was collected and analyzed.Results:The patient was well recovered after surgery, and during the post-operative follow up, the fasting blood glucose was 5.72 mmol/L, HbA1c was 6.1%, remained insulin independent, the liver function was kept well.Conclusions:Combined Laparoscopic spleen-preserving distal pancreatectomy and autologous islet transplantation can effectively prevent diabetes after distal pancreatectomy.
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With the development and marketing of a variety of new anti-tumor drugs, it the patients with liver cancer were benefited but it also raised a series of new problems. How to develop individualized therapeutic plans for the patients with liver cancer has always been bothering the clinicians. Patient-derived xenograft model retains the histological characteristics, molecular diversity and microenficity of human-derived tumors, and it can help conduct in vitro experiments, which can solve the above problems to a certain extent. This article summarizes the research progress of the application of patient-derived xenograft models on the diagnosis and treatment of primary liver cancer.
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Mixed reality, as a new virtual simulation technology, has been initially applied in the field of surgery. In hepatectomy for primary liver cancer, mixed reality technology has its unique advantages in formulating and evaluating surgical plans before surgery, precise real-time navigation during surgery, and virtual liver teaching, making liver resections more accurate and personalized. This article summarizes the relevant literature at home and abroad in recent years, summarizes the research progress of mixed reality technology in assisted liver resection for primary liver cancer, and discusses its application potential and limitations.
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Liver disease-associated sarcopenia is a type of secondary sarcopenia, which is a common muscle abnormality in patients with liver cirrhosis and is often ignored by doctors. Patients with chronic liver disease often have reduced appetite, insufficient protein intake, indigestion caused by portal hypertension, and high metabolism, which accelerate the wasting of skeletal muscle. At present, sarcopenia is recognized as a risk factor which is closely related with postoperative complications and morbidity in liver surgery, and also affects the quality of life of patients with liver disease. This article reviews the current diagnosis and treatment options of sarcopenia and the impact of sarcopenia on the prognosis of liver disease, thus to provide references in clinical practice.
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Both diabetes and hepatocellular carcinoma are important global health issues. A large number of studies have confirmed that diabetes and hepatocellular carcinoma are inseparable. The main reasons include the imbalance of insulin-like growth factor system caused by insulin resistance, increased reactive oxygen species and disorder of adipokines. Hepatitis C virus infection may also cause diabetes. This article reviewed the common pathogenesis and related pathways of the two diseases, and provided therapeutic options for the diseases.
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Combined hepatocellular-cholangiocarcinoma is a rare and aggressive primary liver malignant tumor with significant histological and biological heterogeneity. It has worse survival than either hepatocellular carcinoma or cholangiocarcinoma and because it’s difficultly to be diagnosed. Understanding the genetic and molecular phenotypes of combined hepatocellular-cholangiocarcinoma will help us to identify the pathogenesis and develop new treatment strategies. This article reviewed the recent research progress on the diagnosis and treatment of combined hepatocellular-cholangiocarcinoma, and explored its characteristics that are different from hepatocellular carcinoma and intrahepatic cholangiocarcinoma in pathology, genetics, clinical manifestations, diagnosis, and treatment, and looks forward to its future research.
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Objective:To explore the independent risk factors of preoperative CT findings affecting the overall survival of patients with clear cell renal cell carcinoma (ccRCC) and to draw a nomogram.Methods:The retrospective study was performed on 238 patients with ccRCC who underwent preoperative CT scan and were pathologically confirmed in First Affiliated Hospital of Air Force Medical University from October 2011 to December 2015. CT findings of each patient were evaluated by two radiologists, and general information, renal function examination, and World Health Organization/International Society for Urology and Pathology (WHO/ISUP) grading were collected. The Kaplan-Meier survival curve was plotted, and survival rates were compared using log-rank test. Cox proportional hazard regression was used for univariate and multivariate analysis, and the nomogram was drawn according to the results of multivariate analysis, and the C-index was calculated after internal validation by Bootstrap 1000.Results:After 3-74 months of follow-up for 238 patients, 32 cases were in the death group and 206 cases were in the censored group. The tumor diameter of the death group [(65.70±27.29) mm] was larger than that of the censored group [(46.25±26.16) mm], with a statistically significant difference ( t=-3.889, P<0.001). The incidence rate of tumor necrosis ( χ2=45.716, P<0.001), regional lymph node enlargement ( χ2=43.342, P<0.001) and perirenal fat invasion ( χ2=19.324, P<0.001) in the death group were higher than those in the censored group. Survival rates were different in patients with different tumor diameter of ccRCC, with a statistically significant difference ( χ2=17.108, P<0.001). The survival rate of patients with tumor necrosis was lower than those without necrosis ( χ2=48.195, P<0.001). The survival rate of patients with regional lymph node enlargement was lower than those without regional lymph node enlargement ( χ2=47.232, P<0.001). The survival rate of patients with perirenal fat invasion was lower than those without perirenal fat invasion ( χ2=19.964, P<0.001). Survival rates were also different in ccRCC patients with different WHO/ISUP grades, with a statistically significant difference ( χ2=27.765, P<0.001). In Cox multivariate analysis, tumor diameter ( HR=2.90, 95% CI: 1.37-6.14, P=0.006), necrosis ( HR=8.88, 95% CI: 3.33-23.69, P<0.001) and regional lymph node enlargement ( HR=4.48, 95% CI: 2.04-9.86, P<0.001) in CT findings were independent risk factors for death in patients with ccRCC. The C-index of nomogram was 0.870. Conclusion:Preoperative CT findings are correlated with survival rate of patients with ccRCC, in which tumor diameter, tumor necrosis and regional lymph node enlargement are independent risk factors for death, and the nomograms has high accuracy.
