Aims: Immune checkpoint inhibitors (ICIs) have been recognized as an effective treatment for advanced gastric or gastroesophageal junction cancer (AG/GEJC). However, the safety of ICIs in patients has not been established. We aimed to systematically assess the risk of all common treatment-related adverse events (TRAEs) in immunotherapy of AG/GEJC.Methods: A systematic search of randomized controlled trials (RCTs) published until May 2022 was performed using PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. And a meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Results: A total of nine RCTs, including 2918 patients, met the eligibility criteria. The pooled overall incidences of all grade TRAEs, grade 3 or higher TRAEs and treatment-related death were 54.5% (95% confidence interval [CI]: 48.7%-60.2%, I2=75.55%), 12.8% (95% CI: 10.2%-15.7%, I2=51.61%) and 0.11% (95% CI: 0.00%-0.51%, I2=1.63%). Subgroup analyses showed that CTLA-4 inhibitors had a higher risk of any type of TRAEs, when compared with PD-1 and PD-L1 inhibitors. Meta-regression showed significant correlation between all grade TRAEs and proportion of female. Fatigue and diarrhoea were involved in common TRAEs.

Aims: To evaluate risk of adverse events (AEs) in advanced hepatocellular carcinoma (AHCC) with immune checkpoint therapy in this setting. Methods: A systematic search of original articles published until November 2019 was performed using PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. And a meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: A total of eight studies, including 597 patients, met the eligibility criteria. The median cohort size of patients was 75 (range: 18-267). The pooled incidence rates of grade >= 3 AEs and fatal adverse events (FAEs) at last follow-up were 20.87 per 100 person-years (95% CI: 11.00-39.59, I-2 = 91.0%) and 4.98 per 100 person-years (95% CI: 1.83-13.56, I-2 = 82.8%). Subgroup analyses showed that pembrolizumab had a lower risk of grade >= 3 AEs, but a higher risk of FAEs, when compared with nivolumab and tremelimumab. Meta-regression showed significant correlation between grade >= 3 AEs rate and proportion of Child-Pugh A stage. Fatigue (16.9%), adrenal insufficiency (8.5%) and rash (6.8%) were involved in common non-laboratory AEs. Conclusions: Immune checkpoint therapy significantly increases the risk of AEs in AHCC patients. And the risk of grade >= 3 AEs is associated with Child-Pugh classification. Future retrospective analyses and prospective cohort studies are warranted to evaluate the safety of immune checkpoint therapy in AHCC. (C) 2020 Published by Elsevier Masson SAS.

• What is already known on this subject? Hepatic inflammatory angiomyolipoma is a rare and easily misdiagnosed disease, lacking systematic summaries. • What are the new findings? Analysis of all reported cases provides thorough information regarding clinical manifestations, diagnoses, treatments, and prognoses. • How might it impact clinical practice in the foreseeable future? Better understanding of this disease will reduce misdiagnosis and guide treatment.

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.

肝脏是各种恶性肿瘤发生转移的主要靶器官,肝癌易复发和转移,预后效果差[1].对于转移性肝癌,手术切除、化疗、放疗、介入栓塞治疗、局部治疗、靶向药物等一直扮演着重要的角色,但对于不可切除的转移性肝癌,常规治疗方法往往效果不佳.而肝移植提供了彻底治愈的可能,但由于早期实践过程中适应证把控不严,一些转移性肝癌病例行肝移植效果不理想,导致转移性肝癌一度成为肝移植的绝对或相对禁忌证.近年来,随着各种转移性肝癌治疗方案的优化,尤其是多学科综合诊疗模式的推动,肝移植在部分类型的转移性肝癌治疗中的作用重新得到认可或重视,目前主要集中在神经内分泌肿瘤(neuroendocrine neoplasms,NEN)和结直肠癌两方面,其他来源的转移性肝癌肝移植仅见个案报道.

目的 探讨过继性回输调节性T细胞(Treg)对同种胰岛移植术后胰岛功能恢复及移植物存活时间的影响.方法 以C57BL/6小鼠为受体建立糖尿病模型,以Balb/c小鼠为供体进行肾包膜下同种小鼠胰岛移植.根据处理方法不同将受体小鼠分为3组:Treg实验组(Treg组,术前1 d经尾静脉注射1×106个Treg细胞)、阳性对照组[西罗莫司(SRL)组,术前1 d开始给予300μg/(kg·d)SRL灌胃]和空白对照组(对照组,术前1 d开始每日给予等体积生理盐水灌胃),每组3只.采用酶联免疫吸附试验(ELISA)检测小鼠术后14 d内血糖、C肽变化情况;通过活体成像技术动态监测小鼠移植物术后14 d内存活情况.结果 与移植术前比较,术后3 d各组小鼠血糖水平均显著降低(均为P<0.001).术后1 d各组小鼠C肽水平均出现不同程度的爆发性回升,术后3 d各组小鼠C肽水平较术前明显升高(均为P<0.001).在术后14 d观察期结束时,与对照组比较,SRL组与Treg组C肽水平仍相对较高[(427±50)、(833±57)pmol/L];而两组的血糖水平[(14.5±0.5)、12.1±0.6)mmol/L]均显著低于对照组(均为P<0.001).与SRL组比较,Treg组C肽爆发性释放量更低,下降趋势明显更加平缓,观察期结束时C肽水平较高(均为P<0.001).术后14 d对照组的移植物几乎完全凋亡,SRL组有>50％ 的移植物存活,Treg组有>80％ 的移植物存活.结论 过继性回输Treg能有效保护胰岛移植物,延长移植物存活时间,维持移植小鼠血糖以及C肽的正常水平.

Aims: Islet autotransplantation (IAT), in conjunction with total pancreatectomy (TP), is used to relieve pain in patients with chronic pancreatitis (CP), while reducing the incidence of brittle diabetes. We aimed to evaluate the efficacy and safety of IAT after TP (TPIAT) in this setting. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials since 1977. Data were extracted from published papers. Random-effects meta-analysis and meta-regression models were built to assess the outcomes and effect of different factors. Subgroup and sensitivity analyses were conducted to examine the between study heterogeneity, which was assessed using Cochrane's Q and I2 statistic. Results: A total of 17 studies, including 1024 patients, met the eligibility criteria. The median cohort size was 21 patients (range: 5-409). The pooled incidence rates of insulin independence, narcotic independence and mortality at last follow-up were 11.47 per 100 patient-years (95% CI: 6.79-21.60, I-2 = 91.0%), 18.11 per 100 patient-years (95% CI: 5.29-62.04, I-2 = 98.8%) and 2.88 per 100 patient-years (95% CI: 1.75-4.74, I-2 = 46.8%), respectively. However, the heterogeneity level of our results was high, which was due to differences in research methods and definitions of outcomes between studies. Therefore, our results should be interpreted with caution. Conclusions: TPIAT can effectively relieve pain and reduce the risk of surgical diabetes with no increase in mortality or morbidity. Prospective, randomized, clinical trials are required to further evaluate selection of patients and the timing of TPIAT. (C) 2019 Elsevier Masson SAS. All rights reserved.

目的 研究同种异体胰岛移植治疗1型糖尿病与肾移植后糖尿病的临床效果.方法 对27位(其中5位行二次移植术)1型糖尿病患者或糖尿病肾病肾移植后患者施行同种异体胰岛移植.胰腺供体来自于公民死亡捐献,经消化、纯化后获得纯度≥50％、活力≥80％的胰岛,重悬于CMRL1066液体后,采用经皮肝门静脉穿刺,将胰岛悬液重力输注与肝内.术前采用巴利昔单抗诱导,术后采用口服他克莫司+吗替麦考酚酯诱导免疫耐受.定期检测移植受者血糖、C肽和糖化血红蛋白水平等指标.结果 移植后平均随访7.6个月.随访期内,其中16例完全停用胰岛素,9例胰岛素用量减少50％～90％,2例效果不明显,术后C肽无显著增加.25例有效移植受者空腹血糖从移植前的(8.8±13.7)mmol/L降至(5.1±4.3)mmol/L,控制更加平稳;糖化血红蛋白A1从(7.63±4.53)％降至(5.30±1.43)％.平均C肽增量为1.34nmol/L.常见并发症为术后短暂的恶心、呕吐和转氨酶上升,无严重并发症发生.结论 经肝门静脉胰岛移植是治疗1型糖尿病与肾移植后糖尿病的有效手段,短期临床疗效较好,远期疗效尚需进一步观察.

To the Editor:Inflammation-cancer transformation and metabolomics are hot topics in hepatocellular carcinoma （HCC）. Cancer-related inflammation and anti-cancer immunity co-exist in cancer progression and

Objective To explore the effects of Qa-1 and PD-L1 loaded artificial liposomal treatment in allograft rejection and its outcomes .Methods The extracellular domains of Qa-1 and PD-L1 were loaded on liposome surface by streptavidin-biotin system . Mixed lymphocyte reaction (MLR) was performed for measuring Qa-1/PD-L1 liposome biological function .Then liposome was co-transplanted with allo-islets via portal vein .The levels of blood glucose and C-peptide were detected daily after transplantation .Also hepatic lymphocytes after transplantation were isolated for determining the proportion of activated cells and signaling pathway changes .Results Artificial liposome could be easily loaded with biotinylated peptide and its diameter was between 50 to 500 nm . Qa-1/PD-L1 liposome could significantly suppress lymphocyte proliferation , activation and secretion of IFN-γ in MLR by an activation of SHP1/2 and an inhibition of Syk pathway .Qa-1/ PD-L1 liposomes could suppress the activation of hepatic lymphocytes in vivo by activating SHP1/2 ,protecting islet allografts and maintaining a normal level of blood glucose in recipients .Conclusions Qa-1/PD-L1 loaded liposome can effectively suppress allograft rejection and improve the outcomes of islet transplantation .

Objective To study liver transplantation in the treatment of alcoholic liver disease (ALD).Methods A retrospective study was conducted on 40 patients with ALD who underwent liver transplantation in the Changzheng Hospital of the Second Military Medical University from April 2005 to June 2017.The data were expressed as mean ± standard deviation ((-x) ±s) in populations with a normal distribution,and as median (min～max) in populations with an abnormal distribution.The survival rate was analyzed by life tables,and the Cox regression analysis was used for multivariate analysis.Results All patients were followed up until August 31,2017.The follow-up time was 2 ～ 4518 days,with a median of 997 days.Among the 40 patients,8 had already died (3 died of multiple organ failure,2 of biliary complications,1 of liver failure,1 of sepsis and 1 of recurrence of hepatocellular carcinoma (HCC).The 1-year survival rate was 81.0％,and the 5-year survival rate was 77.0％.Four of 40 patients developed tumor recurrence.The initial recurrence time was 189 ～ 337 days (median 236.5).The recurrence sites included the liver,colon combined with lungs,lungs,and lumbar vertebrae.Six of 40 (15.0％) patients had relapse in alcoholism.Multivariate analysis showed that age was a prognostic factor (RR =1.109,P ＜0.05).Years of drinking,daily amount of alcohol intake,abstinence,a previous history of upper gastrointestinal bleeding,a previous history of splenectomy,co-existing hepatocellular carcinoma,preoperative MELD score,preoperative Child-Pugh score,total operation time,anhepatic period,cold ischemia time,amount of intraoperative bleeding,postoperative alcoholism relapse,tumor recurrence or new onset of tumor were not significantly correlated with the postoperative survival rate (P＞0.05).Conclusions ALD patients were mostly 40 ～ 60 years old.Age was an independent factor affecting survival.The younger the patient,the better the prognosis.Other factors were of no prognostic significance.

Objective To summarize our experience in the diagnosis and treatment of hepatic epithelioid angiomyolipoma (HEAML),with the aim to reduce the future misdiagnosis rate.Methods The PubMed,Medline,China Science Periodical Database (CSPD),and VIP Databases were searched from January 2000 to March 2018 on all reports on HEAML.Results There were 409 cases of HEAML in 97 reports.The ratio of men to women was 1∶4.84.The age ranged from 12 to 80 years and the median age was 44 years.61.9％ of patients (205/331) were asymptomatic,while 34.7％ (115/331) had upper or right upper quadrant abdominal discomfort.Some patients presented with abdominal mass,gastrointestinal reaction,low grade fever or weight loss.The clinical symptoms in 78 patients were not mentioned in the reports.The misdiagnostic rate of HEAML was as high as 40.3％ (165/409).The imaging findings of HEAML were nonspecific.Ultrasound,CT and MRI scan usually showed contrast enhancement in the arterial phase.Most lesions were accompanied by central vessels with early drainage veins.The enhanced scans showed varied characteristics.The ratios of fast wash-in and fast wash-out,to fast wash-in and slow wash-out,and to delayed enhancement were roughly 4∶ 5∶ 1.A definitive diagnosis of HEAML is based on the pathological findings of epithelioid cells in the lesions and the expressions of HMB45,SMA,Melan-A and Actin on immunohistochemical staining.HEAML had a relatively low malignant rate of 3.9％.Surgical resection was the main treatment for HEAML.Conclusion HEAML was a rare and easily misdiagnosed disease.,which could be diagnosed by taking into account the clinical course,imaging,pathological and immunohistochemical findings.HEAML.

To the Editor:Primary hepatic squamous cell carcinoma（PHSCC）is a rare and easily misdiagnosed disease.We reported a PHSCC case with abdominal incision metastasis after hepatectomy,and reviewed the clinical course,imaging,pathology and immunohistochemical findings.Our case may provide a better understanding of PHSCC.