超声内镜引导肝脏穿刺活检术（endoscopic ultrasound-guided liver biopsy，EUS-LB）是利用超声内镜细针穿刺活检技术对肝脏穿刺活检，获取组织条用于病理诊断的技术。本文阐述了EUS-LB的发展历史、技术优势和技术要点，并与传统肝脏穿刺方法做了对比，期望推动此项技术在国内的开展。

Objective:To investigate the clinical characteristics of de novo malignancies (DNMs) after liver transplantation (LT) and to study the clinical management strategies.Methods:Adult LT recipients who were regularly followed-up in the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2005 to April 2021 were enrolled in this study. The clinical characteristics of DNMs were retrospectively analyzed. Of 601 LT recipients, there were 105 females and 496 males, aged (51.4±9.6) years old. They were divided into the DNMs group ( n=26) and the non-DNMs group ( n=575) according to whether there were DNMs on followed-up. Clinical data including age, sex, basic diseases before LT and operation time were collected. These patients were follow-up in outpatient clinics. Results:Twenty-six patients were diagnosed to develop DNMs after LT, but there were 28 DNMs (of which 2 patients were diagnosed to have DNMs twice). The incidence of DNMs after LT was 4.3% (26/601), the median time from LT to DNMs was 42 (20, 70) months, and the cumulative incidence rates of DNMs were 0.5%, 2.0%, 6.3%, 21.0% and 34.5% at 1, 3, 5, 10 and 15 years after LT, respectively. Among the 28 DNMs, digestive system tumors were most common, with 17 lesions (60.7%), followed by 3 lesions (11.1%) of lung cancer, 2 lesions (7.4%) of lymphoproliferative diseases, and 1 lesion (3.7%) of cervical cancer, thyroid cancer, soft palate cancer, eyelid cancer, laryngeal cancer, and prostate cancer. The follow-up time of 55.9 (36.6, 102.5) months in the DNMs group after LT was longer than the 33.4 (18.5, 58.9) months in the non-DNMs group ( P<0.001). The 1, 5, and 10 year survival rates of patients with DNMs after LT were 96.3%, 83.5%, and 49.8%, respectively. The 1, 5, and 10 year survival rates of patients with non-DNMs after LT were 94.5%, 77.7%, and 75.4%, respectively. There was no significant difference in the cumulative survival rates between the two groups (log rank=0.402, P=0.526). Conclusion:The incidence of DNMs in LT recipients was 4.3%. The majority of them were digestive system tumors. Early diagnosis and treatment of DNMs significantly improved the prognosis and quality of life of these patients.

Objective:To explore the clinical applications and therapeutic outcomes of immune checkpoint inhibitors(ICIs)on liver transplantation(LT)recipients after tumor development.Methods:Eight databases including PubMed, China National Knowledge Infrastructure, Wanfang Data, CQVIP, PubMed, EMBASE, Web of Science and Google scholar were accessed for searching the relevant literature articles in both Chinese and English from the establishment of databases to December 31, 2021. Disease response, adverse reactions and prognoses of patients with malignant tumors after LT and receiving ICIs were analyzed.Results:The patient was diagnosed as chronic rejection plus drug-induced liver injury by liver biopsy. After intermittent treatment with DPMAS plus plasma exchange and immunosuppressants, he finally died of tumor recurrence at 37 months after LT. After screening, a total of 28 articles on the application of ICIs after LT were retrieved. In these articles, there were 47 patients(37 males and 10 females)with a median age of 57(14-71)years and the predominant type of tumor after LT was hepatocellular carcinoma(28/47, 59.6%), followed by malignant melanoma in 11 cases (23.4%), non-small cell lung cancer in 3 cases(6.4%), colorectal cancer, cholangiocarcinoma, squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and post transplant lymphoproliferative disease(PTLD) in 1 case(2.1%). The overall remission rate after ICI treatment was 29.8%(14/47)and the disease progression rate 68.1%(32/47). Among them, 31.9%(15/47)had immune rejection. Case fatality rate was 61.7%(29/47)and median survival time 6.5(0.3-48.0)months.Conclusions:Depending on existing publications, among those LT recipients with malignant tumors treated by ICIs, the rate of graft rejection and patient mortality are higher. ICIs should be carefully considered for LT patients and further researches are required.

目的 分析肝移植受者术后结直肠腺瘤性息肉(CAP)的发生情况及危险因素.方法 选取肝移植受者77例,并选取同期行结肠镜检查的体检者231例,分析结直肠息肉发生情况及病理检查结果.收集肝移植受者的临床资料,并根据CAP的发生情况,将肝移植受者分为CAP组(28例)和非CAP组(49例),分析肝移植术后发生CAP的危险因素.结果 肝移植受者和体检者结直肠息肉的5年累积发生率分别为43％和34％,CAP的5年累积发生率分别为29％和23％,差异均无统计学意义(均为P>0.05).肝移植受者中,除1例因息肉较多未统计外,其余息肉共计65个,部分受者发现多个息肉.5个体积较小者未送病理,有病理结果的共60个,包括炎性息肉25个,CAP 33个(其中8个伴有低级别上皮内瘤变,3个伴有高级别上皮内瘤变),高分化腺癌2个.Cox模型分析提示肝移植受者术后服用环孢素是发生CAP的独立危险因素.结论 肝移植术后CAP发生风险略有增高,服用环孢素是肝移植受者术后发生CAP的独立危险因素,应重视肝移植受者术后结肠镜检查.

本文就肝移植受者幽门螺杆菌(Hp)感染诊治的研究进展做一综述，为提高肝移植的整体诊疗水平，防治术后并发症并改善肝移植受者总体预后提供依据。

Objective:To determine the prevalence of Helicobacter pylori (Hp) infection in orthotopic liver transplantation (LT) recipients, and to study the efficacy and safety of Hp eradication therapy.Methods:13C-urea breath test was carried out between July 2018 and October 2019. There were 104 males and 26 females with an average age of 52.1 year for these LT recipients who were regularly followed-up in the Organ Transplant Center, the Affiliated Hospital of Qingdao University. Propensity scoring was used to match age and gender in a ratio of 1∶3. A healthy group of individuals consisting of 299 males and 91 females, with an average age of 51.8 years, were selected as the control group also in a ratio of 1∶3. All patients underwent 13C-urea breath test to evaluate Hp infection and results of quadruple therapy. Results:The prevalence of Hp infection among the LT recipients was 18.5%(24/130) which was significantly lower than the control group 36.4% (142/390) (χ 2=14.400, P<0.001). Among the recipients who received LT and 13C-urea breath test for less than 1 year, 1-3 years and more than 3 years, the prevalences of Hp infection were 14.3% (6/42), 17.8%(8/45) and 23.3%(10/43), respectively. Although the prevalence of Hp showed a gradually increasing trend, no correlation between Hp infection and duration from LT was observed (χ 2=1.321, P=0.517). Seventeen Hp positive recipients underwent Hp eradication therapy. The success rate of Hp eradication was 100.0%(17/17). Immunosuppressant concentration was monitored regularly in 10 patients. During Hp eradication, the blood concentration of immunosuppressant increased from 1.7 to 3.6 times, and the drug dosage was reduced to one half to one third of what it was before Hp eradication. Seven of these 17 recipients suffered from adverse effects caused by increased levels of blood concentration of immunosuppressants, including headache, hypertension, insomnia and irritability. Normal liver and kidney functions were observed during eradication. Conclusion:In this study, the prevalence of Hp infection among liver transplant recipients was 18.5%. The success rate of Hp eradication was 100% using bismuth-containing quadruple therapy. The dosage of immunosuppressant required to be monitored, and if necessary, adjusted during eradication to reduce adverse side effects.

本综述介绍了免疫检查点抑制剂在肝癌肝移植中的研究进展，总结了近几年国内外对肝癌肝移植术后免疫检查点抑制剂药物应用的临床报道，分别从免疫检查点抑制剂的作用机制、临床应用、发生排斥反应的相关因素及机制等方面做了详细描述，以期为临床管理人员制定肝癌肝移植术后诊疗计划提供参考。

目的 探讨乙型肝炎病毒(hepatitis B virus,HBV)相关肝移植(liver transplantation,LT)后停用乙肝免疫球蛋白(hepatitis B immunoglobulin,HBIG)单用替诺福韦(tenofovir disoproxil fumarate,TDF)预防HBV复发的有效性、安全性及经济性.方法 选取我院HBV相关LT患者,将患者分为TDF单药组和恩替卡韦(entecavir,ETV)联合HBIG用药组,收集患者临床及实验室数据并比较两种用药方案的效果、不良反应及用药花费.结果 截止到2019年6月30日,本研究终纳入单药组10例和联用组28例,分别平均随访13.50个月和13.03个月,单药组1例(10.00％)和联用组2例(7.14％)出现乙肝表面抗原(hepatitis B surface antigen,HBsAg)阳性复发,所有患者术后乙肝DNA(hepatitis B virus DNA,HBV-DNA)始终为阴性,联用组1例(3.57％)死亡,单药组费用明显低于联用组(490元/月比1952.55元/月,P<0.01).结论 与ETV联合HBIG相比,LT后TDF单药预防HBV复发,具有良好的有效性、安全性和经济性.

Objective:To investigate the clinical efficacy and safety of sorafenib sequential regorafenib in the treatment of recurrence of hepatocellular carcinoma after liver transplantation.Methods:The clinical data of 14 patients with hepatocellular carcinoma who had tumor recurrence after liver transplantation and received sorafenib and regorafenib were collected from the Affiliated Hospital of Qingdao University from February 2014 to September 2020. After the clinical diagnosis of recurrence of liver cancer, sorafenib (400 mg/time, twice a day, oral) was added for treatment. When the disease progressed or the adverse events of sorafenib was not tolerated, sequentially treated with regorafenib (160 mg/time, once a day, oral, continuous medication for 21 days, stop medication for 7 days, every 28 days is a cycle) treatment. The medication was supplemented with symptomatic support treatment, followed up regularly, alpha-fetoprotein (AFP), liver function, immunosuppressive blood concentration, ultrasound or CT and other imaging examinations were monitored, and adverse events were recorded.Results:Among the 14 patients who finally met the inclusion criteria, 12 were males and 2 were females; the median age was 56.5 (40.0-65.0) years. The median interval from tumor recurrence after liver transplantation to initiation of sorafenib was 1.0 (0.1-6.4) months. The median treatment time for sorafenib was 2.7 (0.9-9.2) months, and the median time to progression (mTTP) was 4.4 (0.9-14.1) months. The median time between cessation of sorafenib and initiation of regorafenib was 16.5 (1-366) d; the median treatment time of regorafenib was 9.3 (1.3-20.4) months, the mTTP was 2.8 (1.0-9.7) months, and the median overall survival (mOS) was 20.1 (95%CI 0.7-39.5) months. There were no significant differences in AFP and liver function indexes before and after sorafenib treatment (all P>0.05). AFP increased and serum albumin decreased after treatment, with statistical significance (all P<0.05). ALT, AST and total bilirubin changes had no statistical difference (all P>0.05). Adverse events during the treatment of sorafenib and regofinib included: diarrhea (9 cases and 10 cases), fatigue (9 cases and 6 cases), decreased body mass (3 cases and 2 cases), and hand-foot skin reactions (1 case and 2 cases), respectively. Among them, sorafenib treatment was terminated in 2 cases due to severe diarrhea, and the dosage of regogafenib was reduced in 1 case, and the treatment of regogafenib was discontinued in 1 case due to hand and foot skin reaction, respectively. The other patients had adverse reactions and were tolerated after symptomatic treatment. By September 2020, the median follow-up time was 12.4 (5.6-34.2) months, and a total of 7 patients died, all due to tumor progression after liver cancer recurrence. Of the 7 patients who survived, 3 were discontinued due to lung tumor progression, and 4 were continued with regofinib. The mOS was 14.4 (95%CI 3.4-25.4) months for 14 patients who received sorafenib sequential regolfinib, and the 1-year and 2-year cumulative survival rates were 67.7% and 48.4%, respectively.Conclusion:Sorafenib sequential regorafenib for the treatment of tumor recurrence after liver transplantation of hepatocellular carcinoma has good clinical efficacy and safety, but a larger sample size of research support is still needed.

Hepatitis B virus (HBV) reactivation is one of the common problems faced by HBV-related recipients after liver transplantation. Recently, the application of nucleos(t)ide analogues (NAs) has greatly reduced the recurrence rate of HBV after liver transplantation, and long-term medication has also brought many disadvantages, such as drug resistance, kidney damage. Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) are both high genetic barrier NAs, and clinical applications show that they have good efficacy and tolerability, especially NAs monoprophylaxis have a good application prospect against HBV reactivation after liver transplantation. This article reviews the latest application progress of TDF and TAF after liver transplantation.

Objective:To summarize the experience of diagnosing and treating de novo gastric cancer after liver transplantation(LT).Methods:The clinical data were analyzed for 3 LT patients with de novo gastric cancer during follow-ups.Results:The mean diagnostic age was 57(47~67)years, mean time interval between LT and diagnosis of de novo gastric cancer 82(40~122)months and mean follow-up time 23(4~42)months. After surgical resections, 2 survived and another died of recurrence.Conclusions:LT recipients are recommended for regular screening of de novo malignancies. Regular endoscopic screening of gastric tumors contributes to early detection, diagnosis and treatment. It may improve long-term survival outcomes in LT recipients.

肝移植是目前治疗乙型肝炎病毒(HBV)相关终末期肝病最为有效的方法，但肝移植术后出现乙型肝炎复发易损伤移植肝功能，并影响受者的长期存活。尽管乙型肝炎免疫球蛋白(HBIG)和核苷(酸)类似物(NA)的临床应用，可以显著抑制HBV复制并改善受者的长期存活率，而且低剂量HBIG联合NA方案仍然是目前肝移植术后乙型肝炎复发的标准预防方案。然而，近年来，随着高耐药基因屏障NA的出现，肝移植术后NA和(或)短期联合HBIG的单一用药预防方案也取得了良好的临床疗效，本文就肝移植术后单一NA预防乙型肝炎复发的研究进展做一综述。

分析肝移植术后结直肠疾病发病情况。选择2004年3月至2018年2月青岛大学附属医院乙肝肝移植受者32例纳入肝移植组，其中男性27例，女性5例，年龄(57.2±9.8)岁。选择2016年1月至2018年5月青岛大学附属医院行电子结肠镜检查的慢性乙肝患者96例纳入乙肝组，其中男性80例，女性16例，年龄(56.8±9.9)岁；体检正常者96例纳入对照组，其中男性78例，女性18例，年龄(56.4±7.7)岁。肝移植组中结直肠息肉20例(62.5%，20/32)，乙肝组结直肠息肉53例(55.2%，53/96)，对照组结直肠息肉46例(47.9%，46/96)。三组结直肠息肉发生率比较差异无统计学意义(P>0.05)。肝移植术后结直肠息肉发生率偏高，肝移植临床医生应重视肝移植受者术后的常规电子结肠镜检查。

目的 调查乙型肝炎相关性终末期肝病肝移植(以下简称乙肝肝移植)受者上消化道疾病的发生情况,并对其影响因素进行初步探讨.方法 对2006年7月至2018年12月青岛大学附属医院符合入选标准的63例乙肝肝移植受者进行电子胃镜检查.同时,以年龄和性别作为匹配因素,按1:3进行倾向性评分匹配,选取于本院行电子胃镜检查的慢性乙型肝炎患者和健康体检者各189例作为对照.比较3组受者消化系统症状和胃镜检出疾病情况,并进一步分析乙肝肝移植受者上消化道疾病发生的危险因素.结果 乙肝肝移植组受者术后经胃镜检出的上消化道疾病主要包括慢性萎缩性胃炎(36/63,57.1％)、反流性食管炎(13/63,20.6％)及食管静脉曲张和/或胃底静脉曲张(10/63,15.9％).乙肝肝移植受者慢性萎缩性胃炎发生率高于慢性乙型肝炎组和体检组(P均<0.017),幽门螺旋杆菌感染发生率低于慢性乙型肝炎组和体检组(P均<0.017).肝移植受者中,慢性萎缩性胃炎组年龄高于非慢性萎缩性胃炎组,分别为(58±8)岁和(51±7)岁,差异有统计学意义(t=2.232,P<0.05).结论 乙肝肝移植受者术后上消化道疾病发生率高且种类多,其中慢性萎缩性胃炎和反流性食管炎最为常见,应重视肝移植受者术后电子胃镜定期筛查.

目的 探讨我国肝移植(LT)术后新发消化系统恶性肿瘤的情况.方法 检索万方数据、中国知网及维普资讯三大中文数据库中的相关文献.检索时间从各数据库建库至2019年5月9日.中文检索词为“肝移植+术后/新发+恶性肿瘤/癌”.分析我国LT术后新发消化系统恶性肿瘤受者的年龄分布、性别构成、新发肿瘤的诊断时间和累及器官、治疗及预后.结果 经过筛选最终纳入文献16篇,LT后新发消化系统恶性肿瘤47例,男性受者居多;年龄51 (23～65)岁,以中年(45～59岁)最多;术后新发消化系统恶性肿瘤的平均确诊时间为43 (2～156)个月,以术后1～3年内发生的例数最多;结肠和胃是最为常见的肿瘤发生部位;治疗主要以手术联合放射治疗和化学药物治疗居多,但LT术后新发消化系统恶性肿瘤总体预后不佳,病死率高达51％.结论 我国LT术后新发消化系统恶性肿瘤以结肠癌和胃癌为主,新发肿瘤的患者总体预后不佳,应重视术后的监测和预防.

成人肝肾联合移植术后发生水痘(varicella，chickenpox)感染的报道比较少见，本文报道了1例肝肾联合移植受者术后水痘感染并成功诊治的病例。该受者于肝肾联合移植术后39个月出现全身皮疹，以躯干为著，头面部、四肢散在，含红色基底水泡，丘疹、水泡及结痂同时存在，伴咽痛及发热，外周血VZV-DNA定性(PCR法)示阳性。经给予静脉应用阿昔洛韦(0.25 g，每日2次)、输注人免疫球蛋白，同时调整免疫抑制剂及对症支持治疗后，皮疹消退，好转出院，7个月后复查VZV-DNA结果示阴性。对于肝肾联合移植术后水痘受者，应给予及时应用阿昔洛韦抗病毒、输注人免疫球蛋白等治疗及调整免疫抑制剂用量，早期诊断及早期治疗，可取得良好疗效。

本文报道了1例累及齿状线的直肠侧向发育型肿瘤的隧道法内镜黏膜下剥离术治疗情况,并就术前准备、术中注意事项、手术策略、术后并发症的发生和处理方面进行了讨论.

As the best choice for end-stage organ diseases,solid organ transplantation (SOT) has been applied more and more in clinical practice for years.With the improvement of surgical techniques,the application of new immunosuppressive agents and the improvement of postoperative management,the survival rate and quality of life of SOT recipients have been continuously improved.However,studies have found that the complications of lower digestive tract after SOT increased gradually with the time goes on,including diverticulitis,colon polyps and colorectal cancer,et al,which have influenced SOT recipients' survival time and their quality of life significantly.There are few studies in this aspect published in China,and most of which are published as case reports.The aim of this article is to review the epidemiology and impact factors of lower digestive tract diseases among the SOT recipients,providing data support for clinical prevention and early intervention in order to improve the prognosis in these recipients ultimately.

出血、术后电凝综合征、穿孔和腹部不适是内镜下结直肠息肉切除术的主要并发症,其中又以出血最为常见,对医院及患者均是较大的负担.本文对结直肠息肉切除后并发出血的研究进展作一综述,旨在加深对此种并发症的认识,以便指导临床工作.

随着肝移植技术在终末期肝病患者中的广泛应用,术后长期存活的受者数量日益增多,随之而来的新发恶性肿瘤逐渐受到广泛关注[1-3]。然而,既往国内研究大多局限于单个器官移植中心的病例报道[4-9],尚缺乏大规模、多中心的研究报道,无法对我国肝移植受者术后新发恶性肿瘤情况进行总体描述及分析。本研究通过检索既往国内相关文献,统计肝移植术后新发恶性肿瘤受者的临床资料,旨在提高我国肝移植医务人员对术后新发恶性肿瘤的认识。