肾移植术后恶性肿瘤

目的 总结我们中心肾移植病人恶性肿瘤的发病情况,探讨预防及治疗措施。方法 回顾分析我们中心从1979年12月-2001年5月1037例临床资料。结果 在1037例肾移植病人中发现15例恶性肿瘤,发病率为1.4％。其中最多的是肝癌(6/15),其次是卡帕氏肉瘤(4/15),再其次是肺癌(2/15)。结论 肾移植术后病人恶性肿瘤的发病率较一般人群高;治疗的效果取决于早期发现肿瘤并及早施行手术;同时,用最小的免疫抑制剂维持移植肾的正常功能。     

The use of local allograft irradiation following renal transplantation

Over a 10 year period, 67 recipients of 71 renal allografts received graft irradiation following the diagnosis of rejection. The majority of kidneys were treated with a total dose of 600 rad, 150 rad per fraction, in 4 daily fractions. Fifty-three kidneys were irradiated following the failure of standard systemic immunosuppression and maximally tolerated antirejection measures (pulse high dose steroids, Actinomycin, ATG) to reverse an episode of acute rejection. Seven of these patients (13%) had greater than a 50% improvement in serum creatinine (Cr) 1 week following completion of the irradiation. Twenty-two (42%) of these allografts were noted to have stable (i.e. no deterioration) or improved function 1 month following the treatment with irradiation. Eleven (21%) of these allografts maintained function 1 year following transplantation. There were 10 patients whose allografts were irradiated because of renal dysfunction in a clinical setting which did not permit the administration of further immunosuppression, i.e., infection or hematologic dyscrasias. Three of these patients (30%) had greater than a 50% improvement in serum Cr 1 week following completion of the irradiation. Nine (90%) of these allografts had stable or improved function 1 month following the treatment with irradiation. Biopsies were obtained of 41 allografts. Of the 24 renal allografts with predominantly cellular rejection, 10 (42%) had the process reversed or stabilized at 1 month following irradiation. Five (21%) of these allografts were functioning at 1 year following irradiation. Rejection was reversed or stabilized in 6 of 17 (35%) allografts at 1 month when the histologic features of renal biopsy suggested predominantly vascular rejection. One (6%) of these allografts was functioning at 1 year following transplantation. Local graft irradiation has helped maintain a limited number of allografts in patients whose rejection has failed to respond to systemic immunosuppression. Irradiation may also benefit patients with ongoing rejection in whom further systemic immunosuppression is contra-indicated.     

肾移植后卡波西肉瘤临床病理观察

背景与目的：肾移植者所发生的卡波西肉瘤是由长期免疫抑制性治疗所引起，而确切的肿瘤发生过程至今尚未阐明。病理组织研究发现此类肉瘤与其他几种类型并无区别。新疆的地方性卡波西肉瘤较为常见，尤其是维族人群，可能是中国患病率最高的。为了解其可能的病因发病学机制以及与其他类型卡波西肉瘤的关系，我们对3例肾移植后卡波西肉瘤进行组织病理学与免疫组化研究。方法：取自本院3例（2例维吾尔族及1例汉族患者）肾移植相关型卡波西肉瘤标本，经存档蜡块切片分别行HE染色与CD34、第Ⅷ因子、Vimentin、Actin（平滑肌）及纤连蛋白（FN）的S—P法免疫组织化学染色检测。结果：所有标本的组织切片其病理组织学结构和细胞特点与典型的卡波西肉瘤无明显不同。其早期病变非常局限，只有少数不规则扩张的血管裂隙和聚集肥胖（上皮样）细胞；中期，病变范围变宽，并出现梭形细胞增生，呈束状，编织状，血管受压，管腔呈裂隙状，但病灶周边的增生血管仍扩张充血；晚期，增生的梭形细胞异型性明显，核分裂象增多。免疫组化：肿瘤细胞CD34，血管内皮细胞第Ⅷ因子有较强阳性染色反应，而Vimentin阳性较弱，Actin（平滑肌）与FN呈阴性反应。结论：肾移植相关型卡波西肉瘤的病理组织学与免疫组化特性与其他类型的卡波西肉瘤并无明显本质性差别，可能反映了这类病变具有相似的病因发病学变化。而明显的种族与地域患病率不同，说明基因背景在卡波西肉瘤的发生发展过程中可能起关键性作用。     

Central nervous system aspergillus infection complicating renal transplantation

A case of catastrophic intracerebral haemorrhage secondary to aspergillus infection in an immunocompromised renal transplant patient is presented. The pathological features and related images are described and the radiology of CNS aspergillus infection is reviewed.     

Management of hepatocellular carcinoma in renal transplant recipients

BACKGROUND AND OBJECTIVE: In Hong Kong where hepatitis B virus (HBV) infection is endemic, hepatocellular carcinoma (HCC) accounts for 20% of all malignant transformations in renal transplant recipients. The aim of the present study was to review the management and outcome of HCC in renal transplant recipients at a specialized surgical center. METHOD: A retrospective analysis on the data collected prospectively in a tertiary referral center. RESULTS: From January 1991 to December 2002, five renal transplant recipients were diagnosed to have primary HCC and received treatment in our center. There were four men and one woman with a median age of 47 (range, 38-68) years. Four of them had cadaveric renal transplantation whereas one had live donor transplantation. All of them were HBV carriers. The median tumor size was 3.5 cm (range, 1.8-8 cm). All tumors, except one, were diagnosed in sub-clinical stage by surveillance serum alpha-fetoprotein assay and percutaneous ultrasonography. Four patients were treated with surgical resection and one received transarterial oily chemoembolization (TOCE) as their primary treatments. There was one peri-operative death and the remaining three surgically treated patients were alive 4, 62, and 64 months after the resection. One patient developed recurrence 18 months after curative resection and was treated with TOCE. The patient with unresectable disease was alive for 50 months after the initial diagnosis. The surgical resection and overall survival rates of these patients were better than the published results. CONCLUSION: Early detection with regular serum alpha-fetoprotein assay and ultrasonographic study, vigilant care in the peri-operative period, long-term follow-up for detection and treatment of recurrence, as well as close collaboration between renal physicians and liver surgeons may improve the outcome of treatment of HCC in renal transplant recipients.     

Risk factors for malignancy in Japanese renal transplant recipients

BACKGROUND: Among recipients of renal transplants, the incidences of renal cancer and gastrointestinal cancer are higher and that of skin cancer is much lower in Japan than in Europe and North America. METHODS: The risk factors for the development of malignant tumors were examined in Japanese recipients of renal transplants. A total of 556 patients underwent renal transplantation at the Department of Urology, Osaka University Faculty of Medicine between March 1, 1965, and April 31, 2004. Of these patients, 366 were retrospectively studied in whom risk factors potentially related to the development of malignancy could be evaluated on the basis of medical records. The incidence of malignancy, survival rate, and risk factors for malignancy were examined. RESULTS: The overall incidence of malignancy was 6.8% (25/366 patients). Six of the 25 patients with malignancy died of cancer, but there was no correlation between the occurrence of malignancy and the survival rate (P = .8058, log-rank test). A Cox proportional-hazards model identified treatment with tacrolimus (hazard ratio [HR] = 4.376; 95% confidence interval [CI]: 1.647-11.627; P = .0031) and age at transplantation (HR = 1.562; 95% CI: 1.089-2.240; P = .0155) as risk factors for malignancy. CONCLUSIONS: The results of multivariate analysis suggested that age at transplantation and the use of tacrolimus were independent risk factors for the development of malignancy in recipients of renal transplants.     

Colon and rectal cancer after renal transplantation

Increased cancer risk after renal transplantation is believed to be a consequence of continuous immunosuppression. However, the risk of colorectal cancer (CRC) after renal transplantation is controversial and has received limited study. Accumulating evidence suggests that colon and rectal cancers have different characteristics in the post-renal transplant patient (PRTP) and should be evaluated separately in transplant registries. This article reviews the current literature evaluating CRC diagnosed in PRTPs, focusing on clinical characteristics and treatment outcomes.     

肾移植后直肠癌的诊治及预后分析

 【摘要】　目的　探讨肾移植后结直肠癌的诊断与治疗,并对其预后进行分析。方法　1035例次的肾移植患者中,4例患直肠癌。3例行全直肠系膜切除（TME）的直肠癌前切除术（AR）或腹会阴联合切除术（APR）,其中2例术后接受卡培他滨正规辅助化疗,1例术后拒绝接受任何辅助治疗,但在术后29个月发现肝、肺多发转移,予姑息化疗和最佳支持治疗。1例在诊断时即为直肠癌伴肝脏多发转移,行姑息化疗和最佳支持治疗。结果　术后接受化疗的2例分别为术后8个月和21个月,已完成术后6个月的常规化疗,近期随访显示一切正常。其他2例分别于开始治疗后5个月和31个月时死于疾病进展。结论　尽管肾移植患者患结直肠癌的预后不佳,但只要一般情况和移植器官的功能良好,就应该给予积极的抗肿瘤治疗,包括手术和辅助治疗。对肾移植患者进行定期结直肠癌筛检是十分必要的。     

Liver resection for hepatocellular carcinoma in patients who have undergone prior renal transplantation

BACKGROUND AND OBJECTIVES: Because renal transplantation recipients require immunosuppressive drugs, they have a higher incidence of subsequent malignancies. Among them, hepatocellular carcinoma (HCC) is common. Although liver resection remains an option for curing HCC, the role of liver resection in renal transplantation recipients remains unclear. METHODS: A retrospective review of liver resection for newly diagnosed HCC in 680 patients was conducted. Among them, 18 patients had undergone prior renal transplantation (RT group). The patient background, tumor characteristics, early and long-term results after liver resection were compared with the other 662 patients who had not previously undergone renal transplantation (non-RT group). RESULTS: The patient's background characteristics were comparable between RT and non-RT group. The tumor characteristics, postoperative morbidity, and mortality were not significantly different between the two groups. The 5-year disease-free survival rates in RT and non-RT groups were 18.8% and 41.2%, respectively (P = 0.242), whereas 5-year actuarial survival rates in RT and non-RT groups were 59.1% and 58.3%, respectively (P = 0.738). Two patients lost their graft kidney 3 and 8 years after liver resection. CONCLUSION: With careful protection of the graft kidney, liver resection is still a justified treatment option for HCC in patients who have undergone renal transplantation.     

肾移植后晚发型淋巴组织增生性疾病的临床病理特点

目的 移植后淋巴组织增生性疾病(post-transplant lymphoproliferative disorders,PTLD)是实体器官移植或造血干细胞移植后的一种严重并发症,主要与医源性免疫抑制和Epstein-Barr病毒(EBV)感染有关.由于发生率低,临床表现和病理形态多样,前瞻性临床研究少,目前对该病的认识还很不充分.本研究旨在探讨肾移植后晚发型PTLD的临床病理特点及治疗和预后.方法 2001-01-30-2013-12 30在南京军区南京总医院根据WHO造血与淋巴组织肿瘤分类标准共确诊4例肾移植后PTLD,回顾性分析该组患者的临床病理资料、EBV相关检查结果及治疗和预后,并对相关文献进行复习.结果 4例患者肾移植后均采用三联或四联免疫抑制治疗,肾移植至PTLD诊断时间为2.5～18年(中位9.5年).4例的病理类型均为单形型,其中1例非特指型外周T细胞淋巴瘤(PTCL NOS)和3例非生发中心型弥漫大B细胞淋巴瘤(DLBCL).外周血EBV-DNA和病理组织原位杂交检测EBER均阴性.1例PTCL-NOS以皮肤病变起病,合并噬血细胞淋巴组织细胞增生症,3例DLBCL分别以颌下肿块、腰背痛和下肢无力起病.确诊后均予免疫抑制剂减量,同时行联合化疗或利妥昔单抗联合化疗.4例患者中,2例早期死亡,分别为疾病进展和化疗后并发感染性休克.另2例分别在完全缓解4个月和10个月后疾病复发,再次治疗未缓解.结论 肾移植后晚发型PTLD以单形型为主,DLBCL最常见,结外侵犯多见,与EBV感染无明显关系,化疗或免疫化疗效果差,预后不良.     

肾移植术后恶性肿瘤39例临床分析

目的分析总结肾移植术后恶性肿瘤的发生情况,探讨其诊断方法和治疗措施。方法回顾性分析1978年9月至2009年12月接受免疫抑制治疗的肾移植受者中恶性肿瘤的发生情况。结果1945例（2106例次）肾移植共发生恶性肿瘤39例,发生率为2％。恶性肿瘤于移植术后8～124个月（中位时间57个月）得到明确诊断,其中泌尿系统肿瘤22例,消化系统肿瘤8例,肺癌、淋巴瘤、乳腺癌各2例,硬脑膜小细胞癌、胸膜低分化癌各1例,另有1例转移性肝癌患者人院后3d死亡,原发肿瘤不明。28例获手术治疗,随访至2010年12月,生存16例,其余12例在术后3-96个月（中位时间33个月）死于肿瘤转移;11例未手术者于诊断后3d一36个月（中位时间5个月）死亡。结论肾移植受者中恶性肿瘤的发生以泌尿系统肿瘤最为多见,肿瘤恶性程度高,早期发现、早期治疗是提高生存率的关键,治疗上应尽早采取以手术为主的综合治疗。     

肾移植患者并发泌尿系统恶性肿瘤(附9例报告)

目的 分析我院肾移植受者并发泌尿系统恶性肿瘤的特点。方法 对我院1978年6月-2001年12月的2300例肾移植受者进行回顾分析。结果 在2300例中,共发生27例(发生率1.22％)恶性肿瘤,其中泌尿系统恶性肿瘤9例(0.39％,男性6例,女性3例),占肿瘤发生的1/3,其它肿瘤包括皮肤癌、肝右叶囊性腺癌、肝细胞癌、胃癌、直肠癌、结肠癌、回盲部腺癌、唇癌、舌癌、肺恶性淋巴瘤和乳癌共18例。泌尿系统恶性肿瘤中肾细胞癌1例,双侧肾盂癌2例,单侧肾盂癌3例,输尿管癌1例,膀胱癌2例。平均发病年龄57.5±5.6(49-63)岁,平均术后时间58±18(36-94)个月。6例服用CsA+Aza+Pred,3例服用CsA+MMF+Pred。8例施行了根治性手术,1例术后不久并发脑溢血死亡。结论 泌尿系统恶性肿瘤,尤其是移行上皮癌,是肾移植受者的一个重要并发症,其发病率是一般泌尿系统肿瘤病例的10倍,其中肾盂移行细胞癌发生率最高,其次是膀胱移行细胞癌。免疫抑制剂的使用与肿瘤发生密切相关,应定期评估移植受者的免疫状态,重视无痛性肉眼血尿的检查,早期发现肿瘤,及时手术治疗,并减少免疫抑制剂用量。     

Risk of bladder cancer in renal transplant recipients: a meta-analysis

Background:

Renal transplantation has been associated with a significantly increased risk of developing cancers during long-term follow-up, but for bladder cancer, this risk is less clear. We therefore performed a meta-analysis to determine whether bladder cancer risk in renal transplant recipients was increased.

Methods:

Eligible studies were identified through searches of PubMed and other public resources. Random-effects meta-analyses were used to pool overall estimates for standardised incidence ratios (SIRs). Heterogeneity test, sensitivity analysis, and assessment of publishing bias were also performed.

Results:

We identified a 3.18-fold higher SIR (95% confidence intervals (CI): 1.34–7.53, P=0.008) of bladder cancer in patients following renal transplantation compared with the general population, based on data from 79 988 patients with a total follow-up of 308 458 patient-years. When stratified by ethnicity, the SIRs for bladder cancer were 2.00 (95% CI: 1.51–2.65, P=0.001) and 14.74 (95% CI: 3.66–59.35, P<0.001) between European and Asian renal transplant recipients, respectively.

Conclusions:

Our study demonstrated that the risk of developing bladder cancer in transplant populations was increased. Such association suggests that physicians should be more vigilant in checking for bladder cancer in transplantation recipient population.     

自体干细胞移植治疗伴有严重肾功能不全的多发性骨髓瘤

 肾衰竭是多发性骨髓瘤（MM）患者常见的临床表现。伴有肾衰竭的MM患者对传统化疗的总缓解率为35 %～50 %（完全缓解少见）,中位生存期为4个月～1年,均显著低于肾功能正常患者。有许多中心应用大剂量美法仑以及自体干细胞移植（ASCT）治疗伴有严重肾衰竭的MM患者。目前研究发现,患者肾功能严重程度以及是否接受透析对干细胞动员以及干细胞植入无明显影响。大剂量美法仑以及ASCT后,伴有肾衰竭MM患者的完全缓解率、无事件生存率以及总生存率,分别增加到30 %、20个月以及40个月左右。相当一部分患者脱离透析。但是,该领域存在的问题仍然相当多,如APBSCT导致较高的移植相关死亡率。另外,在沙利度胺、硼替佐米以及雷利度胺等新药应用于临床之后,对于ASCT治疗伴有肾衰竭MM患者的影响如何,也需要进一步探讨。     

肾移植术后并发泌尿系统肿瘤6例报告并文献复习

 目的　探讨肾移植术后泌尿系统肿瘤的发生情况、临床特点、诊断及治疗。方法　对本院自1991年～ 2 0 0 1年十年间行同种异体肾移植术 10 96例术后泌尿系统肿瘤的发生情况进行回顾性分析 ,并结合复习文献。结果　本组发现泌尿系统肿瘤 6例 ,发生率为 0 .5 5 %。其中肾盂癌 2例 (其中 1例为双侧肾盂癌 ) ,膀胱癌 1例 ,肾盂癌合并膀胱癌 2例 ,输尿管癌 1例。 6例均行手术治疗 ,平均随访11.4个月 ,效果良好。结论　肾移植术后出现血尿 ,除排斥反应外 ,还应注意泌尿系统肿瘤的可能性。     

High-dose ifosfamide,carboplatin, and etoposide pharmacokinetics: correlation of plasma drug levels with renal toxicity

An autologous bone marrow transplant regimen of ifosfamide, carboplatin, and etoposide (ICE) has been developed as treatment for certain malignancies. At maximum tolerated doses renal insufficiency precludes dose escalation. The objective was to examine whether measurement of plasma drug levels early during treatment would provide warning of renal failure. Nine patients received a 96-h continuous infusion of ifosfamide 16000 mg/m², carboplatin 1600 mg/m², and etoposide 1200 mg/m². Pharmacokinetics, including drug levels and plasma concentration-time curves, of ifosfamide, ultrafiltrable platinum (uPt) and etoposide were analyzed and correlated with renal function. One of the nine patients developed anuric renal failure requiring hemodialysis. By 17 h from the start of infusion, this patient showed substantially higher drug levels of ifosfamide (200 vs mean 217 M) and uPt (19 vs mean 10M) than those patients with preserved renal function. The 95% confidence intervals suggested that a 16–22 h ifosfamide level >153 M and an uPt level >M predict the development of significant renal dysfunction. Although drug levels were substantially higher at 56 h, the serum creatinine did not yet reflect kidney injury. This study suggests that high plasma ifosfamide and uPt levels, analyzed early in the course of a 96-h infusion of high-dose ICE, provide warning of severe and potentially fatal renal injury. Since ICE has substantial activity in a number of malignancies, but significant renal morbidity, real-time pharmacokineticguided dosing may reduce treatment-related toxicity.Supported in part by US. Public Health Service Grants PO1-CA-38493 and CA-06516 and a grant from the Mathers Foundation. Drs. Ayash and Schwartz are recipients of a Career Development Award from the American Cancer Society     

Early detection of hepatocellular carcinoma in hepatitis-B-positive renal transplant recipients

Hepatocellular carcinoma (HCC) is a leading cause of malignancy after renal transplantation in Asia, where hepatitis B virus infection is endemic. Early detection and resection are the key to successful treatment because the mortality rate for HCC is high. The value of α-fetoprotein monitoring in the early detection of HCC in renal transplant recipients has not been reported before. We describe 2 patients who had successful resection of HCC following early diagnosis by α-fetoprotein monitoring. The epidemiology of post-transplant HCC in various parts of the world and its pathogenesis are discussed. J. Surg. Oncol. 1999;72:99–101. © 1999 Wiley-Liss, Inc.     

Malignancies after renal transplantation during 33 years at a single center

This study provides an analysis of incidence and characteristics of malignant tumors of 2535 patients who underwent renal transplantation between 1973 and 2007 at the Transplantation Center in Budapest. One hundred ninety-three malignant diseases were found in 188 patients (7.6%). The incidence of thyroid-, renal-hepatic-, skin- and gastric cancers as well as of Kaposi sarcoma and lymphomas increased in our transplant patient cohort compared to the figures of the general population based on the data of our Cancer Registry. On the other hand, colorectal-, oralprostate and lung cancers were underrepresented in our patient cohort. The mean time of diagnosis of malignancies following kidney transplantation was 58.5± 44.8 months. One fifth of the tumors were detected within the first year. Patients with malignancies were distributed into four groups based on the immunosuppressive regimen: group I (8.5%), azathioprine + prednisone; group II (59.0%), cyclosporine + prednisone; group III (26.6%), cyclosporine + mycophenolate mofetil + prednisone; group IV (5.9%), tacrolimus + mycophenolate mofetil + prednisone. The mean age of patients was 47.3, 53.5, 55.5 and 58.1 years in group I, II, III and IV, respectively. Oncologic and immunosuppressive therapy was decided individually. Immunosuppression was switched to rapamycin-containing regimens in 63 cases. We lost 92 patients (48.9%) with a mean survival time of 25.8± 39.4 months. Cumulative 1- and 5-year survivals were 69.5% and 52%, respectively. The increasing number of cancers seen early after transplantation and the increased risk of developing a cancer due to the older age of recipients draw attention to the importance of regular oncologic screening in patients on the waiting list and after transplantation.     

肾移植患者术后肿瘤发病特点及预后

背景与目的由于肾移植患者长期应用免疫抑制剂,与普通人群相比更易发生肿瘤。本研究中我们主要分析肾移植患者术后发生肿瘤的临床特点和预后,并评价根治性手术(radicalsurgery,RS)对其预后的影响。方法对本院1987年11月～2004年5月行肾移植手术的2160例患者进行回顾性分析,分析肾移植术后肿瘤的发生时间、肿瘤类型及生存时间等,总结肾移植术后肿瘤的发病特点。按是否行RS将肿瘤患者分为两组,对比研究RS对其预后的影响。结果2160例肾移植手术的患者中33例术后发生肿瘤,以消化系统肿瘤为主(33.3%)。10例行RS治疗(RS组)的患者中位生存时间为41.5个月;23例未行RS治疗(非RS组)者中位生存时间为6.0个月。两组20个月生存率分别为70.0%和13.0%。结论肾移植患者比普通人群更易发生肿瘤,肿瘤类型与普通人群所患不同,以肝癌、皮肤癌、淋巴瘤、甲状腺癌等为主。早期发现、早期治疗,尤其是病情允许行根治性手术者,近期疗效较好,远期效果有待进一步观察。     

In vivo regeneration of renal vessels post whole decellularized kidneys transplantation

Nearly 50 million patients in China live with end-stage renal disease (ESRD), and only about 4000 patients may receive kidney transplantation. The purpose of this study was to investigate regeneration of renal vessels post whole decellularized kidneys transplantation in vivo. We decellularized kidneys of donor rats by perfusing a detergent through the abdominal aorta, yielding feasible extracellular matrix, confirmed for acellularity before transplantation. Based on the concept of using the body as a bioreactor, we orthotopically transplanted the kidney and ureter scaffolds in recipient rats, and found the regeneration of vessels including artery and vein in the renal sinus following a spontaneous recanalization. Although the findings only represent an initial step toward the ultimate goal of the generation of fully functional kidneys in vivo, these findings suggest that the body itself, as the bioreactor, is a viable strategy for kidney regeneration.