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.     

肾移植受者新发恶性肿瘤的生存分析

  目的  探讨肾移植受者发生肾癌的临床特征和诊疗特点。  方法  回顾性分析2011年3月至2023年3月天津市第一中心医院收治的27例肾移植受者发生肾癌患者的临床资料,其中男性25例、女性2例。27例患者中24例行肾癌根治性切除术（包括1例行双侧肾癌根治性切除术、1例行肾输尿管全长切除术）,3例行保守治疗。手术方式包括开放、腹腔镜和机器人手术,并对患者的诊疗过程、病理特征和手术预后进行分析。  结果  手术中位时间为148（100～210）min,术后中位住院时间为7（4～10）天。24例手术患者为原肾肾癌,肿瘤直径平均为（4.03±2.49）cm,其中6例为肾乳头状细胞癌、1例为肾嫌色细胞癌、17例为肾透明细胞癌。3例行保守治疗中的1例患者发现移植肾肿物,行穿刺活检病理为肾透明细胞癌。27例患者的临床TNM分期分别为T1aN0M0为 18例、T1bN0M0为4例、T2aN0M0为2例、T4N1M1为3例。患者首次诊断肿瘤的平均年龄为（51.21±7.60）岁。至移植前中位透析时间为19（1.2～72.0）个月,诊断肿瘤至移植手术的中位时间为95（12～180）个月。27例患者中位随访时间为47（3～147）个月,随访至129个月和95个月后有2例死亡,死亡原因分别为肺炎和脓毒血症。  结论  肾移植术后发生肾癌患者的早期诊断较为困难,有多发、囊性变、坏死倾向,重视规范的随访及确定预防性切除术时机尤为重要。     

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.     

De novo cancers in paediatric renal transplant recipients: a multicentre analysis within the North Italy Transplant programme (NITp), Italy

The purpose of this study was to determine the frequency and the outcome of de novo malignancies in a cohort of renal transplant paediatric patients. The records of 493 kidney transplants, carried out in 454 paediatric recipients at the three paediatric transplant centres of the North Italy Transplant programme (NITp, Italy) were reviewed. 10 cases of malignancies (2.2%) comprising both PTLD (post-transplant lymphoproliferative disorders) (6 cases, 1.3%) and non-PTLD malignancies (4 cases, 0.88%) were reported. Non-PTLD included one urothelial carcinoma and one Wilms' tumour of the recipient's left native kidney, one abdominal dysgerminoma and one optic nerve glioma of the left eye. The PTLD consisted of localised or disseminated Epstein-Barr virus (EBV)--associated B-lymphocyte monoclonal (5 cases) and polyclonal (1 case) proliferations. All patients suffering from PTLD had been EBV-negative at the time of transplantation, but developed EBV primary infection after transplantation. All PTLD patient donors were EBV-positive. In addition, all but 1 patient received, before and/or after transplantation, a range of immunosuppressive drugs in addition to the baseline prophylactic immunosuppressive regimen. Moreover, 3 patients suffered from syndromes associated with a genetic predisposition to cancer. Finally, the malignancies reported here were associated with 20% graft failure and 20% mortality rates.     

Cancer in renal transplant recipients

The incidence of cutaneous malignancies and non-Hodgkin lymphomas is higher in transplant recipients than in the general population. From 1968 to 1984, 200 kidney grafts were transplanted to 180 patients with end-stage renal disease. All patients were on azathioprine (Aza) and prednisolone. In selected cases ALG and/or small doses of CsA were added. Six patients developed malignant tumors (two Kaposi sarcoma, one squamous cell and one squamous plus basal cell skin cancers, one reticulosarcoma, and one glioma). Mean age of patients was 43 years (range 35-53 years), and mean time of appearance of the tumor after transplantation was 62 months (range 24-98 months). Treatment consisted of reduction of the dosage of Aza, surgical removal or local irradiation of the tumor, and chemotherapy in case of systemic involvement (two cases). Three patients died (one Kaposi sarcoma, one reticulosarcoma, and one glioma) 3 to 6 months after diagnosis, and all three had previously been on high doses of Aza. The remaining three cases (one Kaposi) were cured by stopping or decreasing Aza, by excision, and/or local irradiation of the tumor. It seems that late diagnosis and Aza in high dosage are the main factors leading to the rapid dissemination of the initially localized tumor.     

Merkel cell carcinoma in a renal transplant patient

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer which seems to be common in transplant recipients. We describe the case of a renal transplant patient who developed a MCC on the right glutaeus eight years after transplantation.     

Hodgkin's disease in renal transplant recipients

The association between renal transplantation and malignancy, particularly histiocytic lymphoma, is well known. Hodgkin's disease also occurs in renal transplant recipients. We report such a case and also review three other reports in the literatures. The Hodgkin's disease was insensitive to conventional MOPP chemotherapy in two of two, and was sensitive to combined MOPP-Bleomycin in one patient. The disease was rapidly fatal in three of four cases.     

Bilateral renal cell carcinoma in a horseshoe kidney

We report a case of bilateral renal cell carcinoma in a horseshoe kidney. To the best of our knowledge this is the second reported case in the international literature. We performed different radiological examinations preoperatively to identify of blood supply, because correct preoperative location of vessels is mandatory.     

Bronchogenic carcinoma in solid organ transplant recipients

Opinion statement Malignancies are increased in some types of solid organ transplant patients receiving immunosuppressive therapy and are a significant contributor to patient morbidity and mortality. There may be a 100-fold increase in the incidence of de novo neoplasia in this population. The risk of lymphoproliferative malignancies is well appreciated. In contrast, the risk of solid tumors with their consequent morbidity and mortality is less well known, probably because of their common occurrence in the general population. Lung cancer is the most common cause of cancer death in the United States; therefore, lung cancer in patients undergoing organ transplantation would be expected to occur frequently on the basis of chance alone. However, the lung cancer risk is approximately 20 to 25 times that of the general population, with an incidence of 0.28% to 4.1% in patients after heart and lung transplant. Risk factors thought to contribute include cigarette smoking, advanced age at transplantation, and chronic immunosuppressive therapy. The role of transplantation (and consequent therapy) in the development of lung cancer in this high-risk population remains unclear. As in the nontransplant population, adequate screening techniques are lacking, making early diagnosis and treatment a challenge. Despite close follow-up and routine imaging with chest radiography and CT, lung cancers continue to be discovered incidentally and at advanced stages. Treatment is similar to that of patients who are nontransplanted with similar stage, histology, and performance status.     

Systemic therapy for squamous cell carcinoma of the skin in organ transplant recipients

During the second half of the 20th century, organ transplantation saved thousands of lives. This, unfortunately, also led to unforeseen consequences that need to be addressed to help extend the lives of patients who require these life-saving procedures. Secondary malignancies have been recognized as a potential consequence for decades. One of these malignancies, squamous cell carcinoma of the skin, not only appears more frequently in organ transplant recipients than the general population, but also is more aggressive in organ transplant recipients. It also shows a high propensity to nodal spread and metastasis in transplant patients. Unfortunately, there are no clear guidelines for a chemotherapy in this population, who have an increased need for alternative therapies to surgery given the high recurrence and metastasis rate. In this review, we attempt to describe the characteristics of squamous cell carcinoma of the skin in transplant recipients and discuss what chemotherapeutic options can be used to treat this aggressive malignancy.     

Donor-derived small cell lung carcinoma in a kidney transplant recipient.

BACKGROUND: Transplantation of donor-derived malignancies during organ transplantation fortunately is very rare. Discontinuation of immunosuppressive medications under these circumstances has previously resulted in complete tumor rejection. Ectopic adrenocorticotropic hormone (ACTH) production may result in Cushing syndrome and is not an uncommon paraneoplastic feature of small cell carcinoma of the lung. Theoretically, in the organ transplantation setting, the resulting high cortisol levels could suppress a tumor-rejection immune response. However, to the authors' knowledge, no such clinical scenario has been described in the literature published to date. METHODS: A 25-year-old living related kidney transplant recipient presented with Cushing syndrome 32 months after transplantation. The donor had been diagnosed with small cell carcinoma of the lung 22 months earlier. On further evaluation, the kidney recipient was diagnosed with donor-derived small cell lung carcinoma of the transplanted kidney. She was found to have extensive disease involving the liver and retroperitoneum. Despite discontinuation of immunosuppressive medications, the disease progressed and cortisol levels remained elevated during 6 weeks of observation. RESULTS: The patient received six cycles of cisplatin and etoposide, which resulted in resolution of her hypercortisolemia and a complete remission of her donor-derived small cell carcinoma. At last follow-up, she was 12 months from completing her therapy and continued in complete remission. CONCLUSIONS: Donor-derived small cell carcinoma and ectopic ACTH production can occur in a patient after kidney transplantation.     

Survival after the diagnosis of de novo malignancy in liver transplant recipients

In the setting of liver transplant (LT), the survival after the diagnosis of de novo malignancies (DNMs) has been poorly investigated. In this study, we assessed the impact of DNMs on survival of LT recipients as compared to corresponding LT recipients without DNM. A nested case–control study was conducted in a cohort of 2,818 LT recipients enrolled in nine Italian centres between 1985 and 2014. Cases were 244 LT recipients who developed DNMs after LT. For each case, two controls matched for gender, age, and year at transplant were selected by incidence density sampling among cohort members without DNM. The survival probabilities were estimated using the Kaplan–Meier method. Hazard ratios (HRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. The all-cancer 10-year survival was 43% in cases versus 70% in controls (HR = 4.66; 95% CI: 3.17–6.85). Survival was impaired in cases for all the most frequent cancer types, including lung (HR = 37.13; 95% CI: 4.98–276.74), non-Hodgkin lymphoma (HR = 6.57; 95% CI: 2.15–20.01), head and neck (HR = 4.65; 95% CI: 1.81–11.95), and colon-rectum (HR = 3.61; 95% CI: 1.08–12.07). The survival gap was observed for both early and late mortality, although the effect was more pronounced in the first year after cancer diagnosis. No significant differences in survival emerged for Kaposi's sarcoma and nonmelanoma skin cancers. The survival gap herein quantified included a broad range of malignancies following LT and prompts close monitoring during the post-transplant follow-up to ensure early cancer diagnosis and to improve survival.     

A clinicopathological analysis of renal cell carcinoma in solitary kidney

Seven patients with renal cell carcinoma, who had undergone uninephrectomy or who had only one functioning kidney were clinicopathologically studied. They were 5 males and 2 females, with ages ranging from 51 to 74 years (mean: 61 years). Of these cases, 4 had undergone uninephrectomy for renal cell carcinoma, and 1 had received uninephrectomy because of renal calculus. In the remaining 2 cases, one kidney did not function (hypoplastic kidney). Renal cell carcinoma was discovered by macroscopic hematuria in 2 cases, during the follow-up observation after a previous surgical treatment of renal cell carcinoma in 4 cases and by abdominal computed tomography during treatment of abdominal aneurysm in 1 case. Excluding one case with multiple metastases, all cases were surgically treated (3 with partial nephrectomy and 3 with enucleation). During surgery, renal blood vessels were clamped for 24-60 minutes (mean: 38 minutes). After operation, 5 cases showed an elevation in serum creatinine (greater than or equal to 2.0 mg/ml), which, however, was normalized rapidly by conservative treatment. They have been followed up for 6 months to 7 years and 8 months after operation (mean: 2 years and 11 months). The case which had undergone before and recently received enucleation (2 pieces) showed metastasis of cancer to the pancreas 2.5 years after the recent operation. Therefore, this case additionally received partial pancreatectomy. The results of this study suggest that conservative surgical treatments are appropriate for the treatment of renal cell carcinoma in patients with solitary kidney from viewpoint of the quality of life, so long as postoperative management is sufficiently made.     

Cytomegalovirus in hematopoietic stem cell transplant recipients

This article examines the clinical manifestations of and risk factors for cytomegalovirus (CMV). Prevention of CMV infection and disease are also explored. Antiviral resistance and management of CMV are examined.     

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.     

Cancer incidence in kidney transplant recipients: a study protocol

Background  

Different publications show an increased incidence of neoplasms in renal transplant patients. The objective of this study is to determine the incidence of cancer in the recipients of renal transplants performed in the A Coru?a Hospital (Spain) during the period 1981–2007.     

Expression of cadherin-8 in renal cell carcinoma and fetal kidney

Cadherins represent a family of calcium-dependent cell adhesion molecules with an important regulatory function for maintenance of tissue architecture. Alterations of cadherin expression have been demonstrated in the development and progression of different epithelial tumors. In renal cell carcinoma (RCC), the majority of tumors express N-cadherin and cadherin-6. Screening a series of 16 RCC cell lines for the expression of different novel type II cadherins by RT-PCR revealed a complex pattern of cadherin expression: cadherins 6 and 14 were expressed in most of the RCC cell lines, whereas cadherins 11, 12 and 13 could not be detected at all. Interestingly, cadherin-8, previously shown in mice to be restricted to the CNS and thymus during development, was detected by RT-PCR, immunofluorescence and in situ hybridization in 4 of 16 RCC cell lines as well as in paraffin sections of the corresponding human RCC biopsies. In normal renal tissue, however, cadherin-8 could be detected only during the early stages of kidney development. These results suggest that alterations of type II cadherin expression may play a role in RCC development. In particular, cadherin-8 may be involved in both kidney morphogenesis as well as tumorigenesis in some types of RCC.     

Clinical and mycological features of dermatophytosis in renal transplant recipients

Dermatophytosis was detected in 42% of 100 renal transplant recipients screened, of whom 17% had the infection for more than 1 year. Tinea cruris and tinea corporis were the common clinical types observed. Tinea unguium presented as proximal subungual white onychomycosis (PSWO) in 3% of patients. The lesions in the majority were non-inflammatory, scaly and without central clearance. The commonest isolate was Trichophyton rubrum.