Donor Cancer Transmission in Kidney Transplantation: A Systematic Review

Transplantation of any biological material from a donor to a host will carry some inherent risk of disease transmission. Our aims were to summarize the totality of the published evidence about donor cancer transmission among kidney transplant recipients and to determine the cancer‐specific survival of these patients. We systematically reviewed all case reports, case series and registry studies that described the outcomes of kidney transplant recipients with donor cancer transmission published to December 2012. A total of 69 studies with 104 donor‐transmitted cancer cases were identified. The most common transmitted cancer types were renal cancer (n = 20, 19%), followed by melanoma (n = 18, 17%), lymphoma (n = 15, 14%) and lung cancer (n = 9, 9%). Patients with melanoma and lung cancers had the worst prognosis, with less than 50% of recipients surviving after 24 months from transplantation. Recipients with transmitted renal cancers had the best outcomes, with over 70% of recipients surviving for at least 24 months after transplantation. Overall, the risk of donor transmission of cancer appears low, but there is a high likelihood of reporting bias. Our findings support the current recommendations for rejecting organs from donors with a history of melanoma and lung cancer, but suggest that the use of donor kidneys with a history of small, incidental renal cell cancer may be reasonable.     

Liver Transplantation for HCC: A Review

Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease or cirrhosis. Liver transplantation for hepatocellular carcinoma has the potential to eliminate both the tumor as well as the underlying cirrhosis and is the ideal treatment for HCC in cirrhotic liver as well as massive HCC in noncirrhotic liver. Limitations in organ availability, necessitate stringent selection of patients who would likely to derive most benefit. Selection criteria have considered tumor size, number, volume as well as biological features. The Milan criteria set the benchmark for tumors that would benefit from liver transplantation but were found to be excessively restrictive. Modest expansion in criteria has also been shown to be associated with equivalent survival. Microvascular invasion is the single most important adverse prognostic factor for survival. Living donor liver transplantation has expanded donor options and has the advantage of lower waiting period and not impacting the non-HCC waiting list. Acceptable outcomes have been obtained with living donor liver transplantation for larger and more numerous tumors in the absence of microvascular invasion. Downstaging of tumors to prevent progression while waiting for an organ or for reduction in size to allow enrolment for transplantation has met with variable success.     

Cancer Mortality in Kidney Transplantation

Immunosuppression is associated with an increased risk of cancer in kidney transplant recipients compared to the general population. It is less clear whether standardized cancer mortality ratios (SMRs) are also increased. This study's hypothesis is that SMRs are not increased because of competing risks of death. During the median follow-up of 5.05 years (Q1–Q3: 2.36–8.62), there were 1937 cancer deaths and 36 619 noncancer deaths among 164 078 first kidney-only transplant recipients captured in the United States Renal Data System between January 1990 and December 2004. The observed cancer death rate was 206 per 100 000 patient-years compared to an expected rate of 215 per 100 000 patient-years in the general population. The overall age- and sex-adjusted SMR was only 0.96 (95% CI 0.92–1.00). However, patients <50 years had SMRs significantly greater than unity while patients >60 had SMRs lower than unity. Up to 25% of cancer-related deaths occurred after allograft failure. These findings challenge the notion that cancer is a major cause of premature death in all kidney transplant recipients and has implications for design of cancer prevention strategies in kidney transplant recipients .     

mTOR,Cancer and Transplantation

One of the most clinically important molecular signalling networks to emerge over the past decade is the mammalian target of rapamycin (mTOR) pathway. mTOR, the protein kinase at the core of this intricate and continually evolving pathway, controls cellular growth and behavior, impacting vital processes from immune reactivity to cancer progression. As researchers, surgeons and physicians in the field of organ transplantation, we have acquired a keen interest in regulating mTOR activity, because this molecule is not only able to block IL‐2 signalling in T cells, and thus alloimmune reactivity, it is a critical part of the cellular circuitry which is often constitutively activated in neoplastic cells, leading to the all‐too‐often occurrence of cancer. Since allograft rejection and the development of cancer lead most lists for causing excess morbidity and mortality in our organ transplant population, a thorough and current understanding of the mTOR pathway becomes essential. In this review, we endeavor to unravel the latest molecular developments in mTOR signalling and use this basic knowledge to generate perspectives on how pharmacologic mTOR intervention may form a balance to impact long‐term antidonor immune responses and the development of malignancy in transplant recipients.     

Efficacy and Safety of Antifibrinolytic Drugs in Liver Transplantation: A Systematic Review and Meta-Analysis

Although several randomized controlled trials (RCTs) have shown the efficacy of antifibrinolytic drugs in liver transplantation, their use remains debated due to concern for thromboembolic complications. None of the reported RCTs has shown a higher incidence of these complications in treated patients; however, none of the individual studies has been large enough to elucidate this issue completely. We therefore performed a systematic review and meta-analysis of efficacy and safety endpoints in all published controlled clinical trials on the use of antifibrinolytic drugs in liver transplantation. Studies were included if antifibrinolytic drugs (epsilon-aminocaproic acid, tranexamic acid (TA) or aprotinin) were compared with each other or with controls/placebo. Intraoperative red blood cell and fresh frozen plasma requirements, the perioperative incidence of hepatic artery thrombosis, venous thromboembolic events and mortality were analyzed. We identified 23 studies with a total of 1407 patients which met the inclusion criteria. Aprotinin and TA both reduced transfusion requirements compared with controls. No increased risk for hepatic artery thrombosis, venous thromboembolic events or perioperative mortality was observed for any of the investigated drugs. This systematic review and meta-analysis does not provide evidence for an increased risk of thromboembolic events associated with antifibrinolytic drugs in liver transplantation.     

Interdisciplinary Management of Pediatric Intestinal Failure: A 10-Year Review of Rehabilitation and Transplantation

Management of children with intestinal failure is optimized by interdisciplinary coordination of parenteral and enteral nutrition support, medical management of associated complications, surgical lengthening procedures, and intestinal transplantation. Three hundred eighty-nine pediatric patients have been referred to our center for interdisciplinary assessment of intestinal failure since 1996 (median age = 1 year; range 1 day–28.8 years). Factors predictive of weaning from parenteral nutrition without transplantation included increased mean bowel length for patients with gastroschisis (44 vs. 23 cm, p < 0.05) and atresia (35 vs. 20 cm, p < 0.01) and lower mean total bilirubin for patients with NEC (6.1 vs. 12.7 mg/dL, p < 0.05). Others were also more likely to survive if referred with a lower mean total bilirubin (NEC, 7.9 vs. 12.7 mg/dL, p < 0.05; pseudo-obstruction, 2.3 vs. 16.3 mg/dL, p < 0.01). Patients weaned from parenteral nutrition by 2.5 years after referral achieved 95% survival at 5 years vs. 52% for those not weaned. Bowel lengthening procedures were performed on 25 patients. Eight subsequently weaned from parenteral nutrition without transplantation. Aggressive medical and nutritional intervention along with early referral, intestinal lengthening procedures, and intestinal transplantation in children with intestinal failure dependent on parenteral nutrition can result in the achievement of enteral autonomy and improved survival. Presented at Digestive Disease Week on Tuesday, May 22, 2007 in Washington, DC.     

Solid Organ Transplantation After Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective,Multicenter Study of the EBMT

To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984 and 2007 in Europe. Forty‐five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2‐year‐incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft‐versus‐host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence for underlying malignant diseases was 4% at 5 years (95% CI, 0% to 12%). In summary, this study shows that selected patients receiving SOT after HSCT have a remarkably good overall and organ survival. These data indicate that SOT should be considered in selected patients with single organ failure after HSCT.     

Race and Ethnicity in Access to and Outcomes of Liver Transplantation: A Critical Literature Review

Racial/ethnic disparities in access to and outcomes of liver transplantation are an important topic given the increasing diversity in the United States. Most reports on this topic predate the advent of allocation based on the model for end‐stage liver disease (MELD). For many patients with a variety of lethal conditions, liver transplantation is the only effective therapy, signifying the importance of equitable access to care. Racial/ethnic disparities have been described at various steps of the liver transplant process, including liver disease prevalence and treatment, access to a transplant center and its waitlist, receipt of a liver transplant and posttransplant outcomes. The purpose of this minireview is to critically evaluate the published literature on racial/ethnicity‐based disparities in liver disease prevalence and treatment, transplant center referral, transplant rates and posttransplant outcomes. We identify the shortcomings of previous reports and detail the barriers to completing properly constructed analyses, particularly emphasizing deficits in requisite data and the need for improved study design. Understanding the nature of race/ethnicity‐based disparities in liver transplantation is necessary to improve research initiatives, policy design and serves the broader responsibility of providing the highest quality care to all patients with liver disease.     

Renin Angiotensin System Blockade in Kidney Transplantation: A Systematic Review of the Evidence

ACE-inhibitors and angiotensin receptor blockers (ARB) slow the progression of renal disease in non-transplant patients. A systematic review of randomized trials (n = 21 trials with 1549 patients) was conducted to determine the effect of ACE-inhibitor or ARB use following kidney transplantation. With a median follow-up of 27 months, ACE-inhibitor or ARB use was associated with a significant decrease in glomerular filtration rate (-5.8 mL/min; 95% CI -10.6 to -0.99). ACE-inhibitor or ARB use resulted in a lower hematocrit (-3.5%; 95% CI -6.1 to -0.95), reduction in proteinuria (-0.47 gm/d; 95% CI -0.86 to -0.08) but no change in the serum potassium (0.18 mmol/L; 95% CI -0.03 to 0.40). ACE-inhibitor or ARB use results in clinically important reductions in proteinuria, hematocrit and glomerular filtration rate in renal transplant recipients, but there are insufficient data to determine the effect on patient or graft survival. Randomized trials of sufficient power and duration that examine these hard outcomes should be conducted. Until such trials are completed, this study provides quantitative estimates of the risks and benefits of ACE-inhibitor or ARB use that can be used by clinicians considering prescribing these medications to kidney transplant recipients or to researchers designing future trials.     

Managing Cancer Risk and Decision Making After Kidney Transplantation

Kidney transplant recipients are at higher risk of cancer at most sites, and cancer after transplantation causes considerable morbidity and mortality. To optimize long‐term patient outcomes, clinicians balance the prospect of graft failure and dialysis, with competing risks of diabetes, cardiovascular and cerebrovascular disease and the risk of malignancy. In this paper we critically examine the assumptions underpinning primary prevention, immunization, chemoprevention and screening programs, and highlight considerations when applying evidence to the kidney transplant population, and suggest a clinical research agenda that aims to define a rational approach to managing posttransplant cancer risk.     

支撑喉内镜下吸引旋切法治疗小儿喉乳头状瘤

目的探讨支撑喉内镜下吸引旋切法治疗小儿喉乳头状瘤的手术效果。方法对39例小儿喉乳头状瘤在支撑喉内镜下采用喉旋切技术治疗,并对其中27例肿瘤范围较广泛,创面容易出血或易形成喉粘连的患儿结合射频治疗。结果手术时间(11.2±2.6)min,出血量<30ml。术后3个月28例发音质量良好。37例随访2~5年,3年复发率51%(19/37),其中初发患儿复发率30%(3/10),复发患儿再次复发率59%(16/27)。结论采用喉内镜下喉旋切术,可以精确切除肿瘤,最大可能保留正常的喉黏膜,手术出血少,时间短,术后住院时间短,疗效确切。     

Kidney and Pancreas Transplantation in the United States, 1996–2005

Kidney and pancreas transplantation in 2005 improved in quantity and outcome quality, despite the increasing average age of kidney graft recipients, with 56% aged 50 or older. Geography and ABO blood type contribute to the discrepancy in waiting time among the deceased donor (DD) candidates. Allocation policy changes are decreasing the median times to transplant for pediatric recipients. Overall, 6% more DD kidney transplants were performed in 2005 with slight increases in standard criteria donors (SCD) and expanded criteria donors (ECD). The largest increase (39%) was in donation after cardiac death (DCD) from non-ECD donors. These DCD, non-ECD kidneys had equivalent outcomes to SCD kidneys. 1-, 3- and 5-year unadjusted graft survival was 91%, 80% and 70% for non-ECD-DD transplants, 82%, 68% and 53% for ECD-DD grafts, and 95%, 88% and 80% for living donor kidney transplants. In 2005, 27% of patients were discharged without steroids compared to 3% in 1999. Acute rejection decreased to 11% in 2004. There was a slight increase in the number of simultaneous pancreas-kidney transplants (895), with fewer pancreas after kidney transplants (343 from 419 in 2004), and a stable number of pancreas alone transplants (129). Pancreas underutilization appears to be an ongoing issue.