Skin cancers are the most common tumors in patients who have received organ transplants. This review discusses the epidemiology, pathogenesis, and management of squamous-cell and basal-cell carcinomas, cancers of the anogenital region, Kaposi's sarcoma, melanoma, neuroendocrine skin carcinoma, and cutaneous manifestations of lymphoma in transplant recipients.

Skin cancers after organ transplantation.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death in Asia, and its incidence is also on the rise in Western countries. 1,2 Hepatic resection has been the mainstay of surgical treatment for HCC. It is now well established that liver transplantation is the treatment of choice for unresectable small HCC (≤5 cm) in patients with decompensated Child-Pugh class B or C cirrhosis. 3–5 The best treatment strategy for small HCC in patients with preserved liver function is controversial. Studies have shown superior survival results after transplantation compared with resection, especially in terms of disease-free survival rates. 6–10 On that basis, some authors have recommended transplantation as the treatment of choice even for resectable small HCC in Child-Pugh class A patients. 7–10 However, other studies have shown similar overall survival rates after resection and transplantation for small HCC, and hence concluded that resection rather than transplantation should be the first-line treatment for small HCC in patients with preserved liver function. 11–13 In one study, the disease-free survival rates after resection and transplantation for HCC 5 cm or smaller were found to be comparable. 11

Whether a patient with an HCC 5 cm or smaller and preserved liver function should be treated by resection or transplantation is not only a debatable issue, 14 but also a therapeutic dilemma that many hepatic surgeons are facing with increasing frequency because of the growing number of small HCCs detected by screening of patients with chronic hepatitis or cirrhosis. 15 The donor organ shortage has been a major deterrent to the use of liver transplantation for small resectable HCC. 13,16,17 In a recent intent-to-treat analysis comparing resection and transplantation for early HCC, a high dropout rate from tumor progression as a result of a long waiting time was identified as a major factor hampering survival in patients with early HCC listed for transplantation. 18

Recently an alternative strategy of primary resection followed by transplantation for recurrence or deterioration of liver function (salvage transplantation) has been proposed for patients with small HCC and preserved liver function. 13,16,19,20 Although no study has formally evaluated the efficacy of such a strategy, it is already being used in some transplantation units under the pressure of organ shortage. 19 Such a strategy depends on the premise that the majority of recurrences after resection of small HCC are still transplantable. However, so far there have been no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are fundamental in determining whether a strategy of primary resection and salvage transplantation is practicable. Hence, we conducted a study of the long-term survival outcome and pattern of recurrence after resection of potentially transplantable small HCC in a cohort of Child-Pugh class A patients. Based on the results, we examined the implications on the strategy of salvage transplantation.

Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function : implications for a strategy of salvage transplantation

Liver transplantation (LT) is the most effective treatment of patients with small hepatocellular carcinomas (HCC).1–4 The international transplantation community has largely adopted an approach to LT for HCC based upon the criteria proposed by Bismuth et al,5 which were amended and popularized by Mazzafero et al6 and adopted by UNOS.7 LT based on these Milano criteria (solitary liver nodule not exceeding 5 cm in maximum diameter, or 2 or 3 tumors not exceeding 3 cm in diameter) has been shown to provide very good disease-free survival, so that it is considered to be the optimal treatment of small HCC, especially in patients with underlying chronic liver disease.1–4,6,8,9 The evidence that LT should be therefore the preferred treatment choice for these patients has increased the demand resulting in longer waiting lists in the face of a relative shortage of available donors.10 During long waiting times, some patients suffer progression of disease such that they can never benefit from LT. Bridge treatments to halt or delay tumor progression during the waiting period for LT include radiofrequency tumor ablation, transarterial chemoembolization, and liver resection.11–16 Poon et al proposed to resect HCC in selected patients eligible for LT and to reserve LT for those who develop recurrence or deterioration of liver function.11 This approach, which proposes resection as a bridge treatment to prevent tumor progression during the waiting period, has not been studied in detail. Further, resection might enable selection of patients with HCCs who are likely to obtain the maximum benefit from LT. However, transplant surgeons are concerned that prior liver resection could complicate the operative transplant procedure, increase the risk of postoperative complications, and even impair the survival advantage of transplantation over resection alone.

To evaluate the impact of liver resection prior to LT, we retrospectively studied a homogeneous group of patients with cirrhosis and HCC who strictly fulfilled Milano criteria based on pathologic analysis of the explanted specimen after LT. The aim of this study was to report the perioperative course, morbidity, and survival in the group of patients who underwent secondary liver transplantation (SLT) after liver resection compared with those who underwent primary liver transplantation (PLT) for HCC.

Resection prior to liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a morbid condition for which surgical and ablative therapy are the only options for cure. Nonetheless, over half of patients treated with an R0 resection will develop recurrence. Early recurrences within 2 years after resection are thought to be due to the presence of residual microscopic disease, while late recurrences > 2 years after resection are thought to be de novo metachronous HCCs arising in chronically injured liver tissue. Microvascular invasion (MVI) is defined as the presence of micrometastatic HCC emboli within the vessels of the liver, and is a critical determinant of early recurrence and survival. In this review, we summarize the pathogenesis and clinical relevance of MVI, which correlates with adverse biological features, including high grade, large tumor size, and epithelial–mesenchymal transition. Multiple classification schemas have been proposed to capture the heterogeneous features of MVI that are associated with prognosis. However, currently, MVI can only be determined based on surgical specimens, limiting its clinical applicability. Going forward, advances in axial imaging technologies, molecular characterization of biopsy tissue, and novel serum biomarkers hold promise as future methods for non-invasive MVI detection. Ultimately, MVI status may be used to help clinicians determine treatment plans, particularly with respect to surgical intervention, and to provide more accurate prognostication.

Prognostic and Therapeutic Implications of Microvascular Invasion in Hepatocellular Carcinoma

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines.The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) prioritization of questions, (iii) systematic literature review and critical appraisal of available evidence and (iv) formulation of recommendations and grading according to Grades of Recommendation Assessment, Development, and Evaluation (GRADE). The strength of each recommendation is rated 1 or 2, with 1 being a 'We recommend' statement, and 2 being a 'We suggest' statement. In addition, each statement is assigned an overall grade for the quality of evidence: A (high), B (moderate), C (low) or D (very low). The guideline makes recommendations for the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and perioperative recipient care.All together, the work group issued 112 statements. There were 51 (45%) recommendations graded '1', 18 (16%) were graded '2' and 43 (38%) statements were not graded. There were 0 (0%) recommendations graded '1A', 15 (13%) were '1B', 19 (17%) '1C' and 17 (15%) '1D'. None (0%) were graded '2A', 1 (0.9%) was '2B', 8 (7%) were '2C' and 9 (8%) '2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/gft218 and can be downloaded freely from http://www.oxfordjournals.org/our_journals/ndt/era_edta.html.

European Renal Best Practice Guideline on kidney donor and recipient evaluation and perioperative care

Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization

Kidney transplantation is now recognized as the treatment of choice for patients with chronic renal failure. Despite the extension of indications to patients suffering severe hypertension, ischemic heart disease, and chronic heart failure, the worldwide results are superb. However, perioperative cardiac complications occur in 6% to 10% of transplanted patients. Aggressive intraoperative volume expansion is still recommended to maximize graft functional recovery (up to 30 mL/kg/h, central venous pressure [CVP] > 15 mm Hg), but patients with preexistent cardiac disease or poor myocardial function are exposed to the risk of fluid overload, acute respiratory failure, and prolonged ventilation. Among the last 90 cases performed at our institution, good functional recovery of the graft was present in 94% of the patients within 2 weeks, despite a much more conservative intraoperative hydration policy (crystalloids 2400 +/- 1000 mL, 15 mL/kg/h, CVP 7-9 mm Hg). Graft failure which occurred in 5 patients was significantly correlated only with donor age, while perioperative cardiovascular complications had been present in 9 cases (10%) who were coronary artery disease patients (55%). Age above 50 years was the only significant risk factor. Supranormal volume loading is probably not always warranted in kidney transplantation.

Perioperative fluid management in kidney transplantation : Is volume overload still mandatory for graft function?

To investigate whether early postoperative changes in blood lactate concentration indicate the functional recovery of the newly grafted liver, changes in oxygen supply, oxygen consumption, acid-base equilibrium, and blood lactate concentrations were prospectively studied in a group of 53 postnecrotic cirrhotic patients during the various phases of orthotopic liver transplantation (preanhepatic, anhepatic, neohepatic) and for the first 48 h following reperfusion. The patients were divided into two groups according to the quality of the early graft function, as indicated by alanine aminotransferase, bile flow, and prothrombin activity: group A (49 patients), good immediate graft function and group B (4 patients), immediate graft non-function. Lactate levels rose in the same manner during the preanhepatic and anhepatic stages and peaked after revascularization of the graft. Following reperfusion, however, distinctly different blood lactate profiles were recorded in the two groups of patients. A fall in lactate concentration was recorded in group A patients, whereas a continuous rise occurred in group B patients: the difference becoming significant by the end of surgery (P<-0.05). During the first 48 h following revascularization of the graft, opposite trends in lactate concentration, bile flow, alanine aminotransferase, and prothrombin activity were evident in the two groups of patients: 24 h after reperfusion, lactate levels were below 2 mmol/1 in 47 of 49 patients from group A, while they plateaued above 4 mmol/1 in all patients from group B. Group A patients had lower alanine aminotransferase levels (P<-0.001), higher prothrombin activity, (P<-0.01), and greater bile flow (P<-0.02). If validated in larger series, the blood lactate profile, probably more than the absolute level, appears to be a useful indicator of the early recovery of liver metabolic capacities in the immediate postoperative period of orthotopic liver transplantation.

Lactate blood levels in the perioperative period of orthotopic liver transplantation.

Is hepatocellular carcinoma in cirrhosis an actual indication for liver transplantation

Early ribavirin treatment and avoidance of corticosteroids in hepatitis C virus (HCV)-positive liver transplant recipients: interim report of a prospective randomized trial.

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