Skin Cancer in Renal Transplant Patients
Screening of Renal Transplant Patients for Skin Cancer
2009 Report
Gillian M Murphy MD FRCPI FRCP Edin Consultant Dermatologist
Dermatology Department Beaumont Hospital, Dublin 9
In the year 2009 our ongoing screening programme for renal transplant patients has gone from strength to strength. The programme to screen renal transplant patients for skin cancer has been greatly assisted by the decision in 2008 to divide patients into risk categories to enable appropriate screening and patient education. The transplant programme for renal transplants continues to expand, and each year, 100–150 additional patients are added to the transplant population.
More than 3200 patients are enjoying the benefits of transplantation. Most newly transplanted patients have excellent quality of life and few complications. We have new renal physicians now in Beaumont Hospital all very aware of the need for patient surveillance and are seeing patients earlier in their transplant lives to educate them on the need for protection from the sun. With early detection skin cancers are cured by simple surgical removal. For those who are recently transplanted we provide education for all aspects of cancer prevention. My experience is that patients are now much better informed about safe behaviour.
As in the previous report, Risk categories include the low risk recently transplanted young patients with no visible sun-induced damage. Such patients are instructed regarding safe behaviour in the sun, appropriate clothing, use of sunscreens and eradication of viral warts. Low risk patients are followed up by the renal physicians and only seen annually by dermatology unless other skin problems occur.
Medium risk patients include those with sun-induced change on the skin indicating high levels of sun exposure, such as actinic keratoses, (scaly spots caused by the sun). Other risk factors might include one skin cancer such as a basal cell carcinoma or well differentiated squamous cell carcinoma. Medium risk patients are usually seen every 6 months and any premalignant lesion are eradicated. Preventative measure for such patients may include the use of various creams used to treat recurring sun-damage. Sun protection as above is encouraged on an ongoing basis.
High risk patients are those who have had 2 or more skin cancers, these patients are surveyed carefully to detect any new skin cancers, field change is vigorously treated. Preventative measures such as reduction of immunosuppressive drugs where possible is actively examined. Use of retinoids to halve the numbers of skin cancers is considered, and the possibility of switching to a new class of immunosuppressive drug, mTOR inhibitors is considered. These patients are reviewed every 3-6 months depending on tumour type.
Very high risk patients enter an exponential phase of tumour development, or have aggressive deeply invasive or metastatic disease. Such patients require careful multidisciplinary management which may require total cessation of immunosuppressive drugs and reversion to dialysis.
In the last year a new multidisciplinary group has been convened to discuss optimal management for patients with complicated skin cancers. Thus patients get world class management with all relevant doctors meeting together to discuss how best to treat such patients. New treatments are also on the horizon and studies continue to ensure Irish transplant patients receive the best treatment.
Thankfully most patients are in the first two categories with only some in the high and very high risk categories. Our screening programme is an now essential part of the management of renal transplant patients and we are very grateful for the ongoing support from The Punchestown Charitable Trust which supports the ongoing programme. Currently Mary Laing is supported by this research grant and apart from the screening of patients her work is looking at genetic changes, which contribute to risk for individual patients. Depending on the outcome of this research it may be possible to prevent some risk by taking folic acid as a supplement. However, this has to be proven in clinical studies before we can recommend it. Mary Laing, who has been very helpful in screening transplant patients in the last year will return to do this again this coming year enabling us to continue to offer Beaumont patients the best of care from a dermatology point of view.
Screening of Renal Transplant Patients for Skin Cancer
2008 Report
Gillian M Murphy MD FRCPI FRCP Edin Consultant Dermatologist
Dermatology Department Beaumont Hospital, Dublin 9
Over the past year, the programme to screen renal transplant patients for skin cancer has continued. We have divided patients into risk categories to enable appropriate screening and patient education. The transplant programme for renal transplants continues to expand, and each year, 100–150 additional patients are added to the transplant population. Now more than 3000 patients are enjoying the benefits of transplantation. With long term immuno-suppression and advancing age, skin cancer becomes increasingly common. With early detection such skin cancers are cured by simple surgical removal. For those who are recently transplanted we provide education for all aspects of cancer prevention.
Risk categories include the low risk recently transplanted young patients with no visible sun-induced damage. Such patients are instructed regarding safe behaviour in the sun, appropriate clothing, use of sunscreens and eradication of viral warts. Low risk patients are followed up by the renal physicians and only seen annually by dermatology unless other skin problems occur.
Medium risk patients include those with sun-induced change on the skin indicating high levels of sun exposure, such as actinic keratoses, (scaly spots caused by the sun). Other risk factors might include one skin cancer such as a basal cell carcinoma or well differentiated squamous cell carcinoma. Medium risk patients are usually seen every 6 months and any premalignant lesion are eradicated. Preventative measure for such patients may include the use of various creams used to treat recurring sun-damage. Sun protection as above is encouraged on an ongoing basis.
High risk patients are those who have had 2 or more skin cancers, these patients are surveyed carefully to detect any new skin cancers, field change is vigorously treated. Preventative measures such as reduction of immunosuppressive drugs where possible is actively examined. Use of retinoids to halve the numbers of skin cancers is considered, and the possibility of switching to a new class of immunosuppressive drug, mTOR inhibitors is considered. These patients are reviewed every 3–6 months depending on tumour type.
Very high risk patients enter an exponential phase of tumour development, or have aggressive deeply invasive or metastatic disease. Such patients require careful multidisciplinary management which may require total cessation of immunosuppressive drugs and reversion to dialysis.
Thankfully most patients are in the first two categories with only some in the high and very high risk categories. Our screening programme is an essential part of the management of renal transplant patients and we are very grateful for the ongoing support from The Punchestown Charitable Trust which supports the ongoing programme. Currently Mary Laing is supported by this research grant and apart from the screening of patients her work is looking at genetic changes, which contribute to risk for individual patients. Depending on the outcome of this research it may be possible to prevent some risk by taking folic acid as a supplement. However, this has to be proven in clinical studies before we can recommend it.
Beaumont Hospital
Report for Punchestown Charitable Trust
for the Years 2004–2006, up to June 2007
Beaumont Hospital Dermatology services has received €30,000 each year donated by the Board of the Charitable trust in 2005 and 2006. These funds have enabled employment of a dermatology registrar dedicated to the renal transplant recipients, specifically to screen these patients for signs of skin cancer. In addition to screening all these patients, we have been compiling a detailed database of the patients, to examine who has developed skin cancers and why. We have now screened over 700 patients.
We have conducted multiple studies to find out why patients do develop these cancers and have found out that some patients have genetic changes in several genes which predispose to skin cancer. These include changes in the genes which control folic acid, alterations in the genes which control Vitamin D metabolism leads to ability to predict renal graft survival but did not predispose to skin cancer.
We are currently studying genes which control inflammation (COX2) as we might expect also an influence for skin cancer predisposition but do not yet have the results of these data.
We have participated in a European study to study Malignant melanoma in transplant patients. We found this to be increased 6–8 fold in renal transplant recipients in Ireland. Gathering all cases together in Europe showed no adverse outcome for renal transplant patients compared with the normal population. This is good news for patients who previously have had a melanoma as they then are eligible for transplantaion.
We are also analysing the results of switching patients from standard immunosuppression to a new drug Rapamycin to see if this drug helps to prevent the development of skin cancers in patients developing large numbers of skin cancers.
Projects for the forthcoming year:
- We wish to continue our plans to continue monitoring all renal transplant patients on an ongoing basis. Patients are stratified into risk groups, some patients needing reassessment at 3 month intervals, others needing just annual assessment depending on the level of clinical problems.
- We are engaged in a Europe-wide study of rare skin cancers "Merkel Cell Carcinoma" to determine how common it is in the transplant population. Our view is that this is considerably increased compared with what might be expected in transplant patients, and that it is sun-induced.
We await the full results of this study. Mary Laing who previously did the Dermatology renal transplant registrar post is very keen on continuing research in the area of factors contributing to skin cancer. She is keen to study the folic acid story. She would study the consequence of folic acid deficiency on cancer risk and study how this causes skin cancer. She has a detailed protocol complied with me, Elaine Kay (Pathologist Beaumont Hospital) and with funding would be available to continue the excellent renal transplant research which has been so successful to date. We think that in the absence of folic acid cells fail to protect themselves against the effects of ultraviolet radiation. The project will examine whether supplementation with folic acid could prevent these effects. We are also engaged in a project designed to screen all human genes to pick out the genes which are particularly important for skin cancer, this will form part of Mary Laings work and add to the information we need for the important work which needs to be done before we can predict those at most risk of skin cancer. We are very grateful for funding received up to now, and would deeply appreciate any ongoing funding available as this would enable continuation of the hitherto very successful project for the foreseeable future.
Gillian M Murphy MD FRCPI FRCP Edin Consultant Dermatologist
Dermatology Dept
Beaumont Hospital
Skin Cancer in Renal Transplant Patients
Proposed Project 2005–2006
Mary Laing, Tony O'Grady, Elaine Kay, Peter Conlon, Gillian Murphy
Skin cancer is extremely common in renal transplant patients, with age and duration of transplantation being two of the commonest risk factors. A recent study by Fergal Moloney showed that genetic polymorphisms which are relevant in the metabolism of azathioprine contribute to a drop in white cell count in people who are heterozygous for TPMT genes, in other words those who metabolise the drug poorly tend to drop their white cell count more readily than those who metabolise the drug well. Renal transplant patients in whom this happens usually have the dose of azathioprine adjusted or stopped. This is usually happens early in the post transplant period. Only about 7% of RTR are heterozygotes for the polymorphism. The remaining 93% metabolise the drug well. There was a trend for patients who were heterozygotes for TPMT who remained on azathioprine to develop more skin cancers in addition. The second finding from the study was that certain genes which control skin and hair colour contribute to the risk for skin cancer, independently to the risk conferred from having the genes known to lead to red hair. We also had the opportunity to look for polymorphisms in Cyclooxygenase 1 and 2 genes which are genes expressed in skin cancers. We know that COX-2 is expressed in skin cancers and that the use of drugs which inhibit COX-2 expression prevent or slow down the growth of skin cancers.