DERMATOETHICS
CONSULTATION
A pigmented lesion on a brain-dead organ donor: Should the dermatologist intervene before transplant? Rajini K. Murthy, MD,a Sarah S. Chisolm, MD,a and Benjamin K. Stoff, MDa,b Atlanta, Georgia
CASE SCENARIO A 58-year-old white man with poorly controlled hypertension presented to the emergency department with a massive intracranial hemorrhage. Shortly after presentation, the patient was declared brain dead by established criteria.1 After discussion with the family, organ donation was considered and the organ procurement evaluation process was initiated. During the routine pretransplantation skin examination, the transplant coordinator and medical director noticed an irregular pigmented lesion on the donor’s back. The donor had no personal or family history of melanoma. The history of the lesion in question was not known. The dermatology service was consulted for additional evaluation. The dermatology team should: A. Refuse the consult because the patient is deceased. B. Accept the consult and assess the likelihood of malignancy of the lesion based on clinical examination alone. C. Accept the consult and obtain a skin biopsy specimen of the lesion without local anesthesia and epinephrine. D. Accept the consult and obtain a skin biopsy specimen of the lesion with local anesthesia and epinephrine.
COMMENTARY Solid organ transplantation is now routinely offered as a therapeutic option for patients with end-stage organ disease. As a result, the demand for donor organs far exceeds the supply, and many patients succumb to disease while awaiting transplantation. To increase the supply of organs, some have proposed expanding eligibility criteria for organ donation to include, for example, older donors and those with a history of malignancy who have been disease-free for a number of years.2 These proposals have engendered intense debate, because there is a risk of transmission of donor malignancy to the transplant recipient. Data from the Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/ UNOS) revealed a donor-derived malignancy From the Departments of Dermatology at Emory University School of Medicinea and The Emory Center for Ethics,b Atlanta. Funding sources: None. Conflicts of interest: None declared. Correspondence to: Benjamin K. Stoff, MD, Department of Dermatology, Emory University School of Medicine, 1525 Clifton Road NE, Atlanta, GA 30312. E-mail: [email protected].
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incidence of 0.2% among 108,062 transplant recipients.3 The risk of transmission of a donor malignancy to an organ recipient varies based on the type of malignancy (Table I). For example, in a review of [120 solid organ transplants from donors with prostate cancer, no cases of transmission were noted.4 The risk of transmission of donor melanoma to the transplant recipient, however, appears to be substantial, with a transmission rate of 74% and associated mortality rate of 58% in 1 study of 296 donors with known or incidentally discovered malignancies.5,6 This number is surprisingly high, and selection bias is undoubtedly present. Strauss and Thomas7 reported a case of tumor transmission from a donor with a remote history of melanoma to a lung transplant recipient. In this case, the donor had J Am Acad Dermatol 2015;73:1062-5. 0190-9622/$36.00 Ó 2015 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2015.08.032
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Murthy, Chisolm, and Stoff 1063
VOLUME 73, NUMBER 6
Table I. Donor transmission rates and recommendations for transplant for select malignancies4,5,7 Tumor type
Cutaneous squamous cell carcinoma Melanoma Choriocarcinoma Renal cell carcinoma Prostate
Donor transmission to recipient (%)
0 74 93 61 Incidental (0-1%)
a history of melanoma that had been treated and ostensibly cured 32 years before organ donation. The donor was disease-free until death related to head trauma. This case highlighted the dormancy of melanoma cells. Based on the available data, then, the current recommendation is that concurrent melanoma in the donor—or previous melanoma even with no evidence of disease after therapy— precludes transplantation.7,8 The principle of nonmaleficence underlies the bioethical rationale for prohibiting organ donation from patients with a history of malignancy. This principle addresses the obligation of the physician to avoid inflicting harm on patients and is grounded in the familiar phrase ‘‘first, do no harm.’’9 Nonmaleficence is often in tension with the principle of beneficence, which reflects the obligation of physicians to act in a manner that benefits patient health. Finding a balance between these 2 principles requires weighing the burdens of a specific health intervention against the potential benefits. The community of patients with end-organ disease may benefit from allowing donation from patients with a history of malignancy, thereby increasing the pool of available organs. However, the principle of nonmaleficence constrains this aggregate benefit by holding that the primary duty of the health care provider is to avoid harming the individual patient. For certain types of donor-derived malignancy, such as melanoma, the risk of transmission to the transplant recipient almost certainly outweighs the benefits of the transplantation. Another source of debate in the pretransplantation evaluation and organ procurement process is the role of general anesthesia in the deceased donor. For donation after circulatory death, some have considered general anesthesia unnecessary given that the donor is deceased and therefore cannot be suffering. In addition, the presence of an anesthesiologist and administration of anesthesia may lead the family to misperceive that the donor is not actually dead.10
Recommendations for transplant
Proceed Avoid Avoid Proceed based on clinical factors (ie, localization, size, and excision potential) Proceed if localized; Gleason score #3
However, general anesthesia is often administered to the brain-dead donor for its physiologic effects on organ perfusion. Here, the end goal is to maintain and preserve physiologic function of organs to ensure successful transplantation.11 In dermatology, local anesthetics are primarily used to maintain comfort and hemostasis during procedures. No guidelines currently exist regarding their use in patients who have been declared dead. Local anesthetics may be considered for the practical benefit of epinephrine for hemostasis, analogous to the use of general anesthetics for preservation of organ function. From a bioethical standpoint, the use of local anesthetics may also create an environment that builds trust among the family of the deceased, ensuring that the procedure is carried out in accordance with standard practices of care. However, the dermatologist must be forthright with the family that use of a local anesthetic does not mean that the donor is still alive. Determining a history of malignancy or current malignancy poses a major challenge in assessment of the imminent donor.5 Overall, guidelines for cancer screening in brain-dead organ donors are limited. The evaluation of skin-related malignancies in the imminent donor warrants a total body skin examination, with particular attention to excision scars.12 Here, the dermatologist may be involved through direct consultation, the use of photographs, or through education of transplant coordinators regarding the appropriate evaluation of pigmented lesions. The presence of excision scars alone should not preclude candidacy for organ donation. The scar may represent a previous melanoma, in which case organ transplantation is contraindicated, but alternatively may represent a nonmelanoma skin cancer, in which case the risk of transmission from donor to recipient is minimal. Assessment should note the length of the scar, skin grafting, and axillary nodal dissection scars, which may be more indicative of melanoma. The acquisition of a pathology report—while often the most valuable resource—is
1064 Murthy, Chisolm, and Stoff
not always feasible given the limited time duration to organ procurement. Thorough gross examination of the body cavity and donated organs during procurement has also been suggested.5 A screening protocol has been proposed to evaluate brain-dead donors for an undiagnosed malignancy deriving from 4 common sites: the breasts, lungs, prostate, and colon.2 The protocol seeks to determine the level of risk for malignancy in a given donor. For example, heavy smokers (or donors with heavily smoking spouses) between 55
ANALYSIS OF CASE SCENARIO Option A is not an ideal choice. While there is debate regarding the moral status of a brain-dead organ donor, melanoma is considered a limiting factor for potential organ donation. Analogous to the standard in other fields of medicine, it is appropriate for dermatologists to take part in the evaluation of donors to ensure that harm to the organ recipient is as limited as possible. Option B could be an acceptable choice if the lesion is not suspicious for malignancy. However, if there is clinical suspicion, obtaining a biopsy specimen should be considered, consistent with the approach of other specialists in evaluation of malignancy deriving from other organs. A major limitation to obtaining a biopsy specimen in this setting may be the time required for processing and interpretation of the specimen. This may require frozen section evaluation, which is suboptimal for melanocytic lesions, but in many cases may be preferable to a clinical diagnosis alone. Option C addresses the ongoing debate about the use of anesthetics in organ donors who have been declared dead. The use of local anesthesia with epinephrine in this context is consistent
BOTTOM LINE Organ transplantation for end-organ disease requires a thorough assessment of the risks and benefits of the procedure to the organ recipient and a respectful approach to the donor and the donor’s family. The fundamental bioethical principles of nonmaleficence and beneficence are considered when determining whether the risk of transmission of a donor-derived malignancy in an organ recipient outweighs the benefit of receipt of the donated organ. Donor-derived melanoma has been documented and tends to follow an aggressive course. To guard
J AM ACAD DERMATOL
DECEMBER 2015
and 75 years of age were recommended to undergo screening with a helical computed tomography scan. For breast cancer, recommendations include breast ultrasonography for females [50 years of age who have not had a mammogram within the past 2 years, with further recommendations to obtain a biopsy specimen from any suspicious lesion. To our knowledge, there are no similar recommendations or guidelines regarding the screening of suspicious skin lesions in brain-dead potential organ donors.
with the use of general anesthesia during vital organ procurement, where anesthesia is administered for physiologic purposes. From a bioethical perspective, the use of local anesthesia could be justified by helping to build trust with the family by showing respect for the donor. On the contrary, the use of anesthesia in a donor who has been declared dead may send the false message to the family that the donor is not dead, as previous authors have suggested. Therefore, it is imperative to convey to the family that the use of anesthesia is to ensure that the procedure is performed in a standard fashion and to create an environment that is respectful of the dead donor—not to imply that the donor is alive. Option D is a reasonable choice. The use of local anesthesia with epinephrine would improve hemostasis, as stated above. In addition, it shows respect for and builds trust with the donor’s family by ensuring that the procedure is carried out in a standard fashion. However, the use of anesthesia could also convey that the donor is not dead, and therefore could potentially experience harm or suffering from the procedure.
against this possibility, additional donor screening guidelines are needed. Dermatologists should develop screening protocols for the evaluation of brain-dead organ donors that are analogous to those used within other specialties. These protocols might include additional screening for patients who have not had a total body skin examination within a certain amount of time (eg, the past year) or for those who have a strong family history of melanoma. Such screening tools would be similar to the guidelines proposed for breast cancer screening in imminent organ donors with significant risk factors. If appropriate, dermatologists or other providers may
J AM ACAD DERMATOL VOLUME 73, NUMBER 6
consider obtaining skin biopsy specimens from brain-dead donors in a manner similar to other medical specialties. It is standard for the transplant organization that requested the dermatology consultation to cover the costs associated with the skin examination, skin biopsy, and pathology evaluation. Clearly, tissue processing and interpretation in a manner timely enough for the transplant may pose challenges. Ultimately, however, these efforts should ensure that harm to the recipient is as limited as possible. REFERENCES 1. Rodriguez-Arias D, Smith MJ, Lazar NM. Donation after circulatory death: burying the dead donor rule. Am J Bioeth. 2011;11:36-43. 2. Hassanain M. Novel guidelines for organ donor cancer screening. Ann Transplant. 2014;19:241-247. 3. Kirk A, Knechtle S, Larsen C, Madsen J, Pearson T, Webber S. Textbook of organ transplantation. Oxford: John Wiley & Sons, Ltd; 2014:1139.
Murthy, Chisolm, and Stoff 1065
4. Doerfler A, Tillou X, Le Gal S, Desmonts A, Orczyk C, Bensadoun H. Prostate cancer in deceased organ donors: a review. Transplant Rev. 2014;28(1):1-5. 5. Buell JF, Alloway RR, Woodle S. How can donors with a previous malignancy be evaluated? J Hepatol. 2006;45:503-507. 6. Buell JF, Beebe TM, Trofe J, et al. Donor transmitted malignancies. Ann Transplant. 2004;9:53-56. 7. Strauss DC, Thomas JM. Transmission of donor melanoma by organ transplantation. Lancet Oncol. 2010;11:790-796. 8. Giessing M. Donors with malignancies—risk or chance? Transplant Proc. 2012;44:1782-1785. 9. Beauchamp TL, Childress JF. Principles of biomedical ethics. 6th ed. New York: Oxford University Press; 2009:288-310. 10. Van Norman G. Another matter of life and death: what every anesthesiologist should know about the ethical, legal, and policy implications of the non-heart-beating cadaver organ donor. Anesthesiology. 2003;98:763-773. 11. Anderson TA, Bekker P, Vagefi PA. Anesthetic considerations in organ procurement surgery: a narrative review. Can J Anesth. 2015;62:529-539. 12. Zwald FO, Christenson LJ, Billingsly EM, et al. Melanoma in solid organ transplant recipients. Am J Transplant. 2010;10:1297-1304.
CONSULTATION
A pigmented lesion on a brain-dead organ donor: Should the dermatologist intervene before transplant? Rajini K. Murthy, MD,a Sarah S. Chisolm, MD,a and Benjamin K. Stoff, MDa,b Atlanta, Georgia
CASE SCENARIO A 58-year-old white man with poorly controlled hypertension presented to the emergency department with a massive intracranial hemorrhage. Shortly after presentation, the patient was declared brain dead by established criteria.1 After discussion with the family, organ donation was considered and the organ procurement evaluation process was initiated. During the routine pretransplantation skin examination, the transplant coordinator and medical director noticed an irregular pigmented lesion on the donor’s back. The donor had no personal or family history of melanoma. The history of the lesion in question was not known. The dermatology service was consulted for additional evaluation. The dermatology team should: A. Refuse the consult because the patient is deceased. B. Accept the consult and assess the likelihood of malignancy of the lesion based on clinical examination alone. C. Accept the consult and obtain a skin biopsy specimen of the lesion without local anesthesia and epinephrine. D. Accept the consult and obtain a skin biopsy specimen of the lesion with local anesthesia and epinephrine.
COMMENTARY Solid organ transplantation is now routinely offered as a therapeutic option for patients with end-stage organ disease. As a result, the demand for donor organs far exceeds the supply, and many patients succumb to disease while awaiting transplantation. To increase the supply of organs, some have proposed expanding eligibility criteria for organ donation to include, for example, older donors and those with a history of malignancy who have been disease-free for a number of years.2 These proposals have engendered intense debate, because there is a risk of transmission of donor malignancy to the transplant recipient. Data from the Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/ UNOS) revealed a donor-derived malignancy From the Departments of Dermatology at Emory University School of Medicinea and The Emory Center for Ethics,b Atlanta. Funding sources: None. Conflicts of interest: None declared. Correspondence to: Benjamin K. Stoff, MD, Department of Dermatology, Emory University School of Medicine, 1525 Clifton Road NE, Atlanta, GA 30312. E-mail: [email protected].
1062
incidence of 0.2% among 108,062 transplant recipients.3 The risk of transmission of a donor malignancy to an organ recipient varies based on the type of malignancy (Table I). For example, in a review of [120 solid organ transplants from donors with prostate cancer, no cases of transmission were noted.4 The risk of transmission of donor melanoma to the transplant recipient, however, appears to be substantial, with a transmission rate of 74% and associated mortality rate of 58% in 1 study of 296 donors with known or incidentally discovered malignancies.5,6 This number is surprisingly high, and selection bias is undoubtedly present. Strauss and Thomas7 reported a case of tumor transmission from a donor with a remote history of melanoma to a lung transplant recipient. In this case, the donor had J Am Acad Dermatol 2015;73:1062-5. 0190-9622/$36.00 Ó 2015 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2015.08.032
J AM ACAD DERMATOL
Murthy, Chisolm, and Stoff 1063
VOLUME 73, NUMBER 6
Table I. Donor transmission rates and recommendations for transplant for select malignancies4,5,7 Tumor type
Cutaneous squamous cell carcinoma Melanoma Choriocarcinoma Renal cell carcinoma Prostate
Donor transmission to recipient (%)
0 74 93 61 Incidental (0-1%)
a history of melanoma that had been treated and ostensibly cured 32 years before organ donation. The donor was disease-free until death related to head trauma. This case highlighted the dormancy of melanoma cells. Based on the available data, then, the current recommendation is that concurrent melanoma in the donor—or previous melanoma even with no evidence of disease after therapy— precludes transplantation.7,8 The principle of nonmaleficence underlies the bioethical rationale for prohibiting organ donation from patients with a history of malignancy. This principle addresses the obligation of the physician to avoid inflicting harm on patients and is grounded in the familiar phrase ‘‘first, do no harm.’’9 Nonmaleficence is often in tension with the principle of beneficence, which reflects the obligation of physicians to act in a manner that benefits patient health. Finding a balance between these 2 principles requires weighing the burdens of a specific health intervention against the potential benefits. The community of patients with end-organ disease may benefit from allowing donation from patients with a history of malignancy, thereby increasing the pool of available organs. However, the principle of nonmaleficence constrains this aggregate benefit by holding that the primary duty of the health care provider is to avoid harming the individual patient. For certain types of donor-derived malignancy, such as melanoma, the risk of transmission to the transplant recipient almost certainly outweighs the benefits of the transplantation. Another source of debate in the pretransplantation evaluation and organ procurement process is the role of general anesthesia in the deceased donor. For donation after circulatory death, some have considered general anesthesia unnecessary given that the donor is deceased and therefore cannot be suffering. In addition, the presence of an anesthesiologist and administration of anesthesia may lead the family to misperceive that the donor is not actually dead.10
Recommendations for transplant
Proceed Avoid Avoid Proceed based on clinical factors (ie, localization, size, and excision potential) Proceed if localized; Gleason score #3
However, general anesthesia is often administered to the brain-dead donor for its physiologic effects on organ perfusion. Here, the end goal is to maintain and preserve physiologic function of organs to ensure successful transplantation.11 In dermatology, local anesthetics are primarily used to maintain comfort and hemostasis during procedures. No guidelines currently exist regarding their use in patients who have been declared dead. Local anesthetics may be considered for the practical benefit of epinephrine for hemostasis, analogous to the use of general anesthetics for preservation of organ function. From a bioethical standpoint, the use of local anesthetics may also create an environment that builds trust among the family of the deceased, ensuring that the procedure is carried out in accordance with standard practices of care. However, the dermatologist must be forthright with the family that use of a local anesthetic does not mean that the donor is still alive. Determining a history of malignancy or current malignancy poses a major challenge in assessment of the imminent donor.5 Overall, guidelines for cancer screening in brain-dead organ donors are limited. The evaluation of skin-related malignancies in the imminent donor warrants a total body skin examination, with particular attention to excision scars.12 Here, the dermatologist may be involved through direct consultation, the use of photographs, or through education of transplant coordinators regarding the appropriate evaluation of pigmented lesions. The presence of excision scars alone should not preclude candidacy for organ donation. The scar may represent a previous melanoma, in which case organ transplantation is contraindicated, but alternatively may represent a nonmelanoma skin cancer, in which case the risk of transmission from donor to recipient is minimal. Assessment should note the length of the scar, skin grafting, and axillary nodal dissection scars, which may be more indicative of melanoma. The acquisition of a pathology report—while often the most valuable resource—is
1064 Murthy, Chisolm, and Stoff
not always feasible given the limited time duration to organ procurement. Thorough gross examination of the body cavity and donated organs during procurement has also been suggested.5 A screening protocol has been proposed to evaluate brain-dead donors for an undiagnosed malignancy deriving from 4 common sites: the breasts, lungs, prostate, and colon.2 The protocol seeks to determine the level of risk for malignancy in a given donor. For example, heavy smokers (or donors with heavily smoking spouses) between 55
ANALYSIS OF CASE SCENARIO Option A is not an ideal choice. While there is debate regarding the moral status of a brain-dead organ donor, melanoma is considered a limiting factor for potential organ donation. Analogous to the standard in other fields of medicine, it is appropriate for dermatologists to take part in the evaluation of donors to ensure that harm to the organ recipient is as limited as possible. Option B could be an acceptable choice if the lesion is not suspicious for malignancy. However, if there is clinical suspicion, obtaining a biopsy specimen should be considered, consistent with the approach of other specialists in evaluation of malignancy deriving from other organs. A major limitation to obtaining a biopsy specimen in this setting may be the time required for processing and interpretation of the specimen. This may require frozen section evaluation, which is suboptimal for melanocytic lesions, but in many cases may be preferable to a clinical diagnosis alone. Option C addresses the ongoing debate about the use of anesthetics in organ donors who have been declared dead. The use of local anesthesia with epinephrine in this context is consistent
BOTTOM LINE Organ transplantation for end-organ disease requires a thorough assessment of the risks and benefits of the procedure to the organ recipient and a respectful approach to the donor and the donor’s family. The fundamental bioethical principles of nonmaleficence and beneficence are considered when determining whether the risk of transmission of a donor-derived malignancy in an organ recipient outweighs the benefit of receipt of the donated organ. Donor-derived melanoma has been documented and tends to follow an aggressive course. To guard
J AM ACAD DERMATOL
DECEMBER 2015
and 75 years of age were recommended to undergo screening with a helical computed tomography scan. For breast cancer, recommendations include breast ultrasonography for females [50 years of age who have not had a mammogram within the past 2 years, with further recommendations to obtain a biopsy specimen from any suspicious lesion. To our knowledge, there are no similar recommendations or guidelines regarding the screening of suspicious skin lesions in brain-dead potential organ donors.
with the use of general anesthesia during vital organ procurement, where anesthesia is administered for physiologic purposes. From a bioethical perspective, the use of local anesthesia could be justified by helping to build trust with the family by showing respect for the donor. On the contrary, the use of anesthesia in a donor who has been declared dead may send the false message to the family that the donor is not dead, as previous authors have suggested. Therefore, it is imperative to convey to the family that the use of anesthesia is to ensure that the procedure is performed in a standard fashion and to create an environment that is respectful of the dead donor—not to imply that the donor is alive. Option D is a reasonable choice. The use of local anesthesia with epinephrine would improve hemostasis, as stated above. In addition, it shows respect for and builds trust with the donor’s family by ensuring that the procedure is carried out in a standard fashion. However, the use of anesthesia could also convey that the donor is not dead, and therefore could potentially experience harm or suffering from the procedure.
against this possibility, additional donor screening guidelines are needed. Dermatologists should develop screening protocols for the evaluation of brain-dead organ donors that are analogous to those used within other specialties. These protocols might include additional screening for patients who have not had a total body skin examination within a certain amount of time (eg, the past year) or for those who have a strong family history of melanoma. Such screening tools would be similar to the guidelines proposed for breast cancer screening in imminent organ donors with significant risk factors. If appropriate, dermatologists or other providers may
J AM ACAD DERMATOL VOLUME 73, NUMBER 6
consider obtaining skin biopsy specimens from brain-dead donors in a manner similar to other medical specialties. It is standard for the transplant organization that requested the dermatology consultation to cover the costs associated with the skin examination, skin biopsy, and pathology evaluation. Clearly, tissue processing and interpretation in a manner timely enough for the transplant may pose challenges. Ultimately, however, these efforts should ensure that harm to the recipient is as limited as possible. REFERENCES 1. Rodriguez-Arias D, Smith MJ, Lazar NM. Donation after circulatory death: burying the dead donor rule. Am J Bioeth. 2011;11:36-43. 2. Hassanain M. Novel guidelines for organ donor cancer screening. Ann Transplant. 2014;19:241-247. 3. Kirk A, Knechtle S, Larsen C, Madsen J, Pearson T, Webber S. Textbook of organ transplantation. Oxford: John Wiley & Sons, Ltd; 2014:1139.
Murthy, Chisolm, and Stoff 1065
4. Doerfler A, Tillou X, Le Gal S, Desmonts A, Orczyk C, Bensadoun H. Prostate cancer in deceased organ donors: a review. Transplant Rev. 2014;28(1):1-5. 5. Buell JF, Alloway RR, Woodle S. How can donors with a previous malignancy be evaluated? J Hepatol. 2006;45:503-507. 6. Buell JF, Beebe TM, Trofe J, et al. Donor transmitted malignancies. Ann Transplant. 2004;9:53-56. 7. Strauss DC, Thomas JM. Transmission of donor melanoma by organ transplantation. Lancet Oncol. 2010;11:790-796. 8. Giessing M. Donors with malignancies—risk or chance? Transplant Proc. 2012;44:1782-1785. 9. Beauchamp TL, Childress JF. Principles of biomedical ethics. 6th ed. New York: Oxford University Press; 2009:288-310. 10. Van Norman G. Another matter of life and death: what every anesthesiologist should know about the ethical, legal, and policy implications of the non-heart-beating cadaver organ donor. Anesthesiology. 2003;98:763-773. 11. Anderson TA, Bekker P, Vagefi PA. Anesthetic considerations in organ procurement surgery: a narrative review. Can J Anesth. 2015;62:529-539. 12. Zwald FO, Christenson LJ, Billingsly EM, et al. Melanoma in solid organ transplant recipients. Am J Transplant. 2010;10:1297-1304.
