2. You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from brain tumour; the radiologist suggested that it is most likely primary tumour. No histological diagnosis available at the time of retrieval also, no evidence of primary tumours elsewhere to suggest cerebral metastasis. Her baseline S Cr was 60 µmol/L and 71 µmol/L just before retrieval. She had excellent urine output (120mls/h during the last hour and 3.5 L over the last 24 hours).
- Would you accept this donor?
- If yes, what is the prognosis?
Dear All
It would be helpful if we could have a histological diagnosis, but imaging of the brain is very advanced these days. We can rely on it, but also we need to discuss it with the potential recipient if you decided to go ahead and accept this donor.
Dear Prof,
*Half of this scenerio’s answer is the role of neuroradiology in diagnosing and differentiating DBD brain tumors and prognosis
*Many donors with primary brain tumours have a diagnosis based on imaging characteristics alone. While in some cases it is possible to obtain a rapid histological examination of the brain immediately after retrieval, in many cases that is not possible.
*In such circumstances it is advisable to review the radiological images with an experienced neuroradiologist to look for pathognomonic appearances of a primary brain tumour, remembering that half of all intracranial cancers are secondaries.
*The risk associated with using organs from donors with a radiological diagnosis alone which must be interpreted by an expert neuroradiologist, is likely to be higher than in cases where the diagnosis has been confirmed histologically.
According to the Council of Europe guidelines: Donors with primary CNS tumors have historically been regarded as suitable, but cumulative data suggesting that aggressive interventions (craniotomy and ventricular shunting) and/or unfavorable histology (glioblastoma and medulloblastoma) may pose a prohibitive transmission risk.
*Primary tumors of CNS represent 3-4% of the causes of brain death of organ donors.Although CNS tumors rarely develop extracranial metastases,these have been described in 0.4-2.3% of cases.
According to the literature, the risk factors for transmission of primary CNS tumors are:
– High-grade malignancy tumors;
– The presence of ventriculo-peritoneal or ventriculo-
atrial derivations
– Previous chemotherapy
– Previous radiotherapy
– Previous craniotomy
– Duration of disease may also be important
Prognosis:
*The Australian and New Zealand Registry reported 46/1.781 donors with primary brain tumor providing 153 organs.Of these donors,there were eight with a high-grade glioma and five with a medulloblastoma.They reported no cases of donor-derived malignancy at mean follow-up of 40 months .
*According to the UNOS registry review from 2002 of 397 donors with a history of primary CNS tumors, from whom 1220 organs were transplanted and after the followup of 36 months, no tumor transmission to the recipient was observed.
*Israel Penn International Tumor Registry (USA) states that, when there are no risk factors (listed above) the rate of transmission from donors with primary CNS tumors to organs recipients is 7%. If 2 risk factors are present, the rate of transmission to recipients rises to 36-43%.
*Based on a UK review of 448 recipients of organs from 177 donors with primary CNS tumours without any evidence of tumour transmission , recommendations for the use of organs from potential donors with CNS tumours were published . The data were obtained by reviewing the outcomes of 246 UK recipients of organs from donors with CNS tumours.It was concluded that use of kidneys from such donors was associated with a gain of eight life-years compared to waiting for another offer.
i will accept this donor even if grade 4 brain tumor by the neuroradiology ,as there is no evidence of ICH , shunt , sugery , or other risk factors increasing the risk for transmission so yes i will accept this donor after discussing everything with our recipient.
References:
1. Desai, R., D. Collett, C.J. Watson, et al., Cancer transmission from organ donors- unavoidable but low risk. Transplantation 2012; 94(12): p. 1200-7.
2. NHS Blood and Transplant and British Transplantation Society NHSBT BTS Responsibilities of clinicians for the acceptance of organs from deceased donors. 2012.
3. European Directorate for the Quality of Medicines and Healthcare, Guide to the Quality and Safety of Organs for Transplantation. 7th ed. 2018, Strasbourg: Council of Europe.
4. Nalesnik, M.A., E.S. Woodle, J.M. Dimaio, et al., Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. American Journal of Transplantation 2011; 11(6): p. 1140-7.
5. Watson, C.J.E., R. Roberts, K.A. Wright, et al., How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK Registry data. American Journal of Transplantation 2010; 10(6): p. 1437-44.
6. Warrens, A.N., R. Birch, D. Collett, et al., Advising potential recipients on the use of organsfrom donors with primary central nervous system tumors. Transplantation 2012; 93(4): p. 348-53.
7. Desai, R., D. Collett, C.J. Watson, et al., Estimated risk of cancer transmission from organ donor to graft recipient in a national transplantation registry. British Journal of Surgery 2014; 101(7): p. 768-74.
8. Fiaschetti, P., R. Pretagostini, D. Stabile, et al., The use of neoplastic donors to increase the donor pool. Transplantation Proceedings 2012; 44(7): p. 1848-50.
Thank you, Mohamed
Excellent answer and review of the literature. Well done
Thank you so much dear Professor
I would echo what Prof Halawa states about this short review dear Dr Essmat. However, I may not accept a kidney if a neuro-radiologist suggests this as grade 4 in UK. I am not trying to pass judgement about similar donor in a health-care system where the dialysis access is desperate and is life-threatening or dialysis not available at all.
Ajay
● 59 male donor with primary brain tumor without metastasis with excellent kidney function and urine output
This donor is considered low risk donor so ● I will accept him after I assesst his medical history and the treatment he underwent
● Surely I should counseled the recipiant regarding the small but definite risk of transmission, as well as his chance of survival if he chooses to remain on the waiting list
● the brognosis is good and the risk transmission is very low
Thank you, Huda
Reference, please!!!!
thanks prof
been primary tumour with no evident of distal metasis the risk will be small to moderate a though first ineed neurologist opinion to elaborate more information help in the decision and finally explain the hall situation for the recipient to be involve in the decision.
I will accept this donor with good kidney function and good UOP
The risk of transmission is very rare.
With close follow up
With the advancement of neuroimaging especially using microstructure imaging, neuroradilogists could give an accurate diagnosis of the brain lesions. Microstructure MRI characterizes tissue preoperatively in situ and provides images of the whole tumour rather than of a few biopsy samples and, as such, it can avoid mistakes from inadequately targeted biopsy. It may also improve diagnosis by guiding the biopsy and might even replace a biopsy in situations where these are too risky.
So we could accept this donor based on radiological evaluation as well as histopathological evaluation would be time consuming or unavailable
reference:
Nilsson M, Englund E, Szczepankiewicz F, van Westen D, Sundgren PC. Imaging brain tumour microstructure. Neuroimage [Internet]. 2018;182(May):232–50. Available from: https://doi.org/10.1016/j.neuroimage.2018.04.075
i will accept this donor but will.
taking in account that the radiologist is well skilled and no metastasis
Would you accept this donor?
The potential donor is a 59 year old male , with primary brain tumor , but no histological biopsy or other primary source or metastasis. As well as normal KFTs and Urine output.
Risk factors for extraneural spread are : V/A shunts , previous chemo or radio , stereotactic biopsy , long duration between diagnosis and death , Crainiotomy history .
If yes, what is the prognosis?
Yes , we shall proceed with the transplantation, due to the absence of risk factors associated with extra neural spread , so the outcome is relatively good with remote possibility for acquiring malignancy post Tx .
I will accept this 59 year potential donor despite no histological diagnosis after
References:
1) Watson CJ, Roberts R, Wright KA, Greenberg DC, Rous BA, Brown CH, Counter C, Collett D, Bradley JA. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK Registry data. Am J Transplant. 2010 Jun;10(6):1437-44. doi: 10.1111/j.1600-6143.2010.03130.x. Epub 2010 May 10. PMID: 20486904
To answer this we need the histological classification of this brain tumor. Having that we can then apply the following guidelines:
1- Group 1 : Tumors that are not a contraindication to multiple organ donation
Includes: Benign meningioma, Acoustic neuroma, Pituitary adenoma, Craniopharyngioma, Pilocytic astrocytoma (Grade I), Epidermoid cyst, Third ventricle choroid plexus cyst, Choroid plexus papilloma, Hemangioblastoma, Ganglion cell tumor, Pineocytoma, Low-grade oligodendroglioma (Schmidt A and B), Ependymoma, Well-differentiated teratoma
2- Group 2: Tumors that might not be a contraindication to donation according to circumstances
Includes : Low-grade astrocytoma (Grade II) and Gliomatosis cerebri
3- Group 3:Tumors that are not a contraindication to multiple organ donation
Includes: Anaplastic astrocytoma (Grade III), Glioblastoma multiforme, Medulloblastoma, Anaplastic oligodendroglioma (Schmidt C and D), Malignant ependymoma, Pineoblastoma, Anaplastic and malignant meningioma, Intracranial sarcoma, Germ cell tumor (except for well-differentiated teratoma), Chordoma and Primary lymphoma of the brain(1)
As long as there is no possibility of obtaining the histopathology, we can proceed with high risk consent.
From the transplantation perspective, the critical question is to what extent do occult metastatic glioma cells exist either in the circulation or in transplantable organs that can give rise to systemic glioma in immunosuppressed organ recipients. There are two primary sources of information regarding the risk of transmission of primary CNS malignancy through organ transplantation: individual case reports and registry data. Unfortunately, both of these data sources are likely incomplete in either the numerator and/or the denominator, resulting in under- or over-estimation of transmission risk. When reviewing the data in toto, one must remember that practice has definitely evolved over time. For example, it is well-known that organs from donors with active cancer and even organs with locally excised tumor were transplanted in the early days of transplantation. The high rate of transmission to recipients with resultant morbidity and even mortality changed practice dramatically, engendering our current cautious approach to donors with cancer. Although donors with primary CNS tumors have historically been regarded as suitable, cumulative data suggesting that aggressive interventions (craniotomy and ventricular shunting) and/or unfavorable histology (GBM and medulloblastoma) may pose a prohibitive transmission risk has refined our practice over time.The published data demonstrating the risk of glioma transmission to organ recipients are sparse. From 1987 to the present, the literature has eight case reports of CNS cancer transmission involving seven donors (GBM = five; medulloblastoma = one; malignant meningioma = one; 5–12). Twenty organs were transplanted into 19 recipients (one recipient underwent simultaneous kidney-pancreas transplantation). Eleven recipients developed donor-transmitted cancer with five tumor-associated deaths. Notably, all liver (n = 3) and heart (n = 1) recipients with evidence of donor-transmitted cancer died. The other reported death was the kidney-pancreas recipient. All six survivors were kidney recipients who underwent nephrectomy with cessation of immunosuppression. Among these donors, five had GBM, corresponding to 15 transplanted organs (three livers, 10 kidneys, and two hearts) with seven cases of GBM transmission (three liver and four kidney recipients). All three liver recipients died while all four kidney recipients remain alive after nephrectomy and cessation of immunosuppression. Case reports comprise the numerator; unfortunately, the relevant denominator is entirely unknown.Three registries have recently provided data regarding cancer transmission from organ donors with primary CNS tumors. In 2002, the United Network for Organ Sharing (UNOS) Transplant Tumor Registry reported on 397 donors (1/1/92–12/31/99) with history of CNS tumor or CNS tumor listed as the cause of death . Unfortunately, histologic diagnosis was available for only 30 of these donors (7.5%); 17 donors had GBM and two had medulloblastoma. No case of donor-transmitted tumor was identified in the 1220 recipients with mean follow up of 36 months (range 0–111 months) . In 1999, the Australian and New Zealand Organ Donation Registry reported on 46 donors with primary CNS tumors (1/89 12/96) of whom 28 had malignant tumors (four unspecified glioma, four GBM, 10 unspecified astrocytoma, five medulloblastoma, one malignant meningioma and four unspecified tumors) . None of 151 recipients with mean follow up of 40 months (range 1–96 months) demonstrated evidence of donor tumor transmission. In 1997, however, the Israel Penn International Transplant Tumor Registry (IPITTR) reported on 46 donors (1969–97) with primary CNS tumors with very different results . Eight donors transmitted tumor to 10 of 55 possible recipients for an incidence of nearly 18%. The reason for this apparent discrepancy is unclear but the broad timespan of the IPITTR data compared with that reported by the other two registries may explain the substantially different risk attributed to transplantation of organs from donors with primary CNS malignancy.(2)
From January 1, 2005 to December 31, 2014, 28 donors with CNS tumor and 91 recipients who received solid organs from these donors were included. Twenty one donors were categorized into four histologic grades by WHO except 7 donors who has no detailed report of CNS tumor classification. Among them, 11 donors were grouped in grade I tumor (52.4%), and 3 were in group II(14.3%), 4 in grade III(19.0%) and 3 in grade IV(14.3%). According to high risk categories defined by the malignancy subcommittee of DTAC committee, intracranial surgery were done in 11 donors, chemo-radiotherapy in 2 patients, and 3 patients had chemo-radiotherapy after surgery. Therefore, 76.2% of those donors were in the high risk category. A total of 91 transplants (25 livers, 52 kidneys, 7 hearts, 3 lungs, and 4 multi-organ transplants) were performed from donors with CNS tumors, and 85 recipients were finally analyzed after excluding 6 recipients whose current status were not confirmed. Of the 85 recipients, 14 were dead, of which 11 recipients were not associated with brain tumor as a death cause, and remaining 3 recipients, causes of death were unable to identify. However, there were 7 recipients who developed tumor after transplantation. One of them had recurred original recipient tumor (HCC) and remained 6 patients were diagnosed as non-CNS tumor (renal cell carcinoma, carcinoma in situ of cervix, B cell lymphoma, thyroid ca., kaposi’s sarcoma and colon ca). Even though the possibility of tumor transmission from donor with CNS tumor is rare, we still have to focus de novo malignancy incidence after transplantation. (3)
a population-based cohort study in NSW of all potential donors 2010–2015. Included 2957 potential donors, 76 (3%) had primary brain tumours (PBTs). There was agreement of risk assessment in 44 (58%) cases. PBT potential donors had fewer comorbidities (1.6 vs. 2.1, P = 0.006) than non-PBT potential donors. Forty-eight (63%) potential donors were declined for non-PBT reasons, 18 (24%) were declined because of perceived PBT transmission risk and 10 (13%) donated. All PBT donors had WHO-I or -II tumours, and none had a ventriculo-pertioneal shunt. No transmission events occurred. Donors with WHO-I/II PBT appear to have minimal risk of tumour transmission in solid organ transplantation; it is reassuring that no PBT transmission occurred. There is evidence of risk aversion to referrals with WHO-III/IV tumours. There exists an opportunity to improve potential donor risk assessment at the time of referral using integrated data sets, and to increase organ donation and transplantation rates through greater utilization of PBT referrals.(4)
1- Westphal GA, Garcia VD, Souza RL, Franke CA, Vieira KD, Birckholz VR, Machado MC, Almeida ER, Machado FO, Sardinha LA, Wanzuita R, Silvado CE, Costa G, Braatz V, Caldeira Filho M, Furtado R, Tannous LA, Albuquerque AG, Abdala E; Associação de Medicina Intensiva Brasileira; Associação Brasileira de Transplante de Órgãos. Guidelines for the assessment and acceptance of potential brain-dead organ donors. Rev Bras Ter Intensiva. 2016 Sep;28(3):220-255. doi: 10.5935/0103-507X.20160049. PMID: 27737418;
2- Collignon, F.P., Holland, E.C. and Feng, S. (2004), Organ Donors with Malignant Gliomas: An Update. American Journal of Transplantation, 4: 15-21. https://doi.org/10.1046/j.1600-6143.2003.00289.x
3- Lee, Misung1; Oh, Jaesook1; Bok, Chunhee1; Ha, Jongwon2; Cho, Wonhyun1, Is It Safe to Transplant Organs from Deceased Donors with CNS Tumor? ransplantation 101():p S100, August 2017. | DOI: 10.1097/01.tp.0000525133.84684.b5
4- Thomson, I.K., Hedley, J., Rosales, B.M., Wyburn, K., O’Leary, M.J. and Webster, A.C. (2022), Potential organ donors with primary brain tumours: missed opportunities for donation and transplantation identified in Australian cohort study 2010–2015. ANZ Journal of Surgery, 92: 2996-3003. https://doi.org/10.1111/ans.18037
Organs from donors with CNS tumors can be used with a low risk of donor tumor transmission in the absence of the following risk factors: high-grade tumors, ventriculoperitoneal or ventriculoatrial shunts, prior craniotomy, and systemic chemotherapy.
A histological diagnosis should be obtained where possible. Generally, the radiological diagnosis of meningeal tumors and tumors of cranial and paraspinal nerves is reliable.
Information from UK Transplant Registry on organ donors between 1985 and 2001 inclusive with primary intracranial tumors to identify risk of transmission to recipients
Of 11 799 organ donors in the study period, 179 were identified as having had a primary intracranial malignancy, including 33 with high-grade malignancy (24 grade IV gliomas and 9 medulloblastomas). A total of 448 recipients of 495 organs from 177 of these donors were identified. No transmission of donor intracranial malignancy occurred.
Other smaller series from transplant registries suggested that the risk of transmission of donor intracranial cancer is small, although the numbers of high-risk donors reported, such as those with GBM or medulloblastoma, were very small. The Australia and New Zealand registry reported no cases of transmission in 96 recipients of organs from 28 donors with malignant primary brain tumors (4 with GBM and 5 medulloblastoma), including 10 with previous craniotomy of whom 3 had ventriculo-peritoneal shunts, and 3 others with VP shunts without craniotomy.
Accordingly , the risk of transmission is less than the risk of death in waiting list
I will accept him
Warrens, Anthony N.etal. Advising Potential Recipients on the Use of Organs From Donors With Primary Central Nervous System Tumors. Transplantation 93(4):p 348-353, February 27, 2012.
Watson CJ, Roberts R, Wright KA, et al. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK Registry data. Am J Transplant. 2010 Jun;10(6):1437-44.
To answer this we need the histological classification of this brain tumor. Having that we can then apply the following guidelines:
1- Group 1 : Tumors that are not a contraindication to multiple organ donation
Includes: Benign meningioma, Acoustic neuroma, Pituitary adenoma, Craniopharyngioma, Pilocytic astrocytoma (Grade I), Epidermoid cyst, Third ventricle choroid plexus cyst, Choroid plexus papilloma, Hemangioblastoma, Ganglion cell tumor, Pineocytoma, Low-grade oligodendroglioma (Schmidt A and B), Ependymoma, Well-differentiated teratoma
2- Group 2: Tumors that might not be a contraindication to donation according to circumstances
Includes : Low-grade astrocytoma (Grade II) and Gliomatosis cerebri
3- Group 3:Tumors that are not a contraindication to multiple organ donation
Includes: Anaplastic astrocytoma (Grade III), Glioblastoma multiforme, Medulloblastoma, Anaplastic oligodendroglioma (Schmidt C and D), Malignant ependymoma, Pineoblastoma, Anaplastic and malignant meningioma, Intracranial sarcoma, Germ cell tumor (except for well-differentiated teratoma), Chordoma and Primary lymphoma of the brain(1)
As long as there is no possibility of obtaining the histopathology, we can proceed with high risk consent.
From the transplantation perspective, the critical question is to what extent do occult metastatic glioma cells exist either in the circulation or in transplantable organs that can give rise to systemic glioma in immunosuppressed organ recipients. There are two primary sources of information regarding the risk of transmission of primary CNS malignancy through organ transplantation: individual case reports and registry data. Unfortunately, both of these data sources are likely incomplete in either the numerator and/or the denominator, resulting in under- or over-estimation of transmission risk. When reviewing the data in toto, one must remember that practice has definitely evolved over time. For example, it is well-known that organs from donors with active cancer and even organs with locally excised tumor were transplanted in the early days of transplantation. The high rate of transmission to recipients with resultant morbidity and even mortality changed practice dramatically, engendering our current cautious approach to donors with cancer. Although donors with primary CNS tumors have historically been regarded as suitable, cumulative data suggesting that aggressive interventions (craniotomy and ventricular shunting) and/or unfavorable histology (GBM and medulloblastoma) may pose a prohibitive transmission risk has refined our practice over time.The published data demonstrating the risk of glioma transmission to organ recipients are sparse. From 1987 to the present, the literature has eight case reports of CNS cancer transmission involving seven donors (GBM = five; medulloblastoma = one; malignant meningioma = one; 5–12). Twenty organs were transplanted into 19 recipients (one recipient underwent simultaneous kidney-pancreas transplantation). Eleven recipients developed donor-transmitted cancer with five tumor-associated deaths. Notably, all liver (n = 3) and heart (n = 1) recipients with evidence of donor-transmitted cancer died. The other reported death was the kidney-pancreas recipient. All six survivors were kidney recipients who underwent nephrectomy with cessation of immunosuppression. Among these donors, five had GBM, corresponding to 15 transplanted organs (three livers, 10 kidneys, and two hearts) with seven cases of GBM transmission (three liver and four kidney recipients). All three liver recipients died while all four kidney recipients remain alive after nephrectomy and cessation of immunosuppression. Case reports comprise the numerator; unfortunately, the relevant denominator is entirely unknown.Three registries have recently provided data regarding cancer transmission from organ donors with primary CNS tumors. In 2002, the United Network for Organ Sharing (UNOS) Transplant Tumor Registry reported on 397 donors (1/1/92–12/31/99) with history of CNS tumor or CNS tumor listed as the cause of death . Unfortunately, histologic diagnosis was available for only 30 of these donors (7.5%); 17 donors had GBM and two had medulloblastoma. No case of donor-transmitted tumor was identified in the 1220 recipients with mean follow up of 36 months (range 0–111 months) . In 1999, the Australian and New Zealand Organ Donation Registry reported on 46 donors with primary CNS tumors (1/89 12/96) of whom 28 had malignant tumors (four unspecified glioma, four GBM, 10 unspecified astrocytoma, five medulloblastoma, one malignant meningioma and four unspecified tumors) . None of 151 recipients with mean follow up of 40 months (range 1–96 months) demonstrated evidence of donor tumor transmission. In 1997, however, the Israel Penn International Transplant Tumor Registry (IPITTR) reported on 46 donors (1969–97) with primary CNS tumors with very different results . Eight donors transmitted tumor to 10 of 55 possible recipients for an incidence of nearly 18%. The reason for this apparent discrepancy is unclear but the broad timespan of the IPITTR data compared with that reported by the other two registries may explain the substantially different risk attributed to transplantation of organs from donors with primary CNS malignancy.(2)
From January 1, 2005 to December 31, 2014, 28 donors with CNS tumor and 91 recipients who received solid organs from these donors were included. Twenty one donors were categorized into four histologic grades by WHO except 7 donors who has no detailed report of CNS tumor classification. Among them, 11 donors were grouped in grade I tumor (52.4%), and 3 were in group II(14.3%), 4 in grade III(19.0%) and 3 in grade IV(14.3%). According to high risk categories defined by the malignancy subcommittee of DTAC committee, intracranial surgery were done in 11 donors, chemo-radiotherapy in 2 patients, and 3 patients had chemo-radiotherapy after surgery. Therefore, 76.2% of those donors were in the high risk category. A total of 91 transplants (25 livers, 52 kidneys, 7 hearts, 3 lungs, and 4 multi-organ transplants) were performed from donors with CNS tumors, and 85 recipients were finally analyzed after excluding 6 recipients whose current status were not confirmed. Of the 85 recipients, 14 were dead, of which 11 recipients were not associated with brain tumor as a death cause, and remaining 3 recipients, causes of death were unable to identify. However, there were 7 recipients who developed tumor after transplantation. One of them had recurred original recipient tumor (HCC) and remained 6 patients were diagnosed as non-CNS tumor (renal cell carcinoma, carcinoma in situ of cervix, B cell lymphoma, thyroid ca., kaposi’s sarcoma and colon ca). Even though the possibility of tumor transmission from donor with CNS tumor is rare, we still have to focus de novo malignancy incidence after transplantation. (3)
a population-based cohort study in NSW of all potential donors 2010–2015. Included 2957 potential donors, 76 (3%) had primary brain tumours (PBTs). There was agreement of risk assessment in 44 (58%) cases. PBT potential donors had fewer comorbidities (1.6 vs. 2.1, P = 0.006) than non-PBT potential donors. Forty-eight (63%) potential donors were declined for non-PBT reasons, 18 (24%) were declined because of perceived PBT transmission risk and 10 (13%) donated. All PBT donors had WHO-I or -II tumours, and none had a ventriculo-pertioneal shunt. No transmission events occurred. Donors with WHO-I/II PBT appear to have minimal risk of tumour transmission in solid organ transplantation; it is reassuring that no PBT transmission occurred. There is evidence of risk aversion to referrals with WHO-III/IV tumours. There exists an opportunity to improve potential donor risk assessment at the time of referral using integrated data sets, and to increase organ donation and transplantation rates through greater utilization of PBT referrals.(4)
1- Westphal GA, Garcia VD, Souza RL, Franke CA, Vieira KD, Birckholz VR, Machado MC, Almeida ER, Machado FO, Sardinha LA, Wanzuita R, Silvado CE, Costa G, Braatz V, Caldeira Filho M, Furtado R, Tannous LA, Albuquerque AG, Abdala E; Associação de Medicina Intensiva Brasileira; Associação Brasileira de Transplante de Órgãos. Guidelines for the assessment and acceptance of potential brain-dead organ donors. Rev Bras Ter Intensiva. 2016 Sep;28(3):220-255. doi: 10.5935/0103-507X.20160049. PMID: 27737418;
2- Collignon, F.P., Holland, E.C. and Feng, S. (2004), Organ Donors with Malignant Gliomas: An Update. American Journal of Transplantation, 4: 15-21. https://doi.org/10.1046/j.1600-6143.2003.00289.x
3- Lee, Misung1; Oh, Jaesook1; Bok, Chunhee1; Ha, Jongwon2; Cho, Wonhyun1, Is It Safe to Transplant Organs from Deceased Donors with CNS Tumor? ransplantation 101():p S100, August 2017. | DOI: 10.1097/01.tp.0000525133.84684.b5
4- Thomson, I.K., Hedley, J., Rosales, B.M., Wyburn, K., O’Leary, M.J. and Webster, A.C. (2022), Potential organ donors with primary brain tumours: missed opportunities for donation and transplantation identified in Australian cohort study 2010–2015. ANZ Journal of Surgery, 92: 2996-3003. https://doi.org/10.1111/ans.18037
This a deceased donor with most likely primary CNS tumour with good kidney function and good urine out put
I will accept this donor
the prognosis will be good because this type of tumour had low tendency to recurrent
Would you accept this donor?
I would accept this donation offer.
in real practice; this is an offer that can be accepted and rejected depending on the balance between risks and benefits for the recipient as it is a deceased donor.
Pre-transplantation counselling is very important between the transplant team and the potential recipients.
A deceased donor with grade IV CNS malignant tumor having had a ventriculo-atrial shunt 3 months ago raises the question about transmission to the recipients.
Primary CNS malignancies are low risk of metastasis and risk of transmission to recipients ranges from 0-23% based on few numbers of retrospective observational studies.
The transmission risk factors include the following:
1- High grade tumors especially glioblastomas and medulloblastoma.
2- Systemic chemotherapy.
3- Previous craniotomy, V-A shunt or V-P shunt which disrupt blood brain barrier.
In presence of multiple risk factors the risk of transmission may increase to 53% from 7%. Another study had reported no transmission of donor malignancy in all 33 cases with high grade gliomas and medulloblastoma and in all other 146 cases of other primary intra-cranial malignancy.
If yes, what is the prognosis?
Prognosis depends on many factors, there no difference between graft and patient survival unless there is metstasis.
REFERENCES
1. Kotloff RM, Blosser S, Fulda GJ, et al. Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med 2015; 43:1291.
2. Buell JF, Trofe J, Sethuraman G, et al. Donors with central nervous system malignancies: are they truly safe? Transplantation 2003; 76:340.
Two absolute contraindication for donation in a patient with
CNS tumors are primary cerebral lymphoma and all secondary
intracranial tumors.
In this donor primary CNS lymphoma could be ruled out by
imaging on the other hand, there is no metastasis, his tumor will
be low grade. Low grade CNS tumors have low risk of
transmission (less than 2%)
So, he could be a potential donor.
Prognosis:
According to UK registry of 448 recipients from 177 donors
with intracranial malignancy no transmission of malignancy
occurred.
So, the prognosis for this transplantation would be good enough.
Warrens AN, Birch R, Collett D, Daraktchiev M, Dark JH, Galea G, Gronow K, Neuberger J, Hilton D, Whittle IR, Watson CJ; Advisory Committee on the Safety of Blood, Tissues and Organs, UK. Advising potential recipients on the use of organs from donors with primary central nervous system tumors. Transplantation. 2012 Feb 27;93(4):348-53.
Kumar S, Modi PR, Pal BC, Modi J. Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation? Indian J Urol. 2016 Jan-Mar;32(1):74-6. doi: 10.4103/0970-1591.173104.
Watson CJ, Roberts R, Wright KA, Greenberg DC, Rous BA, Brown CH, Counter C, Collett D, Bradley JA. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK Registry data. Am J Transplant. 2010 Jun;10(6):1437-44
I will accept this donor, the risk of transmission is vey low especially in the absence of blood brain barrier disruption, no history of chemotherapy or radiotherapy, on the other hand, the benefits from transplantation are much higher than remaining on dialysis waiting for a better offer with a better quality of life and improved patient survival.
Warrens AN, Birch R, Collett D, Daraktchiev M, Dark JH, Galea G, Gronow K, Neuberger J, Hilton D, Whittle IR, Watson CJ. Advising potential recipients on the use of organs from donors with primary central nervous system tumors. Transplantation. 2012 Feb 27;93(4):348-53.
This 59 year old DBD, with excellent renal functions, imaging suggestive of primary brain tumour, without evidence of distant metastasis can be accepted for donation according to the advice of Council of Europe in 1997, it is considered safe for transplantation as in primary brain tumors ,with low grade malignancy ,no basement membrane disruption or distant extraneural metastasis ,with no suggestive history of interventions as craniotomy ,shunts ,chemotherapy or radiotherapy .prior to proceeding for donation expert opinion of neuroradiology personnel is necessary as well as recipient counselling regarding the minimal risk of disease transmission must be explained.
The prognosis is actually better compared to the maintenance on the waiting list for donation due to organ shortage, as well as better than maintenance on the dialytic support with its known disadvantages. In addition to the better quality of life achieved after transplantation.
Reference:
American Journal of Transplantation 2010; doi: 10.1111/j.1600-6143.2010.03130.x
I will accept this donation.
CNS malignancies in the potential kidney transplant donor
Kidney transplant is the best treatment for ESRD patients. the main problem is donor shortage and to solve this problem potential donors who were diagnosed with CNS malignancies were studied to evaluate the safety of accepting solid organs from such donors. Generally, CNS malignancies have a low risk of metastasis, and the overall risk of transmission ranges from 0-23% (1). but this risk (based on the available weak evidence) increases up to 53% in a high-risk patient in which BBB was compromised like
As mentioned before the evidence is weak and there is a retrospective study evaluating the results of 179 deceased donors with primary intracranial malignancy in this study 33 included donors were high risks donors (24 grade IV gliomas and 9 medulloblastomas) and the results showed no malignancy transmission in all cases that why more studies are needed.
Also, we should consider that half of all intracranial cancers are secondaries that why a radiological diagnosis alone even when interpreted by an expert neuroradiologist will be associated with higher errors than those whose diagnosis has been confirmed histologically.
Based on the available evidence, I will accept this donor with low-risk factors of transmission after reviewing the images with the expert radiologist, histological confirmation during retrieval to avoid increasing transmission by compromising BBB, and after clear counseling of the potential recipient about documented risk.
references:
1. Desai, R., D. Collett, C.J. Watson, et al., Cancer transmission from organ donors- unavoidable but low risk. Transplantation 2012; 94(12): p. 1200-7.
2. NHS Blood and Transplant and British Transplantation Society NHSBT BTS Responsibilities of clinicians for the acceptance of organs from deceased donors. 2012.
3. European Directorate for the Quality of Medicines and Healthcare, Guide to the Quality and Safety of Organs for Transplantation. 7th ed. 2018, Strasbourg: Council of Europe.
4. Nalesnik, M.A., E.S. Woodle, J.M. Dimaio, et al., Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. American Journal of Transplantation 2011; 11(6): p. 1140-7.
5. Watson, C.J.E., R. Roberts, K.A. Wright, et al., How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK Registry data. American Journal of Transplantation 2010; 10(6): p. 1437-44.
6. Warrens, A.N., R. Birch, D. Collett, et al., Advising potential recipients on the use of organsfrom donors with primary central nervous system tumors. Transplantation 2012; 93(4): p. 348-53.
7. Desai, R., D. Collett, C.J. Watson, et al., Estimated risk of cancer transmission from organ donor to graft recipient in a national transplantation registry. British Journal of Surgery 2014; 101(7): p. 768-74.
8. Fiaschetti, P., R. Pretagostini, D. Stabile, et al., The use of neoplastic donors to increase the donor pool. Transplantation Proceedings 2012; 44(7): p. 1848-50.
I will accept this donor with excellent graft function and good urine output…
The donor has primary intracranial malignancy..Clinically there is no evidence of spread of the tumour as per the available imaging and radiologist description….
As per the BTS guidelines donors with primary intracranial malignancy, with low grade tumours like Grade 1 astrocytoma/meningioma can be operated if there is no exgtra cranial spread or no procedure associated with breach in the blood brain barrier or any procedure like radiotherapy and biopsy where the chance of tumor spillage is there…..
although we don’t know the nature of the brain tumor as it is localized tumor we can consider the donor and go ahead…the recipient and the recipient family need to be informed about the decision and given the picture of a very small absolute risk of door transmission. .But this risk should be outweighed as compared to the benefit of transplant in terms of overall mortality reduction as compared to waiting on dialysis
Yes I would accept this donor.
British Transplant Association 2018
Transplant is possible for low grade CNS tumors (WHO Grade 1 & 2)
this will be according to Clinical grades of astrocyte gliomas and their histological criteria
Grade Designation Histological criteria
1 > Pilocytic astrocytoma
Rosenthal fibers, piloid cells; no criteria
2 > Diffuse astrocytoma One criterion, usually nuclear atypia
3 > Anaplastic astrocytoma Two criteria, usually nuclear atypia
and mitosis
4 >>Glioblastoma multiforme Three or four criteria; the two above plus
endothelial proliferation and/or necrosis
*Group I tumors do not contraindicate organ donation.
*Group II CNS tumors can be considered for organ donation when there is an absence of other risk factors.
* Group III tumors should not be considered for organ donation. They can be only used in cases of life-threatening emergency transplant in which the recipient’s risk of dying while on the waiting list is greater than the probability of tumor transmission.
In such cases, donors with a high risk of tumor transmission (prior surgical intervention) should not be used
-the patient needs to be counseled before implanting the organ and intensive follow-up with a high index of suspicion should be maintained.
European Committee of Experts on Organ Transplantation
(CD-P-TO). Guide to the safety and quality assurance for
the transplantation of organs, tissue and cells. Druckerei
C.H.Beck, Germany, 2011: 135-183.
# Would you accept this donor?
*Yes, I would accept this donor, but MDT including neurologist and radiologist should be involved, also we need to counseling the recipient about the risk of being on dialysis or low risk of tumor transmission.
*Despite the huge gap between the demand for and supply of organs for transplantation, it is important to ensure that the risk of transmitting disease with a transplanted organ is minimized. Use of organs from donors with primary cerebral tumors has recently been in focus because of the low risk of extraneural spread, which is reported as 0.4–2.3%.It has been suggested that it is safe to use such donors, if their tumors are known to be low histological grade, but not so for high-grade lesions or where there has been a breach of the blood–brain barrier, such as with craniotomy or insertion of a cerebrospinal fluid shunt.As a result of this, few such patients become donors.
A review of the literature suggests that organs donated by deceased individuals with primary CNS tumors can be used for transplantation. However, two important caveats must be kept in mind. Firstly, risk of extraneural metastasis in the presence of a shunt is likely to be <1% as majority of extraneural spread occurs without a ventriculo–systemic shunt. Therefore, absence of shunt does not provide security against possibility of spread. Although there are occasional reports of extraneural metastasis in patients who have undergone surgery, chemotherapy or radiotherapy to the tumor, there is no convincing evidence that these forms of treatment will put the recipient at significantly increased risk of tumor transfer and should not represent an absolute contraindication to transplantation. Secondly, if the lesion is a metastasis or a lymphoma, even if it is primary CNS lymphoma, these patients should not be used as organ donors.
Rubinstein has reported that distant dissemination may occasionally occur with histologically benign astrocytoma of the cerebellum, third ventricle and hypothalamus. Dissemination within neuraxis in histologically benign intracranial astrocytoma has been described. Metastasis from the astrocytomas through the cerebrospinal fluid pathway is rare. It is more likely to arise once growth has breached through the ventricular ependyma and, in most cases, it is accompanied by anaplastic change. The available literature suggests that deceased donor harboring low-grade astrocytoma (as in our case) carries a very low risk of tumor transmission (0.1–1%) to the recipient. Occasional case reports of metastasis to the kidney graft from high-grade lesions (glioblastoma multiforme) has been documented in the literature.However, one of our recipients (who underwent repeat kidney transplant) may be at slightly higher risk for skin malignancy and lympho-proliferative disorders because of immunological risk factors: Sensitization from prior transplant and cumulative immune-suppression. This small risk of tumor transmission should be balanced against the likely mortality for potential recipients who remain on the transplant waiting list.
# If yes, what is the prognosis?
*Successful outcome.
*Indian J Urol. 2016 Jan-Mar; 32(1): 74–76.
doi: 10.4103/0970-1591.173104 PMCID: PMC4756557
PMID: 26941500
Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation?
Suresh Kumar, Pranjal R. Modi, Bipin C. Pal, and Jayesh Modi
As donor has brain tumor, the histopathology and grade of tumor is not known, hence i will not accept this donor.
If it turns out to be a Low grade CNS tumor (WHO grade I or II), then we can consider the donor with risk of transmission of around 0.1 % to 1.0 %.
we can consider this organ, in recipients at significant risk without transplant but Informed consent required.
The available donor is 59 years old male with DBD who suffered from brain tumour which is most likely to be primary depend on radiologist no evidence of other primary tumor elsewhere to suggest that is primary one and history of good UOP and good Kidney function.
– firstly we need comprehensive history regard if there were any evidence of ventricular-atrial shunning, radiotherapy, chemotherapy or craniotomy.
– comprehensive general examination chest, Cardio and GIT .
–.I will accept this donor with primary brain tumour with good kidney function n and good UOP with low risk of transmission.
BUT
we must consider biopsy to Clarify nature of brain tumour.
Council patient for mortality risk of Transplantation from donor with DBD with primary brain tumour.
I would accept this donor as-
The two ways to diagnose brain tumor in this patient would be
Stereotactic biopsy – would increase the chance of tumor seeding and thus metastasis
Immediate brain biopsy after organ retrieval – may be difficult
Even if we had histological diagnosis of brain tumor, we would have accepted this donor after informed consent and excluding
Prognosis:
Watson CJ, Roberts R, Wright KA, Greenberg DC, Rous BA, Brown CH, Counter C, Collett D, Bradley JA. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK Registry data. American Journal of Transplantation. 2010 Jun;10(6):1437-44.
Armanios MY, Grossman SA, Yang SC et al. Transmission of glioblastoma multiforme following bilateral lung transplantation from an affected donor: Case study and review of the literature. Neuro Oncol 2004; 6: 259–263.
Chui AK, Herbertt K, Wang LS et al. Risk of tumor transmission in transplantation from donors with primary brain tumors: An Australian and New Zealand registry report. Transplant Proc 1999; 31: 1266–1267.
Pokorna E, Vitko S. The fate of recipients of organs from donors with diagnosis of primary brain tumor. Transpl Int 2001; 14: 346–347.
Garrido G, Matesanz R. The Spanish national transplant organization (ONT) tumor registry. Transplantation 2008; 85(8 Suppl):S61–S63.
Primary central nervous system (CNS) tumors represent 3–4% of the causes of brain death among organ donors but, in one series, <0.5% of 13,000 patients dying with a glioma became organ donors
Despite the huge gap between the demand for and supply of organs for transplantation, it is important to ensure that the risk of transmitting disease with a transplanted organ is minimized.
Use of organs from donors with primary cerebral tumors has recently been in focus because of the low risk of extraneural spread, which is reported as 0.4–2.3%.
Several important factors should be considered while accepting such a donor. These include
1-cell types
2-grade of the tumor((The deceased donor with low-grade astrocytoma carries a very low risk of tumor transmission (0.1–1%) to the recipient))
3-prior history of craniotomy, ventriculo–systemic shunt 4-duration of patient’s disease.
It is safe to use donors, if their tumors are known to be low histological grade, but not so for high-grade lesions or where there has been a breach of the blood–brain barrier, such as with craniotomy or insertion of a cerebrospinal fluid shunt.
So I will accept this donor after consult expert neuroradiologist to ensure the benign nature of tumor and rule out the secondary metastasis
Prognosis is good
the risk of transmitting disease with a transplanted organ is minimized.
References
1-Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation?
Suresh Kumar, Pranjal R. Modi, Bipin C. Pal, Jayesh Modi
Department of Urology, Institute of Kidney Disease and Research Centre, Institute of Transplant Sciences (IKDRC-ITS), Ahmedabad, India.
© 2016 Indian Journal of Urology | Published by Wolters Kluwer – Medknow
donor with 1ry brain tumor diagnosis made based on radiological evaluation with excellent kidney function is usually accepted as a potential donor because the risk of metastasis of brain tumors is very rare and the patient has a risk factor that increases the risk of metastasis like the destruction of the natural barrier by craniotomy or shunt. histopathology will make me more confident in accepting the donor because highly undifferentiated tumors like glioblastoma may be associated with an increased risk of metastasis but a risk not exceeding 20%.
so, my decision is regarding the donor I will try to get a histopathology result if possible and at the same time I will start to counsel potential recipient especially patient who needs urgent dialysis due to vascular access problem or are on the waiting list for a long duration
prognosis: risk of malignancy transmission is from 2-23%
reference:
–Watson CJ, Roberts R, Wright KA, Greenberg DC, Rous BA, Brown CH, Counter C, Collett D, Bradley JA. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK Registry data. Am J Transplant. 2010
You were offered kidneys from a 59-year-old male DBD (donor after brain stem death) donor who suffered from brain tumour; the radiologist suggested that it is most likely primary tumour. No histological diagnosis available at the time of retrieval also, no evidence of primary tumours elsewhere to suggest cerebral metastasis. Her baseline S Cr was 60 µmol/L and 71 µmol/L just before retrieval. She had excellent urine output (120mls/h during the last hour and 3.5 L over the last 24 hours).
There is paucity of data in this case. No biopsy to tell type of tumour. But we have radiology data suggesting it is primary tumour and no evidence of metastasis.
We know that primary brain tumour has very low chance of transmission.
So accepting this donor with limited data and counselling recipient about lack of some information.
Acknowledging the limited data, the prognosis seems to be good with risk of transmission of <1%.
Clinical scenario
Above 50 years aged DBD donor with likely primary CNS tumor.
No evidence for cerebral metastasis.
Yes I would accept this donor because risk of metastasis is less than 10% when there is no evidence of metastasis, ventriculosystemic shunt, prior chemotherapy or radiotherapy, and if the time between diagnosis and time of death is less.
Thus prognosis would be good for this patient and much better than going back to the waiting list since chances of mortality increase with every day on list and dialysis. This risk weighed against the very small risk of cancer occurrence makes me think I would rather accept this donor for my patient.
Counseling of the patient regarding risk of cancer transmission from donor will be done before obtaining consent for transplant. At the same time, the recipient will also be informed of the risks of remaining on waiting list for longer period of time, and the fact that there is always a shortage of donor organs.
References :
I will accept because risk of transmission is low and no metastatic features but should be counselling the recipient regarding little risk of recurrence.
The prognosis depend upon radiological and histological appearance of tumor because CNS lymphoma and melanoma carrying worst prognosis but in general of this case primary brain tumor unknown histology and no metastatic features, so it’s good
reference:
Suresh Kumar, Pranjal R. Modi,et al:Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation:
Indian J Urol. 2016 Jan-Mar; 32(1): 74–76.
doi: 10.4103/0970-1591.173104.
*By history, This potential DBD donor 59years old with mostly primary brain tumor with no metastasis and after exclusion of the risk factors for transmission of primary CNS tumors are:
no history of ventriculo-peritoneal or ventriculo-
atrial shunt or craniotomy nor chemo neither radiotherapy. Having normal creatinine with good urine out put. So, I will accept donor after neurologist assessment and clearance towards nature and incidence of transmission and discuss all of the possibilities with the recipient.
*Prognosis will be good due to low transmission risk 1%.
References:
Collett D, Daraktchiev M, etal.,: Advising potential recipients on the use of organs from donors with primary central nervous system tumors. Transplantation 2012 , 27;93(4):348-53.
As we have a shortage of resources, organs from donors with primary cerebral TM became of interest due to the low risk of extraneural dissemination; 0.4-2.3%(1). As this is probably primary according to the radiologist, we can accept this donor after discussion with the recipients. metastasis may occur without a ventriculoperitoneal shunt. So, this would be considered. A risk of less than 0.1% deserves utilization of the organ. mortality of continuing with dialysis is expected to be less, providing that transplanted patients will be under close follow-up. In other words, this donor can be accepted if he has low-grade tm
1. Gandhi MJ, Strong DM. Donor-derived malignancy following transplantation: A review. Cell Tissue Bank. 2007;8:267.
( OPTN/UNOS)committee reviewed the largely anecdotal literature and held discussions to generate a framework to approach risk evaluation in this circumstance. Six levels of risk developed by consensus. Suggested approach to donor utilization is given for each category, recognizing the primacy of individual clinical judgment and often emergent clinical circumstances. Categories are populated with specific tumors based on
:1- available data including active or historical cancer.
2- Benign tumors are considered in relation to risk of malignant transformation. ,
3- patients with central nervous system tumors. This resource document is tailored to clinical practice in the United States and should aid clinical decision making in the difficult circumstance of an organ donor with potential or proven neoplasia.
To accept this donor or not this available infromation is not enough
first what about the recipent is he highly senstized ,multiacess faiulre .time been in the wating list ,age , HLA match and cross match.
2- the deceased donor has primary brain tumor ,we can discuss with radilogist and the neurologist what the most like type by the image and if alternative image can be done to add more information about this primary tuomor but however even the histological type of this tuomor even stage 3 the risk mild to moderate to transimmitted to the recipent and after cather all information the decision can be made
references
1. Buell JF, Beebe TM, Trofe J, et al: Donor transmitted malignancies. Ann Transplant 9:53, 2004 2. Myron Kauffman H, Cherikh WS, McBride MA, et al: Deceased donors with a past history of malignancy: an organ procurement and transplantation network for organ sharing update. Transplantation 84:272, 2007 3. Garrido G, Matesanz R: The Spanish National Transplant Organization (ONT) Tumor Registry Transplantation 85:S61, 2008
Would not receive. Despite some evidence that it is a primary tumor of the central nervous system, I would not take the risk without the diagnosis.
However, I would discuss it with the recipient if he/she had some high risk factor for death.
In addition to what Prof Halawa’s arguments in this index case and would reiterate the same, I would state that getting an intracranial biopsy may not be easy at all. Organ retrieval teams are not training such kind of intracranial procedures.
I will accept this donor but multiple factors need assessment including cell types, grade of the tumor, prior history of craniotomy, ventriculo–systemic shunt and duration of patient’s -disease.
Organs from donors with primary cerebral tumors has low risk of extraneural spread, published as 0.4–2.3%. It has been suggested that it is safe to use such donors, if their tumors are known to be low histological grade, but not so for high-grade lesions
This small risk of tumour transmission should be evaluated against the possible mortality for potential recipients who remain on the waiting list.
the patient need to be counseled before implanting the organ and intensive follow-up with a high index of suspicion is to be continued .
Reference
-Kumar S, Modi PR, Pal BC, Modi J. Can deceased donor with recurrent primary brain tumour donate kidneys for transplantation? Indian J Urol. 2016 Jan-Mar;32(1):74-6.
– Watson et al. How Safe Is It to Transplant Organs from Deceased Donors with Primary Intracranial Malignancy? An Analysis of UK Registry Data. American Journal of Transplantation 2010; 10: 1–8
Decision making about organ usage for transplantation is seldom straightforward, and has become less so in recent years . As the number of deceased organ donors diminishes, surgeons are forced to consider using organs from potential donors that would previously have been considered unsuitable, hence the renewed interest in donors with a history of intracranial malignancy.
Organs from patients dying from primary intracranial malignancy, including those with high-grade tumors, should be considered for transplantation and the small risk of tumor transmission should be balanced against the likely mortality for potential recipients who remain on the transplant waiting list.
As a result, organs from potential donors who have active or recently treated malignant disease are not normally considered suitable for transplantation, even when there is no evidence of metastasis.
An important exception to this rule is the use of organs from donors with primary intracranial malignancy, where the risk of spread outside the central nervous system, and hence the risk to transplant recipients, is low. Organs from such donors have been used for transplantation over many years, on the basis that disease transmission was rare.
However, there have been case reports of recipients where transmission of malignancy has occurred from donors with primary malignancy of the central nervous system. Since such cases typically involve high-grade malignant tumors in donors who have under- gone interventions that compromise the blood brain barrier, a more selective policy for use of organs from donors with primary brain malignancy has emerged.
Advice from the Council of Europe in 1997 stated that while the use of organs from donors with low-grade primary malignancy was safe, organs from potential donors with high-grade malignant tumors of the CNS, especially where the in- tegrity of the blood brain barrier is compromised, should no longer be considered safe for transplantation .
The shortage of donor organs available for transplantation is such that the risks of disease transmission by organs from a donor with primary CNS malignancy have to be balanced carefully against the risk of a potential recipient remaining on the waiting list for transplant
When potential donors with intracranial malignancy are referred, it is essential the surgeon should be aware of all the relevant information, including tumor histology and treat- ment, including radiotherapy and surgery. At the time of organ retrieval a thorough examination of the thoracic and abdominal cavities for metastatic tumor should be undertaken, as well as careful assessment of any craniotomy site and related lymph nodes for evidence of extraneural spread; if found, and confirmed histologically, the organs should probably not be considered for transplantation. Finally, it is important that any patient being considered for transplantation where organs from donors with intracranial malignancy may be used, should be counseled regarding the small but definite risk of transmission, as well as their chance of survival if they choose to remain on the waiting list .
Reference:
How Safe Is It to Transplant Organs from Deceased Donors with Primary Intracranial Malignancy? An Analysis of UK Registry Data
C. J. E. Watsona,!, R. Robertsa, K. A. Wrightb, D. C. Greenbergb, B. A. Rousb, C. H. Brownb, C. Counterc, D. Collettc and J. A. Bradleya
I will accept him but after :
*Careful history taking, revision of his imaging if there is distant metastasis, and consultation of neuroradiology
* Excluding other risk factors that increase the risk of distant metastasis after transplantation ( Previous Ventricular shunting, previous craniotomy, history of chemotherapy, or radiotherapy, and type of pathology )
* The period between the time of diagnosis and the time of death
* During Retrieval Obtaining of pathology, a good examination of the chest and abdominal cavities for distant metastasis
* Counseling of the recipient for risk of mortality for being on the waiting list or from transplantation from this donor
Prognosis
good if primary tumor with no distant metastasis and low-grade tumor so I can proceed with the operation
In contrast to the above scenario, this index DBD donor has a most likely primary brain tumor (However, no histology is available at the time of retrieval) and there is no evidence of primary tumors elsewhere and no evidence to suggest cerebral metastasis(contraindication for donation and need to be excluded).
So my decision in this scenario is to accept this offer keeping in mind the following:
1. According to most registries the overall risk of primary brain transmission from deceased donors are low (2.2%) even with high-grade tumors (grade 4, e.g. Glioblastoma).
2. Absence of the important risk factors that breach the blood brain barrier and increase the transmission risk like craniotomy, ventriculo-atrial or ventriculo-peritoneal shunts and systemic chemotherapy.
3. The diagnosis of this primary brain tumor was based on the imaging characteristics alone(by an expert neuroradiology who looked for pathognomonic appearances of a primary brain tumor keeping in mind that half of all intracranial cancers are secondaries).
4. In some cases it is not feasible to delay implantation of the donated organ until the histology reports (gold standard for diagnosis) are available and sometimes rapidly fixed specimens are less reliable.
5. Provide a full explanation to the recipient about the risks of inadvertent cancer transmission VS dying waiting for a transplant and explain that the risk of transmission is higher than in cases where the diagnosis has been confirmed histologically. Finally, respect the recipient wishes and if he agreed to obtain an organ from a donor with cancer and obtain an informed consent.
6. Intensive follow-up plan with high index of suspicion.
References:
1) Mingxin Zhu. Et al. Rapid screening for safety of donation from donors with central nervous system malignancies. Systemic Review and Meta-analysis. Medicine (2020) 99:49.
2) Suresh Kumar. Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation? Indian Journal of Urology.2016
3) Desai, R., D. Collett, C.J. Watson, et al., Cancer transmission from organ donors- unavoidable but low risk. Transplantation 2012; 94(12): p. 1200-7
The index prospective donor is
a) 59-year-old male DBD
b) Brain tumor on imaging: suggestive of primary tumor
c) No histological diagnosis available
d) No other primary source in body
e) Excellent urine output
f) Serum creatinine 71 micromol/L
Risk factors associated with extraneural spread (and consequent donor cancer transmission to recipient) include history of craniotomy, stereotactic biopsy, ventriculosystemic shunts, prior radiotherapy and chemotherapy, and increased time between diagnosis of tumor and death (1,2).
As the renal function is good and the above-mentioned risk factors are absent, the donor should be accepted.
Comparing the risk of death due to dialysis versus death due to the transmitted tumor, the literature suggests a gain of 8 years due to transplant in addition to gain due to transplant itself (3). As the factors for extraneural spread are lacking in this scenario, chances of tumor transmission are low, hence the prognosis is good (even in absence of histological diagnosis).
The patient should be counselled regarding the risk of transmission of tumor in detail and the transplant should be performed only after informed consent.
References:
1) Watson CJ, Roberts R, Wright KA, Greenberg DC, Rous BA, Brown CH, Counter C, Collett D, Bradley JA. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK Registry data. Am J Transplant. 2010 Jun;10(6):1437-44. doi: 10.1111/j.1600-6143.2010.03130.x. Epub 2010 May 10. PMID: 20486904.
2) Ammendola S, Barresi V, Bariani E, Girolami I, D’Errico A, Brunelli M, Cardillo M, Lombardini L, Carraro A, Boggi U, Cain O, Neil D, Eccher A. Risk factors of extraneural spreading in astrocytomas and oligodendrogliomas in donors with gliomas: A systematic review. World J Transplant. 2022 Jun 18;12(6):131-141. doi: 10.5500/wjt.v12.i6.131. PMID: 35979537; PMCID: PMC9258267.
3) Warrens AN, Birch R, Collett D, Daraktchiev M, Dark JH, Galea G, Gronow K, Neuberger J, Hilton D, Whittle IR, Watson CJ; Advisory Committee on the Safety of Blood, Tissues and Organs, UK. Advising potential recipients on the use of organs from donors with primary central nervous system tumors. Transplantation. 2012 Feb 27;93(4):348-53. doi: 10.1097/TP.0b013e31823f7f47. PMID: 22258288.
In view of the mentioned data:
I would accept him as a donor although no definite pathological diagnosis of the brain tumor
However; this needs a very clear documented discussion with the potential recipient that there is still a risk to get a tumor.
The prognosis will not differ from other deceased donors without a primary brain tumor
Thank you, Mike
What do you mean by the prognosis is not different with or without the primary tumours?
Would you accept this donor?
In this 58 year Old DBD, a brain tumour has been found . There is no histology available. There is no other primary malignancy. Excellent renal functions.
Radio logically it is primary CNS tumour.
Biopsy is only indicated to know the source primary pathology if metastasis is suspected and know the grade.
The risk factors of transmission of CNS tumours include-
High grade disease
Recurrent disease
Duration of disease
Biopsy in high grade disease
Shunt surgery
I will accept him for donation after properly counselling the recipient as the risk of breach of blood brain barrier is low.
If yes, what is the prognosis?
The prognosis will depend on histology. It will be excellent if histology shows primary brain tumour with no obvious evidence of metastasis.
Warrens AN, Birch R, Collett D, Daraktchiev M, Dark JH, Galea G, Gronow K, Neuberger J, Hilton D, Whittle IR, Watson CJ; Advisory Committee on the Safety of Blood, Tissues and Organs, UK. Advising potential recipients on the use of organs from donors with primary central nervous system tumors. Transplantation. 2012 Feb 27;93(4):348-53.
Thank you.
Would you accept this donor?
I would accept this potential donor
a) This is most likely a primary brain tumor without evidence of metastasis, carries low risk for transmission(0.1-1%)1.
b) The potential donor has excellent kidney function and good urine output.
If yes, what is the prognosis?
The prognosis is good, as it carries very low risk of transmission.
Reference
1. M. A. Nalesnik et.al. Donor-Transmitted Malignancies in Organ Transplantation: Assessment of Clinical Risk American Journal of Transplantation 2011; 11: 1140–1147
Thank you.
Would you accept this donor?
-Yes,I would accept this donor .
-Donor had no risk factors for extraneural metastasis :
– Craniotomy and major resection and stereotactic biopsy
– Ventriculosystemic shunts, prior radiotherapy or chemotherapy, and an increased time between diagnosis of tumor and death.
The recipient should be counseled regarding the small but definite risk of transmission of malignancy.
-Tumour biopsy can be done during the retrieval of kidneys.
If yes, what is the prognosis?
Good prognosis because there are no risk factors of extraneural metastasis. Reference
-C. J. E. Watsona et al. How Safe Is It to Transplant Organs from Deceased
Donors with Primary Intracranial Malignancy? An Analysis of UK Registry Data .American Journal of Transplantation 2010; 10: 1–8
Thank you.
Would you accept this donor?
Yes, I would accept this 59-year-old male DBD who proved to have a primary CNS tumor.
Generally, the risk of transmission of cancer from the donor organ is minimal (0·01–0·05%) , especially when we balance this against the risks to the individual of not receiving an organ & remaining on the waiting list. In the UK, up to 6% of those awaiting kidney transplants die or are withdrawn before they find a graft.
================
If yes, what is the prognosis?
The prognosis is generally good compared to remaining wait-listed or dying before finding a donor organ. Between 2001 & 2010 in the UK, 15 (0·05 %) of 30 765 transplant recipients developed donor transmitted cancers, of whom 3 died as a consequence. During the same period, 4093 patients died while awaiting transplantation.
Although a rare occurrence, any donor transmitted cancers are often reported in the media, whereas deaths among patients awaiting a transplant receive little or no publicity.
References
1.R. Desai, D. Collett, C. J. E. Watson, P. Johnson, T. Evans and J. Neuberger. Estimated risk of cancer transmission from organ donor to the graft recipient in a national transplantation registry. BJS 2014; 101: 768–774 Published by John Wiley & Sons Ltd.
Thank you.
The donor can be accepted as the tumor is localized without evidence of metastasis; the prognosis is good as risk of malignancy transmission is low due to absence of risk factors
Thank you, can write more?
References?
Yes, I accept this donor, as a primary CNC tumor is not contraindicated for donation ,if there is no evidence of metastasis or secondary CNS tumor, it is also considered high risk of transmission if craniotomy, VP or VA shunts, chemotherapy, or metastasis extracrenially.
Thank you, can write more?
References?
This scenario presented that 59 years old with PRIMARY CNS TUMOUR without metastases, diagnosed SOLELY by radiological investigation without histopathological diagnosis. As for kidney function, it has been good for retrieval.
Emerging studies have shown that primary CNS tumours without intervention and metastases are less likelihood to transmit following kidney transplant.
Does it matter to do HPE diagnosis?
Data from Czechoslovakia, Australia and New Zealand registry, United Network for Organ Sharing in the United States and other smaller series reported that only small risk of transmission even with high grade tumours. So, in this sense, HPE diagnosis will not change the decision of transplant surgeon.
Halpern SD et al emphasized on Informing candidates for solid-organ transplantation about donor risk factors. I would counsel regarding the small but definite risk of transmission and emphasis on their chance of survival will be lesser compared to DCD transplant if they choose to remain on the waiting list.
As a transplant team, I would proceed with the transplant but the final decision will be given by the recipient.
Thank you, Theepa
You said:small but definite risk of transmission”. Can you explain this to us?
59 yr old DBD donor, primary brain tumor by CT imaging, reported by radiologist.
no histological diagnosis at the time of retrieval no evidence of primary tumor elsewhere
excellent kidney function and urine output in the last 24 hours.
Would you accept this donor?
Yes, i will accept this donor kidneys, as the radiologist said that he has most probably primary brain tumor with no evidence of other primary tumor., and the patient is having an excellent kidney function and urine output. But i’ll need to have better knowing his medical history and record, DM, HTN, cardiac status …etc
If yes, what is the prognosis?
Primary CNS malignancies have a low rate of metastasis, patients with nonmetastatic primary CNS malignancies can be considered for organ donation.
The transmission rates are highly variable 0-23%., Breaking the blood-brain barrier, other than with an uncomplicated biopsy, may increase the risk of tumor transmission. Risk factors for tumor transmission included high-grade tumors, the presence of a
ventriculoperitoneal or ventriculoatrial shunt, previous craniotomy, insertion of VP or VA shunt and systemic chemotherapy has a higher risk of tumor transmission[1].
Metastases to the brain can be misdiagnosed as primary CNS tumors or intracranial hemorrhage, and transplantation of organs from these donors has a poor prognosis for the recipients, recurrence >70% and 63% decreased survival. Thus, in donors who present with unexplained intracranial hemorrhage or a suspected primary CNS neoplasm without a biopsy, an evaluation for metastatic disease should be considered [2].
However, it is better to be transplanted to those on long time on waiting list, while on HD.
[1] Buell JF, Trofe J, Sethuraman G, Hanaway MJ, Beebe TM, Gross TG, Alloway R, First MR, Woodle ES. Donors with central nervous system malignancies: are they truly safe? Transplantation. 2003 Jul 27;76(2):340-3. doi: 10.1097/01.TP.0000076094.64973.D8. PMID: 12883189.
[2] Buell JF, Gross T, Alloway RR, Trofe J, Woodle ES. Central nervous system tumors in donors: misdiagnosis carries a high morbidity and mortality. Transplant Proc. 2005 Mar;37(2):583-4. doi: 10.1016/j.transproceed.2004.12.125. PMID: 15848464.
Dear Dr Alshaikh,
I like your decision as you quote literature supporting your argument. I like your approach.
Ajay
Having an available donor in an era of donors shortage, with radiological diagnosis of primary brain tumor with no metastasis or previous intervention and no evidence of other primary tumors, we have to compromise taking into account the low risk of transmission and proper counselling of the recipient.
Dear Dr Alaa,
Your answer is too short. We expect you to provide quoting literature supporting your argument. I like your approach to informed consent by counselling.
Ajay
This 59 year male with primary benign tumor with no metastasis and normal renal function with good urine output can be considered as a donor ,the risk factors which contraindicate donation are absent in this patient like tumor type i.e., high grade or histological type , previous history of brain surgery like craniotomy ,chemotherapy use, duration of disease, or presence of shunts and also the patient should be counseled in detail about the transmission risks as is recommended by Europe Council .
If yes, what is the prognosis?
Such type of primary benign brain tumors have low risk of transmission (0-23%)to recipient and also less chance of metastasis.
REFERENCE:
Council of Europe. Criteria for preventing the transmission of neoplastic diseases in organ donation. Europe Council of Europe Publishing;2006
Dear Dr Butt,
When you state, ‘…..can be considered as a donor’, it does not give me a clear answer as if you will accept this donor or not.
Ajay
I will accept this donor as he localized tumor with no Mets besides he has excellent kidney function
In general , Primary CNS tumors known to have low risk of Mets.
Risk factors associated with transmission:
• High grade tumors
• Received chemotherapy
• History of craniotomy
• Presence of shunt
_ I will accept the current cadaveric donor as :
_ risk of recurrence of 1ry intracranial malignancy is very low as no history of previous radiotherapy, ventriculoatrial or ventriculoperitoneal shunt.
_ Although no available biopsy to determine the grade of the tumor which also determines the long term prognosis, we can still accept the donor, as renal transplantation with extended donor criteria has better outcome than being on wait-list on dialysis.
_ counseling of the recipient regarding the risk of cancer transmission must be clear and a written consent must be obtained before proceeding.
Dear Dr Mai,
I like your approach to decision-making and informed consent.
Ajay
As we mentioned in previous case brain tumor with high risk factor of transmission are
Giving the data above in this case 59-year-old male DBD who suffered from brain tumor and the radiologist suggested that it is most likely primary tumour. No histological diagnosis available at the time of retrieval, also no evidence of primary tumours elsewhere to suggest cerebral metastasis, with good renal function.
So I would like to accept this donor , also I would like if available to do biopsy by neuroradiologist before donation and to inform the recipient about the case and the low risk of transmission.
the possibility of tumor transmission from donor with CNS tumor is rare in general with some exceptions mentioned above
Hi Dr Huda,
I do not think you get CT guided biopsy of a brain lesion at 2 am.
A neuroradiologist would have already seen and reported those pictures. A biopsy is not always available, we have to decide based on the information given to us. Moreover, there is not enough time to do any MDT for such referrals often made at 3-4 o’clock in morning !
Ajay