1. You were offered kidneys from 43-year-old female DBD (donor after brain stem death) donor who suffered from SAH secondary to recurrent grade IV astrocytoma (glioblastoma) diagnosed by MRI 2 days ago. She had ventriculo-atrial shunt 3 months ago. Her baseline S Cr was 89 µmol/L and 100 µmol/L before retrieval. She had excellent urine output (110mls/h during the last hour and 3 L over the last 24 hours).
- Would you accept this donor?
- If yes, what is the prognosis?
Dear All
The questions from now on, are about your decision and the justification of your decision. Remember, these are real-life scenarios where the decision will be made under a very suboptimal condition and based on limited data.
I think the answer not easy but i will acccept this donor because primary tumour per se carry very minimal and small risk of metastasis with variable transmmission 0.23%,
Hi Dr Wadi,
I am quoting: M. A. Nalesnika et al. Donor-Transmitted Malignancies in Organ Transplantation: Assessment of Clinical Risk American Journal of Transplantation 2011; 11: 1140–1147
High risk (>10% transmission)
CNS tumor (any) with ventriculoperitoneal or ventriculoatrial shunt, surgery (other than
uncomplicated biopsy), irradiation or extra-CNS metastasis
CNS Tumor WHO grade III or IV
Would this information change your decision?
Yes of course
Thanks alot for you Prof .Sharma for important iformative
I note your response, Dr Wadi. It is so nice of you to keep debating using sound arguments and supportive literature.
Thanks you very much Prof.Sharma
i will not accept this donor because high risk
The risk of transmission of cancer from donors with High Grade (Grade 4) Central Nervous System (CNS) tumours to recipients is 2.2%.
The overall risk of cancer transmission from deceased donors with high-grade tumours (grade 4, e.g. Glioblastoma) has been estimated to be around 2.2%.
The presence of a cerebrospinal fluid shunt will increase the risk of extra-neural metastasis but this is estimated at less than 1%.
The shunt track must be inspected carefully at the time of retrieval.
TRANSPLANTATION OFORGANS FROM DECEASEDDONORS WITH CANCER OR A HISTORY OF CANCER 2014
I will not accept this donor because
This increase the possibility of metastasis and systemic implant of malignant cells
REFERENCE
Journal club
HowSafe Is It to Transplant Organs from Deceased Donors with Primary Intracranial Malignancy? An Analysis of UK Registry Data
Thank you for repeating your answer
Thank you, Professor Ahmed, for this teaching case, and thanks to Dr. Sharma for quoting with the paper published in 2011 (Donor-Transmitted Malignancies in Organ Transplantation: Assessment of Clinical Risk). As we can conclude from table 2, this patient carries a risk of more than 10% (high). I will not accept it for young patients, may accept it if it is low-grade or without shunts. mTOR inhibitors reported to have a powerful anti-GBM effect (https://onlinelibrary.wiley.com/doi/full/10.1046/j.1600-6143.2003.00289.x: Organ Donors with Malignant Gliomas: An Update; published 2003). really challenging, but for this case, I do not prefer to transplant young patients. Still, we have 90% of free-tumour survival !!; Do you agree?
Other source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756557/. (Can deceased donor with recurrent primary brain tumour donate kidneys for transplantation?)
Thank you, of course, but under special conditions. See my question above.
According to counsel of Europe for guild lines , patients with primary intracranial tumers can be accepted as organ donor if
-low grade tumer , no metastasis, no disruption of BBB integrity
In this patient, the risk points are
– recurrent high grade glioblastoma
– previous ventriculo – atrial shunt
So , despite the excellent kidney function
I wouldn’t accept her as a donor
Thank you
References Fatima, please.
Generally speaking, primary CNS malignancies have low risk of metastasis and the overall risk of transmission ranges from 0-23% (1)
Risk factors associated with malignant transmission include:
These risk factors were found to be associated with higher risk of tumor progression compared to those without these risk factors (53 versus 7 percent).(2)
On the other hand a retrospective study evaluating 179 deceased donor with primary intracranial malignancy of which 33 were high grade (24 grade IV gliomas and 9 medulloblastomas) reported no transmission of donor malignancy in all cases, and the authors concluded that deceased donors with primary intracranial malignancy can be considered for donation since they have very low risk of malignant transmission to the recipients even those with high grade malignancy or with interventions that alter the BBB.
For me, deceased donor with primary brain tumor can be considered for donation if the following are met
So I will not accept this donor because of the presence of high grade tumor with ventriculo-atrial shunt which will be associated with poor outcome
REFERANCES
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.
Thank you, for repeating your answer
This donor has several risk factor
1 – recurrent high-grade IV malignant tumors of the CNS ( Glioblastoma )
2 – possibility of integrity of the blood brain barrier as She had ventriculo-atrial shunt 3 months ago
So I will not consider this doonor safe for transplant though the kidney function is excellent as the risk for transmission is high
Thank you, Huda
References, please!!
I note your response, Dr Huda. It is so nice of you to keep debating using sound arguments and supportive literature. In spite of additional infomation about this recipient appearing to be in a desperate situation, you are convinced that your logical approach is unshakeable, such profound is the risk.
Ajay
Dear All
Suppose you have been offered this donor for a 23-year-old male CKD patient on dialysis for 11 years. 000 mismatch, he is highly sensitised with cPRA 96%. Crossmatch was negative. He is also running out of access and has no living donor available.
1. Will you accept this kidney for him?
2. What are you going to tell him about the risk of malignancy vs the risk of death on dialysis?
3. What would your immunosuppression (induction and maintenance) will be?
At this condition I will accept this donor and the rational for acceptance is as follow:
1- This patient is highly sensitized, waitlisted for long time and the possibility to find a compatible donor while have cPRA of 96% is negligible
2- Renal transplantation offers the highest survival benefit for ESRD patients when compared to other modalities of renal replacement therapies (1, 2)
3- Based on the available studies, there is conflicting results, some found higher risk of progression in high grade tumors especially if the BBB is disrupted by ventriculo- peritoneal shunts, while other study reported no transmission of donor malignancy in all cases even those with high grade malignancy or with interventions that alter the BBB.
4- 000 HLA mismatch is considered very low immunological risk transplantation and so lower immunosuppression will be given to this recipient which will be associated with even lower incidence of malignancy flare up if it accidentally transmitted
The proposed immunosuppression for the current recipient
A- No antibody induction is recommend, only corticosteroids to prevent reperfusion injury
B- Maintenance therapy differ in white vs African-American
So … I will assure the patient and tell him that there is conflicting data about tumor transmission, and with this low risk transplantation, immunosuppression will be minimal adding for the anticipated good outcome, on the other hand mortality is high if the patient is lifted on hemodialysis and the possibility to find a compatible donor is very low due to high sensitization
REFERANCES
1- Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med 1994; 331:365.
2- Gill JS, Tonelli M, Johnson N, et al. The impact of waiting time and comorbid conditions on the survival benefit of kidney transplantation. Kidney Int 2005; 68:2345.
1. Will you accept this kidney for him?
Considering the comorbidities: High cPRA, long vintage dialysis (11 years), poor vascular access with non-availability of living donor and a negative crossmatch with 000 mismatch, the offer for transplant should be accepted.
2. What are you going to tell him about the risk of malignancy vs the risk of death on dialysis?
Considering his long history of dialysis and high cPRA, the chances of getting a 000 mismatch kidney for him are rare. The risk of extraneural spread of the malignancy would be 2.2% (with upper limit of 6.4%).
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 (1).
3. What would your immunosuppression (induction and maintenance) will be?
In view of 000 mismatch, transplant can be proceeded without induction and tacrolimus, MMF and steroid based immunosuppression.
DSA monitoring with a low threshold for kidney biopsy will be required.
Reference:
1) 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.
Thank you for this brain storming scenario Prof.Ahmad Halawa;
Suppose you have been offered this donor for a 23-year-old male CKD patient on dialysis for 11 years. 000 mismatch, he is highly sensitised with cPRA 96%. Crossmatch was negative. He is also running out of access and has no living donor available.
1. Will you accept this kidney for him?
In this scenario I will accept, this donors kidney, because the risk of death is higher while being on dialysis than to be transplanted with only 10 % risk of tumor recurrence in such high risk tumor with VA shunt.
2. What are you going to tell him about the risk of malignancy vs the risk of death on dialysis?
Each year being on dialysis increases risk of death by 6%, cardiovascular disease is the major cause of death (50% of cases) followed by infections, access problems and malignancy[1].
The risk of malignancy in dialysis patients increases 1.3 folds than the general population, young patients were more at risk[2], and this could be due to elevated serum soluble interlukin -2 receptor level[3]. However the risk of transmission of such high risk malignancy in such donor (estimated 10% in 20 years follow up), with high grade astrocytoma and VA shunt, it is beneficial to him to have this kidney with low immunological risk (000- MM)[4].
3. What would your immunosuppression (induction and maintenance) will be?The goal of organ transplantation is to provide durable graft function while minimizing risks of infections and cancer[5]With moderate immunological risk full HLA match, and negative cross match, in spite of c-PRA 96% .I’ll use basiluximab induction therapy for sure, and maintenance with prednisolone, m-TOR inhibitor , and low dose CNI [5&6].
References:
[1] Chertow GM, Johansen KL, Lew N, Lazarus JM, Lowrie EG. Vintage, nutritional status, and survival in hemodialysis patients. Kidney Int. 2000 Mar;57(3):1176-81. doi: 10.1046/j.1523-1755.2000.00945.x. PMID: 10720970.
[2] Taborelli M, Toffolutti F, Del Zotto S, Clagnan E, Furian L, Piselli P, Citterio F, Zanier L, Boscutti G, Serraino D; Italian Transplant & Cancer Cohort Study. Increased cancer risk in patients undergoing dialysis: a population-based cohort study in North-Eastern Italy. BMC Nephrol. 2019 Mar 28;20(1):107. doi: 10.1186/s12882-019-1283-4. PMID: 30922296; PMCID: PMC6437907.
[3] XiaoHong C, Bo S, FangFang X, Man G, JianZhou Z, ZhongHua L, WenLv L, XueSen C, XiaoQiang D, Boheng Z. Elevated serum soluble interleukin-2 receptor levels increase malignancy-related risk in patients on chronic hemodialysis. Int J Clin Oncol. 2019 Sep;24(9):1151-1160. doi: 10.1007/s10147-019-01455-5. Epub 2019 Jun 10. PMID: 31183777.
[4] 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.
[5] Wagner SJ, Brennan DC. Induction therapy in renal transplant recipients: how convincing is the current evidence? Drugs. 2012 Mar 26;72(5):671-83. doi: 10.2165/11631300-000000000-00000. PMID: 22439670.
[6] Samaniego M, Becker BN, Djamali A. Drug insight: maintenance immunosuppression in kidney transplant recipients. Nat Clin Pract Nephrol. 2006 Dec;2(12):688-99. doi: 10.1038/ncpneph0343. PMID: 17124526.
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 (1). Primary intracranial tumors has newly been in focus because of the low risk of extra-neural spread, which is described as 0.4–2.3%(2,5) I found the evidence of transmission in those with intervention like craniotomy or in the presence of shunt is diverse and some reported as low as < 1% and in others between 2.3-6% or even 10% all available evidence limited to small studies(2, 3,4). 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 (2). the only absolute contraindication is the primary CNS Lymphoma and secondary metastatic brain tumors (2).
So with the limited evidence then the decision should be individualized based on the assessment of the recipient circumstances he is a young have high risk of mortality if staying on dialysis while he had the chance of getting this offer with intermediate chance for transmission however we need to explained to the recipient the risk and benefit and if get his informed consent to go ahead with transplant the induction Immunosuppression will be with basiliximab as he had zero match and negative crossmatch however he had high PRA and on long waiting list also he is highly sensitized and preferred to keep on maintenance triple IS including tacrolimus , MMF and steroid then with close monitoring in the first 3 – 6 months if stable graft function no proteinuria no DSA will consider shift to everolimus and minimizing dose of tacrolimus and stop MMF with close fu and monitoring with high index of suspicion should be continued upon intensive follow up .
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.
2. 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.
3. Gandhi MJ, Strong DM. Donor derived malignancy following transplantation: A review. Cell Tissue Bank. 2007;8:267.
4. Europe: Council of Europe Publishing; 2006. Council of Europe. Criteria for preventing the transmission of neoplastic diseases in organ donation.
5.Warrens AN, Birch R, Collett D, Daraktchiev M, Dark JH, Galea G, et al. Advising potential recipients on the use of organs from donors with primary central nervous system tumors. Transplantation. 2012;93:348–53.
I agree with my colleagues regarding accepting this kidney offer in this particular scenario. the comparison of the risk-benefit ratio when getting this offer is much better than the risk-benefit ratio of keeping this patient on dialysis with exhausted access. Nevertheless, I will explain to the patient the minor risk of transmission of malignancy and the limited options if kept on dialysis.
Regarding the induction and maintenance immune suppression. The recipient has a 000 mismatch with a negative crossmatch so I will consider his immunological risk low despite the very high cPRA. Therefore, I will recommend induction with steroids only and maintenance immune suppression using triple immune suppression (Tacrolimus, MMF and steroid).
This reply is for the new scenario by Dr Ahmed
Dear All
Suppose you have been offered this donor for a
23-year-old male CKD patient on dialysis for 11 years. 000 mismatch, he is
highly sensitised with cPRA 96%. Crossmatch was negative. He is also running
out of access and has no living donor available.
1. Will you accept this kidney for him?
2. What are you going to tell him about the risk
of malignancy vs the risk of death on dialysis?
3. What would your immunosuppression (induction
and maintenance) will be?
Multiple factors need assessment while accepting this donor.
These include cell types, grade of the tumor, prior history of craniotomy, ventriculo–systemic shunt and duration of patient’s disease.
On the other hand in this case attributed to the donors characteristics of having long dialysis vintage , running out of access ,being highly sensitised with negative cross match the transplantation can be accepted provided that the patient is counseled before implanting the organ and intensive follow-up with a high index of suspicion is to be continued as well as their chance of survival if they choose to remain on the waiting list.
-Since this case has 000 mismatch ,highly sensitised c PRA 96%so for induction Basiliximab can be given and for maintenance MMF, Tacrolimus and steroids with DSA monitoring as well as follow up for any tumour occurrence.
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
Iwill accept as the patient has vascular acess problem,highly senstized and this deceased donor is mismatched 000 but ineed to explain to the recipient the risk of transmission but in his been highly sensitized we need to weight risk versus the advantage.
the risk of death from HD and cvs mortality and been multiacess failure is more serous and common than maligancy transmission .
3-no induction and maintance thearpy should be steroid plus TAC and MMF
and follow up for DSA every 3 month .
references
Schnuelle P, Lorenz D, Trede M, Van Der Woude FJ. Impact of renal cadaveric transplantation on survival in end-stage renal failure: Evidence for reduced mortality risk compared with hemodialysis during long-term follow-up. J Am Soc Nephrol 1998; 9: 2135–2141.
1- yes, i will accept the donor for him
2- we face a recipient young age , long waiting time on dialysis, running out of access, no mismatch, negative cross match…so, i will explain to him the risk of death from cardiovascular complications when staying on dialysis versus risk of tumor transmission especially he has excellent match may not need strong immunosuppression even with cPRA 96%, so the recipient can take the decision.
3- induction will be basiliximab, and maintenance will be tacrolimus , MMF, prednisolone
I will accept this donor.
The benefit from survival and best qualify of life is highly better with transplantation than keep on dialysis.
000 mismatch so I will give basiliximab as induction and maintenance with tacrolimus MMF and steroid.
iwill not accept this DBD donor as these causes :
the type of tumor is glioblastoma and recurrent and high grate.
having ventriculo-perotinal shunt lead to homogenous and lymphatic spread.
Dear Dr Ahmed,
I will not accept organs from this donor due to the high risk of transmission of malignancy to the recipients, as shown in the attached table summarizing the risk of transmission of different tumor categories from the deceased donors (1).
References:
1) Gary F Marklin, and Ron Shapiro. Evaluation of the potential deceased organ donor (adult). http://www.uptodate.com © 2022 UpToDate (accessed on 13 October 2022).
Sir,
I would not accept this donor as
Incereased risk of extra neural spread and donor cancer transmission
Penn, Israel MD. QUESTIONS ABOUT THE USE OF ORGAN DONORS WITH TUMORS OF THE CENTRAL NERVOUS SYSTEM12. Transplantation: July 15, 2000 – Volume 70 – Issue 1 – p 249-250
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.
This case is not an absolute contraindication for donation. The risk of malignancy transmission is 2.2 up to 6.4%. Therefore, we should consider the risk-benefit ratio of staying on the waiting list without dialysis access to a zero mismatch HLA compatible transplantation from a donor to a highly sensitized recipient with the risk of malignancy transmission. The patient should be informed and consent.
The immunosuppression considering low immunological mismatch would be induction with steroid and then triple maintenance therapy.
Given the donor data including brain tumor with ventriculoperitoneal shunt which carry poor prognosis.
VPS offers is considered as an effective, safe and valid palliative option for symptom relief and improvement of quality of life, even in patients with very poor overall prognosis. However, the presence of hydrocephalus is very poor.
So, I would not accept this donor offer
Reference:
(1) NIGIM F, CRITCHLOW JF, KASPER EM. Role of ventriculoperitoneal shunting in patients with neoplasms of the central nervous system: An analysis of 59 cases. Mol Clin Oncol. 2015;3(6):1381–6.
i will not accept this donor in view of his recurrence of malignancy and also he underwent ventriculo- atrial shunt which carries high risk of transmission to the recipient.
if i had to do i will counsel the recipient and inform about chances of malignancy transmission and weighing against waiting in the list for another donor
Would you accept this donor?
The potential donor is 43 year old female with brain stem death due to SAH , after recurrent grade IV Glioblastoma with excellent urine output and normal serum creatinine .
This donor has a CNS tumor with V/A shunt , the risk of risk of transmission is more than 10 % .
Despite being a perfect match, with normal KFTs and optimum urine output. Acceptance of such donor will be at risk of cancer transmission with life expectancy about 10 years .
If yes, what is the prognosis?
Although the patient may acquire malignancy form extraneural glioblastoma, Yet he will gain more years than staying on hemodialysis.
And proceeding for such donation will be after proper councilling of the recipient and explaining the risks and benefits.
I will not accept this donor due to
these two factors incraese the risk of malignant transmission
reference : Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation?Suresh Kumar, Pranjal R. Modi, Bipin C. Pal, and Jayesh Modi
No .
Neoplastic conditions that absolutely disqualify a potential donor include a recent history of or an active malignant neoplasm, excluding tumors with a low risk of transmission, such as skin basal cell carcinoma, cervical carcinoma in situ and primary CNS tumors (excluding high-grade medulloblastoma, glioblastoma and astrocytoma).Only two cases of transmission of primary CNS tumors have been reported, with both patients having glioblastoma multiforme. Decision-making is difficult in cases with old or theoretically cured neoplasms.
Accidental transmission of neoplasms from donors to recipients is rare. According to a United Network for Organ Sharing (UNOS) report, 35,503 deceased donors and 109,749 transplanted organs were assessed from April 1994 through December 2000, among which 9 donors transmitted neoplasms (donor transmission rate of 0.025%) to 12 recipients (organ transmission rate of 0.01%). However, due to the serious consequences, all potential donors must be subjected to careful investigation to avoid the occurrence of inadvertent transmission. Donors diagnosed with neoplasms should not be considered for organ or tissue and cell donation, except in cases of tumors with a low degree of malignancy or localized neoplasms as follows:
a. Skin tumors, such as basal cell and squamous cell carcinoma;
b. Carcinomas in situ, such as cervical carcinoma in situ;
c. Kidney tumors diagnosed during removal or implantation, which may be accepted when their size is ≤ 4cm, they exhibit Fuhrman grade I-II and their margins are free.
d. Primary CNS tumors, according to the Council of Europe recommendations :
Group 1 – Metastases outside the CNS are rare; organs may be considered for donation.
Group 2 – There is risk of transmission when other risk factors are also present; organs may only be considered for donation in the absence of these risk factors.
Group 3 – There is a considerable risk of transmission; organs may only be used for urgent cases and with due communication to the recipients.
Although there are some reports of the transmission of primary CNS tumors to recipients, data for transplants performed in the 1990s recorded in registries from the United Kingdom, Australia, New Zealand, Czech Republic and Spain, i.e., prior to publication of the Council of Europe recommendations, do not contain a single instance of tumor transmission. According to UNOS, in the United States, of 175 recipients and donors with glioblastoma multiforme, transmission occurred in three recipients (1.7%), all from a single donor. Based on these data, the Advisory Committee on the Safety of Blood, Tissues and Organs concluded that the risk of dying while still on the waiting list is higher than the risk of the transmission of primary CNS tumors. Consequently, since 2012, these tumors were no longer considered a contraindication for donation independently of their histological type, and the donors are considered “marginal”. This recommendation is currently applied in the United Kingdom only, and potential recipients are informed as to the small (but definite) risk of transmission, as well as to their survival odds if they decided to remain on the waiting list.
The main risk factors for the transmission of primary CNS tumors are histological type and malignancy grade; previous history of craniotomy or stereotactic surgery; ventricular systemic shunt; previous history of chemotherapy or radiotherapy; disease duration; and length of survival after surgery.
The decision to accept donors with primary CNS tumors must be based on a judicious analysis following the classification formulated in the Council of Europe recommendations (1)
Twenty-six organs were transplanted from donors with gliomas or glioblastomas. Eight organs were recovered from donors with a grade III or IV glioblastoma, whereas the remaining 18 organs were from donors with gliomas. High-grade glioblastoma multiforme lesions were defined as grade IV glioblastomas. Fifteen patients received organs from donors with at least a single risk factor associated with the potential for malignancy transmission. These include prior surgical intervention (n=10) or high-grade malignancies (n=9). Eight transmissions were identified, with all appearing between 2 and 15 months posttransplant (Fig. 1). Three of the eight cases of malignancy transmission were confined to the allograft (two kidney and one liver). Both kidney recipients underwent graft nephrectomy. One recipient was rendered disease-free, whereas the other developed metastatic disease and died from metastatic tumor. The liver recipient died after developing liver failure. The remaining five cases of donor transmission resulted in patients dying between 6 and 26 months posttransplant
Risk factors associated with donor transmission of malignancy were examined in 14 recipients who experienced donor-transmitted malignancies. These risk factors included ventriculoperitoneal shunts (n=5), high-grade tumors (n=6), extensive craniotomies (n=3), and cerebellar lesions (n=2). Thirty-three patients had at least one risk factor present; 14 of those had two risk factors. When a single risk factor was present, the donor malignancy transmission rate was 36%, whereas two risk factors resulted in an equivalent transmission rate of 43%. As an independent factor, a high-grade malignancy was associated with a 43% transmission rate. In the absence of risk factors, the incidence of donor-transmitted malignancies was 7% The findings of this study indicate the selective use of donors with CNS tumors, that is, donors with low histologic grade lesions or benign tumors. Donors with one or more risk factors should be avoided or used only in cases in which a life-saving transplant is urgently needed. The IPITTR data indicate that a donor with a low-grade CNS malignancy (astrocytoma, glioblastoma, or medulloblastoma) in the absence of any known risk factor carries a 7% risk of tumor transmission. Given that SRTR and ANZODR data indicate a lower transmission rate, this 7% rate may be an overestimation of the true risk. Thus, the use of such organs may seem reasonable for the patient with a high expected mortality on the wait list for a life-sustaining organ transplant. The series indicates that donors with high-grade malignancies, ventriculoatrial or ventriculoperitoneal shunts, previous surgical intervention, or previous prolonged chemotherapy carry a significant risk of tumor transmission, and their use is discouraged.(2)
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; PMCID: PMC5051181.
2-Buell, Joseph F.; Trofe, Jennifer; Sethuraman, Gopalan; Hanaway, Michael J.; Beebe, Thomas M.; Gross, Thomas G.; Alloway, Rita; First, M. Roy; Woodle, E. Steve, Donors with central nervous system malignancies: are they truly safe?,Transplantation 76(2):p 340-343, July 27, 2003. | DOI: 10.1097/01.TP.0000076094.64973.D8
Primary cerebral tumors has a low risk of extraneural spread about 0.4–2.3%.
Patient with primary cerebral tumors can be safe for donation
1.If their tumors are known to be low histological grade, but not so for high-grade lesions 2. There is no disruption of brain barrier, such as with craniotomy or insertion of a cerebrospinal fluid shunt.
the patient had high grade tumor
the patient had ventriculo-atrial shunt I do not accept him for donation.
Gandhi MJ, Strong DM. Donor derived malignancy following transplantation: A review. Cell Tissue Bank. 2007;8:267.
Collignon FP, Holland EC, Feng S. Organ donors with malignant gliomas: An update. Am J Transplant. 2004;4:15–21.
Europe: Council of Europe Publishing; 2006. Council of Europe. Criteria for preventing the transmission of neoplastic diseases in organ donation.
Suppose you have been offered this donor for a 23-year-old male CKD patient on dialysis for 11 years. 000 mismatch, he is highly sensitised with cPRA 96%. Crossmatch was negative. He is also running out of access and has no living donor available.
1. Will you accept this kidney for him?
2. What are you going to tell him about the risk of malignancy vs the risk of death on dialysis?
3. What would your immunosuppression (induction and maintenance) will be?
1.Yes I will accept him.
2.tell the patient that the risk of transmission is low when compared to risk of death on waiting list
3.low risk so induction by Basiliximab , maintenance steroids,Tac,MMF
Would you accept this donor?
I will not accept this patient as donor due to grade IV astrocytoma which is aggressive tumor, have high chance of recurrence and invade locally adjacent structures and also in the above case, blood brain barrier is disrupted because of VP shunt done 03 months back which increases the chances of dissemination.
If yes, what is the prognosis?
Transmission risk of grade IV astrocytoma is about 2.2% and one or more risk factors like ventriculo-atrial/ventriculo-peritoneal shunt, craniotomy and chemotherapy if present increases the risks from 7% to 53%. Different studies stated different percentages of transmission risk. One of the study mentioned more than 10 percent risk in patients having grade IV CNS tumor with shunt .Therefore, decision of transplantation should be individualized and recipient should be counseled in detail about the risk and benefits and with the advice of close follow up post –op.
REFERENCES:
1- 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.
2- 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
Would you accept this donor?
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.
We don’t have any data bout the potential recipients who may accept this offer especially if they are older, highly sensitized, long waiting time, or multiple access problems.
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.
· According to the OPTN/UNOS malignancy subcommittee, six levels of risk were developed. This donor belongs to the high risk category with more than 10% risk of transmission.
· Any CNS tumor with ventriculoperitoneal or ventriculoatrial shunt
and CNS tumor WHO grad III or IV are classified in this category and could be
completely transmitted by donation. Therefore, I wouldn’t accept this donor.
· If we accept this donor, the recipient will also be affected by
malignancy which would be a disaster.
Nalesnik MA, Woodle ES, Dimaio JM, Vasudev B, Teperman LW, Covington S, Taranto S, Gockerman JP, Shapiro R, Sharma V, Swinnen LJ, Yoshida A, Ison MG. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am J Transplant. 2011 Jun;11(6):1140-7.
This donor with grade IV astrocytoma and ventriculo-atrial shunt should be declined as high grade malignant brain tumors especially in the presence of disruption of blood brain barrier carries a high risk for transmission to the recipient.
Kumar S, Modi PR, Pal BC, Modi J. Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation?. Indian Journal of Urology: IJU: Journal of the Urological Society of India. 2016 Jan;32(1):74.
This DBD can’t be accepted for organ retrieval and further donation , based on the presence of high grade IV brain tumor( glioblastoma ) with high possibility of basement membrane disruption ,subsequent metastasis has probably occurred posing the recipient at high risk of transmission of malignancy which would be augmented by the effect of immunosuppression as well .In addition to the history provided the existence of ventriculo-atrial shunt 3 months previously which would further accelerate the metastasis of malignant cells to other organs including kidneys; increasing the risk of burden of malignant transformation .
According to the advice of Council of Europe in 1997, it would not be safe for the recipient at all.
If yes, the use of mTORi as a cornerstone of the immunosuppressive regimen would be mandatory, with their possible complications of less protection against graft rejection as well as bad wound healing which may pose the recipient for worse outcome. Transmission of malignant cells from the DBD donor cannot be prevented if it happens which would require more surveillance for early detection.
Reference:
American Journal of Transplantation 2010; doi: 10.1111/j.1600-6143.2010.03130.x
Usually brain tumor metastasis is very rare in literature otherwise very aggressive tumor. according to current scenario the deceased donor has a highly malignant tumor, there is >10 risk of transmission and metastasis. there is also VP shunt with risk of membranoproliferative glomerulonephritis too.
I will accept this donation.
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 high-risk patients 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.
So based on the available evidence I will not accept this donor because of the presence of a high-grade tumor with a ventriculi-atrial shunt which will be associated with a high risk of transmission
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.
Would you accept this donor?
The donor has a high grade glioblastoma (grade IV astrocytoma)…There is history of ventrivuo atria shunt 3 months ago…I will not accept this donor…. AS the chance of donor transmission of cancer is high in this patient due to a high grade tumor and there is breach of the blood brain barrier due to the shunt procedure….As per the BTS guidelines in 2018, the donor is contraindicated for organ donation due to high grade malignancy
What is the prognosis?
In general the prognosis after transplant from a CNS malignancy of a donor to a recipient is very rare…..The Israel Transplant Penn Registry quotes a rate of transmission upto 40% in intracranial malignancy but the UK registry analysis data which is a retrospective analysis did not quote a very high rate of donor derived intracranial malignancy spread…..
Prof Ahemd Halawa question:
The given recipient is a highly sensitized recipient with cPRA of 99%..The chance of him getting an another deceased donor is very less given the high cPRA…he being young with no vascular access will be very difficult to continue the dialysis…I will counsel hm regarding the small but an absolute risk of donor derived intracranial malignancy and take him up for transplant if the risk is accepted…
Reject the donation as this patient having recurrent high grade astrocytoma.
British Transplant Society 2018
Transplant may be consider only for low grade CNS tumors (WHO Grade 1 & 2)
age is 43 yrs with good kidney function, but the recurrent astrocytoma , with recent shunt, ill not accept this patient
Several important factors should be considered while accepting such a donor. These include cell types, grade of the tumor, prior history of craniotomy, ventriculo–systemic shunt and duration of patient’s disease.
if this donor will be accepted so the potential inherent risks of the organs from a deceased donor need to be clearly documented and the patient needs to be counseled before implanting the organ and intensive follow-up with a high index of suspicion should be maintained.
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6. Warrens AN, Birch R, Collett D, Daraktchiev M, Dark JH, Galea G, et al. Advising potential recipients on the use of organs from donors with primary central nervous system tumors. Transplantation. 2012;93:348–53. [PubMed] [Google Scholar]
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9. Fernando VB, Ruiz JC, Cotorruelo JG, Arias M. Glioblastoma multiforme of donor origin after renal transplantation: Report of a case. Hum Pathol. 1993;24:1256–9. [PubMed] [Google Scholar]
* I, would not accept this donor ,because there is still risk of tumor transmission, that can lead to poor outcome
*The transplant community has been struggling with the chronic shortage of donor’s organs for transplantation. In order to increase the donor pool, criteria for donation have been expanded, accepting as donors individuals with a history of malignancies of low metastatic potential. However, transplantation from these donors carries a risk of cancer transmission that should be carefully assessed for each tumor type.
Organs from donors with a history of a primary brain tumor (PBT) may be considered eligible for transplantation under extended criteria since these tumors have a low propensity to metastasize outside the central nervous system (CNS). These patients represent a relevant subgroup of donors that can increase the number of transplants performed, reducing times on the waiting list. According to the 7th edition of the guidelines on quality and safety of organ transplantation, the risk of transmission for patients with a history of PBT is mainly influenced by the tumor histotype and grade. The risk of tumor transmission in donors with a history of CNS tumors is graded as minimal, low to intermediate, and high or unacceptable; in detail, donors with World Health Organization (WHO) grade I and II PBTs are considered at minimal risk of tumor transmission, while grade III tumors are now considered at low to intermediate risk in the absence of any recognized risk factors, such as previous surgical resections, ventriculo-peritoneal (VP) or ventriculo-atrial shunt placement, and/or chemotherapy/radiotherapy that increase the risk from intermediate to high. These procedures disrupt the blood-brain barrier, increasing the risk of hematogenous and lymphovascular spread of these tumors. Extra-CNS metastases from PBTs do however occur, with a reported prevalence of up to 4.3% and metastases mainly occur in patients with a history of high-grade gliomas and, in particular, of glioblastoma. Ventriculo-atrial and VP shunts have also been reported as risk factors for tumor spread.
* Risk factors of extraneural spreading in astrocytomas and oligodendrogliomas in donors with gliomas: A systematic review
Serena Ammendola, Valeria Barresi, Elena Bariani, Ilaria Girolami, Antonia D’Errico, Matteo Brunelli, Massimo Cardillo, Letizia Lombardini, Amedeo Carraro, Ugo Boggi, Owen Cain, Desley Neil, and Albino Eccher
2022 Jun 18; 12(6): 131–141.
Published online 2022 Jun 18.
I will no accept this donor , as she has recurrent Grade IV astrocytoma with ventriculo-atrial shunt.
“CNS tumor (any) with ventriculoperitoneal or ventriculoatrial shunt, surgery (other than uncomplicated biopsy), irradiation or extra-CNS metastasis” are included in high (>10%) risk of transmission. and
Use of these donors is discouraged except in rare and extreme circumstances. Informed consent required.
If you accept it risk of transmission of tumor will be 10 %.
This is a real challenging case. It has been suggested that it is safe to use donors with primary cerebral tumours, if their tumours 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. 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 harbouring low-grade astrocytoma carries a very low risk of tumor transmission (0.1–1%) to the recipient.
So I might take this donor. This small risk of tumour transmission should be balanced against the likely mortality for potential recipients who remain on the transplant waiting list.
Ref:
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. PMID: 26941500; PMCID: PMC4756557.
The available donor is 43 years old female DBD where SAH is a cause of death with history of recurrent astrocytoma ( glioblastoma) which diagnosed 2 days ago.
And three month ago there was ventricular-atrial shunt with good UOP and good kidney function.
– this associated tumour carry high transmission risk and the precipitating factors are radiotherapy chemotherapy ventriculo-atrial shunt or craniotomy.
– according to WHO gliobrastoma is grade 4 tumour with risk of extra-neural spread
I will not accept this donor
if yes what is prognosis
Firstly we asses cast and benefit of transplant. With donor with brain tumour.
Mist council patient for t your transmission risk
.
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. 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.
So, back to our potential will donor. He has grade 4 recurrent brain astrocytoma, with ventriculo peritoneal shunt. This put the potential recipient at significant risk of disease transmission. So, I will reject this offer.
The prognosis is not favourable as risk of transmission of tumour is > 10%.
So, should not be accepted unless in extreme circumstances where it is life saving operation for the recipient. Example, like patient running out of dialysis access.
I would not accept this donor since she had a ventriculoatrial shunt which increases the chance of cancer metastasis for the recipient if the transplant is done. This risk would be above 10% in comparison with the usually low risk when the donor does not have any of the below :
References
Watson C J, Roberts R, Wright K, Greenberg DC, et al. How safe is it to transplant organs from deceased donors with primary intracranial malignancy? An analysis of UK registry data. Am J Trans; 2010; 10 : 1-8. doi: 10.1111/j.1600-6143.2010.03130.x
If this donor is accepted, then prognosis in the long term will be poor because cancer metastasis is a highly possible risk and cancer is a leading cause of death in long term kidney transplant recipients with such donors.
The recipient would need to be counseled about risks of cancer and intense follow up that would be required in the long term before the transplant is done.
Need for focussed long term cancer surveillance protocols would need to be initiated in order to improve prognosis for this recipient if this donor is accepted.
Reference :
*This potential DBD donor 43 years old, had SAH 2ry to recurrent glioblastoma( high grade tumour ) , having ventriculo-atrial shunt leading to disruption of the blood brain barrier so it increase risk of transmission so; i will refuse this potential donor although her good renal function ,excellent UOP.
*Prognosis if yes , will be very poor due to high risk of transmission >10%.
References:
Nalesnik MA, Woodle ES, et al. :Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am J Transplant. 2011 Jun;11(6):1140-7.
I will not accept this donor because there’s risk of transmission of malignancy to recipient.
Risk of transmission is small in primary intracranial malignancy but should not accept especially if there’s history of ventriclar shutting and history of irradiation and high grade of glioblastoma and medulloblastoma
Q2: If accept this donor should counselling regarding small risk of transmission
1- Iwill not accept this donor as: risk of primary brain tumour is based on the assessment of tumour histology ,grate previous surgery ,chemotherapy and ventculo -perotional shunt placement can lead to disruption of the blood brain barrier so it increase the transimission risk also in our pateint is vetrculo atrial shunt.
2- the prognosis is not good as high grate tumour (3) considered at low to intermate risk in the absence if the shunt.
usully the risk of metasis in high grate glioblastoma (4) so it is better to avoid this donor.
erferences
1-. Nalesnik MA, Woodle ES, Dimaio JM, Vasudev B, Teperman LW, Covington S, Taranto S, Gockerman JP, Shapiro R, Sharma V, Swinnen LJ, Yoshida A, Ison MG. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am J Transplant. 2011;11:1140–1147. [PubMed] [Google Scholar]
Yes, I would. This is a high-risk donor due to CNS malignancy. I believe that the risk is valid for patients who cannot wait that long on the transplant list, for example: those with restricted venous access for dialysis, or even those highly sensitized who already have a long waiting time .
Although the risk of transmission is feared, there are some case series that point to a relatively low risk: “The series included 175 recipients where the donor tumor was a GBM and the only recorded transmission occurred to three recipients (1.7%) of organs from one donor with a GBM”
Source: How Safe Is It to Transplant Organs from Deceased Donors with Primary Intracranial Malignancy? An Analysis of UK Registry Data
– This is young female, potential DBD donor with hx of Recurrent grade IV astrocytoma with venriculo- atrial shunt with excellent UOP & cr. Criteria.
– Generally , I will not accept her for donation , due to high risk of cancer transmission .
– But in the term of organ shortage , we have to be opened to keep the thinking of considering such organ for special recipients who have long time on the waiting list especially if suffering on dialysis with vascular access failure & with no living related donors , if I have such recipient , especially if good cross match is found , I will offer him this organ & explain to him the better outcome of accepting this organ if compared with being on waiting list & I will explain clearly the risk of cancer transmission .
Dear colleagues,
I note your responses. It is so nice of you to keep debating using sound arguments and supportive literature. Despite additional information about this recipient appearing to be in a desperate situation, you are convinced that your logical approach is unshakeable, a potential transplant from such a donor poses a profound risk to this recipient.
Ajay
The risk of malignancy transmission from the donor with primary CVS tumour as glioblastoma to a recipient need to be assessed compared to remaining on waiting list for a longer duration.
So I will reject this case for donation
Because the donor has high risk of tumour transmission to the donor because of
-high-grade cerebral tumour ,recurrent grade IV astrocytoma (glioblastoma)
-ventriculo-atrial shunt done indicating possibility of breakage of the blood–brain barrier that can increase the risk of extraneural spread, and donor
cancer transmission.
Case reports of metastasis to the kidney graft from high-grade lesions (glioblastoma multiforme) has been published.
Glioblastoma has intermidate risk of transmission.
In fact there remains a small but definite risk of transmitting cancer from donors with primary intracranial malignancy.
Reference
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.
– 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
Primary CNS malignancies and cadaveric donation
The studies evaluating the risk of transmission of CNS malignancies most of it is retrospective observational studies of low number (evidence III) but primary CNS malignancies are considered of low risk of metastasis and the overall risk of transmission ranges from 0-23% (1)
there are some Risk factors that increase the risk of transmission including:
These risk factors may increase the risk of metastasis according to some studies to 53% from 7 percent. (2)
On the other hand, a retrospective study evaluating 179 deceased donors with primary intracranial malignancy of which 33 were high grade (24 grade IV gliomas and 9 medulloblastomas) reported no transmission of donor malignancy in all cases.
But again, as long as the evidence is weak more studies are needed before generalizing the rule of acceptance or rejection
So, generally, I will not accept the donor but in very limited circumstances if the recipient is old and failed vascular access or is on the waiting list for a long duration so I will counsel him, and if he accepted, we will accept the risks to avoid keeping the patient on dialysis.
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.
Good positive data
43 year
good basal creatinine (100 µmol/L before retrieval) with excellent urine output
However the presence of a high-grade brain tumor (recurrent grade IV astrocytoma (glioblastoma) ) with a history of ventriculoatrial shunt 3 months ago so the risk of transmission is high According to
the Council of Europe guidelines, organs from donors with
high-grade brain tumors should not be used because of the
Perceived high risk of cancer transmission.
Also increased risk of transmission if associated with craniotomy, previous chemotherapy or radiotherapy, and an increased period between the time of diagnosis of tumor and time of death
So I will not accept this donor
It is essential to calculate the risk of cancer metastasis in the recipient and the risk of the waiting list for transplantation mortality and the low number of donors available for kidney transplantation.
Can be accepted if there is a high risk of mortality for the recipient for being waiting for renal transplantation ( for ex has no vascular access for dialysis )
so careful history taking, tumor histology,previous operations, good examination of the thoracic cavity and abdominal cavity during retrieval to exclude any distant metastasis
Ref :
Council of Europe. International consensus document: Standardisation
of organ donor screening to prevent transmission of neoplastic
diseases. Council of Europe, 1997.
Halpern SD, Shaked A, Hasz RD, Caplan AL. Informing candidates
for solid-organ transplantation about donor risk factors. N Engl J
Med 2008; 358: 2832–2837.
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 cell types, grade of the tumor, prior history of craniotomy, ventriculo–systemic shunt and duration of patient’s disease. In view of organ shortage, potentially no organ should be wasted. However, the potential inherent risks of the organs from a deceased donor need to be clearly documented and the patient needs to be counseled before implanting the organ and intensive follow-up with a high index of suspicion should be maintained.
A review of the literature suggests that organs donated by deceased individuals with primary CNS tumors can be used for transplantation.
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.
So I will not accept this potential donor as she has high grade recurring CNS tumor with breaching the BBB , although 000 mismatch with the recipient.
Reference:
Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation?
Suresh Kumar, Pranjal R. Modi, and Jayesh Modi
The index prospective donor is
a) 43-year-old female DBD
b) Cause of death: SAH
c) Recurrent Grade IV astrocytoma (glioblastoma) – diagnosed 2 days back
d) Ventriculo-atrial shunt: 3 months back
e) Excellent urine output
f) Serum creatinine 100 micromol/L
A prospective donor with any CNS tumor and ventriculo-atrial shunt is a high risk (>10%) for transmission (1). Factors associated with increased risk of extraneural spread (and consequent donor cancer transmission to recipient) include craniotomy, stereotactic biopsy, ventriculosystemic shunts, prior radiotherapy and chemotherapy, and increased time between diagnosis of tumor and death (2,3).
Glioblastoma is a WHO grade 4 tumor, with intermediate risk (2.2%, with upper limit of 6.4%) of extraneural spread (4,5).
Although the renal function is good, she has issues which contraindicate the donation, namely history of ventriculo-atrial shunt and a recurrent glioblastoma.
Hence the donor should not be accepted.
The scenario in which such a donor can be accepted is in older individuals and those with multiple comorbidities due to potential of gaining number of life years, which according to estimates, is between 2 to 8 years (5). The patient should be counselled regarding the risk of transmission of tumor in detail and the transplant shpuld be proceeded with only after informed consent.
References:
1) Nalesnik MA, Woodle ES, Dimaio JM, Vasudev B, Teperman LW, Covington S, Taranto S, Gockerman JP, Shapiro R, Sharma V, Swinnen LJ, Yoshida A, Ison MG. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am J Transplant. 2011 Jun;11(6):1140-7. doi: 10.1111/j.1600-6143.2011.03565.x. PMID: 21645251.
2) 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.
3) 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.
4) 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. PMID: 26941500; PMCID: PMC4756557.
5) 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.
I will not accept this patient although the shortage of organ transplant organ ,we need to weight the risk of malignancy transmion versus the benefits of transplantation
first has recurrent of this high grate malignancy with complication ventriculoarterial shunt 3 month back .there were some cases reports of glioblastoma in recipient postrenal transplantation
if yeas the prognosis is not good as has recurrence and ventriculoarterial shunt a though the intracranial CA are no contra indicated
This donor has a few risk factors that make me against accepting her as a donor:
– High-grade type of malignancy
– Recurrent (so she received some interventions to treat the primary one which increases the chance of dissemination of cancer cells)
– Presence of AV shunt
It is a difficult decision to lose a chance for setting a patient free of a dialysis machine but it is preferable to put him/her in risk to develop malignancy, especially since we don’t know the behavior of malignant cells under immunosuppressant condition.
I will not accept this donor as he has high grade malignancy with high risk of transmission with ventriculo-atrial shunt .
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 shunts
Would you accept this donor?
I wouldn’t accept this donor
a) there is a risk for transmission of cancer cells provided recurrence of the tumor and the 3 months prior history of ventriculo-atrial shunt which is a known risk factor for transmission.
b) There were reported cases of glioblastoma multiforme of donor origin after renal transplantation, even without a history of ventriculo-systemic shunt1-2.
c) Donors with a history of incurable cancer, insufficient follow-up, or cure probability <90% are considered at high risk for tumor transmission3.
Factors reported to increase the risk of extraneural spread:
a) Craniotomy.
b) Ventriculosystemic shunts.
c) Prior radiotherapy or chemotherapy.
d) An increased time between diagnosis of tumor and death.
If yes, what is the prognosis?
a) Prognosis is poor, carries high risk with >10% transmission as per suggested risk categorizations for specific tumor types3.
b) GBM is an aggressive incurable cancer and the Healthgrades USA state that only 4 percent of the people diagnosed with glioblastoma survive for 5+ years.
Reference
1. Val-Bernal F, Ruiz JC, Cotorruelo JG, Arias M. Glioblastoma multiforme of donor origin after renal transplantation: report of a case. Hum Pathol. 1993 Nov;24(11):1256-9. doi: 10.1016/0046-8177(93)90224-5. PMID: 8244327.
2. Ruiz JC, Cotorruelo JG, Tudela V, Ullate PG, Val-Bernal F, de Francisco AL, Zubimendi JA, Prieto M, Canga E, Arias M. Transmission of glioblastoma multiforme to two kidney transplant recipients from the same donor in the absence of ventricular shunt. Transplantation. 1993 Mar;55(3):682-3. PMID: 8384384.
3. M. A. Nalesnik et.al. Donor-Transmitted Malignancies in Organ Transplantation: Assessment of Clinical Risk American Journal of Transplantation 2011; 11: 1140–1147
Would you accept this donor?
–I wouldnot accept this donor because ha had recuuent of high grade brain tumor (grade IV astrocytoma) and ventriculo-atrial shunt 3 months ago.
-Donors with primary intracranial malignancy who have undergone interventions such as debulking surgery, radiotherapy and ventriculosystemic shunt placement, all of which breach the blood brain barrier are potentially associated with systemic dissemination of tumor cells
If yes, what is the prognosis?
Poor prognosis because he had high risk of transmission of malignancy.
Referrence
-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
Would you accept this donor?
This 43 year DBD from SAH due to recurrent Grade 1V astrocytoma.
So a High Grade tumour with recurrence
Secondly there is breach of blood brain barrier due to Ventriculoatrial shunt
So there is high risk of breach and metastasis.
Factors leading to high risk of metastasis include-
Shunts-Both ventriculoatrial or ventriculo peritoneal shunts.
Surgery
Complicated biopsy
Donation is contraindicated in the presence of above factors or if there are systemic metastasis.
So in this situation I will not accept this donor
If yes, what is the prognosis?
There will be high risk of metastasis and prognosis will be grim.
References-
1-Nalesnik MA, Woodle ES, Dimaio JM, et al. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am J Transplant. 2011 Jun;11(6):1140-7.
2-Watson CJ, Bradley JA. Evaluating the risk of cancer transmission to optimize organ usage. Am J Transplant. 2011 Jun;11(6):1113-4
Thank you
This scenario discusses the possibility of DBD donation from a lady with recurrent high grade glioblastoma grade 4 who had a procedure ventriculo-atrial shunt) that disrupted the blood brain barrier(BBB) .
Primary CNS tumors represent 3–4% of the causes of brain death among organ donors.
To expand organ donor pool, organs from donors with primary cerebral tumors has recently been in focus because of the low risk of extra-neural spread( 0.4–2.3%).
Accordingly, multiple data registries included patients dying of primary CNS tumors including those with high WHO malignancy grade tumors including:
– UK Transplant Registry (UKTR, no donor-transmitted malignancies out of 179 donors with a history of primary intracranial malignancy donating to 448 recipients.)
– United Network for Organ Sharing (UNOS, 3 recipients had transmitted malignancies from 642 donors with primary CNS tumors)
– Australia and New Zealand Organ Donation Registry (ANZODR, 151 recipients of 46 donors with primary CNS tumors and no case of transmission of donor malignancy was identified
Risk factors of transmission from donors to recipients has been attributed to (The more related factors, the more risk of cancer transmission):
1) donor tumor histology (WHO grade IV).
2) disruption of the blood-brain barrier (craniotomy and chemoradiation therapy)
3) cerebrospinal fluid extra-CNS (ventriculo-atrial and ventriculo-peritoneal shunts)
4) natural characteristics of tumor (high level of EGFR-amplified).
Would you accept this donor?
From the given information, I would not accept this donor with multiple risk factors of tumor recurrence including:
– High grade tumor histology(grade IV)
– Recurrent tumor (high risk of distant metastasis to the pleura, lungs, liver, bone marrow and regional lymph nodes.)
– Breach of the blood brain barrier with the ventricular-atrial shunt that increases the risk of extra-neural metastasis.
If yes, what is the prognosis?
Reliable data on the actual percentage of cancer transmission significantly varies in between registries.
– Accordingly, an individualized decision making is required to avoid spreading of a lethal disease. Moreover, the recipient needs counseling before implanting the organ regarding the small but definite risk of transmission vs the chances of survival if he chosen to remain on the waiting list. This should be coupled with intensive follow-up with a 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) 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
Thank you
Would you accept this donor?
This 43-year-old female DBD donor has good quality kidneys (good urine output & normal serum creatinine), however, she has a history of recurrent grade 4 astrocytoma & had ventriculo -atrial shunt few months ago.
The risks & benefits of transplanting organs from this donor should be assessed for the potential recipient.
Before accepting kidney from this donor, I should take all possible measures to exclude any residual or recurrent cancer. An extensive laparotomy & thoracotomy should be done at the time of organ retrieval to look for any evidence of spread of cancer.
A high level of suspicion should be taken in donors with a past cancer presenting with an intracranial bleed or presumed primary central nervous system tumour.
When the cause of brain death is cerebral haemorrhage or an apparently primary brain
tumour diagnosed without histological examination as in this index case, the possibility of cerebral metastasis from melanoma should also be considered.
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· If yes, what is the prognosis?
In the UK, the experience of transplanting from donors with CNS cancers has been studied for the period 1985–2001, from which recommendations have been developed. No case of transmission of cancer was reported.
So, the prognosis seems to be favorable.
References
R. Desai1, D. Collett, C. J. E. Watson, P. Johnson, T. Evans and J. Neuberger.
Original article: Estimated risk of cancer transmission from organ donor to graft recipient in a national transplantation registry. BJS 2014; 101: 768–774
Thank you
This scenario is about receiving kidneys from a donor who had suffered RECURRENT HIGH GRADE (grade 4) astrocytoma ( glioblastoma) who had procedure which BREACHED THE BLOOD BRAIN BARRIER( Ventriculo-atrial shunt).
The history of recurrence indicates that the patient might have distant metastases to sentinel lymph nodes or adjacent lymph nodes. High grade tumour and systemic metastases made this donor unlikely to be selected as likelihood of transmission of malignancy is high.
Procedures that breach the blood brain barrier are potentially associated with systemic dissemination of tumor cells. This patient has Ventriculo-atrial shunt done, so high likely the dissemination of tumor happened.
Having gathered those information, I would not accept the donor.
Thank you
Potential donors with anaplastic astrocytoma (WHO grade III) can be accepted as organ donors.
Transmission risk is considered low to intermediate for tumours without any risk factors. Potential donors with glioblastoma multiforme (WHO grade IV) are considered intermediate to high risk for transmission depending on the different national recommendations, which are expected to be adjusted with increasing evidence. The transmission risk is increased (high risk) in all cases with previous interventions such as tumour resection, ventriculo-peritoneal/-atrial drainage and/or cranial chemo- /radiotherapy
So, I will not proceed with transplantaion!
Thank you, Alaa
References please
This is high grade tumor with history of ventriculo atrial shunt. I’ll not accept in my setting.
Thank you,
References??
Thanks sir,
High risk with more than 10% transmission in any CNS tumor with ventriculoperitoneal or ventriculoatrial shunt surgery.
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
First I would not like to accept such donor fearing form increasing risk for developing cancer through years after transplantation.
Below some data about why I am taking this decision.
Glioblastoma (GBM) is the most malignant, aggressive and common (60%) form of astrocytomas. Histologically, it is characterized by very abnormal-appearing cells, proliferation, areas of dead tissue and formation of new vessels. GBM can present either as a malignant progression from a previously existing lower grade astrocytoma (usually in 10% of cases) or originate directly as a grade 4 tumor (90% of cases). The former scenario is most common in younger patients, while the latter is most common after age 60. Regardless of its presentation, this tumor is a highly aggressive cancer, with pronounced brain invasion and destruction and very fast progression.
Several important factors should be considered while accepting such a donor. These include cell types, grade of the tumor, prior history of craniotomy, ventriculo–systemic shunt and duration of patient’s disease.
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.
And according to Donor-Transmitted Malignancies in Organ
Transplantation: Assessment of Clinical Risk Donor Malignancy Transmission Risk
Table 2 showed Suggested risk categorizations for specific tumor types
that High risk (>10% transmission)
There is sufficient evidence that 40% of renal graft recipients develop cancer after 20 years,which may be related to impaired immunosurveillance, the direct neoplastic actions of immunosuppressive agents, oncogenic viruses, or genetic predisposition.
Also There are three situations in which malignancy typically occurs: malignancy is transmitted via the donor, a known or latent prior malignancy has already developed in the recipient, and de novo malignancy that develops in the recipient after transplantation.
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Reference
Can deceased donor with recurrent primary brain tumor donate kidneys for transplantation?
Suresh Kumar, Pranjal R. Modi, […], and Jayesh Modi
Astrocytoma in a renal transplant recipient: A rare case report
American Journal of Transplantation 2011
Wiley Periodicals Inc.
Journal compilation
2011 The American Society of
Transplantation and the American Society of Transplant Surgeons
Personal Viewpoint
Donor-Transmitted Malignancies in Organ
Transplantation: Assessment of Clinical Risk
Thank you
you were offered kidneys from a 43-year-old female DBD (donor after brain stem death) donor who suffered from SAH secondary to recurrent grade IV astrocytoma (glioblastoma) diagnosed by MRI 2 days ago. She had a ventriculoatrial shunt 3 months ago. Her baseline S Cr was 89 µmol/L and 100 µmol/L before retrieval. She had excellent urine output (110mls/h during the last hour and 3 L over the last 24 hours).
Would you accept this donor?
This is an offer of DD from DBD with high-grade stage 4 glioblastoma, 3 months ago underwent intervention with the ventriculoatrial shunt (risk of seeding of tumor high-grade glioblastoma characterized by vascular invasion and possible systemic spread to the lymph nodes and bone, bone marrow, the additional risk for the systemic spread of this high-grade aggressive type of tumor is the history of shunt so in this scenario we should make our decision based on the mentions risk factors from the limited available evidence and recipient status
Risk categories from donor tumor transmission (1)
Risk category
1. Zero no significant risk and frequency estimate 0% can be accepted as a standard donation
2.Minimal, the evidence suggests the minimal risk of tumor spread with a frequency range (0-< 1%), which needs clinical judgment with informed consent
3. Low evidence of spread in the range of 0.1<1%, use in recipients at significant risk without transplantation, and informed consent required
4. Intermediate risk of tumor transmission with frequency rate 1%-< 10%, use of such donors not recommended on occasion like life-saving transplant may be acceptable like recipient high risk with short survival without transplantation (like days) informed consent needed.
5. High risk with frequency rate > 10 % also such donors should be rejected except in rare and extreme circumstances with informed consent.
6. Unknown risk and NA frequency due to incomplete or no evidence to assess the risk in such cases we have to decide based on clinical judgment with informed consent.
Based on the above-limited evidence this offer considers the high risk with a frequency rate of transmission > 10%, I will reject the donor if the recipient is not at high risk of death from long waiting.
If yes, what is the prognosis?
Accepting such an offer should be limited to individualized cases in relation to the recipient risk stratification
he is a high-risk score with a frequency estimated of transmission > 10% and according to the recommended clinical use, this donor should be rejected except in rare and life-threatening situations like the short survival rate of the recipient and informed consent required with a detailed discussion about the poor prognosis.
References:
1. Nalesnik MA, Woodle ES, Dimaio JM, Vasudev B, Teperman LW, Covington S, Taranto S, Gockerman JP, Shapiro R, Sharma V, Swinnen LJ, Yoshida A, Ison MG. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am J Transplant. 2011 Jun;11(6):1140-7.
2.How Safe Is It to Transplant Organs from Deceased Donors with Primary Intracranial Malignancy? An Analysis of UK Registry Data, JC 3 Week 7
Thank you
Recently there has been evidence that use of organs from donors with primary cerebral tumors can be promoted because of the low risk of extraneural spread, which is reported as 0.4–2.3%. This will increase the availability of kidneys.
But in the above scenario, I will not accept kidneys from this deceased donor for following reasons:
Ref:
Thank you
This is a female donor with a recurrent grade 4 astrocytoma that was diagnosed 2 days prior and she has had a history of a ventricle-atrial shunt 3 months before her current admission.
The Disease Transmission Advisory Committee (DTAC) established by the OPTN/UNOS has categorized any CNS tumor, regardless of grade with a ventriculoperitoneal or ventriculoatrial shunt, surgery, chemotherapy or extra-CNS metastasis to be provisionally placed in the high risk category.
The DTAC has categorized risk for donor transmission from risk category 0 to risk category 4 where 0 implies no significant risk and 4 implies high risk. There is also the category U which signifies unknown risk.
Even though the potential donor has excellent urine output and kidney function, the presence of recurrence and the prior ventriculoatrial shunt puts the donor in the high risk category. I will also get an oncology consult from neuro-oncolgist but I will not accept the kidneys
American Journal of Transplantation 2011; 11: 1140–1147
Thank you
I will not accept this donor as because only low grade CNS tumor can be accepted as a donor.
Thank you Tufayel, could you explain more? References????
no this patient is not a candidate for donation .
the cause :
On the basis of the current analysis, it is recommended that organs donated by deceased individuals with primary central nervous system (CNS) tumors should be used. We suggest the following two caveats:
(These recommendations do not deal with a metastatic deposit from a presumed extracranial primary. A retrieval surgeon should always perform a thorough laparotomy and thoracotomy at the time of retrieval, whether or not there is a known malignancy, but it is particularly important to do so in the context of the finding of an intracranial mass. Ideally, the donor will have had previous imaging, including chest radiography, abdominal ultrasound, and possibly also whole body computed tomography scanning, and histological assessment of any lesion found. However, we recognize that this is not always possible and should not act as a brake on proceeding.).
reference :
Council of Europe. Criteria for preventing the transmission of neoplastic deseases in organ donation. Council of Europe Publishing, 2006.
Thank you, Dr Hindawi
The risk of acceptance of that donor must be balanced against risk of keeping recipient in waiting list with associated morbidity and mortality with dialysis. Patient counselling regarding malignancy transmission is important.
Prognosis in case of acceptance:
WHO grade iv tumors including glioblastoma has intermediate risk of cancer transmission of 2.2%.Risk factors for cancer transmission include the high grade of the tumor ,ventriculo atrial shunt, craniotomy and chemotherapy ;if any.
One or more of these risk factors increases risk of transmission from 7% to 53%.
Other authors consider CNS tumor grade iv with shunt having high risk of malignancy transmission more than 10 %.Generally speaking, tumor transmission varies from 0 to 23 %
References
De Hert,et al :Preoperative evaluation of adults undergoing elective non cardiac surgery .Updated guideline from the European Society of Anaethsiology. Eur J Anaesthiol.2018;35:407-65.
Kotoloff,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.
Thank you