|Year : 2017 | Volume
| Issue : 3 | Page : 117-122
Incidental malignancy in cadaver donor: What is the real impact?
Manish Ashokkumar Madnani1, Hitesh J Chavda2
1 Department of GI and HPB Surgery, Shalby Hospital, Ahmedbad, Gujarat, India
2 Department of GI and HPB Surgeries and Liver Transplantation, Sterling Hospital, Ahmedbad, Gujarat, India
|Date of Web Publication||20-Dec-2017|
Dr. Manish Ashokkumar Madnani
302, Suvidha Park, 18 Patel Society, Opp Madhavpura Market, Shahibaugh, Ahmedabad - 380 004, Gujarat
Source of Support: None, Conflict of Interest: None
Worldwide organ shortage is one of the most common hurdles while treating patients with end-stage liver disease, especially in countries where there is lack of interest in organ donation. Apart from this, cost of this remedy is one reason, which makes this treatment distant dream for many. In such a situation, to lose even a single donor becomes too costly, cost of which is life of some other patients. Extended criteria for liver donation are already in use, though in some situations clinicians feel like trapped between providing best care and managing organ demands. One of such tricky situations is incidentally found malignancy in donor. Recently, we came across such situation during the harvest of liver from a cadaver donor, which made us go through the literature and find the answer. Here, in this review, we share that experience and try to throw light on this enigmatic issue with special focus on incidentally found malignancies in cadaver donor.
Keywords: Cadaver donor malignancy, extended criteria organ donors, incidental donor malignancy, liver transplantation, marginal organ donors
|How to cite this article:|
Madnani MA, Chavda HJ. Incidental malignancy in cadaver donor: What is the real impact?. Indian J Transplant 2017;11:117-22
| Introduction|| |
Organ shortage for transplant program is one of the most common hurdles faced by transplant centers worldwide; to add cherry on the cake, developing nations have to meet with costs of this highly advanced and expensive treatment in many ways, i.e., lack of central donor distribution system, social taboos which prevent people from donating their organs, absence of strong local administrative systems which prevent usage of received organs, and long waiting list.,
Even after long list of problems faced by transplant teams, their dedicated efforts have changed many lives and such programs are gearing up to their next level. In the best intention of the patient, sometimes, transplant surgeon has to take some difficult decisions. One of such situations is when one has to use organ from a donor who was not a diagnosed case of any cancer but found to have one during organ procurement.
We met this kind of problem during recent liver procurement operation of a cadaver donor, which stimulated us to find the answer to this problem. Here, we present the review of world literature on this particular question.
| Burden of Problem|| |
South Asian countries such as India and South Korea are more dependent on living-related donors, while cadaver donations provide only one-tenth to one-fifth organs in this part of the world; developed nations are more dependent on cadaver donation. Hence, naturally unexpected malignancies in cadavers will have more effects in regions where cadavers are prime source of organs.
Recently, Sens et al. in 2009 showed that unexpected malignancies occur nearly 7% in retrospective review of 412 autopsies performed during 5-year duration at North Dakota University. While 40% of those having cancers died of their disease, nearly 60% of them were potential donors who could not be denied for organ donation on any other grounds, if they would have opted to do so. This number is worrisome for transplant surgeons. Although the authors of this study have suggested complete forensic autopsies of donors, it is neither routinely practiced nor a practical option.
Carver et al. in 1999 reported that incidentally found renal cell carcinoma was met 0.9% time during kidney harvesting from cadaver donors. That means nearly 1 in every 111 donors and 1 kidney out of 222 kidneys are affected by renal cell carcinoma which was not known before. They suggested careful palpation of both kidneys before any organ harvested.
Different studies have reported rate of tumor transmission from 0% to 42%.,,,,,, This wide range is criticized in literature. One of the reasons for high rate of tumor occurrence reported in the Israel Penn Transplant Tumor Registry by Buell et al. is thought to be because of voluntary kind of reporting system by transplant surgeons, where tumor recurrence in recipient being an eye-catching event was reported more and the true denominator is not well known. On the contrary, mandatory registries such as United Network for Organ Sharing (UNOS) have reported tumor occurrence in recipients who received organs from donors who had history of cancer is low, only 0.2%.
If we consider that, both the scenarios, as denoted by Sens et al. and UNOS registry stand true, then for every 11,905 transplanted organs from donors without history of cancer, one patient may get donor transmitted tumor; though chance of getting tumor when donor is already known case of cancer is very high, one in 500.,
| Tumor-Specific Decision-Making|| |
While Level 1 and 2 evidences are not present and even not likely will be available in the near future, concrete guidelines cannot be expected. Although there are some tumors which are more commonly encountered in clinical practice and experience of transplant teams is increasing with few particular varieties of tumors, guideline cannot be made for every kind of malignancy. Clinical acumen of treating team, desperation of situation, and possibility of finding another organ within specified time limit may influence the decision in such situation.
Guidelines are laid by leading authorities in the field, i.e., guidelines by Malignancy subcommittee of Disease Transmission Advisory Committee (Part of UNOS), Council of Europe guidelines, and Caring for Australians with Renal Impairment guidelines. More or less they are similar in providing help in decision-making to use organs from donors with history of particular cancers.
Central nervous system tumors
A known malignancy, which itself is the cause of death, is contraindication for organ donation, except central nervous system (CNS) tumors, which can cause brain death due to brain hemorrhage. Without any previous history of such a tumor, it is least likely that any invasive procedure that can violate blood-brain barrier such as transcranial biopsy, ventricular-peritoneal shunt was carried out. In such donors, if at the time of procurement, metastasis is ruled out and tumor is World Health Organization Grade I or II, then organs of such donors can be used safely.,
Due to its high prevalence in general population, well-preserved organ function and low chance of spread outside blood-brain barrier, donors with low-grade CNS malignancies are potential donors with very small risk of tumor transmission to recipient.
Any donor who presents suddenly with subarachnoid hemorrhage or intra-cerebral hemorrhage of unknown origin (absence of history of trauma, hypertension, and ischemic heart disease) is seen with suspicion. Cases are reported where such presentations were because of intracranial tumors (primary or metastasis).
Melanoma carries 74%–78% risk of transmission in recipient, with mortality in range of 58%–68% patients who develop malignancy. Less than 1 mm melanomas have been reported to recur even after 10 years of duration, so it is not considered as cured. Detection at the time of organ procurement definitively rules out use of these organs. It can also present with intra-cerebral hemorrhage; when no other systemic signs of disease are present, such cases are nearly impossible to diagnose beforehand.,,,,,
Non-melanoma skin cancers are not very aggressive. Basal cell carcinoma is known for its indolent course. Squamous cell carcinoma is more aggressive than basal cell carcinoma though less than melanoma. In the absence of any local or distant spread, organs from donors harboring small non-melanoma skin cancers or treated before for them can be used safely.,
Gynecological and breast cancer
Choriocarcinoma has high transmission rate, nearly 93% with mortality of 64% in patients who develop tumor. Any female donor of reproductive age group presenting with unknown intra-cerebral hemorrhage without any history of malignancy should be screened carefully; it can be because of metastasis from choriocarcinoma. Like melanoma, any slightest doubt of this particular malignancy will disqualify that donor.,
Endometrial cancer is diagnosed early and has good prognosis. Though the data available on this cancer are limited, 65 organs transplanted from donors with history of endometrial cancer did not show any tumor recurrence in recipients. It is placed in intermediate category, so without large data, tailor-made approach is advisable.,
In recipients receiving organs from donors who had history of breast cancer, tumor transmission rate is nearly 29%. Though it is not reported with in situ carcinomas, it has high propensity for delayed recurrence, so minimum waiting of 5 years after cure is necessary. No guidelines give clear verdict on this tumor. In the best favor of patients, organs from donor having invasive carcinoma of breast should be rejected if possible.
Renal cell carcinoma, being hypervascular tumor and with high chance of hematogenous spread, is rejected straightforward for organ procurement. There is extensive literature available on organ donation from donors having history of treated renal cell carcinoma or presenting at the time of organ harvest. Largest series is published by Nicol et al. from Princess Alexandra Hospital; they showed that when tumors were less than 3 mm, only one recipient out of 43 developed tumor recurrence, that too after 9 years of transplantation. Literature also suggests use of tumor-ectomized kidneys is safe in the absence of local or distant metastases and when R0 resection can be achieved.,,,,,,
Tumors with Fuhrmann Grading I or II, <4 cm in size without any tumor thrombus in renal vein or inferior vena cava are not an absolute contraindication against transplant. Our encounter was similar, where we found incidental 2.3 cm solid renal mass on the upper pole of right kidney, which on frozen section showed it to be renal cell carcinoma with oncocytic change. Final histopathology confirmed mucinous tubular and spindle cell carcinoma of kidney which showed tubular predominance and oncocytic change.
Prostate cancer being the disease of old age is not common in donors as they are not eligible for donation because of other issues. There are no large data to support or reject use of organs from donors having prostate cancer. However, our native wit would suggest on the basis of long natural history of prostate cancer that organs from these donors should not be rejected if there is only local disease. European society considers this and allows organ procuring from donors with history of prostate cancer, Gleason score below 6 being safe. However, we have to remember this is not validated by other authorities; individualization on case-to-case basis would be recommended.,,,,
Mitsuhata et al. reported eight patients with lower ureteral cancer successfully donated kidneys, only one patient developed metastasis. Hence, they suggested kidneys of donors with ureteral cancer are to be used if frozen section shows tumor-free margin. Similarly, bladder cancer patients can donate other organs though kidney donation requires caution.,
- Lung cancers: Three out of seven transplanted organs with a history of lung cancer developed malignancy in recipients. Due to its high risk of transmission (41%), it is not recommended to use organs from donors with history of lung cancer
- Hematological malignancies: This kind of malignancy is easily missed on complete examination and work up of donor without confirmatory evidence, and due to its high transmission in recipient, even a history suspicious of such disease is contraindication for organ procurement from that donor ,
- Colon cancers: Literature suggests transmission of malignancy in recipients after transplantation from donors with a history of colon cancer, though these are usually case reports, so it is difficult to derive definite risk of transmission from literature. Thus, without good evidence, it is better to reject patients with history of colorectal cancers. The dilemma remains for donors who belong to families with hereditary cancer syndromes. Till date, no guidelines have focused on this subgroup of donors; it is understood that organs from donors without personal history of colorectal cancer but with family history of cancer syndromes to be considered for organ donation with utmost care and stringent follow-up in recipient ,,,,,,
- Other intra-abdominal malignancies: Reports of donor transmitted malignancies are rarely reported from donors with pancreas and liver cancer; most of the times, such history is not available in donors and only diagnosed retrospectively with occurrence of metastasis in recipient. Institutional protocols should include clear mention of such situations beforehand to avoid the confusion at desperate situation of major transplant operation. Along with this, history of other aggressive neoplasm, i.e., sarcomas, lymphomas, etc., forces transplant team to reject such donors.,,
Some cancers are known to have delayed recurrence; in such cases, the remote history of such cancers cured in the past may or may not be available at the time of organ procurement, though immunosuppression provokes the recurrence rapidly in recipient. Examples of these tumors are melanoma, choriocarcinoma, and carcinoma of the breast. If there is even slightest doubt about such cancers in donor, a surgeon must withhold himself from using organs from these donors.,,
In situ squamous cell carcinomas of various organs are low-risk tumors, i.e., vocal cord, cervical cancer. Sub-centimeteric well-differentiated thyroid tumors of papillary of follicular histology are also considered low-risk tumors.
| Why to Consider Donors with Malignancy?|| |
As already discussed above, donor organ pool is always a restrain for transplant programs. With achievement of sophistication in this kind of operations in the form of better patient selection, use of imaging, better anesthetic drugs and equipment, and better intensive care, liver transplant is no more an experimental treatment. In-hospital mortality has reduced much in patients undergoing liver transplant, and 5-year survival rate is obviously far better than any other comparable treatments for many of liver diseases.
In such situation, when one rejects a particular donor with speculated increased risk to recipient's life, one has to consider risk-benefit ratio of that option. In their original article, Tector et al. showed that when extended criteria donor organs are used, significant reduction in waiting time for transplant is achieved and rapid clearance of waiting list is possible with no significant difference in recipient survival or chance of getting donor transmitted tumor. In their study, 2.3% donors has a history of nonskin cancers, but recurrence of tumor in recipient was not different whether or not history of cancer in donor was present.
| Measures to Avoid Surprises|| |
No surgeon would like to meet this kind of situation where already prepared patient is deferred transplant. To avoid incidental tumors being picked up during donor operation, we suggest below-mentioned measures (for cadaveric donors).
- A detailed history of donor from all possible sources available family members, friends, medical records, etc. In hurry of preparing operation theater and recipient, this part is not to be overlooked; one dedicated member of the team should go through detailed history of donor. History of hospitalization or surgery should dictate further evaluation and exact information is acquired as much as possible
- Head to toe examination of donor. During critical period of preserving donor till organ procurement, one is likely to overlook clinical examination of donor. Clinical examination of donors in Intensive Care Unit is neither time-consuming nor requires any special efforts; it just needs special attention. Donor is to be examined thoroughly, hidden areas such as scalp and back; genitals are to be carefully examined to rule out any suspicious findings. The presence of unexplained surgical scars anywhere on body should dictate further interrogation
- Imaging contrast-enhanced computerized tomography screening of the body cavities, cranium, thorax, and abdomen is to be sought for when possible. If that much of time or transfer cannot be given, bedside ultrasound of the abdomen and X-ray chest must be done and doubly checked by radiologists and reported. Any suspicious finding is to be communicated with surgical team
- Cause of brain death is to be captured, and without putative etiology, it should raise the suspicion 
- Gynecological examination for female donors is to be performed by gynecologist
- Recipient surgery should be timed in such a way that, after all checks only, any irreversible steps would be performed
- Before exsanguination of donor, examination of all viscera by palpation is to be performed by harvesting team
- Full-body autopsy as suggested by some authors should be done if possible depending on facilities and institutional protocols.
| Posttransplant Malignancy in Recipient|| |
Malignancy after transplant in recipient is either recurrence or de novo. Again the recurrence can be of recipient's past malignancy of tumor derived from donor. To differentiate between donor-derived and recipient's own malignancy in situ hybridization of sex chromosomes, human leukocyte antigen typing, DNA polymorphism, or microsatellite analysis can be done.,,
De novo malignancies are tackled in a standard way. While recurrence of recipient's past tumor aggravates with immunosuppression, in such cases, apart from standard treatment of tumor, dose of immunosuppression is lowered. Though there is no evidence, as suggested by some studies, mammalian target of rapamycin inhibitors (i.e., sirolimus) has anti-neoplastic activity, which is then included in immunosuppression regimen.,
For donor-derived malignancy, when high-risk tumors such as melanoma and choriocarcinoma, which were not diagnosed till after transplant, urgent re-transplantation is suggested if the malignancy remains localized within transplanted organ. Nonvital organs (i.e., kidney, pancreas) are removed urgently and the patient can be placed on replacement therapy. Unfortunately, for vital organs such as heart, liver no other way than urgent retransplant is helpful. When malignancy is disseminated already, retransplant has no role and only palliative treatment can be offered.
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Conflicts of interest
There are no conflicts of interest.
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