- Email: [email protected]
Prostate Cancer in Deceased Liver Donors
Prostate Cancer in Deceased Liver Donors M. Skalskia,*, B. Gierejb, B. Ziarkiewicz-Wróblewskab, W. Hołówkoa, and M. Krawczyka a Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland; and bDepartment of Pathology, Medical University of Warsaw, Warsaw, Poland
ABSTRACT Background. Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. Methods. A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n ¼ 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. Results. In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P ¼ .578) or age (P ¼ .730) was not statistically significant. Conclusions. Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation.
E
XTENSION OF THE AGE CRITERIA among donors (to >65 years) is increasingly reported in response to the current lack of organs for transplantation. The risk of prostate cancer occurrence rises simultaneously with age. According to data from the National Cancer Registry, prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. More than 9000 new cases are diagnosed annually, and the prevalence is systematically growing; 87% of all prostate cancer cases are reported among male subjects aged >60 years [1]. A similar trend has been observed in the rest of Europe. The most significant risk factors for prostate cancer are age, obesity, and a diet rich in saturated fatty acids [2]. Two methods are used for screening: digital rectal examination (DRE) and assessment of prostate-specific antigen (PSA)
serum concentration [3]. As the norm, serum concentrations <4 ng/mL are determined. According to the European Association of Urology, the risk of a prostate cancer diagnosis with PSA serum concentrations of 3 to 6 ng/mL and >10 ng/mL after 7 years is 34% and 71%, respectively [4]. For histopathologic staging, the Gleason grading system with a score of 0 to 10 points is used. Scores of 2 to 4 points are associated with well-differentiated carcinoma, whereas scores of 8 to 10 points are associated
*Address correspondence to Michał Skalski, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 1A Banacha St, 02-097 Warsaw, Poland. E-mail: [email protected]
0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.03.012
ª 2016 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1378
Transplantation Proceedings, 48, 1378e1380 (2016)
PROSTATE CANCER IN DECEASED LIVER DONORS
with poorly differentiated, highly invasive carcinoma [5]. Increased PSA serum concentrations, however, may also be observed among male subjects with benign prostatic hyperplasia after urinary catheterization [6]. The goal of the present study was to assess the prevalence of prostate cancer in a group of deceased liver donors and to describe the course of action if prostate cancer is suspected during the organ procurement process. MATERIALS AND METHODS A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n ¼ 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of prostate, performed before making the decision regarding liver graft utilization. The decision to perform a histopathologic examination of the prostate was made on the basis of an increased PSA serum concentration (>10 ng/mL) and abnormal result on DRE. Prostate glands were analyzed by experienced pathologists from the Department of Pathology, Medical University of Warsaw, who work together with the transplant team. First, a macroscopic assessment of 5-mm prostate cuts was performed to search for focal lesions, combined with palpations to evaluate the gland consistency. Frozen biopsy was applied in cases of macroscopically changed area of parenchyma. Although no focal lesions of differentiated consistency were distinguished, 3 to 4 random biopsy specimens were collected. Tissue samples for microscopic assessment were taken from the periphery, where prostate cancer statistically develops most frequently. After the frozen section of the selected samples was performed, the whole prostate gland was analyzed in a routine section. A Student t test was applied for estimated P values.
RESULTS
In the group of 30 donors with prostate examinations, 3 (10%) were diagnosed as having prostate cancer of moderate invasive stage (according to the Gleason grading system: case no. 1, 6 points; case no. 2, 6 points; case no. 3, 7 points). In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine sections. Liver transplantation was not performed in the cases of suspicion of prostate cancer (5 of 30 [17%]) in the fresh frozen biopsy sample. The rest of the examined prostate glands were diagnosed as acute inflammation (7 of 30 [23%]) or benign hyperplasia (18 of 30 [60%]). The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to PSA serum concentration (P ¼ .578) or age (P ¼ .730) was not statistically significant (Table 1). DISCUSSION
Extended donor criteria are widely applied in experienced transplant centers. The aim of this application is to optimize the utilization of available organs for donation and to reduce the mortality rate among patients on the waiting list
1379 Table 1. Comparison of Donors With Benign Prostate Disease and Donors With Prostate Cancer Donor Variable
Donors With Benign Prostate Disease
Donors With Prostate Cancer
P
Age, median (range), y 56 (28e66) 58 (44e67) .730 PSA serum concentration, 16.0 (15.1e23.8) 21.7 (6.6e40.4) .578 median (range), ng/dL Cause of death Cerebral trauma 8 (29.6%) 0 e Cerebral edema 5 (18.6%) 0 e Cerebral hemorrhage 14 (51.8%) 3 (100%) e Body mass index, 26.5 (20.9e35.2) 28.4 (22.1e34.0) e median (range), kg/m2 Abbreviation: PSA, prostate-specific antigen.
for organ transplantation [7]. The number of organs can be increased by accepting older donors. Age is a risk factor for prostate cancer, however. In Poland, the median age of male subjects is expected to increase to 50.1 years in the next 25 years (current median age, 37.4 years) [8]. Chedid et al [9] present good results of liver transplantations from donors aged >70 years. It is therefore obligatory to identify the risk factors for prostate cancer and to determine a course of action during organ procurement when prostate cancer is suspected. According to the literature, PSA serum concentration screening combined with DRE should be performed in donors aged >50 years [10]. Doerfler et al [11] proposed a PSA serum concentration cutoff point of 20 ng/mL to define donors with a higher risk of prostate cancer and cancer transmission. Moreover, they propose performing histopathologic examination or discontinuation of organ procurement in case of pathologic iliac lymph nodes. Organs should not be used in case of T3 or T4 prostate cancer stage during DRE (tumor invades the whole prostate gland or invades surrounding tissues) [12]. Histopathologic examination of the frozen biopsy sample has a limited diagnostic value, especially in cases of no obvious focal lesion. Particularly small tumors (<5 mm) may be omitted during macroscopic examination; no fresh frozen section is performed. In such cases, only routine section of the whole gland may allow diagnose of the neoplastic proliferation. Therefore, a negative result of fresh frozen section does not exclude the presence of prostate cancer, and this possibility should be considered, particularly when linked to poor clinical data. Moreover, a prostate cancer diagnosis based on fresh frozen section does not always allow correct assessment of histopathologic cancer staging according to the Gleason grading system. This scenario is mainly caused by the freezing process artifacts, which disturb the cytology of the cancer cells and limit the assessment of inappropriate glandular tubes architecture. Examination of a limited number of tissue samples during fresh frozen section does not allow precise evaluation of the number of lesions in case of multifocal tumor, neuroinvasion and angioinvasion, or invasion of surrounding tissues, all of which are important for assessing the clinical staging of prostate cancer.
1380
Based on the prevalence of prostate cancer, the risk of cancer transmission between donor and recipient is low [13]. Until now, only 1 case of prostate cancer transmission between donor and recipient (heart transplant) has been reported [14]. The risk of prolonged waiting time for transplantation outweighs the risk of prostate cancer transmission. This fact should be taken into consideration when accepting the donor [15]. However, the authors recommend performing a histopathologic examination of the prostate gland in every suspicious case. CONCLUSIONS
An increased PSA serum concentration without a diagnosis of prostate cancer in histopathologic examination should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the fresh frozen section, the procured organ should not be used for transplantation. REFERENCES [1] Wojciechowska U, Didkowska J, Zato nski W. Cancers in Poland in 2012. Polish National Cancer Registry; 2014. http:// onkologia.org.pl/raporty/. [2] Huang M, Natria S, Inoue T, et al. Diet-induced macrophage inhibitory cytokine 1 promotes prostate cancer progression. Endocr Relat Cancer 2013;21:39.
SKALSKI, GIEREJ, ZIARKIEWICZ-WRÓBLEWSKA ET AL [3] Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate-specific antigen in serum as screening test for prostate cancer. N Engl J Med 1991;324:1156. [4] Heidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68. [5] Epstein JI. An update of the Gleason grading system. J Urol 2010;183:433. [6] Batislam E, Arik Al, Karaoke A, et al. Effect of transurethral indwelling catheter on serum prostate-specific antigen level in benign prostatic hyperplasia. Urology 1997;49:50. [7] Renz JF, Kin C, Kinkhabwala M, et al. Utilization of extended donor criteria liver allografts maximizes donor use and patient access to liver transplantation. Ann Surg 2005;242:556. [8] Central Statistical Office Population Projection 2014-2050. http://stat.gov.pl. [9] Chedid MF, Rosen CB, Nyberg SL, et al. Excellent long-term patient and graft survival are possible with appropriate use of livers from deceased septuagenarian and octogenarian donors. HPB (Oxford) 2014;16:852. [10] Hassanain M. Novel guidelines for organ donor cancer screening. Ann Transplant 2014;19:241. [11] Doerfler A, Tillou X, Le Gal S, et al. Prostate cancer in deceased organ donors: a review. Transplant Rev (Orlando) 2014;28:1. [12] American Joint Committee on Cancer. Prostate cancer staging 7th edition. http://cancerstaging.org. [13] Giessing M. Donors with malignanciesdrisk or chance? Transplant Proc 2012;44:1782. [14] Loh E, Couch FJ, Hendrickson C, et al. Development of donor-derived prostate cancer in a recipient following orthotropic heart transplantation. JAMA 1997;277:133. [15] Dholakia S, Johns R, Moorhead L, Papalois V, Crane J. Renal donors with prostate cancer, no longer a reason to decline. Transplant Rev (Orlando) 2016;30:48e50.
ABSTRACT Background. Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. Methods. A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n ¼ 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. Results. In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P ¼ .578) or age (P ¼ .730) was not statistically significant. Conclusions. Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation.
E
XTENSION OF THE AGE CRITERIA among donors (to >65 years) is increasingly reported in response to the current lack of organs for transplantation. The risk of prostate cancer occurrence rises simultaneously with age. According to data from the National Cancer Registry, prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. More than 9000 new cases are diagnosed annually, and the prevalence is systematically growing; 87% of all prostate cancer cases are reported among male subjects aged >60 years [1]. A similar trend has been observed in the rest of Europe. The most significant risk factors for prostate cancer are age, obesity, and a diet rich in saturated fatty acids [2]. Two methods are used for screening: digital rectal examination (DRE) and assessment of prostate-specific antigen (PSA)
serum concentration [3]. As the norm, serum concentrations <4 ng/mL are determined. According to the European Association of Urology, the risk of a prostate cancer diagnosis with PSA serum concentrations of 3 to 6 ng/mL and >10 ng/mL after 7 years is 34% and 71%, respectively [4]. For histopathologic staging, the Gleason grading system with a score of 0 to 10 points is used. Scores of 2 to 4 points are associated with well-differentiated carcinoma, whereas scores of 8 to 10 points are associated
*Address correspondence to Michał Skalski, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 1A Banacha St, 02-097 Warsaw, Poland. E-mail: [email protected]
0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.03.012
ª 2016 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1378
Transplantation Proceedings, 48, 1378e1380 (2016)
PROSTATE CANCER IN DECEASED LIVER DONORS
with poorly differentiated, highly invasive carcinoma [5]. Increased PSA serum concentrations, however, may also be observed among male subjects with benign prostatic hyperplasia after urinary catheterization [6]. The goal of the present study was to assess the prevalence of prostate cancer in a group of deceased liver donors and to describe the course of action if prostate cancer is suspected during the organ procurement process. MATERIALS AND METHODS A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n ¼ 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of prostate, performed before making the decision regarding liver graft utilization. The decision to perform a histopathologic examination of the prostate was made on the basis of an increased PSA serum concentration (>10 ng/mL) and abnormal result on DRE. Prostate glands were analyzed by experienced pathologists from the Department of Pathology, Medical University of Warsaw, who work together with the transplant team. First, a macroscopic assessment of 5-mm prostate cuts was performed to search for focal lesions, combined with palpations to evaluate the gland consistency. Frozen biopsy was applied in cases of macroscopically changed area of parenchyma. Although no focal lesions of differentiated consistency were distinguished, 3 to 4 random biopsy specimens were collected. Tissue samples for microscopic assessment were taken from the periphery, where prostate cancer statistically develops most frequently. After the frozen section of the selected samples was performed, the whole prostate gland was analyzed in a routine section. A Student t test was applied for estimated P values.
RESULTS
In the group of 30 donors with prostate examinations, 3 (10%) were diagnosed as having prostate cancer of moderate invasive stage (according to the Gleason grading system: case no. 1, 6 points; case no. 2, 6 points; case no. 3, 7 points). In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine sections. Liver transplantation was not performed in the cases of suspicion of prostate cancer (5 of 30 [17%]) in the fresh frozen biopsy sample. The rest of the examined prostate glands were diagnosed as acute inflammation (7 of 30 [23%]) or benign hyperplasia (18 of 30 [60%]). The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to PSA serum concentration (P ¼ .578) or age (P ¼ .730) was not statistically significant (Table 1). DISCUSSION
Extended donor criteria are widely applied in experienced transplant centers. The aim of this application is to optimize the utilization of available organs for donation and to reduce the mortality rate among patients on the waiting list
1379 Table 1. Comparison of Donors With Benign Prostate Disease and Donors With Prostate Cancer Donor Variable
Donors With Benign Prostate Disease
Donors With Prostate Cancer
P
Age, median (range), y 56 (28e66) 58 (44e67) .730 PSA serum concentration, 16.0 (15.1e23.8) 21.7 (6.6e40.4) .578 median (range), ng/dL Cause of death Cerebral trauma 8 (29.6%) 0 e Cerebral edema 5 (18.6%) 0 e Cerebral hemorrhage 14 (51.8%) 3 (100%) e Body mass index, 26.5 (20.9e35.2) 28.4 (22.1e34.0) e median (range), kg/m2 Abbreviation: PSA, prostate-specific antigen.
for organ transplantation [7]. The number of organs can be increased by accepting older donors. Age is a risk factor for prostate cancer, however. In Poland, the median age of male subjects is expected to increase to 50.1 years in the next 25 years (current median age, 37.4 years) [8]. Chedid et al [9] present good results of liver transplantations from donors aged >70 years. It is therefore obligatory to identify the risk factors for prostate cancer and to determine a course of action during organ procurement when prostate cancer is suspected. According to the literature, PSA serum concentration screening combined with DRE should be performed in donors aged >50 years [10]. Doerfler et al [11] proposed a PSA serum concentration cutoff point of 20 ng/mL to define donors with a higher risk of prostate cancer and cancer transmission. Moreover, they propose performing histopathologic examination or discontinuation of organ procurement in case of pathologic iliac lymph nodes. Organs should not be used in case of T3 or T4 prostate cancer stage during DRE (tumor invades the whole prostate gland or invades surrounding tissues) [12]. Histopathologic examination of the frozen biopsy sample has a limited diagnostic value, especially in cases of no obvious focal lesion. Particularly small tumors (<5 mm) may be omitted during macroscopic examination; no fresh frozen section is performed. In such cases, only routine section of the whole gland may allow diagnose of the neoplastic proliferation. Therefore, a negative result of fresh frozen section does not exclude the presence of prostate cancer, and this possibility should be considered, particularly when linked to poor clinical data. Moreover, a prostate cancer diagnosis based on fresh frozen section does not always allow correct assessment of histopathologic cancer staging according to the Gleason grading system. This scenario is mainly caused by the freezing process artifacts, which disturb the cytology of the cancer cells and limit the assessment of inappropriate glandular tubes architecture. Examination of a limited number of tissue samples during fresh frozen section does not allow precise evaluation of the number of lesions in case of multifocal tumor, neuroinvasion and angioinvasion, or invasion of surrounding tissues, all of which are important for assessing the clinical staging of prostate cancer.
1380
Based on the prevalence of prostate cancer, the risk of cancer transmission between donor and recipient is low [13]. Until now, only 1 case of prostate cancer transmission between donor and recipient (heart transplant) has been reported [14]. The risk of prolonged waiting time for transplantation outweighs the risk of prostate cancer transmission. This fact should be taken into consideration when accepting the donor [15]. However, the authors recommend performing a histopathologic examination of the prostate gland in every suspicious case. CONCLUSIONS
An increased PSA serum concentration without a diagnosis of prostate cancer in histopathologic examination should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the fresh frozen section, the procured organ should not be used for transplantation. REFERENCES [1] Wojciechowska U, Didkowska J, Zato nski W. Cancers in Poland in 2012. Polish National Cancer Registry; 2014. http:// onkologia.org.pl/raporty/. [2] Huang M, Natria S, Inoue T, et al. Diet-induced macrophage inhibitory cytokine 1 promotes prostate cancer progression. Endocr Relat Cancer 2013;21:39.
SKALSKI, GIEREJ, ZIARKIEWICZ-WRÓBLEWSKA ET AL [3] Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate-specific antigen in serum as screening test for prostate cancer. N Engl J Med 1991;324:1156. [4] Heidenreich A, Aus G, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68. [5] Epstein JI. An update of the Gleason grading system. J Urol 2010;183:433. [6] Batislam E, Arik Al, Karaoke A, et al. Effect of transurethral indwelling catheter on serum prostate-specific antigen level in benign prostatic hyperplasia. Urology 1997;49:50. [7] Renz JF, Kin C, Kinkhabwala M, et al. Utilization of extended donor criteria liver allografts maximizes donor use and patient access to liver transplantation. Ann Surg 2005;242:556. [8] Central Statistical Office Population Projection 2014-2050. http://stat.gov.pl. [9] Chedid MF, Rosen CB, Nyberg SL, et al. Excellent long-term patient and graft survival are possible with appropriate use of livers from deceased septuagenarian and octogenarian donors. HPB (Oxford) 2014;16:852. [10] Hassanain M. Novel guidelines for organ donor cancer screening. Ann Transplant 2014;19:241. [11] Doerfler A, Tillou X, Le Gal S, et al. Prostate cancer in deceased organ donors: a review. Transplant Rev (Orlando) 2014;28:1. [12] American Joint Committee on Cancer. Prostate cancer staging 7th edition. http://cancerstaging.org. [13] Giessing M. Donors with malignanciesdrisk or chance? Transplant Proc 2012;44:1782. [14] Loh E, Couch FJ, Hendrickson C, et al. Development of donor-derived prostate cancer in a recipient following orthotropic heart transplantation. JAMA 1997;277:133. [15] Dholakia S, Johns R, Moorhead L, Papalois V, Crane J. Renal donors with prostate cancer, no longer a reason to decline. Transplant Rev (Orlando) 2016;30:48e50.