Prostate Cancer and Prostatic Diseases (2006) 9, 115–120 & 2006 Nature Publishing Group All rights reserved 1365-7852/06 $30.00 www.nature.com/pcan
REVIEW
Prostate activity and prostate cancer in spinal cord injury HB Shim, TY Jung, JK Lee, and JH Ku Department of Urology, Seoul Veterans Hospital, Seoul, Korea
In addition to androgen, autonomic nerves may be involved in prostatic function. As patients with spinal cord injury (SCI) have impaired innervation of the prostate, the prostate volume and prostatespecific antigen (PSA) level in patients with SCI may be different from those of healthy men. Experiments in rats with SCI indicate that neurogenic factors play an important role in prostate growth and function but the same phenomena may not occur in men with SCI because the current animal models differ from clinical results in humans in several respects. Although many of studies indicate the importance of intact peripheral innervation on the secretory function of the prostate, the effect of more central denervation such as occurs in complete SCI at the cervical, thoracic, or lumbar levels on prostatic function is unclear. In addition, the impact of central nervous system injury on prostatic secretory activity, and consequently on serum PSA levels, is also not clear. Furthermore, the impact of hormonal changes on prostate cancer development and prognosis observed in patients with SCI may also be affected by the level of injury and patient age at the time of injury, which have not been studied. In this article, we review prostate activity and prostate cancer in SCI and discuss how they may relate to neurogenic factors.
Prostate Cancer and Prostatic Diseases (2006) 9, 115–120. doi:10.1038/sj.pcan.4500865; published online 14 March 2006 Keywords: spinal cord injury; prostate; prostate-specific antigen; prostate cancer
Introduction As a result of substantial improvements in surgery, urology and rehabilitation within the past 20 years, a significantly decreased morbidity and increased life expectancy have been achieved in men with spinal cord injury (SCI).1 Today, the life expectancy for paraplegic patients does not differ from the life expectancy for the normal population. Therefore, most male patients with SCI are likely to encounter the problems of the aging male during their lifespan. Among men, prostate cancer is the most common cancer diagnosed, and the second leading cause of death from cancer in the industrialized countries. In 2005, approximately 232 090 American men will be diagnosed with prostate cancer, and 30 350 will die from this disease.2 The prostate is one of the male accessory sex glands that produce fluid components of the seminal plasma. In addition to androgen, the extensive presence of adrenergic and cholinergic receptors in the prostate suggests that autonomic nerves may be involved in prostatic function.3 As patients with SCI have impaired innervation of the
Correspondence: Dr JH Ku, Department of Urology, Seoul Veterans Hospital, 6-2, Doonchon Dong, Kangdong Ku, Seoul 134-791, Korea. E-mail:
[email protected] Received 6 January 2006; revised 31 January 2006; accepted 31 January 2006; published online 14 March 2006
prostate, the prostate volume and PSA level in patients with SCI may be different from those of healthy men. Although experiments in rats with SCI indicate that neurogenic factors play an important role in prostate growth and function, in human, the influence of neurogenic factors on prostate enlargement is not well examined. In this article, we review prostate activity in SCI and discuss how they may relate to neurogenic factors.
Effect of denervation on prostate The prostate is innervated by branches of pelvic ganglia composed of pelvic (parasympathetic) and hypogastric (sympathetic) nerves.4 In experimental animals, denervation of the prostate gland results in alterations of growth, cellular morphology and function. In the rat, the secretory function of prostate cells was reported to be affected by neural agents.5,6 It has been shown that in the rat, pelvic plexus denervation changes in the glandular epithelium.7 Denervation of the prostate of the rat by surgical removal of the pelvic ganglion resulted in a decrease in organ weight, epithelial height and secretory activity of the prostate.8 Botulimum toxin type A injection in the rat prostate, causing selective denervation, led to significant volume reduction of the gland.9 Wang et al.8 reported that the decrease in prostate weight after the removal of the pelvic ganglia was not associated with a decrease on DNA content per organ. These results
Prostate Cancer and Prostatic Diseases
Control
Abbreviations: SCI, spinal cord injury; NA, not available; Urol, urological; NU, not urological; Aut, autopsied.
NA
NA
NA
NA
NA
NA
XT10: 1373 (8–16) oT10: 28718 (10–70) Urol: 44726 NU: NA Aut 31 NA NA NA NA NA NA
XT10: 6479 oT10: 61711 Urol: 6879 NU: 60–69 Aut: 56–75 XT10: 9 oT10: 12 Urol: 12 NU: 158 Aut: 77 SCI
NA 575 Control
Frisbie et al.15
NA
2378.9, n ¼ 100 27.2715.9, n ¼ 575 NA
26.279.8, n¼9 29.6715.1, n ¼ 168 25.7710.9, n ¼ 22 27.9718.8, n ¼ 231 23.177.5, n ¼ 35 22.9710.3, n ¼ 136 20.7710.1, n ¼ 23 20.379.8, n ¼ 26 22.577.4, n ¼ 11 19.475.6, n ¼ 14 100 SCI Pannek et al.14
53.7711.3
NA NA 25.2711.4 (13–44), n¼8 23.3710.9 (13–41), n ¼ 10 22.177.2 (9–42), n ¼ 21 22.473.8 (17–27), n¼5 43 SCI Benaim et al.13
5179.8 (27–73)
80–89 70–79 60–69 30–39
40–49
50–59
Prostate volume (ml) Age (year) No. Group
Prostate volume according to patient characteristics Pannek et al.14 found no significant difference in prostate size according to the completeness of the lesion, the level of the lesion or the duration of SCI. Inconsistent with these observations, Frisbie et al.15 reported that the size of the prostate gland revealed smaller prostate glands in the severely paralyzed than the less severely paralyzed. The prostate glands in the severely paralyzed were also
References
Comparison of prostate volume in men with spinal cord injury and noninjured men Pannek et al.14 evaluated the prostate size in 100 male patients with SCI and 575 noninjured men. They found no statistically significant difference was found in prostate size in any of the age groups although there was a trend toward a lower prostate volume in patients with SCI.
Prostate volume according to age cohort in patients with spinal cord injury
Prostate volume in men with spinal cord injury Contrary to animal experiments, human studies assessing prostate volume in men with SCI reported conflicting results (Table 1).13–15 In a study of humans, anatomy and innervation of the prostate gland were compared in men with and without SCI by transrectal ultrasound guided prostate biopsies. No significant differences in prostatic architecture were found but subtle differences in the patterns of autonomic (mainly adrenergic) innervation were noted in men with SCI.16 These findings suggest that prostate development in patients with SCI closely resembles the normal development of the prostate in noninjured humans and that prostate dysfunction may be secondary to lack of neurological control of the organ.
Overall
suggest that a decrease in synthetic and/or secretory activities, rather than a decrease in cell number, might be responsible for the smaller prostate in the denervated animals. These results demonstrate the importance of normal innervation for the maintenance of the structural and functional integrity of the prostate. Growth, and possibly function, of the prostate may also be compromised after SCI because SCI often results in neuropathic dysfunction of pelvic organs including prostate. The prostates of SCI rats were smaller than those of sham-operated control animals.10,11 More specifically, SCI in rats has been shown to alter prostatic cellular morphology and function.12 Huang et al.12 examined the effects of SCI on the androgen-related biochemical properties and morphology of the prostate in the rat at various times after surgically induced SCI. In rat prostate, there was an acute but temporal change in the autoregulation of androgen receptor mRNA by its own ligand shortly after SCI but a persistent elevation of testosterone-repressed prostate message (TRPM) 2 mRNA. The latter was associated with a decrease in prostate epithelial cell height and prostate weight. As serum testosterone in the SCI rats returned to normal level within 3 weeks of SCI, these abnormalities may result from a lack of normal androgen regulation of prostate function, perhaps attributable to the absence of normal innervation to the prostate after SCI. Together, these evidences point to a possible role for the autonomic nervous system in maintaining the normal prostate architecture and function.
Table 1
116
NA
Prostate activity and prostate cancer SCI HB Shim et al
Prostate activity and prostate cancer SCI HB Shim et al
smaller than those of the nonparalyzed urological patients and of the autopsied subjects. However, since examinations from the onset of paralysis over a period of years have not been carried out, it is not clear when the atrophy occurs.
Prostate volume according to age cohort The growth of the prostate is related to aging.17 Benaim et al.13 have reported that patients with SCI do not show the expected age-related increase in prostate volume. In contrast to the group of Benaim et al.13 and Pannek et al.14 found that with increasing age, the mean prostate volume increased in the patients with SCI and in the control group. Serum prostate-specific antigen levels in men with spinal cord injury Several investigators chose serum prostate-specific antigen (PSA) as a marker of prostatic function in men with SCI (Table 2).13–15,18–21 However, some conflicting results regarding serum PSA levels in SCI patients have been reported. Comparison of serum prostate-specific antigen levels in men with spinal cord injury and noninjured men Lynne et al.18 compared serum PSA concentrations in 21 SCI men and 22 noninjured normal men to determine if the prostate gland functions normally in SCI men. They suggest that prostatic secretory dysfunction is present in men with SCI because serum PSA concentrations were higher in SCI men than in noninjured men. However, subsequent studies have revealed that no statistically significant differences were found in serum PSA values between the SCI group and the non-SCI control group,14,18–21 although there was a trend toward a lower serum PSA level in patients with SCI in the study of Pannek et al.14 Pramudji et al.21 presented the largest study concerning PSA levels in patients with SCI. They analyzed the PSA levels of 366 men with SCI aged 40–79 years and compared them with randomly selected age-matched controls from the Baylor community screening program database of more than 19 000 patient tests. They did not find significant age-related differences in the mean PSA value between patients with SCI and the noninjured control group. The range of PSA values and percent of study participants with PSA greater than 4 ng/ml were also similar in the two groups. Variation in serum PSA among studies may be attributed to asymptomatic urinary tract infection in patients with a neurogenic bladder. It has been previously observed that subclinical prostatitis may be correlated with high serum PSA,22 which may be an explanation for the results of Lynne et al.18 Serum prostate-specific antigen levels according to patient characteristics Most groups have demonstrated that patient characteristics, including a history of urinary tract infection,18 a positive urine culture,19 the bladder management techniques,21 the level of SCI,14,19,20 the completeness of the lesion,14 or the duration of the lesion,14,20 do not influence the serum PSA values in the SCI groups. However, the presence of a catheter was noted as an
independent factor that were correlated with higher serum PSA values in this group in some studies.19 Furthermore, the level of the injury and its corresponding neurologic deficit may be important variable. In the study of Frisbie et al.,15 the PSA level of the severely paralyzed group tended to be lower than that of the less severely paralyzed group. When compared to the nonparalyzed urological patients and the healthy ablebodied, the difference was also easily significant.
117
Serum prostate-specific antigen levels according to age cohort Although the serum PSA level of the patients with SCI showed this trend to a far lesser extent than that of noninjured men in some studies,14 most investigators reported that serum PSA in men with SCI increased with age in a manner described previously in men without known prostatic diseases.13,19,21 Thus, only a few patients exceeded the age-specific reference ranges13 and the agespecific PSA values obtained in the SCI group were comparable to those reported for the general population.19,21 Particularly, Benaim et al.13 suggest that the fact that the size of the prostate in patients with SCI did not increase at the same rate as seen in neurologically intact men despite normal serum PSA increase with age provides some evidence that some of the stimuli that promote prostate growth in men without SCI, are absent or altered in men who suffered from a SCI. Seminal plasma prostate-specific antigen levels in men with spinal cord injury Prostate-specific antigen is produced almost exclusively in the prostate epithelium and is normally regarded as an indicator of the activity in the prostate gland. Seminal plasma PSA concentration is approximately 105–106 times higher than serum PSA concentration and the majority of PSA in seminal plasma is present in the catalytically active single-chain form.23 Brasso et al.24 evaluated the seminal plasma PSA concentrations in 16 patients with SCI compared to 20 normal controls. The concentration of PSA in seminal plasma depended on the level of SCI, with significantly lower concentrations in patients with lesions below T7 compared to both normal age-matched controls and patients with lesions at or above T7. No difference in seminal plasma PSA was found between patients with lesions at or above T7 and normal controls. This finding suggests that some neurogenically mediated factor plays a role in the PSA production and that this spinal cord level (T7) represents a crucial point in the neurogenic stimulation of the prostate gland. Lynne et al.18 and Alexandrino et al.20 also found that seminal PSA concentrations obtained from patients were lower than those obtained from controls. However, in the study of Alexandrino et al.,20 total seminal PSA was lower in patients compared to controls regardless of lesion level with no difference between levels at T7 and below T7. The results are shown in Table 3.18,20,24 Prostate cancer diagnosis in men with spinal cord injury It has been theorized that central denervation of an organ is protective against malignancy and changes in Prostate Cancer and Prostatic Diseases
118
Prostate Cancer and Prostatic Diseases
Table 2 Serum prostate-specific antigen levels according to age cohort in patients with spinal cord injury References
Group
No.
Age (year)
SCI
43
5179.8 (27–73)
Pannekb et al.14,
SCI
100
53.7711.3
30–39
40–49
50–59
60–69
70–79
80–89
1.070.8 (0.1–2.2), n¼5
1.870.6 (0.1–1.9), n ¼ 21
2.071.8 (0.6–6.6), n ¼ 10
2.071.4 (0.7–4.6), n¼8
NA
NA
NA
1.571.5, n ¼ 11 1.270.7, n ¼ 14
1.070.6, n ¼ 23 1.070.8, n ¼ 26
1.270.9, n ¼ 35 1.171.0, n ¼ 136
1.370.9, n ¼ 22 1.771.8, n ¼ 231
1.770.7, n¼9 2.775.9, n ¼ 168
NA
1.270.9, n ¼ 100 1.971.6, n ¼ 575
Control 575
NA
SCI
XT10: 6479
NA
NA
NA
NA
NA
NA
XT10: 0.770.9 (0.5–2.1)
oT10: 12 Control Urol: 12 NU: 158 Aut: 77
oT10: 61711 Urol: 6879 NU: 60–69 Aut: 56–75
NA
NA
NA
NA
NA
NA
oT10: 2.272.2 (0.5–10.4) Urol: 7.975.7 NU: 2.971.7 Aut: NA
SCI
21
33.371.2 (24–42)
NA
NA
NA
NA
NA
NA
1.2070.19 (0.3–25,
Control 22
30.371.5 (19–44)
NA
NA
NA
NA
NA
SCI
40–89
NA
40–89
NA
0.85 (0.5–1.7), n ¼ 46 0.7 (0.4–1.1), n ¼ 100
0.7 (0.2–2.2), n ¼ 16 0.9 (0.65–1.7), n ¼ 100
1.8 (0.4–3.9), n¼6 0.9 (0.5–2.0), n ¼ 102
1.1 (0.2–3.3), n¼8 1.4 (0.1–2.6), n ¼ 100
Alexandrino SCI 44 a et al.20, Control 44
33.9879.12 (18–58)
NA
NA
NA
NA
NA
NA
34.0979.16 (18–58)
NA
NA
NA
NA
NA
NA
Pramudji a et al.21,
366
40–79
NA
Control 371
40–79
NA
Frisbiea et al.15,
Lynne a et al.18,
Konetya et al.19,
XT10: 9
79
Control 501
SCI
1.0570.96 (0.4–1.3), 1.4772.62 (0.45–1.5), 1.3971.47 (0.42–1.7), 2.573.72 (0.6–2.58), n ¼ 112 n ¼ 111 n ¼ 88 n ¼ 55 0.8670.5 (0.4–1), 1.4771.18 (0.5–1.4), 1.7171.09 (0.7–2.18), 3.4172.85 (0.9–3.82), n ¼ 111 n ¼ 112 n ¼ 85 n ¼ 63
Abbreviations: PSA, prostate-specific antigen; SCI, spinal cord injury; NA, not available; Urol, urological; NU, not urological; Aut, autopsied. a Mean7standard deviation (range). b Mean7standard deviation. c Median (25th and 75th percentiles). d Mean7standard deviation (25th and 75th percentiles).
NA
Overall
median 1.17) 0.6970.07 (0.2–1.06, median 0.59) 1.5, n ¼ 3 0.9 (0.5–1.9), n ¼ 79 1.6 (0.6–2.7), 1.0 (0.6–2.1), n ¼ 99 n ¼ 501 NA
0.91870.665 (0.140–3.010, median 0.755) 0.97670.853 (1.60–4.57, median 0.685)
NA
NA
NA
NA
Prostate activity and prostate cancer SCI HB Shim et al
Benaima et al.13,
Serum PSA (mg/ml)
Prostate activity and prostate cancer SCI HB Shim et al
119
Table 3 Seminal plasma prostate-specific antigen levels in patients with spinal cord injury References 18
Lynne et al.
Alexandrino et al.20 Brasso et al.24
Group
No.
Age (year)
Seminal plasma PSA (mg/ml)
SCI Control SCI Control SCI Control
21 22 44 44 XT7: 10oT7: 6 20
33.371.2 (24–42) 30.371.5 (19–44) 33.9879.12 (18–58) 34.0979.16 (18–58) XT7: 31 (21–45) oT7: 32 (25–44) 34 (25–48)
0.5970.11 (0.009–1.71, median 0.48) 1.2970.15 (0.39–3.0, median 1.17) 0.60970.785 (0.001–3.26, median 0.320) 0.77370.460 (median 0.604) XT7: 0.46 (0.24–1.53) oT7: 0.11 (0.05–0.94) 0.54 (0.23–2.38)
Abbreviations: PSA, prostate-specific antigen; SCI, spinal cord injury.
the hypothalamic–pituitary–gonadal axis but no persuasive data are available. Historically, since SCI patients rarely survived into the years during which prostate cancer becomes a significant medical issue, they were not screened and death from prostate cancer in patients with SCI was rare.25 Additional reasons for avoiding screening patients with SCI include the perception that chronic inflammation and catheterization frequently yield falsely elevated PSA levels in these patients,18 that the abbreviated life expectancy diminishes the benefit of early detection that the decreased levels of circulating androgens experienced by patients with SCI26,27 is thought to be somewhat protective, and decreased neurogenic stimulation of prostate growth is suspected in patients with a damaged spinal cord.13,18 In studies of patients with SCI, the incidence of prostate cancer has been found to be low compared with the general population.28 Also, a retrospective analysis of the records from the Department of Veterans Affairs medical database for a 7-year period, 1986–1992, showed that severe paralysis due to myelopathy was a low risk factor for carcinoma of the prostate gland.29 Frisbie30 calculated the incidence among SCI patients at a single VA facility. The incidence of prostate cancer was lower in myelopathy patients with higher levels of paralysis (T10 or above) than in those with lesions at T11 or below. The incidence was 0 per 100 patient-years among 218 patients with complete C2 to T10 SCI and 2.1 per 100 patient-years among 60 patients with complete T11 to S1 SCI. However, this observation was based on clinically detected prostate cancer and patient groups were not age matched. As the life expectancy of SCI patients approaches that of the general population, prostate cancer is likely to become a more clinically significant disease in these men.31 Advanced prostate cancer has been shown to have significant effects on the quality of life and life expectancy of patients with SCI.31 In a large SCI population, preliminary biopsy data implied that the rate of PSA detected cancer in SCI patients was similar to that in other populations. Recently, Scott et al.32 reported that although the proportion of patients with a prostate cancer diagnosis was greater in the able-bodied patients, the prostate cancer detected in the patients with SCI tended to be of a more advanced stage and grade. The difference was likely a result of the decreased use of prostate cancer screening in this population because the average PSA level at diagnosis was 15.4 ng/ml in the able-bodied patients with prostate cancer, and the men with SCI and prostate cancer had an average PSA level at diagnosis of 28.5 ng/ml. However, the usefulness of enrolling them in screening programs is not clear at this time.
Prostate cancer treatment in men with spinal cord injury Theoretically, the low testosterone levels typical of patients with SCI may provide some protection against prostate cancer.13,25,27,33,34 However, Several studies have supported a relationship between inflammation and the development of prostate cancer.35,36 Thus, the prostatic inflammation in patients with SCI may actually put these patients at increased risk of prostate cancer. Scott et al.32 demonstrated that an increased rate of high-grade, highstage disease and a poor response to hormonal therapy in patients with SCI and prostate cancer compared with the able-bodied population with prostate cancer. The trend toward more rapid development of hormone resistance in patients with SCI and prostate cancer may be secondary to the higher grade and stage of the tumor at presentation. However, low pretreatment testosterone levels have been found to be associated with a poor prognosis from prostate cancer.37,38 Thus, the low androgen levels commonly observed in patients with SCI may actually worsen their prostate cancer outcome by increasing the tendency of their tumors to develop hormone resistance. In a recent nationwide study by Gammon et al.,39 surgical approaches in SCI patients was especially difficult because of pressure ulcers, contractures, ectopic ossification and sequelae of the event that caused the SCI. Furthermore, urinary tract colonization and chronic prostatitis were common among SCI patients and increased the risk of wound infection. Conclusions Animal studies have demonstrated that the lack of neurological control of the prostate due to traumatic SCI generates atrophy and decreased function of the gland, as is also the case when the integrity of the peripheral innervation of the gland is lost. However, the same phenomena may not occur in men with SCI because the current animal models differ from clinical results in humans in several respects. Furthermore, the results of the majority of human studies may be considered preliminary, because of the small sample sizes, the different inclusion and exclusion criteria, the different duration of SCI, the different age range of the patients or the different assay used for measurements. A further cause of different results may be the various neurogenic bladder management techniques, which can cause recurrent urinary tract infection and/or direct prostate trauma. Nonetheless, these studies suggest hypotheses, which require evaluation in well-designed population-based studies. Although many of these studies indicate the importance of intact peripheral innervation on the secretory function of the prostate, the effect of more central Prostate Cancer and Prostatic Diseases
Prostate activity and prostate cancer SCI HB Shim et al
120
denervation such as occurs in complete SCI at the cervical, thoracic, or lumbar levels on prostatic function is unclear. In addition, the impact of central nervous system injury on prostatic secretory activity, and consequently on serum PSA levels, is also not clear. Furthermore, the impact of hormonal changes on prostate cancer development and prognosis observed in patients with SCI may also be affected by the level of injury and patient age at the time of injury, which have not been studied. Further studies on the possible effect of neurogenic stimulation of prostate activity in humans are warranted.
References 1 Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55: 10–30. 2 Spinal Cord Injury: Facts and Figures at a Glance. National Spinal Cord Injury Statistical Center: Birmingham, Alabama, 1994. 3 Vaalasti A, Hervonen A. Autonomic innervation of the human prostate. Invest Urol 1980; 17: 293–297. 4 Vaalasti A, Hervonen A. Innervation of the ventral prostate of the rat. Am J Anat 1979; 154: 231–243. 5 Farnsworth WE, Lawrence MH. Regulation of prostate secretion in the rat. Proc Soc Exp Biop Med 1965; 119: 373–376. 6 Wang JM, McKenna KE, Lee C. Determination of prostatic secretion in rats: effect of neurotransmitters and testosterone. Prostate 1991; 18: 289–301. 7 Martinez-Pineiro L, Dahiya R, Tanagho EA, Schmidt RA. Pelvic plexus denervation in rats causes morphologic and functional changes of the prostate. J Urol 1993; 150: 215–218. 8 Wang JM, McKenna KE, McVary KT, Lee C. Requirement of innervation for maintenance of structural and functional integrity in the rat prostate. Biol Reprod 1991; 44: 1171–1176. 9 Doggweiler R, Zermann DH, Ishigooka M, Schmidt RA. Botoxinduced prostatic involution. Prostate 1998; 37: 44–50. 10 Linsenmeyer TA, Pogach LM, Ottenweller JE, Huang HF. Spermatogenesis and the pituitary-testicular hormone axis in rats during the acute phase of spinal cord injury. J Urol 1994; 152: 1302–1307. 11 Huang HF, Pogach LM, Nathan E, Giglio W, Seebode JJ. Synergistic effects of follicle-stimulating hormone and testosterone on the maintenance of spermiogenesis in hypophysectomized rats: relationship with the androgen-binding protein status. Endocrinology 1991; 128: 3152–3161. 12 Huang HF, Li MT, Linsenmeyer TA, Ottenweller JE, Pogach LM, Irwin RJ. The effects of spinal cord injury on the status of messenger ribonucleic acid for TRPM 2 and androgen receptor in the prostate of the rat. J Androl 1997; 18: 250–256. 13 Benaim EA, Montoya JD, Saboorian MH, Litwiller S, Roehrborn CG. Characterization of prostate size, PSA and endocrine profiles in patients with spinal cord injuries. Prostate Cancer Prostatic Dis 1998; 1: 250–255. 14 Pannek J, Berges RR, Cubick G, Meindl R, Senge T. Prostate size and PSA serum levels in male patients with spinal cord injury. Urology 2003; 62: 845–848. 15 Frisbie JH, Kumar S, Aguilera EJ, Yalla S. Prostate atrophy and spinal cord lesions. Spinal Cord 2006; 44: 24–27. 16 Benaim EA, Soboorian H, Roehrborn CG, McConnell JD. The structure and intrinsic innervation of the prostate in patients with spinal cord injuries. J Urol 1998; 159 (Suppl 2): 106. 17 Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human benign prostatic hyperplasia with age. J Urol 1984; 132: 474–479.
Prostate Cancer and Prostatic Diseases
18 Lynne CM, Aballa TC, Wang TJ, Rittenhouse HG, Ferrell SM, Brackett NL. Serum and semen prostate specific antigen concentrations are different in young spinal cord injured men compared to normal controls. J Urol 1999; 162: 89–91. 19 Konety BR, Nguyen TT, Brenes G, Lewis N, Saul M, Nelson JB et al. Evaluation of the effect of spinal cord injury on serum PSA levels. Urology 2000; 56: 82–86. 20 Alexandrino AP, Rodrigues MA, Matsuo T. Evaluation of serum and seminal levels of prostate specific antigen in men with spinal cord injury. J Urol 2004; 171: 2230–2232. 21 Pramudji CK, Mutchnik SE, DeConcini D, Boone TB. Prostate cancer screening with prostate specific antigen in spinal cord injured men. J Urol 2002; 167: 1303–1305. 22 Hasui Y, Marutsuka K, Asada Y, Ide H, Nishi S, Osada Y. Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia. Prostate 1994; 25: 91–96. 23 Abrahamsson PA, Lilja H, Oesterling JE. Molecular forms of serum prostate-specific antigen. The clinical value of percent free prostate-specific antigen. Urol Clin North Am 1997; 24: 353–365. 24 Brasso K, Sonksen J, Sommer P, Odum L, Biering-Sorensen F, Iversen P et al. Seminal plasma PSA in spinal cord injured men: a preliminary report. Spinal Cord 1998; 36: 771–773. 25 Ito TY, Mehta M. Adenocarcinoma of the prostate in paraplegics. Paraplegia 1976; 14: 101–104. 26 Bauman WA, Spungen AM. Metabolic changes in persons after spinal cord injury. Phys Med Rehabil Clin North Am 2000; 11: 109–140. 27 Huang TS, Wang YH, Lee SH, Lai JS. Impaired hypothalamuspituitary-adrenal axis in men with spinal cord injuries. Am J Phy Med Rehabil 1998; 77: 108–112. 28 Federman Q, Tannenbaum M, Vereczkey Z. Reduced incidence risk of prostatic carcinoma in patients with spinal cord injury. Am J Paraplegia 1993; 16 (Suppl): 280. 29 Frisbie JH, Binard J. Low prevalence of prostatic cancer among myelopathy patients. J Am Paraplegia Soc 1994; 17: 148–149. 30 Frisbie JH. Cancer of the prostate in myelopathy patients: lower risk with higher levels of paralysis. J Spinal Cord Med 2001; 24: 92–94. 31 Wyndaele JJ, Iwatsubo E, Perkash I, Stohrer M. Prostate cancer: a hazard also to be considered in the ageing male patient with spinal cord injury. Spinal Cord 1998; 36: 299–302. 32 Scott Sr PA, Perkash I, Mode D, Wolfe VA, Terris MK. Prostate cancer diagnosed in spinal cord-injured patients is more commonly advanced stage than in able-bodied patients. Urology 2004; 63: 509–512. 33 Safarinejad MR. Level of injury and hormone profiles in spinal cord-injured men. Urology 2001; 58: 671–676. 34 Bauman WA, Spungen AM, Adkins RH, Kemp BJ. Metabolic and endocrine changes in persons aging with spinal cord injury. Assist Technol 1999; 11: 88–96. 35 Wilson DW, Harper ME, Jensen HM, Ikeda RM, Richards G, Peeling WB et al. A prognostic index for the clinical management of patients with advanced prostatic cancer: a British Prostate Study Group investigation. Prostate 1985; 7: 131–141. 36 De Marzo AM, Marchi VL, Epstein JI, Nelson WG. Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol 1992; 155: 1985–1992. 37 Harper ME, Pierrepoint CG, Griffiths K. Carcinoma of the prostate: relationship of pretreatment hormone levels to survival. Eur J Cancer Clin Oncol 1984; 20: 477–482. 38 Ribeiro M, Ruff P, Falkson G. Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer. Am J Clin Oncol 1997; 20: 605–608. 39 Gammon SR, Berni KC, Virgo KS, Johnson FE. Surgical treatment for prostate cancer in patients with prior spinal cord injury. Ann Surg Oncol 2005; 12: 674–678.
