Dietary Supplement
Ionic Minerals Research
The following research abstracts
are presented to reflect the findings of possible benefits from
minerals as a dietary supplement and nutritional supplement.
For more information on individual minerals, please visit the
ionic minerals page.
Prostate cancer:
Diagnosis and Treatment
Morote J, Raventos CX, Lorente
JA, LopezPacios MA, Encabo G, deTorres I, Andreu J Journal
of Urology, 1997, Vol 158, Iss2, pp 502-504
Univ Autonoma Barcelona, Vall Dhebron Hosp,
Dept Urol, E-08193 Barcelona, SPAIN
Purpose: We analyzed the behavior
of prostate specific antigen (PSA) density and percent free
PSA to enhance the specificity of PSA in the early diagnosis
of prostate cancer in men with normal digital rectal examination
and PSA serum level between 4.1 and 10 ng./ml. Materials and
Methods: PSA serum level, PSA density and percent free PSA were
analyzed in 74 men with normal digital rectal examination and
PSA serum level between 4.1 and 10 ng./ml. All men underwent
systematic prostate biopsy, and the diagnosis was benign prostate
hyperplasia in 52 and prostate cancer in 22. Furthermore, we
determined the decrease in unnecessary biopsies and the cancer
detection rate using 0.10 versus 0.15 as cut points for PSA
density, and 20 versus 25 as cut points for percent free PSA.
Results: In patients with benign prostatic hyperplasia and prostate
cancer, respectively, the median PSA level was 6.7 and 7.0 ng./ml.
(p > 0.05), median prostate volume was 50 and 37 cc (p <
0.04), median PSA density was 0.14 and 0.19 (p < 0.007) and
median percent free PSA was 18.9 and 10.1 (p < 0.005). Using
PSA density cut points of 0.15 and 0.10, the decrease in negative
biopsies was 53.8 and 36.5% with a sensitivity of 86.4 and 90.9%,
respectively. However, using percent free PSA cut points of
20 and 25, the decrease in negative biopsies was 36.5 and 26.9%
with a sensitivity of 77.3 and 95.5%, respectively. Conclusions:
Although both methods could minimize unnecessary biopsies in
men with normal digital rectal examination and PSA serum level
between 4.1 and 10 ng./ml., the percent free PSA was more cost-effective
since transrectal ultrasound was not required. In this small
series of symptomatic patients a percent free PSA cut point
of 25 could detect at least 95% of prostate cancers and decrease
26.9% of negative biopsies.
NE Fleshner, M O'Sullivan, WR
Fair Journal of Urology, 1997,
Vol 158, Iss 2, pp 505-508
Fleshner NE, Mem Sloan Kettering Canc Ctr,
Urol Serv, New York,NY 10021 USA
Purpose: We determined the prevalence
of and risk factors for carcinoma in patients with 1 previously
negative prostate biopsy. Materials and Methods: Transrectal
ultrasound guided prostate needle biopsies were repeated in
130 men. Risk factors analyzed included age, pathological result
of initial biopsy, inter-biopsy interval, prostate specific
antigen (PSA), PSA density, PSA velocity, digital rectal examination,
abnormal transrectal ultrasound and family history of prostate
cancer. Results: A total of 39 patients (30%) had positive biopsies
for cancer. Univariate analysis revealed that PSA more than
20 ng./ml. And abnormal transrectal ultrasound were more frequent
in men with positive second biopsies. Using multivariate logistic
regression analysis only PSA more than 20 ng./ml. Was a significant
risk factor (adjusted odds ratio 4.48, 95% confidence interval
1.02 to 20.1). We determined the incidence of carcinoma in patients
who represent the lowest risk group as defined by PSA less than
10 ng./ml., PSA density less than 0.15 mg./ml./cm.(3), PSA velocity
less than 0.75, ng./ml. Per year, no prostatic intraepithelial
neoplasia plus negative transrectal ultrasound, digital rectal
examination and family history. Of 21 patients who fit this
cohort 5 (23.8%) had carcinoma on repeat biopsy. Conclusions:
A significant false-negative rate for initial transrectal ultrasound
guided prostate biopsies exists. Baseline risk in lowest risk
patients is sufficiently high such that one cannot define a
subset of patients for whom repeat biopsy is unnecessary. We
recommend repeat biopsy in all patients who meet the criteria
for a transrectal ultrasound guided biopsy and in whom the initial
biopsy is negative.
JA Connolly, JC Presti, ML Cher,
K Chew, K Shinohara, PR Carroll
Journal of Urology, 1997, Vol 158, Iss 2, pp 515-518
Carroll PR, Univ Calif San Francisco, Dept Urol, Sch Med,
Program Urol Oncol, Mt Zion Canc Ctr, U-575, San Francisco,CA
94143 USA
Purpose: We compared the growth
rates of primary cancer and prostatic fossa recurrence after
radical prostatectomy. Materials and Methods: Tumor proliferative
rates were studied in 26 patients with biopsy proved prostatic
fossa recurrences after radical prostatectomy. Proliferation
was calculated in the prostatectomy specimens and in recurrent
cancer using Ki-67 antibody to detect dividing cells. Results:
Mean and median labeling indexes for radical prostatectomy specimens
were 2.96 and 2.51, respectively. Labeling indexes in locally
recurrent tumors were significantly higher (mean 6.47, median
5.59, p < 0.001). The increase in labeling index between
parent and recurrent tumors was unrelated to pathological staging
at prostatectomy or interval from radical prostatectomy. Conclusions:
Tumors that recur locally after radical prostatectomy appear
to have a higher proliferative rate compared to parent tumors.
M Bolla, D Gonzalez, P Warde,
JB Dubois, RO
Mirimanoff, G Storme, J Bernier, A Kuten, C Sternberg,
T Gil, L Collette, M Pierart
New England Journal of Medicine, 1997, Vol 337, Iss 5, pp
295-300
Bolla M, Univ Hosp, Dept Radiotherapy, BP 217,
F-38043 Grenoble 9, FRANCE
Background We conducted a randomized,
prospective trial comparing external irradiation with external
irradiation plus goserelin (an agonist analogue of gonadotropin-releasing
hormone that reduces testosterone secretion) in patients with
locally advanced prostate cancer. Methods From 1987 to 1995,
415 patients with locally advanced prostate cancer were randomly
assigned to receive radiotherapy alone or radiotherapy plus
immediate treatment with goserelin. The patients had a median
age of 71 years (range, 51 to 80). Patients in both groups received
50 Gy of radiation to the pelvis over a period of five weeks
and an additional 20 Gy over an additional two weeks as a prostatic
boost. Patients in the combined-treatment group received 3.6
mg of goserelin (Zoladex) subcutaneously every four weeks starting
on the first day of irradiation and continuing for three years;
those patients also received cyproterone acetate (150 mg orally
per day) during the first month of treatment to inhibit the
transient rise in testosterone associated with the administration
of goserelin. Results Data were available for analysis on 401
patients. The median follow-up was 45 months. Kaplan-Meier estimates
of overall survival at five years were 79 percent (95 percent
confidence interval, 72 to 86 percent) in the combined-treatment
group and 62 percent (95 percent confidence interval, 52 to
72 percent) in the radiotherapy group (P=0.001). The proportion
of surviving patients who were free of disease at five years
was 85 percent (95 percent confidence interval, 78 to 92 percent)
in the combined-treatment group and 48 percent (95 percent confidence
interval, 38 to 58 percent) in the radiotherapy group (P<0.001).
Conclusions Adjuvant treatment with goserelin, when started
simultaneously with external irradiation, improves local control
and survival in patients with locally advanced prostate cancer.
(C) 1997, Massachusetts Medical Society.
DJ Getty, SE Seltzer, CMC Tempany,
RM Pickett, JA Swets, BJ McNeil
Radiology, 1997, Vol 204, Iss 2, pp 471-479
Getty DJ, Bbn Syst & Technol Corp,
10 Moulton St, Cambridge,MA 02138 USA
PURPOSE: To determine the effects
on the accuracy of staging prostate gland cancer of diagnostic
prediction rules based on demographic, clinical, histologic,
and magnetic resonance (MR) image variables. MATERIALS AND METHODS:
A total of 200 cases from four medical centers were evaluated
by nine radiologists experienced in MR imaging. The accuracies
of the four diagnostic variables (age, prostate specific antigen
level, Gleason tumor grade, and MR imaging findings) were measured,
both singly and combined in a particular sequence, by calculating
the area index of the receiver operating characteristic curve.
RESULTS: The accuracy of staging with single variables (age,
0.58; prostate specific antigen level, 0.74; Gleason grade 0.73,
MR image findings, 0.74) increased as the variables were optimally
merged. The first two variables combined to yield an accuracy
of 0.74; the first three combined to yield an accuracy of 0.81;
and all four variables resulted in an accuracy of 0.86. In a
clinically important subset of 69 cases for which antigen level
and Gleason grade together were inconclusive for the purposes
of staging, the addition of MR imaging findings resulted in
an increase in accuracy from 0.55 to 0.73. CONCLUSION: Optimal
merging of diagnostic test results yields an improvement in
the accuracy of prostate cancer staging.
N FukunagaJohnson, HM Sandler,
PW McLaughlin,
MS Strawderman, KH Grijalva, KE Kish, AS Lichter
International Journal of Radiation Oncology
Biology Physics, 1997, Vol 38, Iss 2, pp 311-317
FukunagaJohnson N, Univ Michigan Hosp,
Dept Radiat Oncol, Ann Arbor,MI 48109 USA
Purpose: 3D conformal radiotherapy
(3D CRT) has been shown to decrease acute morbidity in the treatment
of prostate cancer. Therapeutic outcome and late morbidity data
have been accumulating. To evaluate the results of 3D CRT for
the treatment of prostate cancer, we analyzed the outcome of
a large series of patients treated with conformal techniques.
Material and Methods: From January 1987 through June 1994, 707
patients with localized prostate cancer were treated with 3D
CRT. Patients with pathologically-confirmed pelvic lymph node
metastasis, treated with preirradiation (preRT) androgen ablation,
or treated post-prostatectomy were excluded. All had CT obtained
specifically for treatment planning, multiple structures contoured
on the axial images, and beam's-eye view conformal beams edited
to provide 3D dose coverage. Median follow-up is 36 mos; 70
patients have been followed longer than 5.5 Sears. Six hundred
three had T1-T2 tumors. PreRT prostate specific antigen (PSA)
was available for 649 patients: median preRT PSA was 12.9 ng/ml,
209 patients had preRT PSA > 20 ng/ml. The median dose of
radiation was 69 Gy; 102 patients received greater than or equal
to 69 Gy. Biochemical failure was defined as: 1) two consecutive
PSA rises over 2.0 ng/ml if nadir PSA less than or equal to
2.0 ng/ml, 2) two consecutive PSA rises over nadir if nadir
PSA > 2.0 ng/ml, or 3) initiation of hormonal therapy after
RT. Complications were graded using the RTOG system. Results:
PreRT PSA and Gleason score emerged as independent indicators
of biochemical control (bNED). Patients with preRT PSA >
10 had a significantly worse bNED at 5 years than patients with
preRT PSA less than or equal to 10. Five-year bNED was determined
according to preRT PSA: PSA less than or equal to 4, 88%; PSA
> 4 less than or equal to 10, 72%; PSA > 10 less than
or equal to 20, 43%; and PSA > 20, 30%. Patients with Gleason
score greater than or equal to 7 also had a significantly worse
bNED than patients with Gleason score < 7. Patients were
divided into two prognostic groups: a favorable group with PSA
less than or equal to 10, Gleason score < 7, and T1-T2 tumors,
and an unfavorable group with PSA > 10, Gleason score greater
than or equal to 7 or T3-T4 tumors and studied for the effect
of dose on bNED status. The bNED at 5 years was 75% for the
favorable group and 37% for the unfavorable group. In addition,
a group that might be considered a surgical subset was reviewed:
patients with PSA less than or equal to 10, Gleason score less
than or equal to 7, and T1-T2 tumors who were <70 years old.
This subset had an 84% 5-year bNED rate and 98% 5-year overall
survival. Complications with the techniques used here are very
low: 3% risk at 7 years of Grade 3-4 complications and 1% risk
at 7 years of Grade 3 bladder complications (no Grade 4). Conclusion:
3D CRT allows for treatment of prostate cancers with a very
low risk of complications. Patients with relatively early disease
as defined by preRT PSA, Gleason score < 7, and T1-2 tumors
and patients who are candidates for radical prostatectomy have
excellent 5-year bNED rates. Patients with adverse prognostic
factors have a high risk of biochemical recurrence and are candidates
for innovative therapy. (C) 1997 Elsevier Science Inc.
TC Hsieh, JM Wu
Biochemical and Biophysical Research Communications, 1997,
Vol 235, Iss 3, pp 539-544
Wu JM, New York Med Coll, Dept Biochem
Mol Biol, Valhalla,NY 10595 USA
In addition to suppressing prostate
cell growth, vitamin D also up-regulates the expression of androgen
receptor (AR) and prostate-specific antigen (PSA). To study
the mechanism involved in the control of these proteins, LNCaP
cells were treated with 10 nM 1 alpha,25-dihydroxyvitamin D-3
and separated into cytosol and nuclear fractions. AR and PSA
were analyzed by western blot analysis. A second approach involved
incubating control and treated cells with [H-3]R1881, fractionating
the cells into the cytosolic and nuclear components, and quantifying
the amount of radioactivity associated with the respective fractions.
Alternatively, immunohistochemical assays were performed by
staining cells with cognate antibodies for AR and PSA, Both
biochemical and immunohistochemical analyses show proportionately
greater increased presence of AR in the nucleus, accompanied
by relatively reduced AR in the cytosol, following treatment
of LNCaP cells with vitamin D-3. Surprisingly, PSA was found
to be present in the nuclear fraction in both control and treated
cells. These results suggest that vitamin D-3 promotes the translocation
of AR from the cytosol to the nucleus. The presence of PSA in
the nucleus of LNCaP cells raises the possibility of an autogenous
mode of control of PSA gene expression. (C) 1997 Academic Press.
Nakashima J.; Imai Y.; Tachibana
M.; Baba S.; Hiramatsu K.; Murai M.
Cancer (USA) , 1997, 80/2 (237-241)
Dr. J. Nakashima, Department of Urology, Keio University
School of Medicine,
35 Shinanomachi, Shinjuku-ku, Tokyo 160 Japan
Background: Little effort has
been made at the quantitative and qualitative evaluation of
patients with prostate carcinoma, including downsizing and downstaging
of the primary lesion, after conservative therapy. The current
study was undertaken to investigate the qualitative and quantitative
effects of endocrine therapy on the primary prostate carcinoma
using magnetic resonance imaging (MRI). METHODS. The primary
prostate carcinoma was evaluated by endorectal MRI approximately
4 months after the initiation of endocrine therapy in 48 patients
with histologically confirmed prostate carcinoma detected by
endorectal MRI before therapy. RESULTS. The volumes of the prostate
gland, the carcinoma, and the noncarcinomatous components were
reduced to 60.2 plus or minus 2.7%, 25.5 plus or minus 2.9%,
and 83.2 plus or minus 6.3% of their pretreatment volumes respectively
after endocrine therapy, indicating that the tumors are more
susceptible to endocrine therapy than the nontumorous components.
The number of prostate carcinomas that demonstrated low signal
intensity compared with the normal peripheral zone on T2-weighted
images decreased after endocrine therapy and the number of carcinomas
with enhancement of T1-weighted contrast-enhanced images increased
after therapy. Seven of the 48 patients underwent downstaging
after endocrine therapy, based on the endorectal MRI evaluation.
CONCLUSIONS. The results of the current study suggest that downsizing
and occasionally downstaging of the carcinoma may occur after
endocrine therapy in patients with prostate carcinoma. In addition,
the androgen sensitivity of the prostate carcinoma tissue is
relatively high compared with the residual noncancerous prostate
gland.
C Coker, RA Sherwood, T Crayford,
F Saadeh,
D Mulvin, E Brakenbury, MJ Coptcoat
Prostate, 1997, Vol 32, Iss 2, pp 85-88
Background: To determine if altered
tissue perfusion during cardiac surgery results in ischemic
tissue damage to the prostate, as suggested by a rise in prostatic-specific
antigen (PSA). METHODS. Twenty-nine male patients undergoing
elective coronary artery bypass grafting were studied. Ten male
patients undergoing elective gastrointestinal surgery served
as controls. PSA levels were determined preoperatively and six
hourly intervals postoperatively for 48 hr. All patients underwent
urethral catheterization at induction of anesthesia. RESULTS.
All patients (100%) who had undergone cardiac bypass surgery
showed rises in serum PSA during 48 hr of postoperative follow-up.
At the 6-hr postoperative interval, the mean PSA was significantly
different from the mean baseline value (paired two tailed Student's
t test, P < 0.001) in 27 of the 29 (93%) patients. In contrast,
the PSA values in the 10 gastroenterological controls did not
change at 6 hr (P > 0.2) or during the next 48 hr. One patient
in the cardiac group showed a very marked elevation in serum
PSA of greater than 50 times normal preoperative levels. CONCLUSIONS.
Statistically significant rises in PSA levels are seen following
coronary bypass surgery. This rise may be caused by ischemic
nontrauma related damage to the prostate and suggests a possible
pathophysiological mechanism for the clinically episodic symptoms
of prostatism seen in elderly men. (C) 1997 Wiley-Liss, Inc.
Douglas TH; McLeod DG; Mostofi
FK;
Mooneyhan R; Connelly R; Moul JW; Sesterhenn IA
Prostate (UNITED STATES) Jun 15 1997, 32 (1) p59-64,
Department of Surgery, Walter Reed Army Medical Center,
Washington, DC 20307-5001, USA.
Background: Clinical and pathological
staging of prostate cancer has been, and remains, problematic.
Since prostate-specific antigen (PSA)-detected tumors are often
discerned during "screening," what are their significance?
METHODS: We analyzed 67 consecutive patients with stage T1c
prostate cancer undergoing radical prostatectomy at our institution
from August 1, 1991-September 12, 1995, and who had whole-mount
specimen processing. Diagnosis was determined in all cases by
transrectal ultrasound-guided biopsy. RESULTS: The mean age
of our patients was 63 years, and the mean PSA at time of diagnosis
was 8.6 ng/ml (median, 7.2 ng/ml). There was organ-confined
cancer in 31/67 (46%) patients; 17/67 (25%) had periprostatic
fat infiltration, and of these 5(7%) had seminal vesicle involvement.
Thirty-one of 67 (46%) had positive surgical margins. Twenty-two
(33%) had a Gleason sum of > or = 7 in the final pathological
specimen. Insignificant tumors (dominant tumor volume < 0.20
cc) were found in only 4 cases. Smaller tumors were more likely
to be found when the PSA was < 10 ng/ml. Multifocal disease
was found in 64/67 (96%) prostate specimens. CONCLUSIONS: This
study adds impetus to the growing realization that nonpalpable
prostate cancer, detected because of elevated PSA, is rarely
insignificant. Our findings add further emphasis to the fact
that patients diagnosed by PSA elevation have, for the most
part, significant cancer that should be treated aggressively.
