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L Klotz

Publications and source records attributed to L Klotz.

At least 19 recordsLinked to original sources
PubMed2004

Cavernosal nerve mapping: current data and applications.

Although nerve-sparing prostatectomy is widely practised, the results with respect to preserving potency often do not meet expectations. The concept of intraoperative cavernosal nerve stimulation is reasonable. Data that link the response to sildenafil after prostatectomy with bilateral nerve sparing has increased the importance of optimizing nerve sparing. The cavernosal nerves are often difficult to visualize and may have a variable course. A tumescent response to nerve stimulation can be shown consistently; the response may be subtle, and characterized by a minimal increase in penile circumference and blood flow. Immediately after prostatectomy, proximal nerve stimulation identifies whether neural continuity has been maintained, and is predictive of recovery of erectile function. The Cavermap system (Uromed Corporation, Boston, MA, USA) was developed to permit intraoperative nerve stimulation with tumescence monitoring. An initial phase 2 and subsequent phase 3 single-blinded, randomized, multicentre study that compared Cavermap-assisted prostatectomy with conventional nerve sparing showed a significant benefit in terms of the duration of nocturnal tumescence at 1 year. Other approaches are being explored, including incorporating the device into sural or genito-femoral nerve grafting, use of nerve stimulation during cystectomy or abdominal-perineal resection, and direct corpus cavernosal pressure monitoring during nerve stimulation. These approaches warrant further evaluation.

Diagnostic Techniques, Neurological↗
PubMed2004

Comparison of histologic grade between initial and follow-up biopsy in untreated, low to intermediate grade, localized prostate cancer.

OBJECTIVE: To examine the change of histologic grade of untreated, low to intermediate grade, clinically localized prostate cancer over time on repeat prostate biopsy. METHODS AND MATERIALS: In a prospective single-arm cohort study, patients were managed with observation alone unless they met pre-defined criteria of disease progression (PSA, clinical or histologic progression). Sixty-seven (54%) of a total of 123 eligible patients underwent follow-up prostate biopsy. Median time to the follow-up biopsy was 22 months (range: 7-60). RESULTS: On the follow-up biopsy, Gleason score was unchanged in 20 patients (30%), upgraded in 19 (28%), and downgraded in 27 (40%). Twenty-one (31%) had no malignancy on the follow-up biopsy. Sixteen (37%) of 43 patients with < or = 2 positive cores on the initial biopsy had negative follow-up biopsy, while only 2 (11%) out of 18 with > or = 3 positive cores on the initial biopsy did. Five (7%) patients were upgraded to Gleason score 8. There was no correlation between the extent of grade change and baseline variables (age, clinical stage, and initial PSA) as well as PSA doubling time. CONCLUSIONS: There was no consistent histologic upgrade on the follow-up biopsy at a median of 22 months in untreated, low to intermediate grade, clinically localized prostate cancer.

Aged↗
PubMed2003

Are serial bone scans useful for the follow-up of clinically localized, low to intermediate grade prostate cancer managed with watchful observation alone?

OBJECTIVE: To assess the predictive value of serial bone scans as a surveillance tool for bone metastasis in men with clinically localized prostate cancer and managed with watchful observation. PATIENTS AND METHODS: A prospective single-arm study was conducted to assess the feasibility of a watchful observation protocol with selective delayed intervention for patients with clinically localized prostate cancer, i.e. T1b-T2bN0M0, a Gleason score of 15 ng/mL the patient underwent bone scintigraphy every year. RESULTS: In all, 244 eligible patients were enrolled into the study. With a median follow-up of 30 months, 449 bone scans were taken (150 at baseline and 299 in follow-up evaluations); all 299 follow-up scans were negative for bone metastasis. Hence, the true rate of positive follow-up bone scans was estimated to be 0-1.0% (95% confidence). In all, 171 patients had at least one follow-up bone scan; of these, the number (%) of patients who had 1, 2, 3, 4 and >or= 5 follow-up scans was 89 (52), 53 (31), 17 (10), eight (4.7) and four (2.3), respectively. The PSA levels (ng/mL) corresponding to all follow-up bone scans were: 214 scans at PSA < 10, 61 at 10-14.9, 18 at 15-19.9 and six at >or= 20 (range 20.2-24.9). The probability of a negative bone scan was estimated to be 88-100% (95% confidence interval) when a PSA threshold of 15 ng/mL was used. CONCLUSION: The probability of positive findings in serial bone scans in untreated, localized, low to intermediate grade prostate cancer was low when the follow-up PSA level remained < 15 ng/mL. Avoiding bone scans in this group of patients would translate into a significant cost saving and reduction in their psychological and physical burden. As for those with a follow-up PSA of> 15 ng/mL, the role of serial bone scintigraphy remains undefined, as a longer follow-up and a larger sample are needed.

Aged↗
PubMed2003

Is there a progression of histologic grade from radical prostatectomy to local recurrence in patients with clinically isolated local recurrence following surgery?

OBJECTIVE: To evaluate whether there is any histologic progression from radical prostatectomy (RP) to local recurrence in patients with clinically isolated local recurrence following RP. METHODS AND MATERIALS: A total of 43 patients with clinically isolated, biopsy proven, local recurrence following RP were retrospectively analyzed with respect to the change in Gleason score (GS) from RP to local recurrence. Central pathology review was undertaken for both RP and local recurrence biopsy specimens. The changes in primary and secondary Gleason grade (GG), and any potential correlation between the extent of GS change and other variables were also examined. RESULTS: Median age at the time of local recurrence was 67 years (range: 55-78). Median interval between RP and local recurrence was 3.6 years (range: 0.3-17.7). Eight had a short course (<3 months) of hormone therapy prior to RP. Initial GS of RP specimens was 5, 6, 7, 8, and 9 in 1, 3, 29, 1, and 9 patients, respectively. At the time of local recurrence, GS was upgraded in 13, unchanged in 23, and downgraded in 7. The extent of GS change was correlated with the interval between RP and local recurrence, but not with pathological T stage or age. CONCLUSION: There was no statistically significant change in GS from RP to local recurrence, although there was a trend toward a higher GS at the time of local recurrence. The extent of GS change was associated positively with the elapsed time to local recurrence.

Adenocarcinoma↗
PubMed2002

The role of serial free/total prostate-specific antigen ratios in a watchful observation protocol for men with localized prostate cancer.

OBJECTIVE: To examine the change in the free/total prostate specific antigen ratio (f/tPSA) with time and to assess the potential value of serial measurements of f/tPSA as a determinant of disease progression in untreated, low-to-intermediate grade prostate cancer (T1b-T2b N0M0, Gleason score < or = 7 and PSA < or = 15 ng/mL). PATIENTS AND METHODS: In a prospective single-arm cohort study from November 1995, patients were conservatively managed with watchful observation alone unless they met arbitrarily defined criteria (clinical, histological and biochemical) of disease progression. Patients were followed regularly and underwent blood tests including PSA and f/tPSA. The initial and mean f/tPSA and the rate of change of f/tPSA with time were evaluated against the rate constant for the PSA doubling time (PSATd). Correlation analyses were used to evaluate any association between baseline clinical variables and either the rate of change of f/tPSA or initial f/tPSA. RESULTS: As of December 2000, 161 of a total of 206 accrued patients had three or more f/tPSA measurements and formed the basis of the study (median age 70 years; median follow-up 2.7 years). The median initial f/tPSA was 0.16; there was a significant negative correlation between this value and the initial total PSA. The mean f/tPSA and rate of change of f/tPSA with time were significantly negatively correlated with the rate constant for PSATd. Also, the rate of change of f/tPSA correlated negatively with clinical T stage, but not with other baseline variables, including initial PSA, age and Gleason score. CONCLUSION: The f/tPSA in men with untreated, clinically localized prostate cancer varied widely. The negative correlation between the rate of change of f/tPSA with time and rate constant for PSATd suggests that both might provide valuable information to allow clinicians to develop a strategy for optimizing the timing of therapeutic intervention for those patients choosing watchful observation alone.

Adenocarcinoma↗
PubMed2001

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PURPOSE: To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. METHODS AND MATERIALS: A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. RESULTS: As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. CONCLUSION: Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

Adenocarcinoma↗
PubMed2001

Systematic overview of the evidence for brachytherapy in clinically localized prostate cancer.

BACKGROUND: Brachytherapy (permanent implantation of radioactive seeds) has emerged as an alternative to existing standard therapy with radical prostatectomy or external beam radiotherapy in the treatment of clinically localized (T1 and T2) prostate cancer. The Genitourinary Cancer Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative examined the role of brachytherapy in treating clinically localized prostate cancer. METHODS: A systematic review of articles published from 1988 to April 1999, retrieved through a search of MEDLINE and CANCERLIT databases, was combined with a consensus interpretation of the evidence in the context of conventional practice. RESULTS: Although there were no randomized trials comparing brachytherapy with standard treatment, evidence was available from 13 case series and 3 cohort studies. Rates of freedom from biochemical failure (biochemically no evidence of disease [bNED]) varied considerably from one series to another and were highly dependent on tumour stage, grade and pretreatment serum prostate-specific antigen (PSA) levels. Results in patients with favourable tumours (T1 or T2 tumour, Gleason score of 6 or lower, serum PSA level of 10 ng/mL [microgram/L] or less) were comparable to those in patients undergoing radical prostatectomy. Acute urinary retention was reported in 1%-14% of patients. Long-term sequelae occurred in less than 5% of patients and included urinary incontinence, cystitis, urethral strictures and proctitis. Sexual potency was maintained after implantation in 86%-96% of patients. INTERPRETATION: At present, there is insufficient evidence to recommend the use of brachytherapy over current standard therapy for localized prostate cancer. Brachytherapy using transrectal ultrasound guidance for seed implantation is promising in terms of freedom from biochemical failure in selected patients with early-stage prostate cancer. Brachytherapy is currently available outside of clinical trials, but whenever possible patients should be asked to participate in randomized trials comparing brachytherapy and current standard therapy. Brachytherapy should be available to selected patients (those with T1c or T2a tumours, a Gleason score of 6 or lower and a serum PSA level of 10 micrograms/L or less), after discussion of the available data and potential adverse effects.

Brachytherapy↗
PubMed2001

Early experience in intermediate-risk penile cancer with sentinel node identification using the gamma probe.

OBJECTIVES: To report the initial experience with sentinel node identification using the gamma probe in patients with intermediate-risk penile cancer (T2NXM0, or T1 with intermediate or high-grade disease) and impalpable groin nodes. METHODS: Technetium-99m-labeled sulfur colloid was injected at the site of primary penile carcinoma 1 hour before surgery. The sentinel lymph nodes were located using the gamma probe and excised through a 3-cm inguinal incision. A full groin dissection was performed only in cases in which frozen section of the node demonstrated metastasis. RESULTS: Nine sentinel nodes were identified by the gamma probe and excised in 5 men. In 3 patients, the sentinel nodes were negative bilaterally. In 2 patients, the sentinel node, although grossly normal, showed a single focus of metastasis by frozen section analysis. In both of these patients, a full groin dissection was carried out and revealed no other nodal metastases. All 5 remained free of recurrence (median follow-up 18 months, range 16 to 23). CONCLUSIONS: In patients with microscopic involvement of a single lymph node only (confirmed by full groin dissection), gamma probe identification was 100% accurate. None of the patients with negative sentinel nodes had a recurrence. Biopsy of the sentinel nodes using the gamma probe can predict the presence or absence of inguinal node metastasis in patients with intermediate-risk penile cancer, sparing many patients the long-term morbidity of a full groin dissection. These initial results suggest further study is warranted.

Adult↗
PubMed2001

The role of serial transrectal ultrasonography in a 'watchful waiting' protocol for men with localized prostate cancer.

OBJECTIVE: To determine the value of serial 6-monthly transrectal ultrasonography (TRUS) in a cohort of men with localized prostate cancer who consented to a programme of watchful waiting with selective delayed intervention. PATIENTS AND METHODS: Since November 1995, 180 men were accrued into an ongoing prospective study of watchful waiting with selective delayed intervention; 174 patients enrolled before 31 December 1999 comprised the cohort for the present study. The prospectively collected clinical data, including the TRUS reports, were reviewed systematically. Twenty-eight men met the arbitrarily predefined criteria of disease progression and required definitive treatment. The TRUS findings were scored as being consistent with the clinical scenario (i.e. clinical, biochemical or histological progression) if they reported a new or enlarging hypoechoic peripheral zone lesion, or a > or = 30% increase in overall prostate volume at the time of progression. In 136 men who had undergone two or more serial TRUS examinations the relationships between the rate of change of prostate-specific antigen (PSA) and changes in both gland volume and the number of hypoechoic lesions were also examined. RESULTS: The group of 28 men who progressed to require radical intervention underwent 83 TRUS examinations (median number per patient, three). Two men underwent TRUS only once at baseline because of progression within 6 months. Of these 28 men, only seven had changes on TRUS that were regarded as being consistent with progression; all seven consisted of the growth of an existing nodule or the appearance of a new nodule. In only one case was this accompanied by an increase of > or = 30% in gland volume. In the 136 men who underwent two or more serial TRUS examinations (median three, maximum nine), there was no correlation between the rate of change of PSA and changes in either gland volume or the number of peripheral zone hypoechoic lesions. CONCLUSION: The use of serial TRUS in men with known but untreated prostate cancer is of limited value as a determinant of disease progression.

Clinical Protocols↗
PubMed2000

Hormone therapy for patients with prostate carcinoma.

BACKGROUND: Androgen ablation as a treatment for patients with prostate carcinoma was described 60 years ago. Despite the long pedigree for this treatment, the optimal use of androgen ablation therapy remains extremely controversial. Monitoring the level of prostate specific antigen (PSA) has created a dramatic shift in the population of patients in whom androgen ablation is initiated. This has resulted in a number of changing concepts of treatment. Patients with recurrent prostate carcinoma after the failure of local therapy are now diagnosed with recurrent disease on the basis of a rising PSA level. These patients have a median life expectancy of 10-15 years compared with 3 years for patients who present with metastatic disease. This means that the systemic side effects of androgen ablation and the impact on quality of life have become more important. Controversies exist with respect to the timing of therapy, the use of intermittent androgen ablation, and the role of total androgen blockade. METHODS: A critical review of the literature, with an emphasis on quality of life and recent publications, was performed. RESULTS: Data support the early initiation of androgen ablation for patients with locally advanced or lymph node positive prostate carcinoma. There are no data supporting a particular PSA trigger point or a PSA doubling time for the initiation of androgen ablation therapy after the failure of local radical therapy. The combined results of 27 prospective randomized trials of total androgen blockade support the finding of a modest survival benefit for patients who undergo androgen ablation with combined therapy. The average, absolute 5-year survival rate was improved by 3% (a 10% reduction in the risk of dying), with a 95% confidence interval between 0.4% and 6.0%. Intermittent therapy resulted in an improved quality of life in the off-treatment interval. Uncertainty remains with respect to the long term effect of intermittent androgen ablation therapy on patient survival. This is being studied in a prospective intergroup trial comparing continuous therapy with intermittent therapy carried out by the National Cancer Institute Criteria/Canadian Uro-Oncology Group and the Southwest Oncology Group. CONCLUSIONS: Androgen ablation therapy is an effective treatment for patients with advanced prostate carcinoma. It has serious limitations, however. Although it improves patient survival, it is not curative, and it is associated with a substantial adverse impact on the quality of life for patients, particularly when its use is prolonged. The advent of intermittent therapy may reduce this impact. The real challenge, however, is to develop better means to avert hormone-refractory prostate carcinoma and better treatments for patients with hormone-refractory disease when it occurs.

Androgen Antagonists↗
PubMed2000

Involvement of p27Kip1 in G1 arrest by high dose 5 alpha-dihydrotestosterone in LNCaP human prostate cancer cells.

The cell cycle is governed by cyclin dependent kinases (cdks), which are activated by binding of cyclins, inhibited by cdk inhibitors and regulated by phosphorylation and dephosphorylation. Exposure to high dose dihydrotestosterone (DHT) inhibits population growth of the human prostate carcinoma cell line, LNCaP. To determine the mechanism of growth arrest by high dose DHT, we assayed the changes in cell cycle profile and the cell cycle regulators that mediate these effects. Treatment of asynchronously growing LNCaP cells with 100 nM DHT caused a G1 arrest. The proportion of cells in S phase fell from 22 to 2%, while the G1 fraction rose from 74 to 92% by 24 h. Loss of phosphorylation of the retinoblastoma protein was noted and cdk4 and cyclin E/ cdk2 activities fell. Inhibition of these G1 cyclin dependent kinases was not due to loss of either cyclin or cdk proteins nor to increases in the cdk inhibitors p16INK4A and p21CiP1. p21Cip1 protein levels remained constant, and cyclin E-associated p21CiP1 fell, suggesting that p21CiP1 is not relevant to this form of cyclin E/cdk2 inhibition. Of note, total p27KiP1 levels and cyclin E-associated p27Kip1 increased as cells arrested and the amount of the CAK activated cdk2 bound to cyclin E decreased. p27KiP1 immunodepletion experiments demonstrated that the DHT-mediated increase in p27Kip1 was sufficient to fully saturate and inhibit target cyclin E/ cdk2. The inhibition of cyclin E/cdk2 by p27Kip1 contributes to G1 arrest of LNCaP following high dose DHT. p27KiP1 may be a key effector of androgen dependent growth modulation in prostate cancer cells.

CDC2-CDC28 Kinases↗
PubMed2000

Hyperproliferative hepatocellular alterations after intraportal transplantation of thyroid follicles.

The thyroid hormone 3,5,3'-triiodo-L-thyronine (T3) is a strong direct hepatocyte mitogen in vivo. The effects of T3 resemble those of peroxisome proliferators, which are known to induce hepatocellular tumors in rats. With the aim of studying long-term local effects of thyroid hormones on liver parenchyma, small pieces of thyroid tissue were transplanted via the portal veins into the livers of thyroidectomized male Lewis rats. At 1 week, 3 weeks, 3 months, and 18 months after transplantation, the transplants were found to proliferate, to synthesize thyroglobulin, and to release thyroxine and T3. At 3 and 18 months after transplantation, the hepatocytes of the liver acini downstream of the transplanted follicles showed an increase in cytoplasmic basophilia, a loss of glycogen, an enlargement and hyperchromasia of their nuclei, and a strong increase in cell turnover compared with unaltered liver acini. The altered hepatocytes exhibited an increase in the activities of glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, malic enzyme, mitochondrial glycerol-3-phosphate dehydrogenase, cytochrome-c-oxidase, and acid phosphatase; the activities of glycogen synthase and glycogen phosphorylase were strongly decreased. The hepatocytic alterations downstream of the transplanted follicles could be explained by effects of T3. On the other hand, they resembled alterations characteristic of amphophilic preneoplastic liver foci observed in different models of hepatocarcinogenesis.

Animals↗
PubMed2000

Hepatocellular alterations after intraportal transplantation of ovarian tissue in ovariectomized rats.

The mechanisms of hepatocarcinogenesis by certain synthetic estrogens seem to involve both nongenotoxic and indirect genotoxic effects. However, the natural estrogen estradiol did not exert any carcinogenic effects in established experimental protocols. To elucidate specific long-term effects of natural estrogens on hepatocytes, small pieces of ovarian tissue were transplanted via the portal vein into the livers of ovariectomized female rats. One week, 3 weeks, and 3 months after transplantation the transplants were found to proliferate and to secrete estradiol. Three weeks after transplantation the hepatocytes of the liver acini downstream of the stimulated transplants already showed a remarkable loss of glycogen, distinct cytoplasmic amphophilia, enlargement of their nuclei, a strong increase in the number and size of peroxisomes, an increase in proliferative activity and apoptotic elimination, and changes in the activity of certain key enzymes of energy metabolism. All hepatocellular alterations could be inhibited by the estrogen receptor antagonist toremifene and are, therefore, attributed to specific effects of estradiol produced by the transplants. The observed alterations resemble in some respects amphophilic preneoplastic liver foci, which particularly occur after long-term administration of nongenotoxic hepatocarcinogens, including the adrenal steroid hormone dehydroepiandrosterone. In a preliminary experiment three of six animals exhibited a hepatocellular carcinoma, and another animal developed a hepatocellular adenoma 18 months after intrahepatic ovarian tissue transplantation.

Adenoma↗