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H Huland

Publications and source records attributed to H Huland.

At least 37 records · Page 2Linked to original sources

[Indications for and results of radical prostatectomy].

Radical prostatectomy represents the mainstay of therapy for clinically localized prostate cancer. The combination of diagnostic parameters such as PSA or biopsy Gleason grade in nomograms allows a safe prediction of pathologic stage and prognosis of the disease. Imaging techniques are useful in a subset of patients. International studies have proven a high cancer control rate of radical prostatectomy. A nerve-sparing modification of the operative technique does not compromise radicality of the procedure if patients are carefully selected. For this purpose simple and reliable algorithms are available.

Decision Support Systems, Clinical↗

[Serum markers for early detection and staging of prostate cancer. Status report on current and future markers].

Prostate-specific antigen (PSA) is by far the most important tumor marker in urology and has revolutionized early detection, staging, treatment, and aftercare of prostate cancer [77]. Despite these merits, inadequacies have surfaced which prohibit characterizing PSA as a perfect tumor marker. First, PSA is not a marker for prostate cancer as such:benign prostate hyperplasia, prostatitis [40,69], or prostatic manipulation [66] influence serum concentrations of PSA and lead to biopsies that are costly and potentially harmful. In the entire PSA range between 4 and 10 ng/ml, the specificity at a sensitivity of 95% continues to remain unsatisfactory. Furthermore, 30-40% of all men develop prostate cancer, but only 9-11% a clinically significant tumor burden, and 2.5-4.3% of all men die from prostate cancer. The vast majority of all carcinomas are thus in significant in terms of the patient's life expectancy. PSA is incapable of differentiating these clinically insignificant carcinomas from significant ones. Finally, prevalence of prostate cancer is increasing due to higher life expectancy. On the other hand, particularly patients aged 50-70 years are the ones who develop an aggressive form of carcinoma and profit from early detection and treatment. The global term "total PSA"encompasses a heterogeneous blend of bound and free molecular forms of PSA. Complexed PSA represents the major form of total PSA. The smaller portion, free PSA, is enzymatically inactive. In addition, different isoforms of free PSA exist Recent studies provide support for clinical application of these isoforms for early detection of prostate cancer. Clinical measurement of human glandular kallikrein 2 (hK2) serves as a complementary marker to PSA for early detection of prostate cancer and constitutes a considerable improvement over PSA as a staging marker for clinically localized prostate cancer. This overview summarizes established and potentially new forms of PSA and hK2 for early detection and staging of prostate cancer.

Biomarkers, Tumor↗

[Functional results of various surgical techniques for radical prostatectomy].

Radical prostatectomy for the treatment of prostate cancer can be performed by various techniques using a retropubic, perineal, or laparoscopic approach. Besides tumor control, the postoperative urinary continence rates and potency rates impact patients' quality of life after radical prostatectomy. This paper shows the results of our own center and compares the data in the literature regarding functional results of radical prostatectomy with respect to various operative techniques.

Aged↗

[Immunotherapy of renal cell carcinoma. With special emphasis on therapy of the elderly patient].

Interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha) induce remissions and prolong life in patients with metastatic renal cell carcinoma when carefully selected for a possibly toxic treatment. However, better-tolerated and more effective therapies are needed, especially in the elderly and patients with comorbidities. Recent achievements in the treatment of advanced renal cell carcinoma highlight potentially significant improvements. Immune cells within the tumor correlate with response and survival indicating the importance of local immune modulation. Such modulation has allowed introducing well-tolerated treatments such as inhalation of IL-2 to control lung metastases, which results in a significant survival benefit for high-risk patients as suggested by a recent cohort study in 200 patients. Antibody-based tumor targeting against cG250, specifically expressed on RCC, seems to stabilize progressive metastatic disease and does not induce toxicity. Vaccination strategies are also well tolerated, but have not shown convincing results in advanced disease so far. Other approaches have not fulfilled expectations. Stem cell transplantation still has significant toxicity and cannot be recommended for the elderly.

Administration, Inhalation↗

Differences in biopsy features between prostate cancers located in the transition and peripheral zone.

OBJECTIVE: To identify the zonal location of prostate cancers before surgery, by analysing the mapping of ultrasonography-guided systematic sextant biopsies for differences between cancers located in the transition zone (TZ) and peripheral zone (PZ); and to compare the correlation between Gleason scores of needle biopsies and those of radical prostatectomy (RP) specimens. PATIENTS AND METHODS: In all, 186 patients with TZ (46) and PZ cancers (140) underwent ultrasonography-guided systematic sextant biopsy and RP at the same institution. The clinical and pathological characteristics, and the anatomical location of positive biopsies, were determined and compared using t-tests and chi-square tests. Differences between Gleason scores of needle biopsies and those of RP specimens were evaluated and compared by Cohen kappa testing. RESULTS: TZ cancers had a significantly lower rate of positive biopsies in the middle (63% vs 80%) and base (50% vs 80%) of the prostate than had PZ cancers. Positive biopsies were exclusively obtained from the apex in 19.6% of TZ and 5% of PZ cancers (P = 0.002). There was exact agreement between Gleason scores of needle biopsies and those of RP specimens in 15.2% of TZ (kappa = 0.02) and 55% of PZ cancers (kappa = 0.25), respectively. CONCLUSION: Compared with PZ cancers, TZ cancers had a different anatomical pattern of positive biopsies, with lower rates in the middle and base of the prostate. The finding of positive biopsies exclusively in the apex favoured prostate cancer located in the TZ. Furthermore, the correlation between needle biopsy Gleason scores and those of the RP specimens was clearly lower in TZ cancers.

Adult↗

Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrence.

OBJECTIVE: To investigate the effect of cyclooxygenase-2 (COX-2) on microvessel density (MVD) and on the clinical prognosis in patients with non-muscle invasive urothelial carcinoma of the bladder, as COX-2 expression is significantly greater in epithelial tumours and there is increasing evidence that COX-2 might contribute to tumour neovascularization. PATIENTS AND METHODS: We assessed tumour samples from 110 patients undergoing transurethral resection for primary pTa/pT1 bladder carcinoma (pTa, 84; pT1, 26; grade 1, 22; grade 2, 81; grade 3, seven). Paraffin sections were assessed immunohistochemically using antibodies against COX-2, CD34 (endothelial cells) and CD105 (proliferating vessels). COX-2 expression was quantified by the number of stained cells (negative, +, ++) and the MVD calculated as vessels per field. RESULTS: Of the 110 tumours, 45 (41%) had no immunostaining for COX-2, 40 had faint staining with at least isolated positive cells (+) and 25 stained ++. COX-2 positive tumours had significantly greater vascularization for proliferating vessels. In COX-2 negative tumours the MVD was 22.1, identified by CD34 immunostaining, and 3.4 for proliferating vessels (CD105), whereas COX-2 positive tumours had a MVD of 18.3 (CD34), and of 5.8, respectively (CD105). Complete follow-up data were available in 91 patients; after a mean follow-up of 25 months, 18 (20%) had tumour recurrences. There was no significant difference in the recurrence rates or disease-free survival between COX-2-positive (19%, 25.6 months) or -negative patients (21%, 25.2 months). CONCLUSION: These results confirm the involvement of COX-2 in angiogenesis in bladder cancer, as COX-2 promoted blood vessel proliferation in the tumour zone, and indicate the usefulness of COX-2-inhibiting drugs in preventing and treating superficial bladder cancer.

Adult↗

Comparison of multitarget fluorescence in situ hybridization in urine with other noninvasive tests for detecting bladder cancer.

OBJECTIVES: To present a single-centre study investigating aneuploidy at chromosomes 3, 7, 17 and 9p21 (e.g. loss at 9p21) using a multitarget fluorescence in situ hybridization (FISH) system, as identifying genetic alterations in urine specimens is a promising approach for the noninvasive detection of bladder cancer. PATIENTS AND METHODS: Urine samples from 103 patients were evaluated, including those from 46 with histologically confirmed urothelial carcinoma, two with other urological malignancies, and 55 who acted as controls. The urine samples were taken before any manipulation. The validity of FISH (Urovision, Vysis, Downers Grove, Ill, USA) was compared with other noninvasive urine tests, including the BTA-Stat test, the nuclear matrix protein (NMP)-22 test, and immunocytology against 486p3/12 and LewisX. Those evaluating the tests were unaware of the clinical and histopathological data. FISH was considered positive if five or more urinary cells had gains of two or more chromosomes. The threshold for the urine tests were 10 U/mL (NMP-22), 30% positive cells (486p3/12), or 5% positive cells, respectively (LewisX). RESULTS: The sensitivity was 69% (FISH), 67% (BTA-Stat), 69% (486p3/12), 96% (LewisX) and 71% (NMP22), respectively; the respective specificity was 89%, 78%, 76%, 33% and 66%. CONCLUSION: Multitarget FISH had a better specificity than the other urine markers but because of its inadequate sensitivity it does not seem to be powerful enough to replace endoscopy. Optimizing the marker panel could provide a higher sensitivity.

Aneuploidy↗

[Treatment of localized prostate cancer].

OBJECTIVE: Discussed is the clinical use of radical prostatectomy in patients with clinically localized prostate cancer regarding outcome, quality of life, and morbidity based on own data and results of the literature. METHODS: A review of the currently available literature was performed. Moreover, data of 1755 patients who underwent radical retropubic prostatectomy between 1992 and 2001 at our institution were analyzed in uni- and multivariate analyses and included. RESULTS: 5-year disease-specific survival of about 80% is reported. Pathologic stage and the Gleason score are the most influencing factors on postoperative outcome. Continence rates of about 90% are common; nerve-sparing radical prostatectomy seemed to have a protecting factor on continence. Rates of erection depend on the extent of nerve sparing and achieve up to 90% after bilateral nerve sparing. 30-day perioperative morbidity decreased to less than 5% in mayor series with a mortality rate of nil. CONCLUSIONS: Selecting the right patient with clinically localized disease, radical prostatectomy showed excellent data on long-term follow-up. Due to respectful understanding of anatomical structures and improvements in surgical techniques, morbidity of the operation decreased and with the nerve-sparing technique quality of life increased.

Disease-Free Survival↗

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Administration, Inhalation↗

[Immunotherapy of metastatic renal cell carcinoma in Germany. An assessment of the current status].

This survey was established to evaluate everyday use of interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) in metastatic renal-cell carcinoma (mRCC). Of 186 centers (with 2200 patients per year) that responded, 182 support immunotherapy by using it themselves (147 centers) or by referring patients (35 centers). Effectiveness and tolerance are the main reasons for use. 133 centers use IL-2 subcutaneously, 64 by inhalation, 24 use it locally or intratumorally. Continuous intravenous IL-2 is used in 13 centers only. Most centers use subcutaneous combinations of IL-2 and IFN-alpha, either alone or with 5-fluorouracil and/or isotretinoin; IFN-alpha/Vinblastin combinations, IFN-alpha-monotherapy, and IL-2 s.c.-monotherapy are used with similar frequency. Average treatment duration is 3-6 months. Maintenance therapy is used in responding patients in 118 centers. Subcutaneous and local application of IL-2 is standard treatment for mRCC in Germany and subcutaneous IL-2 and IFN-alpha represents the most frequently used combination.

Antineoplastic Agents↗

[Regional immunotherapy of metastatic renal cell carcinoma].

We summarized the current literature concerning regional immunotherapy of pulmonary metastases in metastatic renal cell carcinoma and other malignancies using inhaled interleukin-2 (IL-2). Inhaled IL-2 therapy is associated with minimal toxicity and is effective in preventing progression in metastatic renal cell carcinoma, melanoma, and possibly other diseases such as breast cancer. Local (physiologic) use and systemic (pharmacologic) use of IL-2 are not mutually exclusive; a combination may be very appropriate in metastatic cancer. Local physiologic therapy intensifies treatment without intensifying toxicity.

Administration, Inhalation↗

Pathological and clinical characteristics of large prostate cancers predominantly located in the transition zone.

Prostate carcinomas located in the transition zone are suspected to behave differently from the more frequent peripheral zone cancers. In this study, large transition zone prostate cancers were investigated for pathological and clinical features. From 365 consecutive radical prostatectomy specimens, 73 cases were disclosed with tumours larger than 10 cm(3). Of these, 14 were predominantly (>70% tumour area) located in the transition zone. Pathological investigations included a complete histological work-up, immunohistochemistry for p53 and bcl-2, and interphase cytogenetics for chromosomes 7, 8, 17, and X. Despite large tumour volumes and high preoperative prostate specific antigen (PSA)-values, most tumours showed quite favourable pathological features. Only two of these patients suffered from a postoperative PSA-recurrence during a median follow-up of 50 months. For comparison, 36 cases that contained tumours predominantly located in the peripheral zone mostly displayed adverse prognostic signs and 68.8% of these patients suffered from postoperative PSA-recurrence. We conclude that the peculiar pathological and clinical characteristics of large prostate cancers in the transition zone might be important for prognostic considerations.

Adenocarcinoma↗

Human glandular kallikrein 2 levels in serum for discrimination of pathologically organ-confined from locally-advanced prostate cancer in total PSA-levels below 10 ng/ml.

BACKGROUND: We measured serum levels of human glandular kallikrein 2 (hK2) in patients treated with radical retropubic prostatectomy (rrP) for clinically localized prostate cancer (PCa) with a total PSA (tPSA)-level below 10 ng/ml to investigate whether hK2 can be applied to preoperatively distinguish organ-confined (pT2a/b) from nonorgan-confined (> or = pT3a)-PCa more accurately than total PSA. Further, we evaluated hK2, free- and tPSA-concentrations in all pathologic stages of PCa. METHODS: 161 serum samples from men scheduled for rrP were collected 1 day before surgery prior to any prostatic manipulation. Pathologic work-up revealed > or = pT3a-PCa in 48 and pT2a/b-PCa in 113 patients. HK2-levels in serum were measured using an immunofluorometric assay with an analytical sensitivity of 0.5 pg/ml, a functional sensitivity of 5 pg/ml and insignificant cross-reactivity with PSA (< 0.005%). Total (tPSA) and free PSA (fPSA) levels were measured using a commercially available assay from which we calculated %fPSA and an algorithm that combined hK2 and PSA-levels [hK2] x [tPSA/fPSA]. Means, medians, and ranges were calculated for pT2a/b vs. >/= pT3a-PCa and for all pathologic stages. Statistical significance of differences was calculated using Mann-Whitney-U and Kruskal-Wallis tests. Calculation of receiver-operator-characteristic (ROC) curves were performed for hK2, [hK2] x [tPSA/fPSA] and tPSA to compare diagnostic performance. RESULTS: A mean tPSA level in serum of 6.12 ng/ml in > or = pT3a-PCa was not significantly different (P = 0.366) from 5.78 ng/ml in pT2a/b-PCa. Also, there were no statistically significantly different levels of fPSA (P = 0.947) or %fPSA (0.292) for these two groups. By contrast, mean hK2-level in pT2a/b-PCa of 80 pg/ml was significantly different (P = 0.004) from a mean hK2 level of 120 pg/ml in > or = pT3a-PCa as shown by Mann-Whitney-analysis Moreover, the algorithm of [hK2] x [tPSA/fPSA] was significantly lower (P = 0.0004) in pT2a/b-PCa vs. > or = pT3a-PCa. Calculation of areas under curve (AUC) by receiver-operator-characteristics (ROC) demonstrated that the AUC for hK2 (0.64) was larger and the AUC for [hK2] x [tPSA/fPSA] (=0.68) significantly larger (P = 0.007) compared to the AUC of tPSA (0.55). Furthermore, Kruskal-Wallis Test revealed a highly significant correlation to pathologic stage using hK2 (P = 0.008) and [hK2] x [tPSA/fPSA] (P = 0.0015) compared to no significant differences in serum concentration of tPSA (P = 0.296). Also at tPSA-levels from 10-20 ng/ml, the hK2-levels in pT2a/b-PCa were close to significantly different (P = 0.051) from those in men with >/= pT3a-PCa, while the algorithm of [hK2] x [tPSA/fPSA] in that tPSA-range was significantly lower (P = 0.002) in pT2a/b-PCa compared to > or = pT3a0-PCa. CONCLUSIONS: Highly significant differences in serum concentration enable hK2 to be a powerful predictor of organ-confined disease and pathologic stage of clinically localized prostate cancer, especially in the PSA-range below 10 ng/ml. As such, there are important clinical consequences for the application of hK2 for the adequate treatment of prostate cancer patients, i.e., the option of nerve-sparing surgery. (c) 2001 Wiley-Liss, Inc.

Area Under Curve↗

Do serum C-reactive protein measurements help to discriminate episodes of renal dysfunction in patients after renal transplantation?

INTRODUCTION: This study investigated whether serial daily measurements of serum C-reactive protein (sCRP) could help differentiate episodes of transplant dysfunction due to rejection, infection, cyclosporine A (CsA) nephrotoxicity, or acute tubular necrosis (ATN) in renal-allograft recipients. MATERIALS AND METHODS: Morning serum was obtained daily from 134 patients during the first 30 days after renal transplantation. All episodes of graft dysfunction were recorded and differentiated with transplant biopsies. CRP concentrations were correlated with post-operative graft function and the various causes of graft dysfunction. RESULTS: All patients showed an increase in sCRP in response to surgery, with a maximum on day 2 after transplantation. The sCRP concentration was significantly higher in patients with delayed graft function (mean 61.50 microg/ml) than in patients with primary graft function (mean 38.01 microg/ml) (p=0.001). Bacterial infections other than asymptomatic bacteriuria (mean sCRP 33.98 microg/ml), interstitial graft rejection (mean sCRP 16.43 microg/ml), and ATN (mean sCRP 30.50 microg/ml) were accompanied by significant increases in sCRP compared with uneventful courses. sCRP was unchanged in the presence of viral infections or CsA toxicity. CONCLUSION: Serial sCRP measurements help to identify renal-transplant dysfunction of different origins. However, rejection, infection and ATN show similar patterns of sCRP increase. Thus, sCRP is unable to discriminate the causes of renal-graft dysfunction. Biopsy remains the gold standard for the differential diagnosis of renal-allograft dysfunction.

Adolescent↗

Human prostate cancer regulates generation and maturation of monocyte-derived dendritic cells.

BACKGROUND: The progression of prostate cancer is accompanied by a marked suppression of the immune system, including the apoptotic death of dendritic cells (DC) responsible for the induction of antitumor immunity. In this study, we evaluated whether prostate cancer might inhibit DC generation and maturation in vitro. METHODS: DC were generated from peripheral blood monocytes in the presence of the human prostate cell line LNCaP or nonmalignant cells, and characterized by light microscopy, FACScan analysis, and ability to stimulate T-cell proliferation. RESULTS: Prostate cancer significantly inhibited the conversion of monocytes into DC, which was assessed by the expression of DC markers CD1a and CD83. These cells were weak stimulators of T-cell proliferation, suggesting that DC generated in the prostate cancer microenvironment are functionally inhibited. CONCLUSIONS: Prostate cancer not only kills mature DC, but also inhibits their generation and maturation, resulting in decreased production of antigen-presenting cells and inhibition of their functional activity.

Antigens, CD↗

[Nerve-sparing radical retropubic prostatectomy. Results of a patient survey].

Improved selection criteria have led to an increasing number of nerve-sparing radical retropubic prostatectomies (RRP) in patients with clinically localized prostate cancer. The results based on patient questionnaires regarding postoperative erectile function are described. Between January 1992 and March 1999, 366 patients (mean age: 62.5 years) underwent uni- or bilateral nerve-sparing RRP at our institution. For evaluation of postoperative patient-reported rates of sexual and erectile function, a questionnaire was used after a follow-up of at least 12 months. Data of five operation periods were analyzed. The results of the unilateral procedure for the five operation periods revealed consistent rates of 13-29% for erections sufficient for intercourse. Bilateral nerve-sparing procedures were almost exclusively performed in periods 3 to 5; only four patients from period 2 underwent the bilateral procedure. The rates of intercourse-sufficient erections were 25% (period 2), 61% (period 3), 50% (period 4), and 52% (period 5), respectively. The results of the unilateral procedure were disappointing. However, the bilateral nerve-sparing method achieved much better results inasmuch as about 50% of the patients reported recovery of erections sufficient for sexual intercourse.

Aged↗

[Hyaluronic acid and hyaluronidase. 2 new bladder carcinoma markers].

The heterogeneity of bladder cancer concerning progress of recurrence is an essential characteristic of this disease. Hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are intricately associated with bladder cancer angiogenesis and metastasis. Tumor-associated HA and HAase are secreted in urine. In 513 urine specimens (261 bladder cancer patients, 252 patients without bladder cancer) and 83 bladder tissue specimens (71 bladder tumors, 12 normal bladder tissues), the accuracy of HA and HAase as tumor markers was studied. Elevated urinary HA levels (> or = 500 ng/ml), indicating a positive HA test, suggest the presence of bladder cancer regardless of tumor grade. Elevated urinary HAase levels (> or = 10 mU/mg) indicate high-grade (G2/G3) bladder cancer. The combined HA-HAase urine test showed 91% sensitivity and 84% specificity to detect bladder cancer. The HA-HAase test is equally sensitive for monitoring tumor recurrence. Immunohistochemistry (IHC) staining of HA and HAase in the G1 and G2/G3 bladder cancer specimens was significantly (p < 0.001) higher than in normal bladder tissue. HA and HAase appear to be useful markers in the diagnosis of bladder cancer. When compared with other noninvasive tests, the HA-HAase urine test may be less expensive and more accurate.

Aged↗