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Biomedical subjects

H Huland

Publications and source records attributed to H Huland.

At least 73 records · Page 4Linked to original sources

The correction of penile curvature with the Essed-Schröder technique: a long-term follow-up assessing functional aspects and quality of life.

OBJECTIVES: To investigate, in a retrospective analysis using a detailed questionnaire, the long-term functional results in and quality of life (QoL) of patients after undergoing the Essed-Schröder procedure, a standard technique for correcting penile curvature. PATIENTS AND METHODS: From 1994 to 1999, 40 patients (median age 24 years) had their penile curvature corrected using a modified Essed-Schröder technique. Assessments by the investigators and a self-completed questionnaire were used to evaluate the functional and cosmetic aspects of the procedure, and QoL issues. RESULTS: Complete follow-up data were available in 31 of the 40 (78%) patients (19 with congenital curvature and 12 with Peyronie's disease). The median follow-up was 22 months. The degree of penile angulation before surgery was estimated as < 45 degrees in five patients, 45-90 degrees in 22 and > 90 degrees in four. In 21 patients (68%) sexual intercourse was uncomfortable or impossible; 26 (84%) reported an impaired QoL because of the penile curvature. After surgery the cosmetic and functional result was good or sufficient in 25 patients (81%); all 25 were able to have sexual intercourse with no problems. Penile shortening (> 2 cm) was reported by six patients. A significant improvement in QoL was reported by 15 patients (48%), but of the 12 patients with Peyronie's disease before surgery, six reported impaired rigidity and two recurrence of their penile curvature afterward. Whereas only seven of 12 patients with Peyronie's disease reported good functional results, 18 of the 19 with congenital curvature reported good or excellent results after surgery. CONCLUSION: The Essed-Schröder method is a simple operation which provides good functional and cosmetic results. Patients with congenital curvature of the penis have better results than those with Peyronie's disease.

Adolescent↗

Stage migration in clinically localized prostate cancer.

OBJECTIVES: To determine whether migration of pathological tumor stages in patients with clinically localized prostate cancer exists and whether this is due to an increasing frequency of treating patients with clinically insignificant cancer. METHODS: 1,063 radical retropubic prostatectomies were performed in patients with clinically localized prostate cancer in one institution within 7.5 years (from 1992 until June 1999). All specimens were prospectively processed according to the Stanford protocol. These were then analyzed regarding the migration of pathological tumor stages and cancer volumes. RESULTS: Within the observation period, the annual rate of radical retropubic prostatectomies increased by 225% from 69 to 224 cases. The authors noted a decline of advanced tumor stages (from 65 to 40%) and an increase in pathological T2 tumors (from 30 to 55%). The rate of small cancers (<0.5 cm(3)) remained stable between 2 and 5% over the last 5 years. CONCLUSION: The data confirm trends which were observed in large US centers with increasing detection and treatment of localized prostate cancer without unnecessary treatment of clinically insignificant cancers.

Humans↗

Advanced prostate cancer is associated with a decrease in serum luteinizing hormone.

OBJECTIVE: Depletion of serum LH by LHRH agonists is used as a therapeutic treatment in hormone-sensitive prostate cancer (PCa). However, little information on serum LH in different patient groups is available. METHODS: Patients with biopsy-proven PCa, men with BPH (biopsy-proven absence of PCa), two subgroups (serum PSA <4 ng/ml; PCa and BPH), and a PCa cohort before and after radical prostatectomy were analyzed for serum LH, testosterone (T), dihydrotestosterone (DHT), total and free PSA by immunological procedures. RESULTS: PCa patients with cancer volumes >10 cm(3), or with advanced Gleason scores, had significantly lower LH values than men in a cancer-free control group (PSA <4 ng/ml). Eight weeks after radical prostatectomy, LH levels had returned to the level of the control group (p<0.0001). These alterations were not accompanied by corresponding changes of serum androgens. Introduction of a PSA/LH ratio appeared to increase the differences between BPH and PCA groups ranked according to Gleason scores, versus PSA or LH alone. However, the calculation of ROC curves indicated that PSA/LH ratios may not improve the discrimination of malignant and benign forms of the disease, compared to presently used parameters. CONCLUSIONS: A significant reduction of circulating LH is observed in the most advanced forms of PCa. The effect does not come about by T- or DHT-mediated feedback inhibition. Since LH values after prostatectomy returned to practically the same levels as seen in the control group (BPH with <4 ng/ml PSA), it appears that the healthy prostate has no marked influence on serum LH while advanced PCa induces a decrease in serum LH.

Adult↗

A comparison of systemic versus inhaled recombinant IL-2 administration for the treatment of metastatic renal cell carcinoma.

The aim of the current study was to compare the objective response and survival rates of patients with mRCC treated with IL-2 administered either systemically (SYST, subcutaneously) or via inhalation (INH), using relatively large sample sizes to afford a more meaningful comparison. We used univariate and multivariate analyses to retrospectively evaluate the data from two different databases generated from 277 patients treated with IL-2 during the 1993-1997 period, one developed at the University Hospital Hamburg-Eppendorf, and the other at Chiron-Amsterdam. Patients treated with INH IL-2 tended to have a poorer ECOG performance status than patients receiving SYST IL-2. Of 75 patients receiving INH IL-2, eight (10.7%) achieved an objective response; of 202 patients administered SYST IL-2, 45 (22.2%) achieved an objective response. The median survival time was 13.8 months for patients receiving INH IL-2 and 13.1 months for patients treated with SYST IL-2. One- and two-year survival rates were also comparable for the two treatment modalities (one-year: INH, 55%; SYST, 56%; two-year: INH, 28%; SYST, 26%). There was no significant difference in the likelihood of survival for patients receiving INH IL-2 versus SYST IL-2 (risk ratio = 0.82, P = 0.27). Patients administered INH IL-2 experienced considerably less toxicity and complications than patients administered SYST IL-2. We conclude that INH IL-2 treatment is at least as effective as SYST IL-2 treatment in promoting the survival of patients with mRCC. Given that INH IL-2 treatment of patients with a poorer ECOG performance status elicited a survival rate comparable to that seen with SYST IL-2 treatment of patients with a superior performance status, the potential exists for INH IL-2 treatment to be even more effective for patients having a better performance status. Additionally, INH IL-2 treatment is considerably less toxic and associated with fewer complications than SYST IL-2 treatment, thus providing a therapeutic option for otherwise untreatable patients, offering patients a relatively good quality of life, and requiring fewer co-medications. Nonetheless, selection of an IL-2 treatment modality should be based on several patient-related considerations. Moreover, these two IL-2 treatment modalities need not be mutually exclusive.

Administration, Inhalation↗

Overview of interleukin-2 inhalation therapy.

PURPOSE: Locoregional administration of interleukin (IL)-2, which acts physiologically as a local hormone, is an effective therapeutic modality. Diverse preclinical and clinical models have described methods of administration that expose tumor tissues to continuously high levels of cytokines. Regional administration of IL-2 that does not raise intravascular IL-2 levels induces local and systemic immunomodulation and produces objective local tumor responses. Most importantly, regional therapy is much less toxic than systemic IL-2 therapy. PATIENTS AND METHODS: We review clinical experiences using inhaled IL-2 therapy for the treatment of pulmonary metastases in roughly 300 patients with a variety of primary tumors. This includes our own 10-year single-institution experience with inhaled IL-2 therapy in the treatment of 188 metastatic renal cell carcinoma patients with progressive pulmonary metastases. Patients in our clinic are treated with 18 to 36 million IU of recombinant IL-2, administered 90% by inhalation and 10% subcutaneously, until disease progression. A variety of doses and schedules of inhaled IL-2 have been investigated alone and in combination with systemic therapies. RESULTS: Inhalation of IL-2 has been reported to prevent progression of pulmonary and mediastinal metastases of metastatic renal cell carcinoma, breast and ovarian carcinoma, and melanoma. Inhaled IL-2 alone is well tolerated; a dose-dependent cough is the major adverse event. A significant dose-dependent increase in lymphocytes and eosinophils has been observed in bronchoalveolar lavage in patients and animals. Dose and schedule can influence outcome. In a phase I trial using inhaled IL-2 alone in patients with a variety of primary malignancies, once-daily inhalation of IL-2 at doses up to 15 million IU/m2 was well tolerated but did not result in prolonged stabilization of pulmonary disease. In a multidose phase I trial, using 5-times-daily inhalation of natural IL-2, pulmonary lesions in three of 14 (21%) metastatic renal cell carcinoma patients responded, and a similar multicenter trial demonstrated a 29% response rate. Among 188 metastatic renal cell carcinoma patients treated with inhaled recombinant IL-2 at the Clinic Eppendorf, progression of pulmonary metastases was prevented in 68% of patients for a median duration of 7 months, and overall survival was significantly improved compared with expected survival (Elson's risk analysis; 17.2 vs 5.3 mo). All patients, including high-risk patients, appeared to benefit. Encouraging results have also been reported in patients with metastatic melanoma and gynecologic tumors when inhaled IL-2 was used as second-line therapy to treat pulmonary metastases. CONCLUSIONS: The efficacy of inhaled IL-2, alone or in combination with systemic immunotherapy, immunochemotherapy, or chemotherapy, has been documented in a variety of malignancies. All reports confirm low toxicity, thus providing important quality-of-life benefits. Moreover, patients not eligible for systemic IL-2 therapy may be treated with inhalation therapy.

Administration, Inhalation↗

Detection of loss of heterozygosity in the p53 tumor-suppressor gene with PCR in the urine of patients with bladder cancer.

PURPOSE: Detection of loss of heterozygosity (LOH) has been described in various carcinomas on the basis of meticulous molecular techniques. Because of lack of simple and rapid techniques, LOH has not achieved common use in routine tumor diagnosis. A recently found variable number of tandem repeats (VNTR) segment in intron 1 of the p53 gene was described as highly polymorphic and therefore useful in detecting LOH. We used a rapid technique for detection of LOH in the p53 gene of patients with transitional cell carcinoma (TCC) of the bladder. The technique was based on the polymerase chain reaction (PCR) and agarose gel electrophoresis as described for other carcinomas previously. We evaluated whether TCC screening and surveillance could be performed detecting LOH in the urinary sediment. MATERIALS AND METHODS: We investigated 29 patients with TCC of the bladder (pTa 12 patients; pT1 10 patients; pT2 - pT4 seven patients; grade 1 one patient; grade 2 19 patients; grade 3 nine patients). DNA was prepared by standard methods from white blood cells, tumor tissue, normal bladder mucosa, and urinary sediments. The amplification of the VNTR region was performed with PCR. PCR products were run in parallel lanes on 4.5% agarose gels. RESULTS: Of the 29 patients, 23 (79.3%) were found to have two different alleles ("informative cases") for the VNTR region. Of the 23 informative cases LOH was detected in the tumor tissue of 10 patients (43.5%). Referring to the total population 10 of 29 patients (34.4%) revealed LOH. In all patients with LOH in the tumor, LOH was also detected in the urinary sediment. LOH was not detected in the histologically benign bladder mucosa. CONCLUSION: We present a simple and rapid technique based on PCR and agarose gel electrophoresis for the detection of LOH in tumor and urinary sediment of patients with TCC of the bladder. The ability to detect LOH not only in tumor tissue but also in urinary sediment offers an attractive approach for noninvasive diagnosis and surveillance of bladder cancer patients.

Carcinoma, Transitional Cell↗

Detection rate of histologically insignificant prostate cancer with systematic sextant biopsies and fine needle aspiration cytology.

PURPOSE: We evaluate the detection rate of insignificant prostate cancer and the rate of significant prostate cancer overlooked in the results of systematic sextant biopsy and fine needle aspiration biopsy of the prostate of asymptomatic men with serum prostate specific antigen concentrations less than 4.0 ng./ml. MATERIALS AND METHODS: We analyzed specimens from 133 consecutive patients with a mean age of 60 years undergoing cystoprostatectomy for bladder cancer. Six systematic biopsy specimens and 2 fine needle aspiration cytology samples were taken from the prostate immediately after cystoprostatectomy. The specimens were step sectioned and examined for prostate cancer. Insignificant prostate cancer was defined as any cancer with an aggregate volume 0.5 cm.3 or less. RESULTS: Incidental prostate cancer was found in 58 of the 133 patients (44%). Tumor volume was 0.5 cm.3 or less in 47 cases. Sextant biopsy detected 7 cancers, including 4 of 47 (9%) that were insignificant and 3 of 11 (27%) that were significant. Fine needle aspiration cytology also detected 7 cancers, including 3 (6%) and 4 (36%) that were insignificant and significant, respectively. CONCLUSIONS: Systematic sextant biopsy and fine needle aspiration cytology each diagnose prostate cancer in about 5% of asymptomatic men who have normal digital rectal examination and serum prostate specific antigen less than 4.0 ng./ml. However, many of the cancers thus detected are insignificant and most of the significant cancers are missed. Therefore, routine screening of such patients with sextant biopsy or aspiration cytology does not appear to be justified.

Adenocarcinoma↗

[Perioperative incidence of transfusions after allogenic kidney transplantation].

The requirement of blood transfusions was evaluated in a two compartment (retrospective/prospective) study in our renal transplantation program. Between July 1st, 1993 and December 31st, 1994 (observation period 1) we retrospectively investigated 110 patients with end stage renal disease and anemia undergoing kidney transplantation. Between January 1st, 1995 and December 31st, 1996 (observation period II) the requirement of blood transfusions was followed prospectively in 134 patients after allogenic renal transplantation. The amount of blood drawn for preoperative diagnostic investigations was in observation period 1 significantly higher (280 ml) than in observation period II (150 ml) (p = 0.02). For postoperative diagnostic tests in observation period II significantly less blood (240 ml) was needed than in observation period 1 (510 ml) (p = 0.01). The intraoperative blood loss was similar in both periods (170 ml vs. 190 ml; p = 0.6). The need for closer graft observation was the reason for significantly increased amount of blood transfusions in patients with delayed graft function. The number of blood transfusions was significant lower in patients with primary graft function (p = 0.0001). There was no correlation between blood transfusions and the use of ATG/OKT3, surgical complications and reoperations. With an improved management of blood drawing for diagnostic tests after allogenic kidney transplantation the number of perioperative blood transfusions can be reduced significantly.

Adolescent↗

[Ureterorenoscopy (URS) in treatment of ureteral calculi. I. Safety and effectiveness of URS as auxiliary treatment after ESWL].

We were interested in the effectivity and morbidity of URS as an auxiliary treatment in patients who underwent ESWL for ureteral (n = 71) and kidney stones (n = 31). Between 1991 and 1995, 102 URS were performed for treatment of ureteral fragments. 28 (27.5%) were located in the proximal, 24 (23.5%) in the middle and 50 (49%) in the distal ureter. In 25 cases, fragments were found as "Steinstrasse". In the same period of time, 2554 patients with ureteral stones were treated with ESWL alone, therefore the overall rate of URS was low (4%). URS alone had a stonefree success rate of 58.9%. The success rate depended on the location of the ureteral stone: proximal 25%, middle 50% and distal 82%. URS combined with ESWL showed an overall success rate of 97.9%. Finally, only 2 patients (2.1%) required an open surgery. 29.3% of the stones were treated by extraction only. The extraction of stone was the most frequent procedure to remove the fragments after ESWL. The rate of complications were 6.9%. None of the patients suffered from late complications like stricture of the ureter. The URS for the treatment of stone fragments after ESWL has been shown to be an effective and safe procedure with a low rate of complications.

Adolescent↗

[Ureterorenoscopy (URS) in treatment of ureteral calculi. II. Ureteroscopic treatment of calculus debris after ESWL].

We were interested in the efficacy and morbidity of the ureteroscopy (URS) in the treatment of "steinstrasse" after ESWL. From 1991 to 1996, 27 patients with "steinstrasse" were treated with a total of 32 ureteroscopic procedures. The URS alone had a stonefree success rate of 43.7% (n = 14). URS combined with ESWL was effective in 43.7% (n = 14), leading to an overall success rate of 87.4%. In 4 cases (12.6%) a second therapy was necessary (in 3 cases a second URS + ESWL and in one patient a nephrectomy due to septic pyonephrosis. The overall rate of auxiliary ESWL after URS was 53.1%. Mean operating time was 72 minutes (20-180 min). The rate of complications was 21.8% (n = 7) and mainly due to ureteral perforations or postoperative fever but none suffered from late complications like ureteral stricture. All treated patients received a double-J-stent and antibiotics. The treatment of "steinstrasse" in the middle portion of the ureter proved to be more difficult due to the anatomical position of the ureter and lasted in a longer operating time as the upper or distal "steinstrasse". The stone extraction and the lithoclast-lithotripsy alone or in combination were the most frequent used ureteroscopic procedures to eliminate stone fragments. The URS alone or in combination with the ESWL for the treatment of "steinstrasse" is a highly effective and safe approach.

Adolescent↗

[Treatment of pulmonary metastases from kidney cell carcinoma with inhalational interleukin-2. 10-year experience Hamburger Unicenter].

Systemic immunotherapy, notably with interleukin-2 (IL-2) and interferon-alpha (IFNalpha), has yielded a response rate of 10 % to 30 % in metastatic renal cell carcinoma. However, systemic immunotherapy is limited by severe side effects, and long-lasting response is rare. Tumor palliation and quality-of-life are important end points for evaluating the clinical benefits of immunotherapy. Experimental and clinical treatment models have proved that local IL-2 application is less toxic than systemic treatment and is therapeutically effective. Here we report long-term experience with inhalation IL-2 therapy in 188 patients who had progressive pulmonary metastatic renal cell carcinoma. High-dose inhalation of IL-2 was used with low-dose systemic IL-2 or IFNalpha. Maximal toxicity over the total treatment time was mild, and the low incidence of WHO grade 3 toxicity (24 %) allowed social activities and performance of social roles. Comedication for systemic side effects was required only in half of the patients. Inhaled IL-2 prevented progress of pulmonary metastases in 68 % of patients for a median period of 9.8 months. Median survival was 12.4 months compared with the expected 5.3 months and quality-of-life did not differ substantially from pretreatment status. Local treatment can be applied alone or in combination with systemic therapy and can increase therapeutic efficacy.

Administration, Inhalation↗

Significance and metabolism of complexed and noncomplexed prostate specific antigen forms, and human glandular kallikrein 2 in clinically localized prostate cancer before and after radical prostatectomy.

PURPOSE: We studied plasma concentrations and elimination rates of prostate specific antigen (PSA) complexed to alpha1-antichymotrypsin and alpha2-macroglobulin, free PSA, total PSA (free PSA plus PSA alpha1-antichymotrypsin) and human glandular kallikrein 2 before, during and after radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: Plasma was collected and frozen within 10 minutes after sampling from 18 patients undergoing radical retropubic prostatectomy for prostate cancer. One sample was drawn preoperatively. Subsequent sampling intervals were 5 to 20 minutes perioperatively, 2 to 4 hours during the first 12 postoperative hours and 24 to 48 hours until postoperative day 14. Free PSA, PSA alpha1-antichymotrypsin, total PSA, PSA alpha2-macroglobulin and human glandular kallikrein 2 were measured with time resolved immunofluorometric assays. RESULTS: Preoperatively PSA alpha2-macroglobulin was undetectable (less than 2 ng./ml.) in 17 of 18 patients. Human glandular kallikrein 2, free PSA and total PSA but not PSA alpha1-antichymotrypsin were significantly higher in patients with extraprostatic cancer (pT3a-pT4a, pN1) compared to those with organ confined cancer (pT2a/b). Surgical manipulation of the prostate caused no detectable elevation of human glandular kallikrein 2, PSA alpha1-antichymotrypsin or PSA alpha2-macroglobulin. In contrast, a mean 9.6-fold increase (range 3.4 to 22) in free PSA was noted 5 minutes after prostatectomy. Free PSA was eliminated from plasma in a biphasic exponential pattern with an early plasma half-life of 55 minutes and a late plasma half-life of 18 hours. PSA alpha1-antichymotrypsin decreased slowly, whereas human glandular kallikrein 2 was detectable only 12 hours after prostatectomy. PSA alpha2-macroglobulin remained at insignificant, nondetectable concentrations during the entire perioperative and postoperative period. CONCLUSIONS: Release of free PSA contributes to the elevation of plasma total PSA after prostatectomy. Free PSA is enzymatically inactive as the release does not result in subsequent elevation of PSA alpha1-antichymotrypsin or PSA alpha2-macroglobulin. Biphasic exponential elimination of free PSA may be explained by rapid extracellular redistribution (early half-life) and glomerular filtration in the kidneys (late half-life). Our data suggest rapid metabolism of human glandular kallikrein 2 but do not support suggestions of the significance in vivo of complex formations with alpha2-macroglobulin as a major means to eliminate PSA from plasma in patients with clinically localized prostate cancer.

Aged↗