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Biomedical subjects

H Heinzer

Publications and source records attributed to H Heinzer.

34 records · Page 2Linked to original sources

Immunotherapy of pulmonary metastatic renal cell carcinoma: success dependant on risk factors?

BACKGROUND/AIMS: Risk factors may influence not only prognosis in metastic renal cell carcinoma but also probability of response to immunotherapy. Response of patients treated with inhalation of interleukin-2 (IL-2), which can be offered to those not suitable for systemic therapy, was compared to risk factors. We report on 116 patients who used inhaled IL-2 and were treated in different protocols with natural, recombinant glycosylated and recombinant non-glycosylated. METHODOLOGY: All protocols had in common a high-dose inhalation of IL-2, either exclusively (11%), with low-dose systemic IL-2 (33%), or with low-dose systemic IL-2 and interferon-alpha (56%). Maximal toxicity per total treatment time (median treatment time: 7.2 months) was mild and there was a low incidence (16%) of WHO grade 3 toxicity. Treatment response was analyzed in a subgroup of patients having at least one given risk factor and treated with recombinant IL-2 (n=86). In all patients having risk factors the following distribution was found: more than 1 metastic location (86%), diagnosis to treatment interval (DTI) <12 months (62%), weight loss prior to therapy (41%), and ECOG performance status > or =2 (13%). In comparison, a group of patients having no risk factors at all was analyzed accordingly. RESULTS: Response to immunotherapy is dependant on risk factors, the most prominent one being the ECOG. Patients with an ECOG > or =2 achieved no overall response compared to patients with no risk factors who responded to immunotherapy (33%). Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range: 4.133) and were stabilized in 55% for a median of 6.6 months (range: 3-51.7). Overall response rate was 16%, 49%, and 35%, respectively. Median overall response duration was 9.6 months. Median achieved survival was 11.8 months (range: 1.7-68.8). CONCLUSIONS: We conclude that risk factors have to be considered in the interpretation of response to immunotherapy. Exclusion of patients because of risk factors alone does not seem to be justified according to our data. Responses, including long-term stabilization, can be achieved in 27-57% of such patients. IL-2 immunotherapy can also be considered as useful antitumor therapy in patients with risk factors, especially if given without major toxicity.

Administration, Inhalation↗

Thromboembolic complication rate after radical retropubic prostatectomy. Impact of routine ultrasonography for the detection of pelvic lymphoceles and hematomas.

OBJECTIVES: The impact of routine ultrasonography for diagnosis and rapid treatment of pelvic lymphoceles and hematomas on the rate of thromboembolic complications was studied. METHODS: From June 1987 to December 1995, 508 patients underwent radical retropubic prostatectomy with low-dose heparin prophylaxis at our medical institution. Beginning with patient 321, routine pelvic ultrasonography was started on each patient on postoperative day 1 for diagnosis of lymphoceles and hematomas. The rate of thromboembolic complications in patients 321-508 was compared with that in patients 1-320 (without routine ultrasonography). RESULTS: In patients 1-320, a total of 20 (6.2%) symptomatic thromboembolic complications occurred: five (1.6%) pulmonary emboli and 15 (4.7%) cases of deep venous thrombosis. In patients 321-508, the total rate of thromboembolic complications was significantly reduced (p = 0.049): only 4 patients (2.1%) had thromboembolic events (1 pulmonary embolism and 3 cases of deep venous thrombosis): all but 1 of the complications were associated with small hematomas, which were first negative on routine pelvic ultrasonography but positive on CT scan only done when clinical suspicion of symptoms occurred or during open surgery and showed compression of the iliac vein. CONCLUSIONS: Pelvic lymphoceles and hematomas seem to be important cofactors in the pathophysiology of thromboembolic complications after radical retropubic prostatectomy. Most lymphoceles and hematomas can be diagnosed with pelvic ultrasonography although small hematomas can be overseen with pelvic ultrasonography Surgeons should become more aware of these postoperative complications particularly in patients on heparin prophylaxis.

Adult↗

[Long-term results of Stamey bladder neck suspension. Effect of data analysis technique on surgical result].

The methodology used to assess postoperative continence has a significant effect on the outcome of incontinence surgery. Retrospective chart review studies consistently report higher success rates than patient questionnaire-based outcome analyses. The purpose of this study was to evaluate the true long-term results of the Stamey bladder neck suspension procedure using an anonymous patient questionnaire. Of 172 consecutive patients, 138 (80.2%) returned a questionnaire on long-term continence, complications and subjective satisfaction with the operative result. With a mean follow-up of 66 months, 65 of 130 evaluable patients (50.0%) remained completely continent while 15 (11.5%) never became continent and 50 (38.5%) had recurrent incontinence 6-90 months postoperatively. Almost two-thirds of the patients felt either cured or substantially improved more than 5 years after surgery. Stamey bladder neck suspension leads to a persistently improved quality of life despite a considerable failure rate. Our study demonstrates the advantages of patient questionnaires for outcome analyses and emphasizes the need for standardisation and validation to allow comparisons between the results of different incontinence procedure in the future.

Adult↗

Early complication of anatomical radical retropubic prostatectomy: lessons from a single-center experience.

OBJECTIVES: The purpose of this study is to report the rate of early complications in 316 of 600 patients who underwent anatomical radical retropubic prostatectomy for localized prostatic cancer from June 1988 to July 1996 and to measure the effect of increasing experience in a single institution. METHODS: From January 1992 to August 1995, 316 patients with prostatic cancer underwent anatomical radical retropubic prostatectomy at our medical institution. Early complications were recorded prospectively and the rate of complications of the first 166 patients was compared with the rate in the next 150 patients. RESULTS: Comparison of the 2 groups showed a significant decrease in blood loss with time (mean 1,397 vs. 967 cm3, p = 0.0011). The rates of anastomotic urinary leakage (21.7 vs. 10%, p = 0.0056), lymphoceles (22.3 vs. 2%, p < 0.0001), rectal injury (7.8 vs. 2%, p = 0.02), reoperation (10.2 vs. 4%, p = 0.049), and thromboembolic complications (7.8 vs. 2.7%, p = 0.0479) also decreased significantly. Only ureteral transsection showed an increase in the later group (0 vs. 4.7%, p = 0.005). CONCLUSIONS: The low percentage of early complications suggests that anatomical retropubic radical prostatectomy is a safe approach. Our single-center study showed a learning pattern that appears unavoidable when this operation is as radical as possible so as to keep the percentage of positive margins low especially in patients with advanced tumors (> pT2).

Adult↗

Inhaled interleukin-2 therapy in pulmonary metastatic renal cell carcinoma: six years of experience.

PURPOSE: Patients with advanced metastatic renal cell carcinoma often cannot or do not want to tolerate high-dose systemic interleukin-2 (IL-2) therapy and the toxicity associated with it. To reduce toxicity and still maintain or even increase effectiveness, we developed a method to deliver IL-2 locally for the treatment of pulmonary and mediastinal metastases in metastatic renal cell carcinoma patients. PATIENTS AND METHODS: We report here 6 years of experience treating 116 metastatic renal cell carcinoma patients who had pulmonary or mediastinal metastases with inhaled IL-2. We have utilized three different IL-2 preparations (natural human IL-2 purified from the supernatants of mitogen-activated peripheral blood lymphocytes, glycosylated recombinant IL-2 produced by Chinese hamster ovary cells, and non-glycosylated recombinant IL-2 produced by bacteria). All protocols used high-dose inhalation of IL-2, either exclusively (11%), with coadministration of low-dose systemic IL-2 (33%), or with coadministration of low-dose systemic IL-2 and interferon-alpha (56%). RESULTS: Maximal toxicity per total treatment time was mild (median treatment time, 7.2 months); there was a low incidence (16%) of World Health Organization grade 3 toxicity. Toxicity associated with exclusive inhalation of IL-2 was local and consisted mainly of cough. Thus, patients who could not tolerate high-dose systemic IL-2 were able to tolerate inhalation IL-2 therapy. Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range, 4.1-33 months) and were stabilized in 55% of patients for a median of 6.6 months (range, 3-51.7 months). The overall response rate was 16%; disease was stabilized in 49% of patients and disease progressed in 35% of patients. The overall median response duration was 9.6 months. Median survival was 11.8 months (range, 1.7-68.8 months); expected survival according to risk analysis was 5.3 months. CONCLUSIONS: Inhalation of IL-2 is a nontoxic and effective treatment for patients with progressive pulmonary and mediastinal metastases. Inhaled IL-2 effectively prevented progress of pulmonary metastases in 70% of patients. Furthermore, patients could be treated as outpatients and remain employed. Local administration of IL-2 increases therapeutic effectiveness with little or no toxicity.

Administration, Inhalation↗

Toxicity of local, continuous and cyclic, high-dose bladder perfusion with recombinant and natural interleukin-2 in advanced cancer of the urinary bladder.

We evaluated the toxicity of high-dose local interleukin-2 (IL-2) in 18 patients not eligible for standard treatment of advanced transitional cell bladder carcinoma. Seven received continuous high-dose local natural IL-2 via pump system in the bladder for up to 420 days. 11 received cyclic high-dose local natural IL-2 or recombinant IL-2 for up to 420 days. Treatment was well tolerated and, considering the low rate of toxicity, could be offered in an outpatient setting. Except for local contrast-media hypersensitivity, no serious side-effects were observed. This study provides a basis for the non-toxic use of local IL-2 in future studies to evaluate effectiveness of the treatment or prophylaxis of patients with superficial bladder cancer in order to prevent recurrences.

Administration, Intravesical↗

[Transurethral laser therapy of benign prostatic hyperplasia].

During the last 4 years, transurethral laser therapy for benign prostatic hyperplasia (BPH) has become an increasingly popular alternative to transurethral resection of the prostate (TURP) for the treatment of obstructive BPH symptoms. Clinical data so far published prove the efficacy of this new therapeutic modality, although the results are up to now possibly inferior to those achieved with TURP. On the other hand, the incidence of severe perioperative complications is significantly lower in patients treated with laser prostatectomy than in those undergoing TURP. Therefore, laser prostatectomy is a reasonable adjunct to the therapeutic spectrum for BPH in high-risk patients. Nevertheless, its role in the treatment of obstructive BPH in low-risk patients cannot be defined until long-term follow-up data are available.

Contraindications↗

Inhaled interleukin-2 in combination with low-dose systemic interleukin-2 and interferon alpha in patients with pulmonary metastatic renal-cell carcinoma: effectiveness and toxicity of mainly local treatment.

We describe here a mainly topical interleukin-2 (IL-2) application in pulmonary metastatic renal-cell carcinoma: a high-dose long-term inhalation of IL-2 (90% of IL-2 dose) and low-dose systemic subcutaneous IL-2 (10% of IL-2 dose) and systemic subcutaneous interferon alpha (IFN alpha). The effectiveness of this treatment is remarkable. No pulmonary metastases progressed during treatment. One complete response, 8 partial responses, and 6 cases of stable disease were achieved in the lungs of the 15 patients. In addition, 3 of 7 patients had partial responses and 1 of 7 had stabilization of non-pulmonary metastases. Overall response according to WHO criteria was 1 complete response, 6 partial responses, 2 mixed responses, 5 stable diseases and 1 progressive disease. Toxicity was low. Only WHO grade I toxicity occurred, except for a single grade II event (bronchospasm). This allowed long-term ambulatory treatment (1-23 months) inclusion of high-risk patients, and inclusion of patients with advanced disease. The expected mean survival of patients was 9.9 months, the actual mean survival is now 19.1 months, and 11 of 15 patients are still alive. Quality of life during treatment was good. Inhalation of IL-2 serves as a clinical model for high effectiveness and low toxicity of long-term local IL-2 application. We conclude that mainly local treatment might be the key to successful nontoxic use of IL-2 in cancer patients.

Administration, Inhalation↗

Virus-related serology and in situ hybridization for the detection of virus DNA among patients with testicular cancer.

Viral infections have been implicated in the pathogenesis of several malignancies. A high incidence of the Epstein-Barr virus (EBV) genome and increased EBV-specific antibody titers were frequently observed in Hodgkin's disease. Some epidemiologic and clinical similarities have been demonstrated between Hodgkin's disease and human testicular germ-cell carcinoma. However, we investigated testicular biopsies from 16 patients with testicular cancer and 16 noncancer controls for the presence of EBV, cytomegalovirus (CMV), and herpes simplex virus (HSV) genomes with in situ hybridization and evaluated serum antibodies against EBV, CMV, and mumps among 52 patients with testicular carcinoma and 54 age-matched controls without cancer. There were no statistically significant differences in increased virus titer between patients with testicular cancer and controls, and we detected no EBV or CMV DNA in tumor cells, although the HSV genome was found in 50% of the testicular-tumor patients and 37.5% of controls. The findings suggest that viral infections have no direct role in the etiology of testicular carcinoma. The detection of HSV DNA in both tumor patients and controls might be a sign of latent infection, rather than a risk factor for testicular cancer.

Antibodies, Viral↗

Distribution of 486P 3/12 antigen, ABO(H) blood group antigen and T antigen in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder.

We used monoclonal antibody 486P 3/12, anti-ABO(H) antibodies and anti-T antigen lectins to detect malignant transformation in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder. We used an immunoperoxidase technique to do extensive chessboard-like mapping studies in 6 cystectomy bladders with stage T2 lesions and 1 normal bladder from a multiorgan donor as control to characterize antigen expression. Increased 486P 3/12 antigen expression, decreased ABO(H) expression and T antigen deletion were detectable not only in the tumor area but also in tumor-surrounding areas classified as benign. We believe that cells with abnormal antigen expression are a source of tumor recurrence and can be identified with our method of quantitative immunocytology.

ABO Blood-Group System↗

Interleukin-2 by inhalation: local therapy for metastatic renal cell carcinoma.

We report the use of inhaled natural interleukin-2 in patients with metastatic disease. Six patients with metastatic renal cell carcinoma received 100,000 units natural interleukin-2, 5 times per day by inhalation in addition to a 4-day cycle of intravenous natural interleukin-2 every 2 weeks and subcutaneous interferon 5 days per week. Response was clearly correlated with metastatic site. Distinct tumor burden and the poor condition of the patient did not impair success. Pulmonary metastases responded in 5 of 5 patients. Metastases in the mediastinum, liver, abdomen and pelvis were stabilized in 4 patients. No response was noted in 3 solitary bone metastases, which were successfully removed surgically after several months of therapy, and a pleural metastasis progressed despite a clear response of the pulmonary disease in the same patient. New metastases did not develop in any of the patients during treatment (median followup 183 days of treatment, range 97 to 296 days). The over-all importance of the low toxicity of this novel route of administration (World Health Organization classification not exceeding grade 1) making long-term outpatient treatment possible must be emphasized because limitations of systemic interleukin-2 application are mainly caused by pulmonary side effects, for example pulmonary capillary leakage syndrome and edema. However, this new type of topical natural interleukin-2 application and combination with low dose intravenous interleukin-2 achieved considerable antitumor responses.

Administration, Inhalation↗

Unusual differential diagnosis of testis tumor: intrascrotal sarcoidosis.

We report 2 cases of sarcoidosis with extrapulmonary manifestations in the testis, epididymis and spermatic cord. Each patient presented with an intrascrotal mass of unknown origin that suggested a testicular tumor. Sarcoidosis was confirmed in case 1 by radical orchiectomy and further small sarcoid foci were detected in 1 of the lacrimal glands. In case 2 sarcoidosis was confirmed by biopsy and there were no further extrapulmonary indications. Both cases were stage II disease so no specific therapy was applied. The patients were without signs of progression at 2 and 10 years, respectively, after initial diagnosis.

Adult↗

Treatment of pulmonary metastatic renal-cell carcinoma in 116 patients using inhaled interleukin-2 (IL-2).

BACKGROUND: We report 6 years of experience in 116 patients who used inhaled interleukin-2 (IL-2) and were treated in different protocols with natural, recombinant glycosylated and recombinant nonglycosylated IL-2. MATERIALS AND METHODS: All protocols had in common high-dose inhalation of IL-2, either exclusively (11%), with low-dose systemic IL-2 (33%), or with low-dose systemic IL-2 and interferon-alpha (56%). Maximal toxicity per total treatment time (median treatment time, 7.2 months) was mild and at a low incidence (16%) of WHO grade 3 toxicity. Treatment was allowed in patients for whom systemic IL-2 was not suitable. RESULTS: Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range 4.1-33) and were stabilized in 55% for a median of 6.6 months (range, 3-51.7). Overall response rate was 16%, 49%, and 35%, respectively. Median overall response duration was 9.6 mo. Median achieved survival was 11.8 months (range 1.7-68.8). CONCLUSIONS: Inhaled IL-2 prevents progress of pulmonary metastases effectively in 70% of patients. Local use of IL-2 allows the use of the full potential of cytokines with little or no toxicity.

Administration, Inhalation↗