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Lothar Hertle

Publications and source records attributed to Lothar Hertle.

At least 19 recordsLinked to original sources
PubMed2007

The dual serotonin and noradrenaline reuptake inhibitor duloxetine for the treatment of interstitial cystitis: results of an observational study.

PURPOSE: We report an observational study to evaluate the efficacy and tolerability of duloxetine for interstitial cystitis. MATERIALS AND METHODS: A total of 48 women were prospectively treated for 2 months following an uptitration protocol to the target dose of 2 x 40 mg duloxetine per day. Patients received the target dose for 5 weeks. The efficacy of duloxetine treatment was assessed at week 8. The primary end point was a change in the overall well-being evaluated by a patient reported global response assessment. Secondary end points were changes in pain and urgency (visual analog scales), frequency and functional bladder capacity (48-hour voiding log), and changes in overall symptom severity (O'Leary-Sant index). RESULTS: There were 5 patients (10.4%) who were identified as responders and 17 patients (35.4%) who dropped out of the study exclusively due to side effects, with nausea present in all dropouts. No severe adverse events were reported. All 5 responders reported onset of symptom improvement but not until they had reached the target dose. Regarding secondary outcome parameters, duloxetine treatment did not result in statistically significant improvement of symptoms. Maximum urinary flow rate and residual volume were influenced more prominently in patients at the target dose, however, the changes did not appear to be clinically meaningful. CONCLUSIONS: Treatment of interstitial cystitis with duloxetine did not result in significant improvement of symptoms. The drug administration was safe but the tolerability of the drug was poor mainly due to nausea occurring with the starting dose of 20 mg per day. Based on the preliminary data of this observational trial we currently cannot recommend duloxetine as a therapeutic approach for interstitial cystitis.

Adrenergic Uptake Inhibitors↗
PubMed2007

Expression of the Endothelin-axis in the different histologic subtypes of renal cell carcinoma: a tissue microarray analysis.

Endothelin-1 and its receptors ETAR and ETBR, commonly referred to as the Endothelin-axis, are emerging to play a role in cancer. The Endothelin-axis has been shown to be involved in proliferation, angiogenesis and metastasis in various human tumours. To assess the role of the Endothelin-axis in renal cell carcinoma, we analysed its expression in archival tumour tissue of 183 patients. Representative tumour blocks were selected for constructing a tissue microarray. Paraffin sections were assessed immunohistochemically using monoclonal and polyclonal antibodies for Endothelin-1, ETAR and ETBR. Staining intensities were analysed semiquantitatively and the results were correlated with various histopathologic factors. Overexpression of Endothelin-1, ETAR and ETBR was identified in 12.8%, 84.1% and 93.3% of cases, respectively. No association with pathological tumour stage and histologic grading was found. Papillary renal cell carcinomas expressed highly significantly more Endothelin-1 than clear cell renal cell carcinomas (34.5% vs. 6.7%, p<0.001), while there was no difference between ETAR- and ETBR-expression in these histologic subtypes. However, ETAR tended to be overexpressed in the subgroup of G3-tumours (p=0.044). Studies are underway assessing the role of the Endothelin-axis and its potential use as a molecular target in renal cell carcinoma.

Antibodies, Monoclonal↗
PubMed2006

Histologic subtype of metastatic renal cell carcinoma predicts response to combined immunochemotherapy with interleukin 2, interferon alpha and 5-fluorouracil.

OBJECTIVES: Combined immunochemotherapy with interleukin 2 (IL-2), interferon alpha (IFN-alpha), and 5-fluorouracil (5-FU) is an established first-line therapy for metastatic renal cell carcinoma (RCC). However, data on histologic parameters predictive of clinical benefit are rare. In this study, we evaluated the response to immunochemotherapy in the main histologic subtypes of renal cell carcinoma and performed a subgroup analysis of inoperable patients. METHODS: From 164 patients treated with one or two cycles of combined immunochemotherapy, radical nephrectomy had revealed 22 cases of papillary RCC (pRCC; 13.4%) and 131 cases of clear cell RCC (ccRCC; 79.9%). In the remaining 11 (6.7%) their disease was inoperable. The overall response rates were evaluated according to World Health Organization criteria. RESULTS: For ccRCC and inoperable disease, responses of 34.4% and 27.3% after one cycle and 28.8% and 16.7% after two cycles, respectively, were noted. In contrast, no patient with pRCC showed any response after two cycles of combined immunochemotherapy. CONCLUSIONS: No objective response was seen in patients with pRCC. Hence, the use of immunotherapeutic agents must be questioned in this histologic subtype.

Adult↗
PubMed2006

Safety and efficacy of hyperbaric oxygen therapy for the treatment of interstitial cystitis: a randomized, sham controlled, double-blind trial.

PURPOSE: We conducted a double-blind, sham controlled study to evaluate the safety, efficacy and feasibility of hyperbaric oxygenation for interstitial cystitis. MATERIALS AND METHODS: A total of 21 patients with interstitial cystitis were randomized to 90 minutes treatment in a hyperbaric chamber pressurized with 100% O2 to 2.4 atmosphere absolute for 30 treatments sessions or 1.3 atmosphere absolute, breathing normal air in the control group. Moderate or marked improvement in a global response assessment questionnaire was defined as treatment response (primary outcomes). Secondary measurements included changes of pain and urgency evaluated by visual analog scales, functional bladder capacity and frequency. Changes in the O'Leary-Sant Interstitial Cystitis Index and rating of overall satisfaction with the therapeutic outcome were also reported. RESULTS: There were 3 of 14 patients on verum and no control patients who were identified as responders (p < 0.52) [corrected] At 12-month followup 3 patients (21.4%) still reported treatment response. Hyperbaric oxygenation resulted in a decrease of baseline urgency intensity from 60.2 +/- 15.0 to 49.9 +/- 35.2 mm at 3 months and decrease of pain intensity from 43.1 +/- 20.5 to 31.2 +/- 19.8 mm, respectively (p < 0.05). The Interstitial Cystitis Symptom Index score sum decreased from 25.7 to 19.9 points in patients on verum. Sham treatment did not result in improvement of the baseline parameters. CONCLUSIONS: A total of 30 treatment sessions of hyperbaric oxygenation appear to be a safe, effective and feasible therapeutic approach to interstitial cystitis. In the treatment responders application of hyperbaric oxygenation resulted in a sustained decrease of interstitial cystitis symptoms with a discordant profile regarding the peak amelioration of the various interstitial cystitis symptoms compared with a normobaric, normoxic sham treatment.

Adult↗
PubMed2006

The endothelin axis in urologic tumors: mechanisms of tumor biology and therapeutic implications.

Endothelin (ET)-1 and its receptors ET-A and ET-B, referred to commonly as the endothelin axis, have been identified in various human cancers, especially gynecologic tumors, such as breast cancer or ovarian cancer, but also including urologic tumor entities. They play a key role in tumor growth and progression by influencing critical cancer pathways, such as apoptosis, angiogenesis and proliferation. In prostate cancer, overexpression of the ET-A receptor increases with tumor progression, and clinical trials with selective ET-A receptor antagonists, such as atrasentan (ABT-627), have shown promising early results. In preclinical models of bladder cancer, overexpression of the ET axis has been demonstrated and ET-targeting agents are under investigation. This paper reviews the role of the ET axis in human cancers and focuses on preclinical and clinical studies in urologic tumor entities to further define the role of ET-targeting agents as targeted molecular therapy.

Apoptosis↗
PubMed2005

Treatment of bone metastases and local recurrence from renal cell carcinoma with immunochemotherapy and radiation.

Immunotherapies using interferons and/or interleukins are currently the treatment of choice for metastatic renal cell carcinoma (RCC). Bone metastases and non-resectable local recurrence are negative predictors for successful immunotherapy and signs of poor prognosis. The present study was designed to evaluate the effectiveness of combined immunochemotherapy (ICT) and radiation therapy (RT) for bone metastases or local recurrence from RCC in a prospective fashion. From September 1997 to September 1999, 20 patients with progressive RCC were treated with a combination of RT and ICT [s.c. interleukin-2a (IL-2), s.c. interferon alpha (IFN-alpha) and i.v. 5-fluorouracil]. RT started in week 2 of ICT. The radiation field was limited to the symptomatic bone metastases (15 patients) or the local recurrence (five patients). The total dosages of the RT ranged between 45 and 50 Gy, administered in fractions of from 1.8 to 2 Gy daily. In case of objective response or stable disease, the patients received up to two further ICT courses. All patients had good pain relief. Three out of 20 achieved complete remission, three had a partial remission, nine were stable and five patients had progressive disease under the combined treatment. Median survival was 21 months, mean survival 24 months (range: 5-59 months). The side effects of the combined treatment are in the same range as with ICT alone (World Health Organisation grade 2 and 3). Of 20 patients, 19 had their pain medication reduced after treatment. The combination of ICT and RT is feasible. There is remarkable pain relief. Our data suggest that the combination of immunochemotherapy and radiation therapy may induce a synergistic antitumor effect for the treatment of bone metastases or local recurrence from RCC compared to data from the literature for ICT or RT alone.

Aged↗
PubMed2005

Expression of the endothelin axis in bladder cancer: relationship to clinicopathologic parameters and long-term survival.

OBJECTIVES: Endothelin-1 (ET-1) and its receptors ET(A)R and ET(B)R, referred to as the Endothelin-axis, play an emerging role in cancer. We examined the ET-axis immunohistochemically in invasive bladder cancer. METHODS: Tumor specimens from 157 patients after cystectomy were stained immunohistochemically for ET-1, ET(A)R and ET(B)R. After semiquantitative analysis the staining results were correlated with clinicopathological parameters and survival rates. RESULTS: Overexpression of ET-1, ET(A)R and ET(B)R was identified in 26.8%, 58.8% and 76.9% of cases, respectively. No association with TNM staging and histologic grading was found. However, patients with ET(B)R expression tended to have organ-confined tumors (p=0.16) and no vascular invasion (p=0.09), the latter being statistically significant in the subgroup of G3 tumors (p=0.02). ET(B)R overexpression was associated with favorable disease-free survival (p=0.04). CONCLUSIONS: The ET-axis is overexpressed in bladder cancer, ET(B)R predominating in this entity and being associated with a more favorable prognosis. Further studies are warranted to elucidate the role of the ET-axis as a molecular target in bladder cancer.

Adult↗
PubMed2005

Safety and efficacy of concurrent application of oral pentosan polysulfate and subcutaneous low-dose heparin for patients with interstitial cystitis.

OBJECTIVES: To conduct a prospective controlled study assessing the safety and efficacy of the additional administration of subcutaneous low-dose heparin in patients receiving oral pentosan polysulfate (PPS) medication for interstitial cystitis. METHODS: A total of 41 patients with interstitial cystitis who reported efficacy of oral PPS medication were divided into three groups (major, intermediate, and minor PPS response), according to their therapeutic response to PPS. Patients received 3 x 5000 IU/day heparin for 2 days, followed by 2 x 5000 IU/day for 12 days. The maintenance dose was 5000 IU/day heparin. We used 17 patients randomly taking PPS alone as the control group. The primary endpoint was a change in overall well-being. Secondary endpoints were changes in pain, urgency, frequency, functional bladder capacity, and the O'Leary-Sant index. RESULTS: Overall, 10 patients were identified as responders at 3 months (24.4%) and 9 patients at 6 months (21.9%) compared with no responders in the control group (P < or = 0.001). At 3 months, 7 (31.8%) of 22 patients in the minor response group reported a statistically significant overall improvement in their well-being compared with 1 (12.5%, P < or = 0.001) of 8 patients of the intermediate group and 2 (18.2%, P < or = 0.001) of 11 patients of the major response group. A significant amelioration of pain intensity was observed in the minor response group at 3 and 6 months. CONCLUSIONS: The concurrent administration of low-dose heparin and oral PPS appears to be a safe and efficacious treatment modality. The subcutaneous administration of heparin appeared to be predominantly of value for patients with interstitial cystitis and an initial minor response to PPS.

Administration, Oral↗
PubMed2005

Long-term results of amitriptyline treatment for interstitial cystitis.

PURPOSE: We performed a prospective, open label study to examine the safety and efficacy of the long-term administration of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). MATERIALS AND METHODS: A total of 94 patients were stratified into 2 groups, namely a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) group of those who fulfilled NIDDK criteria for IC and a nonNIDDK group of those who presented with characteristic IC symptoms but met at least 1 NIDDK exclusion criterion. Amitriptyline was received strictly at bedtime following an established self-titration protocol without a limitation of the maximum daily dose. Patients reporting improvement in a global response assessment questionnaire were considered treatment responders. Further efficacy measures were changes in pain and urgency, functional bladder capacity and frequency. Changes in the O'Leary-Sant IC index and rating of overall satisfaction with the therapeutic outcome were also reported. RESULTS: Mean study followup +/- SD was 19.0 +/- 12.5 months. The response rate was 64% (60 patients). The overall mean dose was 55 mg (range 12.5 to 150). Side effects occurred in 79 patients (84%), including dry mouth in 79% and weight gain in 59%. Patient overall satisfaction with the therapeutic result was excellent or good in 43 (46%). The dropout rate was 31% (29 patients) after a mean treatment period of 6 weeks at a mean dose of 70 mg. Nonresponse to treatment was the primary reason for dropout in all cases, while side effects contributed to dropout in 25 (86%). Improvement in the various IC symptoms was statistically significant compared with baseline. CONCLUSIONS: Long-term administration of amitriptyline is a feasible, safe and effective treatment for IC, provided that the drug is used judiciously to minimize adverse effects. The therapeutic response to amitriptyline was uniformly observed in patients fulfilling NIDDK criteria and in those with the pure clinical diagnosis of IC.

Administration, Oral↗
PubMed2005

Expression of endothelin-1 and endothelin-A and -B receptors in invasive bladder cancer.

Overexpression of endothelin-1, endothelin-A- and endothelin-B-receptors has been shown in various human tumors. To assess the role of the ET-axis in bladder cancer, we analyzed its expression in tumor specimens and bladder cancer cell lines. Samples were obtained by radical cystectomy at two urologic institutions. ET-axis expression was investigated by reverse-transcription polymerase chain reaction (RT-PCR) (n=22) and immunohistochemistry (n=42). Additionally, four bladder cancer cell lines were analyzed. RT-PCR analysis for the ET-axis showed positive signals in the majority of cDNA probes. Signals for endothelin-1 (ET-1), endothelin-A-receptor (ET(A)R) and endothelin-B-receptor (ET(B)R), as identified semiquantitatively and by densitometry, were found in 22, 22 and 15 of 22 cases, respectively. Immunohistochemistry revealed expression of ET-1, ET(A)- and ET(B)-receptor in 18, 29 and 37 of the 42 cases, respectively, whereas normal urothelium was negative. All cell lines expressed ET-1, and all but the RT-112 cell line produced ETAR, whereas no cell line expressed ET(B)R. The identification of the ET-axis at the mRNA and protein level in the majority of bladder tumor samples suggests a role in the carcinogenesis of bladder cancer. Further studies on regulation of the ET-axis and the future use of selective ET(A)-receptor inhibitors for targeted molecular therapy in bladder cancer are in progress.

Adult↗
PubMed2005

Cox-2 and Her2/neu co-expression in invasive bladder cancer.

We examined the expression of Her2/neu and Cox-2 in bladder cancer and its relationship to clinicopathological factors, survival data and patient outcome. From 153 consecutive patients who had undergone radical cystectomy for bladder cancer, tumour tissue was analysed for Her2/neu amplification by fluorescent in situ hybridisation and for Her2/neu and Cox-2 protein expression by immunohistochemistry. Results were correlated with clinical data and survival times. Cox-2 and Her2/neu co-expression was present in 44 (33%) of 132 transitional cell carcinomas. Although this association was significant (p = 0.003), there was no significant association between Cox-2 and Her2/neu amplification status. Each marker was independent of primary tumour stage and lymph node status, as well as histological grading. However, the co-existence of Her2/neu amplification and Cox-2 expression correlated with distant metastases: of 5 Cox-2-positive samples, 2 (40%) showed Her2/neu amplification. This was only a trend, amounting to no more than borderline statistical significance (p = 0.046). Kaplan-Meier survival analysis did not demonstrate any relationship between Cox-2 or Her2/neu expression or amplification alone or in combination with respect to overall and disease-free survival. Analysing the co-expression of Cox-2 and Her2/neu status does not add any prognostic information in patients with bladder cancer. Nevertheless, combined treatment with Her2/neu and Cox-2 inhibitors may be beneficial for the subgroup of Her2/neu- and Cox-2-expressing tumours and will have to be assessed in further preclinical and clinical studies.

Adult↗
PubMed2004

Cyclooxygenase-2 expression in bladder cancer: correlation with poor outcome after chemotherapy.

OBJECTIVES: Cycylooxygenase-2 (Cox-2) has been shown to play a significant role in the carcinogenesis of various human tumours. Recent experimental work suggests that Cox-2 expression may reduce the cytotoxic effects of chemotherapy and radiation therapy. We examined Cox-2 expression in bladder cancer and its relationship to clinicopathologic factors, survival data, and outcome in patients receiving cisplatin-based chemotherapy. METHODS: In 157 patients after cystectomy for bladder cancer, Cox-2 was assessed immunohistochemically; 62 patients had received chemotherapy, either adjuvant or for metastatic disease. Results were correlated with clinical data, survival and outcome of chemotherapy. RESULTS: Cox-2 expression was present in 131 patients (83.4%). Expression did not correlate with tumour stage and histologic grade, but was significantly related to histologic subtype (TCC vs. SCC, p=0.038). Survival analysis showed no relation between Cox-2 expression and overall and disease-free survival; however, in the subgroup of 62 patients who received chemotherapy, strong Cox-2 expression significantly correlated with poor overall survival (p=0.01). CONCLUSIONS: High expression of Cox-2 in bladder cancer patients receiving chemotherapy was significantly associated with shorter survival. Further studies are warranted to clarify if combining chemotherapy with Cox-2-inhibition has an impact on response and survival rates.

Adult↗
PubMed2004

Hyperbaric oxygen for the treatment of interstitial cystitis: long-term results of a prospective pilot study.

OBJECTIVE: We conducted a prospective pilot study to assess the safety and efficacy of hyperbaric oxygen (HBO) for the treatment of interstitial cystitis (IC). METHODS: Six patients underwent 30 sessions of 100% oxygen inhalation in a hyperbaric chamber and were followed up over 15 months. The measures of efficacy were changes in pain and urgency (visual analog scales), alteration in the patient's assessment of overall change in his well-being (Patient Global Assessment Form), and changes in frequency and functional bladder capacity (48-hours voiding log). Evaluation of symptom severity regarding pain and voiding problems was done using the O'Leary-Sant index. RESULTS: Four patients rated the therapeutic result as either excellent or good and assessed their well-being after HBO treatment as improved. Two patients showed only short-term amelioration of some of their symptoms. At 12 months follow-up the baseline functional bladder capacity increased from 37-161 ml (range) to 160-200 ml in the responder group. The 24-hour voiding frequency decreased from 15-27 to 6-11 voids per day, a pain scale improvement from 20-97 mm at baseline to 3-30 mm at 12 months follow-up and an urgency scale improvement from 53-92 mm to 3-40 mm, respectively was observed at 12 month follow-up. The symptom and pain index score decreased from 23-35 at baseline to 3-17 at 12 months follow-up. CONCLUSION: HBO appears to be effective to treat IC patients. Treatment was well tolerated and resulted in a sustained decrease of pelvic pain and urgency, improvement of voiding patterns and increase of functional bladder capacity for at least 12 months.

Adult↗
PubMed2004

A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis.

PURPOSE: We conducted a prospective study to examine the safety and efficacy of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). MATERIALS AND METHODS: The study comprised 44 women and 6 men who all met the symptom criteria of the National Institute of Diabetes, Digestive and Kidney Diseases for IC. The patients were randomly assigned to amitriptyline or placebo. Patients were prospectively treated for 4 months with a self-titration protocol that allowed them to escalate drug dosage in 25 mg increments in 1 week-intervals (maximum dosage 100 mg). The change from baseline in the O'Leary-Sant IC symptom and problem index was the primary outcome parameter. Changes in functional bladder capacity and frequency (48-hour voiding log), and intensity of pain and urgency (visual analog scales) were chosen as secondary outcome parameters. RESULTS: Two patients (1 on amitriptyline, 1 on placebo) dropped out of the study due to side effects. Thus, the data of 48 patients (24 patients in each group) were available for evaluation. Mean symptom score decreased from 26.9 to 18.5 in the amitriptyline group compared with 27.6 to 24.1 in the placebo group (p = 0.005). Pain and urgency intensity improved statistically significantly in the amitriptyline group compared with the placebo group (p <0.001). The frequency and functional bladder capacity improved to a much greater degree in the amitriptyline group but the differences were not statistically significant (p = 0.063, p = 0.083). Anticholinergic side effects were reported by all except 2 patients in the amitriptyline group (92%) and by 5 patients in the placebo group (21%). Mouth dryness was the most frequent side effect reported in the amitriptyline group (79%). CONCLUSIONS: Amitriptyline therapy for 4 months is safe and effective for treating IC. A statistically significant change in the symptom score and statistically significant improvement of pain and urgency intensity compared with placebo were observed. Anticholinergic side effects constitute the major drawback of amitriptyline treatment for IC.

Adult↗
PubMed2003

Semi-quantitative immunochromatographic test for prostate specific antigen in whole blood: tossing the coin to predict prostate cancer?

OBJECTIVES: A strip test for the semi-quantitative determination of prostate specific antigen (PSA) based on whole blood was evaluated by the Working Group on Laboratory Diagnostics of the German Urological Association. METHODS: In 301 men (156 volunteers and 145 referred patients, mean ages 57 years and 64 years) handling and capability of the strip test to predict PSA serum concentrations (Access Hybritech, Beckman Coulter, Inc., Fullerton, CA, USA) relative to a cutoff of 4 micro g/l were investigated. For patients, the strip test was performed by investigators, volunteers accomplished it according to leaflet instructions. Each test result was interpreted by both, the patient/volunteer and an investigator. RESULTS: 24% of the volunteers required assistance with test performance. The overall agreement between Access PSA (range 0.1-29.7) and strip test was 76% (read by participants) and 79% (read by investigators). Within the PSA ranges 0.1-3, 3.1-5 and 5.1-10, participants yielded agreement rates of 89%, 40% and 56%, respectively. Studying the 2.1-10 PSA range most relevant for prostate cancer screening, agreement rate (53%), sensitivity (50%) and specificity (67%) were barely superior to random chance. Volunteers alone (PSA range 0.1-11.3 micro g/l) yielded a specificity of 92%, however, all PSA values above the cutoff (n=8) went unrecognized and all positive strip tests (n=12) were incorrect (sensitivity 0%, positive predictive value 0%). CONCLUSIONS: Test handling and interpretation was difficult. The rate of false strip test results is disappointing even for PSA ranges remote from the cutoff. In its present form the strip test fails to meet the clinical requirements and its launch to the market was therefore discontinued.

Diagnostic Errors↗