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Axel Heidenreich

Publications and source records attributed to Axel Heidenreich.

At least 19 recordsLinked to original sources
PubMed2006

Impact of evidence-based interdisciplinary guidelines on testis cancer management.

BACKGROUND: In 1999, interdisciplinary evidence-based guidelines were elaborated for treatment of germ cell tumors in Germany. The aims of the current study were to analyze failures in diagnosis and therapy and to demonstrate the influence of guidelines on individual therapeutic approaches and clinical outcome. Therefore, patient collectives treated before the introduction of guidelines (Group A, 1990-1999, n = 234) and those thereafter (Group B, 2000-2002, n = 84) were compared for recurrence and survival. METHODS: In both groups, medical and/or surgical treatment and clinical outcome were evaluated for therapeutic mistakes and violations of guidelines. These were analyzed for their clinical consequences. RESULTS: There was no significant difference between groups concerning median age of patients or clinical stage before therapy. Altogether, 27.8% and 8.3% of all patients in Group A and B, respectively, displayed therapeutic mistakes (P < 0.005); 63% of these patients in Group A and 100% of these patients in Group B received an overtreatment. In Group A, 19/234 (8.1%) patients relapsed and 53% of these patients had been treated insufficiently (P < 0.005). Advanced disease caused the death of 3/234 patients in this study. As of this writing, only 3 of 84 (3.6%) patients in Group B have relapsed, and no patient has died because of tumor or consecutive treatment. CONCLUSIONS: The integration of interdisciplinary evidence-based guidelines for treatment of testicular germ cell tumors has led to significant reduction of both overtreatment and treatment failure and/or relapse that were due to inappropriate primary therapy. Evidence-based guidelines should serve as internal quality controls in all institutions treating patients with testicular germ cell tumors.

Adolescent↗
PubMed2006

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.

Chromosome Mapping↗
PubMed2006

Clinical significance of a prostate-specific antigen flare phenomenon in patients with hormone-refractory prostate cancer receiving docetaxel.

Docetaxel has shown promise for the treatment of hormone-refractory prostate cancer and has become the standard of care. The flare phenomenon is a known entity in androgen-deprivation therapy of advanced prostate cancer and it has also been described in palliative chemotherapy of hormone-refractory prostate cancer. The aim of this study was to evaluate the clinical impact of a prostate-specific antigen flare phenomenon in docetaxel-treated hormone-refractory prostate cancer patients. From December 2002 to August 2005, we treated 44 patients with hormone-refractory prostate cancer applying docetaxel-based regimens. Prostate-specific antigen levels were determined before therapy and weekly thereafter. Patients were divided into three groups: response (group 1), progression (group 2) and flare (group 3). Flare was defined as initially rising prostate-specific antigen under therapy, dropping thereafter to values below baseline. The groups were compared for overall survival by Kaplan-Meier analysis. We observed a prostate-specific antigen flare phenomenon in eight (18%) of 44 evaluable patients; 24 (54.5%) patients were primary responders and 12 (27.3%) experienced progressive disease. In group 3, prostate-specific antigen levels rose to 107-180% from baseline and then dropped to 21-68%. Kaplan-Meier analysis showed significantly better overall median survival for groups 1 (18 months, P=0.0005) and 3 (19 months, P=0.006) than for group 2 (7 months). Survival in groups 1 and 3 was comparable. Grade 3 and 4 toxicity was below 5% and equally distributed between the 3 groups. In our limited patient cohort, prostate-specific antigen flare phenomenon does not seem to be a clinically relevant issue in terms of overall survival. Thus, an initial rise of prostate-specific antigen under docetaxel therapy in hormone-refractory prostate cancer does not indicate therapeutic failure and should not lead to early withdrawal from therapy in the absence of clinical signs of progression.

Androgens↗
PubMed2005

The Y deletion gr/gr and susceptibility to testicular germ cell tumor.

Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility. Recently, a 1.6-Mb deletion of the Y chromosome that removes part of the AZFc region--known as the "gr/gr" deletion--has been associated with infertility. In epidemiological studies, male infertility has shown an association with TGCT that is out of proportion with what can be explained by tumor effects. Thus, we hypothesized that the gr/gr deletion may be associated with TGCT. Using logistic modeling, we analyzed this deletion in a large series of TGCT cases with and without a family history of TGCT. The gr/gr deletion was present in 3.0% (13/431) of TGCT cases with a family history, 2% (28/1,376) of TGCT cases without a family history, and 1.3% (33/2,599) of unaffected males. Presence of the gr/gr deletion was associated with a twofold increased risk of TGCT (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3-3.6; P = .005) and a threefold increased risk of TGCT among patients with a positive family history (aOR 3.2; 95% CI 1.5-6.7; P = .0027). The gr/gr deletion was more strongly associated with seminoma (aOR 3.0; 95% CI 1.6-5.4; P = .0004) than with nonseminoma TGCT (aOR 1.5; 95% CI 0.72-3.0; P = .29). These data indicate that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT.

Alleles↗
PubMed2005

Repeat retroperitoneal lymphadenectomy in advanced testicular cancer.

OBJECTIVES: Repeat retroperitoneal lymph node dissection (RPLND) for the treatment of metastatic testicular cancer is an uncommonly performed procedure. We evaluated the location, pathohistological results, postoperative complications and therapeutic outcome in 17 patients being referred for repeat RPLND after failure of the primary retroperitoneal approach. PATIENTS AND METHODS: 18 patients underwent repeat RPLND after failed primary RPLND or residual tumour resection. We retrospectively analyzed preoperative patient characteristics, operative and pathohistological data from primary and repeat RPLND, morbidity and oncological outcome after surgery. RESULTS: All patients had nonseminomatous primaries with metastatic retroperitoneal lymph nodes; 4 and 14 patients had undergone primary RPLND and residual tumor resection (RTR), respectively, for metastatic testicular cancer. Prior to repeat RPLND all patients had undergone 4 cycles of salvage chemotherapy for locoregional recurrences only with negative tumour markers at time of surgery. All patients demonstrated residual masses requiring repeat RPLND. Retroperitoneal recurrences were located at multiple sites: retrocaval area with infiltration of the vena cava, interaortocaval and paraaortic region, retrocrural space, suprahilar region, outfield metastases in the iliac region. Two cases required resection of the vena cava due to infiltration, in one case an aortic graft and an iliac graft was necessary due to tumour infiltration of the adventitial layer of the vessels; nephrectomy and resection of the sigmoid was required in another 2 patients. The most significant complication was chylous ascites 1 and prolonged paralytic ileus in 1 patient. Pathohistological examination of the resected specimen revealed viable germ cell tumour elements in 4 patients (22.2%), necrosis/fibrosis in 8 patients (44.4%) and mature teratoma in 6 patients (33.3%). At a mean follow-up of 22 (1-45) months, the disease specific survival rate was 89% with significant differences between patients with necrosis (100%), mature teratoma (85%) and viable cancer (50%). CONCLUSION: Recurrences after RPLND usually reflect inadequate primary surgery especially in the retrocaval and suprahilar region. Repeat RPLND is safe and effective in the majority of patients; however, it requires careful preoperative planning with regard to potential involvement of adjacent vascular and visceral structures making close interdisciplinary collaboration necessary in many cases. Repeat RPLND is a mandatory surgery to be performed at centres of expertise.

Germinoma↗
PubMed2005

Application of thalidomide/interleukin-2 in immunochemotherapy-refractory metastatic renal cell carcinoma.

Thalidomide has been reported to yield anti-tumor activity in advanced renal cell carcinoma (RCC). We evaluated safety and efficacy of a combination therapy comprising interleukin (IL)-2 and thalidomide in patients with metastatic RCC refractory to both immuno- and chemotherapy. Twelve patients with progressive metastatic RCC who had failed prior treatment with immunochemotherapy and desired further active therapy were enrolled in this study. Oral thalidomide was started at 200 mg/day and escalated after 2 days to 400 mg/day at week 0. IL-2 at 7 MIU/m was given by s.c. injection, starting at week 1, days 1-5, weeks 1-4, with rest from IL-2 at weeks 5 and 6. Response was assessed every two therapy cycles. Ten patients were evaluable for response. There was no objective response; four patients showed stable disease for 14+, 11+, 10+ and 9 months, respectively. Toxicities were predominantly grade I-II, and included somnolence and constipation, as well as flu-like symptoms associated with IL-2. However, one patient developed serious constipation which led to a paralytic ileus and discontinuation of treatment. Another patient left the study after 7 weeks due to increasing disorientation/confusion. Eight patients required IL-2 dose reduction. Time on therapy ranged from 3 to 44 weeks (median 20 weeks). Median overall survival was 12+ months. At present, all patients have discontinued treatment. We conclude that outpatient administration of thalidomide/IL-2 is feasible in patients with heavily pretreated and progressive RCC who desire further active treatment. However, toxicity and costs are considerable, and clinical benefit is uncertain. Therefore, thalidomide/IL-2 might not represent a promising therapeutic approach for this subgroup of patients.

Adult↗
PubMed2004

Prospective randomized Phase II trial of pegylated doxorubicin in the management of symptomatic hormone-refractory prostate carcinoma.

BACKGROUND: Liposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells. On the basis of doxorubicin's demonstrated clinical efficacy against hormone-refractory prostate carcinoma (HRPCA), the authors conducted a prospective, randomized Phase II clinical trial to evaluate the feasibility, toxicity, and therapeutic efficacy associated with the pegylated form of this agent. METHODS: Forty-eight patients with symptomatic HRPCA were randomized to receive pegylated liposomal doxorubicin at either 25 mg/m2 every 2 weeks for 12 cycles (Group A) or 50 mg/m2 every 4 weeks for 6 cycles (Group B). Thirty-eight of these 48 patients (79%) presented with severe pain (corresponding to a pain score of 7.5 on a visual analog scale [VAS] ranging from 0 to 10) due to osseous metastases. Therapeutic efficacy was assessed by serial evaluation of serum prostate-specific antigen (PSA) concentrations and by serial measurement of pain levels (using a VAS ranging from 0 to 10). Toxicity data were obtained using the National Cancer Institute of Canada/Cancer and Leukemia Group B criteria and the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: The median patient age was 68.9 years (range, 58-79 years), and the mean follow-up duration was 42 months. The mean pretreatment PSA level was 660.4 ng/mL (mean, 8-6340 ng/mL); an objective decrease in PSA levels (i.e., a decrease of > 50%) was observed in 8 of 31 patients (25.8%) in Group B, whereas no other patient in either group experienced such a decrease. The mean time to disease progression was 6.5 months, and the mean survival duration was 13.4 months. Patients in Group B had a significantly higher rate of response with respect to pain (52.6% vs. 28.6%; P = 0.04), and the mean 1-year survival rate also was significantly higher in Group B (42% vs. 15%; P = 0.02). Severe side effects were observed, with 24 patients (50%) experiencing World Health Organization Grade 3/4 toxicity. Toxicity types differed significantly between Group A and Group B; palmar-plantar erythrodysesthesia developed in 60% of patients in the former group (P < 0.0005), whereas tachycardia was more common in the latter group (39% of patients; P < 0.0005). No dose-limiting cardiotoxicities or hematotoxicities were documented. CONCLUSIONS: Pegylated liposomal doxorubicin yielded a noteworthy objective palliative response rate and a mean survival of 13 months for patients with symptomatic HRPCA. The dosage tested in the current study should be used in future Phase II and Phase III trials of pegylated liposomal doxorubicin-containing combination regimens for patients with HRPCA.

Aged↗
PubMed2004

Preoperative imaging in renal cell cancer.

Renal cell cancer (RCC) represents the fifth most common cancer in men, with a rising incidence. Radical cancer surgery remains the only curative treatment in localized and advanced RCC. Therefore, preoperative imaging is most important for the planning of the surgical approach and strategy. The aim of any preoperative imaging in RCC is to differentiate benign from malignant lesions, to adequately assess tumor size, localization and organ confinement, to identify lymph node and/or visceral metastases, and to reliably predict the presence and extent of any thrombus of the vena cava. It is our aim to review the current status of preoperative imaging modalities in RCC. Computed tomography (CT) remains the most appropriate imaging modality to differentiate benign from malignant lesions. Although RCC can appear as iso-, hyper- or hypodense lesions on native CT scans, it usually demonstrates a significant contrast enhancement of about 115 HU and intratumoral areas of necrosis following the intravenous application of contrast medium. Benign masses such as renal oncocytoma are most often homogenous lesions exhibiting hypodensity compared to the normal renal parenchyma following the i.v. application of contrast dye. CT accurately predicts the tumor size with only a 0.5 cm difference as compared to the pathological size of the lesion. The identification of lymph node metastases still remains a problem since the limiting size is 4 mm and CT will result in a false negative rate of about 10%, especially in the presence of micrometastases; the false positive rate of 3-43% is mainly due to reactive hyperplasia. New technologies, such as the multidetector CT with thin collimation and multiplanar reformatting, might result in a diagnostic improvement. The involvement of the adrenal gland can be accurately predicted by CT scans or MRI, allowing an adrenal sparing approach in the case of unsuspicious findings. The detection of visceral metastases appears to be crucial since it has been shown that even patients with metastatic disease might benefit from radical nephrectomy followed by systemic immunotherapy in the case of a good performance status, and the presence of lymph node and pulmonary metastases only. Involvement of the renal vein and the vena cava with tumor thrombus formation will change the surgical strategy. Preoperatively, the presence and the cranial extent of the thrombus need to be known in order to plan the surgical approach. With regard to the extent of renal vein thrombi, a three phase helical CT scan is most appropriate; for vena caval thrombi only a MRI examination is able to accurately identify any infra- or suprahepatic as well as intracardial extension of the thrombus. The identification of multifocal lesions remains another unsolved problem in preoperative imaging techniques for RCC. Compared to the pathohistological analysis of nephrectomy specimens, neither ultrasonography, color duplex sonography nor regular CT scans are able to identify multifocal lesions with acceptable sensitivity and specificity. The evaluation of unenhanced CT scans together with the enhanced corticomedullary and the nephrogenic phase result in a 100% sensitivity and might represent a valuable option. Angiography has basically been abandoned from the armory of routine imaging techniques. It has, however, a current role in terms of the embolization of large tumors to reduce intraoperative blood loss, and in the palliative management of pain and bleeding due to RCC not amenable to surgery. Finally, we present a diagnostic algorithm for the most informative imaging techniques in the evaluation of RCC.

Algorithms↗
PubMed2004

Surgical management of vesicoureteral reflux in pediatric patients.

Vesicoureteral reflux (VUR) represents one of the most significant risk factors for acute pyelonephritis in children. The current indications for the surgical correction of VUR depend on the presence or absence of renal scars. If no scars are present, primary ureteral reimplantation is only indicated in high-grade bilateral VUR, whereas in the presence of renal scars surgical correction is indicated in low/high grade reflux at a young age. Since there are numerous techniques for antireflux surgery available, it is the purpose of this article to critically review these techniques with their specific advantages, typical complications and postoperative management. In general, all surgical technique have a high success rate of 92-98%. The extravesical Lich-Gregoir technique is primarily indicated in unilateral VUR. Children with a high-grade VUR, who are under the age of 3 years and boys are prone to the development of postoperative urinary retention and might be considered for intravesical surgical techniques. The Politano-Leadbetter technique is very helpful in correcting bilateral VUR of any grade in one session to create a neo-ostium in an anatomically correct position which is easily accessible for endourological manipulations. The Psoas hitch ureteroneocystotomy is an excellent technique to correct VUR associated with megaureter, or with duplicated ureters, and VUR failures. Endoscopic subureteral injections are primarily reserved for low grade VUR with a one session success rate of >90%. Endoscopic subureteral injections appear to be an alternative to long-term antibiotics in grade I-III VUR. Laparoscopic antireflux surgery has not gained widespread use due to the very long operating times. Contralateral VUR will occur in about 20% of children undergoing unilateral antireflux surgery; risk factors are severe VUR and VUR into a duplicated system. Postoperative follow-up nowadays consists of urinalysis and ultrasonography; voiding cystourethrography is only indicated in case of febrile urinary tract infection. Despite the excellent success rates following antireflux surgery one has to keep in mind that surgery only corrects the anatomical abnormality. The long-term outcome with regard to renal function, posttherapeutic febrile urinary tract infections and arterial hypertension does not differ significantly from the medication group except for those patients with a demonstrated a genetic background. Therefore, the indication for surgery and the surgical technique applied have to be discussed thoroughly and must be associated with a minimal complication rate.

Child↗
PubMed2004

Genetic pathways and new progression markers for prostate cancer suggested by microsatellite allelotyping.

PURPOSE: At diagnosis, the biological behavior of prostate cancer is uncertain, making the choice of an adequate therapy option difficult. Performing microsatellite allelotyping on a large series of consecutive prostate cancers procured during radical prostatectomy at our institution, we sought to identify molecular markers associated with disease progression. EXPERIMENTAL DESIGN: A total of 156 consecutive fresh tumor samples was prospectively collected and macroscopically dissected from the whole prostatectomy specimen immediately after operation. Histologically 100 samples contained >75% tumor cells and were therefore enrolled in the microsatellite allelotyping, using a total of 24 polymorphic markers for the chromosomal regions 5p, 5q, 7q, 8p, 9p, 9q, 13q, 17p, 17q, and 18q. Fresh paired normal and tumor DNA was investigated in fluorescent microsatellite analysis with automated laser product detection. RESULTS: The incidence of tumor-DNA alterations [loss of heterozygosity or allelic imbalance (AI)] was highest for chromosomal regions 13q and 8p with 72 and 71%, respectively, followed by chromosomes 7q, 18q, 5q, and 17p with 57, 53, 41, and 39%, respectively. Alterations at chromosomes 8p, 9p, 13q, and 17p were significantly (P < 0.05) associated with advanced tumor stage, whereas AI at 8p and 17p was also associated with high Gleason score (P < 0.05). AI at 5q and 9p was associated with regional lymph node metastasis (P < 0.05). The combination of AI at 8p and 13q was strongly associated with advanced tumor stage (P < 0.0001). CONCLUSIONS: With the obtained results, we are able to postulate three distinct pathways in prostate carcinogenesis, and we identified microsatellite markers of prognostic value.

Alleles↗
PubMed2004

Molecular serological detection of DNA alterations in transitional cell carcinoma is highly sensitive and stage independent.

PURPOSE: To evaluate the efficacy of fluorescent microsatellite analysis (MSA) for the serological diagnosis of transitional cell carcinoma (TCC) of the urinary tract analyzing free tumor DNA in the serum of cancer patients. EXPERIMENTAL DESIGN: We applied fluorescent MSA to detect serum-DNA alterations in patients suffering from bladder and upper urinary tract TCC and prospectively collected fresh tumor, peripheral blood, and serum specimens from 61 consecutive patients to obtain the corresponding DNA. Fluorescent MSA was performed with a total of 17 polymorphic markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q, and 20q in the 61 cancer patients, as well as in 20 healthy controls. RESULTS: Molecular serological analysis led to tumor-specific diagnosis of TCC in 80.3% (49 of 61) of cases. Four healthy controls displayed serum-DNA artifacts rendering a specificity of 80%. The highest frequency of serum-DNA alterations was detected for chromosomal region 8p with 36%. Chromosomes 5q, 9p, and 20q showed serum-DNA alterations in 18 to 21%. The identification of serum-DNA alterations was not statistically associated with underlying local tumor stage (P = 0.29) but was more frequent in high-grade tumors (P = 0.08). CONCLUSIONS: MSA offers a highly sensitive method for serological diagnosis of TCC. To optimize specificity, simultaneous analysis of tumor DNA is advised to rule out artifacts resembling allelic imbalance in MSA of serum DNA.

Biomarkers, Tumor↗
PubMed2004

Genetic pathways and new progression markers for prostate cancer defined by microsatellite allelotyping.

A prospective study was carried out on a large cohort of males undergoing radical retropubic prostatectomy in order to identify genetic marker regions significantly associated with tumor formation. By comprehensive allotyping of chromosomes known to be associated with prostate carcinogenesis, an algorithm could be formulated for the genetic pathway and a method of discrimination between aggressive and less aggressive forms could be identified.

Alleles↗
PubMed2004

Ibandronate in metastatic bone pain.

Bone pain is a frequent complication of metastatic bone disease, with severe consequences for patient mobility and quality of life. Bisphosphonates can reduce bone pain and augment palliative radiotherapy, although relief is often for a relatively short period of time. Ibandronate is the first bisphosphonate to provide sustained bone pain relief over 2 years and, unlike other bisphosphonates, has shown improvements in quality of life. In phase III studies of patients with bone disease from breast cancer, intravenous ibandronate 6 mg and oral ibandronate 50 mg reduced bone pain below baseline levels within 6 weeks. Significant reductions were maintained throughout the 96-week study phase compared with placebo ( P < or =.001). Two open, nonrandomized studies examined the effect of intensive, high-dose intravenous ibandronate (4 mg on 4 consecutive days, or 6 mg on 3 consecutive days) in patients with breast cancer or other tumor types with opioid-resistant bone pain and in patients with urologic cancer. In each study, ibandronate rapidly relieved moderate-to-severe metastatic bone pain, improving quality of life and patient functioning. Both intravenous and oral ibandronate provide effective long-term relief from metastatic bone pain. This clinical benefit may reduce the burden of metastatic bone disease on health care resources by limiting the need for analgesics and radiotherapy to the bone.

Administration, Oral↗
PubMed2004

Managing metastatic bone disease: three case studies.

Metastatic bone disease constitutes a major clinical problem. Skeletal complications are common and lead to significant morbidity, and patients live with metastatic bone disease for several years, increasing the prevalence of this problem. Effective management aims to reduce the incidence of skeletal complications and relieve symptoms, such as severe bone pain, which adversely affect patient mobility and quality of life. This article describes and discusses strategies for managing metastatic bone disease, with particularly emphasis on the role of the bisphosphonate ibandronate. Two case histories show the long-term efficacy and tolerability of oral ibandronate in the treatment of metastatic breast cancer. The third case history illustrates the benefits of rapid pain relief from an intensive, high-dose regimen of intravenous ibandronate in metastatic prostate cancer.

Administration, Oral↗