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Dorothea Weckermann

Publications and source records attributed to Dorothea Weckermann.

12 recordsLinked to original sources
PubMed2006

Limitations of radioguided surgery in high-risk prostate cancer.

OBJECTIVES: To determine how many men with high-risk prostate cancer (prostate-specific antigen [PSA]>20 ng/ml or biopsy Gleason score 8-10) have positive lymph nodes (sentinel lymph nodes [SLNs] and nonsentinel lymph nodes [NSLNs]) and whether these positive nodes are localised in the region of SLN dissection or in other regions, too. METHODS: In 228 men with high-risk prostate cancer radical retropubic prostatectomy combined with radioguided pelvic lymph node dissection and extended lymphadenectomy were performed. Serial sections of the SLNs were analysed immunohistochemically. RESULTS: A median of 7 SLNs (mean, 7) and 11 NSLNs (mean, 11) were dissected per patient. Ninety-six of 228 men (42.1%) had lymph node metastases. Most men had positive lymph nodes along the internal iliac artery alone or in combination with other regions. Twenty-two men had only micrometastatic disease. In 94 of 96 men the SLNs were positive. Twenty-six of 96 men had also positive NSLNs. When SLNs and NSLNs were positive, in more than half the patients the NSLNs were localised outside the region of sentinel lymphadenectomy. CONCLUSIONS: The dissection of SLNs in prostate cancer has a high sensitivity in detecting positive nodes. When SLNs are negative, the other pelvic lymph nodes are also negative in a high percentage of men (sensitivity 97.1%). When the SLNs are positive, patients with high-risk disease also have a high incidence of positive NSLNs. Therefore, when it is aspired to remove all pelvic lymph node metastases sentinel and extended lymphadenectomy should be performed.

Aged↗
PubMed2006

A phase I study with adecatumumab, a human antibody directed against epithelial cell adhesion molecule, in hormone refractory prostate cancer patients.

AIM OF THE STUDY: Adecatumumab (also known as MT201) is a human recombinant IgG1 monoclonal antibody binding with low affinity to epithelial cell adhesion molecule (EpCAM). To explore safety, pharmacokinetics and pharmacodynamics of adecatumumab, a phase I trial in patients with hormone refractory prostate cancer (HRPC) was performed. METHODS: Twenty patients were treated with two adecatumumab infusions on days 0 and 14 in cohorts with doses of ten up to 262 mg/m2. RESULTS: Adecatumumab was well tolerated at all doses tested, and no maximum tolerated dose reached. Most adverse events were mild or moderate with pyrexia and nausea being most frequent. The highest dose of adecatumumab induced shortly after infusion robust and transient increases of TNF-alpha serum levels. At all doses, significant transient declines of peripheral natural killer cells were observed shortly after antibody infusions. Adecatumumab had a serum half-life of 15 days, and immune responses to the antibody were not detected. CONCLUSIONS: A benign safety profile, long serum half-life and low immunogenicity do warrant further exploration of adecatumumab for treatment of EpCAM-expressing neoplasia.

Aged↗
PubMed2006

Incidence of positive pelvic lymph nodes in patients with prostate cancer, a prostate-specific antigen (PSA) level of < or =10 ng/mL and biopsy Gleason score of < or =6, and their influence on PSA progression-free survival after radical prostatectomy.

OBJECTIVE: To investigate how many men with low-risk prostate cancer had positive lymph nodes detected by radio-guided surgery and whether they had a higher biochemical relapse rate after radical prostatectomy, because in such patients most urologists dispense with operative lymph node staging, as nomograms indicate only a low percentage of lymph node metastases. PATIENTS AND METHODS: The study included 474 men with a prostate-specific antigen (PSA) level of < or = 10 ng/mL, biopsy Gleason score of < or = 6 and positive biopsies in one (group 1, 315 men) or both lobes (group 2, 159 men); follow-up data were available in 357 men. Men with adjuvant radiation or hormone therapy before the occurrence of biochemical relapse were excluded. RESULTS: Positive lymph nodes were detected in 17 men in group 1, and in 18 in group 2. In more than half of the patients (19/35) these nodes were found outside the region of standard lymphadenectomy. Men with node-positive disease had a higher biochemical relapse rate (P < 0.001). When the tumour was organ-confined and well differentiated in node-positive disease (Gleason score < or = 6) the biochemical relapse rate was lower than in men with higher tumour stage and grade. CONCLUSIONS: When dissecting pelvic lymph nodes, extended or sentinel lymphadenectomy should be preferred. Removing the diseased nodes could improve the PSA progression-free survival, especially in well differentiated organ-confined disease.

Adult↗
PubMed2005

Chlamydia pneumoniae in an ex vivo human artery culture model.

The role of the obligate intracellular pathogen Chlamydia pneumoniae in the development of atherosclerosis could not be completely clarified. Reasons are the highly discrepant results obtained in the hitherto existing studies and the lack of an experimental system allowing the direct examination of chlamydial effects in the human vasculature. We established a human ex vivo organ culture model for the characterization of vascular chlamydial infection. Ninety sections of renal arteries, obtained from nephrectomies, were inoculated with Chlamydia pneumoniae. Using a monoclonal FITC-conjugated antibody, chlamydial LPS was broadly detected in inoculated arteries during the entire observation period of 35 days. However, recultivation of viable organisms from the artery vessel wall was impossible, indicating that productive infection in human arteries did not occur even under optimized conditions. This was substantiated by low recovery rates of Chlamydia pneumoniae, low amounts of detectable chlamydial 16S rRNA and ultramorphological presence of polymorph multilamellar bodies in experimentally infected smooth muscle cells originating from aortas, coronary and renal arteries. We could demonstrate that the complex environment of a human artery did not support the growth of Chlamydia pneumoniae although the presence of chlamydial LPS in the artery vessel wall following experimental infection was a common event. The presence of chlamydial LPS in the absence of viable organisms within the artery vessel wall may explain the failure of antibiotic treatment strategies for atherosclerosis.

Aged↗
PubMed2005

Prostate cancer relapse after therapy with curative intention: a diagnostic and therapeutic dilemma.

Prostate cancer is the most common malignant disease and second in causes of cancer death among men in Western Europe and North America. Despite improved surgical and irradiation techniques tumor relapse after curatively intended therapy is not uncommon. Due to the difficulty in discriminating local and systemic progression, it is often difficult to decide what this means for the patient and what kind of second-line treatment has to be given. Modern imaging techniques (MRI with endorectal coil, Choline-PET-CT, ProstaScint-Scan) are used for diagnosis of prostate cancer relapse. Nevertheless, early detection of local tumor relapse and likewise the detection of disseminated tumor cells often fails. To differentiate between local and systemic progression, prognostic factors of the primary tumor (grading, surgical margins, infiltration of the seminal vesicles, lymph node metastases) and PSA kinetics are used. The time from initial treatment to biochemical relapse and PSA doubling time are of highest prognostic relevance. Local progression allows second-line local treatment with potentially curative results (local irradiation after radical prostatectomy, salvage-surgery / cryotherapy / HIFU after irradiation), while in the case of systemic progress a palliative systemic therapy (hormonal treatment, chemotherapy, bisphosphonates) is indicated. Before deciding on the most appropriate therapy, prognostic factors and the patient's individual situation (co-morbidity, life expectancy, individual wishes) should be taken into account.

Biomarkers, Tumor↗
PubMed2005

Is there a need for pelvic lymph node dissection in low risk prostate cancer patients prior to definitive local therapy?

OBJECTIVES: In men with low risk prostate cancer the need for pelvic lymph node dissection is controversial. Therefore, we examined how many men with favorable preoperative risk factors had positive lymph nodes. METHODS: 235 men with preoperative PSA < or =10 ng/ml, Gleason score < or =6 and positive biopsies in only one lobe, had radio-guided pelvic sentinel lymph node (SLN) dissection and radical retropubic prostatectomy (RRP) or-in case of no positive lymph nodes detected-a transperineal I(125) seed implantation. Eighty-four men with positive biopsies in both lobes and identical PSA and Gleason score had SLN dissection and RRP. RESULTS: In 187 men with positive biopsies in one lobe RRP was performed. Sixteen patients had positive lymph nodes. Median 6 SLN (mean 6.8) and 6 non-sentinel lymph nodes (NSLN) (mean 7.3) were dissected. All men with positive lymph nodes also had positive SLN. Eighty-four men with positive biopsies in both lobes had RRP. Nine men had positive lymph nodes (10.7%). A median of 6 SLN (mean 6.6) and 5 NSLN (mean 7.5) were dissected. All men with positive nodes had a single positive SLN. CONCLUSIONS: In patients with PSA < or =10 ng/ml and biopsy Gleason score < or =6, positive lymph nodes were identified by radio-guided surgery in 6.8% (positive biopsies in one lobe) and 10.7% (positive biopsies in both lobes). Up to 4 positive SLN were found. Therefore, we suggest not to dispense with an operative lymph node staging, even in low risk disease.

Aged↗
PubMed2004

Hormone therapy in prostate cancer: LHRH antagonists versus LHRH analogues.

GnRH agonists have a proven and well-established role in the management of prostate cancer. Further adaptations of the amino-acid sequence led to the development of antagonists with potential therapeutic uses, including a possible role in prostate cancer patients. Treatment of prostate cancer with GnRH agonists results in an initial flare of symptoms that may be prevented by co-administration of a steroidal or non-steroidal antiandrogen. However, this can be associated with additional adverse effects. Clinical studies have shown that GnRH antagonists produce a rapid decline in testosterone but without the disease flare. However these short-term effects have yet to be proven to lead to long-term survival benefits. There have been some reports that antagonists may be associated with adverse effects due to histamine release leading to severe allergic reactions. GnRH agonists are currently available in a range of depot formulations, allowing treatment to be tailored to the patient's needs. At present, the antagonists are only available as on-month depot formulations, which may limit their clinical use. Abarelix should be given intramuscularly. It is the first GnRH antagonist which is approved by the FDA for patients with advanced prostate cancer who should be treated under a risk management program. In Europe, abarelix has not been registered yet.

Antineoplastic Agents, Hormonal↗
PubMed2003

The influence of serial sections, immunohistochemistry, and extension of pelvic lymph node dissection on the lymph node status in clinically localized prostate cancer.

OBJECTIVES: Pelvic lymph node metastases indicate a poor prognosis for patients with clinically localized prostate cancer. The aim of the study was to investigate the value of extended histopathological techniques considering the extent of pelvic lymphadenectomy and preoperative risk factors. METHODS: Total of 194 patients with prostate cancer were examined. At first all patients had a sampling of the sentinel lymph nodes (SLN) followed in most cases by a modified or extended pelvic lymphadenectomy. Step sections, serial sections and immunohistochemistry (IHC, pancytokeratin antibody) were analyzed in all SLN and so-called non-SLN of the first 100 patients. Later serial sections and IHC of non-SLN were left out. RESULTS: In 26.8% lymphatic metastases were found. The detection rate of lymph node-positive patients depend significantly on the chosen extension of pelvic lymphadenectomy. Limiting the histopathological investigation to the lymph node specimen of the obturator fossa only 44.2% of lymph node-positive cases would have been identified. An additional inclusion of all lymph nodes surrounding the external iliac vessels improves the sensitivity to 65.4% (46.7% and 73.3% for the first 100 patients). Compared to the extension of pelvic lymphadenectomy the diagnostic gain of serial section and IHC (13.8% versus 53.3%) was comparably low. CONCLUSIONS: The extension of pelvic lymph node dissection is of outstanding value for the identification of node-positive patients. Limiting the number of lymph nodes to the ones with the highest probability of bearing lymphatic spread (SLN) makes the use of extensive histopathological techniques more feasible.

Humans↗
PubMed2003

Prostate lymphoscintigraphy and radio-guided surgery for sentinel lymph node identification in prostate cancer. Technique and results of the first 350 cases.

INTRODUCTION: Having in mind the promising results of lymphoscintigraphy and intraoperative gamma probe application for the detection of sentinel lymph nodes (SLN) in malignant melanoma, breast and penis cancer, we tried to identify the SLN in prostate cancer by applying a comparable technique. MATERIALS AND METHOD: 350 patients with prostate cancer were examined after providing informed consent. The day before pelvic lymphadenectomy technetium-99m nanocolloid was transrectally injected into the prostate under ultrasound guidance. A single central application was done per prostate lobe in most cases. Activity attained 90- 400 MBq, and the total injected volume was about 2-3 ml. Hereafter, lymphoscintigraphy was carried out. Those lymph nodes having been identified as SLN by means of gamma probe detection and lymphoscintigraphy were removed intraoperatively. Later, most of the cases had different types of pelvic lymphadenectomy. SLN received serial sections and immunohistochemistry, non-SLN step sections. RESULTS: 335 patients showed at least 1 SLN in lymphoscintigraphy. 24.7% had lymph node metastases. In 2 patients, metastases in non-SLN were found without at least one SLN being affected (false-negative patient). CONCLUSION: Our experience suggests that the SLN identification is not only feasible in breast cancer and malignant melanoma, but also in prostate cancer with a comparable technique.

Humans↗
PubMed2002

Heterogeneous expression of MAGE-A genes in occult disseminated tumor cells: a novel multimarker reverse transcription-polymerase chain reaction for diagnosis of micrometastatic disease.

Systemically disseminated tumor cells have become the subject of intensive research as the presumed seminal precursors of later distant metastasis. We describe here a novel sensitive multimarker nested reverse transcription (RT)-PCR capable of detecting the individual expression of human MAGE-A genes MAGE-1, -2, -3/6, -4, and -12 by rare, disseminated tumor cells in bone marrow and blood of patients with many different types of cancer. We analyzed bone marrow aspirates from 106 patients with breast, lung, colorectal, and prostate cancer and with different sarcomas. Heterogeneous expression of the different MAGE genes was found frequently in all those kinds of malignancies, in sharp contrast to 30 bone marrow and 20 blood samples from healthy donors, which were completely MAGE negative. Expression of at least one MAGE gene in bone marrow was more frequent than cytokeratin-positive tumor cells detected by immunocytochemistry, although the results of both tests overlapped considerably. In 30 patients with clinically localized prostate cancer, analysis by the multimarker MAGE RT-PCR of bilateral bone marrow aspirates from the right and left iliac crest revealed a positivity rate of 60%, which was twice as high as that obtained with either an established prostate-specific antigen RT-PCR or by cytokeratin-based immunocytochemistry. Analysis of primary prostate cancer revealed MAGE expression patterns considerably concordant with those found in the corresponding bone marrow aspirates. Prostate cancer patients carrying an exceptionally high risk of metastatic relapse, as defined by clinical prognostic factors, were significantly more often MAGE positive than patients with a distinctly lower risk (P = 0.02, Fisher's exact test). More frequent MAGE expression in the peripheral blood of patients with metastatic prostate cancer compared with those with clinically localized disease added further evidence for the prognostic impact of the multimarker MAGE RT-PCR. Moreover, MAGE-positive bone marrow samples from a small group of seven sarcoma patients demonstrated the relevance of our multimarker RT-PCR in nonepithelial tumors. Because MAGE antigens can induce autologous cytolytic T lymphocytes in vivo, the determination of individual MAGE expression patterns in cancer patients may furthermore identify candidate vaccine targets for adjuvant immunotherapy.

Antigens, Neoplasm↗
PubMed2002

Low dose unenhanced helical computerized tomography for the evaluation of acute flank pain.

PURPOSE: Unenhanced helical computerized tomography (CT) has proved to be an excellent diagnostic tool for evaluating acute flank pain with reported 95% to 100% sensitivity, 92% to 100% specificity, 96% to 100% positive and 91% to 100% negative predictive values. The diagnostic value of a new low dose protocol was prospectively studied and compared with the results of conventional unenhanced helical CT in a previous series with an effective dose equivalent (HE) of 3.1 to 4.3 mSv. and in current literature with an estimated HE of 4.3 to 4.7 mSv. MATERIALS AND METHODS: In 109 patients 18 to 86 years old with acute flank pain we performed low dose unenhanced helical CT in addition to abdominal ultrasound and urinalysis with new CT parameters (120 kV. 70 mA., 5 mm. collimation, pitch 2 and incremental reconstruction each 5 mm.) that led to a more than 50% decrease in radiation exposure to 1.50 mSv. in females and 0.98 mSv. in males. Ureteral calculi were confirmed or excluded by retrograde ureteropyelography in 51 cases. In the other cases the diagnosis was verified by the clinical and ultrasound course, and/or stone asservation. RESULTS: In 80 of the 109 patients the flank pain was caused by a ureteral calculus. Low dose unenhanced helical CT precisely identified 77 ureteral calculi with 1 false-positive finding. Thus, the sensitivity and specificity of low dose unenhanced helical CT were 96% and 97% with a 99% positive and 90% negative predictive value. In 15 of 29 patients with CT findings negative for stone disease different causes of pain were established by low dose unenhanced helical CT. CONCLUSIONS: Even with the significantly decreased radiation exposure of the low dose protocol unenhanced helical CT is still an excellent and rapid diagnostic tool for evaluating acute flank pain with lower radiation exposure than excretory urography (HE 1.3 to 2.3 mSv.) at our departments. Only in obese patients with a body mass index of greater than 31 kg./m.2 is conventional unenhanced helical CT with higher radiation exposure recommended to achieve adequate image quality.

Acute Disease↗