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Biomedical subjects

Paul H Lange

Publications and source records attributed to Paul H Lange.

At least 19 recordsLinked to original sources
PubMed2006

Two-year outcome of unilateral sural nerve interposition graft after radical prostatectomy.

OBJECTIVES: To study 41 men treated for prostate cancer with unilateral nerve-sparing radical prostatectomy and contralateral sural nerve grafting from January 2000 to September 2003. METHODS: Patients were considered for sural nerve grafting if they were considered at high risk of extracapsular extension before or during surgery, were younger than 70 years of age with good preoperative erectile function, were sexually active, and had no significant risk factors for erectile dysfunction. Potency was assessed by patient-reported questionnaires, including the International Index of Erectile Function erectile domain and Rigiscan testing. RESULTS: The mean follow-up was 27.4 +/- 14.5 months. At 24 months, 24 (63.2%) of 38 men had erections sufficient for intercourse, with or without phosphodiesterase type 5 inhibitor use. Four men had partial erections that were occasionally satisfactory (10.5%), and 10 men reported no sexual activity, no spontaneous erections, or partial erections unsatisfactory for intercourse (26.3%). In contrast, in a group of 49 men who underwent unilateral nerve-sparing prostatectomy without nerve grafting during the same period at our institution, 13 (26.5%) had rigid erections adequate for intercourse with or without phosphodiesterase type 5 inhibitor use at 24 months of follow-up. CONCLUSIONS: At 24 months of follow-up, men who had undergone unilateral nerve-sparing prostatectomy with contralateral sural nerve interposition graft repair of a cut cavernosal nerve had a greater rate of return of erectile function than men undergoing unilateral nerve-sparing prostatectomy alone.

Follow-Up Studies↗
PubMed2006

Differences in survival among patients with urachal and nonurachal adenocarcinomas of the bladder.

BACKGROUND: Primary adenocarcinomas of the bladder and urachus are rare malignancies, and knowledge of the patient demographics, pathologic characteristics, and survival associated with these tumors is poor. The current study compares disease-specific characteristics and survival associated with urachal and nonurachal primary bladder adenocarcinomas. METHODS: Incident cases of urachal and nonurachal primary adenocarcinomas of the bladder were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Demographic and pathologic characteristics at the time of diagnosis were compared. Risks of mortality among urachal and nonurachal primary adenocarcinomas of the bladder were compared using multivariate Cox regression. RESULTS: A total of 151 urachal and 1374 nonurachal adenocarcinomas of the bladder patients were identified. Compared to those with nonurachal tumors, patients with urachal adenocarcinoma were more likely to be younger (median age, 56 vs. 69 years, P <.0001) and female (45% vs. 36%, P = .02). Urachal lesions were less likely to be high grade (35% vs. 66%, P < .001), but more likely to involve distant metastases (30% vs. 15%, P < .001). Partial cystectomy was more common in urachal tumors (66% vs. 16%, P <.001). In multivariate analysis, subjects with urachal tumors had a lower risk of all cause (hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.38-0.83) and disease-specific (HR = 0.59, 95% CI: 0.35-0.98) mortality compared with patients with nonurachal tumors. CONCLUSIONS. Urachal adenocarcinomas represent 10% of all primary adenocarcinomas of the bladder. Overall and disease-specific mortality risks are improved in patients with urachal lesions, even after controlling for numerous patient and tumor characteristics.

Adenocarcinoma↗
PubMed2006

The distribution of serum prostate-specific antigen levels among American men: implications for prostate cancer prevalence and screening.

BACKGROUND: The purpose of this study was to describe the distribution of serum prostate-specific antigen (PSA) among American men and to estimate the number of prevalent cases of biopsy detectable prostate cancer among men with normal serum PSA. METHODS: We analyzed data of the National Health and Nutrition Examination Survey 2001-2002 (NHANES 2001-2002) data and combined these results with published data from the Prostate Cancer Prevention Trial (PCPT). RESULTS: Most men in the US have a serum PSA < or = 4.0 ng/ml, and mean and median serum PSA values rise steadily with age. There are an estimated 1,607,585 (95% CI 1,370,848-1,844,322) prevalent cases of biopsy detectable prostate cancer in men aged 62-85 years with a serum PSA < or = 4 ng/ml. Among men aged 62-75 years, there are an estimated 1,252,143 (95% CI 1,054,677-1,449,609) prevalent cases, including an estimated 195,499 (95% CI 140,234-250,764) high-grade tumors. CONCLUSION: A large number of prevalent cases of biopsy detectable prostate cancer exist in American men with a normal PSA.

Adult↗
PubMed2006

Telomerase activity in disseminated prostate cancer cells.

OBJECTIVE: To analyse telomerase activity in disseminated prostate cancer cells isolated from bone marrow aspirates taken from men with localized prostate cancer before radical prostatectomy (RP). PATIENTS AND METHODS: Disseminated epithelial prostate cancer cells were isolated from bone marrow aspirates from 69 men with localized prostate cancer before RP, by magnetic column-chromatography enrichment, followed by isolation of fluorescently labelled epithelial cells by micropipetting. We used pools of 10 non-epithelial bone marrow cells after tumour cell enrichment as control samples. These pure cell pools were tested for the presence of telomerase activity. RESULTS: In all, 49 of the patient samples contained disseminated prostate cancer cells. Homogeneous pools of 10 cells were obtained from 35 of these; 49% of the 35 specimens showed telomerase activity, whereas all five control samples did not. Telomerase activity in the 35 samples was not significantly associated with Gleason score, preoperative prostate-specific antigen level, tumour stage, or surgical margin status. Follow-up is continuing to assess an association with disease recurrence. CONCLUSION: This work shows the feasibility of isolating disseminated cancer cells for analysing individual or pooled cells. Compared to tissue staining, where telomerase is detected in 80-90% of samples, we found lower rates of telomerase activity in the disseminated tumour cells (49%). Telomerase-negative cells might provide information about cell dormancy, as telomerase is a marker of cell proliferation in immortal and cancer cells. Telomerase-positive cells might predict early disease recurrence, but a longer follow-up is needed to test this possibility.

Bone Marrow↗
PubMed2005

Evidence for the presence of disease-perturbed networks in prostate cancer cells by genomic and proteomic analyses: a systems approach to disease.

Prostate cancer is initially responsive to androgen ablation therapy and progresses to androgen-unresponsive states that are refractory to treatment. The mechanism of this transition is unknown. A systems approach to disease begins with the quantitative delineation of the informational elements (mRNAs and proteins) in various disease states. We employed two recently developed high-throughput technologies, massively parallel signature sequencing (MPSS) and isotope-coded affinity tag, to gain a comprehensive picture of the changes in mRNA levels and more restricted analysis of protein levels, respectively, during the transition from androgen-dependent LNCaP (model for early-stage prostate cancer) to androgen-independent CL1 cells (model for late-stage prostate cancer). We sequenced >5 million MPSS signatures, obtained >142,000 tandem mass spectra, and built comprehensive MPSS and proteomic databases. The integrated mRNA and protein expression data revealed underlying functional differences between androgen-dependent and androgen-independent prostate cancer cells. The high sensitivity of MPSS enabled us to identify virtually all of the expressed transcripts and to quantify the changes in gene expression between these two cell states, including functionally important low-abundance mRNAs, such as those encoding transcription factors and signal transduction molecules. These data enable us to map the differences onto extant physiologic networks, creating perturbation networks that reflect prostate cancer progression. We found 37 BioCarta and 14 Kyoto Encyclopedia of Genes and Genomes pathways that are up-regulated and 23 BioCarta and 22 Kyoto Encyclopedia of Genes and Genomes pathways that are down-regulated in LNCaP cells versus CL1 cells. Our efforts represent a significant step toward a systems approach to understanding prostate cancer progression.

Cell Line, Tumor↗
PubMed2005

Cystoprostatectomy and neobladder construction for florid cystitis glandularis.

Cystitis glandularis is a benign proliferative disease of the bladder mucosa with a characteristic histopathologic appearance. If a mass lesion is identified, it is resected transurethrally. More extensive surgical management for severe or recurrent cases is poorly characterized in published studies. We present a patient with multiple rapid recurrences of polypoid masses on the trigone causing irritative voiding symptoms. He developed a low-compliance small-capacity bladder and bilateral ureteral obstruction. The patient underwent total cystoprostatectomy with cavernosal nerve sparing and ileal neobladder construction. We advocate such aggressive surgical management in select cases of this disease.

Adenoma, Villous↗
PubMed2004

Phase I study of weekly mitoxantrone and docetaxel before prostatectomy in patients with high-risk localized prostate cancer.

PURPOSE: The purpose is to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of mitoxantrone and docetaxel administered weekly before prostatectomy in men with localized prostate cancer at high risk for recurrence. EXPERIMENTAL DESIGN: Twenty-two patients were treated with four cycles of docetaxel 35 mg/m(2) and increasing doses of mitoxantrone starting at 2 mg/m(2) repeated weekly for 3 weeks of a 4-week cycle before prostatectomy. The MTD was defined as that dose at which fewer than one-third of patients experienced a DLT (>or=grade 4 hematological or >or=>grade 3 nonhematological toxicity). Changes in serum prostate-specific antigen and serum testosterone, and pathological outcome with surgery were secondary endpoints. RESULTS: The MTD for mitoxantrone in combination with this dose of docetaxel was 4 mg/m(2). Neutropenia was the DLT for the combination. Ten of 12 patients treated at the MTD completed the planned 16 weeks of chemotherapy, whereas 2 discontinued therapy early because of toxicity. The median reduction in PSA was 41% (range, 4-88%). Serum testosterone levels remained constant postchemotherapy. CONCLUSIONS: In this patient population, the planned Phase II regimen is 4 mg/m(2) mitoxantrone and 35 mg/m(2) docetaxel weekly for 3 of every 4 weeks. Delivery of this regimen before prostatectomy is feasible with acceptable toxicity. Additional studies are needed to determine whether this combined modality approach will reduce cancer recurrence rates in this high-risk population. Because extent of disease and exposure to prior therapy may impact treatment tolerance these safety data may not be applicable to patients with advanced prostate cancer.

Aged↗
PubMed2004

Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group.

PURPOSE: To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA). RESULTS HYPOTHESIS: A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population. PATIENT POPULATION: The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed. INTERVENTION: Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation. OUTCOMES: An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned. TRIAL DESIGN: The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative. CONCLUSION: Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.

Clinical Trials as Topic↗
PubMed2003

Detection and isolation of prostate cancer cells from peripheral blood and bone marrow.

OBJECTIVES: To detect and isolate disseminated prostate cancer cells because significant effort has been directed toward defining the characteristics of the primary tumor that predict progression, but little progress has been made on evaluating the disseminated prostate cancer cell. Prostate-specific antigen (PSA) reverse transcriptase-polymerase chain reaction results in the bone marrow (BM) and peripheral blood (PB) of men with prostate cancer suggest many have disseminated cancer cells. METHODS: Disseminated epithelial cells were isolated from the BM and PB using Miltenyi antibody-coated paramagnetic microparticle technology. In the two-step selection process, anti-CD45 and anti-CD61 were used for negative selection, and anti-human epithelial antigen was used for positive selection. Cells were then stained for Ber-EP4 (a distinct epitope of the human epithelial antigen) and PSA. PSA reverse transcriptase-polymerase chain reaction was performed on an enriched aliquot. RESULTS: The normal controls were negative. Before prostatectomy, PSA-expressing epithelial cells were detected in 54% of BM and 24% of PB samples. At a median of 4 months after prostatectomy, PSA-expressing cells were detected in 33% of BM and 9% of PB specimens from men without evidence of disease. In men more than 5 years after prostatectomy, PSA-expressing cells were detected in the BM of 4 (29%) of 14, 2 of whom subsequently developed evidence of disease recurrence. CONCLUSIONS: The findings suggest that dissemination of cells is an early event in prostate cancer that is insufficient for the development of metastases. Isolation will allow interrogation of the phenotype and genotype of the cells.

Bone Marrow Cells↗
PubMed2003

Extensive palliative surgery for advanced mesothelioma of the tunica vaginalis.

Malignant mesothelioma of the tunica vaginalis is a rare tumor managed principally by radical surgical resection. Chemotherapy and radiotherapy have limited efficacy. We report on a 67-year-old man with severe debilitation from multiple scrotal and inguinal recurrences of a malignant mesothelioma originating in the right tunica vaginalis. Local pain from extensive tumor spread prevented ambulation. Aggressive surgical debridement (total penectomy and scrotectomy) and perineal urethrostomy afforded the patient significant improvement in his quality of life before he finally died of the disease 3 years after diagnosis.

Aged↗