Biomedical subjects

Edward Messing

Publications and source records attributed to Edward Messing.

13 recordsLinked to original sources

PubMed2006

Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial.

CONTEXT: Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. OBJECTIVE: To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer. DESIGN, SETTING, AND PATIENTS: Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. INTERVENTION: Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). MAIN OUTCOME MEASURES: Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. RESULTS: Among the 425 men, median follow-up was 10.6 years (interquartile range, 9.2-12.7 years). For metastasis-free survival, 76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% CI, 0.58-1.09; P = .16). PSA relapse (median PSA relapse-free survival, 10.3 years for radiotherapy vs 3.1 years for observation; HR, 0.43; 95% CI, 0.31-0.58; P<.001) and disease recurrence (median recurrence-free survival, 13.8 years for radiotherapy vs 9.9 years for observation; HR, 0.62; 95% CI, 0.46-0.82; P = .001) were both significantly reduced with radiotherapy. Adverse effects were more common with radiotherapy vs observation (23.8% vs 11.9%), including rectal complications (3.3% vs 0%), urethral strictures (17.8% vs 9.5%), and total urinary incontinence (6.5% vs 2.8%). CONCLUSIONS: In men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00394511.

Adult↗

PubMed2006

Surveillance for recurrent bladder cancer using a point-of-care proteomic assay.

CONTEXT: At least 50% of patients with a history of bladder cancer have recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but can fail to detect some bladder cancers, so a urine test is frequently part of the evaluation. OBJECTIVE: To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could improve detection of recurrence during monitoring of patients with a history of bladder cancer. DESIGN, SETTING, AND PATIENTS: From September 2001 to February 2002, 23 academic, private practice, and hospital facilities in 9 US states prospectively enrolled 668 consecutive patients with a history of bladder cancer in this cross-sectional study. Patients provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. MAIN OUTCOME MEASURES: Diagnosis of bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. RESULTS: Bladder cancer was diagnosed in 103 patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95% confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P = .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during initial cystoscopy, including 7 that were high-grade. The sensitivity and specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and 87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only 3 of the malignancies missed during initial cystoscopy and did not significantly increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08). CONCLUSION: The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the ability to detect recurrent bladder cancer, with test results available during the patient visit.

Adult↗

PubMed2006

Randomized prospective phase III trial of difluoromethylornithine vs placebo in preventing recurrence of completely resected low risk superficial bladder cancer.

PURPOSE: Ornithine decarboxylase catalyzes the rate limiting step in polyamine synthesis and its activity can be inhibited by difluoromethylornithine, which has been shown in preclinical studies, to prevent bladder cancer. MATERIALS AND METHODS: To assess the ability of difluoromethylornithine to prevent recurrence of low risk superficial bladder cancer, 454 patients with newly diagnosed (283) or occasionally recurrent (171), stage Ta (425) or T1 (29), grade 1 (263) or grade 2 (191), completely resected urothelial cancer were randomized to receive 1 gm difluoromethylornithine daily or placebo for 1 year. Patients were followed with cystoscopy every 3 months for 2 years and then semiannually for 2 years or until first recurrence. Index and recurrent tumors underwent central pathology review. RESULTS: No serious drug related toxicities were seen in either arm. Two patients died of bladder cancer at 2 and 4 years after randomization, both in the difluoromethylornithine arm. At 42 months followup, 103 patients in the difluoromethylornithine arm (46%) and 97 in the placebo arm (43%) (p = 0.30) experienced at least 1 tumor recurrence. Over 73% of recurrences occurred within 1 year in each arm. Each arm had similar responses for each stratification factor. During the 42 months of followup, 10 (4.4%) difluoromethylornithine and 9 (3.9%) placebo treated patients had progression to TIS or grade 3 disease, and 2 (0.9%) in the difluoromethylornithine arm and none in the placebo arm developed stage T2+ cancers. CONCLUSIONS: A year of difluoromethylornithine did not prevent recurrence of completely resected low risk superficial bladder cancer, when started shortly after surgery.

Aged↗

PubMed2006

Transrectal sonography in prostate evaluation.

Prostate cancer is the most prevalent newly diagnosed noncutaneous malignancy in men. With the continued use of prostate-specific antigen screening, there has been a dramatic rise in the number of prostate biopsied performed. Transrectal ultrasonography (TRUS) is an essential tool used for detecting prostate pathology and performing prostate biopsies. This article review the indications and principles of TRUS of the prostate, the technique of TRUS, and controversies pertaining to prostate core biopsy.

Biopsy↗

PubMed2006

Hybrid dosimetry: feasibility of mixing angulated and parallel needles in planning prostate brachytherapy.

Pubic arch interference (PAI) often caused inadequate prostate coverage during transperineal brachytherapy using all parallel needles. In this paper, a hybrid implantation approach is presented in which additional angulated needles can be used to avoid PAI. This approach can be applied in prostate brachytherapy using a robotic assisted device. To examine the feasibility of this approach, volume data from three prostate seed implant patients were selected, which represent small, medium, and large prostates. As the blocking area was artificially increased simulating pubic arch overlap, the dosimetry outcomes and ratio of number of angulated needles to the total number of needles were analyzed. The hybrid dosimetry broke down when blocking is over 42%. As the percent of blocking increased, the ratio of the number of angulated needles to the total number of needles increased, while the dosimetry outcomes only had a slight trend of worsening. When close to the breakdown point, the dosimetry outcomes worsen drastically. Therefore, for moderate PAI the hybrid dosimetry is feasible.

Brachytherapy↗

PubMed2006

Vivo motion and force measurement of surgical needle intervention during prostate brachytherapy.

In this paper, we present needle insertion forces and motion trajectories measured during actual brachytherapy needle insertion while implanting radioactive seeds in the prostate glands of 20 different patients. The needle motion was captured using ultrasound images and a 6 degree-of-freedom electromagnetic-based position sensor. Needle velocity was computed from the position information and the corresponding time stamps. From in vivo data we found the maximum needle insertion forces to be about 15.6 and 8.9 N for 17 gauge (1.47 mm) and 18 gauge (1.27 mm) needles, respectively. Part of this difference in insertion forces is due to the needle size difference (17G and 18G) and the other part is due to the difference in tissue properties that are specific to the individual patient. Some transverse forces were observed, which are attributed to several factors such as tissue heterogeneity, organ movement, human factors in surgery, and the interaction between the template and the needle. However, theses insertion forces are significantly responsible for needle deviation from the desired trajectory and target movement. Therefore, a proper selection of needle and modulated velocity (translational and rotational) may reduce the tissue deformation and target movement by reducing insertion forces and thereby improve the seed delivery accuracy. The knowledge gleaned from this study promises to be useful for not only designing mechanical/robotic systems but also developing a predictive deformation model of the prostate and real-time adaptive controlling of the needle.

Brachytherapy↗

PubMed2005

Detection of bladder cancer using a point-of-care proteomic assay.

CONTEXT: A combination of methods is used for diagnosis of bladder cancer because no single procedure detects all malignancies. Urine tests are frequently part of an evaluation, but have either been nonspecific for cancer or required specialized analysis at a laboratory. OBJECTIVE: To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could enhance detection of malignancy in patients with risk factors or symptoms of bladder cancer. DESIGN, SETTING, AND PATIENTS: Twenty-three academic, private practice, and veterans' facilities in 10 states prospectively enrolled consecutive patients from September 2001 to May 2002. Participants included 1331 patients at elevated risk for bladder cancer due to factors such as history of smoking or symptoms including hematuria and dysuria. Patients at risk for malignancy of the urinary tract provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. MAIN OUTCOME MEASURES: The diagnosis of bladder cancer, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to cancer detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. RESULTS: Bladder cancer was diagnosed in 79 patients. The NMP22 assay was positive in 44 of 79 patients with cancer (sensitivity, 55.7%; 95% confidence interval [CI], 44.1%-66.7%), whereas cytology test results were positive in 12 of 76 patients (sensitivity, 15.8%; 95% CI, 7.6%-24.0%). The specificity of the NMP22 assay was 85.7% (95% CI, 83.8%-87.6%) compared with 99.2% (95% CI, 98.7%-99.7%) for cytology. The proteomic marker detected 4 cancers that were not visualized during initial endoscopy, including 3 that were muscle invasive and 1 carcinoma in situ. CONCLUSION: The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the accuracy of cystoscopy, with test results available during the patient visit.

Adult↗

PubMed2005

Bouquet brachytherapy: feasibility and optimization of conically spaced implants.

PURPOSE: To examine the dosimetric feasibility of a conical implantation approach to robotic-assisted prostate brachytherapy. METHODS AND MATERIALS: An in-house inverse planning software based on the genetic algorithm (GA) was used to optimize the needle angulations and the seed positions along needles that form one or two bouquets. Volume data from 20 prostate seed implant patients (six 125I and 14 103Pd) previously treated using the conventional rectilinear template approach were used. The dosimetry outcomes of the optimized treatment plan in the conical approach were compared with those from the original treatment plans based on the conventional rectilinear template approach. RESULTS: When seed spacing is restricted to nominal 1 cm center-to-center spacing, dosimetry results in the conical approach suffer from a higher urethra dose and higher dose heterogeneity compared with the original rectilinear template plans. When the seed loading patterns are optimized as part of inverse planning, the resulting dosimetry plans exhibit adequate dose coverage and uniformity through the target volume, as well as satisfactory sparing of the urethra and rectum. CONCLUSIONS: Conically spaced implantation for prostate brachytherapy with 125I and 103Pd seeds is feasible in terms of dosimetry outcomes. Techniques for optimized inverse planning for this approach have been developed.

Brachytherapy↗

PubMed2005

Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers.

This is the first of 2 articles that summarize the findings of the International Consensus Panel on cytology and bladder tumor markers. The objectives of our panel were to reach a consensus on the areas where markers are needed, to define the attributes of an ideal tumor marker, and to identify which marker(s) would be suitable for diagnosis and/or surveillance of bladder cancer. Our panel consisted of urologists and researchers from Europe, Asia, and the United States who reviewed original articles, reviews, and book chapters on individual bladder tumor markers published in the English language mainly using the PubMed search engine. Panel members also met during 3 international meetings to write recommendations regarding bladder tumor markers. The panel found that the most practical use of noninvasive tests is to monitor bladder cancer recurrence, thereby reducing the number of surveillance cystoscopies performed each year. Markers also may be useful in the screening of high-risk individuals for early detection of bladder cancer. However, more prospective studies are needed to strengthen this argument. Case-control and cohort studies show that several markers have a higher sensitivity to detect bladder cancer. However, cytology is the superior marker in terms of specificity, although some markers in limited numbers of studies have shown specificity equivalent to that of cytology. Our panel believes that several bladder tumor markers are more accurate in detecting bladder cancer than prostate-specific antigen (PSA) is in detecting prostate cancer. However, bladder tumor markers are held to a higher standard than PSA. Therefore, use of bladder tumor markers in the management of patients with bladder cancer will require the willingness of both urologists and clinicians to accept them.

Biomarkers, Tumor↗

PubMed2005

Prognostic markers for bladder cancer: International Consensus Panel on bladder tumor markers.

The International Consensus Panel on cytology and bladder tumor markers evaluated markers that have the ability to predict tumor recurrence, progression, development of metastases, or response to therapy or patient survival. This article summarizes those findings. The panel mainly reviewed articles listed in PubMed on various prognostic indicators for bladder cancer. Based on these studies, most of which were case-control retrospective studies, various prognostic indicators were classified into 6 groups: (1) microsatellite-associated markers, (2) proto-oncogenes/oncogenes, (3) tumor suppressor genes, (4) cell cycle regulators, (5) angiogenesis-related factors, and (6) extracellular matrix adhesion molecules. The panel concluded that although certain markers, such as Ki-67 and p53, appear to be promising in predicting recurrence and progression of bladder cancer, the data are still heterogeneous. The panel recommends that identifying definitive criteria for test positivity, a clearly defined patient population, standardization of techniques used to evaluate markers, and clearly specified endpoints and statistical methods will help to bring accurate independent prognostic indicators into the clinical management of patients with bladder cancer.

Angiogenic Proteins↗

PubMed2004

Is there a favorable subset of patients with prostate cancer who develop oligometastases?

OBJECTIVE: To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions. METHODS AND MATERIALS: The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival. RESULTS: The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with < or =5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with < or =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively). CONCLUSIONS: Patients with < or =5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.

Aged↗

PubMed2003

Automatic localization of implanted seeds from post-implant CT images.

An automatic localization method of implanted seeds from a series of post-implant computed tomography (CT) images is described in this paper. Post-implant CT studies were obtained for patients who underwent prostate brachytherapy. Bright areas were segmented using binary thresholding in each CT slice, and geometrical information on these areas was collected. Large areas (possibly containing two connected seeds) were split into smaller ones by geometry-based filtering in each slice. The area connectivity along the longitudinal direction was analysed using a geometry-based connection search algorithm executed on every area slice by slice, so that the connected areas were combined into one object. The weighted centroid of each object was taken as the seed position. This method was tested on a seed-containing prostate phantom as well as using CT studies from patients. Statistical analysis demonstrates that it can achieve above 99% detection rate with reliable localization accuracy and high speed. It is reliable and convenient for localizing implanted seeds on CT and can be used to assist post-implant dosimetry for prostate brachytherapy.

Algorithms↗

PubMedDate not supplied

The timing of hormone therapy for men with asymptomatic advanced prostate cancer.

The most appropriate time to introduce hormonal therapy for patients with advanced prostate cancer is a contentious issue. Recent prospective studies comparing immediate and deferred hormonal therapy (medical or surgical castration) on survival outcome are reviewed with the aim of redefining the most appropriate time to initiate hormonal therapy for individual patients. The evidence supports the use of immediate hormonal therapy in previously untreated patients with advanced disease (M1) and also the use of adjuvant hormonal therapy after radical prostatectomy and lymphadenectomy for node-positive (but clinically localized) disease. Immediate hormonal therapy may also be advantageous in advanced local/regional disease when it is the primary treatment contemplated (i.e., without any definitive curative therapy to the prostate), although not all studies show this. Adjuvant hormonal therapy has significantly improved survival in some studies in the radiotherapy setting; the lack of statistically significant benefits in other studies may be a result of the timing of hormonal therapy in relation to the administration of external beam irradiation. Decisions on the immediate initiation of hormonal therapy should also take into account the patient's life expectancy and the side effects and long-term complications of androgen deprivation therapy. Recent epidemiological studies indicate that prostate cancer mortality has fallen in the USA. This decline in prostate cancer mortality is likely to be multifactorial with early application of hormonal therapy being one potential contributory factor. It is recommended that after an assessment of their disease risk, patients should be informed about the benefits and side effects of all potential treatment options and allowed to make an informed choice about their treatment.

Antineoplastic Agents, Hormonal↗