Biomedical subjects

Jonathan L Wright

Publications and source records attributed to Jonathan L Wright.

14 recordsLinked to original sources

PubMed2026

Evolution and heterogeneity of lethal metastatic bladder cancer subtypes.

Histological variation is a prognostic feature of metastatic urothelial cancer1-3, but its evolutionary trajectory remains poorly defined. We developed a metastatic bladder cancer rapid autopsy programme enriched in histological subtypes4 to profile individuals with terminal disease. Here by reconstructing the evolutionary histories of patient tumours, we show that metastasis-to-metastasis seeding is the dominant pattern of cancer spread and that increased polyclonal migration predicts poor prognosis. The burden, heterogeneity and timing of genomic alterations differ markedly among histological subtypes. Plasmacytoid and neuroendocrine variants develop early driver alterations associated with shorter survival. Mutational signature analyses and experimental models demonstrated that plasmacytoid tumours uniquely use the Fanconi anaemia pathway to mitigate chemotherapy-induced genomic scarring. Single-nucleus profiling revealed mixed cell states in histological subtypes and an association between transcriptional heterogeneity and patient survival. Characterization of the tumour microenvironment uncovered distinct immune states across subtypes, with plasmacytoid tumours exhibiting immune-inflamed profiles, whereas squamous tumours are predominantly immunosuppressive. Last, we demonstrate that post-mortem cell-free DNA captures genomic and transcriptional heterogeneity of the subtypes, which provides a potential strategy for noninvasive assessment of tumour identity and aggressiveness. Our results provide new insights into how tumour heterogeneity shapes the evolutionary history of disease progression in bladder cancer histological subtypes.

Journal Article↗

PubMed2006

An abnormal digital rectal examination is an independent predictor of Gleason > or =7 prostate cancer in men undergoing initial prostate biopsy: a prospective study of 790 men.

OBJECTIVE: To evaluate our experience with a referral population of 790 patients undergoing initial prostate biopsy in the prostate-specific antigen (PSA) era, to assess the role of a digital rectal examination (DRE) in predicting the outcome of prostate needle biopsy (PNB) and to evaluate if DRE findings were associated with cancer grade. PATIENTS AND METHODS: We analysed 790 consecutive men who had an initial PNB from September 1999 to July 2005 by one urologist (C.P.). All data were collected in a prospective database. Multivariate logistic regression analysis was used to determine the relationship between an abnormal DRE and the presence of cancer and cancer grade on PNB. RESULTS: An abnormal DRE was an independent predictor for prostate cancer on multivariate analysis (odds ratio 2.18, 95% confidence interval 1.53-3.10, P < 0.001). In all patients biopsied, an abnormal DRE was associated with a Gleason sum of > or = 7 on multivariate analysis (odds ratio 3.39, 2.07-5.53, P = 0.001). CONCLUSION: A DRE is a useful and important tool to use when assessing patients for a PNB. An abnormal DRE independently predicted high-grade disease in these men. These results might have important implications in the prediction of men with other than indolent prostate cancer.

Adult↗

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

Radiographic and clinical predictors of bladder rupture in blunt trauma patients with pelvic fracture.

RATIONALE AND OBJECTIVES: Bladder rupture is a potentially serious injury in blunt trauma patients. We determined whether location and displacement of pelvic fractures and the degree of hematuria can accurately predict bladder injury. MATERIALS AND METHODS: A retrospective database of 721 blunt trauma pelvic fractures that presented to a single large regional level 1 trauma center between January 1, 1997, and July 15, 2003, was expanded to include data on bladder injury and the initial urinalysis. Multiple logistic regression was performed to determine if an association exists between pelvic fracture pattern, degree of hematuria, and bladder injury. A potential clinical prediction rule was then derived using a point system for four independent, significant risk factors identified from the logistic regression results. RESULTS: There were 37 bladder ruptures (5.0%), all of which presented with hematuria >30 red blood cells per high-powered field (RBC/HPF). Pelvic injuries that were independently associated with bladder injury included diastasis of the pubic symphysis >1 cm, RR = 9.8 (95% CI 4.6-20.9), and fracture of the obturator ring with displacement >1 cm RR = 3.2 (95% CI 1.6-6.5). No patient with isolated acetabular fractures sustained bladder injury. A clinical prediction rule was derived, consisting of a single point for each of the significant pelvic injury sites in patients with hematuria >30 RBC/HPF. Patients with a prediction score of 0 had a 2.3% probability of bladder injury, whereas patients with scores of 1 and 2 had probabilities of bladder injury of 9.2% and 43.7%, respectively. CONCLUSIONS: Patients with isolated acetabular fractures and patients with <30 RBC/HPF did not sustain bladder injury. In addition to hematuria, specific pelvic injury patterns are associated with bladder rupture. If validated, a clinical prediction rule derived from this data has the potential to guide the care of the blunt trauma patient.

Adult↗

PubMed2006

Specific fracture configurations predict sexual and excretory dysfunction in men and women 1 year after pelvic fracture.

PURPOSE: We determined the prevalence and predictors of sexual and excretory dysfunction in patients 1 year after pelvic fracture. MATERIALS AND METHODS: The multicenter Pennsylvania Trauma Outcomes Study enrolled 1,238 patients and contacted them 1 year after injury. Sexual limitations and excretory dysfunction (bladder/bowel incontinence) were defined based on responses from the Functional Capacity Index. Health related quality of life was determined using SF-36. The relationship between specific fracture patterns and dysfunction along with the effect of dysfunction on quality of life in patients with pelvic fracture were evaluated by multivariate analysis. RESULTS: Of 1,160 eligible patients 292 (26%) had pelvic fractures. Sexual dysfunction was reported in 21% vs 14% of those with vs without pelvic fractures and bowel or bladder incontinence was reported in 8% vs 4%. On multivariate analysis men with sacroiliac fractures were at higher risk for sexual (RR 4.0, 95% CI 2.3 to 6.8) and excretory (RR 4.3, 95% CI 1.4 to 13.5) dysfunction. In women symphyseal diastasis was associated with sexual (RR 4.8, 95% CI 2.0 to 11.2) and excretory (RR 12.5, 95% CI 1.9 to 80.2) dysfunction. Of patients with pelvic fractures men with sexual dysfunction and women with excretory dysfunction had significantly worse quality of life than those without dysfunction. CONCLUSIONS: One year after trauma men with sacroiliac fractures and women with symphyseal diastasis were at increased risk for sexual and excretory dysfunction independent of overt pelvic organ injury. In patients with pelvic fracture male sexual dysfunction and female excretory dysfunction were associated with decreased quality of life. Our data highlight the need for further study of dysfunction following pelvic trauma and interventions to decrease the risk of long-term disability.

Coccyx↗

PubMed2006

Intermittent androgen deprivation: clinical experience and practical applications.

Prostate cancer is more frequently being diagnosed at an earlier age, men are dying of prostate cancer at an older age, and men are now treated with androgen deprivation for biochemical relapse. As a result, the amount of time that patients are potentially subjected to androgen deprivation is increasing. Intermittent androgen deprivation (IAD) has been investigated as a potential alternative to continuous androgen deprivation (CAD) in order to improve quality of life and potentially delay the progression to androgen independence. Along with the increased use of primary hormonal therapy in clinically localized prostate cancer, IAD may supplant the traditional surgical or radiotherapy options, specifically in men who have underlying co-morbidities and decreased life expectancy. There are ongoing multi-institutional, randomized trials that will lend insight into the utility, efficacy, and feasibility of IAD versus CAD. This article discusses the theoretical benefits and rationale of IAD and reviews the completed and on-going IAD trials. Finally, the controversies, practical applications, and future directions of IAD are addressed.

Androgen Antagonists↗

PubMed2006

What is the most cost-effective treatment for 1 to 2-cm bulbar urethral strictures: societal approach using decision analysis.

OBJECTIVES: Direct vision internal urethrotomy (DVIU) and urethroplasty are the primary methods of managing urethral stricture disease. Using decision analysis, we determine the cost-effectiveness of different management strategies for short, bulbar urethral strictures 1 to 2 cm in length. METHODS: A decision tree was constructed, with the number of planned possible DVIUs before attempting urethroplasty defined for each primary branch point. Success rates were obtained from published reports. Costs were estimated from a societal perspective and included the costs of the procedures and office visits and lost wages from convalescence. Sensitivity analyses were conducted, varying the success rates of the procedures and cost estimates. RESULTS: The most cost-effective approach was one DVIU before urethroplasty. The incremental cost of performing a second DVIU before attempting urethroplasty was $141,962 for each additional successfully voiding patient. In the sensitivity analysis, urethroplasty as the primary therapy was cost-effective only when the expected success rate of the first DVIU was less than 35%. CONCLUSIONS: The most cost-effective strategy for the management of short, bulbar urethral strictures is to reserve urethroplasty for patients in whom a single endoscopic attempt fails. For longer strictures for which the success rate of DVIU is expected to be less than 35%, urethroplasty as primary therapy is cost-effective. Future prospective, multicenter studies of DVIU and urethroplasty outcomes would help enhance the accuracy of our model.

Cost-Benefit Analysis↗

PubMed2006

Renal and extrarenal predictors of nephrectomy from the national trauma data bank.

PURPOSE: The kidney is injured in 1.4% to 3.0% of all trauma cases. The management of renal injuries is controversial, as reflected in regional and institutional variations in treatment preferences. Using a national trauma database we identified independent risk factors for nephrectomy. MATERIALS AND METHODS: The population was selected from the National Trauma Data Bank, a voluntary data repository containing all trauma admissions to 268 participating trauma centers. Patients with renal injuries were identified by Abbreviated Injury Scale codes. Patient demographic, associated injuries and facility characteristics were recorded. Univariate and Poisson regression analysis with clustering by facility was performed. RESULTS: Renal injury was present in 8,465 patients. Nephrectomy was performed in 4% of all blunt and 21% of all cases of penetrating renal injuries. Only 0.5% of blunt renal injury cases underwent repair compared with 15% of those of penetrating injuries. On multivariate analysis renal injury severity was the strongest predictor of nephrectomy. The relative risk of nephrectomy for grade V renal injuries was 146 (95% CI 74 to 289) and 33 (95% CI 13 to 89) in the blunt and penetrating models, respectively. The need for laparotomy and surgery on other intra-abdominal organs predicted nephrectomy in patients with blunt and penetrating injuries. Hospital trauma designation did not statistically impact nephrectomy rates. CONCLUSIONS: The severity of renal injury based on the AAST organ injury scale for Renal Trauma is the strongest risk factor for nephrectomy. The need for surgery on other intra-abdominal injuries increases the risk of nephrectomy to a lesser extent. In cases of blunt trauma severe renal injury usually necessitates nephrectomy.

Adult↗

PubMed2006

American Association for the Surgery of Trauma Organ Injury Scale for kidney injuries predicts nephrectomy, dialysis, and death in patients with blunt injury and nephrectomy for penetrating injuries.

BACKGROUND: Despite broad clinical use of the American Association of the Surgery of Trauma (AAST) injury scale for kidney, it has only been found to predict the need for renal surgery in single institution series. We sought to validate this scheme for morbidity and mortality in a national cohort of patients with renal injury. METHODS: A retrospective cohort design was used to determine the association between increasing AAST scores and nephrectomy, dialysis, and mortality. The cohort included all patients with a renal injury in the National Trauma Data Bank (NTDB) from 1994 and 2003. Univariate and multivariate prediction models were used for analysis of data. RESULTS: At the time of review, a total of 742,774 patient records were registered in the NTDB. Renal injury occurred in 8465 patients (1.2%). Increasing injury grade was associated with a greater nephrectomy (RR 12-127), dialysis (RR 1.3-4.7), and mortality (RR 1.3-1.9) rate for blunt kidney injury. For penetrating injury, nephrectomy was the only outcome that was associated with higher grades of renal injury with a RR of 7.7 to 31 for grades III to V injuries. CONCLUSION: The AAST injury scale for kidney predicts for morbidity in blunt and penetrating renal injury and for mortality in blunt injury. Thus, we continue to support its use as a clinical and research tool.

Abbreviated Injury Scale↗

PubMed2005

Renal artery pseudoaneurysm after laparoscopic partial nephrectomy.

Delayed bleeding from a renal artery pseudoaneurysm is a rare occurrence after partial nephrectomy. We present 2 cases of renal artery pseudoaneurysm after laparoscopic partial nephrectomy. One patient presented with gross hematuria and flank pain and the other presented with flank pain and a decreasing hematocrit. The patients were treated with selective angioembolization of the pseudoaneurysm. The etiology and management of this potentially life-threatening condition are discussed.

Aneurysm, False↗

PubMed2005

Virtual reality as an adjunctive pain control during transurethral microwave thermotherapy.

The management of pain during clinic transurethral microwave thermotherapy (TUMT) can be challenging. Pain can lead to increased pelvic blood flow, which dissipates the energy delivered, limiting the amount of heat delivered to the prostate. In this report, we describe the novel use of virtual reality distraction as an adjunctive mechanism for local anesthesia during TUMT in a 67-year-old man. This report is novel in being, to our knowledge, the first to demonstrate the efficacy of virtual reality in an elderly patient and the first documented use for a urologic clinic procedure. We believe it is also the first to demonstrate efficacy for the control of thermally induced pain.

Aged↗

PubMed2005

Laparoscopic partial nephrectomy: comparison of transperitoneal and retroperitoneal approaches.

PURPOSE: Laparoscopic partial nephrectomy has become an effective alternative for small renal tumors. Previous reports include transperitoneal and retroperitoneal approaches but to our knowledge the indications for when to apply the techniques have not been defined. We report our experience with comparing the 2 techniques. MATERIALS AND METHODS: A retrospective review of 51 laparoscopic partial nephrectomies was performed. Patients were analyzed based on the surgical approach, operative parameters and postoperative recovery. The 2 approaches used similar operative techniques to control parenchymal bleeding and collecting system entry. RESULTS: There were 32 retroperitoneal and 19 transperitoneal partial nephrectomies. Mean operative time (3.5 vs 5.4 hours, p = 0.000001) and blood loss (192 vs 403 cc, p = 0.002) was significantly less for the retroperitoneal approach. Renal vessel clamping was performed in 81% of retroperitoneal and 63% of transperitoneal operations. Warm ischemia time was not significantly different between the groups. Patients undergoing the retroperitoneal approach had a statistically significant decrease in time to tolerating a regular diet (1.2 vs 1.7 days, p = 0.02), catheter removal (1.4 vs 2.5 days, p = 0.004) and discharge home (2.3 vs 3.6 days, p = 0.0008). CONCLUSIONS: Based on tumor location as the selection criteria the retroperitoneal approach was associated with shorter operative time, less blood loss, more rapid return of bowel function and shorter hospitalization compared with those in patients selected for the transperitoneal technique. Based on our experience we believe that the decision on the approach should be based on the tumor location on the kidney surface. For polar or posterolateral masses the retroperitoneal approach is preferred. The transperitoneal approach is best suited to anterior and medial lesions.

Blood Loss, Surgical↗

PubMed2005

Tumor lysis syndrome in a patient with metastatic, androgen independent prostate cancer.

Tumor lysis syndrome (TLS) is an uncommon, but well described, clinical entity that typically occurs following chemotherapy in patients with rapidly growing hematological malignancies. It is rarely described in patients with solid tumors. We report a case of TLS in a patient with metastatic adenocarcinoma of the prostate after treatment with paclitaxel chemotherapy.

Adenocarcinoma↗

PubMedDate not supplied

Improved prostate cancer detection with anterior apical prostate biopsies.

PURPOSE: Research to improve prostate cancer detection with transrectal ultrasound-guided prostate biopsies has focused on increasing the number of cores and the directing of biopsies laterally. In this study, we describe our experience with the addition of anterior apical biopsies. MATERIALS AND METHODS: A total of 164 consecutive patients with an increased or increasing prostate-specific antigen and/or abnormal digital rectal examination underwent transrectal ultrasound and systematic biopsy. We performed our standard laterally directed sextant biopsies plus additional mid parasagittal plane biopsies at the base and mid-gland, and an anteriorly directed biopsy at the apex. Site-specific detection and tumor characteristics are reported. RESULTS: Prostate cancer was detected in 71 patients (43.3%). The most commonly unique site was the anterior apex. Excluding these biopsies would have missed 17% of the cancers detected. The cancers limited to the anterior apex had tumor characteristics similar to all other cancers detected. CONCLUSION: In our experience, the anterior apical biopsies increase the detection of prostate cancer on transrectal ultrasound-guided biopsies. Further study on incorporating this site into the biopsy scheme is indicated.

Adenocarcinoma↗