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Peter E Clark

Publications and source records attributed to Peter E Clark.

31 records · Page 2Linked to original sources
PubMed2004

Utility of frozen section analysis of resection margins during partial nephrectomy.

OBJECTIVES: To evaluate the utility of routine intraoperative frozen-section histologic analysis during partial nephrectomy to ensure negative surgical margins. Partial nephrectomy has gained acceptance for surgical treatment of small renal cancers. Many surgeons send specimens for intraoperative frozen section histologic analysis to ensure negative margins. METHODS: We reviewed the records of 78 patients who underwent partial nephrectomy for presumed malignancy. Patient demographics, intraoperative findings, and pathologic and clinical outcomes were analyzed. RESULTS: Seventy-nine partial nephrectomies were performed in 78 patients. Frozen sections were obtained intraoperatively in 76 cases. In 1 case (1.3%), a single margin was interpreted as positive for carcinoma, prompting deeper resection. The final histopathologic finding was interpreted as angiomyolipoma rather than carcinoma. The final pathologic examination revealed renal cell carcinoma in 52 (66%) of 79 cases. The mean oncologic follow-up was 16.2 months. One local recurrence was noted (1.9%). It arose in the resection bed 19 months after removal of a 4.5-cm tumor (pathologic Stage T3a). Both intraoperative frozen section margins and final pathologic margins were negative in this case. One patient developed pulmonary metastases and represented the only metastatic recurrence, as well as the only cancer-related death in our cohort (1.9%). CONCLUSIONS: Our data suggest that when partial nephrectomy is performed with attention to excising a perimeter of grossly normal-appearing parenchyma, sending specimens for intraoperative frozen section analyses may provide an unnecessary expense without providing meaningful, reliable information. Additional studies, including larger cohorts and extended follow-up, are needed to support these results.

Adenoma, Oxyphilic↗
PubMed2004

Bladder cancer.

PURPOSE OF REVIEW: This article reviews recent advances in the diagnosis and management of bladder cancer. RECENT FINDINGS: Bladder cancer is a significant cause of morbidity and mortality. Recent research has attempted to improve the care of patients with this disease. Evidence suggests that bacillus Calmette-Guerin is the most effective intravesical therapy for the treatment of superficial bladder cancer and that maintenance therapy is superior to an induction course alone. In patients with muscle-invasive disease, nodal status and extent of lymphadenectomy have been shown to correlate with survival after radical cystectomy. The role of chemotherapy in the treatment of bladder cancer continues to evolve as well. Neoadjuvant chemotherapy has recently demonstrated a survival benefit, and trials are ongoing to define the optimal regimen of chemotherapy for urothelial carcinoma. SUMMARY: Improved understanding and advancements in the management of all stages of bladder cancer continue to improve the care of patients with this disease.

Humans↗
PubMed2004

Microscopic and gross extravesical extension in pathological staging of bladder cancer.

PURPOSE: We evaluated clinical outcomes in patients with pathological microscopic (pT3a) and gross (pT3b) extravesical tumor extension with transitional cell carcinoma (TCC) of the bladder following radical cystectomy. MATERIALS AND METHODS: A total of 236 patients, including 173 males (73%) and 63 females, underwent radical cystectomy for pathological primary bladder TCC with extravesical extension (pT3), of whom 69 (29%) had pT3a and 167 (71%) had pT3b disease. At a median followup of 8.9 years (range 0 to 19.4) lymph node involvement, local and distant recurrences, and clinical outcomes were determined. RESULTS: Of the 236 patients with pT3 tumors 106 (45%) had lymph node positive disease, including 34 of 69 (49%) with pT3a and 72 of 167 (43%) with pT3b disease. The 10-year recurrence-free survival rate for patients with pT3a tumors was 48% compared with 47% for those with pT3b disease (p = 0.89). Recurrence-free survival was significantly better in patients with lymph node negative disease than in those with positive lymph nodes irrespective of the extent of extravesical involvement (pT3a vs pT3b). Local pelvic recurrence developed in 13 of the 236 patients (6%), while 84 (36%) had distant metastatic disease. Of the patients with recurrence, the type of recurrence (local or distant) was not associated with tumor stage (pT3a vs pT3b, p = 0.71). Lymph node involvement was a significant risk factor for distant tumor recurrence (p <0.001). CONCLUSIONS: Differentiating between microscopic (pT3a) and gross (pT3b) extravesical tumor involvement of TCC as outlined in the revised 1997 TNM staging system does not appear to have prognostic significance.

Adult↗
PubMed2004

The management of urethral transitional cell carcinoma after radical cystectomy for invasive bladder cancer.

PURPOSE: Previous reports have identified risk factors for urethral recurrence following radical cystectomy for transitional cell carcinoma (TCC). However, reports of the clinical presentation, treatment and outcome in these patients are lacking. We report our experience with the diagnosis, management and outcome of urethral TCC after radical cystectomy for bladder cancer. MATERIALS AND METHODS: A database of 1,054 patients who underwent radical cystectomy and urinary diversion for TCC from 1971 to 1997 was retrospectively reviewed. All patients with urethral TCC after surgery were identified. RESULTS: Urethral TCC was diagnosed in 47 men a median of 18.5 months (range 2 to 116) after cystectomy with 20 (42%) diagnosed within 1 year. Symptomatic recurrence developed in 24 of 42 evaluable patients (57%), 21 had bloody urethral discharge and 7 had pain or a palpable mass. A total of 13 patients (31%) were asymptomatic with abnormal cytology. The remaining 5 patients underwent prophylactic urethrectomy based on cystectomy pathology. Overall 41 patients underwent urethrectomy, which was total in 36 and distal with perineal urethrostomy in 5, including later conversion to total urethrectomy in 2. Overall at a median followup of 26 months (range 3 to 275) since diagnosis 36 of 47 patients (76%) were dead, including 25 of metastatic disease. Only 10 patients (21%) remained disease-free. Median overall survival in patients with urethral TCC after radical cystectomy was only 28 months after the diagnosis of urethral TCC. Urethral stage (superficial vs invasive disease) at diagnosis was the most import predictor of overall survival in this cohort of patients. CONCLUSIONS: Most patients with urethral recurrence present with symptoms. However, screening cytology alone still detects a significant proportion. The median survival of patients with urethral TCC after radical cystectomy is only 28 months after diagnosis. Urethral stage (superficial vs invasive disease) at diagnosis is the most import predictor of overall survival in this cohort of patients.

Adult↗
PubMed2004

Percutaneous CT-guided radiofrequency ablation of renal neoplasms: factors influencing success.

OBJECTIVE: The objective of our study was to evaluate the success rate for radiofrequency ablation of renal tumors and to determine the risk of serious complications. CONCLUSION: No serious complications occurred after 27 CT-guided radiofrequency ablation sessions in 22 patients. In total, no residual tumor was detected on follow-up contrast-enhanced CT or MRI 1-35 months (mean, 7 months) after final tumor ablation in 20 (91%) of 22 patients. Two patients with residual viable tumor deferred further treatment. Complete tumor ablation was achieved after a single treatment session in 83% of patients, and in 8% of patients after subsequent ablation sessions. Size was the major determinant for achieving tumor eradication with a single session of ablation, with all 11 tumors 3 cm or smaller being completely ablated after one session. Tumor location, histology, and the presence of renal disease did not correlate with treatment success. Contrast-enhanced CT performed immediately after ablation is reliable to exclude residual viable tumor. CT-guided radiofrequency ablation of renal tumors is safe and has a high rate of success in the treatment of small renal tumors, with no evidence of recurrence at midterm follow-up of treated patients.

Aged↗
PubMed2003

Natural history of surgically treated bladder carcinoma with extravesical tumor extension.

BACKGROUND: The current TNM classification for bladder carcinoma stratifies extravesical extension into microscopic (pT3a) and macroscopic (pT3b) tumor involvement. The authors evaluated the outcomes of patients with pT3a and pT3b disease after radical cystectomy. METHODS: Patients (n = 129) with transitional cell carcinoma of the bladder treated with radical cystectomy alone demonstrated pathologic extravesical tumor extension: 37 (29%) had pT3a disease and 92 (71%) had pT3b disease. No patient received any adjuvant therapy. With a median follow-up of 13.6 years, the presence of lymph node involvement, margin positivity, local (pelvic) and distant disease recurrence, and clinical outcomes were determined. RESULTS: Of the 129 patients, 43 (33%) had lymph node tumor involvement: 13 of 37 patients with pT3a disease (35%) and 30 of 92 patients with pT3b disease (33%). The 10-year recurrence-free and overall survival for the entire group was 54% and 20%, respectively. No statistical difference between pT3a and pT3b disease was observed with regard to recurrence-free (P = 0.54) and overall (P = 0.66) survival. Lymph node involvement was predictive of a significantly worse 10-year recurrence-free survival (32%) compared with lymph node-negative disease (60%; P = 0.003). Local disease recurrence was reported to occur in 12 patients (9%), whereas 37 patients (29%) were reported to develop distant metastases. Among those who had disease recurrence, the type of disease recurrence (local or distant) was not found to be associated with tumor stage (pT3a vs, pT3b, P = 0.47). CONCLUSIONS: This cohort of surgically managed patients provided insight into the long-term natural history of pathologically confirmed extravesical bladder carcinoma after radical cystectomy. There was no important difference in the incidence of lymph node involvement, survival rates, and disease recurrence rates between patients with microscopic and macroscopic extravesical extension. Adjuvant protocols should be undertaken for these high-risk patients to further improve on these clinical outcomes.

Adult↗
PubMed2003

Bladder cancer.

Bladder cancer is a significant public health problem responsible for more than 130,000 deaths annually worldwide. Disease prevalence is also remarkable, with more than 500,000 patients carrying the diagnosis in the United States alone. Significant progress has been made in understanding the underlying molecular and genetic events in bladder cancer. However, there remains a great need for the development of reliable markers that can provide clinically useful information regarding diagnosis and prognosis and to facilitate the selection of appropriate therapy in the individual patient. Ongoing and future investigation is anticipated to refine treatment of patients with high-risk superficial disease, to determine the role of neoadjuvant and adjuvant chemotherapy for high-risk invasive disease, and to improve the efficacy of chemotherapy for patients with metastatic bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Prostate cancer and bone metastases: medical treatment.

Prostate cancer is the most common malignancy in men in the United States. With the long natural history of the disease, management of skeletal morbidity related to advanced prostate cancer becomes a major public health issue. The standard of care in advanced prostate cancer is androgen deprivation therapy. This may accelerate the development of osteoporosis and further exacerbate the risks of having adverse skeletal-related events develop. Recently, the use of bisphosphonates in men who have not responded to androgen deprivation therapy has been shown to reduce the incidence of skeletal-related events with time. Questions remain as to whether bisphosphonates should be broadly applied to earlier stages of the disease or tailored to men at higher risk of having bone-related morbidity. Work is ongoing to improve other approaches to the medical treatment of bone metastases in patients with advanced prostate cancer including the use of radiopharmaceuticals and combined chemotherapy.

Antineoplastic Agents, Hormonal↗
PubMed2003

Androgen receptor activity at the prostate specific antigen locus: steroidal and non-steroidal mechanisms.

Ligand-activated androgen receptors (ARs) occupy target genes and recruit histone modifiers that influence transcriptional competency. In LNCaP prostate cancer cells, the natural ligand 5alpha-dihydrotestosterone (DHT) activates transiently transfected AR-responsive promoter constructs; concurrent treatment with the protein kinase A activator forskolin enhanced AR stimulation induced by DHT. Additional treatment with the cytokine IL-6, purportedly an AR activator, markedly inhibited receptor activity. To assess AR activity on natural chromatin-integrated promoters/enhancers, we determined AR occupancy of the endogenous prostate specific antigen (PSA) promoter/enhancer as well as PSA expression in LNCaP cells treated with DHT; AR occupancy of the PSA enhancer was rapid (within 1 h of stimulation), robust (10-fold over background), and sustained (8-16 h). In contrast, AR occupancy of the PSA promoter was only increased by 2-fold. Histone H3 acetylation at both the enhancer and promoter was evident 1-2 h after DHT treatment. Detectable pre- and mature PSA mRNA levels appeared after 1 and 6 h treatment, respectively. Substantial qualitative and quantitative differences in PSA expression and AR occupancy of the PSA enhancer were observed when DHT-induced and ligand-independent activations of the AR were compared; forskolin stimulated PSA mRNA and protein expression, whereas IL-6 inhibited both DHT- and forskolin-stimulated expression. IL-6 did not diminish DHT-dependent AR occupancy of the PSA enhancer but inhibited CBP/p300 recruitment, histone H3 acetylation, and cell proliferation. These findings provide a contextual framework for interpreting the contribution of non-steroidal activation of the AR to signaling in vivo, and have implications for prostate cancer cell growth.

Acetylation↗
PubMed2002

Urinary diversion after radical cystectomy.

At most centers with experience in urinary diversion, an orthotopic urinary reservoir is the diversion of choice after radical cystectomy for bladder cancer. The paradigm has shifted in the past 10 years from actively looking for reasons to do an orthotopic diversion to carefully considering why a patient cannot undergo reconstruction to their native urethra. In our institution, any patient who is to undergo a radical cystectomy for bladder cancer is a potential candidate for orthotopic diversion provided they do not have chronic renal insufficiency. In addition, they must have a negative urethral margin on frozen section at the time of cystectomy, and have the mental and physical capacity to understand what is required to manage the reservoir after surgery. Proper patient selection is the key to success. Notably, chronologic age is not an absolute contraindication to orthotopic diversion. Instead, careful consideration of the patient's comorbid conditions should guide eligibility. In addition, locally advanced disease is not a contraindication to an orthotopic diversion. To have the flexibility to manage whatever situation presents itself intraoperatively, the surgeon performing a urinary diversion after radical cystectomy must be facile with several diversion techniques. At the very least, the surgeon must be comfortable with one type of each major form of urinary diversion, a conduit (incontinent) diversion, a continent cutaneous diversion, and an orthotopic diversion. As a result, radical cystectomy and urinary diversion should be performed at centers with significant experience in all three types of diversions.

Cystectomy↗
PubMedDate not supplied

Prognostic significance of clinicopathologic and deoxyribonucleic acid flow cytometric variables in non-metastatic renal cell carcinoma in the modern era.

OBJECTIVE: The prognostic value of deoxyribonucleic acid (DNA) ploidy in renal cell carcinoma (RCC) is not well-defined among modern surgical nephrectomy series. We sought to determine which variables correlated with overall survival and recurrence-free survival in the modern era. METHODS: We reviewed all patients from 1992 to 2000, who prospectively had DNA ploidy analysis of their primary tumor determined at the time of nephrectomy for nonmetastatic RCC. Variables examined included age, gender, ethnicity, presentation (incidental vs. symptomatic), preoperative laboratory studies, American Society for Anesthesiology class, tumor size, tumor-nodes-metastasis stage, histology, Fuhrman grade, and diploid versus nondiploid tumor. Statistical analyses of overall survival and recurrence-free survival were performed using the Kaplan-Meier method, log-rank test, and Cox regression model using commercially available software. RESULTS: Sixty men and 41 women, median age 61 years (range, 23-85), were included. Pathologic stage included T1 (54 patients), T2 (14), and T3 (33). Eighty-four patients had conventional RCC. A total of 58 patients had well-differentiated (Fuhrman Grade 1 [12] or Grade 2 [46]), 28 had moderately differentiated (Grade 3), 12 had poorly differentiated tumors (Grade 4), and 3 were not specified. There were 52 patients who had diploid tumors, and 49 had aneuploid tumors. Median follow-up was 39 months (range, 0-109). Actuarial 5-year overall survival was 70%, and 5-year recurrence-free survival was 76%. Diploid tumors were significantly associated with better recurrence-free survival (P = 0.02) but not overall survival (P = 0.17). On multivariate analysis, the American Society for Anesthesiology class (P = 0.01), abnormal preoperative platelet count (P = 0.03), and tumor differentiation (P = 0.01) were independent predictors of overall survival, whereas only tumor differentiation (P = 0.05) was an independent predictor of recurrence-free survival. CONCLUSIONS: In the modern era, DNA ploidy is not an independent predictor of either overall survival or recurrence-free survival in patients with nonmetastatic RCC. The most important predictor of recurrence-free survival is tumor differentiation.

Adult↗