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Biomedical subjects

F F Marshall

Publications and source records attributed to F F Marshall.

At least 55 records · Page 3Linked to original sources

Distal nephron renal tumors: microsatellite allelotype.

Tumors of varying malignant potential arise from the complex epithelial lining of the nephron. Although the molecular characteristics of renal clear cell carcinomas, which arise from the proximal tubule, have been studied, little is known about tumors that develop from other parts of the renal tubular system. To elucidate common molecular lesions that may contribute to the development or progression of nonproximal tubule renal tumors, we performed a detailed microsatellite allelotype of lesions thought to arise from the renal collecting duct. Eighteen collecting duct carcinomas (CDCs) and 13 renal oncocytomas were studied using highly informative microsatellite markers on all autosomal arms. Loss of heterozygosity (LOH) was identified on multiple chromosomal arms in CDCs and renal oncocytomas. Microsatellite analysis revealed LOH of 1q in 57% of informative CDCs. LOH was also observed on arms 6p (45%), 8p (40%), and 21q (40%). In renal oncocytomas, LOH of 1q occurred in approximately 30% of tumors, but 1p LOH was observed in 57% of informative cases analyzed. High levels of LOH were also observed on arms 8p, 14q, 19q, and 21q in the oncocytomas studied. Loss of chromosomal arm 3p was infrequent in both tumor types. Our results suggest that the molecular events that contribute to the development of distal nephron tumors are distinct from those associated with the etiology of proximal tubule renal cancers.

Adenoma, Oxyphilic↗

High-intensity focused ultrasound ablation of rabbit kidney tumors.

High-intensity focused ultrasound (HIFU) is a noninvasive surgical technique in which ultrasound energy is delivered transcutaneously to a discrete area within the body. This energy can result in a well-defined zone of cellular death within the targeted tissue. We used HIFU in an effort to ablate rabbit VX-2 kidney tumors. A tumor cell suspension was injected into a renal segmental artery (Phase 1, nine rabbits) or directly into the lower pole parenchyma (Phase 2, nine rabbits). After a 2-week incubation period, open direct contact (Phase 1) or transcutaneous ablation (Phase 2) was performed. In Phase 1, after sonablation, there was pathologic evidence of tissue destruction in nine animals, and seven had both gross and histologic evidence of tumor ablation. There was sharp demarcation between viable and ablated tissue. In Phase 2, pathologic evidence of kidney ablation was seen in seven of nine animals. However, only two rabbits showed the well-demarcated effects of ablation in the tumor. High-intensity focused ultrasound can be effective at causing cell death in renal tumors and surrounding renal tissue. However, with the present ultrasound technology, imaging of renal lesions in the rabbit model is not adequate to consistently localize and completely ablate tumor.

Animals↗

Local recurrence and survival following nerve sparing radical cystoprostatectomy for bladder cancer: 10-year followup.

PURPOSE: The efficacy of nerve sparing radical cystoprostatectomy for the treatment of bladder cancer has been evaluated. We reviewed our 10-year experience with this technique to ascertain survival and local recurrence rates. MATERIALS AND METHODS: The charts of 101 patients treated with nerve sparing cystoprostatectomy between March 1982 and November 1989 were reviewed and updated. RESULTS: The disease-specific 10-year survival rate for all stages of bladder cancer treated was 69% and the 10-year survival rate free of local recurrence was 94%. Recovery of sexual function following nerve sparing cystectomy correlated with patient age: 62% in men 40 to 49 years old, 47% in men 50 to 59 years old, 43% in men 60 to 69 years old and 20% in men 70 to 79 years old. CONCLUSIONS: Nerve sparing radical cystoprostatectomy does not compromise cancer control and provides improved postoperative quality of life.

Actuarial Analysis↗

Inhibition of transport processes of intestinal segments following augmentation enterocystoplasty in rats.

PURPOSE: Sodium and chloride transport was measured by using the Ussing chamber-voltage clamp technique to evaluate alterations occurring in ileal segments interposed in the urinary tract in a rat enterocystoplasty model. MATERIALS AND METHODS: In adult male Sprague-Dawley rats which had undergone augmentation ileocystoplasties 3 months earlier, intestinal segments were explanted from the neobladders and native ileal segments were removed separately for electrolyte transport and morphometric analysis. RESULTS: Basal ileal active sodium and chloride absorption and cyclic nucleotide-induced chloride secretion were attenuated in transplanted ileum in contrast to control tissue. Morphologically, there was villus epithelial hyperplasia, crypt hyperplasia and chronic inflammation in transplanted segments, but villus height:crypt length ratios were unchanged. CONCLUSIONS: Pathophysiologic derangements in intestinal segments interposed in the urinary tract include inhibition of sodium and chloride transport processes and mucosal hyperplasia. The use of the Ussing chamber/voltage clamp technique described herein offers a new approach for additional studies of the metabolic consequences following urinary diversion.

Animals↗

Frequent loss of chromosome arms 8p and 13q in collecting duct carcinoma (CDC) of the kidney.

Collecting duct carcinoma (CDC) is a malignant renal neoplasm that is believed to arise from the epithelium of the ducts of Bellini in the distal nephron. These tumors are clinically aggressive and more often occur in a younger population than is typical of the more common clear cell renal carcinoma (RCC). Using highly informative polymorphic microsatellite markers on chromosome arms 3p, 5q, 6q, 9p, 9q, 11p, 13q, 17p, and 18q, we analyzed DNA from nonmalignant and tumor tissue in 6 cases of CDC. We found no evidence of 3p loss of heterozygosity (LOH) in these renal tumors by using multiple markers, a finding that distinguishes CDC from RCC in which 3p LOH has frequently been observed. We found LOH of 8p in 50% of the tumors examined; in addition, we observed LOH of 13q in 50% of the tumors studied. Interestingly, 8p LOH may be associated with high stage and poor clinical prognosis. These data suggest that the molecular events responsible for the development of CDC differ from those associated with the origin of RCC, and that tumor suppressor genes on 8p and 13q may be involved in the pathogenesis of CDC.

Adolescent↗

Radical surgery for renal-cell carcinoma: caval neoplastic excision, adrenalectomy, lymphadenectomy, adjacent organ resection.

A radical nephrectomy typically includes early ligation of the renal vessels, excision of the kidney and perinephric tissue, a regional lymphatenectomy, and an adrenalectomy. More controversial may be excision of supradiaphragmatic caval neoplastic extension and adjacent organ resection. Although survival is low in these unfavorable groups of patients, some patients may benefit from the extensive local resection of tumor, including adrenalectomy, lymphatenectomy, caval resection, and resection of adjacent organs.

Adrenalectomy↗

Serum ferritin as a clinical marker for renal cell carcinoma: influence of tumor volume.

OBJECTIVES: At present, 35% to 50% of patients with clinically localized renal cell carcinoma (RCC) unpredictably have a recurrence after surgical therapy. Presently, no clinical serum marker exists to detect occult metastases and to allow measurement of response to therapy in RCC. Serum ferritin was previously reported to correlate with pathologic stage. We postulated that this increase in serum ferritin with increasing stage might reflect tumor volume, since higher stage tumors are often larger. METHODS: Serum ferritin levels were measured preoperatively in 30 patients with radiologic evidence of RCC. Tumor volume and the largest tumor dimension were calculated from either the pathologic specimen (n = 24) or from the computed tomography or magnetic resonance imaging (n = 30). Pathologic stage was determined for all patients undergoing surgery (T1 = 3, T2 = 12, and T3 = 9). RESULTS: Preoperative serum ferritin levels did not correlate with age, blood urea nitrogen levels, creatinine levels, hematocrit, race, or gender. Although mean serum ferritin levels increased with increasing stage (T1 = 113 +/- 75, T2 = 254 +/- 270, and T3 = 425 +/- 257 ng/mL), these differences did not reach statistical significance (P > 0.05). Serum ferritin did, however, correlate with tumor volume (R = 0.75; P < 0.0001) and the largest tumor dimension measured from radiographic studies (R = 0.8; P < 0.0001). Serum ferritin measured intraoperatively from the renal vein (666 ng/mL) and the inferior vena cava (564 ng/mL) from a patient with a 500 cc tumor (preoperative serum ferritin, 552 ng/mL) suggested that the tumor was the source of the elevated ferritin levels. Histologic sections from tumors taken from patients with high serum ferritin levels were more necrotic and stained intensely positively for iron and immunohistochemically for ferritin, whereas adjacent histologically normal tissue did not. CONCLUSIONS: These data suggest that ferritin may be a useful serum marker for monitoring patients with RCC, but the actual source of the ferritin remains unclear and dictates further investigation.

Adult↗

Partial nephrectomy: technique, complications and pathological findings.

PURPOSE: We evaluate whether partial nephrectomy can be performed safely and efficaciously for renal tumors. MATERIALS AND METHODS: The results of 67 partial nephrectomies performed between 1977 and 1994 for renal cell carcinoma (51), oncocytoma (9), angiomyolipoma (3), transitional cell carcinoma (3) and other nonneoplastic lesions (2) were analyzed retrospectively in detail. RESULTS: Diminished complication rates were noted after 1988, and were attributed to improvements in surgical technique and an increased incidence of smaller, serendipitously discovered tumors. Although 35.5% of the patients had preoperative renal impairment (mean serum creatinine 2.1 mg./dl.), there were minimal changes in renal function and no patient required acute hemodialysis following partial nephrectomy. Among 42 patients with clinical stage T1 to T2 renal cell carcinoma undergoing partial nephrectomy local recurrence was identified in 8.3% of those with primary neoplasms. All 6 patients with local recurrence had negative surgical margins, recurrence often, distant from the operative site and multifocal disease, implicating multicentricity as the etiology of local recurrence. Five patients (83.3%) with local recurrence were alive and asymptomatic at a mean of 138 months after partial nephrectomy. Since capsular penetration was identified in 5 of 27 renal cell carcinomas (18.5%) with a diameter of 3.5 cm. or less, aggressive surgical resection with adequate tumor-free parenchymal and perinephric margins is necessary even for small lesions. CONCLUSIONS: With improved surgical techniques, including regional hypothermia, intraoperative sonography, meticulous dissection and injection of the collecting system with methylene blue, partial nephrectomy is safe and effective in properly selected patients.

Adolescent↗

Selection of men at high risk for disease recurrence for experimental adjuvant therapy following radical prostatectomy.

OBJECTIVES: Following surgery, men with recurrent prostate cancer have an isolated elevation in serum prostate-specific antigen (PSA) well in advance of measurable metastatic disease. Rational patient selection for new forms of adjuvant therapy, for example, gene therapy, is imperative. METHODS: In a retrospective study of two cohorts, we used proportional hazards regression analysis to develop and validate a multifactor model for identifying men who are at high risk of cancer recurrence. The model cohort consisted of 216 men with clinical Stage T2b and T2c treated by 1 urologist. The validation cohort consisted of 214 men with Stage T2b and T2c disease. RESULTS: A model for log relative risk, Rw, used serum PSA with a sigmoidal transformation (PSAST), radical prostatectomy Gleason score (GS), and pathologic stage (PS) as specimen confined or nonspecimen confined: Rw = (PSAST x 0.06) + (GS x 0.54) + (PS x 1.87). Recurrence risk categories were determined as low risk if Rw is less than 4.0, intermediate risk if it is 4.0 to less than 5.75, and high risk if Rw is more than 5.75. The observed Kaplan-Meier actuarial analysis of the three risk groups correlated well with the predictions determined for the model cohort. We then validated this model independently using a second cohort of 214 men with similar age, stage, and grade treated by 3 different urologists at two different institutions. CONCLUSIONS: The recurrence rates for men in the high-risk group are similar to those for men with positive lymph nodes and justifies exploration of experimental adjuvant therapy within this group using this model of patient selection.

Actuarial Analysis↗

The use of dynamic magnetic resonance imaging to evaluate orthotopic continent urinary diversion.

OBJECTIVES: The purpose of this study was to evaluate a dynamic magnetic resonance (MR) examination in patients after radical cystoprostatectomy with a neobladder. METHODS: All 12 subjects were studied with the injection of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) and showed normal renal enhancement patterns and upper urinary tracts, except 1 patient who had mild right hydronephrosis. All neobladders were also visualized with gadolinium and 9 of 11 patients were able to void on command. There was close agreement in all cases with the MR findings and other imaging studies. RESULTS: A static and dynamic Gd-DTPA contrast medium MR did image the entire urinary system, similar to a computed tomographic scan or intravenous urogram. Renal function data, similar to a renal radioisotope scan, was obtained from the Gd-DTPA scans. A dynamic voiding study provided visualization of the lower genitourinary tract similar to a conventional voiding cystourethrogram. CONCLUSIONS: We conclude that this single MR technique may provide information similar to that obtained from multiple standard imaging studies in the postoperative assessment of the radical cystectomy patient with a neobladder. It may be especially helpful in the presence of azotemia or contrast allergy.

Adult↗

Intraoperative sonography for the evaluation and management of renal tumors: experience with 100 patients.

PURPOSE: Intraoperative sonography was used to evaluate prospectively the renal parenchyma of patients undergoing surgery for presumed renal neoplasia. MATERIALS AND METHODS: One surgeon (F.F.M.) evaluated 100 kidneys using a triple-head sector ultrasonic transducer (5 MHz., 7.5 MHz. and 10 MHz. with duplex Doppler imaging). The size, number, echo texture, location, and relationship of suspected lesions to the collecting system, vasculature and renal capsule were recorded. Real-time Doppler imaging was used to distinguish among renal arteries, renal veins and the collecting system. Sonography was used to delineate the extent of the tumor and presence or absence of satellite lesions. All patients were evaluated preoperatively with abdominal computerized tomography. RESULTS: Under ultrasonic guidance partial nephrectomy was done in 40 cases, radical nephrectomy in 56, unroofing of renal cysts in 3 and renal biopsy in 1. Of the patients 8 were considered candidates for partial nephrectomy but underwent radical nephrectomy after intraoperative sonography revealed more extensive tumor, especially at the renal hilum. Similarly, 3 patients with a suspected malignancy were spared nephrectomy after intraoperative sonography and frozen section analysis revealed benign multilocular cysts. All surgical margins after sonographic evaluation were negative in patients undergoing partial nephrectomy. CONCLUSIONS: Intraoperative ultrasound is a useful adjunct for the dynamic evaluation of renal tumors in the surrounding environment of renal cysts, the collecting system and the renal vasculature. It is particularly beneficial in defining preoperative indeterminate renal lesions and in evaluating extrarenal structures for tumor involvement, such as the renal vein, inferior vena cava, adrenal gland and liver. Intraoperative sonography is most useful during partial nephrectomy and may improve tumor-free surgical margins. Sonography is routinely used during partial nephrectomy.

Adult↗

Differential diagnosis and evaluation of the incidentally discovered renal mass.

Recent advances in technology, coupled with decreasing costs, have led to a substantial rise in the diagnosis of the incidentally discovered renal mass. In virtually all of these cases, the underlying signs and symptoms of an occult renal tumor were either absent or sufficiently minor as to escape the notice of the referring physician. Although the majority of the renal masses are benign renal cysts, many are indeterminate or frankly malignant. The evaluation of these tumors is typically completed with contrast-enhanced static or spiral computed tomography; however, ultrasound may be sufficient in many cases to definitively diagnose renal cysts. The size and location of these tumors often dictates treatment, and recently, less conservative management has found to be reasonably safe and effective. For instance, small localized tumors are now being considered for tumor enucleation, heminephrectomy or partial nephrectomy, even in the presence of an otherwise normal contralateral kidney. Recent innovations, including intraoperative sonography, have given the urologic surgeon an additional tool for complete evaluation of the indeterminate renal mass. These issues are discussed in detail, in order to achieve a rational approach to the differential diagnosis and evaluation of the incidental renal mass.

Biopsy, Needle↗

Solitary late recurrence of renal cell carcinoma.

Late recurrence of renal carcinoma is an unusual manifestation of this tumor but can occur in as many as 11 percent of patients surviving ten years. We describe a case of a solitary lesion occurring in the nephrectomy scar ten years following surgery. The literature is reviewed. Aggressive surgical management is warranted in the treatment of these solitary lesions. The use of advanced imaging studies such as computed tomography (CT) and magnetic resonance imaging (MRI) can assist greatly in the management of patients.

Adult↗