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D G Skinner

Publications and source records attributed to D G Skinner.

At least 55 records · Page 3Linked to original sources

Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression.

BACKGROUND: Thrombospondin-1 (TSP) is a 430-kd glycoprotein that is an important component of the extracellular matrix and is known to be a potent inhibitor of angiogenesis (i.e., formation of new blood vessels) both in vitro and in vivo. Several reports suggest that TSP possesses tumor suppressor function, possibly through its ability to inhibit tumor neovascularization. It has recently been shown that TSP expression is enhanced by the product of the p53 gene (also known as TP53). PURPOSE: We examined the role of TSP expression in tumor recurrence and overall survival in patients with invasive bladder cancer. We also examined the relationship between alterations in p53 protein expression, TSP expression, and tumor angiogenesis. METHODS: Tumors from 163 patients (with a median follow-up of 7.7 years) who underwent radical cystectomy for invasive transitional cell carcinoma of the bladder (63 patients with organ-confined disease and no lymph node involvement, 48 patients with extravesical extension of the disease and no lymph node involvement, and 52 patients with metastasis to regional lymph nodes) were examined for TSP expression by immunohistochemistry, utilizing monoclonal antibody MA-II, which recognizes an epitope in the amino-terminal region of TSP. For each tumor, microvessel density counts and p53 protein expression status (via immunohistochemistry) were also determined. TSP expression was graded as low, moderate, or high without knowledge of clinical outcome, p53 status, and microvessel density count; tumors with moderate and high TSP levels were considered as one group. Groups of patients were compared by Kaplan-Meier product limit estimates of overall survival, the complement of cumulative incidence curves for recurrence-free survival, and the stratified logrank test. Reported P values are two-sided. RESULTS: TSP expression was significantly associated with disease recurrence (P = .009) and overall survival (P = .023). Patients with low TSP expression exhibited increased recurrence rates and decreased overall survival. TSP expression was an independent predictor of disease recurrence (P = .002) and overall survival (P = .01) after stratifying for tumor stage, lymph node status, and histologic grade, but it was not independent of p53 status. TSP expression was significantly associated with p53 expression status (P = .001) and microvessel density counts (P = .001). Tumors with p53 alterations were significantly more likely to demonstrate low TSP expression, and tumors with low TSP expression were significantly more likely to demonstrate high microvessel density counts. Results of an analysis of variance were compatible with the hypothesis that p53 affects tumor angiogenesis by regulating the level of TSP expression. CONCLUSIONS AND IMPLICATIONS: These data support the concept that TSP may possess a tumor-inhibitory function. TSP may act, in part, through the regulation of tumor neovascularity. These results may also provide insight into one mechanism by which p53 exerts its tumor suppressor effects, i.e., through the control of tumor angiogenesis.

Adult↗

Vena caval resection for bulky metastatic germ cell tumors: an 18-year experience.

PURPOSE: The operative management and followup of vena caval resection for bulky metastatic germ cell tumors have been previously described in 3 series. In 1989 Ahlering and Skinner described their experience with 12 patients. We now update this experience with the most recent followup on 19 patients. MATERIALS AND METHODS: From April 1978 to May 1995, 19 men underwent retroperitoneal lymph node dissection for stage B3 (N3) or C (N3, M+) germ cell tumor after induction chemotherapy. In all cases the inferior vena cava was resected because of extensive thrombosis or direct involvement of the vessel wall by a tumor. The inferior vena cava was resected from just below the renal veins to beyond the level of disease involvement. Complete resection of retroperitoneal disease was accomplished in all patients. Morbidity and mortality were examined. RESULTS: The mean hospital stay was 10 days (range 7 to 13) for uncomplicated recoveries (9 patients) versus 19 days (range 6 to 32) for complicated recoveries (10 patients). Followup ranged from 1 month to 16 years. Complications included prolonged ileus, small bowel obstruction, fascial dehiscence and pneumonia with pleural effusion. Chronic edema persisted in 3 of 11 patients with followup of greater than 6 months. Of the 6 patients who died of disease recurrence 4 did not have normalization of tumor markers before surgery, and all 4 had persistence of cancer in the resected specimen. Seven patients are without disease at followup of 24 months to 16 years. All survivors had normalized tumor markers before surgery. Only 1 patient (5%) had retroperitoneal recurrence. CONCLUSIONS: En bloc vena caval resection for tumor involvement or extensive thrombosis can be associated with short and long-term morbidity, is feasible, and may contribute to a prolonged tumor-free interval and a chance for cure.

Adolescent↗

Horseshoe kidney with a retrocaval ureter.

Horseshoe kidney and retrocaval ureter are two uncommon congenital anomalies of the genitourinary system that have rarely been reported to occur in the same patient. In each case previously reported, the isthmus of the horseshoe was positioned posterior to the inferior vena cava and anterior to the aorta. In no case was the diagnosis of both anomalies made preoperatively. We report a case of simultaneous horseshoe kidney and retrocaval ureter diagnosed by preoperative imaging studies and discuss the diagnostic evaluation and surgical management of this rare entity.

Abnormalities, Multiple↗

New technique of vaginal reconstruction following anterior exenteration.

Vaginal reconstruction is important in sexually active females undergoing anterior exenteration for malignant disease. We describe a technique for vaginal reconstruction used in two women who underwent radical cystectomy that required en bloc removal of the anterior vaginal wall. A polyglycolic acid mesh with a pedicle graft of greater omentum creates the anterior 270 degrees and the apex of the neovagina. The technique is simple and adds to the urologist's armamentarium of reconstructive procedures that improve quality of life following exenterative surgery.

Female↗

Quality of life and sexuality following radical prostatectomy in patients with prostate cancer who use or do not use erectile aids.

OBJECTIVES: It is well established that prostate cancer patients undergoing radical prostatectomy may experience disruptive side effects, most notably urinary incontinence and erectile dysfunction. The purpose of this study is to compare relevant outcomes between patients awaiting radical prostatectomy for prostate cancer and patients who already underwent the surgery, taking into account type of prostatectomy and use of erectile aids. METHODS: We compared self-reports of global quality of life, sexuality, urinary continence, and physical capabilities in 86 nerve-sparing patients, 89 standard-prostatectomy patients, 74 prostatectomy patients who used erectile aids, and a comparison group of 45 patients awaiting radical prostatectomy. RESULTS: Regardless of type of surgery, use of erectile aid, or preoperative status, most patients reported good quality of life. The best outcomes in sexuality were reported by patients who used erectile aids, who appeared similar in sexuality to patients awaiting surgery. When differences were detected, standard prostatectomy patients who did not use erectile aids scored worse in most areas of sexuality than nerve-sparing patients who did not use erectile aids. There were no differences in frequency of urinary leakage among the three surgery subgroups. CONCLUSIONS: Although most patients reported problems in sexual and urinary function, global quality of life does not appear to be compromised following radical prostatectomy. Findings suggest that postsurgical sexuality differs depending on type of prostatectomy and use of erectile aids, while urinary function is similar across surgery groups. We conclude that erectile aids should be offered routinely to patients who are ineligible for nerve-sparing surgery or experience erectile difficulties following the nerve-sparing procedure.

Aged↗

Adrenal cortical carcinoma associated with venous tumour thrombus extension.

OBJECTIVE: To report the diagnosis and treatment of six patients with adrenocortical adenocarcinoma and venous tumour thrombus extension. PATIENTS AND METHODS: All six patients (four female and two male, age range 14-83 years) were approached surgically through a thoracoabdominal incision and all underwent radical ablative surgery with removal of the primary tumour, regional retroperitoneal lymphadenectomy and en bloc extraction of the venous tumour thrombus. RESULTS: Five patients with right-sided tumours had vena caval tumour thrombus involvement and one patient with a left-sided tumour had extension of tumour thrombus into the splenic vein. All patients had appropriate radiographic evaluation pre-operatively and all underwent successful radical surgery with en bloc resection of the venous tumour thrombus. CONCLUSION: For optimal management of this rare neoplasm, it is paramount that accurate diagnostic imaging be performed pre-operatively to help dictate the ideal surgical approach and to optimize successful treatment of this disease.

Adolescent↗

Orthotopic lower urinary tract reconstruction in women using the Kock ileal neobladder: updated experience in 34 patients.

PURPOSE: Orthotopic lower urinary tract reconstruction has revolutionized urinary diversion following cystectomy. Initially performed solely in male patients, orthotopic diversion has now become a viable option in women. Currently, the orthotopic neobladder is the diversion of choice for women requiring lower urinary tract reconstruction at our institution. We evaluate and update our clinical and functional experience with orthotopic reconstruction in female patients. MATERIALS AND METHODS: Since June 1990, 34 women 31 to 86 years old (median age 67) have undergone orthotopic lower urinary tract reconstruction following cystectomy. Indications for cystectomy included transitional cell carcinoma in 29 patients, urachal adenocarcinoma in 1, mesenchymal tumor of endometrial origin in 1, cervical carcinoma in 1 and a fibrotic radiated bladder in 1. In addition, 1 woman underwent undiversion to the native urethra following a previous simple cystectomy and cutaneous diversion for eosinophilic cystitis. Data were analyzed according to postoperative early and late complications, survival, tumor recurrence, pathological evaluation of the cystectomy specimen, continence status, voiding pattern and patient satisfaction. The median followup in this group of patients was 30 months (range 17 to 70). RESULTS: There were no perioperative deaths, and 4 early (11%) and 3 (9%) late complications. Four patients died, none with a urethral recurrence, including 3 of metastatic bladder cancer and 1 of unrelated causes. In another patient with an extensive mesenchymal tumor of the uterus a sigmoid tumor recurred requiring conversion of the orthotopic reservoir to a cutaneous diversion. All of the remaining 29 patients are alive without evidence of disease. Intraoperative frozen section of the distal surgical margin (proximal urethra) accurately evaluated (confirmed by permanent section) the proximal urethra prospectively for tumor in all 29 specimens removed for transitional cell carcinoma, including 28 specimens (97%) without evidence of tumor and 1 specimen with carcinoma in situ. Complete daytime and nighttime continence was reported by 29 (88%) and 27 (82%) of 33 evaluable patients, respectively. A total of 28 patients (85%) void to completion, while 5 (15%) require some form of intermittent catheterization to empty the neobladder. Patient satisfaction is overwhelming. CONCLUSIONS: The excellent clinical and functional results demonstrated with further followup confirm our initial experience with orthotopic diversion in women. Careful selection of appropriate female candidates for orthotopic diversion is critical, and includes preoperative evaluation of the bladder neck and intraoperative frozen section analysis of the distal cystectomy margin. Furthermore, close monitoring of the retained urethra is mandatory in all women undergoing orthotopic diversion. We believe that the orthotopic neobladder is the urinary diversion of choice in women following cystectomy.

Adult↗

p53 protein and gene alterations in pathological stage C prostate carcinoma.

PURPOSE: We determined the extent of p53 immunoreactivity in pathological stage C prostate cancer as well as its correlation to tumor grade, substage, recurrence and proliferation rate. To define better the temporal relationship of p53 nuclear reactivity in prostate cancer p53 immunoreactivity was evaluated in all associated prostatic intraepithelial neoplasia lesions. MATERIALS AND METHODS: Using immunohistochemistry p53 status and proliferation rate were determined in 96 tumors from patients with pathological stage C prostate cancer. Single strand conformational polymorphism in exons 5 to 8 was used in a subset of specimens to assess the association of p53 nuclear accumulation with mutations in the p53 gene. RESULTS: p53 Nuclear reactivity was demonstrated in 10 tumors (10.4%), including 6 with high and 4 with low level nuclear reactivity. Of the tumors 86 (89.6%) had no evidence of p53 immunoreactivity. Each of the 6 tumors with high level p53 reactivity had associated areas of prostatic intraepithelial neoplasia that also showed p53 nuclear reactivity. Furthermore, pathological stage C substage (C1, 2 or 3) was significantly associated with p53 nuclear reactivity (p = 0.04). Proliferation rates were correlated with p53 nuclear reactivity (p = 0.09), while there was no association with tumor grade or recurrence. p53 Gene alterations were noted in 2 of the 3 p53 positive tumors versus no alterations in the p53 gene of 3 p53 negative tumors. CONCLUSIONS: p53 Nuclear accumulation is uncommon in pathological stage C prostate cancer and its presence in premalignant prostatic intraepithelial neoplasia lesions suggests that it may be an early event in a subset of prostate cancers.

Aged↗

Early cystectomy for clinical stage T1 transitional cell carcinoma of the bladder.

Early radical cystectomy for a high-grade tumor invading the lamina propria (T1) remains controversial. In 1997, we cannot identify accurately which of these high-risk tumors will progress to muscle-invasive disease and metastases. In the near future, urologists may be able to use the presence of genetic alterations, such as p53 mutations, to help make therapeutic decisions. Previous reports on superficial bladder cancer treated with intravesical bacillus Calmette-Guérin immunotherapy have demonstrated a decrease in recurrence and progression. Unfortunately, there is no reliable method to predict which patients with a high-grade T1 tumor will fail to respond to intravesical therapy. Failure of intravesical therapy to control these aggressive tumors is associated with a significant rate of pathological upstaging and metastases. Radical cystectomy will cure a high percentage of these T1 tumors with acceptable morbidity and low mortality. In an era of nerve-sparing cystectomy and orthotopic neobladder reconstruction, early radical cystectomy is an alternative that should be discussed with the patient before instituting intravesical therapy.

Adjuvants, Immunologic↗

Orthotopic reconstruction in a woman following cystectomy and cutaneous urinary diversion. The 1st reported case.

Orthotopic lower urinary tract reconstruction has become the procedure of choice in selected male and female patients at our institution following cystectomy with excellent functional results. A natural extension of the orthotopic neobladder is undiversion to the intact native urethra in patients who had previously undergone cystectomy and cutaneous urinary diversion. Undiversion has been successfully performed in selected male patients; however, to our knowledge, undiversion has not been reported in women. Herein, we present the 1st case of undiversion in a female patient who had undergone prior cystectomy and cutaneous urinary diversion.

Anastomosis, Surgical↗

[Carcinoma of the bladder: experience of the USC Los Angeles (antireflux nipple according to Ghoneim)].

A pelvic lymph node dissection, using continent urinary diversion and lower urinary tract reconstruction can significantly improve the patient's quality of life After almost 25 years of experience in treating 930 patients with carcinoma of the bladder, the Author concludes that most patients with superficial bladder cancer (grade 1 or grade 2) can be managed conservatively. Patients in the Urology Department at University of Southern California, who had grade 3 T1 tumours showing a mutation of P53 received early aggressive therapy, namely, cystectomy. The probability of recurrence for such patients was just 14% and the survival rate among all 930 patients (including grades 1-3) was over 75%. Lower urinary tract reconstruction using the Kock neobladder was found to give highly functional results, with few complications and a high satisfaction rate among patients (62% very happy, 20% happy and 18% satisfied with the results).

Carcinoma, Transitional Cell↗

Relationship of tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer.

The purpose of this investigation was to evaluate the relationship between tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer. We studied 161 patients with invasive transitional cell carcinoma of the bladder who had previously undergone radical cystectomy. Analysis was performed to determine the presence of p53 nuclear accumulation and extent of tumor-associated angiogenesis. p53 status identified a group of patients at high risk for tumor progression (p53-altered tumors), and microvessel density determinations added additional prognostic information by identifying a subset of aggressive tumors within the wild-type p53 subgroup. At 5 years, patients with tumors exhibiting no evidence of p53 alterations and low microvessel counts demonstrated 3% recurrence and 88% survival, compared to 43% recurrence and 59% overall survival for patients with intermediate vessel counts and 61% recurrence and 43% overall survival for patients with the highest vessel counts (P < 0.001 and P = 0.003, respectively). Angiogenesis also provides additional prognostic information to patients with tumors that demonstrate p53 alterations. An association between angiogenesis and p53 status did exist (P = 0. 05); however, 27% of the tumors that showed no evidence of p53 alterations exhibited high microvessel counts, and 26% of tumors with evidence of p53 alterations had low microvessel counts. Tumor-associated angiogenesis adds additional useful prognostic information to that which is obtained from p53 status in patients with invasive transitional cell carcinoma of the bladder. Although an association between p53 status and the degree of angiogenesis was identified, other factors appear to play a role in the regulation of tumor-induced neovasularization.

Biomarkers, Tumor↗

The use of orthotopic neobladders in women undergoing cystectomy for pelvic malignancy.

Since June 1990, 21 women aged from 31 to 78 years (mean, 62 years) have undergone lower urinary tract reconstruction by means of an orthotopic Kock ileal reservoir following cystectomy. The indication for cystectomy included 15 patients with transitional-cell carcinoma of the bladder, 2 patients with urachal adenocarcinoma, 1 patient with cervical carcinoma, 1 patient with a mesenchymal tumor of endometrial origin, 1 patient with interstitial cystitis, and 1 patient with a fibrotic irradiated bladder. A total of four complications (two early and two late) have occurred in this group of patients. Excellent continence has been achieved during the day and night in 95% and 89% of the patients, respectively. In all, 16 of 20 patients void volitionally per urethra without a residual urine volume, whereas 4 patients require intermittent catheterization to empty the neobladder. All patients are completely satisfied. One patient died of metastatic transitional-cell carcinoma without a pelvic recurrence. Of the remaining 20 patients, 18 are currently alive without evidence of recurrent disease. Tumor recurrence has occurred in two patients: one patient with an extensive mesenchymal tumor developed a sigmoid recurrence necessitating conversion to a continent cutaneous diversion, and one patient developed a right iliac recurrence. This initial experience with lower urinary tract reconstruction in women has yielded extraordinary results, and we feel that the option of orthotopic reconstruction following cystectomy can safely be offered to selected female patients.

Adult↗

Orthotopic urinary diversion: the Kock ileal neobladder.

Orthotopic urinary diversion via the Kock ileal neobladder is the preferred form of bladder reconstruction in men and, now, in women undergoing cystectomy at the University of Southern California. Through June of 1993, 266 men were diverted in this fashion. There were 3 perioperative mortalities (1.1%); early complications occurred in 47 men (17.7%), whereas 35 (15.0%) experienced late complications. Approximately 85% of the men enjoy good or satisfactory continence day and night, with a large majority having a normal voiding pattern. Through May of 1993, 14 women were similarly diverted; 2 patients (14.2%) experienced early complications, whereas 1 patient (7.1%) had a late complication. The continence and voiding pattern appear to be even better in this small group of women as compared with the men. Orthotopic Kock continent urinary diversion yields an extraordinary functional result that can be accomplished with minimal complication and high patient satisfaction.

Adult↗

The Kock ileal neobladder: updated experience in 295 male patients.

PURPOSE: Since 1986 orthotopic lower urinary tract reconstruction using the Kock ileal neobladder has been our diversion of choice in patients undergoing cystectomy. We report on the first 295 male patients undergoing this procedure from May 1986 through December 1993. MATERIALS AND METHODS: Complications were assessed, tabulated, subdivided into early (3 months or less postoperatively) and late types, and further categorized with respect to relationship to neobladder construction. Continence was individually evaluated via a detailed patient questionnaire. RESULTS: The pouch related early and late complication rates were 7.2 and 11.6%, respectively, and pouch related abdominal reoperation rates were 0.0 and 1.4%, respectively. Analysis of late pouch related complications revealed 4.1% stone formation and 2.4% afferent nipple stenosis rates, and only 1 case (0.3%) of ileal urethral anastomotic stricture. Of the patients 87 and 86% reported good or satisfactory daytime and nighttime continence, respectively. With regard to age, while overall continence was similar, a significantly greater percentage of patients younger than 70 years experience good daytime and nighttime continence relative to the older counterparts. Of the patients 5% perform regular intermittent catheterization and 2.7% required an artificial urinary sphincter due to unacceptable continence. CONCLUSIONS: The Kock orthotopic ileal neobladder can be constructed with minimal morbidity and extraordinary functional results. We strongly advocate its use when possible.

Adult↗

Management of complex urologic injuries.

The management of complex urologic trauma requires considerable experience and familiarity with reconstructive techniques. The goal should always be maximum preservation of normal function, with the fewest serious complications. Ideally these cases are treated by a multidisciplinary team rather than the trauma surgeon alone.

Amputation, Traumatic↗

Long-term disease-free survival after plasmacytoma of the urethra: a case report and review of the literature.

Plasmacytoma is an unusual soft-tissue collection of neoplastic monoclonal plasma cells. The most common site of presentation is the upper respiratory tract, although any site of disease is theoretically possible. We report the fifth known case of primary urethral plasmacytoma. This case is unique in that the patient received only radiation as definitive treatment and has remained well, without recurrence for more than 12 years.

Adult↗