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Biomedical subjects

D G Skinner

Publications and source records attributed to D G Skinner.

At least 19 recordsLinked to original sources

Massive retroperitoneal hemorrhage from adrenal gland metastasis.

We report an unusual case of spontaneous massive retroperitoneal hemorrhage from an adrenal gland metastasis. After medical therapy failed to stabilize the patient's condition, surgical exploration revealed a large retroperitoneal hematoma arising from a right adrenal gland metastasis. At the time of thoracoabdominal exploration in the lower lobe of right lung a small tumor nodule was palpated and resected. Pathologic examination of both lung and abdominal lesions revealed squamous cell carcinoma thought to have been primary in the lung. A review of the literature reveals that metastatic lesions to the adrenal gland are infrequently encountered clinically and rarely hemorrhage; the first such case in which massive retroperitoneal hemorrhage was a complication is reported in the urologic literature.

Adrenal Gland Diseases

Salvage surgery plus androgen deprivation for radioresistant prostatic adenocarcinoma.

We report on 34 patients with persistent local radiation resistant prostate cancer who underwent salvage surgical resection and hormonal deprivation. Initially, salvage prostatectomy was done in 11 patients but in 1 disease recurred locally and cystectomy was performed, for a total of 24 patients undergoing cystoprostatectomy. There were no postoperative complications in the prostatectomy group and the average postoperative stay was 7.6 days (range 6 to 12 days). Of 11 patients 4 (36%) are completely continent. There were 2 complications in the cystoprostatectomy group (1 small bowel obstruction and 1 prolonged ileus). The average postoperative stay without complication was 11 days (range 7 to 16 days). Of the 34 patients 24 (71%) are alive without radiographic evidence of disease, including 2 with detectable prostate specific antigen values at a mean of 53 months after surgery (range 25 to 93 months). Of the patients 3 (9%) are alive with radiographically evident recurrent disease (mean 53 months, range 49 to 77 months) and 7 (21%) are dead of disease (mean 52 months, range 20 to 120 months).

Adenocarcinoma

Experience with fossa recurrence of renal cell carcinoma.

We describe the surgical management and followup of 11 patients with local recurrence of renal cell carcinoma in the renal fossa, 10 of whom demonstrated no evidence of distant metastatic disease at the time of recurrence. Average interval to recurrence was 31 months from nephrectomy, with the majority of patients presenting with symptoms of weight loss, fatigue and lumbar discomfort. A total of 13 resections of recurrent carcinoma was performed with 3 immediate postoperative complications, including a retroperitoneal abscess, jejunal necrosis requiring resection and a duodenal obstruction requiring duodenojejunostomy. There were 2 postoperative deaths, 2 patients died of disseminated disease at 8 and 22 months, and 3 died of causes unrelated to cancer recurrence at 4 months, 6 months and 10 years. Four patients were without disease at a followup of 35, 46, 48 and 211 months. We include in this review a report on 1 patient who maintains a disease-free survival of 17 years after resection of a recurrent spindle cell carcinoma. We conclude that an aggressive surgical approach to recurrent renal cell carcinoma within the renal fossa can produce long-term disease-free survival and is justified when compared to the results reported for chemotherapy.

Adult

Radical cystectomy in regionally advanced bladder cancer.

The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients.

Carcinoma, Transitional Cell

Study of antireflux nipple valves of Kock ileal urinary reservoir. Experimental investigation in dogs.

To better assess the construction, maintenance, and function of the Kock ileal urinary reservoir with its continent antirefluxing nipple valves, laboratory investigations in dogs were done simultaneously with clinical trials in humans in 1983. Fifteen dogs underwent creation of hemi-Kock ileal reservoirs (without the efferent valve and limb) that were anastomosed to their bladders as enterocystoplasties. The afferent antirefluxing nipple valves were intussuscepted after 7 cm of underlying mesentery had been removed. The nipples were further stabilized with metal and absorbable (Polysorb) staples and Marlex collars. The right ureters were anastomosed to the afferent limb of the reservoirs with the contralateral systems left intact as controls. Ten dogs were able to be followed at the vivaria for twelve to thirty-six months and then studied. All nipple valves remained intact, viable, and nonrefluxing without revision. All kidneys remained histologically normal except those in dogs with dilated ureters secondary to ureteroileal stenosis with concurrent calculi formation. Calculi formed on exposed metal staples and Marlex. The absorbable staples were found to promote appropriate healing and were never the nidus for stone formation. It appears that the intussuscepted nipple valve (with its mesentery removed) is reproducible and functionally reliable in preventing reflux. It also appears these valves can histologically preserve diverted kidneys if the upper urinary tract drainage is normal and calculi are minimized. The proper placement of staples and the elimination of Marlex-anchoring collars are indicated to minimize calculi.

Anastomosis, Surgical

Radiotherapy following radical prostatectomy in patients with adenocarcinoma of the prostate.

From 1973 to 1986, 160 patients with adenocarcinoma localized to the prostate were treated with radical prostatectomy and pelvic lymphadenectomy. In 78 (49%) patients more advanced stage of disease was found at surgery and they received local pelvic irradiation (RT). This consisted of 45 Gy for microscopic and 55 Gy for macroscopic residual disease. RT was given at 1.8 Gy a day, using the four-field "box" technique with the 23 MV X ray beam. Pelvic lymph node metastases were found in 28 (36%) patients who, in addition to RT, received systemic therapy: 20 with cyclophosphamide alone, 4 combined with 5-Fluorouracil, and 4 patients received DES. The 5- and 10-year overall actuarial survival was 95 and 77%, respectively, and the 5- and 10-year disease-free survival was 58 and 43%, respectively. Recurrent tumor was found in 34 (44%) patients. Of these 34 patients, 32 (94%) had distant metastatic tumor and 2 (6%) had local recurrence in the pelvis. The presence of metastatic disease in pelvic lymph nodes had clinical significance since it influenced disease-free survival and the incidence of tumor recurrence. The 10-year disease-free survival for the 50 patients with no lymph node metastases was 51%, as compared to 28% for the 28 patients with such metastases, p = 0.001. Similarly, recurrent tumor was found in 28% of the former and 68% of the latter patients, p = 0.002. Other important parameters predicting recurrence were: clinical stage, p = 0.018, histological grade, p = 0.013, and Gleason's grade, p = 0.002. This treatment program was very well tolerated and of low toxicity. There was no surgical mortality. Surgical complications were seen in 10 (13%) patients including: minor in 5 and major in 5. At 1 year, 77% of the patients remained continent, while 10% had mild stress incontinence. Of the remaining 13% only 3 (4%) patients had severe incontinence (greater than 5 pads daily). RT toxicity was mild with 38% experiencing diarrhea. Severe toxicity was seen in 2 (3%) patients who, early in the study, developed scrotal and lower extremity edema. Severe chemotherapy complications were seen in 1 (4%) patient who had severe neutropenic sepsis. Postoperative radiotherapy is a well tolerated, safe and effective treatment in patients who have microscopic or macroscopic residual tumor following radical prostatectomy.

Adenocarcinoma

Lower urinary tract reconstruction following cystectomy: experience and results in 126 patients using the Kock ileal reservoir with bilateral ureteroileal urethrostomy.

Between May 1986 and February 1990, 126 consecutive men underwent lower urinary tract reconstruction by means of bilateral ureteroileal urethrostomy using a Kock ileal reservoir. The early complication rate was 11.1%. Late complications requiring rehospitalization or reoperation have been surprisingly few: 1 for prolapse of the afferent antirefluxing nipple valve, 1 for calculi and 4 for artificial urinary sphincter placement due to unsatisfactory continence. Good continence has been achieved in 94% of the patients during the day and in 84% at night. Tumor recurred in the pelvis in 5 patients, with 4 requiring cutaneous urinary diversion. All patients had progression or died of metastatic disease. Our experience has yielded extraordinary results in terms of patient acceptance with few late complications or need for reoperation.

Adult

The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial.

We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2 cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection.

Antineoplastic Combined Chemotherapy Protocols

Urinary tract stones: a complication of the Kock pouch continent urinary diversion.

Urinary tract stone disease has been found to be a later complication associated with the construction of the Kock pouch continent urinary diversion. Of 383 patients who underwent Kock pouch diversion between August 1982 and December 1986 stones developed in the pouch in 64 (16.7%), usually on exposed staples or eroded Marlex used to construct the nipple valves. Stones have recurred in 13 of the 64 patients (22%). Most stones were removed endoscopically with techniques similar to those used for percutaneous stone removal. Risk factors for stone formation include Marlex collar erosion and acute pyelonephritis. Changes in surgical techniques with elimination of the Marlex collar and a reduction in the number of staples have reduced the incidence of this later complication to 10%.

Female

Primary adenocarcinoma of bladder.

Between April 1983 and December 1987, we have treated and followed 16 patients at the University of Southern California for adenocarcinoma of the bladder. In 10 patients, the cancer originated from a nonurachal source; all underwent radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion. The other 6 patients had an apparent urachal origin of their cancer. Half of these patients were treated with radical cystectomy and urinary diversion and half were treated initially with segmental cystectomy. Presenting characteristics (age, sex ratio, and symptoms) were similar for both groups. Three-year adjusted acturial tumor-free survival rates for the two groups were 48 percent and 31 percent, respectively. We advocate an aggressive approach of radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion for all invasive adenocarcinoma of the bladder, regardless of location.

Actuarial Analysis

Kock pouch bladder replacement.

Between May 1986 and February 1990, 126 consecutive male patients have undergone lower urinary-tract reconstruction by means of Kock bladder replacement at our institution. The early and late complication rates have been minimal. Good continence has been achieved in 94% of patients during the day and in 84% at night. Our experience with bladder replacement has yielded extraordinary results in terms of patients acceptance. It is anticipated that our experience as well as the experience of others with this surgery will encourage patients afflicted with high-grade bladder cancer and their physicians toward an earlier decision for aggressive therapy by cystectomy while cure is still possible.

Adult

Allelic loss of chromosome 17p distinguishes high grade from low grade transitional cell carcinomas of the bladder.

Forty-three transitional cell carcinomas of the bladder of differing grades and stages were examined for reduction to homozygosity for chromosomes 9q, 11p, and 17p. Allelic loss of chromosome 9q was seen in 24 of 38 informative grades II, III, and IV tumors providing further evidence for a bladder tumor suppressor gene on this chromosome. In contrast to the grade-independent involvement of chromosome 9q, allelic losses of chromosomes 11p and 17p were seen only in grade III and IV tumors. The results with chromosome 17p were particularly striking and showed that 0 of 10 grade II versus 20 of 31 grade III and IV tumors had allelic losses for this chromosome harboring the p53 tumor suppressor gene often mutated in other human cancers. The data suggest that cumulative genetic damage is sustained in transitional cell carcinomas and that one of the underlying molecular mechanisms distinguishing low grade from high grade tumors involves chromosome 17p.

Alleles

Allelic losses of chromosomes 9, 11, and 17 in human bladder cancer.

Twenty-five human bladder tumors were examined for loss of heterozygosity of markers on chromosomes 6p, 9q, 11p, 14q, and 17p. These studies show that all of the markers were reduced to homozygosity in at least some of the tumors. They also confirmed earlier studies by Fearon et al. [Nature (Lond.), 318: 377-380, 1985] that approximately 40% of bladder tumors were reduced to homozygosity for markers on chromosome 11p. However, the greatest frequency of allelic loss was seen for chromosomes 9q (67% of informative cases) and 17p (63% of informative cases) with both chromosomes being lost concordantly in 10 out of 20 informative tumors. Allelic loss of chromosome 9q has not been previously observed with other human cancers; however, deletions of 17p have been reported in breast, lung, and colorectal carcinomas. The data raise the interesting possibility that allelic losses of specific chromosomes might be a feature of cancer in a particular differentiated cell type whereas loss of other chromosomes harboring more generally acting tumor suppressor genes might be a common feature of human cancers.

Alleles

Development of upper tract carcinoma after cystectomy for bladder carcinoma.

Two hundred twenty patients who underwent a radical cystectomy and en bloc pelvic lymph node dissection with urinary diversion were reviewed to define the incidence of upper tract carcinoma developing after cystectomy. Each patient was followed for at least five years or until death. In 5 of 220 (2.4%) upper tract lesions developed, with a disease-free interval from cystectomy of twenty-two to fifty-four months. All patients died within two to twenty-seven months of diagnosis. Common pathologic features included the presence of high-grade multifocal lesions or carcinoma in situ (CIS) in the cystectomy specimen, tumor invasion of the intramural ureter, and positive findings on urethrectomy specimens. Although the incidence of this disease process is low, heightened surveillance of the upper urinary tracts would seem appropriate in patients displaying these pathologic features.

Aged

The role of radical cystectomy in the management of high grade superficial bladder cancer (PA, P1, PIS and P2)

Between January 1979 and 1987, 411 consecutive patients were considered candidates for bilateral pelvic iliac lymph node dissection and radical cystectomy for the management of bladder cancer. From this group 160 were identified as having pathological stage P2 or less disease, including 11 who also had positive nodes. The 5-year actuarial survival rate for the respective stages at 95% confidence limits was 100% for stage P0/A, 80% for stage P1, 78% for stage P1 with stage PIS, 85% for pure stage PIS, 76% for stage P2 and 87% for stage P2 with stage PIS. Additionally, we identified a group of patients with stage P2 transitional cell carcinoma who were at significant risk for development of metastatic disease. Of 46 patients with stage P2 transitional cell carcinoma 18 had vascular space invasion resulting in 6 of 18 cancer-related deaths (33%). Our study demonstrates that radical cystectomy has been highly effective in curing patients with high grade superficial disease, including those with superficially invasive disease associated with nodal metastases.

Carcinoma, Transitional Cell