Biomedical subjects

J W Slaton

Publications and source records attributed to J W Slaton.

30 records · Page 2Linked to original sources

PubMed1998

Timely delivery of biological therapy after cytoreductive nephrectomy in carefully selected patients with metastatic renal cell carcinoma.

PURPOSE: We determine whether cytoreductive surgery delays or precludes the administration of systemic biological therapy in patients with previously untreated metastatic renal cell carcinoma. MATERIALS AND METHODS: We evaluated 79 patients 22 to 73 years old with untreated renal cell carcinoma for possible cytoreductive surgery before the administration of systemic biological therapy. Based on performance status, overall disease burden and subjective clinical assessment 13 patients were referred for initial systemic biological therapy and 66 underwent cytoreductive surgery as initial treatment. We evaluated patient ability to receive postoperative biological therapy, time to therapy, surgical complications and mortality. RESULTS: Cytoreductive surgery had a minimal impact on the administration of timely systemic biological therapy in these carefully selected patients. Of the 66 patients 54 (82%) received postoperative systemic biological therapy beginning a median of 40 days after nephrectomy. Two patients (3%) died postoperatively (within 30 days) and in 1 (1.5%) postoperative deterioration in performance status precluded the administration of systemic therapy. The other 9 patients did not have measurable residual disease postoperatively, did not need or refused systemic therapy, or were followed elsewhere. CONCLUSIONS: Systemic biological therapy can be administered in a timely manner (median 40 days) to the majority of patients (82% treated) after cytoreductive surgery. Surgery alone does not preclude the administration of systemic biological therapy in carefully selected patients.

Adult↗

PubMed1997

Nephrectomy and vena caval thrombectomy in patients with metastatic renal cell carcinoma.

OBJECTIVES: To report out experience with performing nephrectomy and vena caval thombectomy in patients with metastatic renal cell carcinoma. METHODS: A retrospective review was performed of 15 patients who underwent surgical excision of the primary tumor and a caval thrombus and treatment of concurrent metastases between 1989 and 1995. The sites of metastases included lungs (n = 8), bone (n = 3), bulky retroperitoneal or mediastinal lymph nodes (n = 2), liver (n = 1), and contralateral adrenal (n = 1). The level of caval involvement was suprahepatic in 3 cases, retrohepatic in 2 cases, and infrahepatic in 10 cases. Three patients had an Eastern Cooperative Oncology Group performance score of 0, 11 had a score of 1, and 1 had a score of 2. Median follow-up was 17 months. RESULTS: Median operative time was 6.5 hours and median hospitalization was 10 days. Two patients required re-exploration for postoperative hemorrhage. There were no perioperative deaths. Four patients underwent surgery for resection of solitary metastases (1 lung, 2 spine, and 1 humerus); 2 of the 4 received adjuvant radiotherapy. Two patients received biologic therapy preoperatively, 3 received it both preoperatively and postoperatively, and 6 received it only postoperatively. The median time to initiation of postoperative biologic therapy was 48 days (range 25 to 110). Eleven patients are currently alive, 7 with no evidence of disease at a median follow-up of 17 months (range 6 to 66) and 4 with stable metastases at 14 months (range 4 to 22). Ten of the 13 symptomatic patients had improved performance scores after surgery. Four patients have died from metastatic disease: 2 from rapid progression at 2 and 5 months after surgery and the other 2 at 17 and 42 months. CONCLUSIONS: Nephrectomy and vena caval thrombectomy can be safely performed in selected patients with metastatic disease. Furthermore, in patients receiving biologic therapy, nephrectomy may enable a better quality of life and prolonged survival.

Aged↗

PubMed1997

Deoxyribonucleic acid ploidy enhances the cytological prediction of recurrent transitional cell carcinoma of the bladder.

PURPOSE: We determined whether deoxyribonucleic acid (DNA) ploidy analysis by image analysis cytometry enhances the cytological diagnosis of recurrent transitional cell carcinoma of the bladder. MATERIALS AND METHODS: A retrospective study was performed during a 5-year period to evaluate the cytological diagnosis and DNA ploidy analysis of 469 patients with previously diagnosed superficial transitional cell carcinoma. Cytological and DNA ploidy analysis was performed on 1,034 urine and bladder wash specimens, and the patients were monitored with cystoscopy and biopsies as clinically indicated. Cytology results were classified as normal, atypical, dysplastic or cancerous, and DNA ploidy was defined as normal if the diploid index was 1.2 or less, the S phase+G2M fraction was less than 21% or if there were 3% or less hyperploid cells, or abnormal if there was an increased S phase+G2M fraction, an aneuploid peak on the histogram or tetraploidy or hyperploidy was present. RESULTS: The majority of patients (85 of 88, 97%) with a cytological diagnosis of cancer had an abnormal DNA ploidy, and in 60 of 85 of these patients (71%) recurrence was diagnosed within 6 months. Only 5 of 284 specimens (2%) with normal cytology had abnormal DNA ploidy and 1 of these 5 (20%) heralded transitional cell carcinoma recurrence. However, in 145 patients with atypical cytological findings 29 (20%) with abnormal DNA ploidy had a recurrence, compared to 20 of 391 (5%) with normal DNA ploidy (p < 0.0001). Similarly, in 101 patients with dysplastic cytological findings 39 (39%) with abnormal DNA ploidy had transitional cell carcinoma recurrence compared to 4 of 25 with normal ploidy (p = 0.033). CONCLUSIONS: Abnormal DNA ploidy determined by image analysis significantly enhances the detection of bladder tumor recurrence in patients with atypical or dysplastic cytology but not in those with normal cytology or frank carcinoma on cytological findings.

Adult↗

PubMed1996

Case report--sirolimus rescue therapy for refractory renal allograft rejection.

Sirolimus not only displays prophylactic activity, it also reverses acute rejection in rats with ongoing renal allograft rejection. The present case of a human renal allograft recipient documents the utility of dual-drug cyclosporine (CsA)/sirolimus therapy for a patient experiencing ongoing acute rejection and renal dysfunction that had not abated after treatment with corticosteroids equine antilymphocyte globulin (ATGAM), or the mouse anti-human CD3 monoclonal antibody OKT3. The patient described herein underwent induction therapy with 7 days of OKT3, and anti-rejection treatment with 14 days of ATGAM followed by 6 days of OKT3 therapy for biopsy-proved rejection episodes that rendered the patient dependent on dialysis treatments, oliguric with a urine output less than 650 ml per day, and uremic with a serum creatinine (sCr) value above 7 mg/dl. When OKT3 therapy was ceased because of the presence of human anti-mouse antibodies, sirolimus was added to the CsA/steroid regimen to treat the ongoing rejection and to reverse the markedly decreased renal perfusion, as revealed by a 99mTc-DTPA scan. Within 6 weeks the patient's sCr value decreased to 1.4 mg/dl, and urine output returned to greater than 2000 ml per day. To date the patient has exhibited no significant side effects after over 4 months of sirolimus therapy and the withdrawal of corticosteroids.

Cyclosporine↗

PubMed1996

Proximal ureteral stent migration: an avoidable complication?

PURPOSE: The parameters responsible for proximal ureteral stent migration were quantitated. MATERIALS AND METHODS: We compared 16 patients seen between 1990 and 1993 with stent migration to 32 patients whose stents did not migrate. RESULTS: The stent indwelling time and number of stents with a proximal curl of less than 180 degrees were similar between the groups. More patients with migration had stents that were shorter than the ideal length, with a distal curl of less than 180 degrees and a proximal curl in the upper calix versus the renal pelvis. CONCLUSIONS: A shorter than ideal stent, inadequate distal curl and a proximal curl in the upper calix appear to be significant factors in the process of stent migration.

Case-Control Studies↗

PubMed1995

Use of ileal urinary diversion in conjunction with intraoperative radiotherapy.

Intraoperative radiotherapy (IORT) was introduced in the 1970s as a new modality of cancer therapy. It has been especially useful after local irradiation or surgical failure. We report on the use of IORT in 13 patients with pelvic tumors requiring urinary diversion. All 13 were managed with ileal conduits. Despite the associated problems of prior abdominal procedures (11/13 patients), prior external beam radiation to the pelvis (11/13 patients), systemic chemotherapy (4/13 patients), and prolonged operative time (> 10 hours), perioperative mortality (1/13) and morbidity rates were low. We conclude that in cases of prior colonic resection and pelvic radiation, potentially irradiated ileum can be safely used for urinary diversion.

Aged↗

PubMed1994

Exposure to alkyllysophospholipids inhibits in vitro invasion of transitional cell carcinoma.

Alkyllysophospholipids (ALP) are a group of synthetic analogs of a naturally occurring 2-lysophosphocholine. They are directly cytotoxic to a variety of neoplastic cell lines and can modulate the activation of macrophages against tumor cells. Moreover, recent reports have demonstrated the ability of racemic 1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (ET-18-O-CH3) to prevent tumor cell invasion when given in noncytotoxic concentrations. Using an in vitro model, we studied the ability of ET-18-O-CH3 to prevent transitional cell carcinoma invasion. Cytostatic activity was determined by clonal growth assay (25,000 cells per plate). Suppression of colony growth was found at concentrations greater than 4 micrograms/ml. of ET-18-O-CH3 in rat and mouse transitional cell carcinoma (TCC) cell lines and greater than 2 micrograms/ml. in a human TCC line. Inhibition of tumor cell invasion was assessed by the effects on cell migration through Matrigel-coated 8 microns-pore polycarbonate filters (using 1 x 10(5) cells per chamber). Invasion was reduced to 50 to 70% of controls in both the mouse and rat TCC lines at the highest concentration (4.0 micrograms/ml.). In the human TCC line, invasion was reduced to less than 30% of controls at concentrations as low as 0.5 micrograms/ml. Motility (without invasion) of the human TCC line, as measured by cell migration through the micropore filter without the Matrigel coating, was inhibited at the same concentration of ET-18-O-CH3 found to inhibit invasion. The anti-invasive effect seen with noncytotoxic concentrations of ALP may prove useful in the treatment of transitional cell carcinoma.

Animals↗

PubMed1994

Conservative management of suspected bladder rupture after augmentation enterocystoplasty.

Bladder rupture after augmentation enterocystoplasty is a potentially life-threatening condition. We reviewed our experience with 13 patients who presented to our institution with 15 episodes of sudden onset of abdominal pain and rebound tenderness, and were diagnosed on clinical grounds to have peritonitis secondary to a suspected bladder augmentation rupture. (Three patients had had similar episodes treated previously elsewhere with abdominal exploration and repair of an augmentation rupture.) These episodes were initially managed with hospitalization, bladder drainage with an indwelling catheter, intravenous antibiotics and serial abdominal examinations. Cystogram and/or computerized tomography was diagnostic in only 3 of 7 cases in which it was performed. In 13 of 15 instances signs and symptoms of peritonitis quickly resolved, and intermittent catheterization was resumed after a mean of 12 days. In the remaining 2 patients delayed surgical repair of a bladder rupture was done in 1, and exploration and repair of an incarcerated internal hernia were done in 1. Although prompt abdominal exploration is the gold standard for suspected bladder augmentation rupture, treatment of peritonitis as bladder rupture in patients with a bladder augmentation by nonoperative techniques was successful in 87% of episodes.

Adolescent↗

PubMed1994

Cyclosporine versus azathioprine: a 5-year followup of 200 consecutive cadaver renal transplant recipients.

When cyclosporine was introduced as an immunosuppressive agent, there was concern that cyclosporine could be detrimental to long-term renal allograft function and survival. In response to this concern, we report a 5-year followup of 200 consecutive renal transplant recipients among whom initial immunosuppression and risk factors were similar except for the substitution of cyclosporine for azathioprine in the second 100 recipients. The azathioprine and cyclosporine groups had similar 1-year (89% versus 91%) and 5-year (74% versus 80%) patient survival rates. Cyclosporine treated patients had superior 1-year (83% versus 58%) and 5-year (61% versus 29%) graft survival rates. At the 5-year interval, cyclosporine treated grafts had an elevated, yet stable, mean serum creatinine level compared to azathioprine treated grafts. Despite ongoing mild renal dysfunction in cyclosporine treated grafts, cyclosporine does not induce an inexorable decrease in graft function and continues to provide long-term graft survival superior to azathioprine.

Azathioprine↗

PubMed1993

Massive necrotizing pancreatitis in an immunosuppressed renal transplant recipient (successful therapy).

Severe pancreatitis may be associated with massive necrosis of the pancreas and/or retroperitoneal adipose tissue. Toxicity results from the dead tissue and secondary infection. A 45 year old patient, while fully immunosuppressed, developed this complication following cadaveric renal transplantation. He survived continued immunosuppression, 16 operative debridements of the retroperitoneum, and maintained a functioning renal transplant. In view of the previously reported high mortality rates from mild pancreatitis after transplantation, the current experience warrants further evaluation of the open method of treatment.

Acute Disease↗

PubMedDate not supplied

Differential expression of progression-related genes in the evolution of superficial to invasive transitional cell carcinoma of the bladder.

It is generally accepted that there are dichotomous biologic pathways that lead to the development of either: i) superficial papillary (Ta) transitional cell carcinoma (TCC) or ii) precursor lesions to muscle-invasive (CIS, T1) TCC and muscle-invasive (> or =T2) TCC. We investigated the expression of several progression-related genes to characterize the phenotype of these tumors within these divergent developmental pathways. Using a colorimetric in situ hybridization technique, we examined the expression of mRNAs of several progression-related genes in archival, pathologic specimens from 77 patients with bladder TCC. These genes included basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), interleukin (IL)-8, matrix metalloproteinase (MMP)-9, and epidermal growth factor receptor (EGFR). Relative gene expression was quantified using image analysis. Gene expression was normalized using poly (dT) and the expression of each factor in a panel of specimens of normal urothelium. Patients were stratified according to disease stage, and the level of gene expression among the stratified groups was compared. VEGF, bFGF, IL-8, and MMP-9 expression was increased in muscle-invasive compared with superficial papillary tumors, (p<0.05) and VEGF expression was increased in muscle-invasive tumors compared with CIS specimens (p<0. 05). bFGF, IL-8, and EGFR expression was increased in CIS specimens compared with superficial papillary tumors (p<0.05). The pattern of expression of bFGF, VEGF, IL-8, MMP-9, and EGFR represent the divergent developmental pathways in the pathogenesis of bladder TCC, which characterizes superficial or invasive bladder cancer. bFGF, IL-8, and EGFR appear to be upregulated in early precursor lesions (CIS), whereas VEGF appears to be upregulated at later stages in the development of muscle-invasive TCC.

Carcinoma in Situ↗

PubMedDate not supplied

Adenoviral-mediated gene therapy of human bladder cancer with antisense interleukin-8.

We previously demonstrated the importance of interleukin-8 (IL-8) as a mediator of angiogenesis, tumorigenicity, and metastasis of transitional cell carcinoma (TCC) of the bladder. In the present study, we evaluated the feasibility of adenoviral mediated antisense IL-8 gene transfer (Ad IL-8-AS) as therapy for established TCC. In vitro, Ad IL-8-AS inhibited endothelial cell proliferation and enhanced endothelial cell apoptosis. The highly metastatic human TCC cell line 253J B-V(R) was implanted into the subcutis of athymic nude mice, and intralesional therapy with Ad IL-8-AS commenced when the tumors reached a diameter between 5 and 7 mm. Tumor growth was significantly inhibited compared with therapy in controls (saline and beta-galactosidase adenovirus). Ad IL-8-AS therapy decreased the in vivo expression of IL-8 and matrix metalloproteinase type 9 (MMP-9), reduced microvessel density, and enhanced endothelial cell apoptosis. These results indicate that Ad IL-8-AS therapy targets both tumor cells and host endothelial cells resulting in endothelial cell apoptosis and significant inhibition of tumor growth.

Adenoviridae↗