An adenovirus 5 vector containing wild-type p53 cDNA (Ad5-p53) and a cytomegalovirus promoter was used to generate p53 transgene expression. Control vector (Ad5-pA) contained the poly-adenosine sequence. PC3 cells (2 x 10(6)) were injected s.c. into the legs of nude mice. Treatment with Ad5-p53 was initiated at a tumor volume of 200 mm3. Three intratumoral injections (days 1, 4, and 7) were given with 3 x 10(8) plaque-forming units, followed by 5 Gy pelvic irradiation (day 8) in one fraction using a cobalt-60 source. Tumor volume measurements were obtained every 2 days. LNCaP cells (2 x 10(6)) were injected orthotopically into the prostates of nude mice, and tumor weight was approximated using serum prostate-specific antigen (PSA) obtained from weekly tail vein bleedings. The target PSA for the start of the studies was 5 ng/ml. The intraprostatic injections of Ad5-p53 were done twice (days 1 and 2) and followed by 5 Gy pelvic irradiation on day 3. The PC3 tumor volume growth curves were log transformed and fitted using linear regression. The times (in days) for the tumors to reach 500 mm3 were calculated as 10.7 +/- 0.7 (+/- SE) for the saline control (no virus), 9.8 +/- 2.1 for Ad5-pA, 15.6 +/- 1.6 for Ad5-p53, 14.6 +/- 1.5 radiation therapy (RT; 5 Gy), 14.6 +/- 1.5 for Ad5-pA plus RT, and 31.4 +/- 5.3 for Ad5-p53 plus RT. The Ad5-p53 plus RT times were significantly different from the other groups. An enhancement factor of 3.4 was calculated, indicating supra-additivity. LNCaP tumor growth was determined via weekly serum PSA measurements. Treatment failure was determined using two PSA-based methods; a serum PSA of > 1.5 ng/ml or two rises in PSA during 6 weeks posttreatment. The results were similar using either end point. Treatment with Ad5-p53 plus 5 Gy resulted in significantly fewer PSA failures (<30%), as compared with Ad5-p53 alone (64-73%) and the other controls (approximately 80-100%) These results are also consistent with a supra-additive inhibition of tumor growth. Tumor growth in vivo was inhibited supra-additively when p53null and p53wildtype prostate tumors were treated with Ad5-p53 and 5 Gy radiation.

Adenoviridae↗

PubMed2000

[Surgery for blepharoptosis in muscular dystrophy].

In some muscular dystrophies there is ocular involvement characterized by blepharoptosis and ophthalmoplegia. These conditions occur in chronic progressive external ophthalmoplegia, oculopharyngeal muscular dystrophy, mitochondrial myopathy, myotonic dystrophy, and ocular myasthenia, among others. Although they differ in their systemic clinical manifestations and in genetic inheritance, ocular involvement is common to all of them. Manifestations include bilateral progressive blepharoptosis with or without extraocular muscle malfunction. During surgical repair of the ptotic eyelid, consideration must be given to eyeball movements, in addition to maximal eyelid elevation, and to avoiding overcorrection and consequent corneal overexposure, leading to dryness and visual impairment. With these muscular dystrophic disorders, resection of the levator muscle or blepharoplasty alone does not suffice. Follow-up shows that most patients need a secondary repair after a short while. Operative correction uses a frontalis sling for eyelid elevation and support. A series of 8 patients with these diseases, operated on by various surgical techniques during the past 7 years, is presented.

Adolescent↗

PubMed1999

Relationship of Ki-67 labeling index to DNA-ploidy, S-phase fraction, and outcome in prostate cancer treated with radiotherapy.

BACKGROUND: Our purpose was to evaluate the relationship of Ki-67 labeling index (Ki67-LI) to deoxyribonucleic acid (DNA) ploidy, S phase fraction (SPF), other clinical prognostic factors, and clinical outcome for patients with prostate cancer treated by external beam radiotherapy. METHODS: Tissue was retrieved from 42 patients who underwent transurethral resection of the prostate before treatment with external beam radiotherapy between 1987-1993. DNA histogram profiles were classified as diploid (diploid + near-diploid) and nondiploid (tetraploid + aneuploid). Immunohistochemical staining of Ki-67 by the MIB-1 monoclonal antibody was used to calculate Ki67-LI. Median patient follow-up was 62 months. Treatment failure was defined as two consecutive rises in serum prostate-specific antigen (PSA) or clinical evidence of disease recurrence. RESULTS: The mean and median Ki67-LIs were 3.1 and 2.4, respectively (range, 0-12.4). Mean Ki67-LI values were significantly associated with higher stage, Gleason score, and pretreatment PSA. Nondiploid tumors had significantly higher Ki67-LIs, as did patients who failed radiotherapy over the follow-up period. SPF was not significantly correlated with Ki67-LI. As a categorical variable, the most significant relationships were seen when Ki67-LI was subdivided into thirds around the median (Ki67-LI </=1.5%, Ki67-LI >1.5-3.5%, and Ki67-LI >3.5%). This trichotomous variable correlated significantly with pretreatment PSA (P = 0.0008), tumor stage (P = 0.016), Gleason score (P = 0.024), and treatment failure (P = 0.0015), but not with DNA-ploidy (P = 0.15). In actuarial univariate analyses, Ki67-LI appeared to be a more significant predictor of patient outcome (P = 0.003) than DNA-ploidy (P = 0.035). CONCLUSIONS: The Ki67-LI correlated with known prognostic factors such as pretreatment PSA, tumor stage, and Gleason score, and was also weakly related to DNA-ploidy. In comparison to DNA-ploidy, Ki67 LI seems to be a better correlate of treatment outcome.

Aged↗

PubMed1999

Conventional external-beam radiation therapy alone or with androgen ablation for clinical stage III (T3, NX/N0, M0) adenocarcinoma of the prostate.

PURPOSE: To evaluate the outcome of clinical Stage III (T3, N0/NX, M0) prostate cancer treated by conventional radiation alone or with adjuvant androgen ablation. METHODS AND MATERIALS: Three hundred forty-four men with T3, N0/NX, M0 adenocarcinoma of the prostate who received conventional radiation alone (260) or with androgen ablation (84) were analyzed for relapse or rising prostate-specific antigen (PSA), using univariate and multivariate techniques. RESULTS: With a median follow-up of 68 months, the 260 men treated with radiation alone had a 10-year actuarial rate of relapse or rising PSA of 76%. Pretreatment PSA level (< or = 10 ng/ml vs. > 10 < or = 20 ng/ml vs. > 20 ng/ml) and radiation dose (< 68 Gy vs. > or = 68 Gy) were the only independently significant determinants of biochemical failure; Gleason score (2-7 vs. 8-10) was an additional determinant of metastatic relapse. Patients treated to doses < 68 Gy experienced 6-year failure rates exceeding 50% regardless of PSA level. Patients with PSA < or = 10 ng/ml and receiving 68-70 Gy had a 6-year failure of 24%, but those with PSA > 10 ng/ml had relapse rates exceeding 50% even at doses of 70 Gy. At a median follow-up of 44 months, the 84 patients treated with radiation and androgen ablation had a 6-year biochemical failure rate of 22%. The only significant determinant of outcome in this group was pretreatment PSA; patients with PSA < or = 80 ng/ml had a 6-year failure rate of only 12% compared to a failure rate of 53% for those with PSA > 80 ng/ml. The outcome for those treated with combined modalities was significantly better than for those treated with radiation alone in all PSA strata. CONCLUSION: Conventional radiation alone has little curative potential for Stage III disease. Doses < 68 Gy are particularly ineffective. Patients with PSA < or = 10 ng/ml may be candidates for conventional radiation to a dose of 70 Gy. Other patients are probably best served by combined radiation-androgen ablation or high-dose conformal radiation.

Acid Phosphatase↗

PubMed1999

Transrectal ultrasound for staging prostate carcinoma prior to radiation therapy: an evaluation based on disease outcome.

BACKGROUND: Despite its subjectivity and inaccuracy, digital rectal examination (DRE) has a long history of well-documented prognostic significance in patients with prostate carcinoma. To the authors' knowledge, very few studies have evaluated the relative prognostic merits of transrectal ultrasound (TRUS) versus DRE. This question is addressed in this study. METHODS: The outcome for 558 men with T1-T3, N0, M0 adenocarcinoma of the prostate who underwent both DRE and TRUS and received external beam radiation without androgen ablation was evaluated relative to the prognostic information from DRE, TRUS, or both. The outcome endpoints were no evidence of disease (NED) (no relapse or rising prostate specific antigen level) and freedom from metastases. Prognostic factors were evaluated with univariate and multivariate techniques. The median follow-up was 55 months. RESULTS: Both purely DRE-based and purely TRUS-based T categories correlated significantly with NED status. For DRE T categories, 6-year NED rates for T1/T2 and T3 disease were 64% and 36%, respectively (P < 0.001). For TRUS T categories, the rates for T1/T2 and T3 were 63% and 39%, respectively (P < 0.001). There were significant differences in patient composition between DRE and TRUS T categories. Only 40% of patients were in the same DRE and TRUS category, but the majority of the reclassification based on TRUS was within rather than between major T categories (T1/T2 vs. T3). Changes between the prognostically significant T1/T2 versus T3 categories occurred in < or =25%. This accounted for the similarity in NED outcome for DRE and TRUS T categories. However, TRUS categories did not discriminate significantly for metastatic recurrence between T1/T2 and T3 categories, whereas DRE categories did. Upstaging or downstaging by TRUS relative to DRE did not alter the DRE prognostic groupings substantially. CONCLUSIONS: There was no clinically meaningful superiority of TRUS over DRE in the definition of prognostically useful T categories. Moreover, the addition of TRUS to DRE did not enhance the prognostic value of DRE findings in any meaningful way. Despite its subjectivity and inaccuracy, DRE provides prognostic information at least equivalent to TRUS and is preferable because of its low cost.

Adenocarcinoma↗

PubMed1999

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Explore the source record for details and available documents.

Humans↗

PubMed1999

Familial prostate cancer: outcome following radiation therapy with or without adjuvant androgen ablation.

PURPOSE: To compare the outcome of familial versus sporadic prostate carcinoma after definitive external radiation. METHODS AND MATERIALS: Between 1987 and 1996, 1214 men with clinically localized prostate cancer (T1-T4, N0/NX, M0) received definitive radiation therapy in our department. By retrospective review of charts and questioning of patients, a record on the presence or absence of prostate cancer in a first degree relative was obtained in 1164 men. Univariate and multivariate analysis was performed on these cases with relapse or rising prostate-specific antigen (PSA), local recurrence, metastasis, and survival as endpoints. RESULTS: Familiar prostate cancer was present in 148 of 1164 men (13%). Men with familial disease were slightly but significantly younger (mean 66 years) at diagnosis than those with sporadic disease (mean 68 years) (p = 0.02). Apart from this there were no significant differences between the two groups in T-stage, Gleason score, pretreatment PSA levels, DNA ploidy, or serum testosterone levels. There were no significant differences in treatment parameters including radiation dose and the use of adjuvant androgen ablation. With a median follow-up of 42 months, there was no difference in freedom from relapse or rising PSA at 6 years between those with a family history (54%) and those without a family history (58%) (p = 0.171). Likewise there was no difference between the two groups when local recurrence or metastasis was the endpoint. Multiple subgroup analyses (younger and older; T1/T2 and T3; low Gleason and high Gleason; no androgen ablation and androgen ablation; race) failed to reveal any differences in outcome in any category between familial and sporadic disease. Among patients with a rising post-treatment PSA profile, PSA doubling times were similar in those with sporadic and familial disease. CONCLUSIONS: This study provides no evidence for any substantial difference between familial and sporadic prostate cancer either in clinicopathological features, in response to treatment, or in ultimate outcome.

Age Factors↗

PubMed1999

Patterns of recurrence in extremity liposarcoma: implications for staging and follow-up.

BACKGROUND: Liposarcoma is one of the most common histologic types of soft tissue sarcoma and presents a wide spectrum of clinical behavior. The authors examined the correlation among histologic subtypes, outcomes, and patterns of recurrence among patients with extremity liposarcomas. METHODS. A retrospective review of all patients with intermediate and high grade extremity liposarcoma referred to the University of Texas M. D. Anderson Cancer Center from January 1, 1980, to December 31, 1992, was performed. Data on clinical presentation, treatment, patterns of treatment failure, and outcome were evaluated. RESULTS: During the 13-year study period, 122 patients with intermediate or high grade extremity liposarcoma were identified: 102 patients (84%) with myxoid subtype, 18 patients (15%) with pleomorphic subtype, and 2 patients (2%) with mixed histology. There were no differences between the myxoid and pleomorphic subtype groups in tumor size (T1 vs. T2), depth in relation to the muscular fascia, or anatomic site. The median follow-up was 70 months. The 5-year overall survival rate for all intermediate and high grade extremity liposarcoma patients presenting with primary disease (n=85) was 74%; the 5-year local recurrence free survival, distant recurrence free survival, and disease free survival rates were 93%, 78%, and 73%, respectively. Among the 102 patients with myxoid tumors, 33 had distant recurrences; 31 of these were to extrapulmonary soft tissue sites (e.g., the retroperitoneum, chest wall, pleura, pericardium, pelvic sidewall, and soft tissue of the back), and 2 were to the lung only. Among the 18 patients with pleomorphic tumors, 10 had distant recurrences; 3 occurred at extrapulmonary sites, and 7 occurred in the lung only (P < 0.05 for myxoid vs. pleomorphic subtypes). CONCLUSIONS: Myxoid liposarcomas often metastasized to extrapulmonary sites and did so significantly more frequently than pleomorphic tumors. Imaging of the abdomen, retroperitoneum, and extrapleural chest should be performed for accurate staging and posttreatment follow-up of patients with myxoid liposarcoma. Patients presenting with "primary" myxoid liposarcoma of the trunk should be carefully evaluated for an occult primary tumor in an extremity.

Adolescent↗

PubMed1999

Cataract development in sand and galactosemic rats fed a natural tomato extract.

This study investigated the effect of a natural tomato extract (TE) on cataract formation in two animal models. A TE containing 5% lycopene was included in the diet of diabetic sand rats at 0.2%, and Sprague Dawley rats were fed a high-galactose diet (30 g/100 g of diet), supplemented with either the lycopene-rich extract at concentrations of 0.2, 0.4, and 0.8% or BHT (0.2%). TE had no significant effect on plasma glucose levels or cataract development in sand rats; however, in rats maintained on a diet rich in galactose, both BHT and TE decreased cataract incidence, and grades were lower than in control animals. In addition, lens protein and reduced glutathione levels were higher and aldose reductase activity was lower than in the control group. The results suggest that antioxidants act as protective agents when oxidative stress is a primary cause of cataract formation but may be less effective in preventing cataracts in hyperglycemic animals.

Analysis of Variance↗

PubMed1999

Predictive value of family data for the management of infantile bilateral partial cataract.

PURPOSE: To examine the data on outcome of surgery performed over a wide age range in members of a family affected by familial infantile bilateral partial cataract, with the purpose of assessing their predictive value concerning the timing of surgery. METHODS: A retrospective clinical study was carried out of a family with dominant inheritance of familial infantile bilateral partial cataract. The family spanned four generations and consisted of 53 members, 31 of whom were examined in our department. Of these, 18 were affected. Cataract surgery was performed in 26 eyes of 15 patients, whose ages ranged from 6 to 58 years at the time of operation. As the surgical procedures spanned the years from 1978 to 1996, different techniques were used. RESULTS: In 24 eyes (92%) the post-operative visual acuity was 6/9 or better. One eye achieved 6/12 and another 6/15. CONCLUSIONS: In this particular family there was no relationship between the post-operative visual acuity and the age at which surgery was performed. In deciding when to operate on family members with infantile bilateral partial cataract with similar morphology, in addition to the commonly used criteria the family data should also be taken into account. In infants and young children, delaying surgery may allow better development of visual acuity aided by accommodation, stabilisation of binocularity and more precise determination of the power of an intraocular lens. Success of very early surgery in such cases may not be attributable to the timing of the operation.

Adolescent↗

PubMed1999

Desmoid tumor: prognostic factors and outcome after surgery, radiation therapy, or combined surgery and radiation therapy.

PURPOSE: To evaluate the therapeutic value of resection and the potential benefits of and indications for adjuvant and definitive radiation therapy for desmoid tumors. MATERIALS AND METHODS: We performed a retrospective review of 189 consecutive cases of desmoid tumor treated with surgical resection, resection and radiation therapy, or radiation therapy alone. Treatment was surgery alone in 122 cases, surgery and radiation therapy in 46, and radiation therapy alone in 21. Median follow-up was 9.4 years. RESULTS: Overall, 5- and 10-year actuarial relapse rates were 30% and 33%, respectively. Uncorrected survival rates were 96%, 92%, and 87% at 5, 10, and 15 years, respectively. For the patients treated with surgery, the actuarial relapse rates were 34% and 38% at 5 and 10 years, respectively. Among 78 patients with negative margins, the 10-year recurrence rate was 27%, whereas 40 margin-positive patients had a 10-year relapse rate of 54% (P = .003). Tumors located in an extremity also had a poorer prognosis than did those in the trunk. For patients treated with radiation therapy for gross disease, the 10-year actuarial relapse rate was 24%. For patients treated with combined resection and radiation therapy, the 10-year actuarial relapse rate was 25%. The addition of radiation therapy offset the adverse impact of positive margins seen in the surgical group. CONCLUSION: Wide local excision with negative pathologic margins is the treatment of choice for most desmoid tumors. Function-sparing resection is appropriate because adjuvant radiation therapy can offset the adverse impact of positive margins. Unresectable disease should be treated with definitive radiation therapy.

Adolescent↗

PubMed1999

Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas.

PURPOSE: It has been suggested that patients with small (< 5 cm), high-grade extremity soft tissue sarcomas (STS) have an excellent overall prognosis and, consequently, may not require adjuvant therapies. PATIENTS AND METHODS: A comprehensive review of all patients with extremity STS treated at a tertiary care cancer hospital over a 9-year period (January 1984 to December 1992) was performed. Prognostic factors, treatment data, and long-term outcome were evaluated in the subset of 111 patients with American Joint Committee on Cancer stage IIB (G3/4, T1a/b) disease. RESULTS: The median tumor size was 3.0 cm (range, 0.6 to 4.9 cm), and 55 tumors (50%) were deep in location. All patients underwent surgical resection; 68 (61%) received pre- or postoperative radiotherapy, and 32 (29%) received doxorubicin-based chemotherapy. The median follow-up was 76 months. Forty patients (36%) experienced 59 recurrences. First recurrences occurred at local, regional, and distant sites in 21, five, and 14 patients, respectively. The 5-year actuarial local recurrence-free, distant recurrence-free, disease-free, and overall survival rates were 82%, 83%, 68%, and 83%, respectively. The presence of a microscopically positive surgical margin was an independent adverse prognostic factor for both local recurrence (relative risk [RR] = 3.75; 95% confidence interval [CI], 1.25 to 11.25; P =.02) and disease-free survival (RR = 2.57; 95% CI, 1.33 to 4.98; P =.005). CONCLUSION: Event-free outcome for this subset of patients with high-grade STS does not seem as favorable as previously reported by other investigators. Patients who undergo maximal surgical resection with microscopically positive margins represent a subset of T1 STS patients who warrant consideration for adjuvant therapies.

Adolescent↗

PubMed1999

Spontaneous spinal subdural hematoma in a young adult with hemophilia.

Spontaneous spinal subdural hemorrhage is a rare clinical problem that usually manifests with a sudden onset of pain and paralysis. This article reports on an 18-year-old male with hemophilia A and cerebral palsy, who experienced a several month history of transient back, hip, and leg pain accompanied by gait difficulties that ultimately culminated in a more striking episode of lower extremity weakness, irritability, and diffuse pain involving the neck, back, and legs. In the absence of any clinical or radiographic evidence of hemarthrosis, osteomyelitis, or intracranial hemorrhage, imaging of the spine disclosed a large, apparently multicompartmentalized intraspinal lesion, consistent with old hemorrhage. This extended from the thoracic to the sacral region, with the largest extent at the lumbosacral junction. Following correction of factor VIII levels, surgical exploration was undertaken and demonstrated liquefied blood within the subdural space without violation of the underlying arachnoid. Because the chronic subdural blood flowed quite easily through the dural opening by simply angling the operating table, a limited exposure was required to achieve a substantial evacuation of the clot. This case calls attention to the often protean manifestations of this process, the potential for a chronic course to the clinical symptoms, and the possibility of achieving substantial clot evacuation and clinical recovery with a limited operative approach.

Adolescent↗

PubMed1999

Prostate cancer treatment with radiotherapy: maturing methods that minimize morbidity.

Technological advances in treatment delivery and planning have provided the backdrop for an unprecedented number of options in the treatment of prostate cancer with radiotherapy. The more common choices include classical external-beam radiotherapy, external-beam radiotherapy using three-dimensional treatment planning and conformal radiotherapy (3DCRT), ultrasound-guided transperineal implant monotherapy alone or in combination with external-beam radiotherapy, and intensity-modulated radiotherapy (IMRT) techniques. This chapter reviews the data from these methods with an emphasis on dose escalation, provides comparisons with prostate-specific antigen (PSA)-era radical prostatectomy series where appropriate, and highlights future initiatives designed to further improve outcome.

Brachytherapy↗