Is there really an ethical conflict in clinical trials?
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Breast Neoplasms↗
Biomedical subjects
W Lawrence
Publications and source records attributed to W Lawrence.
Conservative management of uterine pediatric rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study III and IV pilot.
Previous studies have suggested that women with uterine rhabdomyosarcomas (RMS) represent a distinct group of patients who present at an older age, are less responsive to treatment, and have a poorer prognosis than patients with vaginal RMS. During the Intergroup Rhabdomyosarcoma Study (IRS) III and the IRS IV pilot study, 14 patients were registered with uterine primary RMS. Three patients presented with cervical tumors that were completely removed (group 1). Eight patients had initial biopsies with gross residual disease (group 3), and 3 had metastatic disease at presentation (group 4). Of the 5 patients treated with primary chemotherapy or chemotherapy and radiation, 2 had delayed hysterectomy and vaginectomy, 1 had no further surgery, and 2 had exploratory laparotomy with no evidence of disease. There were no relapses or deaths in this group. One patient underwent initial resection of a broad ligament mass, experienced an early (3-week) recurrence of the mass while on chemotherapy, and progressed to developing distant metastases and death. Four patients died of chemotherapy toxicity or sepsis, one after achieving a complete response from chemotherapy and hysterectomy. This primary chemotherapy or chemotherapy and radiotherapy regimen resulted in 8 of 9 (89%) patients (not including those who died of chemotoxicity) surviving between 1.5 and 6 years without evidence of disease. Of the surviving patients, 2 had hysterectomy and vaginectomy, but pathological specimens showed only localized microscopic residual tumor. This report suggests that less vigorous operative resection may be possible in combination with primary chemotherapy when treating uterine rhabdomyosarcomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Conservative surgical management of vaginal and vulvar pediatric rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study III.
The current management of pediatric vaginal and vulvar rhabdomyosarcoma (RMS) uses cytoreductive chemotherapy before surgical intervention. During the Intergroup Rhabdomyosarcoma Study (IRS)-III (1984 to 1988), 27 evaluable patients were entered on a preoperative chemotherapy protocol. Among 24 patients with vaginal primaries, 20 had an initial biopsy with gross residual (group III), 3 had resection with positive margins (group IIA) and 1 had metastatic disease (group IV). At subsequent surgery, 7 patients underwent partial or complete vaginectomy and 6 of them had no viable tumor identified in the specimen. Only 1 of these 7 patients underwent a cystectomy, whereas 5 underwent hysterectomy. Seventeen patients in this group have no evidence of disease 66 to 108 months after diagnosis; 2 died of chemotoxicity and 1 of unknown causes after achieving a complete response. Ten of these 17 patients were treated with biopsy and chemotherapy only. Four of these 10 had radiotherapy as well. All group IIA patients have no evidence of disease. The 1 group IV patient had rapidly progressive disease with early death. This primary chemotherapy protocol resulted in less need for operative intervention or irradiation compared with previous experience. There was no local recurrence, and 20 of 24 patients remain continuously relapse-free with no evidence of disease. All 3 patients with vulvar primaries were treated by wide local excision and chemotherapy and have no evidence of disease. Conservative surgical intervention for vaginal RMS with primary chemotherapy and adjunctive radiation when necessary appears to result in excellent disease-free survival.
Adolescent↗
Improved survival with preoperative chemotherapy followed by resection uncompromised by tumor response for advanced squamous cell carcinoma of the head and neck.
BACKGROUND: A total of 93 patients were treated with one of two preoperative chemotherapy regimens over a 15-year period. The study supports the importance of strict adherence to guidelines for ablative surgery. METHODS: A single surgeon performed the surgery and evaluated each patient prior to treatment. The extent of the planned operation was documented. RESULTS: The 5-year absolute survival of 88 patients who completed the protocol was estimated at 55%. The 40 cisplatin/5-fluorouracil-treated patients exhibited a significantly better outcome than the 48 cisplatin/bleomycin-treated patients (76% versus 43%, respectively). Comparison of a subset of 37 patients with a matched group from the standard control arm of the Head and Neck Contracts Program demonstrated a statistically significant improvement in overall survival over standard treatment. CONCLUSIONS: These data suggest that strict adherence to preoperative chemotherapy planning of ablative uncompromised surgery contribute to improved survival. Selective rather than routine postoperative radiotherapy may be advantageous.
Antibiotics, Antineoplastic↗
A multicenter, randomized, prospective study of endoscopic laser ablation versus transurethral resection of the prostate.
OBJECTIVES: To assess the safety and efficacy of endoscopic laser ablation of the prostate (ELAP), performed with the Urolase fiber and the neodymium:yttrium-aluminum-garnet laser, compared to transurethral resection of the prostate (TURP) in patients with bladder outflow obstruction secondary to benign prostatic hyperplasia (BPH). METHODS: In this multicenter, prospective, randomized study, a total of 151 patients were treated (ELAP, 76; TURP, 75) of whom 137 completed 1 year follow-up (ELAP, 67; TURP, 70). Safety parameters included measurement of preoperative and 24-hour postoperative sodium, hematocrit, and hemoglobin values and careful monitoring of adverse events. Efficacy was assessed with the American Urological Association symptom score (6), urinary flow rates, and residual urinary volume measurements. RESULTS: There was 1 death in each group during the study period unrelated to the treatment procedure. There was a clinically significant improvement in all efficacy parameters in both groups. Between group comparisons favored TURP in maximum flow rate, residual urinary volume, and symptom score. ELAP had a better safety profile than TURP in the defined safety parameters of drop in hemoglobin and hematocrit values. In 16% of patients, a blood transfusion was required after TURP compared with no transfusions in the ELAP group. Urinary tract infections and dysuria were more frequent in the ELAP group. CONCLUSIONS: ELAP performed with the Urolase fiber is a useful alternative therapy to TURP in patients presenting with bladder outflow obstruction secondary to BPH.
Aged↗
Children with vesical rhabdomyosarcoma (RMS) treated by partial cystectomy with neoadjuvant or adjuvant chemotherapy, with or without radiotherapy. A report from the Intergroup Rhabdomyosarcoma Study (IRS) Committee.
PURPOSE: Children with bladder rhabdomyosarcoma (RMS) are currently treated with primary chemotherapy and usually with local irradiation. More than 30% of this group ultimately require total cystectomy. The purpose of this study was to review the results of the use of partial as opposed to total cystectomy in 40 patients with bladder RMS during Intergroup Rhabdomyosarcoma Study (IRS)-I, -II, and -III (1972-1989). PATIENTS AND METHODS: A total of 171 children with primary RMS of the bladder were enrolled in the IRS during this interval. Partial cystectomy was performed in 40, in 33 before any other therapy and in seven after 10-57 weeks of chemotherapy (primarily vincristine, actinomycin-D, and cyclophosphamide, i.e., VAC) +/- radiotherapy. Surviving patients have been observed for 4-22 years. RESULTS: Thirty-one of 40 patients (78.5%) have been disease free for 2-16 years. Survival among all other IRS cases with bladder RMS during the same interval was 79.5%. Of the 31 surviving patients, one required secondary total cystectomy and two required bladder augmentation procedures for benign bladder contracture. Three quarters of the total group of living patients who have undergone partial cystectomy are without bladder-related symptoms or demonstrable lower urinary tract disease. The remaining patients have a history of functional bladder problems related to contracture or incontinence. CONCLUSIONS: Partial cystectomy is an alternative to total cystectomy for bladder RMS when the tumor site makes it anatomically feasible. In such patients, it should be considered before total cystectomy and in patients with persistent areas of questionable residual tumor after otherwise apparently successful regimens of primary chemotherapy +/- radiotherapy.
Adolescent↗
Retroperitoneal node biopsy in paratesticular rhabdomyosarcoma.
UNLABELLED: Retroperitoneal lymph node dissection (RPLND) was used in 121 Intergroup Rhabdomyosarcoma Study (IRS) III patients with nonmetastatic paratesticular (PT) rhabdomyosarcoma (RMS) to assess retroperitoneal lymph node (RPLN) involvement so as to determine the need for x-ray therapy (XRT). Clinical node evaluation (CNE) was accomplished by a computed tomography (CT) scan in 105 and a sonogram in six. Pathological node evaluation (PNE) was performed in 113: lymphadenectomy (9 bilateral, 85 unilateral) and biopsy in 19. Vincristine and actinomycin D were used for 1 year postoperatively in 89%; all patients who had positive PNE received RPLN XRT. This study compares CNE with PNE and evaluates predictors of relapse and survival. FINDINGS: There were clinically negative nodes (cN0) in 81% of the 121 patients. Among cN0 patients, 14% had positive nodes (pN1). Of the clinically positive (cN1) patients, 94% had pN1. RPLN relapse occurred in only two of the 121 patients. Initially both had cN0 and one had PNE that was negative. For all 121 patients, the 5-year survival was 91%. For cN0 patients, the 5-year survival was 96% compared with 69% for cN1 patients (P < .001). Among the children in whom treatment failed, nodes were cN1 in 5 of 11 (45%) compared with 15 of 107 (14%) in those whose treatment did not fail (P < .008). CONCLUSIONS: (1) Results of RPLN imaging studies were negative in 81% of patients with PT RMS (specificity 99%, sensitivity 57%). (2) RPLN recurrence is uncommon (even when RPLN are initially involved) if regional XRT and appropriate chemotherapy are used.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Diastolic compliance of hypertrophied ventricle is not acutely altered by pharmacologic agents influencing active processes.
OBJECTIVE: To test, by studying the acute effects of drugs that influence active processes, the hypothesis that in humans with marked ventricular hypertrophy, reduced chamber compliance is primarily caused by passive structural changes. DESIGN: An uncontrolled (before-after) study. SETTING: University Medical Center. PATIENTS: Fourteen patients with ventricular hypertrophy (19 +/- 4.5-mm diastolic-wall thickness) and normal resting systolic function were studied while they had invasive cardiac catheterization. INTERVENTION: Intravenous beta-blocker (esmolol) or calcium channel blocker (verapamil) or both. MEASUREMENTS: Left ventricular function was determined by pressure-volume relations. Volume was measured using conductance catheter, providing a continuous voltage signal proportional to chamber volume. Pressure was measured by micromanometer. Cardiac-specific assessment of change in chamber contractility and diastolic compliance due to each drug was determined. RESULTS: Both drugs lowered contractility by approximately 30% (P < 0.01). Esmolol slowed relaxation and reduced early peak filling rate, whereas verapamil delayed the time to peak filling (all P < 0.05). In contrast to the effects of both drugs on active contraction and early diastole, late-diastolic compliance was unaltered, and end-diastolic pressure-volume relations were almost identical. CONCLUSION: Neither beta-receptor nor calcium channel blockade acutely alters left ventricular compliance despite substantial active effects manifest in systole and early diastole. This supports the notion that chamber compliance is principally determined by passive structural elements in the heart rather than by active processes.
Adrenergic beta-Antagonists↗
The effects of group housing on the research use of the laboratory rabbit.
This project evaluated the influence of group housing on common aspects of research use of female laboratory rabbits (Oryctolagus cuniculus). Eight rabbits housed individually in conventional cages were compared to a second group of 8 housed as a social group in a proportionately larger enclosure. The group housing method provided increased opportunities for exercise, social contact, and a more novel environment. As a function of housing style, the 2 experimental groups were compared on humoral and delayed hypersensitivity response, feed intake, growth rate, and selected physiological parameters that are considered to reflect stress in most species. Single and group housed rabbits did not significantly differ in physiological and immunological measurements, indicating that the practical research performance (immune response, stress level, growth rates etc.) of these rabbits was not significantly affected by group housing compared with the more traditional single housing. Analysis of group social behaviour indicated that the rabbits preferred small social groups, had preferences for microenvironments within the enclosure, and exhibited behaviours that are not possible when housed singly. Group housing appeared to be a successful method for enriching the environment of female rabbits and aspects of it should be considered in the approach to housing rabbits used in research.
Animals↗
Modulation of cell cycle kinetics in human cancer with total parenteral nutrition.
Prior DNA flow cytometric data from the laboratory of the Division of Surgical Oncology, Massey Cancer Center, demonstrated an increase in the hyperdiploid compartment of tumor cells taken from patients with squamous cell carcinoma of the head and neck after a course of total parenteral nutrition (TPN). To assess a putative increase in the percentage of tumor cells actively synthesizing DNA in this system, the authors administered bromodeoxyuridine (BrdU) intravenously to ten patients before and after the administration of TPN. Cell suspensions prepared from biopsy specimens of normal oral mucosa and tumor tissue were analyzed with flow cytometric study. Before TPN administration, the mean percentage of tumor cells incorporating BrdU was 2.47 +/- 1.11%. After TPN administration, the percentage of S-phase cells increased significantly (P less than 0.05) to a mean of 4.52 +/- 2.67%. Before TPN was given, normal mucosa demonstrated a mean of 7.97 +/- 2.69% of cells incorporating BrdU. After TPN was given, a mean of 8.47 +/- 2.51% was seen (not significant [NS]). A potential strategy for the use of TPN to enhance tumor cell susceptibility to S-phase-specific chemotherapy is strongly suggested by these data.
Adult↗
Formal hepatic resection of colorectal liver metastases. Ploidy and prognosis.
Fifty consecutive patients who underwent 52 formal hepatic resections (excluding isolated wedge resections) for metastatic colorectal cancer were analyzed to determine whether DNA content was of prognostic significance. The Dukes' stages of the colorectal primaries were: A (10%), B (20%), C (40%), D (28%), and unknown in 2%. Four patients whose liver metastases were discovered at the time of resection of the primary bowel cancer underwent concomitant liver resection, and the remaining patients underwent delayed resections. The hepatic resections performed were right lobectomy (50%), extended right lobectomy (19%), left lobectomy (13%), left lateral segmentectomy (6%), left lobectomy and right wedge (6%), extended left lobectomy (4%), and right lobectomy and left wedge (2%). The overall morbidity rate was 29%. The in-hospital mortality rate was 9%. As of November 1991, 36 patients have recurred. The 5-year actuarial survival was 28%. Flow cytometry could be performed on 37 archival specimens, 15 of which were found to be diploid whereas 22 were aneuploid. All metastases from Dukes A colorectal primaries demonstrated a diploid DNA content. In addition, there was no difference in actuarial survival between diploid and aneuploid tumors. These data suggest that in selected patients, formal hepatic resection of colorectal liver metastases can be performed with an acceptable morbidity rate, mortality rate, and survival, but ploidy of the resected tumor is not of prognostic significance.
Adult↗
Reduced left ventricular compliance in human mitral stenosis. Role of reversible internal constraint.
BACKGROUND: The mechanisms of depressed left ventricular (LV) pump performance in human mitral stenosis (MS) remain poorly understood, because reduced filling alone affects many hemodynamic measurements. Therefore, pressure-volume relations were examined in nine subjects with MS and compared with eight age-matched normal controls. METHODS AND RESULTS: Data were obtained by conductance catheter/micromanometer technique with transient inferior vena cava occlusion used to alter load and generate pressure-volume relations. In a subset of patients (n = 5), data were obtained both acutely and at 3 months (n = 4) after balloon valvuloplasty. MS patients had reduced cardiac output (3.3 +/- 0.9 versus 5.6 +/- 1.7 l/min) and end-diastolic volume (68.0 +/- 6.9 versus 115 +/- 31 ml) versus controls (p less than 0.001), with a mean transvalvular gradient of 14 +/- 6 mm Hg and estimated valve area of 0.6 +/- 0.2 cm2. Systolic function as assessed by the end-systolic pressure-volume relation was virtually the same in MS and control subjects. In contrast, end-diastolic pressure-volume relations in MS were consistently shifted leftward and had an increased slope (lower compliance) at matched pressure ranges (6.5 +/- 3.0 versus 2.2 +/- 0.53 ml/mm Hg at a mean diastolic pressure of 8 mm Hg, p less than 0.001). This change was not a result of reduced LV filling or probably of increased right heart loading. Valvuloplasty acutely returned chamber compliance to near normal, a change that was sustained at 3-month follow-up. Systolic function was little altered at this time. CONCLUSIONS: These data indicate an impairment of diastolic function in human MS that can be acutely reversed by balloon valvuloplasty. Lowered LV compliance probably results from a functional restriction caused by ventricular attachment to a thickened and immobile valve apparatus.
Cardiac Catheterization↗
The role of asparagine-linked oligosaccharides in the subunit structure, steroid binding, and secretion of androgen-binding protein.
Testicular androgen-binding protein (ABP) and liver sex hormone-binding globulin are encoded by the same gene. These proteins have the same primary amino acid sequences, but they differ in attached oligosaccharides; the differences are presumably due to cell-specific glycosylation mechanisms. To investigate the role of oligosaccharides in ABP/sex hormone-binding globulin subunit structure, secretion, and steroid binding, mutant rat ABP proteins were constructed that eliminated one or both of the two potential sites of asparagine (Asn)-linked glycosylation. Immunoblot analysis of wild type recombinant ABP yielded the typical heterogeneous banding pattern. Secreted ABP was composed of two protomers of M(r) 46,000 and M(r) 43,000, while cellular ABP yielded three mol wt species (M(r) 43,000, 41,000, and 39,000). Substitution of the Asn residue in either consensus sequence for Asn-linked glycosylation with an Ile residue resulted in increased mobility of the immunoreactive ABP species. These changes are consistent with the loss of an Asn-linked oligosaccharide. Substitution of both Asn residues yielded a single immunoreactive species in the medium and cell extracts that migrated as a M(r) 39,000 protein. These results demonstrate that the mol wt heterogeneity of ABP is due to differential Asn-linked glycosylation of both potential sites. All three mutant forms of ABP were secreted by the COS cells. However, the amount of immunoreactive ABP and [3H]5 alpha-dihydrotestosterone binding in the medium was lower than wild type (100%) in one of the single mutants (65%) and in the double mutant (29%). Unlike the glycosylation mutants, alteration of other residues, not involved in glycosylation, yielded cellular ABP and no detectable medium ABP.(ABSTRACT TRUNCATED AT 250 WORDS)
Androgen-Binding Protein↗
Advocacy. Necessary to achieve cancer control goals.
As resources become increasingly scarce, oncology professionals and consumers of oncology services are increasingly engaging in advocacy efforts to achieve goals in cancer control. Effective advocacy includes both legislative and direct educational efforts.
Aged↗
Prevalence of cryptosporidiosis in dogs and human beings in San Bernardino County, California.
Fecal specimens from 200 stray dogs impounded at the San Bernardino City and County animal shelters were screened for Cryptosporidium sp oocysts, using the auramine-rhodamine fluorescent staining procedure. The University of California, Los Angeles acid-fast stain was used for confirmation. Only 4 (2%) dogs were passing cryptosporidial oocysts. Likewise, stool specimens from 664 people were submitted to the San Bernardino County Department of Public Health Laboratory for routine parasitologic examination and were screened for Cryptosporidium sp. Cryptosporidial oocysts were detected in 20 human fecal specimens (3.01%). On the basis of these findings, it appears that the human and canine populations of San Bernardino County are at low risk for development of cryptosporidiosis at this time.
Age Factors↗
Some problems with clinical trials. James Ewing lecture.
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Clinical Trials as Topic↗
Diagnosis and management of sacrococcygeal chordoma.
Chordoma is a rare, slow-growing but locally aggressive malignant tumor derived from the primitive notochord and located along the axial skeleton. Between 1973 and 1991, of 15 patients with chordomas treated at the Medical College of Virginia, eight originated in the sacrococcygeal area. There was a median one year interval between the onset of symptoms and diagnosis (range of four months to six years) for this latter group. Two patients had undergone coccygectomies and one patient a lumbar discectomy prior to establishing the correct diagnosis of sacral chordoma. Seven patients underwent resection and one refused therapy. The four patients who had an initial wide radical resection had a longer disease-free survival than the three who underwent local excision. Three of four patients had metastatic disease at the time of death. Early diagnosis and aggressive initial surgical resection are necessary for long-term survival.
Adult↗
Evidence that antibodies eluted from rejected kidneys of HLA-identical transplants define a non-MHC alloantigen expressed on human kidneys.
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Autoantibodies↗