Biomedical subjects
Publications and source records attributed to R E Greenberg.
We report a rare case of duplication of the bladder, urethra, uterus, vagina, and associated anomalies in a woman. As an infant, she initially underwent successful surgical reconstruction. As an adult, she developed adenocarcinoma within the defunctionalized bladder moiety. The surgical management and pathology of this cancer are detailed and the pertinent literature reviewed.
OBJECTIVES: This study was designed to assess the pharmacokinetics, safety, and antitumor activity of intravesically administered AD 32, a novel anthracycline, in patients with transitional cell carcinoma (TCC) of the bladder. METHODS: Six weekly doses of AD 32 (200 to 900 mg) were administered to 32 patients with superficial TCC who were candidates for intravesical treatment. Serum drug levels were measured during the 6-hour period after administration of the first, third, and sixth doses. Patients underwent bladder evaluations at 3-month intervals to determine responses to treatment. RESULTS: Very low levels of unmetabolized AD 32 and its two primary metabolites were measured in serum. The lack of systemic exposure was confirmed by the finding of only a few minor systemic adverse events. Local bladder irritation, the main toxicity associated with intravesical administration of AD 32, persisted for several days after each instillation. The maximum tolerated dose was 800 mg. Thirteen patients had complete responses to treatment, including 8 who remained disease free for 12.1 to 38.5 months. CONCLUSIONS: AD 32 is an active drug for the treatment of superficial bladder cancer. Further studies of intravesical administration of AD 32 are warranted.
OBJECTIVES: To evaluate the utility of staging pelvic lymphadenectomy and to identify factors associated with nodal metastases in which a node dissection would be of clinical benefit. PATIENTS AND METHODS: A retrospective analysis (1989-1993) was performed on 303 consecutive patients who underwent staging bilateral modified pelvic lymph node dissection for clinically localized prostate cancer. Multivariate logistic regression analysis was used to evaluate age, race, clinical stage, prostate-specific antigen (PSA) level and Gleason score for predicting nodal metastases. RESULTS: Twenty-eight patients had nodal metastases, giving an overall prevalence of 9.2%. PSA and Gleason score (both P < 0.001) were significantly predictive of nodal involvement when combined or as independent variables. Relative to PSA and Gleason score, the patients' age, race and clinical stage were less relevant. Sensitivity analysis determined that combining a PSA of > or = 20 ng/mL (normal 0-4) and a Gleason score of > or = 8 gave a negative predictive value of 92% with a specificity of 99%, a positive predictive value of 67% and an overall accuracy of 91% for predicting nodal metastases. CONCLUSION: From this data, lymph node metastases are unlikely in patients with clinically localized prostate cancer who have a PSA of < 20 ng/mL and a Gleason score < 8, and that a pelvic lymph node dissection as an adjunctive procedure should be avoided in such individuals.
The preoperative diagnosis for primary leiomyosarcoma of the renal vein, an extremely rare tumor, is difficult. The tumor predominantly occurs in women and on the left side. Its natural history is toward distant metastases and a poor 5-year survival rate. Nephrectomy and en-bloc surgical resection remain the mainstay of therapy. We present three such cases and review the world literature.
We carried out a complete genome scan for loss of heterozygosity (LOH) in four renal oncocytomas by using highly polymorphic CA repeat microsatellite loci. Three of the four tumors exhibited LOH for chromosome arm 1p, and the oncocytomas of both female patients lost Xq. Therefore, these chromosome arms may harbor tumor suppressor genes involved in the etiology of this disease. Although the genomes of ontocytomas are relatively stable, two different microsatellite loci in one tumor were mutated by + or - 2 nt. Similar alterations in CA repeats that are probably due to spontaneous mutation have been observed in renal cell carcinomas.
A comprehensive genome scan for loss of heterozygosity (LOH) in 33 renal cell carcinomas indicates that mutations of tumor suppressor genes on several different chromosomes are required for malignant transformation in this disease. In the case of nonpapillary renal carcinomas chromosomes 3p, 6q, 8p, 9pq, and 14q exhibit elevated levels of LOH. Although 3p is the most frequently lost chromosome arm, in no case is 3p observed as the sole allelic loss because it always occurs in conjunction with the loss of either 6q, 8p, or 14q. This result indicates that the mutation of a tumor suppressor gene on 3p, most likely von Hippel-Lindau disease (VHL), may be necessary but is not sufficient for the development of nonpapillary renal cell carcinoma. In papillary renal tumors, LOH is observed most often for chromosomes 6pq, 9p, 11q, 14q, and 21q. This suggests that tumor suppressor genes located on chromosomes 6q, 9pq, and 14q may be involved in the development and/or progression of both nonpapillary and papillary renal cell carcinomas. However, LOH in papillary tumors appears to be especially elevated for 11q and 21q and reduced for 3p and 8p indicating that there are also tumor suppressor genes specific to each form of the disease. There is no correlation between stage of disease and the extent of LOH, loss of a particular chromosome, or the number of chromosomes that show allele imbalance. Early and late stage tumors may exhibit either extensive LOH or no apparent allele loss; similarly, allelic imbalances are observed in both early and late stage renal cell carcinomas. This suggests that a gene (or genes) regulating mitotic chromosome stability may be mutated in some renal tumors. Preliminary evidence points to an association between genome instability and LOH of 14q. Finally, a distinct type of microsatellite instability has been detected in 21% of renal cell carcinomas and occurs at a frequency of 4.4 x 10(-4)/locus. The most common mutation is a 2-bp insertion in a CA repeat. This alteration is not restricted to a particular histopathology or clinical stage, and it is not associated with allelic loss of a specific chromosome. The frequency of this event is similar to that which occurs spontaneously in germline microsatellite loci and is probably not the result of a defect in a mismatch repair gene. It is possible that this type of microsatellite instability is general and may occur in most, if not all, carcinomas.
The von Hippel-Lindau locus on chromosome 3p is a tumor suppressor gene known to be involved in nonpapillary renal cell carcinoma. A previous loss of heterozygosity (LOH) study aimed at determining the allelotype of kidney tumors has indicated that in addition to 3p, chromosome arms 5q, 6q, 10q, 11q, 17p, and 19p may also harbor tumor suppressor genes. However, cytogenetic studies reveal that chromosomes 3p, 6q, 8p, 9pq, and 14q most frequently undergo karyotypic changes in renal tumors. To resolve these differences, a collection of microsatellite DNA probes has been used to scan for LOH so that 90% of individual tumor genomes were rendered informative for allele loss. The assay is capable of detecting quantitative genomic alterations in tumor cells as well. We find that LOH is most frequent for chromosome arm 3p. However, in no tumor is 3p exclusively affected. LOH for 6q, 8p, 9pq, and 14q is also distinctly elevated for both nonpapillary as well as papillary tumors and suggest that many of the tumor suppressor loci involved may be common to the etiology of both forms of kidney cancer.
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The first reported case of an isolated metastasis to the larynx from a regionally localized renal cell carcinoma presenting clinically as hoarseness is discussed. Aggressive management and outcome are presented.
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Postnatal patterns of growth and protein turnover were studied in suckling rats derived from expanded (EL) as compared to contracted (control) suckling rats (Widdowson and McCance, 1960). Maximum deviation of body weight growth velocity in EL vs. control litters of animals occurred early in the postnatal period (days 3-9). Fractional protein synthesis (Ks) in heart, diaphragm and gastrocnemius at 15 postnatal days were not significantly different in animals from expanded vs. control litters (e.g., Ks in heart 35.5 +/- 3.8% per day in control and 36.1 +/- 9.2% in expanded litters). Fractional growth rates in these 3 tissues were comparable in EL and controls, while fractional rates of protein breakdown (Kd) were somewhat reduced in diaphragm and gastrocnemius from EL animals (e.g., Kd in diaphragm 10.4% per day in control and 6.1% per day in EL). Absolute rates of protein synthesis and degradation were lower in EL animals, with rates of degradation reduced more than rates of synthesis. RNA activity of striated muscle tissues at 15 postnatal days in EL animals was not reduced vs. controls in contrast to results obtained in malnourished weanling and adult rats.
Malignant mesothelioma of the tunica vaginalis is an extremely rare tumor. Appropriate treatment consists of inquinal orchiectomy with close followup. Treatment of locally recurrent malignant mesothelioma of the tunica vaginalis has not been standardized. We recommend radical resection for the initial presentation of locally recurrent disease rather than saving surgical resection as salvage therapy after other treatment modalities have failed. We report case 37 of malignant mesothelioma of the tunica vaginalis and review the literature.
Pancreatic abscess is a severe complication of pancreatitis usually caused by alcohol, gallstones, abdominal trauma, or prior operative procedures. Pancreatic cancer is a rare cause of acute pancreatitis and an extremely rare cause of pancreatic abscess. We report three patients with pancreatic abscess caused by cancer who experienced a prolonged, complicated course with delay in diagnosis and substantial morbidity.
The effects of fetal hyperinsulinemia on protein turnover in various tissues of fetal rats were determined after transuteral injection of insulin to rat fetuses at day 19 of gestation. Tissue protein content was measured on the subsequent days of gestation (days 20-22), and protein synthesis was determined at day 20 of gestation in fetal tissues after intravenous injection of [3H]phenylalanine into the maternal circulation, followed by measurements of tissue free and protein-bound phenylalanine specific radioactivity in fetal diaphragm, brain, heart, and liver. Rates of protein degradation in these fetal tissues were calculated by subtracting protein accretion rates from rates of protein synthesis. The injection of insulin to rat fetuses at day 19 of gestation resulted in relative macrosomia versus saline-injected controls from the same litter (body wt at day 20 of gestation, 3.26 +/- 0.15 g for saline-injected fetuses and 3.60 +/- 0.25 g for insulin-injected fetuses, P less than 0.001) and increased protein and RNA content of brain, heart, and liver. Although fractional rates of protein synthesis were not significantly elevated in tissues from the hyperinsulinemic fetuses, absolute rates of protein synthesis were increased in brain, heart, and liver of hyperinsulinemic fetuses. Hyperinsulinemia did not reduce calculated rates of protein breakdown in fetal brain, heart, or liver but did in fetal diaphragm. We conclude that the major effect of fetal hyperinsulinemia on protein turnover in rats is to increase protein synthesis in selected tissues without simultaneously affecting protein breakdown.
Helicobacter pylori (formerly Campylobacter pylori) is causally related to active antral gastritis and is highly associated with duodenal and gastric ulcers. However, the relationship of H pylori to nonulcer dyspepsia is less clear. We determined the presence of H pylori in unselected patients who were undergoing upper gastrointestinal tract endoscopy, and we found a prevalence of 37% in 110 patients with nonulcer dyspepsia that was similar to previous data. Patients with nonulcer dyspepsia who had H pylori were found to be significantly older than patients with nonulcer dyspepsia who did not have H pylori. In addition, when stratified according to age, we detected an increased prevalence of H pylori in patients with nonulcer dyspepsia with increasing age, similar to that reported for asymptomatic control populations. This finding casts doubt as to the causal role of H pylori for most patients with nonulcer dyspepsia and stresses the importance of considering epidemiologic factors, such as age, when evaluating the role of H pylori in specific disease states.