Overexpression of cyclin D mRNA distinguishes invasive and in situ breast carcinomas from non-malignant lesions.

The elucidation of molecular alterations that occur during human breast cancer progression may contribute to the development of preventative strategies. Using in situ hybridizations on a cohort of 94 biopsy lesions, quantitatively increased cyclin D mRNA expression levels were observed in only 18% of benign lesions, which confer no or slightly increased breast cancer risk, and 18% of premalignant atypical ductal hyperplasias, which confer a four to fivefold increase in breast cancer risk. The transition to carcinoma was accompanied by frequent cyclin D mRNA overexpression in 76% of low-grade ductal carcinomas in situ, 87% of higher grade comedo ductal carcinomas in situ and 83% of infiltrating ductal breast carcinomas. The data identify a molecular event that may separate benign and premalignant human breast lesions from any form of breast carcinoma.

Immunolocalization of transforming growth factor-alpha in normal and diseased human gastric mucosa.

Roles for transforming growth factor-alpha (TGF alpha) in the stomach include cell migration and proliferation, inhibition of acid secretion, and cytoprotection. The authors have previously shown increased TGF alpha expression in rat gastric mucosa in response to acute gastric injury. They also have shown that TGF alpha immunoreactivity is increased in the gastric mucosa of four patients with Ménétrier's disease. To further characterize TGF alpha immunoreactivity in human gastric mucosa, the authors have performed immunohistochemical analysis with an anti-TGF alpha monoclonal antibody on human gastric biopsies (n = 25) showing either normal (n = 8), mild reactive/reparative change in common conditions with or without associated gastritis (n = 13), and exaggerated mucosal change in proliferative conditions (Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic polyps) (n = 17). All normal biopsies showed a predictable pattern of TGF alpha immunostaining, with significant positivity found only in foveolar cells at the luminal surface and parietal cells, sparing foveolar cells in the gastric pits, mucous neck cells and chief cells of the gastric glands. Three patients with mild foveolar hyperplasia without associated inflammation did not deviate from the normal pattern except in foci of reactive epithelial change. Ten of 11 patients with chronic active gastritis, in addition to this normal staining pattern, demonstrated significant immunoreactivity in deeper foveolar cells and mucous neck cells showing reactive epithelial changes, defined as the presence of nuclear enlargement and nucleolar prominence with or without mucin depletion. Three cases of ulceration with associated reactive epithelial changes also showed increased immunoreactivity. Furthermore, five cases of Ménétrier's disease with massive foveolar hyperplasia and minimal inflammation (MFH) and six cases with hypertrophic lymphocytic gastritis (HLG) have been studied, and both show full-thickness TGF alpha immunoreactivity restricted to the gastric epithelium. This pattern of staining is indistinguishable from that observed in two cases of hyperplastic polyps but differs significantly from that observed in cases of mild foveolar hyperplasia. These results further define patterns of TGF alpha immunostaining in normal, reactive/reparative and exaggerated proliferative human gastric biopsies, confirm participation of TGF alpha in the response to gastric mucosal injury, and provide additional support for a possible role for TGF alpha in the pathogenesis of proliferative gastric disorders including Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic gastric polyps.

Differentiation of reactive from neoplastic small-cell lymphoid aggregates in paraffin-embedded marrow particle preparations using L-26 (CD20) and UCHL-1 (CD45RO) monoclonal antibodies.

The pathologic findings in 1,390 consecutive patients who had bone marrow examinations at Nashville Veterans Administration Hospital from 1977 through 1979 were reviewed. Seventy-three patients who did not meet diagnostic criteria for a small-cell lymphoid neoplasm (SCLN) and 11 patients with SCLN had, on marrow particle preparations: (1) at least three lymphoid aggregates and (2) suitable material available for immunoperoxidase studies with monoclonal antibodies UCHL-1 (CD45RO, pan T cell) and L-26 (CD20, pan B cell). Staining with UCHL-1 was difficult to interpret due to high background positivity in myeloid elements. With L-26, three distinct patterns of lymphocyte marking were identified within aggregates: (1) homogeneous--uniform marking of almost all lymphocytes; (2) mixed--even distribution of marking and nonmarking lymphocytes; (3) and focal homogeneous--collections of uniformly marking lymphocytes either surrounding or surrounded by nonmarking lymphocytes. A homogeneous marking pattern was the predominant pattern in 8 of 11 patients (73%) with SCLN. Only 6 of 73 patients without overt SCLN marked in a homogeneous pattern, and these were always associated with aggregates with other staining patterns. All patients with apparently non-neoplastic lymphoid infiltrates had mixed (67 of 73) or focal homogeneous (32 of 73) patterns of aggregate marking, whereas only 5 of 11 patients (45%) with extramarrow SCLN had aggregates with these patterns. The size and number of aggregates with a homogeneous marking pattern further helped discriminate between the patients with SCLN and those with apparently non-neoplastic lymphoid aggregates. These findings suggest that a homogeneous pattern of lymphoid aggregate staining with L-26 is more common in patients with SCLN than in those patients with lymphoid aggregates and no evidence of neoplasia. Paraffin immunoperoxidase staining with L-26 may be a helpful adjunct to histopathologic examination in evaluating marrow lymphoid aggregates.

Renal cell carcinoma in patients with end-stage renal disease: a comparison of clinical significance in patients receiving hemodialysis and those with renal transplants.

OBJECTIVES: This review was undertaken to determine the clinical significance of renal cell carcinoma in the populations undergoing renal transplantation and those undergoing chronic dialysis. METHODS: We reviewed all medical records of patients with renal cell carcinoma treated at our institutions over the last 10 years. From this review we identified 20 patients with end-stage renal disease and renal cell carcinoma. Patients' charts were reviewed to determine presenting features, tumor histologic type, and clinical outcome. RESULTS: Seven patients had functioning renal transplants and 13 patients were on chronic maintenance hemodialysis. Ninety-two percent of the dialysis group had no metastatic disease and there were no deaths from renal cancer. In contrast, 53% of the transplant group did have metastatic disease and 2 patients died of renal cancer. Despite similar pathologic appearances of the tumors in these 2 groups, patients with renal cell carcinoma and renal transplant presented with higher-stage disease and had less favorable clinical courses. CONCLUSIONS: Considering the morbidity of hemodialysis as well as the other comorbidities of this patient population, the clinical significance of renal cell carcinoma in patients undergoing chronic dialysis must be questioned. In contrast, renal cancer in the transplant population behaves aggressively and warrants careful attention both before and after renal transplantation.

Serial assessment of adnexal masses with transvaginal color Doppler sonography.

Transvaginal color Doppler sonography (TV-CDS) was performed on 64 women with adnexal masses at 3, 6 and 12 weeks after initial presentation. In 47 (72% of patients studied), the pelvic mass demonstrated a decrease in size and increase in pulsatility index (PI) after 12 weeks. Of the patients undergoing surgery in this group, one had a tubo-ovarian abscess, one diverticular abscess and one hydrosalpinx. In seven patients (10%), there was no change in size or PI. Three in this group had an endometrioma, whereas two had a peritoneal cyst. In five (7%), there was no change in size and an increase in PI. One of these patients had a mucinous cystadenoma. In three (5%), there was a decrease in size and PI. Two of these patients had a tubo-ovarian abscess. In two (3%) patients studied, the mass showed an increase in size and decrease in PI; both had corpora luteum cysts with acute hemorrhage. Seventy-two percent of masses with high impedance underwent regression, whereas only 21% of lesions with low impedance did. Only 20% of masses demonstrating low impedance or morphologically complex structure regressed. Sixty-five percent of lesions that regressed had a significant drop in PI, whereas all the lesions that showed no change in size or enlargement had either no change or decrease in PI. Probability of regression was the greatest in young women (less than 40 years of age) and in masses < 5 cm. Ninety-three percent of women with persistent masses that underwent progestational suppression demonstrated regression with decrease of PI and peak systolic velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Color Doppler sonography of tubal torsion.

These case reports illustrate the clinical and color Doppler sonographic findings in two cases of isolated tubal torsion. This condition may be associated with prior tubal ligation. The presence of high impedance or absent flow in a tubular structure in a patient with a history of tubal ligation should make one suspect this condition.

Renal trauma: re-evaluation of the indications for radiographic assessment.

We studied prospectively 359 consecutive patients with blunt (306) or penetrating (53) renal trauma to refine the indications for radiographic evaluation. Various factors, including the degree of hematuria, presence of shock and associated injuries easily assessable at the time of initial evaluation, were correlated with the severity of renal injury to determine whether any combination of parameters will separate patients with renal contusions from those with significant renal injuries (minor and major lacerations, and vascular injuries). We identified 3 groups: group 1-85 patients with gross hematuria or microscopic hematuria and shock after blunt trauma (including all 23 with significant renal injuries), group 2-221 patients with microscopic hematuria but no shock after blunt trauma (all with renal contusions) and group 3-53 patients with penetrating trauma. No combination of parameters was able to predict a severe injury in group 3. Our data support radiographic evaluation in groups 1 and 3. However, because all patients in group 2 had renal contusions and experienced no complications from nonoperative management we believe that excretory urography, which is time-consuming and costly, can be avoided in patients with microscopic hematuria but no shock after blunt renal trauma.

The Trauma Score as a triage tool in the prehospital setting.

Implementation of a regional trauma care system requires a field triage tool that identifies the severely injured patient and transports him to a trauma center, while preserving the flow of minimally injured patients to community hospitals. We prospectively tested the Trauma Score (TS) as a field triage tool and evaluated its accuracy against that of the Injury Severity Score (ISS), calculated after the patients' injuries were fully defined. During an 18-month period, 1106 patients admitted to the trauma center at San Francisco General Hospital had a TS determined in the field (TS1) and on arrival at the emergency department. A TS1 of 14 or less defined a subgroup of 222 patients in whom 93% of the deaths occurred. Using an ISS of 20 or more as an indicator of life-threatening injury, we determined the predictive value of TS1. There were 66 false-negatives (ISS, greater than or equal to 20; TS1, 15 or 16) and 107 false-positives (ISS, less than 20; TS1, less than or equal to 14). Using a prehospital TS of 14 or less as an indicator of serious injury, only 20% of a major urban trauma population would qualify for diversion to a trauma center.

Establishment and characterization of primary gallbladder epithelial cell cultures in the prairie dog.

BACKGROUND: The prairie dog has become the established animal gallstone model. This species has a unique propensity to form cholesterol gallstones in response to dietary manipulations. The development of a reliable gallbladder cell culture technique is critical for understanding pathogenic mechanisms of gallstone formation. MATERIALS AND METHODS: Prairie dogs underwent laparotomy and cholecystectomy, followed by initiation of cell cultures. [3H]Thymidine incorporation was used to assess cell growth, and cell lines were assessed using routine histochemical and immunohistochemical staining. RESULTS: Cell yields from prairie dog gallbladders were 4-8 x 10(6) viable cells per animal with viability ranging from 80 to 95%. When plated at 5 x 10(5) cells/cm2, cell clusters, visible within 24 h, coalesced into confluent monolayers within 3-5 days. Cultures remained viable for 6-8 weeks and could be passed for three to four subcultures. Immunohistochemical staining demonstrated a high degree of epithelial purity with immunopositivity for AE1/AE3, and cytokeratin, with no vimentin positivity (mesenchymal antigen). Intracytoplasmic vacuoles demonstrated positive staining for Alcian blue, periodic acid-Schiff, and mucicarmine and an anti-gallbladder mucin antibody confirmed the presence of the glycoprotein mucin. CONCLUSIONS: This study demonstrates a reliable method for initiation and maintenance of prairie dog gallbladder epithelial cell cultures with a high degree of purity. This technique should allow further studies into the pathogenesis of cholesterol gallstones in this model.