Multicentric breast cancer: clonality and prognostic studies.

Clonality of multicentric breast cancer has traditionally been difficult to assess. We aimed to assess this using analysis of TP53 status (expression and mutation status). These results were then incorporated into an analysis of prognostic factors in multicentric tumours in a 10-year follow up study. Clonal status of multicentric breast cancer foci (n = 88 foci) was determined by immunohistochemical and molecular studies of TP53 in a total of 40 patients. Prognostic factors from these patients were also compared with 80 age- and stage-matched controls with unicentric breast cancer from the Royal Marsden NHS Foundation Trust Breast Cancer Database. Our results indicate that multicentric breast cancer foci were polyclonal within an individual patient in at least 10 patients (25%) with respect to immunohistochemical staining and in four patients (10%) with respect to abnormal band shifts on single strand conformational polymorphism (SSCP) molecular analysis. No individual variable was predictive of multicentric or unicentric disease. However, there was a worse overall survival in the multicentric breast cancer patients in whom at least two cancer foci stained positively on TP53 immunohistochemistry compared with the matched control group (P = 0.04). In conclusion, these results suggest that a proportion of multicentric breast cancer foci are polyclonal with respect to TP53 status and that TP53 over-expression predicts for a poorer prognosis in multicentric breast cancer.

Sweat-gland tumours: a clinical review of cases in one centre over 20 years.

AIMS: Sweat-gland tumours (SGTs) are uncommon, but malignant varieties are very rare. We have added our data on 30 new cases seen at the Royal Marsden NHS Foundation Trust to the published literature, particularly concentrating on clinical issues. We include a literature review. MATERIALS AND METHODS: The Royal Marsden NHS Foundation Trust database was searched for cases of SGT from 1972. Data were collected on all cases, including patient demographics and tumour characteristics, treatment and outcome. RESULTS: Thirty cases were confirmed histologically to be SGTs. Fourteen were malignant, 15 benign and the degree of malignancy in one was histologically indistinguishable. Mean age was 55 years (64 for malignant, 47 for benign tumours). The 15 patients with benign tumours were almost all treated with complete excision. Those with local relapse underwent successful re-excision. Their 5-year disease-free survival was 78% and cause-specific survival was 100%. Twelve of the 14 malignant tumours had localised disease at diagnosis, one had nodal disease and one had metastatic tumour nodules. All except one were treated with wide local excision. The patient with nodal involvement also had a lymph-node dissection. Two received adjuvant radiotherapy to the tumour bed. One received a melphalan limb perfusion. Eight of the 14 had no relapse. Six had locoregional relapse, and four of these also developed distant metastases. Visceral disease was always fatal. Radiotherapy and chemotherapy at relapse were unsuccessful. Five-year disease-free survival was 45%, and cause-specific survival was 57%. CONCLUSION: These rare tumours should be treated initially with complete wide local excision. In malignant tumours, lymph-node involvement is a poor prognostic sign. Wide local excision remains the primary treatment. Adjuvant radiotherapy may be useful in high-risk cases.

Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours: molecular and immunohistochemical findings.

We report a constitutional mutation of codon 273 in exon 8 of the p53 gene. The affected individual has developed multiple independent benign and malignant tumours (tricholemmoma of the scalp, multiple trichoepitheliomata of the face, osteosarcoma of the ovary, bilateral breast cancer, malignant fibrous histiocytoma of the thigh and endometrial adenocarcinoma) and belongs to a family with some, but not all, features of the Li-Fraumeni syndrome. The mutation, found in both blood lymphocyte and tumour specimens, is a cytosine to thymine transition at codon 273, resulting in an amino acid change from arginine to cysteine. The mother and sister of the index case both died of tumours at an early age. We have demonstrated that formalin-preserved material from these tumours contains the same C-->T mutation at codon 273, indicating that this mutation has probably been transmitted through the germline. All tumours from the index case, both benign and malignant, showed immunohistochemical positivity with four antibodies to the p53 protein. Positive staining was also seen in scattered nuclei of morphologically normal epidermal keratinocytes and pilosebaceous cells, but not in lymphocytes or other morphologically normal cells from the index case. However, a similar staining pattern in apparently normal tissue was also observed in 13/48 sections from other individuals with various skin conditions (melanocytic naevi, psoriasis and normal skin adjacent to malignant melanoma and fibrous histiocytomas), suggesting that this pattern of p53 staining may not be unique to individuals with constitutional p53 mutations.

Sequential alterations in tissue lipoprotein lipase, triglyceride secretion rates, and serum tumor necrosis factor alpha during Escherichia coli bacteremic sepsis in relation to the development of hypertriglyceridemia.

The time sequence and the mechanisms leading to the development of the hypertriglyceridemia of bacteremic sepsis are not fully understood. This study was conducted to determine the mechanisms leading to the early rise in serum triglycerides (TG). Bacteremic sepsis was induced in fasted and parenterally fed rats by intravenous infusion of live Escherichia coli colonies over a 1 h period every 24 h up to 96 h. Body temperature was elevated from 12 to 48 h after E. coli infusion in fasted rats and from 24 to 72 h after E. coli infusion in fed rats. The initial rise in serum TG was observed at 3 h after E. coli infusion; in fasted rats this elevation was maintained over 72 h. In the parenterally fed rats, hypertriglyceridemia was evident only at the 3 h time point. Serum concentrations of tumor necrosis factor alpha (TNF-alpha) were elevated significantly at 60 min after initiating the E. coli infusion, peaked at 90 min, and declined by 120 min. Immunization with neutralizing goat anti-TNF-alpha IgG did not block the initial increase in serum TG induced by E. coli. This early rise in TG in fasted E. coli-treated rats was accompanied by a 33% increase in TG secretion in comparison with control rats. TG secretion declined by 27% at 9 h and remained depressed at 12 and 24 h in comparison with time-matched control rats. By 24 h lipid accumulation was evident in the livers of the fasted and fed E. coli-treated rats. Most of the fasted E. coli-treated rats died by 72 h. Parenteral feeding extended survival of E. coli-treated rats until 120 h. These findings along with the observation that two mechanisms are involved in maintaining the elevation of serum TG during E. coli sepsis suggests that the hypertriglyceridemia may be important in host survival.

Detection of the ovulatory luteinizing hormone (LH) surge with a semiquantitative urinary LH assay.

We examined blood concentrations of ovarian steroid hormones (E2, P) and serum LH concentrations to establish that the Ovu-STICK assay reliably reflects endocrine events in the periovulatory period. In all 16 cycles studied, which included 2 cycles in which the women received CC, the ovulatory surge of LH was detected with the use of the Ovu-STICK assay. In contrast, BBT monitoring correctly predicted the ovulatory event in only half the cycles.

A patient with 17 primary tumours and a germ line mutation in TP53: tumour induction by adjuvant therapy?

We report the case history of a woman with a germ line mutation in the TP53 gene who developed 17 separate primary tumours. The incidence of new tumours rose steeply after adjuvant tamoxifen treatment for breast cancer and adjuvant vaginal vault radiotherapy for endometrial cancer. This increase could be due to cumulative genetic damage from environmental agents and the fact that the patient lived to the relatively late age of 60 years, or to a high inherent deleterious somatic mutation rate, which could represent the inability of cells from patients with TP53 mutations to repair therapy-induced genetic damage.

Clinical evaluation of two urine tests for the early diagnosis of pregnancy.

We compared the performance of two immunologic tests for hCG in urine with a qualitative serum hCG assay. The latex agglutination assay ( Sensi -Tex) was found to be superior to a hemagglutination assay (Beta-Stat) in that fewer equivocal results were obtained with it. Excluding equivocal results, both urine tests agreed well with the results of the serum qualitative hCG assay. Interference by human menopausal gonadotropins occurred at higher concentrations with Sensi -Tex than with Beta-Stat, suggesting that the Sensi -Tex reagents have greater specificity. We recommend that laboratories examine the performance of available urine pregnancy tests on site before selecting a reagent system for routine use.

A simplified procedure for separating amniotic fluid phospholipids with thin-layer chromatography.

A simple, unidimensional, thin-layer-chromatographic separation of amniotic fluid phospholipids involving detection with a phosphorus-specific spray was compared to the two-dimensional, thin-layer-chromatographic method described by Gluck et al. There were close correlations between the two techniques for lecithin/sphingomyelin ratios and for the presence of phosphatidylglycerol. The advantages of the unidimensional method are a shorter procedure time, the ability to analyze multiple samples on a single plate and the simplicity of a single-solvent system.

Thrombosis within an external jugular venous aneurysm.

Jugular plebectasia is rare, and most patients present in childhood. We describe a thrombotic episode within an external jugular venous aneurysm in an adult. This has not previously been described in the medical literature.

Intraluminal bile duct hepatocellular carcinoma.

Jaundice is usually a late feature in the course of hepatocellular carcinoma and is only rarely due to obstruction. We present two cases of obstructive jaundice, in which the cause of obstruction in both patients was a massive intraluminal filling defect within the common bile duct which proved to be hepatocellular carcinoma. The radiological features are described.

Breast infection due to dirofilariasis.

We describe a case of dirofilariasis of the breast in a woman presenting with a breast lump. The mammogram and ultrasound appearances are described with histopathological correlation. The suspicion of a parasitic infection was raised by the presence of rod-like structures within a hypoechoic nodule on sonography, appearances that have not been previously described. The case illustrates an unusual diagnostic problem since it presented in a non-endemic area.

Detection of hepatitis C virus antibodies and specific hepatitis C virus ribonucleic acid sequences in cord bloods from a heterogeneous prenatal population.

OBJECTIVE: Our aim was to quantify the prevalence of at-risk pregnancies for maternal-fetal hepatitis C virus transmission in a heterogeneous prenatal population by detection of both hepatitis C virus-specific antibody and hepatitis C virus ribonucleic acid sequences in cord bloods from their deliveries. STUDY DESIGN: An anonymous serosurvey of 1432 consecutive umbilical cord blood samples were analyzed for hepatitis C virus antibodies with a second-generation enzyme immunoassay with all hepatitis C virus antibody-positive samples batched and analyzed for both human immunodeficiency virus antibodies and hepatitis C virus ribonucleic acid sequences by polymerase chain reaction. RESULTS: Forty-seven of the samples (3.2%) were positive for hepatitis C virus antibodies; seropositivity rates differed significantly by socioeconomic status but not by race. Significantly more of the antibody-positive women underwent cesarean section for delivery (31.9% vs 21.9%, p = 0.03). Three (6.4%) hepatitis C virus antibody-positive samples were also human immunodeficiency virus-antibody positive, whereas nine (19.1%) were hepatitis C virus ribonucleic acid positive. CONCLUSION: As many as 19% of hepatitis C virus antibody-positive women in this study also had hepatitis C virus ribonucleic acid isolated from their delivery cord blood samples, which may indicate an increased risk of vertical hepatitis C virus transmission in those pregnancies. Hepatitis C virus-specific antibody and ribonucleic acid detection may also be markers for other pregnancy complications that result in higher rates of cesarean section for these women.

Hepatitis C virus in pregnancy: seroprevalence and risk factors for infection.

OBJECTIVES: Our purpose was to define the prevalence of antibodies to hepatitis C virus among inner-city prenatal patients. We also sought to examine both the reliability of traditional hepatitis risk factors to predict evidence of infection among these women and the incidence of coinfection in this population with other blood-borne and sexually transmissible agents. STUDY DESIGN: An anonymous serosurvey was performed to define and compare anti-hepatitis C virus prevalences among women registering for prenatal care at both an inner-city, university hospital-based clinic and an academic private practice based at the same institution. RESULTS: Anti-hepatitis C virus antibodies were detected in 4.3% of 599 pregnant women screened. In comparison, 0.8% had positive antibody tests for human T-lymphotropic virus and 0.5% were positive for antibodies to human immunodeficiency virus. Evidence of chronic hepatitis B infection was seen in 0.8%. The relative risk of other coexisting infections was significantly higher among women with anti-hepatitis C virus antibodies than among those who were antibody negative. Substance abuse was the most commonly identified risk factor for anti-hepatitis C virus-positive status, although risk factor-targeted screening would have failed to detect half of the anti-hepatitis C virus-positive women in this study. CONCLUSIONS: Hepatitis C virus infection among inner-city pregnant women, with its potential for maternal-fetal transmission, represents a public health issue of sufficient magnitude to warrant more extensive study. More information is needed, given this documented reservoir of maternal seropositivity, regarding the vertical transmissibility of the virus and the effects of coinfections on neonatal disease.

Penetrating gastric ulcer as a cause of mixed bacterial and fungal pericarditis.

We describe a case of pneumopyopericarditis caused by a mixture of fungal and bacterial pathogens. This originated from a gastric ulcer (within a hiatus hernia) which had eroded into the pericardial sac. Further complications included the late discovery of the ulcer and asplenism. Similar cases have been reported, but to the best of the authors' knowledge, none with an actual mixture of the two pathogens.

Identification of hyperthyroid patients by means of a sensitive assay for thyrotropin.

We evaluated a new assay (TSH3 MAIAclone) for thyrotropin (TSH) with improved sensitivity, testing a series of hospital inpatients with increased free thyroxin indices (thyroxin concentration X triiodothyronine uptake on resin). This assay involves use of three monoclonal antibodies and an antibody-magnetic particle conjugate that rapidly and completely separates bound and free tracer in a magnetic field. The assay turnaround time is 3 h. By the TSH3-MAIAclone assay, 65% of these patients with an increased free thyroxin index were identified on the basis of a TSH value less than or equal to 0.50 milli-int. unit/L. In contrast, another commercially available assay for TSH detected suppressed TSH concentrations in less than 5% of these patients. We conclude that the TSH3 MAIAclone assay markedly improves our ability to discriminate hyperthyroidism from euthyroidism.

Primary breast cancer: mammographic changes after neoadjuvant chemotherapy, with pathologic correlation.

PURPOSE: To correlate changes depicted at mammography during neo-adjuvant chemotherapy for operable breast carcinoma with subsequent pathologic status. MATERIALS AND METHODS: Patients (n = 107) underwent mammography before and after neoadjuvant chemotherapy, prior to surgery. Four retrospectively determined grades of response at mammography included complete, mammographic (decreased size and/or density), stable disease, or progressive disease. RESULTS: In 95 fully assessable patients, grade of response to chemotherapy was complete in eight (9%), mammographic in 78 (82%), stable disease in seven (7%), and progressive disease in two (2%). Before and after treatment, respectively, 64 (67%) and 20 (21%) masses were greater than 2 cm in bidimensional diameter. Response was not complete in any of the 44 (46%) cases of microcalcifications. At histologic examination after surgery in 95 fully assessable patients, five of eight patients with complete response were found to have residual tumor (three with an invasive component); eight were found to have no residual tumor (response in three was complete; in four, mammographic; and in one, stable disease). CONCLUSION: Whereas mammograms in most patients showed some response to chemotherapy, prediction of pathologic outcome was not possible.

Rapid progression of fibrosing alveolitis and thyrotoxicosis after antithymocyte globulin therapy for aplastic anemia.

Antithymocyte globulin (ATG) therapy is an established form of treatment for aplastic anaemia and has also been used as prophylaxis against graft rejection of bone marrow and renal allografts. Administration of ATG preparations has been associated with many mild clinical reactions, as have other forms of immunomodulatory therapy. However, serious adverse effects appear to be rare. We report a case of rapidly progressive fibrosing alveolitis and thyrotoxicosis in relation to ATG therapy, highlighting its potential toxicity and emphasising that its administration should be undertaken by experienced physicians in specialised centres.