The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy.

The optimal extent of breast resection before irradiation for treatment of early breast cancer has not been defined. Increasing the size of the resection may decrease the risk of local recurrence but will also have an adverse impact on the cosmetic outcome. The 5-year likelihood of a recurrence of the tumor was analyzed in relation to the volume of resected breast tissue in 507 patients with infiltrating ductal carcinoma treated with conservative surgery and radiation therapy between 1968 and 1982. Patients were stratified by clinical T-stage and for each T-stage patients were divided into three groups of equal numbers based on the volume of excised tissue. All patients had at least a gross excision of the tumor and the extent of breast resection was determined at the discretion of the surgeon without knowledge of the histologic features of the tumor. The median follow-up time was 100 months. The 5-year actuarial recurrence rates were analyzed in relation to clinical T-stage (T1 or T2) and the presence or absence of an extensive intraductal component (EIC+ or EIC-). For patients with EIC+ tumors, the largest resections were associated with a substantially lower risk of recurrence in the breast than the smallest resections. This effect was seen both for T1 tumors (10% versus 29%, p = 0.07) and for T2 tumors (9% versus 36%, p = 0.04). For patients with EIC-tumors, recurrence rates were significantly lower than for EIC+ tumors and were not influenced by the volume of resection to the same degree as EIC+ tumors. In the absence of an EIC, recurrence rates for the largest and smallest resections were 0% and 9% (p = 0.02) for T1 tumors and 3% and 6% (p = NS) for T2 tumors. It is concluded that a limited breast resection is acceptable for an EIC- tumor but that a more extensive resection is required for an EIC+ tumor. These results stress the importance of assessing the presence or absence of an EIC in determining the optimal extent of breast resection required before radiation therapy.     

Efficacy of specimen radiography of clinically occult noncalcified breast lesions

Breast biopsy specimen radiography is required to ensure the accurate removal of clinically occult lesions discovered by mammography. Although used routinely for calcified lesions, it has not been widely accepted for those abnormalities that do not contain calcium. To determine the efficacy of film-screen specimen radiography for confirming the presence of clinically occult, noncalcified lesions, we undertook a prospective study of 104 specimen radiographs obtained after mammographically guided hookwire localization and planned excision of these lesions. Ninety-seven (93%) of the excised abnormalities were visualized on specimen mammograms. Malignancy was found in 22 (21%) of them. Thirty-five percent of the specimen radiographs showed better anatomic detail of the lesion, 48% showed the same detail, and 16% showed less detail than the original mammograms. Specimen radiographs failed to show the lesion in only seven cases. Five of the seven were true-negative specimen radiographs, making the efficacy rate 98%. Film-screen specimen radiography of clinically occult, noncalcified lesions is a highly effective procedure for correctly identifying the presence of a mammographic abnormality.     

Benign schwannoma of the esophagus presenting as a giant fibrovascular polyp.

The case of a 62-year-old man with benign schwannoma associated with a giant polyp of the esophagus is presented. His initial symptom was dysphagia. The polyp was removed through cervical esophagotomy. He had no recurrence of symptoms 5 years after this procedure. Pathologic examination showed a rare histology.     

Expression and function of galectin-3, a beta-galactoside-binding protein in activated T lymphocytes

A soluble beta-galactoside-binding lectin, galectin-3 has been shown to be involved in cell adhesion and activation of immune cells. Although galectin-3 is known to be expressed in various types of cells, it has not been shown whether galectin-3 is expressed in T lymphocytes. We present evidence here that galectin-3 is expressed in activated murine T lymphocytes including CD4+ and CD8+ T cells but not in resting T cells. Galectin-3 expression was induced by anti-CD3 mAb or mitogen and enhanced by common gamma-chain signaling cytokines, IL-2, IL-4, and IL-7, in activated T lymphocytes, whereas the inflammatory cytokines including TNF-alpha and IFN-gamma did not. Galectin-3 expression and proliferation were down-regulated by withdrawal of IL-2 and gamma irradiation. Antisense but not sense phosphorothioated oligonucleotides for galectin-3 inhibited galectin-3 expression and blocked proliferation of T cells significantly. This study suggests that up-regulation of galectin-3 plays an important role in proliferation of activated T lymphocytes.     

Comparative pharmacodynamics of clarithromycin and azithromycin against respiratory pathogens

Summary The differences between the antibacterial activities of new macrolides such as clarithromycin (CLA) and azithromycin (AZI) against common respiratory tract pathogens are only minor. However, CLA and AZI constitute macrolides with extremely different pharmacokinetic profiles. This constellation presents an opportunity to evaluate the effect of the pharmacokinetic profile on antibacterial kinetics comparatively. In a pharmacodynamic model simulating the dynamics of serum concentrations in bacterial cultures, both CLA and AZI demonstrate bactericidal activity at concentrations reached in human blood at recommended dosages (CLA 250 mg b.i.d., AZI 500 mg o.i.d.). Bactericidal activity of CLA against the variety of pathogens included is superior to that of AZI in the rate and the extent of killing in this model. These results are considered to correlate with the antibacterial effect of macrolidesin vivo in cases where pathogens enter the blood stream. Furthermore, mutants with susceptibility reduced between 8 and 16 times in relation to the initial strain of all strains having an initial minimal inhibitory concentration (MIC) 0.25 mg/l, are selected during exposure to AZI, but not to CLA. The pharmacokinetic profiles of CLA and AZI thus strongly influence their antibacterial effect in the pharmacodynamic model, allowing both higher bactericidal activity and greater reduction of the risk of selection of resistant mutants with CLA than with AZI. As a whole, the pharmacodynamics of these macrolides are determined more by the proportion of the MICs to the maximum serum concentration than by the relation of the MICs to the area under the curve.

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Vergleich der Pharmakodynamik von Clarithromycin und Azithromycin bei Erregern von Atemwegsinfektionen

Zusammenfassung Die antibaktericlle Aktivität neuer Makrolide, z. B. von Clarithromycin (CLA) oder Azithromycin (AZI), gegenüber Atemwegspathogenen ist nahezu identisch. CLA und AZI unterscheiden sich jedoch beträchtlich in ihren pharmakokinetischen Eigenschaften. Dies eröffnet die Möglichkeit, den Einfluß der Pharmakokinetik auf die bakterielle Abtötekinetik zu untersuchen. In einem pharmakodynamischen Modell, bei dem die Serumkonzentrationsverläufe in der Bakterienkultur simuliert werden, zeigten sowohl CLA als auch AZI bei üblichen Dosierungen (CLA 250 mg 2 × tgl., AZI 500 mg 1 × tgl.) bakterizide Aktivität. CLA erwies sich in diesem Modell als schneller und stärker bakterizid als AZI gegenüber den untersuchten Erregern. Diese Ergebnisse sollten Bedeutung haben für die Therapie von Infektionen mit Makroliden, wenn die Erreger auch im Blut auftreten können (z. B.Streptococcus pneumoniae undHaemophilus influenzae). Mutanten mit verminderter Empfindlichkeit im Vergleich zum Ausgangsstamm wurden in den Experimenten mit AZI, nicht jedoch mit CLA selektioniert, u. z. bei allen Stämmen mit einer Anfangs-MHK von 0.25 mg/l. Die pharmakokinetischen Eigenschaften von CLA und AZI beeinflussen demnach ihre antibakterielle Aktivität, u. z. sowohl die Bakterizidie als auch das Risiko der Selektion resistenter Mutanten. Ausschlaggebend für den antibakteriellen Effekt dieser Makrolide ist also das Verhältnis MHK zu maximaler Serumkonzentration und nicht das Verhältnis MHK zu AUC.

     

Malignant hyperthermia

Malignant hyperthermia (MH) is a rare syndrome seen when susceptible individuals are exposed to one or more of various triggering agents, most commonly a depolarizing muscle relaxant or an inhalational anaesthetic agent. There is a dramatic rise in metabolic rate and oxygen consumption which if not treated promptly and effectively results, in the majority of cases, in the patient's death. Fatal responses to physical stress associated with the familial muscular disease known as MH are being increasingly reported in situations not related to anaesthesia or drugs. Moreover, cases of MH were recognized to be "induced" in the postoperative period when obviously the major effects of anaesthesia were no longer of important consideration. Therefore a more expanded concept of MH seems to develop, including the assumption that one of the other factors in MH is stress. The implication of this extends far beyond the scope of anaesthesiology. The acute hypermetabolic state in MH, resulting in acidosis, heat production and muscular activity is probably due to an inability to control calcium concentration within the skeletal muscle fiber, and may involve a generalized alteration in cellular or subcellular membrane permeability. The susceptibility to develop MH is controlled by several genetic factors. Evaluation of affected families is guided by in vitro analysis of drug-induced contractures in muscle biopsy specimens; a practical and reliable non-invasive test to predict the susceptibility is still being sought. At the present time there is incontrovertible evidence that the hydantoin derivate dantrolene sodium is the only known specific drug in treatment and prophylaxis of MH. A concept for the treatment of MH and guidelines for the management of a patient at risk are presented; medico legal aspects of the complication are stressed.     

Soft-tissue sarcomas

Sarcomas of the soft tissues are challenging lesions for the surgical oncologist. Careful planning must be done at all stages of diagnosis and treatment, because every sarcoma is unique with respect to histologic type, size, and location. Pretreatment discussions in a multidisciplinary format are useful to ensure appropriate and effective management of these tumors.