Surgical impact of new treatments in breast cancer.

Local treatment of breast cancer with tumor-free surgical margins is the standard procedure in the treatment of T1 and small T2 breast cancers. Surgery is followed by radiation therapy, and adjuvant systemic therapy is offered depending on primary tumor characteristics, such as tumor size, grade of differentiation, number of involved axillary lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and the expression of the human epidermal growth factor 2 (HER2) receptor. Although this approach implies a higher risk of ipsilateral breast tumor recurrence, the total risk of recurrence is low (1% per year), with rates of overall survival similar to that after radical procedures. The most peripheral part of epithelial tumors, the tumor margin, is the part which is most likely to remain in loco after surgical resection. Thus, understanding the biology of the invasion front is important as these tumor cells have been reported to lose epithelial properties, such as cohesiveness and keratin expression, and to acquire features of mesenchymal cells. The parallel appearance of tumor cells in different states of cell dedifferentiation implicates a dynamic equilibrium that is determined by the induction of epithelial-mesenchymal transition (EMT). EMT has been suggested to be of prime importance for tissue and vessel invasion. Furthermore, features of EMT are associated with the activity of tumor stem cells (TSC). TSC exist in breast cancer and their appearance varies depending on the used marker profile. Consequently, intratumoral heterogeneity is reflected by the grade of EMT activation. A specific function at the invasion front is hypothesized but has not yet been proven. Nevertheless, the molecular differentiation between the tumor center and the invasion front enhances the importance of tumor-free surgical margins.

Enhanced expression of the PDGFR/Abl signaling pathway in aromatase inhibitor-resistant breast cancer.

BACKGROUND: We have found that the platelet-derived growth factor receptor (PDGFR)/Abl signaling pathway is up-regulated as a determinant of the acquisition of resistance to estrogen deprivation in vitro. We aimed to determine its clinical relevance in aromatase inhibitor (AI)-resistant breast cancer. PATIENTS AND METHODS: We identified a cohort of 45 patients with estrogen receptor-positive breast cancer who had been treated with an AI, subsequently relapsed and had biopsy material available from both the presentation and post-AI recurrent lesion. PDGFRα, PDGFRß and Abl expression was assessed in formalin-fixed paraffin-embedded sections. RESULTS: Tumor protein expression of PDGFRα (1.39-fold, P=0.0065), PDGFRß (4.32-fold, P=0.006) and Abl (1.8-fold, P=0.001) was increased at the point of relapse. Tumor and stromal expression of PDGFRα as well as PDGFRß was significantly correlated in pre-treatment and relapse samples. High post-treatment tumor and stromal PDGFRß levels were associated with a short time to treatment failure (TTF). Expression of PDGFRα in relapsing tumor specimens was correlated with Abl expression and Ki67 levels. Furthermore, changes in Abl correlated significantly with changes in ER expression. CONCLUSIONS: These clinical data support a role for enhanced PDGF/Abl signaling in AI-resistant disease and provide a rationale for targeting the pathway in endocrine-resistant breast cancer.

An in vitro model showing adaptation to long-term oestrogen deprivation highlights the clinical potential for targeting kinase pathways in combination with aromatase inhibition.

Aromatase inhibitors (AI) have improved the treatment of oestrogen receptor positive (ER+) breast cancer. Despite the efficacy of these agents over 40% of patients relapse with endocrine resistant disease. Here we describe an in vitro model of acquired resistance to long-term oestrogen deprivation (LTED). The LTED cells retain expression of the ER and appear hypersensitive to oestrogen as a result of altered kinase activity. Furthermore analysis of temporal changes in gene expression during the acquisition of resistance highlight growth factor receptor pathways as key mediators of this adaptive process.

Augmentation mentoplasty using Mersilene mesh.

Many different materials are available for augmentation mentoplasty. However, the optimal implant material for chin implantation has yet to be found. During the past several years, a number of experienced surgeons have turned to the use of Mersilene mesh. Mersilene mesh is a non-absorbable Dacron polyester fiber that can be conformed easily into layers to achieve tailored dimensions and shape. At the McCollough Plastic Surgery Clinic PA, Birmingham, Ala, 277 patients over a 10-year period underwent chin augmentation with Mersilene mesh implants. The material provides excellent tensile strength, durability, and surgical adaptability. The overall complication rate was 3.2% (nine patients); infection rate, 2.5% (seven patients); and removal secondary to infection, 1.7% (five patients). Based on this 10-year experience, Mersilene mesh remains our material of choice for chin augmentation.

Auditory acuity in adrenocorticoid insufficiency.

Studies in man have proposed that individuals with adrenocorticoid insufficiency show a heightened auditory detection threshold. This hyperacuity was shown to be specific for deficits in carbohydrate-active steroids, with threshold levels improved at least 13 dB between 1,000 Hz and 4,000 Hz. These reversible changes in auditory detection have been related to specific influences of glucocorticoids on the metabolism of neural tissue. The present study was designed to examine the hypothesis that glucocorticoid deficiencies cause decreased electrocochleographically measured auditory thresholds with interference in the central conduction of these impulses. A rat model was employed in an attempt to demonstrate the mechanism for a state of increased neural excitability in the absence of carbohydrate-active steroid influence. Electrocochleographic and auditory brain-stem evoked response threshold and latency determinations were made in eight experimental rats. Adrenalectomies were then performed in all animals with postoperative electrocochleographic and auditory brain stem responses being made at 3, 7, and 21 days. Threshold recordings for all experimental animals showed no significant changes following the cessation of glucocorticoid production. Latency measurements revealed impaired central neural transmission of the first and second order neurons. The possible mechanisms for these findings are discussed.

Treatment of the clinically negative neck in advanced cancer of the head and neck.

The proper management of the clinically negative neck in primary squamous cell carcinomas of the head and neck remains controversial. Although many clinicians believe that elective neck dissection or neck irradiation are equally effective for controlling subclinical disease, previous studies have not directly addressed this question. The charts of 195 patients with advanced primary squamous carcinoma, yet with clinically negative necks, were reviewed. There were no significant differences in the rates of neck cancer recurrence among the elective neck irradiation, dissection, and combined treatment groups. Elective neck irradiation and neck dissection in patients with clinically negative nodes seemed equivalent in their ability to control neck disease. The decision as to which form of therapy is preferable must therefore be based on other criteria.

A prospective randomized study of four commonly used tympanostomy tubes.

Tympanostomy tube placement has clearly been shown to be an efficacious treatment for recurrent bouts of acute otitis media or chronic otitis media with effusion. However, there are few objective, prospective, randomized studies present in the literature to aid the clinical otolaryngologist with the proper tube choice for middle ear aeration. A prospective, randomized study was undertaken of four commonly used tympanostomy tubes. Shepard Teflon grommet, Armstrong beveled tube, Reuter-Bobbin tube, and Goode T-tube. This study was undertaken to determine which of these tubes had the fewest number of postplacement complications, including otorrhea, plugging, residual perforation, or chronic persistence in the tympanic membrane. Average follow-up was 17 months. The Shepard and Armstrong tubes showed a comparatively low rate of plugging and otorrhea. Both tubes had extrusion times that averaged less than 1 year. The Reuter-Bobbin tube had a much greater rate of plugging, compared to the other tubes. The T-tube had an increased incidence of otorrhea and persistence in the tympanic membrane well beyond 1 year. The T-tube was also the only tube in this study associated with residual perforations.