Edgar D. Staren

Matrix metalloproteinase expression in breast cancer

BACKGROUNDnMatrix metalloproteinases (MMPs) have been implicated as possible mediators of invasion and metastasis in some cancers. Our objective was to investigate which MMPs were constitutively expressed in breast tumor cells versus those that could be up-regulated by a number of agents known to affect MMP expression in other cell systems.nnnMETHODSnWe evaluated expression of MMPs 1-16 in breast tumor cell lines MDA-MB-231, T47D, and MCF-7 using semiquantitative RT-PCR and gelatin zymography. Exposure to 12-O-tetradecanoylphorbal-3-acetate (TPA), concanavalin-A (Con-A), the fibronectin-mimetic peptide GRGDSP (RGD), extracellular matrix (ECM) components, and anti-integrin antibodies was used to test for possible MMP up-regulation. Mitogen-activated protein kinase inhibitors (MAPK-I) were used to evaluate signal transduction pathways and regulation of MMP expression.nnnRESULTSnMMPs 1, 2, 7-11, 13, 14, and 16 were constitutively expressed in some tumor cell lines but not in normal breast epithelial cells. Administration of TPA, Con-A, and RGD increased the expression of MMPs 1, 2, 9, and 10. No MMP up-regulation was seen in MDA-MB-231 or MCF-7 after exposure to ECM components or after exposure to anti-integrin antibodies. MAPK-I had no effect on constitutive MMP expression but reduced or abolished the TPA up-regulation of MMP-9 in MDA-MB-231 and MCF-7.nnnCONCLUSIONSnBreast tumor cell lines constitutively express a number of MMPs. Because MMP expression can be up-regulated by Con-A, the fibronectin-mimetic peptide RGD, and TPA while being susceptible to inhibition by MAPK antagonists, MAPK signaling appears to play a role in this expression.

Adhesion and Migration of Extracellular Matrix-Stimulated Breast Cancer

BACKGROUNDnExtracellular matrix (ECM) components, such as vitronectin and fibronectin, have been shown to enhance the metastatic potential of breast cancer cells. We hypothesized that ECM binding to integrin receptors on breast cancer cells influenced cellular adhesion and migration.nnnMATERIALS AND METHODSnAdhesion assays were performed using breast cancer cell lines MDA-MB-435 and MDA-MB-231 and various concentrations of vitronectin or fibronectin. Migration assays were performed using the same cell lines and invasion chambers with 8 microm pore polycarbonate membranes. Blocking antibodies and specific peptidomimetic inhibitors to integrin receptors were used to identify the integrin subunits reacting with vitronectin and fibronectin.nnnRESULTSnWhile both breast cancer cell lines adhered to and migrated toward vitronectin and fibronectin, MDA-MB-435 had a higher maximum binding to vitronectin and MDA-MB-231 had a higher maximum binding to fibronectin. Anti-beta1 antibody inhibited the adhesion and migration of MDA-MB-231 to fibronectin and the adhesion of MDA-MB-231 to vitronectin but had no effect on vitronectin-induced adhesion or migration of MDA-MB-435. The alpha(v)beta3/alpha(v)beta5 antagonist, SB 265123, inhibited MDA-MB-231 and MDA-MB-435 adhesion and migration to vitronectin but had no effect on migration to fibronectin in either cell line.nnnCONCLUSIONSnWe conclude that the integrin subunits beta1, alpha(v)beta3, and alpha(v)beta5 can be involved in breast cancer cell adhesion and migration to vitronectin and fibronectin. Because more than one integrin inhibitor was required to block adhesion or migration in the cell lines studied, breast cancer therapy based on integrin antagonists would most likely require concomitant use of multiple agents.

Surgery residents’ perception of the objective structured clinical examination (OSCE)

PURPOSEnBeginning in July 2003, residency programs will be required to incorporate new educational assessment methods as defined by the Accreditation Council for Graduate Medical Education (ACGME) outcome initiative. The Objective Structured Clinical Examination (OSCE) is an assessment tool that is favorably viewed by the ACGME. Our institution has utilized the OSCE for evaluation of surgery trainees since 1996. Despite the positive acceptance of the OSCE by students, residents expressed dissatisfaction with the examination. This study was therefore undertaken to specifically evaluate resident perception of the OSCE.nnnMETHODSnTwo sequential surveys were administered to surgery residents at the Medical College of Ohio. Response of medical students to a standard survey following completion of the OSCE was tabulated.nnnRESULTSnOn the first, general survey, residents felt that the OSCE was not an adequate measure of either clinical (15 of 17 residents) or technical (15 of 18 residents) skills; 14 of 16 residents felt that the OSCE should not be used when considering promotion. When specifically queried in a follow-up survey, residents indicated that the OSCE was an adequate measure of clinical knowledge (2.2 +/- 0.3); however, most still felt that the OSCE should not be used when considering promotion (4.3 +/- 0.3). (Scores = mean +/- SEM on a Likert scale where 1 = strongly agree and 5 = strongly disagree). By contrast, 97.6% of 663 medical students surveyed (September 1996 through February 2002) felt the OSCE was useful.nnnCONCLUSIONSnThe OSCE has been shown to be a reliable and valid measure of basic clinical and technical competence. Despite our residents current perception, we believe that the OSCE is an important method for resident evaluation, particularly within the context of the current ACGME outcome initiative.

Ultrasound-guided needle biopsy of the breast

BACKGROUNDnTo determine the role of office-based ultrasound in the early clinical evaluation of breast masses, a consecutive series of diagnostic and interventional breast ultrasounds performed in the surgeons office were prospectively studied.nnnMETHODSnA series of 1028 diagnostic ultrasounds were performed in 662 patients over 2 years. The clinical-pathologic data from those patients undergoing ultrasound-guided fine-needle aspiration biopsy (FNAB; n = 267 patients) and/or core needle biopsy (CNB; n = 210 patients) were reviewed.nnnRESULTSnOf the 267 patients undergoing initial FNAB, 179 cysts were identified; 25 patients underwent no additional intervention, and 63 patients with apparently solid lesions underwent subsequent CNB. Core needle biopsy was the initial interventional approach in 147 cases. Of the 210 total patients in whom a CNB was performed, needle biopsy pathologic findings included:fibroadenoma, 57 patients; fibrocystic breast change, 82 patients; carcinoma, 53 patients; abscess/cyst, 12 patients; and other, 6 patients. Operative excision was performed in 106 of these 210 patients. There was a significantly higher false-negative rate among those patients who underwent an initial FNAB (20%; 2/10 patients) as compared with those patients undergoing CNB (3.6%; 2/55 patients; P < . 05). No cancers have been identified in those patients undergoing a benign CNB and followed for 6 to 30 months (median, 18 months).nnnCONCLUSIONnOffice-based diagnostic ultrasound and interventional ultrasound that uses core needle biopsy is an effective adjunct to the early clinical evaluation of breast masses.

Diagnostic and interventional ultrasound for breast disease.

The availability of reliable, portable computer-enhanced ultrasonography with high-frequency transducers has improved breast ultrasonography such that its role has increased dramatically. Diagnostic characteristics of breast lesions may be used to categorize these lesions according to their relative risk for malignancy. Furthermore, breast ultrasonography may be used to guide needle aspiration and biopsy of lesions so indicated by diagnostic evaluation. Results of ultrasound-guided aspiration and core biopsy accurately diagnose specific histopathology thereby avoiding unnecessary open biopsy for benign lesions and facilitating therapeutic planning for malignant lesions.

Radiographic assessment of the infiltrating retropharyngeal lipoma.

658 Neoplasms of the retropharyngeal space (RPS) are uncommon tumors that frequently remain asymptomatic until they reach a critical size that induces a mass effect on surrounding structures. Consequently, these neoplasms often remain undiagnosed until they are quite large, resulting in dysphagia or airway obstruction. The retropharyngeal lipoma is an extremely rare neoplasm. Although 31 cases of retropharyngeal lipoma have been described in the literature since the late 1800s, only 1 case of an infiltrating retropharyngeal lipoma has previously been documented.1 Because the recurrence rate of the infiltrating lipoma has been reported to be as high as 62.5%, preoperative determination of infiltration would allow the surgeon to widely resect the neoplasm in order to minimize the chance for recurrence.2 We present a patient in which preoperative diagnostic imaging was predictive of an infiltrating retropharyngeal lipoma and detail the patient’s management and follow-up. CASE REPORT A 49-year-old African American female presented to the Medical College of Ohio with a history of progressive dysphagia, increased upper airway resistance, loud snoring, and frequent nighttime awakening, as well as daytime somnolence. The patient had undergone polysomnography that demonstrated an apnea-hypopnea index of 14 events per hour of sleep, consistent with mild obstructive sleep apnea. On physical examination, the patient demonstrated no evidence of airway restriction or alteration in vocal quality. Inspection of the oropharynx demonstrated a submucosal prominence of the posterior pharyngeal wall that on palpation was homogeneous and doughy. The overlying mucosa was normal. Laryngoscopy documented the posterior pharyngeal prominence with extension caudally behind the larynx, compressing the laryngeal inlet anteroposteriorly. The larynx and hypopharyngeal region were otherwise normal and no masses were appreciated on palpation of the neck. A CT scan was performed on the basis of the patient’s examination findings that demonstrated a radiolucent mass involving the retropharyngeal space that compressed and displaced the larynx, trachea, and esophagus anteriorly and the left carotid sheath laterally (Fig 1A). There was also radiographically evident destruction of the prevertebral musculature posteriorly and the irregular interface between the mass and the prevertebral muscles suggested infiltration of the mass into the prevertebral musculature. To better define the radiographic extent and quality of

Management of nonpalpable ultrasound-indeterminate breast lesions

BACKGROUNDnA series of such lesions was studied to determine the validity of applying criteria routinely used to manage palpable breast cysts to the management of mammographically detected, nonpalpable breast lesions characterized as indeterminate on ultrasound (US).nnnMETHODSnThe clinicopathologic data from a series of 134 patients who underwent US-guided fine needle aspiration biopsy for nonpalpable, mammographically detected breast lesions, categorized as indeterminate on US, were reviewed.nnnRESULTSnOf 139 indeterminate lesions, 78 were consistent with complex cysts, whereas in 61, the cystic-versus-solid nature was indistinguishable. All 71 complex cyst lesions that contained nonbloody fluid and resolved completely were benign. Two of 7 complex cyst lesions that had incomplete resolution, bloody aspirate, or both were malignant. Of 61 cystic-versus-solid lesions, 29 and 32 were primarily solid and cystic, respectively. Three of the 29 solid lesions were malignant. Of the 32 cystic lesions, all 26 that contained nonbloody fluid and resolved completely were benign, whereas 1 of 6 lesions that had incomplete resolution, bloody aspirate, or both was malignant.nnnCONCLUSIONnCriteria such as complete resolution and nonbloody aspirate are an effective adjunct to the management of nonpalpable, mammographically detected breast lesions categorized as indeterminate by US.

Symptomatic heterotopic pancreas following seat belt injury

Heterotopic pancreas is defined as the presence of normal pancreatic tissue in an abnormal location and lacking continuity with the main body of the pancreas. Autopsy studies note an incidence of 0.55–13% [1] for this congenital anomaly, but it is usually of limited clinical importance. Although uncommon, when symptomatic, complaints are generally gastrointestinal and include nausea, vomiting, epigastric pain, and upper gastrointestinal bleeding [2]. Men are more often affected than women and clinical symptoms peak in the sixth decade. Heterotopic pancreas can lead to serious complications including gastric/duodenal ulceration, pancreatitis, massive gastrointestinal bleeding or gastric outlet obstruction [3]. Garrett and Braunstein independently described the seat belt syndrome in 1962 [4]. In addition to duodenal haematoma formation and rupture, closed pancreatic injuries with associated traumatic pancreatitis and pseudocyst formation have also been reported following such injuries [4]. We present a case report of heterotopic pancreas which developed symptoms immediately after a seat belt injury suffered at the time of motor vehicle accident (MVA).