Amy Waer

Human breast tissue disposition and bioactivity of limonene in women with early stage breast cancer

Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonenes role for breast cancer prevention or treatment. Cancer Prev Res; 6(6); 577–84. ©2013 AACR.

Trends in post-mastectomy reconstruction: A SEER database analysis

This study was performed to investigate recent trends and factors associated with immediate breast reconstruction (IBR) using a large population‐based registry. We hypothesized that rates of IBR have increased since passage of the Womens Health and Cancer Rights Act of 1998.

The use of a lightly preserved cadaver and full thickness pig skin to teach technical skills on the surgery clerkship—a response to the economic pressures facing academic medicine today

BACKGROUND In response to declining instruction in technical skills, the authors instituted a novel method to teach basic procedural skills to medical students beginning the surgery clerkship. METHODS Sixty-three medical students participated in a skills training laboratory. The first part of the laboratory taught basic suturing skills, and the second involved a cadaver with pig skin grafted to different anatomic locations. Clinical scenarios were simulated, and students performed essential procedural skills. RESULTS Students learned most of their suturing skills in the laboratory skills sessions, compared with the emergency room or the operating room (P = .01). Students reported that the laboratory allowed them greater opportunity to participate in the emergency room and operating room. Students also felt that the suture laboratory contributed greatly to their skills in wound closure. Finally, 90% of students had never received instruction on suturing, and only 12% had performed any procedural skills before beginning the surgery rotation. CONCLUSIONS The laboratory described is an effective way of insuring that necessary technical skills are imparted during the surgery rotation.

Intensive laparoscopic training course for surgical residents: program description, initial results, and requirements

IntroductionThe Department of Surgery at the University of Arizona has created an intensive laparoscopic training course for surgical residents featuring a combined simulation laboratory and live swine model. We herein report the essential components to design and implement a rigorous training course for developing laparoscopic skills in surgical residents.Materials and methodsAt our institution, we developed a week-long pilot intensive laparoscopic training course. Six surgical residents (ranging from interns to chief residents) participate in the structured, multimodality course, without any clinical responsibilities. It consists of didactic instruction, laboratory training, practice in the simulation laboratory, and performance (under the direction of attending laparoscopic surgeons) of surgical procedures on pigs. The pigs are anesthetized and attended by veterinarians and technicians, and then euthanized at the end of each day. Three teams of two different training-level residents are paired. Daily briefing, debriefing, and analysis are performed at the close of each session. A written paper survey is completed at the end of the course.ResultsThis report describes the results of first 36 surgical residents trained in six courses. Preliminary data reveal that all 36 now feel more comfortable handling laparoscopic instruments and positioning trocars; they now perform laparoscopic surgery with greater confidence and favor having the course as part of their educational curriculum.ConclusionA multimodality intensive laparoscopic training course should become a standard requirement for surgical residents, enabling them to acquire basic and advanced laparoscopic skills on a routine basis.

Spinal Cord Injury With a Narrow Spinal Canal: Utilizing Torg’s Ratio Method of Analyzing Cervical Spine Radiographs

A 65-year-old inebriated man crashed his car and presented with spinal shock and neurogenic shock from a cervical spinal cord injury without cervical spine fracture or dislocation. The lateral cervical spine radiography was initially read as normal, except for degenerative disk disease; however, Torgs ratio method of analyzing cervical spinal canal sagittal width indicated the spinal canal was congenitally narrow. Magnetic resonance imaging confirmed this and showed bulging and herniation of multiple invertebral disks between C2 and C7. This case illustrates the value of using Torgs ratio method of analyzing lateral cervical spine radiographs. Although Torgs method has not been prospectively validated, it may be useful to identify patients at risk for cervical spinal cord injuries without fractures or dislocations. An abnormal Torgs ratio may be the only clue to the fact that the patient is at higher risk of spinal cord injury when the patients history or examination is questionable because of head injury, drug intoxication, or therapeutic sedation and paralysis.

Plasmatic hypercoagulation in patients with breast cancer: Role of heme oxygenase-1

Breast cancer is an important health threat to women worldwide, and is associated with a 9–14% incidence of thrombophilia. Of interest, patients with breast cancer have been noted to have an increase in endogenous carbon monoxide production via upregulation of heme oxygenase-1 activity. Given that it has been demonstrated that carbon monoxide enhances plasmatic coagulation in vitro and in vivo, we sought to determine whether patients with breast cancer had an increase in endogenous carbon monoxide and concurrent plasmatic hypercoagulability. Breast cancer patients who were not smokers scheduled to undergo partial or complete mastectomy (n = 18) had 15 ml of whole blood collected via an indwelling intravenous catheter and anticoagulated with sodium citrate. Whole blood was centrifuged and citrated plasma assessed with a thromboelastometric method to measure coagulation kinetics and the formation of carboxyhemefibrinogen. Breast cancer patients were determined to have an abnormally increased carboxyhemoglobin concentration of 2.5 ± 1.3%, indicative of heme oxygenase-1 upregulation. Breast cancer patient plasma on average clotted 73% more quickly and had 32% stronger thrombus strength than normal individual (n = 30) plasma. Further, 44% of breast cancer patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal individuals, and 75% of this hypercoagulable subgroup had carboxyhemefibrinogen formation. Future investigation of the role played by heme oxygenase-1-derived carbon monoxide in the pathogenesis of breast cancer-related thrombophilia is warranted.

Tissue-type plasminogen activator-induced fibrinolysis is enhanced in patients with breast, lung, pancreas and colon cancer:

Although cancer-mediated changes in hemostatic proteins unquestionably promote hypercoagulation, the effects of neoplasia on fibrinolysis in the circulation are less well defined. The goals of the present investigation were to determine if plasma obtained from patients with breast, lung, pancreas and colon cancer was less or more susceptible to lysis by tissue-type plasminogen activator (tPA) compared to plasma obtained from normal individuals. Archived plasma obtained from patients with breast (n = 18), colon/pancreas (n = 27) or lung (n = 19) was compared to normal individual plasma (n = 30) using a thrombelastographic assay that assessed fibrinolytic vulnerability to exogenously added tPA. Plasma samples were activated with tissue factor/celite, had tPA added, and had data collected until clot lysis occurred. Additional, similar samples had potato carboxypeptidase inhibitor added to assess the role played by thrombin-activatable fibrinolysis inhibitor in cancer-modulated fibrinolysis. Rather than inflicting a hypofibrinolytic state, the three groups of cancers demonstrated increased vulnerability to tPA (e.g. decreased time to lysis, increased speed of lysis, decreased clot lysis time). However, hypercoagulation manifested as increased speed of clot formation and strength compensated for enhanced fibrinolytic vulnerability, resulting in a clot residence time that was not different from normal individual thrombi. In sum, enhanced hypercoagulability associated with cancer was in part diminished by enhanced fibrinolytic vulnerability to tPA.

A Comparison of Unguided vs Guided Case-Based Instruction on the Surgery Clerkship

BACKGROUND Guided case-based instruction is an effective and efficient means of learning for third year medical students on the surgery clerkship. Compared with an unguided format for teaching biliary disease, we observed greater student satisfaction as well as a more efficient utilization of student as well as faculty time with the guided instruction. OBJECTIVE While case-based instruction (CBI) has become an extremely popular teaching modality during the first 2 years of medical school, there has been little published regarding its utilization during the clinical years of medical school. The purpose of our study was to compare guided CBI (G-CBI) to unguided CBI (UG-CBI) during the surgery clerkship. DESIGN From July 2007 to July 2008, we utilized a UG-CBI format to teach biliary disease, formerly taught by a standard lecture. The unguided style is used by our institution for the first 2 years of medical school education, where the role of the facilitator is minimal. From July 2008 to December 2010, we changed to a G-CBI format where 5 different clinical scenarios were presented that all dealt with some form of biliary disease. A Likert-like scale was used to analyze student opinion comparing guided to the traditional unguided format. Questions regarding biliary disease contained in the National Board of Medical Examiners (NBME) shelf examination, given to all students at the end of the rotation, were also compared between the 2 groups. Cohens d statistic was used to assess effect size. SETTING The study took place at the University of Arizona College of Medicine. PARTICIPANTS There were 88 students in the UG-CBI group and 146 in the G-CBI group. RESULTS Ninety-six percent of the students preferred G-CBI over the unguided format utilized during the basic science years. Eighty-two percent felt that the guided format sessions were a more efficient method of instruction and 91% of students agreed or strongly agreed that time was more efficiently utilized in preparing for the case discussion during the guided format. Shelf examination scores analyzing biliary disease questions (2-4 per examination) showed a moderate size effect favoring the G-CBI, although the numbers were too small to draw definite conclusions in this regard. CONCLUSIONS G-CBI is more suited for the surgery clerkship than the UG-CBI utilized during the first 2 years of medical school. Lack of a clinical knowledge base among the students rotating on the surgery clerkship as well as time limitations for both the student and clinical faculty favor this more efficient means of learning.

Development of an Enhanced Interprofessional Chief Resident Immersion Training (IP-CRIT) Program.

Using interprofessional faculty, the authors reviewed and enhanced the nationally renowned Chief Resident Immersion Training (CRIT) in the Care of Older Adults Program to include Triple Aim objectives and interprofessional competency-based content and developed the Interprofessional CRIT. Evaluations were positive and sustained. The authors educated chief residents about value-based care, linking them to key interprofessional staff to build team-based care. The authors addressed quality improvement issues identified by the Institute of Medicine and our health network. Chief residents are now better prepared to train medical students and residents using a team-based, patient-centered approach, and a culture of continual quality improvement toward improved care of older patients.

Mapping a curriculum database to the USMLE Step 1 content outline

Assessing the completeness of topic coverage in medical curricula is difficult to establish as no universal standard for completeness has been agreed upon. However, the United States Medical Licensing Examination (USMLE) Step 1 Exam Content Outline may provide a beginning framework. This project developed a computer-based tool that matched ArizonaMed curriculum content (Tucson track) against a modified USMLE content outline. The project involved three phases: (1) the USMLE Step 1 content outline was deconstructed and translated using equivalent Medical Subject Heading (MeSH) terms; (2) a report was made of all MeSH terms used to identify the content in the ArizonaMed curriculum database, compared to the MeSH-modified USMLE outline, and the resulting matches are graphically expressed. The frequency with which each MeSH term appeared across the years also was reported; and (3) a retreat was held with faculty and others to ensure the MeSH-translated outline was accurate and complete. Faculty were able to visualize how content was being expressed among instructional blocks across the first two years. Results also assured faculty and students that all subjects contained in the USMLE content outline were covered in the curriculum. The success of this effort is leading to improvements in content-tracking capability for the ArizonaMed database.