D. Scott Lind

Adjuvant radiation therapy for resectable retroperitoneal soft tissue sarcoma: the University of Florida experience.

Background:In the management of retroperitoneal sarcomas it is necessary to achieve local control to ensure survival. The role of adjuvant radiation therapy (RT), either pre- or postoperative, remains controversial. Methods:Outcomes for 40 patients with retroperitoneal sarcoma treated with surgery and postoperative RT (n = 25) or preoperative RT (n = 15) were analyzed for variables prognostic for local control, survival, and associated complications. Results:Patterns of failure for patients treated by resection and postoperative RT were local (n = 4), local and distant (n = 3), and distant (n = 3). The failure patterns for preoperative RT cases were local (n = 2), local and distant (n = 2); and distant (n = 4). Median time to local recurrence in the postoperative and preoperative RT series were 1 year and 2.5 years respectively. The margin status was predictive for local control (P = 0.0065) and survival (P = 0.0012), regardless of treatment sequence. Absolute 5-year survival was 12% with positive margins versus 69% if negative. Histologic grade was indicative of the risk for distant metastasis (low grade 8% vs high grade 64%; P = 0.1373), and significantly predicted 5-year absolute survival (low grade 77% vs high grade 34%; P = 0.0267). Postoperative RT was associated with significant complications (infection, hemorrhage, and bowel obstruction—2 cases each). Conclusion:Compared with the surgery-alone series, adjuvant RT appears to improve the probability of local control. Preoperative RT may be the preferred sequence potentially to improve tumor resectability and local–regional control with less risk of complications than with postoperative RT.

The validity of a virtual human experience for interpersonal skills education

Any new tool introduced for education needs to be validated. We developed a virtual human experience called the Virtual Objective Structured Clinical Examination (VOSCE). In the VOSCE, a medical student examines a life-size virtual human who is presenting symptoms of an illness. The student is then graded on interview skills. As part of a medical school class requirement, thirty three second year medical students participated in a user study designed to determine the validity of the VOSCE for testing interview skills. In the study, participant performance in the VOSCE is compared to participant performance in the OSCE, an interview with a trained actor. There was a significant correlation (r(33)=.49, p<.005) between overall score in the VOSCE and overall score in the OSCE. This means that the interaction skills used with a virtual human translate to the interaction skills used with a real human. Comparing the experience of virtual human interaction to real human interaction is the critical validation step towards using virtual humans for interpersonal skills education.

Comparing Interpersonal Interactions with a Virtual Human to Those with a Real Human

This paper provides key insights into the construction and evaluation of interpersonal simulators¿systems that enable interpersonal interaction with virtual humans. Using an interpersonal simulator, two studies were conducted that compare interactions with a virtual human to interactions with a similar real human. The specific interpersonal scenario employed was that of a medical interview. Medical students interacted with either a virtual human simulating appendicitis or a real human pretending to have the same symptoms. In Study I (n = 24), medical students elicited the same information from the virtual and real human, indicating that the content of the virtual and real interactions were similar. However, participants appeared less engaged and insincere with the virtual human. These behavioral differences likely stemmed from the virtual humans limited expressive behavior. Study II (n = 58) explored participant behavior using new measures. Nonverbal behavior appeared to communicate lower interest and a poorer attitude toward the virtual human. Some subjective measures of participant behavior yielded contradictory results, highlighting the need for objective, physically-based measures in future studies.

Arginine and Cancer

Arginine is a dibasic, cationic, semiessential amino acid with numerous roles in cellular metabolism. It serves as an intermediate in the urea cycle and as a precursor for protein, polyamine, creatine and nitric oxide (NO) biosynthesis. Arginine is conditionally essential since it becomes necessary under periods of growth and after recovery after injury. Arginine also promotes wound healing and functions as a secretagogue stimulating the release of growth hormone, insulin-like growth factor 1, insulin, and prolactin. Furthermore, arginine has several immunomodulatory effects such as stimulating T- and natural killer cell activity and influencing pro-inflammatory cytokine levels. The discover that l-arginine is the sole precursor for the multifunctional messenger molecule nitric oxide (NO) led to investigation into the role of arginine in numerous physiologic and pathophysiologic phenomena including cancer. Although NO was first identified in endothelial cells, it is now recognized to be generated by a variety of cell types, including several tumor cell lines and solid human tumors. Unfortunately, the precise role of NO in cancer is poorly understood but it may influence tumor initiation, promotion, and progression, tumor-cell adhesion, apoptosis angiogenesis, differentiation, chemosensitivity, radiosensitivity, and tumor-induced immunosuppression. The biological effects of NO are complex and dependent upon numerous regulatory factors. Further research is necessary to enhance our understanding of the complex mechanisms that regulate NOs role in tumor biology. A better understanding of the role of arginine-derived NO in cancer may lead to novel antineoplastic and chemopreventative strategies.

External beam radiotherapy for primary and adjuvant management of aggressive fibromatosis

PURPOSE To review a large single-institution experience in the management of aggressive fibromatosis to determine the effectiveness of external beam radiotherapy (EBRT) and identify the presentation and treatment variables predictive of locoregional control. METHODS AND MATERIALS Between 1975 and 2000, 72 patients were treated with EBRT for a pathologically confirmed diagnosis of aggressive fibromatosis. Thirty patients were treated at the primary presentation and 42 at the time of a locoregional recurrence. Minimal 2-year follow-up data were available for 65 patients (median 6 years). Megavoltage irradiation with 60Co to 20 MV photons or electron therapy was used for all patients. Most patients were treated after attempted complete surgical resection; 16 patients underwent pretreatment biopsy alone. The prescribed treatment was standard (1.8 Gy) daily fractions in 42 cases and 1.2 Gy fractions b.i.d. in 23 cases. The median prescribed dose was 54 Gy. The prognostic variables and treatment results were evaluated by Kaplan-Meier actuarial analysis. RESULTS Locoregional control was achieved in 52 of 65 patients. The 5-year actuarial locoregional control was 83%. Locoregional failure occurred in 13 patients (11 in patients with recurrent tumors). Only two failures occurred within the irradiation fields; nine failures occurred at the field margins. Eleven patients were salvaged by surgery: wide excision in nine and amputation in two. The only prognostic factor significant for locoregional control was primary vs. recurrent presentation (p = 0.0193). The 5-year locoregional control rates for irradiation at initial presentation and at recurrence were 96% and 75%, respectively. The variables without significance for locoregional control included primary tumor location, surgical procedures performed, resection margins, and gross vs. microscopic residual tumor at irradiation. Lymphedema was the most common late effect, occurring in 7 patients, 5 with prior treatment. Bone fracture occurred in 3 patients; all 3 had fibromatosis involving the bone at presentation but without recurrence at the time of fracture. CONCLUSION EBRT is effective treatment for aggressive fibromatosis. The probability of locoregional control decreases with multiple prior recurrences.

Incidental PET/CT findings in the cancer patient: How should they be managed?

BACKGROUND Despite a paucity of evidence-based guidelines, the use of PET/CT (positron emission tomography/computed tomography) in the management of cancer patients is increasing. As widespread clinical application increases, unexpected radiographic findings are occasionally identified. These incidental findings are often suspicious for a second primary malignancy. The purpose of this study was to determine the clinical impact of these incidental PET/CT findings. METHODS A query of our prospectively acquired Nuclear Medicine database was performed to identify patients with a known malignancy being staged or serially imaged with PET/CT. Patients with incidental findings suggestive of a second primary malignancy were selected. Statistical analysis was performed to determine the ability of PET/CT to identify a second primary malignancy. All PET/CT were interpreted by board certified nuclear radiologists. RESULTS Of 3,814 PET/CT scans performed on 2,219 cancer patients at our institution from January 1, 2005, to December 29, 2008, 272 patients (12% of all patients) had findings concerning for a second primary malignancy. An invasive work-up was performed on 49% (133/272) of these patients, while 15% (40/272) had no further evaluation due to an advanced primary malignancy. The remaining 36% (99/272) had no further evaluation secondary to a low clinical suspicion determined by the treating team, a clinical plan of observation, or patients lost to follow-up. Of the 133 patients evaluated further, clinicians identified a second primary malignancy in 41 patients (31%), benign disease in 62 patients (47%), and metastatic disease from their known malignancy in 30 patients (23%). The most common sites for a proven second primary malignancy were: lung (N = 10), breast (N = 7), and colon (N = 5). Investigation of these lesions was performed using several techniques, including 24 endoscopies (6 malignant). A surgical procedure was performed in 74 patients (29 malignant), and a percutaneous biopsy was performed on 34 patients (12 malignant). The overall positive predictive value for PET/CT to detect a second primary malignancy was 31% in this subgroup. At a median follow-up of 22 months, 9 of 41 patients with a second primary were dead of a malignancy, 20 were alive with disease, and 12 had no evidence of disease. CONCLUSION Incidental PET/CT findings consistent with a second primary are occasionally encountered in cancer patients. In our data, approximately half of these findings were benign, a third were consistent with a second primary malignancy or a metastatic focus, and the remainder were never evaluated due to physician and patient decision. Advanced primary tumors are unlikely to be impacted by a second primary tumor suggesting that this subset of patients will not benefit from further investigation. Our data suggests that, despite the high rate of false positivity, incidental PET/CT findings should be investigated when the results will impact treatment algorithms. The timing and route of investigation should be dictated by clinical judgment and the status of the primary tumor. Further investigation will need to be performed to determine the long-term clinical impact of incidentally identified second primary malignancies.

Carcinoid heart disease: A case report and literature review

We report a patient who presented for elective exploratory laparotomy, and resection of a pelvic mass, which was thought to be ovarian carcinoma. Intraoperative transesophageal echocardiography demonstrated right-sided valvular heart lesions, which suggested the diagnosis of carcinoid syndrome before a pathologic confirmation was obtained. This article discusses the classical presentation and anesthetic management of patients with carcinoid syndrome and emphasizes the importance of proper preoperative diagnosis and careful planning if the incidence and severity of the symptoms that this condition can provoke are to be reduced.

Evolving an immersive medical communication skills trainer

This paper presents our experiences in evolving the Virtual Objective Structured Clinical Exam (VOSCE) system. This system allows medical students to experience the interaction between a patient and a medical doctor using natural methods of interaction with a high level of immersion. These features enable the system to provide training on medical communication skills. We discuss the experiences of a group of medical and physician assistant students that pilot tested the system. Further, we examine the impact of evolving the system based on their feedback. The VOSCE systems performance in subsequent studies has indicated that end-user feedback improvements have significantly impacted overall performance and efficacy.

Human-Centered Distributed Conversational Modeling: Efficient Modeling of Robust Virtual Human Conversations

Currently, applications that focus on providing conversations with virtual humans require extensive work to create robust conversational models. We present a new approach called Human-centered Distributed Conversational Modeling. Using this approach, users create conversational models in a distributed manner. To do this, end-users interact with virtual humans to provide new stimuli (questions and statements), and domain-specific experts (e.g. medical/psychology educators) provide new virtual human responses. Using this process, users become the primary developers of conversational models. We tested our approach by creating an example application, Virtual People Factory. Using Virtual People Factory, a pharmacy instructor and 186 pharmacy students were able to create a robust conversational model in 15 hours. This is approximately 10% of the time typical in current approaches and results in more comprehensive coverage of the conversational space. In addition, surveys demonstrate the acceptability of this approach by both educators and students.

Increasedl-arginine transport in a nitric oxide-producing metastatic colon cancer cell line

AbstractBackground: Little is known about amino acid transport in human neoplastic cells. We previously characterizedl-arginine transport in the primary human colon cancer cell line, SW480, and found it is principally mediated by the sodium-independent system y+. In this study, we characterizedl-arginine transport in the metastatic cell line, SW620, and compared it with that in the primary cell line, SW480. Methods: Transport of3H-l-arginine in cell monolayers was analyzed in the presence and absence of sodium. Kinetic studies were performed over a range ofl-arginine concentrations to determine transporter affinity (Km) and maximal transport velocity (Vmax). Transport was further characterized through blockade with known amino acids. In addition, the effect of cell age (i.e., time in culture) on arginine transport was examined at 2 and 9 days after seeding. Cellular proliferation was asssessed by using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Results:l-Arginine uptake was primarily sodium independent in the SW620 cell line. Kinetic and amino acid-inhibition studies revealed a single high-affinity, sodium-independentl-arginine transporter (Vmax=1286.3 ± 158.3 pmol/mg protein/30 s; Km=46.8 ± 4.2 µM). Sodium-independent transport was blocked by system y+ substratesl-homoarginine,l-ornithine andl-lysine. Sodium-dependent uptake occurs through a single transporter with system BO,+ characteristics (Km=16.15 ± 2.1 µM; Vmax=329.94 ± 29.7 pmol/mg protein/30 s). Arginine transport increased with time in culture with day 2 cells transport velocity =241.7 ± 33.6 pmol/mg protein/30s, whereas day 9 cells transport velocity =377 ± 15.4 pmol/mg protein/30 s (p<0.01). Cellular-proliferation studies revealed a doubling time of 3.2 days for SW620 and 5.4 days for SW480 (p<0.05). Conclusions:l-Arginine transport in these neoplastic cell lines occurs primarily through sodium-independent, high-affinity system y+. Vmax was increased 180% in the metastatic variant (SW620), suggesting upregulation of the y+ transporter. The increased y+ activity may be a mechanism to provide continuous substrate for tumor growth.