Veterans Affairs general surgery service: the last bastion of integrated specialty care.

BACKGROUND: In a time of increasing specialization, academic training institutions provide a compartmentalized learning environment that often does not reflect the broad clinical experience of general surgery practice. This study aimed to evaluate the contribution of the Veterans Affairs (VA) general surgery surgical experience to both index Accreditation Council for Graduate Medical Education (ACGME) requirements and as a unique integrated model in which residents provide concurrent care of multiple specialty patients. METHODS: Institutional review board approval was obtained for retrospective analysis of electronic medical records involving all surgical cases performed by the general surgery service from 2005 to 2009 at the Nashville VA. Over a 5-year span general surgery residents spent an average of 5 months on the VA general surgery service, which includes a postgraduate year (PGY)-5, PGY-3, and 2 PGY-1 residents. Surgeries involved the following specialties: surgical oncology, endocrine, colorectal, hepatobiliary, transplant, gastrointestinal laparoscopy, and elective and emergency general surgery. The surgeries were categorized according to ACGME index requirements. RESULTS: A total of 2,956 surgeries were performed during the 5-year period from 2005 through 2009. Residents participated in an average of 246 surgeries during their experience at the VA; approximately 50 cases are completed during the chief year. On the VA surgery service alone, 100% of the ACGME requirement was met for the following categories: endocrine (8 cases); skin, soft tissue, and breast (33 cases); alimentary tract (78 cases); and abdominal (88 cases). Approximately 50% of the ACGME requirement was met for liver, pancreas, and basic laparoscopic categories. CONCLUSIONS: The VA hospital provides an authentic, broad-based, general surgery training experience that integrates complex surgical patients simultaneously. Opportunities for this level of comprehensive care are decreasing or absent in many general surgery training programs. The increasing level of responsibility and simultaneous care of multiple specialty patients through the VA hospital systems offers a crucial experience for those pursuing a career in general surgery.

Identification and optimization of small molecules that restore E-cadherin expression and reduce invasion in colorectal carcinoma cells.

E-cadherin is a transmembrane protein that maintains intercellular contacts and cell polarity in epithelial tissue. The down-regulation of E-cadherin contributes to the induction of the epithelial-to-mesenchymal transition (EMT), resulting in an increased potential for cellular invasion of surrounding tissues and entry into the bloodstream. Loss of E-cadherin has been observed in a variety of human tumors as a result of somatic mutations, chromosomal deletions, silencing of the CDH1 gene promoter, and proteolytic cleavage. To date, no compounds directly targeting E-cadherin restoration have been developed. Here, we report the development and use of a novel high-throughput immunofluorescent screen to discover lead compounds that restore E-cadherin expression in the SW620 colon adenocarcinoma cell line. We confirmed restoration of E-cadherin using immunofluorescent microscopy and were able to determine the EC(50) for selected compounds using an optimized In-Cell Western assay. The profiled compounds were also shown to have a minimal effect on cell proliferation but did decrease cellular invasion. We have also conducted preliminary investigations to elucidate a discrete molecular target to account for the phenotypic behavior of these small molecules and have noted a modest increase in E-cadherin mRNA transcripts, and RNA-Seq analysis demonstrated that potent analogues elicited a 10-fold increase in CDH1 (E-cadherin) gene expression.

Narrative medicine in surgical education.

PURPOSE: Narrative medicine is a patient-centered approach to the practice of medicine that rescues the patients' stories and integrates what is important to them into decisions regarding their health care. Our hypothesis is that narrative understanding enhances the patient-provider relationship and contributes to optimizing patient care. We propose to use written narrative reflection to capture and measure the general competencies of systems-based practice, practice-based learning, communication skills, and professionalism. DEVELOPMENT/METHODS: The development of this narrative-based project is based on a pilot study that we conducted at our institution with third-year surgical clerkship students. In the pilot, students produced in-depth narrative write-ups on a patient they had had the opportunity to "know." We plan a similar approach for surgical resident education. After a brief discussion of narrative medicine during our scheduled didactic conference, the residents are asked to initiate a written narrative reflection on a patient of their choosing. The narratives will be collected 1 week later. Our plan is to repeat this assessment quarterly so that 4 narratives will be generated annually from internship through the chief resident year. EVALUATION: The narratives will be analyzed for content and recurring themes that capture the resident's communication skills, professionalism, as well as self-critique (practice-based learning) and value attributed to health-care teams (systems-based practice). OUTCOME MEASURES: After completion of the narratives, a 5-point Likert response survey will be given to the residents to assess their experience and the perceived value of written reflection. The written narratives will become part of the resident's ongoing portfolio. IMPLEMENTATION/EXPERIENCE TO DATE: Feedback from the medical student pilot study was favorable. When asked in a follow-up questionnaire, most students reported the experience to be valuable and recommended the use of narrative reflection in medical education. To assess the feasibility of this approach in surgical residency, we introduced the concept of narrative reflection to our residents during surgery grand rounds. Thirty-three narratives were collected 1 week later. CONCLUSION/NEXT STEPS: This preliminary experience suggests that acquisition of resident-authored narrative reflection is feasible during surgical residency. Use of this narrative-based approach in surgical resident education has the potential to capture and measure the general competencies of systems-based practice, practice-based learning, communication skills, and professionalism.

Cost-effective use of breast biopsy techniques in a Veterans health care system.

BACKGROUND: Breast health has become an increasingly important issue among the veteran population. Options for the evaluation of a breast mass or a suspicious mammographic finding include open surgical biopsy at the Veterans Affairs (VA) hospital or percutaneous image-guided biopsy at an affiliated academic institution. We examined the costs and trends in the use of surgical versus percutaneous image-guided biopsy procedures in this diagnostic algorithm. METHODS: A retrospective review was performed of 62 patients who presented to the VA General Surgery Clinic with a breast mass or abnormal mammogram from 2003 to 2005. The Massachusetts Utilization Multiprogramming System and the Decision Support System software packages were used to track costs of procedures, by Current Procedure Terminology code and date of service, performed at the affiliated academic institution and at the VA hospital. These data were analyzed and described using the R statistical computing environment. RESULTS: Forty-six patients were evaluated using open biopsy techniques in the VA operating room, including 8 incisional biopsies, 21 excisional biopsies, and 17 needle-localization excisional biopsies. Sixteen patients were evaluated using minimally invasive biopsies at the affiliated academic institution, including 3 ultrasound-guided cyst aspirations, 6 ultrasound-guided core biopsies/vacuum-assisted core biopsies, 10 stereotactic breast biopsies, and 1 fine-needle aspiration. The average cost to evaluate a breast mass or abnormal mammographic finding in the operating room was 4,368.00 dollars (SD, 2,586.00 dollars), with a median cost of 3,479.00 dollars. The average cost to evaluate a breast mass or mammographic abnormality using percutaneous image-guided procedures was 1,267.00 dollars (SD, 536.00 dollars), with a median of 1,239.00 dollars. From 2003 to 2005, the proportion of percutaneous biopsies increased from 13% to 48%, whereas the proportion of open biopsies decreased from 88% to 52%. CONCLUSIONS: Over a recent 3-year period, we observed a 3.8-fold increase in the use of percutaneous image-guided techniques for the evaluation of breast lesions in the VA Tennessee Valley Healthcare System. Diagnosis by percutaneous techniques allows planning for a definitive surgery if a lesion is malignant or possible avoidance of a surgical intervention if the lesion is benign. Our data show that the costs associated with open biopsy techniques exceed those associated with percutaneous biopsies. For VA hospitals with available resources, the option of image-guided percutaneous biopsy techniques is a cost-effective alternative to open surgical biopsy.

Endoscopic ultrasound: impact on survival in patients with esophageal cancer.

BACKGROUND: Esophageal carcinoma is an aggressive malignancy and long-term survival is poor. Endoscopic ultrasound (EUS) is an additional staging modality to assess locoregional extent of this disease. We hypothesized that EUS may improve survival through more effective staging and better optimization of treatment. METHODS: We performed a retrospective review of all patients presenting with esophageal cancer at our institution from 1993 to 2003 (n = 97) and compared outcomes between patients who underwent staging EUS and computed tomography (CT) versus CT alone. Survival was calculated using Kaplan-Meier methods and compared between groups using the log-rank test. Mean survival was compared using analysis of variance (ANOVA) methods. RESULTS: Overall 3-, 6-, and 12-month survival did not differ between the 2 groups (EUS: 92%, 84%, and 80% and CT: 83%, 67%, and 43%, log-rank P = .1), which held true despite stratification by treatment modality (all P >.1). The mean survival for the EUS group was 16 +/- 3 months and for the CT group, 12 +/- 1.5 months (P = .2). Further analysis by stage showed no difference in survival between the 2 groups (all P >.1). However, stage 2A and 3 surgical patients had better survival than nonsurgical patients (both P = .02) irrespective of staging modality. EUS patients were no more likely to receive surgical, neoadjuvant, or definitive chemoradiation than CT patients (all P >.1). CONCLUSIONS: Overall survival as well as survival by stage did not differ between patients who underwent staging via EUS and CT versus CT alone, and patients staged with EUS were not more likely to receive any one intervention. Irrespective of staging modality, stage 2A and 3 patients who underwent surgical intervention had better survival than those who did not receive an operation.

E-cadherin is regulated by the transcriptional repressor SLUG during Ras-mediated transformation of intestinal epithelial cells.

BACKGROUND: Loss of the cell membrane protein E-cadherin is a critical event during Ras-mediated transformation of intestinal epithelial cells. The purpose of our study is to determine if activation of the transcriptional repressor SLUG is an important component of the mechanism of Ras-induced loss of E-cadherin. METHODS: Rat intestinal epithelial (RIE) cells were engineered to express mutated human Ha-Ras(Val12) complementary DNA (H-Ras cells). Cell morphology was examined by light microscopy. RNA and protein expression were measured by semiquantitative polymerase chain reaction and Western blot analyses, respectively. Short interfering RNA with 2 different oligos was used to knock down the expression of SLUG. RESULTS: Oncogenic ras induces upregulation of the transcriptional repressor SLUG and subsequent downregulation of the junctional protein E-cadherin. Gene silencing of SLUG by short interfering RNA allows E-cadherin to be reexpressed. E-cadherin protein reexpression allows partial rescue of the transformed phenotype. CONCLUSION: These data suggest a mechanism whereby Ras signaling causes an upregulation of transcriptional repressors and subsequent downregulation of E-cadherin as a malignant phenotype is propagated.

Effect of race on long-term survival of breast cancer patients: transinstitutional analysis from an inner city hospital and university medical center.

Black women have the highest mortality for breast cancer. Our hypothesis is that racial disparities in breast cancer survival persist after controlling for stage of disease and treatment at both a city hospital as well as at a university hospital. Data from tumor registries of breast cancer patients at a city hospital and a university center were analyzed for overall and disease-specific survival, controlling for stage and treatment. Black patients presented with more advanced stages and had significantly worse survival compared with whites. After controlling for stage of disease and treatment, a difference in survival persisted for stage II patients, with blacks doing worse than whites at both institutions. Although there were socioeconomic differences, race was an independent prognostic factor, with black patients having the worse prognosis. The lower survival of black women with breast cancer is only partially explained by their advanced stage at diagnosis. Black women with potentially curable stage II cancer had a lower survival that is not explained by the variables measured.

Oncogenic Ras dominates overexpression of E-cadherin in malignant transformation of intestinal epithelial cells.

BACKGROUND: Loss of the adherens junction protein E-cadherin is a critical event during Ras-mediated transformation of intestinal epithelial cells. The purpose of our study was to determine if overexpression of E-cadherin prevents Ras-induced malignant transformation and suppresses cell growth. METHODS: Rat intestinal epithelial cells were constructed with a mutated human Ha-RasVal12 cDNA. In these cells, Ras is constitutively expressed or induced by addition of isopropyl-1-thio-B-D-galactopyranoside. Cells were transfected with a bicistronic retroviral system that expressed green fluorescent protein alone or this protein and human E-cadherin. E-cadherin expression was measured by Western blot analysis, and localization by immunofluorescence. Anchorage-independent growth in soft agar was examined as well as tumor growth in nude mice. RESULTS: After Ras induction, endogenous E-cadherin was downregulated, whereas overexpression of human E-cadherin was sustained. Oncogenic Ras dominated overexpression of E-cadherin by causing malignant transformation and E-cadherin mislocalization. Ras also promoted growth in soft agar and tumors in nude mice despite E-cadherin overexpression. CONCLUSIONS: Oncogenic Ras subverts the tumor suppressor activity of E-cadherin in Ras-transformed intestinal epithelial cells by downregulating endogenous E-cadherin and mislocalizing transfected E-cadherin. The role of E-cadherin as a tumor suppressor in intestinal malignancies may be restricted by mutated or overactive Ras.

Dysregulation of E-cadherin by oncogenic Ras in intestinal epithelial cells is blocked by inhibiting MAP kinase.

BACKGROUND: Mutations in oncogenic Ras contribute to colorectal tumorigenesis. Loss of the cell adhesion protein E-cadherin is associated with tumor invasion and metastasis. METHODS: Expression of oncogenic Ras was induced in intestinal epithelial cells. Changes in cell morphology, E-cadherin protein expression, and E-cadherin localization were examined by light microscopy, Western blot, and immunofluorescence respectively. Expression of E-cadherin in human colorectal tumors was examined by immunohistochemistry. RESULTS: Induction of oncogenic Ras results in an epithelial to mesenchymal transformation with loss of membranous E-cadherin expression and mis-localization to the cytoplasm. Removal of Ras stimulus or blockade of the MAP kinase pathway allowed reversion to a normal cellular phenotype and return of E-cadherin to the cell membrane. Loss of or decreased expression of E-cadherin was observed in seven of eight colorectal tumors. CONCLUSIONS: Oncogenic Ras contributes to malignant transformation and altered E-cadherin expression in intestinal epithelial cells. Similar dysregulation of E-cadherin is found in human colorectal tumors. Ras effects on E-cadherin are critical to malignant transformation in our in-vitro model and may be an important event in human colorectal tumors.