Effects of summer internship and follow-up distance mentoring programs on middle and high school student perceptions and interest in health careers.

BACKGROUND: Minorities are underrepresented in health professions and efforts to recruit minority students into health careers are considered a way to reduce health disparities. There is little research about the effectiveness of these programs, other than satisfaction. This study aimed to measure program effects on student understanding of and interest in health careers. METHODS: Students took a career interest inventory, completed a scale measuring their self-reported understanding and interest in health careers, and wrote essays about health careers before and after completing a 1 week on campus internship on health careers and after a 9 month follow up distance mentoring program where they continued to interact with university faculty by videoconference about career options. Changes in inventory, scale, and essay scores were analyzed for changes over time using Wilcoxon and Mann-Whitney tests. RESULTS: Inventory scores were unchanged over time, but scale and essay scores trended upward significantly post internship and mentoring. CONCLUSION: Health career education and mentoring programs can positively affect student knowledge of health careers and their attitudes about them. The study's methods extend measures of program impact beyond satisfaction.

Activated wnt signaling in stroma contributes to development of pancreatic mucinous cystic neoplasms.

BACKGROUND & AIMS: Pancreatic mucinous cystic neoplasm (MCN), a cystic tumor of the pancreas that develops most frequently in women, is a potential precursor to pancreatic ductal adenocarcinoma. MCNs develop primarily in the body and tail of the pancreas and are characterized by the presence of a mucinous epithelium and ovarian-like subepithelial stroma. We investigated the involvement of Wnt signaling in KRAS-mediated pancreatic tumorigenesis and development of MCN in mice, and Wnt activation in human MCN samples. METHODS: LSL-Kras(G12D), Ptf1a-cre mice were crossed with elastase-tva mice to allow for introduction of genes encoded by the replication-competent avian sarcoma-leukosis virus long-terminal repeat with splice acceptor viruses to pancreatic acinar cells and acinar cell progenitors, postnatally and sporadically. Repeat with splice acceptor viruses that expressed Wnt1 were delivered to the pancreatic epithelium of these mice; pancreatic lesions were analyzed by histopathology and immunohistochemical analyses. We analyzed levels of factors in Wnt signaling pathways in 19 MCN samples from patients. RESULTS: Expression of Wnt1 in the pancreatic acinar cells and acinar cell progenitors of female mice led to development of unilocular or multilocular epithelial cysts in the pancreas body and tail, similar to MCN. The cystic lesions resembled the estrogen receptor- and progesterone receptor-positive ovarian-like stroma of MCN, but lacked the typical mucinous epithelium. Activated Wnt signaling, based on nuclear localization of ß-catenin, was detected in the stroma but not cyst epithelium. Wnt signaling to ß-catenin was found to be activated in MCN samples from patients, within the ovarian-like stroma, consistent with the findings in mice. CONCLUSIONS: Based on studies of mice and pancreatic MCN samples from patients, the canonical Wnt signaling pathway becomes activated and promotes development of the ovarian-like stroma to contribute to formation of MCNs.

The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis.

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by KRAS activation. Here we find that transcriptional activation mediated by the Gli family of transcription factors, although dispensable for pancreatic development, is required for Kras-induced proliferation and survival in primary pancreatic epithelial cells in culture and for Kras-driven pancreatic intraepithelial neoplasia and PDAC formation in vivo. Further, ectopic Gli1 activation in the mouse pancreas accelerates Kras-driven tumor formation, underscoring the importance of Gli transcription factors in pancreatic tumorigenesis. Interestingly, we demonstrate Gli-regulated I-kappa-B kinase epsilon (IKBKE) and NF-κB activity in pancreatic cancer cells and show that this activity is a critical downstream mediator for Gli-dependent PDAC cell transformation and survival. Together, these studies demonstrate the requirement for Gli in Kras-dependent pancreatic epithelial transformation, suggest a mechanism of Gli-NF-κB oncogenic activation, and provide genetic evidence supporting the therapeutic targeting of Gli activity in pancreatic cancer.

Age as a deciding factor in the consideration of futility for a medical intervention in patients among internal medicine physicians in two practice locations.

OBJECTIVES: This study explores physicians' concepts of futility and use of age as a deciding factor in considering medical futility in clinical interventions. DESIGN: Survey. SETTING: Five academic hospitals in the United States. PARTICIPANTS: Participants were 355 internal medicine physicians, including 162 residents, 98 fellows, and 95 attending physicians. MEASUREMENT: Anonymous questionnaire in which respondents were asked to define futility and to rate patient scenarios as futile or not, unaware that these were pairs of patient scenarios with similar clinical severity and treatment, but different age. RESULTS: Forty-five percent (n = 159) of physicians used the most accepted definition of futility in the literature: "a therapy that will not benefit the patient in attaining a specific goal." Physicians rated patient scenarios as futile for 58% of elder (> or =65 years) and for 59% of nonelder (<65 years) cases (P = .21). By training level, resident physicians rated more elder cases as futile (60%) than fellow/attending physicians (56%, P = .03). Rating of medical futility did not differ by practice location (59% in Missouri and 59% in Puerto Rico, P = .13). CONCLUSION: Physicians did not use age as a factor in deciding the futility of a medical intervention. In patient scenarios with comparable clinical severity of illness, medical interventions were similarly rated as futile in elder and nonelder persons. Less-experienced physicians (residents) were more likely to rate elder cases as futile compared with experienced physicians (attending/fellows).

Mismatch repair protein expression and colorectal cancer in Hispanics from Puerto Rico.

Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.

Serrated adenomas.

Serrated adenomas are categorized as sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs). SSAs are more prevalent in the proximal colon and lack classic dysplasia, whereas TSAs are more prevalent in the rectosigmoid and have cytologic dysplasia. Serrated adenomas may progress to colorectal adenocarcinoma through diverse molecular alterations. Colonoscopy is the only test for the early detection of serrated adenomas that allows inspection of the entire colon and same-session biopsy sampling or polypectomy, if necessary. If an endoscopic biopsy at the right colon reveals SSA without cytologic dysplasia or biopsy at the rectosigmoid reveals SSA or TSA, those polyps should be excised or surgically resected as necessary. Postpolypectomy surveillance for removed SSAs without dysplasia and TSAs must be performed at 5- and 3-year intervals, respectively, with colonoscopy to prevent recurrence and progression to colorectal adenocarcinoma.

MSH-2 and MLH-1 protein expression in Muir Torre syndrome-related and sporadic sebaceous neoplasms.

BACKGROUND: Muir-Torre Syndrome (MTS) is a rare autosomal-dominant disorder characterized by the predisposition to both sebaceous neoplasm and internal malignancies. MTS-associated sebaceous neoplasms reveal mutations in DNA mismatch repair (MMR) genes and microsatellite instability. A significant part of MTS patients represents a phenotypic variant, the hereditary nonpolyposis colorectal cancer (HNPCC). A strong correlation between microsatellite instability and immunostaining has been demonstrated. The early recognition of sebaceous neoplasm as part of MTS, and their differentiation from sporadic sebaceous neoplasm may have an important application in a clinical setting. The absence of MLH-1 or MSH-2 expression by immunostaining identifies tumors with mismatch repair deficiency. OBJECTIVES: Our aim is to determine whether an immunohistochemical approach, targeting DNA repair proteins MSH-2 and MLH-1 in MTS-related sebaceous neoplasm and their sporadic counterparts, can be used for their identification. METHODS: We examined 15 sebaceous neoplasms (including 6 internal malignancy- associated sebaceous neoplasms and 8 sporadic sebaceous neoplasms) from 11 patients for the expression of MSH-2 and MLH-1 by immunohistochemistry. RESULTS: Four of 5 internal malignancy-associated sebaceous neoplasms showed loss of expression of MSH-2 or MLH-1. Correlation of the immunostaining pattern of the sebaceous neoplasms and the patients' positive history of colon carcinoma was 80%. Seven of 8 sporadic sebaceous neoplasms showed a positive expression of MSH-2 and MLH-1. The prevalence for loss of expression of MMR proteins in sebaceous neoplasms was 38.5%. MMR immunostaining had 87.5% specificity and 80% sensitivity. LIMITATIONS: This study is limited by a small sample size, and by bias selection due to the use of non nationwide data-base as the resource of cases. CONCLUSIONS: Our findings demonstrate that immunohistochemical testing for internal malignancy-associated sebaceous neoplasms is a practical approach to confirm a suspected inherited MMR gene defect, and an accurate method to distinguish between sporadic and MTS-associated sebaceous lesions.

Dysphagia and lung aspiration secondary to anterior cervical osteophytes: a case report and review of the literature.

INTRODUCTION: Two of the most common causes of anterior cervical bony outgrowths are diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS). These osteophytes have been associated with serious complications. The objective of this case report is to highlight how commonly occurring anterior cervical osteophytes may become an uncommon cause for life-threatening dysphagia and potential lung aspiration in elderly patients. CASE REPORT: An 80-year-old man came to the hospital with dyspnea and cough productive of sputum. These symptoms were associated with progressive dysphagia for the previous 10 years, which was evaluated with a barium esophagogram that was discontinued due to aspiration of barium. The patient was placed on mechanical ventilation. Neck computed tomography showed anterior cervical osteophytes displacing the upper airway and compressing the esophagus and calcification of the posterior longitudinal ligament with a "bamboo" appearance. The patient underwent surgical removal of the osteophytes. DISCUSSION: The patient had onset of symptoms at > 50 years of age, dysphagia, osteophytes in the clavicle and shoulders, anterior cervical osteophytes, calcified posterior longitudinal ligament, and spinal stenosis, all of which are associated with DISH. AS is associated with the patient's history of stooped posture, anterior displacement of the head while walking, and bamboo spine. The final diagnosis, either DISH or AS, causing these life-threatening anterior cervical osteophytes is undetermined because of the inability to evaluate for the respective diagnostic criteria. However, these osseous pathologies must be considered as causes of life-threatening dysphagia and aspiration in an elderly person.

Response to combination therapy of interferon alfa-2b plus ribavirin in Hispanics with chronic hepatitis C.

OBJECTIVE: To evaluate the response rate of Hispanics with chronic hepatitis C to combination therapy of interferon alfa-2b plus ribavirin and to assess its adverse events. BACKGROUND: Hepatitis C virus may lead to chronic infection and multiple complications. Response to combination therapy of interferon plus ribavirin has been studied in many populations. African Americans have been found to have a lower response rate than Caucasians. However, little data exist for Hispanics. METHODS: Hispanic patients from Puerto Rico with chronic hepatitis C were eligible for the study between November 1997 and February 2000. The Institutional Review Boards of the participating institutions approved the study. Written informed consents were obtained. Combination therapy was given for 48 weeks and patients were followed for 24 weeks after treatment. Analysis of response to therapy was performed in an intention-to-treat basis. RESULTS: The most frequent adverse event was anemia (89%), associated to ribavirin. Sustained response was 23% for naive patients, 45% for relapsers, and 8% for non-responders to previous interferon monotherapy (p < 0.001). Data to analyze response was not available in 27% of patients. Hispanic patients had a low response rate to combination therapy. CONCLUSIONS: Response rates to combination therapy for Hispanic naive and previously non-responder patients are lower than in other reported populations. This may be due to a high prevalence of genotype 1 in Puerto Rico, which is associated to poor response. The higher response rate of relapsers, similar to those reported previously, was expected since these patients showed a previous response to interferon monotherapy. Ethnic factors may play a role in the response to therapy and should be further studied to determine proper treatment strategies for this population.

Crohn's disease associated to chordoma: a case report.

Crohn's disease is an inflammatory bowel disease characterized by remissions and exacerbations. Immunosuppressants are frequently used to induce and maintain remission in these patients. The use of the immunomodulator azathioprine has been associated to malignancies. Chordomas are rare, locally aggressive tumors arising from remnants of the notochord. A specific trigger for this tumor has not been identified and association to any medication has not been reported. The purpose of this report is to present the first case reported in the literature of Crohn's disease associated to a chordoma. The patient to be presented was on azathioprine therapy, among other medications. A review of literature revealed that Crohn's disease and chordoma have abnormalities in chromosomes 1 and 10. Inflammatory bowel disease and chordoma also have abnormalities in chromosomal regions 1p, 3p, and 7q. Despite these findings, a direct genetic relationship between these diseases is speculative.