Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45873/1/268_2006_Article_154.pd

The Pros and Cons of Prophylactic Central Compartment Lymph Node Dissection for Papillary Thyroid Carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78140/1/thy.2009.1578.pd

Gardner's syndrome in a 40-year-old woman: successful treatment of locally aggressive desmoid tumors with cytotoxic chemotherapy

BACKGROUND: Desmoid tumors that present as a part of Gardener's syndrome can present very difficult management problems. CASE PRESETATION: We report a case of intra-abdominal desmoid tumor causing distal small bowel obstruction that complicated the management of a more proximal enterocutaneous fistula from the jejunum. After failure of more conventional management options including imatinib, the patient's disease responded to doxorubicin and ifosfamide. The response resolved the bowel obstruction and allowed small intestinal resection to resolve the enterocutaneous fistula. CONCLUSION: Systemic cytotoxic therapy with doxorubicin and ifosfamide can be useful for patients with complications from intra-abdominal desmoid tumor

Differentiation of Human Embryonic Stem Cells to a Parathyroid-Like Phenotype

Iatrogenic hypoparathyroidism is the most common complication of cervical endocrine surgery. Current management is limited and palliative. As the molecular steps in parathyroid development have been defined, they may be replicable in vitro, with a goal of cellular replacement therapy. Human embryonic stem cell (hESC) lines were investigated as a model for parathyroid regeneration in vitro. BG01 was selected as a model based on expression of genes of interest in embryoid bodies (EBs). Established strategies for mouse embryonic stem cell differentiation into definitive endoderm were modified and extended to maximize the expression of definitive markers of parathyroid development. The optimal approach included the use of Activin A at 100 ng/mL with BG01 cells grown on murine embryonic fibroblasts for 5 days under conditions of increasing serum concentration. After 5 days, the cells were allowed to mature further in tissue culture without murine fibroblasts but with continuous Activin A. Our strategy produced differentiated cell cultures that expressed intermediate markers of endoderm and parathyroid development (CXCR4, EYA1, Six1, and Pax1), as well as markers of committed parathyroid precursors or developed parathyroid glands (glial cell missing-2 [Gcm2], CCL21, calcium sensing receptor [CaSR], and parathyroid hormone [PTH]). We further characterized the cells by testing conditioned medium from various time points in our differentiation scheme for the presence of PTH. We found that by keeping the cells in culture 2 weeks after the withdrawal of Activin A, the cells were able to produce PTH. Further in vivo work will be needed to demonstrate proper functionality of the cells developed in this way.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78132/1/scd.2008.0337.pd

Directed Trans-Differentiation of Thymus Cells into Parathyroid-Like Cells Without Genetic Manipulation

Replacement of a diseased organ with an autologously derived tissue is an ideal therapy for some medical problems. However, it is difficult to recreate many adult human tissues in vitro due to the functionally necessary architecture of most organs and the lack of understanding of methods to direct the development of the organ of interest. The parathyroid gland is ideal for in vitro organ development because this gland is relatively simple, is transplantable, and is commonly affected by a surgical complication rather than an autoimmune disease. We have investigated thymus as a source of autologous endoderm and parathyroid-like precursor cells. Human thymus cells were treated with a differentiation protocol we developed with human embryonic stem cells (The Bingham Protocol) that utilizes timed exposures to Activin A and soluble Sonic hedgehog (Shh). We incrementally changed the protocol to optimize the differentiation of the thymus cells into parathyroid-like cells. The final protocol used 50-ng/mL Activin A and 100-ng/mL Shh over 13 weeks. The differentiated cells expressed the parathyroid markers parathyroid hormone (PTH), calcium sensing receptor, chemokine receptor type-4 (CXCR4), and chorian-specific transcription factor (GCM2) as measured by reverse transcription-polymerase chain reaction and PTH enzyme-linked immunosorbent assay. Cultured thymus cells without Activin A or Shh exposure did not secrete PTH nor express similar markers. The differentiated cells released PTH, which was suppressed in response to increased calcium concentration. The chemically differentiated cells did not form tumors in immune-compromised mice. Our protocol recreated cells with markers of parathyroid tissue that responded as parathyroid cells to physiologic stimuli. This approach is a further step toward a strategy to restore parathyroid function using autologous cells that were directed to differentiate by nongenetic in vitro manipulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90464/1/ten-2Etec-2E2011-2E0170.pd

Communication skills training in undergraduate medicine.

Good communication with patients is now recognised as the cornerstone in effective medical practice. Medical students do not automatically acquire the art of good communication through clinical training. A new course to promote the development of communication skills at undergraduate level is described. The course was provided at the juncture between pre-clinical and clinical training. Course evaluation illustrated the value of the course as perceived by students themselves and highlighted the areas of greatest need for students in communication skills training

Localization of IFN-γ-Activated Stat1 and IFN Regulatory Factors 1 and 2 in Breast Cancer Cells

The aim of the present work was to evaluate the induction and localization of Stat1, interferon (IFN) regulatory factor-1 (IRF-1), and IRF-2 after IFN-γ exposure of human breast cancer cell lines, SKBR3, MDA468, MCF7, and BT20. Results from growth assays, Western staining, electrophoretic mobility shift assay (EMSA), and immunohistochemical staining were collated to test our hypothesis that immunohistochemical analysis of Stat1, IRF-1, and IRF-2 would provide additional information about the functionality of the IFN-γ signaling pathway in human tumor lines. EMSA results showed that in each of four cell lines, Stat1 expression was increased and demonstrated functional activity after IFN-γ stimulation. Western and EMSA analysis showed upregulation of IRF-1 but not IRF-2 in each cell line. Confocal microscopy of cells stained for Stat1, IRF-1, and IRF-2 confirmed the results and also provided novel information about the intracellular localization of proteins and intercellular variations in responses. The proportion of cells with IRF-1 stimulation and translocation was positively correlated with the IFN-γ growth suppression in vitro. In conclusion, using four independent assays, we have demonstrated that heterogeneity in IFN-γ-mediated upregulation of signal transduction proteins can be detected in vitro and that these differences can explain distinct cellular growth effects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63148/1/107999003322558755.pd

Communication skills training in undergraduate medicine: attitudes and attitude change.

The importance of communication skills training in undergraduate medical education is now widely accepted. However little is known about student attitudes towards their own communication skills and whether their attitudes changes as a result of participating in communication skills courses. The aim of the present study was to identify these attitudes prior to commencing such a course and to further evaluate changes in these attitudes on completion of the course. Results demonstrated an improvement in perceived confidence regarding a number of specific communication skills. The study provides further evidence of the value of such courses in undergraduate medical training

The Most Commonly Occurring Papillary Thyroid Cancer in the United States Is Now a Microcarcinoma in a Patient Older than 45 Years

Background: The incidence of papillary thyroid cancer (PTC) is growing at a faster rate than any other malignancy. However, it is unknown what effect age is having on the changing PTC incidence rates. With the goal of understanding the role of age in thyroid cancer incidence, this study analyzes the changing demographics of patients with PTC over the past three decades. Methods: This was a retrospective evaluation of the incidence rates of PTC from 1973 to 2006 reported by the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Results: From 1973-2006 the age group most commonly found to have PTC has shifted from patients in their 30s to patients in the 40-50-year-old age group. In 1973 60% of PTC cases were found in patients younger than 45, and the majority of cases continued to occur in younger patients until 1999. After 1999 PTC became more common in patients older than 45 years, and in 2006, 61% of PTC cases were in patients older than 45 years. From 1988 to 2003 there has been an increasing incidence of all sizes of PTC in all age groups with the largest increase in tumors <1-cm in patients older than 45. Forty-three percent of tumors in patients older than 45 are now <1-cm, whereas only 34% are <1-cm in patients younger than 45. Of the nearly 20,000 thyroid cancer cases in 2003, 24% were microcarcinomas in patients over the age of 45. Conclusions: The incidence of PTC is increasing disproportionally in patients older than 45 years. The number of PTC tumors smaller than 1-cm is increasing in all age groups, and now the most commonly found PTC tumor in the United States is a microcarcinoma in a patient older than 45 years. These changing patterns relating age and incidence have important prognostic and treatment implications for patients with PTC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90466/1/thy-2E2010-2E0137.pd

Multiple Endocrine Neoplasia Type 1 Parathyroid Adenoma Development over Time

Multiple gland parathyroid disease is one of the hallmarks of multiple endocrine neoplasia (MEN) type 1. Often mislabeled parathyroid hyperplasia, the process is actually the development of multiple adenomas. Some clinicians have reported results of selective parathyroidectomy in this group, removing only grossly enlarged glands. We argue that all the glands are at risk and should be addressed at any planned parathyroid intervention. Our hypothesis is that, given sufficient time, patients would all develop adenomas in each of the parathyroid glands. Our available data to address this issue are the parathyroidectomy results from a single institution series. Patients who had initial parathyroid exploration for hyperparathyroidism in the setting of MEN-1 were reviewed. This study includes those patients who had the weights of the resected glands documented; 23 men and 21 women met the criteria. The total weight of the parathyroid glands did not vary with the age of the patient at operation. However, the number of normal glands identified did vary significantly with age ( p < 0.02), with older patients being less likely to have any normal parathyroid glands. Although total parathyroid weight may correlate with development of hypercalcemia and indications for operation, the involvement of multiple parathyroid glands in MEN-1 is a function of time, as independent events in each gland must occur. Given time, MEN-1 patients all develop multiple gland disease, and this reality must be used in planning operative management for patients with this syndrome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41299/1/268_2004_Article_7560.pd