Papers by Dakota Thompson
Journal of Laparoendoscopic & Advanced Surgical Techniques, 2021
Restorative proctocolectomy (RPC) with ileal pouch anal-anastomosis (IPAA) is commonly performed ... more Restorative proctocolectomy (RPC) with ileal pouch anal-anastomosis (IPAA) is commonly performed for patients with ulcerative colitis, familial adenomatous polyposis, and selected phenotypes of Crohn's disease (CD). Due to concerns about the effects of surgical complications on pouch functional outcomes, debate remains surrounding when and whether RPC with IPAA should be performed in a staged manner. Particularly debated are the timings of the IPAA, whether it is constructed at time of the proctocolectomy and whether to utilize temporary fecal diversion with a loop ileostomy. RPC with IPAA can be performed in one, two, or three stages, with each stage typically separated by 3-6 months. Proponents of a staged approach argue that poor pouch function, which is often a result of IPAA complications, including leak and infection, can be difficult to overcome and mandate additional, major surgeries, and that staging pouch creation and pairing with a protective ileostomy reduce those complications. However, subjecting patients to multiple surgeries and prolonging their time with an ileostomy present unique risks as well. Surgeons' experience and preference and patient characteristics need to be considered when determining operative planning. Highly selected patients with CD can be considered for RPC with IPAA, although with an acknowledgment of inherently higher pouch failure rates. Understanding the short- and long-term consequences of RPC with IPAA construction can help surgeons determine the appropriate approach.
International Journal of Surgery Case Reports, 2022
Gastroenterology clinics of North America, 2021
Intra-abdominal and anorectal abscesses are common pathologies seen in both inpatient and outpati... more Intra-abdominal and anorectal abscesses are common pathologies seen in both inpatient and outpatient settings. To decrease morbidity and mortality, early diagnosis and treatment are essential. After adequate drainage via a percutaneous or incisional approach, patients need to be monitored for worsening symptoms or recurrence and evaluated for the underlying condition that may have contributed to abscess formation.
Summary Mammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (... more Summary Mammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2γ transcription factor, encoded by Tfap2c, has a central role in mammary gland development but its effect in mammary lineages and specifically MaSCs is largely unknown. Here, we utilized an inducible, conditional knockout of Tfap2c to elucidate the role of AP-2γ in maintenance and differentiation of MaSCs. Loss of AP-2γ in the basal epithelium profoundly altered the transcriptomes and decreased the number of cells within several clusters of mammary epithelial cells, including adult MaSCs and luminal progenitors. AP-2γ regulated the expression of genes known to be required for mammary development, including Cebpb, Nfkbia, and Rspo1. As a result, AP-2γ-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2γ can regulate development of mammary gland structur...
Molecular Cancer Research, 2021
Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influen... more Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer. CRISPR-Cas9 and short hairpin RNA were used to eliminate TFAP2A expression in HCT116 and a panel of colon cancer cell lines. AP-2α target genes were identified with RNA sequencing and chromatin immunoprecipitation sequencing. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts, and phosphorylated histone H3 (PHH3). Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2–M and decreased phosphorylation of AKT, effects that were mediated through regulation...
Cancer Research, 2021
In melanoma metastasis, the role of the AP-2α transcription factor, which is encoded by TFAP2A, i... more In melanoma metastasis, the role of the AP-2α transcription factor, which is encoded by TFAP2A, is controversial as some findings have suggested tumor suppressor activity while other studies have shown high TFAP2A expression in node-positive melanoma associated with poor prognosis. Here we demonstrate that AP-2α facilitates melanoma metastasis through transcriptional activation of genes within the E2F pathway including EZH2. A BioID screen found that AP-2α interacts with members of the nucleosome remodeling and deacetylase (NuRD) complex. Loss of AP-2α removed activating chromatin marks in the promoters of EZH2 and other E2F target genes through activation of the NuRD repression complex. In melanoma cells, treatment with tazemetostat, an FDA-approved and highly specific EZH2 inhibitor, substantially reduced anchorage-independent colony formation and demonstrated heritable antimetastatic effects, which were dependent on AP-2α. Single-cell RNA sequencing analysis of a metastatic melan...
Journal of the American College of Surgeons, 2020
Journal of Surgical Oncology, 2020
Mutation of the KRAS oncogene (mKRAS) in colorectal cancer has been associated with aggressive tu... more Mutation of the KRAS oncogene (mKRAS) in colorectal cancer has been associated with aggressive tumor biology, resistance to epidermal growth factor inhibitors, and decreased overall survival (OS). The aim of the current study was to analyze the association of mKRAS with pathologic complete response (pCR) and neoadjuvant rectal (NAR) score, and its impact on the survival of patients with locally advanced rectal cancer who were managed with multimodality therapy.
SUMMARYMammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (M... more SUMMARYMammary gland ductal morphogenesis depends on the differentiation of mammary stem cells (MaSCs) into basal and luminal lineages. The AP-2γ transcription factor, encoded by Tfap2c, has a central role in mammary gland development but its effect in mammary lineages and specifically MaSCs is largely unknown. Herein, we utilized an inducible, conditional knockout of Tfap2c to elucidate the role of AP-2γ in maintenance and differentiation of MaSCs. Loss of AP-2γ in the basal epithelium profoundly altered the transcriptomes and decreased the number of cells within several clusters of mammary epithelial cells, including adult MaSCs and luminal progenitors.AP-2γ regulated the expression of genes known to be required for mammary development including C/EBPβ, IκBα, and Rspo1. As a result, AP-2γ-deficient mice exhibited repressed mammary gland ductal outgrowth and inhibition of regenerative capacity. The findings demonstrate that AP-2γ is required for maintenance of pluripotent MaSCs and...
Mini-invasive Surgery, 2020
The current obesity pandemic has a clear impact on quality of life and health resource utilizatio... more The current obesity pandemic has a clear impact on quality of life and health resource utilization; hence it has become a significant global health concern. Multiple obesity-related comorbidities such as gastroesophageal reflux disease (GERD) are frequently observed among this patient population. GERD is a complex disease with multiple elements contributing to the failure of the anti-reflux barrier. If left untreated, the excessive reflux of gastric contents into the esophagus can give rise to multiple complications such as esophagitis, strictures, metaplasia, and cancer. When surgical treatment of GERD is indicated in an obese patient, adequate preoperative evaluation and treatment are critical to achieve durable resolution of symptoms attributed to GERD as well as other obesity related comorbidities. To maximize the potential for a positive outcome, when suitable, gastric bypass surgery rather than sleeve gastrectomy or fundoplication should be strongly considered in the obese patient with GERD.
Mini-invasive Surgery , 2020
The current obesity pandemic has a clear impact on quality of life and health resource utilizatio... more The current obesity pandemic has a clear impact on quality of life and health resource utilization; hence it has become a significant global health concern. Multiple obesity-related comorbidities such as gastroesophageal reflux disease (GERD) are frequently observed among this patient population. GERD is a complex disease with multiple elements contributing to the failure of the anti-reflux barrier. If left untreated, the excessive reflux of gastric contents into the esophagus can give rise to multiple complications such as esophagitis, strictures, metaplasia, and cancer. When surgical treatment of GERD is indicated in an obese patient, adequate preoperative evaluation and treatment are critical to achieve durable resolution of symptoms attributed to GERD as well as other obesity related comorbidities. To maximize the potential for a positive outcome, when suitable, gastric bypass surgery rather than sleeve gastrectomy or fundoplication should be strongly considered in the obese patient with GERD.
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Papers by Dakota Thompson