Medicine and Health Sciences Commons^™

Upregulation Of Cd36, A Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis By Increasing Mmp28 And Decreasing E-Cadherin Expression, James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva

Surgery Faculty Publications

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation …

Development Of A Novel Mir-3648-Related Gene Signature As A Prognostic Biomarker In Esophageal Adenocarcinoma, Donglei Zhang, Hang Yin, Thomas L. Bauer, Michael P. Rogers, Jeffrey B. Velotta, Clinton T. Morgan, Weijia Du, Ping Xu, Xiaozhe Qian

Surgery Faculty Publications

Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature.

Methods: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression …

Neurotensin Regulates Proliferation And Stem Cell Function In The Small Intestine In A Nutrient-Dependent Manner, Stephanie A. Rock, Kai Jiang, Yuanyuan Wu, Yajuan Liu, Jing Li, Heidi L. Weiss, Chi Wang, Jianhang Jia, Tianyan Gao, B. Mark Evers

Surgery Faculty Publications

BACKGROUND & AIMS: Intestinal stem cells (ISCs) are sensitive to dietary alterations and nutrient availability. Neurotensin (NT), a gut peptide localized predominantly to the small bowel and released by fat ingestion, stimulates the growth of intestinal mucosa under basal conditions and during periods of nutrient deprivation, suggesting a possible role for NT on ISC function.

METHODS: Leucine-rich repeat-containing G-protein coupled receptor 5-Enhanced Green Fluorescent Protein (Lgr5-EGFP) NT wild type (Nt^+/+) and Lgr5-EGFP NT knockout (Nt^-/-) mice were fed ad libitum or fasted for 48 hours. Small intestine tissue and crypts were examined by gene …

Association Between Obesity And Histological Tumor Budding In Patients With Nonmetastatic Colon Cancer, Tong Gan, Kurt B. Schaberg, Daheng He, Akila Mansour, Harit Kapoor, Chi Wang, B. Mark Evers, Therese J. Bocklage

Surgery Faculty Publications

Importance: Obesity is associated with increased risk of colorectal cancer (CRC) and a more aggressive disease course. Tumor budding (TB) is an important prognostic factor for CRC, but its association with obesity is unknown.

Objective: To evaluate the association of TB with obesity and other prognostic factors in colon cancer.

Design, Setting, and Participants: This cohort study involved a histological review of colon cancer specimens obtained during 7 years (January 2008 to December 2015) at the University of Kentucky Medical Center; data analysis was conducted from February 2020 to January 2021. Specimens came from 200 patients with stage I to …

Sudden Cardiac Death: Epidemiology, Pathogenesis And Management, Akshay Kumar, Dor Mordehay Avishay, Calvin Richard Jones, Juber Dastagir Shaikh, Roopvir Kaur, Michael Aljadah, Asim Kichloo, Nimisha Shiwalkar, Suresh Keshavamurthy

Surgery Faculty Publications

Sudden cardiac death (SCD) is an unexpected sudden death due to a heart condition, that occurs within one hour of symptoms onset. SCD is a leading cause of death in western countries, and is responsible for the majority of deaths from cardiovascular disease. Moreover, SCD accounts for mortality in approximately half of all coronary heart disease patients. Nevertheless, the recent advancements made in screening, prevention, treatment, and management of the underlying causes has decreased this number. In this article, we sought to review established and new modes of screening patients at risk for SCD, treatment and prevention of SCD, and …

Management Of The Sensitized Cardiac Transplantation Recipient, Michael Mazzei, Suresh Keshavamurthy, Olga Timofeeva, Yoshiya Toyoda

Surgery Faculty Publications

Preoperative sensitization of the cardiac transplant recipient, defined as the presence of anti-Human Leukocyte Antigen (HLA) antibodies before transplant, represents a significant management challenge for physicians. Sensitization prolongs the pre-transplant wait time and is associated with postoperative transplant complications and death. It is critical that sensitized heart transplant candidates be identified and optimized before surgery. In this review, we describe the risk for sensitization, discuss the means through which sensitization may be diagnosed, and highlight some of the new therapeutic options for managing the sensitized cardiac transplant patients.

Laparoscopic Partial Splenectomy For A Splenic Hamartoma, Vashisht Madabhushi, Timothy Horrell, John M. Draus

Surgery Faculty Publications

Objective

We discuss current knowledge and management of splenic hamartoma, an uncommon form of benign tumor.

Summary background data

A splenic hamartoma is a rare form of benign splenic mass, often found incidentally while working up other complaints, and is typically treated by surgical resection of the mass. In this case, we discuss the management of an incidentally found splenic hamartoma that was treated with laparoscopic partial splenectomy.

Methods

The patient presented in the Emergency Department complaining of periumbilical pain after having been struck in the abdomen with a soccer ball the previous day. Following a physical exam and blood …

Cardioplastic Approach To Omental Flap Coverage For Severe Aortic Root Infections In The Opioid Era, Alisha R. Bonaroti, R. Wesley Edmunds, Ryan C. Decoster, James Y. Liau, Michael E. Sekela, Henry C. Vasconez

Surgery Faculty Publications

Aortic root abscesses are severe sequelae of endocarditis that clinically manifest as life-threatening infection. As the opioid epidemic continues to yield a national crisis, the incidence and severity of this disease process have increased. Reconstruction of the aortic root is a challenging undertaking and carries the risk of recurrent infection. The omentum has an established reputation as a reliable flap in thoracic reconstruction, given its amorphous form and immunogenic properties, but it has not been utilized for aortic root infections. We present a novel indication for the omental flap using a cardioplastic approach in coverage of aortic root reconstruction. Four …

From Leads To Leadless: A Convoluted Journey, Vipin Dulam, Joshua M. Cooper, Chethan Gangireddy, Mohammed A. Kashem, Yoshiya Toyoda, Suresh Keshavamurthy

Surgery Faculty Publications

No abstract provided.

A Rare Case Of Rapidly Enlarging Myelolipoma In Sickle Cell Disease, Paran Davari, Cortney Y. Lee, James T. Lee

Surgery Faculty Publications

Objective
Adrenal myelolipoma (AM) is a benign tumor composed of mature fat cells and hemopoietic elements. Most AMs are incidental findings on imaging and clinically asymptomatic. The purpose of this case report is to describe a rare case of AM and explore its clinical manifestations, imaging features, and treatment.

Methods
In this study, we report a case of a rapidly growing right AM in a patient with uncontrolled hemoglobin sickle cell disease. A 38-year-old male presented to our institution's endocrine surgery clinic for evaluation of an enlarging right adrenal mass. This mass was incidentally found during an abdominal ultrasound performed …

Transfusion Rates In Emergency General Surgery: High But Modifiable, Andrew Medvecz, Andrew C. Bernard, Courtney Hamilton, Kevin M. Schuster, Oscar Guillamondegui, Daniel L. Davenport

Surgery Faculty Publications

Background: Transfusion of red blood cells (RBC) increases morbidity and mortality, and emergency general surgery (EGS) cases have increased risk for transfusion and complication given case complexity and patient acuity. Transfusion reduction strategies and blood-conservation technology have been developed to decrease transfusions. This study explores whether transfusion rates in EGS have decreased as these new strategies have been implemented.

Methods: This is a retrospective review of the American College of Surgeons' National Surgical Quality Improvement Program (ACS NSQIP) data from three academic medical centers. Operations performed by general surgeons on adults (aged ≥18 years) were selected. Data were analyzed from …

Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, …

Impact Of The Affordable Care Act On Colorectal Cancer Screening, Incidence, And Survival In Kentucky, Tong Gan, Heather F. Sinner, Samuel C. Walling, Quan Chen, Bin Huang, Thomas C. Tucker, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Surgery Faculty Publications

Background

Kentucky ranks first in the US in cancer incidence and mortality. Compounded by high poverty levels and a high rate of medically uninsured, cancer rates are even worse in Appalachian Kentucky. Being one of the first states to adopt the Affordable Care Act (ACA) Medicaid expansion, insurance coverage markedly increased for Kentucky residents. The purpose of our study was to determine the impact of Medicaid expansion on colorectal cancer (CRC) screening, diagnosis, and survival in Kentucky.

Study Design

The Kentucky Cabinet for Health and Family Services and the Kentucky Cancer Registry were queried for individuals (≥20 years) undergoing CRC …

P-21 Activated Kinase As A Molecular Target For Chemoprevention In Diabetes, Kyle Dammann, Vineeta Khare, Clyde Coleman, Henrik Berdel, Christoph Gasche

Surgery Faculty Publications

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling. Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here, we performed a mini-meta-analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways, to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using the online …

Improving Follow-Up Skeletal Survey Compliance In Suspected Nonaccidental Trauma Patients: What's The Fuss About?, Tong Gan, John M. Draus Jr.

Surgery Faculty Publications

Introduction: Nonaccidental trauma (NAT) victims account for a significant percentage of our pediatric trauma population. The skeletal survey (SS) and follow-up skeletal survey (FUSS) are essential in the evaluation of selected NAT patients. We identified that our clinically indicated FUSS completion rate was suboptimal. We hypothesized that implementing an intervention of postdischarge follow-up in our pediatric surgery clinic would improve FUSS completion rates. Methods: A follow-up clinic for NAT patients was established in July 2013. A retrospective review was performed of all suspected NAT cases younger than 2 years old seen at Kentucky Children’s Hospital between November 2012 and February …

A Breast Prosthesis Infection Update: Two-Year Incidence, Risk Factors And Management At Single Institution, Ashley Nadia Boustany, Shady Elmaraghi, Nneamaka Agochukwu, Benjamin Cloyd, Adam J. Dugan, Brian Rinker

Surgery Faculty Publications

Background: Infection following augmentation and prosthetic-based breast reconstruction can cause significant physical and psychological distress for patients. It may delay adjuvant therapies and compromise aesthetic outcomes. The aim of this study is to identify modifiable risk factors for infection and identify common bacterial isolates to achieve optimal outcomes for patients.

Methods: A retrospective cohort study was performed for patients undergoing implant-based breast reconstruction over a 2-year period. In each case, we documented demographics, co-morbidities, complications and antibiotic use. We reviewed treatments, infectious species cultured where applicable and all outcomes.

Results: A total of 292 patients met the inclusion criteria. Fifty-five …

Laparoscopic Harvest Of The Rectus Abdominis For Perineal Reconstruction, Nneamaka Agochukwu, Alisha Bonaroti, Sandra Beck, James Liau

Surgery Faculty Publications

The rectus abdominis is a workhorse flap for perineal reconstruction, in particular after abdominoperineal resection (APR). Laparoscopic and robotic techniques for abdominoperineal surgery are becoming more common. The open harvest of the rectus abdominis negates the advantages of these minimally invasive approaches. (Sentence relating to advantages of laparoscopic rectus deleted here.) We present our early experience with laparoscopic harvest of the rectus muscle for perineal reconstruction. Three laparoscopic unilateral rectus abdominis muscle harvests were performed for perineal reconstruction following minimally invasive colorectal and urological procedures. The 2 patients who underwent APR also had planned external perineal skin reconstruction with local …

Report Of The Ishlt Working Group On Primary Lung Graft Dysfunction Part Iii: Mechanisms: A 2016 Consensus Group Statement Of The International Society For Heart And Lung Transplantation, Andrew E. Gelman, Andrew J. Fisher, Howard J. Huang, Maher A. Baz, Ciara M. Shaver, Thomas M. Egan, Micheal S. Mulligan

Surgery Faculty Publications

No abstract provided.

Ovarian Cysts, Vaginal Bleeding And Hypothyroidism In A 4-Year-Old Female With Down Syndrome: A Case Of Van Wyk-Grumbach Syndrome, Suniah S. Ayub, Ana Ruzic, Janice A. Taylor

Surgery Faculty Publications

Van Wyk-Grumbach Syndrome (VWGS) is a constellation of symptoms including precocious puberty without adrenarche, delayed bone age, ovarian cysts, and hypothyroidism. We report here a four-year-old Down Syndrome patient who presented for evaluation of abdominal distension, vaginal bleeding, and bilateral ovarian cysts. Her work-up and management demonstrates the importance of screening for hypothyroidism in Down Syndrome, as well as considering the diagnosis of VWGS when evaluating a patient with precocious puberty and an apparent intra-abdominal surgical process. Given the presence of ovarian masses, a surgical emergency such as ovarian torsion or rupture must be ruled out. Even when the diagnosis …

The Surgical Infection Society Revised Guidelines On The Management Of Intra-Abdominal Infection, John E. Mazuski, Jeffrey M. Tessier, Addison K. May, Robert G. Sawyer, Evan P. Nadler, Matthew R. Rosengart, Phillip K. Chang, Patrick J. O'Neill, Kevin P. Mollen, Jared M. Huston, Jose J. Diaz Jr., Jose M. Prince

Surgery Faculty Publications

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations.

Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published …

Increasing Incidence Within Pubmed Of The Use Of The Misspelling "Pruritis" (Sic) Instead Of "Pruritus" For Itch, Alan B. Fleischer Jr.

Surgery Faculty Publications

Writers generally benefit from word processing technology, and the use of other forms of formal writing such as typewriters is archaic. The first stand-alone spell checker programs originated in the early 1980s, and by 1995 they were embedded within word processing programs such as Word 95 (1). With the ubiquity of such software, spelling errors in the medical literature should be extinct. Yet, as a reader of the medical literature with an interest in itch, this author is impressed with the numbers of misspellings of the word «pruritus.» The word pruritus is derived from the Latin pruritus, past participle …

Targeting Wnt/Β-Catenin Pathway In Hepatocellular Carcinoma Treatment, Valery Vilchez, Lilia M. Turcios, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug …

An Ex Vivo Approach To Complex Renal Artery Aneurysm Repair, Noah T. Scherrer, Roberto Gedaly, Ramakrishna Venkatesh, Michael A. Winkler, Eleftherios S. Xenos

Surgery Faculty Publications

Ex vivo repair technique for a complex renal artery aneurysm may have several advantages. Smaller incision size and use of minimally invasive techniques may decrease incisional morbidity and improve recovery time, especially in patients with a high body mass index. Improved visualization afforded by back-table methods may also be valuable when repair of aneurysms involving multiple branches is necessary. We report of a successful case of laparoscopic nephrectomy, followed by back-table aneurysmorrhaphy and autotransplant, in a patient with a renal artery aneurysm.

When Operating On Dead People Saves Lives: Benefits Of Surgical Organ Donor Intensivists, Kristin Long, Cynthia Talley, Rebecca B. Yarrison, Andrew Bernard

Surgery Faculty Publications

Solid organ transplantation has emerged as a life-saving treatment for many patients suffering from end-stage organ failure. Organs have been successfully recovered after a variety of aggressive interventions. We propose that decompressive laparotomy, when clinically indicated, should be considered in the aggressive resuscitation of potential organ donors. A thorough literature review examining aggressive interventions on potential organ donors was conducted after experience with a unique case at this institution. Articles were reviewed for the types of interventions performed as well as the time frame in relation to organ donation. In our case, several ethical issues were raised when considering decompressive …

Cystic Multiglandular Maternal Hyperparathyroidism Diagnosed By Neonatal Hypocalcemic Seizures, Kristin Long, Tessa Cartwright, David A. Sloan, Cortney Y. Lee

Surgery Faculty Publications

A 7-day-old male infant born to a healthy 33-year-old female at 37 weeks of gestation was brought to the local emergency department (ED) with sudden-onset tonic-clonic seizures. Laboratory testing revealed extreme hypocalcemia (ionized calcium of 3.2 mg/dl) and undetectable parathyroid hormone (PTH/ml). Concomitant evaluation of the mother revealed both elevated ionized calcium (5.9 mg/dl) and PTH (116 pg/ml). The mother underwent preoperative ultrasound localization and sestamibi scan, followed promptly by parathyroidectomy. Given the cystic appearance and presence of multiglandular disease, evaluation for familial cystic parathyroid adenomatosis (hyperparathyroidism-jaw bone-tumor syndrome) and MEN 1 were undertaken. The infant was stabilized and discharged …

Esophageal Fistula Complicating Thyroid Lobectomy, Nicholas D. Ward, Cortney Y. Lee, James T. Lee, David A. Sloan

Surgery Faculty Publications

Thyroidectomy is associated with low morbidity and mortality. Esophageal perforation following thyroidectomy has been reported only three times previously, with subsequent fistulization occurring in two of these cases. The authors present the first such case report in the English-speaking literature.

A New Cecal Slurry Preparation Protocol With Improved Long-Term Reproducibility For Animal Models Of Sepsis, Marlene E. Starr, Allison M. Steele, Mizuki Saito, Bill J. Hacker, B. Mark Evers, Hiroshi Saito

Surgery Faculty Publications

Sepsis, a life-threatening systemic inflammatory response syndrome induced by infection, is widely studied using laboratory animal models. While cecal-ligation and puncture (CLP) is considered the gold standard model for sepsis research, it may not be preferable for experiments comparing animals of different size or under different dietary regimens. By comparing cecum size, shape, and cecal content characteristics in mice under different experimental conditions (aging, diabetes, pancreatitis), we show that cecum variability could be problematic for some CLP experiments. The cecal slurry (CS) injection model, in which the cecal contents of a laboratory animal are injected intraperitoneally to other animals, is …

Wound Healing: Biologics, Skin Substitutes, Biomembranes And Scaffolds, Krishna S. Vyas, Henry C. Vasconez

Surgery Faculty Publications

This review will explore the latest advancements spanning several facets of wound healing, including biologics, skin substitutes, biomembranes and scaffolds.

Thoracoabdominal Aortic Aneurysm Repair: Current Endovascular Perspectives, Nathan Orr, David Minion, Joseph L. Bobadilla

Surgery Faculty Publications

Thoracoabdominal aneurysms account for roughly 3% of identified aneurysms annually in the United States. Advancements in endovascular techniques and devices have broadened their application to these complex surgical problems. This paper will focus on the current state of endovascular thoracoabdominal aneurysm repair, including specific considerations in patient selection, operative planning, and perioperative complications. Both total endovascular and hybrid options will be considered.

Acute Demyelinating Polyneuropathy After Lung Transplantation: Guillain-Barré Syndrome Or Tacrolimus Toxicity?, Nirmal S. Sharma, Keith M. Wille, Charles W. Hoopes, Enrique Diaz-Guzman

Surgery Faculty Publications

Guillain-Barré syndrome (GBS) has been described after solid organ and bone marrow transplantation mostly due to viral infections and possibly calcineurin inhibitors. Incidence after bone marrow transplant is 0.3-0.7%, though incidence in other transplants is not well known. We present the first description of tacrolimus associated GBS in lung transplant recipients in the English language literature. The pathophysiology of tacrolimus-induced polyneuropathy is not known, but some have hypothesized that tacrolimus induces an inflammatory phenomenon by differential effects on T cell subsets. Diagnosis of association may be challenging and requires high index of suspicion. The optimal treatment of GBS-associated with tacrolimus …