Gastroenterology Commons^™

Reduction In Racial And Ethnic Disparity In Survival Following Liver Transplant For Hepatocellular Carcinoma In The Direct-Acting Antiviral Era, Anjiya Shaikh, Karthik Goli, Tzu-Hao Lee, Nicole E Rich, Jihane N Benhammou, Stephanie Keeling, Donghee Kim, Aijaz Ahmed, John Goss, Abbas Rana, Amit G Singal, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC.

METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, …

Transcriptional Profiling And Consensus Molecular Subtype Assignment To Understand Response And Resistance To Anti-Epidermal Growth Factor Receptor Therapy In Colorectal Cancer, Saikat Chowdhury, Ria Gupta, Joshua Millstein, Kangyu Lin, Valsala Haridas, Mohammad A Zeineddine, Christine Parseghian, Heinz-Josef Lenz, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

PURPOSE: Activating mutations in KRAS, NRAS, and BRAF are known to cause resistance to anti–epidermal growth factor receptor (EGFR) therapy; however, only approximately 40% of patients with colorectal cancer (CRC) with RASWT tumors respond to anti-EGFR treatment. We sought to discover novel biomarkers to predict response to anti-EGFR antibody treatment in CRC and to understand mechanisms of resistance to anti-EGFR therapy.

MATERIALS AND METHODS: Transcriptomic profiles from three clinical and two preclinical cohorts treated with cetuximab were used to assign consensus molecular subtypes (CMS) to each sample and correlated with outcomes.

RESULTS: Restricting to RASWT patients, …

Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy Via Inhibition Of Proliferative Signaling Pathways, Haizhou Liu, Hui Liu, Zhiyi Zhou, Jessica Chung, Guojing Zhang, Jin Chang, Robert A Parise, Edward Chu, John C Schmitz

Abington Jefferson Health Papers

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and …

Comparative Analyses Of The Clinicopathologic Features Of Short-Term And Long-Term Survivors Of Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy And Pancreatoduodenectomy, Tom Z Liang, Matthew H G Katz, Laura R Prakash, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D Tzeng, Naruhiko Ikoma, Robert A Wolff, Dan Zhao, Eugene J Koay, Anirban Maitra, Suprateek Kundu, Huamin Wang

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15-60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated …

Colon Cancer Screening And The Association With Colon Cancer Incidence And Mortality Rates In Ethnic Minority Groups, Jovonne Smith

Student Scholar Showcase

Colorectal cancer (CRC) continues to be a public health burden and is the second leading cause of American cancer deaths. Strides have been made in the medical community, and there has been an overall decrease in CRC rates. This decrease is primarily due to a cumulative decline in late-onset colorectal cancer diagnosis (LOCRC), defined as CRC cancer in adults over the age of 50 years. CRC continues to burden American Indians and Alaska Natives (AIAN) and Non-Hispanic Black individuals (NHB) disproportionately. The incidence and mortality rates remain disproportionately higher than other ethnic groups, and the survival rate is lower than …

Multivisceral Transplant Prognosis And Complications In Patients With Metastatic Neuroendocrine Tumor, Austin Mueller, Syed-Mohammed Jafri

Medical Student Research Symposium

Neuroendocrine tumors (NETs) are a rare subset of cancers that most commonly arise in the gastrointestinal tract, but can also arise in the pancreas, lungs, ovaries, thyroid, pituitary gland, and adrenal gland. When patients present with metastatic NETs, physicians have a variety of therapeutic options. Considering these options, transplant specialists are often involved due to the profound therapeutic effects of multi-organ transplantation. However, little information is available on prognosis/complications for patients that receive multi-organ transplants due to severe metastatic NETs.

With the incidence of NETs in the United States trending in an upward direction, researchers and physicians must understand the …

Fine Needle Aspiration Of Pancreatic Lesions Focusing On Secondary Tumors With Emphasis Of Metastatic Breast Cancer: A Clinicopathological Study With Follow-Up, Maria Yanqing Chen, Neda Zarrin-Khameh, Ya Xu

Faculty, Staff and Students Publications

BACKGROUND: The data on metastatic tumors to the pancreas diagnosed by fine needle aspiration (FNA) biopsy is limited. We report our experience of FNA of primary and secondary pancreatic tumors emphasizing metastatic breast cancer in the pancreas.

METHOD: Total 274 cases of pancreatic FNA in 10 years were retrospectively reviewed. Literature review of metastatic breast cancers to the pancreas was performed.

RESULTS: Out of the 274 cases, 7 (7/274, 2.6%) cases were non-diagnostic, 46 (46/274, 16.8%) cases were negative for malignancy, and 40 (40/274, 14.6%) cases were under the category of atypical cells. There were 133 (133/274, 48.5%) cases diagnosed …

Delphi Initiative For Early-Onset Colorectal Cancer (Direct) International Management Guidelines, Giulia Martina Cavestro, Alessandro Mannucci, Francesc Balaguer, Heather Hampel, Sonia S Kupfer, Alessandro Repici, Andrea Sartore-Bianchi, Toni T Seppälä, Vincenzo Valentini, Clement Richard Boland, Randall E Brand, Tineke E Buffart, Carol A Burke, Riccardo Caccialanza, Renato Cannizzaro, Stefano Cascinu, Andrea Cercek, Emma J Crosbie, Silvio Danese, Evelien Dekker, Maria Daca-Alvarez, Francesco Deni, Mev Dominguez-Valentin, Cathy Eng, Ajay Goel, Josè G Guillem, Britt B S L Houwen, Charles Kahi, Matthew F Kalady, Fay Kastrinos, Florian Kühn, Luigi Laghi, Andrew Latchford, David Liska, Patrick Lynch, Alberto Malesci, Gianluca Mauri, Elisa Meldolesi, Pål Møller, Kevin J Monahan, Gabriela Möslein, Caitlin C Murphy, Karlijn Nass, Kimmie Ng, Cristina Oliani, Enrico Papaleo, Swati G Patel, Marta Puzzono, Andrea Remo, Luigi Ricciardiello, Carla Ida Ripamonti, Salvatore Siena, Satish K Singh, Zsofia K Stadler, Peter P Stanich, Sapna Syngal, Stefano Turi, Emanuele Damiano Urso, Laura Valle, Valeria Stella Vanni, Eduardo Vilar, Marco Vitellaro, Yi-Qian Nancy You, Matthew B Yurgelun, Raffaella Alessia Zuppardo, Elena M Stoffel, Associazione Italiana Familiarità Ereditarietà Tumori, Collaborative Group Of The Americas On Inherited Gastrointestinal Cancer, European Hereditary Tumour Group, And The International Society For Gastrointestinal Hereditary Tumours

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.

METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%.

RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that …

"Keep Your Chin Up, And Keep Eating": Perceptions Of Barriers And Facilitators To Healthful Dietary Behaviors Among Individuals With Gastrointestinal Cancer And Caregivers, Brandy-Joe Milliron, Cynthia Klobodu, Jonathan Deutsch, Karon Martyn, Dan Dychtwald, Emily Riahi, Shawn Carro, Taylor Hisek, Natalie Darcy, Ann C. Klassen

Kimmel Cancer Center Faculty Papers

BACKGROUND: This study explored perceptions of barriers and facilitators to healthful dietary behaviors among patients with gastrointestinal (GI) cancer and their caregivers, including caregiver preparedness, patient and caregiver self-efficacy for symptom management, and other environmental, social, and familial factors that may serve as barriers and facilitators to healthful eating.

METHODS: Using a concurrent mixed methods cross-sectional study design, individuals with GI cancer receiving outpatient chemotherapy and their caregivers completed surveys, dietary assessments, and interviews. Caregiving preparedness, self-efficacy for symptom management, and dietary intake were assessed using validated instruments. Dietary quality was measured using the Healthy Eating Index (HEI)-2020. In-depth interviews …

Targeted Exome-Based Predictors Of Patterns Of Progression Of Colorectal Liver Metastasis After Percutaneous Thermal Ablation, Iwan Paolucci, Yuan-Mao Lin, Yoshikuni Kawaguchi, Harufumi Maki, A Kyle Jones, Marco Calandri, Scott Kopetz, Timothy E Newhook, Kristy K Brock, Jean-Nicolas Vauthey, Bruno C Odisio

Faculty, Staff and Student Publications

BACKGROUND: Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood.

METHODS: In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM.

RESULTS: A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway …

Comparative Effectiveness Of Surveillance Colonoscopy Intervals On Colorectal Cancer Outcomes In A National Cohort Of Patients With Inflammatory Bowel Disease, Hyun-Seok Kim, Ruben Hernaez, Shubhada Sansgiry, Akbar K Waljee, Frank I Scott, James D Lewis, Hashem B El-Serag, Jason K Hou

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Surveillance colonoscopy is recommended to reduce colorectal cancer (CRC)-related morbidity and mortality in patients with inflammatory bowel disease (IBD). The comparative effectiveness of varying colonoscopy intervals on CRC outcomes among patients with IBD is unknown.

METHODS: We performed a retrospective cohort study of patients with confirmed CRC within a cohort of 77,824 patients with IBD during 2000 to 2015 in the National Veterans Health Administration. We examined the association between colonoscopy surveillance intervals on CRC stage, treatment, or all-cause and cancer-specific mortality. The interval of colonoscopy prior to CRC diagnosis was categorized as those performed within <1 >year, …

Seeing The Big Picture: System Architecture Trends In Endoscopy And Led-Based Hyperspectral Subsystem Intergration, Craig M. Browning

Graduate Theses and Dissertations (2019 - present)

Early-stage colorectal lesions remain difficult to detect. Early development of neoplasia tends to be small (less than 10 mm) and flat and difficult to distinguish from surrounding mucosa. Additionally, optical diagnosis of neoplasia as benign or malignant is problematic. Low rates of detection of these lesions allow for continued growth in the colorectum and increased risk of cancer formation. Therefore, it is crucial to detect neoplasia and other non-neoplastic lesions to determine risk and guide future treatment. Technology for detection needs to enhance contrast of subtle tissue differences in the colorectum and track multiple biomarkers simultaneously. This work implements one …

Neoadjuvant Chemotherapy Is Associated With Altered Immune Cell Infiltration And An Anti-Tumorigenic Microenvironment In Resected Pancreatic Cancer, Andressa Dias Costa, Sara A Väyrynen, Akhil Chawla, Jinming Zhang, Juha P Väyrynen, Mai Chan Lau, Hannah L Williams, Chen Yuan, Vicente Morales-Oyarvide, Dalia Elganainy, Harshabad Singh, James M Cleary, Kimberly Perez, Kimmie Ng, William Freed-Pastor, Joseph D Mancias, Stephanie K Dougan, Jiping Wang, Douglas A Rubinson, Richard F Dunne, Margaret M Kozak, Lauren Brais, Emma Reilly, Thomas Clancy, David C Linehan, Daniel T Chang, Aram F Hezel, Albert C Koong, Andrew J Aguirre, Brian M Wolpin, Jonathan A Nowak

Faculty, Staff and Student Publications

PURPOSE: Neoadjuvant chemotherapy is increasingly administered to patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC), yet its impact on the tumor immune microenvironment is incompletely understood.

DESIGN: We employed quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institution cohort of up-front resected primary tumors (n = 299) and in a comparative set of resected tumors after FOLFIRINOX-based neoadjuvant therapy (n = 36) or up-front surgery (n = 30). Multivariable-adjusted Cox proportional hazards models were used to evaluate associations between the immune microenvironment and patient …

Metabolic Targeting Of Nrf2 Potentiates The Efficacy Of The Trap1 Inhibitor G-Tpp Through Reduction Of Ros Detoxification In Colorectal Cancer, Hong-Yuan Tsai, Mary P Bronner, Jordon K March, John F Valentine, Noah F Shroyer, Lisa A Lai, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between …

International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lag-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah

Faculty, Staff and Student Publications

BACKGROUND: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG.

METHODS: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient …

A Cop1-Gata2 Axis Suppresses Ar Signaling And Prostate Cancer, Tao Shen, Bingning Dong, Yanling Meng, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Androgen receptor (AR) signaling is crucial for driving prostate cancer (PCa), the most diagnosed and the second leading cause of death in male patients with cancer in the United States. Androgen deprivation therapy is initially effective in most instances of AR-positive advanced or metastatic PCa. However, patients inevitably develop lethal castration-resistant PCa (CRPC), which is also resistant to the next-generation AR signaling inhibitors. Most CRPCs maintain AR expression, and blocking AR signaling remains a main therapeutic approach. GATA2 is a pioneer transcription factor emerging as a key therapeutic target for PCa because it promotes AR expression and activation. While directly …

Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg

Dissertations and Theses (Open Access)

Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …

Depletion Of Transmembrane Mucin 4 (Muc4) Alters Intestinal Homeostasis In A Genetically Engineered Mouse Model Of Colorectal Cancer, Ramesh Pothuraju, Priya Pai, Sanjib Chaudhary, Jawed A Siddiqui, Jesse L Cox, Sukhwinder Kaur, Satyanarayana Rachagani, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

Mucins are components of the mucus layer overlying the intestinal epithelial cells, which maintains physiological homeostasis. Altered mucin expression is associated with disease progression. Expression of MUC4 decreases in colorectal cancer (CRC); however, its functional role and implications in the intestinal pathology in CRC are not studied well. Therefore, we generated a genetically engineered Muc4 knockout (Muc4-/-) CRC mouse model by crossing with Muc4-/- and Apc^flox/flox mice in the presence of colon-specific inducible Cre. We observed that deficiency of Muc4 results in an increased number of macroscopic tumors in the colon and rectal region and leads to poor survival. …

Predicted Vitamin D Status And Colorectal Cancer Incidence In The Black Women's Health Study, Lauren E Barber, Kimberly A Bertrand, Jessica L Petrick, Hanna Gerlovin, Laura F White, Lucile L Adams-Campbell, Lynn Rosenberg, Hemant K Roy, Julie R Palmer

Faculty, Staff and Students Publications

BACKGROUND: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations.

METHODS: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of …

The Sulfur Microbial Diet Is Associated With Increased Risk Of Early-Onset Colorectal Cancer Precursors, Long H. Nguyen, Yin Cao, Jinhee Hur, Raaj S. Mehta, Daniel R. Sikavi, Yiqing Wang, Wenjie Ma, Kana Wu, Mingyang Song, Edward L. Giovannucci, Eric B. Rimm, Walter C. Willett, Wendy S. Garrett, Jacques Izard, Curtis Huttenhower, Andrew T. Chan

Food for Health: Publications

Background and aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H₂S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking.

Methods: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses’ Health Study II …

A Rare Complication In A Covid-19 Positive Patient With Sigmoid Colon Cancer-Hemoperitoneum Due To Gallbladder Necrosis Following Micro-Thrombosis, Mihai Faur, Andrei Moisin, Calin Mohor, Dan Sabau

Journal of Mind and Medical Sciences

Covid-19, also known as acute respiratory syndrome 2019-nCoV, severe acute respiratory syndrome (SARS) 2, and Wuhan pneumonia, is a viral respiratory disease caused by a SARS-associated coronavirus (SARS-CoV-2). The most serious complications of Covid-19 are due to the development of micro-thrombosis in various organs and systems as a result of the high levels of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin 1 and 6) which initiate the activation of coagulation and the generation of thrombin. Several studies demonstrated the poor outcome of Covid-19-infected patients who underwent surgery, suggesting that surgery may accelerate and exacerbate Covid-19 progression. We report the case …

Intestinal Dysbiosis – A New Treatment Target In The Prevention Of Colorectal Cancer, Florinela-Andrada Dumitru, Sergiu Ioan Micu, Roxana Emanuela Popoiag, Marilena Musat, Andreea Daniela Caloian, Valentin Calu, Vlad Denis Constantin, Daniela Gabriela Balan, Cornelia Nitipir, Florin Enache

Journal of Mind and Medical Sciences

The gastrointestinal microbiome contains at least 100 trillion microorganisms (bacteria, viruses, fungi), whose distribution varies from the mouth to the rectum spatially and temporally throughout one's lifetime. The microbiome benefits from advancing research due to its major role in human health. Studies indicate that its functions are immunity, metabolic processes and mucosal barrier. The disturbances of these functions, dysbiosis, influence physiology, lead to diabetes, inflammatory bowel disease, obesity and colon tumorigenesis. The third most common form of cancer, colorectal cancer, is the result of many factors and genes, and although the link between dysbiosis and this type of cancer is …

How Opportune Is Multigene Testing In Metastatic Colorectal Cancer? A Review, Cristina Orlov-Slavu, Andreea Parosanu, Mihaela Olaru, Dragos Serban, Ioana Paunica, Cornelia Nitipir

Journal of Mind and Medical Sciences

Personalized treatment in oncology is the most innovative method of care. The best method to establish personalized treatment is by genetic characterization of the malignant cell.

Theoretically, the more detailed the characterization, the more effective the choice of treatment becomes. Currently, there are fast and relatively low-cost options that allow such genetic characterization. However, test results sometimes do not detect targetable alterations and, even if they do detect, the use of the treatment-alteration combination does not always generate a satisfactory oncological response.

The present paper aims to answer two questions. First, how targetable can the most common gene alterations in …

Patient-Reported Barriers Are Associated With Receipt Of Hepatocellular Carcinoma Surveillance In A Multicenter Cohort Of Patients With Cirrhosis, Amit G Singal, Jasmin A Tiro, Caitlin C Murphy, James-Michael Blackwell, Jennifer R Kramer, Aisha Khan, Yan Liu, Song Zhang, Jessica L Phillips, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt.

METHODS: We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration.

RESULTS: Of 2871 patients …

Automated Software-Assisted Diagnosis Of Esophageal Squamous Cell Neoplasia Using High-Resolution Microendoscopy, Mimi C Tan, Sheena Bhushan, Timothy Quang, Richard Schwarz, Kalpesh H Patel, Xinying Yu, Zhengqi Li, Guiqi Wang, Fan Zhang, Xueshan Wang, Hong Xu, Rebecca R Richards-Kortum, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm.

METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) …

Mapk4 Promotes Prostate Cancer By Concerted Activation Of Androgen Receptor And Akt, Tao Shen, Wei Wang, Wolong Zhou, Ilsa Coleman, Qinbo Cai, Bingning Dong, Michael M Ittmann, Chad J Creighton, Yingnan Bian, Yanling Meng, David R Rowley, Peter S Nelson, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Prostate cancer (PCa) is the second leading cause of cancer death in American men. Androgen receptor (AR) signaling is essential for PCa cell growth/survival and remains a key therapeutic target for lethal castration-resistant PCa (CRPC). GATA2 is a pioneer transcription factor crucial for inducing AR expression/activation. We recently reported that MAPK4, an atypical MAPK, promotes tumor progression via noncanonical activation of AKT. Here, we demonstrated that MAPK4 activated AR by enhancing GATA2 transcriptional expression and stabilizing GATA2 protein through repression of GATA2 ubiquitination/degradation. MAPK4 expression correlated with AR activation in human CRPC. Concerted activation of both GATA2/AR and AKT by …

Comparisons Of Oral, Intestinal, And Pancreatic Bacterial Microbiomes In Patients With Pancreatic Cancer And Other Gastrointestinal Diseases, Mei Chung, Naisi Zhao, Richard Meier, Devin C. Koestler, Guojun Wu, Erika De Castillo, Bruce J. Paster, Kevin Charpentier, Jacques Izard, Karl T. Kelsey, Dominique S. Michaud

Department of Food Science and Technology: Faculty Publications

Background: Oral microbiota is believed to play important roles in systemic diseases, including cancer. Methods: We collected oral samples (tongue, buccal, supragingival, and saliva) and pancreatic tissue or intestinal samples from 52 subjects, and characterized 16S rRNA genes using high-throughput DNA sequencing.

Results: Bray–Curtis plot showed clear separations between bacterial communities in the oral cavity and those in intestinal and pancreatic tissue samples. PERMANOVA tests indicated that bacterial communities from buccal samples were similar to supragingival and saliva samples, and pancreatic duct samples were similar to pancreatic tumor samples, but all other samples were significantly different from each …

Mucins, Gut Microbiota, And Postbiotics Role In Colorectal Cancer, Ramesh Pothuraju, Sanjib Chaudhary, Satyanarayana Rachagani, Sukhwinder Kaur, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host …

Goblet Cell Carcinoma Of The Appendix: A Case Report On Goblet Cell Carcinoid, Sheliza Kabani, Aubtin Saedi, Austin Lehr, Lina O'Brien

HCA Healthcare Journal of Medicine

Goblet cell carcinoid of the appendix is a rare neoplasm with histological features of both neuroendocrine and adenocarcinomas. The combination of its aggressive behavior, infrequent occurrence, and variable clinical presentation convolutes the management of this tumor. We report the case of a 75-year-old female presenting with acute appendicitis. A laparoscopic appendectomy was performed. The pathology report showed goblet cell carcinoid at the base of the appendix with involvement of the proximal surgical margins. At her postoperative visit, the patient’s pathology report and options for management were reviewed, and the patient agreed to proceed with a right hemicolectomy 8-10 weeks after …

Risk Prediction Rule For Advanced Neoplasia On Screening Colonoscopy For Average-Risk Individuals, Ala I Sharara, Ali El Mokahal, Ali H Harb, Natalia Khalaf, Fayez S Sarkis, Mustapha M El-Halabi, Nabil M Mansour, Ahmad Malli, Robert Habib

Faculty, Staff and Students Publications

BACKGROUND: In resource-limited countries, risk stratification can be used to optimize colorectal cancer screening. Few prospective risk prediction models exist for advanced neoplasia (AN) in true average-risk individuals.

AIM: To create and internally validate a risk prediction model for detection of AN in average-risk individuals.

METHODS: Prospective study of asymptomatic individuals undergoing first screening colonoscopy. Detailed characteristics including diet, exercise and medications were collected. Multivariate logistic regression was used to elucidate risk factors for AN (adenoma ≥1 cm, villous histology, high-grade dysplasia or carcinoma). The model was validated through bootstrapping, and discrimination and calibration of the model were assessed.

RESULTS: …