Digestive System Diseases Commons^™

Interim Results From An Ongoing, Open-Label, Single-Arm Trial Of Odevixibat In Progressive Familial Intrahepatic Cholestasis, Richard J Thompson, Reha Artan, Ulrich Baumann, Pier Luigi Calvo, Piotr Czubkowski, Buket Dalgic, Lorenzo D'Antiga, Angelo Di Giorgio, Özlem Durmaz, Emmanuel Gonzalès, Tassos Grammatikopoulos, Girish Gupte, Winita Hardikar, Roderick H J Houwen, Binita M Kamath, Saul J Karpen, Florence Lacaille, Alain Lachaux, Elke Lainka, Kathleen M Loomes, Cara L Mack, Jan P Mattsson, Patrick Mckiernan, Quanhong Ni, Hasan Özen, Sanjay R Rajwal, Bertrand Roquelaure, Eyal Shteyer, Etienne Sokal, Ronald J Sokol, Nisreen Soufi, Ekkehard Sturm, Mary Elizabeth Tessier, Wendy L Van Der Woerd, Henkjan J Verkade, Jennifer M Vittorio, Terese Wallefors, Natalie Warholic, Qifeng Yu, Patrick Horn, Lise Kjems

Faculty, Staff and Students Publications

BACKGROUND & AIMS: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis.

METHODS: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up …

Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma: Pathogenesis And Treatment, Josep M Llovet, Catherine E Willoughby, Amit G Singal, Tim F Greten, Mathias Heikenwälder, Hashem B El-Serag, Richard S Finn, Scott L Friedman

Faculty, Staff and Students Publications

Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation, nonalcoholic steatohepatitis (NASH), has a global prevalence of 20-25% and is a major public health problem. Its incidence is increasing in parallel to the rise in obesity, diabetes and metabolic syndrome. Progression from NASH to NASH-related hepatocellular carcinoma (HCC) (~2% of cases per year) is influenced by many factors, including the tissue and immune microenvironment, germline mutations in PNPLA3, and the microbiome. NASH-HCC has unique molecular and immune traits compared with other aetiologies of HCC and is equally prevalent in men and women. Comorbidities associated with NASH, such as obesity …

Editorial: Gut Physiology—Microbes And Inflammatory Diseases, Shubha Priyamvada, Suhail Akhtar

All KCOM Faculty Publications

Editorial on the Research Topic Gut physiology—microbes and inflammatory diseases

Two Pediatric Cases Within A Familial Cluster And Hereditary Diffuse Gastric Carcinoma: A Tale Of 2 Sisters, Lacey Falgout, Lawrence L. Gensler

School of Medicine Faculty Publications

Hereditary diffuse gastric cancer is a familial form of poorly differentiated signet ring cell carcinoma (SRCC) caused by a mutation in the CDH1/E-cadherin gene-mediating cell adhesion. CDH1 mutations are inherited in an autosomal dominant fashion and exhibit a high level of penetrance. SRCC diagnosis is exceedingly rare in the pediatric population. We report a case of SRCC in 2 sisters (10 and 15 years) and their father (41 years).

Many Pediatric Patients With Gastroparesis Do Not Receive Dietary Education, Debra Eseonu, Deepa Dongarwar, Hamisu Salihu, Bruno P Chumpitazi, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: Gastroparesis is delayed gastric emptying in the absence of obstruction; dietary modifications are first-line treatment. However, we do not know the factors related to provision of dietary recommendations.

METHODS: We sought to determine how often pediatric patients with gastroparesis receive dietary education (from a gastroenterology provider vs dietitian), the recommendations given, and factors related to these outcomes. We performed a retrospective chart review of children 2- to 18-years-old managed by pediatric gastroenterology providers at our institution. Patient demographics and clinical data, dietary advice given (if any), and dietitian consultation (if any), practice location, and prokinetic use were captured. An …

Effects Of A Pragmatic Home-Based Exercise Program Concurrent With Neoadjuvant Therapy On Physical Function Of Patients With Pancreatic Cancer: The Pancfit Randomized Clinical Trial, An T Ngo-Huang, Nathan H Parker, Lianchun Xiao, Keri L Schadler, Maria Q B Petzel, Laura R Prakash, Michael P Kim, Ching-Wei D Tzeng, Jeffrey E Lee, Naruhiko Ikoma, Robert A Wolff, Milind M Javle, Eugene J Koay, Shubham D Pant, Justin P Folloder, Xuemei Wang, Alicia M Cotto, Ye Rang Ju, Naveen Garg, Huamin Wang, Eduardo D Bruera, Karen M Basen-Engquist, Matthew H G Katz

Faculty, Staff and Student Publications

OBJECTIVE: To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer.

BACKGROUND: We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer.

METHODS: In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included …

Measuring Quality At The Surgeon Level, Elias A Chamely, Jonah J Stulberg

Faculty, Staff and Student Publications

Patients expect high-quality surgical care and increasingly are looking for ways to assess the quality of the surgeon they are seeing, but quality measurement is often more complicated than one might expect. Measurement of individual surgeon quality in a manner that allows for comparison among surgeons is particularly difficult. While the concept of measuring individual surgeon quality has a long history, technology now allows for new and innovative ways to measure and achieve surgical excellence. However, some recent efforts to make surgeon-level quality data publicly available have highlighted the challenges of this work. Through this chapter, the reader will be …

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, …

Closure Of Refractory Gastrocutaneous Fistula With Endoscopically Guided Percutaneous Suturing With The Use Of Miniature Biopsy Forceps, Rogelio Garcia, Juan D Gomez Cifuentes, Fuad Aloor, Tara Keihanian, Marvin Ryou, Wasif M Abidi

Faculty, Staff and Students Publications

A PEG tube is an ideal option for enteral nutrition in patients with impaired swallowing or for nutrition optimization. After PEG tube removal, the tract usually closes spontaneously. However, persistent gastrocutaneous fistula (GCF) is a rare but well-known adverse event of long-term PEG tube use.¹ Despite the evolution of endoscopic techniques over the last decade, such as over-the-scope clips (OTSCs), endoscopic suturing, and biosynthetic glue plaque, the management of GCF remains challenging.2, 3, 4, 5, 6 Although endoscopic suturing results in full-thickness closure of the gastric wall, persistent leakage from the cutaneous site may …

Actionable Solutions To Achieve Health Equity In Chronic Liver Disease, Patricia D Jones, Jennifer C Lai, Jasmohan S Bajaj, Fasiha Kanwal

Faculty, Staff and Students Publications

There are well-described racial and ethnic disparities in the burden of chronic liver diseases. Hispanic persons are at highest risk for developing nonalcoholic fatty liver disease, the fastest growing cause of liver disease. Hepatitis B disproportionately affects persons of Asian or African descent. The highest rates of hepatitis C occur in American Indian and Alaskan Native populations. In addition to disparities in disease burden, there are also marked racial and ethnic disparities in access to treatments, including liver transplantation. Disparities also exist by gender and geography, especially in alcohol-related liver disease. To achieve health equity, we must address the root …

Association Of Chronic Pancreatitis Pain Features With Physical, Mental, And Social Health, Dhiraj Yadav, Robert L Askew, Tonya Palermo, Liang Li, Dana K Andersen, Minxing Chen, William E Fisher, Evan L Fogel, Christopher E Forsmark, Phil A Hart, Mohamed O Othman, Stephen J Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Santhi Swaroop Vege, Yunlong Yang, Jose Serrano, Darwin L Conwell, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities.

METHODS: We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants …

The Predictive Performance Of Contemporary Guideline Recommendations For Helicobacter Pylori Testing In A United States Population, Theresa Nguyen Wenker, Frederick B Peng, Ikenna Emelogu, Niharika Mallepally, Fasiha Kanwal, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: The Houston Consensus Conference and American College of Gastroenterology (ACG) have recommended Helicobacter pylori screening in United States populations with specific risk factors. However, the performance of these guidelines in clinical practice is not known.

METHODS: We identified consecutive patients undergoing upper endoscopy with gastric biopsies for any indication in a safety-net hospital in Houston, TX during January 2015-December 2016. We tested the association between the presence of H pylori (histopathology, stool antigen, urea breath test, immunoglobulin G serology, or prior treatment) and H pylori risk factors using logistic regression models, reported as odds ratios and 95% confidence intervals …

Radiological-Histopathological Discordance In Patients Transplanted For Hcc And Its Impact On Post-Transplant Outcomes, Islam B Mohamed, Mohamed Saleh Ismail, Ahmed El Sabagh, Ahmed M Afifi Abdelwahab, Efstathia Polychronopoulou, Yong-Fang Kuo, Manal Hassan, John A Goss, Fasiha Kanwal, Prasun K Jalal

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Contrast-enhanced cross-sectional imaging is the cornerstone in the diagnosis, staging, and management of HCC, including eligibility for liver transplantation (LT). Radiological-histopathological discordance may lead to improper staging and may impact patient outcomes. We aimed to assess the radiological-histopathological discordance at the time of LT in HCC patients and its impact on the post-LT outcomes.

METHODS: We analyzed further the effect of 6-month waiting policy on the discordance. Using United Network for Organ Sharing-Organ Procurement and Transplantation Network (UNOS-OPTN) database, we examined the discordance between pre-LT imaging and explant histopathology for all adult HCC patients who received liver …

The Utility Of Fecal Calprotectin In The Diagnosis And Management Of Microscopic Colitis, Busara Songtanin, Abbie Evans, Kenneth Nugent, Vanessa Costilla

Journal of Community Hospital Internal Medicine Perspectives

Background: The incidence of microscopic colitis has increased over time. To date, there is no specific biomarker for microscopic colitis, and the diagnosis relies on histopathological tissue obtained during colonoscopy which is an invasive and costly procedure. Unlike Crohn’s disease and ulcerative colitis, the utility of fecal calprotectin in diagnosing or monitoring microscopic colitis has not been established, and studies on the role of fecal calprotectin in microscopic colitis are limited. In this retrospective study, we analyzed the utility of this biomarker in the diagnosis of microscopic colitis. Methods: The medical records of patients who have been diagnosed with collagenous …

Gata6-As1 Regulates Intestinal Epithelial Mitochondrial Functions, And Its Reduced Expression Is Linked To Intestinal Inflammation And Less Favourable Disease Course In Ulcerative Colitis, Katya E Sosnovski, Tzipi Braun, Amnon Amir, Danielle Moshel, Marina Benshoshan, Kelli L Vandussen, Nina Levhar, Haya Abbas-Egbariya, Katia Beider, Rakefet Ben-Yishay, Syed Asad Ali, Sean R Moore, Subra Kugathasan, Ifat Abramovich, Efrat Glick Saar, Batya Weiss, Iris Barshack, Eyal Gottlieb, Tamar Geiger, Shomron Ben-Horin, Igor Ulitsky, Jeffrey S Hyams, Lee A Denson, Yael Haberman

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Widespread dysregulation of long non-coding RNAs [lncRNAs] including a reduction in GATA6-AS1 was noted in inflammatory bowel disease [IBD]. We previously reported a prominent inhibition of epithelial mitochondrial functions in ulcerative colitis [UC]. However, the connection between reduction of GATA6-AS1 expression and attenuated epithelial mitochondrial functions was not defined.

METHODS: Mucosal transcriptomics was used to conform GATA6-AS1 reduction in several treatment-naïve independent human cohorts [n=673]. RNA pull-down followed by mass spectrometry was used to determine the GATA6-AS1 interactome. Metabolomics and mitochondrial respiration following GATA6-AS1 silencing in Caco-2 cells were used to elaborate on GATA6-AS1 functions.

RESULTS: GATA6-AS1 …

Hematopoietic Progenitor Kinase 1 Inhibits The Development And Progression Of Pancreatic Intraepithelial Neoplasia, Hua Wang, Rohan Moniruzzaman, Lei Li, Baoan Ji, Yi Liu, Xiangsheng Zuo, Reza Abbasgholizadeh, Jun Zhao, Guangchao Liu, Ruiqi Wang, Hongli Tang, Ryan Sun, Xiaoping Su, Tse-Hua Tan, Anirban Maitra, Huamin Wang

Faculty, Staff and Student Publications

Ras plays an essential role in the development of acinar-to-ductal metaplasia (ADM) and pancreatic ductal adenocarcinoma (PDAC). However, mutant Kras is an inefficient driver for PDAC development. The mechanisms of the switching from low Ras activity to high Ras activity that are required for development and progression of pancreatic intraepithelial neoplasias (PanINs) are unclear. In this study, we found that hematopoietic progenitor kinase 1 (HPK1) was upregulated during pancreatic injury and ADM. HPK1 interacted with the SH3 domain and phosphorylated Ras GTPase-activating protein (RasGAP) and upregulated RasGAP activity. Using transgenic mouse models of HPK1 or M46, a kinase-dead mutant of …

Antitumor Efficacy Of Dual Blockade With Encorafenib + Cetuximab In Combination With Chemotherapy In Human Brafv600e-Mutant Colorectal Cancer, Stefania Napolitano, Melanie Woods, Hey Min Lee, Vincenzo De Falco, Giulia Martini, Carminia Maria Della Corte, Erika Martinelli, Vincenzo Famiglietti, Davide Ciardiello, Amanda Anderson, Natalie Wall Fowlkes, Oscar Eduardo Villareal, Alexey Sorokin, Preeti Kanikarla, Olu Coker, Van Morris, Lucia Altucci, Josep Tabernero, Teresa Troiani, Fortunato Ciardiello, Scott Kopetz

Faculty, Staff and Student Publications

PURPOSE: Encorafenib + cetuximab (E+C) is an effective therapeutic option in chemorefractory BRAFV600E metastatic colorectal cancer (mCRC). However, there is a need to improve the efficacy of this molecular-targeted therapy and evaluate regimens suitable for untreated BRAFV600E in patients with mCRC.

EXPERIMENTAL DESIGN: We performed a series of in vivo studies using BRAFV600E mCRC tumor xenografts. Mice were randomized to receive 5-fluoruracil (5-FU), irinotecan, or oxaliplatin regimens (FOLFIRI or FOLFOX), (E+C) or the combination. Patients received long-term treatment until disease progression, with deescalation strategies used to mimic maintenance therapy. Transcriptomic changes after progression on cytotoxic chemotherapy or targeted therapy were …

Comparative Analyses Define Differences Between Bhd-Associated Renal Tumour And Sporadic Chromophobe Renal Cell Carcinoma, Ryosuke Jikuya, Todd A Johnson, Kazuhiro Maejima, Jisong An, Young-Seok Ju, Hwajin Lee, Kyungsik Ha, Woojeung Song, Youngwook Kim, Yuki Okawa, Shota Sasagawa, Yuki Kanazashi, Masashi Fujita, Seiya Imoto, Taku Mitome, Shinji Ohtake, Go Noguchi, Sachi Kawaura, Yasuhiro Iribe, Kota Aomori, Tomoyuki Tatenuma, Mitsuru Komeya, Hiroki Ito, Yusuke Ito, Kentaro Muraoka, Mitsuko Furuya, Ikuma Kato, Satoshi Fujii, Haruka Hamanoue, Tomohiko Tamura, Masaya Baba, Toshio Suda, Tatsuhiko Kodama, Kazuhide Makiyama, Masahiro Yao, Brian M Shuch, Christopher J Ricketts, Laura S Schmidt, W Marston Linehan, Hidewaki Nakagawa, Hisashi Hasumi

Faculty, Staff and Student Publications

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated.

METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated …

Patient-Reported Bowel Function And Bowel-Related Quality Of Life After Pelvic Radiation For Rectal Adenocarcinoma: The Impact Of Radiation Fractionation And Surgical Resection, Michael K Rooney, Brian De, Kelsey Corrigan, Grace L Smith, Cullen Taniguchi, Bruce D Minsky, Ethan B Ludmir, Eugene J Koay, Prajnan Das, Albert C Koong, Oliver Peacock, George Chang, Y Nancy You, Van K Morris, Graciela Nogueras-González, Emma B Holliday

Faculty, Staff and Student Publications

INTRODUCTION: Multimodality treatment for locally advanced rectal cancer (LARC) can include long-course radiotherapy (LCRT) or short course radiotherapy (SCRT). Nonoperative management is increasingly pursued for those achieving a complete clinical response. Data regarding long-term function and quality-of-life (QOL) are limited.

METHODS: Patients with LARC treated with radiotherapy from 2016 to 2020 completed the Functional Assessment of Cancer Therapy- General (FACT-G7), the Low Anterior Resection Syndrome Score (LARS) and the Fecal Incontinence QOL Scale (FIQOL). Univariate and multivariable linear regression analyses identified associations between clinical variables including radiation fractionation and the use of surgery versus non-operative management.

RESULTS: Of 204 patients …

Targets And Study Design For Symptom-Focused Trials Aimed At Patients With Cirrhosis: An Expert Consensus, Arpan A Patel, Elliot B Tapper, Fasiha Kanwal, Christopher D Woodrell, Lissi Hansen, Jennifer C Lai, Shari Rogal, Cara Mcdermott, Mina Rakoski, Nneka N Ufere

Faculty, Staff and Students Publications

BACKGROUND: Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures.

METHODS: A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in …