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  • Clinical management and outcomes of hepatobiliary disease in the cystic fibrosis transmembrane conductance regulator modulator era. Current opinion in gastroenterology Trocchia, C., Lazar, L., Sellers, Z. M. 2025

    Abstract

    Multiple cystic fibrosis transmembrane conductance regulator (CFTR) modulators are approved for the treatment of cystic fibrosis (CF) and show significant improvement in lung function, BMI, quality of life, and sweat chloride. However, their ability to impact liver disease is unclear. This review highlights the current published literature on CFTR modulators and liver health and briefly reviews considerations for clinical management of hepatobiliary disease in the CFTR modulator era.Currently, the primary data available on the clinical efficacy of CFTR modulators on CF hepatobiliary involvement (CFHBI) or advanced CF liver disease (aCFLD) is from small to moderate sized single-center studies, although more recently large, multicenter studies are emerging. Studies report opposing changes in aminotransferases, and mixed liver fibrosis index and elastography results. Yet, in total CFTR modulators generally do not worsen liver disease and may improve it in some individuals. Additional clinical management considerations are necessary in those on CFTR modulators who received an organ transplant or during nutritional evaluations.To better understand the possible benefit of CFTR modulator therapies on hepatobiliary health, additionally larger, longer-term, multicenter studies with sub-group phenotyping are necessary. Until then, providers should watch for liver-related adverse events, and be cognizant on how CFTR modulators may impact areas of clinical care for individuals with CF.

    View details for DOI 10.1097/MOG.0000000000001148

    View details for PubMedID 41442752

  • Gastrointestinal Burden in Patients with Pancreatic Insufficient Cystic Fibrosis Before and After Elexacaftor/Tezacaftor/Ivacaftor Use. Pancreas Abi-Aad, S., Trocchia, C., Mosha, M., Mark, J. A., Leung, D. H., Khalaf, R. 2025

    Abstract

    BACKGROUND: The advent of highly effective modulator therapies (HEMT), namely elexacaftor, tezacaftor and ivacaftor (ETI), has resulted in substantial improvements in lung function, growth, and quality of life, for people with cystic fibrosis (PwCF). However, the understanding of the impact of ETI on gastrointestinal (GI) disease burden is evolving. This study aims to describe and compare the prevalence of GI manifestations, prescribed GI medications, and GI procedures between two time periods pre and post-ETI approval in children with CF (CwCF).METHODS: This is a retrospective cohort study utilizing TriNetX, a multicenter database. The study includes patients between 6 to 21 years old with ICD-10 diagnostic codes for CF and a prescription for pancreatic enzyme replacement therapy (PERT) to match disease severity. We included 4 years before and 4 years after the release of ETI combination therapy.RESULTS: When comparing CwCF taking PERT, on or off ETI, the prevalence of diagnostic codes for chronic pancreatitis, constipation, unspecified noninfective gastroenteritis, and colitis significantly decreased after ETI use (all P < 0.0001). The prevalence of other luminal disorders, liver disorders, and acute pancreatitis did not differ between the two groups. The prevalence of prescribed medications including mucolytics, vitamins, PPI, and antidiarrheal was similar for both groups except for a reduction in prescribed laxatives (p-value = 0.0001). The prevalence of GI procedures was also similar in both groups.CONCLUSION: The reduction in constipation and non-infective gastroenteritis and colitis is important as GI symptoms are linked to the quality of life of CwCF. There remains a great clinical need to evaluate the effects of ETI on GI disorders, especially as the age of initial use of this therapy decreases, and the duration of use increases.

    View details for DOI 10.1097/MPA.0000000000002522

    View details for PubMedID 40540361

  • Prevalence and characteristics of gastrointestinal disorders, medication use, and diagnostic interventions in pediatric patients with cystic fibrosis: a nested case-control analysis from the TriNetX EMR-derived global research network real-world dataset FRONTIERS IN GASTROENTEROLOGY Trocchia, C., Mosha, M., Hamner, B., Goldenberg, N., Khalaf, R. 2025; 3

    View details for DOI 10.3389/fgstr.2024.1489876

    View details for Web of Science ID 001537292300001

  • Venous Thromboembolism Occurrence and Association with Gastrointestinal Disorders in Children with Cystic Fibrosis: An Analysis from the TriNetX Research Network Global Multicenter Real-World Dataset. Seminars in thrombosis and hemostasis Trocchia, C., Ashour, D., Mosha, M., Hamner, B., Betensky, M., Goldenberg, N., Khalaf, R. 2025

    Abstract

    The purpose of this study is to (1) estimate and compare the prevalence of venous thromboembolism (VTE) in children (age 0 to ≤21) with versus without cystic fibrosis (CF); (2) investigate putative associations between specific gastrointestinal (GI) manifestations and the development of VTE among children with CF. This was a multicenter case-control analysis among patients aged 0 to ≤ 21 years between 2010 and 2020, using the TriNetX Research Network. Data queries included ICD-9/10 (International Classification of Diseases-9th/10th Revision) diagnosis codes. Bivariate associations with VTE among CF patients were compared using Chi-square testing for categorical variables and Student's t-test for continuous variables. We used multivariable logistic regression to test for independent associations of GI manifestations with VTE among children with CF, with adjustment for other salient covariates. There was a total of 7,689 children with and 22,327,660 without CF. The frequency of occurrence of VTE was increased nearly 20-fold among those with, as compared with without CF (130 vs. 7 per 10,000 patients). Acute pancreatitis (adjusted odd ratio [aOR]=3.80, [95% confidence interval, CI: 2.00-7.22]), biliary disease (aOR=2.17 [95% CI: 1.17-4.03]), gastrostomy status (aOR=2.01 [95% CI: 1.27-3.18]), and malabsorption/malnutrition (aOR=2.41 [95% CI: 1.52-3.82]) were each associated with a higher likelihood of VTE among children with CF. In conclusion, we found a significantly increased frequency of VTE occurrence and association of specific GI diseases as independent risk factors for VTE among children with CF compared with those without.

    View details for DOI 10.1055/s-0044-1801825

    View details for PubMedID 39805291

  • Pulling instead of pushing: A case report of gastrostomy-assisted pull technique as an alternative method for endoluminal sponge placement in EVAC therapy Trocchia, C., Shieh, H., Dolan, I., Wilsey, M., Smithers, C. Johns Hopkins All Children’s Hospital. 2024
  • Percutaneous-Endoscopic Rendezvous Procedure in a Pediatric Patient With Biliary Obstruction and Altered Anatomy. Journal of pediatric gastroenterology and nutrition Mauer, T. L., Trocchia, C., Collard, M., Chandler, N. M., Poulos, N., Wilsey, M. 2023; 77 (4): e67

    View details for DOI 10.1097/MPG.0000000000003842

    View details for PubMedID 37229766

  • Navigating Uncertainty in Medicine With Our Families. Pediatrics Trocchia, C., Singh, P., Inglese, C., Goding, D., Matta, E., Dudas, R. 2023; 151 (4)

    View details for DOI 10.1542/peds.2022-059783

    View details for PubMedID 36866465

  • Pediatric ERCP in the Setting of Acute Pancreatitis: A Secondary Analysis of an International Multicenter Cohort Study. Journal of pediatric gastroenterology and nutrition Trocchia, C., Khalaf, R., Amankwah, E., Ruan, W., Fishman, D. S., Barth, B. A., Liu, Q. Y., Giefer, M., Kim, K. M., Martinez, M., Dall'oglio, L., Torroni, F., De Angelis, P., Faraci, S., Bitton, S., Werlin, S., Dua, K., Gugig, R., Huang, C., Mamula, P., Quiros, J. A., Zheng, Y., Piester, T., Grover, A., Fox, V. L., Wilsey, M., Troendle, D. M. 2023

    Abstract

    Previous studies have demonstrated the safety of performing Endoscopic Retrograde Cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs. One hundred and ninety-four (17%) of these procedures were performed in the setting of AP. There were no difference in the procedure success rate, procedure time, cannulation time, fluoroscopy time or American Society of Anesthesiology class despite patients with AP having higher ASGE difficulty grading scores. This study suggests that ERCP can be safely and efficiently performed in pediatric patients with AP when appropriately indicated.

    View details for DOI 10.1097/MPG.0000000000003762

    View details for PubMedID 36913706

  • Lymphatic Leakage in Pediatric Heart Transplantation: Early Recognition and Timely Management with Interventional Radiologic and Endoscopic Therapy Trocchia, C., Mauer, t., Mitchell, S., Collard, M., Asante-Korang, A., Wilsey, M. JPGN Reports. 2023
  • A Milk-Fat Based Diet Increases Metastasis in the MMTV-PyMT Mouse Model of Breast Cancer. Nutrients Velazquez, F. N., Viscardi, V., Montemage, J., Zhang, L., Trocchia, C., Delamont, M. M., Ahmad, R., Hannun, Y. A., Obeid, L. M., Snider, A. J. 2021; 13 (7)

    Abstract

    A high-fat diet (HFD) and obesity are risk factors for many diseases including breast cancer. This is particularly important with close to 40% of the current adult population being overweight or obese. Previous studies have implicated that Mediterranean diets (MDs) partially protect against breast cancer. However, to date, the links between diet and breast cancer progression are not well defined. Therefore, to begin to define and assess this, we used an isocaloric control diet (CD) and two HFDs enriched with either olive oil (OOBD, high in oleate, and unsaturated fatty acid in MDs) or a milk fat-based diet (MFBD, high in palmitate and myristate, saturated fatty acids in Western diets) in a mammary polyomavirus middle T antigen mouse model (MMTV-PyMT) of breast cancer. Our data demonstrate that neither MFBD or OOBD altered the growth of primary tumors in the MMTV-PyMT mice. The examination of lung metastases revealed that OOBD mice exhibited fewer surface nodules and smaller metastases when compared to MFBD and CD mice. These data suggest that different fatty acids found in different sources of HFDs may alter breast cancer metastasis.

    View details for DOI 10.3390/nu13072431

    View details for PubMedID 34371939

    View details for PubMedCentralID PMC8308868

  • Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer. PloS one Velazquez, F. N., Zhang, L., Viscardi, V., Trocchia, C., Hannun, Y. A., Obeid, L. M., Snider, A. J. 2021; 16 (5): e0252311

    Abstract

    Breast cancer is a very heterogeneous disease, and ~30% of breast cancer patients succumb to metastasis, highlighting the need to understand the mechanisms of breast cancer progression in order to identify new molecular targets for treatment. Sphingosine kinase 1 (SK1) has been shown to be upregulated in patients with breast cancer, and several studies have suggested its involvement in breast cancer progression and/or metastasis, mostly based on cell studies. In this work we evaluated the role of SK1 in breast cancer development and metastasis using a transgenic breast cancer model, mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT), that closely resembles the characteristics and evolution of human breast cancer. The results show that SK1 deficiency does not alter tumor latency or growth, but significantly increases the number of metastatic lung nodules and the average metastasis size in the lung of MMTV-PyMT mice. Additionally, analysis of Kaplan-Meier plotter of human disease shows that high SK1 mRNA expression can be associated with a better prognosis for breast cancer patients. These results suggest a metastasis-suppressing function for SK1 in the MMTV-PyMT model of breast cancer, and that its role in regulating human breast cancer progression and metastasis may be dependent on the breast cancer type.

    View details for DOI 10.1371/journal.pone.0252311

    View details for PubMedID 34043703

    View details for PubMedCentralID PMC8158862