Schupack, Daniel

Abstract Background: Aberrations in telomere length have important implications in cancer development and progression. This study aimed to determine whether leukocyte telomere length (LTL) in patients with colorectal cancer (CRC) is associated with survival outcomes. We also investigated whether genetic variants in telomere maintenance genes are associated with survival in these patients. Methods: Blood specimens were collected from 1,007 patients prior to receiving chemotherapy or radiation. Genomic DNA was extracted using the Promega Maxwell RSC instrument. LTL was measured in triplicate using monochrome multiplex PCR, where the average amplification value of telomeric repeats was termed T. Similarly, PCR amplification of a single-copy reference gene was performed, and its average amplification value was termed S. The telomere length for each sample was expressed as the T/S ratio. Genotyping of single-nucleotide polymorphisms (SNPs) in TERC, TERT, and OBFC1 genes was conducted at the institutional Genome Analysis Core facility. Kaplan-Meier survival curves were generated to evaluate patient survival outcomes. Results: Younger individuals (∼25 years) exhibited nearly a twofold longer LTL compared with older individuals (∼75 years). No significant difference in LTL was observed between stage II and stage III CRC patients. A strong inverse correlation was observed between patient age and LTL (Spearman’s r = -0.48; p = 1.13 × 10-58). Females had significantly longer LTL than males (p = 3.97 × 10-5). The TERC SNP rs1317082 was significantly associated with both overall survival (OS) and disease-free survival (DFS) in the combined stage II and stage III patient cohort (p = 0.017 and p = 0.023, respectively). Similarly, the OBFC1 SNP rs9419958 was significantly associated with OS (p = 0.016). Importantly, LTL itself was significantly associated with both OS and DFS (p = 0.008 and p = 0.044, respectively) among the combined stage II and stage III patients. Kaplan-Meier survival analyses demonstrated that age- and sex-adjusted LTL was predictive of long-term survival outcomes. Conclusions: Survival among patients with stage II and III colorectal cancer is significantly influenced by LTL. Additionally, specific allelic variants of telomere maintenance genes, including TERC and OBFC1, are independently associated with improved survival, irrespective of LTL. These findings suggest that peripheral blood LTL measurement, along with telomere-related genotyping, may serve as a valuable prognostic marker for colorectal cancer outcomes. Funding: Individualizing colorectal cancer patient care using the host and tumor telomere phenotype (RO1 CA204013), Curtiss Fund (92541775), C-SiG Core(s): Epigenomics & Spatial Biology Core, and Clinical Core of the Mayo Clinic Center for Cell Signaling in Gastroenterology (P30DK084567) Citation Format: Estela M. Cruz Garcia, Gobinda Sarkar, Jun Chen, Shubham Sood, Kim Kossick, Daniel Schupack, Rondell Graham, Brooke Druliner, Zahra Heydari, Lauren Helgeson, Richard G. Cawthon, Lisa A. Boardman. Longer leukocyte telomeres and specific alleles of telomere maintenance genes are independently associated with improved survival of colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1919.

Background and aims: Aberrations in telomere length can have important implications in cancer. Using a cohort of 1007 patients, we investigated whether leukocyte telomere length (LTL) in patients with colorectal cancer (CRC) is associated with survival. We also investigated whether some telomere maintenance genes are associated with survival in these patients. Methods: The Biobank for Gastrointestinal Health Research (BGHR), an ongoing project involving collection of biospecimens at the Mayo Clinic, was utilized to obtain data from patients diagnosed with stage II or III CRC. Blood samples were collected prior to chemotherapy/radiation and DNA was extracted for measuring median LTL. The main outcome measures were overall survival (OS) and disease-free survival (DFS) by disease stage. Results: A significant inverse relationship was observed with patient age and LTL (spearman correlation coefficient (r) = −0.48, 95%; p = 1.13 × 10−58). Females had significantly longer LTL than males (p = 3.97 × 10−5). The rs1317082 SNP in the TERC gene was significantly associated with both OS and DFS in combined stage II and stage III patients (p = 0.017 and p = 0.023, respectively). A statistically significant association of the OBFC1 SNP (rs9419958) was observed for OS for the combined stage II and stage III patients (p = 0.016). Importantly, LTL was significantly associated with both OS and DFS (p = 0.008 and 0.044 respectively) in combined stage II and stage III patients. Conclusions: Our results show that LTL is predictive of OS and DFS for stage II and III CRC patients, particularly over a longer follow-up, extending beyond five years after a diagnosis of CRC, and certain SNPs in genes involved in telomere maintenance are significantly associated with patient outcomes, independent of telomere length.

Summary Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

BACKGROUND: Acute ileitis is most classically associated with inflammatory bowel disease. However, several infections can also cause inflammation or obstruction of the terminal ileum. Clinical presentation is usually acute and characterized by abdominal pain of the right abdomen. CASE REPORT: We report the case of a healthy 24 year-old man who presented with a two month history of right lower quadrant pain, nausea and emesis after returning from a trip to South Africa. Over the subsequent two months, he had continued symptoms and an ileocecal obstruction was demonstrated both on cross-sectional imaging and on colonoscopy. A stool pathogen panel was positive for Campylobacter jejuni, and he completed an empiric three-day course of azithromycin. Endoscopic biopsies were negative for histologic features of inflammatory bowel disease. After three hospitalizations for recurrent obstruction, an ileocecal resection was performed. The resection specimen revealed marked eosinophilia within the muscularis propria and submucosal fibrosis. The patient made an uneventful recovery following his surgery. CONCLUSION: Although inflammatory bowel disease should be excluded during the workup of terminal ileitis, this case illustrates the importance of including infections and post-infectious sequelae in the differential, especially in otherwise healthy patients with recent travel history.

INTRODUCTION: Histologic response rates to steroids for eosinophilic esophagitis (EoE) vary from < 50% to >90% in controlled trials. We have used varied steroid preparations and higher doses than typically used and aimed to study if steroid dose and delivery vehicle might explain the wide variation in response. METHODS: A database of patients with EoE created in our esophageal clinic was reviewed and patients treated with at least an 8 week course of topical steroid therapy and undergoing pre and post-steroid histologic evaluation were included. Histologic remission was defined as eosinophil count < 15/hpf. Symptomatic remission was defined as complete resolution of symptoms and eating an unlimited diet. Endoscopy reports were reviewed. RESULTS: 94 patients were included, 45 on 3 mg budesonide-Rincinol gel twice daily (HBRG), 29 on 3 mg budesonide capsules BID (BC), and 20 on lower doses of BRG (1.5 mg daily to 2 mg BID) (LBRG). 88.5% had dysphagia at time of steroid initiation. Mean eosinophil count before steroids was 58.6/hpf. 38.3% had esophageal dilation just prior to steroids. Average EFERS prior to steroid treatment was 1.8. There were not significant differences between the groups in terms of demographics, initial eosinophil counts, symptoms, visual EoE assessment (EREFS) or dilation rates. Histologic remission rate for HBRG was 82.2% vs 55.1% for all others combined ( P < 0.001), 51.7% for BC ( P = 0.005 vs 3 mg BRG BID), and 60.0% for LBRG ( P = 0.06 vs 3 mg BRG BID). Symptomatic remission was similar between groups, as was change in EREFS and change in eosinophil counts. Non-responders to HBRG had mean decrease in eosinophil count of only 0.3/hpf (vs 53.2/hpf for responders, P < 0.003) and mean change in EREFS of +1.6 (vs −1.1 for responders, P < 0.001). 62.5% of non-responders to HBRG actually had increase in eosinophil count after steroids. Response rate to HBRG at < 5 eos/hpf was 77.8% overall and 94.6% in those achieving remission. CONCLUSION: A higher remission rate achieved with a more viscous steroid preparation compared to other formulations suggests the importance of both dose and esophageal delivery in treatment of EoE. Further, with adequate mucosal delivery and dosing of topical steroids, steroid refractory EoE appears to be uncommon. On the other hand, these results suggest the existence of a small truly steroid refractory group of EoE patients with negligible histologic, symptomatic and endoscopic response to high dose steroids that warrant further investigation.

Background Esophageal food impaction is relatively common and increasing over time. Treatment ranges from medications to invasive endoscopic therapies. The endoscopic push technique has been advised against in favor of endoscopic retrieval for safety concerns. We sought to assess use patterns and safety of treatments for food impaction in a population‐based retrospective review. Methods A database of recorded esophageal food impactions in Olmsted County, MN, USA, from 1975–2011 was reviewed for patient demographics, treatment, and complications. Results A total of 645 impactions occurred, with increasing incidence over time, peaking at 23.2 per year (2000–2004). Medications (almost exclusively glucagon) were successful in relieving impactions 34.5% of the time when trialed. Urgent endoscopy was common (74.0%), as was the need for endoscopic therapy (67.1%). Endoscopic therapy increased over time, with the endoscopic push technique becoming most common. Esophageal complications (deep mucosal injury or perforation) increased over time but remained rare (peak 11%). There was no difference in complications between push and retrieval techniques. Conclusions The endoscopic push technique is safe in comparison to endoscopic retrieval in esophageal food impactions. While complications surrounding impaction have increased, they remain rare. Medication trials are reasonable, as long as they do not delay endoscopy, and may prevent the need for emergent endoscopy in one‐third of cases.