Goals: We aimed to characterize risk factors for early versus advanced-stage early-onset colorectal cancer (eoCRC) at our safety-net hospital system. Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Rates of CRC diagnosis in young adults (age below 50) have been rising despite an overall decrease in CRC. CRC in this group is often detected late due to screening historically being for persons 50 years and older. Etiologies for the increase in rates of eoCRC remain unclear, as do the risk factors for advanced-stage, defined as stage III or IV, at presentation. Study: We conducted a retrospective cohort study of 556 adults younger than 50 years of age with an ICD-10 diagnosis of malignant neoplasm of the colon or rectum within a 10-year span. Data collected included demographics, age at diagnosis, time to diagnosis, and cancer stage at diagnosis. Multivariable analysis was used to determine factors associated with advanced-stage CRC. Results: A total of 279 patients met the inclusion criteria. Most were Hispanic (67.03%), followed by non-Hispanic Black (NHB, 24.01%). Most had advanced-stage CRC at diagnosis (85.7%, n=239), despite 67.7% (n=189) being diagnosed within 3 months of symptom onset. When compared with non-Hispanic White (NHW) patients, NHB (OR: 2.02, CI: 0.59-6.96) and Hispanic (OR: 1.68, CI: 0.57-4.95) patients had higher odds of advance-stage CRC, albeit not statistically significant. Conclusions: Most patients were diagnosed with advanced-stage disease. NHB and Hispanic patients had a nonstatistically significant higher odds of presenting at advanced-stage CRC compared with NHW patients. System-wide quality improvement interventions may be needed to screen for eoCRC in safety-net hospital systems.

Background: Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital. Methods: This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021. Results: In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P <0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P <0.001). Because gastric biopsy location was known in 90% of patients ( P <0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% ( P <0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort. Conclusions: GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations.

Background The rate of change in the incidence of colorectal cancer (CRC) among persons younger than 50 years in the United States appears to vary by demographics, tumor location, and geography. This study analyzed data from all 50 states to examine recent changes in the incidence of CRC among persons younger than 50 years and to identify key subgroups with disproportionate risk. Methods Annual incidence rates for CRC, colon cancer, and rectal cancer in persons aged 20 to 49 years were extracted from the US Cancer Statistics for the period 2001-2017. Secular trends were examined overall and by age group, sex, race/ethnicity, stage, and state. Joinpoint regression was used to compute annual percent changes and average annual percent changes (AAPCs) as well as corresponding 95% confidence intervals (95% CIs). Results The incidence of CRC increased by 1.27% (95% CI, 0.95%-1.60%) annually from 2001 to 2012 and by 3.00% (95% CI, 2.06%-3.95%) annually from 2012 to 2017. AAPCs for the period 2001-2017 were higher among persons aged 20 to 24 years (AAPC, 6.62%; 95% CI, 3.86%-9.45%) in comparison with other age groups and higher among non-Hispanic Whites (AAPC, 2.38%; 95% CI, 1.98%-2.79%) in comparison with other racial/ethnic groups. In 2001-2002, only 1 state had an age-standardized incidence rate > 13.0 per 100,000, but this number increased to 32 states by 2016-2017. Conclusions CRC rates among US adults aged 20 to 49 years increased from 2001 to 2017, with the fastest increases observed from 2012 to 2017. Increases were observed among the youngest age groups, among non-Hispanic Whites, and in states in the West, Midwest, and Rocky Mountain regions. Increasing rates across all tumor stages suggest a real increase in CRC incidence.

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in American men and women combined. While overall incidence and mortality of CRC have seen consistent declines over the last several decades, rates of CRC in young adults have been rising. Many patients with early onset CRC (EOCRC) present at late stages of disease, including a high proportion who present with stage 4 cancer when the prognosis is poor. The objective of this study is to characterize the epidemiology of EOCRC in a safety-net hospital system and identify characteristics associated with Stage 4 diagnosis. Methods: We conducted a retrospective cohort study of young adults (age< 50) with CRC (based on ICD-10 code diagnosis) between 12/2010 and 12/2020. Patients were excluded if there were significant data deficiencies in the chart, or if they had a history of inflammatory bowel disease or a familial cancer syndrome. Medical records were reviewed to abstract data regarding demographics and cancer diagnosis. Patients with EOCRC were characterized with descriptive statistics. Multivariable analysis was used to assess characteristics independently associated with stage 4 EOCRC. Results: Of 556 patients identified, 311 met the specified inclusion criteria. Over half the patients were between ages 40-49 (53%), with only 8% under age 30. Most patients were male (58%). Most patients were of Hispanic descent (62%), followed by Non-Hispanic (NH) Blacks (22%). A majority of CRC cases were left-sided (74%). Most cases were diagnosed at an advanced stage of disease, with 40% of cases diagnosed at stage 3 and 45% at stage 4. Most patients had a timely diagnosis from presentation (68% within 3 months; 80% within 6 months). In multivariable analyses, the odds of stage 4 EOCRC diagnosis was nearly two times higher among NH Blacks compared to all other races (OR 1.98, P=0.017). There was no difference in time to diagnosis between NH Whites, Hispanic Whites, and NH blacks (P=0.337). Conclusion: Incidence of EOCRC has been on the rise despite declining overall CRC cases. Patients with EOCRC are often diagnosed at later stages of disease, which has been attributed in part to diagnostic delays. Interestingly, this study demonstrated a short average interval to diagnosis. Despite this, an overwhelming majority of patients were diagnosed with late-stage disease. NH Blacks were significantly more likely to present with stage 4 EOCRC despite similar times to diagnosis. Further research is warranted to elucidate these trends.Table 1.: Multivariate Logistic Regression Model Describing Variables Associated with Stage 4 CRC at Diagnosis.

INTRODUCTION:Colorectal cancer (CRC) remains the second-leading cause of cancerrelated death in the United States (US), despite being highly curable, or even preventable, through effective screening programs.Multiple options are available and endorsed by major guidelines for average-risk CRC screening, including endoscopic (colonoscopy [COL], flexible sigmoidoscopy [FS]), radiologic (CT colonography [CTC]) and stool-based (fecal occult blood test [FOBT], fecal immunochemical test [FIT], multi-target stool DNA [mt-sDNA]) modalities.Further insights regarding the proportional distribution of endorsed test options would help to inform ongoing efforts to achieve the national CRC screening adherence target of ‡ 80%.The aim of this study was to analyze and compare recent trends in COL, FS, FOBT, FIT, and mt-sDNA utilization, using Medicare claims data.Since CTC is not covered by Medicare, this screening modality was not included in our analyses.METHODS: Medicare claims data for CRC screening for a specific time analysis period (2014-2018) were aggregated and analyzed by CPT code frequency: COL (G0121, G0105), FS (G0104), FOBT (82270, G0107), FIT (G0328), and mt-sDNA (G0464, 81528).A generalized linear model was used to examine differences in CRC screening test frequencies during the analysis period.Compound annual growth rate (CAGR) and year-over-year (Y/Y) growth rates were also analyzed for each modality over the analysis period (2014)(2015)(2016)(2017)(2018).RESULTS: FS represented < 1% of all CRC screening tests over the entire analysis period and was not further considered in the analyses.Utilization of the mt-sDNA test increased significantly over time (from 2,481 claims in 2014 to 335,455 claims in 2018; p<0.001), as compared to the other analyzed CRC screening tests.Conversely, FOBT exhibited the most striking decline in utilization (from 623,455 claims in 2014 to 333,715 claims in 2018; p<0.001).The CAGR was higher for mt-sDNA (166.81%)than for COL (0.52%), FOBT (-11.75%), and FIT (0.67%).CONCLUSIONS: Based on this analysis of Medicare claims data from 2014-2018, utilization of the mt-sDNA test for average-risk CRC screening has increased rapidly since it received FDA approval in August 2014, while utilization of other endorsed CRC screening modalities has either declined (FOBT) or remained relatively stable (COL, FIT) over the same time period.These data support growing patient and provider interest in the molecularly-based mt-sDNA test as a non-invasive option for average-risk CRC screening.Of note, screening COLs may be underestimated by our methodology, as screening COLs resulting in polyp removal may be coded as diagnostic and thus not captured with the applied codes.Further investigation using data from other sources, including those that include non-Medicare patients, are encouraged to confirm and extend these findings.

INTRODUCTION: Kaposi's sarcoma (KS) is a tumor characterized by mesenchymal differentiation and angiogenesis secondary to infection by human herpesvirus-8 (HHV-8). Low CD4 cell count is a major risk factor for development of KS in immunocompromised patients with HHV-8. KS typically exhibits pink to purple plaque-like or papular lesions most commonly on the skin, oral mucosa, and visceral organs. We present a case of an AIDS patient with significant upper GI (UGI) bleeding secondary to KS associated linitis plastica. CASE DESCRIPTION/METHODS: A 45 year-old Nigerian woman with history of anemia and peptic ulcer disease presented with 2 days of fatigue, small-volume coffee-ground emesis, and diarrhea in the setting of 6 months of worsening dyspnea on exertion and cutaneous lesions. She was found to be septic requiring ICU admission and aggressive fluid resuscitation with initiation of empiric antibiotics. Physical examination showed violaceous hyperpigmented nasal, perioral, perianal and thoracic cutaneous papules approximately 1–2 cm in diameter (Image 1). Initial laboratory investigations revealed anemia with a hemoglobin level of 6.5 g/dL. Infectious studies resulted in a new AIDS/HIV diagnosis with HIV-1 RNA of 136,000 copies/mL and an absolute CD4 count of 32 cells/μL. Computerized tomography imaging showed diffuse gastric wall thickening and edema and inguinal lymphadenopathy. Biopsy of skin lesions were histologically positive for KS. Given abnormal imaging and (UGI) bleed, she underwent esophagogastroduodenoscopy (EGD) which indicated erythematous nodular lesions in the antrum and diffuse nodular appearance of gastric body with friability on contact reminiscent of linitis plastica (Image 2). Biopsies taken during EGD were positive for KS and HHV-8. DISCUSSION: GI involvement of KS is commonly asymptomatic but can also present with bleeding, nausea, vomiting, and weight loss. GI KS is an infrequent finding but visceral involvement of KS mandates systemic chemotherapy and is associated with a worse prognosis. As the diagnosis of upper GI KS is made endoscopically, proceduralists must be familiar with its varied appearance. As 20% of GI KS may not have concomitant skin lesions, accurate endoscopic diagnosis has direct effects on disease management.Image 1.: Physical examination showing perioral violaceous papules and plaques.Image 2.: Diffuse nodular appearance of gastric body wall with friable mucosa.

Background Microscopic colitis (MC), a subtype of inflammatory bowel disease, is a chronic condition of unknown etiology. Recent evidence has linked MC with intriguing changes in the stool microbiota, which may be linked to disease pathogenesis. The composition of the mucosal microbiome in patients with MC remains unclear. Methods We performed a cross-sectional study comparing colonic tissue samples from patients with MC to those of healthy controls at the Michael E. DeBakey VA Medical Center. We included adults older than 18 who underwent a colonoscopy with biopsies to evaluate chronic diarrhea. Cases were defined by histology consistent with MC and controls by the absence of histologic disease. We conducted structured chart review to exclude other gastrointestinal diseases and obtain demographic (age, sex, race) and clinical (duration of symptoms and concurrent medications) information for cases and controls. We extracted bacterial DNA from formalin-fixed paraffin-embedded tissue samples and sequenced the v4 region of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering was performed using UPARSE, and OTUs were assigned using the SILVA database. Statistical analysis was performed in QIIME and LEfSe. Comparisons with FDR-adjusted p values of less than 0.05 were considered statistically significant. Results We included 20 MC patients and 20 controls with mean ages of 62 and 54, respectively. Most cases were White (95%), 60% had symptoms for greater than 12 months, and 50% were taking PPIs and NSAIDs at the time of their diagnosis. Compared to controls, MC patients had a significant increase in the proinflammatory sulfur-reducing bacterial family Desulfovibrionales. The Coriobacteriaceae family, abundant in the healthy gut, was significantly decreased in MC cases. There was also an increase in the genus Actinomyces in MC patients on PPI and an increase in the class Bacilli among those taking NSAIDs. Discussion Patients with MC have an increase in the proinflammatory family Desulfovibrionales. Actinomyces and Bacilli were associated with medications (PPI and NSAID) known to increase the risk of MC. Our findings may have important implications for understanding the pathogenesis of MC.

Background: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). However, there are few data comparing outcomes between IBD and non-IBD-associated CRC. Methods: Retrospective cohort study of patients with CRC identified from the Veteran Affairs (VA) Central Cancer Registry from 1998 to 2012 linked to national VA administrative claims to identify patients with IBD using a previously validated algorithm. The association between IBD status and stage of disease and overall risk of death were evaluated using multivariable logistic and Cox regression, respectively. Results: Among 34,570 CRC patients, 217 had IBD. IBD patients were significantly younger for both colon and rectal cancer. IBD patients who developed rectal cancer were significantly more likely to present with locally advanced or metastatic disease (P = 0.007), but there was no difference in stage among patients with colon cancer. This difference persisted after multivariable adjustment (overall-odds ratio [OR] 1.40, 95% confidence interval [1.03-1.90]; colon-OR 1.22 [0.84-1.78]; rectum-OR 2.04 [1.22-3.40]). Total colectomy was more commonly performed among IBD patients. Overall, IBD was associated with a 52% increased risk of death (hazard ratio 1.52 [1.21-1.91]). Conclusions: Although IBD is associated with more advanced stage at diagnosis for rectal cancer, it is associated with a worse survival primarily in patients with colon cancer. Further work is needed to better understand the reason for these observed differences between IBD and non-IBD patients and to better delineate the impact of endoscopic surveillance on CRC care and outcomes in IBD patients. Published by Elsevier Inc.

INTRODUCTION: Amyloidosis is a rare condition caused by the extracellular deposition of protein fibrils. The presence of these proteins in organs and tissues interferes with their ability to function normally. Amyloidosis commonly causes cardiomyopathy, neuropathy, and proteinuria. Gastrointestinal involvement in amyloidosis is less common and can either be isolated to the GI tract or systemic. When the GI tract is involved, patients typically present with symptoms such as bleeding, diarrhea, constipation, and steatorrhea. We present a case of gastrointestinal amyloidosis with rapidly progressive dysphagia as the presenting symptom. CASE DESCRIPTION/METHODS: A 70-year-old man presented with progressive dysphagia over one month. At first he noted difficulty swallowing meat. However, in the days leading up to admission he found that it took more effort to swallow liquids. He denied difficulty initiating swallow and endorsed a globus sensation after swallowing. Laryngoscopy was unremarkable. On EGD, the esophagus and duodenum appeared normal. Mild gastric erythema was present and biopsies were obtained of the esophagus and stomach. The esophageal biopsies were consistent with AL (lambda)-type amyloidosis. Congo red-positive amyloid deposits were present. Liquid chromatography tandem mass spectrometry (LC MS/MS) detected a peptide profile consistent with this diagnosis. Biopsies from the stomach and duodenum also had increased lamina propria fibrosis consistent with amyloidosis. Several weeks after this diagnosis was made, the patient expired due to an unrelated cause. DISCUSSION: AL amyloid is the most common type of amyloidosis however it very rarely involves the GI tract. Biopsy proven disease is found in approximately 8% of cases with only 1% of patients experiencing symptoms at the time of diagnosis. AL amyloidosis is typically associated with systemic disease due to an underlying clonal plasma cell proliferation or B-cell lymphoma. The patient described expired before further work-up could be completed. Dysphagia is an uncommon symptom of gastrointestinal amyloidosis and very few cases have been reported in the literature to date. Our case demonstrates an unusual presentation of a rare illness.

Non-adherence to Infliximab (IFX) is associated with an increased risk of anti-drug antibodies which can lead to loss or response. We performed a retrospective review of IFX use among Veterans with inflammatory bowel disease (IBD) with the aim of quantifying adherence and assessing the relationship between adherence and outcomes such as persistence on IFX, dose escalation, and hospitalizations. The Veteran’s Health Administration (VHA) electronic medical records of 4 institutions were reviewed to identify patients newly initiated on IFX for IBD between 2000–2017. Patients were excluded if they received <4 infusions or if they were on IFX prior to receiving care in the VHA system. Adherence to IFX was assessed as receiving ≥7 infusions within 1st year and ≤7 day cumulative delay during induction infusions. Descriptive statistics were calculated using SAS 9.4. During the study period, 95 patients were initiated on IFX in the VA who met our inclusion criteria. Of these patients, 78 (82.1%) had a diagnosis of Crohn’s disease with a mean age of 45.3 years (± 10.9) and 88.4% were male. Over 9 infusions, 47 (49.5%) were escalated. Of the 95, 76 underwent ≥7 infusions and of these 87.4% were adherent as defined by 7 infusions within 1 year. A delay during induction was common (23.2%). Patients with delays during induction were more likely to stop the drug before 9 infusions (40.9% vs. 16.4%, p=0.02) and more likely to undergo escalation (72.7% vs. 42.5%, p=0.01). There was no difference in hospitalization rates between those who were adherent or not adherent. No predictors of delays during induction could be identified. While adherence to IFX using the definition of 7 infusions in 1 year was high, 23.2% had significant delays during induction. Since patients who missed days during induction were less likely to persist and more likely to be escalated, more attention should be focused on adherence during this critical time period.