United States

Background
Colorectal cancer is one of the leading causes of cancer in the United States and there are estimated to be over 150,000 new cases in 2024. Although the rate of new cases of colorectal cancer has decreased over the past few decades, some populations are experiencing increased incidence rates. Native American and Alaskan Native (NA/AN) populations are known to have higher rates of colorectal cancer when compared to whites. In this study we examined the regional and gender related rates in recent new cases of colorectal cancer.

Methods
A retrospective cohort study was performed on 28,609 patients from 2016 to 2020 using the CDC and NCI 2022 submission data from years 1999-2020. Analysis of NA/AN patients was restricted to areas where healthcare services were provided by the Indian Health Service (IHS). Analysis of white patients was restricted to those who lived in IHS Purchased/Referred Care Delivery Areas, which consisted of counties containing NA/AN reservations. Rates were age-adjusted to the US standard population in 2000.

Results
The overall rate of colorectal cancer in the United States was 35.1 per 100,000 in whites and 50.1 per 100,000 in NA/AN, a 1.42 times higher rate in NA/AN. The rate in white males was 39.8 per 100,000 and 57.3 per 100,000 in NA/AN males, a 1.44 times higher rate in NA/AN males. The rate in white females was 31.1 per 100,000 and 44.3 per 100,000 in NA/AN females, a 1.42 times higher rate in NA/AN females. The highest regional rate difference in NA/AN versus whites was in the Alaska region, where NA/ANs had a 2.58 times higher rate of colorectal cancer compared to whites (90.3 vs 35.0 per 100,000). The highest gender-related rate difference was seen in the Alaska region, where NA/AN females had a 2.77 times higher rate of colorectal cancer compared to white females (87.2 vs 31.5 per 100,000).

Conclusion
Our study has demonstrated that Native American and Alaskan Natives have much higher rates of colorectal cancer compared to whites. This rate is even higher in certain regions, particularly the Alaska region. This finding suggests that much more research needs to be done about these regional differences, particularly in Alaska, to determine if any genetic factors or access to care issues exist in these areas. Physicians in these higher risk areas must be aware of these findings and ensure that their patients get colorectal cancer screening appropriately.

AMA Research Challenge 2024 

Elevated Rate of Colorectal Cancer in the Native Populations in 
Alaska Compared to in Other Regions

poster

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Introduction 
Non-alcoholic fatty liver disease (NAFLD) can involve advanced fibrosis and has implications with cardiovascular and liver disease related mortality. The definitive diagnosis of NAFLD and non-alcoholic steatohepatitis (NASH) is liver biopsy. We aim to evaluate and compare the accuracy of the fibrosis-4 (Fib-4) index in predicting hepatic fibrosis among young and adult age groups with biopsy proven NAFLD or NASH. 

Methods 
We conducted a retrospective chart review to identify patients who were 18 years of age and over who underwent a liver biopsy between 2020 and 2023. Data was collected on patient demographics, comorbidities, and liver biopsy findings. Stage of fibrosis was determined using the Metavir Scoring System (F0-F4). Exclusion criteria for the study focused on identification of other causes of acute or chronic liver disease. Patients were split into two age groups: young (18-44 years) and older (45 years or more). All statistical analyses were conducted using Stata V.18 to compute means and frequencies of patient data to determine accuracy of Fib-4 index. 

Results 
A total of 254 patients were included with a mean age of 53.1 years, 62.2% females, and 80.3% Caucasians. The majority of patients had metabolic syndrome (50.8%), obesity (75.2%), hypertension (62.6%), and dyslipidemia (64.9%). Fib-4 index was interpretable in 171 out of 254 patients, out of which 28.7% were predicted to have advanced fibrosis. Fib-4 index was indeterminate in the remaining 83 patients out of whom 6% had advanced fibrosis on liver biopsy. Overall, Fib-4 index had low sensitivity (10%) and higher specificity (65.7%) in predicting advanced fibrosis with the best outcomes seen in the young age group (Table 1). Area under the receiver operating characteristic (AUROC) curve analysis showed unsatisfactory accuracy of Fib-4 index in the overall sample and older age group with AUROC of 52.6% and 40.9%, respectively. There was good accuracy for the young age group with AUROC of 81.6%. Overall, the Fib-4 index had a better negative predictive value, indicating better accuracy with predicting non-advanced fibrosis cases. 

Conclusion
Our study suggests that there is utility of interpretable Fib-4 index scores in increasing the pre-test probability of non-advanced fibrosis (F0-F2) in both the young and older age groups. Liver biopsy may be needed to exclude advanced fibrosis. Those with indeterminate Fib-4 index scores will benefit from further investigation to determine the degree of liver fibrosis. 







Evaluation of Accuracy of Fibrosis-4 (Fib-4) Index in Various Age Groups with Biopsy-Proven NAFLD or NASH: A Tertiary Health Care Network Retrospective Study

Background: Lactulose is an osmotic laxative used to treat hepatic encephalopathy (HE) in patients with cirrhosis. Here, we examined lactulose-induced hypernatremia (HN) in patients with cirrhosis being treated for HE.

Methods: We identified all patients admitted with cirrhosis and HE at our institution from 1/1/18 to 12/31/23. Treatment details and complete clinical data were abstracted. Matching, followed by propensity score calculation, was used to control for the severity of underlying liver disease using a case control study design (HN patients were matched to patients with HE, but without HN). The primary endpoint was hospital mortality, and secondary endpoints included total and rectal lactulose dose (g), time to mental status resolution, and hospital length of stay (LOS). 

Results: Among 6,742 patients admitted with cirrhosis, 1,809 (27%) were admitted with HE as the primary diagnosis. Of these, 158 patients with liver transplantation were excluded. Of the remaining 1,651 patients, 347 patients (21%) had a sodium level > 145 mEq/L, and 106 patients (6%) had a sodium ≥ 150 mEq/L (hypernatremia (HN) group). Cirrhosis was most commonly caused by alcohol or MASH; the median MELD was 24. In HN patients, the median admission sodium was 137 and the peak was 152; all patients received lactulose. The median average daily lactulose dose to peak sodium was higher in the HN group than in controls (85 vs. 38 g, p<0.001). 67 (63%) patients in the HN group received rectal lactulose and had a median sodium level of 154 mEq/L. Rectal lactulose was the strongest independent predictor of hypernatremia (OR = 4.469, p<0.001). The time to mental status resolution and LOS were 2.4 and 2.4 times longer, respectively, in the HN than in the control group (both p<0.001). Overall, 64 patients (60%) in the HN group died compared to 37 (35%) in the group without HN (p<0.001). Hypernatremia was an independent predictor of mortality (OR = 3.596, 95% CI 1.712 – 7.552, p <0.05).

Conclusion: Lactulose-induced HN is associated with poor outcomes, and patients receiving rectal or high dose lactulose had a remarkably high mortality rate. The data lead us to urge careful monitoring of sodium levels in patients with HE who are treated with lactulose.

Lactulose-induced hypernatremia in cirrhotic patients with hepatic encephalopathy

Background
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, largely due to late diagnosis, high rates of tumor recurrence, and resistance to conventional chemotherapy. Despite advancements in surgical techniques and chemotherapeutic regimens, the prognosis for HCC patients remains poor. Consequently, there is an urgent need for novel therapeutic strategies. The identification of molecular targets has revolutionized treatment in various malignancies, such as lung cancer, highlighting the necessity for similar approaches in HCC. Paternally expressed gene 10 (PEG10), an imprinted gene located on chromosome 7, has been found to be overexpressed in a variety of human cancers, particularly those affecting the gastrointestinal tract. This study aims to investigate the expression of PEG10 in HCC and evaluate its potential as a prognostic biomarker.
Methods
To assess the expression levels of PEG10, mRNA was quantified in human normal liver cell lines and HCC cell lines using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A recombinant plasmid containing PEG10 was utilized in a tumorigenicity assay in a nude mice model to evaluate the in vivo tumor-promoting effects of PEG10. Furthermore, PEG10 mRNA levels were analyzed in a human HCC cDNA array, which included samples from patients with various stages of HCC, inflammatory liver diseases/ non-tumor tissues.
Results
Our findings indicate that PEG10 expression is weak in normal liver cells but significantly elevated in HCC cell lines. In vivo experiments demonstrated that PEG10 enhances tumorigenicity compared to control groups, suggesting its role in promoting tumor growth. Additionally, analysis of the human HCC cDNA array revealed significant differences in PEG10 mRNA levels between early-stage and late-stage HCC, inflammatory liver disease and HCC, and non-tumor and tumor tissues.
Conclusion
PEG10 plays a critical role in the pathogenesis of hepatocellular carcinoma, with augmented expression specifically in HCC and not in benign liver conditions. This differential expression suggests that PEG10 may serve as a valuable diagnostic marker, particularly for well-differentiated HCC. Furthermore, the tumorigenic properties of PEG10 highlight its potential as a molecular target for future therapeutic interventions in HCC. Continued research into the mechanisms regulating PEG10 expression and function could pave the way for novel, targeted treatment strategies, ultimately improving outcomes for patients with HCC.

PEG10, a potential target biomarker in hepatocellular carcinoma

Since the beginning of the COVID-19 pandemic, there have been over 775 million reported cases worldwide. A significant proportion of these patients suffer from long-COVID, experiencing symptoms such as severe fatigue, myalgias, and gastrointestinal (GI) dysfunction. Both chronic post-infectious disorders and GI conditions are linked to persistent sympathetic nervous system activation (PSA), however the specific interactions between long-COVID and GI disorders requires additional investigation. We hypothesized that individuals with pre-existing GI disorders would have higher rates of long-COVID. We also postulated that long-COVID increases the risk for GI disorder diagnosis.

We utilized de-identified electronic health record data from TriNetX, a global health research network with over 124 million patients. We constructed queries to identify subjects with upper functional (UF), lower functional (LF), upper structural (US), or lower structural (LS) GI disorder diagnoses. Afterwards, we analyzed the prevalence of long-COVID (defined as new malaise and fatigue symptoms lasting ≥1 month post-infection and not present in the previous 4 years) in patients with and without GI conditions. Additionally, we compared the rates of GI symptom development in patients with and without long-COVID diagnosis. Changes in GI disorder incidence in the 4 years before and after the pandemic onset (January 1, 2020) were also examined. Data were evaluated with chi-squared analysis.

Subjects with long-COVID had higher pre-COVID GI disorder prevalence compared to subjects without long-COVID [UF (1.12%), LF (2.33%), US (13.13%), and LS (0.80%)] (p<0.001). There was also a 0.65%, 0.83%, 4.93% increase in UF, LF, and LS post-COVID diagnoses prevalence, respectively, and a 5.77% decrease in US diagnoses (p<0.001) between patients with long-COVID and without long-COVID. In the general population, post-pandemic, the prevalence of LF and US diagnoses increased by 0.14% and 0.38% (p<0.001), while UF and LS diagnoses decreased by 0.015% and 0.17% (p<0.001). 

These results suggest that GI disorders, especially upper structural and functional GI disorders, pose a higher risk for long-COVID symptoms. However, the nuanced prevalences of GI conditions following long-COVID reflect a need for further research on the long-term impacts and mechanisms of PSA-mediated GI tract dysfunction following SARS-CoV-2 infection.

The Impact of Gastrointestinal Conditions on Long-COVID: Insights from a Global Health Network

Background: Colorectal Cancer (CRC) is the third most common and deadly cancer in the United States (U.S.). Widespread adoption and utilization of screening programs and patient education have likely contributed to the decline in CRC incidence, but morbidity and mortality still remain high. Racial disparities at every step in the cancer care continuum have been well-reported among large U.S. cohort studies, with Black patients experiencing worse outcomes. Care access, screening enrollment, and timely receipt of cancer treatment are known contributing factors. Our project’s aim was to investigate if racial disparities in CRC care exist in the more-equal access health care system of the national Veterans Affairs (VA) system.

Methods: In this retrospective cohort study, patient data was collected from the VA Central Cancer Registry. All veterans with incidental or first-time diagnosis of CRC from January 2017 to December 2021 were included and categorized as Non-Hispanic White (White) or Non-Hispanic Black (Black) race. Patients of other races were excluded given limited sample size.

Variables of interest included: sociodemographic factors (age, sex, VA priority group, rural vs. urban); BMI; tobacco and alcohol use; diabetes mellitus; and Deyo-Charlson comorbidity score. Study outcomes included stage at diagnosis (American Joint Committee on Cancer staging system), receipt of cancer treatment, and survival. Treatment included surgical resection, chemotherapy, or radiation therapy in any or no combination.

Results: A total of 8,021 patients with CRC (76.3% White, 23.7% Black) were identified, with a median age of 71 (IQR 66-76). Black patients were more likely to be younger at time of cancer diagnosis (median 68 years) compared to White patients (median 71 years; p-value<0.05). On multivariable analysis, after adjusting for the above listed variables of interest, there were no statistically significant differences in the following outcomes by race: stage at diagnosis (odds ratio (OR) 0.98; 95% confidence interval (CI) 0.87-1.11); receipt of any cancer treatment (additionally adjusted for stage: OR 0.86; 95% CI 0.74-1.00); or overall survival (additionally adjusted for stage and treatment: OR 0.97; 95% CI 0.87-1.08).

Conclusion: The well-described racial disparities in timing of cancer diagnosis, receipt of care, and survival seen in patients with CRC throughout the U.S. are not observed in the more equitable VA health care system. These findings highlight that equal access to care, including screening and surveillance programs, largely eliminates racial disparities in CRC outcomes. Adoption of similar systematic efforts in health care systems outside of the VA could lead to reduction in cancer care disparities.

The Impact of Race on Colorectal Cancer Outcomes in the Nationwide Veterans Affairs Health Care System


Background: The COVID-19 pandemic led to a decrease in colorectal cancer (CRC) screening. Preceding the pandemic, CRC screening rates had shown an increase across all racial groups. However, post- pandemic, there has been a decline in screening rates among AA, which will exacerbate existing disparities. 

Objective: This study aims to analyze CRC screening data collected before and after the COVID-19 pandemic to understand the distribution of pandemic- associated screening decreases on CRC disparities in the AA population. 

Methods: A systematic literature search through PubMed, Embase, and Google Scholar was done using keywords “Colorectal cancer screening”, “Covid 19”, “Colorectal Cancer”, “Colonoscopy”, and “African Americans”. The initial search resulted in 367 articles, of which nine studies in the USA (Ohio, Missouri, NYC, California) met the inclusion criteria (adults, 18+, English). We assessed patient colonoscopy records and reviewed the literature to correlate the influence of factors such as reallocation of health resources, financial burdens, decreased advocacy, and psychosocial factors on CRC screening. 

Results: African Americans had a 47% decrease (from 50,129 to 26,713) in CRC screening colonoscopy from 2019 to 2020, whereas Whites had a 39% decrease (from 403,596 to 244,414). Spanish patients had a 31% decrease (from 19,842 to 13,615). Quartile 1 HHI had a 36% decrease (from 455 to 290). Quartile 4 HHI had a 33% decrease (from 166 to 111). Quartile 1 education had a 18% decrease (from 1,905 to 1,557). Quartile 4 education had a 14% decrease (from 2,237 to 1,935). Patients from low SVI had a 20% decrease (from 23,136 to 18,402). High SVI patients had a 22% decrease (from 25,859 to 20,064). 

Conclusion: The pandemic led to an overall decrease in colonoscopies that was significantly more pronounced among AA, especially those from low socioeconomic backgrounds. To address this, enhanced screening programs are essential to mitigate the impact of pandemic-related delays or cancellations on screenings. These efforts are crucial to counteracting the exacerbation of existing disparities tied to socioeconomic status and healthcare access. 


Understanding and Addressing Pre- and Post- COVID-19 Disparities in CRC Screening and Outcomes among African Americans

Background
Protocolizing pain management perioperatively can reduce opioid exposure in children. Our group designed a multi-modal, opioid free pain management protocol with intent to decrease opioids in children undergoing hernia repair. The purpose of this study is to evaluate protocol usage and outcomes after implementation.
Methods
The protocol utilizes non-opioid analgesics, nerve blocks, and child life perioperatively. Patient characteristics, pre plus intra-operative (PIO) and post-operative (PO) opioid use, and protocol adherence were compared pre- and post-implementation. Adherence was stratified by level of opioid use - high (no PIO or PO use), medium (no PIO but + PO use), and low (+PIO, +PO use).
Results
After seven months, 175 cases were analyzed with 103 pre- and 72 post-implementation. There were no significant differences in demographics or hernia type. The median age and weight were 4.00 years (IQR 1.60, 6.00) and 17.60 kg (IQR 11.97, 24.90). Post-implementation, there was a significant increase in nerve blocks (37 (51.4%) vs. 6 (5.8%), p<.0001) and PIO non-opioid analgesics (64 (88.9%) vs. 24 (23.3%), p<.0001). We also saw a significant decrease in PIO opioids (8 (11.1%) vs. 89 (86.4%), p<.0001). Additionally, we noted a significant increase in PO non-opioid pain medications (38 (52.8%) vs. 34 (33%), p=.012). And again, there was a significant decrease in PO opioid usage in the post-implementation group (22 (30.6%) vs. 77 (74.8%), p <.0001). Pain scores where not significantly affected. No significant differences were found in PO complications, including nausea, vomiting or respiratory events. 89% of cases had either high or medium protocol adherence.
Conclusion
Our protocol decreased the use of opioids in pediatric patients undergoing hernia repair. Adherence to the protocol was good and resulted in increased use of non-opioid analgesics for pain.

Implementation of an Opioid Free Pediatric Hernia Repair Protocol​

Background. Unintentional injuries are a major cause of death in the US, with unintentional falls being the most significant cause of hospitalization for injury in adults. A known contributor to fall risk is frailty, an age-related state of physiological decline and vulnerability to life stressors. Frailty itself is a significant predictor of fall risk and poor outcomes among both midlife (50 to 64 years old) and older adults (65 years old and greater), yet CDC fall screening guidelines are restricted to older adults. Moreover, the incidence and impact of frailty on outcomes in midlife trauma patients remains understudied. Herein, we assessed the incidence of frailty among midlife trauma patients from 2012 to 2021 and evaluated the impact of frailty on patients’ outcomes.

Methods. The American College of Surgeons Trauma Quality Improvement Program (TQIP) database was used. Trauma patients aged 50 to 64 were included to assess the incidence of frailty over a 10-year period (2012-2021) and the impact of frailty on outcomes in midlife adults. Demographics, injury and hospital information, comorbidities, complications, mortality, and discharge disposition were extracted. Frailty was scored using the modified frailty index-5 (mFI-5). Descriptive statistics were obtained. Frailty incidence was assessed using Poisson regression analysis, and multivariate analyses were performed on 2021 data to assess the impact of frailty on patients’ outcomes. Our primary endpoints were hospital length of stay (LOS) and discharge disposition; secondary endpoints included ICU LOS, days on a ventilator, complications, and mortality. P < 0.001 was considered significant.

Results. The frailty rate of midlife trauma patients more than doubled over the 10-year period, rising from 2.40% in 2012 to 5.09% in 2021. Upon adjustment for demographics, the incidence of frailty in this population increased by 8% per year (incidence rate ratio (IRR)=1.08 [95% CI 1.08, 1.09]). On multivariate analysis adjusting for demographics, insurance status, injury severity score, vitals on arrival, and mode of transportation, frailty was associated with increased risk of death (OR=2.272 [2.006-2.574]), longer hospital and ICU stay (MR=1.458 [1.427-1.489] and MR=1.297[1.242-1.355]), and discharge requiring higher level of care (OR=2.270 [2.163-2.383]).

Conclusion. Frailty has increased in midlife adult trauma patients over the 10-year period studied. Moreover, frailty is associated with several negative health outcomes for midlife adults. These results underscore the need for fall screening in midlife adult patients and further exploration into methods to delay the onset of frailty.

Incidence and impact of frailty in midlife trauma patients

Background
Compared to standard breast conserving surgery (BCS), oncoplastic breast conserving surgery (OBCS) has improved tumor exposure, resection of wider diameters and higher volumes, low rates of recurrence and re-resection, superior cosmetic outcomes, improved patient satisfaction, and decreased postoperative breast volume requiring lower doses of postoperative radiotherapy. OBCS has no difference in postoperative complications or overall survival compared to BCS. Racial disparities exist in both rates of reconstruction after mastectomy as well as complication rate after breast reconstruction, and though the use of OBCS has increased, there is little research investigating how race affects outcomes in OBCS. Our study compares outcomes between Hispanic and Non-Hispanic patients undergoing OBCS at a large community hospital.

Methods
A retrospective review was performed on patients who underwent oncoplastic surgery for breast cancer. Subjects were divided into Hispanic vs non-Hispanic groups. Primary outcomes included need for re-excision, hematoma formation, wound infection, areolar loss, skin necrosis, and delayed wound healing. 

Results
There were 30 patients (73%) in the Hispanic group and 11 patients (27%) in the non-Hispanic group. There was no significant difference in smoking status, hypertension, and diabetes mellitus (p=0.361, p=0.126, p=0.909) between the two groups. The average age in the Hispanic group was 55.8 +/- 9.1 whereas in the non-Hispanic group it was 58.4 +/-8.6 (p=0.416). The average BMI in the Hispanic group was 29.86 +/- 5.3 compared to 30.98 +/- 4.91 (p=0.549) in the non-Hispanic group. The average tumor size in the Hispanic group was 19.6mm +/- 11.1mm compared to 28.8mm +/- 26.4mm (p=0.148) in the non-Hispanic group. 

There were no significant differences in the need for margin re-excision (p=0.969) or post operative hematoma formation (p=0.478). There was no documented post operative wound infection, areolar loss, or skin necrosis in either group. The Hispanic group had significantly lower rates of delayed wound healing (3% in the Hispanic group vs 27% the non-Hispanic group, p=0.022). 

Conclusion
Oncoplastic breast conserving surgery is a valuable option when considering reconstruction for lumpectomy in the Hispanic population. There were no significant differences in demographics or outcomes amongst our two populations, except the Hispanic group had a lower rate of delayed wound healing. This study is limited by its small sample size and a future study with large samples is needed to corroborate these findings. Nonetheless, the benefits of oncoplastic breast conserving surgery cannot be understated and should always be considered for all patients who are appropriate candidates.


Oncoplastic Breast Conservation Surgery Outcomes are Similar Amongst Hispanic and Non-Hispanic Populations at a Large Community Hospital

Objectives: 
Vascular Ehlers-Danlos Syndrome (VEDS) is a rare connective tissue disorder impacting type III collagen production. We aim to delineate the impact of sex on variation in aortopathy, arteriopathy, and mortality among patients with VEDS. 
Methods: 
A cross-sectional analysis of 557 patients with VEDS and COL3A1 pathogenic variants was performed. Primary outcomes were distribution of aortopathy and arteriopathy, and all-cause mortality. Statistical analysis was performed utilizing Student’s t-tests (continuous data) and Pearson’s c2 tests (categorical data). 
Results:  
In the cohort, males were younger (35.8±16.6 vs. 39.2±16.0 years, P=0.017) and had more diagnoses of hypertension (16.1% vs. 8.1%, P=0.003), inguinal hernias (10.9% vs. 0.6%, P<0.001), and spontaneous pneumothoraces (10.5% vs 5.8%, P=0.043) compared to females. There was no difference in age of VEDS diagnosis, family history, or genotype frequency between males and females. Additionally, there were no statistical differences in stroke, myocardial infarction, intestinal perforation, musculoskeletal conditions. Aortopathy and arteriopathy differed between sexes. Aortopathy and arteriopathy was more common in males (74.2% vs. 57.9%, P<0.001), with more involvement of the visceral arteries (29% vs 18.4%, P=0.003), iliac arteries (23.8% vs 14.9%, P=0.008), and aorta (35.5% vs. 18.8%, P<0.001). Females had more frequent carotid cavernous fistulae (CCF, 6.2% vs 0.8%, P<0.001), carotid and great vessel involvement (23.6% vs. 15.7%, P = 0.21), and spontaneous coronary arterial dissection (SCAD, 3.2% vs 0.8%, P=0.05). Males had higher all-cause mortality (32.3% vs 20.4%, P=.001). 
Conclusions:  
Males with VEDS had more visceral artery, iliac artery, and aortic involvement, and females had greater frequency of SCAD, CCF, and carotid and great vessel involvement. These findings are similar to aortic and arterial disease in the general population. Unlike the general population, the age of onset appears to be similar between males and females with VEDS. These findings demonstrate sex-based differences in VEDS manifestation and highlight potential gaps in our understanding of patient risk factors.

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