Introduction

Colorectal polyposis, characterized by more than 10 adenomas, indicates a higher risk of malignancy and necessitates more frequent screening and genetic assessment. However, there are still a large number of polyposis patients with negative genetic test results. This study aimed to explore the risk genetic variants associated with non-hereditary colorectal polyposis through a genome-wide association study (GWAS).

Aims & Methods

Among patients who underwent colonoscopy at a single referral university hospital from January 2012 to September 2021, a total of 638 patients with 10 or more biopsy-proven cumulative polyps on colonoscopies and without genetic mutations or family history related to colorectal polyposis were included in this study. For the control group, a total of 7087 people who underwent colonoscopy for the purpose of health check-up at the Korea Medical Institute and were normal at least twice in a row were included. To find susceptible loci to non-hereditary colorectal polyposis, GWAS was performed and a genome-wide p-value threshold of 5 × 10^-7 was set to assess statistical significance.
We compared the genetic differences between two groups of patients with non-hereditary colorectal polyposis: those with 10 or more polyp recurrences observed during follow-up colonoscopies and those without such recurrences. We utilized SNPs that were identified as risk variants for non-hereditary colorectal polyposis in this GWAS. For each SNP, we defined the risk allele as the allele associated with increased risk of non-hereditary colorectal polyposis as identified in this GWAS. Genotypes were coded as 0, 1, or 2 based on the number of risk alleles identified at each SNP. We used a polytomous logistic regression model to identify SNPs that significantly increased the risk of polyp recurrence compared to the group without recurrence. Results of all regression analyses were adjusted for age, sex, BMI, smoking history, alcohol consumption history, family history of cancer, history of cancer other than colorectal cancer, comorbidities, and history of medication use.

Results

A total of 71 risk variants were discovered, which were new single-nucleotide polymorphisms (SNPs) not found in previous GWAS associated with colorectal cancer and polyp (Figure 1). 5 genes (UPF3A, BICRA, CBWD6, PDE4DIP, ABCC4) nearest or overlapped with 7 SNPs (rs566295755, rs2770288, rs1012003, rs201270202, rs71264659, rs1699813, rs149368557) previously reported directly or indirectly related to the development of colorectal cancer were proven to be risk variants significantly associated with non-hereditary colorectal polyposis. In addition, two new genes (CNTN4, CNTNAP3B) that have not previously been reported to be associated with colorectal cancer or polyp were newly identified.
The SNP rs149368557 was identified as being significantly associated with an increased risk of polyp recurrence in non-polyposis hereditary colorectal cancer (p-value: 0.049, odds ratio: 2.991, 95% confidence interval: 1.006–8.899).

Conclusion

In this study, we found 71 novel risk variants associated with non-hereditary colorectal polyposis. The SNP rs149368557 was identified as being significantly associated with an increased risk of polyp recurrence in non-hereditary colorectal polyposis. The risk variants and genes discovered in this study might be utilized as novel targets to prevent colorectal cancer in the future.

Introduction

The use of artificial intelligence (AI) systems for decision support has recently gained great popularity in the medicine.¹ However, recent studies have shown possible limitations emerging from the interaction between humans and AI. Among these, the term “automation bias (AB)” refers to human errors deriving from over-relying on AI’s false alarms such that the human changes a correct initial interpretation.² AB is poorly investigated in the medical field and was never tested in the gastroenterological setting.

Aims & Methods

The aim of the study was to investigate the impact of AI on human diagnostic performance in gastrointestinal endoscopy, including AB.
Ninety high-quality endoscopic videoclips (16 seconds) extracted from small bowel (SB) capsule endoscopy (N=60) and proctosigmoidoscopy (N=30) were edited with the addition of a mock AI system designed with diagnostic accuracy, sensitivity and specificity of 80%, 86% and 75%. The ground truth was settled on the agreement of 9 established experts about the presence of SB lesions with significant hemorrhagic potential according to the Saurin classification (30 videoclips), inflammatory lesions relevant for the diagnosis of SB Crohn's disease according to the Lewis score (30 videoclips) and assessing the Ulcerative Colitis (UC) Endoscopic Index of Severity (30 videos). The videoclips were randomly divided into three sessions and submitted around Europe to fully trained endoscopist, trainees and endoscopic technicians. Participants were instructed to the accuracy measures of AI annotations and scored each videoclip first without, then with AI support. Participants’ performances with and without AI were calculated. Subgroup analyses were made after stratification by participants’ experience level in each endoscopic setting and test performances.

Results

A total of 12.660 videoclips (both with and without AI) were visualized in 422 sessions (182, 118 and 122 participants completed the first, second and third session, respectively). A strong and significant difference between the respondents' performance (N=281) when they were unaided by AI (average accuracy (M)=0.78, [0.77, 0.79] and when they were supported by the AI (M=0.81, [0.80, 0.82], paired t-test, t(276)=11.2, p<0.001) was found. Size effect and the evidence in favour of a significant positive effect of AI were large, 0.67 (Cohen's D) and very large (Bayes Factor>100), respectively. Interestingly, no significant difference between trainees and specialists both in regard to their performance, either unaided, M=0.77 [0.74, 0.79] vs M=0.78, [0.77, 0.79] or aided M=0.80 [0.78, 0.82] vs M=0.81 [0.80, 0.82] and their accuracy improvement (M=0.03, [0.02, 0.05] vs M=0.03, [0.02, 0.04] (unaided t-value=-0.89, p=0.37; aided t-value=-0.69, p=0.49, difference t-value=0.54, p=0.59) were found. A strong leveller effect emerged, with low-performers improving their accuracy much more than top-performers (average improvement 5%, [0.04, 0.06] vs 1%, [0.00, 0.02], paired T test, t=6.53, p<0.001). Nine percent of the final decisions involved disregarding correct AI advice in favour of incorrect human judgment, while AB occurred in 2% of cases.

Conclusion

In this study, the application of AI to assess SB bleeding, SB inflammatory lesions, and UC activity brings significant improvement in diagnostic accuracy, with the benefit appearing to be greater in the low-performers. However, in rare cases, AI may induce diagnostic errors due to AB. Future studies directly evaluating the impact of AI in real-life clinical settings are needed to confirm these data.

References

1. Cabitza F, Campagner A, Angius R, Natali C, Reverberi C. 2023. AI Shall Have No Dominion: on How to Measure Technology Dominance in AI-supported Human decision-making. In Proceedings of the 2023 CHI Conference on Human Factors in Computing Systems (CHI '23). Association for Computing Machinery, New York, NY, USA, Article 354, 1–20. https://doi.org/10.1145/3544548.3581095
2. Reverberi, C., Rigon, T., Solari, A. et al. Experimental evidence of effective human–AI collaboration in medical decision-making. Sci Rep 12, 14952 (2022). https://doi.org/10.1038/s41598-022-18751-2

Introduction

The Mediterranean diet identified as a priority because it contributes to the normalization of key metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD). However, it is necessary to take into account the possibilities of following such a diet and the nutrigenetic characteristics of patients in different regions of the world. Purpose: to study the effect of nutrigenetic parameters in patients with NAFLD on the effectiveness of non-drug treatment.

Aims & Methods

Purpose: to study the effect of nutrigenetic parameters in patients with NAFLD on the effectiveness of non-drug treatment. 105 patients (55 men and 50 women) with NAFLD were examined. In patients, the features of eating disorders (ED) were studied (DEBQ questionnaire), nutrigenetic parameters - 5 polymorphisms: Pro12Ala of the PPARG2 gene (rs1801282), 101027 of the ADRB2 gene (rs1042714) and Arg16Gly of the ADRB2 gene (1010282); (rs4994) and Thr54Ala of the FABP2 gene (rs1799883) associated with the risk of metabolic disorders.

Results

Two polymorphisms associated with disorders of the ED gene (Pro12Ala PPARG2 and Trp64Arg ADRB3) were identified. Sex differences in the frequency of genotypes of the Pro12Ala polymorphism of the PPARG2 gene were not found (pχ2 = 0.90). 83.6% of men and 82.0% of women were carriers of the PPARG2 gene polymorphism (OR=1.10, CI=0.24-4.99) of the Pro12Pro genotype (AB=1.10, men and 16.7% of women of the genotype Pro12Ala (OR = 0.91, OR) = 0.20 - 4.13). The distribution of genotypes and allelic variants of the ADRB3 gene polymorphism had significant differences (px2 = 0.05). The Trp64Trp genotype of the ADRB3 gene polymorphism were found in 80.0% of men and 55.0% of women, the Trp64Arg genotype in 20.0% of men and 32.5% of women, the Arg64Arg genotype was found only in women. An analysis of the distribution of 64Trp and 64Arg alleles by sex using a multiplicative model showed that the significance of the association of the minor female 64Arg allele was confirmed by an odds ratio of 3.13 (CI = 1.01–9.70) versus 0.32 (CI = 0.01–9 .70). 10 - 0.99) for the minor allele. A significant association (px2 = 0.02) of the protective minor allele 12Ala with emotionally restrictive types of ED (OR = 0.11, CI = 0.10 - 0.97) was established, while the external type of oblique ED was associated with the carriage of the main allele polymorphism 12Pro of the Pro12Ala PPARG2 gene (OR = 8.71, CI = 1.03-7.66). Analysis of the distribution of 64Trp and 64Arg alleles depending on the type of EP disorder showed a significant association (px2 = 0.006) of the metabolically unfavorable minor 64Arg allele with the external type of ED disorders (OR = 5.53, CI = 1.48-20.68), while emotional and restrictive types were associated with the carrier of the main 64Trp allele (OR = 0.18, CI = 0.05-0.68). In patients with NAFLD, the external type of ED disorder prevails (p<0.05).

Conclusion

To increase the effectiveness of non-drug treatment, one should take into account nutrigenetic features - the presence of ProARA2 polymorphisms of the PPARG2 gene and Trp64Arg of the ADRB3 gene, which are associated with the peculiarities of nutrient metabolism and malnutrition in patients with NAFLD.

Disclosure

Nothing to disclose

Clinical Case Summary

A 74-year-old, female patient was referred to the study center for pancreatic cysts. Magnetic resonance imaging revealed multiple pancreatic cysts up to 15 mm in size distributed from the pancreatic head to the pancreatic tail and enlargement of the main pancreatic duct diameter to 8 mm. T1- and T2-weighted imaging demonstrated showed a 10 mm mass with iso-intensityin the main pancreatic duct in the pancreatic body with diffusion restriction on diffusion-weighted imaging. Endoscopic ultrasonography also demonstrated a mass located in the main pancreatic duct in the pancreatic body, but determining whether the tumor was located in the pancreatic duct or was an extension of the intraparenchymal lesion into the main pancreatic duct was difficult. On contrast-enhanced abdominal computed tomography, the mass was difficult to identify as a lesion because it showed the same contrast as the surrounding pancreatic parenchyma. Endoscopic retrograde choangiopancreatography revealed enlargement of the duodenal papillary entrance, mucus discharge, and a mass-like, translucent image with an irregular surface in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound-guided fine needle aspiration led to the diagnosis of adenocarcinoma, and a distal pancreatectomy was performed on the assumption that the lesion derived from IPMN. Pathological analysis led to the diagnosis of IOPN consisting of papillary cells with an eosinophilic cytoplasm, positive immunostaining for MUC5AC and MUC6, and partially positive staining for MUC1 and HepPar-1. The mass was determined to be within the pancreatic parenchyma by comparing a resection specimen with preoperative images. Fusion gene analysis revealed the presence of ATP1B1-PRKACA, confirming the diagnosis of IOPN.
It is important always to bear in mind the possibility of IOPN if pancreatic cysts are observed. IOPN is relatively rare, and more cases are needed for a better understanding of this disease.

References

Aatur D. Singhi, Laura D.Wood, Emma Parks, Michael S.Torbenson, Matthaus Felsenstein. Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct : Gastroenterology. 2020 Feb ; 158(3) : 573-582.
Eriko Ikeda. Histological Classification of Intraductal Papillary Mucinous Neoplasms of the Pancreas : Journal of Biliary Tract & Pancreas. 2020 ; 41(1) : 27-31

Clinical Case Summary

Introduction: Superior Mesenteric Vein (SMV) Thrombosis accounts for only 5% of all cases of intestinal ischemia. As opposed to acute mesenteric ischemia secondary to an arterial thrombus which has a more drastic presentation, SMV thrombus typically presents with non-specific signs and symptoms. Rarely, when venous congestion leads to bowel wall edema which can consequently head to intestinal obstruction.
Case presentation: We present the case of a 47-year-old male presenting with severe generalized abdominal pain and vomiting. Abdominal CT findings were suggestive of small bowel obstruction and venous thrombosis. CT angiogram confirmed SMV thrombus which was visualized as severe narrowing of the SMV at the midabdomen a few centimeters above the umbilicus, with consequent congestion and decreased contrast enhancement proximal to the area of narrowing. The patient was initially managed conservatively with anticoagulation, however the patient did not improve clinically. Since there were no signs of infarction or peritonitis that would warrant immediate surgical intervention, an alternative approach using endovascular technique was attempted. The patient underwent SMV stenting which subsequently relieved the obstruction.

References

1. Treatment of superior mesenteric and portal vein thrombosis with direct thrombolytic infusion via an operatively placed mesenteric catheter; https://pubmed.ncbi.nlm.nih.gov/1527918
2. A systematic review of the management of acute superior mesenteric vein thrombosis in adults https://mednexus.org/doi/full/10.1097/JP9.0000000000000051
3. Naffouj S, Al-Shammari M, Salgia R. Treatment of colonic varices with a superior mesenteric venous stent: a case report describing a unique approach. Gastroenterol Rep (Oxf). 2021 Feb 4;9(6):597-600. doi: 10.1093/gastro/goab003. PMID: 34925858; PMCID: PMC8677559
4. Vekariya P, Daneti D, Senthamizhselvan K, et al. (June 14, 2021) Acute Intestinal Obstruction as an Initial Presentation of Mesenteric Venous Thrombosis. Cureus 13(6): e15652. doi:10.7759/cureus.15652

Disclosure

None