Introduction

Primary cancer of the appendix is rare and accounts for 0.4% of all gastrointestinal (GI) malignancies with an incidence of approximately 1.2 cases per 100,000 people per year in the United States. Patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC), face increased risk for the development of colorectal dysplasia and carcinoma. Although appendiceal inflammation occurs histologically in 40-80% of colectomy specimens from patients with IBD, appendiceal neoplasms have been reported only infrequently. A direct association between IBD and appendiceal neoplasia, including whether IBD predisposes to the development of appendiceal neoplasia, is unclear.

Aims & Methods

We aimed to describe the clinical characteristics, outcomes, and incidence of appendiceal neoplasms in patients with IBD. Using bioinformatics and natural language processing tools to mine the electronic medical record at our large referral center, all patients > 18-years-old with IBD who had an appendiceal neoplasm were identified from January 1992 to April 2023. Relevant demographic and clinical data were abstracted.

Results

In total, 44 patients were included (61.4% female) with a median age of 53 years at appendix neoplasm diagnosis. A majority had UC (68.2%). Of these, four (13.3%) had backwash ileitis, 27 (90%) had extensive colitis, 12 (40%) had a history of colorectal neoplasia, and 6 (20%) had primary sclerosing cholangitis (PSC). Median duration of IBD prior to appendix neoplasm diagnosis was 17 years. The most common type of appendix neoplasm was adenocarcinoma (36.4%), followed by appendiceal mucinous neoplasm (34.1%), and carcinoid or neuroendocrine tumor (22.7%). The most common presenting symptom associated with diagnosis of appendix neoplasm was abdominal pain/distension (36.4%). Appendix neoplasm diagnosis was made by cross-sectional imaging in a majority of patients (47.7%). The most common type of IBD-directed therapy at the time of appendix neoplasm diagnosis was 5-aminosalicylate (5-ASA) agents (25%). All patients had appendix neoplasm surgically resected. Median appendix neoplasm size was 2.7 cm. The most common histologic tumor grade was grade 1 (31.8%). Two (4.5%) patients had lymph node involvement and 7 (15.9%) patients had metastatic disease at the time of appendix neoplasm diagnosis. Twelve (27.2%) patients received adjuvant chemotherapy. Three patients with UC (6.8%) had recurrence of appendix neoplasm after surgical resection due to peritoneal seeding with a median time to recurrence from initial diagnosis of 78 months.

Conclusion

Appendix neoplasms are more commonly seen in patients with longstanding extensive UC in those presenting with abdominal pain/distension. The most common types of appendix neoplasia included adenocarcinoma and appendiceal mucinous neoplasms. A minority of patients had metastatic disease at the time of appendiceal neoplasia diagnosis. Although the incidence and recurrence of appendix neoplasia in patients with IBD is relatively low, likely related to the small area of mucosa at-risk relative to the colorectum, the recognition of appendix neoplasms as a potential complication of longstanding disease remains unclear. Further studies to compare appendiceal neoplasia in patients with and without IBD are needed to determine if IBD predisposes to the development of this neoplastic complication.

References

1. Ruoff C, Hanna L, Zhi W, Shahzad G, Gotlieb V, Saif MW. Cancers of the appendix: review of the literatures. ISRN Oncol. 2011;2011:728579. doi:10.5402/2011/728579
2. Nehme F, Schneider A, Hamid F. Appendiceal Adenocarcinoma Associated With Ulcerative Colitis. ACG Case Rep J. 2019;6(11):e00255. Published 2019 Nov 25. doi:10.14309/crj.0000000000000255
3. Van de Moortele M, De Hertogh G, Sagaert X, Van Cutsem E. Appendiceal cancer : a review of the literature. Acta Gastroenterol Belg. 2020;83(3):441-448.
4. Orta L, Trindade AJ, Luo J, Harpaz N. Appendiceal mucinous cystadenoma is a neoplastic complication of IBD: case-control study of primary appendiceal neoplasms. Inflamm Bowel Dis. 2009;15(3):415-421. doi:10.1002/ibd.20764

Disclosure

Siri A. Urquhart, M.D.: Discloses no conflicts.
John B. Kisiel, M.D.: Research funding and intellectual property licensed to Exact Sciences.
Nayantara Coelho-Prabhu, M.B.B.S.: Research funding from Fujifilm, Cook Endoscopy, and Alexion Pharma.

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

Walled-off necrosis (WON) may develop in the long-term follow-up after acute pancreatitis due to acute inflammation of the pancreas. It can be managed through endoscopic, percutaneous, or surgical drainage, depending on its clinical condition. The methodology is a topic of debate due to the scarcity of data regarding the progression of asymptomatic WON in patients (1).

Aims & Methods

The aim of this study is to determine the course of asymptomatic individuals who have developed walled-off necrosis (WON) following to an episode of acute pancreatitis over a long time of observation. A retrospective evaluation was conducted on 46 (3.9%) out of 1173 patients diagnosed with acute pancreatitis between June 2016 and December 2019, who developed WON during the follow-up period. Individuals who exhibited symptoms either at the point of diagnosis or during subsequent monitoring had been determined. An analysis was made between the clinical and WON characteristics at baseline of patients who required drainage during follow-up and those who did not.

Results

Out of the total of 46 patients who developed WON, 4 individuals were excluded due to inadequate follow-up data, 9 patients underwent drainage at the time of diagnosis, and 2 patients lost without receiving any form of drainage intervention. During the course of the study, a total of 31 patients were followed up for a mean duration of 25.20±17.40 months. Out of these patients, 10 (32.3%) required interventional intervention within a mean duration of 122.5±152.5 days (Group 1), while the remaining 21 patients (67.7%) were monitored without any intervention. Embolization was executed on a single patient owing to the presence of a splenic artery aneurysm identified in WON, however, drainage was not carried out. Endoscopic drainage was employed in five patients, percutaneous drainage in three patients, and surgical drainage in one patient. The prevalence of biliary etiology was found to be significantly higher in Group 1 compared to Group 2 (90.0% vs 47.6%, p<0.050). The study revealed that the Intra-WON necrosis rate and initial WON size were significantly higher in patients who required drainage at follow-up. The Intra-WON necrosis rate was 68.50±28.50% compared to 38.10±26.90% in the non-drainage group (p<0.05). Similarly, the initial WON size was 125.90±46.60 mm in the drainage group compared to 89.30±45.00 mm in the non-drainage group (p<0.05).

Conclusion

Asymptomatic patients with walled-off necrosis (WON) ought to be managed conservatively through careful ongoing monitoring. It is recommended that the results obtained be validated through extensive longitudinal research.

References

1)Freeman MF, Werner J, van Santvoort HC, et al. International Multidisciplinary Panel of Speakers and Moderators. Interventions for necrotizing pancreatitis: summary of a multi-disciplinary consensus conference. Pancreas. 2012;41(8):1176-1194.

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

Introduction

Crohn's disease (CD) is a chronic inflammatory bowel disease that is characterized by periods of active inflammation followed by periods of remission. Current Methods for defining Crohn's disease activity are limited by various factors including low specificity, bias, invasiveness, high costs, radiation exposure and patient preference. Therefore, an easy, noninvasive, inexpensive, user-friendly, and repeatable method for the assessment of disease activity is warranted. Abnormal body temperature is a natural indicator of illness. Infrared thermography (IRT) can map body surface temperature remotely. With the advent of modern infrared cameras, data acquisition, and processing techniques, it is now possible to have real-time high-resolution thermographic images. Inflamed bowel loops are hyper-vascular and hyperemic, as detected by high doppler signs of intestinal ultrasound and bowel wall contrast enhancement in MRE, and therefore can be detected using IRT.

Aims & Methods

Our aim was to examine thermal imaging using IRT as a noninvasive tool for detecting bowel wall inflammation and disease activity in Crohn's disease patients.
The design of the study was prospective non -interventional. Consecutive adult CD patients referred for an intestinal ultrasound (IUS) exam were included, and adult healthy volunteers were recruited from the general population. Thermal images were captured using a FLIR ONE thermal camera device (FLIR Systems, Inc. Wilsonville, OR, USA) that connects directly to smartphones and utilizes a frame rate frequency of 8.7 Hz, an object temperature range of -20°C to 120°C and thermal sensitivity of 100 mK . Disease activity was defined using IUS. Thermal images of the study population were processed and compared to the results of IUS in all participants. Our novel thermal image processing algorithms extracted texture and shape features of temperature distribution across the skin covering the region of interest (ROI).

Results

The study cohort included 147 CD patients and 14 healthy volunteers. Using IUS, disease activity was found in 100 CD patients (68%). All 14 healthy volunteers had a normal IUS. The average abdominal temperature measured in the Crohn's patients (both active and inactive) was significantly higher than that of the healthy volunteers (30.4⁰±2.9⁰ C vs. 28⁰±2.9⁰ C, p=0.0032). The average abdominal temperature measured in the Crohn's group with the active disease was also found to be significantly higher than that of the healthy volunteers (30.4±2.99 C vs. 28⁰±2.9⁰ C, p=0.0035). To differentiate between active CD and CD in remission, a new parameter was defined and extracted: the fractal dimension of gradient magnitude (FDGM). The mean FDGM was significantly higher in patients with active disease than in patients with normal IUS (1.66 vs 1.63, p=0.045).

Conclusion

We describe a novel easy-to-use tool for monitoring disease activity in CD. This new method can potentially be used by patients at home as well as an office-based exam that allows precise disease follow-up and disease activity monitoring.

Disclosure

Dan Carter: Consulting fees from Takeda, Abbvie, Taro, and Lapidot; speaker fees and/or research support from Takeda, Abbvie, Janssen, and Lapidot.

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