Introduction

Digital single-operator cholangioscopy (DSOC) allows an accurate diagnosis of biliary strictures. Two DSOC-based artificial intelligence (AI) models trained to identify neoplasia were proposed. DSOC-guided pCLE biliary strictures direct visualization, using the Miami and Paris classifications has demonstrated high diagnostic accuracy for neoplasia (higher than expert endoscopists at times). To date, there are no head-to-head studies comparing DSOC-AI vs DSOC-pCLE.

Aims & Methods

We aim to compare the diagnostic accuracy for identifying neoplasia in indeterminate biliary lesions using a novel DSOC-AI model against DSOC-pCLE. Historic cohort-based diagnostic accuracy study in agreement with STARD initiative including patients ≥18 years old who underwent DSOC-pCLE (06/2014 to 11/2021). Patients without available DSOC videos, biopsy, or impossibility for 12-month follow-up were excluded. For DSOC direct visualization, neovasculature constituted neoplasia. For DSOC-pCLE, a higher presence of the Miami classification’s malignancy criteria (thick white and dark bands, dark clumps, epithelium) than the Paris classification’s inflammatory criteria (vascular congestion, roughness aspect, increased inter-glandular space, and thickened reticular structure) constituted neoplasia. For DSOC and pCLE-guided biopsy, corresponding histological findings constituted neoplasia. An offline DSOC-based AI model analysis was performed using the DSOC recorded videos from the selected cases. The DSOC-AI model considered neovasculature as the criterion for neoplasia. The gold standard for neoplasia was based on further clinical evolution, imaging, or surgical specimen findings during a 12-month follow-up. Accuracy of DSOC direct visualization, DSOC-pCLE, DSOC and pCLE-guided biopsy, and DSOC-AI model was calculated in terms of sensitivity, specificity, positive and negative predictive values (PPV and NPV), observed agreement, and area under the curve (AUC). Comparison of obtained diagnostic accuracies were defined through DeLong’s test for two ROC curves.

Results

Ninety patients were selected, median age was 66.4 ± 13.7 years, 56.7% female. Tumour suspicion was the most common indication (55.6%) (Table 1). DSOC-AI reached a 97.7% sensitivity, 75% specificity, 98.8% PPV, 60% NPV and 96.7% observed agreement; whereas, DSOC-pCLE had a 94.2% sensitivity, a 100% specificity, 100% PPV, 44.4% NPV, and 94.4% observed agreement (Table 2). AUC for DSOC-AI was 0.79; for DSOC direct visualization (0.74; P=.763), DSOC-pCLE (0.72; P=.634), and DSOC and pCLE-guided biopsy (0.83; P=.809).

	Sensitivity	Specificity	PPV	NPV	OA
DSOC direct visualization	83/86; 96.51 (90.14 - 99.27)	3/4; 75 (19.41 - 99.37)	83/84; 98.81 (93.54 – 99.97)	3/ 6; 50 (11.81 – 88.19)	86/90; 95.56 (89.01 – 98.78)
DSOC-guided pCLE	81/86; 94.19 (86.95 – 98.09)	4/4; 100 (39.76 – 100)	81/81; 100 (95.55 – 100)	4/ 9; 44.44 (13.7 - 78.8)	85/90; 94.44 (87.51 - 98.17)
DSOC and pCLE-guided biopsy	84/86; 97.67 (91.85 - 99.72)	4/4; 100 (39.76 - 100)	84/84; 100 (95.7 – 100)	4/ 6; 66.67 (22.28 – 95.67)	88/90; 97.78 (92.2 – 99.73)
DSOC-based AI model	84/86; 97.67 (91.85 – 99.72)	3/4; 75 (19.41 – 99.37)	84/85; 98.82 (93.62 - 99.97)	3/ 5; 60 (14.66 - 94.73)	87/90; 96.67 (90.57 - 99.31)
PPV: Positive predictive value; NPV: negative predictive value; OA: observed agreement; pCLE: probed-based confocal laser endomicroscopy.

Conclusion

The DSOC-AI model demonstrated an offline diagnostic accuracy similar to DSOC-pCLE. Larger multicentric head-to-head trials with a proportional sample among neoplastic and non-neoplastic cases are advisable for best estimation of obtained results.

References

1. Koda H, Hara K, Nozomi O, Kuwahara T, Nobumasa M, Haba S, et al. High-Resolution Probe-Based Confocal Laser Endomicroscopy for Diagnosing Biliary Diseases. Clin Endosc. 2021;54(6):924–9.
2. Pilonis ND, Januszewicz W, di Pietro M. Confocal laser endomicroscopy in gastro-intestinal endoscopy: Technical aspects and clinical applications. Transl Gastroenterol Hepatol. 2022;7:1–20.
3. Kahaleh M, Raijman I, Gaidhane M, Tyberg A, Sethi A, Slivka A, et al. Digital Cholangioscopic Interpretation: When North Meets the South. Digestive Diseases and Sciences. 2021;67(4):1345–51.
4. Robles-Medranda C, Oleas R, Sánchez-Carriel M, Olmos JI, Alcívar-Vásquez J, Puga-Tejada M, et al. Vascularity can distinguish neoplastic from non-neoplastic bile duct lesions during digital single-operator cholangioscopy. Gastrointestinal Endoscopy. 2021;93(4):935–41.
5. Robles-Medranda C, Valero M, Soria-Alcivar M, Puga-Tejada M, Oleas R, Ospina-Arboleda J, et al. Reliability and accuracy of a novel classification system using peroral cholangioscopy for the diagnosis of bile duct lesions. Endoscopy. 2018;50(11):1059–70.
6. Sethi A, Tyberg A, Slivka A, Adler DG, Desai AP, Sejpal D v., et al. Digital Single-operator Cholangioscopy (DSOC) Improves Interobserver Agreement (IOA) and Accuracy for Evaluation of Indeterminate Biliary Strictures: The Monaco Classification. Journal of Clinical Gastroenterology. 2022;56(2).

Disclosure

Carlos Robles-Medranda is a key opinion leader and consultant for Pentax Medical, Steris, Medtronic, Motus, Micro-tech, G-Tech Medical Supply, CREO Medical, EndoSound, and mdconsgroup. The other authors declare no conflicts of interest.

Introduction

One third of the world population is affected by obesity. Laparoscopic Sleeve Gastrecotomy (LSG) is the most widely used surgical treatment currently used to treat severe obesity. However, it appears to increase the risk of developing Gastro-Esophageal Reflux Disease (GERD) and its complications, such as Barrett's esophagus (Genco A. et Al, 2017).
Aim of this study was to evaluate possible impairment of the anti-reflux barrier function of the Esophageal-Gastric Junction (EGJ) in patients with severe obesity undergoing LSG by studying functional aspects of the EGJ by High Resolution Esophageal Manometry (HRM) with perfusion system and 24-hour pH-metry.

Aims & Methods

Forty-five obese patients, without evidence of hiatus hernia or GERD, undergoing LSG (34F 11M; 45±12 yrs) were compared with 21 overweight patients (10F 11M; 52±16 yrs) and 21 normal weight patients (17F 4M; 47±14 yrs) with GERD symptoms. Twenty-four of the obese patients (3M 21F; 45±11 yrs) were reevaluated after LSG.
The EGJ was evaluated by the EsophagoGogastic Junction–Contractile Integral (CI) on HRM, that integrates the inspiratory and expiratory pressures, the length and the duration of the contraction of the EGJ during three respiratory cycles at rest. It was calculated for Single Respiratory Cycle (EGG-CI SRC) and corrected for duration of the breathing (EGG-CI CRC). The findings were compared with normal ranges suggested in the literature (EGJ-CI-SRC 205.5±35.6 mmHg·cm·s and EGJ-CI-CRC 46.2±7.6 mmHg·cm) (Gor P. et Al, 2016).

Results

The 3 groups of patients, obese, overweight and normal weight, did not differ statistically for EGJ-CI SRC (120.3 ± 112.7 vs 116 ± 120 vs 103.7 ± 102.6 mmHg·cm·s, respectively) nor for EGJ-CI CRC (42.8 ± 31 vs 33.4 ± 28.2 vs 33.0 ± 28.5 mmHg·cm, respectively). After LSG a statistically significant decrease was observed for EGJ-CI CRC (46.7±36.8 vs 32.3±26.4 mmHg·cm, p=0.02), but not for EGJ-CI SRC (133.6±141 vs 115.2±103.6 mmHg·cm·s, n.s.). Twelve patients (50%) showed after LSG an acid exposure time above the normal limits and this result was related to the degree of reduction of EGJ-CI-CRC (r = 0.525; p = 0.01).The results of this study indicate that the esophagogastric barrier function of the EGJ is reduced in obese patients similarly to GERD patients regardless of BMI and appears to decrease further after LSG surgery, affecting its efficiency and probably favoring the onset of GERD.

Conclusion

In conclusion, the evidence that LSG affects the EGJ and may induce GERD suggests that HRM and 24-hour pH-mertry or 24-hour pH-impedancemetry could be useful in the work-up for bariatric surgery to identify subjects without or scarce reflux symptoms, but showing impaired functions that could worsen with surgery favoring the onset of GERD. It is possible that the functional characteristics of the GEG associated with other variables detected by HRM and pH-impedancemetry may in the future develop a predictive score for risk of MRGE in these patients.

References

Genco A, Soricelli E, Casella G, et al. Gastroesophageal reflux disease and Barrett’s esophagus after laparoscopic sleeve gastrectomy: a possible, underestimated long-term complication. Surg Obes Relat Dis 2017;13:568–74.
Gor P, Li Y, Munigala S, et al. Interrogation of esophagogastric junction barrier function using the esophagogastric junction contractile integral: an
observational cohort study. Dis esophagus Off J Int Soc Dis Esophagus 2016;29:820–8.

Disclosure

No conflict of interest

Introduction

Colonoscopy is highly effective yet inefficient at colorectal cancer (CRC) prevention with a prevalence of target (advanced adenomas) of only about 8%. Thus, finding a modality to risk-stratify for colonoscopy would be of public health implications One approach is to leverage field carcinogenesis, the concept that the gene/environmental interaction that predispose to neoplastic lesions are diffuse and thus rectal mucosa can predict risk of proximal neoplasia (1). Given the diffuse molecular alterations, our group has focused on transcriptional assessment through chromatin nano-architecture. While epigenetics such as methylation, histone acetylation etc will be reflected in chromatin nano-architecture, microRNAs (mIRs) provide an independent impact on gene expression. We, therefore, wanted to test whether chromatin + miR markers from the rectum would predict concomitant adenomas.

Aims & Methods

Chromatin Nano-architecture: We used a novel nanoscale optics technology, partial wave spectroscopic microscopy (PWS) which enables us to go quantify chromatin heterogeneity through pixel-to-pixel variability in refractive indices (2). The calculated marker correlated with fractal dimension (D).
Human Studies: We recruited patients undergoing screening/surveillance colonoscopy with IRB consent. Following colonoscopy 6 biopsies of endoscopically normal rectum. We had 104 controls and 53 advanced adenoma patients for these studies. Advanced adenomas were defined as size >10mm, >25% villous features or high grade dysplasia. Controls were those without adenomas/carcinomas.
miR: We used RT-PCR with internal controls. We used literature to identify 4 candidates miRs and used the delta delta approach to compute fold change of miR expression (case versus control).

Results

We analyzed D from the rectal biopsies with PWS from our clinical dataset and observed excellent diagnostic performance of area under receiver operator characteristic curve (AUC) of = 0.85 for those with and without advanced adenomas sensitivity = 0.74, specificity = 0.83.
The potential of our biomarker is also evaluated via combining with epigenetic regulators microRNAs (miR) in an independent pilot study. Evaluating the 4 oncomiRs in 20 human rectal biopsies (10 control, 10 advanced adenoma) had increased expressions in patients harboring advanced adenomas (fold changes were miR137=3.4, miR92a=5.97, miR-135b-5p=174 and miR361-5p=2.01).
With our PWS marker, the elevation of miR-92a, miR-135b-5p, and D was synergistic for discriminating patients with vs. without advanced adenomas to 0.9 increase in AUC compared to D alone. AUC) = 0.90, sensitivity = 0.88, specificity = 0.85.

Conclusion

We demonstrate, for the first time, that the chromatin nano-architectural parameter, D had excellent performance for identifying patients screen relevant neoplasia elsewhere in the colon. Furthermore, adding several miR markers to provide a more comprehensive epigenetic profile was synergistic diagnostics with D. Future studies will employ more miRs and combine with artificial intelligence to further improve the already strong performance for potential clinical impact.

References

Rebello D, Rebello E, Custodio M, Xu X, Gandhi S, Roy HK. Field carcinogenesis for risk stratification of colorectal cancer. Adv Cancer Res. 2021;151:305-344. doi: 10.1016/bs.acr.2021.03.004. Epub 2021 Mar 31. PMID: 34148616.
Gladstein S, Damania D, Almassalha LM, Smith LT, Gupta V, Subramanian H, Rex DK, Roy HK, Backman V. Correlating colorectal cancer risk with field carcinogenesis progression using partial wave spectroscopic microscopy. Cancer Med. 2018 May;7(5):2109-2120. doi: 10.1002/cam4.1357. Epub 2018 Mar 23. PMID: 29573208; PMCID: PMC5943438.

Disclosure

Hemant Roy, Vadim Backman, and Hariharan Subramanian are co-founders, have equity stakes, own IP and are on the Board of Directors for Nanocytomics LLC, a biomedical company providing cancer risk-stratification tests based on their proprietary biophotonics technology platform, partial wave spectroscopic (PWS) microscopy which is being utilized in this research. Sravya Prabhala is also an employee of Nanocytomics LLC.

Introduction

Despite improvements in endoscopic imaging modalities, there are still significant miss rates in detecting Barrett’s neoplasia. We have previously reported the development of novel deep neural network in detecting Barrett’s neoplasia. The aim of this study was to understand the added value of artificial intelligence (AI) system across a range of expert and non-expert endoscopists.

Aims & Methods

We used WISE VISION® (NEC Corporation, Japan) as an AI platform. We pre-recorded 114 videos and used histology as ground truth. The videos were carefully edited. Using a dedicated computer-based platform, 10 expert (those performing endoscopic resection in Barrett’s centre for more than 5 years) and 10 non-expert endoscopists (<1000 lifetime gastroscopy count) were asked to review the videos without AI and then with AI and to categorise the videos into neoplastic, non-neoplastic or uncertain. The video clips were randomly allocated in the study to reduce the recall bias by the endoscopists.

Results

114 videos (57 neoplastic and 57 non-neoplastic) were collected from 112 patients who were under Barrett’s surveillance or those with known neoplasia referred for endoscopic resection. Of neoplastic videos, 15 were polypoidal and 45 were non-polypoidal. 5 of them were low-grade dysplasia, 18 were high-grade dysplasia and 34 were cancer (pT1a and pT1b).
The sensitivity of neoplasia detection in Barrett's by standalone AI was 84.5%. Table shows a significant improvement in performance of non-experts when using AI (sensitivity of 63% to 81%). Improvement in sensitivity in detecting Barrett’s neoplasia in experts using AI is statistically significant but not clinically significant (69% to 73%). When using AI, non-experts have a greater improvement in achieving fewer uncertain answers compared to experts (12.8% to 4.8% in non-experts vs 11.6% to 8.9% in experts).

	Non-experts (95% CI)	Non-experts with AI (95% CI)	Experts (95% CI)	Experts with AI (95% CI)
Sensitivity	0.63 (0.59-0.67)	0.81 * (0.78-0.85)	0.69 (0.65-0.72)	0.73 * (0.69-0.76)
Specificity	0.63 (0.59-0.67)	0.71 * (0.67-0.75)	0.79 (0.75-0.82)	0.79 (0.76-0.83)
Accuracy	0.63 (0.59-0.67)	0.76 * (0.73-0.8)	0.74 (0.70-0.77)	0.76 (0.73-0.80)
*p value<0.05

Conclusion

Detection of Barrett’s neoplasia remains challenging for experts (69%) and non-experts (63%) as 80% of the neoplasia in this study were non-polypoidal. Sensitivity of AI looks very promising and non-experts seem to agree more with AI, resulting in a greater significant gain in detecting additional Barrett’s neoplasia. Experts, however, seem to disregard AI results more, resulting in very little additional gain in neoplasia detection and this could potentially deprive Barrett’s patients from additional AI related benefits.
Our data gives a very interesting insight into human-machine interaction which needs to be further explored before the widespread use of AI.

Introduction

The impact of underweight and obesity on clinical outcomes for intestinal Behçet’s disease (BD) is unknown. We aimed to identify the association between body mass index (BMI) and clinical outcomes in patients with intestinal BD.

Aims & Methods

We categorized 760 patients with intestinal BD according to the BMI at diagnosis into four groups (underweight, normal, overweight, obese) at Severance Hospital, Seoul, Korea between 1997 and 2021.We performed a Cox proportional hazard analysis to investigate the predictive capability of BMI for clinical outcomes such as biologics use, surgery, hospitalization and emergency room visit.

Results

Of the 760 patients, 130 patients were classified into underweight group (BMI<18.5), 384 patients into normal group (BMI 18.5~22.9), 152 patients into overweight group (BMI 23~24.9), and 94 patients into obese group (BMI≥25). Patients with a higher BMI group showed significantly lower cumulative rates of biologics use (p trend = 0.001), surgery (p trend = 0.008), hospitalization (p trend = 0.002), and emergency room visits (p trend = 0.003) than those with a lower BMI group. In a multivariate analysis, normal BMI group (HR: 0.667, 95% CI 0.483-0.992, p =0.014), overweight group (HR: 0.589, 95% CI 0.394-0.879, p=0.010), and obese group (HR: 0.515, 95% CI 0.321-0.828, p=0.006) were negatively associated with future hospitalization compared to underweight group. Overweight group (HR: 0.490, 95% CI 0.241-0.996, p =0.049) and obese group (HR: 0.312, 95% CI 0.116-0.840, p =0.021) were negatively associated with future biologics use compared to the underweight group. Normal BMI group (HR: 0.706, 95% CI 0.484-1.029, p=0.070) and obese group (HR : 0.556, 95% CI 0.303-1.020, p=0.058) were negatively associated with future surgery compared to the underweight group. Normal BMI group (HR: 0.711, 95% CI 0.513-0.985, p=0.041) and obese group (HR: 0.602, 95% CI 0.376-0.963, p=0.034) were negatively associated with future emergency room visit compared to the underweight group.

Variables		BMI
		<18.5 (n=130) Underweight	18.5~22.9 (n=384) Normal	23~24.9 (n=152) Overweight	≥25 (n=94) Obese	p value for trend
Biologics use	Event	34 (26.2%)	50 (13.1%)	21 (13.8%)	9 (9.6%)	0.001
	Multivariable-adjusteda	Reference	0.619 (0.366-1.047)*	0.490 (0.241-0.966)**	0.312 (0.116-0.840)**
Surgery	Event	45 (34.6%)	87 (22.7%)	35 (23%)	15 (16%)	0.008
	Multivariable-adjusteda	Reference	0.706 (0.484-1.029)*	0.669 (0.411-1.088)	0.556 (0.303-1.020)*
Hospitalization	Event	87 (66.9%)	194 (50.8%)	69 (45.4%)	46 (48.9%)	0.002
	Multivariable-adjusteda	Reference	0.667 (0.483-0.922)**	0.589 (0.394-0.879)**	0.515 (0.321-0.828)**
Emergency room visit	Event	71 (55%)	144 (37.6%)	61 (40.1%)	32 (34%)	0.003
	Multivariable-adjusteda	Reference	0.711 (0.513-0.985)**	0.775 (0.523-1.149)	0.602 (0.376-0.963)**

*p <0.10
**p <0.05
^aMultivariate Cox proportional hazard analysis, including the confounders such as, age, gender, medical aid, smoking, appendectomy history, family history of BD, marriage status, DAIBD score, extraintestinal manifestation, systemic BD, number of ulcers, shape of ulcers, depth of ulcers, type of ulcers, laboratory findings.

Conclusion

Underweight could affect poor outcomes in intestinal Behçet’s disease. Physicians should pay attention to the patients with underweight and make an effort to improve nutritional status.

Introduction

Cholangioscopy-assisted intraductal lithotripsy is a first-line option in the treatment of complex gallstones. Its effectiveness and safety are demonstrated in the literature by multiple studies published after 2017.
However, there are no published studies about the long-term recurrence of choledocholithiasis in patients treated by these techniques.
With this study we intend to answer this question, evaluating the long-term recurrence of choledocholithiasis in patients with complex choledocholithiasis treated with intraductal lithotripsy techniques.

Aims & Methods

Retrospective cohort study of 62 consecutive patients who underwent cholangioscopy-guided intraductal lithotripsy between 2017 and 2022 at our center. Data were collected from a dedicated prospectively maintained database.
Primary outcome: recurrence of choledocholithiasis. Follow-up time: 5 years.
Survival analysis was performed using Kaplan-Meyer curves and Cox regression (Statistical software STATA 17 (StataCorp, TEXAS).

Results

Of the 62 patients, 35 (56.5%) were women, mean age 72 years (min. 28, max. 96), 20 of whom had previously undergone cholecystectomy and with a mean follow-up time after lithotripsy of 28.21 months . 88.7% of patients achieved complete stone removal in the 1st session, with a rate of 100% at the second procedure. The mean number of stones was 2.02 with a size of 18.74mm. There was recurrence of choledocholithiasis in 9 patients, of which 77.8% had cholangitis, with a mean time of 13.33 months after lithotripsy. In patients with recurrence of choledocholithiasis, 22.2% had gallbladder. None of the patients required surgery to explore the biliary tract.

Conclusion

Cholangioscopy-guided lithotripsy is associated with a high success rate in difficult gallstones, with a safety profile similar to conventional techniques and lower rates of choledocholithiasis during follow-up.

Introduction

The number of colonoscopies performed on elderly patients is increasing because of the rapidly progressed aging population, but in the case of elderly patients, safety and advantage of colonoscopy are still insufficient when compared with procedure risk. FI-lab, which is a frailty index calculated by laboratory test and vital sign, and is expected to be a measure that can predict the clinical outcome of elderly patients. We evaluated and analyzed the safety of colonoscopy by analyzing the association between the adverse events of colonoscopy with FI-lab and Charlson's comorbidity index (CCI).

Aims & Methods

A total of 8154 patients were enrolled in this study retrospectively at a Gangnam Severance Hospital from July 2017 to August 2022. Patients were aged 60 or older, underwent colonoscopy for screening, and there were blood test results within two months before and after the procedure. Those who underwent endoscopy for therapeutic purposes, those under the age of 59, and those who missed blood test results or vital sign records were excluded. FI-lab was calculated by the closest blood test results at the time of the procedure and the vital signs at the time of the procedure, and CCI was calculated based on the patient's history recorded in the hospital and the age at the time of the procedure. The occurrence of side effects was based on an unplanned visit to the emergency room or hospitalization within a month after the procedure.

Results

The total number of participants was 8154, with 3102 in the 60-64 age group, 2160 in the 65-69 age group, 1506 in the 70-74 age group, 904 in the 75-79 age group, and 482 in the age group of 80 years or older. The study population comprised 4354 males (53.4%). The mean age of the participants was 67.9 years, ranging from 60 to 94 years. The CCI mean was 3.31. The mean value of the FI-lab was 0.168. Most of the participants (86.2%) had a low frailty index, followed by 11.9% with a moderate frailty index, and 1.9% with a high frailty index. Adverse events of colonoscopy within 30 days were occurred in 115 cases, gastrointestinal events such as perforation or bleeding were 27, mortality cases were 9, major adverse events were 48, minor events were 67. CCI and FI-lab were showed strong associations with complications (p<0.001, each), and categorized FI-lab showed statistically significant differences between low group and moderate or high group (p<0.001).

Table. Factors affected to adverse events
	Without AE	AE	p-value
number	8039	115
Age, mean, years(range)	67.9(60-94)	71.8(60-91)	<0.001
Male sex, number(%)	4277(53.2)	77(67.0)	0.003
CCI, mean	3.29	4.9	<0.001
FI-lab, mean	0.167	0.261	<0.001
low(<0.25), number(%)	6977(86.8)	53(46.1)
moderate(0.25-0.4), number(%)	925(11.5)	44(38.3)
high(>0.4), number(%)	137(1.7)	18(15.6)

Conclusion

CCI and FI-lab can be a predictive scoring system in elderly patients who received screening colonoscopy. Therefore, if CCI or FI-lab is high, physicians should decide and perform colonoscopy carefully.