Introduction

Per-oral cholangioscopy (POC)-targeted biopsies, potential to overcome the problems associated with inadequate tissue sampling and increase the diagnostic sensitivity of bile duct nodular tumors. The utility of frozen section analysis, able to detect malignancy immediately and allows the early surgery in patients with invasive carcinoma.

Aims & Methods

To evaluate the diagnostic yield and efficiency of POC-targeted biopsies combined with frozen section histopathology.
From Oct. 2017 to Dec. 2021, consecutive patients with biliary nodular tumors were included in this study. The cholangioscope (SpyGlass DS, Boston Scientific Co., Natick, MA, USA) was advanced through a standard therapeutic duodenoscope (Olympus). All procedures were performed under moderate sedation or general anesthesia. Before POC, a standard endoscopic retrograde cholangiogram (ERC) with biliary sphincterotomy was performed to localize the bile duct nodular tumor and to facilitate ductal access and therapy. The cholangioscope was introduced into the bile duct through a guidewire via the working channel. The biliary trees were inspected, and suspicious lesions are biopsied. No more than nine biopsies per lesion were taken for histological examination. The specimens of endoscopic biopsies were then sent to the frozen section laboratory for freezing and staining. The slides were read immediately, and a preliminary report was conveyed to the clinician. The pathologist would then assess for the presence or absence of dysplasia or invasive cancer in the specimen.

Results

A total of 8 patients (7 male and 1 female; mean age 65 years) with bile duct nodular tumors undergoing cholangioscopy-targeted biopsies with frozen sections were included. The clinical presentations of the patients were obstructive jaundice 2, abdominal pain 2, and imaging findings 4. Seven of the 8 patients had undergone ERC and ductal biopsies without definite diagnosis. The nodular tumors in the bile ducts, average size 1.5 cm (range 0.8-2.0), were located in proximal (4), middle (1) and distal (3) extrahepatic duct respectively. Among 8 patients with biopsy-proved malignancy, 3.5 times (range 2-9) biopsies were needed to be taken. All except one frozen section histopathology (adenocarcinoma in situ) was not compatible with surgical pathology (high grade dysplasia). Hilar invasion was observed in one patient during cholangioscopy, and subsequently surgery was not performed. One patient developed severe complication associated with acute cholangitis.

Conclusion

In this case series study, combined POC-targeted biopsies with frozen section histopathology provides an immediate and efficient diagnosis and allows an early surgery for patients with bile duct tumors. More patients are need to be included in the further study.

Disclosure

Nothing to disclose

Introduction

Despite the advancements in imaging modalities, diagnosis of biliary strictures remains challenging in some cases. Endoscopic retrograde cholangiopancreatography (ERCP) is the current gold standard for diagnosis. However, the pathological diagnosis via ERCP is limited due to the small specimen. Therefore, a novel device for the diagnosis of biliary stricture has been long-awaited. Although high sensitivity and specificity have been reported for probe-based confocal laser endomicroscopy (pCLE) for the diagnosis of biliary strictures using the Miami Classification, it remains uncertain whether confocal miniprobes can be properly applied to the target site with the use of pCLE under fluoroscopic guidance. The aim of the present study was to prospectively evaluate the clinical utility of pCLE under the direct view of peroral cholangioscopy (POCS) for the diagnosis of biliary strictures.

Aims & Methods

Consecutive patients with biliary strictures were included. All patients underwent imaging examination, such as computed tomography, magnetic resonance imaging, or endoscopic ultrasound, and were found to have biliary disorders. We investigated sensitivity, specificity, and accuracy to diagnose malignancy for: 1) ERCP alone, 2) POCS, 3) pCLE under the direct view of POCS, and 4) tissue sampling under the direct view of POCS. pCLE images were interpreted prospectively using the Miami Classification. We also evaluated other outcomes of pCLE under the direct view of POCS.

Results

A total of 30 patients (17 with malignant lesions) were prospectively enrolled.
1) ERCP alone showed 88.2% sensitive, 46.2% specific, and 70% (95% confidence interval [CI], 52.1%–83.3%) accurate.
2) POCS showed 100% sensitive, 76.9% specific, and 90% (95% CI, 74.4%–96.5%) accurate.
3) pCLE under the direct view of POCS showed 94.1% sensitive, 92.3% specific, and 93.3% (95% CI, 78.7%–98.8%) accurate.
4) Tissue sampling under the direct view of POCS showed 82.4% sensitive, 100% specific, and 90% (95% CI, 74.4%–96.5%) accurate.
The POCS could not pass the biliary stricture in four patients, and we could not complete successful observation of the target area. Therefore, the success rate of pCLE under the direct view of POCS was 88.2% (30/34). The median procedural time for pCLE under the direct view of POCS was 42 min (interquartile range [IQR], 31.3–48 min). Accurate diagnosis rate of common bile duct and accurate diagnosis rate of hilar and intrahepatic bile duct were 86.7% (13/15), 100% (15/15) respectively. There was no significant difference among stricture locations (P=0.48). Adverse events occurred in three patients (one with mild pancreatitis, and two with mild cholangitis).

Diagnosis modality (n=30)	Sensitivity n (%) 95% CI	Specificity n (%) 95% CI	NPV n (%) 95% CI	PPV n (%) 95% CI	Accuracy n (%) 95% CI
1) ERCP alone	15/17 (88.2) 65.7-97.9	6/13 (46.2) 23.3-70.9	6/8 (75) 40.9-95.6	15/22 (68.2) 47.3-83.6	21/30 (70) 52.1-83.3
2) POCS	17/17 (100) 81.6-100	10/13 (76.9) 49.7-91.8	10/10 (100) 72.2-100	17/20 (85) 64.0-94.8	27/30 (90) 74.4-96.5
3) pCLE under the direct view of POCS	16/17 (94.1) 73.0-99.7	12/13 (92.3) 66.7-99.6	12/13 (92.3) 66.7-99.6	16/17 (94.1) 73.0-99.7	28/30 (93.3) 78.7-98.8
4) Tissue sampling under the direct view of POCS	14/17 (82.4) 59.0-93.8	13/13 (100) 77.2-100	13/16 (81.3) 57.0-93.4	14/14 (100) 78.5-100	27/30 (90) 74.4-96.5
2) VS 3) P value	0.50	0.59			>0.99
3) VS 4) P value	0.60	>0.99			>0.99

Table 1. Summary of primary outcomes

Conclusion

pCLE under the direct view of POCS provided highly accurate and sensitive characterization of biliary strictures and showed the potential for more diagnostic reliability and reduction of delays in diagnosis.

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

Endoscopic submucosal dissection is becoming the gold standard for the resection of superficial squamous cell carcinoma. It is unclear whether delaying esophgectomy after endoscopic submucosal dissection is better in terms of mortality and complications than primary esophgectomy in esophageal cancer patients. We compared the long-term outcomes and the complications between these two groups.

Aims & Methods

Between 2003 and 2019, 191 patients underwent primary esophagectomy and 65 patients underwent ESD then delayed esophagectomy. In a matched group of 65 pairs, OS, DSS, and RFS were compared between the 2 groups. The overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and postoperative complications were compared between the propensity-matched groups.

Results

In a matched cohort, OS, DSS, and RFS were comparable between the 2 groups. Even though the overall survival of 6 years was 70% versus 80% (p value=0.041) in the primary esophgectomy versus ESD and consequent esophgectomy respectively, DSS was 25% versus 12.5% (p value=0.21). The RFS was 80% versus 98% with p value of 0.06. In terms of recurrence free survival, differentiation, and tumor size were independent factors. When comparing adverse events between two groups there were non 60 day mortality in both groups and significant difference in early complication in the primary surgery group compared to surgery after ESD group. (47.7% versus 15.4%, p=<0.001)

Conclusion

In management for the superficial esophageal cancer, delayed surgery may have advantage in terms of survival, recurrence-free survival and complications.

References

1. Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Dicker D, et al. The global burden of cancer 2013. JAMA Oncol 2015;1:505-27.
2. Steffen T, Dietrich D, Schnider A, et al. Recurrence patterns and longterm results after induction chemotherapy, chemoradiotherapy, and curative surgery in patients with locally advanced esophageal cancer. Ann Surg. Epub 2017 Jul 24.
3. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012;366:2074-84
4. Ra J, Paulson EC, Kucharczuk J, et al. Postoperative mortality after esophagectomy for cancer: development of a preoperative risk prediction model. Ann Surg Oncol 2008;15:1577-84.
5. Chang AC, Ji H, Birkmeyer NJ, et al. Outcomes after transhiatal and transthoracic esophagectomy for cancer. Ann Thorac Surg 2008;85: 424-9.
6. Connors RC, Reuben BC, Neumayer LA, et al. Comparing outcomes after transthoracic and transhiatal esophagectomy: a 5-year prospective cohort of 17,395 patients. J Am Coll Surg 2007;205:735-40.
7. Takahashi H, Arimura Y, Masao H, et al. Endoscopic submucosal dissection is superior to conventional endoscopic resection as a curative treatment for early squamous cell carcinoma of the esophagus (with video). Gastrointest Endosc 2010;72:255-64

Introduction

Capsule endoscopy (CE) is a minimally invasive exam suitable of panendoscopic evaluation of the gastrointestinal tract. Nevertheless, CE is time-consuming, with suboptimal diagnostic yield in the upper GI tract. Convolutional neural networks (CNN) are human brain architecture-based models suitable for image analysis. However, there is no study about their role in capsule panendoscopy.

Aims & Methods

Our aim was to develop an artificial intelligence (AI) model for panendoscopic automatic detection of pleomorphic lesions (namely vascular lesions, protuberant lesions, hematic residues, ulcers, and erosions). 355110 images (6977 esophageal, 12918 gastric, 258443 small bowel, 76772 colonic) from eight different CE and colon CE (CCE) devices were divided into a training and validation dataset in a patient split design. The model classification was compared to three CE experts’ classifications. The model’s performance was evaluated by its sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the precision-recall curve.

Results

The binary esophagus CNN had a diagnostic accuracy for pleomorphic lesions of 83.6%. The binary gastric CNN identified pleomorphic lesions with a 96.6% accuracy. The undenary small bowel CNN distinguished pleomorphic lesions with different hemorrhagic potential with 97.6% accuracy. The trinary colonic CNN (detection and differentiation of normal mucosa, pleomorphic lesions, and hematic residues) had 94.9% global accuracy.

Conclusion

Our group developed the first AI model for panendoscopic automatic detection of pleomorphic lesions in both CE and colon CE from multiple brands, solving a critical interoperability technological challenge. Deep learning-based tools may change the landscape of minimally invasive capsule panendoscopy.

References

1. Pennazio M, Rondonotti E, Despott EJ, Dray X, Keuchel M, Moreels T, et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. 2023 Jan;55(1):58-95. PubMed PMID: 36423618. Epub 20221124.
2. Le Berre C, Trang-Poisson C, Bourreille A. Small bowel capsule endoscopy and treat-to-target in Crohn's disease: A systematic review. World J Gastroenterol. 2019 Aug 21;25(31):4534-54. PubMed PMID: 31496630. PMCID: PMC6710184.
3. Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature. 2000 May 25;405(6785):417. PubMed PMID: 10839527.
4. Rondonotti E, Pennazio M. Colon capsule for panendoscopy: a narrow window of opportunity. Endosc Int Open. 2021 Dec;9(12):E1860-E2. PubMed PMID: 34917450. PMCID: PMC8670997. Epub 20211214.
5. Vuik FER, Moen S, Spaander MCW. Colon capsule endoscopy as panendoscopy: Using current knowledge to enhance possibilities. Endosc Int Open. 2022 May;10(5):E584. PubMed PMID: 35571484. PMCID: PMC9106432. Epub 20220513.

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.