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).

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

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

Clostridioides difficile infection (CDI) is the most common cause of healthcare associated infectious diarrhea in hospitalized patients, affecting primarily elderly patients with comorbidities after antibiotic exposure. Despite introduction of novel antibiotic options, recurrent CDI (rCDI) remain a major clinical challenge. Bezlotoxumab, an anti-Toxin B monoclonal antibody used in conjunction with standard of care antibiotic therapy, has been shown to reduce the frequency of rCDI in registration trials. To date, there is limited post-marketing data on this compound concerning its clinical efficacy and safety outside trials. The aim of the BODEGA study was to assess the clinical efficacy, safety and logistics of administration of bezlotoxumab in a real-life setting.

Aims & Methods

In this observational, prospective and retrospective multicenter study, we collected data from 100 patients receiving bezlotoxumab in combination with standard of care for the prevention of rCDI. Follow-up with respect to response and safety was performed at days 10, 45 and 90. For each patient, variables with respect to demography, fitness, previous CDI treatments and CDI associated hospitalizations, diagnostic and outcome were documented. Documentation was performed by use of the online platform ClinicalSurveys.Net. For statistical analysis, SPSS version 29.0.0.0 (241) was used.

Results

At the time of this analysis, data from 88/100 unique patients with documented CDI was evaluable, as 12 had not yet completed follow-up. The evaluable study population consists of 62,5% (n=55) females with an average age of 59 years (range: 20-91). Overall, 94,3% (n=83) of patients presented with additional comorbidities. Gastrointestinal (n=33, 37,5,4%) and cardiovascular diseases (n=38, 43,2%) were most frequently documented. Patients experienced a median of 3 episodes (range=0-10) of CDI prior to the episode in which bezlotoxumab was administered. The most recent CDI episode was non-complicated in 90,9% (n=80) and community acquired in 52,9% (n=46). Patients received fidaxomicin standard (n=36, 40,9%), fidaxomicin extended (n=16, 18,2%), vancomycin standard (n=13, 14,8%), vancomycin tapered (n=13, 14,8%) and others (n=4, 4,5%) as antibiotic treatment for the episode during which bezlotoxumab was administered. In their CDI patient history, most patients received the following treatments sequentially: vancomycin and fidaxomicin (n=34, 38,6%) fidaxomicin only (n=25, 28,4%, multiple administrations possible) and vancomycin only (n=16, 18,2%, multiple administrations possible). In 76/88 patients (86,4%) and 67/83 (76,1%) there was no further recurrence on day 45 and 90, respectively.

Conclusion

Preliminary data from the BODEGA study demonstrates comparatively low recurrence rates at days 45 and 90 in a real-life setting. Our study population was characterized by cases of multiply recurrent CDI with an uncomplicated course of CDI, that was often acquired in an ambulatory care setting. In these aspects, the study population differs significantly from patients included in registration trials. Although follow-up is not yet complete for all study patients, we conclude that bezlotoxumab is a promising option for treating patients with multiply recurrent CDI.

References

N/A

Disclosure

Funded with an unrestricted grant from Merck/MSD

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).

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

Quantitative fluorescence molecular endoscopy (qFME) enables real-time in vivo visualization and quantification of fluorescence and can thereby highlight tumor tissue. qFME has proven its potential in detection of lesions and residual disease but is limited to the mucosal side only^1,2. Ultrasound guided needle biopsy (USNB/SFF) single fiber fluorescence spectroscopy may enable assessment of lymph nodes and all tissue layers of the esophageal wall. This pilot study evaluated the clinical impact of USNB/SFF spectroscopy using the fluorescent tracer bevacizumab-800CW for the identification of residual tumor in patients with esophageal cancer.

Aims & Methods

Patients diagnosed with locally advanced esophageal adenocarcinoma scheduled for neoadjuvant chemoradiotherapy followed by surgery were included. Patients were intravenously injected with either 4.5, 10 or 25 mg bevacizumab-800CW 2-3 days prior to the qFME to establish the optimal dose. FME collected real-time white light and fluorescence images of the primary tumor site and normal esophageal tissue. Quantitative fluorescent measurements were acquired superficially using multi-diameter single fiber reflectance / single fiber fluorescence (MDSFR/SFF) and inside the esophageal wall and within lymph nodes using USNB-SFF spectroscopy. Additionally, the reduced scattering coefficient and absorption coefficient were determined from the MDSFR/SFF data.

Results

Fifteen patients were included in the dose-escalation, where 25 mg showed the best differentiation between primary tumor site and normal tissue and was extended with 3 additional patients (TBR: 2.63±0.60, p=0.0002). VEGF immunohistochemistry confirmed the higher uptake of VEGF at the primary tumor site. USNB was evaluated in 6/8 patients from the 25mg cohort. The primary tumor site (p=0.071) and lymph nodes (p=0.090) showed higher fluorescence intensity compared to normal tissue. Fluorescence measurements of normal tissue were comparable between the luminal MDSFR/SFF and USNB/SFF measurements. In 33% of all patients residual tumor was found only below a tumor-free mucosa signifying the need to analyze the deeper tissue layers. Last, the optical properties, the reduced scattering coefficient and absorption coefficient. The combination of the intrinsic fluorescence, absorption and scattering coefficient was converted into the new variable omega and improved the differentiation between tumor and normal tissue even further.

Conclusion

We showed the potential of bevacizumab-800CW combined with qFME and USNB/SFF for response monitoring in esophageal cancer. This combination allows for both in vivo superficial and deeper tissue measurements to ensure that partial responders with a tumor-free mucosa are also adequately selected. A phase II study should establish its value for stratification of patients for active surveillance or surgery.

References

1. Tjalma JJJ, Koller M, Linssen MD, Hartmans E, de Jongh S, Jorritsma-Smit A, et al. Quantitative fluorescence endoscopy: an innovative endoscopy approach to evaluate neoadjuvant treatment response in locally advanced rectal cancer. Gut. 2020;69(3):406-10.
2. Nagengast WB, Hartmans E, Garcia-Allende PB, Peters FTM, Linssen MD, Koch M, et al. Near-infrared fluorescence molecular endoscopy detects dysplastic oesophageal lesions using topical and systemic tracer of vascular endothelial growth factor A. Gut. 2019;68(1):7-10.

Disclosure

Nothing to disclose

Introduction

Esophageal squamous cell carcinoma (ESCC) can be treated curatively with definitive chemoradiotherapy (CRT). However, local failure, characterized by residue just after CRT or recurrence after achieving complete response with CRT, occurs in 20-40% of patients who received this treatment. Salvage endoscopic therapy is one of the treatment options for cT1N0N0 local failure after CRT or radiotherapy (RT) for ESCC, but most reports on its outcomes are at single center.

Aims & Methods

This multicenter study aimed to clarify the short- and long-term outcomes of salvage endoscopic therapy (endoscopic resection [ER: EMR/ESD] and photodynamic therapy using Talaporfin Sodium [PDT]) for cT1N0M0 local failure after CRT/RT for ESCC, and to identify factors that influence the outcomes of salvage endoscopic therapy. Patients who underwent salvage endoscopic therapy (ER, PDT) for cT1N0M0 local failure after CRT/RT for ESCC at two institutions between December 2012 and August 2021 were retrospectively investigated. The patients were excluded if they were not followed up for more than three months after salvage therapy or had a history of salvage therapy. The selection of the procedure was primarily based on the depth of the tumor and the degree of submucosal fibrosis.

Results

A total of 168 patients were analyzed, of which 86 underwent ER (EMR/ESD = 15/71) and 82 underwent PDT. Among the patients, 140 were male, and the median age was 72 (range: 45-88) years. Lesion characteristics were as follows: The clinical T stage before CRT/RT; T1a/T1b/T2/T3/T4a/unknown = 5/78/24/48/9/4 cases. Local failure before salvage therapy; residual/local recurrent lesions = 107/61 cases. Clinical tumor depth before salvage therapy; EP-LPM/MM-SM1/SM2-SM3 = 54/35/79 cases. 53 of the 54 patients with a tumor depth of EP-LPM underwent ER, while 73 of the 79 patients with a tumor depth of SM2-SM3 underwent PDT. The local complete response rate in PDT was 62% (50/81 patients, 1 not evaluated), and the R0 resection rate in ER was 73% (63/84 patients, 2 not evaluated due to burn effect). One patient in the PDT group died from massive gastrointestinal bleeding due to esophageal-aortic fistula on the 69th day after PDT. The median observation period was 33.5 (2-109) months, and the three-year overall survival (OS), disease-specific survival, local recurrence-free survival (LRFS), and esophagectomy-free survival rates were 79% (95% confidence interval: 71-86%), 88% (80-93%), 54% (46-62%), and 76% (67-82%), respectively. Multivariate analysis revealed that age ≥75 years and residual lesion just after CRT were independent risk factors of OS (p = 0.039 and p = 0.024, respectively). Clinical tumor depth was not a significant risk factor for OS and LRFS. The clinical course after salvage treatment was as follows: 93 patients had no recurrence; 28 patients had lymph node and/or distant metastatic recurrence with/without local failure. Of the 53 patients with local failure (residual: 33, local recurrence: 20) after initial salvage endoscopic therapy, 46 underwent re-salvage therapy (ER: 11, PDT: 27, surgery: 8), and 24 of them are alive without the recurrence of ESCC, while 8 died from the primary disease.

Conclusion

Our results suggest that salvage endoscopic therapy including ER or PDT appears to be an effective treatment option for cT1N0M0 local failure after CRT/RT, regardless of clinical tumor depth, resulting in a certain number of patients achieving long-term survival without the primary disease and preserving their esophagus.