Introduction

Recent evolution of image-enhanced endoscopy (IEE) makes it possible to detect ESCC easily. However, we sometimes encounter the cases where IEE cannot detect ESCC. Iodine staining is a gold standard, but it cannot be used for those with allergy to iodine. We developed a novel fluorescence probe (EP-HMRG). EP-HMRG emits green fluorescence immediately after being cleaved by DPP-IV, which is overexpressed in ESCC. The advantages are its ability to be applied topically and its fast reactivity. We confirmed that EP-HMRG achieved high accuracy for ESCC (＞ 90%) even 5 minutes after application using biopsy samples (Sci Rep, 2016).

Aims & Methods

Our aim of the present study is to investigate the safety and feasibility of EP-HMRG through a first-in-human trial. This is a phase 1 trial to assess the safety and efficacy of EP-HMRG for ESCC patients. Those who were scheduled to undergo endoscopic resection (ER) for ESCC were enrolled in this study. After 20 mL of 50 μM EP-HMRG solution was sprayed into the esophagus, one biopsy was taken from each fluorescent and non-fluorescent area under the observation with the prototype fluorescence endoscope. The biopsy specimens were blinded and diagnosed by one board-certified pathologist; ER was performed the day after EP-HMRG spraying, and the patient was discharged 5 days after treatment.

Results

A total of 6 patients were recruited between November 2019 and February 2021. 4 of the 6 patients complained of mild dysphagia and chest pain after ER, which were attributed to ER itself. No adverse events related to EP-HMRG occurred. Fluorescence endoscopy revealed strong fluorescent areas in the esophagus in 3 patients and weak fluorescent areas in the remaining 3 patients. Biopsy pathology results showed that no cancer was proved in any of the non-fluorescent areas. SCC was proved in 4 of the 6 specimens of the fluorescent sites. In 2 cases where the fluorescence was weak, no cancer was proved in the biopsy specimens taken from fluorescent areas. Positive predictive value, negative predictive value and accuracy were 67%, 100%, and 83%, respectively.

Conclusion

Our first-in-human study of a novel fluorescent probe for ESCC revealed safety, whereas the diagnostic accuracy reached only 83%. One possible reason was that the detectability of the prototype endoscope did not reach the level of the dedicated fluorescent imaging device. The fluorescent endoscope used in this study was still under development, and the images were dark, which may have resulted in sampling errors or failure to capture fluorescence coloration. The development of a fluorescence endoscope that is comparable to a dedicated fluorescence imaging device is an issue to be addressed in the future.

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.

Introduction

The duodenum plays a key role in regulating metabolism and is known to be dysfunctional early in the development of metabolic diseases such as type 2 diabetes (T2D). Duodenal mucosal resurfacing (DMR) is a non-pharmacologic, investigational, endoscopic treatment designed to hydrothermally ablate the duodenal mucosa to restore the metabolic functionality of the duodenum in people with T2D. DMR has a CE mark, reimbursement in select medical centres in Germany, and has been evaluated in over 300 patients to date with favorable safety and metabolic benefits observed. As part of the currently enrolling, global, pivotal Revitalize 1 trial for DMR, competency-based training and implementation have evolved to support scalable education of advanced-endoscopist investigators.

Aims & Methods

Here, we describe the current endoscopist training program for DMR, demonstrate its alignment with the European Society of Gastrointestinal Endoscopy¹ and the American Society for Gastrointestinal Endoscopy² training and effectiveness principles, and provide evidence that training methodology for DMR has led to acceptable and consistent safety outcomes in Revitalize 1. The training program consists of three core elements designed to enhance advanced-endoscopist proficiency toward safe and efficacious execution of the DMR procedure:
1) Structured didactic overview of the DMR system, procedure, and core competencies;
2) Initial hands-on tracking of the DMR catheter through the validated DMR training simulator; and
3) Hands-on live-patient cases focused on the successful execution of the DMR procedure and demonstration of core competencies.
The DMR simulator was developed and validated to complement the didactic component of the training program and recapitulate endoscopy skills necessary to perform the procedure as intended. Successful training was defined as completion of the full program with demonstration of competency in core DMR skills and troubleshooting techniques using the simulator. Procedural success was defined as performing ablations along the anatomical length of the duodenum from immediately beyond the ampulla of Vater to the Ligament of Treitz, while minimizing longitudinal gaps between areas of ablated mucosa.

Results

The DMR training program has been used to train therapeutic endoscopists in 6 centres in the EU and US as investigators in Revitalize 1. All centres successfully completed training in ~3 hours within 2 weeks of the first case. Nine open-label patients have been treated, to date, with 100% procedural success rate. Baseline characteristics were consistent with uncontrolled T2D despite multiple glucose‑lowering medications and insulin: 66.7% male, median (min, max), age 60 (45, 68) years, HbA1c 8.5% (7.6%, 9.1%), weight 96 (85, 128) kg, and diabetes duration 13 (7, 24) years. Adverse events (AEs) definitely or probably related to the device and/or procedure included sore throat (n=2), abdominal bloating (n=1), and abdominal pain (n=1). AEs were mild and resolved without sequalae. No observed long-term device- or procedure-related AEs, no device- or procedure-related SAEs, and no unanticipated AEs have been observed to date.

Conclusion

The three core elements of the DMR training program, inclusive of the DMR simulator, are scalable and have been reproducibly employed to train advanced therapeutic endoscopists to safely perform the DMR procedure. Results thus far suggest that DMR appears to be a safe, broadly accessible, and disease‑modifying approach to treat metabolic disease, such as T2D, via therapeutic endoscopy.

References

¹Boškoski et al. Curriculum for bariatric endoscopy and endoscopic treatment of the complications of bariatric surgery: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy. 2023 Mar;55(3):276-293.
²Yang et al. The status of training in new technologies in advanced endoscopy: from defining competence to credentialing and privileging. Gastrointest Endosc. 2020 Nov;92(5):1016-1025.

Disclosure

IB: consultant–Apollo Endosurgery, Boston Scientific, Cook Medical, ERBE Elektromedizin; lecturer–Boston Scientific, Cook Medical, Microtech; grants–Apollo Endosurgery, Erbe Elektromedizin. CG: speaker–Intuitive Surgical (Proctor), BD, WL Gore, Medtronic. JV: consultant–Boston Scientific, Aspero Medical; research funding–Olympus America. MAG: research support/contracted research–Olympus America, Fractyl, Allurion Technologies; Consultant–Boston Scientific, Ambu. ES, KW, and HR: employees and shareholders of Fractyl Health, Inc. RS: Boston Scientific, Cook Medical, Intuitive Surgical.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease of the pancreas with a high mortality rate due to late diagnosis at an advanced stage for its asymptomatic progression. Chronic pancreatitis, one of the risk factors for the development of PDAC, complicates the diagnostic process as both conditions sometimes share overlapping clinical and pathological features. Identifying individuals at higher risk of developing the disease and detecting pancreatic cancer at an early, curable stage is critical to improving overall patient outcomes. This study investigates the potential of relative telomere length (RTL) in peripheral blood and microbiome composition as biomarkers for PDAC. These biomarkers could support a minimally invasive liquid biopsy approach for early diagnosis of PDAC, differentiation from chronic pancreatitis, and screening of high-risk individuals.

Aims & Methods

A total of 239 participants were enrolled in the study and were divided into four groups: patients with PDAC (n = 36), chronic pancreatitis (n = 60), type II diabetes mellitus (n = 91) and cancer-free individuals (n = 52). Peripheral blood samples were collected to estimate relative telomere length using the multiplex monochrome qPCR method. Stool samples from a subset comprising chronic pancreatitis patients (n = 13), PDAC patients (n = 12), and healthy controls (n = 7) were analysed using 16S rRNA sequencing for metataxonomic analysis of the gut microbiome.

Results

Microbiome analysis revealed dysbiosis in a subset of patients, with an overrepresentation of bacterial species such as Prevotella copri and Akkermansia muciniphila in chronic pancreatitis and PDAC patients. A trend towards reduced microbial diversity was observed in PDAC patients, with changes in bacterial composition already detectable in chronic pancreatitis patients. No significant differences were found in RTL between the PDAC and cancer-free patient groups, and the only risk factors associated with changes were age, gender and smoking.

Conclusion

The pilot findings suggest a general trend towards reduced microbial diversity in PDAC patients, with alterations in bacterial proportions already observed in individuals diagnosed with chronic pancreatitis. These data ptovide a basis for the development of non-invasive diagnostic strategies to improve early detection and clinical outcomes for patients with PDAC. However, relative telomere length has not been shown to be a reliable biomarker.

References

Wu H, Zou WB, Zhou DZ, Gu YT, Liao Z, Li ZS. Longer Leukocyte Telomere Length is Associated With an Increased Risk of Chronic Pancreatitis. Pancreas. 2017;46(8):e65-e66. doi:10.1097/MPA.0000000000000887
Riquelme E, Zhang Y, Zhang L, et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019;178(4):795-806.e12. doi:10.1016/j.cell.2019.07.008
Antwi SO, Petersen GM. Leukocyte Telomere Length and Pancreatic Cancer Risk: Updated Epidemiologic Review. Pancreas. 2018;47(3):265-271. doi:10.1097/MPA.0000000000000995
Campa D, Felici A, Corradi C, et al. Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review. Mutagenesis. 2025;40(1):39-47. doi:10.1093/mutage/gead034
Sexton RE, Uddin MH, Bannoura S, et al. Connecting the Human Microbiome and Pancreatic Cancer [published correction appears in Cancer Metastasis Rev. 2022 Jun;41(2):333. doi: 10.1007/s10555-022-10037-3.]. Cancer Metastasis Rev. 2022;41(2):317-331. doi:10.1007/s10555-022-10022-w

Introduction

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been widely used as a safe and effective method for obtaining samples from Solid masses around the gastrointestinal tract. It is difficult for endosonographers to determine the timing of termination of EUS-FNA. However, several reports have validated macroscopic on-site evaluation (MOSE) as safe and effective.

Aims & Methods

We performed a prospective pilot study to explore the value of MOSE in evaluating the specimen quality during magnifier-based EUS-FNA and confirm the cut-off length of visible tissue core (VTC). 79 consecutive patients who underwent EUS-FNA of solid masses around the gastrointestinal tract using 22-G needles were included in the study. After EUS-FNA, endosonographers used a special observation table to on-site evaluate all puncture specimens. Then, the specimens containing VTC were prepared into cell block and stained with haematoxylin-eosin (HE). Pathologists explored the relationship between VTC length and specimen quality. Finally, the receiver-operating characteristic (ROC) curve of the VTC length, with respect to the final diagnoses were plotted, and the accuracy of the area under the curve (AUC) for diagnostic yield was evaluated and to determine the optimal cut-off VTC length with the Youden index. The utility of optimal cut-off VTC length in diagnosis was investigated.

Results

1. In this study, EUS-FNA was performed on 93 masses in 79 patients, with a total number of needle passes of 249, including 221 needle passes (88.8%) containing VTC. The completion rate of EUS-FNA was 100% and the complication rate was 1.1%. Assisted by MOSE, the sensitivity, specificity, positive predictive value, negative predictive value and histological diagnostic rate of EUS-FNA in this study were 85.9% (73/85), 100.0% (8/8), 100.0% (73/73), 40.0% (8/20) and 87.1% (81/93), respectively. The kappa statistic indicated quite high agreement between EUS-FNA histologic diagnoses and final diagnoses (Kappa=0.511, P<0.05).
2. The pathologist scored the specimen and correlation analysis was performed by Spearman’s rank-order correlation. It is concluded that a positive correlation between specimen quality (integrity of tissue structure) and VTC length (rs=0.427, P<0.05). The ROC curve of the VTC length showed the cut-off VTC length of 7.45 mm with area under the curve of 0.838. With this cut-off level, the sensitivity and specificity of EUS-FNA were 80.8% and 66.7%, respectively.
3. Multivariate analyses of factors affecting the tissue diagnostic rate of EUS-FNA were performed. Inclusion factors were the maximum diameter of lesion, location of lesion, puncture method and the VTC length. The statistical results indicated that the VTC length ≥7.45mm and the maximum diameter of lesion were associated with the higher diagnostic rate of histopathology. However, the tissue diagnostic rate was not related to the location of lesion and puncture method.

Conclusion

1. MOSE could help endosonographers better assess specimen quality, so as to predict the specimen adequacy independently. We determined that the histological diagnostic yields were significantly improved when the VTC lengths obtained by EUS-FNA ≥7.45mm.
2. MOSE based on magnifying glass is practical for improving the specimen quality and reducing the number of needle passes when ROSE is unavailable. It is a safe, effective and economical diagnostic method for the solid masses around the gastrointestinal tract.

References

1. Iglesias-Garcia J, Dominguez-Munoz JE, Abdulkader I, et al. Influence of on-site cytopathology evaluation on the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic masses. Am J Gastroenterol 2011;106:1705-10.
2. Iglesias-Garcia J, Larino-Noia J, Abdulkader I, et al. Rapid on-site evaluation of endoscopic-ultrasound-guided fine-needle aspiration diagnosis of pancreatic masses. World J Gastroenterol 2014;20:9451-7.
3. Leung Ki EL, Lemaistre AI, Fumex F, et al. Macroscopic onsite evaluation using endoscopic ultrasound fine needle biopsy as an alternative to rapid onsite evaluation. Endosc Int Open 2019;7:E189-E194.
4. Iwashita T, Yasuda I, Mukai T, et al. Macroscopic on-site quality evaluation of biopsy specimens to improve the diagnostic accuracy during EUS-guided FNA using a 19-gauge needle for solid lesions: a single-center prospective pilot study (MOSE study). Gastrointest Endosc 2015;81:177-85.
5. Ishiwatari H, Sato J, Fujie S, et al. Gross visual inspection by endosonographers during endoscopic ultrasound-guided fine needle aspiration. Pancreatology 2019;19:191-195.

Disclosure

The authors have nothing to disclose.

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

Pancreatic fibrosis (PF) is a prominent histological feature of chronic pancreatitis and influences on vast majority of pancreatic disorders. So, PF early diagnosis gives a great opportunity to be a part of the strategy for preventing pancreatic diseases progression. It makes non-invasive PF assessment especially via biomarkers level measurement research perspective.

Aims & Methods

Aim was to evaluate the possibility of biomarkers levels measurement in PF grade assessment.
Methods. We measured interleukin-10 (IL-10) and interleukin-36 (IL-36), matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-9 (MMP-9), fibronectin (FN) and hyaluronic acid (HA) plasma levels from 165 patient who underwent surgery from April 2022 to February 2024 due to pancreatic tumors and advanced chronic pancreatitis. We included 69 (41.8%) male and 96 (58.2%) female patients, mean age was 57.91±13.5 (25-89). Serum levels of specified biomarkers were determined by enzyme immunoassay using commercial kits; data registration performed was carried out on a semi-automatic analyzer. PF morphological grade was assessed according to Klöppel & Maillet’s scoring system [1] and scaled into three grades: mild, moderate and severe PF.
This study was conducted within the healthcare research project “Assessment of pancreatic fibrosis as a prognostic factor for its diseases course” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department.

Results

Plasma FN (pFN) level was significantly (p=0.029) higher in patients with mild PF (pFN=110.7±72.7 μg/mL), than in patients with severe PF (pFN=74.9±32.8 μg/mL). The median pFN levels were significantly varied in groups with different grades of intralobular PF (p<0.05), but not in groups divided by perilobular PF grade (p>0.05). Moreover, pFN level significantly negatively correlated with PF integrative grade (Spearmen’s rho = -0.21, p=0.007). Regarding IL-10, IL36, MMP-1, MMP-9 and HA levels, there were no significant differences either in patients with different PF integrative grade, or in groups divided by perilobular and intralobular PF (p>0.05). We revealed no significant correlations between specified biomarkers levels and PF grade (p>0.05).

Conclusion

The FN serum level significantly decreased in patients with severe PF in contrast to patients with mild PF who had comparatively higher serum FN level. Oppositely, IL-10, IL36, MMP-1, MMP-9 and HA had shown no effect in PF grade assessment. It could be useful for noninvasive pancreatic fibrosis diagnosis and even for patients’ selection for advanced diagnostics.

References

1 Esposito I, Hruban RH, Verbeke C, et al. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club. Pancreatology. 2020;20(4):586-593. doi:10.1016/j.pan.2020.04.009