Endoscopic Ultrasound Research Articles

P946 Real life management of patients with active perianal fistulizing Crohn’s disease (ALERT-CD study)

Abstract Background The multitude of medical and surgical treatment options for perianal fistulizing Crohn’s disease (pCD) impels differences in management. This study aimed to assess management of pCD in current clinical practice in the Netherlands. Methods Patients with active pCD (i.e. visible external fistula opening or patent fistula tract on imaging) were included in a prospective multicenter cohort study in 41 Dutch academic and non-academic hospitals from September 2022 to March 2023. pCD-related clinical, radiological and surgical data were prospectively collected during a follow-up period of 6 months and retrospectively collected from pCD diagnosis until inclusion. Primary outcome of the study was adherence to the international guidelines on pCD management during the disease course (from pCD diagnosis until end of follow-up). Adequate adherence was defined as (I) imaging for pCD diagnosis using magnetic resonance imaging (MRI) and/or endo-anal ultrasound (EUS), (II) endoscopic evaluation of concomitant proctitis, (III) use of antibiotics for symptomatic response, (IV) initiation of an anti-tumour necrosis factor (TNF) agent for maintenance therapy, (V) fistula surgery aiming at fistula closure in case of surgically amendable disease and (VI) decision making by a multidisciplinary team (gastroenterologist and surgeon)(Figure 1). Results 449 patients with active pCD (52% female) were included(Table 1). At inclusion, median age and median pCD duration were 37.2 years (IQR 28.8–49.4) and 3.1 years (IQR 1.1–7.1). 54% of patients were treated in a non-academic hospital. 89% of patients were treated with CD medication, which concerned anti-TNF agents in 82% of these patients. As recommended by guidelines, a MRI (99%) and/or EUS (9%) were performed in the vast majority of patients (97%) for pCD diagnosis. Following diagnosis, endoscopy was performed in 81% of patients. During the disease course, antibiotics were initiated in 55% of patients and at least one anti-TNF agent(s) was started in 84% of patients for maintenance therapy (73% infliximab, 53% adalimumab, 26% both agents). Surgery aiming for fistula closure was performed in 38% of patients during the disease course. 60% of patients were discussed in a multidisciplinary team (MDT). Conclusion This study demonstrated a high adherence to international guidelines on pCD management concerning imaging at diagnosis, endoscopic evaluation for concomitant proctitis and treatment with anti-TNF agents. Adherence to use of antibiotics for symptoms, performance of fistula surgery aiming at fistula closure and decision making in a MDT is moderate and standardization may optimize pCD management.

Chemotherapy and chemoradiotherapy for adenocarcinoma of the esophagus and junction with oligometastases: Results of the TNT-OES-1 trial.

328 Background: Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are effective as neoadjuvant regimens for esophageal and junction cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy. Although TNT is increasingly used in rectal cancer, there are no data on combining FLOT and CROSS in esophageal cancer. This study aimed to evaluate the feasibility and safety of the FLOT-CROSS combination in esophageal and junction adenocarcinoma patients with oligometastatic disease. Methods: This phase-II study included patients with oligometastatic (a maximum of four lesions in up to two organs, excluding lymph nodes) esophageal adenocarcinoma. Patients were treated with four biweekly cycles of FLOT. Response was evaluated by CT-scan 4-6 weeks after completion of FLOT. If patients showed regression or stable disease (SD) based on RECIST criteria (v1.1), they received CROSS. Four to six weeks after completion of CROSS, response was assessed by CT-scan, endoscopy with biopsies and endoscopic ultrasonography. The multidisciplinary tumor board discussed whether patients could proceed to four additional cycles of FLOT or local therapy of metastases and/or esophagectomy. Primary endpoint was tolerability of FLOT-CROSS, defined as the proportion completing the full regimens. Secondary endpoints included disease control rate (DCR), objective response rate, toxicity and the proportion proceeding to local therapy of metastases and/or esophagectomy. Results: Twenty patients were included, the majority was male (85%) with a median age of 62.5 years (interquartile range 58-66) Most patients (80%) had a single metastatic lesion. 14 of 20 patients (70%) successfully completed the FLOT regimen, four are still in therapy and two patients died. Eleven of 14 patients completed FLOT-CROSS and three patients showed disease progression following FLOT. Toxicity mainly consisted of grade 1-2 leukopenia/neutropenia during FLOT, leading to treatment delay in seven patients. One patient had malaise grade 2. No grade 3-4 toxicities or treatment delays/discontinuations occurred during CROSS. Following FLOT-CROSS, seven patients underwent four additional cycles of FLOT. Six patients underwent esophagectomy and two of those also underwent local treatment of metastases. A pathologically complete response was seen in two of these six patients (33%). Three of seven patients had a clinically complete response and opted for active surveillance after shared decision making. Three months after completion of FLOT-CROSS, the DCR was 82%. Conclusions: This study showed that sequencing FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity. We saw promising efficacy, with 82% having disease control three months after FLOT-CROSS. Survival data are expected mid-2024. Clinical trial information: NL9269 .

Organ preservation with durvalumab-based immunotherapy in combination with chemoradiation as definitive therapy for early stage, cT1, and cT2N0 esophageal adenocarcinoma with indication for radical surgery: A prospective, multicenter study of the FLOT-AIO Gastric Cancer Group (IKF-t057/PRESTO trial).

TPS431 Background: The outcome of patients (pts) with adenocarcinomas of stomach and esophagogastric junction (GEJ) remains unsatisfactory (5-year survival rates of 24-84%), whereby surgical resection is considered as cornerstone of the curative treatment for pts with early stage esophageal adenocarcinoma (EGA), however, it is associated with mortality, morbidity and an impact on the patient’s quality of life. Recent investigations showed that in locally advanced stage EGA surgery with neoadjuvant chemoradiotherapy (CROSS trial) is beneficial over surgery alone. Further benefit was achieved for locally advanced EGA by perioperative treatment with FLOT acc. to FLOT4- trial data. Immuno-oncology (IO) therapy by using checkpoint inhibitors is approved in the palliative and adjuvant EGA situation. In this trial we aim for the organ preservation treatment of EGA pts with a combination of the anti PD-L1 antibody durvalumab- FLOT - and chemoradio-therapy. Methods: This is a multicenter, single arm, open-label, phase II trial including a total of 32 pts with T1-T2N0 EGA (including GEJ) with indication for radical surgery. Enrolled pts will receive immunotherapy with durvalumab (1500 mg Q4W) in parallel to 2 cycles FLOT (50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate and 2600 mg/m2 5FU, Q2W) induction followed by 3 cycles of mFOLFOX (85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate, 400 mg/m2 5FU bolus and 1600 mg/m2 5FU over 48h, Q2W) plus concomitant radiation (25 daily fractions with 2.0 Gy = Σ50Gy). 8 weeks after last treatment, pts will undergo tumor assessment by esophagogastroduodenoscopy with biopsies, endoscopic ultrasonography, and CT- or MRI-scans. Surgical resection would be offered only to pts in whom a locoregional persistence is confirmed. Pts with complete remission will enter the maintenance phase and will receive durvalumab monotherapy (1500 mg, Q4W) for a maximum of 12 cycles accompanied by regular tumor re-evaluation. Primary endpoint is the rate of cCR/pCR at time of re-evaluation. Secondary endpoints include rate of cCR/pCR at 1, 2 and 3 years, rate of salvage surgery, 90 day and 1 year mortality after start of treatment, safety and quality of life. In this exploratory trial a cCR/pCR rate of ≥75% would indicate that the study treatment should be further investigated, whereas a rate < 55% indicates no further investigation. First patient was enrolled on 2023-08-28. Currently one patient is recruited. Clinical trial information: NCT05713838 .

The history of endoscopic ultrasound-guided fine-needle aspiration: development and progress.

Endoscopic ultrasonography (EUS) is an important diagnostic technique to accurately diagnose diseases originating from organs near the gastrointestinal tract. EUS-guided fine-needle aspiration (FNA) has improved the histopathological diagnosis. EUS-FNA has been further developed over a long period of 40years. The history of the development of endosonographic scopes, ultrasonographic observation systems, puncture needles, and puncture methods will provide a springboard for future development.

Pancreatic biopsy evaluation with nsCanary: A “smart ROSE” device for feedback on sample adequacy and cancer presence in endoscopic biopsies—Initial human clinical trial results.

618 Background: Pancreatic cancer (PC) accounts for 0.5 million new cases and 4.7% of the world's cancer-related deaths in 2020. Endoscopic ultrasound (EUS) guided fine needle biopsies (FNB) are the current standard of care for confirming suspicious lesions, however the diagnostic accuracy is reported below 70%. Rapid on-site evaluation (ROSE) improves the diagnostic performances of biopsies to reduce the number of needle passes, complication rates, and the need for additional procedures. However, availability of an on-site pathologist is often not feasible. NovaScan has pioneered the use of an impedance spectroscopy biomarker for cancer detection in different tissues based on the Cole Relaxation Frequency (CRF). NovaScan has developed the nsCanary, a ”smart ROSE” device that assesses PC presence in FNBs obtained during endoscopic procedures ex vivo, in real-time and on-site, without altering the tissue sample or affecting the workflow. Methods: Data were collected in a double-blind, IRB approved study from a cohort of 53 patients (28 males, 25 females) undergoing EUS procedures for suspected pancreatic lesions at the Texas International Endoscopy Center. FNBs were performed with a 22 gauge biopsy from a transduodenal approach. Each biopsy sample was transferred onto a disposable strainer allowing for any excess fluid to drain. An electrode for scanning was placed onto the core samples for data collection with the nsCanary a low cost, portable device used in the operating room. CRF is measured in the 1 kHz - 10 MHz frequency range via custom-designed hardware and assessment of the sample is completed in a few seconds. Subsequently, the sample is flushed into a pathology jar to undergo the standard workflow for cytology. The algorithm for extracting the CRF from the measurement was developed based on our previous preclinical study with transgenic KPC mice Samples with a CRF below 1 MHz were considered noncancerous, while CRF values above 1MHz or the absence of a CRF reading were considered cancerous. Results: PC assessment provided by nsCanary was validated against pathology outcomes for each biopsy sample. Findings showing a sensitivity of 86.7% and a specificity of 84.2% are reported in the table. Conclusions: We believe the nsCanary device will provide immediate feedback to the endoscopist on cancer presence and on the adequacy of the sample. This device is intended to support the decision-making process, by enabling clinicians to overcome the challenge of proving cancer presence during the first biopsy procedure, ultimately avoiding revisits and unnecessary trauma.[Table: see text]

Developing cell-free DNA (cfDNA) epigenetic signature (ep-Sig) for early detection of malignant transformation of intraductal papillary mucinous neoplasms (IPMN).

616 Background: Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers with poor outcomes. Around 20% arise from premalignant lesions (PML) including IPMN. Current guidelines recommend risk stratifying IPMN based on the location, size, and imaging characteristics after first diagnosis, followed by endoscopic ultrasound (EUS) in high-risk populations, and annual or bi-annual imaging. This approach can be improved with cfDNA testing. Traditional mutation testing in cfDNA is not useful secondary to their poor prevalence/detection rates. We propose ep-Sig to improve surveillance and early detection of PDA transformation. Methods: We curated an 11-gene cfDNA ep-Sig from the literature with a proven role in the malignant transformation of IPMN. Evidence suggests that epigenetic changes in every gene of this panel have a role in carcinogenesis in IPMNs. We compared RNA and gene expression of the genes in this ep-Sig between normal (NT) and PDA tissues using a web-based tool, TNMplot.com that uses the data from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories was used create this tool. It uses Mann-Whitney or Kruskal-Wallis tests to compute statistical significance. We used cell-free epigenome atlas (CFEA) database to examine the prevalence of these markers in cfDNA of PDA patients. Results: RNA expression of all the genes from the ep-Sig combined was significantly lower in PDA than NT (0.45, p=3.13e-26). Gene expression was 8/11 genes was lower in PDA tissues than NT (0.44, p=3.13e-26). The other 2 genes were not detected in the tested samples. Prevalence of all the markers in ep-Sig was > 90%. Conclusions: Our proposed ep-Sig has a high prevalence in PDA patients and has reliable preliminary evidence in tissues suggesting its diagnostic value. This study is the first step in developing non-invasive cfDNA testing with the potential to improve the current surveillance strategies for IPMN pending larger prospective studies.

Comparative efficacies and safeties of cylindrical interstitial laser ablation and radiofrequency ablation on swine pancreas.

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30s, 450J) and cylindrical interstitial LA (CILA) (5 W, 90s, 450J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.

Role of endoscopic ultrasound in gallbladder and biliary system diseases in patients with normal transabdominal ultrasonography

BackgroundThe clinical management of patients experiencing recurrent abdominal pain resembling biliary-type, but with negative findings on conventional transabdominal ultrasound (TUS), poses a challenge. In recent years, endoscopic ultrasound (EUS) has emerged as a valuable tool for diagnosing gallbladder diseases. This study aims to assess the role of EUS in the evaluation of gallbladder and biliary system diseases specifically in patients with normal transabdominal ultrasonography results.MethodsThis study was a cross-sectional analytic study that enrolled 150 patients with any complaints related to the gallbladder and biliary system necessitating transabdominal ultrasound and endosonography in the period between February 2021 and December 2021.ResultsThe mean age of the studied patients was 46.1 ± 10.3 years; 46.7% were males and 53.3% were females. The main complaint was right abdominal pain in 78.0%; meanwhile, 74.7% had a picture of obstructive jaundice. EUS revealed gallbladder wall thickening in 15 patients (10%), mud and/or small stones inside the gallbladder in 73 patients (48.7%), positive GB mass and/or polyp findings in 30 patients (20%), and biliary lesions such as duct strictures and/or dilatations were detected in 48 patients (32%), while transabdominal ultrasound was normal in all those patients.ConclusionEndoscopic ultrasound (EUS) proves to be a valuable diagnostic modality in patients experiencing biliary-type abdominal pain, despite normal transabdominal ultrasonography results. It not only aids in the accurate diagnosis of underlying conditions but also has the potential to impact the management plan for these patients.

Lumen-apposing metal stents for the treatment of pancreatic and peripancreatic fluid collections and bleeding risk: a propensity matched study.

Endoscopic ultrasound (EUS)-guided drainage of symptomatic pancreatic fluid collections (PFCs) using the Hot-Axios device has recently been associated with a significant risk of bleeding. This adverse event (AE) seems to occur less frequently with the use of a different device, the Spaxus stent. The aim of the current study was to compare the rates of bleeding between the two stents. Patients admitted for treatment of PFCs by EUS plus lumen-apposing metal stent in 18 endoscopy referral centers between 10 July 2019 and 28 February 2022 were identified and their outcomes compared using a propensity-matching analysis. 363 patients were evaluated. After a 1-to-1 propensity score match, 264 patients were selected (132 per group). The technical and clinical success rates were comparable between the two groups. Significantly more bleeding requiring transfusion and/or intervention occurred in the Hot-Axios group than in the Spaxus group (6.8% vs. 1.5%; P = 0.03); stent type was a significant predictor of bleeding in both univariate and multivariate regression analyses (P = 0.03 and 0.04, respectively). Bleeding necessitating arterial embolization did not however differ significantly between the two groups (3.0% vs. 0%; P = 0.12). In addition, the Hot-Axios was associated with a significantly higher rate of overall AEs compared with the Spaxus stent (9.8% vs. 3.0%; P = 0.04). Our study showed that, in patients with PFCs, bleeding requiring transfusion and/or intervention occurred significantly more frequently with use of the Hot-Axios stent than with the Spaxus stent, although this was not the case for bleeding requiring embolization.

Role of contrast-enhanced harmonic endoscopic ultrasonography (EUS) and EUS elastography in pancreatic lesions.

Pancreatic cancers have a poor prognosis, and their incident rates have risen. Endoscopic ultrasonography (EUS) is an efficient and reliable diagnostic modality for pancreatic lesions, providing high spatial resolution. However, while EUS helps to detect minor pancreatic lesions, nearly all solid pancreatic lesions are hypoechoic, which creates difficulty in making differential diagnoses of pancreatic lesions. When diagnosing pancreatic lesions, the performance of image-enhanced EUS techniques is essential, such as EUS elastography or contrast-enhanced harmonic EUS (CH-EUS). CH-EUS diagnosis is based on assessing the vascularity of lesions, whereas tissue elasticity is measured via EUS elastography. Elastography is either strain or shear-wave, depending on the different mechanical properties being evaluated. The usefulness of enhanced EUS techniques is demonstrated in this review for the differential diagnosis of pancreatic lesions, including solid and cystic lesions, and pancreatic cancer staging.

Abstract B002: Phase I study of endoscopic ultrasound (EUS)-guided NBTXR3 delivery activated by radiotherapy (RT) for locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC)

Abstract Patients with LAPC or BRPC often receive radiation therapy (RT) after chemotherapy (chemo) if no metastatic progression has occurred. Historically, CA19-9 normalizes in ~20 to 30% of patients after all therapy. While escalated dose radiotherapy (EDR) has shown promising survival in selected patients, extending use of EDR to all patients is challenging due to RT dose limitations of the bowel. To overcome this limitation, we are investigating NBTXR3, composed of functionalized hafnium oxide nanoparticles administered by a single intratumoral injection, locally amplifying the RT dose. In this phase 1 trial, the primary objective is to determine the NBTXR3 recommended phase 2 dose (RP2D). Secondary objectives are to measure anti-tumor effects. The study uses a Bayesian optimal interval design (BOIN) and has two parts: dose-finding (NBTXR3 at [level 1] 33% of gross tumor volume [GTV] or [level 2] at 42% of GTV) and cohort expansion at RP2D. In part 1, eligibility criteria included only LAPC patients with no evidence of metastatic disease after 2-6 months of chemo, part 2 allows BRPC. NBTXR3 was administered once prior to RT via an EUS-guided intratumoral injection. All patients received 45 Gy in 15 fractions with intensity modulated radiation therapy (IMRT). Patients were followed up to 1 year. Dose-limiting toxicities (DLTs) were defined as any grade ≥ 3 adverse events definitely or possibly related to NBTXR3 and/or RT. Target tumor response was per RECIST v1.1 criteria. CA19-9 was measured serially. We defined CA19-9 normalization as a value of 37 U/ml after finishing NBTXR3/RT. We compared rates of CA19-9 normalization in this phase 1 trial to a historical cohort of patients who received modern chemo/RT without NBTXR3. As of July 12, 2023, 15 LAPC patients have been treated with NBTXR3/RT. The median age was 63 years [range 43-81], 8 males, 7 females. The first patient (level 1) and subsequent 14 patients (level 2) had no injection complications. Level 2 had 1 non-serious DLT related to RT. At 4 weeks post RT, 13 had stable disease (SD) locally (2 had progressive disease [PD] overall), 1 had PD locally, and 1 had radiographic complete response (CR). At 3 months post RT, 11 had SD locally (1 PD overall), 1 PD locally, and 1 had surgery with negative margins and no residual viable tumor. 9 patients had elevated CA19-9 before NBTXR3/RT, 7 of these 9 (78%) had a decrease in CA19-9 subsequently, and 2 of these 9 (22%) had CA19-9 normalization eventually. 12 patients had elevated CA19-9 at diagnosis, and 5 out of 12 patients (42%) had normalization of CA19-9 after all therapy. We reviewed 455 patients with LAPC/BRPC between 2015-2019 who were treated at our institution as a comparison cohort for CA19-9 normalization rates. Out of 307 patients with elevated CA19-9 at diagnosis and normal bilirubin, 95 normalized (31%) and 212 did not normalize (69%) within 6 months of receiving cytotoxic therapy. The RP2D of NBTXR3 is 42% of GTV. The responses and CA19-9 results in comparison to historical data suggest promising anti-tumor efficacy of NBTXR3/RT. Citation Format: Gabriela Fuentes, Maria J. Rodriguez, Matthew H.G. Katz, Naruhiko Ikoma, Ching-Wei D. Tzeng, Michael Overman, Shubham Pant, Michael S. Lee, Robert A. Wolff, Milind Javle, Cullen M. Taniguchi, Emma B. Holliday, Ethan B. Ludmir, Prajnan Das, Albert C. Koong, Omar I. Vivar, Suyu Liu, Eric P. Tamm, Leonard A. Farber, Manoop S. Bhutani, Eugene J. Koay. Phase I study of endoscopic ultrasound (EUS)-guided NBTXR3 delivery activated by radiotherapy (RT) for locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B002.

Abstract B001: Impedance based biomarker for “smart ROSE” pancreatic cancer detection: Initial results from an ongoing clinical trial with nsCanary

Abstract Pancreatic cancer (PC) accounts for half a million new cases and 4.7% of cancer-related deaths globally in 2020. Endoscopic ultrasound (EUS) guided fine needle biopsies (FNB) are the current standard for confirming suspicious lesions, although their diagnostic accuracy remains below 70% with a non-diagnostic rate of the first procedure as high as 40%. Rapid on-site evaluation (ROSE) was introduced to improve diagnostic accuracy via on-site pathology assessment. However, ROSE availability is often limited due to resource constraints. NovaScan has developed the nsCanary, a ”smart ROSE” device, which uses a bioimpedance spectroscopy biomarker based on the Cole Relaxation Frequency (CRF) to detect cancer in biopsy samples in real-time and on-site. The aim of this study is to present initial results from a clinical trial that validates the nsCanary’s ability to detect PC in biopsy samples. Data were collected with the nsCanary device in an IRB approved double-blind study including a cohort of 44 patients (20 males, 24 females; average age of 63 years; 66% White, 22% African American, 12% Hispanic) undergoing EUS procedures with FNB sampling for suspected PC at the Texas International Endoscopy Center in Houston, TX. The nsCanary is a small desktop instrument that performs spectral bioimpedance analysis to extract the CRF based biomarker in less than 30 seconds without altering the biopsied tissue. A touch panel user interface allows for the user to input information and start the measurement. Obtained biopsy samples were flushed in a disposable strainer in order to drain any excess fluid. A circular disposable electrode, consisting of an interdigitated array with alternating polarities was placed in contact with the sample to perform measurements of complex bioimpedance in the 1 kHz - 10 MHz frequency range. The design of the electrode allows it to sense the signal from samples as small as FNB cores. Samples with CRF value below 1 MHz for every scan were considered noncancerous. Samples with at least one CRF value above 1MHz or absence of CRF reading (i.e., CRF out of range) were considered cancerous. PC assessment provided by nsCanary was validated against histopathology outcomes for each biopsy sample. Pathology results indicated that out of the cancerous lesions observed, there were 7 cases of pancreatic adenocarcinoma, 2 cases of invasive adenocarcinoma, 1 case of ductal adenocarcinoma, and 1 case of metastatic renal cell carcinoma. Findings showed a sensitivity of 81.8%, specificity of 84.8%, PPV of 64.3% and NPV of 93.3% for a total of n=44 patients. The device is low cost, portable, and can be used in the surgical suite without interfering with the standard workflow or affecting the sample for following pathological assessment. The implementation of the nsCanary device into the clinic will adjunctively support the decision-making process by providing immediate feedback on cancer detection and sample adequacy. This will enable endoscopists to diagnose PC on the first biopsy procedure, ultimately facilitating prompt treatment of patients. Citation Format: Federica Dibennardo, Martina Guidetti, Onur Fidaner, Daniel S. Gehrke, Donato Ceres, Margaret C. John, Constantine H. Bovalis, Isaac Raijman, Les Bogdanowicz. Impedance based biomarker for “smart ROSE” pancreatic cancer detection: Initial results from an ongoing clinical trial with nsCanary [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B001.

Dysphagia associated with esophageal wall thickening in patients with nonspecific high-resolution manometry findings: Understanding motility beyond the Chicago classification version 4.0.

Previous studies have demonstrated that 50% of patients with normal high-resolution manometry (HRM) findings or ineffective esophageal motility (IEM) may have abnormal functional luminal imaging probe (FLIP) results. However, the specific HRM findings associated with abnormal FLIP results are unknown. Herein, we investigated the relationship between nonspecific manometry findings and abnormal FLIP results. We retrospectively analyzed 684 patients who underwent HRM at a tertiary care center in Seoul, Korea, based on the Chicago Classification version 4.0 protocol. Among the 684 patients, 398 had normal HRM findings or IEM. Of these 398 patients, eight showed esophageal wall thickening on endoscopic ultrasonography or computed tomography; however, no abnormalities were seen during esophagogastroduodenoscopy. Among these eight patients, seven showed repetitive simultaneous contractions (RSCs) in at least one of the two positions: 61% (±29%) in 10 swallows in the supine position and 51% (±30%) in five swallows in the upright position. Four patients who underwent FLIP had a significantly decreased esophagogastric junction distensibility index (1.0 ± 0.5 at 60 mL). Two of these patients underwent per-oral endoscopic myotomy (POEM) due to a lack of response to medication. Esophageal muscle biopsy revealed hypertrophic muscle with marginal eosinophil infiltration. A subset of patients (2%) with normal HRM findings or IEM and RSCs experienced dysphagia associated with poor distensibility of the thickened esophageal wall. FLIP assessment or combined HRM and impedance protocols may help better define these patients who may respond well to POEM.

Obesity Is Associated with Distal Migration of Pancreatic Adenocarcinoma to Body and Tail: A Multi-Center Study.

(1) Background: Pancreatic adenocarcinoma (PAC) is one of the most lethal types of cancer. Most cases of PAC occur in the head of the pancreas. Given the proximity of the pancreatic head to the bile duct, most patients present clinically during early stages of the disease, while distally located PAC could have delayed clinical presentation. (2) Aims: To assess predictors of non-head PAC. (3) Methods: A retrospective multicenter study was conducted, including all patients who had endoscopic ultrasound (EUS) for pancreatic masses and who had histologic confirmation of PAC. (4) Results: Of the 151 patients included, 92 (60.9%) had pancreatic head cancer, and 59 (39.1%) had distal pancreatic cancer. PAC at body was the most common location in the distal PAC group (31 patients (52.5%)). Logistic regression analysis demonstrated a significant association of obesity with distal migration of PAC (OR 4.44, 95% CI 1.15-17.19, p = 0.03), while none of the other assessed parameters showed a significant association. Notably, abdominal pain was more significantly associated with distal PAC vs. head location (OR 2.85, 95% CI 1.32-6.16, p = 0.008). (5) Conclusions: Obesity shows a significant association as a clinical predictor of distal PAC. Further studies are needed to better explore this association.

O-08 Mutation in insulin receptor gene with hypoglycemia symptoms

Abstract Introduction Monoallelic/heterozygous mutations in the insulin receptor INSR gene are typically associated with type A insulin resistance syndrome, but less is known about INSR-related hyperinsulinemic hypoglycaemia (HH) characterized by fasting hyperinsulinemia and postprandial hypoglycemia. Clinical Case A 38-year-old woman with a history of migraines not needing preventive medication was admitted to an endocrinology outpatient clinic because of general malaise, weakness, and reduced exercise tolerance. For several years, she has had to eat small snacks during the workday to avoid sudden hypoglycemic symptoms. As a result, she gained nearly 30 kilograms in a few years. The symptoms started after she lost 23 kg and weighed 55 kg after following a ketogenic diet in 2016. The symptoms worsened despite weight regain and dietary changes to attempt to avoid hypoglycemia. Diagnostic evaluation: Initial BMI was 31.5 kg/m2. Continuous glucose monitoring (CGM) showed low blood glucose levels during extended fasting, such as during the night or prolonged meal intervals during the workdays (Figure 1). Hypoglycemia also occurred during and after exercise. She underwent a 2-hour glucose tolerance test, a mixed-meal test and a 72-hour fasting test (Tables 1 and 2), abdominal CT, and endoscopic ultrasonography, none of which led to a specific diagnosis. The glucose profile of this patient had hypoglycemias &amp;lt;3.0 mmol/L only a few times, and normal findings on imaging suggest that insulinoma is unlikely. Blood samples were taken during a postprandial hypoglycemic episode at work, but the plasma glucose (3.2 mmol/L) did not meet the criteria for Whipple's triad (&amp;lt;2.7 mmol/L), despite pronounced symptoms that were relieved by consuming carbohydrates. Finally, gene panel for monogenic causes of hypoglycemia identified a likely pathogenic INSR mutation c.2106T&amp;gt;G, p. (Tyr702*), which turned out to have been found in a symptomatic third-degree relative several years ago. Isolated case reports have found a beneficial effect of metformin in decreasing hypoglycemic symptoms, although the exact mechanisms by which it may decrease symptoms are unclear. We conducted a treatment trial with increasing doses of metformin to manage the patient's symptoms and to decrease the insulin resistance that had developed as a result of the INSR mutation and pronounced weight gain. Before the treatment trial, BMI was 34.4 kg / m2. Patient responded positively to metformin and weight started to decrease. Her quality of health increased subjectively and hypoglycemic episodes decreased during work and exercise. Conclusion The differential diagnostics of hypoglycemia may be challenging. Monogenic causes for adulthood-onset hypoglycemia are very rare but should be considered in cases of prolonged hypoglycemia susceptibility impairing daily activities. Genetic testing is also warranted in cases of family history of hypoglycemia symptoms.Figure 1.Continuous glucose monitor (CGM)Patient had low blood glucose levels (2.9-3.6 mmol/L) during extended fasting, such as during the night or prolonged meal intervals during the workdays. Hypoglycemiasymptoms also occurred during and after exercise. Table 1.Laboratory Values Table 2.72-hour fasting test and 5-hour Mixed-Meal test

P-43 Pancreatic insulinoma with delayed challenging diagnosis by 68Ga-DOTATATE PET/CT scan: Case report

Abstract Introduction Insulinoma (I) is most common neuroendocrine pancreatic tumor with an incidence of 0.1-0.3/100000(1). It is faintly more in females and can develop at any age(2). Usually benign, sporadic, less than 2 cm, solitary and in 10% of cases is multiple and happens as a component of multiple endocrine neoplasia syndrome type I (MEN–I)(3). Nonspecific symptoms may lead to delayed or misdiagnosis. Improper insulin secretion causes clinical features of hypoglycemia(2). Laboratory verification, localization followed by surgical removal are the main steps management. Localization may be difficult and delayed as here. Clinical Case A female of 58 years old with episodes of sweating, palpitation and tremor improved by drinking sweets, weight gain and denied any drugs intake. No personal or family history of diabetes or antidiabetic drugs. Body weight was 87 kg. Investigations during the attack showed low plasma glucose of 36 mg/dL, high serum insulin of 94.8 mIU/L (1.7 - 31), elevated C-peptide of 10.6 ng/mL (0.9-4). Cortisol and thyroid function are normal. Abdominal ultrasound (US), CT scan and MRI are normal. Due to failure of localization of Insulinoma, treatment by diazoxide started with no response. Octreotide long-acting repeatable (Octreotide LAR) 20 mg monthly injection was initiated and increased to 30 mg monthly with good improvement and less attacks. After three years, the patient developed abdominal pain and abdominal US showed multiple gall stones. The patient was advised to do 68Ga-DOTATATE PET/CT Scan, which revealed distal pancreatic mass of 26 mm (Figure1A and B). Distal pancreatectomy and cholecystectomy had been done with smooth postoperative period normal normal plasma glucose, insulin and c-peptide with no further hypoglycemia, histopathological examination confirmed Insulinoma (Figure 2A and B). Hypoglycemic symptoms of I, whether neuroglycopenic or sympathoadrenal are precipitated by fasting or exercise and could precede diagnosis by months and even years(3). Insulinoma, should be suggested when patient has typical Whipple's triad, high insulin, c-peptide and proinsulin during the attack(3). Weight gain noted in about 18% of cases(4). Modalities used to localize Insulinoma include trans-abdominal US, CT scan, MRI, EUS (endoscopic ultrasound), intraoperative US, intraoperative palpation and arteriography. An American study considered 68Ga-DOTATATE PET/CT as an adjuvant tool for diagnosis with 90% detection rate (5). A 90-95% of cases are benign, patients have high survival with complete resolution of symptoms after excision with only 5.4% recurrences(6). Malignant I limited to pancreas and responsive to chemotherapy has 5 years survival rate after resection and 19 months for recurrent tumors(6). Conclusion Insulinoma should be considered in patients with typical clinical and laboratory finding. Follow up, assessment and different imaging techniques are main steps in management with teamwork.Figure 1.68Ga-DOTATATE PET/CT Scan68Ga-DOTATATE PET/CT Scan revealed distal pancreatic mass of 26 mm

The Diagnostic Yield of Endoscopic Ultrasound in Asymptomatic Patients with Unexplained Dilated Common Bile Duct, or Double Duct Sign with Normal Transaminase a Retrospective Study from a Single Urban-based University Endoscopy Center.

Common bile duct dilatation alone or double duct sign (both CBD and dilated pancreatic duct dilatation) and abnormal liver enzymes are highly predictive of biliary disease. This can be identified on ultrasound (US), CT scan, and/or magnetic resonance cholangiopancreatography (MRCP). Unexplained dilatation on imaging might warrant endoscopic ultrasound (EUS) to identify any occult causes. Supporting literature about the importance of using EUS in these conditions is evolving with no clear evidence-based approach to evaluate asymptomatic dilated ducts.We aim to investigate the diagnostic yield of EUS in unexplained CBD dilatation or double duct sign with normal liver enzymes. A retrospective data analysis was conducted from January 2015 to October 2021 on asymptomatic patients with a dilatated CBD of 7 mm or more and 9 mm if the patient had a cholecystectomy history or double duct sign with normal liver enzymes. 32 EUS procedures were indicated for unexplained dilated CBD or double duct sign on imaging with normal liver enzymes. 23 had CBD dilatation alone (72 %), and 9 had a double duct sign (28 %). 20 of the included patients were females (63 %), and 12 were males (37 %), with a mean age of 63.8 ± 17 and 68.2 ± 14 years old, respectively (p = 0.424). The diagnosis after EUS in CBD dilatation alone showed a yield of 56 % as follow; no pathology in 10 (44 %), sludge in 9 patients (39 %), CBD stone in 3 (13 %), malignant stricture in 1 (4 %) (Fig. 1). On the other hand, EUS in those with double duct signs showed a diagnostic yield of 55 %; no pathology in 4 (45 %), pancreatic head adenocarcinoma in 3 patients (33 %), Biliary stone in one patient, and malignant CBD stricture in one patient (11 % each) (Fig. 2). Unexplained CBD dilatation or Double duct sign on imagining in patients with normal liver enzymes should warrant further investigation with EUS to avoid missing serious pathological conditions such as stones, sludge, stricture, or a mass.

Surgical and Endoscopic Intervention for Chronic Pancreatitis in Children: The Kings College Hospital Experience.

Paediatric chronic pancreatitis (CP) is a rare and debilitating pathology that often requires invasive diagnostics and therapeutic interventions either to address a primary cause such as a pancreaticobiliary malunion or to deal with secondary complications such as chronic pain. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are two endoscopic modalities that have an established diagnostic role in paediatric CP, and their therapeutic utilisation is increasing in popularity. Surgical decompression of the obstructed and dilated pancreatic duct plays a role in alleviating pancreatic duct hypertension, a common association in CP. Surgery equally has a role in certain anatomical abnormalities of the pancreaticobiliary draining system, or occasionally in some CP complications such as drainage of a symptomatic pancreatic pseudocyst.

EUS-guided interventional therapies for pancreatic diseases.

Endoscopic ultrasound (EUS) is an integrated diagnostic technique merging endoscope and ultrasound to examine the digestive system. EUS has emerged as a primary diagnostic method for pancreatic diseases due to its distinctive benefits. Over the past four decades, EUS has undergone a transformation, shifting its role from primarily diagnostic to increasingly therapeutic. Additionally, in recent years, EUS has emerged as an increasingly prominent adjunctive or alternative approach to conventional surgical interventions. This review provides a comprehensive analysis of current technological approaches in the treatment of pancreatic diseases. The dynamic interplay with diverse therapeutic approaches has reinvigorated EUS and shaped its trajectory in the management of pancreatic diseases.

Protocol for a Multi-Center Confirmatory Trial to Evaluate the Differential Diagnostic Performance of Contrast-Enhanced Ultrasonography Using Perflubutane in Patients with a Pancreatic Mass: A Multicenter Prospective Study.

For pancreatic masses, an evaluation of their vascularity using contrast-enhanced ultrasonography can help improve their characterization. This study was designed to evaluate the utility and safety of contrast-enhanced transabdominal ultrasonography (CE-TUS) and endoscopic ultrasonography (CE-EUS) in the diagnosis of pancreatic masses including solid or cystic masses. This multi-center comparative open-label superiority study is designed to compare Plain (P)-TUS/EUS alone with P-TUS/P-EUS plus CE-TUS/CE-EUS. Three hundred and one patients with a total of 232 solid pancreatic masses and 69 cystic masses were prospectively enrolled. The primary endpoints are to compare the diagnostic accuracy between P-TUS/P-EUS alone and P-TUS/P-EUS plus CE-TUS/CE-EUS for both the TUS and EUS of solid pancreatic masses, and to compare the diagnostic accuracy between P-EUS alone and P-EUS plus CE-EUS in cystic pancreatic masses. The secondary endpoints are to compare the diagnostic sensitivity and specificity of P-TUS/P-EUS alone and P-TUS/P-EUS plus CE-TUS/CE-EUS for pancreatic solid/cystic masses, and the accuracy of P-TUS alone and P-TUS plus CE-TUS for pancreatic cystic masses. Other secondary endpoints included comparing the diagnostic sensitivity, specificity, and accuracy of CE-TUS, CE-EUS and CE-computed tomography (CT) for solid/cystic pancreatic masses. The safety, degree of effective enhancement, and diagnostic confidence obtained with CE-TUS/CE-EUS will also be assessed.