Challenges and advancing strategies of endoscopic submucosal dissection for early gastric cancer: The puzzle of eCura C1.

In this editorial, we explore the challenges of managing noncurative resections in early gastric cancer after endoscopic submucosal dissection (ESD), starting from the consideration recently made by Zhu et al. Specifically, we evaluate the management of eCura C1 lesions, where decisions regarding further interventions are pivotal yet contentious. Collaboration among endoscopists, surgeons, and pathologists is underscored to refine risk assessment and personalize therapeutic management. Recent advancements in ESD techniques and interdisciplinary collaboration offer opportunities for outcome optimization in managing eCura C1 lesions. Moreover, despite needing further clinical validation, molecular biomarkers have emerged as promising tools for enhancing prognostication. This manuscript highlights the ongoing research attempts to define treatment paradigms effectively and evaluates the potential of emerging options, ultimately aiming to improve patient care and outcomes in this complex clinical scenario.

Urgent ERCP performed with single-use duodenoscope (SUD) in patients with moderate-to-severe cholangitis: Single-center prospective study.

Background and study aims To assess the outcomes of urgent endoscopic retrograde cholangiopancreatography (ERCP) performed with a single-use duodenoscope (SUD) in patients with moderate-to-severe cholangitis. Patients and methods Between 2021 and 2022 consecutive patients with moderate-to-severe cholangitis were prospectively enrolled to undergo urgent ERCP with SUD. Technical success was defined as the completion of the planned procedure with SUD. Multivariate analysis was used to identify factors related to incidence of adverse events (AEs) and mortality. Results Thirty-five consecutive patients (15 female, age 81.4±6.7 years) were enrolled. Twelve (34.3%) had severe cholangitis; 26 (74.3%) had an American Society of Anesthesiologists (ASA) score ≥3. Twenty-eight patients (80.0%) had a naïve papilla. Biliary sphincterotomy and complete stone clearance were performed in 29 (82.9%) and 30 patients (85.7%), respectively; in three cases (8.6%), concomitant endoscopic ultrasound-gallbladder drainage was performed. Technical and clinical success rates were 100%. Thirty-day and 3-month mortality were 2.9% and 14.3%, respectively. One patient had mild post-ERCP pancreatitis and two had delayed bleeding. No patient or procedural variables were related to AEs. ASA score 4 and leucopenia were related to 3-month mortality; on multivariate analysis, leukopenia was the only variable independently related to 3-month mortality (odds ratio 12.8; 95% confidence interval 1.03-157.2; P =0.03). Conclusions The results of this "proof of concept" study suggest that SUD use could be considered safe and effective for urgent ERCP for acute cholangitis. This approach abolishes duodenoscope contamination from infected patients without impairing clinical outcomes.

Predicting residual neoplasia after a non-curative gastric ESD: validation and modification of the eCura system in the Western setting: the W-eCura score.

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

Risk of Residual Neoplasia after a Local-Risk Resection of Colorectal Lesions by Endoscopic Submucosal Dissection: A Multinational Study.

Endoscopic submucosal dissection (ESD) in colorectal lesions is demanding, and a significant rate of non-curative procedures is expected. We aimed to assess the rate of residual lesion after a piecemeal ESD resection, or after an en bloc resection but with positive horizontal margins (local-risk resection-LocRR), for colorectal benign neoplasia. A retrospective multicenter analysis of consecutive colorectal ESDs was performed. Patients with LocRR ESDs for the treatment of benign colorectal lesions with at least one follow-up endoscopy were included. A cohort of en bloc resected lesions, with negative margins, was used as the control. A total of 2255 colorectal ESDs were reviewed; 352 of the ESDs were "non-curative". Among them, 209 were LocRR: 133 high-grade dysplasia and 76 low-grade dysplasia. Ten cases were excluded due to missing data. A total of 146 consecutive curative resections were retrieved for comparison. Compared to the "curative group", LocRRs were observed in lengthier procedures, with larger lesions, and in non-granular LSTs. Recurrence was higher in the LocRR group (16/199, 8% vs. 1/146, 0.7%; p = 0.002). However, statistical significance was lost when considering only en bloc resections with positive horizontal margins (p = 0.068). In conclusion, a higher rate of residual lesion was found after a piecemeal ESD resection, but not after an en bloc resection with positive horizontal margins.

Left colonic localization, non-granular morphology, and pit pattern independently predict submucosal fibrosis of naïve colorectal neoplasms before endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) represents the method of choice for removal of large colorectal neoplasms with suspected submucosal invasion. Presence and degree of submucosal fibrosis increases ESD duration and technical complexity, reduces the rate of curative resection and reduces safety profile. The aim of the study was to identify pre-procedural predictive factors of submucosal fibrosis in naïve colorectal neoplasms and to assess the impact of fibrosis on technical and clinical ESD outcomes. METHODS: All consecutive ESD performed between 2014 and 2021 were retrieved from a prospectively collected database. For each patient, pre-procedural, procedural, and post-procedural data were recorded. Logistic regression was used to identify pre-procedural predictive factors for submucosal fibrosis. The study was approved by Institutional Reviewer Board and registered on ClinicalTrials.gov (NCT04780256). RESULTS: One hundred-74 neoplasms (46.6% rectum, 21.8% left colon, 31.6% right colon; size 34.9 ± 17.5 mm) from 169 patients (55.0% male; 69.5 ± 10.4-year-old) were included. 106 (60.9%) neoplasms were granular type laterally spreading tumor (LST-G), 42 (24.1%) non-granular (LST-NG), and 26 (14.9%) sessile; invasive pit pattern was observed in 90 (51.7%) lesions. No fibrosis (F0) mild (F1) and severe (F2) were observed in 62 (35.6%), 92 (52.9%), and 20 (11.5%), respectively. Left colonic localization [OR 3.23 (1.1-9.31)], LST-NG morphology [OR 5.84 (2.03-16.77)] and invasive pit pattern [OR 7.11 (3.11-16.23)] were independently correlated to submucosal fibrosis. Lower curative resection rate (59.8% vs. 93.5%, P < 0.001) was observed in case of fibrosis; the incidence of adverse events was higher in case of severe fibrosis (35.5%) compared to no (3.2%) and mild fibrosis (3.3%; P < 0.001). Procedure time was significantly impacted by presence and degree of fibrosis (P < 0.001). CONCLUSIONS: Left colonic localization, LST-NG morphology, and invasive pit pattern are independent predictors of fibrosis, affecting technical and clinical ESD outcomes. Pre-procedural stratification is pivotal to estimate procedure time, required operator's experience and advanced dissection techniques. Cecinato P et al. Left colonic localization, non-granular morphology, and pit pattern independently predict submucosal fibrosis of colorectal neoplasms before endoscopic submucosal dissection. Surg Endosc. 2023.

Risk of residual neoplasia after a noncurative colorectal endoscopic submucosal dissection for malignant lesions: a multinational study.

BACKGROUND : Endoscopic submucosal dissection (ESD) in colorectal lesions is technically demanding and a significant rate of noncurative procedures is expected. We aimed to assess the rate of residual lesions after a noncurative ESD for colorectal cancer (CRC) and to establish predictive scores to be applied in the clinical setting. METHODS : Retrospective multicenter analysis of consecutive colorectal ESDs. Patients with noncurative ESDs performed for the treatment of CRC lesions submitted to complementary surgery or with at least one follow-up endoscopy were included. RESULTS : From 2255 colorectal ESDs, 381 (17 %) were noncurative, and 135 of these were performed in CRC lesions. A residual lesion was observed in 24 patients (18 %). Surgery was performed in 96 patients and 76 (79 %) had no residual lesion in the colorectal wall or in the lymph nodes. The residual lesion rate for sm1 cancers was 0 %, and for > sm1 cancers was also 0 % if no other risk factors were present. Independent risk factors for lymph node metastasis were poor differentiation and lymphatic permeation (NC-Lymph score). Risk factors for the presence of a residual lesion in the wall were piecemeal resection, poor differentiation, and positive/indeterminate vertical margin (NC-Wall score). CONCLUSIONS : Lymphatic permeation or poor differentiation warrant surgery owing to their high risk of lymph node metastasis, mainly in > sm1 cancers. In the remaining cases, en bloc and R0 resections resulted in a low risk of residual lesions in the wall. Our scores can be a useful tool for the management of patients who undergo noncurative colorectal ESDs.

Endoscopic submucosal dissection in colorectal neoplasia performed with a waterjet system-assisted knife: higher en-bloc resection rate than conventional technique.

BACKGROUND/AIMS: Colorectal endoscopic submucosal dissection (ESD) is burdened by its associated high risk of adverse events and long procedure time. Recently, a waterjet-assisted knife was introduced to simplify and speed up the procedure. The aim of this study was to evaluate the efficacy and safety of waterjet-assisted ESD (WESD) compared to that of the conventional ESD (CESD) technique. METHODS: The charts of 254 consecutive patients who underwent colorectal ESD between January 2014 and February 2021 for colorectal neoplasms were analyzed. The primary outcome was the en-bloc resection rate. Secondary outcomes were complete and curative resection rates, the need to switch to a hybrid ESD, procedure speed, the adverse event rates, and the recurrence rates. RESULTS: Approximately 174 neoplasias were considered, of which, 123 were removed by WESD and 51 by CESD. The en-bloc resection rate was higher in the WESD group (94.3% vs. 84.3%). Complete resection rates and curative resection rates were similar. The need to switch to a hybrid ESD was greater during CESD (39.2% vs. 13.8%). Procedure speed and adverse event rates were similar. During follow-up, one recurrence occurred after a WESD. CONCLUSION: WESD allows a high rate of en-bloc resections and less frequently requires a rescue switch to the hybrid ESD compared to CESD.

Underwater endoscopic submucosal dissection and hybrid endoscopic submucosal dissection as rescue therapy in difficult colorectal cases.

Background and study aims Colorectal endoscopic submucosal dissection (ESD) is still not widely used due to its technical difficulty and the risk of complications. Rescue therapies such as hybrid ESD (H-ESD) have been proposed for very difficult cases, as has underwater ESD (U-ESD). This study evaluated the safety and efficacy of H-ESD and U-ESD in difficult cases. Patients and methods The hospital charts of consecutive patients referred for colorectal ESD between January 2014 and February 2021 because they were considered difficult cases were retrospectively analyzed. The primary outcome of the study was en bloc resection rate; secondary outcomes were the rate of complete resection, procedure speed, and incidence of adverse events (AEs). Results Fifty-nine colorectal neoplasms were considered, 22 of which were removed by U-ESD and 37 by H-ESD. The en bloc resection rate in the U-ESD group was 100 %, while it was 59.5 % in the H-ESD group. Dissection speed was 17.7mm 2 /min in the U-ESD group and 8.3 mm 2 /min in the H-ESD group. The AE rate was low in the U-ESD group and moderately high during H-ESD (5 % and 21.6 %, respectively; and perforation rate 0 % and 10.8 %, respectively). Larger lesions were treated with U-ESD, while more fibrotic ones were treated with H-ESD. Conclusions U-ESD and H-ESD are both effective and safe techniques in difficult colorectal situations. U-ESD is particularly effective and fast for large lesions when it is not possible to obtain comfortable knife position, while H-ESD is more suitable for very fibrotic lesions.

Fusion radiology in interventional endoscopy (FRIend): a new approach for pancreatic fluid collections.

Background and study aims Fusion imaging consists of overlaying preoperative imaging over live fluoroscopy, providing an augmented live guidance. Since 2017, we have been using a new hybrid operating room (Discovery IGS 740 OR, GE Healthcare) for biliopancreatic endoscopy, combining fusion imaging with traditional endoscopic ultrasound (EUS). This study aimed to assess the advantages that fusion imaging could bring to EUS-guided drainage of post-pancreatitis fluid collections. Patients and methods Thirty-five drainage procedures performed between 2012 and 2019 with traditional guidance and fusion imaging were retrospectively compared, assessing the overall treatment success rate - i. e. symptom improvement with complete PFC emptying - as a primary outcome. Secondary outcomes included technical success rate, time to resolution, hospital stay length, adverse events, recurrence rate, and procedure time. Results Patients treated with standard EUS (n = 17) and with fusion imaging (n = 18) were homogeneous in age, gender, pancreatitis etiology, and indication for drainage; the second group had larger PFCs, more frequently walled-off necrosis than pseudocysts, and were treated more emergently, indicating higher case complexity in this group. During the period when fusion imaging was adopted, procedures had a higher overall treatment success rate than during the period when standard EUS was adopted (83.3 % vs. 52.9 %, P  = 0.075), and complete emptying was reached in less time (61.1 % vs. 23.6 % complete emptying within 90 days, P  = 0.154), differences compatible with random fluctuations. Conclusions This study suggests that fusion imaging in combination with EUS might improve clinical and procedural outcomes of PFC drainage.

The endoscopic ultrasound features of pancreatic fluid collections and their impact on therapeutic decisions: an interobserver agreement study.

BACKGROUND: A validated classification of endoscopic ultrasound (EUS) morphological characteristics and consequent therapeutic intervention(s) in pancreatic and peripancreatic fluid collections (PFCs) is lacking. We performed an interobserver agreement study among expert endosonographers assessing EUS-related PFC features and the therapeutic approaches used. METHODS: 50 EUS videos of PFCs were independently reviewed by 12 experts and evaluated for PFC type, percentage solid component, presence of infection, recognition of and communication with the main pancreatic duct (MPD), stent choice for drainage, and direct endoscopic necrosectomy (DEN) performance and timing. The Gwet's AC1 coefficient was used to assess interobserver agreement. RESULTS: A moderate agreement was found for lesion type (AC1, 0.59), presence of infection (AC1, 0.41), and need for DEN (AC1, 0.50), while fair or poor agreements were stated for percentage solid component (AC1, 0.15) and MPD recognition (AC1, 0.31). Substantial agreement was rated for ability to assess PFC-MPD communication (AC1, 0.69), decision between placing a plastic versus lumen-apposing metal stent (AC1, 0.62), and timing of DEN (AC1, 0.75). CONCLUSIONS: Interobserver agreement between expert endosonographers regarding morphological features of PFCs appeared suboptimal, while decisions on therapeutic approaches seemed more homogeneous. Studies to achieve standardization of the diagnostic endosonographic criteria and therapeutic approaches to PFCs are warranted.

Endoscopic Papillectomy for Ampullary Adenomas: Different Outcomes in Sporadic Tumors and Those Associated with Familial Adenomatous Polyposis.

BACKGROUND: Ampullary adenomas are rare and potentially malignant. Surgery was the standard treatment but endoscopic papillectomy (EP) is a possible alternative. AIM: We retrospectively evaluated the principal clinical outcomes of EP in all patients referred to our unit also dividing sporadic ampullary adenoma (SAA) from familial adenomatous polyposis (FAP)-associated adenomas. METHODS: All consecutive patients who underwent endoscopic papillectomy because of ampullary adenoma were considered. The primary outcome was the technical success of EP. Secondary outcomes included the number of procedures, the adverse event rate, the recurrence rate, the concordance of histology pre- and post-EP, and the evaluation of factors related to technical success. RESULTS: Between January 2001 and December 2015, sixty-two patients were included (21 FAP and 41 SAA). Technical success was achieved in 75.8% and was different in the two groups (FAP 95.2%, SAA 65.8%, p 0.025). Intraductal invasion was negatively associated with technical success (41.7% vs. 84.0%; p 0.005). The intestinal subtype was predictive of success (79.7% vs. 0%; p 0.012) as well as en bloc resection (90.3% vs. 61.3%; p 0.016). Adverse events were reported in 14 patients (22.6%). CONCLUSIONS: EP is an effective and safe procedure and is a viable alternative to surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03494543.

Linked-color imaging versus white-light colonoscopy in an organized colorectal cancer screening program.

BACKGROUND AND AIMS: Linked-color imaging (LCI), a new image-enhancing technology emphasizing contrast in mucosal color, has been demonstrated to substantially reduce polyp miss rate as compared with standard white-light imaging (WLI) in tandem colonoscopy studies. Whether LCI increases adenoma detection rate (ADR) remains unclear. METHODS: Consecutive subjects undergoing screening colonoscopy after fecal immunochemical test (FIT) positivity were 1:1 randomized to undergo colonoscopy with LCI or WLI, both in high-definition systems. Insertion and withdrawal phases of each colonoscopy were carried out using the same assigned light. Experienced endoscopists from 7 Italian centers participated in the study. Randomization was stratified by gender, age, and screening round. The primary outcome measure was represented by ADR. RESULTS: Of 704 eligible subjects, 649 were included (48.9% men, mean age ± standard deviation, 60.8 ± 7.3 years) and randomized to LCI (n = 326) or WLI (n = 323) colonoscopy. The ADR was higher in the LCI group (51.8%) than in the WLI group (43.7%) (relative risk, 1.19; 95% confidence interval, 1.01-1.40). The proportions of patients with advanced adenomas and sessile serrated lesions were, respectively, 21.2% and 8.6% in the LCI arm and 18.9% and 5.9% in the WLI arm (not significant for both comparisons). At multivariate analysis, LCI was independently associated with ADR, along with male gender, increasing age, and adequate (Boston Bowel Preparation Scale score ≥6) bowel preparation. At per-polyp analysis, the mean ± standard deviation number of adenomas per colonoscopy was comparable in the LCI and WLI arms, whereas the corresponding figures for proximal adenomas was significantly higher in the LCI group (.72 ± 1.2 vs .55 ± 1.07, P = .05) CONCLUSIONS: In FIT-positive patients undergoing screening colonoscopy, the routine use of LCI significantly increased the ADR. (Clinical trial registration number: NCT03690297.).

Epidemiology, clinical features and diagnostic work-up of cystic neoplasms of the pancreas: Interim analysis of the prospective PANCY survey.

INTRODUCTION: A prospective survey to evaluate the diagnostic workup of cystic pancreatic neoplasms (CPNs) according to the Italian guidelines. METHODS: An online data sheet was built. RESULTS: Fifteen of the 1385 patients (1.1%) had non cystic neoplastic lesions. Forty percent (518/1295) had at least one 1st degree relative affected by a solid tumor of the digestive and extra-digestive organs. Symptoms/signs associated with the cystic lesion were present in 24.5% of the patients. The cysts were localized in the head of the pancreas in 38.5% of patients. Of the 2370 examinations (1.7 examinations per patient) which were carried out for the diagnosis, magnetic resonance imaging was performed as a single test in 48.4% of patients and in combination with endoscopic ultrasound in 27% of the cases. Of the 1370 patients having CPNs, 89.9% had an intraductal papillary mucinous neoplasm (IPMN) (70.1% a branch duct IPMN, 6.2% a mixed type IPMN and 4.6% a main duct IPMN), 12.7% had a serous cystadenoma, 2.8% a mucinous cystadenoma, 1.5% a non-functioning cystic neuroendocrine neoplasm, 0.7% a solid-pseudopapillary cystic neoplasm, 0.3% a cystic adenocarcinoma, and 1.2% an undetermined cystic neoplasm. Seventy-eight (5.7%) patients were operated upon after the initial work-up. CONCLUSIONS: This prospective study offers a reliable real-life picture of the diagnostic work-up CPN.

Endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction after failed ERCP in low performance status patients.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with the placement of a biliary stent is the treatment of choice for palliation of malignant obstructive jaundice. In 5-10% of cases ERCP fails. In these cases an effective alternative is endoscopic ultrasonography-guided biliary drainage (EUS-BD). AIM: Evaluation of the principal clinical outcomes of direct transluminal EUS-BD. PATIENTS AND METHODS: This study is a retrospective analysis. All consecutive patients with malignant obstructive jaundice, in whom ERCP had failed, were enrolled. The primary outcome was the technical success of EUS-BD defined as the correct placement of the metal or plastic stent across the stomach or duodenum to the biliary tree. The most important secondary outcomes were early and late clinical success, both linked to the decrease of bilirubin haematic level. RESULTS: Between January 2011 and November 2017 thirty-six patients were included. Technical success was obtained in 91.6%. A clinical success, early or late was obtained in 75.8%. The ECOG performance status of less than 3 was correlated with clinical success. Adverse events occurred in 30.3% of patients. CONCLUSIONS: EUS-BD is an effective and safe procedure.

Endoscopic submucosal dissection: Italian national survey on current practices, training and outcomes.

BACKGROUND AND AIMS: Most of the evidence supporting endoscopic submucosal dissection (ESD) comes from Asia. European data are primarily reported by specialized referral centers and thus may not be representative of common European ESD practice. The aim of this study is to understand the current state of ESD practice across Italian endoscopy centers. METHODS: All Italian endoscopists who were known to perform ESD were invited to complete a structured questionnaire including: operator features and competencies, ESD training details and clinical outcomes over a 2-year period. RESULTS: Twenty-nine operators from 23 centers (69% response rate) completed the questionnaire: 18 (62%) were <50 years old; 7 (24%) were female; 16 (70%) were located in Northern Italy. Overall ESD volume was <40 cases in 9 (31%) operators, 40-80 in 8 (27.5%), 80-150 in 4 (13.8%) and >150 in 8 (27.5%). Colorectal ESD was predominant for operators with an experience >80 cases. En-bloc resection rates ranged from 77.2 to 97.2% depending on the anatomic location with an R0 resection rate range of 75.3-93.6%. ESD perforation rates in the colon and rectum were significantly lower when experience was >150 compared to 80-150 cases (p < 0.0001 and p = 0.006 for colon and rectum, respectively). CONCLUSION: ESD in Italy is performed by a significant number of operators. Overall, Italian endoscopists performing ESD have achieved a good competence level. However, there is much variability in training protocols, initial supervision of procedures, practice settings, case mix and procedural volume/year that are likely responsible for some of the suboptimal resectional outcomes and increased perforation risk, mainly in the colon. Standardized training programs, practice parameters and auditing of outcomes are required.