Background/Objectives: As endoscopy is increasingly being used to diagnose superficial nonampullary duodenal epithelial tumors (SNADETs), there is a growing need for their early detection and minimally invasive treatment. This study investigated the diagnostic accuracy of biopsy specimens for SNADETs. Methods: We conducted a retrospective analysis of clinicopathologic data from 98 patients with SNADETs who had undergone endoscopic resection. The presurgical diagnosis, based on biopsy specimens, was compared with the histological diagnosis of the excised specimens. Results: Herein, preoperative biopsies were performed on 98 SNADETs specimens from 91 patients. Of the 68 adenomas and 30 carcinomas, 22.4% adenomas were later found to be carcinomas. Carcinoma biopsy diagnosis sensitivity, specificity, and accuracy were 54.6%, 80.0%, and 71.4%, respectively. Biopsy accuracy for carcinoma differed significantly by location to the papilla of Vater (p = 0.0455). The preoperative biopsy diagnostics' sensitivity, specificity, and accuracy for oral and anal carcinomas to Vater papilla were 69.2%, 92.0%, and 84.2% and 42.1%, 73.2%, and 63.3%, respectively. Conclusions: The diagnostic accuracy of biopsy for SNADETs was low; however, it was higher on the oral side than the anal side of the papilla of Vater. The biopsy of duodenal lesions should be performed after an endoscopic examination, considering their location and reducing the risks of fibrosis.

Endoscopic mucosal resection (EMR) of superficial nonampullary duodenal epithelial tumors (SNADETs) is challenging, and to date, only a few studies assessed the clinical outcomes of EMR in the duodenum. The aim of this study was to evaluate the efficacy and safety of EMR for the treatment of SNADETs >10 mm.

This is a single-center retrospective study reporting data from a cohort of consecutive patients undergoing EMR of large (>1 cm) SNADETs between January 2017 and December 2021.

A total of 81 patients with 83 lesions underwent EMR (70 conventional EMR, 13 underwater EMR). The median size was 20 mm (range: 10-60 mm). The mean procedure time was 45 ± 30 min, and the en-bloc resection rate was 47%. In all patients, SNADETs were successfully removed (i.e. technical success). Delayed bleeding occurred in 5 (6%) of EMRs. One delayed perforation occurred, which was managed surgically. Recurrence rate was 20% with a median follow-up period of 20.5 months. Recurrence was detected at the first endoscopic follow-up in 88% of cases, and all recurrences were successfully treated endoscopically. Lesion size ( P  = 0.04), previous endoscopic resection ( P  = 0.05), and piecemeal resection ( P  = 0.05) were independent risk factors of local recurrence after EMR on multivariate-adjusted analysis.

Large duodenal adenomas can be effectively managed by EMR. However, duodenal EMR of large lesions carries a significant risk of early recurrence, with a nonnegligible risk of adverse events. Lesion dimension, piecemeal resection, and previous endoscopic resection were associated with a higher recurrence rate. Close endoscopic follow-up is recommended given the high incidence of early recurrence, which can be successfully treated endoscopically.

The pathogenesis of non-ampullary duodenal epithelial tumors (NADETs) is not fully understood. NADETs that express gastric-type mucin phenotypes (G-NADETs) are noteworthy because of their high malignancy. Gastric foveolar metaplasia, from which G-NADETs originate, protects the duodenal mucosa from gastric acidity. As gastric acid secretion is affected by endoscopic gastric mucosal atrophy (EGMA), we hypothesized that EGMA would be associated with G-NADETs.

To evaluate the association between EGMA and the occurrence of G-NADETs.

This cross-sectional retrospective study investigated the relationship between EGMA and NADETs in 134 patients. The duodenum was divided into parts 1 (bulb), 2 (superior duodenal angle to the papilla), and 3 (anal side of the papilla to the horizontal part). The effects of gastric acidity and presence of Brunner's glands were considered. EGMA was divided into types C (no or mild atrophy) and O (severe atrophy). Mucin phenotype expressions in NADETs were divided into gastric, intestinal, gastrointestinal, and unclassifiable.

When NADETs were classified according to EGMA, 105 were classified as type C and 29 as type O. G-NADETs were present in 11.9% (16 cases) of all cases, and all 16 cases were of type C. Among G-NADETs, 93.8% (15 cases) were present in part 1 or 2. There was an association between G-NADETs and type C in part 1, and 50.0% (eight of 16 cases) of G-NADETs were associated with a current or previous Helicobacter pylori infection status. Additionally, all eight cases occurred in part 1.

G-NADETs were significantly associated with type C. Gastric acidity and Brunner's gland growth may be associated with G-NADETs.

Endoscopic resection (ER) of non-ampullary duodenal epithelial tumors (NADETs) is associated with a high incidence of delayed bleeding (DB). While previous reports have identified composite risk factors for delayed adverse events, including both DB and delayed perforation, the specific factors associated with DB remain unclear. This study aimed to identify factors associated with DB after ER of NADETs.

This retrospective study included 335 consecutive patients who underwent ER for a NADET between January 2004 and December 2023. Participants were divided into the DB and non-DB groups. We compared baseline characteristics and clinical outcomes between the two groups to identify factors associated with DB. ER included endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) techniques. DB was defined as bleeding that required endoscopic hemostasis or transfusion after ER. Complete mucosal closure (CMC) was defined as the complete closure of the defect with no endoscopically visible exposure of the defect.

Overall, 128 ESD procedures and 207 non-ESD procedures were performed. DB occurred in 13 patients (3.9%) and its incidence was lower when CMC was achieved (1.1% vs. 13.9%, P < 0.001). Multivariate analysis revealed the use of antithrombotic agents (odds ratio (OR) 3.8; 95% confidence interval (CI): 1.0-14.6, P = 0.048) and a defect circumference ≥ 1/2 (OR 6.2; 95% CI 1.2-30.5, P = 0.029) as risk factors for DB, and CMC (OR 0.19, 95% CI 0.038-0.95, P = 0.043) as a protective factor. Among the 66 patients with risk factors, including the use of antithrombotic agents and/or a defect circumference ≥ 1/2, CMC reduced the incidence of DB (4.5% [2/44], vs. 31.8% [7/22], P = 0.005).

We identified significant factors associated with DB after duodenal ER. Particularly, in patients with risk factors for DB, CMC can reduce the incidence of DB.

Optical diagnosis of superficial nonampullary duodenal epithelial tumors using white-light imaging (WLI) and/or narrow-band imaging with magnifying endoscopy (NBI-ME) is used to guide the treatment strategy and avoid biopsy-induced fibrosis. However, the effectiveness of this approach has not been elucidated. We conducted a systematic review and meta-analysis aiming to investigate the diagnostic yield between Vienna classification category 3 (VCL C3) and categories 4 or 5 (VCL C4/C5) using biopsy, WLI, NBI-ME, and WLI + NBI-ME.

A literature search identified studies on the diagnosis of superficial nonampullary duodenal epithelial tumors using biopsy, WLI, or NBI-ME. A bivariate random-effects model was utilized to analyze the summary estimates of sensitivity and specificity, as well as the area under the summary receiver operating characteristic curves for diagnosing VCL C4/C5.

Ultimately, 13 studies were included in the meta-analysis. For the diagnosis of VCL C4/C5, summary estimates of sensitivity, specificity, and area under the curve were for biopsy 47% (95% confidence interval: 37-58), 86% (79-91), and 0.745; for WLI 80% (65-89), 80% (70-87), and 0.859; for NBI-ME were 72% (61-81), 76% (68-85), and 0.811; and for WLI + NBI-ME 88% (67-96), 87% (51-98), and 0.929, respectively.

WLI, NBI-ME, and WLI + NBI-ME showed high values for sensitivity and area under the curve. Biopsies can be replaced by WLI, NBI-ME, and WLI + NBI-ME for the preoperative diagnosis of superficial nonampullary duodenal epithelial tumors. However, further accumulation of research findings is needed.

Early-stage, poorly differentiated, non-ampullary duodenal adenocarcinomas are rare, and their clinicopathological features remain unelucidated. Between September 2006 and April 2022, 205 consecutive patients underwent endoscopic or surgical resection for early-stage non-ampullary duodenal adenocarcinomas at our hospital. There were no cases of poorly differentiated adenocarcinoma among the 188 cases of mucosal carcinoma. Meanwhile, among the 17 cases of submucosal invasive carcinoma, four cases were poorly differentiated adenocarcinomas. Herein, we report four cases of these carcinomas. All four lesions were reddish in color and were located on the oral side of the papilla. The gross types were either protruded (0-I) or mixed, elevated, and depressed (0-IIa + IIc). During preoperative diagnosis, submucosal invasion was suspected in all lesions, and biopsies were performed. Based on histological analyses of biopsy specimens, a diagnosis of poorly differentiated or signet-ring cell components was made in all cases, and a pancreaticoduodenectomy was performed. The median tumor size was 6.5 (range, 5-12) mm, and all lesions were poorly differentiated adenocarcinomas with submucosal invasion and lymph node metastasis. Regarding the tumor immunophenotype, one and three cases exhibited gastric and mixed gastrointestinal phenotypes, respectively. Two patients experienced metastatic recurrence; one of them died from the primary disease.

An increasing number of superficial non-ampullary duodenal epithelial tumors (SNADETs) have been detected recently owing to the development of endoscopic imaging technology and increased awareness of this disease. Endoscopic resection is the first-line treatment for SNADETs, with methods including cold snare polypectomy (CSP), conventional endoscopic mucosal resection (cEMR), underwater EMR (uEMR), and endoscopic submucosal dissection (ESD). Here, we review the current status and recent advances in endoscopic resection for SNADETs. Endoscopic resection in the duodenum is more difficult and has a higher risk of adverse events than that in other organs owing to specific anatomical disadvantages. SNADETs ≤10 mm in size are candidates for CSP, cEMR, and uEMR. Among these lesions, suspected carcinoma lesions should not be treated using CSP because of their low curability. cEMR or uEMR is considered for lesions sized 10 to 20 mm, whereas piecemeal EMR or ESD is considered for tumors >20 mm in size. In particular, ESD or surgical resection should be considered for suspected carcinoma lesions >30 mm in size. The treatment plan should be selected on a case-to-case basis, considering the balance between the risk of adverse events and the necessity of en bloc resection.

Epidemiological research is scarce in Asian countries including Japan. We aimed to clarify the epidemiological trend of nonampullary duodenal cancer (NADC) in Japan using a national database.

All patients with NADC diagnosed between 2016 and 2020 were identified from the Japanese national cancer registry. The crude and age-adjusted incidences were determined and temporal trends including diagnostic mode, tumor stage, and treatments were analyzed.

A total of 14 484 patients were included. The crude and age-adjusted incidences were 21.8-23.5 and 10.7-12.1 per 1 000 000 person-years. Male-to-female ratio was 1.7:1, and the incidence increased with age. The number of patients was highest among 70-79 year age group in both sexes. In total, 55% of patients were diagnosed during screening or surveillance for other diseases. In 54% of patients, the tumor stage was localized. The major treatment was surgery (32%), followed by endoscopic resection (27%). The trends for detection mode, tumor stage, and treatment were consistent during 2016-2020.

This study clarified and confirmed the high incidence of duodenal cancer in Japan. Characteristically, many NADC cases are diagnosed asymptomatically and treated by endoscopic or surgical treatment.

Complete endoscopic resection of superficial non-ampullary duodenal epithelial tumors (SNADETs) is technically difficult, especially with an extremely high risk of adverse event (AE), although various endoscopic resection methods including endoscopic mucosal resection (EMR), underwater EMR (UEMR), and endoscopic submucosal dissection (ESD) have been tried for SNADETs. Accordingly, a novel simple resection method that can completely resect tumors with a low risk of AEs should be developed.

A resection method of Noninjecting Resection using Bipolar Soft coagulation mode (NIRBS) which has been reported to be effective and safe for colorectal lesions is adapted for SNADETs. In this study we evaluated its effectiveness, safety, and simplicity for SNADETs measuring ≤ 20 mm.

This study included 13 patients with resected lesions with a mean size of 7.8 (range: 3-15) mm. The pathological distributions of the lesions were as follows: adenomas, 77% (n = 10) and benign and non-adenomatous lesions, 23% (n = 3). The en bloc and R0 resection rate was 100% (n = 13). The median procedure duration was 68 s (32-105). None of the patients presented with major AEs including bleeding and perforation.

Large studies such as prospective, randomized, and controlled trials should be conducted for the purpose of validating effectiveness, safety, and simplicity of the NIRBS for SNADETs measuring ≤ 20 mm suggested in this study.

Distinguishing between intramucosal cancer and submucosal invasive cancer is vital for optimal treatment selection for patients with superficial nonampullary duodenal adenocarcinoma (SNADAC); however, standard diagnostic systems for diagnosing invasion depth are as yet undetermined.

Of 205 patients with SNADAC who underwent treatment at our institution between 2006 and 2022, 188 had intramucosal cancer and 17 had submucosal invasive cancer. The clinical, endoscopic, and pathological features used in the preoperative diagnosis of invasion depth and the diagnostic performance of endoscopic ultrasonography (EUS) were retrospectively analyzed in 85 patients.

The oral side of the papilla tumor location, protruded or mixed macroscopic type, and moderately-to-poorly differentiated adenocarcinoma based on biopsy specimens were significantly more frequent in submucosal invasive cancer than in intramucosal cancer (88% vs. 48%; 94% vs. 42%; 47% vs. 0%, respectively). From the relationship between the endoscopic features and the submucosal invasive cancer incidence, submucosal invasion risk was stratified as: (i) low-risk (risk, 2%), all lesions located on the anal side of the papilla and superficial macroscopic type on the oral side of the papilla; and (ii) high-risk (risk, 23%), protruded or mixed macroscopic type on the oral side of the papilla. Based on the biopsy specimens, all eight patients with moderately-to-poorly differentiated adenocarcinoma had submucosal invasive cancer. Furthermore, EUS was not associated with invasion depth's diagnostic accuracy improvements.

Optimal treatment indications for SNADAC can be selected based on the risk factors of submucosal invasion by tumor location, macroscopic type, and biopsy diagnosis.

Recently, the detection of superficial non-ampullary duodenal epithelial tumors (SNADETs) including adenomas and superficial duodenal carcinomas has increased. Various endoscopic treatment methods have also been reported for SNADETs, but there are few reports on the natural history. The aim of this study was to analyze factors related to tumor growth and determine the characteristics of SNADETs which need early therapeutic intervention.

A single-center, retrospective study was performed on the medical records of 309 patients with SNADETs who underwent endoscopic or surgical resection between January 2010 and May 2021. Of these, 41 patients who were followed up for more than 1 year by endoscopy were analyzed. The primary outcome was an analysis of the tumor growth speed. Secondary outcomes were the relationship between the tumor growth speed and mucin phenotype, tumor size and findings of magnifying endoscopy with narrow-band imaging (M-NBI).

The observation period was 24 months (13-182). Tumor growth speed was 1.1 mm/year (0-21.6). Tumor diameter ≥10 mm at first detection (p = 0.004; odds ratio 19.5 [2.03-186.96]) and mixed type by M-NBI (p = 0.036; odds ratio 9.69 [1.05-89.88]) were identified as risk factors of tumors growing at a rate of ≥3 mm/year. There was no statistically significant difference in the speed of tumor growth between the different mucin immunohistochemical phenotypes.

Initial tumor size and findings of M-NBI are useful to predict tumor growth and consider early intervention.

Nonampullary duodenal epithelial tumors are rare, but their prevalence is increasing. Various gastrointestinal cancers have been associated with microbiomes. We evaluated the characteristics of the salivary and duodenal microbiomes of patients with nonampullary duodenal epithelial tumors.

Saliva and biopsy samples from the duodenal bulb and descending portion were obtained from 15 patients with nonampullary duodenal epithelial tumors and 10 controls. Next-generation sequencing was performed to identify bacteria for comparison.

Saliva samples had higher Amplicon Sequence Variants (ASVs) and more observed species than duodenal samples. Saliva samples from patients with nonampullary duodenal epithelial tumor were dominated by Bacteroidetes and Prevotella, whereas Proteobacteria and Neisseria were dominant in the control samples. The relative abundance of bacteria was higher in patients with nonampullary duodenal epithelial tumors. Most bacteria were classified as bacteria of oral origin. Oribacterium and Stomatobaculum were significantly higher in the saliva, duodenal bulb, and descending portion of patients with nonampullary duodenal epithelial tumors.

Patients with nonampullary duodenal epithelial tumors had different salivary and duodenal microbiomes than controls. Bacteria types differed between groups at each site, and most bacteria of oral origin were more abundant in patients with nonampullary duodenal epithelial tumors.

Superficial non-ampullary duodenal epithelial tumors (SNADETs) include low-grade adenoma (LGA) and high-grade adenoma or carcinoma (HGA/Ca) and are classified into two different epithelial subtypes, gastric-type (G-type) and intestinal-type (I-type). We attempted to distinguish them by endoscopic characteristics including magnifying endoscopy with narrow-band imaging (M-NBI).

Various endoscopic and M-NBI findings of 286 SNADETs were retrospectively reviewed and compared between G- and I-types and histological grades. M-NBI findings were divided into four patterns based on the following vascular patterns; absent, network, intrastructural vascular (ISV), and unclassified. Lesions displaying a single pattern were classified as mono-pattern and those displaying multiple patterns as mixed-pattern. Lesions showing CDX2 positivity were categorized as I-types and those showing MUC5AC or MUC6 positivity were categorized as G-types based on immunohistochemistry.

Among 286 lesions, 23 (8%) were G-type and 243 (85%) were I-type. More G-type lesions were located oral to papilla (91.3 vs. 45.6%, p < 0.001), and had protruding morphology compared to those of I-types (65.2 vs. 14.4%, p < 0.001). The major M-NBI pattern was ISV in G-type (78.2 vs. 26.3%, p < 0.001), and absent for I-type (0 vs. 34.5%, p = 0.003). Three endoscopic characteristics; location oral to papilla, protruding morphology, and major M-NBI pattern (ISV) were independent predictors for G-type. Mixed-pattern was more common in HGA/Ca than LGA for I-type (77.0 vs. 58.8%, p = 0.01); however, there was no difference for those in G-type.

Endoscopic findings including M-NBI are useful to differentiate epithelial subtypes.

Underwater endoscopic mucosal resection (UEMR) and cold snare polypectomy (CSP) are novel endoscopic procedures for superficial nonampullary duodenal epithelial tumors (SNADET). However, consensus on how to use both procedures appropriately has not been established. In this study, we evaluated treatment outcomes of both procedures, including resectability.

In this single-center randomized controlled study conducted between January 2020 and June 2022, patients with SNADET ≤12 mm were randomly allocated to UEMR and CSP groups. The primary end point was sufficient vertical R0 resection (SVR0), which was defined as R0 resection including a sufficient submucosal layer. We compared treatment outcomes including SVR0 rate between groups.

The SVR0 rate was significantly higher in the UEMR group than in the CSP group (65.6% vs 41.5%, P = 0.01). By contrast, the R0 resection rate was not significantly different between study groups (70.3% vs 61.5%, P = 0.29). The submucosal layer thickness was significantly greater in the UEMR group than in the CSP group (median 546 [range, 309-833] μm vs 69 [0-295] μm, P < 0.01). CSP had a shorter total procedure time (median 12 [range, 8-16] min vs 1 [1-3] min, P < 0.01) and fewer total bleeding events (9.4% vs 1.5%, P = 0.06).

UEMR has superior vertical resectability compared with CSP, but CSP has a shorter procedure time and fewer bleeding events. Although CSP is preferable for most small SNADET, UEMR should be selected for lesions that cannot be definitively diagnosed as mucosal low-grade neoplasias.

The detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD.

To explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched. Autologous myoblast sheets fabricated from muscle tissue obtained seven weeks before ESD were transplanted laparoscopically onto the serous side of the ESD. The primary endpoints were the onset of peritonitis due to delayed perforation within three days after surgery and all adverse events during the follow-up period.

Three patients with SNADETs ≥ 20 mm in size underwent transplantation of a myoblast sheet onto the serous side of the duodenum after ESD. In case 1, The patient's postoperative course was uneventful. Endoscopy and abdominal computed tomography revealed no signs of delayed perforation. Despite incomplete mucosal closure in case 2, and multiple micro perforations during ESD in case 3, cell sheet transplantation could prevent the postoperative massive perforation after ESD, and endoscopy on day 49 after transplantation revealed no stenosis.

This clinical trial showed the safety, efficacy, and procedural operability of this novel regenerative medicine approach involving transplanting an autologous myoblast sheet laparoscopically onto the serosa after ESD in cases with a high risk of delayed perforation. This result indicates the potential application of cell sheet medicine in treating various abdominal organs and conditions with minimal invasiveness in the future.

jRCT, jRCT2073210094. Registered November 8 2021, https://jrct.niph.go.jp/latest-detail/jRCT2073210094 .

Underwater endoscopic mucosal resection (UEMR) is a simpler procedure for superficial non-ampullary duodenal epithelial tumors (SNADET) than conventional endoscopic mucosal resection (cEMR). This study aimed to evaluate whether cEMR can be substituted by UEMR for SNADET in terms of effectiveness, safety, and learning curve.

A total of 157 consecutive patients with 203 SNADETs ≤20 mm in diameter, including 107 lesions resected by cEMR and 96 lesions resected by UEMR, between January 2019 and May 2023, were retrospectively recruited. The treatment outcomes were compared between the cEMR and UEMR groups. The risk factors for incomplete resection by UEMR were analyzed using univariate and multivariate analyses. Lesions in the UEMR group were divided chronologically into five periods; thereafter, the en bloc resection rate and procedure time were compared.

No significant differences existed between the cEMR and UEMR groups in the mean procedure time (3.9 min vs. 3.6 min, p = 0.1380) or en bloc resection rate (91% vs. 94%, p = 0.4138). No perforation was observed in either group. Tumor size was an independent risk factor for incomplete resection using UEMR (p < 0.01). The history of biopsy was not associated with incomplete resection using UEMR. The en bloc resection rate of UEMR was 100% (20/20) in the first period and ranged from 90% to 100% over all periods.

UEMR is safe and effective for SNADET ≤20 mm, regardless of a history of biopsy, and is easy to learn. Thus, UEMR can serve as an alternative to cEMR.

Prophylactic closure with the over-the-scope clip (OTSC) after endoscopic submucosal dissection (ESD) of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been reported to reduce postoperative adverse events (AEs). However, there are few evidences regarding AEs-associated factors and long-term outcomes of OTSCs.

From January 2011 to December 2020, 139 consecutive patients with SNADETs who underwent ESD followed by OTSC closure in five institutions were extracted in this retrospective study. The primary endpoint was the rate of postoperative AEs after prophylactic OTSC closure. The secondary endpoints were the complete closure rate, residual rate, and long-term AEs associated with residual OTSCs.

The rate of complete closure of the mucosal defect was 97.3% (142) in 146 SNADETs, which were completely resected by ESD. Postoperative AEs, including delayed bleeding, delayed perforation, and localized peritonitis, occurred in 6.2%, 3.4%, and 2.1% of patients, respectively; however, all of the cases improved without surgical treatment. In the multivariate logistic regression analysis, the use of two or more OTSCs was a significant independent risk factor for postoperative AEs (odds ratio, 2.94; 95% confidence interval, 1.02-8.46; P = 0.046). The residual OTSC rate was 46.4% at 1 year postoperatively, and long-term AEs included duodenal erosions and ulcers associated with residual OTSCs.

Prophylactic closure with OTSCs after duodenal ESD can provide acceptable short-and long-term outcomes for preventing postoperative AEs. However, multiple OTSCs were the independent risk factors of postoperative AEs due to the gaps between and near the OTSCs.

Mirroring the experience with colonic resections, cold snare-based techniques have been recently proposed for non-ampullary duodenal lesions to reduce the risk of adverse events (AEs). As the duodenal wall is thinner and more vascularized than in the colon, electrocautery-related AEs are relevant issues in this setting.

We performed a systematic review with pooled-analysis to evaluate the efficacy and safety of this technique.

Electronic databases (Medline, Scopus, EMBASE) were searched up to January 2023. Full articles including patients with duodenal lesions resected by cold-snare technique were eligible. The adverse events (i.e., bleeding, perforation, stricture), complete resection, and recurrence rates were pooled using a random model.

Eleven studies were eligible, providing data on 3137 lesions removed from 233 patients. The overall AE rate for cold snaring was 0.25% (95% CI, 0.19%-0.69%). Among the three studies comparing cold- and hot-snare approaches, procedure-related bleeding rate was significantly lower with cold approach (OR 1.21, 0.51-2.85; p = 0.66). The complete resection rate was 99.40% (95% CI, 98.60%-100%), with a residual/recurrence rate of 12.95% (95% CI, 4.75%-21.16%). On univariate meta-regression, lesion size significantly affected both the adverse events and recurrence risk.

Cold-snare resection appears effective and extremely safe for resecting non-ampullary duodenal lesions.

Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion.

This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching.

Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate.

Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection.

While the differential diagnosis of duodenal adenocarcinoma versus adenoma remains the key to determining treatment strategies in patients with suspected duodenal adenocarcinoma, the role of linked color imaging (LCI) in their differential diagnosis remains insufficiently documented. In this case, esophagogastroduodenoscopy (EGD) was performed on a 67-year-old man for anemia, which revealed a 20-mm-sized, whitish, partially reddish, pedunculated lesion located in the duodenal bulb on white light imaging. Using LCI, the lesion was highlighted as a whitish, pedunculated lesion with its central and inferior areas depicted as orangish and reddish, respectively. Endoscopic mucosal resection was performed on the suspicion of an adenocarcinoma for biopsy and endoscopic diagnosis. Histological examination revealed the lesion to be an adenocarcinoma contained in an adenoma: papillary, type 0-Ip, measuring 20x20 mm, pTis (M), involving no lymphovascular invasion. This case appears to underpin the usefulness of LCI in the differential diagnosis of duodenal adenocarcinoma.

Pyloric gland adenoma (PGA) is a duodenal neoplasm expressing MUC6 and is often associated with high-grade dysplasia and adenocarcinoma. MUC6 secreted from the pyloric gland cells carries unique O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). The small peptide trefoil factor 2 (TFF2) is also secreted from pyloric gland cells and binds to αGlcNAc. We recently demonstrated that αGlcNAc serves as a tumor suppressor for gastric neoplasm including PGA, but the significance of TFF2 expression remains unknown. We examined 20 lesions representing low- and high-grade PGA in 22 cases by immunohistochemistry for αGlcNAc, TFF2, MUC6, MUC5AC, MUC2 and p53. αGlcNAc, TFF2 and MUC6 were co-expressed on the cell surface and a dot-like pattern in the cytosol in low-grade PGA lesions. High-grade PGA also expressed MUC6, but reduced αGlcNAc and TFF2 expression. The ratios of αGlcNAc or TFF2 to MUC6 score in high-grade PGA were significantly lower than low-grade PGA (P < 0.001). Co-expression of αGlcNAc-glycosylated MUC6 and TFF2 in PGA suggests the existence of αGlcNAc/TFF2 form complex in PGA cells, a finding consistent with our observations in non-neoplastic Brunner's gland cells. The decreased αGlcNAc and TFF2 expression are associated with high grade atypical cells, indicative of the malignant potential of PGA.

This study aimed to elucidate the clinical course and management of adverse events (AEs) after endoscopic resection (ER) for superficial duodenal epithelial tumors (SDETs).

Consecutive patients who underwent ER of SDETs between January 2008 and July 2018 at 18 Japanese institutions were retrospectively enrolled. The study outcomes included the clinical course, management, and risk of surgical conversion with perioperative AEs after ER for SDETs.

Of the 226 patients with AEs, the surgical conversion rate was 8.0% (18/226), including 3.7% (4/108), 1.0% (1/99), and 50.0% (12/24) of patients with intraoperative perforation, delayed bleeding, or delayed perforation, respectively. In the multivariate logistic analysis, involvement of the major papilla (odds ratio [OR] 12.788; 95% confidence interval [CI] 2.098-77.961, P = 0.006) and delayed perforation (OR 37.054; 95% CI 10.219-134.366, P < 0.001) were significant risk factors for surgical conversion after AEs. Delayed bleeding occurred from postoperative days 1-14 or more, whereas delayed perforation occurred within 3 days in all cases.

The surgical conversion rate was higher for delayed perforation than those for other AEs after ER of SDETs. Involvement of the major papilla and delayed perforation were significant risk factors for surgical conversion following AEs. In addition, reliable prevention of delayed perforation is required for 3 days after duodenal ER to prevent the need for surgical interventions.

Endoscopic submucosal dissection (ESD) for superficial non-ampullary duodenal tumors (SNADETs) is associated with a high rate of en bloc resection. However, the technique for ESD remains challenging. Recent studies have demonstrated the effectiveness of S-O clips in colonic and gastric ESD. We evaluated the efficacy and safety of duodenal ESD using an S-O clip for SNADETs.

Consecutive patients who underwent ESD for SNADETs between January 2011 and December 2021 were retrospectively enrolled. Propensity score matching analysis was used to compare patients who underwent duodenal ESD with the S-O clip (S-O group) and those who underwent conventional ESD (control group). Intraoperative perforation rate was the primary outcome, while procedure time and R0 resection rate were the secondary outcomes.

After propensity score matching, 16 pairs were created: 43 and 17 in the S-O and control groups, respectively. The intraoperative perforation rate in the S-O group was significantly lower than that in the control group (p=0.033). A significant difference was observed in the procedure time between the S-O and control groups (39±9 vs. 82±30 minutes, respectively; p=0.003).

The S-O clip reduced the intraoperative perforation rate and procedure time, which may be useful and effective in duodenal ESD.

With the recent increase in the frequency of duodenal tumor detection, significant progress has been made in endoscopic diagnosis and treatment. Although the first guidelines were issued in Japan, patient treatment varies widely among institutions. There is a need for improving the quality of endoscopic diagnosis and more curative and safer treatments. Biopsy is the standard diagnostic method; however, the diagnostic accuracy of endoscopic biopsy is not so high. Therefore, the differentiation of superficial non-ampullary duodenal epithelial tumors from non-neoplastic lesions is being developed. The incidence of lymph node and distant metastases of duodenal epithelial tumors is extremely rare in intramucosal carcinomas, and they are considered good candidates for endoscopic treatment if the technical difficulties can be resolved. Adverse events associated with endoscopic treatment are greatly reduced at advanced facilities through novel resection and closure methods, and further improvements are expected in the future. Clarifying the risk of metastatic recurrence may lead to the development of more appropriate treatments and curative resection criteria.

Background and study aims Endoscopic treatment strategies for small superficial duodenal epithelial neoplasia (SDET) have not been established, and the R0 resection rates of all previously reported endoscopic techniques are somewhat low. Furthermore, no reports of cap-assisted endoscopic mucosal resection (EMRC), which is reportedly associated with a relatively high R0 resection rate, have been evaluated in sufficient numbers of patients. Therefore, we assessed the efficacy and safety of EMRC for SDETs ≤ 10 mm in a retrospective cohort study. Patients and methods We examined a prospectively maintained database and identified 248 consecutive patients (248 lesions) who had undergone endoscopic resection for SDETs ≤ 10 mm between January 2017 and June 2022. Our treatment strategy was consistent, with EMRC indicated for all SDETs ≤ 10 mm without non-lifting signs. The primary endpoint was the R0 resection rate. Results Overall, 20 lesions had non-lifting signs and were selected for endoscopic submucosal dissection, while the remaining 228 lesions were treated with EMRC. As a result of EMRC, the median tumor size was 5 mm, and the mean procedure time was 5 minutes. Most of the lesions (89.2%) were located in the descending part. The R0 resection rate was 97.4% (222/228 cases), and the en bloc resection rate was 99.6%. Only seven patients(3.1%) experienced adverse events (6 patients, delayed bleeding; 1 patient, acute pancreatitis), which were successfully managed without surgical intervention. Furthermore, no recurrences were observed. Conclusions We have demonstrated that EMRC is an effective and safe treatment for SDETs ≤ 10 mm that do not have non-lifting signs.

Underwater endoscopic mucosal resection (UEMR) is increasingly applied in the treatment of superficial non-ampullary duodenal epithelial tumors (SNADETs). This meta-analysis aimed to assess the efficacy and safety of UEMR for SNADETs ≤20 mm in comparison with conventional endoscopic mucosal resection (CEMR).

The following electronic databases were searched from 2012 until November 20, 2021: PubMed, Embase, Scopus, Web of Science databases, and Cochrane Library. The primary outcomes were the rates of en bloc resection and complete (R0) resection, and the secondary outcomes were procedure time, adverse events (delayed bleeding and delayed perforation), and recurrence rate.

A total of 6 studies with 679 lesions (331 underwent UEMR and 348 CEMR) were included in this study. The pooled analysis showed that UMER achieves a similar en bloc resection rate (87.6 vs. 89.9%; odds ratio [OR], 1.29; 95% confidence interval [CI], 0.45 to 3.73; P =0.64; I2 =74%), a similar R0 resection rate (67.3 vs. 73.6%; OR, 1.11; 95% CI, 0.55 to 2.23; P =0.78; I2 =59%), a shorter procedure time (min) (mean difference [MD], -4.05, 95% CI: -6.40 to -1.71; P =0.0007; I2 =70%) compared with CEMR. There were no significant differences in the rates of delayed bleeding, delayed perforation, and recurrence (2.4 vs. 1.7%, 0 vs. 0.6%, 2.2 vs. 4.4%, respectively).

This meta-analysis demonstrated that UEMR appears to be an effective and safe alternative to CEMR for SNADETs ≤20 mm.

The surface of the small bowel mucosa is covered more than any other section of the digestive canal; however, the overall prevalence of small bowel tumors of the whole gastrointestinal tract is evidently low. Owing to the improvement in endoscopic techniques, the prevalence of small bowel tumors has increased across multiple countries, which is mainly due to an increase in duodenal tumors. Superficial non-ampullary duodenal epithelial tumors (SNADETs) are defined as tumors originating from the non-ampullary region in the duodenum that share similarities and discrepancies with their gastric and colorectal counterparts in the pathogenesis and clinicopathologic characteristics. To date, white light endoscopy (WLE) remains the cornerstone of endoscopic diagnosis for SNADETs. Besides, narrow-band imaging (NBI) techniques and magnifying endoscopy (ME) have been widely used in the clinic and endorsed by multiple guidelines and consensuses for SNADETs' evaluation. Confocal laser endomicroscopy (CLE), endocytoscopy (ECS), and artificial intelligence (AI) are also up-and-coming methods, showing an exceptional value in the diagnosis of SNADETs. Similar to the endoscopic treatment for colorectal polyps, the choices for SNADETs mainly include cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and laparoscopic endoscopic cooperative surgery (LECS). However, owing to the narrow lumen, rich vascularity, weak muscle layer, abundant Brunner's gland, and the hardship of endoscope control, the duodenum ranks as one of the most dangerous operating areas in the digestive tract. Therefore, endoscopists must anticipate the difficulties in endoscopic maneuverability, remain aware of the increased risk of complications, and then select the appropriate treatment according to the advantages and disadvantages of each method.

Optical biopsy using endocytoscopy for superficial nonampullary duodenal epithelial tumors (SNADETs) is practical; however, a diagnostic algorithm has not been established. The aim of this study was to determine correlations of endocytoscopic findings of SNADETs with histology using computer analysis and to establish an algorithm.

Endocytoscopic images and histological images of duodenal lesions from 70 patients were retrospectively collected. The numbers of glands and densely stained areas with methylene blue (DSMs) per 1 mm2 and the percentage of DSMs per screen in endocytoscopy were determined. Moreover, correlations in DSMs and glands between endocytoscopy and histological images were analyzed. Histopathological diagnoses were assessed according to the revised Vienna classification. The primary outcome was correlation between the number of glands in endocytoscopy and that in histology. Finally, a diagnostic algorithm for endoscopic intervention of SNADETs with a statistical program command was established.

The number of glands in endocytoscopic images was correlated with that in histopathological images (ρ 0.64, P < 0.001). There were significant differences in the mean number of glands between category 4/5 and category 3 (P = 0.03) and the mean percentage of DSMs between category 4/5 and category 1 (P < 0.001). When the cutoffs for the number of glands and percentage of DSMs were set at 47 per 1 mm2 and 20.8% in one screen, respectively, the area under the ROC curve was 0.89.

Endocytoscopic images of SNADETs reflect histopathological atypia, and computer analysis provides a practical diagnostic algorithm for endoscopic intervention.

Duodenal polyps have a reported incidence of 0.3% to 4.6%. Sporadic, nonampullary duodenal adenomas (SNDAs) comprise less than 10% of all duodenal polyps, and ampullary adenomas are even less common. Nonetheless, the incidence continues to rise because of widespread endoscopy use. Duodenal polyps with villous features or those that are larger than 10 mm may raise concern for malignancy and require removal. We demonstrate endoscopic resection of SNDAs and ampullary adenomas using some of our preferred techniques.

The duodenum has several components that can make EMR of duodenal polyps technically challenging. Not only does the duodenum have a thin muscle layer, but it is also highly mobile and vascular, which may explain higher rates of perforation and bleeding of duodenal EMR reported in the literature compared with colon EMR. A standard adult gastroscope with a distal cap is commonly used for duodenal EMRs. Based on the location, however, side-viewing duodenoscopes or pediatric colonoscopes may be used. To prepare for EMR, a submucosal injection is performed for an adequate lift. The polyp is then resected via stiff monofilament snares and subsequently closed with hemostatic clips if feasible. The ampullectomy technique differs slightly from duodenal EMRs and carries the additional risk of pancreatitis. Submucosal injection in the ampulla may not lift well; thus, its utility is debatable. Biliary sphincterotomy should be performed, and based on endoscopist preference, the pancreatic duct (PD) guidewire can be left during resection to maintain access. After resection, a PD stent is placed to minimize pancreatitis risk.

The video shows the aforementioned duodenal EMR techniques. Two clips of ampullectomy are also shown in the video.

A few common techniques used to perform duodenal EMR and ampullectomy are highlighted in the video. It is important to understand and manage adverse events associated with these procedures and to have established surveillance plans.

Duodenal endoscopic submucosal dissection (ESD) is associated with high incidences of intraoperative complications and delayed adverse events (AEs). Delayed AEs can be reduced by closing the post-ESD defects. We developed a new method of closure after duodenal ESD, combining endoscopic ligation with O-ring closure (E-LOC) with an over-the-scope clip (OTSC) (Band OTSC; B-OTSC). Here, we conducted a single-center, retrospective, observational study to investigate the efficacy and safety of the B-OTSC method for preventing delayed AEs in patients undergoing duodenal ESD. The study included nine patients with superficial nonpapillary duodenal epithelial tumors who underwent ESD and were closed with B-OTSC from February 2021 to February 2023. There were no delayed AEs (0%), the mean (± standard deviation) closure time was 53 ± 21.6 min, the complete closure rate was 100%, and the mean hospital stay was 7.8 ± 1.8 days. The sustained closure rates at postoperative days 3 and 7 were 88.9% and 88.9%, respectively. The historical analysis indicated a significant difference in cost between B-OTSC and conventional OTSC (p < 0.01). In conclusion, B-OTSC was a safe, secure, and cost-effective method of closure after duodenal ESD, even in patients with post-ESD defects of more than half the circumference.

Due to the high risk of morbidity and mortality associated with surgical resection in this tract, endoscopic resection (ER) has taken the place of surgical resection as the first line treatment for non-ampullary duodenal adenomas. However, due to the anatomical characteristics of this area, which enhance the risk of post-ER problems, ER in the duodenum is particularly difficult. Due to a lack of data, no ER technique for superficial non-ampullary duodenal epithelial tumours (SNADETs) has yet been backed by strong, high-quality evidence; yet, traditional hot snare-based techniques are still regarded as the standard treatment. Despite having a favourable efficiency profile, adverse events during duodenal hot snare polypectomy (HSP) and hot endoscopic mucosal resection, such as delayed bleeding and perforation, have been reported to be frequent. These events are primarily caused by electrocautery-induced damage. Thus, ER techniques with a better safety profile are needed to overcome these shortcomings. Cold snare polypectomy, which has already been shown as a safer, equally effective procedure compared to HSP for treatment of small colorectal polyps, is being increasingly evaluated as a potential therapeutic option for non-ampullary duodenal adenomas. The aim of this review is to report and discuss the early outcomes of the first experiences with cold snaring for SNADETs.

Duodenal underwater endoscopic mucosal resection (UEMR) has been suggested as a feasible treatment option for superficial non-ampullary duodenal epithelial tumors (SNADETs). However, its efficacy and safety have not been fully established yet. Thus, the objective of this systematic review and meta-analysis was to determine the efficacy and safety of UEMR as compared with conventional endoscopic mucosal resection (CEMR) in the treatment of SNADETs.

We conducted a comprehensive literature search in PubMed, EMBASE, the Cochrane Library. Studies comparing CEMR and UEMR for the resection of SNADET were included. Outcomes included en-bloc and complete resection rates, adverse events, and procedure time.

A total of six studies with 2454 lesions were included in the quantitative synthesis. En-bloc and complete resection rates were not significantly different between UEMR and CEMR (OR for en-bloc resection: 0.997 [95% CI 0.439-2.266]; OR for complete resection: 0.960 [95% CI 0.628-1.468]). There was no significant risk difference for perforation (risk difference: - 0.002; 95% CI - 0.009 to 0.005) or delayed bleeding (risk difference: - 0.001; 95% CI - 0.014 to 0.011). Procedure time was significantly shorter in the UEMR (standardized mean difference: - 1.294; 95% CI - 2.461 to - 0.127). The risk of recurrence was not significantly different between UEMR and CEMR (risk difference: 0.001; 95% CI - 0.041 to 0.044).

Although our results did not show any superiority of UEMR over CEMR in the treatment of SNADETs, UEMR showed equivalent efficacy and safety as compared with CEMR and was associated with a shorter procedure time.

Pyloric gland adenoma (PGA) in the duodenum is a rare gastric phenotype duodenal neoplasm. Although heterotopic gastric mucosa in the duodenum has been recognized as a benign lesion, it is a potential precursor of PGA and gastric phenotype adenocarcinoma. Herein, we present a case follow-up of endoscopic and histological changes in the PGA in the duodenum from low-grade to high-grade dysplasia. PGA was considered to arise from the heterotopic gastric mucosa, because the heterotopic gastric mucosa was observed in the initial examination. It is difficult to distinguish heterotopic gastric mucosa from PGAs, both endoscopically and histologically. This increase in size may be useful for their differentiation. Therefore, endoscopists should not underestimate the growth of the heterotopic gastric mucosa compared to that in the previous examination.