Background/Objectives: The main treatment for non-ampullary duodenal adenocarcinoma (NDA) is pancreatoduodenectomy (PD) with lymphadenectomy (LN). Several studies have proposed a minimum number of examined lymph nodes (MNELN) to ensure proper staging. This study investigated the impact of nodal parameters-including the pattern of nodal spread-on oncologic outcomes following PD for NDA. Furthermore, we sought to determine the MNELN to ensure reliable detection of nodal involvement. Methods: This was a single-center, retrospective study. Consecutive patients who underwent PD from 2000 to 2019 with a final diagnosis of NDA were retrieved from a prospectively maintained database. The probability of detecting at least one metastatic LN in a node-positive patient was assessed using a model based on the binomial probability law. Results: A total of 70 patients met the inclusion criteria. The median number of ELNs was 35 (22-43, IQR). Thirty-six patients (51%) had at least one PLN. A node-positive disease was associated with adverse pathologic features, including high tumor grade and perineural and peripancreatic fat invasion. This translated into a greater recurrence rate (p < 0.001). The MNELN yielding a 95% probability of detecting at least one metastatic node in a node-positive patient was 25. After a median follow-up of 73 months, the median recurrence-free survival (RFS) was 33 months (95% CI 13-97), and the overall survival (OS) was 41 months (95% CI 17-96). The LN ratio, tumor grade, and metastases at stations 8 and 12 were independently associated with OS (p < 0.05). Conclusions: Nodal metastases are common among patients with NDA and have a considerable impact on long-term survival. Stations 8 and 12 were associated with OS. Therefore, an adequate lymphadenectomy, possibly including stations 8 and 12, is recommended in patients with NDA.

There is concern that underwater endoscopic mucosal resection (UWEMR) uses buoyancy to elevate the lesion for snare resection, resulting in a shallower resection depth than that in endoscopic mucosal resection (EMR). We aimed to compare conventional EMR and UWEMR in terms of resection depth.

We retrospectively reviewed cases in which EMR or UWEMR was performed for superficial non-ampullary duodenal epithelial tumors of ≤20 mm between April 2018 and February 2024. The endpoints were histological complete resection rate, en bloc resection rate, presence of muscularis mucosa and submucosa in the resection specimen, and submucosal index calculated from the resection specimen.

EMR was performed on 19 lesions and UWEMR was performed on 52 lesions. Histological complete and en bloc resection rates were not significantly different between EMR and UWEMR (57.9% and 63.5%, respectively, p = 0.78; 78.9% and 90.4%, respectively, p = 0.24). No significant differences were observed between EMR and UWEMR in the muscularis mucosa of the resected specimens (78.9% and 92.3%, respectively, p = 0.20). The presence of submucosa in resected specimens was encountered less often in EMR cases than in UWEMR cases (57.9% versus [vs.] 84.6%, p = 0.03). There were significant differences in the submucosal index in the resected specimens between EMR and UWEMR cases (median 0.15 [interquartile range 0-0.39] vs. 0.33 [0.17-0.57], p = 0.04).

UWEMR potentially includes the submucosa within the specimen.

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.

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.

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.

Although the current staging system and therapeutic strategy for duodenal adenocarcinoma (DA) focus on the N status, their validity has not been clarified. In this study, we evaluated the prognostic factors of DA and reviewed the current staging system.

We included 105 patients who underwent surgical resection of DA in our department between September 2006 and October 2020. Patients with localised disease other than an early tumour (pT1a) were classified into the advanced group, and prognostic factors were compared with those for the Union for International Cancer Control (UICC) classification, 8th edition.

The 5-year overall survival (OS) rate in the advanced group (n = 55) was 73%. Multivariate analysis revealed that pT4 and pN2 statuses were independent prognostic factors for OS. The prognosis was stratified based on the pT4 and pN2 statuses, whereas the survival curves for patients with pStage II (pN0) and pStage IIIA (pN1) DA overlapped on staging according to the UICC classification. The new classification indicated a favourable prognosis for patients classified as pT1-3N1 stage IIIA (5-year OS, 86%), whereas the prognosis of patients with pT4N0-1 DA was similar to those classified as pT1-3N2 stage IIIB. Patients with pT4N2 DA had a similar prognosis (5-year OS, 24%) as those with metastases, and 75% of these patients showed distant metastasis within one year after surgery.

Both T and N statuses affect the prognosis of DA. Patients with pT4N2 DA may require intensive adjuvant chemotherapy. (238 words).

Data on endoscopic resection (ER) for superficial duodenal epithelial tumors (SDETs) are insufficient owing to their rarity. There are two main ER techniques for SDETs: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). In addition, modified EMR techniques, such as underwater EMR (UEMR) and cold polypectomy, are becoming popular. We conducted a large-scale retrospective multicenter study to clarify the detailed outcomes of duodenal ER.

Patients with SDETs who underwent ER at 18 institutions from January 2008 to December 2018 were included. The rates of en bloc resection and delayed adverse events (AEs; defined as delayed bleeding or perforation) were analyzed. Local recurrence was analyzed using the Kaplan-Meier method.

In total, 3107 patients (including 1017 undergoing ESD) were included. En bloc resection rates were 79.1 %, 78.6 %, 86.8 %, and 94.8 %, and delayed AE rates were 0.5 %, 2.2 %, 2.8 %, and 6.8 % for cold polypectomy, UEMR, EMR and ESD, respectively. The delayed AE rate was significantly higher in the ESD group than in non-ESD groups for lesions < 19 mm (7.4 % vs. 1.9 %; P < 0.001), but not for lesions > 20 mm (6.1 % vs. 7.1 %; P = 0.64). The local recurrence rate was significantly lower in the ESD group than in the non-ESD groups (P < 0.001). Furthermore, for lesions > 30 mm, the cumulative local recurrence rate at 2 years was 22.6 % in the non-ESD groups compared with only 1.6 % in the ESD group (P < 0.001).

ER outcomes for SDETs were generally acceptable. ESD by highly experienced endoscopists might be an option for very large SDETs.

Background and study aims  Management strategies for sporadic non-ampullary duodenal adenoma with low-grade dysplasia (LGD) are not well established. This study aimed to analyze progression factors and determine suitable treatment strategies for LGD lesions. Patients and methods  We retrospectively analyzed consecutive LGD lesions (n = 125) in patients followed up for ≥ 6 months (median, 45 months) and evaluated the changes in clinicopathological features during follow-up. All LGD lesions were classified into two groups: stable LGD (no increase or < 5 mm increase in tumor size, with unchanged histological dysplasia grade) and progressive LGD (≥ 5 mm increase in tumor size and/or progression to high-grade dysplasia or adenocarcinoma). Results  Eighty-six LGD were classified as stable and 39 as progressive. Location on the oral side of the papilla of Vater, large initial tumor size ( ≥ 10 mm), macroscopically complex type, red color, and nodularity were significantly frequent in progressive LGD than in stable LGD. In multivariate analysis, large initial tumor size (odds ratio [OR], 10.2; 95 % confidence interval [CI], 3.3-32.1; P  < 0.001) and location on the oral side of the papilla of Vater (OR: 1.8, 95 % CI: 1.4-12.5; P  = 0.012) were significant factors for progression. Moreover, initial tumor size < 5 mm rarely progressed (0%-3.9 %); however, initial tumor size ≥ 20 mm and 10-19 mm located on the oral side of the papilla of Vater had a high-risk progression rate (75.0-85.7 %). Conclusions  According to the risk stratification of progression factors by initial tumor size and location, we can determine suitable treatment indications for LGD lesions.

Duodenal polyps are found in 0.1 % to 0.8 % of all upper endoscopies. Duodenal adenomas account for 10 % to 20 % of these lesions. They can be sporadic or occur in the setting of a hereditary predisposition syndrome, mainly familial adenomatous polyposis. Endoscopy is the cornerstone of management of duodenal adenomas, allowing for diagnosis and treatment, primarily by endoscopic mucosal resection. The endoscopic treatment of duodenal adenomas has a high morbidity, reaching 15 % in a prospective study, consisting of bleeding and perforations, and should therefore be performed in expert centers. The local recurrence rate ranges from 9 % to 37 %, and is maximal for piecemeal resections of lesions > 20 mm. Surgical resection of the duodenum is flawed with major morbidity and considered a rescue procedure in cases of endoscopic treatment failures or severe endoscopic complications such as duodenal perforations. In this paper, we review the existing evidence on endoscopic diagnosis and treatment of non-ampullary duodenal adenomas.

An association between specific endoscopic findings and high-grade dysplasia/carcinoma in superficial nonampullary duodenal epithelial tumors ≤ 5 mm in size has not been reported. We sought to identify the endoscopic findings associated with high-grade dysplasia/carcinoma in patients with superficial nonampullary duodenal epithelial tumors ≤ 5 mm.

We retrospectively assessed the data of 84 patients (88 lesions; low-grade dysplasia: n = 35, high-grade dysplasia/carcinoma: n = 53) with superficial nonampullary duodenal epithelial tumors who underwent initial treatment at a single center (from July 2009 to April 2021). All the patients had lesions sized ≤ 5 mm. We assumed that the endoscopic findings were independently associated with high-grade dysplasia/carcinoma and determined the accuracy, sensitivity, and specificity of a combination of independent factors for diagnosing high-grade dysplasia/carcinoma and low-grade dysplasia.

Multivariate logistic regression of significant factors in the univariate analysis revealed that lesions with depressed morphology (odds ratio: 23.9, 95% confidence interval: 2.8-204.2; p = 0.0037) and a reddish color (odds ratio: 175.7, 95% confidence interval: 11.4-2697.1; p = 0.0002) were independently associated with high-grade dysplasia/carcinoma. McNemar's test revealed that combining the macroscopic type and color provided significantly higher sensitivity for diagnosing high-grade dysplasia/carcinoma than color alone (98.1%, 95% confidence interval: 90.1-99.7 vs. 71.7%, 95% confidence interval: 58.4-82.0; p = 0.0002).

Reddish and depressed-type lesions before treatment were associated with high-grade dysplasia/carcinoma. Combining the macroscopic type and color can help detect high-grade dysplasia/carcinoma. These findings could help clinicians determine the best therapeutic strategy for patients with smaller (≤ 5 mm) superficial nonampullary duodenal epithelial tumors in clinical settings.

The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC.

Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed.

The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion.

Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

Superficial nonampullary duodenal epithelial tumors are considered rare but have been increasingly recognized in recent years. Accordingly, the importance of endoscopic treatment for the lesions are also increasing. An endoscopic resection can be considered for duodenal adenoma and mucosal cancer. The choice of resection method should be made based on the size of the lesion, endoscopic findings, pathologic diagnosis, and risk of procedure-related complication. For small adenomas <10 mm in size, endoscopic mucosal resection (EMR), cold snare polypectomy, and underwater EMR can be considered. An en bloc or piecemeal resection using EMR or underwater EMR can be selected for 10-20 mm sized adenomas. For lesions ≥20 mm in size or suspicious for mucosal cancer, an endoscopic submucosal dissection followed by closure of the mucosal defect conducted by an experienced endoscopist is appropriate.

A reliable optical diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) to guide optimal treatment strategy is lacking. The aim of this study was to simulate the treatment outcomes based on optical diagnosis using white light imaging (WLI) or magnifying endoscopy with narrow band imaging (MNBI) and to evaluate the method to extract optimal lesions suitable for cold snare polypectomy (CSP) or not.

We created a decision tree model using WLI and MNBI diagnosis for ideal treatment for SNADETs. Optical diagnoses of Vienna category 3 lesions (C3), category 4/5 (C4/5) were defined based on the WLI scoring system or the MNBI pattern diagnosis. Ideal treatments were CSP for C3 < 10mm, and endoscopic mucosal resection, endoscopic submucosal dissection or surgery for lesions ≥10mm or C4/5. Ideal treatment results based on optical diagnosis were analyzed according to actual pathological results.

A total of 218 lesions with pre-operative diagnosis of SNADETs were included for analysis. Percentage of ideal treatment for C3 < 10mm based on WLI or MNBI or both was 88%, 83% and 97%. When WLI and MNBI diagnoses predicted the same histology, the specificity, positive predictive value and accuracy were significantly higher than those of WLI or MNBI alone (p < .05).

A decision tree model using lesion diameter, WLI scoring and MNBI pattern diagnosis is hypothetically useful to select ideal lesions for CSP among SNADETs. Optical diagnosis using both WLI and MNBI is more useful than WLI or MNBI alone.