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OBJECTIVES: To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology. METHODS: Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs. RESULTS: Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively. CONCLUSION: USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma. CLINICAL RELEVANCE STATEMENT: Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy. REGISTRATION: The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 . KEY POINTS: LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers.

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BACKGROUND: Duodenal cancer is one of the most common subtypes of small intestinal cancer, and distant metastasis (DM) in this type of cancer still leads to poor prognosis. Although nomograms have recently been used in tumor areas, no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer. AIM: To develop and evaluate nomograms for predicting the risk of DM and personalized prognosis in patients with duodenal cancer. METHODS: Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM. Two novel nomograms were established, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 2603 patients with duodenal cancer were included, of whom 457 cases (17.56%) had DM at the time of diagnosis. Logistic analysis revealed independent risk factors for DM in duodenal cancer patients, including gender, grade, tumor size, T stage, and N stage (P < 0.05). Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM, including age, histological type, T stage, tumor grade, tumor size, bone metastasis, chemotherapy, and surgery (P < 0.05). The accuracy of the nomograms was validated in the training set, validation set, and expanded testing set using ROC curves, calibration curves, and DCA curves. The results of Kaplan-Meier survival curves (P < 0.001) indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer. CONCLUSION: The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM, potentially enhancing clinical decision-making.

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Gastrointestinal stromal tumours (GISTs) are rare gastrointestinal (GI) malignancies, but the most prevalent mesenchymal tumours of the GI tract arise from the interstitial cells of Cajal. They account for 1-3% of all GI malignancies, and only 3-5% of all cases of GIST are located at the duodenal. We present a case of a young adult who presented to the ED with symptoms of GI bleeding.

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Small bowel malignancies are relatively rare, accounting for only 3% of all gastrointestinal cancers. Duodenum is the most common location among small bowel cancers, followed by Jejunum and then Ileum. Duodenal adenocarcinoma produces vague symptoms, leading to late presentation and a poor prognosis compared to similarly staged colon cancer. It is rare to have brain metastasis in duodenal adenocarcinoma, and not many case reports have been reported. Only approximately 6% of patients with gastrointestinal malignancy have brain metastasis. Here, we present a case of a 64-year-old female patient diagnosed initially with stage IV duodenal adenocarcinoma presenting with duodenal mass, abdominal lymphadenopathy, and liver metastasis. She had excellent systemic control for over two years with systemic chemotherapy, with a close to complete response on follow-up imaging. She presented with a 2 cm left frontal mass biopsy consistent with duodenal adenocarcinoma metastasis. She underwent resection of the left frontal tumor and gamma knife to the resection cavity. She continues to have good systemic control of disease. This case highlights the rare possibility of brain metastasis with duodenal adenocarcinoma, especially in patients who have good systemic control with chemotherapy.

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Background: Lynch syndrome increases the risk of gastric cancer (GC) and duodenal cancer (DC), particularly in individuals with MLH1 and MSH2 pathogenic variants (PVs). To provide further insight into whether, and from what age, esophagogastroduodenoscopy (EGD) surveillance may be beneficial, we evaluated the cumulative incidence and tumour characteristics of GC and DC in a large nationwide cohort of Dutch individuals with LS. Methods: For this retrospective nationwide cohort study, clinical data of individuals with LS registered at the Dutch Hereditary Cancer Registry were matched with pathology reports filed by the Dutch Pathology registry. All individuals registered between Jan 1, 1989 and Dec 31, 2021 with proven or putative PVs in one of the mismatch repair genes were included. Cumulative incidences of GC and DC were estimated for high-risk (MLH1, MSH2 and EpCAM) and low-risk (MSH6 and PMS2) PVs using competing risk methodology (Fine and Gray method) with death due to other causes as competing risk. Findings: Among 1002 individuals with high-risk and 765 individuals with low-risk PVs, 29 GCs (1.6%) and 39 DCs (2.2%) were diagnosed. Cumulative incidence of GC and DC under the age of 50 was very low (≤1%) for all individuals. At age 70 and 75, cumulative incidence of GC was 3% [95% CI 1%-5%] and 5% [3%-8%] for high-risk PVs and 1% [0%-2%] and 1% [0%-2%] for low-risk PVs (p = 0.006). For DC, cumulative incidence at age 70 and 75 was 5% [3%-7%] and 6% [3%-8%] in high-risk, 1% [0%-1%] and 2% [0%-4%] in low-risk PVs, respectively (p = 0.01). Primary tumour resection was performed in 62% (18/29) of GCs and 77% (30/39) of DC cases. Early-stage GC, defined as TNM stage I, was found in 32% (9/28) of GCs. Early-stage DC, defined as TNM stage I-IIa, was found in 39% (14/36) of DCs. Interpretation: Individuals with MLH1, MSH2, and EpCAM PVs have an increased risk of developing GC and DC at the age of 70 years, but this risk is very low before the age of 50 years. The age of onset of surveillance, the yield of GC and DC during EGD surveillance, and its cost-effectiveness should be subject of future studies. Funding: None.

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Conventional clip closure of mucosal defects after duodenal endoscopic submucosal dissection decreases the incidence of delayed adverse events, but may result in incomplete closure, depending on size or location. This study aimed to assess the effectiveness of the underwater clip closure method for complete duodenal defect closure without the difficulties associated with conventional closure methods. We investigated 19 patients with 20 lesions who underwent endoscopic submucosal dissection of the duodenum and subsequent mucosal defect closure in underwater conditions at our facility between February 2021 and January 2022. The success rate of the underwater clip closure method was defined as the complete endoscopic closure of the mucosal defect; a success rate of 100% was achieved. The median resected specimen size was 34.3 mm, the median procedure time for mucosal defect closure was 14 min, and the median number of clips used per patient was 12. No delayed adverse events were observed. The underwater clip closure method is a feasible option for complete closure of mucosal defects, regardless of the size or location of a duodenal endoscopic submucosal dissection.

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BACKGROUND: There is little information about the relevance of extra-ampullary duodenal adenocarcinoma (EDA) subtypes. The aim of this study was to evaluate the impact of EDA subtypes on surgical and oncological outcomes following pancreatoduodenectomy (PD). METHODS: Consecutive patients undergoing PD for EDA from 2000 to 2019 were analyzed. Results were stratified by pathologic subtype (intestinal versus non-intestinal). Uni-and multivariable analyses were performed using standard statistical methods. RESULTS: The study population consisted of 70 patients, of whom 49 (70%) had an intestinal phenotype. EDA with intestinal phenotype was more frequently proximal to the Ampulla of Vater, while non-intestinal EDA was more frequently found distally (76% vs. 33%, p = 0.002). Patients with intestinal EDA were less likely to experience severe morbidity, with decreased reoperation and unplanned Intensive Care Unit admission rates relative to non-intestinal subtypes (2% vs. 29% p = 0.002, and 2% vs. 19%, p = 0.007, respectively). The median follow-up post-pancreatectomy was 73 months. Intestinal EDA was associated with improved overall and disease-free survival, with 3-year and 5-year survival rates of 71% vs. 29% and 53% vs. 24%, respectively. (p = 0.019 and p = 0.025). CONCLUSION: Intestinal-type EDA, which more often arises from supra-ampullary duodenum, was associated with better postoperative outcomes and improved survival.

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Small bowel adenocarcinoma (SBA) is a rare tumor with an unfavorable prognosis, and due to its rarity, few studies on its treatment are available. Chemotherapy remains the standard of treatment in advanced disease. Recently immunotherapy has demonstrated to be a valid therapeutic option for many solid tumors. We reviewed the data published in literature to understand the impact of immunotherapy in this cancer.

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Infection by certain pathogens is associated with cancer development. We conducted a case-cohort study of ~2500 incident cases of esophageal, gastric and duodenal cancer, and gastric and duodenal ulcer and a randomly selected subcohort of ~2000 individuals within the China Kadoorie Biobank study of >0.5 million adults. We used a bead-based multiplex serology assay to measure antibodies against 19 pathogens (total 43 antigens) in baseline plasma samples. Associations between pathogens and antigen-specific antibodies with risks of site-specific cancers and ulcers were assessed using Cox regression fitted using the Prentice pseudo-partial likelihood. Seroprevalence varied for different pathogens, from 0.7% for Hepatitis C virus (HCV) to 99.8% for Epstein-Barr virus (EBV) in the subcohort. Compared to participants seronegative for the corresponding pathogen, Helicobacter pylori seropositivity was associated with a higher risk of non-cardia (adjusted hazard ratio [HR] 2.73 [95% CI: 2.09-3.58]) and cardia (1.67 [1.18-2.38]) gastric cancer and duodenal ulcer (2.71 [1.79-4.08]). HCV was associated with a higher risk of duodenal cancer (6.23 [1.52-25.62]) and Hepatitis B virus was associated with higher risk of duodenal ulcer (1.46 [1.04-2.05]). There were some associations of antibodies again some herpesviruses and human papillomaviruses with risks of gastrointestinal cancers and ulcers but these should be interpreted with caution. This first study of multiple pathogens with risk of gastrointestinal cancers and ulcers demonstrated that several pathogens are associated with risks of gastrointestinal cancers and ulcers. This will inform future investigations into the role of infection in the etiology of these diseases.

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BACKGROUND: The presence of Spigelman stage (SS) IV duodenal polyposis is considered the most significant risk factor for duodenal cancer in patients with MUTYH-associated polyposis (MAP). However, advanced SS disease is rarely reported in MAP patients, and no clear recommendations on small bowel (SB) surveillance have been proposed in this patient setting. AIM: To research more because that case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced benign SS disease and often involve the distal portion of the duodenum. METHODS: We describe a series of MAP patients followed up at the Regina Elena National Cancer Institute of Rome (Italy). A literature overview on previously reported SB cancers in MAP is also provided. RESULTS: We identified two (6%) SB adenocarcinomas with no previous history of duodenal polyposis. Our observations, supported by literature evidence, suggest that the formula for staging duodenal polyposis and predicting risk factors for distal duodenum and jejunal cancer may need to be adjusted to take this into account rather than focusing solely on the presence or absence of SS IV disease. CONCLUSION: Our study emphasizes the need for further studies to define appropriate upper gastrointestinal surveillance programs in MAP patients.

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BACKGROUND: This study aimed to evaluate the adequate extent of regional lymphadenectomy according to tumor location and the impact of number-based nodal classification on survival in patients with non-ampullary duodenal adenocarcinoma (NADAC). METHODS: A total of 85 patients with NADAC who underwent surgery were enrolled. The frequency of metastasis was calculated for each node group in the respective tumor locations for 63 patients who underwent lymphadenectomy for pT2-pT4 tumor. RESULTS: The frequency of metastasis in the pancreaticoduodenal (nos. 13 and 17) and superior mesenteric artery (no. 14) nodes was high (16.7 %-52.3 %) regardless of tumor location. Metastasis in the perigastric (nos. 3 and 4d) and right celiac artery (no. 9) nodes was not uncommon (14.3 %-22.2 %) for tumors in the first portion. The frequency of metastasis in the pyloric (nos. 5 and 6) and the other peripancreaticoduodenal (nos. 8 and 12) nodes varied depending on tumor location but could not be ignored for staging. When these nodes were classified as regional nodes, the 5-year survival in patients with pN0, pN1 (1-2 positive nodes), and pN2 (≥3 positive nodes) were 82.9 %, 51.7 %, and 19.2 %, respectively (p < 0.001). pN classification independently predicted survival (pN1, p = 0.022; pN2, p < 0.001). CONCLUSIONS: Nos. 5, 6, 8, 12, 13, 14, and 17 nodes in all advanced NADAC and nos. 3, 4d, and 9 nodes in advanced NADAC in the first portion should be considered as regional nodes for accurate staging. The number-based nodal classification allows good patients' prognostic stratification.

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We held four upper gastrointestinal tract advanced diagnostic endoscopy sessions from the 89th to the 92nd Congress of the Japan Gastroenterological Endoscopy Society. The most common region addressed was the stomach in 25 presentations, followed by the esophagus in 23, duodenum in five, and other in one. Looking at techniques discussed, the most common image enhancement method discussed was narrowband imaging in 29 presentations, blue laser imaging, and linked color imaging (LCI) in 10 each, dual red imaging in three, and autofluorescence imaging in one. Furthermore, there were presentations of new techniques such as M-Chromo-LCI and acetic acid-indigo carmine mixture LCI. There were also six presentations regarding probe-based confocal laser endomicroscopy, and one of endocytoscopy techniques. We also saw presentations of images of gastric subepithelial tumors within the submucosa, 3D endoscopy, the development of computer-aided detection systems for early cancers, and fluorescent imaging.

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Intestinal fibrosis is a rare complication of chronic inflammation resulting from various etiologies, including surgery, abdominal radiation, and inflammatory bowel disease. Consequences of intestinal fibrosis include intestinal dysmotility, malabsorption, and obstruction. Patients with Lynch syndrome are predisposed to developing intestinal adenocarcinoma including in the small intestines which typically require intra-abdominal procedures that expose them to fibrogenic triggers. Here, we present a rare case of duodenal fibrosis involving the sphincter of Oddi leading to malabsorption and gastrointestinal symptoms in a patient with Lynch syndrome requiring advanced endoscopy interventions.

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BACKGROUND: Tumors occurring within the pancreatic head commonly arise from the pancreas, duodenal ampulla, distal bile duct, or duodenum. However, they are difficult to distinguish on standard preoperative imaging. PURPOSE: To assess the ability of specialist reporting of preoperative computed tomography (CT) scans to determine the organ of origin of pancreatic cancer (PC). MATERIAL AND METHODS: Blinded re-reporting of preoperative imaging from five hospitals was undertaken of a consecutive cohort of 411 patients undergoing surgery for PC between January 2006 and May 2014. Radiological identification of tumor site was determined by the presence of the main tumor bulk within the pancreatic head parenchyma and estimation of the pathological organ of origin of the PC was based on all the reported features. RESULTS: Each pathological tumor type was noted to have distinct radiological features. Localization of a visible tumor within the pancreatic parenchyma was seen most commonly in PC (92%) than other tumor types (P < 0.0001). Local invasion into the duodenum was a characteristic feature seen in 79% of patients with ampullary tumors and isolated dilation of the bile duct without dilation of the pancreatic duct was seen most commonly in patients with ampullary or bile duct cancer. In the assessment of tumor origin, good agreement (kappa = 0.6, 0.51-0.68) was noted between the consensus radiology opinion and the final histology result. Overall accuracy was greatest for ampullary cancer (88.1%) and lowest for PC (83.2%). CONCLUSION: Radiological assessment of preoperative imaging provides a high degree of accuracy in predicting the organ of origin of peri-ampullary cancer.

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A 51-year-old male patient had four times of massive hematochezia episode three days before arrival. Carbohydrate antigen (CA) 19-9 level was extremely elevated. Computed tomography, magnetic resonance imaging, and positron emission tomography-computed tomography identified 5.7 cm sized periampullary duodenal cancer with regional metastatic lymph nodes and vascular invasion to aberrant right hepatic artery, main portal vein, and superior mesenteric vein. Diagnosed as duodenal adenocarcinoma through endoscopic biopsy, 16 times of FOLFIRI (5-fluorouracil, leucovorin, irinotecan) was conducted. The regimen changed to XELOX (capecitabine, oxaliplatine), four times of administration was done, and the CA19-9 level dramatically decreased. The tumor decreased to 2.1 cm. After R0 laparoscopic pylorus preserving pancreatoduodenectomy, no adjuvant therapy was given. No sign of recurrence or metastasis was reported, and the patient reached complete remission after five years. We reported a case where neoadjuvant chemotherapy for locally advanced duodenal adenocarcinoma was shown to be effective.

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Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).

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A 70-year-old female diagnosed with duodenal cancer was referred to our hospital. Esophagogastroduodenoscopy revealed an 80 mm flat elevated lesion was located in the inner wall of the second part of the duodenum and the lesion completely involved major papilla. Endoscopic submucosal dissection (ESD) was performed and the lesion was resected in a single piece including the part of the major papilla. The pathological examination of the resected specimen showed moderately differentiated adenocarcinoma limited in the mucosa in most parts of the lesion, however, cancer cells invaded into the submucosal layer with an invasion depth of 100 µm in only a small area. Lymph ductal involvement was confirmed in that area. Two months after ESD, pylorus-preserving pancreatoduodenectomy combined with extended lymph node dissection was additionally performed. The postoperative pathological examination revealed lymph ductal involvement was observed in the regional lymph node. While the postoperative clinical course was uneventful, systematic metastasis was pointed out 5 months after surgery. The patient was died 9 months after surgery. Due to its rarity, the natural history of duodenal cancer has been still unclear. In this case, even a lesion with only a localized small area of submucosal invasion developed systemic metastasis, indicating the high malignant potential of duodenal cancer.

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Small bowel cancers are rare diseases whose prognosis is poorer than that of colon cancers. Due to disease rarity, there is little data on small bowel adenocarcinoma (SBA) treatment, and most recommendations come from expert agreements or analogies to the management of colon cancer. Although relatively high rates of local recurrence are observed for duodenal malignancies, distant metastatic relapse remains common and requires adjuvant systemic therapy. Given the similarities between SBA and colorectal cancer, radiotherapy and chemotherapy strategies used for the latter disease are frequently pursued for the former disease, specifically for tumors located in the duodenum. However, no previous randomized study has evaluated the benefit of adjuvant chemotherapy on the overall survival of SBA patients. Most previous studies on treatment outcomes and prognostic factors in this context were based on large international databases, such as the Surveillance, Epidemiology, and End Results or the National Cancer Database. Studies are required to establish and validate prognostic and predictive markers relevant in this context to inform the use of (neo) adjuvant treatment. Among those, deficient mismatch repair tumors represent 20% of SBAs, but their impact on chemosensitivity remains unknown. Herein, we summarize the current evidence on the management of localized SBA, including future perspectives.

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BACKGROUND: Duodenal cancer presents an elusive therapeutic challenge for clinicians to treat because of its highly malignant behavior and anatomical complexity. Endoscopic excision has been administered to treat early-stage cancers of upper gastrointestinal tract, especially esophagus and stomach cancer. There is currently a scarcity of data regarding the application and efficacy of endoscopic resection for early duodenal cancer due to its rarity. This study aimed at exploring the prevalence and efficacy of endoscopic excision in treatment for early duodenal cancer in comparison with major surgery. METHODS: This cohort study retrospectively collected patients with primary Tis/T1-N0-M0 duodenal cancer in the Surveillance, Epidemiology, and End Results database from 2004 to 2017. Prevalence of endoscopic excision in duodenal cancer treatment, overall survival (OS) and disease-specific survival (DSS) of patients who received different tumor-resection procedures were estimated. RESULTS: A total of 1354 patients with Tis/T1-stage duodenal cancer were identified. Most patients (69.4%) underwent tumor resection as initial treatments. Among them, 65.7% underwent endoscopic excision, while 34.3% underwent major surgery. The multivariable Cox analyses revealed that endoscopic excision was associated with a significantly favorable OS (HR: 0.70; 95% CI: 0.52-0.95, p = 0.02) and DSS (HR: 0.32; 95% CI: 0.17-0.60, p < 0.001), compared to major surgery, for Tis/T1-stage cancer patients. In addition to cancer-related deaths (p < 0.001), endoscopic resection manifested significantly lower cumulative mortality rate of post-operative infectious diseases (p = 0.03). CONCLUSION: Endoscopic resection currently accounted for approximately two-thirds of all procedures to resect Tis/T1-stage duodenal tumor. Endoscopic resection represents a viable therapeutic option in the management of Tis/T1-stage duodenal cancer for its oncological superiorities to major surgery and its capacity to reduce operative traumas and morbidities.

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