Non-ampullary Duodenal Adenocarcinoma Research Articles

Laparoscopic Left Side Duodenum Adenocarcinoma Resection (III-IV Segment): A Step-By-Step Surgical Technique.

Nonampullary duodenal adenocarcinoma (NDA) accounts for approximately 5% of all gastrointestinal cancers. Complete surgical resection (R0) with regional draining lymph node removal is mandatory as treatment to potentially cure nonampullary duodenal cancer or to achieve long-term survival. According to existing literature, minimally invasive surgery has been reported to be safe and oncologically equivalent in pancreaticoduodenectomy for pancreatic and duodenal cancer. We describe a fully laparoscopic approach for the left-side adenocarcinoma of the duodenum "left-side" is defined with reference to the mesenteric vessels (III-IV segment). For the first time in literature, this multimedia paper describes a fully laparoscopic complete resection (R0) of the left side of the duodenum (III-IV segment) with locoregional lymph node resection. The main steps of the procedure are described using the concept of the critical view of safety. Reconstruction of intestinal continuity was ensured by full intracorporeal anastomosis. Through the tips and indications presented in this article, we supply a guide to the minimally invasive approach and increase operating surgeons' familiarity with such a complex procedure.

Duodenal Adenocarcinoma: The Relationship between Type of Surgery and Site of Recurrence in a Spanish Cohort

We present a multicenter retrospective study of patients undergoing surgery for duodenal adenocarcinoma, from January 2010 to August 2020, in order to determine the epidemiological characteristics and the oncological results after surgical resection obtained in this rare tumor. Variables: demographics; tumor location; surgical intervention and immediate postoperative period; and post-surgical follow-up information, such as recurrence, overall survival (OS), and disease-free survival (DFS). A total of 32 patients underwent surgery. The median age was 69.74 years (IQR 60.47–79.09) and the male/female distribution was 3:1. The surgeries performed were: pancreaticoduodenectomy (PD) in 16 (50%) patients, segmental resection in 13 (40.6%), and the local excision of the lesion in three (9.4%). The R0 rate was higher in PD (86.7% vs. 42.9%; p = 0.013). The OS and DFS rate at one, three and five years was 95%, 70%, and 60% and 86%, 55%, and 48%, respectively. There was a greater trend towards recurrence in patients who did not undergo PD (53.8% vs. 25%; p = 0.14) and conservative surgery seemed to be associated with more local recurrence than PD (57.1% vs. 33.3%; p = 0.49). PD and limited resection are both valid options in the cases of non-ampullary duodenal adenocarcinoma, although PD presented lower rates of loco-regional recurrence.

Prediction of the invasion depth of superficial nonampullary duodenal adenocarcinoma.

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.

Extent of regional lymphadenectomy and number-based nodal classification for non-ampullary duodenal adenocarcinoma

BackgroundThis 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). MethodsA 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. ResultsThe 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). ConclusionsNos. 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.

Inverted nonampullary duodenal adenocarcinoma treated with underwater EMR

Inverted nonampullary duodenal adenocarcinoma treated with underwater EMR

Clinical outcome of resected nonampullary duodenal adenocarcinoma: A single center experience

Soo Yeun LIM, Dong Il CHUNG, Hye Jeong JEONG, Hyun Jeong JEON, So Jeong YOON, Hongbeom KIM, In Woong HAN, Jin Seok HEO, Sang Hyun SHIN*. Ann Hepatobiliary Pancreat Surg 2023;27:S258. https://doi.org/10.14701/ahbps.2023S1.BP-PP-7-4

Clinical Outcome of Resected Non-Ampullary Duodenal Adenocarcinoma: A Single Center Experience.

(1) Background: This study identified the clinical outcome and prognostic factors of resected non-ampullary duodenal adenocarcinoma (NADA) in a single tertiary cancer center. (2) Methods: The medical records of 109 patients with NADA who underwent curative surgery between 2000 and 2018 were reviewed retrospectively. (3) Results: The mean age was 62.4 years with a male predominance (70.6%). The majority of tumors were located at the 2nd portion (58.7%). Fifty-seven patients (52.3%) had symptoms at diagnosis. CA19-9 was elevated in 32 patients (29.4%). Of this cohort, most patients were diagnosed as stage III (64.2%). The median overall survival was 92.9 months, and the 1-, 3-, and 5-year survival rates were 84.4%, 71.6%, and 53.7%, respectively. In univariate and multivariate analysis, age, symptoms, CA19-9, and margin status were associated with overall survival and symptoms, CA19-9 and margin status were also associated with recurrence. When correlating symptoms with stages, patients with symptoms at diagnosis had more advanced stages (all p < 0.001). (4) Conclusion: Old age, elevated CA19-9, symptoms, and margin status were independent prognostic factors of NADA, and the patients with symptoms at diagnosis tend to have more advanced stages and a poor prognosis.

Gastrointestinal: Multiple metastases of laterally spreading non-ampullary duodenal adenocarcinoma with gastric phenotype.

Non-ampullary duodenal adenocarcinoma could be divided into two major types: gastric and intestinal types with mucin immunohistochemistry. Ushiku et al. reported that the gastric type has a worse prognosis than the intestinal type in patients with duodenal adenocarcinoma. However, few studies have examined the malignant potential of gastric-type duodenal adenocarcinomas. A 76-year-old woman with respiratory symptoms underwent computed tomography, which showed bilateral cavitary pulmonary lesions. Esophagogastroduodenoscopy detected a duodenal tumor spreading from the superior duodenal angle to the prepylorus (Fig. 1a–c). Biopsy showed well-differentiated adenocarcinoma, which was immunohistochemically positive for the MUC5AC (gastric foveolar mucin) and focally positive for the MUC6 (pyloric and Brunner's gland mucin), but negative for MUC2 (major intestinal goblet cell mucin), CDX2 (intestinal transcription factor), and CD10 (intestinal epithelial cells) (Fig. 2a–g). The tumor was soft and flat without any findings suggesting muscle invasion. But positron emission tomography/computed tomography revealed increased uptake in the duodenal bulb, multiple lung lesions, para-aortic lymph nodes, sternum, and ninth thoracic spine (Fig. 1d–f). Histology and immunohistochemistry of lung lesion showed mucinous adenocarcinoma with gastric-type mucin expression, which was similar to the finding of duodenal carcinoma (Fig. 2h–n). Therefore, we diagnosed the patient with multiple metastases from gastric-type duodenal adenocarcinoma. The patient underwent palliative chemotherapy with S-1 plus oxaliplatin, but she died from progressive disease 7 months after diagnosis.

Microsatellite Instability Analysis and Its Prognostic Value in Invasive Nonampullary Duodenal Adenocarcinoma

Purpose: Nonampullary duodenal adenocarcinoma (NADA) is a rare disease. Although several prognostic factors have been reported for this disease, they remain controversial due to their rarity. In this study, we retrospectively analyzed 54 cases of invasive NADA, focusing on the microsatellite instability (MSI) phenotype, programmed cell death-ligand 1 (PD-L1) expression, and prognostic factors. Methods: Expression of the PD-L1 protein and cell differentiation markers in tumors was detected by immunohistochemistry. Microsatellite markers (NR-21, NR-22, NR-24, BAT-25, and BAT-26) were amplified for MSI assessment by PCR. Results: The incidence of MSI in invasive NADA was 35.2%. No significant correlation between the MSI phenotype and clinicopathological factors was observed. Positive expression of PD-L1 by immune cells was common in advanced-stage disease (p = 0.054), and positive expression of PD-L1 in cancer cells correlated significantly with the histologically undifferentiated type (p = 0.016). Kaplan-Meier survival analysis demonstrated a significantly better overall survival (OS) in patients with MSI (p = 0.013) and at early-stage disease (p = 0.000) than in those with microsatellite-stable or at late tumor stages. Univariate and multivariate analyses showed that MSI (hazard ratio [HR]: 0.282, 95% confidence interval [CI]: 0.106–0.751, p = 0.011) and early tumor stage (stage I-II) (HR: 8.81, 95% CI: 2.545–30.500, p = 0.001) were independent better prognostic factors of OS. Conclusions: MSI and early tumor stage (stage I-II) were independent better prognostic factors of OS. A high proportion of MSI phenotypes and positive PD-L1 expression may be helpful for identifying immune checkpoint inhibitors as a novel therapeutic strategy.

The Impact of KRAS Mutation in Patients With Sporadic Nonampullary Duodenal Epithelial Tumors.

INTRODUCTION:The genomic characterization of primary nonampullary duodenal adenocarcinoma indicates a genetic resemblance to gastric and colorectal cancers. However, a correlation between the clinical and molecular characteristics of these cancers has not been established. This study aimed to elucidate the clinicopathological features of sporadic nonampullary duodenal epithelial tumors, including their molecular characteristics and prognostic factors.METHODS:One hundred forty-eight patients with sporadic nonampullary duodenal epithelial tumors were examined in this study. Patient sex, age, TNM stage, tumor location, treatment methods, histology, KRAS mutation, BRAF mutation, Fusobacterium nucleatum, mucin phenotype, and programmed death-ligand 1 (PD-L1) status were evaluated. KRAS and BRAF mutations, Fusobacterium nucleatum, mucin phenotype, and PD-L1 status were analyzed by direct sequencing, quantitative polymerase chain reaction, and immunochemical staining.RESULTS:The median follow-up duration was 119.4 months. There were no deaths from duodenal adenoma (the primary disease). Kaplan-Meier analysis for duodenal adenocarcinoma showed a significant effect of TNM stage (P < 0.01). In univariate analysis of primary deaths from duodenal adenocarcinoma, TNM stage II or higher, undifferentiated, KRAS mutations, gastric phenotype, intestinal phenotype, and PD-L1 status were significant factors. In multivariate analysis, TNM stage II or higher (hazard ratio: 1.63 × 1010, 95% confidence interval: 18.66–6.69 × 1036) and KRAS mutation (hazard ratio: 3.49, confidence interval: 1.52–7.91) were significant factors.DISCUSSION:Only KRAS mutation was a significant prognostic factor in primary sporadic nonampullary duodenal adenocarcinoma in cases in which TNM stage was considered.

Carbonic Anhydrases II and IX in Non-ampullary Duodenal Adenomas and Adenocarcinoma.

Non-ampullary duodenal adenocarcinoma (DAC) is a rare malignancy. Little information is available concerning the histopathological prognostic factors associated with DAC. Carbonic anhydrases (CAs) are metalloenzymes catalyzing the universal reaction of CO2 hydration. Isozymes CAII, CAIX, and CAXII are associated with prognosis in various cancers. Our aim was to analyze the immunohistochemical expressions of CAII, CAIX, and CAXII in normal duodenal epithelium, duodenal adenomas, and adenocarcinoma and their associations with clinicopathological variables and survival. Our retrospective study included all 27 DACs treated in Oulu University Hospital during years 2000-2020. For comparison, samples of 42 non-ampullary adenomas were collected. CAII expression was low in duodenal adenomas and adenocarcinoma. CAIX expression in adenomas and adenocarcinoma was comparable with the high expression of normal duodenal crypts. Expression patterns in carcinomas were largely not related to clinicopathological features. However, low expression of CAII associated with poorer differentiation of the tumor (p=0.049) and low expression of CAIX showed a trend for association with nodal spread, although statistical significance was not reached (p=0.091). CAII and CAIX lost their epithelial polarization and staining intensity in adenomas. CAXII expression was not detected in the studied samples. CAs were not associated with survival. The prognostic value of CAII and CAIX downregulation should be further investigated. Both isozymes may serve as biomarkers of epithelial dysplasia in the duodenum.

Comparison of robotic and open pancreaticoduodenectomy for primary nonampullary duodenal adenocarcinoma: a retrospective cohort study.

Robotic surgery has been increasingly applied in pancreatic surgery and showed many advantages over conventional open surgery. The robotic pancreaticoduodenectomy (RPD) is a surgical option for primary nonampullary duodenal adenocarcinoma (PNDA). However, whether RPD is superior to open pancreaticoduodenectomy (OPD) for PNDA has not been reported. The comparative study was designed to analyze the short- and long-term outcomes of RPD versus OPD on patients with PNDA. Demographics, perioperative, and survival outcomes among patients who underwent RPD (n = 49) versus OPD (n = 43) for PNDAs between January 2013 and March 2018 were collected and analyzed RESULTS: Demographic characteristics were comparable between the RPD group and the OPD group. The RPD group demonstrated a decreased estimated blood loss (100 vs. 200ml, p < 0.001), time to oral intake (4.0 vs. 4.0days, p = 0.04), and postoperative hospital stay (12.9 vs. 15.0days, p = 0.01) compared with the OPD group. However, no differences were observed between the two groups in terms of operative time and the rates of major complications, grade B and C POPF, PPH, grade B and C DGE, biliary fistular, reoperation, and 90-day readmission. No patient died within 90days. There were no significant differences in tumor size, differentiation, TNM stage, number of harvested lymph nodes, and the rates of nerve invasion, lymph node invasion, R0 resection, and the median overall survival between the two groups (p > 0.05) CONCLUSIONS: RPD is a safe, feasible, and effective treatment for PNDA compared with OPD and can be used as an alternative for surgeons in the treatment of PNDA. Further multicenter randomized controlled trials are needed to evaluate the effectiveness of RPD in patients with PNDA.

Surgical treatment of duodenal adenocarcinoma: ampullary vs. non-ampullary, short- and long-term outcomes.

The aim of this study was to evaluate symptoms, diagnostic methods, short- and long-term outcomes of surgical treatment in patients with duodenal adenocarcinoma. A single center, retrospective, observational study of 52 consecutive patients with duodenal adenocarcinoma operated on with curative intent between 2006 - 2019. Duodenectomy as part of a hemipancreatoduodenectomy or total pancreatectomy procedure was performed for ADAC (ampullary duodenal/intestinal adenocarcinoma) or NADAC (non-ampullary duodenal adenocarcinoma). Prevailing symptoms were obstructive jaundice in the ADAC group (P<0.0001) and bleeding in the NADAC group (P=0.005), with larger tumor size in patients with NADAC (P=0.001). Complication rate, morbidity and mortality were comparable. Primary total pancreatoduodenectomy predominated in the NADAC group, 16.6% vs. 2.9%, and salvage completion pancreatectomy in the ADAC group, 6% vs. 0%. Significant prognostic factors for OS were perineural invasion (P=0.006) and adjuvant chemotherapy (P=0.045) in the ADAC group, and for DFS the total number of resected lymph nodes (P=0.042) and lymph node ratio (P=0.031) in the NADAC group. Median OS is 21 months and 5-year survival 27.3% in the NADAC group and 41.5 months and 52% in the ADAC group. Ampullary duodenal/intestinal adenocarcinomas are smaller than non-ampullary at diagnosis, with a higher rate of lymph node metastases, but with a better prognosis and long-term outcome in the presented cohort. Oral localisation of NADAC prevailed in the present cohort. Perineural invasion and postoperative oncological therapy are significant prognostic factors for OS in ADAC, but the total number of lymph nodes and lymph node ratio are significant prognostic factors for DFS in NADAC.

Pancreatic ductal adenocarcinoma and distal cholangiocarcinoma: a proposal of preoperative diagnostic score for differential diagnosis

PurposeThe differential diagnosis between primary adenocarcinoma of the pancreas head and distal cholangiocarcinoma remains a clinical challenge. Recent studies have shown important differences in terms of survival between these tumors. Therefore, different treatments should be considered, but the preoperative histological diagnosis is still difficult. Aim of this study is to create a preoperative diagnostic score for differential diagnosis between primary pancreatic adenocarcinoma and primary distal cholangiocarcinoma.MethodsOne hundred eighty consecutive patients who underwent pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2019 were retrospectively analyzed. Inclusion criteria were pancreatic or biliary histologic origin obtained by definitive postoperative histological examination. Exclusion criteria were diagnosis of ampullary carcinoma, non-ampullary duodenal adenocarcinoma, pancreatic metastasis, and benign disease. One hundred one patients were considered eligible for the retrospective study. Preoperative biological, clinical, and radiological parameters were considered.ResultsCRP > 10 mg/dL (p = 0.001), modified Glasgow Prognostic Score 2 (p = 0.002), albumin < 35 g/L (p = 0.05), CA 19-9 > 230 U/mL (p = 0.001), and Wirsung diameter > 3 mm (p < 0.001) were significant at univariate logistic analysis. Multivariate logistic analysis has shown that parameters independently associated with primary pancreatic adenocarcinoma were CRP > 10 mg/dL (p = 0.012), CA 19-9 > 230 U/mL (p = 0.043), and diameter of the Wirsung > 3 mm (p = 0.005). Through these parameters, a diagnostic score has been developed to predict a primary pancreatic adenocarcinoma when > 1 and a primary distal cholangiocarcinoma when < 1.ConclusionThis feasible and low-cost diagnostic score could have a potential impact to differentiate pancreatic cancer histologic origin and to improve target therapeutic strategy.

Clinicopathological features and risk factors for lymph node metastasis in early-stage non-ampullary duodenal adenocarcinoma.

Management strategies for primary non-ampullary duodenal adenocarcinoma (NADAC) in early stage are not well established given its low incidence. This study aimed to elucidate clinicopathological features of early NADAC, including risk for lymph nodal metastasis (LNM). In total, 166 patients with early NADAC underwent initial treatment at our institution between 2006 and 2019, of whom 153 had intramucosal (M-) and 13 had submucosal (SM-) NADAC. These endoscopic and pathological features were retrospectively analyzed. Risk factors for LNM were evaluated in 46 early NADAC patients who underwent surgery with lymph node dissection. Compared with M-NADAC, SM-NADAC was significantly more frequently located at the proximal side of the papilla, with mixed elevated and depressed macroscopic type, histologically poorly differentiated tumor and lymphovascular invasion (LVI) (85% vs. 47%, P = 0.009; 54% vs. 5%, P < 0.001; 23% vs. 0%, P < 0.001; and 46% vs. 0%, P < 0.001, respectively). The frequency of LNM was significantly higher in SM-NADAC than in M-NADAC (5/12, 42% vs. 0/34, 0%; P < 0.001). In SM-NADAC, the frequency of LNM was higher in poorly differentiated than in well to moderately differentiated tumors (3/3, 100% vs. 2/9, 22%) and higher in tumors with LVI than in those without LVI (3/5, 60% vs. 2/7, 29%). Regarding invasion depth, 2 of 4 patients with SM invasion (400 ≤ × < 500µm) showed LNM. However, in this study, no patients developed very shallow SM invasion (0 < × < 400µm). SM-NADAC showed high LNM risk. Surgical treatment with regional lymph node dissection is recommended as a treatment strategy for SM-NADAC.

Present Status of Endoscopic Submucosal Dissection for Non-Ampullary Duodenal Epithelial Tumors.

Prediction of histology by endoscopic examination is important in the clinical management of non-ampullary duodenal epithelial tumors (NADETs), including adenoma and adenocarcinoma. The use of a simple scoring system based on the findings of white-light endoscopy or magnified endoscopy with narrow-band imaging is useful to differentiate between Vienna category 3 (C3) and C4/5 lesions. Less invasive endoscopic resection procedures, such as cold snare polypectomy, are quick to perform and convenient for small (<10 mm) C3 lesions. Neoplasms with higher grade histology, such as C4/5 lesions, should be treated by endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or surgery. Although EMR often requires piecemeal resection, the complication rate is acceptable. Excellent complete resection rates could be achieved by ESD; however, it remains a challenging method considering the high risk of complications. Shielding or closure of the ulcer after ESD is effective at decreasing the risk of delayed bleeding and perforation. Laparoscopic endoscopic cooperative surgery is an ideal treatment with a high rate of en bloc resection and a low rate of complications, although it is limited to high-volume centers. Patients with NADETs could benefit from a multidisciplinary approach to stratify the optimal treatment based on endoscopic diagnoses.

Molecular alterations and PD-L1 expression in non-ampullary duodenal adenocarcinoma: Associations among clinicopathological, immunophenotypic and molecular features

Non-ampullary duodenal adenocarcinoma (NADC) is extremely rare. Little is known about its clinicopathological and molecular features or its management. Herein we retrospectively analyzed the cases of 32 NADC patients, focusing on microsatellite instability (MSI), genetic mutations, CpG island methylator phenotype (CIMP), and immunostaining including mucin phenotype and PD-L1 expression. The incidence of MSI, KRAS/BRAF/GNAS mutations and CIMP was 51.6%, 34.4%/3.1%/6.5% and 28.1%, respectively. PD-L1 expression was seen in 34.4% of patients. No significant associations between clinicopathological features and KRAS/BRAF/GNAS genetic mutations or CIMP were found. Histologically non-well-differentiated-type NADCs and those in the 1st portion of the duodenum were significantly associated with later stages (stages III–IV) (P = 0.006 and P = 0.003, respectively). Gastric-phenotype NADCs were frequently observed in the 1st portion and in late-stage patients; their cancer cells more frequently expressed PD-L1. Histologically, the non-well-differentiated type was an independent predictor of PD-L1 expression in cancer cells (OR 25.05, P = 0.04) and immune cells (OR 44.14, P = 0.02). Only late-stage disease (HR 12.23, P = 0.01) was a prognostic factor for worse overall survival in a Cox proportional hazards regression model. Our observation of high proportions of MSI and PD-L1 expression may prompt the consideration of immune checkpoint inhibitors as a new treatment option for NADCs.

Clinical and endoscopic findings to assist the early detection of duodenal adenoma and adenocarcinoma.

Sporadic nonampullary duodenal adenocarcinoma is a rare malignant neoplasm in which poor prognosis is often associated with delayed diagnosis. A case-control study was designed to evaluate the clinical and endoscopic characteristics of patients with nonampullary duodenal epithelial tumours (NADETs). Patients with NADETs were chronologically divided into a discovery and a validation sets. Two age- and sex-matched control individuals for each case in the discovery set were randomly selected from individuals without NADET. A prediction model for the presence of NADET, constructed in the discovery set, was evaluated in the validation set. In total, 368 adenomas, 81 adenocarcinomas, and 314 controls were analysed. Current smoking, Barrett oesophagus, fundic gland polyps, history of malignant disease, and absence of dyslipidaemia were independently associated with the presence of NADET. The combination of these five factors enabled significant discrimination for NADET in the bulb with a sensitivity of 0.81 in the validation set. We also showed that duodenal adenocarcinomas in the bulb had greater invasive potential than adenocarcinomas in the second portion. The presence of a duodenal tumour in the bulb could be predicted by clinical and endoscopic findings, which helps improve the prognosis and quality of life of patients.

Expression of Gastric Markers Is Associated with Malignant Potential of Nonampullary Duodenal Adenocarcinoma.

Sporadic nonampullary duodenal epithelial tumors (NADETs) are uncommon, and thus their clinicopathological features have not been fully assessed. In this study, we have analyzed a series of early sporadic NADETs, focusing on various immunohistological features. We conducted a multicenter retrospective analysis of 68 patients with endoscopically resected sporadic NADETs. Associations between immunohistological features and clinicopathological features were statistically analyzed. The 68 patients consisted of 46 men (68%) and 22 women (32%) with a mean age of 60.7 ± 12.2years (range 37-85years). The 68 tumors were composed of 39 adenomas (57%) and 29 early-stage adenocarcinomas (43%). Duodenal adenocarcinomas were larger in size than adenomas and had papillary architecture in their pathological diagnosis with statistical significance. Duodenal adenocarcinomas also demonstrated a significantly higher expression of gastric markers (MUC5AC and MUC6) and a higher MIB-1 index. Duodenal adenomas were contrastively apt to express intestinal markers (MUC2, CDX1 and CDX2). Of the 68 cases analyzed, there were only 3 tumors positive for p53 staining, all of which were adenocarcinoma. When 7 submucosal invasive cancers and 21 intramucosal cancers were compared, submucosal invasion was positively associated with expression of MUC5AC. Also, submucosal invasion showed strong association with double-positivity of MUC5AC and MUC6. Our results indicate that immunohistochemical evaluation is useful for predicting malignant potential of NADETs, especially focusing on the expression of gastrointestinal markers.

Prognostic factors of non-ampullary duodenal adenocarcinoma.

Non-ampullary duodenal adenocarcinoma, excluding carcinoma in the ampulla of Vater, is a rare disease. Although several prognostic factors have been reported, they remain controversial due to the rarity of non-ampullary duodenal adenocarcinoma. The aims of this study were to investigate prognostic factors in patients with non-ampullary duodenal adenocarcinoma and to assess chemotherapy in patients with recurrence. Records of 25 patients who underwent surgical treatment for non-ampullary duodenal adenocarcinoma from 2004 to 2016 were retrospectively reviewed. The relationship between the clinicopathological factors and outcomes was investigated. Serum level of CA19-9, gross appearance, tumor size, tumor invasion, lymph node metastases, TNM stage and lymphatic and vascular invasion were significant risk factors of recurrence. Patients with recurrence who received chemotherapy according to regimens used to treat colorectal cancer had a better prognosis than those without chemotherapy (P = 0.016). Advanced non-ampullary duodenal adenocarcinoma has a poor prognosis, but chemotherapy possibly improves the prognosis in the patients with recurrent non-ampullary duodenal adenocarcinoma.