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Background/Aim There is no standard salvage chemotherapy for metastatic periampullary adenocarcinoma and duodenal adenocarcinoma and the prognosis of those who fail oxaliplatin, irinotecan, and 5FU is dismal. We examined nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) as salvage therapy for these two malignancies. Methods Patients who failed oxaliplatin, irinotecan, and 5FU and whose archival tumors stained immunohistochemical (IHC) tumor positive for CK7 or MUC1 received nab‐paclitaxel and gemcitabine therapy with or without cisplatin. Results Three patients, 2 with metastatic ampullary adenocarcinoma and 1 with duodenal adenocarcinoma with positive IHC staining for CK7 or MUC1 who failed 2 lines of chemotherapy with oxaliplatin, irinotecan, and 5FU received nab‐paclitaxel and gemcitabine with or without cisplatin. All achieved excellent tumor response on CT scans with marked falls in tumor markers CA19‐9 and CEA as well as ≥1 year of progression‐free survival. All 3 have continued to survive 2‐3 years since diagnosed with stage 4 metastatic adenocarcinoma. Conclusions Nab‐paclitaxel plus gemcitabine with or without cisplatin should be investigated as a standard‐of‐care chemotherapy regimen for patients with ampullary adenocarcinoma and duodenal adenocarcinoma.

BACKGROUND: Sporadic nonampullary duodenal adenocarcinoma is a rare malignant neoplasm in which poor prognosis is often associated with delayed diagnosis. OBJECTIVE: A case-control study was designed to evaluate the clinical and endoscopic characteristics of patients with nonampullary duodenal epithelial tumours (NADETs). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Background Pancreaticoduodenectomy is often required in patients with duodenal adenoma and adenocarcinoma and these patients generally have soft pancreatic texture and small pancreatic ducts, the two most significant factors associated with post-operative pancreatic fistula (POPF). The aims of the study were to evaluate the rate of POPF and long-term outcomes for patients with duodenal adenoma and adenocarcinoma who underwent curative resection. Methods This retrospective study (2004-2014) examined patients treated surgically with non-ampullary duodenal tumours (NADTs) in two hepatopancreaticobiliary units in Victoria, Australia, and Swansea, UK. Results There were 49 resections performed including 33 pancreaticoduodenectomies, five pancreas-preserving total duodenectomies and 11 segmental duodenal resections. Median length of follow-up was 23.5 months. Final histopathology revealed 18 duodenal adenomas and 31 adenocarcinomas. POPF rate for NADTs was 28.9% (of which 54.5% were grade C) compared to 14.5% for all other pathologies. Grade C POPF was associated with poorer survival outcomes (hazard ratio = 6.73; P = 0.005). The 5-year overall survival for patients with duodenal adenocarcinoma was 66.5%. Conclusion Due to the soft pancreatic texture and small pancreatic duct, pancreatic resection for NADTs is associated with a high rate of POPF which contributes to reduced survival. Nevertheless, surgery is associated with favourable 5-year survival compared to pancreatic resection for pancreatic adenocarcinoma.

BACKGROUND Genomic alterations of small bowel cancers remain poorly understood due to the rarity of these diseases. In the current study, the authors report the identification of somatic mutations from patients with duodenal adenocarcinoma by whole-exome sequencing. METHODS Whole-exome sequencing and follow-up analysis were conducted in 12 matched tumor-normal tissue duodenal adenocarcinoma tissue pairs to examine the genetic characteristics of this disease. Somatic mutations (single-nucleotide variants and short insertion/deletions) were obtained and filtered and then searched for recurrently mutated genes and pathways. RESULTS An excess of C-to-T transitions at the CpG dinucleotide was observed in the substitution of bases. The authors identified recurrent mutations in tumor protein p53 (TP53), KRAS, catenin (cadherin-associated protein) β-1 (CTNNB1), AT-rich interactive domain 2 (ARID2), adenomatous polyposis coli (APC), erb-b2 receptor tyrosine kinase 2 (ERBB2), ARID1A, cadherin-related family member 1 (CDHR1), NRAS, Bcl-2-related ovarian killer (BOK), radial spoke head 14 homolog (chlamydomonas) (RTDR1), cell division cycle 27 (CDC27), catalytic subunit of phosphoinositide-3-kinase (PIK3CA), and SMAD family member 4 (SMAD4). Pathway scan indicated that the Wnt signaling pathway, regulation of the actin cytoskeleton pathway, ErbB signaling pathway, and the pathway of focal adhesion were the most extensively affected pathways. CONCLUSIONS This genomic characterization of duodenal adenocarcinoma provides researchers with insight into its somatic landscape and highlights the vital role of the Wnt/β-catenin signaling pathway. The study data also indicate that duodenal adenocarcinomas have a genetic resemblance to gastric and colorectal cancers. These discoveries may benefit the future development of molecular diagnosis and personalized therapies. Cancer 2016. © 2016 American Cancer Society.

Background Ampullary (AMP-A) and duodenal adenocarcinomas (DA) are rare tumors. The literature regarding treatment and outcome is very limited. The objective of this project is to compare the outcomes of AMP-A and DA. Methods The records for AMP-A and DA patients between July 1995 and July 2012 at Emory University were reviewed for demographics, pathology, treatment, and survival. Survival rates were estimated by Kaplan–Meier method and compared with log-rank test. A Cox proportional hazard model was fitted to estimate the adjusted effect of AMP-A versus DA on overall survival (OS). Results Ninety-five AMP-A and 66 DA patients were identified. No significant difference between patients with DA and AMP-A was observed for age, gender, or grade. DA presented with larger tumors and higher stages. Treatment included surgery, surgery followed by adjuvant therapy or chemotherapy alone. No OS difference was observed when controlled for stage. AMP-A was sub-classified into intestinal (IAMP), pancreaticobiliary (PBAMP), and unspecified types. IAMP tended to present at a higher grade (P = 0.045) than PBAMP. No OS difference between the IAMP and PBAMP was observed. Conclusions After accounting for stage, OS was not significantly different for AMP-A and DA patients. There was no OS difference comparing PBAMP with IAMP. J. Surg. Oncol. 2014 109:556–560. © 2013 Wiley Periodicals, Inc.

Background Because of the rarity of duodenal adenocarcinoma, little is known regarding its natural history or prognostic factors for survival. We therefore evaluated surgical treatment, and prognostic factors for survival in patients with duodenal adenocarcinoma. Methods We retrospectively reviewed the medical records of patients who were diagnosed with duodenal adenocarcinoma at Asan Medical Center between December 1999 and December 2009. Results Of the 76 patients, 47 (61%) underwent surgery with curative intent and 29 (39%) underwent palliative operation. Of the former, 25 underwent pancreaticoduodenectomy (PD), 19 underwent pylorus-preserving PD, 2 underwent segmental duodenectomy and 1 underwent transduodenal excision. The median survival of the 41 patients who achieved R0 resection was 25.1 months (range 4–134 months), with overall 1-, 3- and 5-year survival rates of 80.4%, 63.4% and 60.9%, respectively. Median survival was significantly longer in patients who underwent curative resection than in those who underwent palliative surgery (28.2 versus 6.6 months, P < 0.001). Univariate analysis showed that transfusion and lymph node metastasis were related to survival, and multivariate analysis revealed that lymph node metastasis was independently associated with survival (P = 0.036). Survival differences were observed between stages of the seventh edition of the American Joint Committee on Cancer staging system. Conclusion In the absence of distant metastasis, curative resection enhances the long-term survival of patients with duodenal adenocarcinoma. Lymph node metastasis is prognostic factor of overall survival.

Background Duodenal adenocarcinoma (DA) is rare, but potentially curable. Prospective data on treatment outcomes is scarce and large retrospective studies show conflicting results on the impact of radical resection, node-status, and adjuvant therapy. Methods In the past 17 years, 30 patients presented with resectable DA. Data on the aforementioned variables were acquired then analyzed for impact on recurrence and survival. Results Overall-survival rates at 1, 2, and 3 years were 70.0%, 53.3%, and 33.3% respectively. Recurrence-free survival rates at 1, 2, and 3 years were 53.3%, 30.0%, and 26.7%. Overall-survival rates for patients with node-positive disease at 1, 2, and 3 years were 68.8%, 43.8%, 12.5%, and for node-negative 70%, 60%, 60%. Recurrence-free survival in node-positive disease at 1, 2, 3 years was 50%, 12.5%, 12.5%, and for node negative 50%, 50%, and 40%. Median survival from diagnosis was 27.5 months (0.5–226.7 months). Significant predictors of recurrence and survival were nodal-status and AJCC stage (P

Background: Although endoscopic treatment of jaundice is increasingly used in the palliation of unresectable malignant disease, surgical bypass still has a role to play in this setting. This study aimed to reappraise the short-term and long-term results of combined biliary/gastric bypass (hepaticojejunostomy and gastrojejunostomy) as palliation for unresectable malignant disease. Methods: All patients undergoing simultaneous biliary and gastric bypass procedures for unresectable malignant disease between August 2000 and January 2006 were identified and outcomes reviewed. Results: One hundred and two patients underwent open surgical biliary drainage procedures for palliation of malignant disease. Underlying malignant disease included pancreatic carcinoma (n = 88), duodenal adenocarcinoma (n = 6) and distal cholangiocarcinoma (n = 3). Thirty-one of the patients underwent a planned palliative bypass procedure, the remainder being carried out after unresectable disease was identified at laparotomy. Postoperative mortality and morbidity rates were higher in the group undergoing planned bypass. During follow up, two patients developed recurrent jaundice that required transhepatic stenting and two patients developed late gastric outlet obstruction requiring refashioning of the gastrojejunostomy. Conclusion: Combined surgical biliary and gastric bypass achieved effective palliation of jaundice and gastric outlet obstruction until death in >95% of patients in this series. It remains first-line therapy in patients identified as having unresectable disease at laparotomy.

Gastrointestinal malignancies are extremely rare in the pediatric population, and duodenal cancers represent an even more unusual entity. Intestinal cancers in young adults and children have been observed to be associated with functional deficiencies of the mismatch repair (MMR) system causing a cancer-predisposition syndrome. We report the case of a 16-year-old female with duodenal adenocarcinoma and past history of medulloblastoma found to have a novel germline bialleleic truncating mutation (c.[949C>T]+[949C>T]) of the PMS2 gene. Pediatr Blood Cancer 2009;53:116–120. © 2009 Wiley-Liss, Inc.

Background and Aim: The impact of obstructive jaundice (OJ) complicated by primary duodenal adenocarcinoma (PDA) on survival, and its treatment options, has rarely been mentioned in literature. The aim of the present study was to review the clinical features of PDA patients in an attempt to determine the prognostic factors and the influence of OJ on survival. Methods: From May 1994 to February 2005, all duodenal malignancies treated at Kaohsiung Chang Gung Memorial Hospital were reviewed. Preliminary findings were made on a total of 116 duodenal adenocarcinoma (DA) cases. After excluding metastatic DA and the papilla of Vater cancer, 23 patients (19.8%), confirmed as having PDA, were enrolled. Results: Among the 23 predominantly male patients with a mean age of 68 years, abdominal pain was the most common symptom. Major tumor origin was the second portion, and the predominantly cytological feature was moderate differentiation. Tumor-node-metastasis (TNM) cancer stage IV accounted for 47.8% of the patients, and cancer-directed surgeries (CDS) were performed on 11 patients. Seven patients experienced complications due to OJ, which could be a sign of grave prognosis predicting survival of less than 1 year. Four of the patients received internal or external biliary drainage before CDS or palliative surgeries. Cigarette smoking, cytology, TNM stage, aspartate aminotransferase (AST), OJ, and CDS were significant factors of overall survival in a univariate analysis. The independent predictors of long-term survival were CDS, TNM stage, cytology, cigarette smoking, and AST using the Cox proportional hazard model. Conclusion: PDA patients who did not smoke and who were eligible for and received CDS had better prognostic outcomes.

A 6-year-old Rottweiler was presented to the North Carolina State University College of Veterinary Medicine for evaluation of multiple cutaneous nodules. The dog had a history of anorexia, vomiting, and hind-limb paraplegia. Results of cytologic examination of the cutaneous nodules were consistent with a round cell tumor. At necropsy, primary tumors were found coalescing in the duodenum and the pancreas and extending into the associated mesentery. Numerous masses also were found throughout the skin, abdominal and thoracic viscera, and lumbar spinal cord. Histologically, the duodenal tumor had variable morphology, with some areas resembling adenocarcinoma and others resembling anaplastic round cell neoplasia; the skin and other metastatic lesions resembled round cell neoplasia. Immunohistochemistry of the cutaneous, duodenal, and pancreatic masses showed the neoplastic cells were positive for pancytokeratin, supporting an epithelial origin. In addition, low numbers of neoplastic cells were positive for periodic acid-Schiff and Alcian blue, consistent with acid mucin production by duodenal epithelium. These findings confirmed that the cutaneous nodules were metastatic lesions originating from the duodenal adenocarcinoma. Cutaneous metastasis of intestinal carcinoma is rare in domestic animals. This case demonstrates the potential difficulty in diagnosing metastatic lesions based on cytologic and histologic morphology alone, because the cutaneous metastases may not resemble the primary neoplasm morphologically.

Seventeen cases of primary duodenal adenocarcinoma occurring in the elderly (older than 65 years) were examined to clarify their clinicopathological features and biological behavior. The mean age was 77.4 years (range, 66-104), and there was no appreciable difference in the incidence between the sexes (female: male ratio, 8: 9). Thirteen patients had tumors located in the first portion of the duodenum, three in the second portion and one in the third portion. Grossly, there were three varieties of lesions: six polypoid, four flat-elevated and seven ulcerative-invasive. Sixteen cases showed well-differentiated adenocarcinoma, three of which were difficult to distinguish from adenoma, and one was poorly differentiated adenocarcinoma. Three of 16 tumors had poor differentiation in the invasive area, whereas mucosal lesions were well differentiated. Eight tumors had invaded the duodenal wall with occasional involvement of the pancreas. Immunohistochemistry demonstrated p53 protein overexpression in two intramucosal (22.2%) and five invasive (62.5%) cancers. In the intramucosal area the mean Ki-67-positive rate (PR) of the tumors with distant metastasis was significantly higher than that of the tumors without metastasis (46.0 vs 31.6%; P < 0.05), while there was no significant difference in the association between PR and gross feature or depth of the tumors. Clinical follow-up showed three of the five patients with invasive cancer died of carcinoma within 28 months. Compared with published data from other investigators, the results of the present study indicate a proximal shift of duodenal carcinoma in the elderly. Furthermore, it is concluded that invasive duodenal adenocarcinomas with high PR should be considered as potentially aggressive tumors, although their histology may indicate a high degree of differentiation.

Background: Surgical resection has been the standard treatment for duodenal adenomas. It has a high associated morbidity rate and a significant recurrence rate. The aim of this study was to evaluate endoscopic treatment of these lesions with argon plasma coagulation. Methods: We retrospectively identified patients with non-ampullary duodenal adenomas without a polyposis syndrome and who were treated endoscopically between 1st January 1999 and 31st December 2003. Their management, follow up and outcomes were reviewed. Results: Fifteen patients were included, with mean age 72 years (range 46–85 years). All were treated with at least one session of argon plasma coagulation. Initially, 13 adenomas were macroscopically cleared. Of these, eight (61%) had no recurrence during mean follow up of 40 months (26–68 months). The mean time to recurrence was 14 months (6–30 months). Eradication was possible a second time in four of five recurrent adenomas. There was one complication, of haemorrhage, from 37 sessions of argon plasma coagulation. No patient developed duodenal adenocarcinoma during the study period. Conclusion: Argon plasma coagulation may be safe and effective for the treatment of duodenal adenomas, but further research is required. Progression of adenomas is slow and perhaps no treatment is required.

BACKGROUND Adenocarcinomas and carcinoid tumors are the most common malignant tumors of the small intestine. K-ras oncogene mutations at codon 12 are common in gastric, pancreatic, and colon carcinomas, with an incidence of 35-88%. K-ras mutations have not been extensively studied in either adenocarcinomas or carcinoid tumors of the small bowel. The purpose of this study was to determine whether ras mutations play an important role in the formation of these tumors. METHODS Archival tissues from 28 adenocarcinomas and 22 carcinoid tumors of the small bowel were studied, along with archival tissues from 32 adenocarcinomas of the large bowel, which were used as controls. DNA from the small intestine tumors was analyzed for K-ras, H-ras, and N-ras oncogene mutations at codons 12, 13, and 61, using polymerase chain reaction and sequence specific oligonucleotide hybridization techniques. Large bowel adenocarcinomas were analyzed for K-ras mutations at codons 12 and 13. RESULTS A point mutation of K-ras at codon 12 was detected in 4 of 28 (14.3%) of the small bowel adenocarcinomas, in 12 of 32 (37.5%) of the large bowel adenocarcinomas, and in 0 of 22 small intestine carcinoid tumors. No other K-ras, H-ras, or N-ras mutations were detected in any of the small bowel tumors. Each small intestine K-ras mutation was found in a duodenal adenocarcinoma (4 of 12 cases, 33%), whereas none occurred in 16 other jejunal or ileal adenocarcinomas. CONCLUSIONS K-ras mutations appear to play a significant role in the pathogenesis of duodenal adenocarcinomas, but they do not appear to be important in the development of jejunal or ileal adenocarcinomas or of carcinoid tumors of the small intestine. Cancer 1997; 79:1804-8. © 1997 American Cancer Society.

Oncogenes, tumor suppressor genes, and growth factors are being explored as to their role in the initiation and progression of most neoplasms, but little information exists on the expression of oncoproteins or growth factors in adenocarcinoma of the duodenum or ampulla of Vater. This report covers expressions of p53, c-neu, TGF-alpha, CEA, and EMA in duodenal adenocarcinoma and ampullary adenocarcinoma, as well as correlations between expressions and tumor stage, histological grade and patient survival. The expression of p53, c-neu, TGF-alpha, CEA, and EMA has been studied in 15 duodenal adenocarcinomas and in eight ampullary adenocarcinomas by avidin-biotin-peroxidase complex indirect immunoperoxidase technique. The positive reaction for p53, c-neu, TGF-alpha, CEA, and EMA in duodenal adenocarcinoma was 20%, 60%, 60%, 73%, and 100%, respectively, and in ampullary adenocarcinoma, 13%, 100%, 50%, 63%, and 100%. Among the duodenal tumors, C-neu and p53 expression was noted more frequently in groups with high histological grades. Patients with c-neu positive duodenal adenocarcinoma had a shorter survival than the patients with c-neu negative duodenal adenocarcinoma (P < 0.01). C-neu product may serve as an unfavorable prognostic indicator in duodenal adenocarcinoma. No statistically significant correlation was found between the expressions of CEA, EMA, p53, and TGF-alpha and patient survival, tumor stage, or histological grade in either duodenal or ampullary adenocarcinomas.

BACKGROUND Because fewer than 1000 cases of primary adenocarcinoma of the duodenum have been reported, earlier series are limited by local referral patterns and the long periods of time needed for retrospective reviews. METHODS This study reports the outcomes of preiampullary duodenal adenocarcinoma treatments in all hospitals of the Department of Veterans Affairs from 1987 through 1991, using computer and tumor registry records. Patients were grouped by their most aggressive treatment (resection > operative bypass > percutaneous biliary intubation) and survival calculated from the date of this procedure. RESULTS Of 2185 patients with periampullary cancers (1753 pancreatic, 432 other periampullary), 85 were duodenal and thus comprised only 4% of periampullary tumors. Thirty-four duodenal cancers were resected, 44 bypassed, and 7 had biliary intubation, with 30-day mortality rates of 6%, 18%, and 0%, respectively. Mean survival exceeded 1 year in all groups, and resection resulted in a significant increase in mean survival (784 vs. 438 days for nonresection, P = 0.01). The projected 5-year survival rate after resection was 23%. Mean survival after resection of 9 Stage I-II cancers was 668 days, but was similar after 5 resections with nodal or other metastases. Similarly, survival did not correlate with cancer stage in 13 palliated patients. CONCLUSIONS This large study of patients with duodenal cancer provides a unique perspective of disease prevalence and response to surgical treatment. Prolonged survival is common with any treatment, but the longest survivals were after resection. Cancer 1996;77:251-4.

Primary adenocarcinoma of the duodenum is rare. An extensive experience with fiberoptic esophagogastro-duodenoscopy in our institution has indicated that duodenal neoplasms may be more frequent than suspected and are readily diagnosed by this modality. With this mind, clinical, pathological, diagnostic and therapeutic aspects of the 71 patients with primary carcinoma of the duodenum reported in the literature in the last 10-year period, 1965-1974, were reviewed. It would appear that fiberoptic endoscopy of the upper gastro-intestinal tract should become the major diagnostic tool for this disease. It enables biopsies, brushings and washings to be taken. A preoperative histological diagnosis ensures that both patient and surgeon can be prepared for major abdominal surgery. It is imperatire that during the endoscopic examination, the entire duodenum be examined. Pancreatico-duodenectomy appears to offer the best chance of long term survival in patients whose lesion is resectable. The role and value of adjuvant chemo- and radiotherapy is still to be determined.