Duodenal adenocarcinoma clinical trials

Peutz-Jeghers syndrome. J Med Genet ; 34 : — Nature ; : — Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet ; 18 : 38 — Br J Cancer ; 89 : — Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology ; : — Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res ; 12 : — Small-bowel cancer in Lynch syndrome: is it time for surveillance? Lancet Oncol ; 9 : — Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis.

Diagnostic approach and management of Lynch syndrome hereditary nonpolyposis colorectal carcinoma : a guide for clinicians. CA Cancer J Clin ; 56 : — Reflex immunohistochemistry and microsatellite instability testing of colorectal tumors for Lynch syndrome among US cancer programs and follow-up of abnormal results. J Clin Oncol ; 30 : — Burt RW. Who should have genetic testing for the Lynch syndrome?

Ann Intern Med ; : — Molecular tumor testing for Lynch syndrome in patients with colorectal cancer. J Natl Compr Canc Netw ; 11 : — Population-based molecular screening for Lynch syndrome: implications for personalized medicine. J Clin Oncol ; 31 : — Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study. Br J Cancer ; : — Genomic profiling of small-bowel adenocarcinoma. JAMA Oncol ; 3 : — Adenocarcinoma of the small bowel: presentation, prognostic factors, and outcome of patients.

Cancer ; : — A single-institution experience with cases of small bowel adenocarcinoma. Am J Surg ; : — Adenocarcinoma of the small bowel: review of the National Cancer Data Base, Cancer ; 86 : — A population-based comparison of adenocarcinoma of the large and small intestine: insights into a rare disease.

Ann Surg Oncol ; 19 : — Most small bowel cancers are revealed by a complication. Einstein Sao Paulo ; 13 : — Uncommon cancers of the small intestine, appendix and colon: an analysis of SEER , and current diagnosis and therapy. Int J Oncol ; 33 : — Imaging of small bowel disease: comparison of capsule endoscopy, standard endoscopy, barium examination, and CT. Radiographics ; 25 : — Sonography of the small intestine. World J Gastroenterol ; 15 : — Double-balloon enteroscopy in small bowel diseases: eight years single-center experience in China.

Medicine Baltimore ; 95 : e Diagnostic and therapeutic impact of double-balloon enteroscopy DBE in a series of patients with suspected small bowel diseases. Dig Liver Dis ; 39 : — Role of double-balloon endoscopy in the diagnosis of small-bowel tumors: the first Japanese multicenter study. Gastrointest Endosc ; 70 : — Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine. World J Gastroenterol ; 11 : — Increased diagnostic yield of small bowel tumors with capsule endoscopy.

Cancer ; : 22 — Diagnosis and outcome of small bowel tumors found by capsule endoscopy: a three-center Australian experience. Capsule endoscopy in small bowel tumors: a multicenter Korean study. J Gastroenterol Hepatol ; 25 : — Small-bowel diseases: prospective evaluation of multi-detector row helical CT enteroclysis in consecutive patients. Radiology ; : — Helical CT-enteroclysis in the detection of small-bowel tumours: a meta-analysis.

Eur Radiol ; 23 : — Magnetic resonance enterography in the evaluation of the small bowel. Semin Roentgenol ; 44 : — Magnetic resonance imaging of small bowel neoplasms. Cancer Imaging ; 13 : 92 — Diagnosis of small-bowel diseases: prospective comparison of multi-detector row CT enterography with MR enterography.

Br J Radiol ; 85 : — The characteristics and outcomes of small bowel adenocarcinoma: a multicentre retrospective observational study. Treatment and survival of small-bowel adenocarcinoma in the United States: a comparison with colon cancer. Dis Colon Rectum ; 59 : — Prognostic value of lymph node evaluation in small bowel adenocarcinoma: analysis of the surveillance, epidemiology, and end results database. Prognostic relevance of lymph node ratio and total lymph node count for small bowel adenocarcinoma.

Surgery ; : — Patients with adenocarcinoma of the small intestine with 9 or more regional lymph nodes retrieved have a higher rate of positive lymph nodes and improved survival. J Gastrointest Surg ; 20 : — A new metastatic lymph node classification-based survival predicting model in patients with small bowel adenocarcinoma: A derivation and validation study.

EBioMedicine ; 32 : — Clinicopathological features, surgical treatments, and survival outcomes of patients with small bowel adenocarcinoma. Medicine Baltimore ; 96 : e Limited resection of the duodenum for nonampullary duodenal tumors, with review of the literature. Am Surg ; 82 : — J Gastrointest Surg ; 16 : — Does the extent of resection impact survival for duodenal adenocarcinoma?

Analysis of 1, cases. Ann Surg Oncol ; 22 : — Raghav K , Overman MJ. Small bowel adenocarcinomas--existing evidence and evolving paradigms. Nat Rev Clin Oncol ; 10 : — National Library of Medicine. Accessed January 9, Efficacy of adjuvant chemotherapy for small bowel adenocarcinoma: a propensity score-matched analysis. Adjuvant concurrent chemoradiation for node-positive adenocarcinoma of the duodenum.

Arch Surg ; : — Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy. Evaluation of prognostic factors and adjuvant chemotherapy in patients with small bowel adenocarcinoma who underwent curative resection. Clin Colorectal Cancer ; 16 : — Meta-analysis of postoperative adjuvant therapy for small bowel adenocarcinoma.

PLoS One ; 13 : e Role of adjuvant chemoradiotherapy for duodenal cancer: a single center experience. Am J Clin Oncol ; 35 : — Is there a role for adjuvant therapy in resected adenocarcinoma of the small intestine? Acta Oncol ; 49 : — Pediatric Supportive Care. Rare Cancers of Childhood Treatment. Childhood Cancer Genomics. Study Findings. Metastatic Cancer Research. Intramural Research. Extramural Research. Cancer Research Workforce. Partners in Cancer Research. What Are Cancer Research Studies.

Research Studies. Get Involved. Cancer Biology Research. Cancer Genomics Research. Research on Causes of Cancer. Cancer Prevention Research. Cancer Treatment Research. Cancer Health Disparities. Childhood Cancers Research. Global Cancer Research. Cancer Research Infrastructure. Clinical Trials. Frederick National Laboratory for Cancer Research. Bioinformatics, Big Data, and Cancer. Annual Report to the Nation. Research Advances by Cancer Type. Stories of Discovery.

Milestones in Cancer Research and Discovery. Biomedical Citizen Science. Director's Message. Budget Proposal. Stories of Cancer Research. Driving Discovery. Highlighted Scientific Opportunities. Research Grants. Research Funding Opportunities. Cloyd et al[ 49 ] recently utilized the surveilance, epidemiology and end results database to retrospectively compare the outcomes of radical resection defined as a resection of the primary duodenal tumor en bloc with an adjacent organ, as is performed in PD vs SR across a population-based cohort of patients with DA.

Although PD may be required for technical reasons in some situations, the study suggests that SR is an appropriate strategy as long as negative margins can be obtained[ 49 ]. Outcomes of surgery for duodenal adenocarcinoma based on type of surgery.

Used with permission: Cloyd et al[ 49 ]. Regardless of the approach, an R0 resection remains the most important goal for surgery with curative attempt. Margin status directly impacts outcomes. The importance of an adequate lymphadenectomy cannot be underscored. Sarela et al[ 51 ] were among the first to report improved prognostic abilities of the N staging system with higher number of lymph nodes retrieved. In fact, a greater lymph node retrieval has independently been associated with improved survival for patients with DA[ 2 , 31 , 49 ].

Although the American Joint Committee on Cancer has recommended a minimum pathologic evaluation of 6 lymph nodes, several authors have questioned whether this minimum number should be raised[ 50 , 52 ]. Intuitively, one might expect operations that enable a better lymphadenectomy, such as a classic PD vs a pylorus-preserving PD or PD vs SR, would therefore be associated with improved survival. However, this has not been found to be the case, either in randomized controlled trials[ 53 ] or population-based analyses[ 49 ].

Although the reasons behind why greater lymph node retrieval is associated with improved survival may be complex and multifactorial, it is likely primarily secondary to improved stage stratification and prognostication. Of the remainder, some will require palliation. Operative interventions for gastroduodenal obstruction may include gastrojejunostomy or duodenojejunostomy; either may be constructed in a roux-en-y or loop fashion.

Minimally invasive approaches are possible in the correct context. Surgery for biliary obstruction typically involves a roux-en-y hepaticojejunostomy. A year prospective study from the United Kingdom examining surgery for DA found that of the patients included in the study, underwent surgery with curative intention and 28 underwent surgery for palliation. Of those who received palliation, 15 had a gastrojejunostomy, 9 had a double bypass and 4 underwent an exploratory laparotomy without further intervention.

Median survival in the palliative surgery group was 8 mo. Not surprisingly, those who undergo palliative surgery are more likely to have a larger tumor, greater degree of invasiveness, as well as regional and distant metastases[ 55 ].

For patients who are not already undergoing surgical exploration and require palliation for enteral or biliary obstruction, endoscopically placed duodenal and biliary stents, when technically feasible, are preferable to avoid laparotomy given the limited prognosis. Although a comprehensive discussion is outside the scope of this review article, pancreas-preserving total duodenectomy PPTD has emerged as an alternative to PD or SR for patients with benign or pre-malignant conditions of the duodenum, most commonly in the setting of FAP.

After total proctocolectomy, upper gastrointestinal cancers are the most common cause of death in patients with FAP[ 56 ]. Intense screening programs utilizing duodenoscopy with endoscopic polypectomy have proven effective in reducing the incidence of DA in this high risk population[ 57 ].

In patients with diffuse polyposis or Spigelman stage IV disease, however, prophylactic duodenectomy may be indicated[ 56 , 58 , 59 ]. Several techniques of PPTD have been described[ 60 - 63 ] including minimally invasive options[ 64 ]. Despite the advantages of organ preservation, short term morbidity and mortality rates remain high[ 65 ]. It is important to note that invasive carcinoma in FAP patients should be treated similarly to sporadic DA with either PD or SR as described above in order to ensure adequate margins and lymphadenectomy.

Pylorus-preserving PD should be avoided in patients with FAP as the residual duodenal bulb remains at risk for new polyp and carcinoma formation[ 66 ]. Unfortunately, little data is currently available to inform the choice of adjuvant chemotherapy following complete surgical resection. The ESPAC-3 trial was a phase 3, multi-institutional, randomized controlled trial comparing observation vs adjuvant fluorouracil vs adjuvant gemcitabine in patients with periampullary cancers ampullary, bile duct, duodenal or other who underwent PD with R0 or R1 resection status.

Given its rarity, most therapeutic studies have traditionally combined DA with either other periampullary cancers or small bowel adenocarcinomas. For this reason, chemotherapeutic regimens are not standardized, but increasingly DA is being treated similar to colorectal adenocarcinoma with oxaliplatin-based chemotherapy.

Given the tendency of this disease to recur systemically, the role of adjuvant chemotherapy warrants further investigation. Current practice at many centers is to treat patients with high risk features e. Definitive, or palliative, chemotherapy should be offered to all eligible patients with metastatic or unresectable disease.

Median time to progression was 11 mo with median overall survival 20 mo[ 68 , 69 ]. Patients should also be considered for clinical trials as appropriate. The role of adjuvant radiotherapy in the treatment of DA is not well defined. Other retrospective series have shown similar results with improvements in locoregional control but not OS[ 72 ]. Nevertheless, this approach targeting improved locoregional control may make CRT particularly useful in patients with lymph node metastases.

In a study of patients at a single institution who underwent curative resection for DA, adjuvant CRT in patients with a higher prevalence of regional lymph node metastases was associated with a similar overall survival to that of a group of patients with limited or no nodal metastases who did not receive adjuvant therapy[ 50 ]. Surgery for DA can be associated with significant morbidity and mortality.

The impact of the type of resection on postoperative outcomes is controversial. Tocchi et al[ 13 ] reviewed their series of 47 patients undergoing surgery for DA and found SR to be associated with less postoperative morbidity, mortality and length of hospital stay.

Other studies have failed to find an effect of surgery type on complication rates[ 43 , 48 ]. The occurrence of a postoperative complication may be associated with worse long term survival[ 73 ]. DA represents an aggressive cancer but in patients with resectable disease, long term outcomes are better than with other periampullary malignancies. A prospective cohort study of patients from six United Kingdom hepatopancreaticobiliary centers undergoing curative intent surgery for DA from found 1-, 3- and 5-year OS rates of Median disease-free survival was 53 mo[ 48 ].

A recent population-based study suggested worse outcomes with 5-year OS rates of Patients with metastatic or unresectable disease have median survival that ranges from mo[ 68 , 69 , 74 , 75 ].

Stage-based disease free A and overall B survival for patients undergoing surgery for duodenal cancer based on seer data. Lymph node metastasis remains one of the most important prognostic determinants[ 41 , 43 , 44 , 49 - 51 , 74 , 76 - 78 ]. In the largest single institution series of patients who underwent PD for DA, the presence of lymph node metastases was the only independent predictor of decreased survival in multivariate analysis.

Another study calculated 3-year survival for node negative patients to be LNR, the ratio of positive LNs to number of LNs excised, may be even a more accurate predictor of prognosis[ 2 , 31 , 49 ]. Because of the nonspecific symptoms it presents with and the difficulty in confirming a diagnosis, patients may often present with advanced disease.

Nonetheless, aggressive surgical resection, when possible, affords the best chance at survival. The decision of whether to perform pancreaticoduodenectomy vs segmental resection depends on the location of the primary tumor as both are acceptable options as long as negative margins can be safely obtained.

Lymph node positivity is one of the most important prognostic indicators and a wide lymphadenectomy should be routinely performed. Although data are limited guiding adjuvant therapy options, oxaliplatin-based chemotherapy is typically offered to high risk patients, such as those with positive lymph nodes.

In some series, adjuvant radiation is associated with improved local control but no difference in overall survival. Previous research on DA has been limited by small sample sizes and single institutional design. Further research would benefit from multi-institutional trials that do not combined DA with other periampullary or small bowel malignancies. Conflict-of-interest statement: The authors report no relevant conflicts of interest. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers.

Peer-review started: August 30, First decision: October 27, Article in press: December 15, National Center for Biotechnology Information , U. World J Gastrointest Surg. Published online Mar Author information Article notes Copyright and License information Disclaimer. Published by Baishideng Publishing Group Inc.

All rights reserved. This article has been cited by other articles in PMC. Abstract Duodenal adenocarcinoma is a rare but aggressive malignancy. Tohoku Journal of Experimental Medicine. Overman MJ. Recent advances in the management of adenocarcinoma of the small intestine. Gastrointest Cancer Res. J Natl Cancer Inst. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C J Clin Oncol.

Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer MRC FOCUS : a randomised controlled trial. Chemotherapy with 5-fluorouracil and a platinum compound improves outcomes in metastatic small bowel adenocarcinoma.

Phase II study of capecitabine and oxaliplatin for advanced adenocarcinoma of the small bowel and ampulla of vater. Journal of Clinical Oncology. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer CROSS : long-term results of a randomised controlled trial.

Lancet Oncol. Outcome after surgical resection for duodenal adenocarcinoma in the UK. The British journal of surgery. Int J Surg. Cea Compton.

New York: Springer; DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease.

Quantifying heterogeneity in a meta-analysis. Stat Med. Accessed 19 Jul What prognostic factors are important in duodenal adenocarcinoma? Arch Surg. Superior prognostic importance of perineural invasion vs. Clinical analysis of primary duodenal adenocarcinoma: an year experience. Journal of Gastroenterology and Hepatology.

BioMed Research International. Survival predictors of patients with primary duodenal adenocarcinoma. Int Surg. Clinicopathological analysis and survival outcome of duodenal adenocarcinoma. Kaohsiung Journal of Medical Sciences. Prognostic factors for primary duodenal adenocarcinoma.

World Journal of Surgery. Long-term outcomes in patients with duodenal adenocarcinoma. ANZ journal of surgery. Adenocarcinoma of the third and fourth portions of the duodenum: results of surgical treatment. Archives of Surgery. Postoperative morbidity is an additional prognostic factor after potentially curative pancreaticoduodenectomy for primary duodenal adenocarcinoma.

Langenbecks Arch Surg. Number of involved lymph nodes is important in the prediction of prognosis for primary duodenal adenocarcinoma.

Journal of the Chinese Medical Association. Duodenal adenocarcinoma: clinicopathologic analysis and implications for treatment. Does the extent of resection impact survival for duodenal adenocarcinoma? Analysis of 1, cases. Should all patients with duodenal adenocarcinoma be considered for aggressive surgical resection?

Role of adjuvant chemoradiotherapy for duodenal cancer: a single center experience. Am J Clin Oncol. Adenocarcinoma of the duodenum: importance of accurate lymph node staging and similarity in outcome to gastric cancer. Radical surgical management of periampullary duodenal adenocarcinoma: a single institution experience.

Journal of the Pakistan Medical Association. Non-ampullary duodenal adenocarcinoma: factors important for relapse and survival. Journal of Surgical Oncology. Adjuvant concurrent chemoradiation for node-positive adenocarcinoma of the duodenum. Adjuvant chemotherapy versus chemoradiotherapy in the management of patients with surgically resected duodenal adenocarcinoma: a propensity score-matched analysis of a nationwide clinical oncology database.

Intestinal-type and pancreatobiliary-type adenocarcinomas: how does ampullary carcinoma differ from other periampullary malignancies?

Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater. Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled trial.