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Clinical and Translational... Mar 2020The diagnostic value of different noninvasive diagnostic modalities and the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) reliability of duodenal...
OBJECTIVES
The diagnostic value of different noninvasive diagnostic modalities and the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) reliability of duodenal gastrointestinal stromal tumors (GISTs) are ambiguous in the present studies.
METHODS
Patients with a histopathological diagnosis of the primary duodenal GISTs between the years 2008 and 2018 were analyzed. Data on the treatment and clinicopathological features were recorded. Furthermore, the computed tomography (CT)/magnetic resonance imaging (MRI), EUS, and EUS-FNA results were collected and compared.
RESULTS
A total of 142 patients were enrolled into the study. In all patients, the most common symptom was gastrointestinal bleeding (44.4%), followed by abdominal pain and bloating (27.5%). Duodenal GISTs were mostly located in the second duodenal portion (52.1%), followed by the first portion (19.0%). EUS had significantly higher sensitivity and positive predictive values than CT or MRI (P = 0.047 and P = 0.005, respectively). The EUS-FNA sensitivity of duodenal GISTs was also significantly higher than the conventional endoscopic biopsy (73.3% vs 33.3%, P = 0.006). A total of 131 patients underwent surgery, including limited resection or pancreaticoduodenectomy. The tumor size and postoperative complication rates were higher in patients who underwent pancreaticoduodenectomy (P = 0.001 and P < 0.001, respectively).
DISCUSSION
The diagnostic value of EUS is significantly higher than that of CT and MRI for duodenal GISTs. The EUS-FNA can provide a histological diagnosis of duodenal GISTs in most cases.
Topics: Adult; Aged; Diagnostic Errors; Duodenal Neoplasms; Duodenum; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endoscopy; Gastrointestinal Stromal Tumors; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pancreaticoduodenectomy; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32352716
DOI: 10.14309/ctg.0000000000000156 -
JAMA Oncology Nov 2017Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other... (Comparative Study)
Comparative Study
IMPORTANCE
Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking.
OBJECTIVE
To perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations.
DESIGN, SETTING, AND PARTICIPANTS
Prospective analysis was performed of clinical samples from patients with SBA (n = 317), colorectal cancer (n = 6353), and gastric carcinoma (n = 889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions.
RESULTS
Of the 7559 patients included in analysis, 4138 (54.7%) were male; the median age was 56 (range, 12-101) years. The frequency of genomic alterations seen in SBA demonstrated distinct differences in comparison with either colorectal cancer (APC: 26.8% [85 of 317] vs 75.9% [4823 of 6353], P < .001; and CDKN2A: 14.5% [46 of 317] vs 2.6% [165 of 6353], P < .001) or gastric carcinoma (KRAS: 53.6% [170 of 317] vs 14.2% [126 of 889], P < .001; APC: 26.8% [85 of 317] vs 7.8% [69 of 889], P < .001; and SMAD4: 17.4% [55 of 317] vs 5.2% [46 of 889], P < .001). BRAF was mutated in 7.6% (484 of 6353) of colorectal cancer and 9.1% (29 of 317) of SBA samples, but V600E mutations were much less common in SBA, representing only 10.3% (3 of 29) of BRAF-mutated cases. The ERBB2/HER2 point mutations (8.2% [26 of 317]), microsatellite instability (7.6% [13 of 170]), and high tumor mutational burden (9.5% [30 of 317]) were all enriched in SBA. Significant differences were noted in the molecular profile of unspecified SBA compared with duodenal adenocarcinoma, as well as in inflammatory bowel disease-associated SBAs. Targetable alterations in several additional genes, including PIK3CA and MEK1, and receptor tyrosine kinase fusions, were also identified in all 3 series.
CONCLUSIONS AND RELEVANCE
This study presents to our knowledge the first large-scale genomic comparison of SBA with colorectal cancer and gastric carcinoma. The distinct genomic differences establish SBA as a molecularly unique intestinal cancer. In addition, genomic profiling can identify potentially targetable genomic alterations in the majority of SBA cases (91%), and the higher incidence of microsatellite instability and tumor mutational burden in SBA suggests a potential role for immunotherapy.
Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Colorectal Neoplasms; Duodenal Neoplasms; Female; Gene Expression Profiling; Genetic Predisposition to Disease; Humans; Intestinal Neoplasms; Intestine, Small; Male; Microsatellite Instability; Middle Aged; Mutation; Phenotype; Precision Medicine; Predictive Value of Tests; Prospective Studies; Stomach Neoplasms; Transcriptome; Young Adult
PubMed: 28617917
DOI: 10.1001/jamaoncol.2017.1051 -
Scientific Reports May 2021Patient-derived xenograft (PDX) and their xenograft-derived organoid (XDO) models that recapitulate the genotypic and phenotypic landscape of patient cancers could help...
Patient-derived xenograft (PDX) and their xenograft-derived organoid (XDO) models that recapitulate the genotypic and phenotypic landscape of patient cancers could help to advance research and lead to improved clinical management. PDX models were established from 276 pancreato-duodenal and biliary cancer resections. Initial, passage 0 (P0) engraftment rates were 59% (118/199) for pancreatic, 86% (25/29) for duodenal, and 35% (17/48) for biliary ductal tumors. Pancreatic ductal adenocarcinoma (PDAC), had a P0 engraftment rate of 62% (105/169). KRAS mutant and wild-type PDAC models were molecularly profiled, and XDO models were generated to perform initial drug response evaluations. Subsets of PDAC PDX models showed global copy number variants and gene expression profiles that were retained with serial passaging, and they showed a spectrum of somatic mutations represented in patient tumors. PDAC XDO models were established, with a success rate of 71% (10/14). Pathway activation of KRAS-MAPK in PDXs was independent of KRAS mutational status. Four wild-type KRAS models were characterized by one with EGFR (L747-P753 del), two with BRAF alterations (N486_P490del or V600E), and one with triple negative KRAS/EGFR/BRAF. Model OCIP256, characterized by BRAF (N486-P490 del), had activated phospho-ERK. A combination treatment of a pan-RAF inhibitor (LY3009120) and a MEK inhibitor (trametinib) effectively suppressed phospho-ERK and inhibited growth of OCIP256 XDO and PDX models. PDAC/duodenal adenocarcinoma have high success rates forming PDX/organoid and retaining their phenotypic and genotypic features. These models may be effective tools to evaluate novel drug combination therapies.
Topics: Animals; Antineoplastic Agents; Biliary Tract Neoplasms; Cell Proliferation; Dose-Response Relationship, Drug; Duodenal Neoplasms; Humans; Mice, Inbred NOD; Mice, SCID; Mutation; Organoids; Pancreatic Neoplasms; Xenograft Model Antitumor Assays; Mice
PubMed: 34011980
DOI: 10.1038/s41598-021-90049-1 -
The British Journal of Surgery Jun 2017Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in improving survival of patients with periampullary cancers, with variable results. The aim of this meta-analysis was to determine the survival benefit of adjuvant therapy for periampullary cancers.
METHODS
A systematic review was undertaken of literature published between 1 January 2000 and 31 December 2015 to elicit and analyse the pooled overall survival associated with the use of either adjuvant chemotherapy or chemoradiotherapy versus observation in the treatment of surgically resected periampullary cancer. Included articles were also screened for information regarding stage, prognostic factors and toxicity-related events.
RESULTS
A total of 704 titles were screened, of which 93 full-text articles were retrieved. Fourteen full-text articles were included in the study, six of which were RCTs. A total of 1671 patients (904 in the control group and 767 who received adjuvant therapy) were included. The median 5-year overall survival rate was 37·5 per cent in the control group, compared with 40·0 per cent in the adjuvant group (hazard ratio 1·08, 95 per cent c.i. 0·91 to 1·28; P = 0·067). In 32·2 per cent of patients who had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were noted. Advanced T category was associated worse survival (regression coefficient -0·14, P = 0·040), whereas nodal status and grade of differentiation were not.
CONCLUSION
This systematic review found no associated survival benefit for adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary cancer.
Topics: Adenocarcinoma; Ampulla of Vater; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Common Bile Duct Neoplasms; Duodenal Neoplasms; Humans; Survival Rate
PubMed: 28518410
DOI: 10.1002/bjs.10563 -
Gastrointestinal Endoscopy Feb 2021Almost all patients with familial adenomatous polyposis (FAP) develop duodenal adenomas, with a 4% to 18% risk of progression into duodenal cancer. Prophylactic...
BACKGROUND AND AIMS
Almost all patients with familial adenomatous polyposis (FAP) develop duodenal adenomas, with a 4% to 18% risk of progression into duodenal cancer. Prophylactic endoscopic resection of duodenal adenomas may prevent cancer and is considered safer than surgical alternatives; however, data are limited. Therefore, the aim of this study was to assess safety and effectiveness of endoscopic duodenal interventions in patients with FAP.
METHODS
We performed a historical cohort study including patients with FAP who underwent an endoscopic duodenal intervention between 2002 and 2018. Safety was defined as adverse event rate per intervention and effectiveness as duodenal surgery-free and duodenal cancer-free survival. Change in Spigelman stage was assessed as a secondary outcome.
RESULTS
In 68 endoscopy sessions, 139 duodenal polypectomies were performed in 49 patients (20 men; median age, 43). Twenty-nine patients (14 men; median age, 49) underwent a papillectomy. After polypectomy, 9 (13%) bleedings and 1 (2%) perforation occurred, all managed endoscopically. Six (21%) bleedings (endoscopically managed), 4 (14%) cases of pancreatitis, and 1 (3%) perforation (conservatively treated) occurred after papillectomy. Duodenal surgery-free survival was 74% at 89 months after polypectomy and 71% at 71 months after papillectomy; no duodenal cancers were observed. After a median of 18 months (interquartile range, 10-40; range, 3-121) after polypectomy, Spigelman stages were significantly lower (P < .01).
CONCLUSIONS
In our FAP patients, prophylactic duodenal polypectomies were relatively safe. Papillectomies showed substantial adverse events, suggesting its benefits and risk should be carefully weighted. Both were effective, however, because surgical interventions were limited and none developed duodenal cancer.
Topics: Adenoma; Adenomatous Polyposis Coli; Adult; Cohort Studies; Duodenal Neoplasms; Endoscopy; Humans; Male; Middle Aged
PubMed: 32535190
DOI: 10.1016/j.gie.2020.05.065 -
Biomedical Papers of the Medical... Sep 2022The aim of this study was to evaluate symptoms, diagnostic methods, short- and long-term outcomes of surgical treatment in patients with duodenal adenocarcinoma. (Observational Study)
Observational Study
BACKGROUND
The aim of this study was to evaluate symptoms, diagnostic methods, short- and long-term outcomes of surgical treatment in patients with duodenal adenocarcinoma.
PATIENTS AND METHODS
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).
RESULTS
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.
CONCLUSION
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.
Topics: Adenocarcinoma; Ampulla of Vater; Common Bile Duct Neoplasms; Duodenal Neoplasms; Humans; Neoplasm Staging; Pancreatic Neoplasms; Prognosis; Retrospective Studies
PubMed: 34012147
DOI: 10.5507/bp.2021.028 -
Gastroenterology Sep 2023Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk...
BACKGROUND & AIMS
Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we assessed the risk of specific primary and secondary cancers among patients with FAP compared with matched controls.
METHODS
All known patients with FAP up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with 4 unique controls matched by birth year, sex, and postal code. The risk of overall cancers, specific cancer types, and risk of a second primary cancer was assessed and compared with controls.
RESULTS
The analysis included 565 patients with FAP and 1890 controls. The overall risk of cancer was significantly higher for patients with FAP than for controls (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.28-5.17; P < .001). The increased risk was mainly due to CRC (HR, 4.61; 95% CI, 2.58-8.22; P < .001), pancreatic cancer (HR, 6.45; 95% CI, 2.02-20.64; P = .002), and duodenal/small-bowel cancer (HR, 14.49; 95% CI, 1.76-119.47; P = .013), whereas no significant difference was observed for gastric cancer (HR, 3.29; 95% CI, 0.53-20.23; P = .20). Furthermore, the risk of a second primary cancer was significantly higher for patients with FAP (HR, 1.89; 95% CI, 1.02-3.50; P = .042). Between 1980 and 2020, the risk of cancer among patients with FAP decreased by ∼50%.
CONCLUSIONS
Despite an absolute reduction in the risk of developing cancer among patients with FAP, the risk remained significantly higher than for the background population due to colorectal, pancreatic, and duodenal/small-bowel cancers.
Topics: Humans; Cohort Studies; Neoplasms, Second Primary; Adenomatous Polyposis Coli; Colorectal Neoplasms; Duodenal Neoplasms; Denmark
PubMed: 37201686
DOI: 10.1053/j.gastro.2023.05.010 -
Journal of Gastrointestinal Surgery :... Feb 2015Benign duodenal and periampullary tumors are uncommon lesions requiring careful attention to their complex anatomic relationships with the major and minor papillae as...
INTRODUCTION
Benign duodenal and periampullary tumors are uncommon lesions requiring careful attention to their complex anatomic relationships with the major and minor papillae as well as the gastric outlet during surgical intervention. While endoscopy is less morbid than open resection, many lesions are not amenable to endoscopic removal. Robotic surgery offers technical advantages above traditional laparoscopy, and we demonstrate the safety and feasibility of this approach for a variety of duodenal lesions.
METHODS
We performed a retrospective review of all robotic duodenal resections between April 2010 and December 2013 from two institutions. Demographic, clinicopathologic, and operative details were recorded with special attention to the post-operative course.
RESULTS
Twenty-six patients underwent robotic duodenal resection for a variety of diagnoses. The majority (88 %) were symptomatic at presentation. Nine patients underwent transduodenal ampullectomy, seven patients underwent duodenal resection, six patients underwent transduodenal resection of a mass, and four patients underwent segmental duodenal resection. Median operative time was 4 h with a median estimated blood loss of 50 cm(3) and no conversions to an open operation. The rate of major Clavien-Dindo grades 3-4 complications was 15 % at post-operative days 30 and 90 without mortality. Final pathology demonstrated a median tumor size of 2.9 cm with a final histologic diagnoses of adenoma (n = 13), neuroendocrine tumor (n = 6), gastrointestinal stromal tumor (GIST) (n = 2), lipoma (n = 2), Brunner's gland hamartoma (n = 1), leiomyoma (n = 1), and gangliocytic paraganglioma (n = 1).
CONCLUSION
Robotic duodenal resection is safe and feasible for benign and premalignant duodenal tumors not amenable to endoscopic resection.
Topics: Adenoma; Adult; Aged; Aged, 80 and over; Blood Loss, Surgical; Duodenal Neoplasms; Female; Gastrointestinal Stromal Tumors; Hamartoma; Humans; Laparoscopy; Leiomyoma; Lipoma; Male; Middle Aged; Neuroendocrine Tumors; Operative Time; Paraganglioma; Retrospective Studies; Robotic Surgical Procedures
PubMed: 25348238
DOI: 10.1007/s11605-014-2668-0 -
Digestive Diseases (Basel, Switzerland) 2019The increasing incidence of duodenal neoplasm has underlined different methods of resection depending on the clinical presentation, endoscopic features and...
BACKGROUND
The increasing incidence of duodenal neoplasm has underlined different methods of resection depending on the clinical presentation, endoscopic features and histopathology. In this comprehensive review, we systematically describe the current knowledge concerning the diagnosis and management of duodenal adenomas (DAs) and discuss data considering all possible therapeutic approaches.
SUMMARY
Among a variety of duodenal lesions, including neuroendocrine tumors and gastrointestinal stromal tumors, DAs present precancerous lesions of the duodenal papilla or non-ampullary region necessitating removal. DAs can occur sporadically (SDA) as rare lesions or relatively common in polyposis syndromes. The endoscopic resections of DA are associated with an increased degree of complexity due to distinctive anatomical properties of the duodenal wall, luminal diameter and the presence of ampulla with pancreatic and biliary drainage. The endoscopic techniques including cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), and argon plasma coagulation ablation are suggested to be less invasive than surgical treatment, associated with shorter hospital stay and lower cost. According to the current clinical practice, surgery has been accepted as standard therapeutic approach in familial adenomatous polyposis patients with severe polyposis or DA not amenable to endoscopic resection. Key Messages: The strategy for endoscopic resection of DAs depends on the lesion size, morphology, location, and histopathology findings. Small adenomas are most frequently diagnosed and removed by standard CSP techniques, while large laterally spreading lesions and ampullary adenoma are referred for EMR or endoscopic papillectomy respectively. Screening colonoscopy is indicated in patients with SDA. Additional studies for new endoscopic strategies and techniques for curative therapy of DAs are needed to refine future management decisions. Complete resection of DA is considered curative, but nevertheless, long-term endoscopic follow-up is still required to detect and treat any recurrent arising lesions.
Topics: Adenoma; Adenomatous Polyposis Coli; Colonoscopy; Duodenal Neoplasms; Humans; Retrospective Studies
PubMed: 30921797
DOI: 10.1159/000496697 -
Abdominal Radiology (New York) Oct 2022Adequate TNM-staging is important to determine prognosis and treatment planning of duodenal adenocarcinoma. Although current guidelines advise contrast-enhanced CT...
PURPOSE
Adequate TNM-staging is important to determine prognosis and treatment planning of duodenal adenocarcinoma. Although current guidelines advise contrast-enhanced CT (CECT) for staging of duodenal adenocarcinoma, literature about diagnostic tests is sparse.
METHODS
In this retrospective single-center cohort study, we analyzed the real life performance of routine CECT for TNM-staging and the assessment of resectability of duodenal adenocarcinoma. Intraoperative findings and pathological staging served as reference standard for resectability, T-, and N-staging. Biopsies, FDG-PET-CT, and follow-up were used as the reference standard for M-staging.
RESULTS
Fifty-two consecutive patients with duodenal adenocarcinoma were included, 26 patients underwent resection. Half of the tumors were isodense to normal duodenum on CECT. The tumor was initially missed in 7/52 patients (13%) on CECT. The correct T-stage was assigned with CECT in 14/26 patients (54%), N-stage in 11/26 (42%), and the M-stage in 42/52 (81%). T-stage was underestimated in (27%). The sensitivity for detecting lymph node metastases was only 24%, specificity was 78%. Seventeen percent of patients had indeterminate liver or lung lesions on CECT. Surgery with curative intent was started in 32 patients, but six patients (19%) could not be resected due to unexpected local invasion or metastases.
CONCLUSION
Radiologists and clinicians have to be aware that routine CECT is insufficient for staging and determining resectability in patients with duodenal adenocarcinoma. CECT underestimates T-stage and N-stage, and M-stage is often unclear, resulting in futile surgery in 19% of patients. Alternative strategies are required to improve staging of duodenal adenocarcinoma. We propose to combine multiphase hypotonic duodenography CT with MRI.
Topics: Adenocarcinoma; Cohort Studies; Duodenal Neoplasms; Fluorodeoxyglucose F18; Humans; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Sensitivity and Specificity
PubMed: 35864264
DOI: 10.1007/s00261-022-03589-z