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Clinical Gastroenterology and... Feb 2022The tumor microbiome of patients with pancreas ductal adenocarcinoma (PDAC) includes bacteria normally present in the upper gastrointestinal tract. If the predominant...
BACKGROUND & AIMS
The tumor microbiome of patients with pancreas ductal adenocarcinoma (PDAC) includes bacteria normally present in the upper gastrointestinal tract. If the predominant source of intratumoral bacteria in patients with PDAC is retrograde migration from the duodenum, duodenal fluid could be a representative biospecimen for determining microbiome profiles of patients with PDAC or at risk of developing PDAC.
METHODS
We performed a case-control study comparing bacterial and fungal (16S and 18S rRNA) profiles of secretin-stimulated duodenal fluid collections from 308 patients undergoing duodenal endoscopy including 134 normal pancreas control subjects, 98 patients with pancreatic cyst(s) and 74 patients with PDAC.
RESULTS
Alterations in duodenal fluid microbiomes with diminished alpha diversity were significantly associated with age >70 and proton pump inhibitor use. Patients with PDAC had significantly decreased duodenal microbial alpha diversity compared with age-matched control subjects with normal pancreata and those with pancreatic cyst(s). There was evidence of enrichment of Bifidobacterium genera in the duodenal fluid of patients with PDAC compared with control subjects and those with pancreatic cyst(s). There were also enrichment of duodenal fluid Fusobacteria and Rothia bacteria among patients with PDAC with short-term survival. Duodenal fluid microbiome profiles were not significantly different between control subjects and patients with pancreatic cyst(s).
CONCLUSION
Patients with PDAC have alterations in their duodenal fluid microbiome profiles compared with patients with pancreatic cysts and those with normal pancreata. ClinicalTrials.gov, Number: NCT02000089.
Topics: Carcinoma, Pancreatic Ductal; Case-Control Studies; Humans; Microbiota; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 33161160
DOI: 10.1016/j.cgh.2020.11.006 -
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 -
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 -
Journal of Gastrointestinal and Liver... Dec 2023Endoscopic ultrasound (EUS) guided biliary drainage (BD) is an accepted salvage procedure in patients with distal malignant biliary obstruction (DMBO) when endoscopic... (Review)
Review
Endoscopic ultrasound (EUS) guided biliary drainage (BD) is an accepted salvage procedure in patients with distal malignant biliary obstruction (DMBO) when endoscopic retrograde cholangiopancreatography (ERCP) is unsuccessful. The potential advantages of EUS-BD include gastric or duodenal biliary access, utilization of novel biliary stents and stent placement away from the area of stenosis, resulting in longer stent patency. These features make EUS-BD very appealing as a primary procedure for biliary drainage. There is a growing body of evidence supporting the utilization of EUS as a primary drainage procedure instead of ERCP, with comparable outcomes.
Topics: Humans; Endosonography; Pancreatic Neoplasms; Duodenum; Cholangiopancreatography, Endoscopic Retrograde; Stents; Drainage; Cholestasis; Ultrasonography, Interventional
PubMed: 38147611
DOI: 10.15403/jgld-4922 -
PloS One 2021More than half of patients with bile duct cancer (BDC) develop recurrence even after curative resection. Recurrent BDC has a poor prognosis, and no optimal treatment...
PURPOSE
More than half of patients with bile duct cancer (BDC) develop recurrence even after curative resection. Recurrent BDC has a poor prognosis, and no optimal treatment modality has been established. We therefore analyzed our experience on the survival outcomes of radiation therapy (RT) for recurrent extrahepatic bile duct cancer (EHBDC).
PATIENTS AND METHODS
We retrospectively analyzed the records of patients with recurrent EHBDC who underwent concurrent chemoradiation therapy (CCRT) or RT alone at our institution between January 2001 and June 2015. Freedom from locoregional progression (FFLP), progression-free survival (PFS), and overall survival (OS) were assessed, and univariate and multivariate analyses were performed to identify the prognostic factors.
RESULTS
A total of 76 patients were included in the analysis. The median OS was 16 months and the rates of 2-year FFLP, PFS, and OS were 61%, 25%, and 33%, respectively. Among the evaluable patients, the first site of failure was the locoregional area in 16 patients, distant metastasis in 27, and both sites in 8. On univariate analysis, disease-free interval (p = 0.012) and concurrent chemotherapy (p = 0.040) were found as significant prognostic factors for OS. One patient with CCRT developed a grade 3 hematologic toxicity, and two patients experienced late grade 3 toxicities including duodenal ulcer bleeding and obstruction.
CONCLUSIONS
RT for recurrent EHBDC showed favorable survival and local control with limited treatment-related toxicities. Considering that the most common pattern of failure was distant metastasis, further studies on the optimal scheme of chemotherapy and RT are warranted.
Topics: Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Chemoradiotherapy; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Risk Factors; Survival Analysis; Young Adult
PubMed: 34133471
DOI: 10.1371/journal.pone.0253285 -
Annals of Surgical Treatment and... May 2022We investigated the clinicopathological features and management for superficial nonampullary duodenal tumors (SNADTs). The safety and feasibility of laparoscopic...
PURPOSE
We investigated the clinicopathological features and management for superficial nonampullary duodenal tumors (SNADTs). The safety and feasibility of laparoscopic management, especially laparoscopic endoscopic cooperative surgery (LECS), were evaluated.
METHODS
A total of 59 patients with SNADTs who underwent operations from January 2009 to December 2018 at all 8 institutions of the Catholic Medical Center were identified in our comprehensive multi-institutional database. Clinicopathological and surgical data on the 4 anatomical regions of the duodenum were collected and compared. Characteristics of conventional laparoscopic procedure (laparoscopy-only) and LECS procedures were also compared.
RESULTS
There were significantly more asymptomatic patients with tumors in the first and second third and fourth duodenal regions. Gastrointestinal stromal tumors (GISTs), carcinoids, and ectopic pancreatic tumors were identified in 32, 12, and 5 cases, respectively. Forty-two patients (71.2%) underwent laparoscopy. Of patients undergoing laparoscopy, the LECS group exhibited significantly more endophytic features and smaller tumor sizes (P < 0.001 and P < 0.001, respectively). Although no significant difference in the wedge resection or postoperative complication rate was seen between the 2 groups (P = 0.096 and P = 0.227, respectively), the wedge resection rate was higher, and the complication rate lower, in the LECS group than the conventional laparoscopic surgery group.
CONCLUSION
Most of the SNADTs located in proximal duodenum were detected incidentally. GISTs were the most common diagnoses of SNADTs in all locations. In treating these tumors, laparoscopic resection is safe and feasible. Especially, LECS may be ideal for treating small endophytic tumors, minimizing over-resection and postoperative complications.
PubMed: 35611085
DOI: 10.4174/astr.2022.102.5.263 -
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 -
Radiology Case Reports Nov 2020Schwannomas are neurogenic tumors that arise from Schwann cells in the neural sheath. Gastrointestinal schwannomas occur most often in the stomach, followed by the colon...
Schwannomas are neurogenic tumors that arise from Schwann cells in the neural sheath. Gastrointestinal schwannomas occur most often in the stomach, followed by the colon and the rectum. Duodenal schwannomas are rare amongst mesenchymal tumors of the gastrointestinal tract and only a few cases have been reported up to the current date with an incidence of approximately 2%-6%. Duodenal Schwannomas do not have characteristic imaging features thereby cannot be easily differentiated from other submucosal and adjacent extraluminal neoplasms. We present a case of a 76-year old male patient that presented to our hospital with abdominal pain and was diagnosed after an upper gastrointestinal endoscopy with an ampullary duodenal neoplasm that proved to be a periampullary duodenal Schwannoma on histopathology. Duodenal Schwannomas although rare should be considered in the differential diagnosis of ampullary neoplasms.
PubMed: 32944106
DOI: 10.1016/j.radcr.2020.08.020 -
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