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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 -
Cancer Medicine Jul 2021Owing to its rarity and heterogeneity, the biological behavior and optimal therapeutic management of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) have not...
OBJECTIVE
Owing to its rarity and heterogeneity, the biological behavior and optimal therapeutic management of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) have not been established. Herein, we aimed to evaluate the clinicopathological characteristics and metastatic patterns of MiNEN.
METHODS
Continuous clinicopathological data of MiNEN patients treated at our hospital were retrospectively collected and analyzed.
RESULTS
This study had enrolled 169 patients since January 2010 to January 2020. Pathological components were assessed in 129 patients with MiNEN (76.3%), and a focal (non-)neuroendocrine component was observed in 40 patients (23.7%; <30% of the tumor). Among the enrolled patients, 80 underwent surgical removal of the primary tumor and lymph nodes (LNs), and 34 with distant metastasis underwent biopsy of both primary tumor and metastatic lesions. In patients with LN metastasis, 68.8% (55/80) exhibited a pure component of either neuroendocrine (NE) or adenocarcinoma/squamous carcinoma (AS) in metastatic LNs, while 20% (16/80) showed different components in different LNs, and only 11.2% (9/80) exhibited both NE and AS components in the same LN. In patients with distant metastases, 26.5% (9/34) possessed coexisting NE and AS components in the distant metastases, 70.6% (24/34) were regarded as a pure NE component, and 2.9% (1/34) were comprised of a pure AS component.
CONCLUSION
Lymph node and distant metastases exhibited distinct metastatic patterns in patients with MiNEN. The major pathological component in regional LNs may have influenced the proportion of the two components within the primary tumor, but distant metastases were dominated by the NE component.
Topics: Adenocarcinoma; Biliary Tract Neoplasms; Carcinoma, Squamous Cell; Colorectal Neoplasms; Digestive System Neoplasms; Duodenal Neoplasms; Esophageal Neoplasms; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Complex and Mixed; Neuroendocrine Tumors; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms
PubMed: 34109756
DOI: 10.1002/cam4.4031 -
BMJ Case Reports Dec 2018Imatinib is a specific tyrosine kinase inhibitor which has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukaemia and c-KIT...
Imatinib is a specific tyrosine kinase inhibitor which has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukaemia and c-KIT (CD117)-positive gastrointestinal stromal tumours. It has been associated with hepatotoxicity ranging from abnormal liver function tests to acute liver failure along with chronic hepatitis B reactivation. We report the case of a patient who was started on adjuvant treatment with imatinib following resection of a primary gastrointestinal stromal cell tumour of jejunum and developed severe hepatotoxicity. There was no history of risk factors for liver disease, and a search for the underlying causes of hepatotoxicity was unremarkable. Imatinib was stopped and she was treated with steroids which resulted in dramatic improvement of liver function tests. Liver biopsy in this case was not performed because liver function tests improved following discontinuation of imatinib and treatment with steroids. Repeat imaging did not reveal any evidence of tumour recurrence.
Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Chemotherapy, Adjuvant; Duodenal Neoplasms; Female; Gastrointestinal Stromal Tumors; Glucocorticoids; Humans; Imatinib Mesylate; Liver Function Tests; Methylprednisolone; Middle Aged; Protein Kinase Inhibitors; Treatment Outcome
PubMed: 30567202
DOI: 10.1136/bcr-2018-226740 -
Medicine Aug 2021To explore the diagnostic value of computed tomography (CT) imaging for duodenal lipoma and the potential clinical significance of the findings.
BACKGROUND
To explore the diagnostic value of computed tomography (CT) imaging for duodenal lipoma and the potential clinical significance of the findings.
METHODS
Clinicopathological and CT data from 57 patients, who were diagnosed with duodenal lipoma at the first affiliated Hospital of Zhengzhou University (Zhengzhou, China) between June 2014 and March 2019, were retrospectively reviewed. Data collected included location and size of the tumor, morphological manifestations (shape, density, boundary), concomitant diseases, pathology and gastroscopy results, and follow-up. Follow-up was performed via telephone, and surgical patients were followed-up for recurrence, metastasis and tumor size, and morphological changes. The follow-up period was up to January 2019.
RESULTS
Of the 57 patients with duodenal lipoma, contrast-enhanced scanning was performed in 7 cases. The tumor was located in the descending duodenum in 33 cases, the ascending in 4 cases, the horizontal in 16 cases, and the bulb in 4 cases. Mean tumor size was 13.0 ± 5.8 mm. CT morphological features of the tumor were as follows: tumor shape, round, quasi-round, or oval (n = 42); long strip (n = 3); nodular (n = 2); triangular (n = 1); and irregular lobulated (n = 9). Among the 57 patients, tumor density was homogeneous in 52 cases, inhomogeneous in 4 cases, and nodular with calcification in 1 case. The tumor boundary was classified as clear and with no capsule. Diseases concomitant with the tumor were as follows: gastritis (n = 23), gastric adenocarcinoma (n = 1), and gastric lymphoma (n = 1). Esophageal disease was found in 16 cases, including reflux esophagitis (n = 12) and esophageal cancer (n = 4). There were 13 cases of gallbladder and biliary disease, including cholecystolithiasis and cholecystitis (n = 9), common bile duct disease (n = 2), colorectal cancer (n = 4), lung cancer (n = 2), duodenal carcinoma with obstruction (n = 1), and ureteral space narrowing (n = 1).
CONCLUSION
CT was an effective, non-invasive method for diagnosis of duodenal lipoma. CT imaging could clearly discern location, size, shape, and nature of duodenal lipomas. Duodenal lipoma can be associated with digestive tract inflammatory diseases and tumors in different locations, and its diagnosis is potentially valuable for their prevention and treatment.
Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Duodenal Neoplasms; Duodenum; Female; Humans; Lipoma; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 34414955
DOI: 10.1097/MD.0000000000026944 -
PloS One 2023Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune...
BACKGROUND
Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune cells and immune checkpoint biomarkers especially programmed cell death ligand-1 (PD-L1) have been shown to significantly impact disease progression. We have analysed the expression of a subset of immune cell and immune checkpoint biomarkers in a cohort of SBA patients and assessed their impact on progression-free survival (PFS) and overall survival (OS).
METHODS
25 patient samples in the form of formalin fixed, paraffin embedded (FFPE) tissue were obtained in tissue microarray (TMAs) format. Automated immunohistochemistry (IHC) staining was performed using validated antibodies for CD3, CD4, CD8, CD68, PD-L1, ICOS, IDO1 and LAG3. Slides were scanned digitally and assessed in QuPath, an open source image analysis software, for biomarker density and percentage positivity. Survival analyses were carried out using the Kaplan Meier method.
RESULTS
Varying expressions of biomarkers were recorded. High expressions of CD3, CD4 and IDO1 were significant for PFS (p = 0.043, 0.020 and 0.018 respectively). High expression of ICOS was significant for both PFS (p = 0.040) and OS (p = 0.041), while high PD-L1 expression in tumour cells was significant for OS (p = 0.033). High correlation was observed between PD-L1 and IDO1 expressions (Pearson correlation co-efficient = 1) and subsequently high IDO1 expression in tumour cells was found to be significant for PFS (p = 0.006) and OS (p = 0.034).
CONCLUSIONS
High levels of immune cells and immune checkpoint proteins have a significant impact on patient survival in SBA. These data could provide an insight into the immunotherapeutic management of patients with SBA.
Topics: Humans; B7-H1 Antigen; Adenocarcinoma; Survival Analysis; Duodenal Neoplasms; Biomarkers, Tumor; Intestine, Small; Prognosis; Lymphocytes, Tumor-Infiltrating; Tumor Microenvironment
PubMed: 37527282
DOI: 10.1371/journal.pone.0289355 -
Surgical Endoscopy Feb 2023Major complications (MCs) after pancreaticoduodenectomy (PD) are a known independent predictor of worse oncologic outcomes. There are limited data on the effect of major...
BACKGROUND
Major complications (MCs) after pancreaticoduodenectomy (PD) are a known independent predictor of worse oncologic outcomes. There are limited data on the effect of major complications on long-term outcomes after robotic PD (RPD). The aim of this study is to compare the effect of MC on overall (OS) and disease-free survival (DFS) after RPD and open PD (OPD).
METHODS
This is a single-center, retrospective review of a prospectively maintained database of all patients undergoing PD for periampullary cancer including ampullary adenocarcinoma, distal cholangiocarcinoma, and duodenal carcinoma. Univariate analysis was performed on all clinical, pathologic, and treatment factors. MCs were defined as Clavien-Dindo ≥ grade 3. Kaplan-Maier survival analysis was performed with log-rank test for group comparison. Multivariable Cox regression analysis was used to identify factors associated with overall survival (OS) in both the OPD and RPD groups.
RESULTS
A total of 190 patients with ampullary carcinoma (n = 98), cholangiocarcinoma (n = 55), and duodenal adenocarcinoma (n = 37) were examined over the study period with 61.1% (n = 116) undergoing RPD and 38.9% (n = 74) undergoing OPD. There was no significant difference in patient demographics between the RPD and OPD cohorts. Furthermore, R0 resection rates, tumor size, and lymph node involvement were similar between the RPD and OPD cohorts. OPD had higher rate of MC (40.5% vs 28.3% in RPD, p = 0.011) including clinically relevant pancreatic fistula (25.7% vs 8.6%, p = 0.001) and wound infection (34.5% vs 13.8%, p < 0.001). MCs were associated with a lower OS in the OPD cohort (HR = 2.18, 95%CI 1.0-4.55, p = 0.038). MCs were not associated with OS in the RPD cohort (HR = 1.55, 95%CI 0.87-2.76, p = 0.14).
CONCLUSION
MCs are associated with worse patient outcomes after OPD but not after RPD. Robotic approach mitigates and possibly abrogates the negative effects of MCs on patient outcomes after PD for malignancy and is associated with improved adjuvant chemotherapy completion rates.
Topics: Humans; Pancreaticoduodenectomy; Robotic Surgical Procedures; Postoperative Complications; Pancreatic Neoplasms; Retrospective Studies; Adenocarcinoma; Duodenal Neoplasms; Cholangiocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Laparoscopy
PubMed: 36163566
DOI: 10.1007/s00464-022-09638-4 -
Cancer Medicine Jul 2019There is no standard salvage chemotherapy for metastatic periampullary adenocarcinoma and duodenal adenocarcinoma and the prognosis of those who fail oxaliplatin,...
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.
Topics: Adenocarcinoma; Albumins; Ampulla of Vater; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Deoxycytidine; Duodenal Neoplasms; Female; Humans; Immunohistochemistry; Male; Neoplasm Metastasis; Neoplasm Staging; Paclitaxel; Tomography, X-Ray Computed; Treatment Outcome; Gemcitabine
PubMed: 31102323
DOI: 10.1002/cam4.2181 -
Annals of Surgical Oncology Jan 2017The surgical management of duodenal gastrointestinal stromal tumors (DGIST) is poorly characterized. Limited resection may be technically feasible and oncologically...
BACKGROUND
The surgical management of duodenal gastrointestinal stromal tumors (DGIST) is poorly characterized. Limited resection may be technically feasible and oncologically safe, but anatomic considerations may compromise the resection margins due to the proximity of critical structures, thereby necessitating more extensive resections such as pancreaticoduodenectomy.
METHODS
Patients undergoing surgery for DGIST at two institutions from 1994 to 2014 were identified. Clinicopathologic and survival data were analyzed to compare outcomes in patients treated with limited or radical resection.
RESULTS
Sixty patients underwent surgery for DGIST. Pancreaticoduodenectomy was performed in 38 % while the rest underwent limited resections. The most common type of limited resection was wedge resection and primary closure (49 %) followed by segmental resection with an end-to-end or side-to-side duodenojejunostomy (27 %). The pancreaticoduodenectomy group tended to have larger tumors with the majority located in D2/3 (87 %) and at the mesenteric border (91 %). The pancreaticoduodenectomy group also had significantly greater intraoperative blood loss, longer operative time, longer hospital stay, and higher 90-day morbidity and readmission rates. The 5-year relapse-free survival, recurrence-free survival, and overall survival for the pancreaticoduodenectomy versus limited resection were 81 versus 56 % (p = 0.05), 64 versus 53 % (p = 0.5), and 76 versus 72 % (p = 0.6), respectively. A surgical algorithm based on the location and size of the tumor is proposed.
CONCLUSIONS
Limited resection of DGIST is safe, but may be associated with lower 5-year relapse-free survival. Pancreaticoduodenectomy is recommended for selected patients with DGIST when an R0 resection cannot be performed without removing the ampulla or part of the pancreas.
Topics: Aged; Blood Loss, Surgical; Duodenal Neoplasms; Duodenoscopy; Female; Gastrointestinal Stromal Tumors; Humans; Jejunostomy; Length of Stay; Male; Middle Aged; Operative Time; Pancreaticoduodenectomy; Patient Readmission; Survival Rate; Treatment Outcome
PubMed: 27624583
DOI: 10.1245/s10434-016-5565-9 -
United European Gastroenterology Journal Mar 2019Sporadic nonampullary duodenal adenocarcinoma is a rare malignant neoplasm in which poor prognosis is often associated with delayed diagnosis.
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.
Topics: Adenocarcinoma; Adenoma; Aged; Biopsy; Case-Control Studies; Duodenal Neoplasms; Duodenoscopy; Early Detection of Cancer; Female; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prevalence; ROC Curve; Risk Factors
PubMed: 31080610
DOI: 10.1177/2050640618817689 -
World Journal of Gastroenterology Nov 2015Superficial non-ampullary duodenal epithelial tumor (SNADET) is defined as a sporadic tumor that is confined to the mucosa or submucosa that does not arise from Vater's... (Review)
Review
Superficial non-ampullary duodenal epithelial tumor (SNADET) is defined as a sporadic tumor that is confined to the mucosa or submucosa that does not arise from Vater's papilla, and it includes adenoma and adenocarcinoma. Recent developments in endoscopic technology, such as high-resolution endoscopy and image-enhanced endoscopy, may increase the chances of detecting SNADET lesions. However, because SNADET is rare, little is known about its preoperative endoscopic diagnosis. The use of endoscopic resection for SNADET, which has no risk of metastasis, is increasing, but the incidence of complications, such as perforation, is significantly higher than in any other part of the digestive tract. A preoperative diagnosis is required to distinguish between lesions that should be followed up and those that require treatment. Retrospective studies have revealed certain endoscopic findings that suggest malignancy. In recent years, several new imaging modalities have been developed and explored for real-time diagnosis of these lesion types. Establishing an endoscopic diagnostic tool to differentiate between adenoma and adenocarcinoma in SNADET lesions is required to select the most appropriate treatment. This review describes the current state of knowledge about preoperative endoscopic diagnosis of SNADETs, such as duodenal adenoma and duodenal adenocarcinoma. Newer endoscopic techniques, including magnifying endoscopy, may help to guide these diagnostics, but their additional advantages remain unclear, and further studies are required to clarify these issues.
Topics: Adenocarcinoma; Biopsy; Diagnosis, Differential; Duodenal Neoplasms; Duodenoscopy; Humans; Image Enhancement; Narrow Band Imaging; Neoplasm Staging; Predictive Value of Tests; Preoperative Care; Reproducibility of Results
PubMed: 26557007
DOI: 10.3748/wjg.v21.i41.11832