-
International Journal of Medical... 2021Ampullary cancer is a rare periampullary cancer currently with no targeted therapeutic agent. It is important to develop a deeper understanding of the carcinogenesis of...
Ampullary cancer is a rare periampullary cancer currently with no targeted therapeutic agent. It is important to develop a deeper understanding of the carcinogenesis of ampullary cancer. We attempted to explore the characteristics of ampullary cancer in our dataset and a public database, followed by a search for potential drugs. We used a bioinformatics pipeline to analyze complementary (c)DNA microarray data of ampullary cancer and surrounding normal duodenal tissues from five patients. A public database from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) was applied for external validation. Bioinformatics tools used included the Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID), MetaCore, Kyoto Encyclopedia of Genes and Genomes (KEGG), Hallmark, BioCarta, Reactome, and Connectivity Map (CMap). In total, 9097 genes were upregulated in the five ampullary cancer samples compared to normal duodenal tissues. From the MetaCore analysis, genes of peroxisome proliferator-activated receptor alpha () and retinoid X receptor ()-regulated lipid metabolism were overexpressed in ampullary cancer tissues. Further a GSEA of the KEGG, Hallmark, Reactome, and Gene Ontology databases revealed that and lipid metabolism-related genes were enriched in our specimens of ampullary cancer and in the NCBI GSE39409 database. Expressions of messenger (m)RNA and the PPAR-α protein were higher in clinical samples and cell lines of ampullary cancer. US Food and Drug Administration (FDA)-approved drugs, including alvespimycin, trichostatin A (a histone deacetylase inhibitor), and cytochalasin B, may have novel therapeutic effects in ampullary cancer patients as predicted by the CMap analysis. Trichostatin A was the most potent agent for ampullary cancer with a half maximal inhibitory concentration of < 0.3 μM. According to our results, upregulation of and lipid metabolism-related genes are potential pathways in the carcinogenesis and development of ampullary cancer. Results from the CMap analysis suggested potential drugs for patients with ampullary cancer.
Topics: Adenocarcinoma; Ampulla of Vater; Antineoplastic Agents; Carcinogenesis; Cell Line, Tumor; Chemotherapy, Adjuvant; Common Bile Duct Neoplasms; Computational Biology; Datasets as Topic; Drug Screening Assays, Antitumor; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Inhibitory Concentration 50; Lipid Metabolism; Male; Oligonucleotide Array Sequence Analysis; PPAR alpha; Up-Regulation
PubMed: 33390794
DOI: 10.7150/ijms.48123 -
BMC Cancer Aug 2016Ampullary adenocarcinoma is a rare gastrointestinal cancer associated with diverse outcomes due to clinical and pathological heterogeneity. Standardized methods to...
BACKGROUND
Ampullary adenocarcinoma is a rare gastrointestinal cancer associated with diverse outcomes due to clinical and pathological heterogeneity. Standardized methods to better prognosticate and inform therapeutic selection for ampullary adenocarcinoma are needed. This study explored the novel use and potential prognostic utility of a 92-gene cancer classifier in ampullary adenocarcinomas.
METHODS
In this prospectively-defined, blinded study of ampullary adenocarcinoma [N =54; stage T3 or higher (57 %); Grade III (44 %); Node positive (55 %)], the performance of a 92-gene classifier was examined to predict the ampullary subtype that was derived from histomorphological examination of resected ampullary samples. Outcome data for relapse-free survival (RFS) and overall survival (OS) were plotted to compare the prognostic utility of histological subtyping, histomolecular phenotyping, and the 92-gene classifier. Multivariate analysis was used to determine clinicopathological variables that were independently associated with overall survival.
RESULTS
The 92-gene classifier demonstrated sensitivities and specificities of 85 % [95 % CI, 66-94] and 68 % [95 % CI, 48-84] and 64 % [95 % CI, 46-79] and 88 % [95 % CI, 70-98] for the pancreaticobiliary and intestinal histological subtypes, respectively. For the 92-gene classifier, improved outcomes were observed for the intestine versus the pancreaticobiliary prediction (median OS 108.1 v 36.4 months; HR, 2.17; 95 % CI, 0.98 to 4.79; P = 0.05). Similar results were seen for ampullary adenocarcinoma stratification by histological subtype (P = 0.04) and histomolecular phenotype (P = 0.02). Within poorly differentiated ampullary adenocarcinomas only the 92-gene classifier demonstrated statistically significant differences in RFS and OS (P < 0.05).
CONCLUSIONS
Prognostic stratification of ampullary adenocarcinoma was similar for the 92-gene classifier, histological subtype, and histomolecular phenotype. The 92-gene classifier provides an unbiased standardized molecular-based approach to stratify ampullary tumors.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; Common Bile Duct Neoplasms; Female; Humans; Male; Middle Aged; Prognosis; Prospective Studies
PubMed: 27549176
DOI: 10.1186/s12885-016-2677-3 -
Neoplasia (New York, N.Y.) Dec 2021Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been...
INTRODUCTION
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been defined that differ in prognosis. Cells of both subtypes can coexist in individual tumors; however, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the spatial tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall, and identify the duodenal epithelium as a distinct PDAC microniche.
MATERIALS AND METHODS
We used serial multiplex quantitative immunohistochemistry (smq-IHC) for 24 proteins to phenotypically chart PDAC tumor cells in patients whose tumors infiltrated the duodenal epithelium. Additionally, we used a genetically engineered mouse model to study the PDAC cell phenotype in the small intestinal epithelium in a controlled genetic background.
RESULT
We show that pancreatic cancer cells revert to non-destructive growth upon integration into the duodenal epithelium, where they adopt traits of intestinal cell differentiation, associated with phenotypical stabilization of the classical subtype. The integrated tumor cells replace epithelial cells in an adenoma-like manner, as opposed to invasive growth in the submucosa. Finally, we show that this phenomenon is shared between species, by confirming duodenal integration and phenotypic switching in a genetic PDAC mouse model.
DISCUSSION
Our results identify the duodenal epithelium as a distinct PDAC microniche and tightly link microenvironmental cue to cancer transcriptional subtypes. The phenomenon of "intestinal mimicry" provides a unique opportunity for the systematic investigation of microenvironmental influences on pancreatic cancer plasticity.
Topics: Aged; Aged, 80 and over; Animals; Carcinoma, Pancreatic Ductal; Duodenum; Female; Humans; Intestinal Mucosa; Male; Mice; Middle Aged; Pancreatic Neoplasms; Phenotype; Tumor Microenvironment
PubMed: 34798385
DOI: 10.1016/j.neo.2021.11.007 -
Medicine Nov 2019We aimed to identify the factors for very early recurrence (within 6 months) of ampullary cancer following curative resection and to compare the immunohistochemical...
We aimed to identify the factors for very early recurrence (within 6 months) of ampullary cancer following curative resection and to compare the immunohistochemical expression rate of various antibodies between the 2 main histologic subtypes of ampullary adenocarcinoma.In this retrospective study, the postoperative outcomes and clinicopathologic factors for very early recurrence that occurred in 14 of 93 patients who underwent pancreaticoduodenectomy (PD) for ampullary adenocarcinoma between January 2002 and August 2014 were analyzed. Thereafter, we identified the factors associated with very early recurrence following surgery. Additionally, we compared the expression rates of CK7, CK20, MUC1, MUC2, MUC5AC, MUC6, S100P, and CDX2 between the 2 main histologic subtypes of ampullary adenocarcinoma (NCC2019-0138).The patients who underwent PD for ampullary cancer were divided into 2 groups: very early recurrence and others. Compared with the other patients, the 14 patients (32.6%) who developed very early recurrence had shorter median disease-free survival (4.2 vs 49.7 months, P = .001) and overall survival (18.2 vs 113.7 months, P < .001). Large tumor, lymph node metastasis, and pancreatobiliary type were independently associated with very early recurrence of ampullary cancer following PD.Large tumor, lymph node metastasis, and pancreatobiliary type were the independent risk factors for very early recurrence of ampullary cancer following curative resection. Therefore, ampullary cancer patients with these factors should be considered to receive aggressive adjuvant treatment and frequent post-operative follow-up.
Topics: Adenocarcinoma; Aged; Ampulla of Vater; Common Bile Duct Neoplasms; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreaticoduodenectomy; Postoperative Period; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 31689805
DOI: 10.1097/MD.0000000000017711 -
Journal of the Chinese Medical... Oct 2008We report a case of coexisting poorly differentiated endocrine carcinoma and conventional adenocarcinoma in the ampulla of Vater. A 70-year-old female had a recent... (Review)
Review
We report a case of coexisting poorly differentiated endocrine carcinoma and conventional adenocarcinoma in the ampulla of Vater. A 70-year-old female had a recent history of symptoms and signs related to obstructive jaundice. An initial endoscopic biopsy of the ampulla of Vater showed a poorly differentiated endocrine carcinoma in the lamina propria of duodenal mucosa. The tumor could also be categorized into large cell neuroendocrine carcinoma under the WHO classification of pulmonary neuroendocrine tumors. The patient underwent Whipple's operation. After thorough microscopic examination of the ampulla of Vater, we incidentally found another conventional adenocarcinoma on the inner side of the duodenal papilla, and the tumor collided with the aforementioned carcinoma. The association of neuroendocrine tumor and adenocarcinoma has been reported in a few case reports and a small series. We also review the literature concerning large cell neuroendocrine carcinoma in this area.
Topics: Adenocarcinoma; Aged; Ampulla of Vater; Carcinoma, Large Cell; Common Bile Duct Neoplasms; Female; Humans; Neuroendocrine Tumors
PubMed: 18955190
DOI: 10.1016/S1726-4901(08)70164-3 -
American Journal of Surgery Jan 2000It has been postulated that segmental duodenal resection (SR) is not an adequate operation for patients with adenocarcinoma of the duodenum and that...
BACKGROUND
It has been postulated that segmental duodenal resection (SR) is not an adequate operation for patients with adenocarcinoma of the duodenum and that pancreaticoduodenectomy (PD) is the procedure of choice, regardless of the tumor site. However, data from previous studies do not clearly support this position.
METHODS
We reviewed the records of 63 patients treated for duodenal adenocarcinoma from 1979 through 1998. Perioperative outcome, patient survival, and extent of lymphadenectomy were compared in patients who underwent PD and SR.
RESULTS
The overall morbidity for PD and SR was 27% and 18%, respectively (not significant [NS]). Patients who underwent SR had a 5-year survival of 60% versus 30% for patients who underwent PD (NS). Lymph node status was a prognostic factor for survival (P = 0.014). The mean number of lymph nodes in the specimens was 9.9 +/- 2.1 for PD and 8.3 +/- 4.4 for SR (NS).
CONCLUSIONS
Segmental duodenal resection for patients with duodenal adenocarcinoma is associated with acceptable postoperative morbidity and long-term survival. The procedure is especially well suited for distal duodenal tumors. Clearance of lymph nodes and outcome are comparable to PD.
Topics: Actuarial Analysis; Adenocarcinoma; Duodenal Neoplasms; Female; Humans; Lymph Node Excision; Male; Middle Aged; Pancreaticoduodenectomy; Proportional Hazards Models; Survival Analysis
PubMed: 10737576
DOI: 10.1016/s0002-9610(99)00269-x -
World Journal of Gastroenterology Mar 2019Endoscopic papillectomy (EP) for benign ampullary neoplasms could be a less-invasive alternative to pancreatoduodenectomy (PD). There are some problems and limitations...
BACKGROUND
Endoscopic papillectomy (EP) for benign ampullary neoplasms could be a less-invasive alternative to pancreatoduodenectomy (PD). There are some problems and limitations with EP. The post-EP resection margins of ampullary tumors are often positive or uncertain because of the burning effect of EP. The clinical outcomes of resected margin positive or uncertain cases after EP remain unknown.
AIM
To investigate the clinical outcomes of resected margin positive or uncertain cases after EP.
METHODS
Between January 2007 and October 2018, all patients with ampullary tumors who underwent EP at Kobe University Hospital were included in this study. The indications for EP were as follows: adenoma, as determined by preoperative endoscopic biopsy, without bile/pancreatic duct extension, according to endoscopic ultrasound or intraductal ultrasound. The clinical outcomes of resected margin positive or uncertain cases after EP were retrospectively investigated.
RESULTS
Of the 45 patients, 29 were male, and 16 were female. The mean age of the patients was 65 years old. Forty-one patients (89.5%) underwent resection, and 4 patients (10.5%) underwent piecemeal resection. After EP, 33 tumors were histopathologically diagnosed as adenoma, and 12 were diagnosed as adenocarcinoma. The resected margins were positive or uncertain in 24 patients (53.3%). Of these cases, 15 and 9 were diagnosed as adenoma and adenocarcinoma, respectively. Follow-up observation was selected for all adenomas and 5 adenocarcinomas. In the remaining 4 adenocarcinoma cases, additional PD was performed. Additional PD was performed in 4 cases, and residual carcinoma was found after the additional PD in 1 of these cases. In the follow-up period, local tumor recurrence was detected in 3 cases. Two of these cases involved primary EP-diagnosed adenoma. The recurrent tumors were also adenomas detected by biopsy. The remaining case involved primary EP-diagnosed adenocarcinoma. The recurrent tumor was also an adenocarcinoma. All of the recurrent tumors were successfully treated with argon plasma coagulation (APC). There was no local or lymph node recurrence after the APC. The post-APC follow-up periods lasted for 57.1 to 133.8 mo. No ampullary tumor-related deaths occurred in all patients.
CONCLUSION
Resected margin positive or uncertain cases after EP could be managed by endoscopic treatment including APC, even in cases of adenocarcinoma. EP could become an effective less-invasive first-line treatment for early stage ampullary tumors.
Topics: Adenocarcinoma; Adenoma; Aged; Ampulla of Vater; Argon Plasma Coagulation; Biopsy; Common Bile Duct Neoplasms; Duodenoscopy; Female; Follow-Up Studies; Humans; Male; Margins of Excision; Middle Aged; Neoplasm Recurrence, Local; Neoplasm, Residual; Pancreaticoduodenectomy; Retrospective Studies; Sphincterotomy, Endoscopic; Treatment Outcome; Uncertainty
PubMed: 30918431
DOI: 10.3748/wjg.v25.i11.1387 -
Hong Kong Medical Journal = Xianggang... Feb 2008Adenocarcinoma of the duodenum is an exceedingly rare disorder. Its vague and non-specific symptoms often lead clinicians and patients to suspect other more benign...
Adenocarcinoma of the duodenum is an exceedingly rare disorder. Its vague and non-specific symptoms often lead clinicians and patients to suspect other more benign differential diagnoses. Improved endoscopy and radiology have enabled more of these cases to be unearthed. Definitive surgery is the only means of potential cure, with the prognosis being significantly better for node-negative patients. We present a case of a 52-year-old man who underwent a Whipple's operation for this uncommon disease and a literature review of the subject.
Topics: Adenocarcinoma; Anorexia; Digestive System Surgical Procedures; Duodenal Neoplasms; Humans; Laparotomy; Male; Middle Aged; Weight Loss
PubMed: 18239248
DOI: No ID Found -
World Journal of Gastroenterology Apr 2015A 62-year-old Japanese man presented to our hospital with a history of weight loss of 6 kg in 4 mo. Imaging examinations revealed a tumor located on the third portion of... (Review)
Review
A 62-year-old Japanese man presented to our hospital with a history of weight loss of 6 kg in 4 mo. Imaging examinations revealed a tumor located on the third portion of the duodenum with stenosis. We suspected duodenal carcinoma and performed pancreas-preserving segmental duodenectomy. Adenocarcinoma arising from a heterotopic pancreas at the third portion of the duodenum was finally diagnosed by immunohistochemical staining. Malignant transformation in the duodenum arising from a heterotopic pancreas is extremely rare; to our knowledge, only 13 cases have been reported worldwide, including the present case. The most common location of malignancy is the proximal duodenum at the first and descending portion. Herein, we describe the first case of adenocarcinoma arising from a heterotopic pancreas, which was located in the third portion of the duodenum, with a review of the literature.
Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Choristoma; Duodenal Neoplasms; Duodenoscopy; Humans; Immunohistochemistry; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 25852297
DOI: 10.3748/wjg.v21.i13.4082 -
Investigational New Drugs Feb 2015Regional chemotherapy is used successfully in the treatment of both primary and secondary malignancies, in particular of the peritoneal surface and the liver, and is...
Duodenal ischemia and upper GI bleeding are dose-limiting toxicities of 24-h continuous intra-arterial pancreatic perfusion of gemcitabine following vascular isolation of the pancreatic head: early results from the Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) study.
BACKGROUND
Regional chemotherapy is used successfully in the treatment of both primary and secondary malignancies, in particular of the peritoneal surface and the liver, and is currently explored as an attractive approach for patients with locally advanced pancreatic ductal adenocarcinoma. To establish the feasibility and toxicity of regional intra-arterial gemcitabine delivered as a 24-h continuous infusion to the pancreas as a novel treatment option for patients with locally advanced PDAC a phase I clinical trial was conducted.
METHODS
Between April 2011 and September 2013 six patients with biopsy confirmed, borderline or unresectable pancreatic adenocarcinoma, and having received at least one line of systemic chemotherapy, underwent vascular redistribution of the inflow to the head of the pancreas by arterial coil embolization followed by perfusion catheter placement within the splenic artery. Patients were treated with increasing doses of gemcitabine administered by continuous splenic arterial infusion over 24 h with inter-patient and intra-patient dose escalation scheme. The primary endpoint was toxicity of the intra-arterial gemcitabine regimen and to establish the maximum tolerated dose.
RESULTS
Catheter placement and gemcitabine infusion was successful in all patients enrolled to date (n = 6). Four out of six patients experienced catheter tip migration requiring replacement or revision. Patients received a median of four doses of 24-h gemcitabine infusion. Two patients developed grade 3 and 4 duodenal ischemia and upper gastrointestinal bleeding. Median overall survival was 15.3 months and median time to progression was 3 months. Three patients (50 %, n = 3/6) progressed systemically. Two patients had stable disease >4 months following treatment and underwent pancreaticoduodenectomy.
CONCLUSIONS
While technically feasible to treat locally advanced pancreatic ductal adenocarcinoma, prolonged regional pancreatic perfusion with gemcitabine following pancreatic arterial redistribution carries a high risk for gastrointestinal toxicity. Shorter infusion schedules with frequent on treatment evaluations should be considered for future clinical trials.
Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Pancreatic Ductal; Catheterization; Deoxycytidine; Duodenal Diseases; Duodenum; Female; Gastrointestinal Hemorrhage; Humans; Ischemia; Male; Maximum Tolerated Dose; Middle Aged; Pancreas; Pancreatic Neoplasms; Perfusion; Splenic Artery; Treatment Outcome; Gemcitabine
PubMed: 25236592
DOI: 10.1007/s10637-014-0157-7