RARE DISEASE
Carcinoma of the ampulla of Vater
Carcinoma of the ampulla of Vater
Carcinoma of the ampulla of Vater
Synonyms: Ampullary carcinoma, Ampulloma
Synonyms: Ampullary carcinoma, Ampulloma
Synonyms: Ampullary carcinoma, Ampulloma
Drug discovery
0
drugs
With orphan designations
Overview
Carcinoma of the Ampulla of Vater (AVC) arises at the confluence of pancreaticobiliary and intestinal epithelia, often presenting with obstructive jaundice due to bile duct involvement. Histologically classified into intestinal, pancreatobiliary, or mixed subtypes, it exhibits molecular heterogeneity (e.g., KRAS, TP53, and ELF3 mutations). Surgical resection (Whipple procedure) is curative for localized disease, while adjuvant chemotherapy (gemcitabine/5-FU-based) is used for high-risk features. Metastatic disease employs platinum-based or XELOX regimens, with 5-year survival post-resection ranging 35–62% [1][4][5][7][8].
Therapies
Categories: rare gastroenterological diseases, rare neoplastic diseases
Research Papers
995 drug discovery papers about Carcinoma of the ampulla of Vater, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
995 drug discovery papers about Carcinoma of the ampulla of Vater, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-02 | Squamous cell carcinoma of the ampulla of Vater: a rare case report and review of the literature
Introduction: Primary squamous cell carcinoma (SCC) of the ampulla of Vater is an exceptionally rare malignancy, with only a limited number of cases reported in the literature. Its pathogenesis, biological behavior, and optimal management remain poorly defined. Case presentation: We report the case of a 68-year-old man presenting with several weeks of atypical abdominal discomfort and cholestatic liver enzyme abnormalities. Upper gastrointestinal endoscopy revealed an ulcerated ampullary lesion, and biopsy confirmed moderately to poorly differentiated SCC. Cross-sectional imaging excluded metastatic disease. The patient underwent pylorus-preserving pancreaticoduodenectomy. Histopathological analysis confirmed primary SCC (pT2N0M0) with negative margins (R0 resection). Adjuvant chemotherapy with cisplatin and 5-fluorouracil was initiated 6 weeks postoperatively, with a planned duration of 6 months. The patient remains disease-free at 6-month follow-up. Discussion: Ampullary SCC is rare but not unique, with several cases reported. Surgical resection remains the cornerstone of treatment. Adjuvant therapy is extrapolated from other SCCs due to a lack of evidence. Prognosis appears variable, with better outcomes in node-negative disease. Conclusion: This case highlights the importance of accurate histopathological diagnosis and reinforces the role of radical surgical resection. Further case accumulation is required to define optimal management strategies.
2026-06-26 | Exploring the Role of MET Gene as a Potential Biomarker and Therapeutic Target in Ampullary Cancer.
The incidence of Ampullary carcinoma (AC) has dramatically increased. Nearly 50% of patients develop recurrence indicating need for additional prognostic markers and treatment options. Emerging evidence suggests that Mesenchymal Epithelial Transition (MET) genes play a role in tumorigenesis and can be a useful therapeutic target, however, its role in AC remains unexplored. This study investigated the methylation status using methylation specific PCR, mRNA expression using quantitative PCR and protein expression using Immunohistochemistry of the MET proto-oncogene in 61 surgically resected AC specimens and further examined its co-expression with HER2. Our findings revealed MET promoter hypomethylation (68.85%), increased expression of MET at mRNA (67.21%) and protein level (54%) in ACs patients. Significant correlation was observed between both hypomethylation and increased mRNA expression (P=0.026; P<0.000), and MET mRNA and protein expression (P=0.037). Further, MET expression was notably higher in early stage (P=0.003) and Intestinal-type (84.21%) than Pancreatobiliary type (PB-type) (61.76%) (P=0.199). Additionally, co-expression of MET and HER2 receptors occurred in a significant subset of cases in AC suggesting receptor tyrosine kinase convergence (P=0.014). In silico analysis of the GSE60979, dataset corroborated these findings, showing increased MET and ERBB2 (HER2) expression in tumor samples compared to normal tissues. At a median follow-up of 34 months the mean survival of AC patient was 37.3±2.5 months. These findings demonstrate that MET dysregulation is a recurrent molecular event in ampullary carcinoma and support further investigation of MET and HER2 co-expression as a basis for future mechanistic and therapeutic studies.
2026-05-27 | A first-in-human phase I/II study evaluating CTS3497, an MTA-cooperative PRMT5 inhibitor, in advanced or metastatic MTAP -deficient solid tumors.
3115 Background: Protein arginine methyltransferase 5 (PRMT5) methylates multiple protein substrates with a variety of biological functions known to be dysregulated in cancer. CTS3497 is an orally available, brain-penetrable, MTA (methylthioadenosine) -cooperative PRMT5 inhibitor that preferentially targets the MTA-bound PRMT5 in MTAP (MTA phosphorylase) -deficient tumors and potently inhibits tumor growth in various preclinical models. Here we present clinical data from an ongoing Phase I/II study of CTS3497 in solid tumors (NCT06971523). Methods: Eligible pts with homozygous MTAP deletion (by next generation sequencing), or MTAP protein loss (by immunohistochemistry [IHC]) and advanced solid tumors in the dose-escalation stage received 50, 200, 300, 400 mg BID of CTS3497 orally, while pts in the dose-expansion stage were treated with 200, 300 or 400 mg BID until disease progression or intolerable toxicity. Efficacy, safety, PK, PD and biomarker profiles were evaluated. Results: As of 22 Jan 2026, 41 patients received ≥1 dose of CTS3497 treatment. No DLT was observed, and MTD was not reached; CTS3497 was well-tolerated. Most common (≥20%) treatment-related adverse events (TRAEs) were anemia (34%), white blood cell count decreased (32%), platelet count decreased (27%) and neutrophil count decreased (22%). The most common Grade ≥3 TRAE (occurring in ≥5% of patients) was platelet count decreased. No central nervous system (CNS) effects were reported. Among 21 centrally-confirmed MTAP-deficient, efficacy-evaluable patients, including 9 gastrointestinal (GI) cancers (ampullary cancer, biliary tract carcinoma, esophageal squamous cell carcinoma, gastric cancer and pancreatic ductal adenocarcinoma), 5 non-small cell lung cancer (NSCLC), 1 urothelial carcinoma and 6 rare cancers, the objective response rate (ORR) was 43%, and the disease control rate (DCR) was 91%. In GI cancers, the ORR and DCR were 56% and 89%. In NSCLC, the ORR and DCR were 60% and 80%. The exposures (Cmax, AUC0-24h) of CTS3497 increased in a linear, dose-proportional manner. The pharmacodynamic (PD) marker, plasma symmetric dimethylarginine (SDMA) level, showed a significant decrease. Conclusions: CTS3497 demonstrated a favorable safety profile and promising efficacy in heavily pretreated pts with MTAP-deficient advanced solid tumors, including GI cancers, NSCLC. Clinical trial information: NCT06971523 .
2026-04-17 | Germline Pathogenic Variants in Homologous Recombination Pathway Genes Are Frequent in Pancreatobiliary Ampullary Carcinoma.
Ampullary carcinoma (AMPCA) is a rare cancer classified into subtypes depending on the histologic appearance and epithelium of origin. To gain insights into the germline genetic factors driving predisposition to AMPCA, the analysis focused on the role of homologous recombination (HR) genes in its oncogenesis. We analyzed germline testing results from 26,159 patients with cancer undergoing clinical tumor-normal sequencing from May 2015 to November 2022, of which 112 individuals had AMPCA. Germline and somatic alteration profiles were analyzed for the different histologic subtypes of AMPCA, and a subset of cases were selected for whole-genome sequencing (WGS) to determine the presence of HR deficiency (HRD). Pathogenic variants in HR pathway genes were identified in 17/72 (23.6%), 0/26 (0.0%), and 1/14 (7.1%) patients with pancreatobiliary (PAMPCA), intestinal (IAMPCA), and other (mixed, neuroendocrine, adenosquamous) subtypes of AMPCA, respectively. Germline pathogenic variants in core HR genes, including BRCA1, BRCA2, and PALB2, were exclusively detected in the PAMPCAs, and one ATM germline pathogenic variant was detected in a case with mixed intestinal and pancreatobiliary features. HRD features were detected in all four representative PAMPCA tumor samples that underwent WGS and HRDetect analysis. Germline pathogenic variants in the HR pathway genes drive oncogenesis in a large subset of PAMPCAs. These findings highlight the importance of germline genetic testing for patients with PAMPCA for informing therapy and assessing familial risk.
2026-03-13 | Histopathologic Subtype as a Determinant of Prognosis and Chemotherapy Benefit in Resected Ampullary Adenocarcinoma.
Ampullary adenocarcinoma (AAC) is a rare malignancy with heterogeneous biological behavior. Although surgical resection is the only potentially curative option, the prognostic role of histopathologic features and adjuvant chemotherapy (AC) remains unclear. Consecutive patients undergoing curative-intent pancreatoduodenectomy for AAC at the University of Colorado Hospital between January 2013 and May 2025 were retrospectively reviewed. Clinicopathologic variables associated with overall (OS) and recurrence-free survival (RFS) were analyzed using multivariable Cox regression. Ninety-seven patients were included. Median OS was 93.9 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 67%, 59%, and 46%. Older age (HR, 3.79; 95% CI, 1.71-8.41), lymph node (LN) involvement (HR, 4.92; 95% CI, 1.87-12.93), and R1 margin (HR, 4.33; 95% CI, 1.09-17.25) independently predicted poorer OS. The pancreatobiliary subtype (pbAAC) showed worse OS than the intestinal subtype (iAAC) (5-year OS, 48% vs. 75%; p = 0.012). In pbAAC, LN metastasis (HR, 4.16; 95% CI, 1.31-13.18) and R1 margin (HR, 5.47; 95% CI, 1.10-27.20) predicted worse OS, whereas AC was associated with improved survival (HR, 0.404; 95% CI, 0.18-0.91). No AC benefit was observed in iAAC (p = 0.323). Histopathologic subtype is a key prognostic factor in AAC, with AC associated with better survival in pbAAC.
proteins
2022-12-25 | Noninvasive endoscopic hemostasis technique for post‐papillectomy bleeding using a novel self‐assembling peptide (with video)
Abstract Although a novel hemostatic agent has been used for endoscopic mucosal resection in submucosal dissection, there are few case reports of its use in pancreato‐biliary endoscopic procedures. We describe a case of post‐endoscopic papillectomy bleeding in which endoscopic hemostasis was achieved using a novel hemostatic agent.
2011-09-08 | Carcinoid tumors of the duodenum and the ampulla of Vater: current diagnostic and therapeutic approach in a series of 8 patients. Case series.
To describe the specific characteristics of duodenal/perivaterian carcinoids and to analyze the diagnostic/therapeutic approach. Eight patients were included in our study. Symptoms on admission included dyspepsia, upper gastrointestinal (GI) bleeding and anemia. All patients underwent upper GI endoscopy and gastrointestinal peptides (gastrin) and neuroendocrine markers (Chromogranin-A, CgA) measurement. Imaging studies were performed in all patients, including OCTREOSCAN, while in patients with ACs MRCP or ERCP was also performed, when necessary. Definite diagnosis was confirmed by histopathologic examination. Polypoid masses (carcinoids) were revealed at duodenal bulb and ampulla of Vater, in 5 and 3 patients, respectively. Serum gastrin was moderately increased in 4 patients, while in one patient it was more than 1000 pg/ml. Serum CgA was moderately increased in one patient, in whom OCTREOSCAN detected a solitary hepatic metastasis. Two patients with DC, of less than 1 cm of diameter, were treated by endoscopic polypectomy, while all the other patients underwent surgery. The patient with hepatic metastasis and positive OCTREOSCAN received also Octreotide LAR, resulting in stabilization of disease. No recurrence or metastases were observed during follow-up (range : 1.5-9.6 years). In DC tumors <1 cm endoscopic excision with close follow-up is an adequate treatment, while in tumors >1 cm and in AC, surgical resection is the treatment of choice. In metastatic tumors, resection of the primary lesion with administration of somatostatin analogues may stabilize the disease and improve patient's quality of life.
2006-10-31 | Octreotide hardens the pancreas.
Leakage from pancreaticojejunostomy and development of pancreatic fistulas are the major postoperative complications in patients undergoing duodenopancreatectomy. The risk of developing these complications is higher when surgery is performed on a soft pancreas. A recent report suggests that octreotide hardens the pancreas when given intraoperatively. The present study aims at verifying this observation by measuring tissue hardness of the pancreas by a commercially available durometer in pigs with and without octreotide pretreatment. Three groups of pigs were investigated: Group 1 (n=6) received no treatment; group 2 (n=6) was treated with 3x100 microg octreotide for 1 day; group 3 (n=6) for 5 days. Thereafter, animals were killed and the pancreas was harvested for performing measurements: Tissue hardness was assessed by a commercially available durometer, and a suture holding test was performed using a Newton dynamometer. There was a significant increase in tissue hardness between untreated control animals [26.3+/-2.5 S.U. (shore units)] and animals with 1 day octreotide pretreatment (29.8+/-2.6 S.U.; p=0.04) as well as between the groups treated for 1 and 5 days (34.8+/-2.8 S.U.; p=0.01). Suture holding capacity was higher in animals treated for 5 days. The present study agrees with a recent report suggesting that octreotide hardens the pancreas. Octreotide pretreatment may therefore be an advantage when performing surgery on a soft pancreas, i.e., in patients scheduled for duodenopancreatectomy for ampullary carcinomas or circumscript pancreatic tumors not associated with chronic pancreatitis.
2005-03-22 | Intra-arterial bolus octreotide administration during Whipple procedure in patients with fragile pancreas: a novel technique for safer pancreaticojejunostomy.
Leakage from the pancreaticojujenostomy is the most serious complication of Whipple. Pancreatic fistula rate is higher in cases of fragile pancreas often seen in duodenal carcinomas and carcinomas of the ampulla of Vater. Octreotide administration has been used for the prevention of fistula formation through the subcutaneous route. Due to its physiologic effects to the pancreatic parenchyma the intra-arterial administration of octreotide could provide tissue hardening that allows for a technically easier anastomosis while maintaining its protective role for fistula formation. Octreotide was injected directly into the distal part of the gastroduodenal artery (GDA) in four patients undergoing Whipple for histologically proven periampullary cancer. Tissue hardening after octreotide administration was evident not only in surgeons' hands but in the intra-operative ultrasound as well. The three patients were discharged on day 9, 11, and 13; they had an uneventful postoperative course, while one patient had a minor bile leak from the choledojejunal anastomosis and was discharged on day 22. The intra-arterial administration of octreotide during Whipple is a safe procedure and provides tissue hardening thus making the performance of the anastomosis technically easier. The actual benefit in terms of morbidity, mortality, and fistula rate are to be further evaluated.
cell therapies
2024-12-21 | Establishment and characterization of a new intestinal-type ampullary carcinoma cell line, DPC-X3.
Ampullary carcinoma (AC) of the intestinal type represents a distinct variant within the broader category of ampullary neoplasms. The scarcity of pertinent cellular models has constrained investigations centered on this particular malignancy. This research effectively generated a cell line (CL) of intestinal-type AC (DPC-X3). This newly developed CL has been continuously cultured for 1 year and has demonstrated stable passaging exceeding 60 generations. Morphologically, DPC-X3 exhibited characteristic attributes of an epithelial tumor. The cell proliferation rate of DPC-X3 exhibited a doubling interval of 79 h. Short tandem repeat (STR) analysis validated the high consistency between DPC-X3 and the patient's primary tumor. Characteristically, DPC-X3 displayed sub diploid karyotypes, primarily featuring 44, XY inv (9), -18, -20, -22, and + mar. Under suspension culture conditions, DPC-X3 could efficiently form organoids, and DPC-X3 cells inoculated subcutaneously into NXG mice could form transplanted tumors. Drug susceptibility assays demonstrated that DPC-X3 resisted paclitaxel, oxaliplatin, 5-fluorouracil(5-FU), and gemcitabine. Immunohistochemical (IHC) evaluation revealed affirmative reactivity for CK7 and CK20 within DPC-X3 cells, while CDX2 exhibited no detectable expression. E-cadherin and Vimentin demonstrated positive immunoreactivity, whereas CEA and CA19-9 displayed faint positivity. The Ki-67 proliferation index was determined to be approximately 40%. DPC-X3 presents a valuable experimental platform for elucidating the pathogenesis of intestinal-type AC and can serve as a driver for drug development efforts.
2024-03-22 | Abstract 5150: An immunohistochemical survey of predictive biomarkers for immunotherapy in ampullary carcinoma identifies strata with unique prognostic signatures
Abstract Introduction: Carcinomas located in the ampulla of Vater are a low incidence malignancy. Therapeutic options for early stage disease largely consist of pancreaticoduodenectomy followed by adjuvant chemotherapy with or without radiation. We explored the localization of CD8 and CD3 positive cells in addition to PDL-1 staining and mismatch repair deficiency markers to gain insight into the potential applicability of immunotherapy for patients with this disease. Methods: Excess material from clinically diagnosed cases collected between 1997 - 2013 were used to construct a duplicate 0.6mm core tissue microarray (TMA). All cases were derived from the Vancouver Coastal Health Region. Immunohistochemical staining was performed with the following markers: CD8, CD3, PD-L1, and the mismatch repair (MMR) markers: MSH2, MSH6, MLH1 and PMS2. CD3 and CD8 were quantified using localization within the tissue. PD-L1 was considered positive with >1% of cells stating positive. MMR markers were confirmed using full section and cases with convincing loss of any MMR marker were considered MMR deficient. Univariable disease specific survival analysis was performed to identify unique prognostic signatures and contingency analysis was performed to identify co-expression of the aforementioned biomarkers. Results: Ninety-eight cases were evaluable for all markers. The median age of the cohort was 69 [41 - 84] years. Forty-two percent were female. Adjuvant chemotherapy was provided to 15% of patients with the remainder undergoing post-surgical observation. Almost 90% were pT3 or pT4 and 48% had regional lymph node metastasis. CD3+ T-cells were either localized in the tumor stroma only (59%) or in both the stroma and epithelial compartments (41%). CD8+ T-cells were principally located in the stroma (66%) and both the epithelial and stroma (24%). Ten percent of cases had no CD8+ T-cells. PD-L1 staining was found in 10% of cases. MMR deficiency was found in 5% of cases. Improved prognostic signatures were found for cases with CD3+ and CD8+ T-cells in both the epithelial and stromal compartments (p <= 0.02). A trend towards a negative prognostic signature was observed for MMR deficient cases and for PD-L1 positive cases. The only significant positive association between biomarkers was found for CD3+ and CD8+ in both the epithelial and stromal compartments. Conclusions: The results of this analysis suggest that enhancement of an immune response yielding an increase CD3+ and CD8+ T-cells in the epithelial compartment may have a beneficial effect on prognosis. The relative scarcity of MMR deficiency in this disease is within the expected prevalence supported by other studies. Further exploration of the potential role of immunotherapy in immune enhanced subgroups of ampullary cancers is warranted. Citation Format: Steve E. Kalloger, Joanna Karasinska, James Topham, Daniel J. Renouf, David F. Schaeffer. An immunohistochemical survey of predictive biomarkers for immunotherapy in ampullary carcinoma identifies strata with unique prognostic signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5150.
2024-01-24 | Elevated levels of peripheral Th17 cells and Th17-related cytokines in patients with periampullary adenocarcinoma.
Periampullary adenocarcinoma (PAC) is a malignant tumor originating at the ampulla of Vater, distal common bile duct, head of the pancreas, ampulla and duodenum. The levels of circulating Th17 cells and Th17-related cytokines in patients with PAC remain unreported. Therefore, the aim of this study was to determine the levels of circulating Th17 cells and Th17-related cytokines in patients with PAC. Flow cytometry was used to measure Th17 cell proportions in PBMCs from 60 PAC patients and 30 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-17A and IL-23 levels in serum samples, while quantitative reverse transcription polymerase chain reaction (qRT-PCR) assessed IL-17A mRNA expression and Th17-related transcription factors (RORγt and STAT3) in tissue samples. The findings showed a substantial increase in Th17 cell percentages, elevated concentrations of IL-17A and IL-23, and higher mRNA expression levels of IL-17A, RORγt, and STAT3 in patients with PAC when compared to healthy controls (HCs). Th17 cells play an important role in the pathogenesis of PAC and may represent potential therapeutic targets.
2014-07-01 | Pancreatic Islet Autotransplantation After Completion Pancreatectomy for Pancreatic Fistula After Hemipancreatoduodenectomy for Carcinoma
Pancreatic islet autotransplantation (IAT) has a potential to prevent brittle diabetes in patients after total pancreatectomy. Because of the fear of tumor spread, IAT has rarely been used in case of malignancy. We report our experience with patients who underwent hemipancreatoduodenectomy for carcinoma and later completion pancreatectomy for pancreatic fistula with islet autotransplantation at our institution. From August 2007 to December 2012, 5 patients underwent IAT after completion pancreatectomy for pancreatic fistula after hemipancreatoduodenectomy for carcinoma. Islets were isolated from the pancreatic tail with the use of digestion with collagenase. Nonpurified islet suspension was infused into the portal vein during surgery. The median number of islets transplanted was 175,000 islet equivalents (range, 70,000–365,000). One patient died after surgery for reasons unrelated to IAT. Another 3 patients had stable diabetes with partial graft function (fasting C-peptide levels 0.23, 0.41, and 0.61 nmol/L and HbA1c 4.8%, 4.6%, and 6.9% at 24, 24 and 9 months after IAT, respectively). The 1st patient, with pancreatic head carcinoma, was alive 28 months after IAT with lymph node and liver recurrence since 18 months after IAT. The 2nd patient, with gall bladder and distal bile duct carcinoma, died 47 months after IAT with tumor recurrence. The 3rd patient, with ampullary carcinoma, died 12 months after IAT with local recurrence and solitary liver metastasis. The last patient had been off insulin 9 months after IAT without tumor recurrence (fasting C-peptide, 0.89 nmol/L; HbA1c, 4.2%). Autotransplantation of pancreatic islets isolated from the residual pancreatic tissue in patients who previously underwent hemipancreatoduodenectomy for cancer may provide stable glucose control and thus improve quality of life. In this small series we did not observe early development of multiple liver metastases caused by islet suspension contamination with malignant cells. Oncologic outcome of the patients was not worse than what would be expected without IAT.
2012-09-07 | Pancreatico-biliary endoscopic ultrasound: A systematic review of the levels of evidence, performance and outcomes
Our aim was to record pancreaticobiliary endoscopic ultrasound (EUS) literature of the past 3 decades and evaluate its role based on a critical appraisal of published studies according to levels of evidence (LE).Original research articles (randomized controlled trials, prospective and retrospective studies), meta-analyses, reviews and surveys pertinent to gastrointestinal EUS were included.All articles published until September 2011 were retrieved from PubMed and classified according to specific disease entities, anatomical subdivisions and therapeutic applications of EUS.The North of England evidencebased guidelines were used to determine LE.A total of 1089 pertinent articles were reviewed.Published research focused primarily on solid pancreatic neoplasms, followed by disorders of the extrahepatic biliary tree, pancreatic cystic lesions, therapeutic-interventional EUS, chronic and acute pancreatitis.A uniform observation in all six categories of articles was the predominance of LE Ⅲ studies followed by LE Ⅳ, Ⅱb, Ⅱa, Ⅰb and Ⅰ a, in descending order.EUS remains the most accurate method for detecting small (< 3 cm) pancreatic tumors, ampullary neoplasms and small (< 4 mm) bile duct stones, and the best test to define vascular invasion in pancreatic and peri-ampullary neoplasms.Detailed EUS imaging, along with biochemical and molecular cyst fluid analysis, improve the differentiation of pancreatic cysts and help predict their malignant potential.Early diagnosis of chronic pancreatitis appears feasible and reliable.Novel imaging techniques (contrast-enhanced EUS, elastography) seem promising for the evaluation of pancreatic cancer and autoimmune pancreatitis.Therapeutic applications currently involve pancreaticobiliary drainage and targeted fine needle injection-guided antitumor therapy.Despite the ongoing development of extra-corporeal imaging modalities, such as computed tomography, magnetic resonance imaging, and positron emission tomography, EUS still holds a leading role in the investigation of the pancreaticobiliary area.The major challenge of EUS evolution is its expanding therapeutic potential towards an effective and minimally invasive management of complex pancreaticobiliary disorders.
antibodies
2026-07-06 | Immunohistochemical profiling of ampullary carcinoma: Molecular subtypes, prognostic markers, and the role of Claudin-18.
Ampullary cancer is a rare malignancy, histologically divided into intestinal and pancreatobiliary subtypes based on histomorphological and immunophenotypic features as they arise from different epithelial origins and exhibit distinct biological behavior, treatment responses, and clinical outcomes. However, current histomorphological and immunohistochemical classification often remains ambiguous, complicating accurate subtype assignment to guide therapeutic approaches. In this retrospective study of 125 ampullary carcinoma cases, we performed immunohistochemical profiling using a panel of markers including CDX2, CK20, mucins (MUC1, MUC2, MUC5AC), and claudins (CLDN1-4, CLDN7, CLDN18) to refine subtype classification and identify prognostic biomarkers. Hierarchical clustering based on marker expression H-scores revealed two molecular subtypes corresponding to intestinal and pancreatobiliary differentiation. While CDX2 and CK20 are routinely used in combination for diagnosis, other markers, particularly CLDN3, CLDN7, and MUC5AC, demonstrated superior diagnostic and prognostic performance to CDX2. CK20, by contrast, remained a robust marker of intestinal differentiation and favorable outcome. Pancreatobiliary-type tumors exhibited elevated MUC1, MUC5AC, and CLDN18 expression, and were associated with advanced stage, invasive features, and significantly worse survival. Multivariate analysis showed high MUC5AC and apical MUC1 expression to be associated with adverse outcomes, whereas CLDN1, CLDN3 and CLDN4 expression were linked to improved survival. Membranous CLDN18 expression was more common in pancreatobiliary-type ampullary cancer, making it a potential therapeutic target. These findings underscore the diagnostic and prognostic value of multiplex immunohistochemical profiling. We propose retaining CK20 but replacing CDX2 with a more informative marker, namely CLDN3, to enhance classification and therapeutic stratification.
2026-06-24 | A Case of Unresectable Ampulla of Vater Carcinoma Successfully Treated with Conversion Surgery Following Sequential Systemic Chemotherapy Including Durvalumab.
The criteria for indications and postoperative treatment strategies for conversion surgery in patients with unresectable ampulla of Vater carcinoma with distant metastasis have not been clarified. We present an unusual case of a patient with initially unresectable ampulla of Vater carcinoma with multiple liver metastases who underwent conversion surgery after treatment with durvalumab and gemcitabine plus cisplatin. A 69-year-old male was found to have ampulla of Vater carcinoma with multiple liver metastases. A diagnosis of unresectable ampulla of Vater carcinoma was made, and the treatment plan was chemotherapy. After 12 cycles of gemcitabine, cisplatin, and S-1, the tumor did not shrink. Six cycles of gemcitabine, cisplatin, and durvalumab were then administered. The metastases were obscured on imaging; however, micrometastases were observed on the liver surface by staging laparoscopy. Six additional cycles of gemcitabine, cisplatin, and durvalumab were administered, and the disappearance of metastases was confirmed by staging laparoscopy. The patient then underwent conversion surgery with subtotal gastric-preserving pancreaticoduodenectomy. Pathology revealed a complete response, and radical resection was successfully performed. Immunostaining of tissue collected during endoscopic ultrasound-guided acquisition revealed less than 1% expression of programmed death ligand-1. Sequential systemic chemotherapy including durvalumab is suggested as a useful future treatment option and may contribute to conversion surgery for unresectable ampulla of Vater carcinoma.
2025-08-30 | Efficacy and Safety of the Combination of Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: A Real-World Retrospective Cohort Study.
Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice.
2025-06-04 | Real-world experience of postoperative adjuvant chemoimmunotherapy in patients with pancreatobiliary subtype ampullary adenocarcinoma.
The efficacy and safety of chemotherapy combined with programmed cell death protein-1 (PD-1) inhibitors in postoperative adjuvant therapy of pancreatobiliary subtype ampullary adenocarcinoma (AAC) are uncertain. This study aims to evaluate the effect of such treatment on the survival of this patient population. We retrospectively collected patients with pancreatobiliary subtype AAC who underwent surgical treatment at the Sun Yat-sen Memorial Hospital from January 2018 to December 2022. Patients with high-risk recurrence factors after surgery were divided into surgery alone group, adjuvant chemotherapy group, and adjuvant chemoimmunotherapy group. The Kaplan-Meier method was used to plot survival curves, and the Log-Rank method was used to compare the differences in overall survival (OS) and recurrence-free survival (RFS) between groups. A total of 71 people were enrolled, including 24 patients received surgery alone, 31 patients received adjuvant chemotherapy, and 16 patients received adjuvant chemoimmunotherapy. The median time of clinical follow-up was 17.8 [IQR 8.3-28.4] months. The 1-year OS rates of the surgery alone group, adjuvant chemotherapy group, and adjuvant chemoimmunotherapy were 41.7%, 71.0%, and 93.3%, respectively. The 2-year OS rates were 28.6%, 47.7%, and 84.0%, respectively. The median OS was 6.8 months and 22.1 months, but the adjuvant chemoimmunotherapy group did not reach (P = .0002). The median RFS was 4.7 months, 15.7 months, and 14.8 months, respectively, but the differences were not statistically significant (P = .0613). Univariate and multivariate Cox analysis results showed that tumor size >2.3 cm (HR = 2.06, 95% CI, 1.06-4.04; P = .034) and the treatment regimen were independent factors affecting prognosis, compared to surgery alone and adjuvant chemotherapy (HR = 0.521, 95% CI, 0.26-1.04; P = .065), adjuvant chemoimmunotherapy (HR = 0.106, 95% CI, 0.02-0.47; P = .003) significantly improves patient survival. There was no statistically significant difference in any complications between the 3 groups (P > .05). Compared with the adjuvant chemotherapy group, patients in the adjuvant chemoimmunotherapy group are more likely to experience hypothyroidism (P = .044) and pruritus (P = .022). There is no statistically significant difference in other AEs between the 2 groups (P > .05). Compared with surgery alone or adjuvant chemotherapy, patients with pancreatobiliary subtype AAC who received adjuvant chemoimmunotherapy showed better OS, and the drug-related toxicity was acceptable.
2025-02-04 | Update for: New developments in systemic therapy for advanced biliary tract cancer.
Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gallbladder, ampullary carcinoma, and intrahepatic cholangiocarcinoma are often identified at advanced stages. The standard therapy for advanced biliary tract cancer has been a combination of cytotoxic agents. Globally, gemcitabine plus cisplatin has been the standard first-line regimen, whereas gemcitabine plus cisplatin plus S-1 and gemcitabine plus S-1 have also been the standard regimens in Japan. Recently, treatment strategies have been updated. As first-line systemic therapy, the addition of an immune checkpoint inhibitor, such as durvalumab or pembrolizumab, to gemcitabine plus cisplatin has been shown to prolong overall survival compared with gemcitabine plus cisplatin. These combined immunotherapies are widely used in clinical practice as internationally standard first-line regimens. Regarding second-line treatment after a gemcitabine-based regimen, fluorouracil and folinic acid plus oxaliplatin have been the standard regimen. Additionally, FGFR2 fusion gene/rearrangement, mutations of IDH1/2, KRAS, and BRAF, and overexpression of HER2 are promising therapeutic targets for which the effectiveness of each targeted therapy has been reported, at this time, as a second-line or later treatment.
other
2026-07-01 | Transcriptomic-based molecular classification of ampullary adenocarcinoma.
Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy with markedly variable clinical outcomes, underscoring the urgent need for molecularly informed classification and personalized therapeutic strategies. Current AMPAC classification relies primarily on morphological and immunohistochemical criteria, which lack prognostic accuracy and fail to capture the underlying molecular and tumor microenvironment heterogeneity. In this study, we integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and clinicopathological data to elucidate the molecular architecture of AMPAC and introduced a transcriptomic-based molecular classification (AMS). The AMS categorized patients into two molecular subtypes: mesenchymal AMPAC (AMS-M) and classical AMPAC (AMS-C). The AMS-M demonstrated increased epithelial-mesenchymal transition (EMT) and stromal activation, correlating with basal-like subtypes associated with unfavorable prognosis. In contrast, AMS-C tumors exhibited metabolic and differentiation programs with relatively preserved immune infiltration. Importantly, we identified MUC16 as a pivotal biomarker specifically overexpressed in AMS-M tumors. MUC16 knockout markedly reversed EMT, attenuated invasive and migratory capacities, and restored chemosensitivity in both cell lines and their xenograft models. Collectively, our findings establish AMS as a prognostically and therapeutically informative molecular classification framework for AMPAC, unveil the critical role of the tumor microenvironment in AMPAC heterogeneity, and provide a translational foundation for precision oncology in this rare tumor.
2023-12-09 | Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment
Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. Histologic examination and immunohistochemistry have been traditionally used to categorize ampullary tumors into intestinal, pancreatobiliary or mixed subtypes. Intestinal-subtype tumors may exhibit improved survival versus the pancreatobiliary subtype, although studies on the prognostic value of immunomorphologic classification have been inconsistent. Genomic classifiers hold the promise of greater reliability, while providing potential targets for precision oncology. Multi-institutional collaboration will be necessary to better understand how molecular classification can guide type and sequencing of multimodality therapy.
2023-03-31 | Data from Genome-Derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care
<div>AbstractPurpose:<p>The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management.</p>Experimental Design:<p>The hidden-genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile-duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA-sequencing data from ampullary adenocarcinomas. Genomic classification (i.e., colorectal vs. pancreatic) was correlated with standard histologic classification [i.e., intestinal (INT) vs. pancreatobiliary (PB)] and clinical outcome.</p>Results:<p>Colorectal genomic subtype prediction was primarily influenced by mutations in <i>APC</i> and <i>PIK3CA</i>, tumor mutational burden, and DNA mismatch repair (MMR)–deficiency signature. Pancreatic genomic-subtype prediction was dictated by <i>KRAS</i> gene alterations, particularly <i>KRAS</i> G12D, <i>KRAS</i> G12R, and <i>KRAS</i> G12V. Distal bile-duct adenocarcinoma genomic subtype was most influenced by copy-number gains in the <i>MDM2</i> gene. Despite high (73%) concordance between immunomorphologic subtype and genomic category, there was significant genomic heterogeneity within both histologic subtypes. Genomic scores with higher colorectal probability were associated with greater survival compared with those with a higher pancreatic probability.</p>Conclusions:<p>The genomic classifier provides insight into the heterogeneity of ampullary adenocarcinoma and improves stratification, which is dictated by the proportion of colorectal and pancreatic genomic alterations. This approach is reproducible with available molecular testing and obviates subjective histologic interpretation.</p></div>
2018-06-01 | IDDF2018-ABS-0244 Screening of chromosomal alterations, K-RAS mutations and DNA methylation status in APC promoter of familial and sporadic cases with carcinoma of the ampulla of yater in tamil nadu population
hypomethylation, p=0.009) despite modest but significant upregulation of expression (0.24, p=8.20E-03).Conclusions Our findings could be the first to suggest that the up-and downregulation of BAG3 and EIF6 expression in MC could be due to hypo-and hypermethylation, however, their specific roles in MC tumourigenesis remains to be elucidated.Beyond mucin genes, upregulation of genes rarely associated with CRC was also observed, suggesting new insight into the aetiology of MC resistance to therapies and their roles as a potential target for MC treatment may be worth investigating.
small molecules
2026-07-02 | Squamous cell carcinoma of the ampulla of Vater: a rare case report and review of the literature
Introduction: Primary squamous cell carcinoma (SCC) of the ampulla of Vater is an exceptionally rare malignancy, with only a limited number of cases reported in the literature. Its pathogenesis, biological behavior, and optimal management remain poorly defined. Case presentation: We report the case of a 68-year-old man presenting with several weeks of atypical abdominal discomfort and cholestatic liver enzyme abnormalities. Upper gastrointestinal endoscopy revealed an ulcerated ampullary lesion, and biopsy confirmed moderately to poorly differentiated SCC. Cross-sectional imaging excluded metastatic disease. The patient underwent pylorus-preserving pancreaticoduodenectomy. Histopathological analysis confirmed primary SCC (pT2N0M0) with negative margins (R0 resection). Adjuvant chemotherapy with cisplatin and 5-fluorouracil was initiated 6 weeks postoperatively, with a planned duration of 6 months. The patient remains disease-free at 6-month follow-up. Discussion: Ampullary SCC is rare but not unique, with several cases reported. Surgical resection remains the cornerstone of treatment. Adjuvant therapy is extrapolated from other SCCs due to a lack of evidence. Prognosis appears variable, with better outcomes in node-negative disease. Conclusion: This case highlights the importance of accurate histopathological diagnosis and reinforces the role of radical surgical resection. Further case accumulation is required to define optimal management strategies.
2026-06-26 | Exploring the Role of MET Gene as a Potential Biomarker and Therapeutic Target in Ampullary Cancer.
The incidence of Ampullary carcinoma (AC) has dramatically increased. Nearly 50% of patients develop recurrence indicating need for additional prognostic markers and treatment options. Emerging evidence suggests that Mesenchymal Epithelial Transition (MET) genes play a role in tumorigenesis and can be a useful therapeutic target, however, its role in AC remains unexplored. This study investigated the methylation status using methylation specific PCR, mRNA expression using quantitative PCR and protein expression using Immunohistochemistry of the MET proto-oncogene in 61 surgically resected AC specimens and further examined its co-expression with HER2. Our findings revealed MET promoter hypomethylation (68.85%), increased expression of MET at mRNA (67.21%) and protein level (54%) in ACs patients. Significant correlation was observed between both hypomethylation and increased mRNA expression (P=0.026; P<0.000), and MET mRNA and protein expression (P=0.037). Further, MET expression was notably higher in early stage (P=0.003) and Intestinal-type (84.21%) than Pancreatobiliary type (PB-type) (61.76%) (P=0.199). Additionally, co-expression of MET and HER2 receptors occurred in a significant subset of cases in AC suggesting receptor tyrosine kinase convergence (P=0.014). In silico analysis of the GSE60979, dataset corroborated these findings, showing increased MET and ERBB2 (HER2) expression in tumor samples compared to normal tissues. At a median follow-up of 34 months the mean survival of AC patient was 37.3±2.5 months. These findings demonstrate that MET dysregulation is a recurrent molecular event in ampullary carcinoma and support further investigation of MET and HER2 co-expression as a basis for future mechanistic and therapeutic studies.
2026-05-27 | A first-in-human phase I/II study evaluating CTS3497, an MTA-cooperative PRMT5 inhibitor, in advanced or metastatic MTAP -deficient solid tumors.
3115 Background: Protein arginine methyltransferase 5 (PRMT5) methylates multiple protein substrates with a variety of biological functions known to be dysregulated in cancer. CTS3497 is an orally available, brain-penetrable, MTA (methylthioadenosine) -cooperative PRMT5 inhibitor that preferentially targets the MTA-bound PRMT5 in MTAP (MTA phosphorylase) -deficient tumors and potently inhibits tumor growth in various preclinical models. Here we present clinical data from an ongoing Phase I/II study of CTS3497 in solid tumors (NCT06971523). Methods: Eligible pts with homozygous MTAP deletion (by next generation sequencing), or MTAP protein loss (by immunohistochemistry [IHC]) and advanced solid tumors in the dose-escalation stage received 50, 200, 300, 400 mg BID of CTS3497 orally, while pts in the dose-expansion stage were treated with 200, 300 or 400 mg BID until disease progression or intolerable toxicity. Efficacy, safety, PK, PD and biomarker profiles were evaluated. Results: As of 22 Jan 2026, 41 patients received ≥1 dose of CTS3497 treatment. No DLT was observed, and MTD was not reached; CTS3497 was well-tolerated. Most common (≥20%) treatment-related adverse events (TRAEs) were anemia (34%), white blood cell count decreased (32%), platelet count decreased (27%) and neutrophil count decreased (22%). The most common Grade ≥3 TRAE (occurring in ≥5% of patients) was platelet count decreased. No central nervous system (CNS) effects were reported. Among 21 centrally-confirmed MTAP-deficient, efficacy-evaluable patients, including 9 gastrointestinal (GI) cancers (ampullary cancer, biliary tract carcinoma, esophageal squamous cell carcinoma, gastric cancer and pancreatic ductal adenocarcinoma), 5 non-small cell lung cancer (NSCLC), 1 urothelial carcinoma and 6 rare cancers, the objective response rate (ORR) was 43%, and the disease control rate (DCR) was 91%. In GI cancers, the ORR and DCR were 56% and 89%. In NSCLC, the ORR and DCR were 60% and 80%. The exposures (Cmax, AUC0-24h) of CTS3497 increased in a linear, dose-proportional manner. The pharmacodynamic (PD) marker, plasma symmetric dimethylarginine (SDMA) level, showed a significant decrease. Conclusions: CTS3497 demonstrated a favorable safety profile and promising efficacy in heavily pretreated pts with MTAP-deficient advanced solid tumors, including GI cancers, NSCLC. Clinical trial information: NCT06971523 .
2026-04-17 | Germline Pathogenic Variants in Homologous Recombination Pathway Genes Are Frequent in Pancreatobiliary Ampullary Carcinoma.
Ampullary carcinoma (AMPCA) is a rare cancer classified into subtypes depending on the histologic appearance and epithelium of origin. To gain insights into the germline genetic factors driving predisposition to AMPCA, the analysis focused on the role of homologous recombination (HR) genes in its oncogenesis. We analyzed germline testing results from 26,159 patients with cancer undergoing clinical tumor-normal sequencing from May 2015 to November 2022, of which 112 individuals had AMPCA. Germline and somatic alteration profiles were analyzed for the different histologic subtypes of AMPCA, and a subset of cases were selected for whole-genome sequencing (WGS) to determine the presence of HR deficiency (HRD). Pathogenic variants in HR pathway genes were identified in 17/72 (23.6%), 0/26 (0.0%), and 1/14 (7.1%) patients with pancreatobiliary (PAMPCA), intestinal (IAMPCA), and other (mixed, neuroendocrine, adenosquamous) subtypes of AMPCA, respectively. Germline pathogenic variants in core HR genes, including BRCA1, BRCA2, and PALB2, were exclusively detected in the PAMPCAs, and one ATM germline pathogenic variant was detected in a case with mixed intestinal and pancreatobiliary features. HRD features were detected in all four representative PAMPCA tumor samples that underwent WGS and HRDetect analysis. Germline pathogenic variants in the HR pathway genes drive oncogenesis in a large subset of PAMPCAs. These findings highlight the importance of germline genetic testing for patients with PAMPCA for informing therapy and assessing familial risk.
2026-03-13 | Histopathologic Subtype as a Determinant of Prognosis and Chemotherapy Benefit in Resected Ampullary Adenocarcinoma.
Ampullary adenocarcinoma (AAC) is a rare malignancy with heterogeneous biological behavior. Although surgical resection is the only potentially curative option, the prognostic role of histopathologic features and adjuvant chemotherapy (AC) remains unclear. Consecutive patients undergoing curative-intent pancreatoduodenectomy for AAC at the University of Colorado Hospital between January 2013 and May 2025 were retrospectively reviewed. Clinicopathologic variables associated with overall (OS) and recurrence-free survival (RFS) were analyzed using multivariable Cox regression. Ninety-seven patients were included. Median OS was 93.9 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 67%, 59%, and 46%. Older age (HR, 3.79; 95% CI, 1.71-8.41), lymph node (LN) involvement (HR, 4.92; 95% CI, 1.87-12.93), and R1 margin (HR, 4.33; 95% CI, 1.09-17.25) independently predicted poorer OS. The pancreatobiliary subtype (pbAAC) showed worse OS than the intestinal subtype (iAAC) (5-year OS, 48% vs. 75%; p = 0.012). In pbAAC, LN metastasis (HR, 4.16; 95% CI, 1.31-13.18) and R1 margin (HR, 5.47; 95% CI, 1.10-27.20) predicted worse OS, whereas AC was associated with improved survival (HR, 0.404; 95% CI, 0.18-0.91). No AC benefit was observed in iAAC (p = 0.323). Histopathologic subtype is a key prognostic factor in AAC, with AC associated with better survival in pbAAC.
proteins
2022-12-25 | Noninvasive endoscopic hemostasis technique for post‐papillectomy bleeding using a novel self‐assembling peptide (with video)
Abstract Although a novel hemostatic agent has been used for endoscopic mucosal resection in submucosal dissection, there are few case reports of its use in pancreato‐biliary endoscopic procedures. We describe a case of post‐endoscopic papillectomy bleeding in which endoscopic hemostasis was achieved using a novel hemostatic agent.
2011-09-08 | Carcinoid tumors of the duodenum and the ampulla of Vater: current diagnostic and therapeutic approach in a series of 8 patients. Case series.
To describe the specific characteristics of duodenal/perivaterian carcinoids and to analyze the diagnostic/therapeutic approach. Eight patients were included in our study. Symptoms on admission included dyspepsia, upper gastrointestinal (GI) bleeding and anemia. All patients underwent upper GI endoscopy and gastrointestinal peptides (gastrin) and neuroendocrine markers (Chromogranin-A, CgA) measurement. Imaging studies were performed in all patients, including OCTREOSCAN, while in patients with ACs MRCP or ERCP was also performed, when necessary. Definite diagnosis was confirmed by histopathologic examination. Polypoid masses (carcinoids) were revealed at duodenal bulb and ampulla of Vater, in 5 and 3 patients, respectively. Serum gastrin was moderately increased in 4 patients, while in one patient it was more than 1000 pg/ml. Serum CgA was moderately increased in one patient, in whom OCTREOSCAN detected a solitary hepatic metastasis. Two patients with DC, of less than 1 cm of diameter, were treated by endoscopic polypectomy, while all the other patients underwent surgery. The patient with hepatic metastasis and positive OCTREOSCAN received also Octreotide LAR, resulting in stabilization of disease. No recurrence or metastases were observed during follow-up (range : 1.5-9.6 years). In DC tumors <1 cm endoscopic excision with close follow-up is an adequate treatment, while in tumors >1 cm and in AC, surgical resection is the treatment of choice. In metastatic tumors, resection of the primary lesion with administration of somatostatin analogues may stabilize the disease and improve patient's quality of life.
2006-10-31 | Octreotide hardens the pancreas.
Leakage from pancreaticojejunostomy and development of pancreatic fistulas are the major postoperative complications in patients undergoing duodenopancreatectomy. The risk of developing these complications is higher when surgery is performed on a soft pancreas. A recent report suggests that octreotide hardens the pancreas when given intraoperatively. The present study aims at verifying this observation by measuring tissue hardness of the pancreas by a commercially available durometer in pigs with and without octreotide pretreatment. Three groups of pigs were investigated: Group 1 (n=6) received no treatment; group 2 (n=6) was treated with 3x100 microg octreotide for 1 day; group 3 (n=6) for 5 days. Thereafter, animals were killed and the pancreas was harvested for performing measurements: Tissue hardness was assessed by a commercially available durometer, and a suture holding test was performed using a Newton dynamometer. There was a significant increase in tissue hardness between untreated control animals [26.3+/-2.5 S.U. (shore units)] and animals with 1 day octreotide pretreatment (29.8+/-2.6 S.U.; p=0.04) as well as between the groups treated for 1 and 5 days (34.8+/-2.8 S.U.; p=0.01). Suture holding capacity was higher in animals treated for 5 days. The present study agrees with a recent report suggesting that octreotide hardens the pancreas. Octreotide pretreatment may therefore be an advantage when performing surgery on a soft pancreas, i.e., in patients scheduled for duodenopancreatectomy for ampullary carcinomas or circumscript pancreatic tumors not associated with chronic pancreatitis.
2005-03-22 | Intra-arterial bolus octreotide administration during Whipple procedure in patients with fragile pancreas: a novel technique for safer pancreaticojejunostomy.
Leakage from the pancreaticojujenostomy is the most serious complication of Whipple. Pancreatic fistula rate is higher in cases of fragile pancreas often seen in duodenal carcinomas and carcinomas of the ampulla of Vater. Octreotide administration has been used for the prevention of fistula formation through the subcutaneous route. Due to its physiologic effects to the pancreatic parenchyma the intra-arterial administration of octreotide could provide tissue hardening that allows for a technically easier anastomosis while maintaining its protective role for fistula formation. Octreotide was injected directly into the distal part of the gastroduodenal artery (GDA) in four patients undergoing Whipple for histologically proven periampullary cancer. Tissue hardening after octreotide administration was evident not only in surgeons' hands but in the intra-operative ultrasound as well. The three patients were discharged on day 9, 11, and 13; they had an uneventful postoperative course, while one patient had a minor bile leak from the choledojejunal anastomosis and was discharged on day 22. The intra-arterial administration of octreotide during Whipple is a safe procedure and provides tissue hardening thus making the performance of the anastomosis technically easier. The actual benefit in terms of morbidity, mortality, and fistula rate are to be further evaluated.
cell therapies
2024-12-21 | Establishment and characterization of a new intestinal-type ampullary carcinoma cell line, DPC-X3.
Ampullary carcinoma (AC) of the intestinal type represents a distinct variant within the broader category of ampullary neoplasms. The scarcity of pertinent cellular models has constrained investigations centered on this particular malignancy. This research effectively generated a cell line (CL) of intestinal-type AC (DPC-X3). This newly developed CL has been continuously cultured for 1 year and has demonstrated stable passaging exceeding 60 generations. Morphologically, DPC-X3 exhibited characteristic attributes of an epithelial tumor. The cell proliferation rate of DPC-X3 exhibited a doubling interval of 79 h. Short tandem repeat (STR) analysis validated the high consistency between DPC-X3 and the patient's primary tumor. Characteristically, DPC-X3 displayed sub diploid karyotypes, primarily featuring 44, XY inv (9), -18, -20, -22, and + mar. Under suspension culture conditions, DPC-X3 could efficiently form organoids, and DPC-X3 cells inoculated subcutaneously into NXG mice could form transplanted tumors. Drug susceptibility assays demonstrated that DPC-X3 resisted paclitaxel, oxaliplatin, 5-fluorouracil(5-FU), and gemcitabine. Immunohistochemical (IHC) evaluation revealed affirmative reactivity for CK7 and CK20 within DPC-X3 cells, while CDX2 exhibited no detectable expression. E-cadherin and Vimentin demonstrated positive immunoreactivity, whereas CEA and CA19-9 displayed faint positivity. The Ki-67 proliferation index was determined to be approximately 40%. DPC-X3 presents a valuable experimental platform for elucidating the pathogenesis of intestinal-type AC and can serve as a driver for drug development efforts.
2024-03-22 | Abstract 5150: An immunohistochemical survey of predictive biomarkers for immunotherapy in ampullary carcinoma identifies strata with unique prognostic signatures
Abstract Introduction: Carcinomas located in the ampulla of Vater are a low incidence malignancy. Therapeutic options for early stage disease largely consist of pancreaticoduodenectomy followed by adjuvant chemotherapy with or without radiation. We explored the localization of CD8 and CD3 positive cells in addition to PDL-1 staining and mismatch repair deficiency markers to gain insight into the potential applicability of immunotherapy for patients with this disease. Methods: Excess material from clinically diagnosed cases collected between 1997 - 2013 were used to construct a duplicate 0.6mm core tissue microarray (TMA). All cases were derived from the Vancouver Coastal Health Region. Immunohistochemical staining was performed with the following markers: CD8, CD3, PD-L1, and the mismatch repair (MMR) markers: MSH2, MSH6, MLH1 and PMS2. CD3 and CD8 were quantified using localization within the tissue. PD-L1 was considered positive with >1% of cells stating positive. MMR markers were confirmed using full section and cases with convincing loss of any MMR marker were considered MMR deficient. Univariable disease specific survival analysis was performed to identify unique prognostic signatures and contingency analysis was performed to identify co-expression of the aforementioned biomarkers. Results: Ninety-eight cases were evaluable for all markers. The median age of the cohort was 69 [41 - 84] years. Forty-two percent were female. Adjuvant chemotherapy was provided to 15% of patients with the remainder undergoing post-surgical observation. Almost 90% were pT3 or pT4 and 48% had regional lymph node metastasis. CD3+ T-cells were either localized in the tumor stroma only (59%) or in both the stroma and epithelial compartments (41%). CD8+ T-cells were principally located in the stroma (66%) and both the epithelial and stroma (24%). Ten percent of cases had no CD8+ T-cells. PD-L1 staining was found in 10% of cases. MMR deficiency was found in 5% of cases. Improved prognostic signatures were found for cases with CD3+ and CD8+ T-cells in both the epithelial and stromal compartments (p <= 0.02). A trend towards a negative prognostic signature was observed for MMR deficient cases and for PD-L1 positive cases. The only significant positive association between biomarkers was found for CD3+ and CD8+ in both the epithelial and stromal compartments. Conclusions: The results of this analysis suggest that enhancement of an immune response yielding an increase CD3+ and CD8+ T-cells in the epithelial compartment may have a beneficial effect on prognosis. The relative scarcity of MMR deficiency in this disease is within the expected prevalence supported by other studies. Further exploration of the potential role of immunotherapy in immune enhanced subgroups of ampullary cancers is warranted. Citation Format: Steve E. Kalloger, Joanna Karasinska, James Topham, Daniel J. Renouf, David F. Schaeffer. An immunohistochemical survey of predictive biomarkers for immunotherapy in ampullary carcinoma identifies strata with unique prognostic signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5150.
2024-01-24 | Elevated levels of peripheral Th17 cells and Th17-related cytokines in patients with periampullary adenocarcinoma.
Periampullary adenocarcinoma (PAC) is a malignant tumor originating at the ampulla of Vater, distal common bile duct, head of the pancreas, ampulla and duodenum. The levels of circulating Th17 cells and Th17-related cytokines in patients with PAC remain unreported. Therefore, the aim of this study was to determine the levels of circulating Th17 cells and Th17-related cytokines in patients with PAC. Flow cytometry was used to measure Th17 cell proportions in PBMCs from 60 PAC patients and 30 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-17A and IL-23 levels in serum samples, while quantitative reverse transcription polymerase chain reaction (qRT-PCR) assessed IL-17A mRNA expression and Th17-related transcription factors (RORγt and STAT3) in tissue samples. The findings showed a substantial increase in Th17 cell percentages, elevated concentrations of IL-17A and IL-23, and higher mRNA expression levels of IL-17A, RORγt, and STAT3 in patients with PAC when compared to healthy controls (HCs). Th17 cells play an important role in the pathogenesis of PAC and may represent potential therapeutic targets.
2014-07-01 | Pancreatic Islet Autotransplantation After Completion Pancreatectomy for Pancreatic Fistula After Hemipancreatoduodenectomy for Carcinoma
Pancreatic islet autotransplantation (IAT) has a potential to prevent brittle diabetes in patients after total pancreatectomy. Because of the fear of tumor spread, IAT has rarely been used in case of malignancy. We report our experience with patients who underwent hemipancreatoduodenectomy for carcinoma and later completion pancreatectomy for pancreatic fistula with islet autotransplantation at our institution. From August 2007 to December 2012, 5 patients underwent IAT after completion pancreatectomy for pancreatic fistula after hemipancreatoduodenectomy for carcinoma. Islets were isolated from the pancreatic tail with the use of digestion with collagenase. Nonpurified islet suspension was infused into the portal vein during surgery. The median number of islets transplanted was 175,000 islet equivalents (range, 70,000–365,000). One patient died after surgery for reasons unrelated to IAT. Another 3 patients had stable diabetes with partial graft function (fasting C-peptide levels 0.23, 0.41, and 0.61 nmol/L and HbA1c 4.8%, 4.6%, and 6.9% at 24, 24 and 9 months after IAT, respectively). The 1st patient, with pancreatic head carcinoma, was alive 28 months after IAT with lymph node and liver recurrence since 18 months after IAT. The 2nd patient, with gall bladder and distal bile duct carcinoma, died 47 months after IAT with tumor recurrence. The 3rd patient, with ampullary carcinoma, died 12 months after IAT with local recurrence and solitary liver metastasis. The last patient had been off insulin 9 months after IAT without tumor recurrence (fasting C-peptide, 0.89 nmol/L; HbA1c, 4.2%). Autotransplantation of pancreatic islets isolated from the residual pancreatic tissue in patients who previously underwent hemipancreatoduodenectomy for cancer may provide stable glucose control and thus improve quality of life. In this small series we did not observe early development of multiple liver metastases caused by islet suspension contamination with malignant cells. Oncologic outcome of the patients was not worse than what would be expected without IAT.
2012-09-07 | Pancreatico-biliary endoscopic ultrasound: A systematic review of the levels of evidence, performance and outcomes
Our aim was to record pancreaticobiliary endoscopic ultrasound (EUS) literature of the past 3 decades and evaluate its role based on a critical appraisal of published studies according to levels of evidence (LE).Original research articles (randomized controlled trials, prospective and retrospective studies), meta-analyses, reviews and surveys pertinent to gastrointestinal EUS were included.All articles published until September 2011 were retrieved from PubMed and classified according to specific disease entities, anatomical subdivisions and therapeutic applications of EUS.The North of England evidencebased guidelines were used to determine LE.A total of 1089 pertinent articles were reviewed.Published research focused primarily on solid pancreatic neoplasms, followed by disorders of the extrahepatic biliary tree, pancreatic cystic lesions, therapeutic-interventional EUS, chronic and acute pancreatitis.A uniform observation in all six categories of articles was the predominance of LE Ⅲ studies followed by LE Ⅳ, Ⅱb, Ⅱa, Ⅰb and Ⅰ a, in descending order.EUS remains the most accurate method for detecting small (< 3 cm) pancreatic tumors, ampullary neoplasms and small (< 4 mm) bile duct stones, and the best test to define vascular invasion in pancreatic and peri-ampullary neoplasms.Detailed EUS imaging, along with biochemical and molecular cyst fluid analysis, improve the differentiation of pancreatic cysts and help predict their malignant potential.Early diagnosis of chronic pancreatitis appears feasible and reliable.Novel imaging techniques (contrast-enhanced EUS, elastography) seem promising for the evaluation of pancreatic cancer and autoimmune pancreatitis.Therapeutic applications currently involve pancreaticobiliary drainage and targeted fine needle injection-guided antitumor therapy.Despite the ongoing development of extra-corporeal imaging modalities, such as computed tomography, magnetic resonance imaging, and positron emission tomography, EUS still holds a leading role in the investigation of the pancreaticobiliary area.The major challenge of EUS evolution is its expanding therapeutic potential towards an effective and minimally invasive management of complex pancreaticobiliary disorders.
antibodies
2026-07-06 | Immunohistochemical profiling of ampullary carcinoma: Molecular subtypes, prognostic markers, and the role of Claudin-18.
Ampullary cancer is a rare malignancy, histologically divided into intestinal and pancreatobiliary subtypes based on histomorphological and immunophenotypic features as they arise from different epithelial origins and exhibit distinct biological behavior, treatment responses, and clinical outcomes. However, current histomorphological and immunohistochemical classification often remains ambiguous, complicating accurate subtype assignment to guide therapeutic approaches. In this retrospective study of 125 ampullary carcinoma cases, we performed immunohistochemical profiling using a panel of markers including CDX2, CK20, mucins (MUC1, MUC2, MUC5AC), and claudins (CLDN1-4, CLDN7, CLDN18) to refine subtype classification and identify prognostic biomarkers. Hierarchical clustering based on marker expression H-scores revealed two molecular subtypes corresponding to intestinal and pancreatobiliary differentiation. While CDX2 and CK20 are routinely used in combination for diagnosis, other markers, particularly CLDN3, CLDN7, and MUC5AC, demonstrated superior diagnostic and prognostic performance to CDX2. CK20, by contrast, remained a robust marker of intestinal differentiation and favorable outcome. Pancreatobiliary-type tumors exhibited elevated MUC1, MUC5AC, and CLDN18 expression, and were associated with advanced stage, invasive features, and significantly worse survival. Multivariate analysis showed high MUC5AC and apical MUC1 expression to be associated with adverse outcomes, whereas CLDN1, CLDN3 and CLDN4 expression were linked to improved survival. Membranous CLDN18 expression was more common in pancreatobiliary-type ampullary cancer, making it a potential therapeutic target. These findings underscore the diagnostic and prognostic value of multiplex immunohistochemical profiling. We propose retaining CK20 but replacing CDX2 with a more informative marker, namely CLDN3, to enhance classification and therapeutic stratification.
2026-06-24 | A Case of Unresectable Ampulla of Vater Carcinoma Successfully Treated with Conversion Surgery Following Sequential Systemic Chemotherapy Including Durvalumab.
The criteria for indications and postoperative treatment strategies for conversion surgery in patients with unresectable ampulla of Vater carcinoma with distant metastasis have not been clarified. We present an unusual case of a patient with initially unresectable ampulla of Vater carcinoma with multiple liver metastases who underwent conversion surgery after treatment with durvalumab and gemcitabine plus cisplatin. A 69-year-old male was found to have ampulla of Vater carcinoma with multiple liver metastases. A diagnosis of unresectable ampulla of Vater carcinoma was made, and the treatment plan was chemotherapy. After 12 cycles of gemcitabine, cisplatin, and S-1, the tumor did not shrink. Six cycles of gemcitabine, cisplatin, and durvalumab were then administered. The metastases were obscured on imaging; however, micrometastases were observed on the liver surface by staging laparoscopy. Six additional cycles of gemcitabine, cisplatin, and durvalumab were administered, and the disappearance of metastases was confirmed by staging laparoscopy. The patient then underwent conversion surgery with subtotal gastric-preserving pancreaticoduodenectomy. Pathology revealed a complete response, and radical resection was successfully performed. Immunostaining of tissue collected during endoscopic ultrasound-guided acquisition revealed less than 1% expression of programmed death ligand-1. Sequential systemic chemotherapy including durvalumab is suggested as a useful future treatment option and may contribute to conversion surgery for unresectable ampulla of Vater carcinoma.
2025-08-30 | Efficacy and Safety of the Combination of Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: A Real-World Retrospective Cohort Study.
Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice.
2025-06-04 | Real-world experience of postoperative adjuvant chemoimmunotherapy in patients with pancreatobiliary subtype ampullary adenocarcinoma.
The efficacy and safety of chemotherapy combined with programmed cell death protein-1 (PD-1) inhibitors in postoperative adjuvant therapy of pancreatobiliary subtype ampullary adenocarcinoma (AAC) are uncertain. This study aims to evaluate the effect of such treatment on the survival of this patient population. We retrospectively collected patients with pancreatobiliary subtype AAC who underwent surgical treatment at the Sun Yat-sen Memorial Hospital from January 2018 to December 2022. Patients with high-risk recurrence factors after surgery were divided into surgery alone group, adjuvant chemotherapy group, and adjuvant chemoimmunotherapy group. The Kaplan-Meier method was used to plot survival curves, and the Log-Rank method was used to compare the differences in overall survival (OS) and recurrence-free survival (RFS) between groups. A total of 71 people were enrolled, including 24 patients received surgery alone, 31 patients received adjuvant chemotherapy, and 16 patients received adjuvant chemoimmunotherapy. The median time of clinical follow-up was 17.8 [IQR 8.3-28.4] months. The 1-year OS rates of the surgery alone group, adjuvant chemotherapy group, and adjuvant chemoimmunotherapy were 41.7%, 71.0%, and 93.3%, respectively. The 2-year OS rates were 28.6%, 47.7%, and 84.0%, respectively. The median OS was 6.8 months and 22.1 months, but the adjuvant chemoimmunotherapy group did not reach (P = .0002). The median RFS was 4.7 months, 15.7 months, and 14.8 months, respectively, but the differences were not statistically significant (P = .0613). Univariate and multivariate Cox analysis results showed that tumor size >2.3 cm (HR = 2.06, 95% CI, 1.06-4.04; P = .034) and the treatment regimen were independent factors affecting prognosis, compared to surgery alone and adjuvant chemotherapy (HR = 0.521, 95% CI, 0.26-1.04; P = .065), adjuvant chemoimmunotherapy (HR = 0.106, 95% CI, 0.02-0.47; P = .003) significantly improves patient survival. There was no statistically significant difference in any complications between the 3 groups (P > .05). Compared with the adjuvant chemotherapy group, patients in the adjuvant chemoimmunotherapy group are more likely to experience hypothyroidism (P = .044) and pruritus (P = .022). There is no statistically significant difference in other AEs between the 2 groups (P > .05). Compared with surgery alone or adjuvant chemotherapy, patients with pancreatobiliary subtype AAC who received adjuvant chemoimmunotherapy showed better OS, and the drug-related toxicity was acceptable.
2025-02-04 | Update for: New developments in systemic therapy for advanced biliary tract cancer.
Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gallbladder, ampullary carcinoma, and intrahepatic cholangiocarcinoma are often identified at advanced stages. The standard therapy for advanced biliary tract cancer has been a combination of cytotoxic agents. Globally, gemcitabine plus cisplatin has been the standard first-line regimen, whereas gemcitabine plus cisplatin plus S-1 and gemcitabine plus S-1 have also been the standard regimens in Japan. Recently, treatment strategies have been updated. As first-line systemic therapy, the addition of an immune checkpoint inhibitor, such as durvalumab or pembrolizumab, to gemcitabine plus cisplatin has been shown to prolong overall survival compared with gemcitabine plus cisplatin. These combined immunotherapies are widely used in clinical practice as internationally standard first-line regimens. Regarding second-line treatment after a gemcitabine-based regimen, fluorouracil and folinic acid plus oxaliplatin have been the standard regimen. Additionally, FGFR2 fusion gene/rearrangement, mutations of IDH1/2, KRAS, and BRAF, and overexpression of HER2 are promising therapeutic targets for which the effectiveness of each targeted therapy has been reported, at this time, as a second-line or later treatment.
other
2026-07-01 | Transcriptomic-based molecular classification of ampullary adenocarcinoma.
Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy with markedly variable clinical outcomes, underscoring the urgent need for molecularly informed classification and personalized therapeutic strategies. Current AMPAC classification relies primarily on morphological and immunohistochemical criteria, which lack prognostic accuracy and fail to capture the underlying molecular and tumor microenvironment heterogeneity. In this study, we integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and clinicopathological data to elucidate the molecular architecture of AMPAC and introduced a transcriptomic-based molecular classification (AMS). The AMS categorized patients into two molecular subtypes: mesenchymal AMPAC (AMS-M) and classical AMPAC (AMS-C). The AMS-M demonstrated increased epithelial-mesenchymal transition (EMT) and stromal activation, correlating with basal-like subtypes associated with unfavorable prognosis. In contrast, AMS-C tumors exhibited metabolic and differentiation programs with relatively preserved immune infiltration. Importantly, we identified MUC16 as a pivotal biomarker specifically overexpressed in AMS-M tumors. MUC16 knockout markedly reversed EMT, attenuated invasive and migratory capacities, and restored chemosensitivity in both cell lines and their xenograft models. Collectively, our findings establish AMS as a prognostically and therapeutically informative molecular classification framework for AMPAC, unveil the critical role of the tumor microenvironment in AMPAC heterogeneity, and provide a translational foundation for precision oncology in this rare tumor.
2023-12-09 | Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment
Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. Histologic examination and immunohistochemistry have been traditionally used to categorize ampullary tumors into intestinal, pancreatobiliary or mixed subtypes. Intestinal-subtype tumors may exhibit improved survival versus the pancreatobiliary subtype, although studies on the prognostic value of immunomorphologic classification have been inconsistent. Genomic classifiers hold the promise of greater reliability, while providing potential targets for precision oncology. Multi-institutional collaboration will be necessary to better understand how molecular classification can guide type and sequencing of multimodality therapy.
2023-03-31 | Data from Genome-Derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care
<div>AbstractPurpose:<p>The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management.</p>Experimental Design:<p>The hidden-genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile-duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA-sequencing data from ampullary adenocarcinomas. Genomic classification (i.e., colorectal vs. pancreatic) was correlated with standard histologic classification [i.e., intestinal (INT) vs. pancreatobiliary (PB)] and clinical outcome.</p>Results:<p>Colorectal genomic subtype prediction was primarily influenced by mutations in <i>APC</i> and <i>PIK3CA</i>, tumor mutational burden, and DNA mismatch repair (MMR)–deficiency signature. Pancreatic genomic-subtype prediction was dictated by <i>KRAS</i> gene alterations, particularly <i>KRAS</i> G12D, <i>KRAS</i> G12R, and <i>KRAS</i> G12V. Distal bile-duct adenocarcinoma genomic subtype was most influenced by copy-number gains in the <i>MDM2</i> gene. Despite high (73%) concordance between immunomorphologic subtype and genomic category, there was significant genomic heterogeneity within both histologic subtypes. Genomic scores with higher colorectal probability were associated with greater survival compared with those with a higher pancreatic probability.</p>Conclusions:<p>The genomic classifier provides insight into the heterogeneity of ampullary adenocarcinoma and improves stratification, which is dictated by the proportion of colorectal and pancreatic genomic alterations. This approach is reproducible with available molecular testing and obviates subjective histologic interpretation.</p></div>
2018-06-01 | IDDF2018-ABS-0244 Screening of chromosomal alterations, K-RAS mutations and DNA methylation status in APC promoter of familial and sporadic cases with carcinoma of the ampulla of yater in tamil nadu population
hypomethylation, p=0.009) despite modest but significant upregulation of expression (0.24, p=8.20E-03).Conclusions Our findings could be the first to suggest that the up-and downregulation of BAG3 and EIF6 expression in MC could be due to hypo-and hypermethylation, however, their specific roles in MC tumourigenesis remains to be elucidated.Beyond mucin genes, upregulation of genes rarely associated with CRC was also observed, suggesting new insight into the aetiology of MC resistance to therapies and their roles as a potential target for MC treatment may be worth investigating.
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