The use of histopathological subtyping in patients with ampullary cancer: a nationwide analysis

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Abstract

Background

Recent guidelines advise to subtype adenocarcinoma at the ampulla and papilla of Vater (here: ampullary cancer) as intestinal, pancreatobiliary, and mixed, because this has consequences for both prognosis and treatment. This nationwide study aimed to investigate how often histopathological subtyping is performed in daily clinical practice in patients with ampullary cancer.

Methods

Pathology reports of all patients with ampullary cancer were retrieved from the Dutch nationwide pathology database (PALGA, 1991-2020). Reports were assessed for the presence and methods used for the classification of these tumors into intestinal, pancreatobiliary, and mixed subtypes. The use of immunohistochemical markers was recorded.

Results

Overall, 5246 patients with ampullary cancer were included. In 1030 (19.6%) patients, a distinction between intestinal, pancreatobiliary, and mixed subtypes was made. Use of subtyping increased from 3% in 1991–1993 to 37% in 2018–2020. In 274 of the 1030 (26.6%) patients, immunohistochemistry was used to make this distinction. A gradual increase in the use of various immunohistochemical markers was seen over time since 2008, with cytokeratin 7, cytokeratin 20, and CDX2 being the most common. Staining of DPC4/SMAD4 was increasingly used since 2012.

Conclusion

Despite recent improvements in the use of subtyping in ampullary cancer, the distinction between intestinal, pancreatobiliary, and mixed subtypes is only made in a minority of patients. Nationwide efforts are required to standardize the pathological distinction of the various subtypes of ampullary cancer.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12957-022-02873-y.

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Most cited references 30

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Pathology Databanking and Biobanking in The Netherlands, a Central Role for PALGA, the Nationwide Histopathology and Cytopathology Data Network and Archive

M. Casparie, A Tiebosch, A Burger … (2007)

Since 1991, a nationwide histopathology and cytopathology network and archive is in operation in The Netherlands under the name PALGA, encompassing all sixty-four pathology laboratories in The Netherlands. The overall system comprises decentralized systems at the participating laboratories, a central databank, and a dedicated communication and information exchange tool. Excerpts of all histopathology and cytopathology reports are generated automatically at the participating laboratories and transferred to the central databank. Both the decentralized systems and the central system perform checks on the quality and completeness of excerpts. Currently, about 42 million records on almost 10 million patients are stored in the central databank. Each excerpt contains patient identifiers, including demographic data and the so-called PALGA diagnosis. The latter is structured along five classification axes: topography, morphology, function, procedure, and diseases. All data transfer and communication occurs electronically with encryption of patient and laboratory identifiers. All excerpts are continuously available to all participating pathology laboratories, thus contributing to the quality of daily patient care. In addition, external parties may obtain permission to use data from the PALGA system, either on an ongoing basis or on the basis of a specific permission. Annually, 40 to 60 applications for permission to use PALGA data are submitted. Among external users are the Dutch cancer registry, population-based screening programs for cancer of the uterine cervix and breast cancer in The Netherlands, and individual investigators addressing a range of research questions. Many scientific papers and theses incorporating PALGA data have been published already. In conclusion, the PALGA system is a unique system that requires a minimal effort on the part of the participating laboratories, while providing them a powerful tool in their daily practices.

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The role of TGF-β/SMAD4 signaling in cancer

Ming Wei Zhao, Lopa Mishra, Chu-Xia Deng (2018)

Transforming growth factor β (TGF-β) signaling pathway plays important roles in many biological processes, including cell growth, differentiation, apoptosis, migration, as well as cancer initiation and progression. SMAD4, which serves as the central mediator of TGF-β signaling, is specifically inactivated in over half of pancreatic duct adenocarcinoma, and varying degrees in many other types of cancers. In the past two decades, multiple studies have revealed that SMAD4 loss on its own does not initiate tumor formation, but can promote tumor progression initiated by other genes, such as KRAS activation in pancreatic duct adenocarcinoma and APC inactivation in colorectal cancer. In other cases, such as skin cancer, loss of SMAD4 plays an important initiating role by disrupting DNA damage response and repair mechanisms and enhance genomic instability, suggesting its distinct roles in different types of tumors. This review lists SMAD4 mutations in various types of cancer and summarizes recent advances on SMAD4 with focuses on the function, signaling pathway, and the possibility of SMAD4 as a prognostic indicator.

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Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.

Helmut Oettle, Stefan Post, Peter Neuhaus … (2007)

The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists. To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more. Open, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups. Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation ([control] n = 175). Primary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat). More than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank). Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas. isrctn.org Identifier: ISRCTN34802808.

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Author and article information

Contributors

Jacob de Bakker: j.debakker@amsterdamUMC.nl

Nicole van Grieken: nct.vangrieken@amsterdamUMC.nl

Journal

Journal ID (nlm-ta): World J Surg Oncol

Journal ID (iso-abbrev): World J Surg Oncol

Title: World Journal of Surgical Oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-7819

Publication date (Electronic): 24 December 2022

Publication date PMC-release: 24 December 2022

Publication date Collection: 2022

Volume: 20

Electronic Location Identifier: 406

Affiliations

[1 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Surgery, Amsterdam UMC, , Vrije Universiteit, ; Amsterdam, The Netherlands

[2 ]GRID grid.16872.3a, ISNI 0000 0004 0435 165X, Cancer Center Amsterdam, ; Amsterdam, The Netherlands

[3 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Medical Oncology, Amsterdam UMC, , University of Amsterdam, ; Amsterdam, The Netherlands

[4 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Surgery, Amsterdam UMC, , University of Amsterdam, ; Amsterdam, The Netherlands

[5 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Pathology, Amsterdam UMC, , Vrije Universiteit, ; Amsterdam, The Netherlands

Article

Publisher ID: 2873

DOI: 10.1186/s12957-022-02873-y

PMC ID: 9789567

PubMed ID: 36566267

SO-VID: a19e2040-6c40-4ff3-ad68-a84e98513cf3

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 25 September 2022

Date accepted : 8 December 2022

Custom metadata

ScienceOpen disciplines: Surgery

Keywords: ampullary cancer,histopathological subtype,intestinal type adenocarcinoma,pancreatobiliary adenocarcinoma,immunohistochemistry

Data availability:

ScienceOpen disciplines: Surgery

Keywords: ampullary cancer, histopathological subtype, intestinal type adenocarcinoma, pancreatobiliary adenocarcinoma, immunohistochemistry

The use of histopathological subtyping in patients with ampullary cancer: a nationwide analysis

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Supplementary Information

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Karger: Oncology

Most cited references 30

Pathology Databanking and Biobanking in The Netherlands, a Central Role for PALGA, the Nationwide Histopathology and Cytopathology Data Network and Archive

The role of TGF-β/SMAD4 signaling in cancer

Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.

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