Advertisement

Impact of histopathological type on the prognosis of ampullary carcinoma: A systematic review and meta-analysis

  • Author Footnotes
    1 These authors contributed equally to this manuscript.
    Dong Woo Shin
    Footnotes
    1 These authors contributed equally to this manuscript.
    Affiliations
    Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this manuscript.
    Sihyun Kim
    Footnotes
    1 These authors contributed equally to this manuscript.
    Affiliations
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
    Search for articles by this author
  • Kwangrok Jung
    Affiliations
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
    Search for articles by this author
  • Jae Hyup Jung
    Affiliations
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
    Search for articles by this author
  • Bomi Kim
    Affiliations
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
    Search for articles by this author
  • Jinwoo Ahn
    Affiliations
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea
    Search for articles by this author
  • Jaihwan Kim
    Affiliations
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea

    Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Jin-Hyeok Hwang
    Affiliations
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea

    Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Jong-chan Lee
    Correspondence
    Corresponding author. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea.
    Affiliations
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea

    Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this manuscript.
Published:October 09, 2022DOI:https://doi.org/10.1016/j.ejso.2022.10.001

      Highlights

      • Prognostic implications of ampullary carcinoma (AC) subtypes remain unclear.
      • Histological AC types: intestinal (INT-AC) and pancreatobiliary (PB-AC) subtypes.
      • PB-AC (more aggressive) had a significantly shorter OS than INT-AC.
      • Recommend routine histopathologic classification even without immunohistochemistry.

      Abstract

      Histologically, ampullary carcinomas (ACs) can be classified into intestinal (INT-AC) and pancreatobiliary (PB-AC) subtypes. However, the prognostic implications of these subtypes remain unclear. This study aimed to evaluate the impact of the histopathologic phenotype of ACs on survival following pancreaticoduodenectomy. We searched PubMed, Embase, and Medline for studies published in English from 1994 to 2021. A meta-analysis was performed using Review Manager 5.3. The primary endpoint was overall survival (OS). We identified 3,890 articles; of these, 37 articles involving 3,455 participants (1,659 INT-ACs and 1,796 PB-ACs) were included. Patients in the PB-ACs group had significantly shorter OS than those in the INT-ACs group (hazard ratio [HR]: 1.79, 95% confidence interval [95% CI]: 1.51–2.13, p < 0.001, I2 = 61%). A similar tendency was observed in the immunohistochemistry staining group (HR: 1.76, 95% CI: 1.33–2.33, p < 0.001, I2 = 67%), which included 24 studies and 1,638 patients, and the non-immunohistochemistry group (HR: 1.84, 95% CI: 1.53–2.22, p = 0.04, I2 = 46%), which included 13 studies and 1,817 patients. Subgroup analysis revealed that patients with PB-AC had higher frequencies of advanced (III, IV) and pT3–4 stage AC, lymph node metastasis, poorly differentiated tumor, positive surgical margins, lymphovascular invasion, and perineural invasion, than those with INT-AC. Patients with PB-AC had a significantly shorter OS than those with INT-AC due to a higher aggressiveness. Because the histopathologic subtype is a major prognostic factor in patients with resected AC, routine histopathologic classification should be considered even in clinical settings without immunohistochemistry.

      Keywords

      Abbreviations:

      AC (ampullary carcinoma), HR (hazard ratio), IHC (immunohistochemistry), INT-AC (intestinal AC), OR (odds ratio), OS (overall survival), PB-AC (pancreatobiliary AC), MOOSE (Meta-analyses Of Observational Studies in Epidemiology)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Surgical Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Zheng-Pywell R.
        • Reddy S.
        • Ampullary Cancer
        Surg Clin. 2019; 99: 357-367
        • Ramai D.
        • et al.
        Demographics, tumor characteristics, treatment, and clinical outcomes of patients with ampullary cancer: a Surveillance, Epidemiology, and End Results (SEER) cohort study.
        Minerva Gastroenterol Dietol. 2019; 65: 85-90
        • Albores-Saavedra J.
        • et al.
        Cancers of the ampulla of vater: demographics, morphology, and survival based on 5,625 cases from the SEER program.
        J Surg Oncol. 2009; 100: 598-605
        • Kim W.S.
        • et al.
        Clinical significance of pathologic subtype in curatively resected ampulla of vater cancer.
        J Surg Oncol. 2012; 105: 266-272
        • Katz M.H.
        • et al.
        Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma.
        Ann Surg Oncol. 2009; 16: 836-847
        • Nienhuijs S.W.
        • et al.
        Nationwide improvement of only short-term survival after resection for pancreatic cancer in The Netherlands.
        Pancreas. 2012; 41: 1063-1066
        • Conroy T.
        • et al.
        FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer.
        N Engl J Med. 2018; 379: 2395-2406
        • Kimura W.
        • et al.
        Different clinicopathologic findings in two histologic types of carcinoma of papilla of Vater.
        Jpn J Cancer Res. 1994; 85: 161-166
        • Albores-Saavedra J.
        • et al.
        The WHO histological classification of tumors of the gallbladder and extrahepatic bile ducts.
        A commentary on the second edition. Cancer. 1992; 70: 410-414
        • Henson D.E.
        • et al.
        Carcinomas of the pancreas, gallbladder, extrahepatic bile ducts, and ampulla of vater share a field for carcinogenesis: a population-based study.
        Arch Pathol Lab Med. 2009; 133: 67-71
        • Lindell G.
        • et al.
        Management of cancer of the ampulla of Vater: does local resection play a role?.
        Dig Surg. 2003; 20: 511-515
        • Brown K.M.
        • et al.
        Pancreaticoduodenectomy is curative in the majority of patients with node-negative ampullary cancer.
        Arch Surg. 2005; 140 (; discussion 32-3): 529-532
        • Balachandran P.
        • et al.
        Long-term survival and recurrence patterns in ampullary cancer.
        Pancreas. 2006; 32: 390-395
        • Duffy J.P.
        • et al.
        Improved survival for adenocarcinoma of the ampulla of Vater: fifty-five consecutive resections.
        Arch Surg. 2003; 138 (; discussion 8-50): 941-948
        • Hsu H.P.
        • et al.
        Predictors for patterns of failure after pancreaticoduodenectomy in ampullary cancer.
        Ann Surg Oncol. 2007; 14: 50-60
        • Beghelli S.
        • et al.
        Ampulla of vater cancers: T-stage and histological subtype but not Dpc4 expression predict prognosis.
        Virchows Arch. 2002; 441: 19-24
        • Zhou H.
        • et al.
        Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up.
        Am J Surg Pathol. 2004; 28: 875-882
        • Sessa F.
        • et al.
        Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability.
        Virchows Arch. 2007; 451: 649-657
        • Carter J.T.
        • et al.
        Tumors of the ampulla of vater: histopathologic classification and predictors of survival.
        J Am Coll Surg. 2008; 207: 210-218
        • Westgaard A.
        • et al.
        Pancreatobiliary versus intestinal histologic type of differentiation is an independent prognostic factor in resected periampullary adenocarcinoma.
        BMC Cancer. 2008; 8: 170
        • Lowe M.C.
        • et al.
        Important prognostic factors in adenocarcinoma of the ampulla of Vater.
        Am Surg. 2009; 75 (; discussion 61): 754-760
        • Ruemmele P.
        • et al.
        Histopathologic features and microsatellite instability of cancers of the papilla of vater and their precursor lesions.
        Am J Surg Pathol. 2009; 33: 691-704
        • Chung Y.E.
        • et al.
        Differential features of pancreatobiliary- and intestinal-type ampullary carcinomas at MR imaging.
        Radiology. 2010; 257: 384-393
        • de Paiva Haddad L.B.
        • et al.
        Lymph node involvement and not the histophatologic subtype is correlated with outcome after resection of adenocarcinoma of the ampulla of vater.
        J Gastrointest Surg. 2010; 14: 719-728
        • Kohler I.
        • et al.
        Phenotypic and genotypic characterization of carcinomas of the papilla of Vater has prognostic and putative therapeutic implications.
        Am J Clin Pathol. 2011; 135: 202-211
        • Chang D.K.
        • et al.
        Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater.
        J Clin Oncol. 2013; 31: 1348-1356
        • Morini S.
        • et al.
        Carcinoma of the ampulla of Vater: morphological and immunophenotypical classification predicts overall survival.
        Pancreas. 2013; 42: 60-66
        • Overman M.J.
        • et al.
        Gene expression profiling of ampullary carcinomas classifies ampullary carcinomas into biliary-like and intestinal-like subtypes that are prognostic of outcome.
        PLoS One. 2013; 8e65144
        • Westgaard A.
        • et al.
        Intestinal-type and pancreatobiliary-type adenocarcinomas: how does ampullary carcinoma differ from other periampullary malignancies?.
        Ann Surg Oncol. 2013; 20: 430-439
        • Okano K.
        • et al.
        Factors predicting survival and pathological subtype in patients with ampullary adenocarcinoma.
        J Surg Oncol. 2014; 110: 156-162
        • Robert P.E.
        • et al.
        Predictors of long-term survival following resection for ampullary carcinoma: a large retrospective French multicentric study.
        Pancreas. 2014; 43: 692-697
        • Shaib W.L.
        • et al.
        Treatment utilization and surgical outcome of ampullary and duodenal adenocarcinoma.
        J Surg Oncol. 2014; 109: 556-560
        • Schiergens T.S.
        • et al.
        Histomorphologic and molecular phenotypes predict gemcitabine response and overall survival in adenocarcinoma of the ampulla of Vater.
        Surgery. 2015; 158: 151-161
        • Schueneman A.
        • et al.
        Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma.
        Br J Cancer. 2015; 113: 64-68
        • Valsangkar N.P.
        • et al.
        Survival in ampullary cancer: potential role of different KRAS mutations.
        Surgery. 2015; 157: 260-268
        • Yun S.P.
        • Seo H.I.
        Prognostic impact of immunohistochemical expression of CK7 and CK20 in curatively resected ampulla of Vater cancer.
        BMC Gastroenterol. 2015; 15: 165
        • Asano E.
        • et al.
        Phenotypic characterization and clinical outcome in ampullary adenocarcinoma.
        J Surg Oncol. 2016; 114: 119-127
        • Kwon M.J.
        • et al.
        Low incidence of KRAS, BRAF, and PIK3CA mutations in adenocarcinomas of the ampulla of Vater and their prognostic value.
        Hum Pathol. 2016; 50: 90-100
        • Leo J.M.
        • et al.
        Immunophenotyping of ampullary carcinomata allows for stratification of treatment specific subgroups.
        J Clin Pathol. 2016; 69: 431-439
        • Reid M.D.
        • et al.
        Ampullary carcinoma is often of mixed or hybrid histologic type: an analysis of reproducibility and clinical relevance of classification as pancreatobiliary versus intestinal in 232 cases.
        Mod Pathol. 2016; 29: 1575-1585
        • Perysinakis I.
        • et al.
        Differential expression of β-Catenin, EGFR, CK7, CK20, MUC1, MUC2, and CDX2 in intestinal and pancreatobiliary-type Ampullary carcinomas.
        Int J Surg Pathol. 2017; 25: 31-40
        • Williams J.L.
        • et al.
        Association of histopathologic phenotype of periampullary adenocarcinomas with survival.
        JAMA Surg. 2017; 152: 82-88
        • Mafficini A.
        • et al.
        Ampulla of vater carcinoma: sequencing analysis identifies TP53 status as a novel independent prognostic factor and potentially actionable ERBB, PI3K, and WNT pathways gene mutations.
        Ann Surg. 2018; 267: 149-156
        • Al Abbas A.I.
        • et al.
        Impact of adjuvant chemotherapy regimen on survival outcomes in immunohistochemical subtypes of ampullary carcinoma.
        J Surg Oncol. 2019;
        • Bowitz Lothe I.M.
        • et al.
        Clinical relevance of pancreatobiliary and intestinal subtypes of ampullary and duodenal adenocarcinoma: pattern of recurrence, chemotherapy, and survival after pancreatoduodenectomy.
        Pancreatology. 2019; 19: 316-324
        • Zimmermann C.
        • et al.
        The pathohistological subtype strongly predicts survival in patients with ampullary carcinoma.
        Sci Rep. 2019; 912676
        • Moekotte A.L.
        • et al.
        Histopathologic predictors of survival and recurrence in resected ampullary adenocarcinoma: international multicenter cohort study.
        Ann Surg. 2020; 272: 1086-1093
        • Nappo G.
        • et al.
        Long-term outcomes after pancreatoduodenectomy for ampullary cancer: the influence of the histological subtypes and comparison with the other periampullary neoplasms.
        Pancreatology. 2021; 21: 950-956
        • Xia T.
        • et al.
        Clinicopathological prognostic factors and Chemotherapeutic outcome for two histopathological types of ampulla of vater adenocarcinoma.
        Front Oncol. 2021; 11616108
        • Brooke B.S.
        • et al.
        MOOSE reporting guidelines for meta-analyses of observational studies.
        JAMA Surg. 2021; 156: 787-788
        • Parmar M.K.
        • et al.
        Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.
        Stat Med. 1998; 17: 2815-2834
        • Tierney J.F.
        • et al.
        Practical methods for incorporating summary time-to-event data into meta-analysis.
        Trials. 2007; 8: 16
        • Liu N.
        • et al.
        IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves.
        BMC Med Res Methodol. 2021; 21: 111
        • Moekotte A.L.
        • et al.
        Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study.
        Br J Surg. 2020; 107: 1171-1182
        • Bolm L.
        • et al.
        Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy - a multicenter cohort study.
        Pancreatology. 2020; 20: 433-441
        • Lai Z.W.
        • et al.
        Characterization of various cell lines from different ampullary cancer subtypes and cancer associated fibroblast-mediated responses.
        BMC Cancer. 2016; 16: 195
        • Campbell F.
        • Cairns A.
        • Duthie F.
        • Feakins R.
        Ampulla of Vater and Common Bile Duct, October 2019 (Royal College of Pathologists. Dataset for Histopathological Reporting of Carcinomas of the Pancreas)
        • Ang D.C.
        • et al.
        The utility of immunohistochemistry in subtyping adenocarcinoma of the ampulla of vater.
        Am J Surg Pathol. 2014; 38: 1371-1379
        • Kumari N.
        • et al.
        Intestinal and pancreatobiliary differentiation in periampullary carcinoma: the role of immunohistochemistry.
        Hum Pathol. 2013; 44: 2213-2219
        • Chu P.G.
        • et al.
        Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2.
        Am J Surg Pathol. 2005; 29: 359-367
        • Liu F.
        • et al.
        Identification of ampullary carcinoma mixed subtype using a panel of six antibodies and its clinical significance.
        J Surg Oncol. 2019; 119: 295-302