The Diagnosis and Treatment of Ampullary Carcinoma

Abstract

Background: Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform treatment recommendations are lacking both for the adjuvant situation and for palliative care.

Methods: A selective literature search was carried out in PubMed in order to identify the most informative publications concerning the epidemiology, clinico-pathological background, and surgical and medical treatment of this condition.

Results: Ampullary carcinoma has an incidence of 0.5 to 0.9 per 100 000 persons and a poor prognosis, with a 5-year survival rate of 41% to 45% for locally confined and 4% to 7% for metastatic disease. Most such tumors are of an intestinal or a pan - creaticobiliary immunohistochemical subtype; the latter has a worse prognosis (median survival, 72-80 vs. 33-41 months). Targeted treatment is not yet available for either subtype, nor is there enough scientific evidence available for the formulation of specific therapeutic recommendations in either the adjuvant or the palliative situation. The treatment of choice for ampullary carcinoma is radical oncological resection of the head of the pancreas with systematic lymphadenectomy. Five-year overall survival is between 10% and 75% depending on the stage. No definitive recommendation for adjuvant therapy can be given. Palliative therapy can be oriented to the published treatment strategies for cancer of the colon, pancreas, and bile duct.

Conclusion: The current state of the evidence on the treatment of ampullary carcinoma is poor. Therapeutic decisions should be discussed in an interdisciplinary tumor board and should, in our opinion, take the histological subtype into account.

Figure 1

Example image of papillary/ampullary carcinomas a) Ulcerating tumor growth; stage: during exploratory laparoscopy, liver metastases were confirmed, immunohistochemically pancreaticobiliary phenotype b) Polypoid tumor growth; after resection pT1b, pN0 (0/15), L0, V0, G2, R0; pancreaticobiliary subtype c) Polypoid-ulcerating tumor growth; after resection pT3a, pN0 (0/22), L0, V0, Pn0, local R0, intestinal type

Figure 2

Histology specimens of ampullary carcinomas Left: Example of the intestinal subtype with HE stain (a) and with strong expression of CK 20 (b) and CDX2 (c) Right: Example of a biliary subtype in HE (d) and with lacking expression of CK 20 (e) and CDX2 (f)

Figure

Possible therapeutic algorithm for the management of patients with ampullary carcinoma in the adjuvant and palliative setting in first-line therapy. Stage III is defined by confirmation of positive lymph nodes or T4 situation without confirmation of distant metastases (classification of the Union internationale contre le cancer [UICC], 8^th edition). *At stage III and in the R1 situation, fluorouracil (5-FU) based radiochemotherapy can be discussed. Therapeutic schemes: CAPOX: capecitabine/oxaliplatin; FOLFOX: folic acid, fluorouracil and oxaliplatin; FOLFIRI: folic acid, fluorouracil, irinotecan; mFOLFIRINOX: oxaliplatin, leucovorin, irinotecan, fluorouracil; FOLFIRINOX: fluorouracil/leucovorin, irinotecan, and oxaliplatin Ca, capecitabine; ECOG, Performance Status der Eastern Cooperative Oncology Group; NGS, next generation sequencing; MSI, microsatellite instability