Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience

BACKGROUND: Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies. METHODS: In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score. RESULTS: Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival. CONCLUSIONS: Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence. BACKGROUNDAmpullary adenocarcinomas (AA) are rare malignant neoplasms arising from the ampulla of Vater, a dilated conduit resulting from the union of intestinal and pancreatobiliary epithelia. Histologically, AA are heterogeneous and are classified into five subgroups: the intestinal (INT) subtype; the pancreatobiliary (PB) subtype; the mixed subtype; the mucinous subtype, and the poorly differentiated subtype. 1 Patient outcome appears to be influenced by histopathological subtype, with the INT subtype being associated with a good prognosis in most studies. 2,3 Moreover, this classification could help to tailor appropriately the chemotherapy regimen using fluoropyrimidine-based regimens for INT subtype tumours and gemcitabine-based regimens for PB subtype tumours. On the other hand, a retrospective AGEO (Association des Gastro-Entérologues Oncologues) study determined a prognostic score based on age, general condition, tumour differentiation and TNM stage which was independent of the histopathological subtype. 4 Recently, immunohistochemistry (IHC)-based classification of AA has been proposed to establish INT versus PB lineage in order www.nature.com/bjc

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“…In a recent study at the Mayo Clinic in a cohort of 121 AA patients, disease stage and ECOG were confirmed as independent prognostic factors. 18 …”

Section: Discussionmentioning

confidence: 99%

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study

et al. 2019

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“…The use of neoadjuvant and adjuvant chemotherapy and/or radiation therapy as well as major venous and/or arterial vascular reconstruction in the setting of pancreatic surgery for borderline or locally advanced PDAC has been expanding recently (2)(3)(4)(5)(6)(7). In fact, pancreatic resection with en bloc portomesenteric venous (PMV) resection and reconstruction is now considered the standard of care for patients with tumors locally invading the portal vein (PV) and/or superior mesenteric vein (SMV), and these advanced resections are cal PMV complications, and the available interventional radiologic techniques for treatment.…”

Section: Introductionmentioning

confidence: 99%

Portomesenteric Venous Complications after Pancreatic Surgery with Venous Reconstruction: Imaging and Intervention

et al. 2020

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Pancreatic surgery with en bloc venous resection and reconstruction is becoming increasingly common in the current era of expanding neoadjuvant oncologic therapies and advanced surgical techniques for patients with more anatomically complex tumors. However, patients who have alterations in their venous outflow are at increased risk for postoperative portomesenteric venous stenosis and/or thrombosis. Cross-sectional imaging for postoperative surveillance, including multiphase CT or MRI, is critical for recognizing portomesenteric venous complications and thus implementing early intervention and preventing complications related to portomesenteric venous hypertension. Hypertension-related complications include ascites, variceal or gastrointestinal bleeding, postprandial abdominal pain, intestinal edema, protein-losing enteropathy, malabsorptive diarrhea, and splenomegaly. Percutaneous transhepatic, transsplenic, and transjugular portomesenteric interventions, including venoplasty, stent placement, and thrombectomy or thrombolysis, are safe and effective options for restoring patency to the portomesenteric venous system. Preintervention CT or MRI and diagnostic catheter venography are important for procedural planning, while postintervention CT or MRI surveillance is critical for detecting recurrent stenosis or thrombosis, or de novo portomesenteric venous disease.

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“…Thirdly, we did not include all potential factors related to prognosis into the risk factor selection procedure because some possible characteristics were not completely recorded, such as family financial situation, patient compliance, and other conditions. Notably, adjuvant therapy is an important prognostic factor [55], but we did not include this predictor into our nomogram owing to the limited use of chemotherapy in our center, which could lead to biased conclusions. We will collect more patient cases receiving adjuvant chemotherapy in the future to perform further analysis.…”

Section: E918882-8mentioning

confidence: 99%

A Nomogram for Individual Prediction of Poor Prognosis After Radical Surgery in Patients with Primary Pancreatic Duct Adenocarcinoma

et al. 2020

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Background: Pancreatic cancer is a highly malignant tumor characterized by poor prognosis. TNM stage cannot always provide accurate prediction of prognosis, which is vital for individualized treatment. Therefore, a novel way to identify patients with poor prognosis after radical surgery is urgently needed. Material/Methods: The nomogram was established based on a discovery cohort that included 554 patients with PDAC who had received radical surgery from 2012 to 2016. The clinicopathological data were collected. Poor prognosis was evaluated using 25 features, in which appropriate features for a prediction model were identified. A prediction model incorporating the selected features was established. The discriminative capacity was assessed by C-index, calibration by calibration plot, and clinical usefulness by decision curve. The bootstrapping approach was used to perform internal validation. Results: Characteristics included in the nomogram were coronary artery disease and stroke history, elevated CA125, AJCC stage >II, R0 resection, operating time >6 h, poor differentiation, nerve invasion, length of stay >30 days, and postoperative complications. A C-index of 0.713 indicated good discrimination of the prediction model, and the calibration curve showed acceptable calibration. Survival analysis showed that this model had better discriminative capacity than the AJCC staging system and could distinguish relatively good prognosis from poor prognosis in patients at stage II (especially IIa) and IV. Conclusions: Our study presents a valid and practical model to predict prognosis of pancreatic cancer patients, which contributes to individualized therapy by assisting surgeons to predict poor prognosis in patients who received radical surgery.

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Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience

Cited by 49 publications

References 40 publications

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study

Portomesenteric Venous Complications after Pancreatic Surgery with Venous Reconstruction: Imaging and Intervention

A Nomogram for Individual Prediction of Poor Prognosis After Radical Surgery in Patients with Primary Pancreatic Duct Adenocarcinoma

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