Introduction: Fit patients with a resectable pancreatic head adenocarcinoma (PDAC), ampullary adenocarcinoma (AA) or distal cholangiocarcinoma (CC) may be offered pancreatoduodenectomy (PD) with curative-intent. However, perioperative morbidity and cancer recurrence rates are high. This thesis aimed to explore the factors influencing PD outcomes. A focus was placed on nutrition, postoperative complications, and recurrence in AA patients. It is hoped the findings will guide patient selection/consenting and have implications for patient management. Methods: A retrospective cohort study of patients who underwent PD for histologically-confirmed malignancy was carried out (2012-2015). Twenty-nine centres from eight countries were involved. Data on the following were collected: preoperative comorbidities and investigations, neoadjuvant treatment, operative details, postoperative complications, histology, adjuvant treatment, cancer recurrence, palliative treatment, and overall survival (OS). Results: In total, 1484 patients were included; 885 (59.6%), 394 (26.5%) and 205 (13.8%) had PDAC, AA and CC, respectively. Overall morbidity, major morbidity (Clavien-Dindo grade 11 ≥III) and 90-day mortality rates were 53.4%, 16.9% and 3.8%, respectively. A high body mass index (BMI), an American Society of Anesthesiologists (ASA) grade >II and a classic Whipple approach all correlated with morbidity. Additionally, ASA grade >II patients were at increased risk of major morbidity and a raised BMI correlated with a greater risk of pancreatic leak. Almost half of the cohort received nutritional support (NS). Of these, 55.6% received parenteral nutrition (PN). In total, 19.6% of the patients who had an uneventful postoperative recovery received PN. Among the PDAC cohort, commencing adjuvant chemotherapy (AC) correlated with improved OS, and those who experienced major morbidity commenced AC less frequently. Among the AA cohort, 176 patients (44.7%) developed recurrence and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). A higher number of resected nodes, histological T stage >II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin all correlated with AA recurrence. Further, ≥1 positive margin, PPFI and PNI were associated with reduced time-to-recurrence. Conclusions: A considerable number of the patients that had an uneventful recovery received PN. Patients with a high BMI or ASA grade had worse perioperative outcomes. Those who experienced major morbidity commenced AC less frequently. Numerous histopathological predictors of AA recurrence and reduced time-to-recurrence were identified.

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