How Does Pre-operative Biliary Drainage in Pancreatic Adenocarcinoma Affect Surgical Outcomes in Pancreatic Cancer Surgery

1. INTRODUCTION 1.1 BACKGROUND Pancreatic cancer is the 10th most common cancer in the UK, responsible for the 5th largest cancer death rate (1). Oncological resection in the form of pancreatico-duodenectomy (PD) is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC) affecting the head of pancreas (2). Significant prognostic factors for resected PDAC include R status, tumour size and differentiation, lymph node involvement, the presence of lymphovascular invasion (LVI) and perineural invasion (PNI). While up to 70% of patients with PDAC in the head of pancreas have concurrent obstructive jaundice, there is much debate in recent years regarding the role of pre-operative biliary drainage (PBD) (3). PBD is used to treat the adverse effects of obstructive jaundice such as cholangitis, pro-inflammatory status, renal and cardiac dysfunction, hepatic dysfunction and coagulopathy, as well as a bridge to allow neoadjuvant therapy(3-5). Randomised control trials have shown that patients who routinely undergo PBD prior to PD experience a greater rate of complications(4, 6, 7). 1.2 Rationale for Current Study While there is an increasing amount of evidence demonstrating that PBD carries with it a risk of post operative complications, there is little evidence in the literature investigating if PBD affects oncological staging and disease progression (4, 6, 7). This retrospective study aims to investigate the effect of PBD on known markers of oncological disease severity, compared against patients who proceeded straight to surgery.
2. Study Objectives To identify level of correlation between PBD and oncological characteristics. 2.1 Study Outcomes It is expected that this study will provide essential information on the association between biliary drainage and oncological progression. Primary Outcome Measures Lymph node Ratio Secondary Outcome Measures Presence of Perineural Invasion Presence of Lymphovascular Invasion Disease Free Survival Overall Survival Pancreatic Fistula Rate Resection Margin Status T Stage N Stage
3. Study Design and Data Collection Methods This will be a retrospective case note review, using data over an 8 year period 2014-2022. Patient information will be gained from the electronic patient record. Statistical analysis will then be performed after gathering information from the electronic patient record. There will be no change in patient care or patient interaction in this study. Subjects will be patients who underwent pancreaticoduodenectomy at ELHT for PDAC of the head of the pancreas. The number of patients is currently unknown. Data will be collected onsite at ELHT, a tertiary HPB referral centre. Data is stored on a secure hospital database that is password protected. A MESh check will be performed to check if patients have opted out from their data being used for research. 3.1 Study Outcome Measures Primary Outcome Measures Lymph node Ratio Secondary Outcome Measures Presence of Perineural Invasion Presence of Lymphovascular Invasion Disease Free Survival (days) Overall Survival (days) Pancreatic Fistula Rate (%) Resection Margin Status (R1/0) T Stage (T1-4) N Stage (N0-2) 3.2 Study Setting Data will be collected on East Lancashire Hospitals NHS Trust site on password protected trust computers. Data will be analysed using statistical analysis software such as SPSS or Jamovi.
4. Sample and Recruitment 4.1 Inclusion criteria

• Procedure - Pancreaticoduodenectomy
• Histology - Pancreatic ductal adenocarcinoma at East Lancashire Hospitals NHS Trust
• Age > 18 years 4.2 Exclusion criteria Patients < 18 years of age Patients who had pancreaticoduodenectomy for benign disease Patients who had pancreaticoduodenectomy with any histology other than pancreatic ductal adenocarcinoma Patients who underwent any other procedure for head of pancreas pancreatic ductal adenocarcinoma Patients who have opted out from being part of research as per the MESH database

4.3 Statistics and Data Analysis Plan This is a retrospective study, therefore sample size calculation in this particular study is not needed as it is only a snapshot study with intent of leading to larger multi-centre study based on the results, however we will aim for 90-100 patients. Patient data will be anonymised and stored on a trust computer.

4.4 Sampling technique

• This study will look at all patients undergoing pancreaticoduodenectomy at East Lancashire Hospitals NHS Trust between 2014 and 2022, regardless of pre operative tumour stage or lymphatic status, with a minimum of 90-100 patients
• Patients with PBD will be included regardless of reason behind PBD

4.5 Participant/Sample Recruitment Potential patients will be identified from the Hospital's electronic patient record, and will be carried out directly by the research team are also part of the care team.

All identifiable data will be stored on a secure trust nhs computer and will not be shared with anyone outside of the research team Patients will not be contacted as part of this research as data will be from already stored electronic healthcare records ICD codes will be used to identify patients who underwent surgery (C25, Z90.410, Z90.41, OFBG0ZZ, ODT90ZZ, OFB90ZZ, ODB90ZZ) Informatics will gather a list of patient details we can access Patients will be cross referenced against MESH database and those who have opted out from being part of research will be excluded from the dataset.

4.6 Participant/Sample identification We intend to identify eligible patients by reviewing histology reports and electronic medical records of patients who underwent pancreatoduodenectomy in the period specified. This will be carried out by the research team who are also part of the clinical care team.

4.7 Pre-Registration Evaluation Data will be collected retrospectively at a tertiary referral centre and it is stored securely at East Lancashire Hospital Trust (ELHT) on a password protected trust computer.

4.8 Participant Consent Process No participant consent will be required as this data is already held in clinical records in the hospitals electronic patient record 4.9.1 Participant Withdrawal Criteria Patient care will not be affected, and data is being collected after they have completed their treatment course. Therefore, there is no withdrawal criteria as it is not applicable. If patients have not consented for their data to be used in research (as per the MESH ), it would not be included.

4.9.2 Study Intervention No procedures will be involved in the study, and no visits will be required, therefore this is not applicable.

4.9.3 Assessment and Follow-Up No follow up or assessment will take place therefore this is not applicable.