ToPanc Trial: Survival After Total Versus Partial Pancreaticoduodenectomy for Adenocarcinoma of the Pancreatic Head, Distal Cholangiocarcinoma, and Ampullary Cancer

The pancreas is located in the upper abdomen and has 2 main functions: Production of digestive juices and of insulin, the latter being most important for blood sugar regulation and energy conservation. Certain types of cancer in the pancreatic head are very aggressive, but with complete surgical removal of the tumor and additional chemotherapy cure is possible. For tumor resection, the head of the pancreas as well as duodenum and part of the bile duct are removed. 3 new connections are built: the remaining pancreas, bile duct and stomach are connected to a loop of small intestine.

This operation takes around 6 hours and leads to complications in 20-30% of cases. A serious complication and unfortunately the most frequent is the leaking of the pancreas remnant, with outflow of the aggressive digestive juice into the surrounding tissue. Consequences may be severe bleeding and/or infections. Many studies show that affected patients have an increased risk of tumor recurrence and a reduced survival.

To avoid pancreatic leak, the entire pancreas can be removed. So far, removal of the whole pancreas has only been chosen in cases of very advanced cancer. After both, partial or total pancreas removal, patients need to substitute digestive enzymes. This can be done by capsules, which need to be taken with every meal. But while some patients after partial removal maintain sufficient function to produce insulin, all patients after total removal are diabetic and need insulin injections. In the past, blood sugar control in the absence of insulin production was difficult and accompanied by low quality of life (QoL). This has changed tremendously by the introduction of continuous glucose monitoring (sensors, which are attached to the arm) and automated insulin delivery systems (also known as "artificial pancreas"). This development renders total pancreas removal a reasonable alternative, with the advantage, that only 2 new connections are made: One between the bile duct and small intestine and one between the stomach and the small intestine.

Study question: Is removal of the whole pancreas in patients at high risk of a pancreatic leakage a preferable alternative to partial removal?

For this study, patients with cancer of the pancreatic head who are planned for surgery can be included. These patients will be randomly assigned to two groups:

1. Standard group: partial removal of the pancreas 2. Study group: total removal of the pancreas

Both techniques are safe and are established techniques to treat cancer in the pancreatic head. After the operation, many clinical data will be recorded. The two most important factors will be survival and quality of life, which will be assessed by questionnaires on a regular base. Additionally, postoperative complications, chemotherapy rates, tumor recurrence and many more data will be monitored.

• Quality of Life (QoL) Pancreatic Cancer [Time frame: At 0.5 year, at 1 year, at 2 years]
• Quality of Life (QoL) Diabetes [Time frame: At 0.5 year, at 1 year, at 2 years]
• Postoperative complications (discriminating minor and major complications) [Time frame: Within 90 day of surgery]
• Mortality [Time frame: Within 90 days of surgery]
• Length of hospital stay in days [Time frame: Within 90 days of surgery]
• Re-admission [Time frame: Within 90 days of surgery]
• Re-operation [Time frame: Within 90 days of surgery]
• Adjuvant Chemotherapy (ACT) initiation [Time frame: At 1 year]
• Adjuvant Chemotherapy (ACT) completion [Time frame: At 1 year]
• Disease-Free Survival (DFS) [Time frame: At follow-up, up to 4.5 years]
• Functional status [Time frame: At 0.5 year, at 1 year, at 2 years]
• Body Mass Index (BMI) [Time frame: At 0.5 year, at 1 year, at 2 years]