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This thesis investigated determinants of and interventions for liver (dys)function after liver surgery for liver cancer. Three main topics were addressed. Firstly, the impact of chemotherapy-associated liver injury on complications after liver surgery for colorectal liver metastases was assessed. It was shown that chemotherapy-associated liver injury led to an increased complication rate after liver surgery. Secondly, current endpoints to define and detect liver failure after liver surgery were investigated. Despite the broad use of definitions and surrogate endpoints, analysis of multiple studies showed that there is little evidence on their validity as true surrogates of clinical endpoints. Lastly, the role of bile salts in liver failure and liver regeneration after liver surgery was examined. Several studies showed that bile salts seem a culprit in liver failure, and that bile salt homeostasis during liver regeneration is already optimal in partial hepatectomy in rodents.

The learning curve associated with the adoption of innovation in surgical practice creates tension between the potential benefits of technological advances and the duty to protect patients from avoidable harm. Fear of learning curve‐associated excess patient morbidity might be a key factor in the delayed adoption of Minimally Invasive HepatoBiliary and Pancreatic (MI-HPB) surgery. This PhD thesis incorporates several studies focused on the safe and effective adoption of MI-HPB surgery. The first study describes the safe and effective implementation of robot-assisted distal pancreatectomy trough a procedure specific, mastery‐based training program. Eye tracking is implicated as a tool to differentiate levels of experience with MI-HPB surgery in the following chapter. The second part of this thesis focusses on the impact of surgical innovation on non-technical skills. New technology increases non-technical demands of surgical teams. Tasks and competences of surgical teams need to evolve with adoption of new technology and innovation to maintain efficiency and safety during surgery. Lastly, the efficacy and safety of robot-assisted median arcuate ligament release and robot-assisted surgery for benign duodenal tumors is implicated.

Shortage of oxygen (ischemia) of the intestine is a potentially life threatening disorder. To gain more insight in the underlying causes our research group developed unique human intestinal ischemia/reperfusion (IR) models. Reperfusion is recovery of the blood supply to tissues that were earlier (partly) devoid of blood. Grootjans discovered that the small intestine disposes of ingenious mechanisms to limit damage to the intestinal wall after short periods of IR. He also discovered that longer ischemia with reperfusion involves damage to the congenital defence of the intestine, which contributes to the development of complications of intestinal ischemia. Future studies now focus on the development of treatments that can reduce death by intestinal ischemia in the future.

Breast cancer is being identified at an earlier stage thanks to the introduction of population screening. This, combined with better treatment options, has improved the survival rates and increased the focus on quality of life among breast cancer survivors. This dissertation asserts that quality of life can only be adequately measured if specific symptoms are measured alongside general quality of life. Extended hormone therapy improves quality of life, as does establishing a connection between lymph vessels and blood vessels to reduce fluid retention in the arm. While breast reconstruction also improves quality of life, the time of the reconstruction does not play a role.

Intestinal oxygen deficiency, or intestinal ischemia, is a common, serious condition associated with a high mortality rate. The high mortality rate is partly determined by the lack of good diagnostic tests, as a result of which intestinal ischemia is often detected at a late stage. This dissertation shows that the new blood tests I-FABP and SM22 are valuable additions in the early diagnostics of patients with intestinal ischemia. In the future, both blood tests may enable us to determine the severity of the intestinal ischemia in daily patient care and thus to choose a better treatment strategy. In addition, the high mortality rate is the result of insufficient knowledge about what exactly happens during times of intestinal ischemia. A better understanding of the processes that occur during intestinal ischemia is needed. This research discovered that the small intestine can tolerate short periods of intestinal ischemia well and recover fully functional. As a result, the small intestine is able to prevent inflammation that spreads to the entire body. Finally, this thesis shows for the first time in humans that during intestinal ischemia digestive enzymes leak out of the intestine and damage body tissues, leading to a severe inflammatory response. This lead will possibly result in the first preventive and therapeutic strategies to combat intestinal ischemia in humans in the future.

Thirty percent of cancer patients (up to 80% in some forms of cancer) suffer from cachexia syndrome, which is characterised by weight loss, muscle loss, loss of fatty tissue, inflammation and decreased appetite. Eventually 20-60% of patients actually die from the effects of cachexia and not the tumour.With the assistance of CT scans, this research mapped the level of muscle and fatty tissue loss in cancer patients. The body composition of a patient appears to be just as important for their prognosis and survival as the characteristics of the tumour. Currently, in most medical care only the tumour characteristics are used when determining prognosis and treatment. With the results of this research, cancer patients can be more precisely examined in order to possibly receive more appropriate treatment.Additionally, this research showed that cancer patients with cachexia are able to produce protein from food. For a long time this was thought to be impossible. This insight offers possibilities to treat cachexia with food and nutritional supplements. Lastly, the protein production of pancreatic tumours and different organs was measured. It appears that the protein production of the tumour is much lower than the protein production of healthy organs. Therefore, the common assumption that the tumour is responsible for the weight and muscle loss in cancer patients because it “eats” the patient’s nutrients appears to be false.Financed by the Dutch Research Council (NOW)

It is obvious: the fitter the patient before surgery, the better they recover after. Therefore, it is safe to consider an operation as a top sport performance. A performance that you need to start fit: well trained, well fed, well rested. Not an easy job. After all, it often concerns fragile patients at old age with a serious condition in an emotional phase of their lives. Out of understandable compassion, everyone grants such patients "no hassle", also because the time to surgery is often short, 2 to 6 weeks, and the recovery time afterwards is hard. To start training anyway requires a lot from the patient, his mantle (care) and the professionals. Physiotherapy helps. It is important to implement this method nationally and evaluate on macro cost effectiveness. After proof was delivered for this substantially different method with patients prior to major heart, lung, stomach, bowel or joint surgery, Van Beijsterveld succeeded in investigating and implementing this with patients with cancer in the pancreas and liver. Parallel to the existing proof, this study with patients and professionals again demonstrated: the fitter the better. Lower risk of complications, faster recovery and a shorter stay in the hospital.

This dissertation aimed to improve aspects of surgical care for gastric cancer. Firstly, vulnerability and nutritional status proved to be important predictors of surgical complications and death after surgery. Secondly, a CT revealed significant loss of muscle mass (sarcopenia) in roughly two-thirds of gastric cancer patients. Keyhole surgery did not appear to be more expensive than conventional open surgery. Finally, gastric cancer patients appeared to have more symptoms in the years after surgery (pain, fatigue, nausea), but did not consider their overall quality of life to be lower than that of healthy people.

Liver surgery is often the last resort for patients with liver tumours. Some patients develop post-operative liver failure. Patients at a high risk of liver failure can be selected by pre-operatively predicting future liver volume and residual liver function. This dissertation demonstrates that the free computer programs ImageJ and Osirix® are both capable of predicting liver volume. A good residual liver function test does not yet exist. Ophthalmate is a new potential biomarker for liver function. Its values were first tested in a model during liver surgery. Although this model is not yet suitable as a functional liver test, the initial results are promising.

This dissertation discusses the improvement of surgical care for patients with a liver disorder. The aim was to evaluate the current treatments of rare disorders of the liver, investigate new techniques for the treatment of life-threatening haemorrhages from liver disorders and to study minimally invasive or laparoscopic surgery in combination with care protocols around the surgery. For this purpose three themes were studied: surgical treatment of echinococcosis (infection of the liver), embolisation (closure of blood vessels) of benign liver tumours (liver adenomas) and laparoscopy for liver tumours. The main conclusions of the research are that embolisation can be a lifesaving treatment for haemorrhages from the liver and that laparoscopic liver surgery contributes to shorter hospitalization, certainly in combination with an accelerated recovery programme.

Faecal incontinence is very common but complex disorder involving high costs for the patient and the community. Besides a considerable psychological burden it has an enormous socially invalidating aspect that has profound consequences for the patient’s well-being. This dissertation summarizes the usability, safety, feasibility and the possible mechanism of action of sacral neuromodulation (SNM) as a treatment for faecal incontinence. After 10 years of clinical experience with SNM in our hospital, we can conclude that SNM is an effective treatment for functional intestinal disorders, particularly in patients with faecal incontinence.