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In Denmark, around 4,500 people are diagnosed with colorectal cancer (CRC) annually. This review investigates that while the efficacy of immunotherapy in CRC is still being studied, immunotherapy is currently only indicated in the treatment of mismatch-repair deficient (dMMR) metastatic CRC, which accounts for 10-15% of patients. Recent studies indicate high rates of pathologic response in dMMR CRC treated with pre-operative immunotherapy while large-scale studies on novel immunotherapy combinations are ongoing., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Interactions in the tumour microenvironment (TME) are complex and pose a major oncological challenge. Immunotherapy has led to significant progress in recent years, however, not all patients benefit from this. An increasing number of trials try to modulate the TME. Interferon type I (IFN-I) proteins play an important role in the immune response, having many beneficial effects in patients with cancer, particularly when administered locally. This review finds that targeted intratumoural delivery of IFN-I to the TME may mediate optimal therapeutic effects in solid cancers, having extensive implications for clinical oncology. However, an increased understanding of the mechanisms is imperative to develop new and better treatments for solid cancers.

Surgical stress response includes an inflammatory response with production of enzymes which promote tumour progression and potentially alter tumour microenvironment in colorectal cancer patients. SEMS placement as a "bridge-to-surgery" approach was introduced alternatively to acute resection to improve short-term outcomes and mortality. However, SEMS may lead to inflammation with potential long-term oncological complications. The anti-inflammatory effect of NSAID is used in gastrointestinal procedures to elude inflammatory complications. This review summarises the current knowledge in this field and asks whether this could be transferred to other GI procedures e.g. self-expandable metal stent placement.

High-level evidence now strongly supports the use of a minimally invasive approach in most abdominal surgical procedures. Minimally invasive surgery is performed with either a laparoscopic or a robotic approach, and the robotic approach has been implemented to overcome some of the inherent limitations of the conventional laparoscopic approach. In Denmark, robotic surgery is widely adopted, and this review describes the application and rationale of a robotic approach in different subspecialties, while also presenting the available high-level evidence.

Closure of an emergency abdominal midline laparotomy is related to potentially serious complications. Main concerns are surgical site infection, wound dehiscence and incisional hernia. In this review, new studies and guidelines are summed up to a set of recommendations applicable to the Danish surgical departments. Surgical strategies concerning primary closure of an emergency laparotomy as well as a strategy towards wound dehiscence are suggested. Suture techniques, negative pressure wound therapy and reinforcement of the abdominal wall with mesh are the topics reviewed.

The incidence of colon cancer increases with age. With national screening in Denmark, the incidence of early stage cancer is high. With the increasing possibilities of personalised treatment for colon cancer, it is important to choose the right treatment for the right patient. Patient characteristics such as age, co-morbidity, low functioning level and frailty increases the risk of post-operative adverse outcomes. The pathologic assessment and assessment of the patient's immune system offers many tools for assessing the patient's long-term outcomes such as relapse and mortality, and this is discussed in this review.

For the past decades, an increase in the incidence of colorectal cancer in young patients has been reported in several countries, including Denmark, and efforts need to be taken in order to halt this tendency. This review characterises the clinical and pathological attributes of young patients with early-onset colorectal cancer (EOCRC). Risk factors such as smoking and sedentary lifestyle have been found to be associated with EOCRC. Further studies are needed to evaluate, if the age of patients entering the Danish screening programme for bowel cancer should be lowered.

This review summarises the current knowledge of exercise training, which is increasingly used to rehabilitate patients with cancer after anti-cancer treatment, aiming to manage acute and long-term side effects and physical limitations. However, exercise training may also play a critical role in the early preoperative management of patients with cancer. In this period, preoperative exercise training may ensure, that patients reach the curative tumour resection by preventing tumour progression, reducing complications to neoadjuvant treatment and lessening physical deterioration, all leading to improved surgical outcome and enhanced long-term survival. †) Pernille Højman died 6 April 2019, after she had written a major part of the script.

Several scoring systems exist for assessing the risk of post-operative organ-specific complications. An accurate estimation can help to identify the high-risk surgical patients, thus providing opportunities for an individualised and improved patient care. Such estimates can guide the pre- and perioperative management, allow shared decision-making with the patient, and target post-operative care.

Upper gastrointestinal bleeding caused by an ulcer is a common condition with approximately 1,500 admissions a year. The mortality is roughly 9%, with an increased risk in elderly with multiple comorbidities. First-line treatment is endoscopic double therapy. If haemostasis is not achieved and/or repeated rebleeding occurs, the choice of treatment is transarterial embolisation (TAE) or traditional surgery. TAE has a higher rate of rebleeding than surgery, but the mortality is comparable, and TAE has fewer complications. Prophylactic TAE may reduce the rate of re-intervention in patients, who have a high risk of rebleeding.

The prognosis for patients with colorectal cancer has improved markedly in recent years due to standardisation of surgical procedures and incorporation of a multidisciplinary approach in treatment planning. Despite clinical advances, systemic disease recurrence following intended curative surgery remains the most prominent clinical challenge. Identification of patients with elevated perioperative risk of complications provides the opportunity for individualised, multimodal treatment strategies aimed at enhanced patient recovery and improved long-term patient outcomes.

In vivo- and in vitro research accumulate mounting evidence, that the interaction between the colorectal microbiota and the immune system plays an important role in the development and progression of colorectal cancer and for the treatment outcomes. In future, modulation of the microbiota and immune system will, by all accounts, become important targets for prevention and treatment of colorectal cancer. In this review, we summarise current knowledge on bacterial drivers, biofilm formation, colon cancer sidedness and oncological treatment of colorectal cancer including the use of checkpoint inhibitors.

Circadian disturbances in relation to surgery have been extensively researched through the latest couple of decades. Surgery has been shown to affect melatonin rhythm, core body temperature, cortisol rhythm, activity rhythm and sleep in the perioperative period. The changes translate into both subjective patients' discomfort, prolonging convalescence and clinical effects on morbidity and mortality. Future research should be performed to show effect across different surgical procedures and to investigate potential interventions to alleviate harmful effects of circadian disturbances.

Acute abdomen is a common cause of admission to hospital. Emergency laparotomy is associated with a significant morbidity and mortality due to deranged physiology and surgery-induced stress. Damage control laparotomy is on the rise as an operative strategy for the septic abdomen as well as for trauma laparotomy but lacks definition in the non-trauma setting. Principles of perioperative care in elective surgery are currently applied to the emergency abdominal surgery patients and should be further studied in the future to reduce morbidity and mortality.

Up to 20% of the patients who undergo radical surgery for colorectal cancer experience recurrence. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery have shown to be effective treatment of peritoneal carcinomatosis. HIPEC administered at the primary operation in high-risk patients may also be effective in preventing peritoneal carcinomatosis and improve survival in patients with advanced gastrointestinal cancer.

Myocardial injury after non-cardiac surgery (MINS) is associated with significant morbidity and mortality. Routine troponin screening is necessary to identify patients with MINS. Although some evidence indicates benefit with aspirin and statin therapy in these patients, a number of clinical considerations must be done in the practical management of MINS. This article describes current experience with identification and treatment in Denmark of patients with MINS.

It is estimated that 15% of patients above 65 years of age are frail. Frail patients have significantly higher risk of post-operative complications when undergoing both elective and emergency surgery than patients who are not frail. Therefore, it is recommended that all patients above 65 years are frailty scored prior to a surgical procedure. It seems advisable to include the following items in a multimodal frailty score: evaluation of the patient's cognitive ability, functional status, nutritional status and pulmonary and cardiac function.

The treatment of colon cancer has undergone a rapid development with improved surgical and medical regimes and the introduction of targeted treatments. This review offers insight into the current available tailored treatment of colon cancer, and some of the new tailored treatment possibilities with focus on preoperative-, surgical- and post-operative treatment are presented.

Post-operative ileus is a condition which occurs after abdominal surgery. The incidence of post-operative ileus after gynaecological surgery is estimated to be 10-15% (range: 5-25%). The highest rates occur after laparotomy. Chewing gum stimulates bowel motility after gynaecological surgery and reduces time to first flatulence and faeces. Data on reduction in ileus symptoms and reduced hospital stay are not sufficient. Chewing gum is well tolerated and this article recommends it for post-operative optimization.

Deep vein thrombosis and pulmonary embolism are well-known complications after surgery. Despite the widespread use of graduated elastic compression stockings as a mechanical prophylaxis method against thromboembolic complications, data supporting their use for patients under-going laparoscopic surgery for benign conditions are sparse. In this paper, we address the evidence for the effectiveness of the stockings as a method of prophylaxis in laparoscopic day surgery.

Anastomotic leak (AL) is one of the most severe complications after colorectal surgery. AL is often diagnosed late when the patient is presenting with septic symptoms. C-reactive protein (CRP) as a tool in the diagnosis of AL has been investigated in several studies. CRP is proven to have a high negative predictive value which allows safe discharge of patients with low CRP measurements on day 3 or 4 after surgery. CRP can assist in the diagnosis of AL but cannot be used as a single parameter.

Identification of patients with high risk for post-operative complications is instrumental in all surgical specialities. Proper identification can in some cases lead to preoperative or intraoperative optimization resulting in reduced morbidity and morbidity. Several scoring systems exist for assessing overall mortality risk. Preoperative functional tests and biochemical risk markers have shown to be effective in predicting post-operative medical complications and mortality. Optimization can be done by medical interventions, improved anaesthesiological care and optimization directed towards improved communication in the surgical team.

Laparoscopic colorectal cancer surgery results in a reduced impact on the immune system compared with open surgery. This is important when taken into consideration that the immune system may have an instrumental role in the advancement of cancer in the perioperative period. Several studies have shown that the perioperative period is characterized by an immune incompetent period, which is believed to favour tumour metastasis. In this paper factors associated with the cellular and innate immune response in relation to laparoscopic and open colorectal cancer surgery are reviewed.

Annually, several million patients undergoing non-cardiac surgery develop myocardial injury or a myocardial infarction in the perioperative period. This frequent complication is associated with a high mortality. Despite an increasing focus on the issue the pathophysiology and the treatment of perioperative myocardial injury and infarction still remains partly unclear. Recently a new risk stratification tool was developed, which allows physicians to identify patients at risk. This review offers insight into the prevalence, pathophysiology, diagnostics, risk stratification and treatment of perioperative myocardial injury and infarction.

Diabetes mellitus (DM) is an established, independent risk factor for colorectal cancer (CRC). Metformin is the first drug of choice for type 2 DM. Several studies have shown a decreased risk of developing CRC in patients with metformin-treated DM, compared with patients with diabetes not treated with metformin. An increased overall survival and CRC-specific survival in patients with CRC and metformin-treated DM has still not been substantially proven. Further studies are needed before a conclusion can be made whether metformin should be used in the treatment of CRC.

Despite surgical treatment of stage II colorectal cancer many patients will experience relapse. Inflammatory and immunologic reactions created due to the surgical stress response result in the production of reactive oxygen species. Oxidative stress in turn, may result in the stimulation of cancer cells that have not been cleared by the immune system to metastasize. In this paper we present an overview of studies where oxidative stress in relation to surgery has been linked to the development of metastatic disease.

Post-operative mortality from colorectal cancer depends on multiple factors and varies across countries and hospitals. Pre-operative risk prediction can be helpful in surgical decision-making. Several scoring systems have been developed to predict the risk of post-operative mortality. The Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality (P-POSSUM) model and a revised Association of Colo-proctology of Great Britan and Ireland (ACPGBI) model are the most accurate predictors in colorectal cancer surgery. No scoring systems have been validated in the Danish population.

Anal fistulas and fissures are frequent disorders. Affected patients may have significant psychosocial and sexual dysfunction. A few studies have investigated patients with anal fissures and fistulas with regard to sexual dysfunction. These studies showed a significant degree of sexual dysfunction among the affected patients. Data are surprisingly limited in this field. More studies are needed to describe this issue and to define a successful treatment for these patients.

Remote ischaemic preconditioning is a non-invasive intervention that is done by transient occlusion of the blood flow to a limb with a blood pressure cuff. The intervention initiates a systemic endogenous protective response, which may confer multi-organ protection against acute ischaemia reperfusion injury. Originally discovered as a therapeutic strategy in cardiac surgery for protecting the myocardium against ischaemia reperfusion injury, it has been discovered that remote ischaemic preconditioning may confer protection against surgical stress and reperfusion injury in non-cardiac surgery.

Persistent postsurgical pain is a major clinical problem. It is not fully understood why some patients develop persistent postsurgical pain while others do not. The genetic profile might play an important role in this development. In this article, we summarize the existing studies examining the effects of single nucleotide polymorphisms on the development of persistent postsurgical pain. The evidence in this area is sparse and the results are heterogeneous. Further studies are needed before firm conclusions can be made.

Long working hours can lead to physical and mental fatigue. Surveys show that many surgeons suffer from musculoskeletal disorders. A method used to counter fatigue is frequent short pauses. Micropauses in prevention of musculoskeletal disorders appear to be effective, but more clinical research is needed. Studies show that micropauses may reduce muscular fatigue and improve concentration and precision of surgeons but the effect on patient outcome is still unknown.

Morbid obesity in teenagers has become an increasing problem. Conventional diet has not yet shown effective long-term weight loss. Alternatively, bariatric surgery on adolescents has resulted in substantial weight loss, recovery from diabetes, improvement of cardiovascular risk factors and improvement in psychosocial status. Still, surgery performed on adolescents provides ethical challenges such as the unknown long-term prognosis after surgery. Despite these challenges, in cases of severe intractable obesity or development of life-threatening complications due to obesity, surgery should be considered.

Confocal laser endomicroscopy (CLE) is a new endoscopic technique that allows in vivo real time histopathology. The method provides "optical" biopsies, giving the endoscopist the possibility of immediate interpretation and intervention. In colorectal cancer CLE has been used to distinguish neoplastic from non-neoplastic lesions. Lately, CLE has been used to monitor anti-angiogenic therapy by fluorescence labelled antibodies targeted against endothelial markers. The review describes CLE and the potential of the method in relation to colorectal polyps, cancer and inflammatory bowel disease.

Identification of patients with high risk for post-operative complications is instrumental in all surgical specialities. Proper identification can in some cases lead to preoperative or intraoperative optimization resulting in reduced morbidity and morbidity. Several scoring systems exist for assessing overall mortality risk. Preoperative functional tests and biochemical risk markers have shown to be effective in predicting post-operative medical complications and mortality. Optimization can be done by medical interventions, improved anaesthesiological care and optimization directed towards improved communication in the surgical team.

Short bowel syndrome is the result of extensive surgical resection, inherited defects or loss of functional absorbing intestine. Parenteral nutrition is associated with high economical expenses, increased morbidity and decreased quality of life. Intestinal transplantation is associated with high morbidity and mortality rates. Segmental reversal of the small bowel can prolong the transit time in the small bowel and in many cases permanently end parenteral nutrition dependency. Segmental reversal of the small bowel should be integrated in the surgical treatment of adults with short bowel syndrome.

The risk of anastomotic leakage is still high. Evaluation of blood perfusion intraoperatively may give the surgeon the possibility of changing strategy during the operation when needed. A review of the literature shows three different methods, none of which have been implemented in the surgical everyday. There is a need for more research in this field before any of the methods are ready to be used in the surgical standard procedure.

Despite surgical treatment of stage II colorectal cancer many patients will experience relapse. Inflammatory and immunologic reactions created due to the surgical stress response result in the production of reactive oxygen species. Oxidative stress in turn, may result in the stimulation of cancer cells that have not been cleared by the immune system to metastasize. In this paper we present an overview of studies where oxidative stress in relation to surgery has been linked to the development of metastatic disease.

Prognosis for colorectal cancer is dependent on radical surgical intervention. Chemotherapy in patients with advanced disease has improved the survival. A considerable proportion of the patients going through radical surgery will subsequently relapse. Adjuvant chemotherapy is reserved for patients with lymph node metastases, why undetected malignant lymph nodes will result in understaging and exclusion from the possible benefit of adjuvant chemotherapy. With sentinel lymph node mapping it may be possible to detect and resect more malignant lymph node and maybe even avoid extensive resections.

The role of physicians' shift work in adverse events causing patient harm is not clear. However, extended shifts reduce psychomotor performance and cognition in daytime after a 24-hour shift. The incidence and preventability of adverse events in Denmark are comparable to other Western countries, despite the fact that Danish physicians do not work extended hours. The role of physicians' shift work in adverse events causing patient harm remains controversial and further research is needed.