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BACKGROUND: Glucocorticoids modulate the surgical stress response. Previous studies showed that high-dose preoperative glucocorticoids reduce levels of postoperative inflammatory markers and specific biomarkers of liver damage compared with placebo, and suggested a reduced complication rate and shorter hospital stay after liver surgery. However, there are no studies with a clinical primary outcome or of early recovery outcomes. The aim of this study was to investigate whether a single high dose of preoperative glucocorticoid reduces complications in the immediate postoperative phase after liver surgery. METHODS: This was a single-centre, double-blinded, parallel-group RCT investigating preoperative methylprednisolone 10 mg/kg (high dose) versus dexamethasone 8 mg (standard-dose postoperative nausea prophylaxis) in patients scheduled for open liver resection. The primary outcome was number of patients with a complication in the postanaesthesia care unit; secondary outcomes included duration of hospital stay, pain and nausea during admission, and 30-day morbidity. RESULTS: A total of 174 patients (88 in high-dose group, 86 in standard-dose group) were randomized and analysed (mean(s.d.) age 65(12) years, 67.2 per cent men); 31.6 per cent had no serious co-morbidities and 25.3 per cent underwent major liver resection. Complications occurred in the postanaesthesia care unit in 51 patients (58 per cent) in the high-dose group and 58 (67 per cent) in the standard-dose group (risk ratio 0.86, 95 per cent c.i. 0.68 to 1.08; P = 0.213). Median duration of hospital stay was 4 days in both groups (P = 0.160). Thirty-day morbidity and mortality rates were similar in the two groups. CONCLUSION: A high dose of preoperative glucocorticoids did not reduce acute postoperative complications after open liver resection compared with a standard dose. Registration number: NCT03403517 (http://www.clinicaltrials.gov); EudraCT 2017-002652-81 (https://eudract.ema.europa.eu/).

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AIM: The aim of this work was to examine (1) the incidence of primary repair, (2) the incidence of recurrent repair and (3) the types of repair performed in patients with parastomal bulging. METHOD: Prospectively collected data on parastomal bulging from the Danish Stoma Database were linked to surgical data on repair of parastomal bulging from the Danish National Patient Register. Survival statistics provided cumulative incidences and time until primary and recurrent repair. RESULTS: In the study sample of 1016 patients with a permanent stoma and a parastomal bulge, 180 (18%) underwent surgical repair. The cumulative incidence of a primary repair was 9% [95% CI (8%; 11%)] within 1 year and 19% [95% CI (17%; 22%)] within 5 years after the occurrence of a parastomal bulge. We found a similar probability of undergoing primary repair in patients with ileostomy and colostomy. For recurrent repair, the 5-year cumulative incidence was 5% [95% CI (3%; 7%)]. In patients undergoing repair, the probability was 33% [95% CI (21%; 46%)] of having a recurrence requiring repair within 5 years. The main primary repair was open or laparoscopic repair with mesh (43%) followed by stoma revision (39%). Stoma revision and repair with mesh could precede or follow one another as primary and recurrent repair. Stoma reversal was performed in 17% of patients. CONCLUSION: Five years after the occurrence of a parastomal bulge the estimated probability of undergoing a repair was 19%. Having undergone a primary repair, the probability of recurrent repair was high. Stoma reversal was more common than expected.

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BACKGROUND: Allograft dysfunction after liver transplantation has a profound impact on the risks of death and retransplantation within the first year. We tested whether elevated hyaluronic acid (HA; a glycosaminoglycan cleared by hepatic sinusoidal endothelium) levels may predict excess risk of graft loss. METHODS: This was a retrospective single-center prognostic cohort study. Patients with either a plasma sample before transplantation, an early post-transplantation sample nearest day 30 (range 10-89 d, 80% within days 15-60), or both were included. Plasma HA was measured with the use of enzyme-linked immunosorbent assays. The primary end point was 1-year graft loss (all-cause mortality and retransplantation). A secondary end point was biliary stricture. RESULTS: In this study, 169 of 196 patients who received a liver transplant in the study period were included. Pre-transplantation HA (n = 152) did not predict graft loss. Post-transplantation HA (n = 124) was higher among patients with graft loss (median, 177 µg/L [interquartile range (IQR), 89-465] vs 54 µg/L [IQR 37-93]) and was a strong predictor of this outcome (hazard ratio per 50 µg/L, 1.24 [95% confidence interval [CI], 1.14-1.34]). The discriminatory ability of HA was high (area under the receiver operating characteristic curve, 0.86 [95% CI, 0.77-0.94]) and noninferior to other liver function tests. When adjusted for known risk factors of graft loss, HA remained an independent predictor of graft loss. CONCLUSIONS: High post-transplantation plasma HA level was a strong predictor of 1-year all-cause mortality and retransplantation, whereas pre-transplantation levels were not, despite variety in the time span of blood sampling. Prospective studies are warranted to assess the utility of HA in liver transplantation.

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AIM: Ileal pouch-anal anastomosis is a procedure offered to patients with ulcerative colitis who opt for restoration of bowel continuity. The aim of this study was to determine the risk of pouch failure and ascertain the risk factors associated with failure. METHOD: The study included 1991 patients with ulcerative colitis who underwent ileal pouch-anal anastomosis in Denmark in the period 1980-2013. Pouch failure was defined as excision of the pouch or presence of an unreversed stoma within 1 year after its creation. We used Cox proportional hazards regression to explore the association between pouch failure and age, gender, synchronous colectomy, primary faecal diversion, annual hospital volume (very low, 1-5 cases per year; low, 6-10; intermediate 11-20; high > 20), calendar year, laparoscopy and primary sclerosing cholangitis. RESULTS: Over a median 11.4 years, 295 failures occurred, corresponding to 5-, 10- and 20-year cumulative risks of 9.1%, 12.1% and 18.2%, respectively. The risk of failure was higher for women [adjusted hazard ratio (aHR) 1.39, 95% CI 1.10-1.75]. Primary non-diversion (aHR 1.63, 95% CI 1.11-2.41) and a low hospital volume (aHR, very low volume vs high volume 2.30, 95% CI 1.26-4.20) were also associated with a higher risk of failure. The risk of failure was not associated with calendar year, primary sclerosing cholangitis, synchronous colectomy or laparoscopy. CONCLUSION: In a cohort of patients from Denmark (where pouch surgery is centralized) with ulcerative colitis and ileal pouch-anal anastomosis, women had a higher risk of pouch failure. Of modifiable factors, low hospital volume and non-diversion were associated with a higher risk of pouch failure.

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BACKGROUND AND OBJECTIVES: Traditionally, Denmark has had a high rate of allogeneic red blood cell transfusion caused by a liberal transfusion practice despite the existence of restrictive guidelines. We established a Patient Blood Management programme in a tertiary hospital and report the results of the implementation of evidence-based transfusion practice. MATERIALS AND METHODS: Red blood cell transfusion quality indicators were compared with the evidence-based guideline at hospital and department level. Based on this evaluation, wards were selected for interventions targeting doctors and nurses. The implementation process was monitored by transfusion quality and utilization data over a 3-year period with totally 166 341 admissions in 98 960 mixed, adult medical and surgical patients. RESULTS: At the hospital level, transfusion above the upper guideline limit decreased from 23 to 10% (P < 0·001), and transfusion at or below the restrictive haemoglobin trigger of 7·3 g/dl increased from 7 to 19% (P < 0·001). The percentage of single-unit transfusions increased from 72 to 78% (P < 0·001), and the majority of transfusion rates and volumes decreased significantly. Red cell use decreased with 41% in surgical procedures and 28% in admissions (P < 0·001). CONCLUSION: The intervention was associated with a significant and sustained overall increase in compliance with national guidelines for red blood cell transfusion for non-bleeding patients, and led to significantly fewer patients being exposed to transfusion.

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BACKGROUND: Complications in the biliary tract occur in 5%-30% after liver transplantation and the main part of the complications is successfully managed with endoscopic retrograde cholangiopancreaticography (ERCP). The incidence and risk factors for post-ERCP complications in liver transplantation patients are not well described. Our objective was to define the frequency of post-ERCP complications in liver transplantation patients at the Abdominal Center, Rigshospitalet, the only Liver Transplantation Center in Denmark. METHODS: Retrospective study of all ERCPs performed in liver transplantation patients during a 9-year period. RESULTS: A total of 292 ERCPs were included. Overall post-ERCP complications occurred in 24 procedures (8.2%): pancreatitis in 8 (2.7%), bleeding in 5 (1.7%), and cholangitis in 13 (4.5%) procedures. Simultaneous pancreatitis and cholangitis, and simultaneous bleeding and cholangitis occurred after two procedures, respectively. Multivariate analysis concerning overall complications identified biliary sphincterotomy (p = 0.006) and time since liver transplantation within 90 days postoperatively (p = 0.044) as risk factors for post-ERCP complications. Specifically concerning post-ERCP pancreatitis (PEP), it was found that pre-ERCP cholangitis was another independent risk factor for PEP (p = 0.026). Stent in the biliary tract prior to ERCP seemed to be protective (p = 0.041). CONCLUSIONS: Complications were of surprisingly mild degree. The rates of post-ERCP complications in our study were in line with previous studies with liver transplantation patients. Cholangitis prior to ERCP may be another risk factor for post-ERCP pancreatitis.

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BACKGROUND: Recent developments in perioperative pathophysiology and care have documented evidence-based, multimodal rehabilitation (fast-track) to hasten recovery and to decrease morbidity and hospital stay for several major surgical procedures. The aim of this study was to investigate the effect of introducing fast-track principles for perioperative care in unselected patients undergoing open or laparoscopic liver resection. METHODS: This was a prospective study involving the first 100 consecutive patients who followed fast-track principles for liver resection. Catheters and drains were systematically removed early, and patients were mobilized and started eating and drinking from the day of surgery. An opioid-sparing multimodal pain treatment was given for the first week. Discharge criteria were: pain sufficiently controlled by oral analgesics alone, patient comfortable with discharge and no untreated complications. RESULTS: Median length of stay (LOS) for all patients was 5 days, with 2 days after laparoscopic versus 5 days following open resection (P < 0·001). Median LOS after minor open resections (fewer than 3 segments) was 5 days versus 6 days for major resections (3 or more segments) (P < 0·001). Simple right or left hemihepatectomies had a median LOS of 5 days. The readmission rate was 6·0 per cent and 30-day mortality was zero. CONCLUSION: Fast-track principles for perioperative care were introduced successfully and are safe after liver resection. Routine discharge 2 days after laparoscopic resection and 4-5 days after open liver resection may be feasible.

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BACKGROUND AND AIMS: The objective was to determine the sensitivity and specificity of Focused Assessment with Sonography for Trauma (FAST) in patients with confirmed liver lesions and also to compare results from surgeons trained in FAST with results from radiologists trained in general abdominal ultrasound as part of the specialist training. Explorative laparotomy or CT served as gold standard. MATERIALS AND METHODS: This retrospective study included all patients admitted to our institution from 2003 to 2010 registered with the diagnosis "Injury of the liver or gallbladder". Of 405 patients, 135 patients were eligible for analysis. Seventy-two patients were examined by radiologists and 63 by surgeons. RESULTS: We found FAST to have a sensitivity, specificity, PPV, and NPV of 79.6%, 100%, 100%, and 68.9%. There was no statistically significant difference between FAST performed by radiologists and surgeons trained in FAST. CONCLUSION: FAST remains an important screening tool in abdominal trauma including liver lesions, and can be performed at a satisfactory level by surgeons trained in the FAST procedure only.

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OBJECTIVE: A systematic review of the literature was undertaken to estimate the differences in length of hospital stay, morbidity, mortality and long-term survival between staged and simultaneous resection of synchronous liver metastases from colorectal cancer to determine the level of evidence for recommendations of a treatment strategy. METHOD: A Pub-med search was undertaken for studies comparing patients with synchronous liver metastases, who either had a combined or staged resection of metastases. Twenty-six were considered and 16 were included based on Newcastle Ottawa Quality Assessment Scale. All studies were retrospective and had a general bias, because the staged procedure was significantly more often undertaken in patients with left-sided primary tumours and larger, more numerous and bi-lobar metastases. Analyses of primary outcomes were performed using the random effects model. RESULTS: For the reason of the heterogeneity of the observational studies, no odds ratios were calculated. In 11 studies, there was a tendency towards a shorter hospital stay in the synchronous resection group. Fourteen studies compared total perioperative morbidity and lower morbidity was observed in favour of a combined resection. Fifteen studies compared perioperative mortality, which seemed to be lower with the staged approach. Eleven studies compared 5-year survival, which seemed to be similar in the two groups. CONCLUSION: No randomized controlled trials were identified, and hence a meta-analysis was not performed. The evidence level is II to III with grade C recommendations. Synchronous resections can be undertaken in selected patients, provided that surgeons specialized in colorectal and hepatobiliary surgery are available.

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BACKGROUND: Topical administration of lidocaine has been suggested to have beneficial clinical effects in patients with active ulcerative colitis, but the mechanism of action, if any, remains obscure. As local anaesthetics may exert anti-inflammatory actions through their inhibition of nervous reflexes, we have studied the local effects of a single rectal dose of ropivacaine gel on rectal concentrations of eicosanoids and neurotransmittors in patients with relapsing ulcerative colitis. METHODS: In a randomized, double-blind, placebo-controlled study, concentrations of leukotriene B4, thromboxane B2 and prostaglandin E2 in rectal dialysates and concentrations of substance P, neurokinin A, somatostatin, vasoactive intestinal polypeptide and calcitonin gene-related peptide in rectal biopsies from 19 patients with active, distally located, ulcerative colitis were measured before and after rectal administration of a 200-mg dose of ropivacaine- or placebo-gel by use of radioimmunoassays. For comparison with normal conditions, concentrations of neuropeptides were measured in another 19 patients with relapsing ulcerative colitis and 14 controls with non-inflamed colon. RESULTS: No significant changes in concentrations of eicosanoids or neuropeptides were observed after ropivacaine or placebo administration. Baseline concentrations of all neuropeptides, except somatostatin, were significantly lower in active ulcerative colitis than in controls with non-inflamed colon. CONCLUSIONS: These findings reveal no evidence of anti-inflammatory actions by ropivacaine in active ulcerative colitis and thus provide no rationale for topical treatment with local anaesthetics.

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INTRODUCTION: The quality of clinical medical training in Denmark has been closely debated and criticised in recent years. Reorganisation of the daily working plans is one of the recommendations for improvement. METHOD: In the Department of Gastrointestinal Surgery, we made changes in the daily working plans in order to improve supervision and training. These changes included firmer attachment of the young residents to specialised medical teams in the department and the creation of more supervised working situations. The morning rounds were done by all the senior and junior doctors in the team together, which meant that the rounds could be completed in half-an-hour and consequently more senior doctors were available for supervision during the rest of the day. This was adopted by the outpatient clinic, the endoscopy unit, and the operating rooms, where activities did not start until after the rounds. RESULTS: The changes led to a considerable increase in the number of working situations with supervision. Assessment by a questionnaire showed that residents also found significant improvements in supervision during all clinical activities. Overall satisfaction with the department and working conditions increased. CONCLUSION: Many different aspects must be considered if clinical medical training is to improve. One key factor is a thorough revision of the daily working plans, so as to establish as many supervised teaching situations as possible.

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AIM: A retrospective study of 69 cases of gastric cancer seen during the period from 1/1-1990 to 31/12-1994 treated in a University Hospital. The aim of the study was to describe morbidity, mortality and identify independent prognostic variables for mortality. METHOD: Patient data were recovered from the hospital's central database. Mortality was chosen as end-parameter. Univariate log-rank-test identified statistically significant variables which were then analysed by Cox backward stepwise regressional analysis. MATERIAL: Sixty-nine patients were available for analysis, median age 73 years. Fifty-one patients underwent operation. Eighteen patients did not have a surgical procedure due to disseminated disease. The overall postoperative morbidity was 25% and postoperative mortality 10%. The overall five-year survival rate was 8%, 12% for operated patients, 35% after radical and 0% after non-radical or omitted surgery. Age, radicality of operation, type of operation, Borrmann's tumour classification, and degree of depth of local infiltration were identified as significant factors for survival. Cox's analysis identified type of operation (p = 0.0002) and Borrmann's tumour classification (p = 0.001) as independent variables. DISCUSSION: The overall five-year survival is low and has not changed over two decades in Denmark, whereas mortality and morbidity rates have improved. It should be recommended that: The treatment of gastric cancer must be centralised in order to develop preoperative examinations, operative technique and the necessary routine for the surgeons. All gastric ulcers must be considered malignant and biopsies taken accordingly.

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Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones are CCK-58, -33, -22, and -8. Their relative abundance in human plasma and intestine, however, is debated. To settle the issue, extracts of intestinal biopsies and plasma from 10 human subjects have been examined by chromatography, enzyme cleavages, and measurements using a library of sequence-specific RIAs. Plasma samples were drawn in the fasting state and at intervals after a meal. The abundance of the larger forms varied with the 8 C-terminal assays in the library, as 2 assays overestimated and 3 underestimated the amounts present. One assay, however, measured carboxyamidated and O:-sulfated CCKs with equimolar potency before and after tryptic cleavage. This assay showed that the predominant plasma form is CCK-33, both in the fasting state ( approximately 51%) and postprandially ( approximately 57%), whereas CCK-22 is the second most abundant ( approximately 34% and 30%, respectively). In contrast, CCK-58 is less abundant in human intestines ( approximately 18%) and plasma ( approximately 11%). Its predominance in feline intestines, however, was confirmed. Hence, the results show a significant species variation and emphasize the necessity of highly specific and well characterized assays in molecular studies of CCK.

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Laparoscopic cholecystectomy (LC) is the treatment of choice in cases of symptomatic gallstones. A 74-year-old female presented with a spontaneously perforated abscess in her right flank and passage through it of gallstones. Four years previously during LC the gallbladder perforated and 10-15 stones were lost intraperitoneally. In case of perforation of the gallbladder during LC it is essential to reduce loss of and remove all gallstones. In case of abdominal symptoms postoperatively, an intra-abdominal abscess must be suspected.

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BACKGROUND: The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. AIMS: To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. METHODS: In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. RESULTS: Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. CONCLUSIONS: ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.

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The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP in the femoral artery blood was significantly higher than in the group of patients with normal liver function (median 145 microg/l, 95% CI 98-195 versus 57 microg/l, 95% CI 42-92, p<0.001). A significant decrease in the concentration of PINP between the femoral artery (median 57 microg/l, 95% CI 42-92) and the hepatic vein (median 45 microg/l, 95% CI 40-70, p<0.001) was found in patients with normal liver function. In this group we also observed a significantly higher concentration of PINP in femoral artery blood (median 60 microg/l, 95% CI 45-87) as compared with that in renal vein (median 50 microg/l, 95% CI 40-65, p<0.001). In contrast, serum-PINP did not differ between arterial and hepatic or venous venous blood in patients with alcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney. It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired/reduced in patients with alcoholic cirrhosis.

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Parvovirus B19 (B19), also known as "erythema infectiosum", is a disease that occurs in smaller outbreaks during late winter and early summer; and in Denmark an epidemic occurs every three years. The symptoms vary from fever, fatigue and the characteristic maculopapoulous erythema to asymptomatic cases in 50% of the infected patients. Two-thirds of the Danish population have been infected. The virus has a broad spectrum of clinical manifestations ranging from erythema nodosum in children, arthralgia/arthritis (especially in adults), aplastic crisis in patients with haemolytic anaemia, chronic anaemia in immunocompromised patients, to hydrops foetalis following acute infection during pregnancy. In two adult females aged 41 and 35 years with persisting fatigue, malaise, transitory swelling and arthralgia we found elevated ALT and alkaline phosphatase (pt. 1), despite no serological evidence of hepatitis, cytomegalovirus (CMV), or Epstein-Barrvirus and no story of alcohol consumption or recent travelling outside Denmark. Ongoing B19 infection was diagnosed by ELISA and confirmed by B19 DNA PCR in case 2 and IgG avidity and epitope-type specificity in case 1, who was B19 DNA negative in three different samples. The concentrations of alkaline phosphatase and ALT returned to normal as the antibody response shifted from acute B19 infection to IgG positivity. In conclusion we suggest that a serological test and/or B19 DNA for B19 infection is a relevant test to undertake when screening patients for viral hepatitis especially during B19 epidemics and in exposed individuals.

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BACKGROUND: Although low arterial oxygen tension (Po2) has been claimed to occur in one to two thirds of patients with cirrhosis, hypoxaemia appears to be rare in clinical practice. AIMS: To assess the frequency of arterial hypoxaemia in cirrhosis in relation to clinical and haemodynamic characteristics. PATIENTS: One hundred and forty two patients with cirrhosis without significant hepatic encephalopathy (grades 0-I) (41 patients in Child class A, 57 in class B, and 44 in class C) and 21 patients with hepatic encephalopathy. RESULTS: Mean Po2 in kPa was 11.3 in Child class A, 10.8 in class B, 10.6 in class C, and 10.6 in patients with encephalopathy (p < 0.05). The fraction of patients with Po2 below the lower normal limit of 9.6 kPa was 10%, 28%, 25%, and 43%, respectively in class A, B, C, and in patients with encephalopathy (p < 0.05). Oxygen saturation (So2) in these groups was respectively: 96%, 96%, 96%, and 93% (NS). So2 was below the lower limit of 92% in 0%, 9%, 7%, and 24% (p < 0.05). In patients without hepatic encephalopathy, a multivariate regression analysis revealed that independent determinants of a low Po2 were a high arterial carbon dioxide tension, a low systemic vascular resistance, and a low indocyanine green clearance (p < 0.0001). CONCLUSION: The prevalence of arterial hypoxaemia in cirrhosis is about 22% in patients without encephalopathy, but it varies from 10-40% depending on the degree of hepatic dysfunction. Arterial hypoxaemia in patients with cirrhosis of differing severity seems lower than previously reported, and patients with severe arterial hypoxaemia are rare.

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