Goal-directed fluid therapy in emergency abdominal surgery: a randomised multicentre trial.

BACKGROUND: More than 50% of patients have a major complication after emergency gastrointestinal surgery. Intravenous (i.v.) fluid therapy is a life-saving part of treatment, but evidence to guide what i.v. fluid strategy results in the best outcome is lacking. We hypothesised that goal-directed fluid therapy during surgery (GDT group) reduces the risk of major complications or death in patients undergoing major emergency gastrointestinal surgery compared with standard i.v. fluid therapy (STD group). METHODS: In a randomised, assessor-blinded, two-arm, multicentre trial, we included 312 adult patients with gastrointestinal obstruction or perforation. Patients in the GDT group received i.v. fluid to near-maximal stroke volume. Patients in the STD group received i.v. fluid following best clinical practice. Postoperative target was 0-2 L fluid balance. The primary outcome was a composite of major complications or death within 90 days. Secondary outcomes were time in intensive care, time on ventilator, time in dialysis, hospital stay, and minor complications. RESULTS: In a modified intention-to-treat analysis, we found no difference in the primary outcome between groups: 45 (30%) (GDT group) vs 39 (25%) (STD group) (odds ratio=1.24; 95% confidence interval, 0.75-2.05; P=0.40). Hospital stay was longer in the GDT group: median (inter-quartile range), 7 (4-12) vs 6 days (4-8.5) (P=0.04); no other differences were found. CONCLUSION: Compared with pressure-guided i.v. fluid therapy (STD group), flow-guided fluid therapy to near-maximal stroke volume (GDT group) did not improve the outcome after surgery for bowel obstruction or gastrointestinal perforation but may have prolonged hospital stay. CLINICAL TRIAL REGISTRATION: EudraCT number 2015-000563-14; the Danish Scientific Ethics Committee and the Danish Data Protection Agency (REG-18-2015).

Colon capsule endoscopy in colorectal cancer screening: a randomised controlled trial.

INTRODUCTION: The use of capsule endoscopy has become an approved method in small bowel diagnostics, but the same level of integration is not seen in large bowel diagnostics. We will use colon capsule endoscopy (CCE) as a filter test in colorectal cancer (CRC) screening between the faecal immunochemical test (FIT) and colonoscopy. We aim to investigate the clinical performance, population acceptability, and economic implications of the procedure in a large-scale clinical trial. METHODS AND ANALYSIS: We will randomly allocate 124 214 Danish citizens eligible for participation in the national CRC screening programme within the Region of Southern Denmark to either an intervention group or a control group. Prior to submitting a FIT, citizens randomised to the intervention group will be informed about their opportunity to undergo CCE, instead of colonoscopy, if the FIT is positive. Suspected cancers; >3 adenomas <10 mm in size, 1 adenoma >10 mm in size or >4 adenomas regardless of size, detected during CCE will generate an invitation to colonoscopy as per regular screening guidelines, whereas citizens with suspected low risk polyps will re-enter the biennial screening programme. Citizens with no CCE findings will be excluded from screening for 8 years. In the control group, citizens will follow standard screening procedures. ETHICS AND DISSEMINATION: All participants must consent prior to capsule ingestion. All collected data will be handled and stored in accordance with current data protection legislation. Approvals from the regional ethics committee (ref. S-20190100) and the Danish data protection agency have been obtained (ref. 19/29858). TRIAL REGISTRATION DETAILS: The study has been registered with ClinicalTrials.gov under: NCT04049357.

Time to colonoscopy, cancer probability, and precursor lesions in the Danish colorectal cancer screening program.

PURPOSE: The aim of this study was to investigate the effect of response time from the Fecal Immunochemical Test (FIT) based screening invitation to the conclusive screening Optical Colonoscopy (OC) on the risk of detecting colorectal cancer (CRC), advanced stage disease and precursor lesions. PATIENTS AND METHODS: We used a cross-sectional study design and included all 62,554 screening participants registered in the Danish Colorectal Cancer Screening Database who tested FIT-positive between March 2014 and December 2016. The main exposure was response time, measured as the time from initial invitation to the conclusive OC. Our main outcomes were the probability of being diagnosed with CRC, advanced stage disease or precursor lesions. RESULTS: Of the 62,554 FIT-positive participants, 53,171 (85%) received an OC and were eligible for analysis (median age 63.7 years, 56% men). In this group, 3,639 cancers were registered, 2,890 of which were registered with a defined stage of disease (79%), and 1,042 (36%) of these were advanced stage (UICC III & IV). In addition, 17,732 high-risk and 10,605 low-risk adenomas were identified. Compared to participants receiving the conclusive examination within 30 days, those receiving the examination more than 90 days after initial invitation were 3.49 times more likely to be diagnosed with any CRC (OR 3.49 [95% CI, 3.13-3.89]) and 2.10 times more likely to have advanced stage disease (OR 2.10 [95% CI, 1.73-2.56]). Those waiting for the longest were also more likely to have one or more high-risk adenomas (OR 1.59 [95% CI, 1.50-1.68]). CONCLUSION: Increased screening response time was associated with a higher probability of detecting high-risk adenomas, any stage CRC and advanced stage cancer. More research is needed to explain what causes these associations.

Reproducibility and accuracy of visual estimation of polyp size in large colorectal polyps.

BACKGROUND: Previous studies indicate that visual size estimation (in situ) of polyp size tends to differ from postfixation measurements, which effects allocation to surveillance intervals. Little is known about interobserver variation of in-situ measurements of large polyps. The primary objective was to assess interobserver variation of in situ measurements of large colorectal polyps. Secondary objectives were the agreement of in situ measurements with postfixation measurements, and the agreement on detection of ≥20 mm polyps between these measurements. MATERIAL AND METHODS: Interobserver variability of in situ polyp size measurements was assessed between a diagnostic colonoscopy and the secondary therapeutic colonoscopy by dedicated endoscopists, in patients that were referred for an advanced polypectomy. After excision pre- and postfixation polyp sizes were measured with a ruler in three dimensions. RESULTS: A total of 40 patients, with 45 polyps, were included in the study. The average difference between the two in situ measurements was 2.4 mm (95% confidence interval (CI): -0.4-5.2). The differences between the first in situ, second in situ and pre-fixation measurement in comparison to postfixation measurements were 1.8 mm (95% CI: -1.2-4.9), 0.1 mm (95% CI: -1.5-1.8) and 1.0 mm (95% CI: -0.2-2.2). Cohen's Kappa on detection of ≥20 mm polyps in agreement with postfixation measurements was 0.65 in the primary and 0.88 in the secondary in situ measurements. CONCLUSION: This study shows a variation between in situ size measurements of large polyps. Improvements in daily clinical routines can be made by using an instrument to compare polyp size with and refraining from rounding sizes up or down. A randomized controlled trial assessing which instruments should be used for in-situ measurements of large polyps is warranted, in order to optimize size measurements of large colorectal polyps.

Patient-reported complications related to colonoscopy: a prospective feasibility study of an email-based survey.

OBJECTIVE: This prospective pilot study assessed the feasibility of electronic email-based questionnaires about patient-reported complications after colonoscopy. MATERIAL AND METHODS: A newly internally validated questionnaire on patient-reported complications related to colonoscopy was conducted as an online survey. RESULTS: Out of 200 patients (mean age 65 years), 83% completed the first questionnaire immediately after the procedure, 77% completed the second follow-up questionnaire after 24 h at home, and 70% the third one after 30 d. Forty-four percent of the patients reported minor adverse events after 24 h, and 23% at the follow-up after 30 d. The rate of sick leave in the 30-d period after the colonoscopy was 6%. CONCLUSIONS: This study shows that email-based questionnaires give a high response rate independent of age or gender, but that the response rate declines with time after colonoscopy. Minor adverse events are underestimated, and colonoscopy could lead to sick leave in a minor subgroup of patients.

Improving quality of care in peptic ulcer bleeding: nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery.

OBJECTIVES: The treatment of peptic ulcer bleeding (PUB) is complex, and mortality remains high. We present results from a nationwide initiative to monitor and improve the quality of care (QOC) in PUB. METHODS: All Danish hospitals treating PUB patients between 2004 and 2011 prospectively registered demographic, clinical, and prognostic data. QOC was evaluated using eight process and outcome indicators, including time to initial endoscopy, hemostasis obtainment, proportion undergoing surgery, rebleeding risks, and 30-day mortality. RESULTS: A total of 13,498 PUB patients (median age 74 years) were included, of which one-quarter were in-hospital bleeders. Preadmission use of anticoagulants, multiple coexisting diseases, and the American Society of Anesthesiologists scores increased between 2004 and 2011. Considerable improvements were observed for most QOC indicators over time. Endoscopic treatment was successful with primary hemostasis achieved in more patients (94% in 2010-2011 vs. 89% in 2004-2006, relative risk (RR) 1.06 (95% confidence intervals 1.04-1.08)), endoscopy delay for hemodynamically unstable patients decreased during this period (43% vs. 34% had endoscopy within 6 h, RR 1.33 (1.10-1.61)), and fewer patients underwent open surgery (4% vs. 6%, RR 0.72 (0.59-0.87)). After controlling for time changes in prognostic factors, rebleeding rates improved (13% vs. 18%, adjusted RR 0.77 (0.66-0.91)). Crude 30-day mortality was unchanged (11% vs. 11%), whereas adjusted mortality decreased nonsignificantly over time (adjusted RR 0.89 (0.78-1.00)). CONCLUSIONS: QOC in PUB has improved substantially in Denmark, but the 30-day mortality remains high. Future initiatives to improve outcomes may include earlier endoscopy, having fully trained endoscopists on call, and increased focus on managing coexisting disease.

[Computer tomographic diagnosis of an internal hernia]. / Diagnostik af et internt hernie ved computertomografi.

A case is presented in which a transmesenteric hernia developed four weeks after transperitoneal laparoscopic left nephrectomy. The diagnosis of an internal hernia is best established by computer tomography; however, the signs have low sensitivity, and on suspicion of an internal hernia, early laparoscopy or laparotomy is recommended.

Risk factors in patients surgically treated for peptic ulcer perforation.

OBJECTIVE: The overall mortality for patients undergoing surgery for perforated peptic ulcer has increased despite improvements in perioperative monitoring and treatment. The objective of this study was to identify and describe perioperative risk factors in order to identify ways of optimizing the treatment and to improve the outcome of patients with perforated peptic ulcer. MATERIAL AND METHODS: Three hundred and ninety-eight patients undergoing emergency surgery in four university hospitals in Denmark were included in the study. Information regarding the pre-, intra- and postoperative phases were recorded retrospectively from medical records. Data were analysed using multiple logistic regression analysis. The primary end-point was 30-day mortality. RESULTS: The 30-day mortality rate was 27%. The following variables were independently associated with death within 30 days of surgery: ASA (American Society of Anaesthesiologists) class, age, shock upon admission, preoperative metabolic acidosis, elevated concentration of creatinine upon admission, subnormal concentration of albumin upon admission and insufficient postoperative nutrition. CONCLUSIONS: Thus, preoperative metabolic acidosis, renal insufficiency upon admission and insufficient postoperative nutrition have been added to the list of independent risk factors for death within 30 days of surgery in patients with peptic ulcer perforation. Finding that shock upon admission, reduced albumin blood levels upon admission, renal insufficiency upon admission and preoperative metabolic acidosis are independently related to 30-day mortality could indicate that patients with peptic ulcer perforation are septic upon admission, and thus might benefit from a perioperative care protocol with early source control and early goal-directed therapy according to The Surviving Sepsis Campaign. This hypothesis should be addressed in future studies.

The insulin-like growth factor (IGF)-system in active ulcerative colitis and Crohn's disease: relations to disease activity and corticosteroid treatment.

BACKGROUND: Metabolic bone disease (MBD) and muscle wasting (MW) are serious complications in adults suffering from inflammatory bowel disease (IBD). The inflammatory process and corticosteroid treatment may lead to changes in the IGF-system associated with MBD and MW. AIM: To assess changes in the IGF-system and clinical and biochemical markers in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We studied 37 IBD patients with severe clinical exacerbation (20 with UC, 17 with CD) before and during high dose corticosteroid treatment and tapering (8-12 weeks). RESULTS: Total IGF-I was reduced in CD (36% p<0.01) and UC (41% p<0.001) before treatment and normalized completely. Free IGF-I baseline levels were unchanged compared to controls. In UC, free IGF-I levels increased significantly at week 1 and week 4 (p<0.01, respectively). In CD, no changes in free IGF-I levels were observed. IGFBP-2 baseline levels were increased by a factor 2.3 in UC and CD compared to controls (p<0.01 respectively) and normalized during treatment. IGFBP-3 was reduced by 38% (p<0.01) in CD and 32% (p<0.01) in UC with only partial normalization. Harvey-Bradshaw index, C - reactive protein and albumin normalized during treatment. CONCLUSIONS: Significant changes in total and free IGF-I and IGFBP-2 and IGFBP-3 were demonstrated in CD and UC patients in exacerbation with only partial normalization during high dose corticosteroid treatment and tapering without differences between UC and CD. These changes may be part of MBD and MW in active IBD.

Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C) activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment. METHODS: Plasma from patients with exacerbations of UC (n = 18) or CD (n = 18) were collected before and during high dose prednisolone treatment (1 mg/kg body weight) and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used RESULTS: Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p < 0.02), and in mannan binding lectin (MBL)-concentration and MBL-C4-activation capacity (AC) values compared to UC patients (p < 0.02). Before treatment, plasma from UC patients showed significant elevations only in the classical pathway-mediated C3-AC compared to values obtained from healthy controls (p < 0.01). After treatment was initiated, significant reductions, which persisted during follow-up, were observed in the classical pathway-mediated C3-AC and MBL-C4-AC in plasma from CD patients (p < 0.05). CONCLUSION: Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation.

Activation capacity of the alternative and classic complement pathways in patients operated on for colorectal cancer.

PURPOSE: Tumor cells may suppress activation of the host's complement system, and the functional state of the complement system may be a prognostic marker of outcome in patients with malignancies. Serial plasma samples from patients undergoing intended curative surgery for colorectal cancer were analyzed for complement factor C3 activation capacity. METHODS: Samples were collected from 91 patients with colorectal cancer and 13 with benign colorectal diseases before surgery and 1, 2, and 7 days after surgery, between 8 and 13 days after surgery, and 3, 6, 12, 18, 24, 36, 48, and 60 months after surgery. The samples were analyzed with an enzyme-linked immunosorbent assay that measured C3 activation capacity by the alternative and classic complement pathways. Cancer patients were compared according to Dukes stage, type of surgery performed, transfusion of blood, development of infection, venous thromboembolism, and cancer recurrence. RESULTS: Plasma samples obtained from cancer patients before surgery showed C3 activation capacities corresponding to those of samples from patients with benign disease. For both patient groups, C3 activation capacity decreased after surgery and normalized within seven days. Significant differences in C3 activation capacities were observed between cancer patients that were related to Dukes stage and in patients with and without buffy coat-depleted red cells suspended in saline, adenine, glucose, and mannitol transfusion, infectious events, and deep venous thromboembolism. Measurement of C3 activation capacity was of predictive value in patients who developed infection. CONCLUSION: Serial measurements of C3 activation capacity in plasma from patients who had undergone surgery for colorectal cancer revealed significant differences related to Dukes staging after surgery and to the development of infections but not to cancer recurrence.