Early detection of colorectal neoplasia: application of a blood-based serological protein test on subjects undergoing population-based screening.

BACKGROUND: Blood-based biomarkers used for colorectal cancer screening need to be developed and validated in appropriate screening populations. We aimed to develop a cancer-associated protein biomarker test for the detection of colorectal cancer in a screening population. METHODS: Participants from the Danish Colorectal Cancer Screening Program were recruited. Blood samples were collected prior to colonoscopy. The cohort was divided into training and validation sets. We present the results of model development using the training set. Age, sex, and the serological proteins CEA, hsCRP, TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, ferritin and B2M were used to develop a signature test to discriminate between participants with colorectal cancer versus all other findings at colonoscopy. RESULTS: The training set included 4048 FIT-positive participants of whom 242 had a colorectal cancer. The final model for discriminating colorectal cancer versus all other findings at colonoscopy had an AUC of 0.70 (95% CI: 0.66-0.74) and included age, sex, CEA, hsCRP, HE4 and ferritin. CONCLUSION: The performance of the biomarker signature in this FIT-positive screening population did not reflect the positive performance of biomarker signatures seen in symptomatic populations. Additional biomarkers are needed if the serological biomarkers are to be used as a frontline screening test.

Functional outcome and quality of life after transanal minimal invasive pouch surgery.

PURPOSE: To investigate functional outcomes and quality of life (QoL) after restorative proctocolectomy (RPC) using transanal minimal invasive surgery (TAMIS). METHOD: The study consists of two sub-studies. A cohort study comprised 98 consecutive patients, who underwent TAMIS RPC. These patients were the first at our department to undergo TAMIS RPC. We collected information about surgery, complications, postoperative morbidity and mortality ≤ 30 days, and pouch problems. Patients were also invited to participate in a case-control study in which the patients would respond to three different questionnaires, the Inflammatory Bowel Disease Questionnaire (IBDQ), the Short Form-36 General Health Questionnaire (SF-36), and questions from the Pouch Dysfunction Score. We compared the responding TAMIS RPC patients to a Danish national cohort (0-10 years from RPC, n = 514) of patients having RPC between 1980 and 2010. We compared functional outcomes and QoL. RESULTS: Four (4%) of the TAMIS patients had an anastomotic leak; none of these required re-operation with removal of the pouch. Anastomotic leak was treated with antibiotics and drain. Out of the four leaks, only one ended up with a permanent stoma; all others had their stoma reversed successfully. The TAMIS patients had the same number of bowel movements as the patients in the Danish national cohort study. The same was seen with regard to incontinence. We had no conversions in our series of TAMIS procedures. CONCLUSION: The TAMIS technique shows acceptable outcomes, both in regard to postoperative complications and also functional outcome and QoL.

Split-Dose Regimen With Bisacodyl Increases the Quality of Bowel Preparation for Colonoscopy.

The aim of the present study was to compare 2 different bowel preparations procedures (split-dose with PicoPrep and bisacodyl vs. same-day preparation with PicoPrep) in patients undergoing colonoscopy with regard to quality of bowel preparation, compliance, and willingness to repeat. A retrospective quasi-experimental investigation was conducted. Adults with outpatient diagnostic and surveillance colonoscopies were included. A total of 540 patients participated: group 'split-dose with bisacodyl' (n = 293) and group 'same-day' (n = 247). Patients in group 'split-dose with bisacodyl' had a higher chance for having an excellent quality of bowel preparation (21.2%; 95% CI [13.5, 28.9]) and a reduced risk of an incomplete colonoscopy (4.1%; 95% CI [1.2, 7.0]). Group 'split-dose with bisacodyl' drank more fluid, had more nightly visits to the bathroom, and had more bathroom stops on the way to the endoscopic site. No differences were found between groups regarding adenoma detection rate, withdrawal time, overall time of colonoscopy, well-being during cleansing, patient satisfaction, the professional's assessment of the patient's tolerability of colonoscopy, and willingness to repeat the bowel preparation process. The split-dose regimen with PicoPrep and bisacodyl is now the standard bowel preparation procedure for patients undergoing elective colonoscopy as it is superior to the same-day regimen with PicoPrep regarding colon cleansing and incomplete colonoscopy. Hence, the written and verbal information at our institution regarding the bowel preparation procedure was altered according to the split-dose regimen, emphasizing the importance of adequate oral fluid intake and complete intake of the solution in order to ensure a safe and effective procedure.

Primary fecal diversion and bowel dysfunction in restorative proctocolectomy for ulcerative colitis: a nationwide cross-sectional study.

PURPOSE: The aim of this study was to explore the effects of primary fecal diversion on the risk of pouch dysfunction. METHODS: Patients operated with an ileal pouch-anal anastomosis in Denmark in 2000-2010 were identified and validated bowel function questionnaires retrieved from a cross-sectional study. Multivariate logistic regression analysis was performed to determine the effect of primary fecal diversion on pouch dysfunction. A diagnostic or procedural code for intraabdominal abscesses and fistulas, occurring within 1 year after pouch creation, and anastomotic leakage or extremely early-onset pouchitis within 30 days of surgery defined a pelvic complication. RESULTS: The questionnaire response rate was 85.6% (504 of 589), with no relevant differences in clinical characteristics between responders and non-responders. Pelvic complications, pouch failure, and death prior to the questionnaire date were more common for patients without primary fecal diversion. Among patients without primary fecal diversion, the prevalence of pouch dysfunction was 48% (95% CI: 34-62%), compared to 30% (95% CI: 26-35%) for those with [adjusted odds ratio = 2.23 (95% CI: 1.20-4.14)]. This difference was primarily caused by a higher risk of 'urgency', 'incomplete emptying', and a higher number of bowel movements per day. CONCLUSION: Omission of primary fecal diversion in ileal pouch-anal anastomosis for ulcerative colitis may have a negative impact on bowel function. Prospective studies are warranted to elaborate these findings and to determine causality with pelvic complications.

Increased Risk of Gallstone Disease Following Colectomy for Ulcerative Colitis.

OBJECTIVES: Biochemical studies suggest that patients who have had a colectomy or restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are at an increased risk of developing gallstone disease, but epidemiological studies are lacking. We evaluated the risk of gallstone disease following colectomy and IPAA. METHODS: Individuals who had a colectomy were identified from a national cohort of patients with ulcerative colitis (UC), and controls without colectomy were sampled from within the same cohort, matching on gender, calendar year, and year of birth. We used Cox regression to examine the effect of colectomy on the hazard rates of gallstone disease and cholecystectomy, adjusting for alcoholism, stroke, chronic obstructive pulmonary disease, cancer, cardiac disease, diabetes mellitus, hypothyroidism, hyperlipidemia, cirrhosis, obesity, renal failure, and transient ischemic attacks. The effect of an IPAA was determined for patients who had colectomy by including the procedure as a time-dependent variable. RESULTS: We identified 4548 patients and matched these to 44 372 controls without colectomy. During a median follow-up of 11.9 years, 1963 patients were hospitalized for gallstone disease. Patients who had a colectomy were at an increased risk (adjusted hazard ratio (HR)=1.63 (1.39-1.91)), and sensitivity analyses of the risk of undergoing cholecystectomy revealed a similar association (adjusted HR=1.55 (1.22-1.98)). An IPAA did not affect the risk of developing gallstones among patients who had a colectomy (adjusted HR=1.03 (0.77-1.37)). CONCLUSION: The risk of gallstone disease increases following colectomy for UC.

Paradoxical Impact of Ileal Pouch-Anal Anastomosis on Male and Female Fertility in Patients With Ulcerative Colitis.

BACKGROUND: Birth rates in males with ulcerative colitis and ileal pouch-anal anastomosis have not been studied. OBJECTIVE: This study aimed to estimate birth rates in males and females with ulcerative colitis and study the impact of ileal pouch-anal anastomosis. DESIGN: This was a retrospective registry-based cohort study that was performed over a 30-year period. SETTINGS: Records for parenting a child from the same period were cross-linked with patient records, and birth rates were calculated using 15 through 49 years as age limits. All data were prospectively registered. PATIENTS: All patients with ulcerative colitis and ulcerative colitis with ileal pouch-anal anastomosis between 1980 and 2010 were identified in Danish national databases. MAIN OUTCOME MEASURES: The primary outcomes measured were birth rates in females and males with ulcerative colitis and ulcerative colitis with ileal pouch-anal anastomosis. RESULTS: We included 27,379 patients with ulcerative colitis (12,812 males and 14,567 females); 1544 had ileal pouch-anal anastomosis (792 males and 752 females). Patients with ulcerative colitis have slightly reduced birth rates (males at 40.8 children/1000 years, background population 43.2, females at 46.2 children/1000 years, background population 49.1). After ileal pouch-anal anastomosis, males had increased birth rates at 47.8 children/1000 years in comparison with males with ulcerative colitis without ileal pouch-anal anastomosis (40.5 children/1000 years), whereas females had reduced birth rates at 27.6 children/1000 years in comparison with females with ulcerative colitis without ileal pouch-anal anastomosis (46.8 children/1000 years). LIMITATIONS: Only birth rates were investigated and not fecundability. Furthermore, there is a question about misattributed paternity, but this has previously been shown to be less than 5%. CONCLUSIONS: Ulcerative colitis per se has little impact on birth rates in both sexes, but ileal pouch-anal anastomosis surgery leads to a reduction in birth rates in females and an increase in birth rates in males. This has clinical impact when counseling patients before ileal pouch-anal anastomosis surgery.

Magnetic endoscopic imaging as an adjuvant to elective colonoscopy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND STUDY AIMS: The use of magnetic endoscopic imaging (MEI) to visualize scope configuration in three dimensions is thought to increase procedural efficiency and diminish discomfort associated with colonoscopy. The aim of this systematic review and meta-analysis was to evaluate the performance of MEI in colonoscopy. METHODS: The electronic databases Medline, EMBASE, and the Cochrane Library of Randomized Trials were searched. Methodological quality was assessed using the Jadad score. Odds ratios (OR) or risk differences for dichotomous variables and mean differences for continuous outcomes were calculated with 95 % confidence intervals (CIs). RESULTS: A total of 13 randomized studies met eligibility criteria and were included in qualitative and quantitative synthesis. MEI was associated with a significantly lower risk of failed cecal intubation (risk difference 4 %, 95 %CI 0 % - 7 %; P = 0.03), lower cecal intubation time (mean difference 0.58 minutes, 95 %CI 0.28 - 0.88; P < 0.001), and lower pain scores as estimated by visual analog scales (mean difference 0.45 cm, 95 %CI 0.03 - 0.86; P = 0.03) compared with conventional colonoscopy. On subgroup stratification of outcome according to endoscopist experience, failure rates were unaffected, but experienced colonoscopists reduced intubation times with MEI (mean difference 0.78 minutes, 95 %CI 0.12 - 1.43; P = 0.02). Sensitivity analyses of high-quality studies (Jadad score ≥ 3) showed no significant difference in failure rate (risk difference 4 %, 95 %CI 0 % - 8 %; P = 0.07) or intubation time (mean difference 0.56 minutes, 95 %CI - 0.15 to 1.28; P = 0.12). CONCLUSION: Adjuvant MEI is associated with a lower failure risk and shorter time to cecal intubation during elective colonoscopy compared with conventional colonoscopy.

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden.

BACKGROUND: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT+) screening population and thereby reduce the colonoscopy burden. MATERIALS AND METHODS: From the Danish National Colorectal Cancer Screening Program, 4048 FIT+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. RESULTS: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. CONCLUSION: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.

Long-term Risk of Cancer Following Ileal Pouch-anal Anastomosis for Ulcerative Colitis.

BACKGROUND: The overall risk of cancer following ileal pouch-anal anastomosis [IPAA] is unknown, and pouch cancer surveillance is controversial. We evaluated long-term risk of cancer in a national cohort of patients with ulcerative colitis and IPAA, with emphasis on pouch cancer. METHODS: Data on incident cancers were extracted from the national Danish Cancer Registry. Incidence rates for all site-specific cancers were compared between patients with IPAA and a gender- and age-matched comparison cohort from the background population to obtain incidence rate ratios [IRRs]. RESULTS: A total of 1723 patients with IPAA, operated for ulcerative colitis in the period 1980-2010, were matched to 8615 individuals from the background population. During a median follow-up of 12.9 years (interquartile range [IQR] 7.7-19.6 years), two pouch cancers [0.12%] were found after 16 and 27 years, respectively. In the population comparison cohort, 38 intestinal cancers [0.45%] were found, of which 35 were colorectal. The risk of hepatobiliary cancer was higher for patients with IPAA {IRR = 13.0 (95% confidence interval [CI]: 3.1-76.1)}, and half of the affected patients had coexisting primary sclerosing cholangitis. The risk of cancer overall following IPAA was identical to that of the comparison cohort: IRR = 1.05 [0.84-1.31]. CONCLUSIONS: Pouch cancer following IPAA is very rare, questioning the need for general, rather than selective, surveillance. The overall cancer risk is comparable to that of the background population, and the increased risk of hepatobiliary cancer is likely an effect of coexisting liver disease and not causally related to IPAA.

Recombinant activated factor VIIa in uncontrolled bleeding: a haemostasis laboratory study in non-haemophilia patients.

Extensive surgery and massive tissue trauma are often associated with severe bleeding. We present retrospective data on the use of recombinant factor VIIa in haemostatic emergencies in13 non-hemophilia patients with uncontrolled bleeding. Recombinant factor VIIa was administered in doses ranging from 16 mug/kg bodyweight to 60 microg/kg bodyweight. Blood loss during 24 h before and after the infusion was registered, showing that 10 out of 13 patients (77%) had a 70% or greater reduction in transfusion requirement decreasing significantly in mean from 28.1 to 9.9 red blood cell units. Coagulation parameters were studied in blood samples collected 10 min before and 10-15 min after the injection of recombinant factor VIIa. Factors VII:C, II:C, and X:C increased significantly while the activated partial thromboplastin time, platelet numbers, and concentration of fibrinogen and D-dimers were unchanged. The dose of rFVIIa correlated significantly with the rise in factor X:C and inversely with transfusion requirements. Dynamic clot velocity of whole blood was recorded before and after rFVIIa infusion in four patients. Judged from red blood cell usage no improvement in haemostasis was seen in one patient suffering thrombocytopenia and low fibrinogen. This patient died 6 h after recombinant factor VIIa infusion, and three other patients died before 1 month. None of the fatalities appeared to be related to recombinant factor VIIa usage. No thromboembolic complications were seen. In conclusion, 12 out of 13 patients survived the first 24 h after treatment with relatively low doses of recombinant factor VIIa for large-scale bleeding. Recombinant factor VIIa was well tolerated and safe in these non-hemophilia patients. With quite low doses of recombinant factor VIIa (

Comparison of fracture risk between patients with ileal pouch-anal anastomosis for ulcerative colitis and the general population.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical treatment for ulcerative colitis (UC). Little is known of how the operation affects bone metabolism and fracture risk. The aim of this retrospective cohort study was to investigate fracture risk and serum markers of bone metabolism following IPAA in a national cohort of Danish UC patients. METHODS: Diagnostic codes for 1757 patients and 8785 controls were obtained from the National Patient Register while blood results were collected from a regional database. Postoperative fracture free survival was evaluated on a Kaplan-Meier plot. Fracture hazard ratios (HR) after IPAA were calculated from Cox proportional hazards regression analysis. RESULTS: Fracture risk after IPAA was significantly reduced (adjusted HR = 0.49, 95% CI: 0.43; 0.55, p<0.001). Prior fractures and alcoholism independently increased fracture risk significantly. Osteoporotic fracture risk after IPAA was reduced, significantly for wrist fractures (aHR = 0.39, 95% CI: 0.22; 0.71, p = 0.002), and borderline insignificantly for spine fractures (aHR = 0.51, 95% CI: 0.26; 1.01, p = 0.054). Vitamin D and calcium levels were significantly higher in the patient group (61.2 nmol/L vs. 58.9 nmol/L, p = 0.04 and 1.24 mmol/L vs. 1.21 mmol/L, p<0.01, respectively), while parathyroid hormone and phosphate levels were significantly lower (4.9 pmol/L vs. 6.2 pmol/L, p<0.01 and 1.08 mmol/L vs. 1.12 mmol/L, p<0.01, respectively). CONCLUSION: Fracture risk after IPAA is significantly reduced compared to the general population. Prospective studies are needed to verify the biochemical results.

[Pancreaticoduodenectomy in Denmark 2005-2008]. / Pankreatikoduodenektomi i Danmark 2005-2008.

INTRODUCTION: Pancreaticoduodenectomy (PD) is associated with high mortality and morbidity. Results can be optimised through centralisation and adjustment of perioperative care. The aim of this study was to describe organisation, postoperative stay, readmission and hospital mortality in the period 2005-2008 and to evaluate postoperative care and treatment after PD in 2007-2008. MATERIAL AND METHODS: The study is based on data from the National Patient Registry for the period 2005-2008 and medical records for 2007-2008 from PD patients. RESULTS: The median duration of postoperative stay in hospital 2005-2008 was 17 days (range 2-649). The readmission rate was 11%, and hospital mortality was 6%. In 2007-2008, both wound infections and intraabdominal abscesses were seen in 12% of cases, and anastomotic leakage of the hepaticojejunostomy and pancreaticojejunostomy occurred in 9% and 12% of cases, respectively. Four percent had no wound-related complications. Nasogastric and nasojejunal tubes were removed postoperatively on median day five and day six, respectively. Clear fluid intake began from median day five and solid food from day seven. The epidural catheter was removed on median day five and abdominal drains on day seven. CONCLUSION: Mortality and postoperative hospital stay after PD were reduced in Denmark from the period 1996-2004 to 2005-2008, but the morbidity remains high. The results suggest a need for adjustment of perioperative care to current evidence-based care standards.