Colonoscopy performance monitoring: do we need to adjust for case mix?

INTRODUCTION: Overall caecum intubation rate(oCIR) and overall polyp detection rate(oPDR) have been proposed as performance indicators, but varying complexity in case mix among endoscopists may potentially affect validity. The study aims to explore the effect of adjusting for case mix on individual endoscopist performance by calculating case mix-adjusted performance estimates (cmCIR and cmPDR) and comparing them to overall performance estimates (oCIR and oPDR). The study also provides an R program for case mix analysis. METHODS: Logistic regression associated endoscopist, colonoscopy indication, patient age and patient gender with the binary outcomes of cecum intubation and polyp detection. Case mix-adjusted performance indicators were calculated for each endoscopist based on logistic regression and bootstraps. Endoscopists were ranked from best to worst by overall and case mix-adjusted performance estimates, and differences were evaluated using percentage points(pp) and rank changes. RESULTS: The dataset consisted of 7376 colonoscopies performed by 47 endoscopists. The maximum rank change for an endoscopist comparing oCIR and cmCIR was eight positions, interquartile range (IQR 1-3). The maximum change in CIR was 1.95 percentage point (pp) (IQR 0.27-0.86). The maximum rank change in the oPDR versus cmPDR analysis was 17 positions (IQR 1.5-8.5). The maximum change in PDR was 11.21 pp (IQR 2.05-6.70). Three endoscopists improved their performance from significantly inferior to within the 95% confidence interval (CI) range of performance targets using case mix-adjusted estimates. CONCLUSIONS: The majority of endoscopists were unaffected by adjustment for case mix, but a few unfortunate endoscopists had an unfavourable case mix that could invite incorrect suspicion of inferior performance.

Improving colonoscopy quality through individualised training programmes.

INTRODUCTION: In Denmark, quality-improvement initiatives aimed at providing a better colonoscopy service are few. The primary objective of this study was to improve colonoscopy quality at Aalborg University Hospital, Denmark, using structured training programmes. The secondary aim was to introduce a system for individual colonoscopist performance monitoring. METHODS: We conducted a colonoscopy-quality pilot study covering two major quality performance indicators: caecum intubation rate (CIR) and polyp detection rate (PDR). The pilot study was followed by colonoscopy training programmes offering experienced colonoscopists colonoscopy skills upgrading, polypectomy and train-the-trainers courses taught by English experts. Junior doctors completed a 20-day module-based colonoscopy-training programme. A regional individual colonoscopy quality-reporting system was developed as a supplementary file within the electronic health records. RESULTS: The CIR increased from 87.1% to 92.1% (p less-than 0.001) and the PDR from 33.7% to 41.7% (p less-than 0.001) in the course of the structured training programme. Multivariable analysis adjusting for patient sex, patient age and colonoscopy indication showed a significant increase in CIR (p less-than 0.001), but not in PDR (p = 0.19). The colonoscopy quality reporting system was introduced and now provides biannual feedback to all colonoscopists. CONCLUSIONS: Quality-improvement initiatives may lead to an improved CIR and possibly PDR. Nationwide training programmes and performance monitoring should be implemented to further improve and monitor colonoscopy quality. FUNDING: none. TRIAL REGISTRATION: not relevant.

Colonoscopy adverse events: are we getting the full picture?

INTRODUCTION: Colonoscopy adverse events (AEs) are commonly underreported and standardised reporting is rarely used. We aimed to investigate AEs associated with colonoscopy in a real world setting, using the American Society of Gastrointestinal Endoscopy (ASGE) lexicon. METHODS: This retrospective cohort study of AEs related to outpatient colonoscopies performed in the North Denmark Region from 2015 to 2018 identified AEs from readmission within eight days or death within 30 days of colonoscopy. AEs were investigated in electronic health records and categorised, attributed and graded according to the ASGE lexicon. RESULTS: Of 49,445 colonoscopies performed, 1141 were potentially associated with AEs (23.07‰). Electronic health record review left 489 AEs attributed to colonoscopy (9.9‰); categorised as cardiovascular (0.65‰), pulmonary (0.36‰), thromboembolic (0.10‰), instrumental incl. perforations (0.99‰), bleeding (3.07‰), infection (0.87‰), drug reactions (0.04‰), pain (2.00‰), integument (damage to skin/bones) (0.34‰) and other (1.62‰) AEs. Ten (0.20‰) AEs were fatal, but only one was procedure related (perforation). All shearing force perforations occurred in the sigmoid colon. Most polypectomy perforations occurred in the caecum (60%). CONCLUSIONS: Colonoscopy carries important procedure and non-procedure related risks. Non-procedure related AEs are likely underreported. Better attention to patients with pre-existing diseases and further colonoscopist training may lower AE rates. A standardised colonoscopy AE reporting system is warranted.

The Influence of Perioperative Fluid Therapy on N-terminal-pro-brain Natriuretic Peptide and the Association With Heart and Lung Complications in Patients Undergoing Colorectal Surgery: Secondary Results of a Clinical Randomized Assessor-blinded Multicenter Trial.

OBJECTIVE: To investigate the influence of intravenous (iv) fluid volumes on the secretion of N-terminal-pro-brain natriuretic peptide (NT-Pro-BNP) in colorectal surgical patients and its association with cardiopulmonary complications (CPC). In addition, to examine if preoperative NT-Pro-BNP can predict the risk for postoperative CPC. METHODS: Blood samples from patients enrolled in a previously published clinical randomized assessor-blinded multicenter trial were analyzed. Included were adult patients undergoing elective colorectal surgery with the American-Society-of-Anesthesiologists-scores of 1-3. Samples from 135 patients were available for analysis. Patients were allocated to either a restrictive (R-group) or a standard (S-group) iv-fluid regimen, commencing preoperatively and continuing until discharge. Blood was sampled every morning until the fourth postoperative day. The primary outcome for this study was NT-Pro-BNP changes and its association with fluid therapy and CPC. RESULTS: The S-group received more iv-fluid than the R-group on the day-of-surgery [milliliter, median (range) 6485 (4401-10750) vs 3730 (2250-8510); P < 0.001] and on the first postoperative day. NT-Pro-BNP was elevated in the S-group compared with the R-group on all postoperative days [area under the curve: median (interquartile range) pg/mL: 3285 (1697-6179) vs 1290 (758-3719); P < 0.001 and in patients developing CPC vs no-CPC (area under the curve), median (interquartile range): 5196 (1823-9061) vs 1934 (831-5301); P = 0.005]. NT-pro-BNP increased with increasing fluid volumes all days (P < 0.003). Preoperative NT-Pro-BNP predicted CPC [odds ratio (confidence interval): 1.573 (0.973-2.541), P = 0.032; positive predictive value = 0.257, negative predictive value = 0.929]. CONCLUSIONS: NT-pro-BNP increases with iv-fluid volumes given to colorectal surgical patients, and the level of NT-Pro-BNP is associated with CPC. Preoperative NT-Pro-BNP is predictive for CPC, but the diagnostic value is low.Clinicaltrials.gov NCT03537989.

Risk of post-colonoscopy colorectal cancer in Denmark: time trends and comparison with Sweden and the English National Health Service.

BACKGROUND: The post-colonoscopy colorectal cancer (PCCRC) rate is a key quality indicator for colonoscopy. Previously published PCCRC rates have been difficult to compare owing to differences in methodology. The primary aim of this study was to compare Danish PCCRC rates internationally and to calculate Danish PCCRC rates using the World Endoscopy Organization (WEO) consensus method for future comparison. The secondary aim was to identify factors associated with PCCRC. METHODS: National registries were used to examine the risk of PCCRC. The Danish 3-year rate of PCCRC (PCCRC-3yr) was calculated using previously published methods from England, Sweden, and the WEO. Poisson regression analysis was performed to identify factors associated with PCCRC. RESULTS: The Danish PCCRC-3yr was significantly higher than the rate in the English NHS (relative risk [RR] 1.12, 95 % confidence interval [CI] 1.05 - 1.19) and Sweden (RR 1.15, 95 %CI 1.06 - 1.24). The Danish PCCRC-3yr based on the WEO consensus method fell from 22.5 % in 2001 to 7.9 % in 2012. The multivariable Poisson regression model found PCCRC to be significantly associated with diverticulitis (RR 3.25, 95 %CI 2.88 - 3.66), ulcerative colitis (RR 3.44, 95 %CI 2.79 - 4.23), hereditary cancer (age < 60 years: RR 7.39, 95 %CI 5.77 - 9.47; age ≥ 60 years: RR 3.81, 95 %CI 2.74 - 5.31), and location in the transverse (RR 1.57, 95 %CI 1.28 - 1.94) and ascending colon (RR 1.85, 95 %CI 1.64 - 2.08). CONCLUSIONS: The PCCRC-3yr was higher in Denmark than in comparable countries. Differences in colonoscopist training, background, and certification are possible contributing factors. A review of colonoscopist training and certification in Denmark, and continuous audit and feedback of colonoscopist performance may reduce PCCRC-3yr.

Consensus on procedures to include in a simulation-based curriculum in ophthalmology: a national Delphi study.

PURPOSE: The number of available simulation-based models for technical skills training in ophthalmology is rapidly increasing, and development of training programmes around these procedures should follow a structured approach. The aim of this study was to identify all technical procedures that should be integrated in a simulation-based curriculum in ophthalmology. METHODS: Key opinion leaders involved in the education of ophthalmologists in Denmark including heads of departments, heads of clinical education, professors and board members of the society were invited to participate in a three-round Delphi process. Round 1 aimed at identifying technical procedures that physicians should be able to perform competently when completing specialty training; round 2 involved characterization of each procedure including frequency, number of operators, risk and/or discomfort for patients associated with an inexperienced physician, and feasibility of simulation-based training; round 3 included a priority ranking of procedures. RESULTS: The response rate for each round was 71%, 64% and 64%, respectively. Sixty-five procedures were reduced to 25 prioritized procedures during the three rounds. Two-thirds of the procedures that were identified and highly prioritized were therapeutic procedures such as intravitreal injection therapy, yttrium-aluminium-garnet laser iridotomy/capsulotomy, minor ocular surface procedures and retinal argon laser therapy. The diagnostic procedures that were prioritized were ocular ultrasound, superficial keratectomy and optical coherence tomography (OCT). CONCLUSION: The Delphi process identified and prioritized 25 procedures that should be practised in a simulation-based environment to achieve competency before working with patients. The list may be used to guide the development of future training programmes for ophthalmologists.

Determining procedures for simulation-based training in radiology: a nationwide needs assessment.

OBJECTIVES: New training modalities such as simulation are widely accepted in radiology; however, development of effective simulation-based training programs is challenging. They are often unstructured and based on convenience or coincidence. The study objective was to perform a nationwide needs assessment to identify and prioritize technical procedures that should be included in a simulation-based curriculum. METHODS: A needs assessment using the Delphi method was completed among 91 key leaders in radiology. Round 1 identified technical procedures that radiologists should learn. Round 2 explored frequency of procedure, number of radiologists performing the procedure, risk and/or discomfort for patients, and feasibility for simulation. Round 3 was elimination and prioritization of procedures. RESULTS: Response rates were 67 %, 70 % and 66 %, respectively. In Round 1, 22 technical procedures were included. Round 2 resulted in pre-prioritization of procedures. In round 3, 13 procedures were included in the final prioritized list. The three highly prioritized procedures were ultrasound-guided (US) histological biopsy and fine-needle aspiration, US-guided needle puncture and catheter drainage, and basic abdominal ultrasound. CONCLUSION: A needs assessment identified and prioritized 13 technical procedures to include in a simulation-based curriculum. The list may be used as guide for development of training programs. KEY POINTS: • Simulation-based training can supplement training on patients in radiology. • Development of simulation-based training should follow a structured approach. • The CAMES Needs Assessment Formula explores needs for simulation training. • A national Delphi study identified and prioritized procedures suitable for simulation training. • The prioritized list serves as guide for development of courses in radiology.

Identifying content for simulation-based curricula in urology: a national needs assessment.

OBJECTIVE: Simulation-based training is well recognized in the transforming field of urological surgery; however, integration into the curriculum is often unstructured. Development of simulation-based curricula should follow a stepwise approach starting with a needs assessment. This study aimed to identify technical procedures in urology that should be included in a simulation-based curriculum for residency training. MATERIALS AND METHODS: A national needs assessment was performed using the Delphi method involving 56 experts with significant roles in the education of urologists. Round 1 identified technical procedures that newly qualified urologists should perform. Round 2 included a survey using an established needs assessment formula to explore: the frequency of procedures; the number of physicians who should be able to perform the procedure; the risk and/or discomfort to patients when a procedure is performed by an inexperienced physician; and the feasibility of simulation training. Round 3 involved elimination and reranking of procedures according to priority. RESULTS: The response rates for the three Delphi rounds were 70%, 55% and 67%, respectively. The 34 procedures identified in Round 1 were reduced to a final prioritized list of 18 technical procedures for simulation-based training. The five procedures that reached the highest prioritization were cystoscopy, transrectal ultrasound-guided biopsy of the prostate, placement of ureteral stent, insertion of urethral and suprapubic catheter, and transurethral resection of the bladder. CONCLUSION: The prioritized list of technical procedures in urology that were identified as highly suitable for simulation can be used as an aid in the planning and development of simulation-based training programs.

Optimizing protein and energy intake in hospitals by improving individualized meal serving, hosting and the eating environment.

OBJECTIVE: Optimizing protein and energy intake by food in nutritional risk patients is difficult. The aim of this study was to improve the ≥75% of energy and protein requirements. We would like to see nurses take on the role of hosting the nutritional-risk patients, including focusing on bringing nutrition to the forefront in the collaboration between nurses and patients. METHODS: This was an interventional study that included patients admitted to the Departments of Infectious Diseases, Hematology, and Heart-Lung Surgery in a baseline and follow-up investigation. It included 24-h food intake registrations (FRs) for 3 d consecutively, a questionnaire, and a semistructured patient interview. The interventions included in this study helped to improve the eating environment and serving, integrated nutrition into the nurse-patient welcome interview, and targeted individual preferences and challenges for eating. RESULTS: The study comprised 76 24-h FRs at baseline and 108 FRs at follow-up. The total group had improved food intake; 75% of individual energy requirements were met by (67.6% vs. 40%; P = 0.036) and the Heart-Lung Surgery group (85.7 vs. 38.5; P = 0.036). This was not reflected for protein (NS). Energy intake improved for the entire group, albeit not significantly (P = 0.862). Patients reported being happy with the interventions regarding individualized food serving, nurse communication, and improved meal environments. CONCLUSION: Only insignificant improvements to overall energy intake were seen in two of the three departments and in the overall group, and no statistical or clinically significant improvements to protein intake were observed. The relative risk of meeting 75% of energy requirements was improved in the overall group and in patients in the Department of Heart-Lung Surgery. This did not include the meeting of protein requirements. Improvements were welcomed by patients and staff. Focus on individualized nutrition from the nursing staff also improved.

Identifying Technical Procedures in Pulmonary Medicine That Should Be Integrated in a Simulation-Based Curriculum: A National General Needs Assessment.

BACKGROUND: Simulation training is a revolutionary addition to health care education. However, developing simulation-based training programs is often dictated by those simulators that are commercially available. Curriculum development requires deliberate planning and a standardized approach, including a 'general needs assessment'. OBJECTIVES: The aim of this study was to perform a national general needs assessment to identify technical procedures in pulmonary medicine that should be integrated in a simulation-based curriculum. METHODS: A three-round Delphi process was initiated among 62 key opinion leaders. Round 1 was an open-ended question to identify technical procedures pulmonologists should learn. Round 2 was a survey using a newly developed needs assessment formula to explore the frequency of procedures, number of operators, risk or discomfort when performed by an inexperienced doctor, and feasibility of simulation-based training. In round 3, results were reviewed and ranked according to priority. RESULTS: The response rates for the three rounds were 74, 63, and 60%, respectively. The Delphi process reduced the 30 procedures identified in round 1 to 11 prioritized technical procedures in round 3. These were: flexible bronchoscopy, pleurocentesis, endobronchial ultrasound, endoscopic ultrasound-guided fine-needle aspiration, noninvasive ventilation treatment, transthoracic biopsy of pleural or lung tumor, focused ultrasound scanning of the lungs, chest tube insertion, needle biopsy of visible lymph node/tumor of the skin, focused ultrasound scanning of the heart, and thoracoscopy. CONCLUSION: We performed a Delphi study using a needs assessment formula, which identified 11 technical procedures that are highly suitable for simulation-based training. Medical educators can use this list as a resource in planning simulation-based training programs for trainees in pulmonary medicine.

Effects of perioperative supplementation with omega-3 fatty acids on leukotriene B4 and leukotriene B5 production by stimulated neutrophils in patients with colorectal cancer: a randomized, placebo-controlled intervention trial.

Omega-3 fatty acids (n-3 FA) may have beneficial clinical and immune-modulating effects in surgical patients. In a randomized, double-blind, prospective, placebo-controlled trial, 148 patients referred for elective colorectal cancer surgery received an n-3 FA-enriched oral nutritional supplement (ONS) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for seven days before surgery. On the day of operation, there was a significant increase in the production of leukotriene B5 (LTB5) (p < 0.01) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p < 0.01), a significant decrease in the production of leukotriene B4 (LTB4) (p < 0.01) and a trend for a decrease in the production of 5-hydroxyeicosatetraenoic acid (5-HETE) (p < 0.1) from stimulated neutrophils in the active group compared with controls. There was no association between LTB4 values and postoperative complications. In conclusion, oral n-3 FA exerts anti-inflammatory effects in surgical patients, without reducing the risk of postoperative complications.

Is current surgical training efficient? A national survey.

OBJECTIVES: Evaluation of surgical training in Denmark is competency based with no requirement for a specific number of procedures. This may affect monitoring of surgical progress adversely and cause an underestimation of the time needed to acquire surgical competencies. We investigated the number of common surgical procedures performed by trainees. Trainees' and consultants' expectations from the training program were also investigated. DESIGN AND PARTICIPANTS: A questionnaire was sent to all 115 surgical trainees in Denmark. We asked how many common surgical procedures the trainees had performed during their postgraduate training, whether self-reported procedural confidence was achieved during their training, and whether their training expectations were met. Another questionnaire dealt with the consultants' expectations of the surgical training. RESULTS: The total number of common surgical procedures (Lichtenstein hernia repair, appendectomy, laparoscopic appendectomy, and laparoscopic cholecystectomy) that were performed varied between trainees. One group performed few common procedures during training. A low number in 1 procedure correlated with a similar pattern in other procedures. Approximately one-third did not perform common elective procedures independently until their fifth year. Consultants and trainees viewed training differently. CONCLUSIONS: Our study reveals no common trend in the numbers and types of procedures performed during training. The number of procedures seems to reflect the individual trainee and a local tradition rather than the particular training program. An informal competency-based assessment system with lack of quantitative requirements evidently involves a risk of skewness in training.

Rapid incorporation of ω-3 fatty acids into colonic tissue after oral supplementation in patients with colorectal cancer: a randomized, placebo-controlled intervention trial.

BACKGROUND: The purpose of the study was to examine whether a preoperative supplement with ω-3 fatty acids (FAs) leads to their incorporation into colonic tissue in patients scheduled for colorectal cancer surgery. This would be of interest because ω-3 FAs have potential beneficial (local) immunological effects that might benefit these patients. METHODS: In a randomized, double-blind, prospective, placebo-controlled, single-center intervention trial, patients referred for elective colorectal cancer surgery received either an ω-3 FA-enriched oral nutrition supplement (ONS) (200 mL twice daily) providing 2.0 g of eicosapentaenoic acid (EPA) and 1.0 g of docosahexaenoic acid (DHA) per day or a standard ONS for 7 days before surgery. Tissue samples from healthy colonic tissue (mucosa and muscular layer) were obtained during surgery, and tissue fatty acid composition was analyzed by gas chromatography. RESULTS: EPA was significantly higher in colonic mucosa (P = .001) and in the colonic muscular layer (P = .004) in the ω-3 FA group compared with controls. Patients in the ω-3 FA group also tended to have higher docosapentaenoic acid and DHA levels in colonic tissue. CONCLUSIONS: EPA is incorporated rapidly into colonic mucosa and colonic muscular layer in patients given 3 g of ω-3 FA daily for 7 days before surgery for colorectal cancer. This may lead to potential beneficially effects on (local) immune function, which might benefit these patients.

MSH6 mutations are frequent in hereditary nonpolyposis colorectal cancer families with normal pMSH6 expression as detected by immunohistochemistry.

INTRODUCTION: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition accounting for 2% to 4% of all colorectal cancer cases worldwide. Families with germ line mutations in 1 of 6 mismatch repair genes are known as Lynch syndrome families. The largest number of mutations has been detected in the mismatch repair genes MLH1 and MSH2, but several mutations in MSH6 have also been demonstrated. AIM: : Whether HNPCC families are screened for mutations in mismatch repair genes often relies on their immunohistochemical profile. The aim of the present study was to evaluate this approach in Lynch families carrying mutations in MSH6. MATERIALS AND METHODS: Results of the screening of the MSH6 gene in HNPCC families were compared with those obtained on immunohistochemical protein analysis. RESULTS: In 56 (7%) of 815 families, at least 1 MSH6 mutation, 23 definitively pathogenic mutations and 38 missense mutations or unclassified variants, and several polymorphisms in the MSH6 gene were detected. In families carrying a pathogenic MSH6 mutation, 69.6% of 23 colon adenocarcinomas showed absence of pMSH6 in tumor tissue by immunohistochemical analysis. In 34.5%, all proteins could be detected, whereas in 34.5% pMSH6 was present and pMLH1/pPMS2 was absent. CONCLUSIONS: If genetic screening of HNPCC families depended on immunohistochemical results, a substantial number of families harboring a pathogenic mutation in MSH6 and the vast majority of families harboring an MSH6 unclassified variant would not be detected.

Biomedical informatics as support to individual healthcare in hereditary colon cancer: the Danish HNPCC system.

The Danish HNPCC register is a publically financed national database. The register gathers epidemiological and genomic data in HNPCC families to improve prognosis by screening and identifying family members at risk. Diagnostic data are generated throughout the country and collected over several decades. Until recently, paper-based reports were sent to the register and typed into the database. In the EC cofunded-INFOBIOMED network of excellence, the register was a model for electronic exchange of epidemiological and genomic data between diagnosing/treating departments and the central database. The aim of digitization was to optimize the organization of screening by facilitating combination of genotype-phenotype information, and to generate IT-tools sufficiently usable and generic to be implemented in other countries and for other oncogenetic diseases. The focus was on integration of heterogeneous data, elaboration, and dissemination of classification systems and development of communication standards. At the conclusion of the EU project in 2007 the system was implemented in 12 pilot departments. In the surgical departments this resulted in a 192% increase of reports to the database. Several gaps were identified: lack of standards for data to be exchanged, lack of local databases suitable for direct communication, reporting being time-consuming and dependent on interest and feedback.

Management and perception of hospital undernutrition-a positive change among Danish doctors and nurses.

BACKGROUND: Undernutrition in hospitals is a common problem associated with increased morbidity and mortality, prolonged convalescence and duration of hospital stay and increased health care costs. During recent years several initiatives have brought hospital undernutrition into focus and guidelines and standards have been published. In 1997, a questionnaire-based survey among Danish hospital doctors and nurses in selected departments concluded that clinical nutrition did not fulfil accepted standards. AIMS: We wished to determine if improvements had occurred in the intervening period. METHOD: Thus, in 2004 a similar questionnaire was sent to 4000 randomly selected Danish hospital doctors and nurses and responses were compared to those from 1997. The questionnaire dealt with attitudes and practice in the areas of nutritional screening, treatment plan, monitoring as well as with knowledge, education, tools and guidelines, organisation and possible barriers to implementation of nutritional screening and therapy. RESULTS: The overall response rate was 38%. We observed a marked improvement especially in screening procedures, calculation of energy intake in at-risk patients and local availability of guidelines. Many departments had appointed staff members with special interest and knowledge in clinical nutrition. CONCLUSION: Although significant positive changes had thus occurred, the main barriers against implementation of good nutrition care continued to be lack of knowledge, interest and responsibility, in combination with difficulties in making a nutrition plan. This will be the focus of future activities.

Cost-effectiveness of surveillance programs for families at high and moderate risk of hereditary non-polyposis colorectal cancer.

OBJECTIVES: Surveillance programs are recommended to both families at high risk (Amsterdam-positive families with known- and unknown mutation) and moderate risk (families not fulfilling all Amsterdam criteria) of colorectal cancer (CRC). Cost-effectiveness has so far only been estimated for the group at high risk. The aim of the present study is to determine cost-effectiveness of surveillance programs where families at both high and moderate risk of HNPCC participate. METHODS: A decision analytic model (Markov model) is developed to assess surveillance programs where families at high and moderate risk of HNPCC are offered surveillance from age 25 and age 45, respectively. The model includes costs for all families referred to genetic counseling, including genetic risk assessment, mutation analysis, and surveillance in relevant families with or without known mutation, plus the costs related to any surgical treatment. The risk of metachronous CRC is also modeled. RESULTS: Incremental costs per life year gained are estimated to be euro 980 when families at both high and moderate risk of HNPCC undergo surveillance (euro 508 for high risk and euro 1600 for moderate risk) and euro 1947 when the moderate risk group is evaluated genetically but not offered surveillance. Sensitivity analysis showed these findings to be robust, although cost-effectiveness can be improved in cases of more conservative referrals to genetic counseling. CONCLUSIONS: The result for high risk families confirms the findings in similar studies. Somewhat surprisingly, cost-effectiveness improves when surveillance of the moderate risk groups are included in the decision model.

Polyposis and early cancer in a patient with low penetrant mutations in MSH6 and APC: hereditary colorectal cancer as a polygenic trait.

Hereditary non-polyposis colorectal cancer and familial adenomatus polyposis are autosomal dominant diseases accounting for 5-7% of all colorectal cancer cases. Inheritance of mutations associated with both syndromes in the same individual has, so far, only been observed in a few cases. This report outlines the findings in a proband of a HNPCC family, who presented with colorectal cancer and with multiple adenomas at the age of 18. He was shown to be compound heterozygous for MSH6 mutations: a nonsense mutation in exon 4 (c.1836 C>A, p.S612X); and a missense mutation in exon 5 (c.3226 C>T, p.R1076C). In addition, an APC missense mutation was revealed (c.7504 G>A, p.G2502S). Immunohisto-chemical analysis showed lack of expression of MSH6 in tumour tissue, as well as accumulation of betacatenin in the nuclei of the tumour cells. We suggest that the presence of mutations in both alleles of one gene and mutations in different genes, may influence the phenotype in hereditary colorectal cancer. Biallelic and/or polygenic mutations should be suspected when facing unusual severe variants of "classic monogenic phenotypes", such as HNPCC.

Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial.

OBJECTIVE: To investigate the effect of a restricted intravenous fluid regimen versus a standard regimen on complications after colorectal resection. SUMMARY BACKGROUND DATA: Current fluid administration in major surgery causes a weight increase of 3-6 kg. Complications after colorectal surgery are reported in up to 68% of patients. Associations between postoperative weight gain and poor survival as well as fluid overload and complications have been shown. METHODS: We did a randomized observer-blinded multicenter trial. After informed consent was obtained, 172 patients were allocated to either a restricted or a standard intraoperative and postoperative intravenous fluid regimen. The restricted regimen aimed at maintaining preoperative body weight; the standard regimen resembled everyday practice. The primary outcome measures were complications; the secondary measures were death and adverse effects. RESULTS: The restricted intravenous fluid regimen significantly reduced postoperative complications both by intention-to-treat (33% versus 51%, P = 0.013) and per-protocol (30% versus 56%, P = 0.003) analyses. The numbers of both cardiopulmonary (7% versus 24%, P = 0.007) and tissue-healing complications (16% versus 31%, P = 0.04) were significantly reduced. No patients died in the restricted group compared with 4 deaths in the standard group (0% versus 4.7%, P = 0.12). No harmful adverse effects were observed. CONCLUSION: The restricted perioperative intravenous fluid regimen aiming at unchanged body weight reduces complications after elective colorectal resection.