The impact of anemia and blood transfusion on mortality after open abdominal surgery in the elderly.

BACKGROUND: Major abdominal surgery is associated with considerable mortality in the elderly. Anemia has been linked to increased mortality in other types of surgery, such as hip and cardiac surgery. This study aimed to assess the impact of preoperative anemia on mortality in the elderly undergoing major abdominal surgery, and how allogeneic red cell blood transfusion influences mortality in these patients. MATERIALS AND METHODS: We conducted a single-center, register-based retrospective study on patients, who were aged beyond 60 years and underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1, 2000, to May 31, 2013, were consecutively identified in the Danish National Patient Registry. Plasma hemoglobin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality. Information about patient transfusions from the hospital blood bank was available from 1998 to 2010. RESULTS: A total of 3199 patients were included of whom 85% underwent emergency surgery. The total mortality after 30 days was 20%. The median preoperative hemoglobin value of survivors was 7.7 mmol/L vs 6.9 mmol/L in those who died. The difference in hemoglobin values, between those who survived or died, decreased from the pre- to the post-operative phase. The 30-day postoperative mortality was 28%, 20%, and 12% in patients with a preoperative hemoglobin level in the lower, median, and upper quartile respectively. Transfusion therapy was associated with higher postoperative mortality, except in patients with very low hemoglobin values. CONCLUSION: Preoperative anemia has a clear association with surgically related mortality. The distribution of hemoglobin values in patients with a fatal outcome differs significantly from that of survivors. Red cell transfusion is associated with increased mortality, except in patients with very low hemoglobin values which supports recent guidelines suggesting a restrictive transfusion strategy.

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.

Establishing Peer Consensus About the Use of Long-Term Biosynthetic Absorbable Mesh for Hernia (Grades 2-3) as the Standard of Care.

BACKGROUND: Standard synthetic and biologic meshes, often used in hernia repair, have commonly been used and each have their strengths but associated drawbacks. Long-term biosynthetic absorbable (LTBA) mesh has been developed to combine the strengths of synthetic and biologic meshes without the associated weaknesses. As a newer type of mesh, the supporting evidence base is still growing, and their optimum use has yet to be defined. This consensus was initiated to provide insight into those situations where a LTBA might be considered the Standard of Care in ventral hernia repair grades 2-3 (original classification, 2010) of the Ventral Hernia Working Group. METHODS: A steering group of expert surgeons identified 35 statements, based around the evidence supporting LTBA, surgical technique, patients type most suitable for LTBA, risk-benefit of LTBA, patient and surgeon considerations, LTBA value. Surgeons involved in hernia repair received an online survey to assess consensus with these statements. Consensus was defined as high if ≥ 70% and very high if ≥ 90% of respondents agreed. Statements that had not achieved consensus agreement were revised and these were then issued for a subsequent round. Finally, 34 statements were included. RESULTS: Two hundred fifty-five surgeons were involved. Fourteen statements (41%) achieved very high consensus, 24 achieved consensuses (≥ 70-< 90%), whilst one (3%) just failed to achieve consensus with an agreement score of 69%. CONCLUSIONS: Expert consensus opinion about the use of LTBA for hernia (Grades 2-3) as the Standard of Care was achieved. Based on the consensus scores, the steering group derived eleven keys.

Preoperative risk factors including serum levels of potassium, sodium, and creatinine for early mortality after open abdominal surgery: a retrospective cohort study.

BACKGROUND: In hospitalized patients, abnormal plasma electrolyte concentrations are frequent and have been linked to poor outcomes following acute surgery. The aim of this study was to assess whether preoperative plasma levels of potassium, sodium, and creatinine at the time of admission were associated with 30-day mortality in patients following open abdominal surgery. METHODS: This was a single-center register-based retrospective study. By means of electronic search in a maintained surgery database, all patients (n = 4177) aged ≥ 60 years old undergoing open surgery in our department from January 2000 to May 2013 were identified. Plasma was assessed within 30 days prior to surgery. The primary endpoint was 30-day postoperative mortality. The association between mortality and plasma levels of potassium, sodium, and creatinine were examined using Cox proportional hazard models. RESULTS: A total of 3690 patients were included in the study cohort. The rates of abnormal preoperative plasma levels were 36, 41, and 38% for potassium, sodium, and creatinine, respectively. The overall 30 day mortality was 20%. A predictive algorithm for 30 day mortality following abdominal surgery was constructed by means of logistic regression showing excellent distinction between patients with and without a fatal postoperative outcome. CONCLUSION: Apart from demographic factors (age, sex, and emergency surgery), preoperative imbalance in potassium, sodium and creatinine levels were significant independent predictors of early mortality following open abdominal surgery.

Multinutrient Supplementation Increases Collagen Synthesis during Early Wound Repair in a Randomized Controlled Trial in Patients with Inguinal Hernia.

BACKGROUND: Inguinal hernia disease is associated with an imbalanced collagen metabolism. Surgical stress has a negative impact on nutrients important for collagen synthesis. OBJECTIVE: We hypothesized that supplementation with a combination of nutrients would enhance collagen biosynthesis in inguinal hernia disease patients when undergoing hernia repair. METHODS: In this exploratory randomized controlled trial, 21 men (age: 55.2 ± 2.8 y; BMI: 25.0 ± 0.7 kg/m2) scheduled for Lichtenstein inguinal hernia repair were assigned to multinutrient supplementation (n = 10; multinutrient group) or no multinutrient supplementation (n = 11; control group). The multinutrient group received 14 g l-arginine, 14 g l-glutamine, 1250 mg vitamin C, and 55 mg zinc daily starting 14 d before surgery and ending 14 d after surgery. The multinutrient and control groups received high-quality protein to ensure a daily intake of 1.5 g protein/kg. Collagen biosynthesis was measured by the biomarkers type I procollagen propeptide (CICP), type III procollagen propeptide (PRO-C3), and type V procollagen propeptide (PRO-C5) in the sera on days -14, 0, and 1, and in the wound fluids on postoperative days 1 and 2. Compliance was recorded after the 28-d intervention period. RESULTS: Serum PRO-C5 concentrations decreased (P < 0.05) postoperatively in the control but not the multinutrient group. Neither CICP nor PRO-C3 serum concentrations differed significantly between the 2 groups. In wound fluid, the CICP concentrations increased (P < 0.05) from days 1 to 2 in the multinutrient group and were 49% higher (P = 0.10) than those in the control group on day 2. Wound fluid concentrations PRO-C3 and PRO-C5 showed no significant time or group differences. The 28-d compliance was similar (P = 0.27) in the 2 groups. CONCLUSION: Oral supplementation with arginine, glutamine, vitamin C, and zinc augment collagen synthesis during the first 2 d after inguinal hernia repair. This trial was registered at clinicaltrials.gov as NCT03221686.

Visceral obesity and short-term outcomes after laparoscopic rectal cancer resection.

BACKGROUND: Complications after rectal resection are frequent. Recently, methods to assess visceral obesity (VO) have become available as an alternative to measurement of body mass index (BMI). The aim of this study was to examine the association between visceral fat volume (VFV) and the short-term outcomes after laparoscopic low anterior resection (LLAR) in patients with rectal cancer. METHODS: We studied a consecutive series of patients undergoing LLAR at Bispebjerg University Hospital from 01.01.2013 to 01.01.2016. Preoperative VFV was calculated from abdominal CT scans using an automatic segmentation tool. The primary outcome was anastomotic leakage (AL). Secondary outcomes included conversion to open surgery, number of lymph nodes harvested, the rates of 30-day complications as well as reoperations, and 1-year survival. RESULTS: A total of 102 patients were included. VO was defined as a VFV above the 75 percentile. Thirteen (12.7%) patients developed AL, four (15.4%) of whom were in the VO group (p = 0.900). At least one postoperative complication developed in 38 (37.3%) patients, with no significant difference between the VO and non-VO patients after univariable analysis (42.3% vs. 35.4%, p = 0.702) or multivariable adjustment (OR 1.01, 95% CI 0.38-2.65, p = 0.984). VO was significantly associated with an increased incidence of conversion to open surgery (OR 4.30, 95% CI 1.29-14.86, p = 0.018). There was a significant difference in the number of harvested lymph nodes between the two groups (mean 23.5 vs. 29.1, p = 0.045). CONCLUSIONS: In this study on patients undergoing laparoscopic rectal resection, VO was not associated with development of AL or other complications. However, we found that visceral obesity was associated with an increased risk of conversion to open surgery.

Incidence of Incisional Hernia Repair After Laparoscopic Compared to Open Resection of Colonic Cancer: A Nationwide Analysis of 17,717 Patients.

BACKGROUND: It remains unknown whether laparoscopic compared to open surgery translates into fewer incisional hernia repairs (IHR). The objectives of the current study were to compare the long-term incidence of IHR and the size of repaired hernias between patients subjected to laparoscopic or open resection of colonic cancer. METHODS: This was a nationwide cohort study comprised of patients undergoing resection for colonic cancer between January 2007 and March 2016 according to the Danish Colorectal Cancer Group database. Patients who subsequently underwent IHR were identified in the Danish Ventral Hernia Database, from which information about the priority of the hernia repair and the size of the fascial defect was retrieved. RESULTS: The study included 17,717 patients, of whom 482 (2.7%) underwent subsequent IHR during a median follow-up of 4.7 (interquartile range 2.8-6.9) years. There was no significant difference in the 5-year cumulative incidence of hernia repair after laparoscopic compared to open colonic resection (3.9%, CI 3.3-4.4% vs 4.1%, CI 3.5-4.6%). After adjustment for confounders, laparoscopic approach was associated with an increased rate of emergency IHR (HR 2.37, 95% CI 1.03-5.46, P = 0.042) as opposed to elective IHR (HR 0.91, 95% CI 0.73-1.14, P = 0.442). Laparoscopic surgery was significantly associated with a decreased fascial defect area compared to open surgery (mean difference -16.0 cm2, 95% CI -29.4 to -2.5, P = 0.020). CONCLUSIONS: There was no difference in the incidence of IHR after open compared to laparoscopic resection. Compared to the open approach, laparoscopic resection increased the rate of subsequent emergency IHR, suggesting that a more aggressive therapeutic approach may be warranted in this patient group upon diagnosis of an incisional hernia.

The density of infiltrating T cells and macrophages in the parental tumour correlates with growth rate of tumoroids established from colorectal adenocarcinoma.

The aim of the present study was to investigate the correlation between the density of infiltrating T cells and macrophages in the parental colorectal cancer (CRC) and the growth rate of tumoroids (i.e. a patient-derived in vitro 3D model). Tumoroids were established from fresh specimens of primary and metastatic CRC from 29 patients. The in vitro growth rate of tumoroids was monitored by automated imaging. The density of infiltrating T cells and macrophages was determined in the centre of the tumour (CT) and at the invasive margin (IM) of the parental tumours. This was performed by digital image analysis on the whole-slide scanned images using Visiopharm® software. Tumoroids with higher density of infiltrating CD3+ lymphocytes in the IM of their parental tumour showed a higher growth rate (P < .0005). The average relative growth rate (log10) during the period from day 1 to day 11 was 0.364 ± 0.006 (mean ± SD) for the CD3+ (IM)-high group and 0.273 ± 0.008 (mean ± SD) for the CD3+ (IM)-low group. In contrast, the density of CD68+ infiltrating macrophages in the parental tumours showed significant inverse effect on the growth rate of the tumoroids (P < .0005). The present study showed that the density of immune cells in the parental CRC correlates with the growth rate of the tumoroids. The future perspective for such a 3D model could be in vitro investigations of the tumour-associated inflammatory microenvironment as well as personalized cancer immunotherapy.

KRAS mutations in the parental tumour accelerate in vitro growth of tumoroids established from colorectal adenocarcinoma.

The aim of the present study was to characterize a patient-derived in vitro 3D model (ie tumoroid) established from colorectal adenocarcinoma. This study investigated the growth rate of tumoroids and whether the Kirsten rat sarcoma (KRAS) mutations in the parental tumour accelerate this rate. The tumoroids were established from surgical resections of primary and metastatic colorectal adenocarcinoma from 26 patients. The in vitro growth rate of these tumoroids was monitored by automated imaging and recorded as relative growth rate. The KRAS hotspot mutations were investigated on the parental tumours by Ion Torrent™ next-generation sequencing. The KRAS mutations were detected in 58% of the parental tumours, and a significantly higher growth rate was observed for tumoroids established from the KRAS-mutated tumours compared to wild-type tumours (P < 0.0001). The average relative growth rate (log10) on day 10 was 0.360 ± 0.180 (mean ± SD) for the KRAS-mutated group and 0.098 ± 0.135 (mean ± SD) for the KRAS wild-type group. These results showed that the presence of KRAS mutations in parental tumours is associated with an acceleration of the growth rate of tumoroids. The future perspective for such a model could be the implementation of chemoassays for personalized medicine.

Quality of life, performance status, and work capacity after post-endoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVES: This study evaluated the long-term consequences of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) on health related quality of life (HRQOL), performance status, and work capacity. MATERIALS AND METHODS: A follow-up study with prospective outcome measurements on patients with previous PEP and matched controls from a Danish cohort of 772 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). HRQOL was evaluated by the short form 36 health surveys, performance status by the Zubrod score, and work capacity by employment status. Multivariable models were applied to adjust for potential confounders. RESULTS: Twenty-nine cases and 49 controls were included. Twelve (41%), eight (28%), and nine (31%) patients had mild, moderate, and severe PEP, respectively. Mean follow-up time was 4.8 ± 1.7 years. PEP was associated with long-term reduced mental HRQOL (-13.0 role-emotional score points, 95% CI: -25.4; -0.52). An increased Zubrod score representing reduced performance status was present in 12 of the 29 cases (41.4%) and in nine of the 49 controls (18.4%), p = .002. Reduced work capacity was present in 14 of the 29 cases (48.2%) and in 12 of the 49 controls (24.4%), p = .023. CONCLUSIONS: This study indicates that PEP has a detrimental effect on long-term HRQOL, performance score, and work capacity.

The Impact of Intraoperative Fluid Therapy and Body Temperature on Surgical Site Infection - Re-Assessment of a Randomized Trial.

Background: Use of supplemental oxygen during surgery to reduce the incidence of SSI was investigated in the PROXI trial, which found no reduced frequency of SSI. Subsequently, it has been suggested that a restrictive fluid regimen and hypothermia in some patients could explain why no beneficial effect of supplemental oxygen was found. We evaluated the association between the occurrence of SSI and two perioperative factors, volume of infused fluid and body temperature (BT). Methods: We used data from the PROXI trial including 1,386 patients undergoing laparotomy randomly assigned to receive 80% or 30% oxygen during surgery. A fluid infusion index (FII) was calculated for each patient as the volume of infused fluids/body weight/duration of surgery. Results: SSI occurred in 18.9% of the patients in the lower FII tertile group (OR=0.86; P=0.41), in 20.4% in the upper FII tertile group (OR=1.49; P=0.05), in 19.7% of the patients with hypothermia (OR=1.28; P=0.25) and in 25.0% with hyperthermia (OR=1.26; P=0.52). An increased risk of SSI (OR=3.15; P=0.01) was found in patients having both hypothermia and emergency surgery. CONCLUSION: A trend towards an increased risk of SSI was seen in patients who received a greater volume of intravenous fluid. No association was found between BT and SSI.

Impaired collagen synthesis in the rectum may be a molecular target in anastomotic leakage prophylaxis.

The underlying molecular mechanisms for anastomotic leakage (AL) after colorectal surgery are unknown and there are no therapeutics for AL prevention. Our aim was to correlate endogenous matrix metalloproteinase (MMP) activity, collagen concentration, and collagen/MMP/cytokine mRNA levels with anatomic location in human colorectal tissue. We enrolled 22 patients in this prospective study: 7 underwent elective laparoscopic sigmoid resection and 15 underwent low anterior resection for colorectal cancer. Full-thickness intestinal tissue rings from anastomoses constructed with a circular stapler were used for the determination of the MMP activity, tissue collagen concentration and mRNA levels. COL1A1 (p = 0.017) and COL3A1 (p = 0.0013) mRNA levels were lower in rectal tissue than in colonic samples. Neither MMP activities nor collagen concentrations differed significantly between the two anatomic locations. By elucidating the factors responsible for the decreased collagen production we may identify specific molecular targets in AL prophylaxis.

Serotonin, calcitonin and calcitonin gene-related peptide in acute pancreatitis.

OBJECTIVE: The aim of this study was to investigate plasma levels of serotonin, calcitonin and calcitonin gene-related peptide (CGRP) in the course of acute pancreatitis (AP) taking organ failure, etiology and severity into consideration. MATERIAL AND METHODS: Sixty consecutive patients with alcohol- or gallstone-induced AP were included over a 15-month period. Patients were treated according to a standardized algorithm and monitored for organ specific morbidity and mortality. Organ functions and blood samples were assessed on days 0, 1, 2 and 14 after hospital admission. Twenty healthy volunteers, matched for age and gender, comprised the reference group. RESULTS: Lower levels of serotonin were observed in patients at admission compared to healthy volunteers (p = .021). Serotonin levels increased from day 2 to 14 (p < .001), but with no relation to severity, etiology or organ failure. No difference in calcitonin levels was found in patients at admission compared to healthy volunteers. However, calcitonin levels decreased over time (p < .001) and higher levels were found in patients with respiratory failure (p = .039). No difference was observed in relation to severity or etiology. CGRP levels in patients at admission did not differ from healthy volunteers, nor did CGRP change over time or show any relationship to severity, etiology or organ failure. CONCLUSION: Our data suggest serotonin and calcitonin levels to be associated to time-course of AP, and calcitonin levels to organ dysfunction. We hypothesize that serotonin plays a pathogenic role in the compromised pancreatic microcirculation, and calcitonin a role as a biomarker of severity in AP.

Selective matrix metalloproteinase inhibition increases breaking strength and reduces anastomotic leakage in experimentally obstructed colon.

PURPOSE: Colonic obstruction causes loss of collagen and impairment of anastomotic integrity by matrix metalloproteinases (MMPs). Unexpectedly, pharmacological MMP inhibition increased anastomotic leakage (AL) in obstructed colon possibly due to the non-selective nature of these compounds and the experimental model applied. We therefore studied the effects of selective MMP inhibition on the healing of anastomoses in colon obstructed by a novel laparoscopic technique. METHODS: Left colon was obstructed in 38 male Sprague-Dawley rats (226-284 g). After 12 h, stenoses were resected and end-to-end anastomoses constructed. Baseline breaking strength was determined in 6 animals on day 0. The remaining 32 rats were randomized to daily treatment with the selective MMP-8, MMP-9, and MMP-12 inhibitor AZD3342 (n = 16) or vehicle (n = 16). On day 3, anastomoses were evaluated for AL and breaking strength. Isolated anastomotic wound tissue was analyzed on total collagen and pepsin-insoluble and pepsin-soluble collagen by hydroxyproline. The soluble collagens were further differentiated into native, measured by Sircol, and fragmented forms. RESULTS: Baseline breaking strength was maintained with AZD3342 but decreased by 25% (P = 0.023) in the vehicle group. The anastomotic breaking strength of AZD3342-treated rats was 44% higher (P = 0.008) than the vehicle-treated rats. Furthermore, the AL rate was reduced (P = 0.037) with AZD3342 compared with vehicle treatment. AZD3342 treatment influenced neither the total or insoluble collagen concentrations nor the degree of fragmentation of the soluble collagen triple helices. CONCLUSION: Selective MMP inhibition increased anastomotic breaking strength and reduced AL after resection of colonic obstruction.

Effect of body weight on fixed dose of diclofenac for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVE: The aim of this study was to assess the influence of patient body weight on the clinical effect of 100 mg diclofenac administered as a single dose for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). MATERIALS AND METHODS: All patients subjected to endoscopic retrograde cholangiopancreatography (ERCP) from 2009 to 2014 were evaluated for inclusion. In total, 772 patients were included of whom 378 (49%) received diclofenac prophylaxis. RESULTS: In the diclofenac prophylaxis group, body weight was higher in patients with PEP (mean ± SD: 82 ± 18 kg) than in patients without PEP (74 ± 18 kg) (p = 0.029). In patients not receiving prophylaxis, body weight was not associated with the occurrence of PEP (mean ± SD: 77 ± 18 vs 75 ± 18 kg, respectively, p = 0.450). In an adjusted analysis, higher patient body weight was inversely associated with the clinical effect of 100 mg diclofenac for the prophylaxis of PEP. CONCLUSIONS: High patient body weight was associated with a reduced effect of 100 mg diclofenac for prophylaxis of PEP.

Association of Comorbidity with Anastomotic Leak, 30-day Mortality, and Length of Stay in Elective Surgery for Colonic Cancer: A Nationwide Cohort Study.

BACKGROUND: Comorbidity has a negative influence on the long-term prognosis in patients with colorectal cancer, whereas its impact on the postoperative course is less clear. OBJECTIVES: The aim of this study was to investigate the influence of comorbidity on anastomotic leak and short-term outcomes after resection for colonic cancer. DESIGN: This is a retrospective nationwide cohort study SETTING: : Data were obtained from the Danish Colorectal Cancer Group and the National Patient Registry. PATIENTS: Patients with colonic cancer undergoing elective resection between 2001 and 2008 were selected. MAIN OUTCOME MEASURES: The primary outcome was the ability of comorbidity to predict anastomotic leak. Secondary outcomes were 30-day mortality and length of stay. Comorbidity was assessed by the Charlson Comorbidity Index. Multivariable logistic regression and receiver operating characteristics curves were used to adjust for confounding. RESULTS: The rate of anastomotic leak was 535/8597 (6.2%). The mean (95% CI) Charlson score was 0.83 (0.72-0.94) and 0.63 (0.61-0.66) for patients with and without anastomotic leak, p < 0.001. The Charlson score, as assessed in the multivariable analysis (adjusted OR, 1.07; 95% CI, 0.99-1.15; p = 0.077) and by receiver operating characteristics curves (area under the curve = 0.548), failed to predict anastomotic leak. Thirty-day mortality was 425/8587 (4.9%). In patients with anastomotic leakage, a Charlson score of ≥ 2 was associated with increased mortality in comparison with a Charlson score of <2 (adjusted HR, 1.58; 95% CI, 1.00-2.51; p = 0.047). Mean length of stay was 8.7 days (95% CI, 8.4-9.2 days) for patients without an anastomotic leak in comparison with 23.3 days (95% CI, 21.5-25.1 days) for patients with anastomotic leak and 25.5 days (95% CI, 21.7-29.3 days) in patients with anastomotic leak and a Charlson score of >2, p < 0.001. LIMITATIONS: This study is limited by the accuracy of the coding used to generate the Charlson Comorbidity Index and the retrospective study design. CONCLUSION: Comorbidity failed to predict anastomotic leak, but it was associated with an inferior short-term outcome in patients with this surgical complication.

Health-related quality of life scores changes significantly within the first three months after hernia mesh repair.

BACKGROUND: Patient-related outcome measures (PROM) such as quality of life (QoL) after hernia repair are important to monitor, since QoL is an important indication of a hernia repair. Carolinas Comfort Scale (CCS) is a hernia-specific questionnaire regarding health-related QoL after a mesh hernia repair. The primary objective of this study was to monitor changes in health-related QoL over time after different mesh hernia repair procedures using the CCS. METHODS: We performed a prospective study with an exploratory, intraobserver design enrolling consecutive patients who were to undergo elective mesh hernia repair. Four different hernia repair techniques were included and analyzed specifically for each surgical group. Patients scored themselves using CCS preoperatively and at several fixed times postoperatively. Since no gold standard exists for either hernia-specific QoL questionnaires or change of scores on PROMs as a function of time after hernia repair, we compared the CCS scores with the visual analog scale (VAS) scores reflecting the subdomains of the CCS. RESULTS: A total of 166 patients completed the study. CCS scores for QoL, pain, sensation of mesh, and activity limitations changed significantly with time during the 90-day study period. Furthermore, CCS and VAS showed significant agreement and correlation (ρ = 0.52-0.82, P < 0.001). CONCLUSIONS: The present study is the first to demonstrate significant changes over time in health-related QoL using the CCS after four different types of hernia repair with mesh.

Early detection of recurrence after curative resection for colorectal cancer - obstacles when using soluble biomarkers?

OBJECTIVE: Results from monitoring studies using biomarkers in blood samples aiming at early detection of recurrent colorectal cancer (CRC) are presently evaluated. However, some serological biomarker levels are influenced by the surgical trauma, which may complicate translation of the levels in relation to recurrence. The primary purpose of the present study was to evaluate the frequency of postoperative surgical interventions during a follow-up period of patients who have undergone surgery for primary CRC. METHODS: In a prospective multicenter, clinical study, 634 patients resected for primary CRC were followed in the outpatient clinic every third month. Blood samples were drawn at each visit. A subgroup of 165 stage II and III patients, who had been followed for at least 3 years, was selected. Any recent surgical intervention associated with the primary disease and/or other diseases were recorded at each visit to the outpatient clinic. RESULTS: Among the 165 patients, 49 developed recurrence (R+), 107 did not (R-) and 11 developed a new primary cancer, including 2 in the R+ group. Within the 3 years of observation, 78 (47.3%) of the 165 patients underwent 117 (range 1-5) postoperative surgical interventions. Seventy-five operations were related to CRC and 42 to benign diseases, while none were related to a new primary, malignant disease. CONCLUSION: Patients resected for CRC are frequently undergoing surgical procedures in the postoperative follow-up period. Therefore, postoperative monitoring using soluble biomarker levels, which may be influenced by the surgical trauma, must be adjusted in relation to postoperative surgical interventions.

Expression and inhibition of matrix metalloproteinase (MMP)-8, MMP-9 and MMP-12 in early colonic anastomotic repair.

PURPOSE: Submucosal collagen is paramount for colonic anastomotic integrity. Matrix metalloproteinases (MMPs) mediate collagen degradation that increases the risk of wound dehiscence. Although broad-spectrum MMP inhibitors are beneficial for anastomotic strength, they can cause adverse reactions. Knowledge of specific MMPs responsible for the weakening of anastomoses can be used to optimise MMP inhibition therapy. We aimed to quantify transcript and protein levels of multiple MMPs in colonic anastomoses and evaluate the effect of inhibiting the MMPs that displayed the highest expression levels on anastomotic repair. METHODS: Left-sided colonic anastomoses were made in male Sprague-Dawley rats. After 3 days when biomechanical strength is lowest, MMP mRNA and protein levels were measured by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays and gelatin zymography. The effects of the MMP-8, MMP-9 and MMP-12 synthetic inhibitor AZD3342 was also studied. RESULTS: MMP-8, MMP-9 and MMP-12 gene and protein expression increased profoundly (p < 0.01), and MMP-13 mRNA and MMP-2 mRNA and protein modestly (p < 0.001) in the anastomoses. MMP-3 mRNA levels were not up-regulated significantly compared with adjacent uninjured colon. Increased anastomotic MMP-12 levels paralleled macrophage infiltration by immunohistochemical analyses. AZD3342 (50 mg/kg) treatment increased the anastomotic breaking strength by 29% (p = 0.015) day 3 compared with vehicle. Improved anastomotic strength was not accompanied with alterations of type I or type III procollagen mRNA but was possibly due to inhibition of the concerted digestive action on the existent submucosal collagens by the targeted MMPs. CONCLUSION: The present findings justify the concept of selective MMP inhibition to enhance anastomotic strength in colon.

Barriers for Participation in the Danish Colorectal Cancer Screening Program: a Qualitative Study.

PURPOSE: The participation rate in the Danish National Screening Program for Colorectal Cancer is around 60%. Since early detection of cancer through the colorectal cancer screening program (CRCS) reduces mortality rates, it is important to understand why people do not participate. The aim of this study was therefore to examine in depth why some people do not participate in the Danish CRCS program. METHODS: Individual semi-structured interviews were conducted with 18 people who had not participated in the national CRCS program. Data was analyzed using an inductive hermeneutic approach. RESULTS: The analysis uncovered three main themes describing barriers to screening: (a) the accountability for ensuring personal health covered the following sub-themes: (i) when invitation is out of sight it is out of mind, (ii) aversion against own stool sample collection, and (iii) the perceived risk of getting colorectal cancer (CRC); (b) attitudes towards the healthcare system and its organization covered the following sub-themes: (i) positivity towards CRCS, (ii) trust in the healthcare system, (iii) lack of internal communication in the healthcare system, and (iv) wish for involvement of the general practitioner (GP); (c) knowledge about disease and screening covered the following sub-themes: (i) knowledge about CRC and CRCS, (ii) wish for information via new channels, and (iii) CRC is rarely something you talk about. CONCLUSION: Among the informants included in this study, lack of participation in the CRCS program was not due to an active opt-out, as most informants had intentions of participating. The informants thought it would motivate them to participate if their GP would remind them of the screening program.