Long-term Outcomes of Robot-assisted Versus Laparoscopic Surgery for Colon Cancer: A Nationwide Register-based Cohort Study.

OBJECTIVE: To determine long-term survival in patients undergoing robot-assisted surgery (RAS) or laparoscopic surgery (LAS) for colon cancer. BACKGROUND: The potential long-term benefits of RAS compared with LAS for colon cancer are not well examined. Using a register-based approach, we aimed to compare these 2 surgical platforms in an analysis of long-term outcomes, including recurrence-free survival and all-cause- and colon cancer-specific mortality. METHODS: A nationwide register-based cohort study of patients with Union for International Cancer Control stage I-III colon cancer undergoing planned RAS or LAS from 2010 through 2018. Patient demographic, clinical, and pathological data were retrieved from Danish national registers. Survival and recurrence rates were estimated by Cox proportional hazard multivariate regression analysis adjusting for baseline covariates. RESULTS: A total of 7565 patients [LAS=6905 (91%) and RAS=660 (9%)] were included in the complete case survival analysis. Patients undergoing LAS had a significantly increased risk of cancer recurrence [LAS=1178 (17.1%), RAS=82 (12.4%), P =0.002] with a mean follow-up time of 4.93 years (standard deviation 2.47). The survival analysis of recurrence-free survival favored RAS [hazard ratio adjusted =0.80, 95% CI (0.64-1.00), P =0.049]. No associations between the 2 surgical platforms were evident regarding all-cause [hazard ratio adjusted =0.98, 95% CI (0.82-1.17), P =0.783] or colon cancer-specific mortality [hazard ratio adjusted =0.89, 95% CI (0.67-1.18), P =0.405]. CONCLUSIONS: Adopting RAS for colon cancer was associated with improved recurrence-free survival. However, it did not cause a lower all-cause- or colon cancer-specific mortality.

Faecal haemoglobin concentrations are associated with all-cause mortality and cause of death in colorectal cancer screening.

BACKGROUND: Colorectal cancer (CRC) screening reduces all-cause and CRC-related mortality. New research demonstrates that the faecal haemoglobin concentration (f-Hb) may indicate the presence of other serious diseases not related to CRC. We investigated the association between f-Hb, measured by a faecal immunochemical test (FIT), and both all-cause mortality and cause of death in a population-wide cohort of screening participants. METHODS: Between 2014 and 2018, 1,262,165 participants submitted a FIT for the Danish CRC screening programme. We followed these participants, using the Danish CRC Screening Database and several other national registers on health and population, until December 31, 2018. We stratified participants by f-Hb and compared them using a Cox proportional hazards regression on all-cause mortality and cause of death reported as adjusted hazard ratios (aHRs). We adjusted for several covariates, including comorbidity, socioeconomic factors, demography and prescription medication. RESULTS: We observed 21,847 deaths in the study period. Our multivariate analyses indicated an association relationship between increasing f-Hb and the risk of dying in the study period. This risk increased steadily from aHR 1.38 (95% CI: 1.32, 1.44) in those with a f-Hb of 7.1-11.9 µg Hb/g faeces to 2.20 (95% CI: 2.10, 2.30) in those with a f-Hb ≥60.0 µg Hb/g faeces, when compared to those with a f-Hb ≤7.0 µg Hb/g faeces. The pattern remained when excluding CRC from the analysis. Similar patterns were observed between incrementally increasing f-Hb and the risk of dying from respiratory disease, cardiovascular disease and cancers other than CRC. Furthermore, we observed an increased risk of dying from CRC with increasing f-Hb. CONCLUSIONS: Our findings support the hypothesis that f-Hb may indicate an elevated risk of having chronic conditions if causes for the bleeding have not been identified. The mechanisms still need to be established, but f-Hb may be a potential biomarker for several non-CRC diseases.

Surgical efficacy and learning curves of laparoscopic complete mesocolic excision with intracorporeal anastomosis for right-sided colon cancer: A retrospective two-center cohort study.

BACKGROUND: There is a potential benefit on long-term outcomes following complete mesocolic excision (CME) for right-sided colon cancer when compared to conventional colectomy. This study aims to analyze the learning curve and short-term outcomes of laparoscopic CME with intracorporeal anastomosis (ICA) for right-sided colon cancer in the hands of experienced colorectal surgeons. METHODS: A two-center cohort study of consecutive patients undergoing right-sided colectomy from September 2021 to May 2022 at two tertiary colorectal centers in Denmark. Learning curves of surgical time were estimated using a cumulative sum analysis (CUSUM). RESULTS: A total of 61 patients were included. According to the CUSUM analysis, 32 cases were needed to obtain a peak in operative time, resulting in a decrease in time consumption (group 1/learning phase: 217.2 min [SD 53.6] and group 2/plateau phase 191.6 min [SD 45.1], p = 0.05). There was a nonsignificant reduction in the rates of severe surgical complications (Clavien-Dindo > 3) (13% vs. 7%, p = 0.67) between the two groups, while the length of hospital stay remained constant (median 3.0 days, interquartile range, IQR [2.0; 4.0]). CONCLUSION: The learning curve of laparoscopic CME with ICA for right-sided colon cancer demonstrated that 32 cases were needed to obtain a plateau phase expressed by operative time.

Colon capsule endoscopy following incomplete colonoscopy in routine clinical settings.

BACKGROUND: Colon capsule endoscopy (CCE) was introduced in our department on two indications; following incomplete colonoscopy as an alternative to CT colonography, and in patients with a history of incomplete colonoscopy as an alternative to anesthesia-assisted (AA) colonoscopy. We aimed to compare the quality of CCE, defined by completion rate and polyp detection rate (PDR), with that of CT colonography and AA colonoscopy, respectively. METHODS: Patients referred for CCE from May 2020 until November 2021 were consecutively included in this prospective cohort study. Demographics, indication and CCE outcomes were registered from the electronic patient record. Completion rate and PDR in CCE as an alternative to CT colonography were compared with those of a historical cohort undergoing CT colonography following incomplete colonoscopy. Completion rate and PDR in CCE as an alternative to AA colonoscopy were compared with those of a time true parallel cohort undergoing AA colonoscopy. RESULTS: In 65 patients undergoing CCE, 36 (57%) were referred as an alternative to CT colonography. The completion rate in this group was 44% compared to 96% in CT colonography (p < 0.001). The PDR in complete CCE in this group was 75% in CCE compared to 20% in CT colonography (p < 0.001). The remaining 27 (43%) of the sample were referred for CCE as an alternative to AA colonoscopy. The completion rate in this group was 33% compared to 100% in AA colonoscopy (p < 0.001). The PDR in complete CCE in this group was 78% in CCE compared to 35% in AA colonoscopy (p = 0.013). CONCLUSIONS: The completion rate of CCE following incomplete colonoscopy is inferior to that of CT colonography and AA colonoscopy. The PDR of CCE was high, indicating an acceptable sensitivity in complete investigations, but in our settings the completion rate of CCE on this indication is unacceptably low. CLINICAL TRIAL REGISTRATION: NCT04307901 (ClinicalTrials.gov, March 13, 2020).

Intracorporeal versus extracorporeal anastomosis in segmental resections for colon cancer: a retrospective cohort study of 328 patients.

PURPOSE: The intracorporeal anastomosis (IA) technique possibly results in enhanced recovery and reduced morbidity rates compared to the extracorporeal anastomosis (EA) technique. This study compared the short-term morbidity rates of IA versus EA in segmental resections for colon cancer. METHOD: We performed a retrospective cohort study of consecutive patients from 2015 to 2020 using the IA or EA technique at a single Danish colorectal center. Comparative outcomes of interest were surgical efficacy and short-term morbidity rates. An inverse probability of treatment weighting (IPTW) analysis of clinically relevant outcomes was conducted to explore potential baseline confounding. RESULTS: We included 328 patients, 129 in the EA and 199 in the IA groups. There was no significant difference in preoperative baseline characteristics between the two groups. The rate of overall surgical (16% in both groups, p = 1.000) and medical complications (EA: 25 (19%) vs. IA: 27 (14%), p = 0.167) was comparable for both groups. The IA technique did not cause a reduction in operative time (EA: 127.0 min [103.0-171.0] vs. IA: 134.0 min [110.0-164.0], p = 0.547). The IPTW analysis indicated that having an IA caused a reduction in the rate of major surgical complications (RRRadjusted = 0.45, 95%CI [0.29-0.69], p = 0.000). CONCLUSION: Adopting IA for colon cancer resulted in similar overall morbidity rates without increasing the duration of the surgical procedure compared to EA. The IA technique had a probable protective effect against developing severe surgical complications. However, this must be interpreted cautiously, limited by the retrospective study design.

Robot-assisted versus laparoscopic short- and long-term outcomes in complete mesocolic excision for right-sided colonic cancer: a systematic review and meta-analysis.

BACKGROUND: Complete mesocolic excision (CME) surgery is increasingly implemented for the resection of right-sided colonic cancer, possibly resulting in improved 5-year overall and disease-free survival compared to non-CME surgery. However, it is not clear what surgical platform should be used. The aim of this study was to compare the following outcomes between robot-assisted and laparoscopic CME-surgery for right-sided colonic cancer: (i) short-term clinical outcomes, (ii) pathological specimen quality, and (iii) long-term oncological outcomes. METHODS: Medline, Embase, and Cochrane Database of Systematic Reviews were searched from inception until August 2021. Pooled proportions were calculated by applying the inverse variance method. Heterogeneity was explored by I-square and supplemented by sensitivity- and meta-regression analyses. The risk of bias was evaluated by either MINORS or Cochrane's risk-of-bias tool (RoB 2). RESULTS: Fifty-five studies with 5.357 patients (740 robot-assisted and 4617 laparoscopic) were included in the meta-analysis. Overall postoperative morbidity was 17% [95% CI (14-20%)] in the robot-assisted group and 13% [95%CI (12-13%)] in the laparoscopic group. Robot-assisted CME was associated with a shorter hospital stay, lower intraoperative blood loss, a higher amount of harvested lymph nodes, and better 3-year oerall and disease-free survival. MINORS and RoB2 indicated a serious risk of bias across studies included. CONCLUSIONS: This review which includes predominantly non-randomized studies suggests a possible advantage of the robot-assisted CME compared with a laparoscopic technique for several short-term outcomes.

Local excision after (near) complete response of rectal cancer to neoadjuvant radiation: does it add value?

PURPOSE: Neoadjuvant radiotherapy is commonly used in rectal cancer. When used prior to radical surgery in locally advanced disease, up to one-quarter of patients have no residual cancer at surgery suggesting that radical surgery was unnecessary; those with complete clinical response may be managed on a rectal-preserving 'watch-and-wait' pathway. In those receiving radiotherapy for early stage cancer, local excision of small volume residual or recurrent tumour is possible, but its value is unclear. METHODS: Data were collected from two institutions (UK and Denmark) which maintain prospective databases on all patients undergoing local excision by transanal endoscopic microsurgery (TEM). The study group was all patients who had TEM after neoadjuvant radiation for rectal cancer over an 11-year period. RESULTS: Forty-five patients had TEM after neoadjuvant radiation, 18 after short course radiotherapy (SCRT) and 27 after chemoradiotherapy (CRT). Local recurrence occurred in 13 (29%) and distant metastases in 11 (24%). Complete pathological response was noted in 10 (22%), 28% after SCRT and 19% after CRT, p = 0.02. However, local recurrence still occurred in 60% of those with ypT0 after SCRT. The recurrence rate may be higher in those with residual disease at TEM compared with complete responders (40 vs 30%). CONCLUSION: If complete response can be determined clinically, local excision of the scar does not confer benefit, but follow-up should be maintained. If there is regrowth or residual tumour at TEM, further recurrence is common, and the benefits of TEM may not outweigh the risks, except in those unsuitable for radical surgery.

Local excision after polypectomy for rectal polyp cancer: when is it worthwhile?

AIM: The optimal management of a polyp cancer that has been removed endoscopically is unclear. Further local excision is often advocated to remove the polyp stalk or scar or to ensure clear margins, but the benefit of this is unclear. The aim of this paper is to determine whether the indications for further local excision can be better defined. METHOD: Data were collected from two institutions (in UK and Denmark) which maintain prospective databases to collect information on all patients undergoing transanal endoscopic microsurgery (TEM). The study group was all patients who had a TEM after macroscopically complete polypectomy for rectal cancer. Data covering an 11-year period were analysed. RESULTS: Sixty three patients had TEM with no residual cancer after macroscopically complete polypectomy. Residual adenoma was found in 23 (37%). A postpolypectomy endoscopy had not detected the residual adenoma in three. Malignant local recurrence occurred in five patients (8%) and distant metastases in another two (3%). Recurrence occurred in 4/23 (17%) when there was residual adenoma in the TEM specimen and in 3/40 (7.5%) where there was scar only, although this did not reach significance. In two instances recurrence was around 10 years after TEM. Those with residual adenoma at TEM tended to have poorer survival. CONCLUSION: Further local excision often reveals no residual cancer despite microscopically involved polypectomy margins. Careful endoscopy is required to assess the polypectomy site as residual tumour can be missed. In the absence of residual adenoma, TEM does not appear to be of benefit, although a small risk of recurrence exists.

Patient-reported minor adverse events after colonoscopy: a systematic review.

OBJECTIVE: The purpose of this systematic review was to investigate the incidence and nature of minor adverse events (MAEs) after colonoscopy, and response rates to questionnaires concerning MAEs in patients undergoing colonoscopy. MATERIALS AND METHODS: A systematic literature search was conducted in the databases PubMed and Embase. Predictor variables were patient-reported MAEs after colonoscopy. The outcome was frequency and types of MAEs and the patients' response rate to questionnaires after colonoscopy. Quality assessment for potential risk of bias and level of evidence was evaluated using the National Health and Medical Research Council guidelines. RESULTS: Seven prospective cohorts were included with a pooled total of 6172 participants. Patients undergoing colonoscopy had a response rate to questionnaires ranging from 64% to 100%, with a mean of 81%. One-third of the patients experienced MAEs, most prominently in the first 1-2 weeks after colonoscopy, and less common at 30 days post colonoscopy. The most frequently reported MAEs were abdominal pain, bloating and abdominal discomfort. CONCLUSIONS: In general, patients undergoing colonoscopy have a high response rate to questionnaires about MAEs. MAEs after colonoscopy are commonly seen. High age and score of American Society of Anesthesiologists (ASA) classification, female gender and duration of procedure seem to be associated with a higher risk of MAEs, whereas adequate sedation seems to decreases the risk. MAEs after colonoscopy seems to be underreported in the current literature and the existing evidence is based on inhomogeneous reports. In the current study, it was not possible to conduct a meta-analysis. There is a need for larger scale studies addressing the MAEs patients experience in conjunction with a colonoscopy. Furthermore, the assessment of the MAEs should rely on questionnaires tested for validity, comprehensibility and reliability, to reflect the patient-reported experience of a colonoscopy as precise as possible.

Differentiation between malignant and benign rectal tumors by dual-energy computed tomography - a feasibility study.

INTRODUCTION: To assess the performance of Dual Energy Computed Tomography (DECT) in the differentiation between benign and malignant tumors in the rectum. MATERIAL AND METHODS: We enrolled 8 subjects with rectal tumors suspected to be an early rectal cancer during colonoscopy. All subjects underwent Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Endorectal Ultrasound (ERUS) for staging. Furthermore, all subjects underwent fast switching of tube voltage between 80 and 140 kVp DECT of the pelvis. The 8 subjects had histopathological verified benign adenomas after transanal endoscopic microsurgery resection (TEM). The 8 subjects were matched with 8 consecutively selected subjects with histopathologically verified malignant rectal tumors. The DECT images were analyzed to assess the difference between malignant and benign rectal tumors. All DECT images were reviewed by experienced radiologists. In each DECT scanning, we applied three regions of interest (ROIs) for the acquisition of the DECT unique quantitative parameters. The mean atomic mass (effective Z value), iodine concentration, dual energy ratio (DER) and dual-energy index (DEI) was determined in both groups. RESULTS: The comparison of the 2 groups showed a significant difference in effective Z and a nonsignificant difference regarding iodine concentration, DER, and DEI in the two groups. CONCLUSION: Dual-energy CT demonstrated a difference in the mean atomic mass in benign colorectal tumors in comparison to malignant colorectal tumors.

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.

Dual energy CT - a possible new method to assess regression of rectal cancers after neoadjuvant treatment.

BACKGROUND AND OBJECTIVES: The measurement of tumor regression after neoadjuvant oncological treatment has gained increasing interest because it has a prognostic value and because it may influence the method of treatment in rectal cancer. The assessment of tumor regression remains difficult and inaccurate with existing methods. Dual Energy Computed Tomography (DECT) enables qualitative tissue differentiation by simultaneous scanning with different levels of energy. We aimed to assess the feasibility of DECT in quantifying tumor response to neoadjuvant therapy in loco-advanced rectal cancer. METHODS: We enrolled 11 patients with histological and MRI verified loco-advanced rectal adenocarcinoma and followed up on them prospectively. All patients had one DECT scanning before neoadjuvant treatment and one 12 weeks after using the spectral imaging scan mode. DECT analyzing tools were used to determine the average quantitative parameters; effective-Z, water- and iodine-concentration, Dual Energy Index (DEI), and Dual Energy Ratio (DER). These parameters were compared to the regression in the resection specimen as measured by the pathologist. RESULTS: Changes in the quantitative parameters differed significantly after treatment in comparison with pre-treatment, and the results were different in patients with different CRT response rates. CONCLUSION: DECT might be helpful in the assessment of rectal cancer regression grade after neoadjuvant treatment.

Dual-Energy CT of Rectal Cancer Specimens: A CT-based Method for Mesorectal Lymph Node Characterization.

BACKGROUND: An accurate method to assess malignant lymph nodes in the mesorectum is needed. Dual-energy CT scans simultaneously with 2 levels of energy and thereby provides information about tissue composition based on the known effective Z value of different tissues. Each point investigated is represented by a certain effective Z value, which allows for information on its composition. OBJECTIVE: We wanted to standardize a method for dual-energy scanning of rectal specimens to evaluate the sensitivity and specificity of benign versus malignant lymph node differentiation. Histopathological evaluation of the nodes was our reference. DESIGN: This was a descriptive and prospective study. SETTINGS: Seventeen rectal specimens were examined in 2 series. The first series was conducted with 3 specimens from patients who were not given perioperative contrast; 3 had iodine-based contrast and 3 had gadolinium-based contrast. We concluded that iodine was the contrast agent of choice and therefore included 8 more patients in a second series, given iodine-based contrast, for further analysis. PATIENTS: Quantitative imaging data were collected from 197 individual lymph nodes from 17 specimens, from patients with rectal cancer. MAIN OUTCOME MEASURES: We measured accuracy of differentiating benign from malignant lymph nodes by investigating the following: 1) gadolinium, iodine, and water concentrations in lymph nodes; 2) dual-energy ratio; 3) dual-energy index; and 4) effective Z value. RESULTS: Optimal discriminations between benign and malignant lymph nodes were obtained using the following cutoff values: 1) effective Z at 7.58 (sensitivity, 100%; specificity, 90%; and accuracy, 93%), 2) dual-energy ratio at 1.0 × 10 (sensitivity, 96%; specificity, 87%; and accuracy, 90%), 3) dual-energy index at 0.03 (sensitivity, 97%; specificity, 88%; and accuracy, 91%), and 4) iodine concentration at 2.58 µg/mL (sensitivity, 86%; specificity, 92%; and accuracy, 89%). LIMITATIONS: The investigation is conducted on isolated surgical specimens from rectal cancer operations. CONCLUSIONS: Dual-energy CT can be performed on rectal specimens. The discrimination between benign and malignant nodes seems promising when using iodine as contrast.

Surgical treatment of right-sided colon cancer with complete mesocolic excision.

Complete mesocolic excision for right-sided colon cancer yields larger specimens with higher lymph node harvest. This has caused a reduction in recurrence rates and improved survival. However, the technique remains controversial and has been associated with a higher risk of intraoperative complications. More recently published studies do not indicate that CME is associated with increased postoperative morbidity rates as summarised in this review. More detailed consensus regarding the use of the technique is needed, and future studies should aim for prospective confirmation of the current positive long-term results.

The incidence of venous thromboembolism after curative colon cancer surgery within an enhanced recovery after surgery programme.

AIM: Based on three randomised controlled trials performed more than a decade ago, several national guidelines recommend prolonged venous thromboprophylaxis for 28 days following elective surgery for colon cancer. None of these studies were conducted within enhanced recovery after surgery setting. Newer studies indicate that prolonged prophylaxis might not be necessary with enhanced recovery after surgery. We aimed to provide further evidence to this unresolved discussion. METHOD: Retrospective study of patients undergoing elective surgery for colon cancer stage I-III with enhanced recovery after surgery in the Capital Region of Denmark from 2014 to 2017. Patients were excluded if discharged on postoperative day 28 or later, dying before discharge, undergoing concomitant rectum resection, or discharged with vitamin K antagonists, direct-oral anticoagulants, or low molecular weight heparin treatment. All patients received only low-dose low molecular weight heparin as prophylaxis during their admission. The primary endpoint was symptomatic lower limb deep venous thrombosis or pulmonary embolism diagnosed within 60 days postoperatively. RESULTS: Out of the included population of 1806 patients, only three experienced a symptomatic venous thromboembolic event; none was fatal. Two had pulmonary embolism associated with pneumonia, while one patient was diagnosed with lower limb deep venous thrombosis at postoperative day 15 after an uncomplicated course with first discharge at postoperative day 2. CONCLUSION: The risk of symptomatic venous thromboembolism after elective surgery for colon cancer with enhanced recovery after surgery seems negligible even without prolonged prophylaxis. The current guidelines need to be reconsidered.

Effect of Oral Intake of Carrot Juice on Cyclooxygenases and Cytokines in Healthy Human Blood Stimulated by Lipopolysaccharide.

In vitro studies and animal studies have shown that chemical compounds contained in carrots, such as falcarinol and falcarindiol, can prevent inflammation. The present study was designed to test whether the oral intake of carrot juice containing falcarinol and falcarindiol affects the activity of cyclooxygenase (COX) enzymes and the secretion of inflammatory cytokines in human blood. Carrot juice (500 mL) was administered orally to healthy volunteers, and blood samples were drawn before and 1 h after juice intake at the time point when peak concentrations of falcarinol and falcariondiol have been shown in the blood. The blood samples were divided, and one sample was allowed to coagulate for 1 h at room temperature before analyzing the synthesis of thromboxane B2 (TBX2) by the COX1 enzyme using an enzyme linked immunosorbent assay (ELISA). The other blood samples were stimulated ex vivo with lipopolysaccharide and incubated at 37 °C for 24 h. The ELISA and cytokine multiplex analysis assessed the levels of COX-2-induced prostaglandin E2 (PGE2) and inflammatory markers interleukin (IL) 1α, IL1ß, IL6, IL16, and tumor necrosis factor α (TNFα). Inflammatory cytokines such as IL1α and IL16 were significantly reduced in the LPS stimulated blood samples with higher concentrations of falcarinol and falcariondiol compared to the control samples taken before the intake of carrot juice. The levels of TBX2, PGE2, IL1ß, IL6, and TNFα were not affected by the carrot juice intake blood samples not stimulated with LPS. In conclusion, carrot juice rich in the polyacetylens falcarinol and falcarindiol affects blood leukocytes, priming them to better cope with inflammatory conditions, evident by the reduced secretion of the proinflammatory cytokines IL1α and IL16.

Carrot Juice Intake Affects the Cytokine and Chemokine Response in Human Blood after Ex Vivo Lipopolysaccharide-Induced Inflammation.

In vitro and animal studies have shown that carrot juice containing bioactive natural products, such as falcarinol (FaOH) and falcarindiol (FaDOH), can affect inflammation. The present study was designed to test whether oral intake of carrot juice containing the bioactive acetylenic oxylipins FaOH and FaDOH affects mediators of acute inflammation or the innate immune response in human blood. Carrot juice (500 mL) was administered orally to healthy volunteers, and blood samples were drawn before and 1 h after juice intake. Next, the blood samples were split in two, and one sample was stimulated ex vivo with lipopolysaccharide (LPS) and incubated at 37 °C for 24 h. The concentrations of 44 inflammatory cytokines and chemokines were examined using multiplex electrochemiluminescence analysis. In blood samples not stimulated with LPS, a significant increase in IL-15 was measured 1 h after carrot juice intake. Cytokines like IFN-É£, IL-12/IL-23(p40), IL-23, IL-17A, IL-17B, IL-17D, and IL-22 were significantly increased in LPS-stimulated blood samples after carrot juice intake. The upregulation of the immunostimulating cytokines belonging to the IL-23/IL-17 Th17 axis suggests that carrot juice intake could benefit diseases where inflammation plays a role, like in the early stages of diabetes or cancers.

Faecal haemoglobin concentration predicts all-cause mortality.

BACKGROUND: Population-based screening for colorectal cancer by a faecal immunochemical test (FIT) is recommended by the European Union. Detectable faecal haemoglobin can indicate colorectal neoplasia as well as other conditions. A positive FIT predicts an increased risk of death from colorectal cancer but might also predict an increased risk of all-cause mortality. METHODS: A cohort of screening participants was followed using the Danish National Register of Causes of Death. Data were retrieved from the Danish Colorectal Cancer Screening Database supplemented with FIT concentrations. Colorectal cancer specific and all-cause mortality were compared between FIT concentration groups using multivariate cox proportional hazards regression models. FINDINGS: In 444,910 Danes invited for the screening program, 25,234 (5·7%) died during a mean follow-up of 56·5 months. Colorectal cancer caused 1120 deaths. The risk of colorectal cancer death increased with the increasing FIT concentration. The hazard ratios ranged from 2·6 to 25·9 compared to individuals with FIT concentrations <4 µg hb/g faeces. Causes other than colorectal cancer caused 24,114 deaths. The risk of all-cause death increased with the increasing FIT concentration, with the hazard ratios ranging from 1·6 to 5·3 compared to individuals with FIT concentrations <4 µg hb/g faeces. INTERPRETATION: The risk of colorectal cancer mortality increased with the increasing FIT concentrations even for FIT concentrations considered negative in all European screening programs. The risk of all-cause mortality was also increased for individuals with detectable faecal blood. For colorectal cancer specific mortality and all-cause mortality, the risk was increased at the FIT concentrations as low as 4-9 µg hb/g faeces. FUNDING: The study was funded by the Odense University Hospital grants A3610 and A2359.