Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy: A European multicenter cohort study.

BACKGROUND AND OBJECTIVES: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status. METHODS: A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAFV600E mutation, and BRAF mutated tumors were further analyzed for hypermethylation status in the promoter region of MLH1 to distinguish between sporadic and hereditary cases. Swedish and Finish patients were matched with their respective National Cancer Registries. For the Czech cohort, thorough scrutiny of medical files was performed to identify any non-colorectal malignancy within 20 years before or after the diagnosis of CRC. Poisson regression analysis was performed to identify the incidence rates of non-colorectal malignancies. For validation purposes, standardized incidence ratios were calculated for the Swedish cases adjusted for age, year, and sex. RESULTS: Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60-75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89-3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67-3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28-2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72-3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05-2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63-3.42, p = 0.005), respectively. CONCLUSION: In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.

Evaluation of Extracellular Matrix Remodeling in Full-thickness Skin Grafts in Mice.

Abdominal hernia is a protruding weakness in the abdominal wall. It affects abdominal strength and life quality and can lead to complications due to intestinal entrapment. Autologous full-thickness skin graft (FTSG) has recently become an alternative material for reinforcement in the surgical repair of large abdominal hernias instead of synthetic mesh. FTSG eventually integrates with the abdominal wall, but the long-term fate of the graft itself is not fully understood. This has implications as to how these grafts should be optimally used and handled intraoperatively. This study investigates the remodeling of FTSG in either the onlay or the intraperitoneal position 8 weeks after FTSG transplantation in an experimental mouse model. There was a significant presence of fibroblasts, indicated by vimentin and S100A4 staining, but there were significant variations among animals as to how much of the graft had been remodeled into dense connective tissue. This correlated significantly with the proportion of vimentin-positive cells in the dense connective tissue. We also found that collagen hybridizing peptide staining intensity, a marker of active remodeling, was significantly associated with the proportion of S100A4-positive cells in the dense connective tissue of the FTSG.

Laparoscopic ventral hernia repair: early follow-up of a randomized controlled study of primary fascial closure before mesh placement.

BACKGROUND: Suturing of the hernia aperture in laparoscopic ventral hernia repair has increased during the past decade. The primary aim of this is to restore the anatomy of the abdominal wall. Closure of the aperture, however, may cause additional tension in the abdominal wall which could increase postoperative pain. The aim of this study was to investigate whether suturing of the hernia aperture affects postoperative pain and hernia-site complications, including seroma, infection, pseudohernia, and mesh migration, 3 months after repair. METHODS: Some 192 patients with a midline hernia between 2 and 8 cm in transverse diameter were included in a randomized controlled double-blinded multicentre study. Patients were randomized to mesh repair with (intervention) or without (control) suturing of the hernia aperture before mesh placement. Patients completed the Ventral Hernia Pain Questionnaire before and 3 months after surgery. Abdominal wall pain and hernia-site complications were assessed 3 months after surgery. RESULTS: Ninety-seven patients were randomized to the intervention group and 95 to the control group. Among all patients, median age and BMI was 56 years and 31 kg/m2 respectively. Overall pain experienced decreased by 3 months after operation (P < 0.001). There was no difference between groups regarding hernia-site complications or pain experienced during the past week (13 versus 23 patients; P = 0.111). Seroma and pseudohernia occurred in 13 and 11 patients in the intervention and control groups respectively (P = 0.975 and P = 0.977). CONCLUSION: Restoration of the abdominal wall anatomy by suturing the hernia aperture before mesh placement does not increase the risk of hernia-site complication or pain 3 months after surgery. This implies that fascial suturing of the aperture can be justified if there are potential long-term benefits such as lower recurrence and/or complication rates. Registration number: ISRCTN51495042 (http://www.controlled-trials.com).

Association of pre-diagnostic physical exercise and peri-diagnostic body composition with mortality in non-metastatic colorectal cancer.

PURPOSE: Sarcopenia and myosteatosis, quantified via computed tomography (CT), are associated with poor colorectal cancer outcomes. These body composition estimates can be influenced by physical exercise. We explored the correlation between pre-diagnostic physical exercise, body composition close to diagnosis, and the combined prognosis impact of these factors. METHODS: We studied 519 stage I-III colorectal cancer (CRC) cases diagnosed 2000-2016 with pre-diagnostic self-reported recreational physical exercise data collected in the prospective, population-based Northern Sweden Health and Disease Study, and CT-estimated skeletal muscle index (SMI) or skeletal muscle density (SMD). Risk estimates were calculated by multivariable logistic regression and Cox proportional hazards models. RESULTS: No association was seen between low pre-diagnostic physical exercise and sarcopenia/myosteatosis in the multivariable model adjusted for age, sex, educational level, tumor stage, and tumor location. In multivariable Cox regression models, the combination of low pre-diagnostic physical exercise and either sarcopenia or myosteatosis at the time of diagnosis was associated with cancer-specific mortality compared to the reference group of high physical exercise combined with no sarcopenia/myosteatosis (adjusted HR 1.94 95% CI 1.00-3.76 for sarcopenia and adjusted HR 2.39 95% CI 1.16-4.94 for myosteatosis). CONCLUSIONS: The combined presence of low pre-diagnostic physical exercise and sarcopenia or myosteatosis was associated with increased CRC-specific mortality. Despite the positive effect on prognosis, physical exercise did not alter body composition estimates at diagnosis, which could indicate attenuation from other factors.

Patients' experiences of living with a stoma in rural areas in Northern Sweden.

Introduction: Stoma complications are common and interfere with many aspects of everyday life. Stoma problems are usually managed by a specialised stoma nurse, a service not present in the rural areas of South Lapland in Sweden. The aim of this study was to describe how stoma patients in rural areas experience living with a stoma.Methods: A qualitative descriptive study with semi-structured interviews were conducted with 17 stoma patients living in rural municipalities and who received a part of their care at the local cottage hospital. Qualitative content analysis was employed.Results: Initially, the stoma was experienced as very depressing. Participants had difficulties in properly managing the dressing. Over time they learned how to properly care for their stoma, making their life easier. Both satisfaction and dissatisfaction with the healthcare were experienced. Those who were dissatisfied expressed a lack of competence in dealing with stoma-related problems.Conclusions: Living with a stoma in a rural area in northern Sweden is experienced as a learning process and acceptance of the stoma's existence is important. This study emphasises the need for increased knowledge of stoma-related problems in rural primary healthcare in order to help patients cope with everyday life.

Ventral hernia repair with concurrent intra-abdominal surgery: Results from an eleven-year population-based cohort in Sweden.

BACKGROUND: One remaining question in ventral hernia repair is whether to perform concurrent abdominal surgery or plan two-stage procedures. The aim was to explore the risk for reoperation and mortality due to surgical complication during index admission. METHOD: Eleven-year data were retrieved from the National Patient Register and 68,058 primary surgical admissions were included, divided into minor and major hernia surgery and concurrent abdominal surgery. Results were evaluated by logistic regression analysis. RESULTS: The risk for reoperation during index admission was higher for patients with concurrent surgery. Major hernia surgery and major concurrent surgery had an OR 37.9 compared to major hernia surgery only. Mortality rate within 30 days increased, OR 9.32. The combined risk for serious adverse event was accumulative. CONCLUSION: These results stress the importance of critically evaluating needs for and planning of concurrent abdominal surgery during ventral hernia repair. Reoperation rate was a valid and useful outcome variable.

Sonographic postpartum anal sphincter defects and the association with pelvic floor pain and dyspareunia.

INTRODUCTION: Pelvic floor pain and dyspareunia are both important entities of postpartum pelvic pain, often concomitant and associated with perineal tears during vaginal delivery. The association between postpartum sonographic anal sphincter defects, pelvic floor pain, and dyspareunia has not been fully established. We aimed to determine the prevalence of postpartum anal sphincter defects using three-dimensional endoanal ultrasonography (3D-EAUS) and evaluate their association with symptoms of pelvic floor pain and dyspareunia. MATERIAL AND METHODS: This prospective cohort study followed 239 primiparas from birth to 12 months post delivery. Anal sphincters were assessed with 3D-EAUS 3 months postpartum, and self-reported pelvic floor function data were obtained using a web-based questionnaire distributed 1 year after delivery. Descriptive statistics were compared between the patients with and without sonographic defects, and the association between sonographic sphincter defects and outcomes were analyzed using logistic regression. RESULTS: At 3 months postpartum, 48/239 (20%) patients had anal sphincter defects on 3D-EAUS, of which 43 (18%) were not clinically diagnosed with obstetric anal sphincter injury at the time of delivery. Patients with sonographic defects had higher fetal weight than those without defects, and a perineum <2 cm before the suture was a risk factor for defects (odds ratio [OR], 6.9). Patients with sonographic defects had a higher frequency of dyspareunia (OR, 2.4), and pelvic floor pain (OR, 2.3) than those without defects. CONCLUSIONS: Our results suggest an association between postpartum sonographic anal sphincter defects, pelvic floor pain, and dyspareunia. A perineal height <2 cm, measured by bidigital palpation immediately postdelivery, was a risk factor for sonographic anal sphincter defect. We suggest offering pelvic floor sonography around 3 months postpartum to high- risk women to optimize diagnosis and treatment of perineal tears and include perineum <2 cm prior to primary repair as a proposed indication for postpartum follow-up sonography.

Use of endoanal ultrasound in detecting obstetric anal sphincter injury immediately after birth.

INTRODUCTION: Obstetric anal sphincter injury (OASI) complicates around 5% of deliveries in primiparas. The study objective was to assess the utility of three-dimensional endoanal ultrasonography (3D-EAUS) in the diagnosis of OASI. MATERIAL AND METHODS: The present study was designed to mirror screening settings with an unselected cohort of nulliparous women. All enrolled patients underwent clinical examination of the perineum by the caregiver, and 3D-EAUS was conducted. Post-processing of ultrasonography volume data was performed by an experienced colorectal surgeon who was blinded to all other data. The sensitivity, specificity, negative predictive value, and positive predictive value of 3D-EAUS in the diagnosis of OASI was evaluated. The trial is registered at ISCRTN: 18006769. RESULTS: A total of 680 scans were performed, of which 18.5% were judged as "non-assessable", resulting in 554 assessable recordings. Sphincter defects were observed in 12.8% of all assessable recordings on 3D-EAUS (n = 71). With clinical examination set as the reference standard, ultrasound sensitivity in the diagnosis of OASI was 30.4%, whereas its specificity was 87.9%. The negative predictive value was 96.7% and the positive predictive value was only 9.9%. Comments were left on 175 examinations, of which 74% referred to the management of the examination. CONCLUSIONS: Using 3D-EAUS in a maternity ward is demanding because staff generally have little experience in endoanal ultrasound, which contributes to difficulties in obtaining good image quality. When 3D-EAUS is performed to mirror screening settings, it adds no convincing diagnostic power to clinical examination in the diagnosis of OASI.

Improved assessment of fecal incontinence in women with previous obstetric injury combining Low Anterior Resection Syndrome and Wexner scores.

OBJECTIVE: The aim of the current study was to assess whether Low Anterior Resection Syndrome (LARS) score could provide additional unique information to the Wexner score when assessing fecal incontinence (FI) in women with previous obstetric injury, thus providing a better foundation for treatment decisions. METHODS: This was a retrospective cohort study with intraindividual comparison of two scoring systems. Women with previous obstetric injury and diagnosed with FI between January 1, 2015, and December 31, 2018, with valid LARS and Wexner scores were included. Statistical methods used were Spearman rank correlation, Kendall τ, scatterplot, and ratios. RESULTS: Seventy women were included. Correlation coefficients varied from 0.42 to 0.66 (Spearman rank correlation) and 0.44 to 0.51 (Kendall τ). Cohen κ values varied from 0.33 to 0.67. No strong association was seen in the correlation analyses or the scatterplot. CONCLUSION: LARS score was shown to provide extra relevant information when assessing FI in women with previous obstetric injury. All symptoms should be considered relevant when assessing FI since it is a complex condition and should be approached accordingly. The authors suggest a combination of LARS and Wexner scores when assessing FI among women with previous obstetric injury.

No Reduction in Parastomal Hernia Rate 3 Years After Stoma Construction With Prophylactic Mesh: Three-year Follow-up Results From STOMAMESH-A Multicenter Double-blind Randomized Controlled Trial.

OBJECTIVE: The primary objective was to compare rates of parastomal hernia (PSH) 3 years after stoma construction with prophylactic mesh or no mesh. A secondary objective was to compare complications requiring reintervention within 3 years. BACKGROUND: Recent studies have shown that a prophylactic mesh does not reduce the rate of PSH contrary to older studies. Long-term data on efficacy and safety is however scarce. METHODS: A randomized controlled double-blind multicenter trial. Patients planned for permanent end colostomy were randomized to either prophylactic mesh in the retromuscular position around the stoma site or no mesh. They were evaluated for PSH clinically and with computed tomography (CT) 3 years after stoma construction. Medical records of all patients included were also reviewed at 3 years to detect any abdominal or abdominal wall surgery during that period. RESULTS: A total of 232 patients were randomized. At 3 years, 154 patients were available for clinical evaluation and 137 underwent a CT scan. No significant difference in PSH rates was seen between the treatment allocation arms (clinical: P =0.829 and CT: P =0.761, respectively), nor was there a significant difference in the number of reinterventions, but 2 patients had their mesh removed at emergency surgery. CONCLUSIONS: Prophylactic mesh does not reduce the rate of PSH and cannot be recommended for routine use.

The impact of a patient's social network on emergency surgery for colon cancer.

AIM: The aim of this study was to investigate if patients with a weak social network and colon cancer are more likely to be operated as an emergency than those with a strong social network. METHODS: Data from patients living in Västerbotten County, Sweden, who underwent colon cancer surgery between 2007 and 2020 were extracted from the Swedish Colorectal Cancer Registry (SCRCR). Patients identified were matched against the Västerbotten Intervention Program (VIP) and the longitudinal study Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA). These two databases include a survey that includes questions regarding quality and size of the patient's social network. Multivariable logistic regression was used for analysis. RESULTS: Six items from the questions on social network, and the composite variables availability of social integration (AVSI) and availability of attachment (AVAT) were analysed. Data from 801 patients were analysed. The odds ratio for emergency surgery was significantly higher for divorced patients (OR 2.01 (CI 1.03-3.91)) and for male gender (OR 1.51 (CI 1.02-2.24)). A higher OR was seen amongst those with no-one to share feelings with (OR 1.57 (CI 0.82-3.03)) or to comfort them (OR1.33 (CI 0.78-2.28)). Quantitative aspects of social life such as the number of people greater than 10 that feel relaxed at the patient's home, showed a lower OR (OR 0.71(CI 0.35-1.43)). CONCLUSION: The impact of social network on the risk for emergency surgery for colon cancer is limited. Divorced status and male gender were associated with an increased risk for emergency surgery.

Autologous full-thickness skin in the repair of complex ventral hernias: an innovative step into the future of complex hernia repair?

The repair of complex ventral hernias, such as giant incisional or parastomal hernia, is associated with a high risk for complications and recurrence. Some serious complications are related to implantation of synthetic mesh as reinforcement material. Autologous full-thickness skin graft (FTSG) as reinforcement material in the repair of these complex hernias may offer a safe alternative. This is a review of the history of FTSG use in hernia surgery and the experiences of our research group regarding its application over the last decade. The results of FTSG used in the repair of giant ventral hernias are promising, and this method may already be recommended in selected cases. We have also conducted a translational chain of preclinical studies, based on a murine model, to gain a greater understanding of the behaviour of FTSG implanted in various positions in the abdominal wall. The use of intraperitoneal FTSG as reinforcement material in parastomal hernia repair is currently being evaluated in a randomised, controlled, multicentre study.

Major complications and mortality after ventral hernia repair: an eleven-year Swedish nationwide cohort study.

BACKGROUND AND AIMS: Ventral hernia repair is one of the most common surgical procedures performed worldwide. Despite the large volume, consensus is lacking regarding indications for repair or choice of surgical method used for reconstruction. The aim of this study was to explore the risk for major complications and mortality in ventral hernia repair using data from a nationwide patient register. METHOD: Patient data of individuals over 18 years of age who had a ventral hernia procedure between 2004 and 2014 were retrieved from the Patient Register kept by the Swedish National Board of Health and Welfare. After exclusion of patients with concomitant bowel surgery, 45 676 primary surgical admissions were included. Procedures were dichotomised into laparoscopic and open surgery, and stratified for primary and incisional hernias. RESULTS: A total of 45 676 admissions were analysed. The material comprised 36% (16 670) incisional hernias and 64% (29 006) primary hernias. Women had a higher risk for reoperation during index admission after primary hernia repair (OR 1.84 (1.29-2.62)). Forty-three patients died of complications within 30 days of index surgery. Patients aged 80 years and older had a 2.5 times higher risk for a complication leading to reoperation, and a 12-fold higher mortality risk than patients aged 70-79 years. CONCLUSION: Age is the dominant mortality risk factor in ventral hernia repair. Laparoscopic surgery was associated with a lower risk for reoperation during index admission. Reoperation seems to be a valid outcome variable, while registration of complications is generally poor in this type of cohort.

Attitudes to and Experiences of Physical Activity After Colon Cancer Diagnosis Amongst Physically Active Individuals - A Qualitative Study.

BACKGROUND: Physical activity improves survival, reduces postoperative complications, and reduces the risk of developing colon cancer. It is important to maintain physical activity after receiving a diagnosis of colon cancer to improve postoperative recovery. Individuals who are physically active and diagnosed with colon cancer presumably have different motivations to maintain physical activity compared to their sedentary counterparts. OBJECTIVE: Enlighten how the diagnosis of colon cancer might affect physically active individuals in their attitude and experiences towards physical activity. METHODS: A qualitative study using content analysis was conducted in northern Sweden based on semi-structured telephone interviews of twenty patients diagnosed with colon cancer. All participants met the recommendations for physical activity issued by the World Health Organization. RESULTS: Participants were between 50 and 88 years and 50% were male. Three main categories were identified: I'll fight the cancer and come out stronger; The diagnosis makes no difference; and The diagnosis is an obstacle for physical activity. These main categories represent the ways the individuals reacted to the diagnosis of colon cancer regarding their physical activity. CONCLUSION: Attitudes to and experience of physical activity after colon cancer diagnosis varied from a will to increase physical activity and fight the cancer, to the diagnosis putting a stop to physical activity. It is important that healthcare professionals recommend physical activity even in already physically active individuals, to encourage continued physical activity after diagnosis of colon cancer.

Full-thickness skin grafts to reinforce the abdominal wall: a cross-sectional histological study comparing intra- and extraperitoneal onlay positions in mice.

INTRODUCTION: In the repair of complex abdominal wall hernia, there can be a strong preference to avoid synthetic or biological implants as reinforcement material. Autologous full-thickness skin grafts (FTSG) have shown promising results. However, there are few clinical data on the use of FTSG in an intraperitoneal position and rudimentary knowledge about postoperative histological appearance of tissue remodelling and repair. OBJECTIVE: To investigate the histological appearance of FTSG in the intraperitoneal onlay mesh (IPOM) position. METHODS: Isogeneic FTSG was positioned in the IPOM (10 mice) and the onlay position (10 mice). After eight weeks, tissues were harvested for histological analysis. Tissue structure, inflammation and cell survival were investigated with histological and immunohistochemical staining. RESULTS: Morphology was similar in both positions. Luciferase staining indicated both onlay and IPOM graft cell survival, with microvascular networks present. In both positions, FTSG showed ongoing tissue remodelling processes and cystic formations containing hair and epidermis. Low-grade acute phase and chronic inflammation were present. Integration was observed in 50% of the mice with similar appearances in IPOM and onlay grafts. CONCLUSION: FTSG is tolerated, with comparable results either inside or outside the abdominal cavity, and in line with historic histological evaluations. The results suggest further research on FTSG as a potential future reinforcement material in selected cases of complex abdominal wall hernia repair.

Autologous full-thickness skin graft as reinforcement in parastomal hernia repair: a randomised controlled trial.

BACKGROUND: Parastomal hernia is a common complication of an enterostomy and can have a significant impact on health-related quality of life. Currently used methods of repair have high recurrence rates and considerable risk for complications. We have developed a new technique for parastomal hernia repair that uses full-thickness skin graft as reinforcement. METHODS: This study protocol describes a multicentre randomised controlled trial on parastomal hernia repair comparing a new full-thickness skin graft technique with conventional synthetic composite mesh as reinforcement of the abdominal wall. Patients with a symptomatic parastomal hernia will be included and followed up at 3, 12 and 36 months, with surgical complication as the primary outcome. Secondary outcomes will be recurrence rate and health-related quality of life assessed with VHPQ, EORTC C30 and CR29. Tissue biology and collagen metabolism will be investigated pre- and postoperatively using biopsies of the abdominal wall fascia and blood samples. DISCUSSION: Parastomal hernia constitutes a major clinical problem where the prospects of a good result after hernia repair are presently poor. This new method of repair with full-thickness skin grafting could be a new alternative in our surgical toolbox, but before then, it must be evaluated properly. TRIAL REGISTRATION: ClinicalTrials.gov NCT03667287. Registered on September 12, 2018.

Surgical treatment of stoma-related hernias: retrospective cohort study of damage claims to the Swedish National Patient Insurance Company 2010-2016.

BACKGROUND: Parastomal hernia and stoma-site hernia are common stoma complications. Parastomal hernia repair is associated with high complication and recurrence rates. Insurance data can provide novel information on the consequences of perioperative complications from the patient's point of view. The aim was to investigate what types of complications associated with stoma-related hernia surgery that cause patients to apply for economic compensation through the patient insurance system and to investigate demographic and clinical differences among cases based on gender and type of center at which the surgery was performed. METHODS: A national patient damage claim database was searched for ICD-10 codes related to parastomal and stoma-site hernia surgery over a seven-year period. Medical records were screened for claims associated with parastomal hernia repair, relocation or reversal due to parastomal hernia, or stoma-site hernia repair. Claims were classified according to one of four primary complaints: surgical, anesthetic, medical or other. Clinical and demographic differences between genders and hospital types were investigated. Reasons for non-compensation were analyzed. RESULTS: Thirty claims met the inclusion criteria. Eighteen were related to parastomal hernia repair, seven to stoma-site hernia repair, three to stoma reversal and two to relocation due to parastomal hernia. Twenty-five claims were primarily surgical, two related to anesthesia and three classified as other. Seven claims were granted compensation. No demographic or clinical differences were found apart from female gender being associated with previous parastomal hernia repair [6 women and 0 men (p = 0.02)]. CONCLUSION: Surgical complaints predominated. Few claims were compensated, reflecting the complexity and unsatisfactory outcomes of these procedures. Many claims were identified in relation to the incidence of stoma-related hernia surgery. TRIAL REGISTRATION: Due to its retrospective and descriptive nature, the study was not registered in any registry.

Density of CD3+ and CD8+ Cells in the Microenvironment of Colorectal Cancer according to Prediagnostic Physical Activity.

BACKGROUND: Physical activity is associated not only with a decreased risk of developing colorectal cancer but also with improved survival. One putative mechanism is the infiltration of immune cells in the tumor microenvironment. Experimental findings suggest that physical activity may mobilize immune cells to the tumor. We hypothesized that higher levels of physical activity prior to colorectal cancer diagnosis are associated with higher densities of tumor-infiltrating T-lymphocytes in colorectal cancer patients. METHODS: The study setting was a northern Swedish population-based cohort, including 109,792 participants with prospectively collected health- and lifestyle-related data. For 592 participants who later developed colorectal cancer, archival tumor tissue samples were used to assess the density of CD3+ and CD8+ cytotoxic T cells by IHC. Odds ratios for associations between self-reported, prediagnostic recreational physical activity and immune cell infiltration were estimated by ordinal logistic regression. RESULTS: Recreational physical activity >3 times per week was associated with a higher density of CD8+ T cells in the tumor front and center compared with participants reporting no recreational physical activity. Odds ratios were 2.77 (95% CI, 1.21-6.35) and 2.85 (95% CI, 1.28-6.33) for the tumor front and center, respectively, after adjustment for sex, age at diagnosis, and tumor stage. The risk estimates were consistent after additional adjustment for several potential confounders. For CD3, no clear associations were found. CONCLUSIONS: Physical activity may promote the infiltration of CD8+ immune cells in the tumor microenvironment of colorectal cancer. IMPACT: The study provides some evidence on how physical activity may alter the prognosis in colorectal cancer.

The Relationship between the Tissue Expression of TLR2, TLR4, TLR5, and TLR7 and Systemic Inflammatory Responses in Colorectal Cancer Patients.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy globally. CRC patients with elevated plasma C-reactive protein (CRP) levels exhibit compromised prognoses. Toll-like receptors (TLRs), activating the innate and adaptive immune systems, may contribute to pro- and antitumorigenic inflammatory responses. We aimed to identify a possible link between local and systemic inflammatory responses in CRC patients by investigating the association between tissue TLRs and plasma CRP. METHODS: Tissue expressions of TLR2, TLR4, TLR5, and TLR7 were assessed using immunohistochemistry of tissue microarray slides from 549 CRC patients surgically treated between 1998 and 2005. Blood samples were drawn preoperatively, centrifuged, aliquoted, and stored at -80°C until analysis. Plasma CRP was determined through high-sensitivity time-resolved immunofluorometric assay. We investigated the association of TLRs to clinicopathologic variables, plasma CRP, and survival. RESULTS: High TLR2 expression (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.41-0.85; p = 0.005), high TLR5 expression (HR 0.60; 95% CI 0.45-0.83; p = 0.002), positive TLR7 expression (HR 0.49; 95% CI 0.33-0.72; p < 0.001), and low CRP (HR 1.48; 95% CI 1.08-2.11; p = 0.017) were associated with a better prognosis. A high TLR2 immunoexpression was associated with a better prognosis among low-CRP patients (HR 0.53; 95% CI 0.35-0.80; p = 0.002), high TLR4 expression among high-CRP patients (HR 2.04; 95% CI 1.04-4.00; p = 0.038), high TLR5 expression among low-CRP patients (HR 0.059; 95% CI 0.37-0.92; p = 0.021), and positive TLR7 expression among low-CRP patients (HR 0.53; 95% CI 0.28-1.00; p = 0.049). In multivariate analyses, no biomarkers emerged as significant independent variables. CONCLUSIONS: High tissue TLR2, TLR5, and TLR7 levels were associated with a better prognosis. Among low-CRP patients, those with high TLR2, TLR5, and TLR7 immunoexpressions exhibited a better prognosis. Among high CRP patients, a high TLR4 immunoexpression was associated with a better prognosis.