Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer

Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon, are known to have favorable survival and dense local immune infiltration. The aim of this study was to see if there is any form of relationship between these seemingly diverse entities.Peer reviewe

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 degrees 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.Peer reviewe

The Prognostic Importance of CD20(+) B lymphocytes in Colorectal Cancer and the Relation to Other Immune Cell subsets

The anti-tumour immune response is critical to patient prognosis in colorectal cancer (CRC). The aim of this study was to investigate infiltration of B lymphocytes into CRC tumours, and their clinical relevance, prognostic value and relation to other immune cell subsets. We used multiplexed immunohistochemistry and multispectral imaging to assay the amount of infiltrating CD20(+) B lymphocytes along with infiltration of CD8(+) cytotoxic T cells, FOXP3(+) T regulatory cells, CD68(+) macrophages and CD66b(+) neutrophils, in 316 archival CRC tissue specimens. A higher density of infiltrating CD20(+) B lymphocytes was associated with tumours of the right colon (P = 0.025) and of lower stages (P = 0.009). Furthermore, patients whose tumours were highly infiltrated by CD20(+) B lymphocytes had a significantly improved disease-specific survival (HR = 0.45, 95% CI 0.28-0.73, P = 0.001), which remained significant in multivariable analysis. CD20(+) B lymphocytes were highly and positively associated with CD8(+) T lymphocytes (P <0.001), and part of the prognostic role was found to be a cooperative effect between these lymphocyte subsets. Our results support a favourable prognostic value of tumour-infiltrating CD20(+) B lymphocytes in CRC. Furthermore, a cooperative prognostic effect between CD20(+) B lymphocytes and CD8(+) T lymphocytes is suggested.Peer reviewe

Innovation Management -How does it work in practice in different organisational structures?

Many authors subscribe to the importance of innovation for modern companies. Yet, the meaning of this term seems rather evasive. It is even more challenging to capture the meaning of innovation management. In this study, we try to answer to What innovation management is and how it works in two different organisational structures. To this aim, we studied how innovation process is managed in Vattenfall AB and Bioprocess Control AB. The task was approached with a qualitative method using interviews, completed with company publications. The results gathered from this were analysed against a theoretical framework about innovation processes, its management and the importance of (organisational) structure. The study concludes that there are discrepancies between theory and practice partly due to the unarticulated approach to innovation in the companies selected. Without labelling activities as part of an innovation process, both companies work with innovation management on a daily basis. A set of management tasks crucial for the innovative capacity of the two companies were identified. Although present in both companies, these tasks were carried out differently due to different organisational structures. The organisational structure in turn reflected on to what extent innovation management was formalised in Vattenfall and Bioprocess Control

Long distance to hospital is not a risk factor for non-reversal of a defunctioning stoma

PURPOSE: To see if road distance to hospital influences stoma reversal rate, time from index operation to stoma reversal, and occurrence of permanent stoma. METHODS: Data from all diagnosed cases of rectal cancer from three counties in northern Sweden were extracted from the Swedish Rectal Cancer Registry. The three counties are sparsely populated, with a population density roughly one fifth the average density in Sweden. Distances to nearest, operating, and largest hospital were obtained using Google Maps™. Matched data on socioeconomic variables were retrieved from Statistics Sweden. RESULTS: In univariate logistic regression analysis, patients living closer to the operating hospital had a higher likelihood of non-reversal than those living farther away (OR 0.3; 95% CI 0.12-0.76). However, no difference was seen in the multivariate analysis. Of the 717 cases included, 54% received a permanent stoma and 38% a defunctioning stoma at index surgery. The reversal rate of a defunctioning stoma was 83%. At follow-up, 61% still had a stoma, 89% of these were permanent, and 11% non-reversed defunctioning stomas. Median time to stoma reversal was 287 days (82-1557 days). Of all 227 stoma reversals, 77% were done more than 6 months after index surgery. CONCLUSIONS: Longer distance to hospital is not a risk factor for non-reversal of a defunctioning stoma. Only 23% had their defunctioning stoma reversed within 6 months after index surgery. Future studies aiming to determine reversal rate need to extend their follow-up time in order to receive accurate results

Rectal cancer patients from rural areas in northern Sweden report more pain and problems with stoma care than those from urban areas

INTRODUCTION: Having a stoma after bowel surgery is associated with inferior quality of life (QoL). The county of Västerbotten in Sweden is a large and sparsely populated area. Competence regarding stoma-related problems is restricted to hospital-based stoma nurses and surgeons. Patients living in rural areas instead largely rely on their general practitioner. The purpose of the study was to investigate the impact of distance to nearest hospital on the QoL of rectal cancer patients who receive a stoma at index surgery. METHODS: A cross-sectional study performed in Västerbotten county, Sweden. Validated questionnaires assessing QoL (EORTC QLQ C-30 and CR-29) were sent to all rectal cancer patients diagnosed in 2007-2014 who received a stoma at index surgery. Socioeconomic variables were retrieved from Statistics Sweden. Distance from home to the nearest hospital was determined using Google Maps™. The effect of distance was assessed using two separate models, the first based on distance to the nearest hospital and the second based on access to a stoma care nurse. Within the first model all patients living in rural areas constituted the study group while all patients living in non-rural areas constituted the control group. Within the second model all patients with no access to stoma care nurse constituted the study group while those with such access constituted the control group. RESULTS: The response rate was 69%. In the first model the rectal cancer patients living further away from the nearest hospital reported significantly more pain and sore skin (p=0.032 and p=0.003, respectively). When considering patients who still had a stoma, those living further away also reported more stoma care problems (p=0.004) and a poorer global QoL (p=0.038). In the second model, access or not to a stoma care nurse had no impact on stoma care problems or QoL. CONCLUSION: Rectal cancer patients receiving a stoma at index surgery and who came from rural areas reported more pain than those living closer to the nearest hospital. The group of rural patients who still had a stoma also reported more stoma care problems and a poorer quality of life. To help these patients, general practitioners are encouraged to arrange an extra follow-up visit focusing on the individual patient's problems.Originally included in thesis in manuscript form. Financial support was received by regional agreement between Umeå University and Västerbotten County Council (VLL-675981), grants from Lion's Cancer Research Foundation, Umeå University and Visare Norr</p

Autologous full-thickness skin graft as reinforcement in parastomal hernia repair : a feasibility study

Background: Parastomal hernia is a common complication of stoma formation and the methods of repair available today are unsatisfactory with high recurrence and complication rates. To improve outcome after surgical repair of parastomal hernia, a surgical method using autologous full-thickness skin grafts as intraperitoneal reinforcement has been developed. The purpose of this study was to evaluate the feasibility of this novel surgical technique in the repair of parastomal hernia. Methods: A pilot study was conducted between January 2018 and June 2019 on four patients with symptomatic parastomal hernia. They had a laparotomy with suture reduction of the hernia and reinforcement of the abdominal wall with autologous full-thickness skin. They were then monitored for at least 1 year postoperatively for technique-related complications and recurrence. Results: No major technique-related complications were noted during the follow-up Two patients developed a recurrent parastomal hernia at the long term follow-up. The other two had no recurrence. Conclusions: Autologous full-thickness skin graft as reinforcement in parastomal hernia repair is feasible and should be evaluated in a larger clinical trial

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.Originally included in thesis in manuscript form.</p

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