Browsing by Subject "Colon cancer"

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  • MISiCOL Task Force (2018)
    Aim: To investigate the rate of laparoscopic colectomies for colon cancer using registries and population based studies. To provide a position paper on mini-invasive (MIS) colon cancer surgery based on the opinion of experts leader in this field. Methods: A systematic review of the literature was conducted using PRISMA guidelines for the rate of laparoscopy in colon cancer. Moreover, Delphi methodology was used to reach consensus among 35 international experts in four study rounds. Consensus was defined as an agreement >= 75.0%. Domains of interest included nosology, essential technical/oncological requirements, outcomes and MIS training. Results: Forty-four studies from 42 articles were reviewed. Although it is still sub-optimal, the rate of MIS for colon cancer increased over the years and it is currently >50% in Korea, Netherlands, UK and Australia. The remaining European countries are un-investigated and presented lower rates with highest variations, ranging 7-35%. Using Delphi methodology, a laparoscopic colectomy was defined as a "colon resection performed using key-hole surgery independently from the type of anastomosis". The panel defined also the oncological requirements recognized essential for the procedure and agreed that when performed by experienced surgeons, it should be marked as best practice in guidelines, given the principles of oncologic surgery be respected (RO procedure, vessel ligation and mesocolon integrity). Conclusion: The rate of MIS colectomies for cancer in Europe should be further investigated. A panel of leaders in this field defined laparoscopic colectomy as a best practice procedure when performed by an experienced surgeon respecting the standards of surgical oncology. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
  • Christensen, Jon; El-Gebali, Sara; Natoli, Manuela; Sengstag, Thierry; Delorenzi, Mauro; Bentz, Susanne; Bouzourene, Hanifa; Rumbo, Martin; Felsani, Armando; Siissalo, Sanna; Hirvonen, Jouni; Vila, Maya R.; Saletti, Piercarlo; Aguet, Michel; Anderle, Pascale (2012)
  • Abdel-Rahman, Wael M.; Ruosaari, Saila; Knuutila, Sakari; Peltomäki, Päivi T (2012)
  • Chakroborty, Deepankar; Emani, Maheswara R; Klén, Riku; Böckelman, Camilla; Hagström, Jaana; Haglund, Caj; Ristimäki, Ari; Lahesmaa, Riitta; Elo, Laura L (BioMed Central, 2019)
    Abstract Background Prognostic markers specific to a particular cancer type can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities. Methods Gene expression data was analyzed from three independent colon cancer microarray gene expression data sets (N = 1052). Survival analysis was performed for the three data sets, stratified by the expression level of the LINE-1 type transposase domain containing 1 (L1TD1). Correlation analysis was performed to investigate the role of the interactome of L1TD1 in colon cancer patients. Results We found L1TD1 as a novel positive prognostic marker for colon cancer. Increased expression of L1TD1 associated with longer disease-free survival in all the three data sets. Our results were in contrast to a previous study on medulloblastoma, where high expression of L1TD1 was linked with poor prognosis. Notably, in medulloblastoma L1TD1 was co-expressed with its interaction partners, whereas our analysis revealed lack of co-expression of L1TD1 with its interaction partners in colon cancer. Conclusions Our results identify increased expression of L1TD1 as a prognostic marker predicting longer disease-free survival in colon cancer patients.
  • Chakroborty, Deepankar; Emani, Maheswara Reddy; Klen, Riku; Bockelman, Camilla; Hagström, Jaana; Haglund, Caj; Ristimäki, Ari; Lahesmaa, Riitta; Elo, Laura L. (2019)
    BackgroundPrognostic markers specific to a particular cancer type can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities.MethodsGene expression data was analyzed from three independent colon cancer microarray gene expression data sets (N=1052). Survival analysis was performed for the three data sets, stratified by the expression level of the LINE-1 type transposase domain containing 1 (L1TD1). Correlation analysis was performed to investigate the role of the interactome of L1TD1 in colon cancer patients.ResultsWe found L1TD1 as a novel positive prognostic marker for colon cancer. Increased expression of L1TD1 associated with longer disease-free survival in all the three data sets. Our results were in contrast to a previous study on medulloblastoma, where high expression of L1TD1 was linked with poor prognosis. Notably, in medulloblastoma L1TD1 was co-expressed with its interaction partners, whereas our analysis revealed lack of co-expression of L1TD1 with its interaction partners in colon cancer.ConclusionsOur results identify increased expression of L1TD1 as a prognostic marker predicting longer disease-free survival in colon cancer patients.
  • Niemeläinen, S.; Huhtala, H.; Ehrlich, A.; Kössi, J.; Jämsen, E.; Hyöty, M. (2020)
    Aim The number of colorectal cancer patients increases with age. Long-term data support personalized management due to heterogeneity within the older population. This registry- and population-based study aimed to analyse long-term survival, and causes of death, after elective colon cancer surgery in the aged, focusing on patients who survived more than 3 months postoperatively. Methods The data included patients >= 80 years who had elective surgery for Stage I-III colon cancer in four Finnish centres. The prospectively collected data included comorbidities, functional status, postoperative outcomes and long-term survival. Univariate and multivariate Cox regression analysis were conducted to determine factors associated with long-term survival. Results A total of 386 surgical patients were included, of whom 357 survived over 3 months. Survival rates for all patients at 1, 3 and 5 years were 85%, 66% and 55%, compared to 92%, 71% and 59% for patients alive 3 months postoperatively, respectively. Higher age, American Society of Anesthesiologists (ASA) score >= 4, Charlson Comorbidity Index >= 6, tumour Stage III, open compared to laparoscopic surgery and severe postoperative complications were independently associated with reduced overall survival. Higher age (hazard ratio 1.97, 1.14-3.40), diabetes (1.56, 1.07-2.27), ASA score >= 4 (3.27, 1.53-6.99) and tumour Stage III (2.04, 1.48-2.81) were the patient-related variables affecting survival amongst those surviving more than 3 months postoperatively. Median survival time for patients given adjuvant chemotherapy was 5.4 years, compared to 3.3 years for patients not given postoperative treatment. Conclusions Fit aged colon cancer patients can achieve good long-term outcomes and survival with radical, minimally invasive surgical treatment, even with additional chemotherapy.
  • 2015 European Soc Coloproctology; Kössi, Jyrki (2019)
    BACKGROUND Right hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC). AIM To investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD. METHODS This is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission. RESULTS Three hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P <0.01), had lower American Society of Anesthesiology score (ASA) grade (P <0.01) and less comorbidity (P <0.01), but were more likely to be current smokers (P <0.01). Patients with CD were more frequently operated on by colorectal surgeons (P <0.01) and frequently underwent ileocecal resection (P <0.01) with higher rate of de-functioning/primary stoma construction (P <0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P <0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers. CONCLUSION Patients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complication's rate was not different between the two groups.
  • Niemeläinen, Susanna; Huhtala, Heini; Ehrlich, Anu; Kössi, Jyrki; Jämsen, Esa; Hyöty, Marja (2020)
    Purpose Patients aged > 80 years represent an increasing proportion of colon cancer diagnoses. Selecting patients for elective surgery is challenging because of possibly compromised health status and functional decline. The aim of this retrospective, population-based study was to identify risk factors and health measures that predict short-term mortality after elective colon cancer surgery in the aged. Methods All patients > 80 years operated electively for stages I-III colon cancer from 2005 to 2016 in four Finnish hospitals were included. The prospectively collected data included comorbidities, functional status, postoperative surgical and medical outcomes as well as mortality data. Results A total of 386 patients (mean 84.0 years, range 80-96, 56% female) were included. Male gender (46% vs 35%, p = 0.03), higher BMI (51% vs 37%, p = 0.02), diabetes mellitus (51% vs 37%, p = 0.02), coronary artery disease (52% vs 36%, p = 0.003) and rheumatic diseases (67% vs 39%, p = 0.03) were related to higher risk of complications. The severe complications were more common in patients with increased preoperative hospitalizations (31% vs 15%, p = 0.05) and who lived in nursing homes (30% vs 17%, p = 0.05). The 30-day and 1-year mortality rates were 6.0% and 15% for all the patients compared with 30% and 45% in patients with severe postoperative complications (p <0.001). Severe postoperative complications were the only significant patient-related variable affecting 1-year mortality (OR 9.60, 95% CI 2.33-39.55, p = 0.002). Conclusions The ability to identify preoperatively patients at high risk of decreased survival and thus prevent severe postoperative complications could improve overall outcome of aged colon cancer patients.
  • Bockelman, Camilla; Beilmann-Lehtonen, Ines; Kaprio, Tuomas; Koskensalo, Selja; Tervahartiala, Taina; Mustonen, Harri; Stenman, Ulf-Hakan; Sorsa, Timo; Haglund, Caj (2018)
    Background: Almost all of the extracellular matrix (ECM) components can be degraded by the endoproteinases matrix metalloproteinases (MMPs). Important regulators of MMPs, and thereby of the extracellular environment, are tissue inhibitors of metalloproteinases (TIMPs), and especially TIMP-1. Early tumor development, as well as distant metastasis, may be results of an MMP/TIMP ratio imbalance altering the ECM. MMPs are elevated in several inflammatory conditions. Our aim is to investigate the prognostic role of MMP-8, -9, and TIMP-1 in colorectal cancer (CRC) and their relationship to inflammation. Methods: We included 337 colorectal cancer patients and 47 controls undergoing surgery at Helsinki University Hospital in Finland, 1998-2011. Serum levels of MMP-8 and plasma levels of C-reactive protein (CRP) were determined with a time-resolved immunofluorometric assay (IFMA), and MMP-9 and TIMP-1 with commercial enzyme-linked immunosorbent assay (ELISA) kits. Association and correlation analyses were performed with the Mann-Whitney U, Kruskal-Wallis, and Spearman rank correlation tests. Survival curves were constructed according to the Kaplan-Meier method and compared with the log-rank test. Results: Among patients with advanced disease, serum levels of MMP-8 and TIMP-1 were elevated. CRC patients with high MMP-8 (HR (hazard ratio) 1.72, 95% confidence interval (CI) 1.17-2.52, P = 0.005) and those with high TIMP-1 (HR 1.80, 95% CI 1.23-2.64, P = 0.002) had worse prognoses. MMP-9 level failed to serve as a prognostic factor. In multivariable survival analysis, Dukes stage, and low MMP-9/TIMP-1 molar ratio (HR 0.46, 95% CI 0.33-0.98, P = 0.042) were independently predicted prognosis. A weak correlation between CRP and MMP-8 (r(S) = 0.229, P <0.001), and TIMP-1 (r(S) = 0.280, P <0.001) was noted. Among patients showing no systemic inflammatory response, MMP-8 (HR 1.66, 95% CI 1.10-2.53, P = 0.017) and TIMP-1 (HR 1.59, 95% CI 1.05-2.42, P = 0.029) were prognostic factors. Conclusions: MMP-8 and TIMP-1 in serum, but not MMP-9, identified CRC patients with bad prognosis. Among patients showing no systemic inflammatory response, MMP-8 and TIMP-1 may associate with poor prognosis.
  • Böckelman, Camilla; Beilmann-Lehtonen, Ines; Kaprio, Tuomas; Koskensalo, Selja; Tervahartiala, Taina; Mustonen, Harri; Stenman, Ulf-Håkan; Sorsa, Timo; Haglund, Caj (BioMed Central, 2018)
    Abstract Background Almost all of the extracellular matrix (ECM) components can be degraded by the endoproteinases matrix metalloproteinases (MMPs). Important regulators of MMPs, and thereby of the extracellular environment, are tissue inhibitors of metalloproteinases (TIMPs), and especially TIMP-1. Early tumor development, as well as distant metastasis, may be results of an MMP/TIMP ratio imbalance altering the ECM. MMPs are elevated in several inflammatory conditions. Our aim is to investigate the prognostic role of MMP-8, − 9, and TIMP-1 in colorectal cancer (CRC) and their relationship to inflammation. Methods We included 337 colorectal cancer patients and 47 controls undergoing surgery at Helsinki University Hospital in Finland, 1998–2011. Serum levels of MMP-8 and plasma levels of C-reactive protein (CRP) were determined with a time-resolved immunofluorometric assay (IFMA), and MMP-9 and TIMP-1 with commercial enzyme-linked immunosorbent assay (ELISA) kits. Association and correlation analyses were performed with the Mann-Whitney U, Kruskal-Wallis, and Spearman rank correlation tests. Survival curves were constructed according to the Kaplan-Meier method and compared with the log-rank test. Results Among patients with advanced disease, serum levels of MMP-8 and TIMP-1 were elevated. CRC patients with high MMP-8 (HR (hazard ratio) 1.72, 95% confidence interval (CI) 1.17–2.52, P = 0.005) and those with high TIMP-1 (HR 1.80, 95% CI 1.23–2.64, P = 0.002) had worse prognoses. MMP-9 level failed to serve as a prognostic factor. In multivariable survival analysis, Dukes stage, and low MMP-9/TIMP-1 molar ratio (HR 0.46, 95% CI 0.33–0.98, P = 0.042) were independently predicted prognosis. A weak correlation between CRP and MMP-8 (rS = 0.229, P < 0.001), and TIMP-1 (rS = 0.280, P < 0.001) was noted. Among patients showing no systemic inflammatory response, MMP-8 (HR 1.66, 95% CI 1.10–2.53, P = 0.017) and TIMP-1 (HR 1.59, 95% CI 1.05–2.42, P = 0.029) were prognostic factors. Conclusions MMP-8 and TIMP-1 in serum, but not MMP-9, identified CRC patients with bad prognosis. Among patients showing no systemic inflammatory response, MMP-8 and TIMP-1 may associate with poor prognosis.
  • Niemeläinen, Susanna; Huhtala, Heini; Ehrlich, Anu; Kössi, Jyrki; Jämsen, Esa; Hyöty, Marja (2021)
    BackgroundThe number of colorectal cancer patients increases with age. The decision to go through major surgery can be challenging for the aged patient and the surgeon because of the heterogeneity within the older population. Differences in preoperative physical and cognitive status can affect postoperative outcomes and functional recovery, and impact on patients' quality of life.Methods / designA prospective, observational, multicentre study including nine hospitals to analyse the impact of colon cancer surgery on functional ability, short-term outcomes (complications and mortality), and their predictors in patients aged >= 80years. The catchment area of the study hospitals is 3.88 million people, representing 70% of the population of Finland. The data will be gathered from patient baseline characteristics, surgical interventional data, and pre- and postoperative patient-questionnaires, to an electronic database (REDCap) especially dedicated to the study.DiscussionThis multicentre study provides information about colon cancer surgery's operative and functional outcomes on older patients. A further aim is to find prognostic factors which could help to predict adverse outcomes of surgery.Trial registrationClinicalTrials.gov (NCT03904121). Registered on 1 April 2019.
  • Dominguez-Valentin, Mev; Seppälä, Toni T.; Sampson, Julian R.; Macrae, Finlay; Winship, Ingrid; Evans, D. Gareth; Scott, Rodney J.; Burn, John; Moeslein, Gabriela; Bernstein, Inge; Pylvaenaeinen, Kirsi; Renkonen-Sinisalo, Laura; Lepistö, Anna; Lindblom, Annika; Plazzer, John-Paul; Tjandra, Douglas; Thomas, Huw; Green, Kate; Lalloo, Fiona; Crosbie, Emma J.; Hill, James; Capella, Gabriel; Pineda, Marta; Navarro, Matilde; Vidal, Joan Brunet; Ronlund, Karina; Nielsen, Randi Thyregaard; Yilmaz, Mette; Elvang, Louise Laurberg; Katz, Lior; Nielsen, Maartje; ten Broeke, Sanne W.; Nakken, Sigve; Hovig, Eivind; Sunde, Lone; Kloor, Matthias; Doeberitz, Magnus v Knebel; Ahadova, Aysel; Lindor, Noralane; Steinke-Lange, Verena; Holinski-Feder, Elke; Mecklin, Jukka-Pekka; Moller, Pal (2019)
    Background We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. Methods The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. Results Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within <1.5, 1.5-2.5, 2.5-3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5-3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p <0.001). Ten-year crude survival when the last colonoscopy had been <1.5, 1.5-2.5, 2.5-3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). Conclusions In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.
  • Dominguez-Valentin, Mev; Seppälä, Toni T; Sampson, Julian R; Macrae, Finlay; Winship, Ingrid; Evans, D. G; Scott, Rodney J; Burn, John; Möslein, Gabriela; Bernstein, Inge; Pylvänäinen, Kirsi; Renkonen-Sinisalo, Laura; Lepistö, Anna; Lindblom, Annika; Plazzer, John-Paul; Tjandra, Douglas; Thomas, Huw; Green, Kate; Lalloo, Fiona; Crosbie, Emma J; Hill, James; Capella, Gabriel; Pineda, Marta; Navarro, Matilde; Vidal, Joan B; Rønlund, Karina; Nielsen, Randi T; Yilmaz, Mette; Elvang, Louise L; Katz, Lior; Nielsen, Maartje; ten Broeke, Sanne W; Nakken, Sigve; Hovig, Eivind; Sunde, Lone; Kloor, Matthias; Knebel Doeberitz, Magnus v; Ahadova, Aysel; Lindor, Noralane; Steinke-Lange, Verena; Holinski-Feder, Elke; Mecklin, Jukka-Pekka; Møller, Pål (BioMed Central, 2019)
    Abstract Background We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. Methods The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. Results Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5–2.5, 2.5–3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5–3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5–2.5, 2.5–3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). Conclusions In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.
  • Beilmann-Lehtonen, Ines; Böckelman, Camilla; Mustonen, Harri K; Hagström, Jaana; Koskensalo, Selja; Haglund, Caj (2020)
    Colorectal cancer (CRC), the second most common cancer globally, resulted in 881,000 deaths in 2018. Toll-like receptors (TLRs) are crucial to detecting pathogen invasion and inducing the host's immune response. This study aimed to explore the prognostic value of TLR2 and TLR4 tumor expressions in colorectal cancer patients. We studied the immunohistochemical expressions of TLR2 and TLR4 using tissue microarray specimens from 825 patients undergoing surgery in the Department of Surgery, Helsinki University Hospital, between 1982 and 2002. We assessed the relationships between TLR2 and TLR4 expressions and clinicopathological variables and patient survival. We generated survival curves using the Kaplan-Meier method, determining significance with the log-rank test. Among patients with lymph node-positive disease and no distant metastases (Dukes C), a strong TLR2 immunoactivity associated with a better prognosis (p <0.001). Among patients with local Dukes B disease, a strong TLR4 immunoactivity associated with a worse disease-specific survival (DSS; p = 0.017). In the multivariate survival analysis, moderate TLR4 immunoactivity compared with strong TLR4 immunoactivity (hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.49-0.89, p = 0.007) served as an independent prognostic factor. In the multivariate analysis for the Dukes subgroups, moderate TLR2 immunoactivity (HR 2.63, 95% CI 1.56-4.44, p <0.001) compared with strong TLR2 immunoactivity served as an independent negative prognostic factor in the Dukes C subgroup. TLR2 and TLR4 might be new prognostic factors to indicate which CRC patients require adjuvant therapy and which could spare from an unnecessary follow-up, but further investigations are needed.