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Background: Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up., Methods: Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842)., Results: In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4)., Conclusions: Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.

Background: Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer., Methods: Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis., Results: Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination., Conclusions: The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.

Background: The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination., Methods: Follow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III)., Results: Loss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio = 5.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas., Conclusion: Deletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.

Background: A randomized study in 1999-2005 of mechanical bowel preparation (MBP) preceding colonic resection found no decrease in postoperative complications. The aim of the present study was to evaluate the long-term effect of MBP regarding cancer recurrence and survival after colonic resections., Methods: The cohort of patients with colonic cancer in the MBP study was followed up for 10 years. Data were collected from registers run by the National Board of Health and Welfare. Register data were validated against information in patient charts. Cox proportional hazards model was used for multivariable analysis of factors predictive of cancer-specific survival., Results: Register analysis showed significantly fewer recurrences, and better cancer-specific and overall survival in the MBP group. After validation, 839 of 1343 patients remained for analysis (448 MBP, 391 no MBP). Eighty (17·9 per cent) of 448 patients in the MBP group and 88 (22·5 per cent) of 391 in the no-MBP group developed a cancer recurrence (P = 0·093). The 10-year cancer-specific survival rate was 84·1 per cent in the MBP group and 78·0 per cent in the no-MBP group (P = 0·019). Overall survival rates were 58·8 and 56·0 per cent respectively (P = 0·186)., Conclusion: Patients receiving MBP before elective colonic cancer surgery had significantly better cancer-specific survival after 10 years., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Background: Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries., Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and metastatic colorectal disease separately. Moreover, evidence based algorithms for diagnostics and treatment were composed which were also submitted to the Delphi process., Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members., Conclusions: Multidisciplinary consensus on key diagnostic and treatment issues for colon and rectal cancer management using the Delphi method was successful. This consensus document embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to assess CT-colonography (CTC) in the follow-up of diverticulitis regarding patient acceptance and diagnostic accuracy for diverticular disease, adenomas and cancer, with colonoscopy as a reference standard., Methods: A prospective comparative study where half of the patients underwent colonoscopy first, followed immediately by CTC. The other half had the examinations in the reverse order. Patient experiences and findings were registered after every examination, blinded to the examiner., Results: Of a total of 110 consecutive patients, 108 were included in the study, with a median age of 56 years (range 27-84). The success rate was 91% for colonoscopy and 86% for CTC. Examination time was 25 min for both methods. The mean time for CTC evaluation was 20 min. Eighty-three per cent of the patients received sedation during colonoscopy. Despite this, patients experienced colonoscopy as more painful (p < 0.001) and uncomfortable (p < 0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a good agreement (κ = 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (κ = 0.17). No cancer was found., Conclusion: CTC was less painful and unpleasant and can be used for colonic investigation in the follow-up of diverticulitis. CTC detected diverticulosis with good accuracy while the detection accuracy of small polyps was poor. CTC is a viable alternative, especially in case of incomplete colonoscopy or in a situation with limited colonoscopy resources.

Background: Evaluating the external validity of clinical trials requires knowledge not only of the study population but also of a relevant reference population. The main aim of this study was to present data from a large, contemporary, population-based cohort of patients with colonic cancer., Methods: Data on patients diagnosed between 2007 and 2011 were extracted from the Swedish Colon Cancer Registry. The data, registered prospectively in a national population of almost 10 million, included over 99 per cent of all diagnosed adenocarcinomas of the colon., Results: This analysis included 18,889 patients with 19,526 tumours (3·0 per cent had synchronous tumours). The sex distribution was fairly equal, and the median age was 74·1 (interquartile range 65-81) years. The overall and relative (cancer-specific) survival rates after 3 years were 62·7 and 71·4 per cent respectively. Some 88·0 per cent of the patients were operated on, and 83·8 per cent had tumours resected. Median blood loss during bowel resection was 200 (mean 311) ml, and the median operating time was 160 min; 5·6 per cent of the procedures were laparoscopic. Preoperative chemotherapy was administered to 2·1 per cent of patients; postoperative chemotherapy was planned in 90·1 per cent of fit patients aged less than 75 years with stage III disease. In patients operated on in an emergency setting (21·5 per cent), the preoperative evaluation was less extensive, the proportion of R0 resections was lower, and the outcomes were poorer, in both the short and long term., Conclusion: These population-based data represent good-quality reference points., (© 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.)

Aim: The aim of this study was to investigate whether patients with diverticulitis can be prioritized with higher urgency for a subsequent full colonic examination based upon the emergency abdominal CT scan performed at the time of presentation., Method: All patients with a diagnosis of diverticulitis, hospitalized during 2006 and having a CT scan on admission and a subsequent 'clean colon' examination, were reviewed. The CT scan was reviewed by two independent and blinded senior radiologists (Radiologist A and Radiologist B) for signs inconsistent with diverticulitis and suggestive of malignancy. The patients were classified on the CT scan results into group 1 (normal findings, nontumour pathology or benign polyps < 1 cm) or group 2 (benign polyps ≥ 1 cm and cancer)., Results: Ninety-three patients (83 in group 1 and 10 in group 2) were reviewed. Radiologist A suggested high-priority colonic examination in 18% and 50% of patients in groups 1 and 2, respectively, and Radiologist B in 63% and 90% of patients, respectively. There was a statistically significant interobserver difference, and also lower accuracy of Radiologist B compared with Radiologist A in predicting a subsequent 'clean colon' examination., Conclusion: Use of an emergency acute CT scan at the time of diagnosis of diverticulitis to predict a clean colon examination for neoplasia is not reliable because there is a considerable degree of interobserver difference between radiologists., (© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.)

Background: Postoperative bowel obstruction caused by intra-abdominal adhesions occurs after all types of abdominal surgery. It has been suggested that the laparoscopic technique should reduce the risk for adhesion formation and thus for postoperative bowel obstruction. This study was designed to compare the incidence of bowel obstruction in a randomized trial where laparoscopic and open resection for colon cancer was compared., Methods: A retrospective analysis was performed, collecting data of episodes of bowel obstruction with or without surgery. Only episodes treated in the hospital where the index surgery took place were included. Data for 786 patients were collected for the 5-year period after cancer surgery., Results: Baseline characteristics for the evaluated laparoscopic (n = 383) and open (n = 403) groups were comparable. The cumulative obstruction percentages at 5 years for the open and laparoscopic groups were 6.5 and 5.1% respectively and did not significantly differ from each other. Tumor stage seemed to influence the risk for bowel obstruction: 2.8% in stage I, 6.6% in stage II, and 7% in stage III, but the differences were not significant., Conclusions: This analysis does not support the hypothesis that laparoscopy leads to fewer episodes of bowel obstruction compared with open surgery.

Objective: To analyse the ongoing process of recruiting patients into a multicenter randomized trial on follow-up after curative surgery for colorectal cancer. The trial is registered in Clinical Trials Registration., Method: Prospective registration of all operated patients as well as inclusions (curative resection, stage II or III disease,

Objective: The colon cancer laparoscopic or open resection (COLOR) trial is an international, randomised controlled trial comparing outcomes of open and laparoscopic surgery for colon cancer. The main purpose of this study was to determine representability by comparing included and nonincluded patients in the participating Swedish centres., Design: At eight centres, which included 391 of the 422 Swedish patients, a local database search was performed to identify retrospectively all patients (n = 2,384) who underwent surgery for colon cancer during the inclusion period, and data was retrieved from medical records., Results: Four hundred fifty-six patients were randomised, 65 of whom were excluded post randomisation (group 2), leaving 391 patients in the study (group 1). For 1,566 patients, valid exclusion criteria were found (group 3). Thus, 362 patients were eligible but not included (group 4). Relative to group 1, patients in group 4 had a significantly higher American Society of Anaesthesiologists (ASA) score, more advanced tumour stage and difference regarding the resections performed. Results showed that 1470 patients (62%) could be calculated as feasible for laparoscopic colon resection (LCR) in a clinical, nontrial situation., Conclusions: The study population in the Swedish part of the COLOR trial was representative of the eligible population with the exception of comorbidity, where those actually included had less severe comorbidity than the nonincluded but eligible patients. In Sweden, 50-60% of colon cancer patients can be operated on by laparoscopy.

DNA hypermethylation of gene promoters is a common epigenetic alteration occurring in cancer cells. However, little is known about the mechanisms instructing these cancer-specific DNA hypermethylation events. Recent reports have suggested that genes bound by polycomb/Histone H3 lysine 27 trimethylation (H3K27me3) in embryonic stem (ES) cells are frequent targets for cancer-specific DNA hypermethylation. This polycomb-premarking is assumed to be restrained to ES cells, even though almost no polycomb/H3K27me3 binding profiles are available for differentiated tissues. We generated H3K27me3 profiles in human normal colon and they significantly overlapped with those of ES cells and genes hypermethylated in colorectal cancer (CRC). Moreover, colon H3K27me3 was more restricted to genes hypermethylated in CRC, while ES H3K27me3 was also common in genes hypermethylated in other tumors. Therefore, the suggested polycomb pre-marking of genes for cancer DNA hypermethylation is not necessarily limited to ES or early precursor cells but can occur later in differentiated tissues.

Background: Laparoscopic surgery for colon cancer has been proven safe, but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer. The aim of the COlon cancer Laparoscopic or Open Resection (COLOR) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer., Methods: Between March 7, 1997, and March 6, 2003, patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2) were randomly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority randomised trial. Disease-free survival at 3 years after surgery was the primary outcome, with a prespecified non-inferiority boundary at 7% difference between groups. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, and blood loss during surgery. Neither patients nor health-care providers were blinded to patient groupings. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00387842., Findings: During the recruitment period, 1248 patients were randomly assigned to either open surgery (n=621) or laparoscopic surgery (n=627). 172 were excluded after randomisation, mainly because of the presence of distant metastases or benign disease, leaving 1076 patients eligible for analysis (542 assigned open surgery and 534 assigned laparoscopic surgery). Median follow-up was 53 months (range 0.03-60). Positive resection margins, number of lymph nodes removed, and morbidity and mortality were similar in both groups. The combined 3-year disease-free survival for all stages was 74.2% (95% CI 70.4-78.0) in the laparoscopic group and 76.2% (72.6-79.8) in the open-surgery group (p=0.70 by log-rank test); the difference in disease-free survival after 3 years was 2.0% (95% CI -3.2 to 7.2). The hazard ratio (HR) for disease-free survival (open vs laparoscopic surgery) was 0.92 (95% CI 0.74-1.15). The combined 3-year overall survival for all stages was 81.8% (78.4-85.1) in the laparoscopic group and 84.2% (81.1-87.3) in the open-surgery group (p=0.45 by log-rank test); the difference in overall survival after 3 years was 2.4% (95% CI -2.1 to 7.0; HR 0.95 [0.74-1.22])., Interpretation: Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95% CI for the difference just exceeded the predetermined non-inferiority boundary of 7%. However, the difference in disease-free survival between groups was small and, we believe, clinically acceptable, justifying the implementation of laparoscopic surgery into daily practice. Further studies should address whether laparoscopic surgery is superior to open surgery in this setting.

Rationale: The aim of this study was to assess whether there are differences in treatment strategy and outcome between different age cohorts among men and women with colon cancer., Methods: All patients with colon cancer included in the regional quality registry in Uppsala/Orebro and Stockholm between 1996 and December 2004 were analysed (n=11002). Patients were divided into three age categories: < or =65 years, 66-80 years and >80 years., Results: Overall and cancer-specific survival decreased with increasing age for stages II and III colon cancer but was not influenced by gender. Older patients with stage III tumours were less likely to be referred for chemotherapeutic treatment and there was a decrease in cancer-specific survival with increasing age, from 63.7% to 51.0% to 38.4% in the three age groups. Postoperative morbidity and the number of reoperations was significantly higher in men than in women., Conclusion: The present study shows lower cancer-specific survival among older patients than among younger patients. Gender was not a prognostic factor in cancer-specific survival.

Disease-free survival is increasingly being used as the primary endpoint of most trials testing adjuvant treatments in cancer. Other frequently used endpoints include overall survival, recurrence-free survival, and time to recurrence. These endpoints are often defined differently in different trials in the same type of cancer, leading to a lack of comparability among trials. In this Commentary, we used adjuvant studies in colon cancer as a model to address this issue. In a systematic review of the literature, we identified 52 studies of adjuvant treatment in colon cancer published in 1997-2006 that used eight other endpoints in addition to overall survival. Both the definition of these endpoints and the starting point for measuring time to the events that constituted these endpoints varied widely. A panel of experts on clinical research on colorectal cancer then reached consensus on the definition of each endpoint. Disease-free survival--defined as the time from randomization to any event, irrespective of cause--was considered to be the most informative endpoint for assessing the effect of treatment and therefore the most relevant to clinical practice. The proposed guidelines may add to the quality and cross-comparability of future studies of adjuvant treatments for cancer.

Background: Preoperative mechanical bowel preparation can be questioned as standard procedure in colon surgery, based on the result from several randomised trials., Methods: As part of a large multicenter trial, 105 patients planned for elective colon surgery for cancer, adenoma, or diverticulitis in three hospitals were asked to complete a questionnaire regarding perceived health including experience with bowel preparation. There were 39 questions, each having 3 - 10 answer alternatives, dealing with food intake, pain, discomfort, nausea/vomiting, gas distension, anxiety, tiredness, need of assistance with bowel preparation, and willingness to undergo the procedure again if necessary., Results: 60 patients received mechanical bowel preparation (MBP) and 45 patients did not (No-MBP). In the MBP group 52% needed assistance with bowel preparation and 30% would consider undergoing the same preoperative procedure again. In the No-MBP group 65 % of the patients were positive to no bowel preparation. There was no significant difference between the two groups with respect to postoperative pain and nausea. On Day 4 (but not on Days 1 and 7 postoperatively) patients in the No-MBP group perceived more discomfort than patients in the MBP group, p = 0.02. Time to intake of fluid and solid food did not differ between the two groups. Bowel emptying occurred significantly earlier in the No-MBP group than in the MBP group, p = 0.03., Conclusion: Mechanical bowel preparation is distressing for the patient and associated with a prolonged time to first bowel emptying.

Objective: To perform a meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic colectomy for cancer is oncologically safe., Data Sources: The databases of the Barcelona, Clinical Outcomes of Surgical Therapy (COST), Colon Cancer Laparoscopic or Open Resection (COLOR), and Conventional vs Laparoscopic-Assisted Surgery in Patients With Colorectal Cancer (CLASICC) trials were the data sources for the study., Study Selection: Patients who had at least 3 years of complete follow-up data were selected., Data Extraction: Patients who had undergone curative surgery before March 1, 2000, were studied. Three-year disease-free survival and overall survival were the primary outcomes of this analysis., Data Synthesis: Of 1765 patients, 229 were excluded, leaving 796 patients in the laparoscopically assisted arm and 740 patients in the open arm for analysis. Three-year disease-free survival rates in the laparoscopically assisted and open arms were 75.8% and 75.3%, respectively (95% confidence interval [CI] of the difference, -5% to 4%). The associated common hazard ratio (laparoscopically assisted vs open surgery with adjustment for sex, age, and stage) was 0.99 (95% CI, 0.80-1.22; P = .92). The 3-year overall survival rate after laparoscopic surgery was 82.2% and after open surgery was 83.5% (95% CI of the difference, -3% to 5%). The associated hazard ratio was 1.07 (95% CI, 0.83-1.37; P = .61). Disease-free and overall survival rates for stages I, II, and III evaluated separately did not differ between the 2 treatments., Conclusion: Laparoscopically assisted colectomy for cancer is oncologically safe.

Aims: To analyse time-trends in survival of patients with colon and rectal cancer in Sweden., Patients and Methods: Data including all patients diagnosed with adenocarcinoma of the colon and rectum between 1960 and 1999, from the Swedish Cancer Registry, were analysed. The observed and relative survival rates were calculated according to the Hakulinen cohort method., Results: Five-year relative survival rate for cancer of the colon improved significantly from 39.6% in 1960--1964 to 57.2% in 1995--1999 and for rectal cancer from 36.1 to 57.6%, respectively. Corresponding observed survival improved from 31.2 to 44.3% for colon cancer and from 28.4 to 45.4% for rectal cancer. The largest improvement of survival were seen during the later part of the period observed., Conclusion: The survival of patients with colon and rectal cancer in Sweden continues to improve, especially in rectal cancer, which now has a 5-year observed and relative survival rate comparable to that for colon cancer. The survival improvement in rectal cancer is probably a result of the implementation of total mesorectal excision and pre-operative radiotherapy.

Correct staging of colon cancer is decisive regarding further oncological treatment, surveillance and prediction of long-term survival. This study investigated the variability in accuracy of pathology reports with focus on differences between pathology departments and their compliance to regional guidelines. Data from the colon cancer register (1997-2002) of the Uppsala/Orebro, Sweden, health care region were analysed and the seven pathology departments in this region were compared. Included were 3735 patients who had undergone resection of a colon cancer. Cumulative 5-year survival was the main end-point. For 64% (n = 2390) of the cases, the number of lymph nodes examined was given (median 8). Survival in stage II was lower when fewer than 12 nodes were examined or when the number of nodes sampled was not given (P = 0.001, log-rank test). In stage III, those with at the most 3 nodes positive (N1) had a better survival than those with 4 or more nodes positive (N2) (P < 0.001, log-rank test). An index of metastases (IM), derived from the number of nodes with metastases divided by the number of nodes examined, was calculated for stage III tumours. Examination of 12 nodes is necessary to assure stage III cases with the median IM (0.32), whereas 20 nodes are necessary to assure 90% of cases with the lower quartile of IM (0.16). Irrespective of the number of nodes investigated, overall survival was better among patients with IM < 0.33 vs. IM > or = 33 (P < 0.001, log-rank test). The prognostic information of the IM was higher than that of the N-stage. Quality of a pathology department, measured by the median number of lymph nodes investigated and by the proportion of reports where the number is given, was determined to indicate correct staging and management of the patient. An index of metastases (IM) is a possible basis for guidance in the choice of adjuvant treatments that appears superior to that of N-stage.

Background: The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable. The multicentre COLOR (COlon cancer Laparoscopic or Open Resection) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon., Methods: 627 patients were randomly assigned to laparoscopic surgery and 621 patients to open surgery. The primary endpoint was cancer-free survival 3 years after surgery. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, metastasis, overall survival, and blood loss during surgery. Analysis was by intention to treat. Here, clinical characteristics, operative findings, and postoperative outcome are reported., Findings: Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection (median 100 mL [range 0-2700] vs 175 mL [0-2000], p<0.0001), although laparoscopic surgery lasted 30 min longer than did open surgery (p<0.0001). Conversion to open surgery was needed for 91 (17%) patients undergoing the laparoscopic procedure. Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups. Laparoscopic colectomy was associated with earlier recovery of bowel function (p<0.0001), need for fewer analgesics, and with a shorter hospital stay (p<0.0001) compared with open colectomy. Morbidity and mortality 28 days after colectomy did not differ between groups., Interpretation: Laparoscopic surgery can be used for safe and radical resection of cancer in the right, left, and sigmoid colon.

Background: High hospital case volume has been associated with improved outcome after open operation for colorectal malignancies., Methods: To assess the impact of hospital case volume on short-term outcome after laparoscopic operation for colon cancer, we conducted an analysis of patients who underwent laparoscopic colon resection within the COlon Cancer Laparoscopic or Open Resection (COLOR) trial., Results: A total of 536 patients with adenocarcinoma of the colon were included in the analysis. Median operating time was 240, 210 and 188 min in centers with low, medium, and high case volumes, respectively (p < 0.001). A significant difference in conversion rate was observed among low, medium, and high case volume hospitals (24% vs 24% vs 9%; p < 0.001). A higher number of lymph nodes were harvested at high case volume hospitals (p < 0.001). After operation, fewer complications (p = 0.006) and a shorter hospital stay (p < 0.001) were observed in patients treated at hospitals with high caseloads., Conclusions: Laparoscopic operation for colon cancer at hospitals with high caseloads appears to be associated with improved short-term results.

Background: The aim of this study was to identify risk factors in emergency surgery for colonic cancer in a large population and to investigate the economic impact of such surgery., Methods: Data from the colonic cancer registry (1997-2001) of the Uppsala/Orebro Regional Oncological Centre were analysed and classified by hospital category. Some 3259 patients were included; 806 had an emergency and 2453 an elective procedure. Data for calculating effects on health economy were derived from a national case-costing register., Results: Patients who had emergency surgery had more advanced tumours and a lower survival rate than those who had an elective procedure (5-year survival rate 29.8 versus 52.4 per cent; P < 0.001). There was a stage-specific difference in survival, with poorer survival both for patients with stage I and II tumours and for those with stage III tumours after emergency compared with elective surgery (P < 0.001). Emergency surgery was associated with a longer hospital stay (mean 18.0 versus 10.0 days; P < 0.001) and higher costs (relative cost 1.5 (95 per cent confidence interval 1.4 to 1.6)) compared with elective surgery. The duration of hospital stay was the strongest determinant of cost (r(2) = 0.52, P < 0.001)., Conclusion: Emergency surgery for colonic cancer is associated with a stage-specific increase in mortality rate.

Background: An increased risk of left-sided colon cancer in patients with diverticular disease of the sigmoid colon has been reported. The aim of this study was to investigate to what extent patients with diverticulitis of the sigmoid colon differ in long-term risk of colon cancer compared to patients with diverticulosis of the colon without any clinical signs of diverticulitis., Methods: A total of 7159 patients (2478 M, 4681 F) discharged with a diagnosis of diverticulosis or diverticulitis in 1965-83 in the Uppsala Health Care Region were followed-up with the Swedish Cancer Registry. Sixty-four cases with colon cancer were identified and compared with 123 controls without cancer matched for sex, age and year of first discharge. Based on information from the patients' charts, an independent observer blinded to the outcome assigned a clinical diagnosis of diverticulitis or not diverticulitis to cases and controls., Results: In patients classified as having sigmoid diverticulitis there was an increased risk of left-sided colon cancer compared with patients with diverticulosis without any clinical signs of diverticulitis (odds ratio = 4.2, 95% CI 1.3-13.0) which remained after mutually adjusting for several clinical parameters in a multivariate conditional logistic regression analysis., Conclusion: The results of the study indicate a causal association between sigmoid diverticulitis and a long-term increased risk of left-sided colon cancer.

Aims: The aim of this study was to describe variability in compliance to clinical guidelines in colorectal cancer surgery related to hospital structure., Methods: All patients registered in the databases of the Regional Oncologic Centre, operated upon electively for colon cancer between the start of the register in 1997 until 2000 (n=1771) and for rectal cancer between the start of the register in 1995 until 2000 (n=1841) were selected for analysis., Results: There was no difference in 5-year survival rate between colon and rectal cancer (mean follow-up 2.6 and 3.0 years, respectively; p=0.22). There was a significant difference in frequency of preoperative liver scan depending on hospital category with an increase in colon cancer from 39 to 46% (p=0.02) and in rectal cancer from 42 to 64% (p<0.001). For colon cancer there was no difference, according to hospital category, in quotient sigmoid and high anterior resection to left-sided resection. Furthermore, high anterior resection was more common at university and general district hospitals (8%) compared with district hospitals (4%) (p=0.01). Sphincter-saving surgery was more common at university hospitals and district general hospitals than at district hospitals (low anterior/abdomino-perineal resection quotients 2.3, 2.4 and 1.6, respectively; p<0.001)., Conclusions: Population-based audit forms an appropriate and valuable basis for quality assurance projects. In addition to describing compliance to guidelines and pointing to process steps that can be improved, such investigations may also indicate changes due to scientific development. Linked to case-costing data, such results may form an important basis for decisions about modifications in health care.

Background: Population-based quality registers have become an important tool in quality assessment during the past decade. For registers to be reliable, however, data must be checked carefully for validity., Methods: The present study describes the validity of surgical complications registered in a national register run by the National Board of Health and Welfare (NBH), a register run by Regional Oncological Centres (ROC) and, for comparison, a local quality assurance system at Uppsala University Hospital (UUH). A specialized, independent surgeon checked 10 per cent of patient records against datasheets from the registers., Results: The local quality assurance system at UUH showed the best validity for surgical complications. Data for complications of colonic cancer surgery were more valid than those for rectal cancer surgery. Registration of serious complications was more valid than that of wound infections. The calculated proportion of missed surgical complications was 0.69, 0.64, 0.40, 0.22 and 0.07 for rectal and colonic cancer in the NBH register, rectal and colonic cancer in the ROC register, and the UUH register respectively. Corresponding figures for reoperation were 0.45, 0.48, 0.04, 0.09 and 0.21., Conclusion: Local interest and routine use of data for quality assurance are crucial factors for valid registers. Careful monitoring of validity is necessary for use of registry data in structured systems for improvement of surgical results., (Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd)

Intratumoral thymidylate synthase (TS) expression and M(r) 53,000 phosphoprotein (p53) overexpression were studied immunohistochemically in sections from stored paraffin-embedded primary colorectal cancers in 70 patients who had undergone surgery during the years 1987-1990. These cancers were classified according to Dukes' stage A-D, using monoclonal antibodies TS 106 and DO-7. In patients with Dukes' stage A-C tumors, univariate analyses showed that there was a significant correlation (P = 0.048) between disease-free survival and TS expression and between TS expression and time to death with colorectal cancer (P = 0.038). In patients with Dukes' stage A-D tumors, overall survival was correlated to TS expression (P = 0.015), Dukes' stage (P < 0.001), and level of tumor differentiation (P = 0.044) but not to p53 overexpression. Patients with low intratumoral TS expression survived significantly longer than patients with high expression. Cox multivariate analysis showed that Dukes' stage (P < 0.001) and TS expression (P = 0.043) could independently serve as prognostic factors for time to death with colorectal cancer in patients with Dukes' stage A-D tumors.

Purpose: To compare immunohistochemical staining using different anti-p53 antibodies, and to evaluate the possible clinical implications of the overexpression of p53 in a series of patients resected for colorectal cancer with a long follow-up., Methods: Tumor biopsy samples were collected from 294 surgical colorectal cancer specimens, obtained from two series of patients with a median follow-up of 4.5 years. The samples stained with four commercially available anti-p53 antibodies, (mouse monoclonal antibodies 421, 1801, and DO-7; and rabbit polyclonal antibody CM1), were evaluated and compared with cryosections from a subset of 20 biopsies from tumors in various stages and grades, obtained from patients with different outcomes., Results: DO-7 gave a homogeneous nuclear staining, which, when further investigated, turned out to be identical in the formalin-fixed paraffin-embedded and in the frozen specimens. Therefore, DO-7 was found to be suitable for the further analysis of archival or frozen sections from the sample. p53 overexpression was shown in 162 (55%) cases, with a significantly higher proportion having DNA aneuploidy (p<0.01) in left-sided colonic and rectal tumors (p<0.01). p53 staining was not associated with tumor stage, tumor grade, or survival., Conclusions: A significantly higher proportion of p53 overexpressing tumors are DNA aneuploid, indicating that mutations in the TP53 gene constitute a sign of genetic instability, which might be of importance in malignant transformation. However, we could not find any indication that TP53 mutations, as reflected in the overexpression of p53, constitute a prerequisite for tumor progression in colorectal cancer.

Fifty patients were randomized to receive adjuvant intraperitoneal 5-fluorouracil (5-FU, 500 mg/m2/day) and intravenous leucovorin (60 mg/m2/day) and 51 to receive placebo after curative surgery for colorectal cancer. Treatment started on the day after surgery and continued for 6 days. One case of stomatitis, one of leucopenia and one case of abnormal liver function tests were the only chemotherapy-related toxic effects. From the second day of treatment, pain during intraperitoneal infusions occurred more frequently in the 5-FU group, although statistical significance was only attained on day 2 (P < 0.05). The groups did not differ substantially regarding any other adverse effects, the incidence of surgical complications, second laparotomies, time from surgery to discharge, or premature treatment terminations. The postoperative course after intraperitoneal 5-FU and intravenous leucovorin was thus not more complicated than that in patients treated with placebo. The tolerance was acceptable and chemotherapy-related toxicity was rare. Thus important prerequisites exist for more widespread use of the present regimen in order to evaluate its impact on survival.

Certain similar epidemiological characteristics suggest a common aetiology for colon cancer and diverticulosis of the colon. The hypothesis that patients with diverticulosis are at increased risk of developing colon cancer was tested in a retrospective, population based, cohort study in Sweden. A total of 7159 patients (2478 men and 4681 women) who had been given a hospital discharge diagnosis of diverticulosis or diverticulitis of the colon between 1965 and 1983 were followed up during 1985 by means of record linkage procedures. After excluding the first 2 years of follow up, there was not a significant increase in risk (SIR) overall for colon cancer (SIR = 1.2; 95% confidence intervals (CI) 0.9, 1.6) or for rectal cancer (SIR = 1.1; 95% CI 0.7, 1.7). The observed number of right sided colon cancers was as expected (SIR = 0.9; 95% CI 0.5, 1.5). In contrast, an increased risk of left sided colon cancer was found both overall (SIR = 1.8; 95% CI 1.1, 2.7) and consistently in men and women as well as in different age groups. This risk increased the longer the follow up (p value for trend < 0.001). These results do not support the hypothesis of a common aetiology in diverticular disease and colonic cancer but suggest a causal relationship between diverticular disease and cancer of the left colon.

The relative survival of all patients (n = 61,769) in the entire Swedish population reported to have a malignant tumour of the colon and rectum between 1960 and 1981 was analysed with special reference to patients under 40 years of age. The 5-year relative survival rate of patients with a tumour of the colon, irrespective of histopathological diagnosis, was 62.0 per cent below the age of 40 years and 44.4 per cent in those 40 years of age or older (P less than 0.05). The corresponding figures for patients with a tumour of the rectum were 46.6 per cent and 39.1 per cent, respectively. When the relative survival was analysed separately for patients with a histopathologically demonstrated adenocarcinoma, the 5-year survival rate among patients with a cancer of the colon was 50.9 per cent in patients below 40 years of age and 48.6 per cent in those 40 years of age or older. In patients with adenocarcinoma of the rectum, the 5-year relative survival rate was 41.1 per cent in patients younger than 40 years of age and 40.7 per cent in patients 40 years of age or older. Thus, patients below the age of 40 years with an adenocarcinoma of the colon and rectum as a group appear to have the same or even a better prognosis than older patients if all tumours are considered, irrespective of histopathological diagnosis.

The occurrence of a second primary malignant disease was analyzed in 38,166 patients with cancer of the colon and 23,603 patients with rectal cancer reported to the Swedish Cancer Registry between 1960 and 1981. The overall relative risk (RR) of developing a second primary malignant disease was significantly (P less than 0.05) increased both after cancer of the colon (women, RR = 1.4; men, RR = 1.3) and rectum (women, RR = 1.4; men, RR = 1.3). Besides confirming an increased risk of metachronous colorectal cancer this study suggests that cancer of the small intestine, breast, endometrium, and possibly of the ovary and prostate may have etiologic factors in common with cancer of the large bowel, notably those located in the colon.

Methotrexate (MTX) (250 mg/m2) was given as an i.v. infusion over 2 hr. At hour three and 23, 5-FU (500 mg/m2, maximally 1000 mg) was given as a bolus i.v. injection. The Leucovorin rescue was initiated hour 24. The chemotherapy course was repeated every 14 days for eight courses, then every third to fourth week. At least four courses of the regime were given to 50 patients with measurable advanced colorectal carcinoma. Toxicity was usually very mild but in seven patients an increase of serum creatinine was registered. Two of these patients had a severe period of uremia. With a more careful observation of kidney function, these episodes should have been foreseen. An objective response rate of 50% with six complete remissions (CR) and 19 partial remissions (PR) was found. Eighty-eight per cent (21/24) of the patients with tumour-related symptoms experienced symptomatic relief. The median response duration amounts to 5 months. It is concluded that the MFL regime is effective in inducing anti-tumour response in patients with advanced colorectal cancer.

Using a radioimmunoassay we have determined serum levels of the carcinoma-associated antigen CA-50 in 266 patients with colorectal cancer. Elevated CA-50 levels were found in Dukes' A (15%), Dukes' B (43%), Dukes' C (31%) and Dukes' D (65%). Patients who had developed a recurrence had 66% elevated levels. 25% of resected patients with no evidence of disease also had elevated CA-50 levels. From 139 patients operated on for a Dukes' A-C, a rise in CA-50 levels from the pre- to the 6-9 month post-operative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On follow-up, a recurrence later developed in all these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. A rise in CA-50 levels after resection of a Dukes' A-C is indicative of a recurrence and may precede any clinical evidence of disease by several months or years. Data is also presented from 552 cases with colorectal cancer analysed with a immunoradiometric assay.

The survival of 61,769 patients diagnosed as having colorectal cancer in the total Swedish population in 1960-1981 was analyzed. The 5-year relative survival rates during the total period were approximately 40%; patients with colonic carcinoma had a somewhat better prognosis than patients with rectal carcinoma, and men had a generally less favorable prognosis than women. Comparison of patients diagnosed in 1960-1964 and in 1975-1979 showed a slight improvement in survival during the more recent study period, i.e., an improvement rate of 7.0% for both cancer of the colon and cancer of the rectum. The improvement occurred mainly during the first months of follow-up. However, the excess mortality due to colorectal cancer 1-5 years after diagnosis as compared to the expected mortality in the general population remained virtually unaltered. A multivariate analysis in which adjustment was made for the possible confounding variables of sex, age, and site (of colonic carcinoma) gave consistent results. Reduced postoperative mortality was considered to be the most likely major explanation for the temporal trend toward a more favorable prognosis. Thus it seemed that the treatment of colorectal cancer in Sweden during the last two decades has not improved significantly except in terms of reduced postoperative mortality. Thus the challenge of improving survival in patients with colorectal cancer must be given high priority.

Using a monoclonal antibody-based radioimmunoassay inhibition method we have determined preoperative serum levels of the carcinoma-associated carbohydrate antigen CA-50 in 266 patients with primary colorectal cancer. CA-50 levels exceeding the mean value for blood donor sera by more than 2 standard deviations (greater than or equal to 17 U/ml) were found in 47% of these patients, with 15%, 43% and 31% being elevated in patients with Dukes' A, Dukes' B and Dukes' C cancer, respectively, and 63% and 66% being elevated in patients with more advanced localized or disseminated cancer. Only 5% of patients with benign colorectal disease had elevated CA-50 level and these were patients with ulcerative colitis of a duration of more than 10 years. Among patients who had developed a recurrence after operation for a primary Dukes' A-C colorectal cancer 66% had elevated levels, and 25% of resected patients with no clinical evidence of disease at corresponding times after operation also had CA-50 levels above the normal concentrations. From 139 patients operated for a Dukes' A-C colorectal cancer a definitive rise in CA-50 levels from the pre- to a 6-9 months postoperative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On prolonged follow-up a clinically manifest recurrence later developed in all of these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. Our findings suggest that a rise in CA-50 levels after resection of a Dukes' A-C primary colorectal cancer is indicative of a recurrence and may precede any clinical evidence of disease by many months or years. Thus CA-50 may be a clinically useful tool for monitoring of patients with colorectal cancer.