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Background: Outcome after colorectal liver metastases (CRLM) resection has improved over time, despite increased resection rates. Hence, it's crucial to identify all patients possible to treat with curative intent. The objectives of this study were to map recurrence pattern, treatment strategy and survival depending on treatment and follow-up strategy.Methods: In the COLOFOL-trial, patients with radically resected stage II-III colorectal cancer were randomized to high-frequency (6, 12, 18, 24 and 36 months; HF) or low-frequency (12 and 36 months; LF) follow-up. In this study, all CRLM within 5 years were identified and medical files scrutinized. Overall survival (OS) was analysed in uni- and multivariable analyses. Primary endpoint was 5-year OS.Results: Of 2442 patients, 235 (9.6%) developed metachronous CRLM of which 123 (52.3%) underwent treatment with curative intent, resulting in 5-year OS of 58%. Five-year OS for patients with CRLM was 43% after HF versus 24% after LF. The survival benefit was confirmed for HF 8 years from resection of the primary tumour, HR 0.63 (CI 0.46-0.85).Conclusion: A high proportion of metachronous CRLM was possible to treat with curative intent, yielding high survival rates. More intense follow-up after colorectal cancer resection might be of value in high-risk patients. Background: Outcome after colorectal liver metastases (CRLM) resection has improved over time, despite increased resection rates. Hence, it's crucial to identify all patients possible to treat with curative intent. The objectives of this study were to map recurrence pattern, treatment strategy and survival depending on treatment and follow-up strategy.Methods: In the COLOFOL-trial, patients with radically resected stage II-III colorectal cancer were randomized to high-frequency (6, 12, 18, 24 and 36 months; HF) or low-frequency (12 and 36 months; LF) follow-up. In this study, all CRLM within 5 years were identified and medical files scrutinized. Overall survival (OS) was analysed in uni- and multivariable analyses. Primary endpoint was 5-year OS.Results: Of 2442 patients, 235 (9.6%) developed metachronous CRLM of which 123 (52.3%) underwent treatment with curative intent, resulting in 5-year OS of 58%. Five-year OS for patients with CRLM was 43% after HF versus 24% after LF. The survival benefit was confirmed for HF 8 years from resection of the primary tumour, HR 0.63 (CI 0.46-0.85).Conclusion: A high proportion of metachronous CRLM was possible to treat with curative intent, yielding high survival rates. More intense follow-up after colorectal cancer resection might be of value in high-risk patients.

Background Patients with colorectal cancer were examined to determine (1) whether elevated carcinoembryonic antigen (CEA) levels, either before treatment or after surgery, was associated with an increased risk of overall or colorectal cancer-specific mortality or recurrence, and (2) whether high intensity follow-up would benefit those patients. Materials and methods Post-hoc analysis based on 2509 patients that underwent surgery for colorectal cancer, stage II or III, in the COLOFOL randomized trial with 5-year follow-up. Serum CEA levels were ascertained before treatment and one month after surgery. Follow-up examinations included computed tomography of the thorax and abdomen and serum CEA sampling. Patients were randomized to examinations at either 6, 12, 18, 24, and 36 months (high-intensity group) or at 12 and 36 months after surgery (low-intensity group). Levels of CEA >5 μg/l were defined as elevated. Results Elevated CEA levels before treatment were associated with increased risk of recurrence (hazard ratio [HR], 1.49; 95% confidence interval [CI]: 1.22–1.83), colorectal cancer-specific mortality (HR, 1.44; 95% CI: 1.08–1.91), and overall mortality (HR, 1.38; 95% CI: 1.07–1.78). Elevated CEA levels after surgery were associated with increased colorectal cancer-specific mortality (HR, 1.68; 95% CI: 1.08–2.61) and overall mortality (HR, 1.79; 95% CI: 1.22–2.63). The intensity of the follow-up regimen had no effect on 5-year outcomes in patients with elevated CEA levels. Conclusion Both pre-treatment and post-surgery elevated serum CEA levels were associated with increased overall and cancer-specific mortality. Intensified follow-up showed no benefit over low-intensity follow-up in this high-risk group of patients with elevated CEA levels.

Modern treatment of rectal cancer comprises the use of radiotherapy where four main aspects have to be taken in consideration, not only by the surgeon, but also by the entire multidisciplinary treatment team (MDT-board).

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. Electronic supplementary material The online version of this article (doi:10.1007/s00464-016-5270-6) contains supplementary material, which is available to authorized users.

BACKGROUND: In the search for prognostic biomarkers, a significant amount of precious biobanked blood samples is needed for conventional analyses. Solid-phase proximity ligation assay (SP-PLA) is an analytic method with the ability to analyze many proteins at the same time in small amounts of plasma. The aim of this study was to explore the potential use of SP-PLA for biomarker validation in patients with colorectal cancer (CRC). MATERIAL AND METHODS: Plasma samples from patients with stage I to IV CRC, with (n = 31) and without (n = 29) disease dissemination at diagnosis or later, were analyzed with SP-PLA using 35 antibodies targeting an equal number of proteins in 5-μl plasma samples. Carcinoembryonic antigen (CEA), analyzed earlier in this cohort using a different technology, was used as a reference. RESULTS: A total of 21 of the 35 investigated proteins were detectable with SP-PLA. Patients in stage II to III with disseminated disease had lower plasma concentrations of HCC-4 (P = .025). Low plasma levels of tissue inhibitor of metalloproteinases–1 were seen in patients with disseminated disease stage II (P = .003). The level of CEA was higher in patients with disease dissemination compared with those without (P = .007). CONCLUSION: SP-PLA has the ability to analyze many protein markers simultaneously in a small amount of blood. However, none of the markers selected for the present SP-PLA analyses gave better prognostic information than CEA.

An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team. publisher: Elsevier articletitle: Managing synchronous liver metastases from colorectal cancer: A multidisciplinary international consensus journaltitle: Cancer Treatment Reviews articlelink: http://dx.doi.org/10.1016/j.ctrv.2015.06.006 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd. ispartof: Cancer Treatment Reviews vol:41 issue:9 pages:729-41 ispartof: location:Netherlands status: published

The first randomized clinical trial of antibiotics in uncomplicated diverticulitis (the AVOD study) showed no benefit of antibiotics. The aim of this study was to re-evaluate the computed tomography (CT) scans of the patients in the AVOD study to find out whether there were CT findings that were missed and to study whether CT signs in uncomplicated diverticulitis could predict complications or recurrence.The CT scan images from patients included in the AVOD study were re-evaluated and graded by two independent reviewers for different signs of diverticulitis, including complications, such as extraluminal gas or the presence of an abscess.Of the 623 patients included in the study, 602 CT scans were obtained and re-evaluated. Forty-four (7 %) patients were found to have complications on the admitting CT scan that had been overlooked. Twenty-seven had extraluminal gas and 17 had an abscess. Four of these patients deteriorated and required surgery, but the remaining patients improved without complications. Of the 18 patients in the no-antibiotic group, in whom signs of complications on CT were overlooked, 15 recovered without antibiotics. No CT findings in patients with uncomplicated diverticulitis could predict complications or recurrence.No CT findings that could predict complications or recurrence were found. A weakness in the initial assessment of the CT scans to detect extraluminal gas and abscess was found but, despite this, the majority of patients recovered without antibiotics. This further supports the non-antibiotic strategy in uncomplicated diverticulitis.

Preclinical studies have suggested that nitinol-based compression anastomosis might be a viable solution to anastomotic leak following low anterior resection. A prospective multicentre open label study was therefore designed to evaluate the performance of the ColonRing(?) in (low) colorectal anastomosis.The primary outcome measure was anastomotic leakage. Patients were recruited at 13 different colorectal surgical units in Europe, the United States and Israel. Institutional review board approval was obtained.Between 21 March 2010 and 3 August 2011, 266 patients completed the study protocol. The overall anastomotic leakage rate was 5.3% for all anastomoses, including a rate of 3.1% for low anastomoses. Septic anastomotic complications occurred in 8.3% of all anastomoses and 8.2% of low anastomoses.Nitinol compression anastomosis is safe, effective and easy to use and may offer an advantage for low colorectal anastomosis. A prospective randomized trial comparing ColonRing(?) with conventional stapling is needed.Colorectal Disease ? 2014 The Association of Coloproctology of Great Britain and Ireland.

Individualized risk assessment for patients with rectal cancer might allow a better selection of patients who will benefit from postoperative treatment and intensified follow-up. The developed nomograms can contribute to better individual risk prediction for local recurrence, distant metastases and overall survival for patients operated on rectal cancer. This makes decision support in the consulting room feasible. Background In many European countries, short-term 5 × 5 Gy radiotherapy has become the standard preoperative treatment of patients with resectable rectal cancer. Individualized risk assessment might allow a better selection of patients who will benefit from postoperative treatment and intensified follow-up. Patients and methods From patient's data from three European rectal cancer trials (N = 2881), we developed multivariate cox nomograms reflecting the risk for local recurrence (LR), distant metastases (DM) and overall survival (OS). Evaluated variables were age, gender, tumour distance from the anal verge, the use of radiotherapy, surgical technique (total mesorectal excision/conventional surgery), surgery type (low anterior resection/abdominoperineal resection), time from randomization to surgery, residual disease (R0 versus R1 + 2), pT-stage, pN-stage and surgical complications. Results Pathological T- and N-status are of vital importance for an accurate prediction of LR, DM and OS. Short-course radiotherapy reduces the rate of LR. The developed nomograms are capable of predicting events with a validation c-index of 0.79 (LR), 0.76 (DM) and 0.75 (OS). The proposed stratification in risk groups allowed significant distinction between Kaplan–Meier curves for outcome. Conclusion The developed nomograms can contribute to better individual risk prediction for LR, DM and OS for patients operated on rectal cancer. The practicality of the defined risk groups makes decision support in the consulting room feasible, assisting physicians to select patients for adjuvant therapy or intensified follow-up.

BACKGROUND:To compare CT and MRI for peritoneal carcinomatosis index (PCI) assessment and to compare assessments made by the radiologist based on their experiences.METHOD AND MATERIALS:MRI and CT o ...

Because favorable effects on survival were seen in randomized trials conducted during the 1980s, adjuvant chemotherapy in colon cancer was established as routine therapy in stage III disease in the United States in 1990. Follow-up trials in the United States, Asia, and Europe soon meant that it became recommended therapy worldwide, not only in stage III but in stage II disease as well, if risk factors for recurrence were present. Additional trials established the combination of a fluoropyrimidine and oxaliplatin as reference treatment for patients with stage II disease with risk factors who are fit for therapy and for those with stage III disease. The addition of oxaliplatin in the treatment of elderly patients has been questioned. Here we present arguments questioning not only the addition of oxaliplatin in the treatment of some younger patients as well but also the offering of adjuvant chemotherapy at all to some of these patients. Medical care continuously develops, and as a consequence, treatment results improve. This development has also been seen in colon (and rectal) cancer, and the improvements actually challenge the established benefit of adjuvant chemotherapy in colon (and rectal) cancer. We question whether the risk of recurrence is sufficiently high for most patients with stage II disease, even when risk factors are present, and for some patients with stage III disease in the presence of high-quality, modern, multidisciplinary team care to motivate adjuvant chemotherapy. In colorectal cancer, there has been a marked change during the past decades regarding surgery. It started with the total mesorectal excision (TME) technique for rectal cancer. This technique has now spread around the world; the majority of surgeons have learned how to operate effectively on rectal cancer, and many centers report low local recurrence rates. Population-based data from national quality registers also show that the local recurrence rate can today reach approximately 5%, equaling the rates achieved in dedicated centers. Surgery for colon cancer may also be about to change, with complete mesocolic excision dissection and the concept of central ligation. These techniques have started to spread among surgeons, and population data already indicate that there may be an overall survival benefit, in addition to improvements reflecting stage migration, if colonic surgery is performed in accordance with such procedures. Preoperative staging of colorectal cancer has also improved, and up-to-date contrast-enhanced computed tomography of the thorax and abdomen, completed with ultrasonography or magnetic resonance imaging with contrast agents in the case of equivocal liver lesions or positron emission tomography– computed tomography in the case of equivocal findings outside the liver, has also resulted in fewer recurrences in those undergoing surgery (ie, the target patients for adjuvant therapy). The scenario has changed from fewer metachronous to more synchronous metastases. Furthermore, although pathologists cannot reduce recurrence risks per se, better pathologic staging results in lower stage-specific recurrence rates, often referred to as stage migration. The rectal cancer radiotherapy story illustrates the same kind of problem the medical community is facing when one or several aspects of multidisciplinary care are improved. The story is well known from literature. The reduction in local recurrence rates seen after preoperative radiotherapy was questioned when surgery was improved (ie, when TME was introduced). The two trials then initiated—the Dutch–Swedish TME trial and the Medical Research Council CR07 trial in the United Kingdom, in which preoperative radiotherapy using the 5 3 5 Gy schedule was tested against selective postoperative (chemo)radiotherapy—showed that preoperative radiotherapy significantly reduced local recurrence rates. Actually, the relative reduction may have been slightly larger with TME (hazard ratio, 0.38; absolute difference, 11% v 4%) than with the older, suboptimal surgery (hazard ratio, 0.46; absolute difference, 27% v 13%). The overall survival gain seen previously in the Swedish Rectal Cancer Trial could not be reproduced; the absolute gain in local recurrences was likely too small to show up in the trials in which TME was used. The gains from postoperative chemoradiotherapy in local recurrence rates and survival have not been tested using TME. In a German trial testing preversus postoperative chemoradiotherapy, it was shown that preoperative chemoradiotherapy was better than postoperative in reducing the local recurrence rate, approximately 10% after postoperative treatment versus 7% after preoperative irradiation. The TME technique was used for most patients in the trial, but no difference in survival could be seen even after long-term follow-up. On the basis of this knowledge, there is an ongoing debate over whether radiotherapy is needed in the majority of rectal cancers because of the low recurrence rates seen today without

Preoperative radiotherapy or chemoradiotherapy (RT/CRT) is used in rectal cancer treatment to decrease the risk of a local recurrence in resectable tumours or to allow radical surgery in non-resectable tumours. In order not to increase the risk of complications after the surgery, surgery should be performed either before the acute radiation-induced toxicity has started, i.e. immediately after short-course RT (2–5 days), or after it has subsided 3–4 weeks after RT/CRT (i.e. 4–8 weeks after the last radiation fraction). Since regression of a rectal adenocarcinoma may take time and there presently is a wish to avoid (major) surgery in many patients, there is a growing interest in prolonging the interval from the RT/CRT to surgery to achieve maximal tumour regression. The pros and cons of delaying surgery are dependent upon the aim of the preoperative RT/CRT.

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.

SUMMARY The treatment philosophy for rectal cancer has changed a lot during the last three decades. In the 1970s it was more or less a pure surgical business and rectal cancer was considered radiation resistant. Owing to the unacceptable high local recurrence rates, surgery was changed (the total mesorectal excision technique) during the 1980s and treatment was, in many countries, concentrated to lager units. Moreover, the addition of adjuvant radiotherapy was tested during the same period in several randomized trials and demonstrated that the local recurrence rate could be reduced by 50%, provided the radiation dose was high enough. Since then, treatment has changed very rapidly with several interesting approaches, such as timing and type of radiotherapy, the place of chemotherapy, surgery with modern technique including laparoscopy; natural orifice transendoscopic surgery or robotics; and the whole idea of ‘wait-and-watch’ program. All of these new aspects are covered and discussed in the view of the standard-of-care in 2014.

The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?

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.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.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 (p0.001) and uncomfortable (p0.001). 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.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.

The rise and fall of a longed for clinical trial in patients with generalized colorectal cancer

Background Fecal incontinence is a rare but well-known adverse effect of hemorrhoidectomy. Objective The objective of this study was to identify possible reasons for incontinence after hemorrhoidectomy. Design We conducted a retrospective comparative study. Settings The study was performed in 1 university hospital and 1 general district hospital serving 2 counties in central Sweden. Patients In a cohort of 418 patients with consecutive Milligan hemorrhoidectomies, 40 reported fecal incontinence that was attributed to surgery. Of these, 19 patients agreed to participate. Fifteen age- and sex-matched patients from the same cohort who were operated on, but without symptoms of incontinence, were also studied, as was a third reference group of 19 age- and sex-matched persons serving as a population-based control group. Intervention All of the participants answered a bowel function questionnaire and underwent clinical evaluation, including rectoscopy, anal manometry, saline infusion test, and endoanal ultrasound. Main outcome measures We evaluated anal resting and squeeze pressures, sphincter defects, and continence function. Results The symptomatic patients had higher incontinence scores than the control groups (p = 0.00002). The mean resting pressure at the high-pressure zone was also reduced in this group (p = 0.047). External sphincter injuries were detected in 4 (20%) of 19 subjects compared with none in the control group (p = 0.11). Saline infusion test in the patients reporting incontinence showed reduced ability to hold liquids compared with healthy controls (p = 0.004). Limitations This study was limited by selection bias and limited numbers in the groups. Conclusions In the group of patients reporting incontinence after hemorrhoidectomy, there was a proportion with sphincter defects and impaired sphincter function. These results indicate a need for cautious patient selection and improved or alternative surgical techniques.

Background. Large international differences in colorectal cancer survival exist, even between countries with similar healthcare. We investigate the extent to which stage at diagnosis explains these differences. Methods. Data from population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK were analysed for 313 852 patients diagnosed with colon or rectal cancer during 2000-2007. We compared the distributions of stage at diagnosis. We estimated both stage-specific net survival and the excess hazard of death up to three years after diagnosis, using flexible parametric models on the log-cumulative excess hazard scale. Results. International differences in colon and rectal cancer stage distributions were wide: Denmark showed a distribution skewed towards later-stage disease, while Australia, Norway and the UK showed high proportions of 'regional' disease. One-year colon cancer survival was 67% in the UK and ranged between 71% (Denmark) and 80% (Australia and Sweden) elsewhere. For rectal cancer, one-year survival was also low in the UK (75%), compared to 79% in Denmark and 82-84% elsewhere. International survival differences were also evident for each stage of disease, with the UK showing consistently lowest survival at one and three years. Conclusion. Differences in stage at diagnosis partly explain international differences in colorectal cancer survival, with a more adverse stage distribution contributing to comparatively low survival in Denmark. Differences in stage distribution could arise because of differences in diagnostic delay and awareness of symptoms, or in the thoroughness of staging procedures. Nevertheless, survival differences also exist for each stage of disease, suggesting unequal access to optimal treatment, particularly in the UK.

Aim The 1-cm rule of distal bowel clearance in patients with low-lying rectal cancer undergoing anterior resection is based mainly on pathological data showing distal intramural spread. Because clinical data are contradictory, a review that includes only cancers located ≤ 5 or ≤ 6 cm from the anal verge was carried out. Method A systematic review of the literature identified seven studies that presented results in relation to a margin of ≤ 1 cm (n = 293) vs > 1 cm (n = 315). In six studies, pre- or postoperative radiotherapy was implemented, and in one study patients were treated with surgery alone. Three studies, all implementing radiotherapy, reported results related to a margin of ≤ 5 mm (n = 51) vs > 5 mm (n = 125). Results In none of the studies were the differences in local recurrence rate between the small and large margin groups statistically significant. The pooled analysis of six studies, in which patients received perioperative radiotherapy, showed a 1.2% [95% confidence interval (Cl) −4.5–7.0%] higher local recurrence rate in the ≤ 1 cm margin group compared with the > 1 cm margin group (P = 0.6). The corresponding figures for the ≤ 5 mm cut-off point were 0.5% (95% CI −7.6–8.7%, P = 0.9). The 5-year local recurrence rate in the only study in which radiotherapy had not been used was 8.6% higher in the ≤ 1 cm margin group compared with the > 1 cm margin group (P = 0.09). Conclusion Clinical evidence does not support the 1-cm rule in patients with low-lying rectal cancer undergoing pre- or postoperative radiotherapy.

Aim Perineal wound sepsis is a common problem after abdominoperineal resection of the rectum (APR), with a reported incidence of 10–15% in previously non-irradiated patients, 20–30% in patients given preoperative radiation and 50% among patients submitted to preoperative radiation combined with chemotherapy. The local application of gentamicin–collagen was evaluated to determine whether its use in the perineal wound reduced risk complications and had an effect on cancer recurrence. Method In this prospective multicentre (seven hospitals) randomized controlled trial, 102 patients undergoing APR due to cancer or benign disease were randomized into two groups including surgery with gentamicin–collagen (GS+, n = 52) or surgery without gentamicin–collagen (GS−, n = 50). Patients were followed at 7, 30 and 90 days and at 1 and 5 years. Results There were no statistically significant differences between the two groups regarding perineal wound complications, infectious or non-infectious, or cancer recurrence. Conclusion There was no statistically significant effect on perineal wound complications or cancer recurrence following the local administration of gentamicin–collagen during APR.

In rectal cancer treatment, surgery is most important. Dissection outside the mesorectal fascia, total mesorectal excision is required for cure in most cases; a local procedure is possible in the earliest tumours. Appropriate staging is required prior to treatment decision to stratify patients into risk groups. In early tumours surgery alone is sufficient whereas in intermediate cancers local recurrence rates are too high and preoperative radiotherapy is indicated. A short-course schedule is convenient, low toxic, although some prefer long-course chemoradiotherapy. The addition of a fluoropyrimidine enhances the radiotherapy. In locally advanced tumours preoperative chemoradiotherapy is required. The value of adjuvant chemotherapy in rectal cancer is controversial, particularly if preoperative chemoradiotherapy was used. Palliative chemotherapy prolongs life and improves well-being in patients with metastatic disease. Targeted drugs further improves the results to some extent. In some patients, chemotherapy may convert non-readily resectable metastases to resectable, and result in long-term cure.

Aim There have been initiatives to create a European audit project. This paper addresses the issue of differences in data collected by different registries. Method Patients with rectal cancer treated in 2008 and recorded in quality registries from Belgium, Germany/Poland, Spain and Sweden were analyzed. The comparison included number of patients, gender, age, American Society of Anesthesiology (ASA) classification, preoperative diagnostic and staging procedures, neoadjuvant therapy, surgical treatment and quality of surgery, postoperative complications and adjuvant treatment. Results The Belgian database consisted of 622 patients, the German/Polish database consisted of 3,393 patients, the Spanish database consisted of 1,641 patients and the Swedish database consisted of 1,826 patients. The percentage of patients in each ASA stage was highly variable. MRI use was highest in Spain and Sweden and very low in Germany/Poland. The percentage of cT4 stage tumours in Sweden was much higher than in all other countries. Sweden recorded the highest percentage of primary metastatic disease (20.3%) and Belgium recorded the lowest (10.2%). Neoadjuvant therapy in different protocols was administered to 41.2% patients in Germany/Poland, to 50.8% in Spain, to 55.2% in Belgium and to 62% in Sweden. Laparoscopic surgery (conversion rate) was performed for cure in 5% (28%) of patients in Sweden, in 20.8% (20.6%) in Spain, in 28.6% (15.2%) in Belgium and in 14.5% (8.9%) in Germany/Poland. The 30-day mortality for anterior resection, abdominoperineal excision and Hartmann’s procedure in Sweden, Belgium and Spain was 2.0%, 2.3% and 3.1%, respectively. The German/Polish database reported an in-hospital mortality of 3.2%. Conclusion A European quality assurance project in rectal cancer is possible only after data collection is standardized.

Aim: The aim of this study was to evaluate long-term functional outcome of ileal pouch-anal anastomosis for ulcerative colitis and to compare symptoms over time.Methods: 188 patients were operated ...

Background and study aim: While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial. Study design: Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. Power analysis: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up. Conclusions: The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population. Trial registration: NCT 00883792.

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

Aims The EURECCA (European Registration of Cancer Care) consortium is currently formed by nine independently founded national colorectal audit registrations, of which most already run for many years. The cumulative experience of EURECCA’s participants could be used to identify a ‘core dataset’ that covers all important aspects needed for high quality auditing and at the same time lacking needless data items that only consumes administrative effort. The aim of this study is to compare the data items used by the nine registries participating in EURECCA to identify a core dataset and explore options for future research. Methods All colorectal outcome registrations participating in the EURECCA project were asked to supply a list with all the data items they score. Items were scored ‘present’ if they appeared literally in a registration or in case they could be calculated using other items in the same registration. The definition of a ‘shared data item’ was that at least eight of the nine participating registries scored the item. Results The number of registered data items varied between 254 (Belgium) and 83 (Norway). Among the 45 variables were patient data, data about preoperative staging, surgical treatment, pre- or postoperative radio- and/or chemotherapy, and follow-up. Items about tumour recurrence or quality of life were scored too little to become shared data items. Conclusions A total of 45 items were collected by 8 or more of the participating registries and subsequently met the criteria for a shared data item.

Background The standard of care for acute uncomplicated diverticulitis today is antibiotic treatment, although there are no controlled studies supporting this management. The aim was to investigate the need for antibiotic treatment in acute uncomplicated diverticulitis, with the endpoint of recovery without complications after 12 months of follow-up. Methods This multicentre randomized trial involving ten surgical departments in Sweden and one in Iceland recruited 623 patients with computed tomography-verified acute uncomplicated left-sided diverticulitis. Patients were randomized to treatment with (314 patients) or without (309 patients) antibiotics. Results Age, sex, body mass index, co-morbidities, body temperature, white blood cell count and C-reactive protein level on admission were similar in the two groups. Complications such as perforation or abscess formation were found in six patients (1·9 per cent) who received no antibiotics and in three (1·0 per cent) who were treated with antibiotics (P = 0·302). The median hospital stay was 3 days in both groups. Recurrent diverticulitis necessitating readmission to hospital at the 1-year follow-up was similar in the two groups (16 per cent, P = 0·881). Conclusion Antibiotic treatment for acute uncomplicated diverticulitis neither accelerates recovery nor prevents complications or recurrence. It should be reserved for the treatment of complicated diverticulitis. Registration number: NCT01008488 (http://www.clinicaltrials.gov).

A high-throughput screen of the cytotoxic activity of 2000 molecules from a commercial library in three human colon cancer cell lines and two normal cell types identified the acridine acriflavin to be a colorectal cancer (CRC) active drug. Acriflavine was active in cell spheroids, indicating good drug penetration and activity against hypoxic cells. In a validation step based on primary cultures of patient tumor cells, acriflavine was found to be more active against CRC than ovarian cancer and chronic lymphocytic leukemia. This contrasted to the activity pattern of the CRC active standard drugs 5-fluorouracil, irinotecan and oxaliplatin. Mechanistic studies indicated acriflavine to be a dual topoisomerase I and II inhibitor. In conclusion, the strategy used seems promising for identification of new diagnosis-specific cancer drugs.

In a register study, the risk of anastomotic leakage correlated to the choice of circular stapling device with a 4% difference between the two brands used. Based on those data, a randomised multicentre study was started to explore the risk of an anastomotic leakage based upon the surgical device.Patients above 18 years with a rectal cancer, able to give informed consent, and scheduled for an anterior resection were eligible for the study. Perioperative randomisation was to Ethicon™ PROXIMATE™ ILS™ or Autosuture™ Premium Plus CEEA™. Anastomotic leakage was defined as a clinically manifest leak.Five hundred twenty-nine patients were randomised (58% male). A leak occurred in 8.3%. The anastomoses created by PROXIMATE™ ILS™ leaked in 25/265 (9.4%) anastomoses, and the Premium Plus CEEA™ leaked in 19/260 (7.3%), p = .419.No difference in the leak rate could be revealed. Several centres replaced one of the staplers by a new product, and the study was ended before the stipulated number of patients was reached. In the future, surgical devices may have to prove superiority in randomised trials or be monitored in quality registers before they can be introduced into day to day surgical practice. The study was registered at ClinicalTrials.gov: NCT00399009.

BACKGROUND: The optimal type of neoadjuvant therapy regimen in rectal cancer is contentious. OBJECTIVE: This study aimed to review the impact of neoadjuvant therapy on oncological outcomes and complications (short and long term) in patients undergoing total mesorectal excision for rectal cancer. DATA SOURCES: An electronic search of MEDLINE, PubMed, EMBASE, and the Cochrane Database of Collected Reviews was performed through March 2010. STUDY SELECTION: Key-word combinations including rectal cancer, total mesorectal excision, radiotherapy, chemotherapy, endorectal ultrasound, and magnetic resonance imaging were used to identify randomized control trials where chemotherapy and/or radiotherapy were deployed before resectional surgery. INTERVENTION(S): Patients underwent total mesorectal excision for rectal cancer who did and did not receive preoperative chemotherapy and/or radiotherapy. MAIN OUTCOME MEASURES: The main outcome measures comprised the impact of the addition of neoadjuvant therapy to total mesorectal excision on the perioperative complication rate, the pathological complete response rate, the rate of local recurrence, and long- term treatment-related complications. RESULTS: A total of 12 randomized control trials involving 9410 patients were included. Both short-course radiotherapy and long-course chemoradiation can offer a relative risk reduction of 50% in local recurrence in appropriately selected patients with stage II and III rectal cancer. This oncological benefit comes at the cost of a relative risk increase of 50% in both acute treatment-related toxicity and long-term anorectal dysfunction. LIMITATIONS: Preoperative staging provides only an estimate of the "true" tumor stage that can only be determined by histological assessment of the tumor specimen which renders appropriate patient selection challenging. CONCLUSIONS: The current treatment trade-off of a relative risk reduction of local recurrence of 50% at the cost of a relative increase of 50% in treatment-related complications underpins the need for more accurate patient staging and more precise delivery of neoadjuvant therapy.

Background The laparoscopic approach is increasingly applied in colorectal surgery. Although laparoscopic surgery in colon cancer has been proved to be safe and feasible with equivalent long-term oncological outcome compared to open surgery, safety and long-term oncological outcome of laparoscopic surgery for rectal cancer remain controversial. Laparoscopic rectal cancer surgery might be efficacious, but indications and limitations are not clearly defined. Therefore, the European Association for Endoscopic Surgery (EAES) has developed this clinical practice guideline. Methods An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. The expert panel constituted for a consensus development conference in May 2010. Thereafter, the recommendations were presented at the annual congress of the EAES in Geneva in June 2010 in a plenary session. A second consensus process (Delphi process) of the recommendations with the explanatory text was necessary due to the changes after the consensus conference. Results Laparoscopic surgery for extraperitoneal (mid- and low-) rectal cancer is feasible and widely accepted. The laparoscopic approach must offer the same quality of surgical specimen as in open surgery. Short-term outcomes such as bowel function, surgical-site infections, pain and hospital stay are slightly improved with the laparoscopic approach. Laparoscopic resection of rectal cancer is not inferior to the open in terms of disease-free survival, overall survival or local recurrence. Laparoscopic pelvic dissection may impair genitourinary and sexual function after rectal resection, like in open surgery. Conclusions Laparoscopic surgery for mid- and low-rectal cancer can be recommended under optimal conditions. Still, most level 1 evidence is for colon cancer surgery rather than rectal cancer. Upcoming results from large randomised trials are awaited to strengthen the evidence for improved short-term results and equal long-term results in comparison with the open approach.

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. 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. 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. This analysis does not support the hypothesis that laparoscopy leads to fewer episodes of bowel obstruction compared with open surgery.

Preoperative irradiation with 5 × 5 Gy in randomized trials reduces local recurrence rate and may improve survival in patients with resectable rectal cancer.The aim of this study was to determine whether the same favorable effects could be observed in a population-based study.This study was conducted via a retrospective analysis of prospectively collected data from the Swedish Rectal Cancer Registry.This study examined population-based data from Sweden.All newly diagnosed rectal cancers in Sweden are reported to the Swedish Rectal Cancer Registry.Between 1995 and 2001, 6878 patients (stages I-III) were operated on with an anterior resection, an abdominoperineal resection, or a Hartmann's procedure. Short-course irradiation was given to 41% of patients preoperatively. To reduce bias, patients operated on with a Hartmann procedure or older than 75 years were excluded when 5-year survival was analyzed (n = 3466). Tumors were analyzed according to height (0-5 cm, 6-10 cm, 11-15 cm).Five-year cumulative local recurrence and survival rates.The 5-year cumulative local recurrence rate was 6.3% (95% CI 5.4-7.4) for patients receiving preoperative irradiation and 12.1% (95% CI 10.8-13.5) for patients not receiving preoperative irradiation. Multivariate analyses indicated the risk of local recurrence was 50% lower for patients receiving preoperative irradiation compared with patients not receiving irradiation (hazard ratio = 0.50; 95% CI 0.40-0.62). Among patients younger than 76 years and operated on with an anterior resection or abdominoperineal resection, the 5-year cumulative survival rate was 0.70 (95% CI 0.69-0.72). Disease-free and overall survivals were higher in irradiated patients, and the difference was statistically significant in low tumors.In this population-based analysis, the favorable effect of preoperative short-course irradiation on local recurrence rates, seen in randomized trials, was confirmed for the entire Swedish population irrespective of tumor height and stage. Data also suggested an effect on 5-year survival, especially in patients with low tumors (0-5 cm).

Background: Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC). Methods: Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay. Results: Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I–III) (HR, 3.9; 95% CI, 1.16–13.15) and in stage III (HR, 10.32; 95% CI, 1.15–92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002). Conclusion: Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

The staging process in a newly diagnosed rectal cancer is divided into three parts. One essential part is the local staging, in which both endorectal ultrasound and MRI are used to disclose the size of the tumor and its correlation to the perirectal fascia, and to identify lymph node deposits and vascular invasion. This local staging process will guide clinicians to decide upon not only the type of surgery (local excision or radical surgery) but also whether or not some type of neoadjuvant treatment, such as radiotherapy and/or chemotherapy, is indicated. The second part is to evaluate whether or not the tumor has already metastasized at diagnosis. The most important organs to evaluate are the liver and lungs, and imaging techniques such as ultrasound, CT-scan, or sometimes PET-CT, and MRI can be used. The third important part is to investigate the rest of the large bowel for synchronous adenomas or cancers. This will preferably be done with colonoscopy or CT-colonography and sometimes barium enema. This article discusses the imaging techniques used for local staging and distant metastases.

BACKGROUND: Discrepancy exists how to surgically approach rectal cancer (open or minimally invasive) and how to implement neoadjuvant oncological concepts into the treatment algorithm. METHODS: Analysis of the literature regarding the surgical treatment of rectal cancer. RESULTS: Oncological criteria (resection margin and lymphnode harvest) are equally met by the laparoscopic and open approach, when conducted in experienced centers. Due to the pelvic anatomy, the open approach seems to be advantageous for low rectal cancers, when compared to laparocopy. Total mesorectal excision should be reserved for low rectal cancers, tumors of the mid and proximal portion of the rectum should be treated by subtotal mesorectal excision. CONCLUSIONS: Laparoscopic rectal surgery can replace the open approach in the majority of the cases. Respective expertise is required to reproduce the excellent results of high volume centers.

Parastomal hernia in patients with a permanent colostomy is common. The aim of this study was to evaluate the reliability of the diagnosis based on clinical examination and to compare this examination with the result of a specially designed questionnaire and computerised tomography (CT) scan.Forty-one patients operated upon with an abdominoperineal resection due to rectal cancer at three hospitals between 1996 and 2002 were included. At minimum of 4 years after the operation, they underwent clinical examination by two or three independent surgeons, answered a colostomy questionnaire and were offered a CT scan of the abdominal wall.At Hospital I, 17 patients were examined by three surgeons, with inter-observer kappa values between 0.35 and 0.64. At Hospital II, 13 patients were examined by three surgeons, the kappa values ranged between 0.29 and 0.43. At Hospital III, 11 patients were examined by two surgeons, with kappa value of 0.73. The kappa value between CT scan and the colostomy questionnaire was 0.45.The inter-observer reliability was low, indicating that parastomal hernia is difficult to diagnose by patient history and clinical examination. Some herniae may not be detected by CT scan, and the correlation to patient-reported complaints is low. A more sensitive radiological method to detect parastomal hernia is needed.

Magnetic resonance imaging (MRI) has established itself as the primary method for local staging in patients with rectal cancer. This is due to several factors, most importantly because of the ability to assess the status of circumferential resection margin. There are several newer developments being introduced continuously, such as diffusion-weighted imaging and imaging with 3 T. Assessment of loco-regional lymph nodes has also been investigated extensively using different approaches, but more work needs to be done. Finally, evaluation of tumours during or after preoperative treatment is becoming an everyday reality. All these new aspects prompt a review of the most recent advances and opinions. In this review, a comprehensive overview of the current status of MRI in the loco-regional assessment and management of rectal cancer is presented. The findings on MRI and their accuracy are reviewed based on the most up-to-date evidence. Optimisation of MRI acquisition and relevant regional anatomy are also presented, based on published literature and our own experience.

BACKGROUND: Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort. METHODS: The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype-phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed. RESULTS: Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype-phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age. CONCLUSIONS: Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations.

The genetic susceptibility to colorectal cancer (CRC) has been estimated to be around 35% and yet high-penetrance germline mutations found so far explain less than 5% of all cases. Much of the remaining variations could be due to the co-inheritance of multiple low penetrant variants. The identification of all the susceptibility alleles could have public health relevance in the near future. To test the hypothesis that what are considered polymorphisms in human CRC genes could constitute low-risk alleles, we selected eight common SNPs for a pilot association study in 1785 cases and 1722 controls. One SNP, rs3219489:G>C (MUTYH Q324H) seemed to confer an increased risk of rectal cancer in homozygous status (OR=1.52; CI=1.06-2.17). When the analysis was restricted to our 'super-controls', healthy individuals with no family history for cancer, also rs1799977:A>G (MLH1 I219V) was associated with an increased risk in both colon and rectum patients with an odds ratio of 1.28 (CI=1.02-1.60) and 1.34 (CI=1.05-1.72), respectively (under the dominant model); while 2 SNPs, rs1800932:A>G (MSH6 P92P) and rs459552:T>A (APC D1822V) seemed to confer a protective effect. The latter, in particular showed an odds ratio of 0.76 (CI=0.60-0.97) among colon patients and 0.73 (CI=0.56-0.95) among rectal patients. In conclusion, our study suggests that common variants in human CRC genes could constitute low-risk alleles.

Background To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rectal cancer, a multicentre trial has randomized patients to preoperative short-course RT with two different intervals to surgery, or long-course RT with delayed surgery. The present interim analysis assessed feasibility, compliance and complications after RT and surgery. Methods Some 303 patients were randomized to either short-course RT (5 × 5 Gy) and surgery within 1 week (group 1), short-course RT and surgery after 4–8 weeks (group 2) or long-course RT (25 × 2 Gy) and surgery after 4–8 weeks (group 3). Results Demographic data were similar between groups and there were few protocol violations (5·0–6 per cent). Eight patients (2·6 per cent) developed radiation-induced acute toxicity. There were no significant differences in postoperative complications between groups (46·6, 40·0 and 32 per cent in groups 1, 2 and 3 respectively; P = 0·164). Patients receiving short-course RT with surgery 11–17 days after the start of RT had the highest complication rate (24 of 37). Conclusion Compliance was acceptable and severe acute toxicity was low, irrespective of fractionation. Short-course RT with immediate surgery had a tendency towards more postoperative complications, but only if surgery was delayed beyond 10 days after the start of RT. Registration number: NCT00904813 (http://www.clinicaltrials.gov).

The aim of this study was to determine if mechanical bowel preparation (MBP) influences the intramucosal bacterial colony count in the colon.Macroscopically normal colon mucosa was collected from 37 patients (20 with and 17 without MBP) who were undergoing elective colorectal surgery at three hospitals. The biopsies were processed and cultured in the same laboratory. Colony counts of the common pathogens Escherichia coli and Bacteroides as well as of total bacteria were conducted. The study groups were comparable with regard to age, gender, antibiotics use, diagnosis and type of resection.MBP did not influence the median colony count of E. coli, Bacteroides or total bacteria in our study.MBP did not affect the intramucosal bacterial count in this study. Further studies are suggested to confirm these findings.

The aim of this study was to present detailed population-based survival estimates for patients with a rectal adenocarcinoma, using cancer register data supplemented with clinical data. Based on cancer register data, differences in rectal cancer survival have been reported between countries in Europe. Variation in the distribution of stage at diagnosis, initial therapy including surgical technique, and comorbidity are possible explanatory factors. Adenocarcinomas in the rectum, diagnosed in 1997 and identified in the national cancer registries in the Nordic countries and Scotland were included. Age standardized 5-year relative survival and multiplicative regression models for the relative excess mortality were calculated. 3888 patients were included in the survival study. Men in Denmark, Finland and Iceland had lower 5-year relative survival and poorer stage distribution compared to Norway, Sweden and Scotland. Danish men had the highest rate of excess deaths in the first six months after diagnosis. Stage adjusted, the elevated relative excess mortality decreased and after six months the excess mortality rates were the same in all countries. The poor 5-year relative survival in Danish men was mainly due to a high excess rate of death during the first six months after diagnosis. The low survival in Finland and Iceland was not in accordance with other periods. For both countries this may be explained by random variation due to small numbers. The study emphasizes the need for high quality and detailed data in order to understand international survival differences, and cautions comparisons between large national samples and those of smaller areas.

Background: Tryptophanyl-tRNA synthetase (TrpRS) is an aminoacyl-tRNA synthetase involved in protein synthesis and regulation of RNA transcription and translation and is an inhibitor of angiogenesis. TrpRS has been shown to be differentially expressed in colorectal cancer (CRC) and has thus been identified as a potential prognostic marker. The aim of this study was to analyze the correlation of TrpRS to the prognosis of patients diagnosed and treated for CRC within a defined population. Methods: With a polyclonal, monospecific IgG antibody, TrpRS expression was assessed by immunohistochemistry on tissue microarrays with tumors from a population-based CRC cohort (n = 320). Staining intensity and fraction of positive tumor cells were recorded. A Cox multivariate model including TrpRS expression, carcinoembryonic antigen, age, stage, tumor differentiation, and lymphatic and vascular vessel invasion was used to calculate the hazard ratio and 95% confidence interval (95% CI) for time to recurrence, disease-free survival, and overall survival. Results: Low expression of TrpRS correlated to increased risk for lymph node metastasis (P = 0.025) and a more advanced tumor stage (P = 0.001). Patients with tumors and increased levels of TrpRS expression had better survival than patients with low expression levels. Multivariate analyses revealed significantly better disease-free survival (relative risk, 0.59; 95% CI, 0.38-0.95) for patients with high expression than for patients with low expression of TrpRS. For colon cancer patients, a reduced risk for recurrence was seen in patients with increased TrpRS expression (relative risk, 0.23; 95% CI, 0.07-0.80). Conclusion: Low expression of TrpRS in tumor tissue correlates with increased risk for recurrence and worse survival in patients with CRC. This can be related to its antiangiogenic properties and could aid in the future selection of new drugs in the treatment of CRC. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2949–56)

Using single cell cytometry the pattern of DNA content in pre-operative samples from 131 carcinomas of the rectum and rectosigmoid has been studied. For comparison, 21 carcinomas of the colon, 44 colorectal polyps and mucosa adjacent to the tumours were also included. The biopsies were classified into near diploid (ND), near diploid with aneuploid cells (ND-anc) and aneuploid (AN). A more specific subclassification of aneuploid samples was not consistent because of a commonly occurring multiclonality, where different clones dominated different parts of the tumours. Fifteen of all 130 representatively sampled rectal carcinomas were ND; however, all the ND scores were based on a single sample. Among 31 multiply-sampled carcinomas none registered as ND in all samples. There were no principal differences in patterns of DNA profiles between rectal and colon carcinomas. Five samples from the pericancerous mucosa and samples from 4 adenomas showed non-ND patterns, which may be a premalignant sign. The main conclusions of these results are that rectal carcinomas, even if they contain a substantial ND cell population, to a very great extent contains cells with an abnormal DNA content. The carcinomas can be classified according to their pre-operatively estimated DNA content. The clinical relevance of this will be judged when the patients have been followed for longer time periods.

AIMS: This study assessed radiotherapy combined with capecitabine and oxaliplatin in patients with primary, inextirpable colorectal adenocarcinoma. PATIENTS AND METHODS: Forty-nine patients entered the trial. Two cycles of XELOX (capecitabine 1000mg/m(2) bid d1-14+oxaliplatin 130mg/m(2) d1, q3w) were followed by radiotherapy (50.4Gy), combined with capecitabine 825mg/m(2) bid every radiotherapy day and oxaliplatin 60mg/m(2) once weekly. The primary end-point was objective response. RESULTS: Forty-seven patients were evaluable. Twenty-nine (62% [95% CI: 46-75%]) achieved complete or partial response. Thirty-eight (81%) went through surgery of whom 37 (97%) had an R0 resection and five (13%) had a pathological complete response. Seventy-eight percent were alive and estimated local progression rate was 11% at 2 years. The most common grade 3+ toxicity during chemoradiotherapy was diarrhoea (24%). CONCLUSIONS: XELOX-RT was feasible and showed promising efficacy when treating patients with primary inextirpable colorectal cancer, establishing high local control rate.