Effect of More vs Less Frequent Follow-up Testing on Overall and Colorectal Cancer-Specific Mortality in Patients With Stage II or III Colorectal Cancer: The COLOFOL Randomized Clinical Trial.

Importance: Intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, but evidence of a survival benefit is limited. Objective: To examine overall mortality, colorectal cancer-specific mortality, and colorectal cancer-specific recurrence rates among patients with stage II or III colorectal cancer who were randomized after curative surgery to 2 alternative schedules for follow-up testing with computed tomography and carcinoembryonic antigen. Design, Setting, and Participants: Unblinded randomized trial including 2509 patients with stage II or III colorectal cancer treated at 24 centers in Sweden, Denmark, and Uruguay from January 2006 through December 2010 and followed up for 5 years; follow-up ended on December 31, 2015. Interventions: Patients were randomized either to follow-up testing with computed tomography of the thorax and abdomen and serum carcinoembryonic antigen at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; n = 1253 patients) or at 12 and 36 months after surgery (low-frequency group; n = 1256 patients). Main Outcomes and Measures: The primary outcomes were 5-year overall mortality and colorectal cancer-specific mortality rates. The secondary outcome was the colorectal cancer-specific recurrence rate. Both intention-to-treat and per-protocol analyses were performed. Results: Among 2555 patients who were randomized, 2509 were included in the intention-to-treat analysis (mean age, 63.5 years; 1128 women [45%]) and 2365 (94.3%) completed the trial. The 5-year overall patient mortality rate in the high-frequency group was 13.0% (161/1253) compared with 14.1% (174/1256) in the low-frequency group (risk difference, 1.1% [95% CI, -1.6% to 3.8%]; P = .43). The 5-year colorectal cancer-specific mortality rate in the high-frequency group was 10.6% (128/1248) compared with 11.4% (137/1250) in the low-frequency group (risk difference, 0.8% [95% CI, -1.7% to 3.3%]; P = .52). The colorectal cancer-specific recurrence rate was 21.6% (265/1248) in the high-frequency group compared with 19.4% (238/1250) in the low-frequency group (risk difference, 2.2% [95% CI, -1.0% to 5.4%]; P = .15). Conclusions and Relevance: Among patients with stage II or III colorectal cancer, follow-up testing with computed tomography and carcinoembryonic antigen more frequently compared with less frequently did not result in a significant rate reduction in 5-year overall mortality or colorectal cancer-specific mortality. Trial Registration: clinicaltrials.gov Identifier: NCT00225641.

Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer.

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.

Detection of Biomarkers with Solid-Phase Proximity Ligation Assay in Patients with Colorectal Cancer.

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.

Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus.

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.

Is England closing the international gap in cancer survival?

BACKGROUND: We provide an up-to-date international comparison of cancer survival, assessing whether England is 'closing the gap' compared with other high-income countries. METHODS: Net survival was estimated using national, population-based, cancer registrations for 1.9 million patients diagnosed with a cancer of the stomach, colon, rectum, lung, breast (women) or ovary in England during 1995-2012. Trends during 1995-2009 were compared with estimates for Australia, Canada, Denmark, Norway and Sweden. Clinicians were interviewed to help interpret trends. RESULTS: Survival from all cancers remained lower in England than in Australia, Canada, Norway and Sweden by 2005-2009. For some cancers, survival improved more in England than in other countries between 1995-1999 and 2005-2009; for example, 1-year survival from stomach, rectal, lung, breast and ovarian cancers improved more than in Australia and Canada. There has been acceleration in lung cancer survival improvement in England recently, with average annual improvement in 1-year survival rising to 2% during 2010-2012. Survival improved more in Denmark than in England for rectal and lung cancers between 1995-1999 and 2005-2009. CONCLUSIONS: Survival has increased in England since the mid-1990s in the context of strategic reform in cancer control, however, survival remains lower than in comparable developed countries and continued investment is needed to close the international survival gap.

Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer.

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.

1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer.

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.

EURECCA colorectal: multidisciplinary management: European consensus conference colon & rectum.

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.

CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy.

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.

EURECCA colorectal: multidisciplinary mission statement on better care for patients with colon and rectal cancer in Europe.

BACKGROUND: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. 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 colon and rectum was held looking for multidisciplinary consensus. 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. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited 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. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. 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: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus 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.

Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPIDO trial.

BACKGROUND: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. METHODS AND DESIGN: Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. DISCUSSION: Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT01558921.

Functional and structural abnormalities after milligan hemorrhoidectomy: a comparison with healthy subjects.

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.

Stage at diagnosis and colorectal cancer survival in six high-income countries: a population-based study of patients diagnosed during 2000-2007.

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.

In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and (67/68Ga)-labeled haptens by pretargeting.

The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from patients with colorectal cancer with trivalent bispecific antibody TF2 and two hapten molecules, [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485 by means of pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala University Hospital, were frozen fresh and cryosectioned. The two hapten molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA) were labeled with (67)Ga or (68)Ga. The autoradiography was conducted by incubating the tissue samples with the bispecific antibody TF2, followed by washing and incubation with one of the radiolabeled hapten molecules. After washing, drying and exposure to phosphor imager plates, the autoradiograms were analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced binding was found in the tissue from colorectal cancer using the bispecific antibody TF2 and either of the haptens [(67/68)Ga]Ga-IMP461 and [(67/68)Ga]Ga-IMP485. Distinct binding was also detected in the epithelium of most samples of neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is concluded that pretargeting CEA with the bispecific antibody TF2 followed by the addition of (67/68)Ga-labeled hapten is extremely sensitive for visualizing this marker for colorectal cancer. This methodology is therefore a very specific complement to other histochemical techniques in the diagnosis of biopsies or in samples taken from surgery. Use of the pretargeting technique in vivo may also be an advance in diagnosing patients with colorectal cancer, either using (67)Ga and SPECT or (68)Ga and PET.

Randomised multicentre trial of circular stapling devices.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Colorectal cancer survival in socioeconomic groups in England: variation is mainly in the short term after diagnosis.

UNLABELLED: The objective of this study was to examine differences in cancer survival between socioeconomic groups in England, with particular attention to survival in the short term of follow-up. PATIENTS AND METHODS: Individuals diagnosed with colorectal cancer between 1996 and 2004 in England were identified from cancer registry records. Five-year cumulative relative survival and excess death rates were computed. RESULTS: For colon cancer there was a very high excess death rate in the first month of follow-up, and the excess death rate was highest in the socioeconomically deprived groups. In subsequent periods, excess mortality rates were much lower and there was less socioeconomic variation. The pattern of variation in excess death rates was generally similar in rectal cancer but the socioeconomic difference in death rates persisted several years longer. If the excess death rates in the entire colorectal cancer patient population were the same as those observed in the most affluent socioeconomic quintile, the annual reduction would be 360 deaths in colon cancer and 336 deaths in rectal cancer patients. These deaths occurred almost entirely in the first month and the first year after diagnosis. CONCLUSION: Recent developments in the national cancer control agenda have included an increasing emphasis on outcome measures, with short-term cancer survival an operational measure of variation and progress in cancer control. In providing clues to the nature of the survival differences between socioeconomic groups, the results presented here give strong support for this strategy.

Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa.

BACKGROUND: Despite their well-established functional roles, histone modifications have received less attention than DNA methylation in the cancer field. In order to evaluate their importance in colorectal cancer (CRC), we generated the first genome-wide histone modification profiles in paired normal colon mucosa and tumor samples. METHODS: Chromatin immunoprecipitation and microarray hybridization (ChIP-chip) was used to identify promoters enriched for histone H3 trimethylated on lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in paired normal colon mucosa and tumor samples from two CRC patients and for the CRC cell line HT29. RESULTS: By comparing histone modification patterns in normal mucosa and tumors, we found that alterations predicted to have major functional consequences were quite rare. Furthermore, when normal or tumor tissue samples were compared to HT29, high similarities were observed for H3K4me3. However, the differences found for H3K27me3, which is important in determining cellular identity, indicates that cell lines do not represent optimal tissue models. Finally, using public expression data, we uncovered previously unknown changes in CRC expression patterns. Genes positive for H3K4me3 in normal and/or tumor samples, which are typically already active in normal mucosa, became hyperactivated in tumors, while genes with H3K27me3 in normal and/or tumor samples and which are expressed at low levels in normal mucosa, became hypersilenced in tumors. CONCLUSIONS: Genome wide histone modification profiles can be used to find epigenetic aberrations in genes associated with cancer. This strategy gives further insights into the epigenetic contribution to the oncogenic process and may identify new biomarkers.