Relative contribution of clinicopathological variables, genomic markers, transcriptomic subtyping and microenvironment features for outcome prediction in stage II/III colorectal cancer.

BACKGROUND: It remains unknown to what extent consensus molecular subtype (CMS) groups and immune-stromal infiltration patterns improve our ability to predict outcomes over tumor-node-metastasis (TNM) staging and microsatellite instability (MSI) status in early-stage colorectal cancer (CRC). PATIENTS AND METHODS: We carried out a comprehensive retrospective biomarker analysis of prognostic markers in adjuvant chemotherapy-untreated (N = 1656) and treated (N = 980), stage II (N = 1799) and III (N = 837) CRCs. We defined CMS scores and estimated CD8+ cytotoxic lymphocytes (CytoLym) and cancer-associated fibroblasts (CAF) infiltration scores from bulk tumor tissue transcriptomes (CMSclassifier and MCPcounter R packages); constructed a stratified multivariable Cox model for disease-free survival (DFS); and calculated the relative proportion of explained variation by each marker (clinicopathological [ClinPath], genomics [Gen: MSI, BRAF and KRAS mutations], CMS scores [CMS] and microenvironment cells [MicroCells: CytoLym+CAF]). RESULTS: In multivariable models, only ClinPath and MicroCells remained significant prognostic factors, with both CytoLym and CAF infiltration scores improving survival prediction beyond other markers. The explained variation for DFS models of ClinPath, MicroCells, Gen markers and CMS4 scores was 77%, 14%, 5.3% and 3.7%, respectively, in stage II; and 55.9%, 35.1%, 4.1% and 0.9%, respectively, in stage III. Patients whose tumors were CytoLym high/CAF low had better DFS than other strata [HR=0.71 (0.6-0.9); P = 0.004]. Microsatellite stable tumors had the strongest signal for improved outcomes with CytoLym high scores (interaction P = 0.04) and the poor prognosis linked to high CAF scores was limited to stage III disease (interaction P = 0.04). CONCLUSIONS: Our results confirm that tumor microenvironment infiltration patterns represent potent determinants of the risk for distant dissemination in early-stage CRC. Multivariable models suggest that the prognostic value of MSI and CMS groups is largely explained by CytoLym and CAF infiltration patterns.

CMS-dependent prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer.

Background: The prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer (CRC) varies with microsatellite instability (MSI) status. The gene expression-based consensus molecular subtypes (CMSs) of CRC define molecularly and clinically distinct subgroups, and represent a novel stratification framework in biomarker analysis. We investigated the prognostic value of these mutations within the CMS groups. Patients and methods: Totally 1197 primary tumors from a Norwegian series of CRC stage I-IV were analyzed for MSI and mutation status in hotspots in KRAS (codons 12, 13 and 61) and BRAF (codon 600). A subset was analyzed for gene expression and confident CMS classification was obtained for 317 samples. This cohort was expanded with clinical and molecular data, including CMS classification, from 514 patients in the publically available dataset GSE39582. Gene expression signatures associated with KRAS and BRAFV600E mutations were used to evaluate differential impact of mutations on gene expression among the CMS groups. Results: BRAFV600E and KRAS mutations were both associated with inferior 5-year overall survival (OS) exclusively in MSS tumors (BRAFV600E mutation versus KRAS/BRAF wild-type: Hazard ratio (HR) 2.85, P < 0.001; KRAS mutation versus KRAS/BRAF wild-type: HR 1.30, P = 0.013). BRAFV600E-mutated MSS tumors were strongly enriched and associated with metastatic disease in CMS1, leading to negative prognostic impact in this subtype (OS: BRAFV600E mutation versus wild-type: HR 7.73, P = 0.001). In contrast, the poor prognosis of KRAS mutations was limited to MSS tumors with CMS2/CMS3 epithelial-like gene expression profiles (OS: KRAS mutation versus wild-type: HR 1.51, P = 0.011). The subtype-specific prognostic associations were substantiated by differential effects of BRAFV600E and KRAS mutations on gene expression signatures according to the MSI status and CMS group. Conclusions: BRAFV600E mutations are enriched and associated with metastatic disease in CMS1 MSS tumors, leading to poor prognosis in this subtype. KRAS mutations are associated with adverse outcome in epithelial (CMS2/CMS3) MSS tumors.

Prognostic markers for colorectal cancer: estimating ploidy and stroma.

Background: We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). Patients and methods: DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Results: Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13-2.77) and HR = 2.95 (95% CI: 1.73-5.03), P < 0.001]. Conclusion: A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals.

Preoperative geriatric assessment and tailored interventions in frail older patients with colorectal cancer: a randomized controlled trial.

AIM: Colorectal cancer (CRC) is prevalent in the older population, and surgery is the mainstay of curative treatment. A preoperative geriatric assessment (GA) can identify frail older patients at risk for developing postoperative complications. In this randomized controlled trial we wanted to investigate whether tailored interventions based on a preoperative GA could reduce the frequency of postoperative complications in frail patients operated on for CRC. METHOD: Patients > 65 years scheduled for elective CRC surgery and fulfilling predefined criteria for frailty were randomized to either a preoperative GA followed by a tailored intervention or care as usual. The primary end-point was Clavien-Dindo Grade II-V postoperative complications. Secondary end-points included complications of any grade, reoperation, length of stay, readmission and survival. RESULTS: One hundred and twenty-two patients with a mean age of 78.6 years were randomized. We found no statistically significant differences between the intervention group and the control group for Grade II-V complications (68% vs 75%, P = 0.43), reoperation (19% vs 11%, P = 0.24), length of stay (8 days in both groups), readmission (16% vs 6%, P = 0.12) or 30-day survival (4% vs 5%, P = 0.79). Grade I-V complications occurred in 76% of patients in the intervention group compared with 87% in the control group (P = 0.10). In secondary analyses adjusting for prespecified prognostic factors, there was a statistically significant difference in favour of the intervention for reducing the total number of Grade I-V complications (P = 0.05). CONCLUSION: A preoperative GA and tailored interventions did not reduce the rate of Grade II-V complications, reoperations, readmission or mortality in frail older patients electively operated on for CRC.

Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.

Background: TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. Patients and methods: After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). Results: TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61-0.68 in the TNM alone model to 0.63-0.71 in models with added molecular markers, 0.65-0.73 with clinicopathological features and 0.66-0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Conclusions: Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include clinicopathological features, particularly in chemotherapy-treated patients.

Resection of synchronous liver metastases between radiotherapy and definitive surgery for locally advanced rectal cancer: short-term surgical outcomes, overall survival and recurrence-free survival.

AIM: There is debate as to the correct treatment algorithm sequence for patients with locally advanced rectal cancer with liver metastases. The aim of the study was to assess safety, resectability and survival after a modified 'liver-first' approach. METHOD: This was a retrospective study of patients undergoing preoperative radiotherapy for the primary rectal tumour, followed by liver resection and, finally, resection of the primary tumour. Short-term surgical outcome, overall survival and recurrence-free survival are reported. RESULTS: Between 2009 and 2013, 45 patients underwent liver resection after preoperative radiotherapy. Thirty-four patients (76%) received neoadjuvant chemotherapy, 24 (53%) concomitant chemotherapy during radiotherapy and 17 (43%) adjuvant chemotherapy. The median time interval from the last fraction of radiotherapy to liver resection and rectal surgery was 21 (range 7-116) and 60 (range 31-156) days, respectively. Rectal resection was performed in 42 patients but was not performed in one patient with complete response and two with progressive metastatic disease. After rectal surgery three patients did not proceed to a planned second stage liver (n = 2) or lung (n = 1) resection due to progressive disease. Clavien-Dindo ≥Grade III complications developed in 6.7% after liver resection and 19% after rectal resection. The median overall survival and recurrence-free survival in the patients who completed the treatment sequence (n = 40) were 49.7 and 13.0 months, respectively. Twenty of the 30 patients who developed recurrence underwent further treatment with curative intent. CONCLUSION: The modified liver-first approach is safe and efficient in patients with locally advanced rectal cancer and allows initial control of both the primary tumour and the liver metastases.

Managing Malignant Colorectal Obstruction with Self-Expanding Stents. A Closer Look at Bowel Perforations and Failed Procedures.

Stent treatment of large bowel obstruction is still controversial. There are concerns regarding complications, particularly bowel perforation, as well as long-term outcome in curable patients. Through a 10-year retrospective study, we have evaluated efficacy, complications, delay in surgical interventions and stent patency in cases of palliative treatment. We treated 183 patients, 85 as bridge to surgery and 98 as definitive, palliative treatment. At presentation, 58 % of patients had advanced local or metastatic disease. Seventeen patients required more than one stent insertion. The total number of procedures was 213. We recorded technical and clinical success or failure, complications, necessity of restenting or surgical intervention, mortality and stent patency in the palliation group. Stenting was clinically successful in 89 % of the bridge to surgery group and 86 % of the palliative group. Complications occurred in 7 %, including 12 perforations. Six patients suffered an early perforation, of which two died. Half of the six late perforations were silent. Procedure related mortality was 1 %. The clinical success rate was high in both the palliative and bridge to surgery setting. The complication rate was low, and the sum of early and late perforations was 5.6 %. Procedure related mortality was low.

Prognostic impact of genomic instability in colorectal cancer.

BACKGROUND: The prognostic impact of an indication of chromosomal instability (CIN) is evaluated in a consecutive series of 952 colorectal cancer patients treated at Aker University Hospital, Norway, during 1993-2003. Microsatellite instability (MSI) in this case series has recently been reported and made it possible to find the co-occurrence and compare the prognostic significance of CIN and MSI. METHODS: Data sets for overall survival (OS; n=855) and time to recurrence (TTR; n=579) were studied. To reveal CIN we used automated image cytometry (ICM). Non-diploid histograms were taken as indicative of the presence of CIN. PCR-based measures of MSI in this material have already been described. RESULTS: As with MSI, CIN was found to be an independent predictor of early relapse and death among stage II patients (TTR: n=278: HR 2.19 (95% CI: 1.35-3.55), P=0.002). Of the MSI tumours (16%), 71% were found to be DNA diploid, 21% were DNA tetraploid and 8% were DNA aneuploid. Among microsatellite stable tumours, 24% were DNA diploid, 15% were DNA tetraploid and 61% were DNA aneuploid. CONCLUSION: For patients presenting with stage II disease, genomic instability as detected by DNA image cytometry has the potential to provide a useful biomarker for relapse and cancer-related death following surgery with curative intent.

The rationale behind complete mesocolic excision (CME) and a central vascular ligation for colon cancer in open and laparoscopic surgery : proceedings of a consensus conference.

BACKGROUND: It has been evident for a while that the result after resection for colon cancer may not have been optimal. Several years ago, this was showed by some leading surgeons in the USA but a concept of improving results was not consistently pursued. Later, surgeons in Europe and Japan have increasingly adopted the more radical principle of complete mesocolic excision (CME) as the optimal approach for colon cancer. The concept of CME is a similar philosophy to that of total mesorectal excision for rectal cancer and precise terminology and optimal surgery are key factors. METHOD: There are three essential components to CME. The main component involves a dissection between the mesenteric plane and the parietal fascia and removal of the mesentery within a complete envelope of mesenteric fascia and visceral peritoneum that contains all lymph nodes draining the tumour area (Hohenberger et al., Colorectal Disease 11:354-365, 2009; West et al., J Clin Oncol 28:272-278, 2009). The second component is a central vascular tie to completely remove all lymph nodes in the central (vertical) direction. The third component is resection of an adequate length of bowel to remove involved pericolic lymph nodes in the longitudinal direction. RESULT: The oncological rationale for CME and various technical aspects of the surgical management will be explored. CONCLUSION: The consensus conference agreed that there are sound oncological hypotheses for a more radical approach than has been common up to now. However, this may not necessarily apply in early stages of the tumour stage. Laparoscopic resection appears to be equally well suited for resection as open surgery.

Risk factors associated with poor lymph node harvest after colon cancer surgery in a national cohort.

AIM: Evaluation of ≥ 12 lymph nodes (LNs) is recommended after surgery for colon cancer. A harvest of ≤ 8 is considered poor, but few reports have evaluated risk factors associated with a poor harvest. This aims of this study were to analyse the clinical, surgical and pathological factors associated with poor LN harvest (LNH), the total number of examined nodes and the effect of LN number on stage. METHOD: All patients reported to the Norwegian Colorectal Cancer Registry during 2007 and 2008 who underwent curative resection for Stage I-III colon cancer were studied. Risk factors for poor LNH and the proportion of Stage III disease were analysed by univariate and multivariate analyses. RESULTS: A total of 2879 patients were included in the study. The median LNH was 14. Overall, 69.9% had ≥ 12 lymph nodes and 14.4% had ≤ 8 LN (poor harvest). Multivariate analysis showed that male sex, age > 75 years, sigmoid tumours, pT category 1-2, failure to use the pathology report template and distance of ≤ 5 cm from the bowel resection margin were all independent factors for poor LNH. Age < 65 years, pT category 3-4, and poor tumour differentiation were independent predictors of Stage III disease. An increased LNH did not increase the proportion of patients identified as being LN positive at the ≤ 8, 9-11 and ≥ 12 LN levels. CONCLUSION: Adequate LNH was achieved in the majority of curative colon cancer resections in this national cohort. Elderly, male patients with sigmoid cancers, and a short distal margin were at increased risk of a poor LNH.

Microsatellite instability has a positive prognostic impact on stage II colorectal cancer after complete resection: results from a large, consecutive Norwegian series.

BACKGROUND: Microsatellite instability (MSI) was suggested as a marker for good prognosis in colorectal cancer in 1993 and a systematic review from 2005 and a meta-analysis from 2010 support the initial observation. We here assess the prognostic impact and prevalence of MSI in different stages in a consecutive, population-based series from a single hospital in Oslo, Norway. PATIENTS AND METHODS: Of 1274 patients, 952 underwent major resection of which 805 were included in analyses of MSI prevalence and 613 with complete resection in analyses of outcome. Formalin-fixed tumor tissue was used for PCR-based MSI analyses. RESULTS: The overall prevalence of MSI was 14%, highest in females (19%) and in proximal colon cancer (29%). Five-year relapse-free survival (5-year RFS) was 67% and 55% (P = 0.030) in patients with MSI and MSS tumors, respectively, with the hazard ratio (HR) equal to 1.60 (P = 0.045) in multivariate analysis. The improved outcome was confined to stage II patients who had 5-year RFS of 74% and 56% respectively (P = 0.010), HR = 2.02 (P = 0.040). Examination of 12 or more lymph nodes was significantly associated with proximal tumor location (P < 0.001). CONCLUSIONS: MSI has an independent positive prognostic impact on stage II colorectal cancer patients after complete resection.

Endoscopic snare resection followed by laser ablation in the treatment of large, sessile rectal adenomas.

BACKGROUND AND AIMS: Large sessile rectal adenomas can be difficult to eradicate, and different treatment modalities are available. The aim of this study was to evaluate outcome after endoscopic snare resection followed by Nd:YAG laser ablation. MATERIAL AND METHODS: Over a 10-year period 92 of 99 (93%) patients were registered prospectively and attended follow-up examinations with endoscopy and biopsies. RESULTS: Fifty-four (59%) men and 38 (41%) women were included; 67 patients (73%) had high grade (severe) intraepithelial dysplasia or intramucosal neoplasia. The adenomas ranged from 2-9 cm (median 4 cm) in diameter, and were located 2-15 cm (median 5 cm) from the anal verge. A median of two (range 1-6) piecemeal snare resection sessions and a median of one (range 1-7) laser treatments were performed for each patient. Complete eradication was achieved in 86 patients (93%). Over a median follow-up period of 26 months, 20/86 (23%) suffered local recurrence, eight of whom were given a second laser treatment without developing further recurrence. In five of eight frail patients considered unsuitable for more radical treatment, repeated laser treatment was effective in keeping the adenoma small and symptoms at a minimum. As a whole the treatment was successful in 74/92 (80%) and partially successful in 5/92 (5%) of the patients. CONCLUSIONS: Snare resection followed by laser ablation is safe and still has a place in the treatment of old, frail patients with large rectal adenomas. However, there is a risk of missing an infiltrating carcinoma, and other treatment options are preferable in fit patients.

CLC and IFNAR1 are differentially expressed and a global immunity score is distinct between early- and late-onset colorectal cancer.

Colorectal cancer (CRC) incidence increases with age, and early onset of the disease is an indication of genetic predisposition, estimated to cause up to 30% of all cases. To identify genes associated with early-onset CRC, we investigated gene expression levels within a series of young patients with CRCs who are not known to carry any hereditary syndromes (n=24; mean 43 years at diagnosis), and compared this with a series of CRCs from patients diagnosed at an older age (n=17; mean 79 years). Two individual genes were found to be differentially expressed between the two groups, with statistical significance; CLC was higher and IFNAR1 was less expressed in early-onset CRCs. Furthermore, genes located at chromosome band 19q13 were found to be enriched significantly among the genes with higher expression in the early-onset samples, including CLC. An elevated immune content within the early-onset group was observed from the differentially expressed genes. By application of outlier statistics, H3F3A was identified as a top candidate gene for a subset of the early-onset CRCs. In conclusion, CLC and IFNAR1 were identified to be overall differentially expressed between early- and late-onset CRC, and are important in the development of early-onset CRC.

SPG20, a novel biomarker for early detection of colorectal cancer, encodes a regulator of cytokinesis.

Colorectal cancer is a common disease with high mortality. Suitable biomarkers for detection of tumors at an early curable stage would significantly improve patient survival. Here, we show that the SPG20 (spastic paraplegia-20) promoter, encoding the multifunctional Spartin protein, is hypermethylated in 89% of colorectal carcinomas, 78% of adenomas and only 1% of normal mucosa samples. SPG20 methylation was also present in a pilot series of stool samples and corresponding tumors from colorectal cancer patients. SPG20 promoter hypermethylation resulted in loss of mRNA expression in various cancer types and subsequent depletion of Spartin. We further showed that Spartin downregulation in cancer cells resulted in cytokinesis arrest, which was reversed when SPG20 methylation was inhibited. The present study identifies SPG20 promoter hypermethylation as a biomarker suitable for non-invasive detection of colorectal cancer, and a possible mechanism for cytokinesis arrest in colorectal tumorigenesis.

Clinical prediction of survival by surgeons for patients with incurable abdominal malignancy.

BACKGROUND AND AIM: Accurate prognosis facilitates decision-making and counselling in incurable cancer. However, predictions of survival are frequently inaccurate and survival is consistently overestimated. The prognostic skills of surgeons are sparsely documented, and the present study was undertaken to assess their prognostic accuracy for patients with advanced abdominal malignancy. PATIENTS AND METHODS: Clinical predictions of survival were made by three consultant surgeons independently in consecutive patients with incurable abdominal cancer. Survival was predicted in intervals ranging from <1 week to 18-24 months. Prognoses were considered accurate when actual survival fell within the expected range. Performance status was classified according to the Eastern Cooperative Oncology Group (ECOG). RESULTS: 243 assessments were made in 178 patients. Prognoses were accurate in 27%, over-optimistic in 42% and over-pessimistic in 31%. Accuracy was inversely related to length of actual survival and did not differ between surgeons (P = 0.466). The proportion of over-optimistic prognoses differed significantly between surgeons (P < 0.001). Prognostic accuracy was 44% in gastric cancer patients, 29% in pancreatic cancer patients and 22% in colorectal cancer patients (P = 0.052). ECOG performance status correlated well with survival. CONCLUSIONS: Surgeons' accuracy in determining prognosis is poor. There are considerable individual differences between surgeons, and accuracy is reduced in cases with prolonged life expectancy.

Long-term functional outcome and quality of life after restorative proctocolectomy with ileo-anal anastomosis for colitis.

AIM: The study aimed to evaluate long-term health-related quality of life (HRQOL) and functional outcome in patients who had undergone restorative proctocolectomy with ileo-anal anastomosis (IPAA) for ulcerative colitis and familial adenomatous polyposis. METHOD: A total of 156 patients who underwent IPAA during the period 1984-2003 and who still had an intact pouch were included. The HRQOL score was compared with 4152 individuals from the general Norwegian population using the SF-36 questionnaire, and function was evaluated using the Wexner Continence Grading Scale. RESULTS: One hundred and ten (71%) patients answered the questionnaires, 60 (55%) of whom were men. All except five patients had ulcerative colitis. Median (range) age at interview was 47 (19-66) years, and time after surgery was 12 (2-22) years. The IPAA patients scored slightly, but significantly, lower in four of six SF-36 health domains than the control subjects, adjusted for age and gender. Multiple regression analysis showed frequency of nocturnal defaecation, faecal incontinence and urgency to be independent negative prognostic factors of quality of life. Frequency of defaecation was a median of 7 (3-12) bowel movements during the day and 2 (0-6) at night. The majority had some degree of faecal incontinence, median (range) Wexner score of 8 (0-17), and 40% reported urgency of defaecation necessitating alterations in lifestyle. CONCLUSION: Patients with IPAA reported slightly lower HRQOL rates than the general population and had an inferior functional outcome.

Short term outcome after emergency and elective surgery for colon cancer.

OBJECTIVE: Emergency presentation of colon cancer is common and associated with high mortality and morbidity following surgical treatment. The purpose of this study was to evaluate postoperative mortality and complications in a consecutive and population based series. METHOD: All patients with adenocarcinoma of the colon diagnosed between 1993 and 2007 were registered prospectively. Postoperative mortality and complication rates in elective and emergency patients were compared. Logistic regression analysis was used to identify independent risk factors for postoperative complications. RESULTS: In the study period 1129 patients were admitted, of whom 279 (25%) presented as an emergency. A total of 999 (89%) patients underwent surgical treatment; 924 patients (82%) had a major resection. The mortality rate was 3.5% after elective and 10% after emergency operation with resection (P < 0.01), and the complication rate was 24% and 38% (P < 0.01), respectively. In patients with left-sided obstruction, the mortality rate after Hartmann's procedure was 19% compared to 3% after resection with primary anastomosis (P < 0.01). Multivariate analyses demonstrated that emergency operation, increasing age, advanced tumour stage and ASA class IV were independent risk factors for postoperative mortality. CONCLUSION: Emergency operation for colon cancer was associated with high rates of complications and mortality, indicating that immediate surgery should be avoided if possible. Decompression of left sided obstruction with a stent seems promising, whereas no conclusion can be made with regard to optimal procedure if stent placement fails; in this study Hartmann's procedure was associated with high mortality and morbidity.

Morbidity related to the use of a protective stoma in anterior resection for rectal cancer.

OBJECTIVE: To evaluate morbidity related to the use of a protective stoma in rectal resection for cancer. METHOD: Seventy-two patients undergoing anterior rectal resection for cancer combined with a protective stoma (1993-2005) were included. Loop ileostomy was applied in 61 patients, loop colostomy in 10, and end ileostomy in one. Data regarding the primary operation were recorded prospectively, and stoma complications retrospectively. RESULTS: Five patients (7%) developed stoma complications immediately after the primary operation, and 14/70 (20%) following hospital discharge. The stoma was closed in 62 (86%) patients after median 4 (range 1-11) months. Five patients (8%) developed complications in hospital after closure. Two patients (3%) died, one of ileal anastomotic leak and one of myocardial infarction. Five patients (8%) had late complications after closure. A total of 19 patients (26%) developed stoma related complications. Eight (11%) of these were reoperated. Premature stoma closure was necessary in two additional patients. Nine patients (13%) ended up with a permanent stoma. Fourteen (19%) patients developed signs of rectal anastomotic failure, six (8%) of whom needed reoperation. One died. CONCLUSION: Significant morbidity is related to the use of defunctioning stomas. A protective stoma cannot always prevent serious complications of a rectal anastomotic leak, and a proportion of the patients will not have the stoma closed.

Tumour location is a prognostic factor for survival in colonic cancer patients.

OBJECTIVE: To evaluate survival and prognostic factors in a consecutive series of colon cancer patients from a defined city population in Norway. METHOD: All patients with adenocarcinoma of the colon diagnosed between 1993 and 2000 were registered prospectively. Five-year actuarial survival and 5-year relative survival rates were calculated. Cox regression analyses were used to study the effect of prognostic factors on survival. RESULTS: In the study period 627 patients were admitted. Overall 5-year relative survival was 50% in females and 52% in males. Five-year relative survival in 410 (65%) patients operated with curative intent, was 74% for females and 79% for males. Tumour location in the transverse colon, splenic flexure and descending colon (OR = 1.8), emergency operation (OR = 1.7), TNM stage (OR = 1.8-2.9), blood transfusion of more than two units (OR = 1.8) and age (OR = 4.0-7.1) were independent negative prognostic factors. CONCLUSION: Colon cancer located in the transverse and descending colon is associated with poor prognosis. Comparison of results from different centres is difficult due to selection and classification differences, and different methods used for calculation of survival.