Mucosal Microbiome in Patients with Early Bowel Polyps: Inferences from Short-Read and Long-Read 16S rRNA Sequencing.

Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in pre-cancerous bowel polyps. The short-read sequencing of variable regions in the 16S rRNA gene has commonly been used to infer bacterial taxonomy, and this has led, in part, to inconsistent findings between studies. Here, we examined mucosal microbiota from patients who presented with one or more polyps, compared to patients with no polyps, at the time of colonoscopy. We evaluated the results obtained using both short-read and PacBio long-read 16S rRNA sequencing. Neither sequencing technology identified significant differences in microbial diversity measures between patients with or without bowel polyps. Differential abundance measures showed that amplicon sequence variants (ASVs) associated with Ruminococcus gnavus and Escherichia coli were elevated in mucosa from polyp patients, while ASVs associated with Parabacteroides merdae, Veillonella nakazawae, and Sutterella wadsworthensis were relatively decreased. Only R. gnavus was consistently identified using both sequencing technologies as being altered between patients with polyps compared to patients without polyps, suggesting differences in technologies and bioinformatics processing impact study findings. Several of the differentially abundant bacteria identified using either sequencing technology are associated with inflammatory bowel diseases despite these patients being excluded from the current study, which suggests that early bowel neoplasia may be associated with a local inflammatory niche.

Deep Sequencing of Early T Stage Colorectal Cancers Reveals Disruption of Homologous Recombination Repair in Microsatellite Stable Tumours with High Mutational Burdens.

Early T stage colorectal cancers (CRC) that invade lymph nodes (Stage IIIA) are rare and greatly under-represented in large-scale genomic mapping projects. We retrieved 10 Stage IIIA CRC cases, matched these to 16 Stage 1 CRC cases (T1 depth without lymph node metastasis) and carried out deep sequencing of 409 genes using the IonTorrent system. Tumour mutational burdens (TMB) ranged from 2.4 to 77.2/Mb sequenced. No stage-related mutational differences were observed, consistent with reanalysis of The Cancer Genome Atlas (TCGA) Stage I and IIIA datasets. We next examined mutational burdens and observed that the top five cancers were microsatellite stable (MSS) genotypes (mean TMB 49.3/Mb), while the other 16 MSS cancers had a mean TMB of 5.9/Mb. To facilitate comparison with TCGA hypermutator CRC, we included four microsatellite instability-high (MSI-H) samples with the high mutation burden MSS cases to form a TMB-High group. Comparison of TMB-High with TMB-Low groups revealed differences in mutational frequency of ATM, ALK, NSD1, UBR5, BCL9, CARD11, KDM5C, MN1, PTPRT and PIK3CA, with ATM and UBR5 validated in reanalysis of TCGA hypermutator Stages I and IIIA samples. Variants in ATM were restricted to the TMB-High group, and in four of five MSS specimens, we observed the co-occurrence of mutations in homologous recombination repair (HRR) genes in either two of ATM, CDK12, PTEN or ATR, with at least one of these being a likely pathogenic truncating mutation. No MSI-H specimens carried nonsense mutations in HRR genes. These findings add to our knowledge of early T stage CRC and highlight a potential therapeutic vulnerability in the HRR pathway of TMB-H MSS CRC.

Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps.

Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium, known as polyps. Polyps themselves arise through the accumulation of mutations that disrupt the function of key tumour suppressor genes, activate proto-oncogenes and allow proliferation in an environment where immune control has been compromised. Consequently, colonoscopic surveillance and polypectomy are central pillars of cancer control strategies. Recent advances in genomic sequencing technologies have enhanced our knowledge of key driver mutations in polyp lesions that likely contribute to CRC. In accordance with the prognostic significance of Immunoscores for CRC survival, there is also a likely role for early immunological changes in polyps, including an increase in regulatory T cells and a decrease in mature dendritic cell numbers. Gut microbiotas are under increasing research interest for their potential contribution to CRC evolution, and changes in the gut microbiome have been reported from analyses of adenomas. Given that early changes to molecular components of bowel polyps may have a direct impact on cancer development and/or act as indicators of early disease, we review the molecular landscape of colorectal polyps, with an emphasis on immunological and microbial alterations occurring in the gut and propose the potential clinical utility of these data.

Molecular Features of Lymph Node Metastasis in T1/2 Colorectal Cancer from Formalin-Fixed Paraffin-Embedded Archival Specimens.

Histological risk factors for lymph node metastasis (LNM) in early-stage colorectal cancers (CRC) have been described, although the predictive utility of these factors varies. Improved LNM risk assessment based on findings in endoscopic colon and rectal excisions is necessary for optimal surgical management of CRC patients with pathologic T1- /T2-staged invasive depth (i.e., tumor not invading beyond the muscularis propria layer); as the current system is overly conservative, and results in many unnecessary radical surgeries. To identify molecular features in early CRC with elevated LNM potential, we carried out proteomic and gene expression profiling to compare T1 lymph node (LN) negative with T1/2 LN positive CRC tumors from formalin-fixed paraffin-embedded (FFPE) specimens. Using a data-independent acquisition mass spectrometry workflow, we detected over 7400 proteins and quantified over 4400 in all 21 specimens. Proteins from tumors with LN metastasis were enriched with effectors of epithelial-mesenchymal transition (EMT) and gene expression profiling confirmed activation of key transcription factors, SNAI1 and ZEB1, as well as a reduction in E-cadherin expression. Toward an implementation pathway, we investigated immunohistochemistry assays targeting four EMT-related proteins. While MS could reliably discern twofold protein abundance changes, we found the semiquantitative nature of IHC scoring limited confirmation of this degree of protein expression difference. This study demonstrated that EMT effectors are associated with locoregional metastasis in T1/T2 CRC and could be used to augment metastatic risk assessment, although further developments are required to enable routine implementation.

Frequency of equivocation in surgical meta-evidence: a review of systematic reviews within IBD literature.

OBJECTIVE: To assess the level of equivocation among level 1 evidence in ulcerative colitis and Crohn's disease and determine whether any predisposing factors are present. METHOD: MEDLINE, Embase, CINHAL and Cochrane were searched from 2006 to 2017. Papers were scored using AMSTAR and categorised into surgical (S), medical (M) or medical and surgical (MS) groups. The ability of each paper to make a recommendation and conclusiveness in doing so was recorded. RESULTS: 278 papers were assessed. 82% (n=227) could make a recommendation, 18% (n=51) could not. There was a significant difference in ability to provide a recommendation between S and M (P=0.003) but not MS and M (P=0.022) nor S and MS (P=0.79). Where a recommendation was made, S papers were more likely to be tempered than M papers (P=0.014) but not MS papers (P=0.987). CONCLUSIONS: Surgical meta-evidence within the inflammatory bowel disease domain is more than twice as likely as medical meta-evidence to be unable to provide a recommendation for clinical practice. Where a recommendation was made, surgical reviews were twice as likely to temper their conclusion.

The impact of open versus closed format ICU admission practices on the outcome of high risk surgical patients: a cohort analysis.

BACKGROUND: In the year 2000, the organizational structure of the ICU in the Zaandam Medical Centre (ZMC) changed from an open to a closed format ICU. The objective of this study was to evaluate the effect of this organizational change on outcome in high risk surgical patients. METHODS: The medical records of all consecutive high risk surgical patients admitted to the ICU from 1996 to 1998 (open format) and from 2003 to 2005 (closed format), were reviewed. High-risk patients were defined according to the Identification of Risk in Surgical patients (IRIS) score. Parameters studied were: mortality, morbidity, ICU length of stay (LOS) and hospital LOS. RESULTS: Mortality of ICU patients was 25.7% in the open format group and 15.8% in the closed format group (p = 0.01). Morbidity decreased from 48.6% to 46.1% (p = 0.6). The average length of hospital stay was 17 days in the open format group, and 21 days in the closed format group (p = 0.03). CONCLUSIONS: High risk surgical patients in the ICU are patients that have undergone complex and often extensive surgery. These patients are in need of specialized treatment and careful monitoring for maximum safety and optimal care. Our results suggest that closed format is a more favourable setting than open format to minimize the effects of high risk surgery, and to warrant safe outcome in this patient group.

POSSUM predicts hospital mortality and long-term survival in patients with hip fractures.

BACKGROUND: Each year, some 18,000 Dutch residents, most of them elderly, suffer a hip fracture. These patients constitute a major, and increasing, healthcare problem with high mortality. In an ageing population, not only the incidence of hip fractures will increase but also comorbidity. Comorbidity is a major cause of high mortality. The physiologic and operative severity score for the enumeration of mortality and morbidity (POSSUM) system predicts mortality and morbidity in surgical patients using physiologic and operative factors. METHODS: For 272 consecutive patients who were treated in our hospital for hip fractures, all complications were registered, and orthopedic POSSUM was performed. Total survival was registered with a mean follow-up of 58 months. Discriminating performance of POSSUM was estimated using receiver-operating curves. After validation, patients were divided into three equal large groups, termed low-risk group, intermediate-risk group, and high-risk group. Kaplan-Meier survival curves were made of each group. RESULTS: Orthopedic POSSUM performed well in predicting mortality with an area under the curve of 0.83 (95% confidence interval 0.76-0.89) and morbidity with an area under the curve of 0.83 (95% confidence interval 0.76-0.90). Three groups that composed of 92 (low risk), 93 (intermediate risk), and 87 (high risk) patients differed significantly in inhospital mortality, all complications, severe complications, and total survival. CONCLUSION: This study has shown that the orthopedic POSSUM is an excellent predictor of inhospital mortality and long-term survival in patients suffering from hip fractures. It is a reasonable predictor of severe postoperative complications. The orthopedic POSSUM is a useful risk stratification and audit tool.

Laparoscopy in combination with fast track multimodal management is the best perioperative strategy in patients undergoing colonic surgery: a randomized clinical trial (LAFA-study).

OBJECTIVE: To investigate which perioperative treatment, ie, laparoscopic or open surgery combined with fast track (FT) or standard care, is the optimal approach for patients undergoing segmental resection for colon cancer. SUMMARY BACKGROUND DATA: Important developments in elective colorectal surgery are the introduction of laparoscopy and implementation of FT care, both focusing on faster recovery. METHODS: In a 9-center trial, patients eligible for segmental colectomy were randomized to laparoscopic or open colectomy, and to FT or standard care, resulting in 4 treatment groups. Primary outcome was total postoperative hospital stay (THS). Secondary outcomes were postoperative hospital stay (PHS), morbidity, reoperation rate, readmission rate, in-hospital mortality, quality of life at 2 and 4 weeks, patient satisfaction and in-hospital costs. Four hundred patients were required to find a minimum difference of 1 day in hospital stay. RESULTS: Median THS in the laparoscopic/FT group was 5 (interquar-tile range: 4-8) days; open/FT 7 (5-11) days; laparoscopic/standard 6 (4.5-9.5) days, and open/standard 7 (6-13) days (P < 0.001). Median PHS in the laparoscopic/FT group was 5 (4-7) days; open/FT 6 (4.5-10) days; laparoscopic/standard 6 (4-8.5) days and open/standard 7 (6-10.5) days (P < 0.001). Secondary outcomes did not differ significantly among the groups. Regression analysis showed that laparoscopy was the only independent predictive factor to reduce hospital stay and morbidity. CONCLUSIONS: Optimal perioperative treatment for patients requiring segmental colectomy for colon cancer is laparoscopic resection embedded in a FT program. If open surgery is applied, it is preferentially done in FT care. This study was registered under NTR222 (www.trialregister.nl).

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitis and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitis in perforated diverticulitis (NTR2037).

BACKGROUND: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy.The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). METHODS/DESIGN: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and power = 90%) in favour of the patients with resection with primary anastomosis. Secondary endpoints for both arms are the number of days alive and outside the hospital, health related quality of life, health care utilisation and associated costs. DISCUSSION: The Ladies trial is a nationwide multicentre randomised trial on perforated diverticulitis that will provide evidence on the merits of laparoscopic lavage and drainage for purulent generalised peritonitis and on the optimal resectional strategy for both purulent and faecal generalised peritonitis. TRIAL REGISTRATION: Nederlands Trial Register NTR2037.

Candidate driver genes in focal chromosomal aberrations of stage II colon cancer.

Chromosomal instable colorectal cancer is marked by specific large chromosomal copy number aberrations. Recently, focal aberrations of 3 Mb or smaller have been identified as a common phenomenon in cancer. Inherent to their limited size, these aberrations harbour one or few genes. The aim of this study was to identify recurrent focal chromosomal aberrations and their candidate driver genes in a well-defined series of stage II colon cancers and assess their potential clinical relevance. High-resolution DNA copy number profiles were obtained from 38 formalin-fixed, paraffin-embedded colon cancer samples with matched normal mucosa as a reference using array comparative genomic hybridization. In total, 81 focal chromosomal aberrations were identified that harboured 177 genes. Statistical validation of focal aberrations and identification of candidate driver genes were performed by enrichment analysis and mapping copy number and mutation data of colorectal, breast, and pancreatic cancer and glioblastomas to loci of focal aberrations in stage II colon cancer. This analysis demonstrated a significant overlap with previously identified focal amplifications in colorectal cancer, but not with cancers from other sites. In contrast, focal deletions seemed less tumour type-specific since they also showed significant overlap with focal deletions of other sites. Focal deletions detected were significantly enriched for cancer genes and genes frequently mutated in colorectal cancer. The mRNA expression of these genes was significantly correlated with DNA copy number status, supporting the relevance of focal aberrations. Loss of 5q34 and gain of 13q22.1 were identified as independent prognostic factors of survival in this series of patients. In conclusion, focal chromosomal copy number aberrations in stage II colon cancer are enriched in cancer genes that contribute to and drive the process of colorectal cancer development. DNA copy number status of these genes correlates with mRNA expression and some are associated with clinical outcome.

Laparoscopic sigmoid resection for diverticulitis decreases major morbidity rates: a randomized control trial: short-term results of the Sigma Trial.

BACKGROUND: No randomized controlled trial has compared laparoscopic sigmoid resection (LSR) to open sigmoid resection (OSR) for symptomatic diverticulitis of the sigmoid colon. This study tested the hypothesis that LSR is associated with decreased postoperative complication rates as compared with OSR. METHODS: This was a prospective, multicenter, double-blind, parallel-arm, randomized controlled trial. Eligible patients were randomized to either LSR or OSR. Endpoints included postoperative mortality, and complications were classified as major and minor. The generator of the allocation sequence was separated from the executor. Blinding was ensured using an opaque wound dressing to cover the abdomen. Symptomatic diverticulitis of the sigmoid colon was defined as recurrent disease Hinchey I, IIa, IIb, symptomatic stricture, or severe rectal bleeding. The decision to discharge patients was made by independent physicians blind to the allocation sequence. Data were analyzed according to the intention to treat principle. RESULTS: From 2002 to 2006, 104 patients were randomized in 5 centers. All patients underwent the allocated intervention. Fifty-two LSR patients were comparable to 52 OSR patients for gender, age, BMI, ASA grade, comorbid conditions, previous abdominal surgery, and indication for surgery. LSR took longer (P = 0.0001) but caused less blood loss (P = 0.033). Conversion rate was 19.2%. Mortality rate was 1%. There were significantly more major complications in OSR patients (9.6% vs. 25.0%; P = 0.038). Minor complication rates were similar (LSR 36.5% vs. OSR 38.5%; P = 0.839). LSR patients had less pain (Visual Analog Scale 1.6; P = 0.0003), systemic analgesia requirement (P = 0.029), and returned home earlier (P = 0.046). The short form-36 questionnaire showed significantly better quality of life for LSR. CONCLUSIONS: LSR was associated with a 15.4% reduction in major complication rates, less pain, improved quality of life, and shorter hospitalization at the cost of a longer operating time.

Comparison of outcome of POSSUM, p-POSSUM, and cr-POSSUM scoring after elective resection of the sigmoid colon for carcinoma or complicated diverticular disease.

OBJECTIVE: To compare POSSUM, p-POSSUM, and cr-POSSUM-predicted mortalities with the observed postoperative mortality in patients undergoing elective sigmoid colectomy for diverticular disease (n=121) or carcinoma (n=120). MATERIAL AND METHODS: The physiologic and operative severity score for the enumeration of mortality and morbidity (POSSUM) was used to identify patient- or disease-related risk factors and to calculate expected mortalities. RESULTS: Patients with carcinoma had significantly higher POSSUM scores, but the observed mortality (1.7%) was lower than that in the diverticular disease group (3.3%). In the carcinoma group, mortality was over-predicted by all the POSSUM systems. In diverticular disease, POSSUM over-predicted mortality while p-POSSUM and cr-POSSUM under-predicted mortality. In the whole group, POSSUM over-predicted mortality. P-POSSUM and cr-POSSUM predicted mortality accurately: observed:expected (O:E) ratio 0.83. Replacing the score for malignancy with a minimum score of 1 gave overall O:E ratios of 0.37 (POSSUM), 1.04 (p-POSSUM), and 0.93 (cr-POSSUM). CONCLUSIONS: In a group of patients who underwent elective resection of the sigmoid colon for carcinoma or diverticular disease, postoperative mortality was predicted accurately by p-Possum and cr-POSSUM, especially when used without a score for malignancy. None of the POSSUM scores were predictive of disease-specific mortality.

Clinical presentation of fecal incontinence and anorectal function: what is the relationship?

OBJECTIVES: Fecal incontinence is classified into various types: passive, urge, and combined. Its clinical presentation is thought to be related to the underlying physiological or anatomical abnormality. The aim of the present study was to evaluate the associations between the frequency of clinical symptoms and anatomic and functional characteristics of the anorectum of patients with severe fecal incontinence. METHODS: Associations were explored in a consecutive series of 162 patients (91% women, mean age 59 [SD +/- 12] yr) with a mean Vaizey incontinence score of 18 (SD +/- 3). RESULTS: Urge incontinence was reported as "daily" by 55%, "often" by 27%, and "sometimes" by 7% of all patients. No significant associations were observed between the frequency of urge incontinence and either manometric data, anal mucosal sensitivity testing, or defects of internal anal sphincter (IAS) or external anal sphincter (EAS). A significant relation was observed between the frequency of urge incontinence and maximal tolerable volume (P= 0.03) and atrophy of the EAS (P= 0.05). Passive incontinence was reported as "daily" by 14%, "often" by 30%, and "sometimes" by 14% of all patients. Resting and maximal squeeze pressure were both associated (P < 0.001) with the frequency of passive incontinence. No relationship could be detected between clinical presentation and rectal sensation, anal mucosal sensitivity, defects, or atrophy of IAS or EAS. CONCLUSION: Most patients reported combined incontinence (59%) and underlying pathophysiologic abnormalities were identified. The hypothesized associations between urge and passive incontinence and functional and anatomical impairment of the anorectum are less clear-cut than previously assumed. Patients presenting with fecal incontinence should undergo physiologic investigation.

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial).

BACKGROUND: Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. METHODS/DESIGN: The LAFA-trial is a double blinded, multicenter trial with a 2 x 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. DISCUSSION: The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease.

Relationship between external anal sphincter atrophy at endoanal magnetic resonance imaging and clinical, functional, and anatomic characteristics in patients with fecal incontinence.

PURPOSE: External anal sphincter atrophy at endoanal magnetic resonance imaging has been associated with poor outcome of anal sphincter repair. We studied the relationship between external anal sphincter atrophy on endoanal magnetic resonance imaging and clinical, functional, and anatomic characteristics in patients with fecal incontinence. METHODS: In 200 patients (mean Vaizey score, 18 (+/-2.9 standard deviation)) magnetic resonance images were evaluated for external anal sphincter atrophy (none, mild, or severe) by radiologists blinded to anorectal functional test results and details from medical history. Subgroups of patients with and without atrophy were compared for medical history, anal manometry, pudendal nerve latency testing, anal sensitivity testing, external anal sphincter thickness, and external anal sphincter defects. Whenever significant differences were detected, we tested for differences between patients with mild and severe atrophy. RESULTS: External anal sphincter atrophy was demonstrated in 123 patients (62 percent): graded as mild in 79 (40 percent), and severe in 44 patients (22 percent). Patients with atrophy were more often female (P < 0.001) and older (P = 0.003). They had a lower maximal squeeze (P = 0.01) and squeeze increment pressure (P < 0.001). Patients with severe atrophy had a lower maximal squeeze (P = 0.003) and squeeze increment pressure (P < 0.001) than patients with mild atrophy. These effects were not attenuated by potential confounding variables. Patients with atrophy could not be identified a priori by other characteristics. CONCLUSIONS: External anal sphincter atrophy at endoanal magnetic resonance imaging was depicted in 62 percent of patients, varying from mild to severe. Because increasing levels of atrophy were associated with impaired squeeze function, further studies are needed to evaluate whether grading atrophy is clinically valuable in selecting patients for anal sphincter repair.

POSSUM predicts decreased overall survival in curative resection for colorectal cancer.

PURPOSE: Poor condition at operation determined by the physiologic POSSUM score is related to postoperative mortality and morbidity of colorectal cancer surgery. This study was designed to analyze the relationship between condition of patients with colorectal cancer at operation and long-term overall survival. METHODS: A total of 542 patients survived a radical resection for Stages I, II, or III colorectal cancer. Physiologic POSSUM score at surgery, exclusive of age, was calculated for all patients. Mean physiologic POSSUM score was used as cutoff point to determine low-risk and high-risk group patients. A Cox proportional hazard analysis was performed to study the effect of low-risk and high-risk group on overall survival and to identify independent risk factors. RESULTS: Five-year overall survival was significantly higher in low-risk group patients than in high-risk group patients (low-risk group 66.6 percent vs. high-risk group 48.5 percent; P < 0.001). Differences in overall survival also were found when patients in Stages I, II, and III were analyzed separately. Risk factors for overall survival were advanced stage of disease, poor tumor differentiation, mucinous adenocarcinoma, older than age 70 years, and poor condition of the patient at time of operation. CONCLUSIONS: Poor condition at operation, as determined by physiologic POSSUM score, is a risk indicator for long-term overall survival in colorectal cancer patients.