J.W.T. Dekker

Predicting the risk of anastomotic leakage in left-sided colorectal surgery using a colon leakage score.

BACKGROUND Anastomotic leakage following colorectal surgery still occurs all too frequently, and this complication is difficult to predict. A nonfunctional stoma may reduce the risk of clinically relevant leaks but is overtreatment for most patients. More accurate assessments of the risk of anastomotic leakage would be very helpful in tailoring treatment in colorectal surgery. Therefore, a Colon Leakage Score (CLS) was developed and tested. MATERIAL AND METHODS The CLS was developed based on information from the literature and expert opinions. It was tested in a retrospective cohort of consecutive patients undergoing left-sided colorectal surgery with primary anastomosis in a teaching hospital in The Netherlands. RESULTS In the test cohort, 10 of 121 patients who were not treated with a nonfunctional stoma experienced anastomotic leakage. The mean CLS in the leakage group was 16 versus eight in the group that did not have a leak (P < 0.01). Using receiver-operating characteristics, the area under the curve (AUC) showed that the CLS was a good predictor (AUC = 0.95, CI 0.89-1.00) of anastomotic leakage. Furthermore, logistic regression analysis with CLS as a predictor for anastomotic leakage showed an odds ratio of 1.74 (95% CI 1.32-2.28, P < 0.01). CONCLUSIONS The CLS can predict the risk of anastomotic leakage following left-sided colorectal surgery. After further validation, this score may help the surgeon make a more individualized, safer decision regarding whether to perform an anastomosis or make a (nonfunctional) stoma.

Metastatic lymph node ratio in stage III rectal cancer; prognostic significance in addition to the 7th edition of the TNM classification

AIMS Optimal staging in rectal cancer is indispensable for the decision on further treatment and estimation of prognosis. This study assesses the prognostic capacity of the metastatic lymph node ratio (LNR) in addition to the new TNM classification. METHODS LNR was determined, in stage III patients from the Dutch TME-trial. Six year median follow up data from the trial database were used to analyse the relation of LNR to overall survival (OS) and local recurrence (LR). The relation of LNR to lymph node yield was assessed and appropriate cut off values of LNR for clinical use were determined. RESULTS 605 patients were analyzed. 278 underwent pre-operative radiotherapy. 82 patients developed a local recurrence and 289 distant metastases. LNR was an independent risk factor for OS, hazard ratio (HR) 2.10 (95% CI 1.35-3.27) (in addition to age >= 65 years, involved circumferential resection margin (CRM) and new TNM stage) and LR, HR 2.25 (95% CI 1.02-4.56) (in addition to pre-operative radiotherapy and involved CRM). LNR is predictive of OS and LR from a lymph node yield of more than one and more than five respectively. A LNR value of 0.60 offers the best cut off to identify high risk patients (5-years OS was 61 vs. 32%, HR 2.45 (95% CI 1.96-3.08) and 5-years LR rate 12.6 versus 16.3%, HR 1.65 (95% CI 1.03-2.64)). CONCLUSIONS LNR is an independent risk factor for OS and LR in addition to the 7th edition of the TNM classification. It can aid in predicting prognosis and identifying patients that should be considered for adjuvant treatment.

Cause of death the first year after curative colorectal cancer surgery; a prolonged impact of the surgery in elderly colorectal cancer patients.

BACKGROUND The 1-year mortality after colorectal cancer surgery is high and explains age related differences in colorectal cancer survival. To gain better insight in its etiology, cause of death for these patients was studied. METHODS All 1924 patients who had a resection for stage I-III colorectal cancer from 2006 to 2008 in the Western region of the Netherlands were identified. Data were merged with cause of death data from the Central Bureau of Statistics Netherlands. To calculate excess mortality as compared to the general population, national data were used. RESULTS Overall 13.2% of patients died within the first postoperative year. One-year mortality increased with age. It was as high as 43% in elderly patients that underwent emergency surgery. In 75% of patients, death was attributed to the colorectal cancer. In 25% of all patients, registered deaths were attributed to postoperative complications. Elderly patients with comorbidity more frequently died due to complications (p < 0.01). Death of other causes was similar to background mortality according to age group. CONCLUSION In the presently studied cohort of patients that died within one year of surgery, cause of death was predominantly attributed to colorectal cancer. However, because it is not to be expected that in this cohort the number of deaths from recurrences is very high, the excess 1-year mortality indicates a prolonged impact of the surgery, especially in elderly patients. Therefore, in these patients we should focus on limiting the physiological impact of the surgery and be more involved in the post-hospital period.

An increasing use of defunctioning stomas after low anterior resection for rectal cancer. Is this the way to go

BACKGROUND The last decade there has been an increased awareness of the problem of anastomotic leakage after low anterior resection for rectal cancer, which may have led to more defunctioning stomas. In this study, current use of defunctioning stomas was assessed and compared to the use of defunctioning stomas at the time of the TME-trial together with associated outcomes. METHODS Eligible patients with rectal cancer undergoing low anterior resection were selected from the Dutch Surgical Colorectal Audit (DSCA, n = 988). Similar patients were selected from the TME-trial (n = 891). The percentages of patients with a defunctioning stoma, anastomotic leakage and postoperative mortality rates were studied. Multivariable models were used to study possible confounding on the outcomes. RESULTS At the time of the TME-trial, 57% of patients received a defunctioning stoma. At the time of the DSCA, 70% of all patients received a defunctioning stoma (p < 0.001). Anastomotic leakage rates were similar (11.4% and 12.1%; p = 0.640). The postoperative mortality rate differed (3.9% in the TME-trial vs. 1.1% in the DSCA; p < 0.001), but was not associated with a more frequent use of a stoma (OR 1.80, 95% CI 0.91-3.58). CONCLUSION In current surgical practice, 70% of patients undergoing LAR for rectal cancer receives a defunctioning stomas. This percentage seems increased when compared to data from the TME-trial. Clinically relevant anastomotic leakage rates remained similar. Therefore, current routine use of defunctioning stomas should be questioned.

Anastomotic leakage as an outcome measure for quality of colorectal cancer surgery

Introduction When comparing mortality rates between hospitals to explore hospital performance, there is an important role for adjustment for differences in case-mix. Identifying outcome measures that are less influenced by differences in case-mix may be valuable. The main goal of this study was to explore whether hospital differences in anastomotic leakage (AL) and postoperative mortality are due to differences in case-mix or to differences in treatment factors. Methods Data of the Dutch Surgical Colorectal Audit were used. Case-mix factors and treatment-related factors were identified from the literature and their association with AL and mortality were analysed with logistic regression. Hospital differences in observed AL and mortality rates, and adjusted rates based on the logistic regression models were shown. The reduction in hospital variance after adjustment was analysed with Levenes test for equality of variances. Results 17 of 22 case-mix factors and 4 of 11 treatment factors related to AL derived from the literature were available in the database. Variation in observed AL rates between hospitals was large with a maximum rate of 17%. This variation could not be attributed to differences in case-mix but more to differences in treatment factors. Hospital variation in observed mortality rates was significantly reduced after adjustment for differences in case-mix. Conclusions Hospital variation in AL is relatively independent of differences in case-mix. In contrast to ‘postoperative mortality’ the observed AL rates of hospitals evaluated in our study were only slightly affected after adjustment for case-mix factors. Therefore, AL rates may be suitable as an outcome indicator for measurement of surgical quality of care.

Time trends in chemotherapy (administration and costs) and relative survival in stage III colon cancer patients – a large population-based study from 1990 to 2008

Abstract Background. Use of adjuvant chemotherapy for stage III colon cancer has increased since several trials have shown the beneficial effect on survival. In this population-based study we show time trends in the administration and costs of chemotherapy and relative survival of patients with stage III colon cancer. Methods. All patients surgically treated for adenocarcinoma of the colon stage III between 1990 and 2008 in The Netherlands were included. Relative survival (using period analyses) and Relative Excess Risks of death (RER) were calculated. The costs of chemotherapy were estimated. Results. A total of 24 111 colon cancer patients with stage III were included in the cohort. The administration (from 9.5% in 1990 to 61.8% in 2008; p < 0.001) and costs of chemotherapy (from €38 467 in 1990 to €3 876 150 in 2008) increased during the study period. Multivariable relative survival improved for patients receiving adjuvant chemotherapy (RER 0.93; 95% CI 0.92–0.94; p < 0.001). In contrast, relative survival remained stable for patients, younger than 80 years, who did not receive chemotherapy (RER 1.00; 95% CI 1.00–1.01; p = 0.3). Patients aged 80 years and older without chemotherapy, relative survival increased during the study period (RER 0.98; 95% CI 0.97–0.99; p < 0.001). Conclusions. The administration, the costs of chemotherapy and the survival of patients with stage III colon cancer increased over time. Whereas the costs and administration of chemotherapy increased extensively, relative survival increased to a lesser extent. For patients treated with adjuvant chemotherapy relative survival increased equally in all age groups.

High complication rate after low anterior resection for mid and high rectal cancer; results of a population-based study

BACKGROUND Surgical resection is the cornerstone of treatment for rectal cancer patients. Treatment options consist of a primary anastomosis, anastomosis with defunctioning stoma or end-colostomy with closure of the distal rectal stump. This study aimed to compare postoperative outcome of these three surgical options. METHODS Data was derived from the national database of the Dutch Surgical Colorectal Audit. Mid and high rectal cancer patients who underwent rectal cancer resection between January 2011 and December 2012 were included. Endpoints were postoperative complications including anastomotic leakage, reinterventions, hospital stay and mortality within 30 days postoperative. RESULTS In total, 2585 patients were included. Twenty-five per cent of all patients received a primary anastomosis; 51% an anastomosis with defunctioning stoma, and 24% an end-colostomy. More than one third of patients developed postoperative complications, the lowest rate being in the primary anastomosis group. Anastomotic leakage rates were 12% in patients with a primary anastomosis, and 9% in patients with an anastomosis with defunctioning stoma (p < 0.05). Multivariate analysis showed more postoperative complications, prolonged hospital stay, and increased mortality rates in patients with a defunctioning stoma or end-colostomy. The latter had proportionally less invasive reinterventions when compared to the other two groups. CONCLUSIONS Patients with a primary anastomosis had the best postoperative outcome. A defunctioning stoma leads to a lower anastomotic leakage rate, though is associated with higher rates of complications, prolonged hospital stay and mortality. The decision to create a defunctioning stoma should be focus of future studies.

Combined analysis of biomarkers of proliferation and apoptosis in colon cancer: an immunohistochemistry-based study using tissue microarray

BackgroundDisturbance of the balance between proliferation and apoptosis is an important hallmark of tumor development. The goal of this study was to develop a descriptive parameter that represents this imbalance and relate this parameter to clinical outcome in all four stages of colon cancer.Material and methodsThe study population consisted of 285 stage I–IV colon cancer patients of which a tumor tissue microarray (TMA) was available. TMA sections were immunohistochemically stained and quantified for the presence of Ki67 and cleaved caspase-3 tumor expression. These results were used to develop the combined apoptosis proliferation (CAP) parameter and correlated to patient outcome.ResultsThe CAP parameter was significantly related to clinical outcome; patients with CAP ++ (high level of both apoptosis and proliferation) showed the best outcome perspectives (overall survival (OS), p = 0.004 and disease-free survival (DFS), p = 0.009). The effect of the CAP parameter was related to tumor microsatellite status and indirectly to tumor location, where left-sided tumors with CAP + − (high level of proliferation, low level of apoptosis) showed a worse prognosis (DFS p value 0.02) and right-sided tumors with CAP + − had a better prognosis (DFS p value 0.032). With stratified analyses, the CAP parameter remained significant in stage II tumors only.ConclusionsThe CAP parameter, representing outcome of the balance between the level of apoptosis and proliferation, can be used as a prognostic marker in colon cancer patients for both DFS and OS, particularly in left-sided, microsatellite stable tumors when tumor–node–metastasis (TNM) stage is taken into account.