Cluster-randomized crossover trial of chlorhexidine-alcohol versus iodine-alcohol for prevention of surgical-site infection (SKINFECT trial).

Background: Surgical-site infection (SSI) is a serious surgical complication that can be prevented by preoperative skin disinfection. In Western European countries, preoperative disinfection is commonly performed with either chlorhexidine or iodine in an alcohol-based solution. This study aimed to investigate whether there is superiority of chlorhexidine-alcohol over iodine-alcohol for preventing SSI. Methods: This prospective cluster-randomized crossover trial was conducted in five teaching hospitals. All patients who underwent breast, vascular, colorectal, gallbladder or orthopaedic surgery between July 2013 and June 2015 were included. SSI data were reported routinely to the Dutch National Nosocomial Surveillance Network (PREZIES). Participating hospitals were assigned randomly to perform preoperative skin disinfection using either chlorhexidine-alcohol (0·5 per cent/70 per cent) or iodine-alcohol (1 per cent/70 per cent) for the first 3 months of the study; every 3 months thereafter, they switched to using the other antiseptic agent, for a total of 2 years. The primary endpoint was the development of SSI. Results: A total of 3665 patients were included; 1835 and 1830 of these patients received preoperative skin disinfection with chlorhexidine-alcohol or iodine-alcohol respectively. The overall incidence of SSI was 3·8 per cent among patients in the chlorhexidine-alcohol group and 4·0 per cent among those in the iodine-alcohol group (odds ratio 0·96, 95 per cent c.i. 0·69 to 1·35). Conclusion: Preoperative skin disinfection with chlorhexidine-alcohol is similar to that for iodine-alcohol with respect to reducing the risk of developing an SSI.

Antecedentes: La infección del sitio quirúrgico (surgical site infection, SSI) es una complicación quirúrgica grave que se puede prevenir mediante una desinfección cutánea preoperatoria. En los países de Europa occidental, la desinfección preoperatoria se realiza habitualmente usando clorhexidina o yodo en una solución a base de alcohol. Nuestro objetivo fue investigar si la clorhexidina alcohólica es superior al yodo con alcohol para prevenir la SSI. Métodos: Este ensayo prospectivo aleatorizado por conglomerados y de grupos cruzados se realizó en cinco hospitales docentes. Se incluyeron todos los pacientes que se sometieron a cirugía mamaria, vascular, colorrectal, biliar y ortopédica entre julio de 2013 y junio de 2015. Los datos de SSI se presentaron de manera rutinaria a la Red Nacional Holandesa de Vigilancia Nosocomial (PREZIES). Los hospitales participantes fueron asignados al azar para realizar una desinfección cutánea preoperatoria con clorhexidina alcohólica (0,5%/70%) o yodo con alcohol (1%/70%) durante los primeros tres meses del estudio; cada 3 meses a partir de entonces, cambiaron a usar el otro agente antiséptico, durante un total de 2 años. El criterio de valoración principal fue el desarrollo de SSI. Resultados: Se incluyeron un total de 3.665 pacientes; 1.835 y 1.830 de estos pacientes recibieron desinfección cutánea preoperatoria con clorhexidina alcohólica o yodo con alcohol, respectivamente. La incidencia global de SSI fue del 3,8% entre los pacientes en el grupo de clorhexidina alcohólica y del 4,0% entre los pacientes en el grupo de yodo con alcohol (razón de oportunidades, odds ratio, OR 0,96; i.c. del 95%: 0,69­1,35). Conclusión: La desinfección cutánea preoperatoria con clorhexidina alcohólica es similar al yodo con alcohol con respecto a la reducción del riesgo de desarrollar una SSI.

Nomograms to predict survival and the risk for developing local or distant recurrence in patients with rectal cancer treated with optional short-term radiotherapy.

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

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.

BACKGROUND: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). PATIENTS AND METHODS: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. RESULTS: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). CONCLUSION: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. REGISTRATION NUMBER: Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.

Differences in pre-operative treatment for rectal cancer between Norway, Sweden, Denmark, Belgium and the Netherlands.

Several studies have shown remarkable differences in colorectal cancer survival across Europe. Most of these studies lacked information about stage and treatment. In this study we compared short-term survival as well as differences in tumour stage and treatment strategies between five European countries: Norway, Sweden, Denmark, Belgium, and the Netherlands. For this retrospective cohort study all patients aged 18 years or older and operated on adenocarcinoma of the rectum without distant metastases and diagnosed in 2008 and 2009 were selected in national audit registries from Norway, Sweden, Denmark, Belgium, and the Netherlands. Differences in pre-operative treatment between the countries were compared using univariable and multivariable logistic regression. One year relative survival and one year relative excess risk of death (RER) were compared between the five countries. Large variation in the use of preoperative radiotherapy and chemoradiation was found between the countries. Even though, there was little variation in relative survival between the countries, except Sweden, which had a significant better one year RER of death among the elderly patients after adjustment. The differences in survival are expected to be caused by differences in peri-operative care, selection of patients, and especially management of elderly patients. The effects of preoperative treatment are expected to be seen on long term follow-up.

Unexpected rectal cancer after TEM: outcome of completion surgery compared with primary TME.

BACKGROUND: Transanal endoscopic microsurgery (TEM) has gained wide-spread acceptance as a safe and useful technique for the resection of rectal adenomas and selected T1 malignant lesions. If the lesion appears >T1 rectal cancer after resection with TEM, a completion TME resection is recommended. The aim of this study was to investigate the results of TME surgery after TEM for rectal cancer. METHODS: In four tertiary referral hospitals for TEM, all patients with completion TME surgery after initial TEM were selected. All eligible patients who were treated with 5 × 5 Gy radiotherapy followed by TME surgery from the Dutch TME trial were selected as reference group. A multivariate logistic regression model was used to calculate odds ratio's (OR) for colostomies and for colo- and ileostomies combined. Local recurrence and survival rates were compared in hazard ratio's (HR) using the multivariate Cox proportional hazard model. RESULTS: Fifty-nine patients were included in the TEM-COMPLETION group and 881 patients from the TME trial. In the TEM-COMPLETION group, 50.8% of the patients had a colostomy compared to 45.9% in the TME trial, OR 2.51 (p < 0.006). There is no significant difference when ileo- and colostomies are analyzed together. In the TEM-COMPLETION group, 10.2% developed a local recurrence compared to 5.2% in the TME trial, HR 6.8 (p < 0.0001). CONCLUSIONS: Completion TME surgery after TEM for unexpected rectal adenocarcinoma results in more colostomies and higher local recurrence rates compared to one stage TME surgery preceded with preoperative 5 × 5 Gy radiotherapy. Pre-operative investigations must be optimized to distinguish malignant and benign lesions and prevent avoidable local recurrence and colostomies.

The EURECCA project: Data items scored by European colorectal cancer audit registries.

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

Systematic review and meta-analysis of the volume-outcome relationship in pancreatic surgery.

BACKGROUND: Many studies have shown lower mortality and higher survival rates after pancreatic surgery with high-volume providers, suggesting that centralization of pancreatic surgery can improve outcomes. The methodological quality of these studies is open to question. This study involves a systematic review of the volume-outcome relationship for pancreatic surgery with a meta-analysis of studies considered to be of good quality. METHODS: A systematic search of electronic databases up to February 2010 was performed to identify all primary studies examining the effects of hospital or surgeon volume on postoperative mortality and survival after pancreatic surgery. All articles were critically appraised with regard to methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random-effects model was done to estimate the effect of higher surgeon or hospital volume on patient outcome. RESULTS: Fourteen studies were included in the meta-analysis. The results showed a significant association between hospital volume and postoperative mortality (odds ratio 0.32, 95 per cent confidence interval 0.16 to 0.64), and between hospital volume and survival (hazard ratio 0.79, 0.70 to 0.89).The effect of surgeon volume on postoperative mortality was not significant (odds ratio 0.46, 0.17 to 1.26). Significant heterogeneity was seen in the analysis of hospital volume and mortality. Sensitivity analysis showed no correlation with the extent of risk adjustment or study country; after removing one outlier study, the result was homogeneous. The data did not suggest publication bias. CONCLUSION: There was a consistent association between high hospital volume and lower postoperative mortality rates with improved long-term survival.

2010 SSO John Wayne clinical research lecture: rectal cancer outcome improvements in Europe: population-based outcome registrations will conquer the world.

During the past two decades, rectal cancer treatment has improved considerably in Europe. Clinical trials played a crucial role in improving surgical techniques, (neo)adjuvant treatment schedules, imaging, and pathology. However, there is still a wide variation in outcome after rectal cancer. In most western health care systems, efforts are made to reduce hospital variation by focusing on selective referral and encouraging patients to seek care in high-volume hospitals. On the other hand, the expertise for diagnosis and treatment of common types of cancer should be preferably widespread and easily accessible for all patients. As an alternative to volume-based referral, hospitals and surgeons can improve their results by learning from their own outcome statistics and those from colleagues treating a similar patient group. Several European surgical (colo)rectal audits have led to improvements with a greater impact than any of the adjuvant therapies currently under study. However, differences remain between European countries, which cannot be easily explained. To generate the best care for colorectal cancer in the whole of Europe and to meet political and public demands for transparency, the European CanCer Organisation (ECCO) initiated an international, multidisciplinary, outcome-based quality improvement program: European Registration of Cancer Care (EURECCA). The goal is to create a multidisciplinary European registration structure for patient, tumor, and treatment characteristics linked to outcome registration. Clinical trials will always play a major role in improving rectal cancer treatment. To further improve outcomes and diminish variation, EURECCA will establish the basis for a strong, multidisciplinary, international audit structure that can be used as a template for similar projects worldwide.

Quality assurance through outcome registration in colorectal cancer: an ECCO initiative for Europe.

In recent years there have been significant improvements in outcome of rectal cancer treatment. Both new surgical techniques as well as effective neoadjuvant treatment regimens have contributed to these improvements. It is key to spread these advances towards every rectal cancer patient and to make sure that not only patients who are treated within the framework of clinical trials may benefit from these advancements. Throughout Europe there have been interesting quality programs that have proved to facilitate the spread of up to date knowledge and skills among medical professionals resulting in improved treatment outcome. Nevertheless, between European countries remain differences in outcome and treatment schedules that cannot be easily explained. The European CanCer Organisation (ECCO) has recognised these importances's and created the 'European Registration of Cancer Care' (EURECCA) framework to develop a European colorectal audit structure. EURECCA will advance future treatment improvements and spread these to all European cancer patients. It provides opportunities to treat elderly and comorbid patients evidence based while it offers an unique insight in social-economical healthcare matters. As such, ECCO has established the basis for a strong, multidisciplinary audit structure with the commitment to improve cancer care for every European cancer patient.

A systematic review and meta-analysis of the volume-outcome relationship in the surgical treatment of breast cancer. Are breast cancer patients better of with a high volume provider?

AIMS: To conduct a systematic review of the literature on the volume-outcome relationship for the surgical treatment of breast cancer with consideration of the methodological quality of the available evidence and to perform a meta-analysis on the studies of considered good quality. METHODS: A systematic search was done to identify all articles examining the effects of hospital or surgeon volume on clinical outcome of the surgical treatment of breast cancer. Reviews, opinion articles and surveys were excluded. All articles were critically appraised on methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random effects model was done to estimate the effect of higher hospital or surgeon volume on patient outcome. RESULTS: We found 12 studies of good methodological quality which could be included for meta-analysis. The results showed a significant association between high volume providers and an improved survival. The association is the most robust for surgeon volume (HR 0.80 (0.71-0.90) and RR 0.85 (0.80-0.90). In addition there is an effect of hospital volume on the in-hospital mortality, although the mortality was very low (0.1-0.2%). Results of meta-analysis were heterogeneous. Sensitivity analysis showed a larger effect size for studies also adjusting for comorbidity for both studies on hospital and surgeon volume. The data were not suggestive for publication bias. CONCLUSIONS: The results show that survival after breast cancer surgery is significantly associated with high volume providers.

Volume and outcome in colorectal cancer surgery.

AIMS: There is a growing consensus to concentrate high-risk surgical procedures to high volume surgeons in high volume hospitals. However, there is fierce debate about centralizing more common malignancies such as colorectal cancer. The objective of this review is to conduct a meta-analysis using the best evidence available on the volume-outcome relationship for colorectal cancer treatment. METHODS: A systematic search was performed to identify all relevant articles studying the relation between hospital and/or surgeon volume and clinical outcomes for colorectal cancer. Using strict inclusion criteria, 23 articles were selected concerning colon cancer, rectal cancer or both diseases together as 'colorectal cancer'. Pooled estimated effect sizes were calculated using the casemix adjusted outcomes of the highest volume group opposed to the lowest volume group. RESULTS: High volume hospitals have a significantly lower postoperative mortality in half of the pooled results. Non significant results show a trend in favour of high volume hospitals. All results showed a significantly better long term survival in high volume hospitals. High volume surgeons have a lower postoperative mortality, although evidence is sparse. All analyses showed a significantly better long term survival in favour of high volume surgeons. CONCLUSIONS: The results show a clear and consistent relation between high volume providers and improved long term survival. This applies to both high volume hospitals and high volume surgeons. Most results show a relation between high volume providers and a reduced postoperative mortality, but evidence is less convincing. In the ideal world, extensive population based audit registrations with casemix adjusted feedback should make rigid minimal volume standards obsolete. Until then, using volume criteria for hospitals and surgeons treating colorectal cancer can improve mortality and especially long term survival.

Improving quality of cancer care through surgical audit.

Quality of healthcare is a hot topic and this is especially true for cancer care. New surgical techniques and effective neoadjuvant treatment regimens have significantly improved colorectal cancer outcome. Nevertheless, there seem to be substantial differences in quality of care between European countries, hospitals and doctors. To reduce hospital variation, most initiatives aim on selective referral, encouraging patients to seek care in high-volume hospitals, where cancer care is concentrated to site-specialist multidisciplinary teams. As an alternative to volume-based referral, hospitals and surgeons can also improve their results by learning from their own outcome statistics and those from colleagues treating a similar patient group. European national audit registries in surgical oncology have led to improvements with a greater impact on survival than any of the adjuvant therapies currently under study. Moreover, they offer the possibility to perform research on patient groups that are usually excluded from clinical trials. Nevertheless, between European countries remain differences in outcome and treatment schedules that cannot be easily explained. The European CanCer Organisation (ECCO) has recognised these importances and created the 'European Registration of Cancer Care' (EURECCA) framework to develop a European colorectal audit structure. EURECCA will advance future treatment improvements and spread these to all European cancer patients. It provides opportunities to treat elderly and comorbid patients evidence based while it offers an unique insight in social-economical healthcare matters such as the consequences of commercialisation, treatment availability and screening initiatives. As such, ECCO has established the basis for a strong, multidisciplinary audit structure with the commitment to improve cancer care for every European cancer patient.

Quality assurance in rectal cancer treatment in the Netherlands: a catch up compared to colon cancer treatment.

BACKGROUND: In the Netherlands, the Total Mesorectal Excision (TME) surgical technique for rectal cancer was introduced together with pre-operative radiotherapy in a quality controlled manner within the framework of the TME trial (1996-1999). The aim of this study is to examine the effects of the structural changes in rectal cancer care on survival compared to colon cancer for patients treated before, during and after the TME trial. METHOD: We compared overall survival of all patients with curatively resected colon (n = 15,266) and rectal cancer (n = 5839) in the regions of Comprehensive Cancer Centres South and West between 1990 and 2005, adjusting for prognostic variables. RESULTS: In the pre-trial period, rectal cancer had a significant lower survival compared to colon cancer (HR 1.248, P < 0.01). However, in the post-trial period, survival after rectal cancer was similar to colon cancer (HR 0.987, n.s.). CONCLUSION: Although survival improved significantly for both colon and rectal cancer in the last 15 years, the substantially worse results after rectal cancer have been eliminated. This study shows the lasting effects that structural surgical training and quality assurance can have on survival outcome.