Evolution of clinical nature, treatment and survival of locally recurrent rectal cancer: Comparative analysis of two national cross-sectional cohorts.

BACKGROUND: In the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. METHODS: Patients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. RESULTS: Use of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). CONCLUSION: Primary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially.

Colorectal anastomotic leak: transcriptomic profile analysis.

BACKGROUND: Anastomotic leakage in patients undergoing colorectal surgery is associated with morbidity and mortality. Although multiple risk factors have been identified, the underlying mechanisms are mainly unknown. The aim of this study was to perform a transcriptome analysis of genes underlying the development of anastomotic leakage. METHODS: A set of human samples from the anastomotic site collected during stapled colorectal anastomosis were used in the study. Transcriptomic profiles were generated for patients who developing anastomotic leakage and case-matched controls with normal anastomotic healing to identify genes and biological processes associated with the development of anastomotic leakage. RESULTS: The analysis included 22 patients with and 69 without anastomotic leakage. Differential expression analysis showed that 44 genes had adjusted P < 0.050, consisting of two upregulated and 42 downregulated genes. Co-functionality analysis of the 150 most upregulated and 150 most downregulated genes using the GenetICA framework showed formation of clusters of genes with different enrichment for biological pathways. The enriched pathways for the downregulated genes are involved in immune response, angiogenesis, protein metabolism, and collagen cross-linking. The enriched pathways for upregulated genes are involved in cell division. CONCLUSION: These data indicate that patients who develop anastomotic leakage start the healing process with an error at the level of gene regulation at the time of surgery. Despite normal macroscopic appearance during surgery, the transcriptome data identified several differences in gene expression between patients who developed anastomotic leakage and those who did not. The expressed genes and enriched processes are involved in the different stages of wound healing. These provide therapeutic and diagnostic targets for patients at risk of anastomotic leakage.

A low incidence of perineal hernia when using a biological mesh after extralevator abdominoperineal excision with or without pelvic exenteration or distal sacral resection in locally advanced rectal cancer patients.

BACKGROUND: Extralevator abdominoperineal excision (ELAPE), abdominoperineal excision (APE) or pelvic exenteration (PE) with or without sacral resection (SR) for locally advanced rectal cancer leaves a significant defect in the pelvic floor. At first, this defect was closed primarily. To prevent perineal hernias, the use of a biological mesh to restore the pelvic floor has been increasing. The aim of this study, was to evaluate the outcome of the use of a biological mesh after ELAPE, APE or PE with/without SR. METHODS: A retrospective study was conducted on patients who had ELAPE, APE or PE with/without SR with a biological mesh (Permacol™) for pelvic reconstruction in rectal cancer in our center between January 2012 and April 2015. The endpoints were the incidence of perineal herniation and wound healing complications. RESULTS: Data of 35 consecutive patients [22 men, 13 women; mean age 62 years (range 31-77 years)] were reviewed. Median follow-up was 24 months (range 0.4-64 months). Perineal hernia was reported in 3 patients (8.6%), and was asymptomatic in 2 of them. The perineal wound healed within 3 months in 37.1% (n = 13), within 6 months in 51.4% (n = 18) and within 1 year in 62.9% (n = 22). In 17.1% (n = 6), the wound healed after 1 year. It was not possible to confirm perineal wound healing in the remaining 7 patients (20.0%) due to death or loss to follow-up. Wound dehiscence was reported in 18 patients (51.4%), 9 of whom needed vacuum-assisted closure therapy, surgical closure or a flap reconstruction. CONCLUSIONS: Closure of the perineal wound after (EL)APE with a biological mesh is associated with a low incidence of perineal hernia. Wound healing complications in this high-risk group of patients are comparable to those reported in the literature.

Multicentre study of short-course radiotherapy, systemic therapy and resection/ablation for stage IV rectal cancer.

BACKGROUND: The optimal treatment sequence for patients with rectal cancer and synchronous liver metastases remains unclear. The aim of this study was to evaluate the feasibility and effectiveness of short-course pelvic radiotherapy (5 × 5 Gy) followed by systemic therapy and local treatment of all tumour sites in patients with potentially curable stage IV rectal cancer in daily practice. METHODS: This was a retrospective study performed in eight tertiary referral centres in the Netherlands. Patients aged 18 years or above with rectal cancer and potentially resectable liver ± extrahepatic metastases, treated between 2010 and 2015, were eligible. Main outcomes included full completion of treatment schedule, symptom control and survival. RESULTS: In total, 169 patients were included with a median follow-up of 49·5 (95 pr cent c.i. 43·6 to 55·6) months. The completion rate for the entire treatment schedule was 65·7 per cent. Three-year progression-free survival and overall survival (OS) rates were 24·2 (95 per cent c.i. 16·6 to 31·6) and 48·8 (40·4 to 57·2) per cent respectively. Median OS of patients who responded well and completed the treatment schedule was 51·5 months, compared with 15·1 months for patients who did not complete the treatment (P < 0·001). Adequate symptom control of the primary tumour was achieved in 87·0 per cent of all patients. CONCLUSION: Multimodal treatment leads to relief of symptoms in most patients, and is associated with good survival rates in those able to complete the schedule. [Correction added on 12 February 2020, after first online publication: the Conclusion has been reworded for clarity].

ANTECEDENTES: La secuencia óptima de tratamiento en pacientes con cáncer de recto y metástasis hepáticas sincrónicas sigue sin estar clara. El objetivo de este estudio fue evaluar en la práctica diaria la viabilidad y efectividad de la radioterapia pélvica de ciclo corto (5 x 5 Gy) seguida de tratamiento sistémico y tratamiento local de todas las localizaciones del tumor primario en pacientes con cáncer de recto estadio IV potencialmente curables. MÉTODOS: Estudio retrospectivo realizado en ocho centros terciarios de referencia en Holanda. Se consideró elegibles a los pacientes mayores de 18 años con cáncer de recto y metástasis hepáticas ± extrahepáticas potencialmente resecables, que fueron tratados entre 2010 y 2015. Los criterios de valoración principales incluyeron la finalización completa del programa de tratamiento, el control de los síntomas y la supervivencia. RESULTADOS: En total se incluyeron 169 pacientes con una mediana de seguimiento de 50 meses (rango 2-89 meses). La tasa de finalización del programa de tratamiento completo fue del 65,7%. Las tasas de supervivencia libre de progresión a 3 años y supervivencia global (overall survival, OS) fueron 24,2% (i.c. del 95% 16,6-31,6) y 48,8% (i.c. del 95% 40,4-57,2), respectivamente. La mediana de OS de los pacientes que respondieron bien y completaron el programa de tratamiento fue de 51,5 meses, en comparación con 15,1 meses en pacientes que no completaron el tratamiento (P < 0,001). Se logró un control adecuado de los síntomas del tumor primario en el 87,0% de todos los pacientes. CONCLUSIÓN: El tratamiento multimodal consigue paliar los síntomas en la mayoría de los pacientes y se asocia con buenas tasas de supervivencia en aquellos pacientes que pueden completar el programa.

Correspondence between primary and secondary care about patients with cancer: a Delphi consensus study.

INTRODUCTION: To provide optimal care for patients with cancer, timely and efficient communication between healthcare providers is essential. In this study, we aimed to achieve consensus regarding the desired content of communication between general practitioners (GPs) and oncology specialists before and during the initial treatment of cancer. METHODS: In a two-round Delphi procedure, three expert panels reviewed items recommended for inclusion on referral and specialist letters. RESULTS: The three panels comprised 39 GPs (42%), 42 oncology specialists (41%) (i.e. oncologists, radiotherapists, urologists and surgeons) and 18 patients or patient representatives (69%). Final agreement was by consensus, with 12 and 35 items included in the GP referral and the specialist letters, respectively. The key requirements of GP referral letters were that they should be limited to medical facts, a short summary of symptoms and abnormal findings, and the reason for referral. There was a similar requirement for letters from specialists to include these same medical facts, but detailed information was also required about the diagnosis, treatment options and chosen treatment. After two rounds, the overall content validity index (CVI) for both letters was 71%, indicating that a third round was not necessary. DISCUSSION: This is the first study to differentiate between essential and redundant information in GP referral and specialist letters, and the findings could be used to improve communication between primary and secondary care.

Stercoral perforation proximal to the stapled anastomosis after low anterior resection with an intraluminal device.

Stercoral perforation of the colon is a rare phenomenon and a potential life-threatening condition requiring acute intervention. A little more than 200 cases have been described to date. The mechanism is not completely understood. In this short communication, we present three patients with a colon perforation proximal to the anastomosis, similar to a stercoral perforation, following colorectal cancer resection with application of an intraluminal device, the C-seal.

Short-Course Radiotherapy Followed by Neoadjuvant Bevacizumab, Capecitabine, and Oxaliplatin and Subsequent Radical Treatment in Primary Stage IV Rectal Cancer: Long-Term Results of a Phase II Study.

BACKGROUND: In a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years. METHODS: Patients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible. Follow-up data were collected for all patients enrolled in the trial. Overall and recurrence-free survival were calculated using the Kaplan-Meier method. RESULTS: Follow-up data were available for all 50 patients. After a median follow-up time of 8.1 years (range 6.0-9.8), 16 patients (32.0%) were still alive and 14 (28%) were disease-free. The median overall survival was 3.8 years (range 0.5-9.4). From the 36 patients who received radical treatment, two (5.6%) had a local recurrence and 29 (80.6%) had a distant recurrence. CONCLUSIONS: Long-term survival can be achieved in patients with primary metastatic rectal cancer after neoadjuvant radio- and chemotherapy. Despite a high number of recurrences, 32% of patients were alive after a median follow-up time of 8.1 years.

Randomized clinical trial of biodegradeable intraluminal sheath to prevent anastomotic leak after stapled colorectal anastomosis.

BACKGROUND: Anastomotic leakage is a potential major complication after colorectal surgery. The C-seal was developed to help reduce the clinical leakage rate. It is an intraluminal sheath that is stapled proximal to a colorectal anastomosis, covering it intraluminally and thus preventing intestinal leakage in case of anastomotic dehiscence. The C-seal trial was initiated to evaluate the efficacy of the C-seal in reducing anastomotic leakage in stapled colorectal anastomoses. METHODS: This RCT was performed in 41 hospitals in the Netherlands, Germany, France, Hungary and Spain. Patients undergoing elective surgery with a stapled colorectal anastomosis less than 15 cm from the anal verge were eligible. Included patients were randomized to the C-seal and control groups, stratified for centre, anastomotic height and intention to create a defunctioning stoma. Primary outcome was anastomotic leakage requiring invasive treatment. RESULTS: Between December 2011 and December 2013, 402 patients were included in the trial, 202 in the C-seal group and 200 in the control group. Anastomotic leakage was diagnosed in 31 patients (7·7 per cent), with a 10·4 per cent leak rate in the C-seal group and 5·0 per cent in the control group (P = 0·060). Male sex showed a trend towards a higher leak rate (P = 0·055). Construction of a defunctioning stoma led to a lower leakage rate, although this was not significant (P = 0·095). CONCLUSION: C-seal application in stapled colorectal anastomoses does not reduce anastomotic leakage. Registration number: NTR3080 (http://www.trialregister.nl/trialreg/index.asp).

High mortality rates after nonelective colon cancer resection: results of a national audit.

AIM: Colon cancer resection in a nonelective setting is associated with high rates of morbidity and mortality. The aim of this retrospective study is to identify risk factors for overall mortality after colon cancer resection with a special focus on nonelective resection. METHOD: Data were obtained from the Dutch Surgical Colorectal Audit. Patients undergoing colon cancer resection in the Netherlands between January 2009 and December 2013 were included. Patient, treatment and tumour factors were analysed in relation to the urgency of surgery. The primary outcome was 30-day postoperative mortality. RESULTS: The study included 30 907 patients. A nonelective colon cancer resection was performed in 5934 (19.2%) patients. There was a 4.4% overall mortality rate, with significantly more deaths after nonelective surgery (8.5% vs 3.4%, P < 0.001). Older patients, male patients and patients with high comorbidity, advanced tumours, perforated tumours, a tumour in the right or transverse colon and postoperative anastomotic leakage were at risk of postoperative death. In nonelective resections, a right-sided tumour and postoperative anastomotic leakage were associated with high mortality. CONCLUSION: Nonelective colon cancer resection is associated with high mortality. In particular, right-sided resections and patients with tumour perforation are at particularly high risk. The optimization of patients prior to surgery and expeditious operation after diagnosis might prevent the need for a nonelective resection.

Cytoreduction and hyperthermic intraperitoneal chemotherapy: The learning curve reassessed.

BACKGROUND: CytoReductive Surgery and Hyperthermic IntraPEritoneal Chemotherapy (CRS-HIPEC) is now the preferred treatment of many peritoneal surface malignancies. In this retrospective study we aimed to analyze how several performance indicators changed during the first 100 CRS-HIPEC procedures in hospitals which recently introduced this treatment, and compare those with an experienced institution. METHODS: The first consecutive 100 CRS-HIPEC procedures of three institutions were compared to those of the pioneer hospital. The training provided by the pioneer hospital consisted of hands-on training during the first ten procedures; hereafter guidance was available on consult basis. Operation characteristics, morbidity and completeness of cytoreduction were evaluated by case sequence. Locally-estimated-scatter-plot smoothing was used to evaluate the learning curve. RESULTS: From four institutions 372 cases were included. A macroscopic complete cytoreduction was reached in 66% of the cases in the pioneer hospital and in 86% in the new hospitals (p < 0.001). Complete cytoreduction rates were higher at start off in the new institutions compared with the experienced institution and increased significantly in the first 100 procedures. The new hospitals started with lower morbidity than the experienced hospital, which did not significantly decrease during the study period. CONCLUSION: New institutions that were trained and mentored by an experienced CRS-HIPEC hospital performed better from the beginning with regard to complete cytoreduction and morbidity rate with than the experienced center. An improvement in complete cytoreduction rate during the first 100 procedures was observed in the new institutions.

Is aortoiliac calcification linked to colorectal anastomotic leakage? A case-control study.

BACKGROUND: Anastomotic leakage in bowel surgery remains a devastating complication. Various risk factors have been uncovered, however, high anastomotic leakage rates are still being reported. This study describes the use of calcification markers of the central abdominal arteries as a prognostic factor for colorectal anastomotic leakage. METHODS: This case-control study includes clinical data from three different hospitals. Calcium volume and calcium score of the aortoiliac tract were determined by CT-scan analysis. Cases were all patients with anastomotic leakage after a left-sided anastomosis (n = 30). Three controls were randomly matched for each case. Only patients with a contrast-enhanced pre-operative CT-scan were included. RESULTS: The measurements of the calcium score and calcium volume of the different trajectories showed that there was one significant difference with regard to the right external iliac artery. Multiple regression analysis showed a significant different negative odds ratio of the presence of calcium in the right external iliac artery. CONCLUSION: This study demonstrates that calcium volume and calcium score of the aortoiliac trajectory does not correlate with the risk of colorectal anastomotic leakage after a left-sided anastomosis.

Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging: Results of the randomized "CEAwatch" trial.

AIM: The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. METHODS: This is a randomized-controlled multicenter prospective study using a stepped-wedge cluster design. From October 2010 to October 2012, surgically treated non-metastasized CRC patients in follow-up were followed in eleven hospitals. Clusters of hospitals sequentially changed their usual follow-up care into an intensified follow-up schedule consisting of CEA measurements every two months, with imaging in case of two CEA rises. The primary outcome measures were the proportion of recurrences that could be treated with curative intent, recurrences with definitive curative treatment outcome, and the time to detection of recurrent disease. RESULTS: 3223 patients were included; 243 recurrences were detected (7.5%). A higher proportion of recurrences was detected in the intervention protocol compared to the control protocol (OR = 1.80; 95%-CI: 1.33-2.50; p = 0.0004). The proportion of recurrences that could be treated with curative intent was higher in the intervention protocol (OR = 2.84; 95%-CI: 1.38-5.86; p = 0.0048) and the proportion of recurrences with definitive curative treatment outcome was also higher (OR = 3.12, 95%-CI: 1.25-6.02, p-value: 0.0145). The time to detection of recurrent disease was significantly shorter in the intensified follow-up protocol (HR = 1.45; 95%-CI: 1.08-1.95; p = 0.013). CONCLUSION: The CEAwatch protocol detects recurrent disease after colorectal cancer earlier, in a phase that a significantly higher proportion of recurrences can be treated with curative intent.

Consequence of restaging after neoadjuvant treatment for locally advanced rectal cancer.

BACKGROUND: Locally advanced rectal cancer is customarily treated with neoadjuvant chemoradiotherapy (CRT) followed by a total mesorectal excision. During the course of CRT, previously non-detectable distant metastases can appear. Therefore, a restaging CT scan of the chest and abdomen was performed prior to surgery. The aim of this study was to determine the frequency of a change in treatment strategy after this restaging CT scan. METHODS: Patients treated with neoadjuvant CRT for locally advanced rectal cancer between January 2003 and July 2013 were included retrospectively. To determine the value of the restaging CT scan, the surgical treatment as planned before CRT was compared with the treatment ultimately received. RESULTS: A total of 153 patients (91 male) were eligible, and median age was 62 (32-82) years. The restaging CT scan revealed the presence of distant metastases in 19 patients (12.4, 95 % confidence interval [CI] 7.0-17.8). In 17 patients (11.1, 95 % CI 6.1-16.1), a change in treatment strategy occurred due to the detection of metastases with a restaging CT scan. CONCLUSION: A restaging CT scan after completion of neoadjuvant CRT may detect newly developed metastases and consequently alter the initial treatment strategy. This study demonstrated the added value of the restaging CT scan prior to surgery.

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.

Risk factors for anastomotic leakage and leak-related mortality after colonic cancer surgery in a nationwide audit.

BACKGROUND: Surgical resection with restoration of bowel continuity is the cornerstone of treatment for patients with colonic cancer. The aim of this study was to identify risk factors for anastomotic leakage (AL) and subsequent death after colonic cancer surgery. METHODS: Data were retrieved from the Dutch Surgical Colorectal Audit. Patients undergoing colonic cancer resection with creation of an anastomosis between January 2009 to December 2011 were included. Outcomes were AL requiring reintervention and postoperative mortality following AL. RESULTS: AL occurred in 7·5 per cent of 15 667 patients. Multivariable analyses identified male sex, high American Society of Anesthesiologists (ASA) fitness grade, extensive tumour resection, emergency surgery, and surgical resection types such as transverse resection, left colectomy and subtotal colectomy as independent risk factors for AL. A defunctioning stoma was created in a small group of patients, leading to a lower risk of leakage. The mortality rate was 4·1 per cent overall, and was significantly higher in patients with AL than in those without leakage (16·4 versus 3·1 per cent; P < 0·001). Multivariable analyses identified older age, high ASA grade, high Charlson score and emergency surgery as independent risk factors for death after AL. The adjusted risk of death after AL was twice as high following right compared with left colectomy. CONCLUSION: The elderly and patients with co-morbidity have a higher risk of death after AL. Accurate preoperative patient selection, intensive postoperative surveillance for AL, and early and aggressive treatment of suspected leakage is important, especially in patients undergoing right colectomy.

High 1-year complication rate after anterior resection for rectal cancer.

BACKGROUND: Surgical options after anterior resection for rectal cancer include a primary anastomosis, anastomosis with a defunctioning stoma, and an end colostomy. This study describes short-term and 1-year outcomes of these different surgical strategies. METHODS: Patients undergoing surgical resection for primary mid and high rectal cancer were retrospectively studied in seven Dutch hospitals with 1-year follow-up. Short-term endpoints were postoperative complications, re-interventions, prolonged hospital stay, and mortality. One-year endpoints were unplanned readmissions and re-interventions, presence of stoma, and mortality. RESULTS: Nineteen percent of 388 included patients received a primary anastomosis, 55% an anastomosis with defunctioning stoma, and 27% an end colostomy. Short-term anastomotic leakage was 10% in patients with a primary anastomosis vs. 7% with a defunctioning stoma (P = 0.46). An end colostomy was associated with less severe re-interventions. One-year outcomes showed low morbidity and mortality rates in patients with an anastomosis. Patients with a defunctioning stoma had high (18%) readmissions and re-intervention (12%) rates, mostly due to anastomotic leakage. An end colostomy was associated with unplanned re-interventions due to stoma/abscess problems. During follow-up, there was a 30% increase in patients with an end colostomy. CONCLUSIONS: This study showed a high 1-year morbidity rate after anterior resection for rectal cancer. A defunctioning stoma was associated with a high risk for late complications including anastomotic leakage. An end colostomy is a safe alternative to prevent anastomotic leakage, but stomal problems cannot be ignored. Selecting low-risk patients for an anastomosis may lead to favorable short- and 1-year outcomes.

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 Levene's 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.

Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer.

BACKGROUND: To evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer. PATIENTS AND METHODS: Adults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m(2), day 1) intravenously and capecitabine (1000 mg/m(2) twice daily orally, days 1-14) for up to six cycles. Surgery was carried out 6-8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated. RESULTS: Of 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%-90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%-84.5%). Toxic effects were tolerable. No treatment-related deaths occurred. CONCLUSIONS: Radical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab-capecitabine-oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.

Late anastomotic leakage in colorectal surgery: a significant problem.

AIM: Reported incidence rates of colorectal anastomotic leakage (AL) vary between 2.5 and 20%. There is little information on late anastomotic leakage (LAL). The aim of this study was to determine the incidence of LAL after colorectal resection. METHOD: All patients undergoing colorectal resection with primary anastomosis between January 2004 and October 2009 at the University Medical Center Groningen were included. LAL was defined as anastomotic leakage diagnosed more than 30 days after surgery. RESULTS: One hundred and forty-one patients were analysed. Indications for surgery included both benign and malignant conditions. The incidence of early anastomotic leakage (EAL) within 30 days after surgery was 13%. The LAL rate was 6%. Eighty-nine per cent of patients with EAL underwent relaparotomy compared with 44% for LAL (P = 0.02). CONCLUSION: One-third of all anastomotic leakages were diagnosed more than 30 days after surgery. Of these, 44% underwent relaparotomy. Patients with leakage diagnosed within 30 days after surgery were more likely to undergo relaparotomy. LAL is a significant problem after colorectal surgery.

To eat or not to eat: facilitating early oral intake after elective colonic surgery in the Netherlands.

BACKGROUND & AIMS: It was shown that patients in the Netherlands remain exposed to unnecessarily prolonged starvation after abdominal surgery. The present study examined whether a structured collaborative effort would help to implement the early start of oral nutrition after colorectal surgery. METHODS: In 2006, twenty-six Dutch hospitals signed up to a "breakthrough project" concerning the implementation of the enhanced recovery after surgery (ERAS) programme with early oral feeding as one of the key elements. Each hospital determined the usual start of food intake by analyzing 50 patients who underwent a colorectal resection in 2004 (n=1126). Subsequently, over the course of one year 861 colorectal surgery patients were treated according to the ERAS programme. The first day that patients were eating before and after the breakthrough project was compared using Kaplan-Meier analyses and Cox regression models. RESULTS: Patients treated according to the ERAS programme were eating 3 days earlier than the patients traditionally treated (p<0.000). Two days after surgery 65% of the ERAS patients were eating normal food versus 7% of the pre-ERAS patients. CONCLUSIONS: The present nationwide collaborative effort was successful in implementing a change towards an early start of oral nutrition after abdominal surgery.