Implementation of robotic rectal cancer surgery: a cross-sectional nationwide study.

AIM: An increasing number of centers have implemented a robotic surgical program for rectal cancer. Several randomized controls trials have shown similar oncological and postoperative outcomes compared to standard laparoscopic resections. While introducing a robot rectal resection program seems safe, there are no data regarding implementation on a nationwide scale. Since 2018 robot resections are separately registered in the mandatory Dutch Colorectal Audit. The present study aims to evaluate the trend in the implementation of robotic resections (RR) for rectal cancer relative to laparoscopic rectal resections (LRR) in the Netherlands between 2018 and 2020 and to compare the differences in outcomes between the operative approaches. METHODS: Patients with rectal cancer who underwent surgical resection between 2018 and 2020 were selected from the Dutch Colorectal Audit. The data included patient characteristics, disease characteristics, surgical procedure details, postoperative outcomes. The outcomes included any complication within 90 days after surgery; data were categorized according to surgical approach. RESULTS: Between 2018 and 2020, 6330 patients were included in the analyses. 1146 patients underwent a RR (18%), 3312 patients a LRR (51%), 526 (8%) an open rectal resection, 641 a TaTME (10%), and 705 had a local resection (11%). The proportion of males and distal tumors was higher in the RR compared to the LRR. Over time, the proportion of robotic procedures increased from 15% (95% confidence intervals (CI) 13-16%) in 2018 to 22% (95% CI 20-24%) in 2020. Conversion rate was lower in the robotic group [4% (95% CI 3-5%) versus 7% (95% CI 6-8%)]. Anastomotic leakage rate was similar with 16%. Defunctioning ileostomies were more common in the RR group [42% (95% CI 38-46%) versus 29% (95% CI 26-31%)]. CONCLUSION: Rectal resections are increasingly being performed through a robot-assisted approach in the Netherlands. The proportion of males and low rectal cancers was higher in RR compared to LRR. Overall outcomes were comparable, while conversion rate was lower in RR, the proportion of defunctioning ileostomies was higher compared to LRR.

An evaluation of short-term outcomes after reoperations for anastomotic leakage in colon cancer patients.

PURPOSE: Scarce data are available on differences among index colectomies for colon cancer regarding reoperation for anastomotic leakage (AL) and clinical consequences. Therefore, this nationwide observational study aimed to evaluate reoperations for AL after colon cancer surgery and short-term postoperative outcomes for the different index colectomies. METHODS: Patients who underwent resection with anastomosis for a first primary colon carcinoma between 2013 and 2019 and were registered in the Dutch ColoRectal Audit were included. Primary outcomes were mortality, ICU admission, and stoma creation. RESULTS: Among 39,565 patients, the overall AL rate was 4.8% and ranged between 4.0% (right hemicolectomy) and 15.4% (subtotal colectomy). AL was predominantly managed with reoperation, ranging from 81.2% after transversectomy to 92.4% after sigmoid resection (p < 0.001). Median time to reoperation differed significantly between index colectomies (range 4-8 days, p < 0.001), with longer and comparable intervals for non-surgical reinterventions (range 13-18 days, p = 0.747). After reoperation, the highest mortality rates were observed for index transversectomy (15.4%) and right hemicolectomy (14.4%) and lowest for index sigmoid resection (5.6%) and subtotal colectomy (5.9%) (p < 0.001). Reoperation with stoma construction was associated with a higher mortality risk than without stoma construction after index right hemicolectomy (17.7% vs. 8.5%, p = 0.001). ICU admission rate was 62.6% overall (range 56.7-69.2%), and stoma construction rate ranged between 65.5% (right hemicolectomy) and 93.0% (sigmoid resection). CONCLUSION: Significant differences in AL rate, reoperation rate, time to reoperation, postoperative mortality after reoperation, and stoma construction for AL were found among the different index colectomies for colon cancer, with relevance for patient counseling and perioperative management.

National differences in implementation of minimally invasive surgery for colorectal cancer and the influence on short-term outcomes.

BACKGROUND: The timing and degree of implementation of minimally invasive surgery (MIS) for colorectal cancer vary among countries. Insights in national differences regarding implementation of new surgical techniques and the effect on postoperative outcomes are important for quality assurance, can show potential areas for country-specific improvement, and might be illustrative and supportive for similar implementation programs in other countries. Therefore, this study aimed to evaluate differences in patient selection, applied techniques, and results of minimal invasive surgery for colorectal cancer between the Netherlands and Sweden. METHODS: Patients who underwent elective minimally invasive surgery for T1-3 colon or rectal cancer (2012-2018) registered in the Dutch ColoRectal Audit or Swedish ColoRectal Cancer Registry were included. Time trends in the application of MIS were determined. Outcomes were compared for time periods with a similar level of MIS implementation (Netherlands 2012-2013 versus Sweden 2017-2018). Multilevel analyses were performed to identify factors associated with adverse short-term outcomes. RESULTS: A total of 46,095 Dutch and 8,819 Swedish patients undergoing MIS for colorectal cancer were included. In Sweden, MIS implementation was approximately 5 years later than in the Netherlands, with more robotic surgery and lower volumes per hospital. Although conversion rates were higher in Sweden, oncological and surgical outcomes were comparable. MIS in the Netherlands for the years 2012-2013 resulted in a higher reoperation rate for colon cancer and a higher readmission rate but lower non-surgical complication rates for rectal cancer if compared with MIS in Sweden during 2017-2018. CONCLUSION: This study showed that the implementation of MIS for colorectal cancer occurred later in Sweden than the Netherlands, with comparable outcomes despite lower volumes. Our study demonstrates that new surgical techniques can be implemented at a national level in a controlled and safe way, with thorough quality assurance.

Long-term stoma-related reinterventions after anterior resection for rectal cancer with or without anastomosis: population data from the Dutch snapshot study.

BACKGROUND: The aim of this study was to analyze the stoma-related reinterventions, complications and readmissions after an anterior resection for rectal cancer, based on a cross-sectional nationwide cohort study with 3-year follow-up. METHODS: Rectal cancer patients who underwent a resection with either a functional anastomosis, a defunctioned anastomosis, or Hartmann's procedure (HP) with an end colostomy in 2011 in 71 Dutch hospitals were included. The primary outcome was number of stoma-related reinterventions. RESULTS: Of the 2095 patients with rectal cancer, 1400 patients received an anterior resection and were included in this study; 257 received an initially functional anastomosis, 741 a defunctioned anastomosis, and 402 patients a HP. Of the 1400 included patients, 62% were males, 38% were females and the mean age was 67 years (SD 11.1). Following a primary functional anastomosis, 48 (19%) patients received a secondary stoma. Stoma-related complications occurred in six (2%) patients, requiring reintervention in one (0.4%) case. In the defunctioned anastomosis group, stoma-related complications were present in 92 (12%) patients, and required reintervention in 23 (3%) patients, in 10 (1%) of these more than 1 year after initial resection. Stoma-related complications occurred in 92 (23%) patients after a HP, and required reintervention in 39 (10%) patients in 17 (4%) of cases more than 1 year after initial resection. The permanent stoma rate was 11% and 20%, in the functional anastomosis and the defuctioned anastomosis group, respectively. The end colostomy in the HP group was reversed in 4% of cases. CONCLUSIONS: Construction of a stoma after resection for rectal cancer with preservation of the sphincter is accompanied with long-term stoma-related morbidity. Stoma complications are more frequent after a HP. Even after 1 year, a significant number of reinterventions are required.

Interhospital referral of colorectal cancer patients: a Dutch population-based study.

PURPOSE: Interhospital referral is a consequence of centralization of complex oncological care but might negatively impact waiting time, a quality indicator in the Netherlands. This study aims to evaluate characteristics and waiting times of patients with primary colorectal cancer who are referred between hospitals. METHODS: Data were extracted from the Dutch ColoRectal Audit (2015-2019). Waiting time between first tumor-positive biopsy until first treatment was compared between subgroups stratified for referral status, disease stage, and type of hospital. RESULTS: In total, 46,561 patients were included. Patients treated for colon or rectal cancer in secondary care hospitals were referred in 12.2% and 14.7%, respectively. In tertiary care hospitals, corresponding referral rates were 43.8% and 66.4%. Referred patients in tertiary care hospitals were younger, but had a more advanced disease stage, and underwent more often multivisceral resection and simultaneous metastasectomy than non-referred patients in secondary care hospitals (p<0.001). Referred patients were more often treated within national quality standards for waiting time compared to non-referred patients (p<0.001). For referred patients, longer waiting times prior to MDT were observed compared to non-referred patients within each hospital type, although most time was spent post-MDT. CONCLUSION: A large proportion of colorectal cancer patients that are treated in tertiary care hospitals are referred from another hospital but mostly treated within standards for waiting time. These patients are younger but often have a more advanced disease. This suggests that these patients are willing to travel more but also reflects successful centralization of complex oncological patients in the Netherlands.

MRI cT1-2 rectal cancer staging accuracy: a population-based study.

BACKGROUND: Adequate MRI-based staging of early rectal cancers is essential for decision-making in an era of organ-conserving treatment approaches. The aim of this population-based study was to determine the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography (ERUS). METHODS: Patients with cT1-2 rectal cancer who underwent local excision or total mesorectal excision (TME) without downsizing (chemo)radiotherapy between 1 January 2011 and 31 December 2018 were selected from the Dutch ColoRectal Audit. The accuracy of imaging was expressed as sensitivity, specificity, and positive predictive value (PPV) and negative predictive value. RESULTS: Of 7382 registered patients with cT1-2 rectal cancer, 5539 were included (5288 MRI alone, 251 MRI and ERUS; 1059 cT1 and 4480 cT2). Among patients with pT1 tumours, 54·7 per cent (792 of 1448) were overstaged by MRI alone, and 31·0 per cent (36 of 116) by MRI and ERUS. Understaging of pT2 disease occurred in 8·2 per cent (197 of 2388) and 27·9 per cent (31 of 111) respectively. MRI alone overstaged pN0 in 17·3 per cent (570 of 3303) and the PPV for assignment of cN0 category was 76·3 per cent (2733 of 3583). Of 834 patients with pT1 N0 disease, potentially suitable for local excision, tumours in 253 patients (30·3 per cent) were staged correctly as cT1 N0, whereas 484 (58·0 per cent) and 97 (11·6 per cent) were overstaged as cT2 N0 and cT1-2 N1 respectively. CONCLUSION: This Dutch population-based analysis of patients who underwent local excision or TME surgery for cT1-2 rectal cancer based on preoperative MRI staging revealed substantial overstaging, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.

ANTECEDENTES: Una adecuada estadificación mediante resonancia magnética nuclear (RMN) de los cánceres de recto en estadios precoces es esencial para la toma de decisiones en una era en la existen diferentes opciones de tratamiento preservadoras del recto. El objetivo de este estudio de base poblacional fue determinar la precisión de la estadificación mediante RMN del cáncer de recto precoz en la práctica diaria, ya sea combinada o no con la ecografía endorectal (endorectal ultrasound, ERUS). MÉTODOS: Los pacientes con cáncer de recto en estadio cT1-2 que se sometieron a resección local o resección total del mesorrecto (total mesorectal excision, TME) sin (quimio) radioterapia neoadyuvante fueron seleccionados a partir del registro auditado ColoRectal holandés, entre el 1 de enero de 2011 y el 31 de diciembre de 2018. La precisión de las imágenes se expresó como sensibilidad, especificidad y valores predictivos positivo y negativo (positive- and negative predicting value, PPV / NPV). RESULTADOS: De un total de 7.382 pacientes registrados con cáncer de recto en estadio cT1-2, se incluyeron 5.539 pacientes (5.288 solamente RMN, 251 RMN + ERUS; 1.059 cT1 y 4.480 cT2). Los pacientes pT1 fueron sobreestadificados cuando se utilizó únicamente la RMN en un 54,7% de los casos (792/1.448) y cuando se combinó RMN y ERUS en un 31,0% (36/116). La infraestadificación de pT2 ocurrió en un 8,2% (197/2.388) y en un 27,9% (31/111), respectivamente. La RMN utilizada como única prueba sobreestadificó los casos pN0 en el 17,3% (570/3.303) y el VPP del estadio cN0 fue del 76,3% (2.733/3.583). De los 834 pacientes con estadio pT1N0, potencialmente adecuado para la resección local, 253 pacientes (30,3%) se clasificaron correctamente como cT1N0, y 484 (58,8%) y 97 (11,6%) pacientes se sobreestadificaron como cT2N0 y cT1-2N1, respectivamente. CONCLUSIÓN: Este estudio de base poblacional holandés en pacientes que se sometieron a una resección local o a cirugía TME por cáncer de recto cT1-2 con estadificación preoperatoria mediante RMN, muestra una considerable sobreestadificación, lo que indica las debilidades y oportunidades en las estrategias de preservación del recto.

International evaluation of circumferential resection margins after rectal cancer resection: insights from the Swedish and Dutch audits.

AIM: This study aimed to determine predictive factors for the circumferential resection margin (CRM) within two northern European countries with supposed similarity in providing rectal cancer care. METHOD: Data for all patients undergoing rectal resection for clinical tumour node metastasis (TNM) stage I-III rectal cancer were extracted from the Swedish ColoRectal Cancer Registry and the Dutch ColoRectal Audit (2011-2015). Separate analyses were performed for cT1-3 and cT4 stage. Predictive factors for the CRM were determined using univariable and multivariable logistic regression analyses. RESULTS: A total of 6444 Swedish and 12 089 Dutch patients were analysed. Over time the number of hospitals treating rectal cancer decreased from 52 to 42 in Sweden, and 82 to 79 in the Netherlands. In the Swedish population, proportions of cT4 stage (17% vs 8%), multivisceral resection (14% vs 7%) and abdominoperineal excision (APR) (37% vs 31%) were higher. The overall proportion of patients with a positive CRM (CRM+) was 7.8% in Sweden and 5.4% in the Netherlands. In both populations with cT1-3 stage disease, common independent risk factors for CRM+ were cT3, APR and multivisceral resection. No common risk factors for CRM+ in cT4 stage disease were found. An independent impact of hospital volume on CRM+ could be demonstrated for the cT1-3 Dutch population. CONCLUSION: Within two northern European countries with implemented clinical auditing, rectal cancer care might potentially be improved by further optimizing the treatment of distal and locally advanced rectal cancer.

A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection.

AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1ß), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool.

The Prognostic Value of a Geriatric Risk Score for Older Patients with Colorectal Cancer.

INTRODUCTION: VMS is a Dutch risk assessment tool for hospitalized older adults that includes a short evaluation of four geriatric domains: risk for delirium, risk for undernutrition, risk for physical impairments, and fall risk. We investigated whether the information derived from this tool has prognostic value for outcomes of colorectal surgery. METHODS: All consecutive patients over age 70 years who underwent elective colorectal cancer surgery in three Dutch hospitals (2014-2016) were studied. The presence of risk was scored prior to surgery and per geriatric domain as either 0 (risk absent) or 1 (risk present). The total number of geriatric risk factors was summed. The primary outcome was long-term survival. Secondary outcomes were postoperative complications, including delirium. Cox proportional hazards models were used to evaluate the sumscore and risk factors associated with overall survival. RESULTS: Five hundred fifty patients were included. Median age was 76.5 years, and median follow-up was 870 days. Patients with intermediate (1-2) or high (3-4) sumscore were independently associated with lower overall survival, with hazard ratio (HR) of 1.9 [95% confidence interval (CI) 1.1-3.5; p = 0.03] and 8.7 (95% CI 4.0-19.2; p < 0.001), respectively. Sumscores were also associated with postoperative complications (intermediate sumscore OR 1.8; 95% CI 1.2-2.7; high sumscore OR 2.4; 95% CI 1.02-5.5). CONCLUSIONS: This easy-to-use geriatric sumscore has strong associations with long-term outcome and morbidity after colorectal cancer surgery. This information may be included in risk models for morbidity and mortality and can be used in shared decision-making.

Multicentre study of non-surgical management of diverticulitis with abscess formation.

This multicentre retrospective cohort study included 447 patients with Hinchey Ib and II diverticular abscesses, who were treated with antibiotics, with or without percutaneous drainage. Abscesses of 3 and 5 cm in size were at higher risk of short-term treatment failure and emergency surgery respectively. Initial non-surgical treatment of Hinchey Ib and II diverticular abscesses was comparable between patients treated with antibiotics only and those who underwent percutaneous drainage in combination with antibiotics, with regard to short- and long-term outcomes. Most do not need drainage.

Transanal total mesorectal excision: how are we doing so far?

AIM: This subgroup analysis of a prospective multicentre cohort study aims to compare postoperative morbidity between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME). METHOD: The study was designed as a subgroup analysis of a prospective multicentre cohort study. Patients undergoing TaTME or LaTME for rectal cancer were selected. All patients were followed up until the first visit to the outpatient clinic after hospital discharge. Postoperative complications were classified according to the Clavien-Dindo classification and the comprehensive complication index (CCI). Propensity score matching was performed. RESULTS: In total, 220 patients were selected from the overall prospective multicentre cohort study. After propensity score matching, 48 patients from each group were compared. The median tumour height for TaTME was 10.0 cm (6.0-10.8) and for LaTME was 9.5 cm (7.0-12.0) (P = 0.459). The duration of surgery and anaesthesia were both significantly longer for TaTME (221 vs 180 min, P < 0.001, and 264 vs 217 min, P < 0.001). TaTME was not converted to laparotomy whilst surgery in five patients undergoing LaTME was converted to laparotomy (0.0% vs 10.4%, P = 0.056). No statistically significant differences were observed for Clavien-Dindo classification, CCI, readmissions, reoperations and mortality. CONCLUSION: The study showed that TaTME is a safe and feasible approach for rectal cancer resection. This new technique obtained similar postoperative morbidity to LaTME.

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative.

BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

Dutch validation of the low anterior resection syndrome score.

AIM: The aim of this study was to validate the Dutch translation of the low anterior resection syndrome (LARS) score in a population of Dutch rectal cancer patients. METHOD: Patients who underwent surgery for rectal cancer received the LARS score questionnaire, a single quality of life (QoL) category question and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. A subgroup of patients received the LARS score twice to assess the test-retest reliability. RESULTS: A total of 165 patients were included in the analysis, identified in six Dutch centres. The response rate was 62.0%. The percentage of patients who reported 'major LARS' was 59.4%. There was a high proportion of patients with a perfect or moderate fit between the QoL category question and the LARS score, showing a good convergent validity. The LARS score was able to discriminate between patients with or without neoadjuvant radiotherapy (P = 0.003), between total and partial mesorectal excision (P = 0.008) and between age groups (P = 0.039). There was a statistically significant association between a higher LARS score and an impaired function on the global QoL subscale and the physical, role, emotional and social functioning subscales of the EORTC QLQ-C30 questionnaire. The test-retest reliability of the LARS score was good, with an interclass correlation coefficient of 0.79. CONCLUSION: The good psychometric properties of the Dutch version of the LARS score are comparable overall to the earlier validations in other countries. Therefore, the Dutch translation can be considered to be a valid tool for assessing LARS in Dutch rectal cancer patients.

The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment.

BACKGROUND: In preoperative blood management of colorectal cancer patients, intravenous iron therapy is increasingly used to treat anaemia and prevent red blood cell transfusions. However, while iron deficiency is the most common cause of anaemia, little is known about the prevalence and namely type of iron deficiency in this population, whereas both types of iron deficiency (i.e. absolute and functional iron deficiency) are recommended to be treated differently by international cancer guidelines. OBJECTIVE: The aim of present study is to investigate the prevalence and namely type of iron deficiency in colorectal cancer patients, and to assess its clinical relevance. METHODS: Preoperative iron status, clinical parameters (i.e. age, ASA classification, tumour location, tumour stage) and postoperative complications were retrospectively collected for all newly diagnosed colorectal cancer patients in our institution over a 3-year period. RESULTS: Iron deficiency was observed in 163 (48.1%) of 339 patients. Of these iron-deficient patients, 3.7% had an isolated absolute iron deficiency (AID) and 15.3% a functional iron deficiency (FID), while the rest had a combination of AID and FID. Anaemia was present in 66.1% of iron-deficient patients. Iron deficiency was significantly associated with an increased postoperative complication rate (univariable OR 1.94, p = 0.03, multivariable OR 1.84, p = 0.07), with right-sided tumours (p < 0.001), high ASA classification (p = 0.002), advanced tumour stage (p = 0.01) and advanced age (p = 0.04). In comparing clinical parameters between patients with AID and FID, advanced age was significantly associated with FID (p = 0.03), and the presence of anaemia with AID (p = 0.02). CONCLUSION: In preoperative colorectal cancer patients, there is a high prevalence of iron deficiency, including a high percentage of patients with-a component of-functional iron deficiency, associated with the increased postoperative complication rate. As both types of iron deficiency require a different treatment strategy, our results illustrate the therapeutic potential of especially intravenous iron supplementation in patients with severe iron deficiency and stress the urgency of routinely monitoring preoperative iron status and differentiation between types of iron deficiency. As iron therapy may also be potentially harmful in respect to stimulation of tumour growth, future clinical trials assessing the long-term effect of iron therapy are necessary.

Association Between the Most Frequent Complications After Surgery for Stage I-III Colon Cancer and Short-Term Survival, Long-Term Survival, and Recurrences.

BACKGROUND: The purpose of this study was to identify the ten most frequent complications after surgery for stage I-III colon cancer and to assess the association between these complications and overall survival, conditional overall survival, and recurrences. METHODS: All patients who underwent surgery for stage I-III colon cancer in five hospitals in the Western region of the Netherlands were identified. Crude and adjusted Cox proportional hazards models were used to study the association between complications and 1-year overall survival, 5-year overall survival, 5-year conditional overall survival, and 5-year disease-free period. RESULTS: Data from 761 patients were used for the analyses. Complications were associated with decreased 1-year overall survival (hazard ratio (HR) 2.87, 95 % confidence interval (CI) 1.82-4.51; p < 0.001), 5-year overall survival (HR 1.59, 95 % CI 1.25-2.04; p < 0.001), and 5-year conditional overall survival (HR 1.34, 95 % CI 1.06-1.69; p = 0.016), whereas an increasing number of complications had no additional impact. Anastomotic leakage, excessive blood loss, and (abdominal) sepsis were associated with reduced 1-year overall survival, anastomotic leakage, delirium, abscess, and (abdominal) sepsis with reduced 5-year overall survival, and anastomotic leakage, delirium, and abscess with reduced 5-year conditional overall survival. Anastomotic leakage, electrolyte disorders, and abscess were risk factors for recurrence within five years. CONCLUSIONS: Our results demonstrate the serious impact of the most frequent complications after surgery for colon cancer on short-term and long-term outcomes. This study confirms the prolonged impact of surgery and demonstrates that complications result not only in reduced 1-year survival, but also in reduced long-term outcomes.

Differences between colon and rectal cancer in complications, short-term survival and recurrences.

PURPOSE: Many apparent differences exist in aetiology, genetics, anatomy and treatment response between colon cancer (CC) and rectal cancer (RC). This study examines the differences in patient characteristics, prevalence of complications and their effect on short-term survival, long-term survival and the rate of recurrence between RC and CC. METHODS: For all stage II-III CC and RC patients who underwent resection with curative intent (2006-2008) in five hospitals in the Netherlands, occurrence of complications, crude survival, relative survival and recurrence rates were compared. RESULTS: A total of 767 CC and 272 RC patients underwent resection. Significant differences were found for age, gender, emergency surgery, T-stage and grade. CC patients experienced fewer complications compared to RC (p = 0.019), but CC patients had worse short-term mortality rates (1.5 versus 6.7 % for 30-day mortality, p = 0.001 and 5.2 versus 9.5 % for 90-day mortality, p = 0.032). The adjusted HR (overall survival) for CC patients with complications was 1.57 (1.23-2.01; p < 0.001) as compared to patients without complications; for RC, the HR was 1.79 (1.12-2.87; p = 0.015). Relative survival analyses showed high excess mortality in the first months after surgery and a sustained, prolonged negative effect on both CC and RC. Complications were associated with a higher recurrence rate for both CC and RC; adjusted analyses showed a trend towards a significant association. CONCLUSION: Large differences exist in patient characteristics and clinical outcomes between CC and RC. CC patients have a significantly higher short-term mortality compared to RC patients due to a more severe effect of complications.

Combined analysis of HLA class I, HLA-E and HLA-G predicts prognosis in colon cancer patients.

BACKGROUND: Evasion of immune surveillance and suppression of the immune system are important hallmarks of tumour development in colon cancer. The goal of this study was to establish a tumour profile based on biomarkers that reflect a tumour's immune susceptibility status and to determine their relation to patient outcome. METHODS: The study population consisted of 285 stage I-IV colon cancer patients of which a tissue micro array (TMA) was available. Sections were immunohistochemically stained for the presence of Foxp3+ cells and tumour expression of HLA Class I (HLA-A, -B, -C) and non-classical HLA-E and HLA-G. All markers were combined for further analyses, resulting in three tumour immune phenotypes: strong immune system tumour recognition, intermediate immune system tumour recognition and poor immune system tumour recognition. RESULTS: Loss of HLA class I expression was significantly related to a better OS (P-value 0.005) and DFS (P-value 0.008). Patients with tumours who showed neither HLA class I nor HLA-E or -G expression (phenotype a) had a significant better OS and DFS (P-value <0.001 and 0.001, respectively) compared with phenotype b (OS HR: 4.7, 95% CI: 1.2-19.0, P=0.001) or c (OS HR: 8.2, 95% CI: 2.0-34.2, P=0.0001). Further, the tumour immune phenotype was an independent predictor for OS and DFS (P-value 0.009 and 0.013, respectively). CONCLUSION: Tumours showing absence of HLA class I, HLA-E and HLA-G expressions were related to a better OS and DFS. By combining the expression status of several immune-related biomarkers, three tumour immune phenotypes were created that related to patient outcome. These immune phenotypes represented significant, independent, clinical prognostic profiles in colon cancer.

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

BACKGROUND: Disturbance 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 METHODS: The 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. RESULTS: The 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. CONCLUSIONS: The 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.

Relief of Obstruction in Left-Sided Obstructive Colon Cancer: Nationwide Analysis of Applied Treatment in the Palliative Setting.

BACKGROUND: For relief of bowel obstruction in left-sided obstructive colon cancer (LSOCC), a self-expandable metal stent (SEMS) or decompressing stoma (DS) can be placed. In a curative setting, these two strategies have been extensively studied as a bridge to elective resection. Guidelines recommend SEMS as the preferred option in the palliative setting, but adherence in daily practice is unknown. Therefore, this study aimed to gain more insight into patients with LSOCC who received palliative treatment with SEMS or DS at a national level. METHODS: A retrospective population-based cohort study was conducted in the Netherlands. Data from the Netherlands Cancer Registry (NCR) on all patients with LSOCC treated with DS or SEMS not followed by resection of the primary tumour between January 1, 2015, and December 31, 2019, were analysed. Type of treatment (DS or SEMS) for different clinical scenarios, was the main outcome of this study, and was also evaluated over the years (2015-2019). RESULTS: Palliative treatment with SEMS or DS for LSOCC was performed in 1077 patients, of whom 79.2% had metastatic disease (M1). Patients without metastatic disease (M0) were older (≥ 80 years M0 67.4%, M1 25.3%, P < 0.001), had a worse clinical condition (ASA III 51.4% versus 36.37%, ASA IV-V 13.3% versus 4.0% P < 0.001) and presented with higher tumour stage (cT4 55.4% versus 33.5%, % P < 0.001). DS was performed in 91.5% of the patients and SEMS in 8.5%. The proportion of DS did not significantly differ between patients with M1 and M0 (91.8% vs. 90.2% respectively, P = 0.525). No increase in SEMS application was observed over the years, with a stable overall proportion of DS of 91-92% per year. In the multivariable analyses, ninety-day mortality and overall survival were not significantly different between SEMS and DS. CONCLUSIONS: This study revealed that DS was the primary treatment modality for palliative management of LSOCC in the Netherlands between 2015 and 2019, while the guidelines recommended SEMS as preferred treatment. For patients with LSOCC eligible for stenting in the palliative setting, SEMS placement should become more available and accessible as the preferred treatment option, to avoid a stoma in the terminal phase of life.

Postoperative complications after colorectal cancer surgery and the association with long-term survival.

BACKGROUND: Complications after colorectal cancer surgery can worsen long-term survival. The aim of this nationwide study was to determine the impact of different types of complications on overall survival (OS) and conditional survival if still alive one year postoperatively (CS-1) after colorectal cancer surgery. MATERIALS AND METHODS: All patients registered in the Dutch ColoRectal Audit after resection of primary colorectal cancer between 2011 and 2017 and with known survival status were included. Multivariable Cox regression models were used to assess the association of complications with OS and CS-1, thereby calculating the Hazard Ratio (HR) with 95% Confidence Interval. RESULTS: 43,908 colon and 16,955 rectal cancer patients were included. Median follow-up time was 66.1 and 66.5 months, respectively. Five-year OS after colon cancer resection was 73.2% without complications, and 65.4% with surgical, 52.9% with non-surgical and 51.8% with combined type of complications (p < 0.001). Corresponding 5-year OS for rectal cancer patients was 76.9%, 72.7%, 64.9%, and 63.2% (p < 0.001). In colon cancer, multivariable analyses revealed HR 1.198 (1.136-1.264) for surgical, HR 1.489 (1.423-1.558) for non-surgical and HR 1.590 (1.505-1.681) for combined type of complications. For rectal cancer, these HRs were 1.193 (1.097-1.2297), 1.456 (1.346-1.329), and 1.489 (1.357-1.633). Surgical complications were associated with worse CS-1 in rectal cancer (HR 1.140 (1.050-1.260), but not in colon cancer (HR 1.007 (0.943-1.075)). CONCLUSION: Non-surgical complications have higher impact on survival than surgical complications. The impact of surgical complications on survival was still measurable after surviving the first year in rectal cancer but not in colon cancer patients.