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.
Aims/hypothesis Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes and reduced insulin secretion. The transcription factor TCF7L2 is an essential ...factor for glucagon-like peptide-1 (GLP-1) secretion from intestinal L cells. We studied whether a defect in the enteroinsular axis contributes to impaired insulin secretion in carriers of TCF7L2 polymorphisms. Methods We genotyped 1,110 non-diabetic German participants for five single nucleotide polymorphisms in TCF7L2. All participants underwent an OGTT; GLP-1 secretion was measured in 155 participants. In 210 participants, an IVGTT combined with a hyperinsulinaemic-euglycaemic clamp was performed. In another 160 participants from the Netherlands and 73 from Germany, a hyperglycaemic clamp (10 mmol/l) was performed. In 73 German participants this clamp was combined with a GLP-1 infusion and an arginine bolus. Results The OGTT data confirmed that variants in TCF7L2 are associated with reduced insulin secretion. In contrast, insulin secretion induced by an i.v. glucose challenge in the IVGTT and hyperglycaemic clamp was not different between the genotypes. GLP-1 concentrations during the OGTT were not influenced by the TCF7L2 variants. However, GLP-1-infusion combined with a hyperglycaemic clamp showed a significant reduction in GLP-1-induced insulin secretion in carriers of the risk allele in two variants (rs7903146, rs12255372, p < 0.02). Conclusions/interpretation Variants of TCF7L2 specifically impair GLP-1-induced insulin secretion. This seems to be rather the result of a functional defect in the GLP-1 signalling in beta cells than a reduction in GLP-1 secretion. This defect might explain the impaired insulin secretion in carriers of the risk alleles and confers the increased risk of type 2 diabetes.
Preoperative low skeletal muscle mass and density are associated with increased postoperative morbidity in patients undergoing curative colorectal cancer (CRC) surgery. However, the long-term effects ...of low skeletal muscle mass and density remain uncertain.
Patients with stage I-III CRC undergoing surgery, enrolled in a prospective observational cohort study, were included. Skeletal muscle mass and density were measured on CT. Patients with high and low skeletal muscle mass and density were compared regarding postoperative complications, disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS).
In total, 816 patients (53.9% males, median age 70) were included; 50.4% had low skeletal muscle mass and 64.1% low density. The severe postoperative complication rate was significantly higher in patients with low versus high skeletal muscle and density (20.9% versus 13.6%, p = 0.006; 20.0% versus 11.8%, p = 0.003). Low skeletal muscle mass (OR 1.91, p = 0.018) and density (OR 1.87, p = 0.045) were independently associated with severe postoperative complications. Ninety-day mortality was higher in patients with low skeletal muscle mass and density compared with patients with high skeletal muscle mass and density (3.6% versus 1.7%, p = 0.091; 3.4% versus 1.0%, p = 0.038). No differences in DFS were observed. After adjustment for covariates such as age and comorbidity, univariate differences in OS and CSS diminished.
Low skeletal muscle mass and density are associated with short-term, but not long-term, outcome in patients undergoing CRC surgery. These findings recommend putting more emphasis on preoperative management of patients at risk for surgical complications, but do not support benefit for long-term outcome.
We implemented a multidisciplinary pre- and rehabilitation program for elderly patients (≥75 years of age) in a single center consisting of prehabilitation, laparoscopic surgery and early ...rehabilitation with the intention to lower 1-year overall mortality.
In this study we compared all patients that underwent elective surgery for stage I-III colorectal cancer before and during development and after implementation of the program (2010–2011, 2012–2013 and 2014–2015). Primary endpoint was 1-year overall mortality, the secondary endpoint was 30-day postoperative outcome.
Eighty-six consecutive patients were included in the study cohort and compared to 63 patients from 2010 to 2011 and 75 patients from 2012 to 2013. Patient characteristics were comparable; median age in the study cohort was 80.6. Seventy-three patients (85%) participated in the program, 54 (63%) of whom followed a prehabilitation program, 46 (53%) of whom were discharged to a rehabilitation center. Laparoscopic surgery increased over the years from 70% to 83% in the study cohort. There was a trend in lower 1-year overall mortality: 11% versus 3% (p=0.08). There was a significant reduction in cardiac complications and the number of patients with a prolonged length of stay (p < 0.01).
Multidisciplinary care for elderly colorectal cancer patients that includes prehabilitation and rehabilitation is feasible and may contribute to lower complications and reduced length of stay. This study did not show a clear benefit of implementing a comprehensive care program including both prehabilitation and rehabilitation. Dedicated multidisciplinary care seems the key attributer to favorable outcomes of CRC surgery in elderly patients.
Background
Treatment strategies for diverticulitis with abscess formation have shifted from (emergency) surgical treatment to non‐surgical management (antibiotics with or without percutaneous ...drainage (PCD)). The aim was to assess outcomes of non‐surgical treatment and to identify risk factors for adverse outcomes.
Methods
Patients with a first episode of CT‐diagnosed diverticular abscess (modified Hinchey Ib or II) between January 2008 and January 2015 were included retrospectively, if initially treated non‐surgically. Baseline characteristics, short‐term (within 30 days) and long‐term treatment outcomes were recorded. Treatment failure was a composite outcome of complications (perforation, colonic obstruction and fistula formation), readmissions, persistent diverticulitis, emergency surgery, death, or need for PCD in the no‐PCD group. Regression analyses were used to analyse risk factors for treatment failure, recurrences and surgery.
Results
Overall, 447 patients from ten hospitals were included (Hinchey Ib 215; Hinchey II 232), with a median follow‐up of 72 (i.q.r. 55–93) months. Most patients were treated without PCD (332 of 447, 74·3 per cent). Univariable analyses, stratified by Hinchey grade, showed no differences between no PCD and PCD in short‐term treatment failure (Hinchey I: 22·3 versus 33 per cent, P = 0·359; Hinchey II: 25·9 versus 36 per cent, P = 0·149) or emergency surgery (Hinchey I: 5·1 versus 6 per cent, P = 0·693; Hinchey II: 10·4 versus 15 per cent, P = 0·117), but significantly more complications were found in patients with Hinchey II disease undergoing PCD (12 versus 3·7 per cent; P = 0·032). Multivariable analyses showed that treatment strategy (PCD versus no PCD) was not independently associated with short‐term treatment failure (odds ratio (OR) 1·47, 95 per cent c.i. 0·81 to 2·68), emergency surgery (OR 1·29, 0·56 to 2·99) or long‐term surgery (hazard ratio 1·08, 95 per cent c.i. 0·69 to 1·69). Abscesses of at least 3 cm in diameter were associated with short‐term treatment failure (OR 2·05, 1·09 to 3·86), and abscesses of 5 cm or larger with the need for surgery during short‐term follow‐up (OR 2·96, 1·03 to 8·13).
Conclusion
The choice between PCD with antibiotics or antibiotics alone as initial non‐surgical treatment of Hinchey Ib and II diverticulitis does not seem to influence outcomes.
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
Abstract
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.
Graphical Abstract
This population-based study determined the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography. The results showed that preoperative MRI led to substantial overstaging in patients who underwent local excision or total mesorectal incision surgery for cT1–2 rectal cancer, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.
Graphical Abstract
Imaging weakness
Textbook outcome is a composite measure of combined outcome indicators, which has been suggested to be of additional value over single outcome parameters in clinical auditing of surgical treatment. ...This study aimed to assess textbook outcome after rectal cancer surgery as short-term marker for quality of care.
Patients who underwent elective rectal cancer surgery between 2012 and 2019 and registered in the Dutch ColoRectal Audit were included. Textbook outcome was achieved when the following criteria were met: 30-day and primary hospital admission survival, no reintervention, tumour-free margins, no postoperative complications, a hospital stay of less than 14 days and no readmission. Hospital variation was evaluated in case-mix corrected funnel-plots. A multilevel logistic regression analysis was performed to identify associated factors with textbook outcome.
The study population consisted of 20,521 patients who underwent primary rectal cancer surgery, of whom 56.3% achieved textbook outcome. Postoperative complications were the main contributor to not achieving textbook outcome. Case-mix corrected funnel plots demonstrated that underperforming hospitals in 2012–2015 were no underperformers in 2016–2019 anymore. Female sex, laparoscopic surgery, and rectal resection without defunctioning stoma creation were positively associated with textbook outcome.
Textbook outcome after rectal cancer resection is mainly driven by postoperative complications. Although textbook outcome showed some discriminating value for identifying underperforming hospitals, it does not fit the plan-do-check-act cycle of clinical auditing. In our opinion, textbook outcome has little added value to the current outcome indicators for rectal cancer surgery.
Aims/hypothesis Genome-wide association studies have recently identified novel type 2 diabetes susceptibility gene regions. We assessed the effects of six of these regions on insulin secretion as ...determined by a hyperglycaemic clamp. Methods Variants of the HHEX/IDE, CDKAL1, SLC30A8, IGF2BP2 and CDKN2A/CDKN2B genes were genotyped in a cohort of 146 participants with NGT and 126 with IGT from the Netherlands and Germany, who all underwent a hyperglycaemic clamp at 10 mmol/l glucose. Results Variants of CDKAL1 and IGF2BP2 were associated with reductions in first-phase insulin secretion (34% and 28%, respectively). The disposition index was also significantly reduced. For gene regions near HHEX/IDE, SLC30A8 and CDKN2A/CDKN2B we did not find significant associations with first-phase insulin secretion (7-18% difference between genotypes; all p > 0.3). None of the variants showed a significant effect on second-phase insulin secretion in our cohorts (2-8% difference between genotypes, all p > 0.3). Furthermore, the gene variants were not associated with the insulin sensitivity index. Conclusions Variants of CDKAL1 and IGF2BP2 attenuate the first phase of glucose-stimulated insulin secretion but show no effect on the second phase of insulin secretion. Our results, based on hyperglycaemic clamps, provide further insight into the pathogenic mechanism behind the association of these gene variants with type 2 diabetes.
Sudden cardiac death from ventricular fibrillation during acute myocardial infarction is a leading cause of total and cardiovascular mortality. To our knowledge, we here report the first genome-wide ...association study for this trait, conducted in a set of 972 individuals with a first acute myocardial infarction, 515 of whom had ventricular fibrillation and 457 of whom did not, from the Arrhythmia Genetics in The Netherlands (AGNES) study. The most significant association to ventricular fibrillation was found at 21q21 (rs2824292, odds ratio = 1.78, 95% CI 1.47-2.13, P = 3.3 × 10−10). The association of rs2824292 with ventricular fibrillation was replicated in an independent case-control set consisting of 146 out-of-hospital cardiac arrest individuals with myocardial infarction complicated by ventricular fibrillation and 391 individuals who survived a myocardial infarction (controls) (odds ratio = 1.49, 95% CI 1.14-1.95, P = 0.004). The closest gene to this SNP is CXADR, which encodes a viral receptor previously implicated in myocarditis and dilated cardiomyopathy and which has recently been identified as a modulator of cardiac conduction. This locus has not previously been implicated in arrhythmia susceptibility.
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.
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.
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)).
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.
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