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Background: Patients with a re-recurrent hernia may account for up to 20% of all incisional hernia (IH) patients. IH repair in this population may be complex due to an altered anatomical and biological situation as a result of previous procedures and outcomes of IH repair in this population have not been thoroughly assessed. This study aims to assess outcomes of IH repair by dedicated hernia surgeons in patients who have already had two or more re-recurrences. Methods: A propensity score matched analysis was performed using a registry-based, prospective cohort. Patients who underwent IH repair after ≥ 2 re-recurrences operated between 2011 and 2018 and who fulfilled 1 year follow-up visit were included. Patients with similar follow-up who underwent primary IH repair were propensity score matched (1:3) and served as control group. Patient baseline characteristics, surgical and functional outcomes were analyzed and compared between both groups. Results: Seventy-three patients operated on after ≥ 2 IH re-recurrences were matched to 219 patients undergoing primary IH repair. After propensity score matching, no significant differences in patient baseline characteristics were present between groups. The incidence of re-recurrence was similar between groups (≥ 2 re-recurrences: 25% versus control 24%, p = 0.811). The incidence of complications, as well as long-term pain, was similar between both groups. Conclusion: IH repair in patients who have experienced multiple re-recurrences results in outcomes comparable to patients operated for a primary IH with a similar risk profile. Further surgery in patients who have already experienced multiple hernia re-recurrences is justifiable when performed by a dedicated hernia surgeon.

Background: Task-specific checklists and global rating scales are both recommended assessment tools to provide constructive feedback on surgical performance. This study evaluated the most effective feedback tool by comparing the effects of the Observational Clinical Human Reliability Analysis (OCHRA) and the Objective Structured Assessment of Technical Skills (OSATS) on surgical performance in relation to the visual-spatial ability of the learners. Methods: In a randomized controlled trial, medical students were allocated to either the OCHRA (n = 25) or OSATS (n = 25) feedback group. Visual-spatial ability was measured by a Mental Rotation Test. Participants performed an open inguinal hernia repair procedure on a simulation model twice. Feedback was provided after the first procedure. Improvement in performance was evaluated blindly using a global rating scal

OBJECTIVE: The objective of this study was to compare the effects of cognitive load and surgical performance in medical students that performed the open inguinal hernia repair after preparation with step-by-step video-demonstration versus continuous video-demonstration. Hypothetically, the step-by-step group will perceive lower extraneous load during the preparation of the surgical procedure compared to the continuous group. Subsequently, fewer errors will be m

Objective: To investigate differences in postoperative outcomes between short-course radiotherapy and delayed surgery (SCRT-delay) and chemoradiation (CRT) in patients with locally advanced rectal cancer (LARC). Background: Previous trials suggest that SCRT-delay could serve as an adequate neoadjuvant treatment for LARC. Therefore, in frail LARC patients SCRT-delay is recommended as an alternative to CRT. However, data on postoperative outcomes after SCRT-delay in comparison to CRT is scarce. Methods: This was an observational study with data from the Dutch ColoRectal Audit (DCRA). LARC patients who underwent surgery (2014–2017) after an interval of ≥6 weeks were included. Missing values were replaced by multiple imputation. Propensity score matching (PSM), using age, Charlson Comorbidity Index, cT-stage and surgical procedure, was applied to create comparable groups. Differences in postoperative outcomes were analyzed using Chi-square test for categorical variables, independent sample t-test for continuous variables and Mann-Whitney U test for non-parametric data. Results: 2926 patients were included. In total, 288 patients received SCRT-delay and 2638 patients underwent CRT. Patients in the SCRT-delay group were older and had more comorbidities. Also, ICU-admissions and permanent colostomies were more common, as well as pulmonic, cardiologic, infectious and neurologic complications. After PSM, both groups comprised 246 patients with equivalent age, comorbidities and tumor stage. There were no differences in postoperative complications. Conclusion: Postoperative complications were not increased in LARC patients undergoing SCRT-delay as neoadjuvant treatment. Regarding treatment-related complications, SCRT-delay is a safe alternative neoadjuvant treatment option for frail LARC patients.

Purpose: To establish optimal management of patients with an umbilical hernia complicated by liver cirrhosis and ascites. Methods: Patients with an

Background Most interventions to improve patient safety (Patient Safety Practices (PSPs)), are introduced without engaging front-line professionals. Administrative staff, managers and sometimes a few professionals, representing only one or two disciplines, decide what to change and how. Consequently, PSPs are not fully adapted to the professionals’ needs or to the local context and as a result, adoption is low. To support adoption, two theoretical concepts, Participatory Design and Experiential Learning were combined in a new model: Adaptive Design. The aim was to explore whether Adaptive Design supports adaptation and adoption of PSPs by engaging all professionals and creating time to (re) design, reflect and learn as a team. The Time Out Procedure (TOP) and Debriefing (plus) for improving patient safety in the operating theatre (OT) was used as PSP. Methods Qualitative exploratory multi-site study using participatory action research as a research design. The implementation process consisted of four phases: 1) start-up: providing information by presentations and team meetings, 2) pilot: testing the prototype with 100 surgical procedures, 3) small scale implementation: with one or two surgical disciplines, 4) implementation hospital-wide: including all surgical disciplines. In iterations, teams (re) designed, tested, evaluated, and if necessary adapted TOPplus. Gradually all professionals were included. Adaptations in content, process and layout of TOPplus were measured following each iteration. Adoption was monitored until final implementation in every hospital’s OT. Results 10 Dutch hospitals participated. Adaptations varied per hospital, but all hospitals adapted both procedures. Adaptations concerned the content, process and layout of TOPplus. Both procedures were adopted in all OTs, but user participation and time to include all users varied between hospitals. Ultimately all users were actively involved and TOPplus was implemented in all OTs. Conclusions Engagi

Background: Incisional hernias can be associated with pain or discomfort. Surgical repair especially mesh reinforcement, may likewise induce pain. The primary objective was to assess the incidence of pain after hernia repair in patients with and without pre-operative pain or discomfort. The secondary objectives were to determine the preferred mesh type, mesh location and surgical technique in minimizing postoperative pain or discomfort. Materials and methods: A registry-based prospective cohort study was performed, including patients undergoing incisional hernia repair between September 2011 and May 2019. Patients with a minimum follow-up of 3–6 months were included. The incidence of hernia related pain and discomfort was recorded perioperatively. Results: A total of 1312 patients were included. Pre-operatively, 1091 (83%) patients reported pain or discomfort. After hernia repair, 961 (73%) patients did not report pain or discomfort (mean follow-up = 11.1 months). Of the pre-operative asymptomatic patients (n = 221), 44 (20%, moderate or severe pain: n = 14, 32%) reported pain or discomfort after mean follow-up of 10.5 months. Of those patients initially reporting pain or discomfort (n = 1091), 307 (28%, moderate or severe pain: n = 80, 26%) still reported pain or discomfort after a mean follow-up of 11.3 months postoperatively. Conclusion: In symptomatic incisional hernia patients, hernia related complaints may be resolved in the majority of cases undergoing surgical repair. In asymptomatic incisional hernia patients, pain or discomfort may be induced in a considerable number of patients due to surgical repair and one should be aware if this postoperative complication.

Background: The pursuit of high standards and continuous self-improvement are important aspects of a professional attitude in medicine. However, when identity and self-esteem are dependent on flawless performance, healthy s

Background: Leakage of the esophago-gastrostomy after esophagectomy with gastric tube reconstruction is a serious complication. Anastomotic leakage occurs in up to 20% of patients and a compromised perfusion of the gastric tube is thought to play an important role. This meta-analysis aimed to investigate whether arterial calcification is a risk factor for anastomotic leakage in esophageal surgery. Method: Embase, Medline, PubMed, Cochrane databases and Google scholar databases were systematically searched for studies that assessed arterial calcification of the thoracic aorta, celiac axis including its branches, or the superior mesenteric artery in patients that underwent esophagectomy with gastric tube reconstruction. The degree of calcification was classified as absent, minor or major. A “random-effects model” was used to calculate pooled Odds Ratios (OR) and 95% confidence intervals (CI). Heterogeneity was assessed using the Q-test and I2-test. Results: From the 456 articles retrieved, seven studies were selected including 1.860 patients. The median (range) of anastomotic leakage was 17.2% (12.7–24.8). Meta-analysis showed a statistically significant association between increased calcium score and anastomotic leakage for the thoracic aorta (OR 2.18(CI 1.42–3.34)), celiac axis (OR 1.62(CI 1.15–2.29)) and right post-celiac axis (common hepatic, gastroduodenal and right gastroepiploic arteries) (OR 2.69(CI 1.27–5.72)). Heterogeneity was observed for analysis on calcification of the thoracic aorta and celiac axis (I2 = 71% and 59%, respectively) but not for the right branches of the celiac axis (I2 = 0%). Conclusion: This meta-analysis, including good quality studies, showed a statistically significant association between arterial calcification and anastomotic leakage in patients who underwent esophagectomy with gastric tube reconstruction.

Background Most interventions to improve patient safety (Patient Safety Practices (PSPs)), are introduced without engaging front-line professionals. Administrative staff, managers and sometimes a few professionals, representing only one or two disciplines, decide what to change and how. Consequently, PSPs are not fully adapted to the professionals’ needs or to the local context and as a result, adoption is low. To support adoption, two theoretical concepts, Participatory Design and Experiential Learning were combined in a new model: Adaptive Design. The aim was to explore whether Adaptive Design supports adaptation and adoption of PSPs by engaging all professionals and creating time to (re) design, reflect and learn as a team. The Time Out Procedure (TOP) and Debriefing (plus) for improving patient safety in the operating theatre (OT) was used as PSP. Methods Qualitative exploratory multi-site study using participatory action research as a research design. The implementation process consisted of four phases: 1) start-up: providing information by presentations and team meetings, 2) pilot: testing the prototype with 100 surgical procedures, 3) small scale implementation: with one or two surgical disciplines, 4) implementation hospital-wide: including all surgical disciplines. In iterations, teams (re) designed, tested, evaluated, and if necessary adapted TOPplus. Gradually all professionals were included. Adaptations in content, process and layout of TOPplus were measured following each iteration. Adoption was monitored until final implementation in every hospital’s OT. Results 10 Dutch hospitals participated. Adaptations varied per hospital, but all hospitals adapted both procedures. Adaptations concerned the content, process and layout of TOPplus. Both procedures were adopted in all OTs, but user participation and time to include all users varied between hospitals. Ultimately all users were actively involved and TOPplus was implemented in all OTs. Conclusions Engagi

Background: Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. Methods: Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. Results: The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. Conclusion: The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.

Purpose: Anastomotic leakage (AL) is the most severe complication following colorectal resection and is associated with increased mortality. The main group of enzymes responsible for collagen and protein degradation in the extracellular matrix is matrix metalloproteinases. The literature is conflicting regarding anastomotic leakage and the degradation of extracellular collagen by matrix metalloproteinase-9 (MMP-9). In this systematic review, the p

Purpose: In this study, a three-step novel surgical technique was developed for incisional hernia, in which a laparoscopic procedure with a mini-laparotomy is combined: so-called ‘three-step incisional hybrid repair’. The aim of this study was to reduce the risk of intestinal lacerations during adhesiolysis and recurrence rate by better symmetrical overlap placement of the mesh. Objectives: To evaluate first perioperative outcomes with this technique. Methods: From 2016 to 2020, 70 patients (65.7% females) with an incisional hernia of > 2 and ≤ 10 cm underwent a elective three-step incisional hybrid repair in two non-academic hospitals performed by two surgeons specialised in abdominal wall surgery. Intra- and postoperative complications, operation time, hospitalisation time and hernia recurrence were assessed. Results: Mean operation time was 100 min. Mean hernia size was 4.8 cm; 45 patients (64.3%) had a hernia of 1–5 cm, 25 patients (35.7%) of 6–10 cm. Eight patients had a grade 1 complication (11.4%), five patients a grade 2 (7.1%), two patients (2.8%) a grade 4 complication and one patient (1.4%) a grade 5 complication. Five patients had an intraoperative complication (7.0%), two enterotomies, one serosa injury, one omentum bleeding and one laceration of an epigastric vessel. Mean length of stay was 3.3 days. Four patients (5.6%) developed a hernia recurrence during a mean follow-up of 19.5 weeks. Conclusion: A three-step hybrid incisional hernia repair is a safe alternative for incisional hernia repair. Intraoperative complications rate was low.

BACKGROUND: Incisional hernia is a frequent complication after abdominal surgery. The aim of this study was to assess the efficacy of prophylactic mesh reinforcement (PMR) after midline laparotomy in reducing the incidence of incisional hernia. METHODS: A meta-analysis was conducted following PRISMA guidelines. The primary outcome was the incidence of incisional hernia after follow-up of at least 12 months. Secondary outcomes were postoperative complications. Only RCTs were included. A random-effects model was used for the meta-analysis, and trial sequential analysis was conducted. RESULTS: Twelve RCTs were included, comprising 1815 patients. The incidence of incisional hernia was significantly lower after PMR compared with sutured closure (risk ratio (RR) 0·35, 95 per cent c.i. 0·21 to 0·57; P < 0·001). Both onlay (RR 0·26, 0·11 to 0·67; P = 0·005) and retromuscular (RR 0·28, 0·10 to 0·82; P = 0·02) PMR led to a significant reduction in the rate of incisional hernia. The occurrence of seroma was higher in patients who had onlay PMR (RR 2·23, 1·10 to 4·52; P = 0·03). PMR did not result in an increased rate of surgical-site infection. CONCLUSION: PMR of a midline laparotomy using an onlay or retromuscular technique leads to a significant reduction in the rate of incisional hernia in high-risk patients. Individual risk factors should be taken into account to select patients who will benefit most. [Correction added on 19 February 2020, after first online publication: J. García Alamino has been amended to J. M. Garcia-Alamino].ANTECEDENTES: La eventración (hernia incisional) es una complicación frecuente de la cirugía abdominal. El objetivo es evaluar la eficacia de la inserción de una malla profiláctica de refuerzo (prophylactic mesh reinforcement, PMR) después de la laparotomía media para reducir la incidencia de eventración. MÉTODOS: Se realizó un metaanálisis siguiendo las recomendaciones PRISMA. La variable principal fue la incidencia de eventración después de un s

Purpose: The optimal surgical approach for perforated diverticulitis with purulent or fecal peritonitis (Hinchey grade III or IV) remains debated. In recent years, accumulating evidence comparing sigmoid resection with primary anastomosis (PA) with the Hartmann’s procedure (HP) was presented. Therefore, the aim was to provide an updated and extensive synthesis of the available evidence. Methods: A systematic search in Embase, MEDLINE, Cochrane, and Web of Science databases was performed. Studies comparing PA to HP for adult patients with Hinchey III or IV diverticulitis were included. Data on mortality, morbidity, stoma reversal, and patient-reported and cost-related outcomes were extracted. Random effects models were used to pool data and estimate odds ratios (ORs). Results: From a total of 1560 articles, four randomized controlled trials and ten observational studies were identified, reporting on 1066 Hinchey III/IV patients. Based on trial outcomes, PA was found to be favorable over HP in terms of stoma reversal rates (OR 2.62, 95% CI 1.29, 5.31) and reversal-related morbidity (OR 0.33, 95% CI 0.16, 0.69). No differences in mortality (OR 0.83, 95% CI 0.32, 2.19), morbidity (OR 0.99, 95% CI 0.65, 1.51), and reintervention rates (OR 0.90, 95% CI 0.39, 2.11) after the index procedure were demonstrated. Data on patient-reported and cost-related outcomes were scarce, as well as outcomes in PA patients with or without ileostomy construction and Hinchey IV patients. Conclusion: Although between-study heterogeneity needs to be taken into account, the present results indicate that primary anastomosis seems to be the preferred option over Hartmann’s procedure in selected patients with Hinchey III or IV diverticulitis.

Background: Several studies have been published favouring sigmoidectomy with primary anastomosis over Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis (Hinchey grade III or IV), but cost-related outcomes were rarely reported. The present study aimed to evaluate costs and cost-effectiveness within the DIVA arm of the Ladies trial. Methods: This was a cost-effectiveness analysis of the DIVA arm of the multicentre randomized Ladies trial, comparing primary anastomosis over Hartmann's procedure for Hinchey grade III or IV diverticulitis. During 12-month follow-up, data on resource use, indirect costs (Short Form Health and Labour Questionnaire) and quality of life (EuroQol Five Dimensions) were collected prospectively, and analysed according to the modified intention-to-treat principle. Main outcomes were incremental cost-effectiveness (ICER) and cost–utility (ICUR) ratios, expressed as the ratio of incremental costs and the incremental probability of being stoma-free or incremental quality-adjusted life-years respectively. Results: Overall, 130 patients were included, of whom 64 were allocated to primary anastomosis (46 and 18 with Hinchey III and IV disease respectively) and 66 to Hartmann's procedure (46 and 20 respectively). Overall mean costs per patient were lower for primary anastomosis (€20 544, 95 per cent c.i. 19 569 to 21 519) than Hartmann's procedure (€28 670, 26 636 to 30 704), with a mean difference of €–8126 (–14 660 to –1592). The ICER was €–39 094 (95 per cent bias-corrected and accelerated (BCa) c.i. –1213 to –116), indicating primary anastomosis to be more cost-effective. The ICUR was €–101 435 (BCa c.i. –1 113 264 to 251 840). Conclusion: Primary anastomosis is more cost-effective than Hartmann's procedure for perforated diverticulitis with purulent or faecal peritonitis.

Background: Most interventions to improve patient safety (Patient Safety Practices (PSPs)), are introduced without engaging front-line professionals. Administrative staff, managers and sometimes a few professionals, representing only one or two disciplines, decide what to change and how. Consequently, PSPs are not fully adapted to the professionals' needs or to the local context and as a result, adoption is low. To support adoption, two theoretical concepts, Participatory Design and Experiential Learning were combined in a new model: Adaptive Design. The aim was to explore whether Adaptive Design supports adaptation and adoption of PSPs by engaging all professionals and creating time to (re) design, reflect and learn as a team. The Time Out Procedure (TOP) and Debriefing (plus) for improving patient safety in the operating theatre (OT) was used as PSP. Methods: Qualitative exploratory multi-site study using participatory action research as a research design. The implementation process consisted of four phases: 1) start-up: providing information by presentations and team meetings, 2) pilot: testing the prototype with 100 surgical procedures, 3) small scale implementation: with one or two surgical disciplines, 4) implementation hospital-wide: including all surgical disciplines. In iterations, teams (re) designed, tested, evaluated, and if necessary adapted TOPplus. Gradually all professionals were included. Adaptations in content, process and layout of TOPplus were measured following each iteration. Adoption was monitored until final implementation in every hospital's OT. Results: 10 Dutch hospitals participated. Adaptations varied per hospital, but all hospitals adapted both procedures. Adaptations concerned the content, process and layout of TOPplus. Both procedures were adopted in all OTs, but user participation and time to include all users varied between hospitals. Ultimately all users were actively involved and TOPplus was implemented in all OTs. Conclusions: En

Purpose: Parastomal hernia (PSH) is a common complication following stoma formation. The incidence of PSH varies widely due to several factors including differences in diagnostic modality, observer, definition, and classification used for diagnosing PSH. The aim of this systematic review was to evaluate the diagnostic accuracy of the modalities used to identify PSH. Methods: Embase, MEDLINE, Cochrane, Web of Science, and Google Scholar databases were searched. Studies reporting PSH incidence rates detected by two or more different diagnostic modalities or inter-observer variation on one diagnostic modality were included. Article selection and assessment of study quality were conducted independently by two researchers using Cochrane Collaboration’s tool for assessing risk of bias. PROSPERO registration: CRD42018112732. Results: Twenty-nine studies (n = 2514 patients) were included. Nineteen studies compared CT to clinical examination with relative difference in incidence rates ranging from 0.64 to 3.0 (n = 1369). Overall, 79% of studies found an increase in incidence rate when using CT. Disagreement between CT and clinical examination ranged between 0 and 37.3% with pooled inter-modality agreement Kappa value of 0.64 (95% CI 0.52–0.77). Four studies investigated the diagnostic accuracy of ultrasonography (n = 103). Compared with peroperative diagnosis, CT and ultrasonography both seemed accurate imaging modalities with a sensitivity of 83%. Conclusion: CT is an accurate diagnostic modality for PSH diagnosis and increases PSH detection rates, as compared with clinical examination. Studies that specially focus on the diagnostic accuracy are needed and should aim to take patient-reported outcomes into account. A detailed description of the diagnostic approach, modality, definition, and involved observers is prerequisite for future PSH research.

_Purpose:_ After closure of laparotomies, sutures may pull through tissue due to too high intra-abdominal pressure or suture tension, resulting in burst abdomen and incisional hernia. The objective of this study was to measure the suture tension in small and large bites with a new suture material. _Methods:_ Closure of the linea alba was performed with small bites (i.e., 5 mm between two consecutive stitches and 5 mm distance from the incision) and large bites (i.e., 10 mm × 10 mm) with Duramesh™ size 0 (2 mm) and PDS II 2-0 in 24 experiments on six porcine abdominal walls. The abdominal wall was fixated on an artificial computer-controlled insufflatable abdomen, kn

Background: The objective of this study was to assess whether a zinc-impregnated polypropylene mesh (ZnMesh) has better antibacterial properties in a contaminated environment compared with a regular polypropylene mesh. Materials and methods: Thirty-eight Wistar Han rats underwent cecal ligation and puncture to induce peritonitis 24 h before implantation of an intraperitoneal ZnMesh or a regular polypropylene mesh. Primary outcome was the number of colony forming units (CFU) per sample (mesh and abdominal wall). Secondary outcomes were macroscopic (incorporation of mesh, abscesses, and adhesions on mesh surface) and histological (inflammatory cell reaction, mesh-specific parameters, and collagen deposition) parameters. All outcomes were evaluated after 30 and 90 d. Results: After 30 d, no significant difference in CFU per sample was present between the ZnMesh and control groups. After 90 d, a lower number of CFU per sample was present in the ZnMesh group compared with the control group (trypticase soy agar with 5% sheep blood: 0 log10 CFU/sample IQR: 0-1.40 versus 1.58 log10 CFU/sample IQR: 0-4.30, P = 0.012; MacConkey: 0 log10 CFU/sample IQR: 0-2.65 versus 1.18 log10 CFU/sample IQR: 0-4.04, P = 0.438). After 90 d, the percentage of adhesions on mesh surface was significantly higher in the ZnMesh group (95% IQR: 60%-100% versus 50% IQR: 23%-75%, P = 0.029). No differences were seen in other macroscopic outcomes or histology. Conclusions: A significantly lower number of CFU per sample was found in the ZnMesh group after 90 d. After 30 d, no statistically significant differences in CFU per sample were seen. This result suggests that the ZnMesh group has better antibacterial properties in a contaminated environment. However, this is at the cost of a significantly higher percentage of adhesions.

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.

Purpose: Simulation training allows trainees to gain experience in a safe environment. Computer simulation and animal models to practice a Lichtenstein open inguinal hernia repair (LOIHR) are available; however, a low-cost model is not. We constructed an inexpensive model using fabric, felt, and yarn that simulates the anatomy and hazards of the LOIHR. This study examined the fidelity, and perceived usefulness of our developed simulation model by surgical residents and expert surgeons. Methods: A total of 66 Dutch surgical residents and ten international expert surgeons were included. All participants viewed a video-demonstration of LOIHR on the simulation model and subsequently performed the surgery themselves on the model. Afterward, they assessed the model by rating 13 statements concerning its fidelity (six model, three equipment, and four psychological) and six usefulness statements on

Background Proper documentation is an essential part of patient safety and quality of care in the surgical field. Surgical procedures are traditionally documented in narrative operative reports which are subjective by nature and often lack essential information. This systematic review will analyze the added value of the newly emerged synoptic reporting technique in the surgical setting. Methods A systematic review was conducted to compare the completeness and the user-friendliness of the synoptic operative report to the narrative operative report. A literature search was performed in EMBASE, Ovid MEDLINE, Web of Science, Cochrane CENTRAL, and Google Scholar for studies published up to April 6, 2018. The Newcastle–Ottawa Scale was utilized for the risk of bias assessment of the included articles. PROSPERO registration number was: CRD42018093770. Results Overall and subsection completion of the operative report was higher in the synoptic operative report. The time until completion of the operative report and the data extraction time were shorter in the synoptic report. One exception was the specific details section concerning the operative procedure, as this was generally reported more frequently in the narrative report. The use of mandatory fields in the synoptic report resulted in more completely reported operative outcomes with completion percentages close to 100%. Conclusions The

Aim Laparoscopic peritoneal lavage has increasingly been investigated as a promising alternative to sigmoidectomy for perforated diverticulitis with purulent peritonitis. Most studies only reported outcomes up to 12 months. Therefore, the objective of this study was to evaluate long-term outcomes of patients treated with

_Background_ Incarceration of primary and incisional hernias often results in emergency surgery. The objective of this study was to evaluate the relation of defect size and location with incarceration. Secondary objectives comprised identification of additional patient factors associated with an incarcerated hernia. _Methods_ A registry-based prospective study was performed of all consecutive patients undergoing hernia surgery between September 2011 and February 2016. Multivariate logistic regression was performed to identify risk factors for incarceration. _Results_ In total, 83 (3.5%) of 2352 primary hernias and 79 (3.7%) of 2120 incisional hernias had a non-reducible incarceration. For primary hernias, a defect width of 3–4 cm compared to defects of 0–1 cm was significantly associated with an incarcerated hernia (OR 2.85, 95% CI 1.57–5.18, p = 0.0006). For incisional hernias, a defect width of 3–4 cm compared to defects of 0–2 cm was significantly associated with an incarceration (OR 2.14, 95% CI 1.07–4.31, p = 0.0324). For primary hernias, defects in the peri- and infra-umbilical region portrayed a significantly increased odds for incarceration as compared to supra-umbilical defects (OR 1.98, 95% CI 1.02–3.85, p = 0.043). Additionally, in primary hernias age, BMI, and constipation were associated with incarceration. In incisional hernias age, BMI, female sex, diabetes mellitus and ASA classification were associated with incarceration. _Conclusion_ For primary and incisional hernias, mainly defects of 3–4 cm were associated with incarceration. For primary hernias, mainly defects located in the peri- and infra-umbilical region were associated with incarceration. Based on patient and hernia characteristics, patients with increased odds for incarceration may be selected and these patients may benefit from elective surgical treatment.

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 c

Background: Incisional hernia is a frequent complication after abdominal surgery. A risk factor for incisional hernia, related to body composition, is obesity. Poor skeletal muscle mass might also be a risk factor, as it may result in weakness of the abdominal wall. However, it remains unknown if sarcopenia (i.e. low skeletal muscle mass) is a risk factor for incisional hernia. Therefore, this study aims to investigate whether a relation between sarcopenia and incisional hernia exists. Methods: Patients from the STITCH trial, who underwent elective midline laparotomy, were included. Computed tomography examinations performed within 3 months preoperatively were used to measure the skeletal muscle index (SMI; cm2/m2). Primarily, SMI measured continuously, sarcopenia based on previously described cut-off values for the SMI, and sarcopenia as the lowest gender-specific SMI quartile were assessed as measures to predict incisional hernia occurrence. Secondary, the association between these three measures and post-operative complications was investigated. Results: In total, 283 patients (45.2% male; mean age 63.7 years; mean BMI 25.36 kg/m2) were included, of whom 52 (18%) develo

BACKGROUND: Incisional heia is a frequent complication of midline laparotomy. The use of mesh in hernia repair has been reported to lead to fewer recurrences compared to primary repair. However, in Ventral Hernia Working Group (VHWG) Grade 3 hernia patients, whose hernia is potentially contaminated, synthetic mesh is prone to infection. There is a strong preference for resorbable biological mesh in contaminated fields, since it is more able to resist infection, and because it is fully resorbed, the chance of a foreign body reaction is reduced. However, when not crosslinked, biological resorbable mesh products tend to degrade too quickly to facilitate native cellular ingrowth. Phasix™ Mesh is a biosynthetic mesh with both the biocompatibility and resorbability of a biological mesh and the mechanical strength of a synthetic mesh. This multi-center single-arm study aims to collect data on safety and performance of Phasix™ Mesh in Grade 3 hernia patients. METHODS: A total of 85 VHWG Grade 3 hernia patients will be treated with Phasix™ Mesh in 15 sites across Europe. The primary outcome is Surgical Site Occurrence (SSO) including hematoma, seroma, infection, dehiscence and fistula formation (requiring intervention) through 3 months. Secondary outcomes include recurrence, infection and quality of life related outcomes after 24 months. Follow-up visits will be at drain removal (if drains were not placed, then on discharge or staple removal instead) and in the 1st, 3rd, 6th, 12th, 18th and 24th month after surgery. CONCLUSION: Based on evidence from this clinical study Depending on the results this clinical study will yield, Phasix™ Mesh may become a preferred treatment option in VHWG Grade 3 patients. TRIAL REGISTRATION: The trial was registered on March 25, 2016 on clinicaltrials.gov: NCT02720042 .

Aim: Stoma reversal might lead to a stoma site incisional hernia. Recently, prophylactic mesh reinforcement of the stoma site has gained increased attention, supporting the need for accurate data on the incidence of and risk factors for stoma site incisional hernia and to identify high-risk patients. The aim of this study was to assess incidence, risk factors and prevention of stoma site incisional hernias. Method: Embase, MEDLINE, Web of Science, Cochrane and Google Scholar databases were searched. Studies reporting the incidence of stoma site incisional hernia after stoma reversal were included. Study quality was assessed with the Newcastle–Ottawa Scale and Cochrane risk of bias tool. Data on incidence, risk factors and prophylactic mesh reinforcement were extracted. Results: Of 1440 articles found, 33 studies comprising 4679 reversals were included. The overall incidence of incisional hernia was 6.5% [range 0%–38%, median follow-up 27.5 (17.54–36) months]. Eleven studies assessed stoma site incisional hernia as the primary end-point, showing an incidence of 17.7% [range 1.7%–36.1%, median follow-up 28 (15.25–51.70) months]. Body mass index, diabetes and surgery for malignant disease were found to be independent risk factors, as derived from eight studies. Two retrospective comparative cohort studies showed significantly lower rates of stoma site incisional hernia with prophylactic mesh reinforcement compared with nonmesh controls [6.4% vs 36.1% (P = 0.001); 3% vs 19% (P = 0.04)]. Conclusion: Stoma site incisional hernia should not be underestimated as a long-term problem. Body mass index, diabetes and malignancy seem to be potential risk factors. Currently, limited data are available on the outcomes of prophylactic mesh reinforcement to prevent stoma site incisional hernia.

Background: Diverticulitis can lead to localized or generalized peritonitis and consequently induce abdominal adhesion formation. If adhesions would lead to abdominal complaints, it might be expected that these would be more prominent after operation for perforated diverticulitis with peritonitis than after elective sigmoid resection. Aims: The primary outcome of the study was the incidence of abdominal complaints in the long-term after acute and elective surgery for diverticulitis. Methods: During the period 2003 through 2009, 269 patients were operat

Purpose: Ventral hernia repair is one of the most frequently performed surgical procedures, though recurrences are common. Recurrence can be caused by impaired collagen formation or maturation; hence, patients with Ehlers-Danlos syndrome (EDS) are potentially at increased risk for hernia recurrence. EDS causes altered collagen metabolism, though little is known about the influen

Purpose: Liver metastasis develops in >50% of patients with colorectal cancer (CRC), and is a leading cause of CRC-related mortality. We aimed to identify which inhibitory immune checkpoint pathways can be targeted to enhance functionality of intra-tumoral T-cells in mismatch repair-proficient liver metastases of colorectal cancer (LM-CRC). Methodology: Intra-tumoral expression of multiple inhibitory molecules was compared among mismatch repair-proficient LM-CRC, peritoneal metastases of colorectal cancer (PM-CRC) and primary CRC. Expression of inhibitory molecules was also analyzed on leukocytes isolated from paired resected metastatic liver tumors, tumor-free liver tissues, and blood of patients with mismatch repair-proficient LM-CRC. The effects of blocking inhibitory pathways on tumor-infiltrating T-cell responses were studied in ex vivo functional assays. Results: Mismatch repair-proficient LM-CRC showed higher expression of inhibitory receptors on intra-tumoral T-cells and contained higher proportions of CD8+ T-cells, dendritic cells and monocytes than mismatch repair-proficient primary CRC and/or PM-CRC. Inhibitory receptors LAG3, PD-1, TIM3 and CTLA4 were higher expressed on CD8+ T-cells, CD4+ T-helper and/or regulatory T-cells in LM-CRC tumors compared with tumor-free liver and blood. Antibody blockade of LAG3 or PD-L1 increased proliferation and effector cytokine production of intra-tumoral T-cells isolated from LM-CRC in response to both polyclonal and autologous tumor-specific stimulations. Higher LAG3 expression on intra-tumoral CD8+ T-cells associated with longer progression-free survival of LM-CRC patients. Conclusion: Mismatch repair-proficient LM-CRC may be more sensitive to immune checkpoint inhibitors than mismatch repair-proficient primary CRC. Blocking LAG3 enhances tumor-infiltrating T-cell responses of mismatch repair-proficient LM-CRC, and therefore may be a new promising immunotherapeutic target for LM-CRC.

Background: Tissue adhesives (TA) may be useful to strengthen colorectal anastomoses, thereby preventing anastomotic leakage (AL). Previous studies have identified cyanoacrylate (CA) TAs as the most promising colonic anastomotic sealants. This study

Background: Tissue adhesives (TA) may be useful to strengthen colorectal anastomoses, thereby preventing anastomotic leakage (AL). Previous studies have identified cyanoacrylate (CA) TAs as the most promising colonic anastomotic sealants. This study

The most dreaded complication of colorectal surgery is anastomotic leakage. Adipose tissue-derived stem cell sheets (ASC sheets) prepared from temperature-responsive culture surfaces can be easily transplanted onto tissues. These sheets are proposed to improve cell transplant efficiency and enhance wound healing. The aim of this study was to investigate whether application of ASC sheets could prevent leakage of sutured colorectal anastomoses. Insufficient suturing of colorectal anastomoses was performed in Wistar rats to create a colorectal anastomotic leakage model. Rats were randomized to ASC sheet application or control group. Leakage, abscess formation, adhesion formation, anastomotic bursting pressure (ABP), and histology were evaluated on postoperative day 3 or 7. ASC sheet

Background: Chronic postoperative inguinal pain (CPIP) is the most common long-term complication of inguinal hernia repair. As such procedures are routinely performed, CPIP can be considered a significant burden to global health care. Therefore, adequate preventative measures relevant to surgical practice are investigated. However, as no gold standard research approach is currently available, study and outcome measures differ between studies. The current review aims to provide a qualitative analysis of the literature to seek out if outcomes of CPIP are valid and comparable, facilitating recommendations on the best approach to preventing CPIP. Methods: A systematic review of recent studies investigating CPIP was performed, comprising studies published in 2007-2015. Study designs were analyzed regarding the CPIP definitions applied, the use of validated instruments, the availability of a baseline score, and the existence of a minimal follow-up of 12 months. Results: Eighty eligible studies were included. In 48 studies, 22 different definitions of CPIP were identified, of which the definition provided by the International Association for the Study of Pain was applied most often. Of the studies included, 53 (66%) used 33 different validated instruments to quantify CPIP. There were 32 studies (40%) that assessed both pain intensity (PI) and quality of life (QOL) with validated tools, 41% and 4% had a validated assessment of only PI or QOL, respectively, and 15% lacked a validated assessment. The visual analog scale and the Short Form 36 (SF36) were most commonly used for measuring PI (73%) and QOL (19%). Assessment of CPIP was unclear in 15% of the studies included. A baseline score was assessed in 45% of the studies, and 75% had a follow-up of at least 12 months. Conclusion: The current literature addressing CPIP after inguinal hernia repair has a variable degree of quality and lacks uniformity in outcome measures. Proper comparison of the study results to provide concl

Background: Tissue adhesives may be useful for sealing bowel anastomoses by preventing anastomotic leakage. Prior to clinical implementation, an in-depth analysis of the clinical and immunohistopathological effects of tissue adhesives on the target tissue and of the mechanical strength of the adhesive bond in an in vivo model is needed. Materials and methods: In 84 rats, two bowel segments were glued using one of the following tissue adhesive: Bioglue, Gelatin-resorcinol-formaldehyde (GRF), Glubran 2, Histoacryl Flex, Omnex, Duraseal Xact, or Tissucol. Rats were followed for 7 or 28 days. Endpoints were clinical complication rate, mechanical strength, and immunohistopathological reactions. Results: Of the seven tissue adhesives, GRF and Bioglue showed the highest rates of bowel wall destruction and ileus and the most severe immunohistopathological tissue reactions at 7 and 28 days. Cyanoacrylates (Histoacryl Flex, Omnex, Glubran 2) showed high mechanical strength and mild immunohistopathological reactions at 7 and 28 days. Duraseal Xact and Tissucol were the most inert tissue adhesives, but exhibited low mechanical strength. At 28 days, mechanical strength was significantly correlated to CD8, CD68, and Ki67 cell counts. Conclusion: Based on the clinical and immunohistopathological outcomes, GRF and Bioglue were found to be the least suitable tissue adhesives for colonic use. Duraseal Xact and Tissucol were inert but also showed low mechanical strength. Cyanoacrylates exhibited mild clinical and immunohistopathological effects while maintaining high strength, which makes them promising as colonic sealants.

Background: Yearly approximately 4500 umbilical hernias are repaired in The Netherlands, mostly under general anesthesia. The use of local anesthesia has shown several advantages in groin hernia surgery. Local anesthesia might be useful in the treatment of umbilical hernia as well. However, convincing evidence is lacking. We have conducted a systematic review on safety, feasibility, and advantages of local anesthesia for umbilical hernia repair. Methods: A systematic review was conducted according to the PRISMA guidelines. Outcome parameters were duration of surgery, surgical site infection, perioperative and postoperative complications, postoperative pain, hernia recurrence, time before discharge, and patient satisfaction. Results: The systematic review resulted in nine included articles. Various anesthetic agents were used, varying from short acting to longer acting agents. There was no consensus regarding the injection technique and no conversions to general anesthesia were described. The most common postoperative complication was surgical site infection, with an overall percentage of 3.4%. There were no postoperative deaths and no allergic reactions described for local anesthesia. The hernia recurrence rate varied from 2 to 7.4%. Almost 90% of umbilical hernia patients treated with local anesthesia were discharged within 24 h, compared with 47% of patients treated with general anesthesia. The overall patient satisfaction rate varied from 89 to 97%. Conclusion: Local anesthesia for umbilical hernia seems safe and feasible. However, the advantages of local anesthesia are not sufficiently demonstrated, due to the heterogeneity of included studies. We, therefore, propose a randomized controlled trial comparing general versus local anesthesia for umbilical hernia repair.

__Background:__ Incisional hernia is a frequent complication after midline laparotomy. Surgical hernia repair is associated with complications, but no clear predictive risk factors have been identified. The European Hernia Society (EHS) classification offers a structured framework to describe hernias and to analyze postoperative complications. Because of its structured nature, it might prove to be useful for preoperative patient or treatment classification. The objective of this study was to investigate the EHS classification as a predictor for postoperative complications after incisional hernia surgery. __Study Design:__ An analysis was performed using a registry-based, large-scale, prospective cohort study, including all patients undergoing incisional hernia surgery between September 1, 2011 and February 29, 2016. Univariate analyses and multivariable logistic regression analysis were performed to identify risk factors for postoperative complications. __Results:__ A total of 2,191 patients were included, of whom 323 (15%) had 1 or more complications. Factors associated with complications in univariate analyses (p < 0.20) and clinically relevant factors were included in the multivariable analysis. In the multivariable analysis, EHS width class, incarceration, open surgery, duration of surgery, Altemeier wound class, and therapeutic antibiotic treatment were independent risk factors for postoperative complications. Third recurrence and emergency surgery were associated with fewer complications. __Conclusions:__ Incisional hernia repair is associated with a 15% complication rate. The EHS width classification is associated with postoperative complications. To identify patients at risk for complications, the EHS classification is useful.

Purpose: When postoperative ileus is not resolved after 5 days or recurs after resolution, prolonged POI (PPOI) is diagnosed. PPOI increases discomfort, morbidity and hospitalisation length, and is mainly caused by an inflammatory response following intestinal manipulation. This response can be weakened by targeting the cholinergic anti-inflammatory pathway, with nicotine as essential regulator. Chewing gum, already known to stimulate gastrointestinal motility itself, combined with nicotine is hypothesised to improve gastrointestinal recovery and prevent PPOI. This pilot study is the first to assess efficacy and safety of nicotine gum in colorectal surgery. Methods: Patients undergoing elective oncological colorectal surgery were enrolled in this double-blind, parallel-group, controlled trial and randomly assigned to a treatment protocol with normal or nicotine gum (2 mg). Patient reported outcomes (PROMS), clinical characteristics and blood samples were collected. Primary endpoint was defined as time to first passage of faeces and toleration of solid food for at least 24 h. Results: In total, 40 patients were enrolled (20 vs. 20). In both groups, six patients developed PPOI. Time to primary endpoint (4.50 [3.00–7.25] vs. 3.50 days [3.00–4.25], p = 0.398) and length of stay (5.50 [4.00–8.50] vs. 4.50 days [4.00–6.00], p = 0.738) did not differ significantly between normal and nicotine gum. There were no differences in PROMS, inflammatory parameters and postoperative complications. Conclusions: We proved nicotine gum to be safe but ineffective in improving gastrointestinal recovery and prevention of PPOI after colorectal surgery. Other dosages and administration routes of nicotine should be tested in future research.

Purpose: Since the introduction of the first prosthetic mesh for abdominal hernia repair, there has been a search for the “ideal mesh.” The use of preclinical or animal models for assessment of necessary characteristics of new and existing meshes is an indispensable part of hernia research. Unfortunately, in our experience there is a lack of consensus among different research groups on which model to use. Therefore, we hypothesized that there is a lack of comparability within published animal research on hernia surgery due to wide range in experimental setup among different research groups. Methods: A systematic search of the literature was performed to provide a complete overview of all animal models published between 2000 and 2014. Relevant parameters on model characteristics and outcome measurement were scored on a standardized scoring sheet. Results: Due to the wide range in different animals used, ranging from large animal models like pigs to rodents, we decided to limit the study to 168 articles concerning rat models. Within these rat models, we found wide range of baseline animal characteristics, operation techniques, and outcome measurements. Making reliable comparison of results among these studies is impossible. Conclusion: There is a lack of comparability among experimental hernia research, limiting the impact of this experimental research. We therefore propose the establishment of guidelines for experimental hernia research by the EHS.

Background: Incisional hernia is one of the most frequent complications after abdominal surgery, with incidences up to 30%. A reliable biomarker for the prediction of this complication is lacking. Advanced glycosylation end products (AGEs), also known as non-enzymatic collagen crosslinks, are correlated with aging, smoking, hyperglycemia, hyperlipidemia and oxidative stress. In this study the accumulation of AGEs and the relation between AGEs and incisional hernia were investigated. Materials and methods: In an explorator

Background: Incisional herniation is a common complication after abdominal surgery associated with considerable morbidity. The aim of this study was to determine whether incisional hernia is an early complication, in order to understand better the aetiology of incisional hernia formation. Methods: This study involved the secondary analysis of a subset of patients included in a large RCT comparing small and large tissue bites (5 mm every 5 mm, or 1 cm every 1 cm) in patients scheduled to undergo elective abdominal surgery by midline laparotomy. The distance between the rectus abdominis muscles (RAM distance) was measured by standardized ultrasound imaging 1month and 1year after surgery. The relationship between the 1-year incidence of incisional hernia and the RAM distance at 1 month was investigated. Results: Some 219 patients were investigated, 113 in the small-bites and 106 in the large-bites group. At 1 month after surgery the RAM distance was smaller for small bites than for large bites (mean(s.d.) 1⋅90(1⋅18) versus 2⋅39(1⋅34)cm respectively; P=0⋅005). At 1year, patients with incisional hernia had a longer RAM distance at 1month than those with no incisional hernia (mean(s.d.) 2⋅43(1⋅48) versus 2⋅03(1⋅19) cm respectively; relative risk 1⋅14, 95 per cent c.i. 1⋅03 to 1⋅26, P = 0⋅015). Conclusion: A RAM distance greater than 2 cm at 1 month after midline laparotomy is associated with incisional hernia. Closure with small bites results in a smaller distance between the muscles.

Background: Laparoscopic peritoneal lavage is an alternative to sigmoid resection in selected patients presenting with purulent peritonitis from perforated diverticulitis. Although recent trials have lacked superiority for lavage in terms of morbidity, mortality was not compromised, and beneficial secondary outcomes were shown. These included shorter duration of surgery, less stoma formation and less surgical reintervention (including stoma reversal) for laparoscopic lavage versus sigmoid resection respectively. The cost analysis of laparoscopic lavage for perforated diverticulitis in the Ladies RCT was assessed in the present study. Methods: This study involved an economic evaluation of the randomized LOLA (LaparOscopic LAvage) arm of the Ladies trial (comparing laparoscopic lavage with sigmoid resection in patients with purulent peritonitis due to perforated diverticulitis). The actual resource use per individual patient was documented prospectively and analysed (according to intention-to-treat) for up to 1 year after randomization. Results: Eighty-eight patients were randomized to either laparoscopic lavage (46) or sigmoid resection (42). The total medical costs for lavage were lower (mean difference € − 3512, 95 per cent bias-corrected and accelerated c.i. −16 020 to 8149). Surgical reintervention increased costs in the lavage group, whereas stoma reversal increased costs in the sigmoid resection group. Differences in favour of laparoscopy were robust when costs were varied by ±20 per cent in a sensitivity analysis (mean cost differe