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Background In up to 10% of patients with Crohn’s disease (CD), a perianal fistula (PAF) or perianal abscess (PAA) is the first presenting symptom. Delay in diagnosis in those patients is common and twice as long as in the general CD population. For the majority of patients (>70%) diagnosis takes >12 months. Delay is associated with more complex fistula formation impairing opportunities for clinical and radiological fistula closure, currently only successful in 65% and 30% respectively (combining anti-TNF and surgery). Moreover, delay in diagnosis is associated with worse outcomes and impaired quality of life (QoL). Since 2017, a low threshold for diagnostic work-up (ileocolonoscopy) for CD in patients presenting with perianal disease was introduced by a dedicated IBD surgeon in order to reduce delay in diagnosis of CD. Methods Patient records of all consecutive patients ≥16 years presenting with perianal disease (before diagnosis of CD) were retrospectively assessed. Differences in delay of diagnosis, defined as the time between first presentation with a PAA/PAF and confirmed diagnosis of CD, and differences in outcome measurements between the period 2007-2016 and 2017-2021 were determined in those eventually diagnosed with CD. Results A total of 25 patients were included in this study (n=13 in 2007-2016 and n=12 in 2017-2021, 52% male) with median age at presentation of 27 years (IQR 21,5-38,5). In the period 2007-2016, a median delay of 33 months (IQR 23-64) in CD diagnosis was observed and less than 20% of patients were diagnosed within one year after the first perianal surgical procedure. In the period 2017-2021 the median time to diagnosis significantly decreased to only 3 months (IQR 0-5, p=,000) and the proportion of patients diagnosed within one year increased drastically up to 79% (p=,000). Due to the relatively limited number of patients, no significant differences in outcome measurements (e.g. (re)interventions before CD diagnosis, number of successful fistula closure rates (clinical/radiological), and stomas/proctectomies) could be demonstrated between the two periods. Conclusion This study showed a significantly reduced delay in diagnosis of CD in patients presenting with perianal disease by introducing a low threshold for diagnostic work-up for CD. The promising results of this study were reason to continue data collection in a larger prospective study (currently ongoing) that forms the basis for the international development of an evidence based clinical decision tool including a perianal Red Flag Index and calprotectin measurement to select those at risk of having CD. Reducing delay in diagnosis by using such a clinical decision tool may improve outcomes and QoL in patients with perianal Crohn de novo.

Background: Current surgical closure techniques for sphincter-sparing treatment of high cryptoglandular fistulas in the Netherlands include the mucosal advancement flap procedure (MAF) and ligation of the intersphincteric fistula tract (LIFT). A relatively novel treatment is the fistula tract laser closure (FiLaC™) method. The aim of this study was to investigate the differences in healing and recurrence rates between FiLaC™ and current standard practices. Methods: This multicenter retrospective cohort study included both primary and recurrent high cryptoglandular anorectal fistulas, treated with either FiLaC™ or standard methods (MAF or LIFT) between September 2015 and July 2020. Patients with extrasphincteric fistulas, Crohn’s disease, multiple fistulas, age < 18 years or missing data regarding healing time or recurrence were excluded. The primary outcomes were the clinical primary and secondary healing and recurrence rates. Primary healing was defined as a closed external opening without fluid discharge within 6 months of treatment on examination, while secondary healing was the same endpoint after secondary treatment. Secondary outcomes included healing time and complaints. Results: A total of 162 high fistulas from 3 Dutch hospitals were included. Ninety-nine high fistulas were treated with FiLaC™ and 63 with either MAF or LIFT. There were no significant differences between FiLaC™ and MAF/LIFT in terms of clinical healing (55.6% versus 58.7%, p =.601), secondary healing (70.0% versus 69.2%, p =.950) or recurrence rates (49.5% versus 54%, p =.420), respectively. Median follow-up duration was 7.1 months in the FiLaC™ group (interquartile range [IQR] 4.1–14.4 months) versus 6 months in the control group (IQR 3.5–8.1 months). Conclusions: FiLaC™ treatment of high anorectal fistulas does not appear to be inferior to MAF or LIFT. Based on these preliminary results, FiLaC™ can be considered as a worthwhile treatment option for high cryptoglandular fistulas. Prospective studies with a longer follow-up period and well-determined postoperative parameters such as complication rates, magnetic resonance imaging for confirmation of fistula healing, incontinence and quality of life are warranted.

Background Perianal abscesses (PAA) and perianal fistulas (PAF) are life impairing conditions associated with Crohn’s disease (CD). A retrospective study at Flevohospital showed a reduced median delay in diagnosis of CD from 33 months (IQR 23-64) in the period 2007-2016 to 3 months (IQR 0-5) in the period 2017-2021, with Methods All consecutive patients ≥16 years presenting with PAA/PAF were included. Patients were prospectively screened for risk factors/red flags from a ‘perianal Red Flag Index Questionnaire’ (pRFI) (identified from previous literature searches/expert opinion) and fecal calprotectin (FC-)samples were taken in all patients. Colonoscopy was performed in case of ≥5 positive answers in the pRFI and/or FC-values ≥150mcg/g. Results Sixty-nine patients were included (72,5% male) with median age of 41 years (IQR 30,5-54,6). Thirty-five patients (50,7%) presented with PAA, whereas 34 patients presented with PAF (49,3%). Thirty-one patients (44,9%) had recurrent PAA/PAF. Additional colonoscopy was performed in 11 patients, in whom 5 patients (7,2%) eventually were diagnosed with CD with a median delay of 44 months (IQR 7,5-87,5, still 5 patients in diagnostic work-up). Median FC-values were 552mcg/g (IQR 198,5-4585) in patients with confirmed CD and 31,5mcg/g (IQR 10-102,75) in patients without CD (p=0,002). Risk factors associated with CD were a younger age, presence of PAF (compared to PAA only), higher number of previous perianal interventions, multiple internal fistula openings, fissures and proctitis (p Conclusion This pilot study reveals several risk factors associated with CD in patients presenting with PAA/PAF and forms the basis for development of a clinical decision tool that incorporates both the pRFI questionnaire and selected FC-measurement to early identify patients at risk of CD when presenting with perianal disease. This clinical decision tool will be subject of a larger prospective multicentre study to reduce diagnostic/treatment delay, thereby improving outcomes in patients with Crohn’s fistulas.

The Lichtenstein hernioplasty has long been seen as the gold standard for inguinal hernia repair. Unfortunately, this repair is often associated with chronic pain, up to 10-35%. Therefore, several new techniques have been developed, such as the transinguinal preperitoneal patch (TIPP) and the endoscopic total extraperitoneal (TEP) technique. Several studies showed beneficial results of the TIPP and TEP compared to the Lichtenstein hernioplasty; however, little is published on the outcome when comparing the TIPP and TEP procedures. This study aimed to evaluate outcomes after the TIPP vs the TEP technique for inguinal hernia repair.A single-center randomized controlled trial was carried out between 2015 and 2020. A total of 300 patients with unilateral inguinal hernia were enrolled and randomized to the TIPP- or TEP technique. Primary outcome was chronic pain (defined as any pain following the last 3 months) and quality of life, assessed with Carolinas comfort scale (CCS) at 12 months. Secondary outcomes were: wound infection, wound hypoesthesia, recurrence, readmission within 30 days, and reoperation.A total of 300 patients were randomized (150 per group). After a follow-up of 12 months, we observed significantly less postoperative chronic groin pain, chronic pain at exertion, wound hypoesthesia, and wound infections after the TEP when compared to the TIPP procedure. No significant differences in quality of life, reoperations, recurrence rate, and readmission within 30 days were observed.We showed that the TEP has a favorable outcome compared to the TIPP procedure, leading to less postoperative pain and wound complications, whereas recurrence rates and reoperations were equal in both the groups.

Purpose: The presence of lateral lymph nodes (LLNs) in patients with rectal cancer is not always acknowledged by the multidisciplinary team or treated in a standardized manner, and (inter)national guidelines concerning this topic are lacking. This study aimed to evaluate current practices regarding the assessment and treatment of LLNs in rectal cancer patients based on a survey among Dutch colorectal surgeons. Methods: An online survey was sent to members of the Dutch Association of Coloproctology. The survey consisted of 16 questions addressing their views on diagnosis, restaging, and treatment approaches for suspicious LLNs. Results: A total of 62 surgeons from 50 Dutch hospitals responded. For patients with a distal cT3/T4 rectal tumor; lateral lymph node compartments were routinely discussed during multidisciplinary meetings in only nine hospitals (18%). When defining what makes an LLN suspicious; the size threshold varied from >3 to >10 mm (median 7, SD 2), and MRI-based malignant features were mentioned by 29 surgeons (47%). Surgeons stated eight different treatment strategies as their designated treatment of suspicious LLNs. A total of 33 surgeons (53%) would add a radiotherapy boost to the neoadjuvant treatment. In cases of surgical resection; 12 surgeons (19%) would remove the suspicious LLN by ‘node-picking’ and 44 surgeons (71%) would perform a lateral lymph node dissection. The variation was not influenced by hospital type or surgeon's experience. Conclusion: These results highlight the vast variation in the awareness, definition of suspicious LLNs in rectal cancer, and different treatment approaches. International guidelines based on further research are warranted.

Background Abdominoperineal resection (APR) carries a high risk of perineal wound morbidity. Perineal wound closure using autologous tissue flaps has been shown to be advantageous, but there is no consensus as to the optimal method. The aim of this study was to evaluate the feasibility of a novel gluteal turnover flap (GT-flap) without donor site scar for perineal closure after APR. Methods Consecutive patients who underwent APR for primary or recurrent rectal cancer were included in a prospective non-randomised pilot study in two academic centres. Perineal reconstruction consisted of a unilateral subcutaneous GT-flap, followed by midline closure. Feasibility was defined as uncomplicated perineal wound healing at 30 days in at least five patients, and a maximum of two flap failures. Results Out of 17 potentially eligible patients, 10 patients underwent APR with GT-flap-assisted perineal wound closure. Seven patients had pre-operative radiotherapy. Median-added theatre time was 38 min (range 35–44 min). Two patients developed a superficial perineal wound dehiscence, most likely because of the excessive width of the skin island. Two other patients developed purulent discharge and excessive serosanguinous discharge, respectively, resulting in four complicated wounds at 30 days. No flap failure occurred, and no radiological or surgical reinterventions were performed. Median length of hospital stay was 10 days (IQR 8–12 days). Conclusions The GT-flap for routine perineal wound closure after APR seems feasible with limited additional theatre time, but success seems to depend on correct planning of the width of the flap. The potential for reducing perineal morbidity should be evaluated in a randomised controlled trial. Electronic supplementary material The online version of this article (10.1007/s10151-019-02055-1) contains supplementary material, which is available to authorized users.

Background Current guidelines on Crohn’s perianal fistulas recommend anti-TNF treatment and suggest to consider surgical closure in amendable patients. However, long-term outcome of both treatments have not been directly compared. The aim of this study was to assess MRI healing in a patient preference RCT comparing both treatment modalities. Methods This multicentre, international trial compared surgical closure following anti-TNF induction (4 months) to anti-TNF therapy without surgery. Patients were counselled for both treatment arms and randomised if there was no preference. Due to the combination of a preference and randomised cohort, the appropriate sample size to detect a clinically relevant increase of 25% closure (from 15% to 40%) was flexible and adjusted for a possible skewed distribution (86 patients in case of 1:1 treatment allocation). All Crohn’s patients ≥ 18 years with a (re)active high perianal fistula and a single internal opening were eligible. Exclusion criteria were previous failure of anti-TNF, recto-vaginal fistula, proctitis, or stoma. Patients received seton placement prior to treatment. Primary outcome was MRI healing after 18 months (defined as a complete fibrotic fistula or MAGNIFI-CD score of 0–5). Secondary outcomes included clinical healing, re-interventions and fistula recurrence. Results Between September 2013 and December 2019, 7 hospitals in the Netherlands and Italy included 93 patients (59% females, median age 34 years) of which 32 were randomised. Thirty-seven patients were treated in the surgical closure group and 56 in the anti-TNF group, with comparable baseline characteristics. After 18 months, MRI healing was significantly higher after surgical closure (41% vs 11%; P=0.002). Although a trend was seen in favour of surgical closure, clinical healing rates and surgical re-interventions were not significantly different between groups (65% vs 45%, P=0.07 and 19% vs 34%, P=0.1). After median 38 months follow-up, 12 patients in the anti-TNF group crossed over to surgical closure. Both long-term MRI healing and clinical closure in the per protocol analysis remained significantly higher for the surgical closure group (46% vs 11%, P=0.002 and 65% vs 29%, P=0.006). One patient (4%) with a MAGNIFI-CD score ≤5 developed a recurrent fistula after 46 months, whereas recurrences occurred in 37% of patients with MAGNIFI-CD score >5 (P=0.004). Conclusion These results demonstrate that surgical closure following anti-TNF induction treatment induces MRI healing more frequently than anti-TNF alone. This is associated with increased long-term clinical closure and reduced recurrences. These data suggest that Crohn’s perianal fistula patients amendable for surgical closure should be counselled for this therapeutic approach.

Background Alterations in the mesentery of Crohn’s disease (CD) patients have long been described, although the functional importance of this tissue is less clear. Some studies hypothesise an anti-inflammatory role for enhanced mesentery, whereas others consider a more pathologic function, given its close proximity to the inflamed intestine. Better phenotypic and functional evaluation of the cells present in this tissue is warranted to improve our understanding of its role in disease. We have previously shown a disproportionate presence of macrophages in CD mesorectum. In this study, we aimed to better characterise the phenotype and function of the macrophages in the mesentery in CD. Methods We collected mesenteric specimens from Crohn’s disease, ulcerative colitis (UC) and non-inflammatory bowel disease (IBD) patients, undergoing surgical bowel resections. In IBD patients, mesentery was collected contiguous to the inflamed region of the intestine, in non-IBD patients, mesentery adjacent to the resection margin. Macrophages were sorted by flow cytometry as CD45+ CD66b-CD14+CD11b+ cells. Sorted cells were analysed by expression profiling and functional analysis. Results Macrophages were present in all analysed tissues. Within the population, a discriminating expression pattern for CD11b was present, dividing CD14+ macrophages in a CD11bhigh and a CD11bdim subset. Transcriptional profiling and gene set enrichment showed the CD11bhigh population to be consistent with IFN-induced pro-inflammatory macrophages, while the CD11bdim population was most consistent with IL4-induced regulatory macrophages. Among the top upregulated genes in CD11bhigh macrophages were S100A8 and S100A9, the two heterodimeric subunits for calprotectin. Flow cytometry confirmed higher expression of calprotectin in the CD11bhigh population also on the protein level. Functionally, CD11bdim macrophages showed higher phagocytic capacity, again consistent a role in tissue repair. Strikingly, the CD11bdim subset was diminished significantly in the mesentery of CD patients, with a near absence in some patients, while the profile in UC was comparable to non-IBD patients. Conclusion Mesenteric macrophages contain two populations, CD11bhigh with a pro-inflammatory profile and CD11bdim with a regulatory profile. In the mesentery of CD patients, the CD11bdim population was strongly decreased, consistent with a pro-inflammatory role for this tissue.

AimLaparoscopic 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 laparoscopic lavage.MethodsBetween 2008 and 2010, 38 patients treated with laparoscopic lavage for perforated diverticulitis in 10 Dutch teaching hospitals were included. Long-term follow-up data on patient outcomes, e.g. diverticulitis recurrence, reoperations and readmissions, were collected retrospectively. The characteristics of patients with recurrent diverticulitis or complications requiring surgery or leading to death, categorized as overall complicated outcome', were compared with patients who developed no complications or complications not requiring surgery.ResultsThe median follow-up was 46 months (interquartile range 7-77), during which 17 episodes of recurrent diverticulitis (seven complicated) in 12 patients (32%) occurred. Twelve patients (32%) required additional surgery with a total of 29 procedures. Fifteen patients (39%) had a total of 50 readmissions. Of initially successfully treated patients (n = 31), 12 (31%) had recurrent diverticulitis or other complications. At 90 days, 32 (84%) patients were alive without undergoing a sigmoidectomy. However, seven (22%) of these patients eventually had a sigmoidectomy after 90 days. Diverticulitis-related events occurred up to 6 years after the index procedure.ConclusionLong-term diverticulitis recurrence, re-intervention and readmission rates after laparoscopic lavage were high. A complicated outcome was also seen in patients who had initially been treated successfully with laparoscopic lavage with relevant events occurring up to 6 years after initial surgery.

In Nederland en Belgie wordt jaarlijks bij 21.000–25.000 patienten een colorectaal carcinoom gediagnosticeerd. Colorectale carcinomen geven over het algemeen pas laat symptomen. Met de start van het bevolkingsonderzoek naar darmkanker wordt een deel van de tumoren en premaligne poliepen tegenwoordig opgespoord door het uitvoeren van een occult-bloedtest. Coloscopie wordt beschouwd als de referentiestandaard voor de detectie van een carcinoom. CT-colografie of MR-colografie als alternatief kan worden overwogen. Wanneer de diagnose colorectaal carcinoom is gesteld, is het TNM-stadium van belang voor het bepalen van het behandelplan. De behandeling van het colorectaal carcinoom omvat meerdere modaliteiten. Chirurgie is nog altijd de hoeksteen en bestaat uit het verwijderen van de tumor, inclusief het bijbehorende lymfedrainagegebied. Bij rectumcarcinomen wordt er eveneens gebruikgemaakt van neoadjuvante radio(chemo)therapie. Een deel van de patienten met een coloncarcinoom dient nog adjuvant behandeld te worden met chemotherapie. Ook bij gemetastaseerde tumoren worden de voor- en nadelen van de verschillende modaliteiten: chemotherapie, radiotherapie en chirurgie, afgewogen. De huisarts speelt een belangrijke rol bij de opsporing van darmkanker, bij de begeleiding tijdens de behandeling, in de nazorgfase en bij eventueel palliatieve zorg.

Background Temporary vascular clamping during local ablation for colorectal liver metastases increases destruction volumes. However, it also causes ischaemia–reperfusion (IR) injury to the liver parenchyma and accelerates the outgrowth of microscopic tumour deposits. The aim of this study was to investigate the effects of selective portal clamping on hepatocellular damage and tumour growth. Methods Mice carrying pre-established hepatic colorectal micrometastases underwent either simultaneous clamping of both the portal vein and the hepatic artery or selective clamping of the portal vein to the median and left liver lobes for 45 min. Sham-operated mice served as controls. Hepatic injury and tumour growth were assessed over time. Results Standard inflow occlusion resulted in a rise in liver enzymes, a local inflammatory response and hepatocellular necrosis. The outgrowth of pre-established micrometastases was accelerated three- to fourfold in clamped compared with non-clamped liver lobes (27·4 versus 7·8 per cent, P < 0·010). Conversely, selective portal clamping induced minimal liver injury, tissue inflammation or hepatocellular necrosis, and completely stopped the accelerated outgrowth of micrometastases. Conclusion Selective portal clamping does not induce liver tissue damage or accelerate micrometastasis outgrowth and may therefore be the preferable clamping method during local ablative treatment of hepatic metastases.

Background Precoagulation of liver tissue before transection is a novel concept in hepatic surgery. Comparative data with conventional techniques are lacking. This study tested the hypothesis that precoagulation results in reduced blood loss during hepatic transection. Methods Precoagulation was performed with two different devices, the TissueLink floating ball (group 1) and a dissecting sealer (group 2), and compared with ultrasonic dissection (group 3). For each technique 12 partial liver resections were performed in six pigs. Blood loss per dissection surface area was the main outcome parameter. Results The transected surface area was similar in all groups. Animals in groups 1 and 2 had significantly less blood loss than those in group 3 (3·6 and 1·3 versus 11·9 ml/cm2 respectively; P = 0·009 and P = 0·002). One pig in group 1 died as a result of wound dehiscence. In one animal in group 2 a gastric perforation was observed after death. In group 3 bile leakage occurred in two animals, and a large haematoma was observed on the transection surface in one animal after death. Conclusion Precoagulation of liver tissue before transection is associated with less blood loss compared with ultrasonic dissection.

Interstitial fluid fluxes are much greater in the fetus than in the adult, and filtration rates are increased over control in most tissues of the anaemic fetus. Increased capillary filtration may lead to cardiac oedema which, in turn, severely impacts cardiac function. Mechanisms that underlie these differences in flux are incompletely understood. One possible mechanism is an increase in capillary water permeability. Therefore, the goal of our study was to determine the level of expression of the water channel aquaporin 1 (AQP1) during cardiac development and in the anaemic fetal sheep heart. Hearts from chronically instrumented anaemic sheep fetuses and hearts from normal early fetal, late fetal, neonatal and adult sheep were used for Northern and Western analyses and immunohistochemistry. We found that AQP1 mRNA levels were lower in the young fetal left ventricle than in the adult left ventricle (P < 0.05). We also found that cardiac AQP1 expression was increased in anaemic fetuses compared to age-matched controls (P < 0.05). Expression of AQP1 in all groups was greatest in the microvascular endothelium. These data suggest that AQP1 plays an important role in the physiological accommodation to fetal anaemia.

Background: Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is associated with poor outcome. This systematic review evaluates the available evidence about adjuvant (hyperthermic) intraperitoneal chemotherapy ((H)IPEC) to prevent the development of PC. Methods: A systematic search of literature was conducted in August 2013 in PubMed, Embase, and the Cochrane database for studies on (H)IPEC to prevent PC in patients who underwent curative surgery for primary CRC. Results: Seven comparative studies and five cohort studies were selected. Treatment schedules varied between repeated fluoropyrimidine-based IPEC administration in the ambulatory setting to intra-operative (H)IPEC procedures using mitomycin-C or oxaliplatin. The reported rates of major complications related to adjuvant (H)IPEC was low. Four out of five evaluable comparative studies reported a significant difference in the incidence of PC in favour of (H)IPEC. All three comparative studies reporting on survival after intra-operative (H)IPEC showed a significant survival benefit in favour of the experimental arm. Substantial heterogeneity in patient selection, treatment protocols, and treatment effect evaluation among studies was observed. Conclusions: The currently available evidence about adjuvant (H)IPEC in high-risk CRC is limited and subject to bias, but points towards improved oncological outcome and supports further randomised studies.

Early feeding after pyloromyotomy for hypertrophic pyloric stenosis (HPS) has been advocated because this would lead to earlier discharge. However, some authors remain reluctant to introduce early feeding because of concern about postoperative vomiting. This study aimed to clarify the effects of early versus later feeding after laparoscopic pyloromyotomy on postoperative vomiting, time required to reach full oral feeding, hospital stay, and follow-up evaluation. During the period from October 1993 through March 2002, 185 infants underwent laparoscopic pyloromyotomy for HPS. Of these patients, 164 patients were included in the study. The initial feeding was within 4 h after surgery in group A and after 4 hours in group B. The outcome variables were postoperative vomiting subdivided into vomiting requiring adjustment of the feeding schedule or not, time required to reach full feeding, hospital stay, and vomiting as well as weight gain at follow-up assessment. In 23% of the 62 patients of group A and in 6% of the 102 patients of group B (p = 0.003), vomiting was so severe that it necessitated modification of the feeding schedule. Th time required to reach full feeding and the postoperative hospital stay were similar in the two groups. Analysis of the subgroups that required modification of the feeding schedule because of vomiting showed a significant delay in time required to reach full feedings as well as a significant delay in hospital discharge. There was an 11% incidence of ongoing vomiting after discharge irrespective of early or later feeding. Weight gain at follow-up assessment did not differ significantly between the two groups, and did not bear any relations to in-hospital vomiting. Feeding within 4 h postoperatively leads to more severe vomiting than later feeding. Vomiting leads to discomfort for the child, anxiety for the parents, a prolonged time required to achieve full oral feeding, and a prolonged postoperative hospital stay. However, clinical outcome after discharge is not adversely affected by early feeding. According to this study, it appears that it would be better to withhold feeding for the first 4 h after surgery.

BackgroundPostoperative pain is one of the main reasons for a prolonged hospital stay after laparoscopic cholecystectomy (LC). Reduced postoperative pain might result in faster recovery and establish LC as a day-care surgical procedure. Peroperative local anaesthesia has been suggested to reduce postoperative pain. The aim of this study was to determine the effect of combined subcutaneous infiltration and intraperitoneal instillation of levobupivacaine before the start of LC on postoperative abdominal pain up to 24 h after surgery.MethodsPatients eligible for elective LC were randomized to receive preincisional infiltration and preoperative intraperitoneal instillation of 80 ml of either 0·125 per cent levobupivacaine (experimental group) or normal saline (placebo group). The primary outcome measure was abdominal pain estimated by means of a visual analogue scale at 0·5, 2, 4, 8 and 24 h after surgery.ResultsEighty of the 101 patients assessed for eligibility were randomized. There was no significant reduction in postoperative abdominal pain with levobupivacaine compared with placebo during the 24-h follow-up; the overall difference in pain score was 2·2 (95 per cent confidence interval − 4·9 to 9·3; P = 0·540). The duration of operation, use of anaesthesia, use of rescue analgesia, shoulder pain, duration of hospital stay and time to resumption of normal daily activities did not differ between the two groups.ConclusionCombined subcutaneous and intraperitoneal administration of levobupivacaine did not influence postoperative abdominal pain after LC. Registration number: NCT01199406 (http://www.clinicaltrials.gov).

Aims The aim of this study was to evaluate the oncological outcome of portal triad clamping during hepatectomy in colorectal cancer patients. Methods 160 patients with colorectal liver metastases underwent a partial hepatectomy with curative intent. Data were collected in a prospective database and were retrospectively analyzed for time to liver recurrence (TTLiR) and time to overall recurrence (TTR). The prognostic significance of portal triad clamping of any type and severe ischemia due to prolonged portal triad clamping was determined by Cox regression models. Results TTLiR was reduced after clamping of any type, although not statistically significant ( p = 0.061). Severe ischemia due to prolonged portal triad clamping significantly decreased TTLiR ( p = 0.022), but not TTR. Furthermore, severe ischemia independently predicted TTLiR in a multivariable analysis ( p = 0.038). Conclusions Severe ischemia due to prolonged portal triad clamping during hepatic resection for colorectal liver metastases appears to be associated with decreased TTLiR. Further research remains necessary to determine the causative effect of prolonged vascular clamping on liver tumour recurrence.

Mortality due to colorectal cancer (CRC) is high and is associated with the development of liver metastases. Approximately 40% of human CRCs harbor an activating mutation in the KRAS oncogene. Tumor cells with activated KRAS are particularly sensitive to Reovirus T3D, a non-pathogenic oncolytic virus. The efficacy of virus-based therapies may be positively or negatively modulated by the host immune system. This study was designed to assess the effect of immunosuppression on Reovirus T3D oncolysis of established colorectal micrometastases in the liver. Mouse C26 CRC cells harbor a mutant Kras gene and are susceptible to Kras-dependent oncolysis by Reovirus T3D in vitro. Isolated C26 liver tumors were established in syngenic immunocompetent BALB/c mice by intrahepatic injection. Reovirus T3D therapy was given as a single intratumoral injection in control mice and in cyclosporin A-treated immunosuppressed mice. Tumor growth was analyzed over time by non-invasive bioluminescence imaging. The outgrowth of established CRC liver metastases in immunocompetent mice was efficiently but temporarily inhibited with a single injection of Reovirus T3D. Immunosuppression with cyclosporin A markedly increased and prolonged the therapeutic effect and allowed complete Reovirus T3D-induced tumor eradication in a subpopulation of the mice. We conclude that Reovirus T3D is an effective therapeutic agent against established C26 colorectal liver metastases and that immunosuppression enhances treatment efficacy. Cancer Gene Therapy (2006) 13, 815-818. doi:10.1038/sj.cgt.7700949; published online 10 March 2006.

There has been discussion about the value of laparoscopic pyloromyotomy (LP) for the treatment of hypertrophic pyloric stenosis (HPS). In their initial small series, the authors reported a relatively high complication rate. The current study was undertaken to investigate the influence of experience with LP on operative time, complication rate, and postoperative hospital stay for a large number of patients. Between October 1993 and March 2002, 182 children underwent LP for HPS. These procedures involved 11 surgeons, 4 consultants, and 7 trainees. The end points of the study were operative time, complications, and postoperative hospital stay. The outcome of 146 LPs performed after July 1996 was compared with the outcome of 36 LPs performed before that period. There was no significant difference in the mean operative time between the two series, but the operative time per surgeon dropped with experience. Mucosal perforation was experienced by 8.3% of the patients in the initial series, as compared with 0.7% in the later series. Insufficient pyloromyotomy occurred in 8.3% of the initial series, as compared with 2.7% of the later series. Other minor complications such as wound infection were infrequent and not influenced by further experience. Major wound-related problems did not occur. The LP procedure was easily learned by novices. After about 15 pyloromyotomies, the operative time was approximately 25 min. The length of postoperative hospital stay also dropped with increasing experience. The value of LP for the treatment of HPS has been proved. The LP procedure is as quick as the open procedure, has a low morbidity, and is devoid of major wound-related problems. Moreover, the procedure seems to be well teachable.