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Background and Aims Inflammatory Bowel Disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. Methods Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. Results 31 members (15 gastroenterologists, 14 colorectal surgeons and two nurse specialists) from 9 countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. Conclusions By consolidating evidence for best practice using literature review, key stakeholder and decision-making expert consultation we have developed international consensus recommendations to support healthcare professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.

Background: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. Methods: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1–2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. Findings: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11–22) before surgery for intravenous iron and 19 days (IQR 13–27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55–2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87–4·58]; p

Systemic delivery of VEGFC induces lymphangiogenesis and TAM recruitment. Related to Figure 2

Supplementary Material and Methods

S5 T cell gating strategy. Related to Figure 3. S6 FACS gating strategy for TAM and tumoral LEC and RNA sequencing validation. Related to Figure 4

Colorectal cancer is a major cause of cancer-related death in Western countries and is associated with increased numbers of lymphatic vessels (LV) and tumor-associated macrophages (TAM). The VEGFC/VEGFR3 pathway is regarded as the principal inducer of lymphangiogenesis and it contributes to metastases; however, no data are available regarding its role during primary colorectal cancer development. We found that both VEGFC and VEGFR3 were upregulated in human nonmetastatic colorectal cancer, with VEGFR3 expressed on both LVs and TAMs. With the use of three different preclinical models of colorectal cancer, we also discovered that the VEGFC/VEGFR3 axis can shape both lymphatic endothelial cells and TAMs to synergistically inhibit antitumor immunity and promote primary colorectal cancer growth. Therefore, VEGFR3-directed therapy could be envisioned for the treatment of nonmetastatic colorectal cancer.Significance:The prolymphangiogenic factor VEGFC is abundant in colorectal cancer and activates VEGFR3 present on cancer-associated macrophages and lymphatic vessels; activation of VEGFR3 signaling fosters cancer immune escape, resulting in enhanced tumor growth.

S7 LEC immunosuppressive function. Related to Figure 5. S8Macrophage depletion strategy. Related to Figure 6

Background: Neuromuscular blocking agent (NMBA) monitoring and reversals are key to avoiding residual curarization and improving patient outcomes. Sugammadex is a NMBA reversal with favorable pharmacological properties. There is a lack of real-world data detailing how the diffusion of sugammadex affects anesthetic monitoring and practice. Methods: We conducted an electronic health record analysis study, including all adult surgical patients undergoing general anesthesia with orotracheal intubation, from January 2016 to December 2019, to describe changes and temporal trends of NMBAs and NMBA reversals administration. Results: From an initial population of 115,046 surgeries, we included 37,882 procedures, with 24,583 (64.9%) treated with spontaneous recovery from neuromuscular block and 13,299 (35.1%) with NMBA reversals. NMBA reversals use doubled over 4 years from 25.5% to 42.5%, mainly driven by sugammadex use, which increased from 17.8% to 38.3%. Rocuronium increased from 58.6% (2016) to 94.5% (2019). Factors associated with NMBA reversal use in the multivariable analysis were severe obesity (OR 3.33 for class II and OR 11.4 for class III obesity, p-value < 0.001), and high ASA score (OR 1.47 for ASA III). Among comorbidities, OSAS, asthma, and other respiratory diseases showed the strongest association with NMBA reversal administration. Conclusions: Unrestricted availability of sugammadex led to a considerable increase in pharmacological NMBA reversal, with rocuronium use also rising. More research is needed to determine how unrestricted and safer NMBA reversal affects anesthesia intraoperative monitoring and practice.

Introduction Intra-abdominal abscesses complicating Crohn’s disease (CD) present an additional challenge as their presence can contraindicate immunosuppressive treatment whilst emergency surgery is associated with high stoma rate and complications. Treatment options include a conservative approach, percutaneous drainage, and surgical intervention. The current multicentre study audited the short-term outcomes of patients who underwent preoperative radiological drainage of intra-abdominal abscesses up to 6 weeks prior to surgery for ileocolonic CD. Methods This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing ileocolic resection for primary or recurrent CD from June 2018 to May 2019. The outcomes of patients who underwent radiological guided drainage prior to ileocolonic resection were compared to the patients who did not require preoperative drainage. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. Results Amongst a group of 575 included patients who had an ileocolic resection for CD, there were 36 patients (6.2%) who underwent abscess drainage prior to surgery. Postoperative morbidity (44.4%) and anastomotic leak (11.1%) were significantly higher in the group of patients who underwent preoperative drainage. Conclusions Patients with Crohn’s disease who require preoperative radiological guided drainage of intra-abdominal abscesses are at increased risk of postoperative morbidity and septic complications following ileocaecal or re-do ileocolic resection.

in the literature on rectal cancer (RC) surgery many studies have focused on the quality of total mesorectal excision (TME) dissection, while there is a scarcity of comparative data on transection and anastomosis. No anastomosis has so far proved to be superior to any other. The aim of this study was to compare anastomotic leak (AL) rates between conventional laparoscopic double-stapled (DS), transanal total mesorectal excision (TaTME) and Transanal Transection and Single-Stapled anastomosis (TTSS) techniques.consecutive mid-low RC patients undergoing elective laparoscopic TME with stapled anastomosis and protective stoma, by either DS, TaTME or TTSS techniques were retrieved from a prospectively collected database.127 DS; 100 TaTME and 50 TTSS were included. Demographics, distance of the tumor from anal verge and neoadjuvant therapy were comparable. Operative time was longer in TaTME over DS and TTSS (p 0.0001). More 90-days complications occurred in DS group vs TTSS (p = 0.029). The AL rate was 17.5% in DS, 6% in TaTME and 2% in TTSS group (p = 0.005). AL grade was: one B (2%) in TTSS; 2 grade B (2%) and 4 grade C (4%) in TaTME; 6 grade A (4.7%), 7 grade B (5.5%) and 9 grade C (7.1%) in DS group. Reintervention rate after AL was higher in DS group over TTSS (12.6% vs 2%; p = 0.003). The rate of stoma closure, pathology data and margin positivity did not differ.TTSS strategy is feasible, safe and leads to very low AL rates after TME for RC.

The incidence of colorectal cancer (CRC) is increasing in the population aged ≤ 49 (early-onset CRC-EOCRC). Recent studies highlighted the biological and clinical differences between EOCRC and late-onset CRC (LOCRC-age ≥ 50), while comparative results about long-term survival are still debated. This study aimed to investigate whether age of onset may impact on oncologic outcomes in a surgical population of sporadic CRC patients. Patients operated on for sporadic CRC from January 2010 to January 2022 were allocated to the EOCRC and LOCRC groups. The primary endpoint was the recurrence/progression-free survival (R/PFS). A total of 423 EOCRC and 1650 LOCRC was included. EOCRC had a worse R/PFS (p < 0.0001) and cancer specific survival (p < 0.0001) compared with LOCRC. At Cox regression analysis, age of onset, tumoral stage, signet ring cells, extramural/lymphovascular/perineural veins invasion, and neoadjuvant therapy were independent risk factors for R/P. The analysis by tumoral stage showed an increased incidence of recurrence in stage I EOCRC (p = 0.014), and early age of onset was an independent predictor for recurrence (p = 0.035). Early age of onset was an independent predictor for worse prognosis, this effect was stronger in stage I patients suggesting a potentially—and still unknown—more aggressive tumoral phenotype in EOCRC.

BACKGROUND Rectal cancer in adolescents and young adults (age ≤39) is increasing. Early diagnosis is a challenge in this subset of patients. OBJECTIVE This study aims to analyze the presentation pattern and outcomes of sporadic rectal cancer in adolescents and young adults. DESIGN This is a retrospective study. SETTING This study was conducted at 3 European tertiary centers. PATIENTS Data on adolescents and young adults operated on for sporadic rectal cancer (January 2008 through October 2019) were analyzed. To compare outcomes, adolescents and young adults were matched to a group of patients aged ≥40 operated on during the same period. MAIN OUTCOME MEASURES The primary outcomes measured were clinical presentation and long-term outcomes. RESULTS Sporadic rectal cancers occurred in 101 adolescents and young adults (2.4%; mean age, 33.5; range, 18-39); 51.5% were male, and a smoking habit was reported by 17.8% of patients. The rate of a family history for colorectal cancer was 25.7%, and of these patients, 24.7% were obese. Diagnosis based on symptoms was reported in 92.1% patients, and the mean time from first symptoms to diagnosis was 13.7 months. The most common symptom at diagnosis was rectal bleeding (68.8%), and 12% and 34% of the adolescents and young adults presented with locally advanced or metastatic disease at diagnosis. Consequently, 68.3% and 62.4% adolescents and young adults received neoadjuvant and adjuvant treatments. The rate of complete pathological response was 24.1%; whereas 38.6% patients had stage IV disease, and 93.1% were microsatellite stable. At a mean follow-up of 5 years, no difference in cancer-specific survival, but a lower disease-free survival was reported in adolescents and young adults (p < 0.0001) vs the matched group. Adolescents and young adults with stages I to II disease had shorter cancer-specific survival and disease-free survival (p = 0.006; p < 0.0001); with stage III disease, they had a shorter disease-free survival (p = 0.01). LIMITATIONS This study was limited by its observational, retrospective design. CONCLUSIONS The significantly delayed diagnosis in adolescents and young adults may have contributed to the advanced disease at presentation and lower disease-free survival, even at earlier stages, suggesting a higher metastatic potential than in older patients. See Video Abstract at http://links.lww.com/DCR/B537. CNCER DE RECTO EN PACIENTES ADOLESCENTES Y ADULTOS JVENES CUADRO DE PRESENTACIN CLNICA Y COMPARACIN DE DESENLACES POR CASOS EMPAREJADOS ANTECEDENTES:El cancer de recto en adolescentes y adultos jovenes (edad ≤ 39) esta aumentando. El diagnostico temprano es un desafio en este subgrupo de pacientes.OBJETIVO:Analizar el cuadro de presentacion y los desenlaces en adolescentes y adultos jovenes con cancer de recto esporadico.DISENO:Estudio retrospectivo.AMBITO:Tres centros europeos de tercer nivel.PACIENTES:Se analizaron los datos de adolescentes y adultos jovenes operados de cancer de recto esporadico (enero de 2008 - octubre de 2019). Para comparar los desenlaces se emparejo a adolescentes y adultos jovenes con un grupo de pacientes mayores de 40 anos operados en el mismo periodo de tiempo.PRINCIPALES VARIABLES ANALIZADAS:Cuadro clinico, resultados a largo plazo.RESULTADOS:Los canceres de recto esporadicos en adolescentes y adultos jovenes fueron 101 (2,4%, edad media: 33,5, rango 18-39). El 51,5% eran hombres, el 17,8% de los pacientes fumaba. El 25,7% tentia antecedentes familiares de cancer colorrectal. El 24,7% eran obesos. El diagnostico con base en los sintomas se informo en el 92,1% de los pacientes, el tiempo promedio desde los primeros sintomas hasta el diagnostico fue de 13,7 meses. El sintoma mas comun en el momento del diagnostico fue el sangrado rectal (68,8%). 12% y 34% de adolescentes y adultos jovenes presentaron enfermedad localmente avanzada o metastasica en el momento del diagnostico. Por lo tanto, el 68,3% y el 62,4% de adolescentes y adultos jovenes recibieron neoadyuvancia y adyuvancia. La tasa de respuesta patologica completa fue del 24,1%; mientras que el 38,6% estaban en estadio IV. El 93,1% eran microsatelite estable. Con una media de seguimiento de 5 anos, no se observaron diferencias en la sobrevida especifica del cancer, pero se informo una menor sobrevida libre de enfermedad en adolescentes y adultos jovenes (p

Background and Aims Crohn’s disease increases colorectal cancer risk, with high prevalence of synchronous and metachronous cancers. Current guidelines for colorectal cancer in Crohn’s disease recommend pan-proctocolectomy. The aim of this study was to evaluate oncological outcomes of a less invasive surgical approach. Methods This was a retrospective database analysis of Crohn’s disease patients with colorectal cancer undergoing surgery at selected European and US tertiary centres. Outcomes of segmental colectomy were compared with those of extended colectomy, total colectomy, and pan-proctocolectomy. Primary outcome was progression-free survival. Secondary outcomes included overall survival, synchronous and metachronous colorectal cancer, and major postoperative complications. Results Ninety-nine patients were included: 66 patients underwent segmental colectomy and 33 extended colectomy. Segmental colectomy patients were older [p = 0.0429], had less extensive colitis [p = 0.0002] and no preoperatively identified synchronous lesions [p = 0.0109]. Median follow-up was 43 [31–62] months. There was no difference in unadjusted progression-free survival [p = 0.2570] or in overall survival [p = 0.4191] between segmental and extended colectomy. Multivariate analysis adjusting for age, sex, ASA score, and AJCC staging, confirmed no difference for progression-free survival (hazard ratio [HR] 1.00, p = 0.9993) or overall survival [HR 0.77, p = 0.6654]. Synchronous and metachronous cancers incidence was 9% and 1.5%, respectively. Perioperative mortality was nil and major complications were comparable [7.58% vs 6.06%, p = 0.9998]. Conclusions Segmental colectomy seems to offer similar long-term outcomes to more extensive surgery. Incidence of synchronous and metachronous cancers appears much lower than previously described. Further prospective studies are warranted to confirm these results.

Background Accurate quality of life (QoL) data and functional results after cancer surgery are lacking for older patients. The international, multicenter Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) Study compares QoL before and after surgery and identifies predictors of decline in QoL. Methods GOSAFE prospectively collected data before and after major elective cancer surgery on older adults (≥70 years). Frailty assessment was performed and postoperative outcomes recorded (30, 90, and 180 days postoperatively) together with QoL data by means of the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L), including 2 components: an index (range = 0-1) generated by 5 domains (mobility, self-care, ability to perform the usual activities, pain or discomfort, anxiety or depression) and a visual analog scale. Results Data from 26 centers were collected (February 2017-March 2019). Complete data were available for 942/1005 consecutive patients (94.0%): 492 male (52.2%), median age 78 years (range = 70-95 years), and primary tumor was colorectal in 67.8%. A total 61.2% of all surgeries were via a minimally invasive approach. The 30-, 90-, and 180-day mortality was 3.7%, 6.3%, and 9%, respectively. At 30 and 180 days, postoperative morbidity was 39.2% and 52.4%, respectively, and Clavien-Dindo III-IV complications were 13.5% and 18.7%, respectively. The mean EQ-5D-3L index was similar before vs 3 months but improved at 6 months (0.79 vs 0.82; P Conclusions GOSAFE shows that older adults’ preoperative QoL is preserved 3 months after cancer surgery, independent of their age. Frailty screening tools, patient-reported outcomes, and goals-of-care discussions can guide decisions to pursue surgery and direct patients’ expectations.

AIM Many factors influence the postoperative length of stay (LOS) in Crohn's disease (CD). This study aims to identify the factors associated with a prolonged LOS after ileocolic resection (ICR) for CD and to develop a scoring system to predict the postoperative LOS in CD. METHOD Patient data were collected from St Marks Hospital, London, UK, and the Humanitas Clinical and Research Center Milan, Italy, for all patients who underwent an ICR for CD from 2005 to 2017. Logistic regression was used for multivariate analysis. The scoring system was developed from the logistic regression model. The performance of the scoring system was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS A total of 628 surgeries were included in the analysis. Eighty eight surgeries were excluded due to missing data. The remaining 543 were divided into two cohorts for the development (n = 418) and validation (n = 125) of the scoring system. The regression model was statistically significant (p

The evidence does not support the routine use of abdominal drainage (AD) in colorectal surgery. However, there is no data on the usefulness of AD, specifically, after ileal pouch-anal anastomosis (IPAA). The aim of this study is to assess post-operative outcomes of patients undergoing IPAA with or without AD at a high volume referral center. A retrospective analysis of prospectively collected data of consecutive patients undergoing IPAA with AD (AD group) or without AD (NAD group) was performed. Baseline characteristics, operative, and postoperative data were analyzed and compared between the two groups. A total of 97 patients were included in the analysis, 46 were in AD group and 51 in NAD group. AD group had a higher BMI (23.9 ± 3.9 kg/m

Perianal fistula represents one of the most disabling manifestations of Crohn's Disease (CD) due to complete destruction of the affected mucosa, which is replaced by granulation tissue and associated with changes in tissue organization. To date, the molecular mechanisms underlying perianal fistula formation are not well defined. Here, we dissected the tissue changes in the fistula area and addressed whether a dysregulation of extracellular matrix (ECM) homeostasis can support fistula formation.Surgical specimens from perianal fistula tissue and the surrounding region of fistulizing CD were analyzed histologically and by RNA sequencing (RNA-seq). Genes significantly modulated were validated by RT-PCR, WB, and immunofluorescence assays. The effect of the protein product of TNF-stimulated gene-6 (TSG-6) on cell morphology, phenotype and ECM organization was investigated with endogenous Lentivirus-induced over-expression of TSG-6 in Caco-2 cells and with exogenous addition of recombinant human TSG-6 protein (rhTSG-6) to primary fibroblasts from region surrounding fistula. Proliferative and migratory assays were performed.A markedly different organization of ECM was found across fistula and surrounding fistula regions with an increased expression of integrins and metalloproteinases (MMPs) and hyaluronan (HA) staining in the fistula, associated with increased newly synthesized collagen fibers and mechanosensitive proteins. Among dysregulated genes associated with ECM, TNFAI6 (gene encoding for TSG-6) was as significantly upregulated in the fistula compared to area surrounding fistula, where it promoted the pathological formation of complexes between heavy chains (HCs) from inter-alpha-inhibitor and HA responsible for the formation of a crosslinked ECM. There was a positive correlation between TSG-6 expression and expression of mechanosensitive genes in fistula tissue. The over-expression of TSG-6 in Caco-2 cells promoted migration, epithelial mesenchymal transition (EMT), transcription factor SNAIL and hyaluronan synthase (Has) levels; while in fibroblasts, isolated from the area surrounding the fistula, it promoted an activated phenotype. Moreover, the enrichment of an HA scaffold with rhTSG-6 protein promoted collagen release, increase of SNAIL, ITGA4, ITGA42B, and PTK2B genes, the latter being involved in the transduction of responses to mechanical stimuli.By mediating changes in the ECM organization, TSG-6 triggers the EMT transcription factor SNAIL through the activation of mechanosensitive proteins. These data point to regulators of ECM as new potential targets for the treatment of CD perianal fistula.

Background: Surgery is considered a cornerstone of inflammatory bowel disease (IBD) treatment. In the last years, robotic surgery has seen an increase in adoption rates for both benign and malignant diseases. Objective: This work aims to review the current applications of robotic surgery in IBD. Discussion and Conclusion: Minimally-invasive techniques have been applied to the treatment of IBD for more than 20 years. Investments in surgical digital and robotic platforms are increasingly arising, with an estimate of getting doubled within the next 5 years. Robotic surgery represents the newest technology available to reduce the impact of surgery on patients affected by IBD, and may theoretically be even more effective than other minimally-invasive techniques given the lower rate of conversion to open surgery as compared to laparoscopy according to many large retrospective series. Data on robotic surgery applied to IBD are still scarce and initial experiences in high-volume centers from retrospective series suggested that robotic surgery may achieve similar results when compared to laparoscopy. A new wave of robotics incorporating artificial intelligence is awaited to empower the capability of IBD surgeon in terms of intraoperative decision-making beyond technical skill enhancement.

Postoperative C-reactive protein (CRP) level allows to rule out infectious complications ensuring safe hospital discharge in colorectal cancer surgery. Since its clinical significance in Crohn’s disease (CD) has not been studied yet, we investigated whether CRP can guide decision-making on hospital discharge in this population. Only consecutive CD patients undergoing resections with primary anastomosis and without covering stoma (2013–2017) were analysed. Pre- and post-operative CRP values, measured daily until discharge, were correlated with postoperative complications including anastomotic leakage (AL), infectious and non-infectious complications. The diagnostic accuracy of CRP in predicting AL was evaluated according to the area under the curve (AUC), using the receiver-operating characteristic (ROC) methodology. Two-hundred and fifty-one consecutive patients undergoing elective surgery for CD were selected. AL was diagnosed in 10 patients (4%). High CRP level was associated with AL on postoperative day (POD) 3–5 (p = 0.002, AUC 0.825) with a positive predictive value of 60%. CRP linear difference of 140 between POD 1 and 3 (AUC 0.800) maximizes sensitivity and specificity with a NPV of 98.6%. CRP trend, measured with the linear difference between POD 1 and 3, is able to rule out anastomotic complications with a high NPV and may allow a safe early hospital discharge after surgery for CD.

Introduction: In recent decades, biologics have resulted in significantly improved medical management of ulcerative colitis (UC). Rates of surgery for UC are declining. However, there is still a co...

The likelihood of a stoma following ileocolic resection (ICR) for Crohn's disease (CD) is an important consideration. This study aims to identify the factors associated with an increased likelihood of a stoma and develop a predictive scoring system (SS).Patient data were collected from St. Marks Hospital, London, UK and Humanitas Clinical and Research Center, Milan, Italy, on all patients who underwent an ICR for CD from 2005 to 2017. A logistic regression analysis was used for multivariate analysis. The SS was developed from the logistic regression model. The performance of the SS was evaluated using receiver operating characteristics area under the curve (AUROC).A total of 628 surgeries were included in the analysis. Sixty-nine surgeries were excluded due to missing data. The remaining 559 were divided into two cohorts for the scoring system's development (n = 434) and validation (n = 125). The regression model was statistically significant (p 0.0001). The statistically significant independent variables included sex, preoperative albumin and haemoglobin levels, surgical access and simultaneous colonic resection. The AUROC for the development and validation cohorts were 0.803 and 0.905, respectively (p 0.0001). Youden's index suggested the cut-off score of - 95.9, with a sensitivity of 87.6% and a specificity of 62.9%.Male sex, low preoperative albumin, anaemia, laparoscopic conversion and simultaneous colonic resection were associated with an increased likelihood of requiring a stoma and were used to develop an SS. The calculator is available online at https://rebrand.ly/CrohnsStoma .

Background Stoma-reversal surgery is associated with high postoperative morbidity, including wound complications and surgical-site infections (SSIs). This study aims to assess whether the application of negative-pressure wound therapy (NPWT) can improve wound healing compared with conventional wound dressing. Methods This was a single-centre, superiority, open-label, parallel, individually randomized controlled trial. Patients undergoing stoma reversal were randomized (1 : 1) to receive NPWT or conventional wound dressing. The primary endpoint of the study was the rate of wound complications and SSIs after stoma closure. The secondary endpoints were postoperative wound pain, rate of wound healing after 30 days from stoma closure, and wound aesthetic satisfaction. Results Between June 2019 and January 2021, 50 patients were allocated to the NPWT group (all received NPWT, 49 were analysed); 50 patients were allocated to the conventional wound dressing group (48 received the treatment, 45 were analysed). No significant difference was found in wound-complication rate (10 per cent NPWT versus 16 per cent controls; odds ratio 0.61 (95 per cent c.i. 0.18 to 2.10), P = 0.542) and incisional SSI rate (8 per cent NPWT versus 7 per cent controls; odds ratio 1.24 (95 per cent c.i. 0.26 to 5.99), P = 1.000). The NPWT group showed less pain, higher aesthetic satisfaction (P < 0.0001), and a higher proportion of wound healing (92 versus 78 per cent; P = 0.081) compared with the control group. Conclusion NPWT does not reduce the incidence of SSI after stoma-reversal surgery compared with conventional wound dressing. However, NPWT improved the healing of uninfected wounds, reduced wound pain and led to better aesthetic outcomes. Registration number: NCT037812016 (clinicaltrials.gov)., The use of negative-pressure wound therapy (NPWT) does not reduce the incidence of surgical-site infections after stoma-reversal surgery; however, its application reduces healing times, provides superior comfort for the patient, reduces wound pain and leads to better aesthetic outcomes compared with standard purse-string suture technique. This is the first randomized trial evaluating pain and discomfort with the application of NPWT in stoma reversal.

ObjectivesIntraoperative fluorescence imaging is currently used in a variety of surgical fields for four main purposes: assessing tissue perfusion; identifying/localizing cancer; mapping lymphatic systems; and visualizing anatomy. To establish evidence-based guidance for research and practice, understanding the state of research on fluorescence imaging in different surgical fields is needed. We evaluated the evidence on fluorescence imaging for perfusion assessments using the Idea, Development,Exploration, Assessment, Long Term Study (IDEAL) framework, which was designed for describing the stages of innovation in surgery and other interventional procedures.DesignNarrative literature review with analysis of IDEAL stage of each field of study.SettingAll publications on intraoperative fluorescence imaging for perfusion assessments reported in PubMed through 2019 were identified for six surgical procedures: coronary artery bypass grafting (CABG), upper gastrointestinal (GI) surgery, colorectal surgery, solid organ transplantation, reconstructive surgery, and cerebral aneurysm surgery.Main outcome measuresThe IDEAL stage of research evidence was determined for each specialty field using a previously described approach.Results196 articles (15 003 cases) were selected for analysis. Current status of research evidence was determined to be IDEAL Stage 2a for upper GI and transplantation surgery, IDEAL 2b for CABG, colorectal and cerebral aneurysm surgery, and IDEAL Stage 3 for reconstructive surgery. Using the technique resulted in a high (up to 50%) rate of revisions among surgical procedures, but its efficacy improving postoperative outcomes has not yet been demonstrated by randomized controlled trials in any discipline. Only one possible adverse reaction to intravenous indocyanine green was reported.ConclusionsUsing fluorescence imaging intraoperatively to assess perfusion is feasible and appears useful for surgical decision making across a range of disciplines. Identifying the IDEAL stage of current research knowledge aids in planning further studies to establish the potential for patient benefit.

Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.

Background and Aims Few recent studies focus on the treatment of rectal cancer in patients with ulcerative colitis. We report treatment options and results for this subset of patients with a multimodal approach at two European referral centres. Methods Ulcerative colitis patients diagnosed with rectal cancer arising at less than 15 cm from the anal verge between January 2010 and December 2020 were analysed. Demographics, clinical data, and details of medical and surgical treatment were retrieved from prospectively collected institutional databases. Results Of 132 patients with ulcerative colitis and concomitant colorectal cancer, rectal cancer was diagnosed in 46. The median time between disease onset and rectal cancer diagnosis was 17.5 years; 21/46 were preoperatively staged as early tumours [cT1-T2/N0]. Eleven patients received neoadjuvant chemoradiotherapy for locally advanced extraperitoneal adenocarcinoma, and the rest underwent surgery first. Over two-thirds of the procedures were restorative [68%]; a minimally invasive approach was used in 96% of patients, with no conversion to open. The median follow-up was 44 months. Local recurrence occurred in three patients [6%]. The cumulative 3-year cancer-specific survival rate was 94% [and the 3-year disease-free rate was 86%]. Conclusions Rectal cancer in ulcerative colitis is a very complex condition. Our results show that surgery for rectal cancer can be delivered with excellent oncological and functional outcomes in patients with ulcerative colitis. A multidisciplinary discussion among surgeons, gastroenterologists, and medical oncologists is key to ensure the appropriate treatment pathway for individual patients.

BACKGROUND while interest on early-onset colorectal cancer (age ≤49) is on the rise, studies on early-onset rectal cancer (EORC) are limited. The aim of this study was to compare predictors for disease progression/recurrence between sporadic EORC and late-onset RC patients (LORC). METHODS 163 EORC and 830 LORC operated between January 1st, 2010 and April 30th, 2021 at a tertiary center were included. Demographics, tumor characteristics, microsatellite status, gene mutations (KRAS, BRAF, NRAS, PI3Kca) and oncologic outcomes were compared. A Cox proportional hazards regression analysis was performed to ascertain the effect of variables on recurrence/progression and death. Recurrence/Progression free survival (R/PFS) and cancer specific survival (CSS) were analyzed by the Kaplan-Meier estimator. RESULTS Mean age of EORC was 42.16, (46% aged 45-49). A majority of EORC patients had a family history for CRC (p = 0.01) and underwent total neoadjuvant treatment (p = 0.01). EORC patients showed a higher rate of low-grade tumor differentiation (p

Background The transanal approach to ileal pouch-anal anastomosis [Ta-IPAA] provides better access to the lower pelvis with lower short-term morbidity in ulcerative colitis [UC]. The aim of this study was to assess the long-term functional outcomes after Ta-IPAA vs transabdominal IPAA [Abd-IPAA] in UC. Methods A multicentre cohort analysis was performed between March 2002 and September 2017. Patient characteristics, surgical details and postoperative outcomes were compared. CGQL [Cleveland global quality of life] score at 12 months with a functioning pouch was considered the primary end point. Results A total of 374 patients [100 Ta-IPAA vs 274 Abd-IPAA] were included. Ta-IPAA demonstrated a comparable overall quality of life [CGQL score] to Abd-IPAA [0.75 ± 0.11 vs 0.71 ± 0.14; respectively, p = 0.1]. Quality of life [7.71 ± 1.17 vs 7.30 ± 1.46; p = 0.04] and energy-level items [7.16 ± 1.52 vs 6.66 ± 1.68; p = 0.03] were significantly better after Ta-IPAA, while the quality of health item was comparable [7.68 ± 1.26 vs 7.64 ± 1.44; p = 0.96]. Analysis excluding anastomotic leaks did not change the overall CGQL scores. Stool frequencies [>10/24 h: 22% vs 21%; p = 1.0] and the rate of a single episode of major incontinence during the following 12-month period [27% vs 26%; p = 0.89] were similar. The differences in 30-day morbidity rates [33% vs 41%; p = 0.2] and anastomotic leak rates were not significant [6% vs 13%; p = 0.09]. Conclusions This study provides evidence of comparable long-term functional outcome and quality of life after Ta-IPAA and Abd-IPAA for UC.

Introduction Single-incision laparoscopic surgery (SILS) aims to minimize the surgical access trauma by reducing the number of abdominal incisions to a single site, potentially offering better cosmetic results and decreased postoperative pain. In this study, we compare the results of SILS ileocolic resection for Crohn’s disease (CD) to conventional laparoscopy and open surgery using a propensity score–matched analysis in a retrospective national multicentre study. Methods All consecutive patients undergoing elective SILS ileocaecal or redo ileocolic resection for primary and recurrent CD from 1 June 2018 to 31 May 2019 were included. Patients were matched 1:1:1 with laparoscopy and open surgery according to perianal disease, recurrent disease, penetrating phenotype of CD, history of previous abdominal surgery, preoperative medical treatment with steroids and anti-TNF. Postoperative morbidity within 30 days of surgery was the primary endpoint. Results Fifty-eight patients were included in each group, for a total of 174 patients. The conversion rate for SILS and laparoscopy was 10.3% and 12%, respectively, with no difference in the incidence of postoperative complications (13.8% and 12%, p = 0.77), whilst open surgery demonstrated a worse morbidity profile, with a complication rate of 25.9% (p < 0.0001). Median length of hospital stay following SILS ileocolic resection was 5 days, significantly shorter compared to 7 days for laparoscopy and 9 for open surgery (p < 0.0001). Conclusions SILS ileocolonic resection for CD demonstrated a comparable morbidity profile compared to laparoscopy in selected patients, with a reduced length of postoperative hospital stay.

Aim: Surgery is indicated in selected patients with inflammatory bowel disease (IBD). However, due to a negative perception, surgery may be delayed, leading to possible unfavourable outcomes. The aim of this work was to investigate patients’ perceptions of surgery and the impact on reported outcomes. Method: An international multilingual online survey was used to query IBD patients’ experiences of surgery, information sources, expectations and concerns, quality of life (QoL) and feelings. Results: The survey was completed by 425 of 510 participants. Crohn's disease was more frequent (61%) than ulcerative colitis (36%). Most patients primarily learned about surgery from their gastroenterologist and were informed of the risks and benefits by the surgeon. In almost one-third of patients indication for surgery was not a shared decision between gastroenterologist and surgeon. Seventy per cent of patients naïve to surgery were not aware of any surgical options. The majority of patients (80%) perceived surgery as the last option after many medical treatments rather than an alternative therapeutic option (20%). Sixteen per cent of patients obtained their primary information from the Internet, while 82.4% used the Internet to obtain additional information. Fear of surgical complications was cited by 73% of patients, while relief from symptoms was indicated by 31%. Most patients coped with their stoma better than expected or as they expected. Negative feelings decreased after surgery, while a lasting improvement in positive feelings and QoL was reported. Conclusion: Despite the negative perception of surgery and the delayed involvement of surgeons as a source of information and in the decision-making process, the majority of respondents experienced positive outcomes from surgery, including improvement QoL and acceptance of the stoma.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Introduction To explore the reported variability in the surgical management of ileocolonic Crohn’ s disease and identify areas of standard practice, we present this study which aims to assess how different colorectal surgeons with a subspecialty interest in inflammatory bowel disease (IBD) surgery may act in different clinical scenarios of ileocolonic Crohn’s disease. Methods Anonymous videos demonstrating the small bowel walkthrough and anonymised patients’ clinical data, imaging and pathological findings were distributed to the surgeons using an electronic tool. Surgeons answered on operative strategy, bowel resections, management of small bowel mesentery, type of anastomosis and use of stomas. Results Eight small bowel walkthrough videos were registered and 12 assessors completed the survey with a questionnaire completion rate of 87.5%. There was 87.7% agreement in the need to perform an ileocolonic resection. However, the agreement for the need to perform associated surgical procedures such as strictureplasties or further bowel resections was only 57.4%. When an anastomosis was fashioned, the side to side configuration was the most commonly used. The preferred management of the mesentery was dissection close to the bowel. Conclusions The decision on the main procedure to be performed had a high agreement amongst the different assessors, but the treatment of multifocal disease was highly controversial, with low agreement on the need for associated procedures to treat internal fistulae and the use of strictureplasties. At the same time, there was significant heterogeneity in the decision on when to anastomose and when to fashion an ileostomy.

Outcomes of inflammatory bowel disease (IBD) patients requiring surgery during the outbreak of Coronavirus disease 19 (COVID-19) are unknown. Aim of this study was to analyse the outcomes depending on the COVID-19 status of the centre. Patients undergoing surgery in six COVID-19 treatment and one COVID-free hospitals (five countries) during the first COVID-19 peak were included. Variables associated with risk of moderate-to-severe complications were identified using logistic regression analysis. A total of 91 patients with Crohn’s disease (54, 59.3%) or ulcerative colitis (37, 40.7%), 66 (72.5%) had surgery in one of the COVID-19-treatment hospitals, while 25 (27.5%) in the COVID-19-free centre. More COVID-19-treatment patients required urgent surgery (48.4% vs. 24%, p = 0.035), did not discontinue biologic therapy (15.1% vs. 0%, p = 0.039), underwent surgery without a SARS-CoV-2 test (19.7% vs. 0%, p = 0.0033), and required intensive care admission (10.6% vs. 0%, p = 0.032). Three patients (4.6%) had a SARS-CoV-2 infection postoperatively. Postoperative complications were associated with the use of steroids at surgery (Odds ratio [OR] = 4.10, 95% CI 1.14–15.3, p = 0.03), presence of comorbidities (OR = 3.33, 95% CI 1.08–11, p = 0.035), and Crohn’s disease (vs. ulcerative colitis, OR = 3.82, 95% CI 1.14–15.4, p = 0.028). IBD patients can undergo surgery regardless of the COVID-19 status of the referral centre. The risk of SARS-CoV-2 infection should be taken into account. Supplementary Information The online version contains supplementary material available at 10.1007/s13304-021-01119-y.

BackgroundSphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whetherS1PR2participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.MethodsWe screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2−/−) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2−/−Lgr5-EGFP- mice.ResultsS1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/minmouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2−/−mice compared to S1PR2+/+controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.ConclusionsIn normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.Graphical Abstract. Schematic drawing of the role of S1PR2 in normal mucosa and colorectal cancer. In the normal mucosa, S1PR2 is highly expressed by differentiated cells at the upper region of both colon and intestinal crypts (S1PR2 ON), but not by the undifferentiated stem cell at the base of the crypts (S1PR2 OFF), in which acts as a negative proliferative regulator promoting epithelial differentiation. Its loss leads to the expansion of stem cells and reduced levels of PTEN and Axin-2, two negative regulators respectively of PI3K/AKT and Wnt signaling that control β-catenin signaling. The translocation of β-catenin into the nucleus promotes the transcription of target genes involved in the proliferation and malignant transformation. Thereby, S1PR2 works in the intestine as a tumor suppressor

Background While during the Covid-19 pandemic elective surgery was shut-down of in most settings, some referral centers were designated as surgery hubs. We sought to investigate how the pandemic scenario hasve impacted the quality of a long-established enhanced recovery protocol (ERP) colorectal surgery (CRS) program in two referral center, designated as colorectal surgery hub, located in the epicentral Italian regions hardest hit by the pandemic. Methods We have compared short-term outcomes of patients undergoing major colorectal surgery with a long-established ERP during the COVID-19 outbreak (group A) with the correspondent timeframe of 2019 (group B). Primary outcomes were morbidity and mortality, LOS, and readmission rate. Results Hundred and thirty-six patients underwent major colorectal surgery in group A and 173 in group B. Post-operative complications and readmission rate were comparable between the two groups. Oncologic case-log was predominant in group A comparing with group B (73.5 vs 61%, p=0.01). A significantly shorter overall LOS was found in group A (p, Elective colorectal surgery, under special precautionary measures, can be safely undertaken with reasonable outcome during COVID 19 pandemic. The empowered infection risk awareness may promote patients engagement with enhanced recovery protocol leading to a significative reduction of the postoperative length of stay.