Perianal fistulizing Crohn's disease-associated anorectal and fistula cancers: systematic review and expert consensus.

BACKGROUND AND AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSION: Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.

Controversies in IPAA for Ulcerative Colitis: A Systematic Review of Different Anastomotic Techniques.

BACKGROUND: Available techniques for IPAA in ulcerative colitis include handsewn, double-stapled, and single-stapled anastomoses. There are controversies, indications, and different outcomes regarding these techniques. OBJECTIVE: To describe technical details, indications, and outcomes of 3 specific types of anastomoses in restorative proctocolectomy. DATA SOURCE: Systematic literature review for articles in the PubMed database according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. STUDY SELECTION: Studies describing outcomes of the 3 different types of anastomoses, during pouch surgery, in patients undergoing restorative proctocolectomy for ulcerative colitis. INTERVENTION: IPAA technique. MAIN OUTCOME MEASURES: Postoperative outcomes (anastomotic leaks, overall complication rates, and pouch function). RESULTS: Twenty-one studies were initially included: 6 studies exclusively on single-stapled IPAA, 2 exclusively on double-stapled IPAA, 6 studies comparing single-stapled to double-stapled techniques, 6 comparing double-stapled to handsewn IPAA, and 1 comprising single-stapled to handsewn IPAA. Thirty-seven studies were added according to authors' discretion as complementary evidence. Between 1990 and 2015, most studies were related to double-stapled IPAA, either only analyzing the results of this technique or comparing it with the handsewn technique. Studies published after 2015 were mostly related to transanal approaches to proctectomy for IPAA, in which a single-stapled anastomosis was introduced instead of the double-stapled anastomosis, with some studies comparing both techniques. LIMITATIONS: A low number of studies with handsewn IPAA technique and a large number of studies added at authors' discretion were the limitations of this strudy. CONCLUSIONS: Handsewn IPAA should be considered if a mucosectomy is performed for dysplasia or cancer in the low rectum or, possibly, for re-do surgery. Double-stapled IPAA has been more widely adopted for its simplicity and for the advantage of preserving the anal transition zone, having lower complications, and having adequate pouch function. The single-stapled IPAA offers a more natural design, is feasible, and is associated with reasonable outcomes compared to double-stapled anastomosis. See video from symposium.

Short-term outcomes of surgical treatment for primary ileocaecal Crohn's disease: Results of the Crohn's(urg) study, a multicentre, retrospective, comparative analysis between inflammatory and complicated phenotypes.

AIM: Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short-term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. METHOD: A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short-term results were compared. RESULTS: A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). CONCLUSION: Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery.

Postoperative Complications Are Associated With an Early and Increased Rate of Disease Recurrence After Surgery for Crohn's Disease.

BACKGROUND: Several potential risk factors for Crohn's disease recurrence after surgery have been identified, including age at diagnosis, disease phenotype, and smoking. Despite the clinical relevance, few studies investigated the role of postoperative complications as a possible risk factor for disease recurrence. OBJECTIVE: To investigate the association between postoperative complications and recurrence in Crohn's disease patients after primary ileocolic resection. DESIGN: This was a retrospective case-control study. SETTING: This study was conducted at 2 tertiary academic centers. PATIENTS: We included 262 patients undergoing primary ileocolic resection for Crohn's disease between January 2008 and December 2018 and allocated the patients into recurrent (145) and nonrecurrent (117) groups according to endoscopic findings. MAIN OUTCOME MEASURES: Postoperative complications were assessed as possible risk factors for endoscopic recurrence after surgery by univariable and multivariable analyses. The effect of postoperative complications on endoscopic and clinical recurrence was evaluated by Kaplan-Meier and Cox regression analyses. RESULTS: On binary logistic regression analysis, smoking (OR = 1.84; 95% CI, 1.02-3.32; p = 0.04), penetrating phenotype (OR = 3.14; 95% CI, 1.58-6.22; p < 0.01), perianal disease (OR = 4.03; 95% CI, 1.75-9.25; p = 0.001), and postoperative complications (OR = 2.23; 95% CI, 1.19-4.17; p = 0.01) were found to be independent risk factors for endoscopic recurrence. Postoperative complications (HR = 1.45; 95% CI, 1.02-2.05; p = 0.03) and penetrating disease (HR = 1.73; 95% CI, 1.24-2.40; p = 0.001) significantly reduced the time to endoscopic recurrence; postoperative complications (HR = 1.6; 95% CI, 1.02-2.88; p = 0.04) and penetrating disease (HR = 207.10; 95% CI, 88.41-542.370; p < 0.0001) significantly shortened the time to clinical recurrence. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Postoperative complications are independent risk factors for endoscopic recurrence after primary surgery for Crohn's disease, affecting the rate and timing of endoscopic and clinical disease recurrence. See Video Abstract at http://links.lww.com/DCR/C48 . LAS COMPLICACIONES POSOPERATORIAS ESTN ASOCIADAS CON UNA TASA TEMPRANA Y AUMENTADA DE RECURRENCIA DE LA ENFERMEDAD DESPUS DE LA CIRUGA PARA LA ENFERMEDAD DE CROHN: ANTECEDENTES: Se han identificado varios factores de riesgo potenciales para la recurrencia de la enfermedad de Crohn después de la cirugía, incluida la edad en el momento del diagnóstico, el fenotipo de la enfermedad y el tabaquismo. A pesar de la relevancia clínica, pocos estudios investigaron el papel de las complicaciones postoperatorias como posible factor de riesgo para la recurrencia de la enfermedad.OBJETIVO: Investigar la asociación entre las complicaciones postoperatorias y la recurrencia en pacientes con enfermedad de Crohn después de la resección ileocólica primaria.DISEÑO: Este fue un estudio retrospectivo de casos y controles.AJUSTE: Este estudio se realizó en dos centros académicos terciarios.PACIENTES: Incluimos 262 pacientes sometidos a resección ileocólica primaria por enfermedad de Crohn entre Enero de 2008 y Diciembre de 2018 y los asignamos en grupos recurrentes (145) y no recurrentes (117) según los hallazgos endoscópicos.PRINCIPALES MEDIDAS DE RESULTADO: Las complicaciones posoperatorias se evaluaron como posibles factores de riesgo de recurrencia endoscópica después de la cirugía mediante análisis univariable y multivariable. El efecto de las complicaciones posoperatorias sobre la recurrencia endoscópica y clínica se evaluó mediante análisis de regresión de Kaplan-Meier y Cox.RESULTADOS: En el análisis, tabaquismo (OR = 1,84; IC 95%: 1,02-3,32; p = 0,04), fenotipo penetrante (OR = 3,14; IC 95%: 1,58-6,22; p < 0,01), enfermedad perianal (OR = 4,03; IC 95%: 1,75-9,25; p = 0,001) y las complicaciones postoperatorias (OR = 2,23; IC 95%: 1,19-4,17; p = 0,01) fueron factores de riesgo independientes para la recurrencia endoscópica. Las complicaciones posoperatorias (HR = 1,45; IC 95%: 1,02-2,05; p = 0,03) y la enfermedad penetrante (HR = 1,73; IC 95%: 1,24-2,40; p = 0,001) redujeron significativamente el tiempo hasta la recurrencia endoscópica; las complicaciones posoperatorias (HR= 1,6; IC 95%: 1,02-2,88; p = 0,04) y la enfermedad penetrante (HR = 207,10; IC 95%: 88,41-542,37; p < 0,0001) acortaron significativamente el tiempo hasta la recurrencia clínica.LIMITACIONES: Este estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES: Las complicaciones postoperatorias son factores de riesgo independientes para la recurrencia endoscópica después de la cirugía primaria para la enfermedad de Crohn, lo que afecta la tasa y el momento de la recurrencia endoscópica y clínica de la enfermedad. Consulte el Video Resumen en http://links.lww.com/DCR/C48 . (Traducción-Dr. Yesenia Rojas-Khalil ).

Factors associated with stoma formation in ileocolic resection for Crohn's disease and the development of a predictive scoring system.

PURPOSE: 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). METHODS: 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). RESULTS: 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%. CONCLUSIONS: 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 .

Surgery versus Medical Therapy in Luminal Ileocecal Crohn's Disease.

The deeper understanding of the inflammatory process which gradually evolves into irreversible fibrosis and tissue damage has provided a precise picture of the disease course of luminal ileocecal Crohn's disease. According to the model of progressive structural damage, ideal time windows for medical and surgical treatment have been identified. While complicated disease clearly profits from surgical treatment, uncomplicated disease has become, in the last years, the most debatable setting in terms of different approaches including early surgery. On one hand, the rationale of traditional escalating medical therapy (step-up approach) has been undermined by the top-down medical approach. Indeed, the step-up approach has the possible drawback of delaying, up to a later disease stage, the use of more effective agents such as anti-tumor necrosis factors. Conversely, the top-down approach might expose patients to an overtreatment along with side effects including hypersensitivity to biologic agents. More recently, it has been shown how early surgery could be a valid option in this subset of patients being more cost-effective than medical therapy. Involving the surgeon at an early stage is considered now a good clinical practice and, in this scenario full of possibilities, the surgeon should be included into the decision-making process from the very beginning of patient management.

Intriguing Role of the Mesentery in Ileocolic Crohn's Disease.

Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease with unknown etiology. Up to 80% of patients will eventually require surgery throughout their lifetime, and often repeated resections are required for disease recurrence. Observations of "creeping fat" surrounding the diseased intestine renewed interest in the mesentery, recently defined as an organ with endocrine and immune functions. According to the inside-out model, the mesentery may be primarily affected in CD and subsequent cause alterations in the mucosa. Recently, lower surgical recurrence rates have been reported with en-bloc excision of the mesentery adjoining the diseased intestine. Results of ongoing randomized controlled trials may clarify the role of the mesentery in CD and possibly lead to its adoption as standard during surgery for Crohn's disease.

Rectal Cancer in Adolescent and Young Adult Patients: Pattern of Clinical Presentation and Case-Matched Comparison of Outcomes.

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 cáncer de recto en adolescentes y adultos jóvenes (edad ≤ 39) está aumentando. El diagnóstico temprano es un desafío en este subgrupo de pacientes.OBJETIVO:Analizar el cuadro de presentación y los desenlaces en adolescentes y adultos jóvenes con cáncer de recto esporádico.DISEÑO:Estudio retrospectivo.ÁMBITO:Tres centros europeos de tercer nivel.PACIENTES:Se analizaron los datos de adolescentes y adultos jóvenes operados de cáncer de recto esporádico (enero de 2008 - octubre de 2019). Para comparar los desenlaces se emparejó a adolescentes y adultos jóvenes con un grupo de pacientes mayores de 40 años operados en el mismo período de tiempo.PRINCIPALES VARIABLES ANALIZADAS:Cuadro clínico, resultados a largo plazo.RESULTADOS:Los cánceres de recto esporádicos en adolescentes y adultos jóvenes 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% tentía antecedentes familiares de cáncer colorrectal. El 24,7% eran obesos. El diagnóstico con base en los síntomas se informó en el 92,1% de los pacientes, el tiempo promedio desde los primeros síntomas hasta el diagnóstico fue de 13,7 meses. El síntoma más común en el momento del diagnóstico fue el sangrado rectal (68,8%). 12% y 34% de adolescentes y adultos jóvenes presentaron enfermedad localmente avanzada o metastásica en el momento del diagnóstico. Por lo tanto, el 68,3% y el 62,4% de adolescentes y adultos jóvenes recibieron neoadyuvancia y adyuvancia. La tasa de respuesta patológica 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 años, no se observaron diferencias en la sobrevida específica del cáncer, pero se informó una menor sobrevida libre de enfermedad en adolescentes y adultos jóvenes (p <0,0001) frente al grupo emparejado. Los adolescentes y adultos jóvenes en estadios I-II tuvieron una sobrevida específica por cáncer y una sobrevida libre de enfermedad más corta (p = 0,006; p <0,0001); el estadio III tuvo una sobrevida libre de enfermedad más baja (p = 0,01).LIMITACIONES:Diseño observacional y retrospectivo.CONCLUSIONES:El diagnóstico notablemente demorado en adolescentes y adultos jóvenes puede contribuir a la presentación de una enfermedad avanzada y a una menor sobrevida libre de enfermedad, incluso en estadios más tempranas, lo cual implica un mayor potencial metastásico en comparación con pacientes mayores. Consulte Video Resumen en http://links.lww.com/DCR/B537.

The Management of the Hospitalized Ulcerative Colitis Patient, the Medical-Surgical Conundrum.

PURPOSE OF REVIEW: In this study we present the evidence based management for patients hospitalized for UC with a special focus on the synergic approach of the two key actors of the inflammatory bowel disease multidisciplinary team (IBD-MDT): gastroenterologist and surgeon. RECENT FINDINGS: Focused treatment by a specialized IBD-MDT and early involvement of the colorectal surgeon in the management of hospitalized ulcerative colitis patients is advocated. The colectomy rate has not changed over the years. Moreover delayed surgery after admission is burden by increase complication and mortality. Thus, it is pivotal to identify the patients who are likely to undergo surgery, by mean of predictors of outcome, and to not prolong ineffective medical treatment. The perfect timing based on clinical close monitoring is crucial. Up to 25% of patients with ulcerative colitis (UC) may require hospitalization. The aim of admission is to evaluate severity of the disease, exclude infections and establish proper treatment while monitoring the response. During admission, the patient has to be closely observed for the possible development of toxic megacolon or perforation, which should prompt emergency colectomy. Up to 30% of UC patients will fail to respond to initial intravenous corticosteroid. Non responder or partial responder to medical therapy should be evaluated for timely surgery or could be considered for rescue medical therapy.

A scoring system to predict a prolonged length of stay after surgery for Crohn's disease.

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 < 0.0001). The statistically significant independent variables included the time since diagnosis, American Society of Anesthesiologists (ASA) grade, perioperative use of steroids, surgical access, strictureplasty and platelet count. The AUROCs for the development and validation cohorts were 0.732 and 0.7, respectively (p < 0.0001). The cut-off score suggested by Youden's index was 50, with a sensitivity of 65.6% and a specificity of 73.3%. CONCLUSION: The time since diagnosis, ASA grade, steroid use, surgical access, strictureplasty and platelet count were associated with a prolonged LOS and were used to develop a scoring system. The calculator is available online at https://rebrand.ly/Crohnscal.

Patients' perceptions of surgery for inflammatory bowel disease.

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.

The Management of the Hospitalized Ulcerative Colitis Patient: the Medical-Surgical Conundrum.

PURPOSE OF REVIEW: In this study, we present the evidence-based management for patients hospitalized for ulcerative colitis (UC) with a special focus on the synergic approach of the two key actors of the inflammatory bowel disease multidisciplinary team (IBD-MDT): gastroenterologist and surgeon. RECENT FINDINGS: Focused treatment by a specialized IBD-MDT and early involvement of the colorectal surgeon in the management of hospitalized UC patients is advocated. The colectomy rate has not changed over the years. Moreover, delayed surgery after admission is burden by increase complication and mortality rates. Thus, it is pivotal to identify the patients who are likely to undergo surgery, by mean of predictors of outcome, and not to prolong ineffective medical treatment. The perfect timing based on clinical close monitoring is crucial. Up to 25% of patients with ulcerative colitis (UC) may require hospitalization. The aim of admission is to evaluate severity of the disease, exclude infections and establish proper treatment while monitoring the response. During admission, the patient has to be closely observed for the possible development of toxic megacolon or perforation, which should prompt emergency colectomy. Up to 30% of UC patients will fail to respond to initial intravenous corticosteroid. Non-responder or partial responder to medical therapy should be evaluated for timely surgery or could be considered for rescue medical therapy.

Lymphatic endothelium contributes to colorectal cancer growth via the soluble matrisome component GDF11.

Colorectal cancer (CRC) is one of the most malignant tumors worldwide. Stromal cells residing in the tumor microenvironment strongly contribute to cancer progression through their crosstalk with cancer cells and extracellular matrix. Here we provide the first evidence that CRC-associated lymphatic endothelium displays a distinct matrisome-associated transcriptomic signature, which distinguishes them from healthy intestinal lymphatics. We also demonstrate that CRC-associated human intestinal lymphatic endothelial cells regulate tumor cell growth via growth differentiation factor 11, a soluble matrisome component which in CRC patients was found to be associated with tumor progression. Our data provide new insights into lymphatic contribution to CRC growth, aside from their conventional role as conduits of metastasis.

MFSD2A Promotes Endothelial Generation of Inflammation-Resolving Lipid Mediators and Reduces Colitis in Mice.

BACKGROUND & AIMS: Alterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation. METHODS: We performed lipidomic and functional analyses of MFSD2A in mucosal biopsies and primary human intestinal microvascular endothelial cells (HIMECs) isolated from surgical specimens from patients with active, resolving UC and healthy individuals without UC (controls). MFSD2A was knocked down in HIMECs with small hairpin RNAs or overexpressed from a lentiviral vector. Human circulating endothelial progenitor cells that overexpress MFSD2A were transferred to CD1 nude mice with dextran sodium sulfate-induced colitis, with or without oral administration of DHA. RESULTS: Colonic biopsies from patients with UC had reduced levels of inflammation-resolving DHA-derived epoxy metabolites compared to healthy colon tissues or tissues with resolution of inflammation. Production of these metabolites by HIMECs required MFSD2A, which is required for DHA retention and metabolism in the gut vasculature. In mice with colitis, transplanted endothelial progenitor cells that overexpressed MFSD2A not only localized to the inflamed mucosa but also restored the ability of the endothelium to resolve intestinal inflammation, compared with mice with colitis that did not receive MFSD2A-overexpressing endothelial progenitors. CONCLUSIONS: Levels of DHA-derived epoxides are lower in colon tissues from patients with UC than healthy and resolving mucosa. Production of these metabolites by gut endothelium requires MFSD2A; endothelial progenitor cells that overexpress MFSD2A reduce colitis in mice. This pathway might be induced to resolve intestinal inflammation in patients with colitis.

Testing of microencapsulated porcine hepatocytes in a new model of fulminant liver failure in baboons.

BACKGROUND: There is no standard therapy for acute liver failure. Hepatocyte transplantation has been proposed for temporary liver function support, while the injured liver regenerates or while waiting for transplantation. We have previously shown such efficacy for microencapsulated porcine hepatocytes in mice with fulminant liver failure. We aimed to establish a large animal model for fulminant liver failure to assess the efficacy of microencapsulated porcine hepatocytes in temporary liver function support. METHODS: The model was developed in baboons; for testing microencapsulated hepatocytes, the best condition was 75% hepatectomy and 60 min warm ischemia time. Fulminant liver failure was characterized by steep increases in liver biochemical parameters, severe steatosis, and massive hepatocyte necrosis during the first 10 days. Hepatocytes from miniature swine were microencapsulated in alginate-poly-l-lysine microspheres, and transplanted intraperitoneally immediately after hepatectomy and warm ischemia (80-120 mL packed hepatocytes in 200-350 mL microspheres, about 30%-50% of the baboon's native liver volume). RESULTS: In the control group, three of five animals were sacrificed after 6-10 days because of fulminant liver failure, and two of five animals recovered normal liver function and survived until elective euthanasia (28 days). In the treatment group of four animals, one animal developed liver failure but survived to 21 days, and three animals recovered completely with normal liver function. CONCLUSIONS: The results indicate that microencapsulated porcine hepatocytes provide temporary liver function support in baboons with fulminant liver failure. These data support development of this cell therapy product toward clinical trials in patients with acute liver failure.

First experience in colorectal surgery with a new robotic platform with haptic feedback.

The use of robotic techniques is increasing in colorectal surgery. Recently, the Senhance™ surgical robotic system was introduced as a novel robotic platform designed to overcome some of the limits of standard laparoscopy. This study describes the initial, single center experience, evaluating feasibility and safety of the new robotic system in performing colorectal surgical procedures. METHODS: From June 2015 to November 2016, perioperative data of the first 45 patients who underwent robotic colorectal surgery with the SenhanceTM surgical robotic system were collected and analyzed. Indications for surgery included inflammatory bowel disease, colorectal cancer, endoscopically unresectable adenomas and complicated diverticular disease. RESULTS: The median age was 57 years (18-92) and the median BMI was 24 Kg/m2 (16-30). Surgical indications were colorectal cancer (66%), complicated inflammatory bowel disease (18%), diverticular disease (11%) and endoscopically unresectable adenoma (4.4%). The median operative time was 256 minutes; the median docking time 10.7 min (range 2-25). There were 3 conversions to standard laparoscopy, and none to laparotomy. All patients operated on for malignancy (28 adenocarcinoma, 2 neuroendocrine tumors) underwent an appropriate oncological procedure. The median time to discharge was 5 days (range 3-19). The incidence of post-operative complications was 35.5% (Clavien-Dindo I/II-14 patients, III-2 patients). One patient was readmitted in the postoperative period. No patient required reoperation. CONCLUSION: The results of this audit suggest that adoption of The Senhance™ surgical robotic system in colorectal surgery is feasible and safe. More clinical data are needed to determine whether this approach can offer any other benefits over other minimally invasive surgical techniques. This article is protected by copyright. All rights reserved.

Fluorescence angiography during transanal trans-stomal proctectomy and ileal pouch anal anastomosis: a video vignette.

Indocanine green (ICG) fluorescence is able to assess in vivo tissue perfusion. This technique has been validated in colorectal surgery and provides, by real time angiography, the evaluation of bowel perfusion before anastomosis[1]. This video shows the usefulness of ICG fluorescence application in ileal pouch anal surgery. This article is protected by copyright. All rights reserved.

Management and outcome of cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer.

The aim of this study was to evaluate management strategies and related outcomes for cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer with gastric conduit reconstruction. Patients with esophageal cancer undergoing transthoracic esophagectomy with cervical anastomosis from October 2003 to December 2014 were identified from a prospectively acquired database. Management strategies and related outcomes among patients with anastomotic leakage confined to the neck were compared to patients with intrathoracic manifestation of anastomotic leakage. From a total of 286 patients, leakage of the cervical anastomosis occurred in 60 patients (21%) at a median time of 7 days after esophagectomy. Leakage was confined to the neck in 23 of 60 patients (38%), whereas 37 of 60 patients (62%) presented with intrathoracic spread. Leakages with intrathoracic manifestation were more frequently accompanied by a positive SIRS score compared to leakages confined to the neck (73% vs. 35%, respectively; P = 0.004). Drainage of the anastomotic leakage through the neck wound was effective in all of 23 patients (100%) with cervical manifestation. In patients with intrathoracic manifestation, mediastinal drainage through the neck was successful in 15 of 37 patients (41%), whereas 22 patients (59%) required an intervention through the thoracic cavity. Compared to patients with leakage confined to the neck, patients with intrathoracic manifestation showed prolonged intensive care unit (ICU) stay (median 6 vs. 2 days, respectively; P = 0.001), hospital stay (median 34 vs. 19 days, respectively; P < 0.001), and time to oral intake (32 vs. 23 days, respectively; P = 0.018). Intrathoracic manifestation of cervical anastomotic leakage occurs in more than half of patients with anastomotic leakage after transthoracic esophagectomy for cancer. A SIRS reaction should raise the suspicion of intrathoracic spread of leakage. Intrathoracic manifestation can be managed effectively by mediastinal drainage through the neck in 41% of patients, but a reintervention through the thoracic cavity is required in 59%. Intrathoracic manifestation of leakage results in prolonged ICU/hospital stay and delays time to oral intake compared with leakage confined to the neck.