Short and long-term outcomes of surgery for inflammatory (uncomplicated) ileocecal Crohn's disease: Multicentric retrospective analysis of 211 patients.

BACKGROUND: Surgical management for patients with inflammatory ileocecal Crohn's disease (CD) could be a reasonable alternative to second-line medical treatment. AIM: To assess short and long-term outcomes of patients operated on for inflammatory, ileocecal Crohn's disease. METHODS: A retrospective analysis of patients intervened at four referral hospitals during 2012-2021 was performed. RESULTS: 211 patients were included. 43% of patients underwent surgery more than 5 years after diagnosis, and 49% had been exposed to at least one biologic agent preoperatively. 89% were operated by laparoscopy, with 1.6% conversion rate. The median length of the resected bowel was 25 cm (7-92) and three patients (1.43%) received a stoma. Median follow-up was 36 (17-70) months. The endoscopic recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 56%, 52%, 45%, 38%, and 33%, respectively. The clinical recurrence-free survival proportion at 24, 48, 72, 96, and 120 months was 83%, 79%, 76%, 74%, and 74%, respectively. In multivariate analysis, previous biological treatment (HR=2.01; p = 0.001) was associated with a higher risk of overall recurrence. CONCLUSION: Surgery in patients with primary inflammatory ileocecal CD is associated with good postoperative outcomes, low postoperative morbidity with reasonable recurrence rates.

The Impact of Crohn's Perianal Fistula on Quality of Life: Results of an International Patient Survey.

Background: Crohn's perianal fistula is a disabling manifestation of Crohn's disease. However, the additional burden of perianal fistula on patients with only Crohn's disease remains to be addressed. This patient-reported survey considered outcomes of two domains: "diagnosis" (eg, symptoms) and "living with the disease" (eg, quality of life, well-being, and relationships). Methods: Patients with perianal fistula and Crohn's disease completed an online, self-selective, anonymous, 46-item survey available in 11 languages hosted on the European Federation of Crohn's & Ulcerative Colitis Associations and national patient association websites. The survey was conducted between July and December 2019 in Europe and other regions. Likert scales and closed questions were used to assess outcomes. Results: Of the 820 respondents with Crohn's disease (67.2% women; median age, 40.0 years), 532 (64.9%) reported the presence of perianal fistula. Patients with perianal fistula reported a greater impact on overall quality of life (P < .001), well-being (P < .001), relationships (P < .001), social life (P = .001), and work life (P = .012) than patients with only Crohn's disease. Conclusions: Perianal fistulas impact several domains of the life of patients with Crohn's disease. These results may help healthcare practitioners plan therapeutic strategies that address the symptomatic and psychological burden experienced by patients with perianal fistulizing Crohn's disease.

Transanal transection and single-stapling techniques are associated with shorter rectal cuff and lower urgency rate after pouch surgery compared with the double-stapled approach.

BACKGROUND: Ileal pouch-anal anastomosis is most commonly performed by double-stapling technique after rectal transection with a linear stapler. Double-stapling is increasingly criticized for the uneven longer cuffs and potential weak points. A transanal rectal transection and single-stapled anastomosis may potentially overcome the limitations of double-stapling. A single-stapled anastomosis may be accomplished through a transanal rectal transection followed by bottom-up dissection (transanal-ileal pouch-anal anastomosis) or through an abdominal, rectal dissection and subsequent transanal transection and single-stapled anastomosis. The purpose of this study is to compare short-term and functional outcomes of double-stapling versus single-stapled techniques for ileal pouch-anal anastomosis. METHODS: This is a single-institution, ambidirectional study. Patients with ulcerative colitis undergoing ileal pouch-anal anastomosis between 2014 and 2021 were included in the study and allocated into 2 groups: group 1, including double stapled ileal pouch anal anastomosis, and group 2, including single-stapled-ileal pouch-anal anastomosis. The primary endpoint was the difference in functional parameters. RESULTS: A total of 130 patients were included, 46 undergoing double-stapling-ileal pouch-anal anastomosis and 84 receiving single-stapled ileal pouch-anal anastomosis. Rectal-cuff length (defined as the distance between the dentate line and ileal pouch-anal anastomosis) was shorter after single-stapled compared with double-stapling ileal pouch-anal anastomosis (1.98 ± 0.21 vs 2.20 ± 0.53 cm, P = .01). Anastomotic leak rate was comparable between group 1 and group 2 (6% vs 5%, P = .69). Functional parameters were comparable except for urgency, which was lower for single-stapled compared with double-stapling ileal pouch-anal anastomosis (8%, vs 30%, P = .002). CONCLUSION: Single-stapled ileal pouch-anal anastomosis was associated with a shorter rectal cuff and lower urgency than double-stapling ileal pouch-anal anastomosis. In our opinion, these results warrant a prospective multicentric trial to scrutinize and confirm these benefits on a larger scale.

Early Age of Onset Is an Independent Predictor for a Worse Response to Neoadjuvant Therapies in Sporadic Rectal Cancer Patients.

The incidence of rectal cancer (RC) is increasing in the population aged ≤ 49 (early-onset RC-EORC). EORC patients are more likely to present with locally advanced disease at diagnosis than late-onset RC (LORC; aged ≥ 50) patients. As a consequence, more EORC patients undergo neoadjuvant therapies. The response to treatment in EORC patients is still unknown. This study aims to explore the effect of age of onset on the pathological response to neoadjuvant therapies in sporadic locally advanced RC (LARC) patients. Based on an institutional prospectively maintained database, LARC patients undergoing neoadjuvant therapies and radical surgery between January 2010 and December 2022 were allocated to the EORC and LORC groups. The primary endpoint was the rate of incomplete response (Dworak 0-2). A total of 326 LORC and 79 EORC patients were included. Pre-neoadjuvant tumor features were comparable. A significantly higher rate of incomplete response was observed in EORC patients (49% vs. 35%; p = 0.028). From multivariable analysis, early age of onset, smoking and extramural invasion presented as independent risk factors for a worse response. This study demonstrates that an early age of onset is related to a worse response and calls for different multimodal strategies in this group of patients.

Single-stapled anastomosis is associated with a lower anastomotic leak rate than double-stapled technique after minimally invasive total mesorectal excision for MRI-defined low rectal cancer.

BACKGROUND: After total mesorectal excision, distal rectal transection and anastomosis are critical for short-term, oncological, and functional outcomes, including anastomotic leak. A double-pursestring, single-stapled anastomosis avoids cross-stapling, overcoming the potential drawbacks of transabdominal rectal transection and double-stapled anastomosis. This study aims to compare the anastomotic leak rate in double-stapled and single-stapled anastomoses after minimally invasive total mesorectal excision for magnetic resonance imaging-defined low rectal cancer. METHODS: Adult patients (>18 years old) undergoing minimally invasive total mesorectal excision for magnetic resonance imaging-defined low rectal cancer with a stapled low anastomosis (below 5 centimeters from the anal verge) between January 2010 and January 2022 at a single institution were allocated to 2 groups according to the anastomosis: double-stapled (abdominal stapled transection and double-stapled anastomosis) or single-stapled (transanal rectal transection and double-pursestring single-stapled anastomosis). The exclusion criteria were nonrestorative procedures or any type of manual anastomosis. The primary endpoint was the rate of 90-day clinical and radiologic anastomotic leak. RESULTS: In total, 185 single-stapled and 458 double-stapled were included. Clinical and tumor characteristics were comparable between the groups. The 90-day anastomotic leak rate was significantly lower in the single-stapled group (6.48% vs 15.28%; P = .002), with similar rates of grade and timing. Thirty- and 90-day complication rates were higher in the double-stapled group (P = .0001; P = .02), with comparable Clavien-Dindo grades. At multivariable analysis, double-stapled anastomosis (P = .01), active smoking (P = .03), and the presence of comorbidities (P = .01) resulted as independent risk factors for an anastomotic leak. CONCLUSION: Transanal transection and double-pursestring, single-stapled anastomosis were associated with a lower anastomotic leak rate after minimally invasive total mesorectal excision for magnetic resonance imaging-defined low rectal cancer.

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 ).

Dysfunctional Extracellular Matrix Remodeling Supports Perianal Fistulizing Crohn's Disease by a Mechanoregulated Activation of the Epithelial-to-Mesenchymal Transition.

BACKGROUND AND AIMS: 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. METHODS: Surgical specimens from perianal fistula tissue and the surrounding region of fistulizing CD were analyzed histologically and by RNA sequencing. Genes significantly modulated were validated by real-time polymerase chain reaction, Western blot, 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 overexpression of TSG-6 in Caco-2 cells and with exogenous addition of recombinant human TSG-6 protein to primary fibroblasts from region surrounding fistula. Proliferative and migratory assays were performed. RESULTS: A markedly different organization of ECM was found across fistula and surrounding fistula regions with an increased expression of integrins and matrix metalloproteinases 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 with area surrounding fistula, where it promoted the pathological formation of complexes between heavy chains from inter-alpha-inhibitor and HA responsible for the formation of a crosslinked ECM. There was a positive correlation between TNFAI6 expression and expression of mechanosensitive genes in fistula tissue. The overexpression of TSG-6 in Caco-2 cells promoted migration, epithelial-mesenchymal transition, transcription factor SNAI1, and HA 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 recombinant human TSG-6 protein promoted collagen release and increase of SNAI1, ITGA4, ITGA42B, and PTK2B genes, the latter being involved in the transduction of responses to mechanical stimuli. CONCLUSIONS: By mediating changes in the ECM organization, TSG-6 triggers the epithelial-mesenchymal transition transcription factor SNAI1 through the activation of mechanosensitive proteins. These data point to regulators of ECM as new potential targets for the treatment of CD perianal fistula.

Routine placement of abdominal drainage in pouch surgery does not impact on surgical outcomes.

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/m2 vs 21.9 ± 3.0 kg/m2; p = 0.007) and more commonly underwent two-stage proctocolectomy with IPAA compared to the NAD group (50.0% vs 3.9%; p < 0.001). There was no difference in anastomotic leak rate (6.5% AD vs 5.9% NAD group; p = 1.000), major post-operative complication (8.6% vs 7.9%; p = 0.893); median length of stay [IQR] (5 [5-7] days vs 5 [4-7] days; p = 0.305) and readmission < 90 days (8.7% vs 3.9%; p = 0.418). The use of AD does not impact on surgical outcome after IPAA and question the actual benefit of its routine placement.

Long-Term Outcomes of the Excluded Rectum in Crohn's Disease: A Multicenter International Study.

BACKGROUND: Many patients with Crohn's disease (CD) require fecal diversion. To understand the long-term outcomes, we performed a multicenter review of the experience with retained excluded rectums. METHODS: We reviewed the medical records of all CD patients between 1990 and 2014 who had undergone diversionary surgery with retention of the excluded rectum for at least 6 months and who had at least 2 years of postoperative follow-up. RESULTS: From all the CD patients in the institutions' databases, there were 197 who met all our inclusion criteria. A total of 92 (46.7%) of 197 patients ultimately underwent subsequent proctectomy, while 105 (53.3%) still had retained rectums at time of last follow-up. Among these 105 patients with retained rectums, 50 (47.6%) underwent reanastomosis, while the other 55 (52.4%) retained excluded rectums. Of these 55 patients whose rectums remained excluded, 20 (36.4%) were symptom-free, but the other 35 (63.6%) were symptomatic. Among the 50 patients who had been reconnected, 28 (56%) were symptom-free, while 22(44%) were symptomatic. From our entire cohort of 197 cases, 149 (75.6%) either ultimately lost their rectums or remained symptomatic with retained rectums, while only 28 (14.2%) of 197, and only 4 (5.9%) of 66 with initial perianal disease, were able to achieve reanastomosis without further problems. Four patients developed anorectal dysplasia or cancer. CONCLUSIONS: In this multicenter cohort of patients with CD who had fecal diversion, fewer than 15%, and only 6% with perianal disease, achieved reanastomosis without experiencing disease persistence.

Patients with distal Crohn's disease often undergo colon resection with a stoma to divert the intestinal stream from the rectum in hopes of achieving sufficient healing to allow ultimate re-establishment of intestinal continuity. Patients and practitioners alike should be aware of the long-term success rates of this procedure. Our retrospective study of 197 patients found that half required later proctectomy and an additional one-quarter remained symptomatic with excluded rectums. Only 14% remained symptom-free after reanastomosis, and only 6% if perianal disease was the initial surgical indication. These data provide estimation of long-term surgical outcomes.

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN).

BACKGROUND: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.

Different Oncologic Outcomes in Early-Onset and Late-Onset Sporadic Colorectal Cancer: A Regression Analysis on 2073 Patients.

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 potentially­and still unknown­more aggressive tumoral phenotype in EOCRC.

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 .

Early age of onset is an independent predictor for worse disease-free survival in sporadic rectal cancer patients. A comparative analysis of 980 consecutive 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 < 0.0001), stage III-IV (p = 0.001), microsatellite instability (p = 0.02), locoregional nodal (p = 0.001) and distant metastases (p < 0.0001). Accordingly, more EORC patients underwent adjuvant treatment (p < 0.0001). Mutations were mostly reported among LORC cases (p = 0.04), whereas EORC patients showed a worse R/PFS (p = 0.02), even at stage I (p = 0.04). CSS did not differ (p = 0.11) across groups. Multivariate analysis indicated age of onset (p = 0.04) was an independent predictor for progression/recurrence. CONCLUSIONS: Age of onset was shown to be an independent unfavorable predictor. Delayed diagnosis could explain this effect in the more advanced stages, while the worse outcomes in stage I may suggest a more aggressive disease behavior.

A Multidisciplinary Approach to Rectal Cancer Treatment in Ulcerative Colitis Results in High Rate of Restorative Minimally Invasive Surgery.

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.

Negative-pressure wound therapy after stoma reversal in colorectal surgery: a randomized controlled trial.

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).

Transanal Transection and Single-Stapled Anastomosis (TTSS): A comparison of anastomotic leak rates with the double-stapled technique and with transanal total mesorectal excision (TaTME) for rectal cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: TTSS strategy is feasible, safe and leads to very low AL rates after TME for RC.

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.

Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver.

Metastasis is facilitated by the formation of a "premetastatic niche," which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of CRC patients, we find that the increased levels of PV-1, a marker of impaired GVB, is associated with liver bacteria dissemination and metachronous distant metastases. Thus, PV-1 is a prognostic marker for CRC distant recurrence and vascular impairment, leading to liver metastases.