Detection rate of colorectal cancer by routine colonoscopy is comparable in patients aged 45-49 and 50-54 years.

OBJECTIVES: Colorectal carcinoma remains one of the most common malignancies worldwide. Colonoscopy screening is most effective for early detection and tumour prevention and is currently recommended in Europe for adults aged over 50 years. However, given that an increasing proportion of patients are diagnosed before the age of 50, we set out to determine the detection rate of colorectal carcinoma in patients younger than 50 years and to determine the best threshold for starting colonoscopy screening. METHODS: Single-centre, retrospective cohort study of all colonoscopies performed, regardless of indication, in our department at a tertiary Swiss university hospital in patients aged ≥18 and <60 years between 2016 and 2021. Colorectal cancer detection rate was calculated per 5-year age group and analysed separately by sex. RESULTS: The current analysis included 2846 colonoscopies performed for any indication. Colorectal carcinoma was found in 5/366 (1.4%) patients aged 45-49 years (3/210 or 1.4% of males and 2/156 or 1.3% of females) and in 9/819 (1.1%) patients aged 50-54 years (5/495 or 1.0% of males and 4/324 or 1.2% of females). Adenomas with high-grade dysplasia were found in 5/366 (1.4%) patients aged 45-49 years and in 11/819 (1.3%) aged 50-54 years; by sex, in 4/210 or 1.9% of males and 1/156 or 0.6% of females aged 45-49 years, and in 6/495 or 1.2% of males and 5/324 or 1.5% of females aged 50-54 years. Detection of adenoma with low-grade dysplasia increased from 14.6% (21/144) at age <30 years to 41% (150/366) at 45-49 years and 43.5% (356/819) at 50-54 years. A similar increasing trend was also seen if we analysed these groups by sex. CONCLUSIONS: The detection rate of colorectal carcinoma, but also adenomas, in our patients aged 45-49 years was similar to that in patients aged over 50, in both sexes. Thus our data are in line with the assumption that lowering the screening age to 45 years might be reasonable from a medical point of view for achieving a reduction in disease-specific mortality by improved screening strategies.

Episodic Abdominal Pain-An Unexpected Cause for a Common Clinical Problem.

A previously healthy 55-year-old male patient presented repeatedly to the emergency department with severe episodic periumbilical abdominal pain. After an extensive diagnostic work-up and subsequent clinical deterioration, appendiceal diverticulitis was diagnosed. We identified a correlation of white blood cell counts and possibly faecal calprotectin with the clinical presentation. We suggest that appendiceal diverticulitis should be considered in middle-aged patients with recurrent episodes of abdominal pain that correlate with laboratory markers of inflammation.

Crosstalk within peripheral blood mononuclear cells mediates anti-inflammatory effects of n-3 PUFA-rich lipid emulsions in parenteral nutrition.

BACKGROUND AND AIMS: Parenteral nutrition (PN) rich in n-6 and n-3 long-chain fatty acids is used in clinical practice for nourishing patients who are unable to receive adequate nutrition through their digestive systems. In this study, we compare the effect on inflammation of the commonly used lipid emulsions Omegaven (n-3-rich) and Intralipid (n-6-rich) in human peripheral blood mononuclear cells (PBMCs). METHODS: PBMCs were treated with different doses of n-3-rich Omegaven and n-6-rich Intralipid and the immune cells were characterized by flow cytometry. RESULTS: We show that incubation of PBMCs with n-3-rich Omegaven leads to an increase in expression of CD1d and CD86 in CD14+monocytes. At the same time, an increased number of NKT cells expressing cytotoxic T cell antigen 4 is observed, suggesting immunological synapse formation. Both CD14+monocytes and NKT cells showed an increase in IL-10 production and a reduction in the pro-inflammatory cytokines IFN-γ, TNF-α, and IL-4, which led to an increase in the number of FOXP3+T regulatory cells. In addition, we show that n-3-rich Omegaven reduces the expression of TNFα, IFNγ and IL-4 in CD4+T and CD8+T cells independent of the presented interaction between CD14+monocytes and NKT cells. The described mechanism of n-3 rich lipid emulsions was confirmed in PBMCs from patients with inflammatory bowel disease but not in colorectal cancer patients which seem to lack the interaction between CD14+monocytes and NKT cells. CONCLUSIONS: These results show a mechanism for the beneficial effect of the n-3-rich Omegaven in patients with inflammatory conditions but questions its use in patients with cancer. Hence, our results may assist in choosing the best lipid emulsion for patients who require PN.

Routine Endoscopy Prior to Surgical Ostomy Closure: An Obsolete Concept.

BACKGROUND: Closure of temporary diverting ostomies is commonly preceded by an endoscopic study of the colonic mucosa and anastomosis, despite lacking evidence of its relevance and impact on subsequent operative management. AIM: We sought to determine the incidence of pathological findings and therefore evaluate the clinical benefit of routine pre-operative endoscopy in asymptomatic patients, hypothesizing sole evaluation of the anastomotic integrity to be sufficient in these cases. METHODS: We retrospectively identified all adult patients with ostomy installations who were followed up for potential reversal surgery between 2002 and 2020 at the University Hospital of Zurich, Switzerland. Main outcome measures were the incidence of endoscopically identified pathological findings in the asymptomatic case cohort and their impact on the subsequent course of treatment. RESULTS: Pre-procedural endoscopic data of 187 cases evaluated for ostomy closure were evaluated. Relevant mucosal findings in the asymptomatic cohort were documented in 26.3% and findings at the anastomotic site detected in 8.7%. A change in subsequent surgical management was noted in 10 patients of the entire cohort (5.3%) and in 9 (5.1%) of all asymptomatic cases. Upon multivariate analyses, the age range of 51 to 60 years old was found to be significantly linked to the presence of endoscopic findings entailing a change in patient management. CONCLUSION: Our findings strongly suggest ostomy closure surgery without previous assessment of the bowel mucosa by means of endoscopy to be acceptable in asymptomatic patients. However, we found it to be indicated in all patients meeting the screening criteria for colorectal carcinoma.

Delivering Safe Surgical Care While Simultaneously Caring for Patients With COVID-19; Assessment of Patient Selection, Volume and Outcomes in a Tertiary Care Hospital.

Objectives: Compare patient selection and postoperative outcomes after surgical treatment for gastrointestinal disorders before and during the SARS-CoV-2 pandemic. Methods: We assessed gastrointestinal surgeries conducted at a tertiary center from 2017-2021 for differences in patient populations and procedures before (up to February 2020) and during the pandemic (March 2020 to December 2021). We analyzed mortality, Intensive Care Unit (ICU) length of stay, admission to ICU and postoperative complications for complex procedures using descriptive statistics and regression models. Results: 7309 procedures were analyzed, showing a caseload reduction in March and October 2020, but no statistical evidence for fewer overall procedures overall. Population characteristics differed with lower Body Mass Indices in 2020 and 2021, more patients smoking and with diabetes treated in 2020. There was no increased mortality, ICU length of stay and in 1,144 complex procedures assessed low overall morbidity at 90 days postoperative. Conclusion: Delivering surgical care while treating patients for COVID-19 in the same hospital was safe. Healthcare officials should consider continuing surgical care during future health crises as consequences of limiting surgical treatment for gastrointestinal disorders may be fatal for patients.

Combining staged laparoscopic colectomy with robotic completion proctectomy and ileal pouch-anal anastomosis (IPAA) in ulcerative colitis for improved clinical and cosmetic outcomes: a single-center feasibility study and technical description.

Robotic proctectomy has been shown to lead to better functional outcomes compared to laparoscopic surgery in rectal cancer. However, in ulcerative colitis (UC), the potential value of robotic proctectomy has not yet been investigated, and in this indication, the operation needs to be adjusted to the total colectomy typically performed in the preceding 6 months. In this study, we describe the technique and analyze outcomes of a staged laparoscopic and robotic three-stage restorative proctocolectomy and compare the clinical outcome with the classical laparoscopic procedure. Between December 2016 and May 2021, 17 patients underwent robotic completion proctectomy (CP) with ileal pouch-anal anastomosis (IPAA) for UC. These patients were compared to 10 patients who underwent laparoscopic CP and IPAA, following laparoscopic total colectomy with end ileostomy 6 months prior by the same surgical team at our tertiary referral center. 27 patients underwent a 3-stage procedure for refractory UC (10 in the lap. group vs. 17 in the robot group). Return to normal bowel function and morbidity were comparable between the two groups. Median length of hospital stay was the same for the robotic proctectomy/IPAA group with 7 days [median; IQR (6-10)], compared to the laparoscopic stage II with 7.5 days [median; IQR (6.25-8)]. Median time to soft diet was 2 days [IQR (1-3)] vs. 3 days in the lap group [IQR 3 (3-4)]. Two patients suffered from a major complication (Clavien-Dindo ≥ 3a) in the first 90 postoperative days in the robotic group vs. one in the laparoscopic group. Perception of cosmetic results were favorable with 100% of patients reporting to be highly satisfied or satisfied in the robotic group. This report demonstrates the feasibility of a combined laparoscopic and robotic staged restorative proctocolectomy for UC, when compared with the traditional approach. Robotic pelvic dissection and a revised trocar placement in staged proctocolectomy with synergistic use of both surgical techniques with their individual advantages will likely improve overall long-term functional results, including an improved cosmetic outcome.

Quality of Surgical Outcome Reporting in Randomised Clinical Trials of Multimodal Rectal Cancer Treatment: A Systematic Review.

INTRODUCTION: Randomised controlled trials (RCTs) continue to provide the best evidence for treatment options, but the quality of reporting in RCTs and the completeness rate of reporting of surgical outcomes and complication data vary widely. The aim of this study was to measure the quality of reporting of the surgical outcome and complication data in RCTs of rectal cancer treatment and whether this quality has changed over time. METHODS: Eligible articles with the keywords ("rectal cancer" OR "rectal carcinoma") AND ("radiation" OR "radiotherapy") that were RCTs and published in the English, German, Polish, or Italian language were identified by reviewing all abstracts published from 1982 through 2022. Two authors independently screened and analysed all studies. The quality of the surgical outcome and complication data was assessed based on fourteen criteria, and the quality of RCTs was evaluated based on a modified Jadad scale. The primary outcome was the quality of reporting in RCTs and the completeness rate of reporting of surgical results and complication data. RESULTS: A total of 340 articles reporting multimodal therapy outcomes for 143,576 rectal cancer patients were analysed. A total of 7 articles (2%) met all 14 reporting criteria, 13 met 13 criteria, 27 met from 11 to 12 criteria, 36 met from 9 to 10 criteria, 76 met from 7 to 8 criteria, and most articles met fewer than 7 criteria (mean 5.5 criteria). Commonly underreported criteria included complication severity (15% of articles), macroscopic integrity of mesorectal excision (17% of articles), length of stay (18% of articles), number of lymph nodes (21% of articles), distance between the tumour and circumferential resection margin (CRM) (26% of articles), surgical radicality according to the site of the primary tumour (R0 vs. R1 + R2) (29% of articles), and CRM status (38% of articles). CONCLUSION: Inconsistent surgical outcome and complication data reporting in multimodal rectal cancer treatment RCTs is standard. Standardised reporting of clinical and oncological outcomes should be established to facilitate comparing studies and results of related research topics.

Prognostic factors in patients with acute mesenteric ischemia-novel tools for determining patient outcomes.

BACKGROUND: Acute mesenteric ischemia (AMI) is a devastating disease with poor prognosis. Due to the multitude of underlying factors, prediction of outcomes remains poor. We aimed to identify factors governing diagnosis and survival in AMI and develop novel prognostic tools. METHODS: This monocentric retrospective study analyzed patients with suspected AMI undergoing imaging between January 2014 and December 2019. Subgroup analyses were performed for patients with confirmed AMI undergoing surgery. Nomograms were calculated based on multivariable logistic regression models. RESULTS: Five hundred and thirty-nine patients underwent imaging for clinically suspected AMI, with 216 examinations showing radiological indication of AMI. Intestinal necrosis (IN) was confirmed in 125 undergoing surgery, 58 of which survived and 67 died (median 9 days after diagnosis, IQR 22). Increasing age, ASA score, pneumatosis intestinalis, and dilated bowel loops were significantly associated with presence of IN upon radiological suspicion. In contrast, decreased pH, elevated creatinine, radiological atherosclerosis, vascular occlusion (versus non-occlusive AMI), and colonic affection (compared to small bowel ischemia only) were associated with impaired survival in patients undergoing surgery. Based on the identified factors, we developed two nomograms to aid in prediction of IN upon radiological suspicion (C-Index = 0.726) and survival in patients undergoing surgery for IN (C-Index = 0.791). CONCLUSION: As AMI remains a condition with high mortality, we identified factors predicting occurrence of IN with suspected AMI and survival when undergoing surgery for IN. We provide two new tools, which combine these parameters and might prove helpful in treatment of patients with AMI.

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD cohort study patients.

BACKGROUND: Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity. METHODS: We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn's disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design. RESULTS: Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients. CONCLUSION: As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma.

Single incision laparoscopic surgery (SILS) versus conventional laparoscopic technique for ileostomy: a retrospective cohort study.

PURPOSE: Minimal-invasive surgery has gained wide acceptance in colorectal surgery. Single incision laparoscopic surgery (SILS) was designed to minimize surgical trauma and improve postoperative outcome. However, the role of SILS in ileostomy formation is unclear. METHODS: In this retrospective cohort study 26 patients were included. Six patients were operated with SILS and 20 with conventional laparoscopic technique for ileostomy. We retrospectively evaluated patient charts for baseline characteristics including prior abdominal surgeries and combination of surgeries. Our primary efficacy objectives were operation time and postoperative hospitalization days. Our safety objectives included the prevalence of postoperative pain, parastomal hernia, incisional hernia, perforation, wound infection, ileus, and infections in general. RESULTS: Baseline characteristics including previous abdominal surgery and concomitant surgeries were comparable in both groups. Total operation time using SILS (37.5 ± 6.2 min [mean ± SD]), compared to laparoscopic surgery (82.2 ± 54.8 min [mean ± SD]) was significantly shorter (p = 0.0002). In a sensitivity analysis excluding patients with combined surgery, ileostomy formation by SILS was shorter (36.5 ± 6.2 min [mean ± SD]), compared to laparoscopy (59.7 ± 28.7 min [mean ± SD]; p = 0.024). Length of postoperative stay was not statistically different between the groups (SILS: 5.5 ± 2.4 days [mean ± SD]; laparoscopic: 13.8 ± 17.3 days [mean ± SD], p = 0.193). Postoperative complication rates were low and comparable in both groups. CONCLUSION: Placement of a loop ileostomy using SILS technique not only reduces surgical trauma but also operation time without affecting postoperative hospital stay or postoperative complication rates. Single-incision laparoscopic surgery for ileostomy is an appealing approach for ileostomy in selected patients.

Pneumatosis intestinalis in abdominal CT: predictors of short-term mortality in patients with clinical suspicion of mesenteric ischemia.

PURPOSE: Pneumatosis intestinalis (PI) in the bowel wall demonstrated in computed tomography (CT) of the abdomen is unspecific and its prognostic relevance remains poorly understood. The purpose of this study was to identify predictors of short-term mortality in patients with suspected mesenteric ischemia who were referred to abdominal CT and showed PI. METHODS: In this retrospective, IRB-approved, single-centre study, CT scans and electronic medical records of 540 patients who were referred to abdominal CT with clinical suspicion of mesenteric ischemia were analysed. 109/540 (20%) patients (median age 66 years, 39 females) showed PI. CT findings were correlated with surgical and pathology reports (if available), with clinical and laboratory findings, and with patient history. Short-term outcome was defined as survival within 30 days after CT. RESULTS: PI was found in the stomach (n = 6), small bowel (n = 65), and colon (n = 85). Further gas was found in mesenteric (n = 54), portal (n = 19) and intrahepatic veins (n = 36). Multivariate analysis revealed that PI in the colon [odds ratio (OR) 2.86], elevated blood AST levels (OR 3.00), and presence of perfusion inhomogeneities in other abdominal organs (OR 3.38) were independent predictors of short-term mortality. Surgery had a positive effect on mortality (88% lower likelihood of mortality), similar to the presence of abdominal pain (65% lower likelihood). CONCLUSIONS: Our study suggests that in patients referred for abdominal CT with clinical suspicion of mesenteric ischemia, location of PI in the colon, elevation of blood AST, and presence of perfusion inhomogeneities in parenchymatous organs are predictors of short-term mortality.

MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model.

Fistula treatment represents a major unmet medical need in the therapy of Crohn's disease (CD). Current medical therapies, such as anti-TNF antibody treatments, are often insufficient and do not achieve permanent fistula closure. Previously published data point toward a critical role for metalloproteinase-9 (MMP-9)/gelatinase B in fistula pathogenesis. The aim of this project was to investigate in detail MMP-9 expression in different fistula types and to confirm that MMP-9 is a potential target for fistula therapy in CD patients.Immunohistochemistry for total and active MMP-9, Cytokeratin 8 (CK-8) and co-staining of active MMP-9/CK-8 was performed in specimen derived from perianal fistulas, entero-enteric fistulas and fistulas from patients not responding to anti-TNF therapy. In addition, fistulas from the xenograft mouse model (anti-TNF treated or untreated) were analyzed.Total and active MMP-9 protein was detectable in cells lining the tracts of perianal and entero-enteric fistulas. Of note, total and active MMP-9 was also expressed in fistulas of CD patients non-responding to anti-TNF treatment. Interestingly, we detected considerable co-staining of active MMP-9 and CK-8 in particular in cells lining the fistula tract and in transitional cells around the fistulas. Furthermore, total and active MMP-9 are detectable in both anti-TNF treated and untreated xenograft fistulas.Taken together, our data suggest that MMP-9 is involved in fistula pathogenesis in CD patients, in fistulas of different origins and particularly in patients non-responding to anti-TNF therapy. Our xenograft fistula model is suitable for in vivo studies investigating a possible therapeutic role for MMP-9 targeting as fistula therapy.

Long-term immune-related adverse events after discontinuation of immunotherapy.

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and ipilimumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Lay abstract Checkpoint inhibitors have revolutionized therapy for suitable cancers. However, they can cause side effects that are reminiscent of autoimmune diseases. While most adverse effects occur during ongoing therapy, there are increasing reports of late-onset adverse effects after discontinuation of therapy and of long-lasting adverse effects after discontinuation of treatment, which may remain latent even if symptom relief could be achieved by immunosuppression. We present a patient case with reappearance of a severe inflammation of the large bowel (colitis) after closure of an ostomy over 1 year after withdrawal of immune checkpoint inhibitor therapy. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Combination of Vedolizumab With Tacrolimus Is More Efficient Than Vedolizumab Alone in the Treatment of Experimental Colitis.

BACKGROUND: Vedolizumab is a widely used and safe therapy in inflammatory bowel disease, particularly in ulcerative colitis (UC), making it a promising candidate for enhanced efficacy by combining it with additional immunomodulatory medications. In this study, we studied the impact of vedolizumab monotreatment vs vedolizumab coadministration with other immunomodulatory drugs on intestinal inflammation and intestinal immune cells in vivo. METHODS: Colon tissue from human patients with UC with active disease or in remission with or without vedolizumab treatment was stained by immunohistochemistry. We reconstituted NOD-SCID-SGM3 mice with human CD34+ cells and treated them with dextran sodium sulfate to induce acute colitis. Mice were treated with vedolizumab alone, or in combination with tacrolimus, ozanimid, or tofacitinib. RESULTS: Vedolizumab reduced the number of CD3+ T cells and CD68+ monocytes/macrophages in the colon of patients with UC with active disease. Vedolizumab moderately decreased immune cell numbers in acute dextran sodium sulfate-induced colitis. The combination of vedolizumab with tacrolimus further reduced the number of infiltrating CD3+ T cells and CD68+ monocytes/macrophages and was superior in ameliorating intestinal inflammation when compared to vedolizumab monotreatment. In contrast, cotreatment using vedolizumab with ozanimod or tofacitinib had no additive effect. CONCLUSIONS: Our data show that vedolizumab reduces the number of innate and adaptive immune cells in the mucosa of patients with UC. Further, the combination of vedolizumab with tacrolimus was more efficient to reduce immune cell numbers and to increase therapeutic efficacy than vedolizumab monotreatment. This finding indicates that combination treatment using these two drugs may be beneficial for patients who do not respond to vedolizumab monotherapy.

Colorectal cancer of the young displays distinct features of aggressive tumor biology: A single-center cohort study.

BACKGROUND: In recent years, a decrease in incidence and mortality of colorectal cancer (CRC) has been observed in developed nations, presumably through public disease awareness and increased screening efforts. However, a rising incidence of CRC in young patients below the age of 50 years has been reported in several studies. AIM: To study tumor biology in CRC patients below 50 years of age. METHODS: All patients with CRC were prospectively enrolled in our single-center oncologic database from January 2013 to December 2018 and were grouped and analyzed according to age (≥ 50 and < 50 years). Clinical as well as histopathological features were analyzed and compared. The study was approved by the local Ethics Committee. Fisher's exact test or t-test was used to test for differences between the groups, as appropriate. All statistical analysis was performed with IBM SPSS software Version 25 (SPSS Inc, Armonk, NY, United States) and with R-Studio using R Version 3.4.1 (RStudio, Boston, MA, United States). RESULTS: Seventeen percent of the 411 patients were younger than 50 years. Young patients were more often diagnosed with locally advanced T4-tumors and lymph node metastases (36.6% and 62% vs 17.7% and 42%; P < 0.01). In addition, a higher frequency of poorly differentiated (G3) tumors (40% vs 22.4% P < 0.05) was observed. More than every second patient below 40 years of age (51.8%) had distant metastases at diagnosis with a significant higher rate ring of signet cell differentiation compared to patients ≥ 50 years (14.8%, P < 0.05). Mutational status (KRAS, NRAS, BRAF, MSI) as well as selected behavioral risk factors showed no significant differences. CONCLUSION: Distinct histopathologic features of increased biologic aggressiveness are found in patients with CRC of young-onset. Those patients present more frequently with more advanced tumor stages compared to older patients. Features of aggressive tumor biology underscore the need for earlier uptake of routine screening measures.

Perianal fistulodesis - A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae.

BACKGROUND: Perianal fistulae strongly impact on quality of life of affected patients. AIM: To challenge and novel minimally invasive treatment options are needed. METHODS: Patients with Crohn's disease (CD) in remission and patients without inflammatory bowel disease (non-IBD patients) were treated with fistulodesis, a method including curettage of fistula tract, flushing with acetylcysteine and doxycycline, Z-suture of the inner fistula opening, fibrin glue instillation, and Z-suture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks. Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included. The primary end point was fistula healing, defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk. RESULTS: Fistulodesis was performed in 17 non-IBD and 3 CD patients, with a total of 22 fistulae. After 24 wk, all fistulae were healed in 4 non-IBD and 2 CD patients (overall 30%) and fistula remained closed until the end of follow-up at 10-25 mo. In a secondary per-fistula analysis, 7 out of 22 fistulae (32%) were closed. Perianal disease activity index (PDAI) improved in patients with fistula healing. Low PDAI was associated with favorable outcome (P = 0.0013). No serious adverse events were observed. CONCLUSION: Fistulodesis is feasible and safe for perianal fistula closure. Overall success rates is at 30% comparable to other similar techniques. A trend for better outcomes in patients with low PDAI needs to be confirmed.

Nighttime Cholecystectomies are Safe When Controlled for Individual Patient Risk Factors-A Nationwide Case-Control Analysis.

BACKGROUND: The aim of this study was to evaluate if the time of day a cholecystectomy was performed affects in-hospital complication rates and mortality. METHODS: A national quality measurement database was retrospectively studied. Study period was 2010 to 2017. The inclusion criteria were operatively treated cholecystitis or another benign disease of the gallbladder. Further, the time of day the operation was performed must have been documented. We defined nighttime as all interventions performed between 7PM until 6AM. A total of 11'459 patients were included. Development of any complication during hospitalization and in-hospital mortality was the main outcomes. The first part of the study was solely descriptive. In the second part, we applied a 1:1 case-control-matching. A matched group of 274 pairs were further investigated. RESULTS: Only 8.4% of the procedures were performed during nighttime. Complications occurred in 6.7% of all patients. We found twice as many complications in the nighttime group compared to the daytime group. Mortality was 0.56% during daytime and 0.52% during nighttime. In a matched-pair analysis, however, we found no significant differences in the overall mortality rate nor in the occurrence of complications when comparing day- vs. nighttime operations. CONCLUSIONS: We found twice as many complications in the nighttime group (12%) compared to the daytime group (6.1%), mainly related to patient risk factors. In contrast to common apprehension, however, nighttime cholecystectomies were not associated with higher mortality rates.

Allogeneic expanded adipose-derived mesenchymal stem cell therapy for perianal fistulas in Crohn's disease: A case series.

AIM: Even with optimal medical and surgical therapy, perianal fistulas in patients with Crohn's disease (CD) have low closure rates. As a new therapeutic option, administration of local mesenchymal stem cells (MSCs) has proved to be an innovative option after failure of treatment with immunosuppressive or immunomodulatory agents. The aim of this work is to share our first experience with MSC administration and demonstrate its efficacy, safety and feasibility outside a clinical trial. METHOD: A total of 11 CD patients with complex perianal fistulas with nonactive or mildly active luminal disease were treated with local injection of 120 million allogeneic adipose-derived stem cells at a tertiary hospital between February 2019 and June 2020. RESULTS: The mean age of the 11 patients was 38.3 years, 72.7% were men and 27.2% were smokers. The mean duration of fistula manifestation was 7.8 years and, except for one patient (therapy with tacrolimus), all other patients had been treated with an antitumour necrosis factor agent without fistula healing in the last 6 months. After a mean follow-up time of 41.5 weeks, 72.7% (8/11) of patients had complete closure of their fistula and three patients failed MSC treatment. Complete fistula healing could be observed 4-6 weeks postoperatively in half of the patients, while 36.5% (4/11) of patients developed a perianal abscess which had to be drained. One patient experienced cytomegalovirus viraemia 2 weeks after MSC administration and one patient developed a testicular carcinoma 16 weeks after treatment. CONCLUSION: This case series demonstrates that the efficacy and safety of darvadstrocel in the ADMIRE trial can be replicated outside a clinical trial. This new modality in the treatment of complex perianal fistulas appears to be a promising therapeutic option for a challenging patient population.