Spatial single cell profiling using imaging mass cytometry - inflammatory versus penetrating Crohn's disease.

BACKGROUND AND AIMS: Fistula formation is a major complication in Crohn's disease (CD) and the role of the immune cell compartment remains to be elucidated. Thus, we compared the immune-cell compartment of CD fistula to inflammatory CD colitis using imaging mass cytometry and immunofluorescence. METHODS: A 36-marker panel including structural, functional and lineage markers for use in imaging mass cytometry (IMC) was established. This panel was applied to analyze paraffin-embedded CD fistula tract (n=11), CD colitis (n=10), and colon samples from non-inflamed controls (n=12). Computational methods for cell segmentation, dimensionality reduction and cell type clustering were used to define cell populations for cell frequency, marker distribution and spatial neighborhood analysis. Multiplex immunofluorescence was used for higher resolution spatial analysis. RESULTS: Analysis of cell frequencies in CD fistulas compared to CD colitis and control colonic samples revealed a significant increase in neutrophils, effector cytotoxic T cells and inflammatory macrophages in CD fistula samples, whereas regulatory T cells were decreased. Neutrophils in CD fistula expressed significantly more matrix metalloproteinase 9 (MMP9), correlating to extracellular matrix remodeling. Neighborhood analysis revealed a strong association between MMP9+ neutrophils and effector cytotoxic T cells in both CD fistulas and colitis. CONCLUSIONS: This study presents the first highly multiplexed single cell analysis of the immune-cell compartment of CD fistulas and their spatial context. It links immune cell dynamics, particularly MMP9+ neutrophils, to extracellular matrix remodeling in CD fistulas, offering insights into the complex network of cellular interactions and potential therapeutic targets for CD complications.

Robotic-Assisted versus Laparoscopic Surgery for Rectal Cancer: An Analysis of Clinical and Financial Outcomes from a Tertiary Referral Center.

Background: The popularity of robotic-assisted surgery for rectal cancer is increasing, but its superiority over the laparoscopic approach regarding safety, efficacy, and costs has not been well established. Methods: A retrospective single-center study was conducted comparing consecutively performed robotic-assisted and laparoscopic surgeries for rectal cancer between 1 January 2016 and 31 September 2021. In total, 125 adult patients with sporadic rectal adenocarcinoma (distal extent ≤ 15 cm from the anal verge) underwent surgery where 66 were operated on robotically and 59 laparoscopically. Results: Severe postoperative complications occurred less frequently with robotic-assisted compared with laparoscopic surgery, as indicated by Clavien-Dindo classification grades 3b-5 (13.6% vs. 30.5%, p = 0.029). Multiple logistic regression analyses after backward selection revealed that robotic-assisted surgery was associated with a lower rate of total (Clavien-Dindo grades 1-5) (OR = 0.355; 95% CI 0.156-0.808; p = 0.014) and severe postoperative complications (Clavien-Dindo grades 3b-5) (OR = 0.243; 95% CI 0.088-0.643; p = 0.005). Total inpatient costs (median EUR 17.663 [IQR EUR 10.151] vs. median EUR 14.089 [IQR EUR 12.629]; p = 0.018) and surgery costs (median EUR 10.156 [IQR EUR 3.551] vs. median EUR 7.468 [IQR EUR 4.074]; p < 0.0001) were higher for robotic-assisted surgery, resulting in reduced total inpatient profits (median EUR -3.196 [IQR EUR 9.101] vs. median EUR 232 [IQR EUR 6.304]; p = 0.004). Conclusions: In our study, robotic-assisted surgery for rectal cancer resulted in less severe and fewer total postoperative complications. Still, it was associated with higher surgery and inpatient costs. With increasing experience, the operative time may be reduced, and the postoperative recovery may be further accelerated, leading to reduced surgery and total inpatient costs.

Optimizing Indocyanine Green Dosage for Near-Infrared Fluorescence Perfusion Assessment in Bowel Anastomosis: A Prospective, Systematic Dose-Ranging Study.

BACKGROUND: Indocyanine green (ICG) near-infrared fluorescence (NIRF) has emerged as a promising technique for visualizing tissue perfusion. However, within the wide range of dosages and imaging conditions currently being applied, the optimal dosage of ICG remains unclear. This study aimed to investigate the feasibility and implications of implementing lower dosages of ICG than commonly used for visual and quantitative perfusion assessment in a standardized setting. METHODS: A prospective single-center cohort study was conducted on patients undergoing ileostomy reversal by hand-sewn anastomosis. ICG-NIRF visualization was performed before (T1) and after (T2) anastomosis with one of four different dosages of ICG (5 mg, 2.5 mg, 1.25 mg, or 0.625 mg) and recorded. Postoperatively, each visualization was evaluated for signal strength, completeness, and homogeneity of fluorescence. Additionally, perfusion graphs were generated by a software-based quantitative perfusion assessment, allowing an analysis of perfusion parameters. Statistical analysis comparing the effect of the investigated dosages on these parameters was performed. RESULTS: In total, 40 patients were investigated. Visual evaluation demonstrated strong, complete, and homogeneous fluorescence signals across all dosages. Perfusion graph assessment revealed a consistent shape for all dosages (ingress followed by egress phase). While the average signal intensity decreased with dosage, it was sufficient to enable perfusion assessment even at the lowest dosages of 1.25 mg and 0.625 mg of ICG. The baseline intensity at T2 (the second intraoperative visualization) significantly decreased with dosage. The slope of the egress phase steepened with decreasing dosage. CONCLUSIONS: Lower dosages of ICG were sufficient for intraoperative perfusion assessment, while causing lower residual fluorescence and quicker egress in subsequent visualizations.

Role of visceral fat on postoperative complications and relapse in patients with Crohn's disease after ileocecal resection: Is it overrated?

INTRODUCTION: The role of visceral fat in disease development, particularly in Crohn´s disease (CD), is significant. However, its preoperative prognostic value for postoperative complications and CD relapse after ileocecal resection (ICR) remains unknown. This study aims to assess the predictive potential of preoperatively measured visceral and subcutaneous fat in postoperative complications and CD recurrence using magnetic resonance imaging (MRI). The primary endpoint was postoperative anastomotic leakage of the ileocolonic anastomosis, with secondary endpoints evaluating postoperative complications according to the Clavien Dindo classification and CD recurrence at the anastomosis. METHODS: We conducted a retrospective analysis of 347 CD patients who underwent ICR at our tertiary referral center between 2010 and 2020. We included 223 patients with high-quality preoperative MRI scans, recording demographics, postoperative outcomes, and CD recurrence rates at the anastomosis. To assess adipose tissue distribution, we measured total fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), and abdominal circumference (AC) at the lumbar 3 (L3) level using MRI cross-sectional images. Ratios of these values were calculated. RESULTS: None of the radiological variables showed an association with anastomotic leakage (TFA p = 0.932, VFA p = 0.982, SFA p = 0.951, SFA/TFA p = 0.422, VFA/TFA p = 0.422), postoperative complications, or CD recurrence (TFA p = 0.264, VFA p = 0.916, SFA p = 0.103, SFA/TFA p = 0.059, VFA/TFA p = 0.059). CONCLUSIONS: Radiological visceral obesity variables were associated with postoperative outcomes or clinical recurrence in CD patients undergoing ICR. Preoperative measurement of visceral fat measurement is not specific for predicting postoperative complications or CD relapse.

Assessment of resectability of pancreatic cancer using novel immersive high-performance virtual reality rendering of abdominal computed tomography and magnetic resonance imaging.

PURPOSE: Virtual reality (VR) allows for an immersive and interactive analysis of imaging data such as computed tomography (CT) and magnetic resonance imaging (MRI). The aim of this study is to assess the comprehensibility of VR anatomy and its value in assessing resectability of pancreatic ductal adenocarcinoma (PDAC). METHODS: This study assesses exposure to VR anatomy and evaluates the potential role of VR in assessing resectability of PDAC. Firstly, volumetric abdominal CT and MRI data were displayed in an immersive VR environment. Volunteering physicians were asked to identify anatomical landmarks in VR. In the second stage, experienced clinicians were asked to identify vascular involvement in a total of 12 CT and MRI scans displaying PDAC (2 resectable, 2 borderline resectable, and 2 locally advanced tumours per modality). Results were compared to 2D standard PACS viewing. RESULTS: In VR visualisation of CT and MRI, the abdominal anatomical landmarks were recognised by all participants except the pancreas (30/34) in VR CT and the splenic (31/34) and common hepatic artery (18/34) in VR MRI, respectively. In VR CT, resectable, borderline resectable, and locally advanced PDAC were correctly identified in 22/24, 20/24 and 19/24 scans, respectively. Whereas, in VR MRI, resectable, borderline resectable, and locally advanced PDAC were correctly identified in 19/24, 19/24 and 21/24 scans, respectively. Interobserver agreement as measured by Fleiss κ was 0.7 for CT and 0.4 for MRI, respectively (p < 0.001). Scans were significantly assessed more accurately in VR CT than standard 2D PACS CT, with a median of 5.5 (IQR 4.75-6) and a median of 3 (IQR 2-3) correctly assessed out of 6 scans (p < 0.001). CONCLUSION: VR enhanced visualisation of abdominal CT and MRI scan data provides intuitive handling and understanding of anatomy and might allow for more accurate staging of PDAC and could thus become a valuable adjunct in PDAC resectability assessment in the future.

Myenteric Plexus Immune Cell Infiltrations and Neurotransmitter Expression in Crohn's Disease and Ulcerative Colitis.

BACKGROUND AND AIMS: Pain is a cardinal symptom in inflammatory bowel disease [IBD]. An important structure in the transduction of pain signalling is the myenteric plexus [MP]. Nevertheless, IBD-associated infiltration of the MP by immune cells lacks in-depth characterisation. Herein, we decipher intra- and periganglionic immune cell infiltrations in Crohn´s disease [CD] and ulcerative colitis [UC] and provide a comparison with murine models of colitis. METHODS: Full wall specimens of surgical colon resections served to examine immune cell populations by either conventional immuno-histochemistry or immunofluorescence followed by either bright field or confocal microscopy. Results were compared with equivalent examinations in various murine models of intestinal inflammation. RESULTS: Whereas the MP morphology was not significantly altered in IBD, we identified intraganglionic IBD-specific B cell- and monocyte-dominant cell infiltrations in CD. In contrast, UC-MPs were infiltrated by CD8+ T cells and revealed a higher extent of ganglionic cell apoptosis. With regard to the murine models of intestinal inflammation, the chronic dextran sulphate sodium [DSS]-induced colitis model reflected CD [and to a lesser extent UC] best, as it also showed increased monocytic infiltration as well as a modest B cell and CD8+ T cell infiltration. CONCLUSIONS: In CD, MPs were infiltrated by B cells and monocytes. In UC, mostly CD8+ cytotoxic T cells were found. The chronic DSS-induced colitis in the mouse model reflected best the MP-immune cell infiltrations representative for IBD.

Postoperative intussusception: a rare but critical complication in adult patients with Crohn's disease - case report and literature review.

Objectives: Postoperative entero-enteric intussusception is a rare complication in adult patients with Crohn's disease (CD). The knowledge of this distinct complication and its timely diagnosis and therapy are of utmost importance to prevent fatal intestinal necrosis. There is no consensus about the optimal management of postoperative entero-enteric intussusception, although surgical exploration is widely advised. Case presentation: In this report we describe an unusual case of postoperative jejuno-jejunal intussusception following small bowel resection in a patient with stricturing CD. Furthermore, this report offers an overview of the available literature and summarizes the best approach and management strategies for adult intussusception associated with CD. Conclusions: Delay in diagnosis and therapy can lead to life-threatening complications. Early diagnosis and emergent surgical treatment prevent intestinal necrosis and reduce the risk of short bowel syndrome.

Standardized digital solution with surgical procedure manager (SPM®)-an opportunity for maximizing patient safety and efficiency in ileostomy reversal?

Background: Standardization and digitalization are getting more and more essential in surgery. Surgical procedure manager (SPM®) is a freestanding computer serving as a digital supporter in the operating room. SPM® navigates step-by-step through surgery by providing a checklist for each individual step. Methods: This was a single center, retrospective study at the Department for General and Visceral Surgery at Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin. Patients who underwent ileostomy reversal without SPM® in the period of January 2017 until December 2017 were compared to patients who were operated with SPM® in the period of June 2018 until July 2020. Explorative analysis and multiple logistic regression were performed. Results: Overall, 214 patients underwent ileostomy reversal: 95 patients without SPM® vs. 119 patients with SPM®. Ileostomy reversal was performed by head of department/attendings in 34.1%, by fellows in 28.5% and by residents in 37.4%; p = 0.91. Postoperative intraabdominal abscess emerged more often in patients without SPM®: ten (10.5%) patients vs. four (3.4%) patients; p = 0.035. Multiple logistic regression showed a risk reduction for intraabdominal abscess {Odds ratio (OR) 0.19 [95% confidence interval (CI) 0.05-0.71]; p = 0.014} and for bowel perforation [OR 0.09 (95% CI 0.01-0.93); p = 0.043] in the group with use of SPM® in ileostomy reversal. Conclusions: SPM® may reduce postoperative complications in ileostomy reversal such as intraabdominal abscess and bowel perforation. SPM® may contribute to patient safety.

Identification of Perioperative Procedural and Hemodynamic Risk Factors for Developing Colonic Ischemia after Ruptured Infrarenal Abdominal Aortic Aneurysm Surgery: A Single-Centre Retrospective Cohort Study.

(1) Background: This retrospective study evaluated perioperative and intensive care unit (ICU) variables to predict colonic ischemia (CI) after infrarenal ruptured abdominal aortic aneurysm (RAAA) surgery. (2) Materials and Methods: We retrospectively analyzed the data of the patients treated for infrarenal RAAA from January 2011 to December 2020 in our hospital. (3) Results: A total of 135 (82% male) patients were admitted to ICU after treatment of infrarenal RAAA. The median age of all patients was 75 years (IQR 68-81 years). Of those, 24 (18%) patients developed CI, including 22 (92%) cases within the first three postoperative days. CI was found more often after open repair compared to endovascular treatment (22% vs. 5%, p = 0.021). Laboratory findings in the first seven PODs revealed statistically significant differences between CI and non-CI patients for serum lactate, minimum pH, serum bicarbonate, and platelet count. Norepinephrine (NE) was used in 92 (68%) patients during ICU stay. The highest daily dose of norepinephrine was administered to CI patients at POD1. Multivariable analysis revealed that NE > 64 µg/kg (RD 0.40, 95% CI: 0.25-0.55, p < 0.001), operating time ≥ 200 min (RD 0.18, 95% CI: 0.05-0.31, p = 0.042), and pH < 7.3 (RD 0.21, 95% CI: 0.07-0.35, p = 0.019), significantly predicted the development of CI. A total of 23 (17%) patients died during the hospital stay, including 8 (33%) patients from the CI group and 15 (7%) from the non-CI group (p = 0.032). (4) Conclusions: CI after RAAA is a sever complication occurring most frequently within the first 3 postoperative days. Our study identified many surrogate markers associated with colonic ischemia after aortic RAAA, including norepinephrine dose > 64 µg/kg, operating time ≥ 200 min, and PH < 7.3. Future studies are needed to support these results.

The Value of Indocyanine Green Image-Guided Surgery in Patients with Primary Liver Tumors and Liver Metastases.

INTRODUCTION: Successful R0 resection is crucial for the survival of patients with primary liver cancer (PLC) or liver metastases. Up to date, surgical resection lacks a sensitive, real-time intraoperative imaging modality to determine R0 resection. Real-time intraoperative visualization with near-infrared light fluorescence (NIRF) using indocyanine green (ICG) may have the potential to meet this demand. This study evaluates the value of ICG visualization in PLC and liver metastases surgery regarding R0 resection rates. MATERIALS AND METHODS: Patients with PLC or liver metastases were included in this prospective cohort study. ICG 10 mg was administered intravenously 24 h before surgery. Real-time intraoperative NIRF visualization was created with the SpectrumTM fluorescence imaging camera system. First, all liver segments were inspected with the fluorescence imaging system and intraoperative ultrasound for identification of the known tumor, as well as additional lesions, and were compared to preoperative MRI images. PLC, liver metastases, and additional lesions were then resected according to oncological principles. In all resected specimens, the resection margins were analyzed with the fluorescence imaging system for ICG-positive spots immediately after resection. Histology of additional detected lesions, as well as ICG fluorescence compared to histological resection margins, were assessed. RESULTS: Of the 66 included patients, median age was 65.5 years (IQR 58.7-73.9), 27 (40.9%) were female, and 18 (27.3%) were operated on laparoscopically. Additional ICG-positive lesions were detected in 23 (35.4%) patients, of which 9 (29%) were malignant. In patients with no fluorescent signal at the resection margin, R0 rate was 93.9%, R1 rate was 6.1%, and R2 rate was 0% compared to an ICG-positive resection margin with an R0 rate of 64.3%, R1 rate of 21.4%, and R2 rate of 14.3% (p = 0.005). One- and two-year overall survival rates were 95.2% and 88.4%, respectively. CONCLUSION: The presented study provides significant evidence that ICG NIRF guidance helps to identify R0 resection intraoperatively. This offers true potential to verify radical resection and improve patient outcomes. Furthermore, implementation of NIRF-guided imaging in liver tumor surgery allows us to detect a considerable amount of additional malignant lesions.

Muscarinic Acetylcholine Receptor M3 Expression and Survival in Human Colorectal Carcinoma-An Unexpected Correlation to Guide Future Treatment?

Muscarinic acetylcholine receptor M3 (M3R) has repeatedly been shown to be prominently expressed in human colorectal cancer (CRC), playing roles in proliferation and cell invasion. Its therapeutic targetability has been suggested in vitro and in animal models. We aimed to investigate the clinical role of MR3 expression in CRC for human survival. Surgical tissue samples from 754 CRC patients were analyzed for high or low immunohistochemical M3R expression on a clinically annotated tissue microarray (TMA). Immunohistochemical analysis was performed for established immune cell markers (CD8, TIA-1, FOXP3, IL 17, CD16 and OX 40). We used Kaplan-Meier curves to evaluate patients' survival and multivariate Cox regression analysis to evaluate prognostic significance. High M3R expression was associated with increased survival in multivariate (hazard ratio (HR) = 0.52; 95% CI = 0.35-0.78; p = 0.001) analysis, as was TIA-1 expression (HR = 0.99; 95% CI = 0.94-0.99; p = 0.014). Tumors with high M3R expression were significantly more likely to be grade 2 compared to tumors with low M3R expression (85.7% vs. 67.1%, p = 0.002). The 5-year survival analysis showed a trend of a higher survival rate in patients with high M3R expression (46%) than patients with low M3R expression CRC (42%) (p = 0.073). In contrast to previous in vitro and animal model findings, this study demonstrates an increased survival for CRC patients with high M3R expression. This evidence is highly relevant for translation of basic research findings into clinically efficient treatments.

Near-infrared Fluorescence Imaging for Detecting Pancreatic Liver Metastasis in an Orthotopic Athymic Mouse Model.

BACKGROUND/AIM: Evidence of metastatic disease precludes oncological resection of pancreatic cancer. Near-infrared (NIR) fluorescent labels, such as indocyanine green (ICG), assist in the intraoperative detection of occult and micrometastatic liver disease. The present study aimed to analyse the role of NIR fluorescence imaging using ICG for pancreatic liver disease as proof of concept in an orthotopic athymic mouse model. MATERIALS AND METHODS: Pancreatic ductal adenocarcinoma was induced by injecting L3.6pl human pancreatic tumour cells into the pancreatic tail of seven athymic mice. After four weeks of tumour growth, ICG was injected into the tail vein and NIR fluorescence imaging was performed at harvest to determine tumour-to-liver ratios (TLR) using Quest Spectrum® Fluorescence Imaging Platform. RESULTS: Pancreatic tumour growth and liver metastasis could be visually confirmed for all seven animals. None of the hepatic metastases showed any detectable ICG-uptake. ICG-staining failed to visualize the liver metastases or to increase fluorescence intensity of the rim around the hepatic lesions. CONCLUSION: ICG-staining fails to visualize liver metastases induced by L3.6pl pancreatic tumour cells in athymic nude mice by NIR fluorescence imaging. Further studies are necessary to delineate the underlying mechanism for insufficient ICG uptake in these pancreatic liver metastases and for the lack of a fluorescent rim around the liver lesions.

[Effectiveness of Mucosal Advancement Flaps in Surgery of Perianal Fistulas from Crohn´s Disease and Cryptoglandular Fistulas - a Long-term Follow-up Study]. / Effektivität von Mukosa Muskel Flaps in der Behandlung von perianalen Fisteln bei Morbus Crohn und kryptoglandulären Fisteln ­ eine Langzeit-Follow-up-Studie.

AIM: Surgical treatment of perianal fistulae originating from Crohn's Disease (CD) or cryptoglandular abscess (CGA) remains a challenge. Data on long-term healing rates are scarce. We aimed to evaluate the long-term success rate of mucosal advancement flap (MAF) operations. METHODS: This single centre retrospective analysis was performed at a tertiary referral centre (Charité University Hospital Berlin, Campus Benjamin Franklin) between March 1, 2010 and March 31, 2020. Patients with complex perianal fistulae originating from CD or CGA treated with MAF were included. Long-time healing rates of MAF in CGA and CD were compared. Regression analysis was used to identify predictive factors for definitive healing. RESULTS: 83 patients (24 CD, 59 CGA,) were included. Median follow-up for CD was 5.4 and 1.9 years for CGA. Definitive healing of fistulae was achieved in 19 (79.2%) CD patients (p = 0.682) and in 44 (74.6%) CGA patients. Healing time was significantly shorter in CGA than in CD (9.3 months [standard deviation: SD= 11.3 months] vs. 30.9 months [SD = 23.5 months]; p < 0.001). Treatment with biologicals (hazard ratio: HR = 0.18, 95%-confidence interval: 95%-CI = 0.06-0.59, p = 0.004) and diverting ileostomy (HR = 0.29, 95%-CI = 0.10-0.85, p = 0.023) in CD were independent predictors for MAF success. Simultaneous medication with azathioprine in CD was an independent predictor for MAF failure (HR = 3.20, 95%-CI = 1.05-9.81, p = 0.041). CONCLUSION: This study demonstrates that surgical therapy of perianal fistulae with MAF is successful in about 75% of patients overall. Patients with MC benefit from biologicals and a diverting ileostomy. Treatment with azathioprine had a negative impact on recurrence rates. Repeated MAF operations did not increase the risk of failure in subsequent operations.

Robotic-Assisted versus Laparoscopic Proctectomy with Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: An Analysis of Clinical and Financial Outcomes from a Tertiary Referral Center.

Background: Robotic-assisted colorectal surgery is gaining popularity, but limited data are available on the safety, efficacy, and cost of robotic-assisted restorative proctectomy with the construction of an ileal pouch and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Methods: A retrospective study was conducted comparing consecutively performed robotic-assisted and laparoscopic proctectomy with IPAA between 1 January 2016 and 31 September 2021. In total, 67 adult patients with medically refractory UC without proven dysplasia or carcinoma underwent surgery: 29 operated robotically and 38 laparoscopically. Results: There were no differences between both groups regarding postoperative complications within 30 days according to Clavien-Dindo classification' grades 1−5 (51.7% vs. 42.1%, p = 0.468) and severe grades 3b−5 (17.2% vs. 10.5%, p = 0.485). Robotic-assisted surgery was associated with an increased urinary tract infection rate (n = 7, 24.1% vs. n = 1, 2.6%; p = 0.010) and longer operative time (346 ± 65 min vs. 281 ± 66 min; p < 0.0001). Surgery costs were higher when operated robotically (median EUR 10.377 [IQR EUR 4.727] vs. median EUR 6.689 [IQR EUR 3.170]; p < 0.0001), resulting in reduced total inpatient profits (median EUR 110 [IQR EUR 4.971] vs. median EUR 2.853 [IQR EUR 5.386]; p = 0.001). Conclusion: Robotic-assisted proctectomy with IPAA can be performed with comparable short-term clinical outcomes to laparoscopy but is associated with a longer duration of surgery and higher surgery costs. As experience increases, some advantages may become evident regarding operative time, postoperative recovery, and length of stay. The robotic procedure might then become cost-efficient.

Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC - Is it the exception to the rule?

BACKGROUND: Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC. METHODS: All eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS. RESULTS: A total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98). CONCLUSIONS: In contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

Feasibility of Novel Software-Based Perfusion Indicators for the Ileal J-Pouch-On the Path towards Objective and Quantifiable Intraoperative Perfusion Assessment with Indocyanine Green Near-Infrared Fluorescence.

BACKGROUND: In restorative proctocolectomy with ileal J-pouch, perfusion assessment is vital to prevent complications such as anastomotic leak (AL). Indocyanine green near-infrared fluorescence (ICG-NIRF) is gaining popularity, while its interpretation and relevance remain subjective. This study aimed to evaluate a standardized ICG-NIRF imaging protocol combined with a novel, software-based assessment to detect areas of impaired perfusion and a possible correlation with AL of the pouch. METHODS: In this prospective study, patients undergoing ileal J-pouch for ulcerative colitis at an inflammatory bowel disease (IBD) referral center were included. Intraoperatively, strictly standardized ICG-NIRF visualization was performed and video-recorded. Postoperatively, a specific software was utilized to determine the change in fluorescence intensity per second (i/s) for systematic regions of interest, generating perfusion-time curves and a pixel-to-pixel map. These were analysed in detail and correlated with clinical outcome (primary end point: AL within 30 days; clearly defined and screened for by pouchoscopy). RESULTS: Four out of 18 included patients developed AL of the ileal pouch-anal anastomosis (IPAA). In the AL group, the perfusion curves on the area adjacent to the IPAA (pouch apex) displayed considerably lower ingress/inflow (median = 1.7; range = 8.5; interquartile-range = 3.8 i/s) and egress/outflow (median = -0.1; range = 0.7; interquartile-range = 0.5 i/s) values than in the non-AL group (ingress: median = 4.3; range = 10.3; interquartile-range = 4.0 i/s); egress: median = (-1.1); range = 3.9; interquartile range = 1.0 i/s). This was confirmed by further novel parameters of pouch perfusion (maximum ingress; maximum egress) and pixel-to-pixel analysis. CONCLUSIONS: This study presents the feasibility of a novel methodology to precisely assess pouch perfusion with ICG-NIRF, identifying comparable, quantifiable, and objective parameters to potentially detect perfusion-associated complications in surgery in real-time.

Diagnostic Accuracy of Magnetic Resonance Enterography for the Evaluation of Active and Fibrotic Inflammation in Crohn's Disease.

Background: Despite the success of standard magnetic resonance enterography (MRE) in detecting Crohn's disease (CD), characterization of strictures and, thus, therapy guidance is still limited. The aim of the study was to determine diagnostic accuracy of MRE in detecting or ruling out active inflammation and identifying fibrotic lesions in patients with terminal ileal CD with histopathology as reference. Methods: Sixty-seven consecutive patients (median age 32 years, range 19-79 years) with terminal ileal CD were retrospectively enrolled between January 2015 and October 2020. The median interval between MRE and surgery was 9 days (range 0-86 days). Sensitivity, specificity, positive and negative predictive value (PPV and NPV, respectively), and area under the curve (AUC) with 95% confidence intervals (CIs) were calculated for the MRE-based AIS (acute inflammation score) using the histopathology of surgical specimens as the reference standard. Results: Sensitivity, specificity, PPV, and NPV for detecting or ruling out active inflammation were 100% (CI, 0.94-1.00; 0.44-1.00; 0.93-1.00; 0.31-1.00) using an AIS cut-off of >4.1. AUC was 1.00 (CI, 1.00-1.00; p < 0.01). In all patients with fibrotic changes only and no active inflammation, AIS was <4.1. Interobserver agreement was substantial (κ = 0.65, p < 0.01). Conclusion: Our study has shown an excellent diagnostic performance of the MRE-based AIS for determining whether active inflammation is present or lesions are due to chronic changes in ileal CD using the histopathology of surgical specimens as reference. These findings indicate that the MRE-based AIS allows a better determination of the inflammatory stage of terminal ileal CD, which facilitates the decision to perform surgery.

Inflammation of the rectal remnant endangers the outcome of ileal pouch-anal anastomosis: a case-control study.

BACKGROUND: Inflammation of the rectal remnant may affect the postoperative outcome of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We aimed to determine the extent of inflammation in the anastomotic area during IPAA and to investigate the impact of proctitis on postoperative complications and long-term outcomes. METHODS: Three hundred thirty-four UC patients with primary IPAA were included in this retrospective case-control study. The histopathologic degree of inflammation in the anastomotic area was graded into three stages of no proctitis ("NOP"), mild to medium proctitis ("MIP"), and severe proctitis ("SEP"). Preoperative risk factors, 30-day morbidity, and follow-up data were assessed. Kaplan-Meier analysis was performed in the event of pouch failure. RESULTS: The prevalence of proctitis was high (MIP 40.4%, and SEP 42.8%). During follow-up, the incidence of complications was highest among SEP: resulting in re-intervention (n = 40; 28.2%, p = 0.017), pouchitis (n = 36; 25.2%, p < 0.01), and pouch failure (n = 32; 22.4%, p = 0.032). The time interval to pouch failure was 5.0 (4.0-6.9) years among NOP, and 1.2 (0.5-2.3) years in SEP (p = 0.036). ASA 3, pouchitis, and pouch fistula were independent risk factors for pouch failure. CONCLUSION: Proctitis at the time of IPAA is common. A high degree of inflammation is associated with poor long-term outcomes, an effect that declines over time. In addition, a higher degree of proctitis leads to earlier pouch failure.

Perfusion Visualization during Ileal J-Pouch Formation-A Proposal for the Standardization of Intraoperative Imaging with Indocyanine Green Near-Infrared Fluorescence and a Postoperative Follow-Up in IBD Surgery.

BACKGROUND: An anastomotic leak (AL) after a restorative proctocolectomy and an ileal J-pouch increases morbidity and the risk of pouch failure. Thus, a perfusion assessment during J-pouch formation is crucial. While indocyanine green near-infrared fluorescence (ICG-NIRF) has shown potential to reduce ALs, its suitability in a restorative proctocolectomy remains unclear. We aimed to develop a standardized approach for investigating ICG-NIRF and ALs in pouch surgery. METHODS: Patients undergoing a restorative proctocolectomy with an ileal J-pouch for ulcerative colitis at an IBD-referral-center were included in a prospective study in which an AL within 30 postoperative days was the primary outcome. Intraoperatively, standardized perfusion visualization with ICG-NIRF was performed and video recorded for postoperative analysis at three time points. Quantitative clinical and technical variables (secondary outcome) were correlated with the primary outcome by descriptive analysis and logistic regression. A novel definition and grading of AL of the J-pouch was applied. A postoperative pouchoscopy was routinely performed to screen for AL. RESULTS: Intraoperative ICG-NIRF-visualization and its postoperative visual analysis in 25 patients did not indicate an AL. The anastomotic site after pouch formation appeared completely fluorescent with a strong fluorescence signal (category 2) in all cases of ALs (4 of 25). Anastomotic site was not changed. ICG-NIRF visualization was reproducible and standardized. Logistic regression identified a two-stage approach vs. a three-stage approach (Odds ratio (OR) = 20.00, 95% confidence interval [CI] = 1.37-580.18, p = 0.029) as a risk factor for ALs. CONCLUSION: We present a standardized, comparable approach of ICG-NIRF visualization in pouch surgery. Our data indicate that the visual interpretation of ICG-NIRF alone may not detect ALs of the pouch in all cases-quantifiable, objective methods of interpretation may be required in the future.

Is There an Association between Intra-Operative Detection of Pathogens in Subcutaneous Tissue and Surgical Site Infections? Results from a Prospective Study.

Background: Surgical site infections (SSIs) are a common complication in visceral surgery. Pathogens causing SSIs vary depending on the type of surgery. Patients and Methods: Within the scope of the Reduction of Postoperative Wound Infections by Antiseptica (RECIPE) trial we analyzed the pathogens cultured in intra-operative, subcutaneous swabs and in swabs from SSI in a single-center, prospective, randomized controlled study. Definition of SSI complied with the criteria of the U.S. Centers for Disease Control and Prevention (CDC). Results: The overall rate of SSI was 28.2% in 393 patients. Colorectal surgery was performed in 68.2% of elective laparotomies. Pathogens were more often detected in intra-operative subcutaneous swabs in patients who developed SSIs than in patients who did not develop SSIs (64.4% vs. 38.0%; p < 0.001). Enterococci were found in 29.1% of intra-operative swabs in patients with SSIs, followed by Escherichia coli in 15.5%. A higher rate of Enterococcus faecium was found in patients with anemia versus those without anemia (9.2% vs. 2.3%; p = 0.006) and in patients who smoked versus those who did not (11.8% vs. 3.6%; p = 0.008). A positive subcutaneous swab (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.47-4.29; p = 0.001), pre-operative anemia (OR, 1.84; 95% CI, 1.08-3.13; p = 0.016), and renal insufficiency (OR, 2.15; 95% CI, 1.01-4.59; p = 0.048) were risk factors for SSIs. Conclusions: There is an association between the intra-operative detection of pathogens in subcutaneous tissue and the development of SSIs in visceral surgery. The most prevalent pathogens causing SSIs were enterococci and Escherichia coli. More efforts are justified to reduce subcutaneous colonization with pathogens, for example by using intra-operative wound irrigation with polyhexanide solution. This trial is registered at www.ClinicalTrials.gov (ID: NCT04055233).