BACKGROUND:Mechanical small-bowel obstruction impairs epithelial barrier function and engages neuroimmune signaling along the gut-brain axis. We hypothesized that obstruction release would restore intestinal barrier function, ileal inflammatory gene expression, and neuroimmune signaling in the nucleus tractus solitarius. METHODS:Small-bowel obstruction was induced in mice by ileal ligation for 3 or 9 hours, with a subgroup undergoing ligation release after 3 hours, followed by a 3-hour recovery. Time-matched sham-operated animals served as controls. Intestinal permeability was quantified by measuring fluorescein ex vivo in Ussing chambers. Ileal messenger RNA expression of inducible nitric oxide synthase, tumor necrosis factor α, and cyclooxygenase-2 was quantified by quantitative real-time polymerase chain reaction. Nucleus tractus solitarius neuronal activation was assessed by c-Fos expression in brainstem sections by immunohistochemistry. RESULTS:Intestinal fluorescein permeability differed between groups (Kruskal-Wallis P = 4.0 × 10-5), with higher permeability during small-bowel obstruction and this effect largely normalized after obstruction release. Despite this early barrier improvement, nucleus tractus solitarius c-Fos activation persisted after release. Ileal inducible nitric oxide synthase expression was markedly suppressed during obstruction (0.06-fold from control, Holm-adjusted P = .010, versus time-matched sham) and remained lower after release (0.03-fold from control, Holm-adjusted P = .062), although this difference did not reach statistical significance after correction, whereas tumor necrosis factor α and cyclooxygenase-2 levels showed no significant changes at the sampled time points. CONCLUSION:Small-bowel obstruction rapidly impairs epithelial barrier function and elicits sustained nucleus tractus solitarius activation beyond obstruction release. Sustained reduction of inducible nitric oxide synthase messenger RNA persists despite early ex vivo barrier improvement. These findings point to distinct epithelial, neuronal, and immune trajectories during obstruction and early recovery.
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.
BACKGROUND:Recent studies have suggested that certain combinations of KRAS or BRAF biomarkers with clinical factors are associated with poor outcomes and may indicate that surgery could be "biologically" futile in otherwise technically resectable colorectal liver metastasis (CRLM). However, these combinations have yet to be validated through external studies. PATIENTS AND METHODS:We conducted a systematic search to identify these studies. The overall survival (OS) of patients with these combinations was evaluated in a cohort of patients treated at 11 tertiary centers. Additionally, the study investigated whether using high-risk KRAS point mutations in these combinations could be associated with particularly poor outcomes. RESULTS:The recommendations of four studies were validated in 1661 patients. The first three studies utilized KRAS, and their validation showed the following median and 5-year OS: (1) 30 months and 16.9%, (2) 24.3 months and 21.6%, and (3) 46.8 months and 44.4%, respectively. When analyzing only patients with high-risk KRAS mutations, median and 5-year OS decreased to: (1) 26.2 months and 0%, (2) 22.3 months and 15.1%, and (3) not reached and 44.9%, respectively. The fourth study utilized BRAF, and its validation showed a median OS of 10.4 months, with no survivors beyond 21 months. CONCLUSION:The combinations of biomarkers and clinical factors proposed to render surgery for CRLM futile, as presented in studies 1 (KRAS high-risk mutations) and 4, appear justified. In these studies, there were no long-term survivors, and survival was similar to that of historic cohorts with similar mutational profiles that received systemic therapies alone for unresectable disease.
BACKGROUND:Current guidelines recommend use of adjuvant imatinib therapy for many patients with gastrointestinal stromal tumours (GISTs); however, its optimal treatment duration is unknown and some patient groups do not benefit from the therapy. We aimed to apply state-of-the-art, interpretable artificial intelligence (ie, predictions or prescription logic that can be easily understood) methods on real-world data to establish which groups of patients with GISTs should receive adjuvant imatinib, its optimal treatment duration, and the benefits conferred by this therapy. METHODS:In this observational cohort study, we considered for inclusion all patients who underwent resection of primary, non-metastatic GISTs at the Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY, USA) between Oct 1, 1982, and Dec 31, 2017, and who were classified as intermediate or high risk according to the Armed Forces Institute of Pathology Miettinen criteria and had complete follow-up data with no missing entries. A counterfactual random forest model, which used predictors of recurrence (mitotic count, tumour size, and tumour site) and imatinib duration to infer the probability of recurrence at 7 years for a given patient under each duration of imatinib treatment, was trained in the MSKCC cohort. Optimal policy trees (OPTs), a state-of-the-art interpretable AI-based method, were used to read the counterfactual random forest model by training a decision tree with the counterfactual predictions. The OPT recommendations were externally validated in two cohorts of patients from Poland (the Polish Clinical GIST Registry), who underwent GIST resection between Dec 1, 1981, and Dec 31, 2011, and from Spain (the Spanish Group for Research in Sarcomas), who underwent resection between Oct 1, 1987, and Jan 30, 2011. FINDINGS:Among 1007 patients who underwent GIST surgery in MSKCC, 117 were included in the internal cohort; for the external cohorts, the Polish cohort comprised 363 patients and the Spanish cohort comprised 239 patients. The OPT did not recommend imatinib for patients with GISTs of gastric origin measuring less than 15·9 cm with a mitotic count of less than 11·5 mitoses per 5 mm2 or for those with small GISTs (<5·4 cm) of any site with a count of less than 11·5 mitoses per 5 mm2. In this cohort, the OPT cutoffs had a sensitivity of 92·7% (95% CI 82·4-98·0) and a specificity of 33·9% (22·3-47·0). The application of these cutoffs in the two external cohorts would have spared 38 (29%) of 131 patients in the Spanish cohort and 44 (35%) of 126 patients in the Polish cohort from unnecessary treatment with imatinib. Meanwhile, the risk of undertreating patients in these cohorts was minimal (sensitivity 95·4% [95% CI 89·5-98·5] in the Spanish cohort and 92·4% [88·3-95·4] in the Polish cohort). The OPT tested 33 different durations of imatinib treatment (<5 years) and found that 5 years of treatment conferred the most benefit. INTERPRETATION:If the identified patient subgroups were applied in clinical practice, as many as a third of the current cohort of candidates who do not benefit from adjuvant imatinib would be encouraged to not receive imatinib, subsequently avoiding unnecessary toxicity on patients and financial strain on health-care systems. Our finding that 5 years is the optimal duration of imatinib treatment could be the best source of evidence to inform clinical practice until 2028, when a randomised controlled trial with the same aims is expected to report its findings. FUNDING:National Cancer Institute.
Colorectal cancer is the second most common cause of cancer death in the United States, and up to half of patients develop colorectal liver metastases (CRLMs). Notably, somatic genetic mutations, such as mutations in RAS, BRAF, mismatch repair (MMR) genes, TP53, and SMAD4, have been shown to play a prognostic role in patients with CRLM. This review summarizes and appraises the current literature regarding the most relevant somatic mutations in surgically treated CRLM by not only reviewing representative studies, but also providing recommendations for areas of future research. In addition, advancements in genetic testing and an increasing emphasis on precision medicine have led to a more nuanced understanding of these mutations; thus, more granular data for each mutation are reviewed when available. Importantly, such knowledge can pave the way for precision medicine with the ultimate goal of improving patient outcomes.
BACKGROUND:Patients with surgically resectable BRAF-mutated colorectal liver metastases (CRLM) or limited extrahepatic disease constitute a highly selective subgroup among BRAF-mutated patients, characterized by a more indolent disease biology. This is evident in their suitability for surgical resection. However, initial studies from a decade ago presented a discouraging outlook for these patients, citing early, frequent, multifocal recurrences and a very limited median overall survival (OS) of less than two years. Our objective was to provide an updated, comprehensive, and critically assessed review of the current literature on the prognostic impact of BRAF variants in CRLM, as well as to explore optimal treatment strategies for these patients through a systematic search. METHODS:A systematic literature search of the Medline, Scopus, and CENTRAL databases for studies reporting long-term outcomes of patients with a known BRAF status was performed. RESULTS:A total of 386 unique studies were screened during the study selection process. After applying the exclusion criteria, a total of 18 studies published between 2012 and 2023 were deemed eligible for inclusion. CONCLUSIONS:In contrast to older studies, more recent studies, with larger sample sizes, have revealed that the rate of extrahepatic recurrence is comparable between BRAF-mutated and wild-type patients. Furthermore, they have reported significantly improved survival outcomes, with OS extending up to 52 months. Notably, patients with non-V600E BRAF mutations may even achieve outcomes comparable to those with wild-type BRAF CRLM. Additionally, a few recent studies have compared surgery and systemic therapies, indicating that surgery is associated with improved survival rates, even for patients with the V600E mutation. This challenges the previous belief that BRAF mutations are absolute contraindications to surgical treatment. Surgical denial for technically resectable patients may now be reserved for specific clinical scenarios, such as the presence of a BRAF V600E mutation and concurrent extrahepatic disease.
Background: For locally advanced rectal cancer, neoadjuvant therapy (NT) is an established element of therapy. Endoscopic vacuum therapy (EVT) has been a relevant treatment option for anastomotic leakage after rectal resection since 2008. The aim was to evaluate the influence of NT on the duration and success of EVT in anastomotic leakage after rectal resection for rectal cancer. Methods: This was a monocentric, retrospective cohort study including patients who underwent rectal resection with primary anastomosis because of histologically proven carcinoma of the rectum in the Department for General and Visceral Surgery of Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin over a period of ten years (2012 to 2022). Results: Overall, 243 patients were included, of which 47 patients (19.3%) suffered from anastomotic leakage grade B with consecutive EVT. A total of 29 (61.7%) patients received NT and 18 patients (38.3%) did not. The median duration of EVT until the removal of the sponge did not differ between patients with and without NT: 24.0 days (95% CI 6.44–41.56) versus 20.0 days (95% CI 17.03–22.97); p = 0.273. The median duration from insertion of EVT until complete healing was 74.0 days with NT (95% CI 10.07–137.93) versus 62.0 days without NT (95% CI 45.99–78.01); p = 0.490. Treatment failure—including early persistence and late onset of recurrent anastomotic leakage—was evident in 27.6% of patients with NT versus 27.8% without NT; p = 0.989. Ostomy was reversed in 19 patients (79.2%) with NT compared to 11 patients (68.8%) without NT; p = 0.456. Overall, continuity was restored in 75% of patients in the long term after EVT. Conclusion: This trial comprised—to our knowledge—the largest study cohort to analyze the outcome of EVT in anastomotic leakage after rectal resection for rectal cancer. We conclude that neoadjuvant therapy neither prolongs EVT nor the time to healing from anastomotic leakage. The rates of treatment failure of EVT and permanent ostomy were not higher when neoadjuvant therapy was used.
Background: To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings. Methods: In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort. Results: Of 170 patients included, 119 underwent hepatectomy and 51 received systemic treatment. Surgically treated patients had a more favourable pattern of recurrence with most recurrences limited to a single site, whereas diffuse progression was more common among patients who received systemic treatment (19 versus 44%; P = 0.002). Surgically treated patients had longer median overall survival (35 versus 20 months; P < 0.001). Hepatectomy was independently associated with better OS than systemic treatment alone (HR 0.37, 95% c.i. 0.21 to 0.65). In the propensity score-matched cohort, surgically treated patients had longer median overall survival (28 versus 20 months; P < 0.001); hepatectomy was independently associated with better overall survival (HR 0.47, 0.25 to 0.88). Conclusion: BRAF V600E mutation should not be considered a contraindication to surgery for patients with resectable, liver-only CRLMs.
Objective:To validate the 7(th) and 8(th) editions of the AJCC staging system for patients with invasive carcinomas arising in association with IPMN (IPMN-associated PDAC). Background Data:Although several studies have validated AJCC systems in patients with conventional PDAC, their applicability to IPMN-associated PDAC has not been assessed. Methods:Two hundred seventy-five patients who underwent resection for IPMN-associated PDAC between 1996 and 2015 at 3 tertiary centers and had data on the size of the invasive component and lymph node status were identified. Concordance probability estimates (CPE) were calculated and recursive partitioning analysis was employed to identify optimal prognostic cutoffs for T and N. Results:The CPE for the 7(th) and 8(th) editions of the AJCC schema were relatively good (0.64 for both) and similar for colloid and tubular subtypes (0.64 for both). The 8(th) edition introduced T1a sub-staging and a new distinction between N1 and N2. The utility of the former was confirmed, although the latter did not improve prognostic discrimination. The successful validation of the 8th edition of the AJCC criteria in patients with tubular and colloid subtypes allowed us to compare these patients in early vs late T and N stages which showed that with advanced disease, the prognostic superiority of colloid tumors over their tubular counterparts diminishes. Conclusions:Our findings support the use of the AJCC 8(th) edition in the IPMN-associated PDAC population, but suggest that certain cutoffs may need to be revisited. In advanced AJCC stages, patients with colloid vs tubular subtypes have comparable prognosis.
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 (Charite 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.
Interleukine-6 plays a key role in the progression and poor survival in pancreatic ductal adenocarcinoma (PDAC). The present study aimed to clarify if targeting the interleukin-6/glycoprotein-130 signaling cascade using the small-molecule gp130 inhibitor SC144 or raloxifene, a non-steroidal selective estrogen receptor modulator, enhances paclitaxel efficacy. MTT/BrdU assays or TUNEL staining were performed to investigate cell viability, proliferation and apoptosis induction in L3.6pl and AsPC-1 human pancreatic cell lines. In vivo, effects were studied in an orthotopic PDAC mouse model. Tumor specimens were analyzed by qPCR, immunohistochemistry and ELISA. Combination of paclitaxel/raloxifene, but not paclitaxel/SC144, enhanced proliferation and viability inhibition and increased apoptosis compared to single treatment in vitro. Synergy score calculations confirmed an additive influence of raloxifene on paclitaxel. In the PDAC mouse model, both combinations of raloxifene/paclitaxel and SC144/paclitaxel reduced tumor weight and volume compared to single-agent therapy or control. Raloxifene/paclitaxel treatment decreased survivin mRNA expression and showed tendencies of increased caspase-3 staining in primary tumors. SC144/paclitaxel reduced interleukin-6 levels in mice's tumors and plasma. In conclusion, raloxifene or SC144 can enhance the anti-tumorigenic effects of paclitaxel, suggesting that paclitaxel doses might also be reduced in combined chemotherapy to lessen paclitaxel side effects.
Diagnostic performance of imaging for regional lymph node assessment in gastric cancer is still limited, and there is a lack of consensus on radiological evaluation. At the same time, there is an increasing demand for structured reporting using Reporting and Data Systems (RADS) to standardize oncological imaging. We aimed at investigating the diagnostic performance of Node-RADS compared to the use of various individual criteria for assessing regional lymph nodes in gastric cancer using histopathology as reference. In this retrospective single-center study, consecutive 91 patients (median age, 66 years, range 33–91 years, 54 men) with CT scans and histologically proven gastric adenocarcinoma were assessed using Node-RADS assigning scores from 1 to 5 for the likelihood of regional lymph node metastases. Additionally, different Node-RADS criteria as well as subcategories of altered border contour (lobulated, spiculated, indistinct) were assessed individually. Sensitivity, specificity, and Youden’s index were calculated for Node-RADS scores, and all criteria investigated. Interreader agreement was calculated using Cohen’s kappa. Among all criteria, best performance was found for Node-RADS scores ≥ 3 and ≥ 4 with a sensitivity/specificity/Youden’s index of 56.8 • Assessment of lymph nodes in gastric cancer is still limited, and there is a lack of consensus on radiological evaluation. • Node-RADS in gastric cancer improves overall diagnostic performance compared to individual criteria including short-axis diameter. • Node-RADS may be a suitable tool for structured reporting of regional lymph nodes in gastric cancer.
Objective:To investigate the clinical implications of BRAF-mutated (mutBRAF) colorectal liver metastases (CRLMs). Background:The clinical implications of mutBRAF status in CRLMs are largely unknown. Methods:Patients undergoing resection for mutBRAF CRLM were identified from prospectively maintained registries of the collaborating institutions. Overall survival (OS) and recurrence-free survival (RFS) were compared among patients with V600E versus non-V600E mutations, KRAS/BRAF comutation versus mutBRAF alone, microsatellite stability status (Microsatellite Stable (MSS) vs instable (MSI-high)), upfront resectable versus converted tumors, extrahepatic versus liver-limited disease, and intrahepatic recurrence treated with repeat hepatectomy versus nonoperative management. Results:A total of 240 patients harboring BRAF-mutated tumors were included. BRAF V600E mutation was associated with shorter OS (30.6 vs 144 mo, P=0.004), but not RFS compared with non-V600E mutations. KRAS/BRAF comutation did not affect outcomes. MSS tumors were associated with shorter RFS (9.1 vs 26 mo, P<0.001) but not OS (33.5 vs 41 mo, P=0.3) compared with MSI-high tumors, whereas patients with resected converted disease had slightly worse RFS (8 vs 11 mo, P=0.01) and similar OS (30 vs 40 mo, P=0.4) compared with those with upfront resectable disease. Patients with extrahepatic disease had worse OS compared with those with liver-limited disease (8.8 vs 40 mo, P<0.001). Repeat hepatectomy after intrahepatic recurrence was associated with improved OS compared with nonoperative management (41 vs 18.7 mo, P=0.004). All results continued to hold true in the multivariable OS analysis. Conclusions:Although surgery may be futile in patients with BRAF-mutated CRLM and concurrent extrahepatic disease, resection of converted disease resulted in encouraging survival in the absence of extrahepatic spread. Importantly, second hepatectomy in select patients with recurrence was associated with improved outcomes. Finally, MSI-high status identifies a better prognostic group, with regard to RFS while patients with non-V600E mutations have excellent prognosis.
Zusammenfassung Hintergrund Die chirurgische Behandlung von perianalen Fisteln, die von Morbus Crohn (MC) oder kryptoglandulären Abszessen (KGA) ausgehen, bleibt eine Herausforderung. Daten zu langfristigen Heilungsraten sind rar. Unser Ziel war es, die langfristige Erfolgsrate von Mukosa-Muskel-Flap-Operationen (MMF-Operationen) zu bewerten. Methoden Diese monozentrische retrospektive Studie wurde zwischen dem 1. März 2010 und dem 31. März 2020 an einem tertiären Referenzzentrum (Charité Universitätsklinikum Berlin, Campus Benjamin Franklin) durchgeführt. Patienten mit komplexen perianalen Fisteln, die durch MC oder KGA entstanden und mit MMF behandelt wurden, wurden eingeschlossen. Die langfristigen Heilungsraten von MMF-Operationen bei KGA und MC wurden verglichen. Regressionsanalysen wurde angewandt, um prädiktive Faktoren für eine definitive Heilung zu identifizieren. Ergebnisse 83 Patienten (24 MC, 59 KGA) wurden eingeschlossen. Die mediane Nachbeobachtungszeit betrug bei MC 5,4 und bei KGA 1,9 Jahre. Eine definitive Heilung der Fisteln wurde bei 19 (79,2%) MC-Patienten (p = 0,682) und bei 44 (74,6%) KGA-Patienten erreicht. Die Heilungszeit war bei KGA signifikant kürzer als bei MC (9,3 Monate [Standardabweichung: SD = 11,3 Monate] vs. 30,9 Monate [SD = 23,5 Monate]; p < 0,001). Die Behandlung mit Biologika (Hazard Ratio: HR = 0,18; 95%-Konfidenzintervall: 95%-KI = 0,06–0,59; p = 0,004) und die Anlage eines protektiven Ileostomas (HR = 0,29; 95%-KI = 0,10–0,85; p = 0,023) bei MC waren unabhängige Prädiktoren für den MMF-Erfolg. Die gleichzeitige Medikation mit Azathioprin bei MC war ein unabhängiger Prädiktor für MMF-Versagen (HR = 3,20; 95%-KI = 1,05–9,81; p = 0,041). Schlussfolgerung Diese Studie zeigt, dass die chirurgische Therapie von perianalen Fisteln mit MMF bei insgesamt etwa 75% der Patienten erfolgreich ist. Patienten mit MC profitieren von Biologika und einem protektiven Ileostoma. Die Behandlung mit Azathioprin hat einen negativen Einfluss auf die Rezidivrate. Eine vorangegangene MMF-Operation erhöht das Risiko eines MMF-Versagens bei wiederholten Operationen nicht.
Although some data suggest that patients with mutRAS colorectal liver metastases (CRLM) may benefit from anatomic hepatectomy, this topic remains controversial. We performed a systematic review and meta-analysis to determine whether RAS mutation status was associated with prognosis relative to surgical technique [anatomic resection (AR) vs. nonanatomic resection (NAR)] among patients with CRLM. A systematic review and meta-analysis of studies were performed to investigate the association of AR versus NAR with overall and liver-specific disease-free survival (DFS and liver-specific DFS, respectively) in the context of RAS mutation status. Overall, 2018 patients (831 mutRAS vs. 1187 wtRAS) were included from five eligible studies. AR was associated with a 40
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 recur-rence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as pro-pensity 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.