Radiological Remission Research Articles

Infliximab versus Cyclophosphamide for Severe Behçet's Syndrome.

Cyclophosphamide and infliximab are recommended as induction therapies for severe Behçet's syndrome. Whether infliximab is safer and more effective than cyclophosphamide in treating severe Behçet's syndrome is not known. In this phase 2, Bayesian, multicenter randomized controlled trial, we assigned patients fulfilling the International Study Group's criteria for Behçet's syndrome who had major vascular or central nervous system involvement to receive either intravenous infliximab (5 mg/kg at weeks 0, 2, 6, 12, and 18) or cyclophosphamide (0.7 g/m2 intravenously at weeks 0, 4, 8, 12, 16, and 20, with a maximal dose of 1.2 g/infusion). All patients received the same glucocorticoid regimen. The primary outcome was complete response (clinical, biological, and radiological remission with a daily prednisone dose ≤0.1 mg/kg) at week 22. Between May 2018 and April 2021, 52 patients with severe Behçet's syndrome (n=37 [71%] with vascular Behçet's syndrome and n=15 [29%] with neuro-Behçet's syndrome) were randomly assigned to receive either infliximab or cyclophosphamide. Complete response was achieved by 22 out of 27 (81%) and 14 out of 25 (56%) patients in the infliximab and cyclophosphamide treatment groups, respectively (estimated difference, 29.8 percentage points; 95% credible interval, 6.6 to 51.7). The posterior probability that at least 70% of treated individuals achieved complete response by week 22 was 97.4% for infliximab and 6.0% for cyclophosphamide. Overall, adverse events were recorded in 8 out of 27 (29.6%) patients receiving infliximab and 16 out of 25 (64%) patients receiving cyclophosphamide (estimated difference, -32.3 percentage points; 95% credible interval, -55.2 to -6.6). Serious adverse events were reported in 15% and 12% of patients receiving infliximab and cyclophosphamide, respectively. Among patients with severe Behçet's syndrome, induction therapy with infliximab had a superior complete response rate at 22 weeks and fewer adverse events than induction with cyclophosphamide. (Funded by the French Ministry of Health.).

Effect of Dupilumab on Radiological Remission in Patients with Chronic Rhinosinusitis with Nasal Polyp: A One Step Forward Toward Clinical Remission.

While achieving complete radiological improvement in patients with nasal polyps is often observed following surgical resection, the impact of biologic therapy, specifically dupilumab, on polyp size is an area of great interest. The objective of this study was to assess the effect of dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by assessing nasal polyps using the computed tomography (CT) staging system, Lund-Mackay score (LMS). A two-year prospective cohort study was conducted on 29 patients diagnosed with CRSwNP and asthma and eligible for dupilumab as an add-on therapy. The study involved comprehensive assessments of patients before biologic initiation and after the study. These assessments included clinical, laboratory, and radiological evaluations. Dupilumab treatment reduces LMS across sinuses (p<0.001) and improves nasal obstruction (p=0.001). Blood eosinophil count (BEC) predicts persistent sinus obstruction, doubling the likelihood per unit increase (odds ratio: 1.67, p=0.02). BEC levels identify persistent nasal obstruction (AUC: 76%, p=0.04), with a cutoff point above 255.5 cells per microliter, revealing a sensitivity of 100% and a specificity of 42%. The probability of persistent nasal obstruction at the 20th month is 55%, regardless of prior nasal polyp surgery (p=0.41). Dupilumab led to significant radiological improvements in patients with CRSwNP, demonstrating a potential role of radiological remission, irrespective of prior nasal polyp surgery. Additionally, BEC levels may guide the likelihood of persistent nasal obstruction.

Closing the internal opening with a rectal advancement flap increases the efficacy of mesenchymal stem cell injection for complex Crohn's disease anal fistulas.

The efficacy of injections of mesenchymal stem cells (MSC) for anal fistula treatment may be impaired by the persistence of stools passing into the fistula, causing bacterial contamination and a local inflammatory reaction. We aimed to compare remission rates between patients treated by MSC injection with simple sutures and those treated with a rectal advancement flap. This single-center prospective study compared the first patients who underwent internal opening closure with sutures with the subsequent patients treated with a flap. Complete clinical remission was defined as complete closure of the external opening(s) without pain or discharge, and complete radiological remission was defined as a Magnifi-CD score of 0. We compared the first 42 patients who had sutures with the 20 subsequent patients who had an advancement flap. The median follow-up was 15.5 [8.8-24.9]months. The cumulative incidence of complete clinical response at M12 was 53.8% [38.1-69.6%] in the suture group versus 93.3% [77.4-100.0] in the flap group (p < 0.001). The Magnifi-CD score was 0 for 41.7% [25.5-59.2%]) of patients treated with sutures versus 72.7% [39.0-63.9%]) of patients treated with a flap (p=0.093). Anal incontinence score did not differ between the two groups. Practicing an advancement flap was the only significant factor associated with complete clinical remission over time (adjusted HR [95% CI] of 2.6 [1.4-4.9], p = 0.003). Complete clinical remission rates following MSC injection are significantly higher after closure of the internal opening with a rectal flap than after closure with sutures, without consequences on anal continence.

Coronary periarteritis and pericarditis are rare but distinct manifestations of heart involvement in IgG4-related disease: a retrospective cohort study

BackgroundThe heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement.MethodsWe conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed.ResultsIgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period.ConclusionsCardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment.

Mesenchymal stem cell therapy for therapy refractory complex Crohn’s perianal fistulas: a case series

BackgroundMesenchymal stem cell treatment (MST) has emerged as a new therapeutic strategy for Crohn’s perianal fistulas. It has been demonstrated that a fibrotic tract on MRI with a MAGNIFI-CD score ≤ 6 is the best predictor for long-term clinical closure. Therefore, the aim of the current study was to analyse the effectiveness of MST for complex Crohn’s perianal fistulas based on MRI.MethodsConsecutive patients with complex Crohn’s perianal fistulas, previously failing both anti-TNF treatment and surgical closure, who had surgical closure of the internal opening with MST were included. The primary endpoint was radiological remission of the fistula(s) defined as a MAGNIFI-CD ≤ 6 on MRI, read by an experienced radiologist.ResultsBetween December 2019 and March 2023, 30 patients (15 males) with 48 fistula tracts were included with a median follow-up of 16.5 months. Radiological remission was achieved in thirteen patients (43.3%) after a median follow-up of 5.0 months (IQR 3.0–6.0). The median MAGNIFI-CD at baseline was 15.0 (IQR 7.0–20.0) which significantly decreased to 8.0 (IQR 3.0–15.0) after treatment (p = 0.001). Clinical closure was achieved in 21 patients (70.0%). Three patients (14.3%) developed a recurrence during long-term FU, all with clinically closed fistula(s), but no radiological remission. The median PDAI decreased significantly from 10.5 (IQR 7.0–14.0) to 4.0 (IQR 0.0-7.3) (p = 0.001).ConclusionMST is a promising treatment strategy for therapy refractory Crohn’s perianal fistulas, resulting in > 40% radiological remission, clinical closure in 70% and a significant improvement in quality of life. No recurrences were seen in patients with radiological remission.

Anti-MAPK Targeted Therapy for Ameloblastoma: Case Report with a Systematic Review.

Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in targeted therapy. We present a case of a 15-year-old girl with ameloblastoma successfully treated with targeted therapy and review the literature with this question: Is anti-MAPK targeted therapy safe and effective for treating ameloblastoma? This systematic review was registered in PROSPERO, adhered to PRISMA guidelines, and searched multiple databases up to December 2023, identifying 13 relevant studies out of 647 records, covering 23 patients treated with MAPK inhibitor therapies. The results were promising as nearly all patients showed a positive treatment response, with four achieving complete radiological remission and others showing substantial reductions in primary, recurrent, and metastatic ameloblastoma sizes. Side effects were mostly mild to moderate. This study presents anti-MAPK therapy as a significant shift from invasive surgical treatments, potentially enhancing life quality and clinical outcomes by offering a less invasive yet effective treatment alternative. This approach could signify a breakthrough in managing this challenging tumor, emphasizing the need for further research into molecular-targeted therapies.

Diagnostic characteristics and management outcome in patients with acromegaly: a 15-year experience at a tertiary care hospital in Pakistan

Objectives: To assess the diagnostic features of acromegaly, and analyse its management outcomes over a 15-year period in a tertiary care setting. Method: The descriptive, cohort, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of adult patients of either gender diagnosed with acromegaly based on biochemical and radiological evidence between January 2005 and December 2019. Data was retrieved from the medical records. Data was analysed using SPSS 19. Results: Of the 84 subjects, 54(64.3%) were males and 30(35.7%) were female. The overall mean age was 38.69±13.52 years. The patients presented 5.43±4.3 years after the onset of symptoms, with somatic growth features, such as enlarged hands and feet which was the most common complaint 81(96.4%). Of all the patients, 73(86.9%) underwent trans-sphenoidal surgery for the removal of the pituitary adenoma, while 11(13.1%) opted out of the surgical option. Further, 9(12.3%) patients showed biochemical and radiological remission 6 months post-surgery. Out of the remaining 64(87.7%) patients, 38(59.4%) received radiosurgery or radiotherapy, 15(23.4%) underwent repeat trans-sphenoidal surgery, and 11(17.2%) chose medical treatment. Conclusion: Majority of patients failed to achieve remission after trans-sphenoidal surgery, which is the first line of treatment. Radiotherapy/repeat surgery was generally the options taken by those with persistent disease. Key Words: Acromegaly, Characteristics, Diagnosis, Management, Outcome, Pituitary tumour, Growth hormone.

The degree of bowel remission predicts phenotype progression in Crohn's disease.

Patients with Crohn's disease (CD) are at risk of progressing from inflammatory to stricturing and penetrating phenotypes. The influence of the depth of remission on the risk of progression has not been adequately evaluated. A retrospective cohort study including surgically naïve CD patients with inflammatory phenotype evaluated concomitantly by magnetic resonance enterography and colonoscopy. The degree of remission was correlated with the risk of progressing to stricturing and penetrating phenotypes. Three hundred nineteen CD patients were included: 27.0% with transmural remission, 16.0% with isolated endoscopic remission, 14.4% with isolated radiologic remission, and 42.6% without remission. Patients with transmural remission presented the lowest rates of phenotype progression (1.2%), with a significant difference compared to isolated radiologic remission (10.9%, p=0.019), to isolated endoscopic remission (19.6%, p≤0.001), and to no remission (46.3%, p≤0.001). In multivariate regression analysis, transmural remission (OR 0.017 95% CI 0.002-0.135, p<0.001), isolated radiologic remission (OR 0.139 95% CI 0.049-0.396, p<0.001), and isolated endoscopic remission (OR 0.301 95% CI 0.123-0.736, p=0.008) resulted in lower rates of phenotype progression compared to no remission. No patient with transmural or isolated radiologic remission progressed to penetrating phenotypes. The degree of bowel remission correlates with the risk of phenotype progression. Patients with transmural remission are at the lowest risk of progressing to stricturing and penetrating phenotypes.

Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study.

Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

Abstract PO5-18-10: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 48 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (&amp;lt; 10% positive cells in IHC) and PgR-negative (&amp;lt; 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2024 -Primary outcome analysis: Q1/2027 Current accrual: In June 2023, 255 patients were recruited; the majority of them in Germany. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy). Citation Format: Toralf Reimer, Bernd Gerber, Thorsten Kuehn, Nikola Bangemann, Anke Kleine-Tebbe, Andrea Stefek, Ulrike Doerste, Carolin Hammerle, Oliver Hoffmann, Alexander Hein, Isabel Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-10.

Alternating chemotherapy with VDC-IE as effective first-line treatment in a patient with SMARCA4-deficient undifferentiated tumor

SummarySMARCA4-deficient undifferentiated tumor (SMARCA4-UTs) is an extremely rare and aggressive entity where no consensus on systemic treatment exists to date. We report the case of a 43-year-old woman with thoracic SMARCA4-UT who presented with rapid progression of disease after surgical resection and achieved complete radiologic remission under VDC-IE chemotherapy (vincristine, doxorubicin, and cyclophosphamide [VDC], alternating with ifosfamide and etoposide [IE]). The detailed case report is followed by a brief discussion and overview of current literature.

PET/CT with &lt;sup&gt;18&lt;/sup&gt;F-FDG for TENIS Syndrome in a Patient with Bone Metastasis of Hurthle Cell Thyroid Cancer: a Clinical Case Report

A significant role in improving the prognosis of differentiated thyroid cancer (DTC) in the presence of bone metastases is determined by early diagnosis of metastases, timely and correctly selected treatment tactics for the patient. During dynamic follow-up of patients with DTC after combined treatment (thyroidectomy with radioiodine therapy) are determination of the level of oncomarkers (serum thyroglobulin and antibodies to thyroglobulin) and ultrasound diagnostic of the neck, scanning with radioactive iodine (if clinically indicated). In some cases, patients have TENIS-syndrome (Thyroglobulin Elevated Negative Iodine Scintigraphy, hereinafter TENIS-syndrome), characterized by high serum thyroglobulin level in blood and absence of radioactive iodine accumulation on post therapeutic scintigraphy. According to the research studies, PET/CT with 18F-FDG has high sensitivity and specificity (89 % and 72 %, respectively) in visualization of metastatic radioiodine refractory foci in TENIS-syndrome.This article presents a clinical case of a patient, a 52-year-old woman with Gurtle cell thyroid cancer (pT3aN0M0, stage I) with established TENIS syndrome. Thyroidectomy was performed in September 2019 and radioiodine therapy was performed in January 2022 due to suspected disease progression given high thyroglobulin levels. Given the absence of pathologic accumulation of 131I according to post-therapy radioiodine scanning, PET/CT with 18F-FDG was performed, which revealed a solitary metastasis in the left iliac bone (41×35×42 mm with SUVmax 17.25). In November 2022, radical treatment of the solitary bone metastasis was performed in the scope of resection of the left iliac bone with reconstructive-plastic component. According to the data of control examinations in June 2023, the patient has a complete biochemical and radiologic remission of the disease.

Abstract A077: The utility of surgical minimal residual disease after frontline treatment for prognostic and investigational opportunities in advanced ovarian cancer

Abstract Cure rates for patients with advanced stage ovarian cancer have not changed significantly over the last four decades likely due to inability to eradicate residual cancer cells after frontline therapy. Identifying clinically undetectable minimal residual disease (MRD) after frontline therapy by second look laparoscopy (SLL) has potential to a) uncover mechanisms of chemoresistance and tumor dormancy, b) identify MRD-specific therapeutic targets, and c) allow for earlier intervention with investigational therapies. The objective of this study is to describe the initial safety and feasibility of SLL and illustrate clinical and pathological correlates. Methods: This IRB-approved observational, single-center study includes patients with epithelial high-grade ovarian cancer with complete CA-125 and radiologic response after frontline treatment (combination of surgery and platinum-taxane chemotherapy) who underwent SLL from 4/2017-6/2023. Patients were subsequently offered standard of care or investigational maintenance therapy options based on homologous recombination deficiency (HRD) and MRD status. Summary statistics described the study population, chi-square tests compared categorical variables, and progression free survival (PFS) based on MRD status was estimated using Kaplan-Meier method and compared using log rank test. Results: 70 patients underwent SLL with a median of 8.5 biopsies (range 3-16). The majority of patients had stage III-IV disease (90%), and high-grade serous histology (90%). Approximately half (51.4%) of patients underwent neoadjuvant chemotherapy (NACT) with interval tumor reductive surgery (TRS). MRD was present in 32 patients (45.7%), and the presence of MRD was associated with a worse PFS (HR 3.0, 95% CI 1.5-5.8; 12.5 vs. 24.8 months; p=0.001). MRD was more frequent among NACT recipients compared to those who underwent primary TRS (63% vs 26%, P=0.002), those with HRD negative tumors (58% vs 24%, P=0.025), and those with R1 versus R0 resections (71% vs 39%, P=0.024). Of patients with MRD, 22 patients (71%) received bevacizumab until progression as part of a clinical trial (NCT02884648), 3 (10%) received bevacizumab off trial, 5 (16%) received a PARP inhibitor (all HRD positive), and 1 received other therapy. There were two (2.9%) intraoperative complications (both enterotomies) requiring conversion to laparotomy. Conclusions: SLL is feasible, overall safe, and detected MRD in 46% of ovarian cancer patients who were in radiologic and CA-125 remission after frontline therapy. PFS was significantly shorter for patients with residual disease, despite those patients all receiving additional therapy. Knowledge of MRD status in this patient population enables interventional, observational, and translational opportunities, as well as personalized prognostic counseling. MRD rate may also have utility as an early surrogate for efficacy in trials evaluating novel frontline investigational therapies. Future studies will compare the performance of circulating tumor DNA (ctDNA) versus surgical MRD. Citation Format: Anne Knisely, Roni Nitecki, J. Alejandro Rauh-Hain, R. Tyler Hillman, Jolyn S. Taylor, Lois M. Ramondetta, Michaela O. Grinsfelder, Lauren P. Cobb, David M. Boruta, Gwyn Richardson, Pamela T. Soliman, Aaron Shafer, Shannon N. Westin, Nicole D. Fleming, Travis T. Sims, Anil K. Sood, Pedro T. Ramirez, Karen H. Lu, Amir A. Jazaeri. The utility of surgical minimal residual disease after frontline treatment for prognostic and investigational opportunities in advanced ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A077.

DOP77 Mesenchymal stem cell therapy for refractory Crohn’s perianal fistulas: a case series

Abstract Background Nearly one-third of patients with Crohn’s disease will develop one or multiple perianal fistulas within the first two decades after diagnosis, with the majority being complex. Treatment options are limited with high recurrence rates after both medical and surgical approaches. It has been demonstrated that a completely fibrotic tract on Magnetic Resonance Imaging (MRI) with a MAGNIFI-CD &amp;lt;6 is the best predictor for long-term clinical closure. Mesenchymal stem cell treatment (MST) has emerged as a new therapeutic strategy for these fistulas. The aim of the current study was to analyse the effectiveness of MST for complex Crohn’s perianal fistulas based on MRI. Methods Consecutive patients with complex Crohn’s perianal fistulas, previously failing both anti-TNF treatment and surgical closure, that underwent surgical closure of the internal opening with MST between December 2019 and March 2023 were included. All patients underwent a MRI preoperatively and between three to six months after MST. For the current study, MRI’s were read by an senior radiologist. The primary endpoint was radiological remission of the fistula(s) defined as a MAGNIFI-CD &amp;lt;6 on MRI. Secondary endpoints were clinical closure (defined as closure of the external opening(s)), recurrence rate, change of MAGNIFI-CD over time, quality of life based on the perianal disease activity index (PDAI), and serious adverse events (SAE). Results In total, 30 patients (16 females) with 48 fistula tracts were included with a median clinical follow-up of 20 months. Radiological remission was achieved in thirteen patients (43.3%) after a median follow-up of 5.0 months (IQR 3.0-6.0). The median MAGNIFI-CD at baseline was 15.0 (IQR 7.0-20.0) which decreased significantly to 8.0 (IQR 3.0-15.0) after treatment (p= 0.001). Clinical closure of the fistula(s) was achieved in 21 patients (70.0%). Three patients (14.3%) developed a recurrence during long-term FU. All three patients had clinically closed fistula(s), but no radiological remission. The median PDAI decreased significantly from 10.5 (IQR 7.0-14.0) to 4.0 (IQR 0.0-7.3) (p= 0.001). Overall, in this patient group one SAE occurred requiring multiple reinterventions and temporary stoma. Conclusion Closure of the internal fistula opening with MST is a promising treatment strategy for therapy refractory Crohn’s perianal fistulas, resulting in &amp;gt;40% radiological remission and clinical closure in 70%. No recurrences were seen in patients with radiological remission. MST was also associated with a significant increase in quality of life. Further research is needed to gain insight in which patients MST is most likely to induce radiological remission.

P933 Closing the internal opening with a rectal advancement flap increases the effectiveness of mesenchymal stem cell (MSC) injection in the treatment of complex Crohn's disease anal fistulas

Abstract Background The injection of MSCs into complex anoperineal fistulas of Crohn's disease gives a combined clinical and radiological remission of between 35 and 50% at 12 months. In our department, surgical closure is now done by rectal advancement flap (and no longer with simple stitches) in order to minimize the passage of stools and contamination of the fistula tract. The aim of this study was to compare the remission rate and the quality of life between patients treated with MSC injection using simple stitches versus a rectal flap to close the internal opening. Methods This single-center prospective study included all our consecutive patients who had a MSC injection. The first patients of the series who had closure of the internal opening(s) with stitches (2020- 2022) were compared with those who had a flap (2022-2023). Complete clinical remission was defined by complete closure of the external opening(s) without pain or discharge, and complete radiological remission by a Magnifi-CD score equal to 0 (Hindryckx P, et al. Gastroenterology 2019). Quality of Life was assessed by the Crohn's Anal Fistula Quality of Life scale (CAF-QoL) (Adegbola SO, et al. Gut 2021). Results We included 68 patients (50% women, mean age: 38 ± 13.8 years). The first 42 had stitches and the following 20 had an advancement flap (6 patients had no procedure due to an anal stenosis). The median follow-up was 12 months [6-24]. The overall complete clinical remission was 66.7% at M12: 51.1% [35.5-66.8] in the "stitches" group versus 87.5% [69.7-100.0] in the "flap" group (p = 0.005) (Figure). The difference was noticed early from M1. The mean overall Magnifi-CD MRI score decreased from 15.5 ± 4.7 to 6.5 ± 7.1 at M12 (p &amp;lt; 0.001) with no difference between the 2 groups. However, more patients in the flap group had a Magnifi-CD score of 0: 62.5% versus 38.2%. The CAF-QoL quality of life score improved from 51.3 ± 24.7 to 21.2 ± 20.8 at M12 (p &amp;lt; 0.001) with no significant difference between the 2 groups. The duration of the procedure was longer on average by 19 ± 7 minutes in the "flap" group. There was no difference in the anal incontinence score between the 2 groups. In logistic regression, the advancement flap was significantly associated with complete clinical remission (p = 0.007, HR (95% CI): 2.3 [1.3-4.3]). Conclusion Closing the internal opening with a rectal advancement flap improves the effectiveness of MSC injections with a complete clinical and radiological remission rate of 87.5% and 62.5% respectively, without consequences on anal continence.

P654 Assessing patient-perceived burden of disease in Ulcerative Colitis: a novel scoring approach in a real-world Australasian cohort

Abstract Background The prevalence and burden of inflammatory bowel disease (IBD) including ulcerative colitis (UC) is rising globally. We present a novel score to evaluate patient-perceived burden of disease (PPBoD) in UC, which we applied to a large real-world Australasian cohort. Methods The Crohn’s Colitis Care (CCCare) Clinical Registry was interrogated in October 2023. Adults with ulcerative colitis (UC) across 17 IBD centres who had an outpatient encounter in the last 14 months were included. A novel PPBoD score was created for UC, including patient-reported components from the Mayo Score (stool frequency and rectal bleeding) as well as general wellbeing, urgency and nocturnal bowel motions. The PPBoD was calculated as detailed in Figure 1. A score of 0 was defined as no PPBoD, 1-2 as mild, 3-4 as moderate and ≥ 5 as significant PPBoD. The correlation between PPBoD and demographics, disease and treatment factors was assessed. Results A total of 2507 people with UC (41.0%) were identified with a clinical assessment in the last 14 months; 92.2% of whom (n = 2311) had adequate data to calculate the PPBoD. In this cohort &amp;gt; 80% had either no or only mild PPBoD (Table 1). Age, gender and BMI did not vary significantly between PPBoD categories. People with lower PPBoD were more likely to be on advanced therapies and had lower rates of steroid use. There was no significant difference in the use of immunomodulators and aminosalicylates across PPBoD categories. The cohort was geographically dispersed across Australia (n = 1786, 77.3%) and New Zealand (n = 525, 22.7%). There was significantly higher PPBoD in New Zealand, but notably those in New Zealand were less likely to be on advanced therapies (p &amp;lt; 0.001). In the subset of 780 people (33.8%) who had a recent faecal calprotectin, people with no PPBoD were more likely to have biochemical remission (faecal calprotectin &amp;lt; 100 μg/g). Data were available for endoscopic and radiological remission in 654 people (28.3%); those with no PPBoD were more likely to be in remission (p &amp;lt; 0.001). Over 98% of people with no PPBoD had no days out of role due to disease, whereas those with higher PPBoD had more days out of role (Table 1). Conclusion We present a novel consumer-focused score to evaluate PPBoD in UC. Within this geographically dispersed cohort, the majority had either no or mild PPBoD. Advanced therapies were associated with lower PPBoD, and their health economic value could be evaluated using this tool. Further studies are required to validate this novel score to assess BoD in UC.

P529 Assessing patient-perceived burden of disease in Crohn’s disease: a novel scoring approach in a real-world Australasian cohort

Abstract Background The prevalence and burden of inflammatory bowel diseases (IBD) including Crohn’s disease (CD) are rising globally. We present a novel score to evaluate the patient-perceived burden of disease (PPBoD) in CD, and explored it in a large real-world Australasian cohort. Methods The Crohn’s Colitis Care (CCCare) Clinical Registry was interrogated in October 2023. Adults with CD across 17 IBD centres with an outpatient encounter in the last 14 months were included. A novel PPBoD score was designed for CD, which included patient-reported components from the Harvey-Bradshaw index (abdominal pain and patient-rated general wellbeing) as well as nocturnal bowel actions, defecation urgency and stool frequency. The PPBoD score was calculated as detailed in figure 1. A total score of 0 was defined as no PPBoD, 1-2 as mild, 3-4 as moderate and ≥ 5 as significant PPBoD. Correlations amongst PPBoD and demographics, disease and treatment factors were explored. Results A total of 3461 people with CD were assessed in the last 14 months and 3233 (93.4%) had adequate data to calculate PPBoD. Of these, 80.0% had either no or mild PPBoD (table 1). While gender varied significantly between PPBoD categories, age and BMI did not. People with lower PPBoD were more likely to be receiving advanced therapies and had lower rates of steroid use than those with higher PPBoD. There were no significant differences in the use of immunomodulators and/or aminosalicylates across PPBoD categories. The cohort was geographically dispersed across Australia (n = 2414, 74.7%) and New Zealand (n = 819, 25.3%). There was significantly higher PPBoD in New Zealand compared to Australia but notably people in New Zealand were less likely to be receiving advanced therapies (p &amp;lt; 0.001). In the subset of 1074 people (33.2%) with a recent faecal calprotectin, those with no PPBoD were more likely to have biochemical remission (faecal calprotectin &amp;lt; 100 μg/g). Data were available to assess endoscopic and radiological remission in 1049 people (32.4%); those with no PPBoD were more likely to be in remission. Less than 1% of people with no PPBoD had any days out of role due to CD, whereas those with higher PPBoD had more days out of role (Table 1). Conclusion We present a novel consumer-focused score to quantify PPBoD in CD. Within this geographically dispersed cohort, the majority had either no or mild PPBoD. Advanced therapy use appeared to be protective against high PPBoD. Further studies are required to validate this novel score to assess PPBoD in CD.

P547 Improved clinical and radiologic healing of Crohn’s perianal fistulas using a novel coordinated care model optimising medical and surgical treatments: A prospective real-world observational study

Abstract Background Despite best standard care, sustained healing rates of Crohn’s perianal fistulas remain low. A novel coordinated multi-disciplinary care model optimising medical and surgical treatment was established with the aim to improve fistula healing rates. Methods A prospective real-world observational study evaluated the efficacy of this new care model in adults with Crohn’s perianal fistulas. Patients seen through the new care model were sequentially invited to participate, between March 2021 to April 2022, and included irrespective of disease activity, duration, or prior treatments. Three dynamic stages of care were directed towards patients’ clinical disease activity: stage A, active disease, focused on medical and surgical treatment optimisation; stage B, optimised treatments with a seton in situ, focused on definitive surgical management; and stage C, healed disease, focused on treatment maintenance. Endpoints included: [1] clinical fistula healing after a minimum of 12 months follow-up; [2] changes in radiologic disease activity and fibrosis on serial magnetic resonance imaging; and [3] proportion of patients requiring treatment optimisation. Results Sixty patients were included. At baseline, 47% were in stage A, 5% stage B, and 48% stage C. Median age was 40 years (IQR: 32-49), 52% were male, median perianal disease duration was 9 years (IQR: 2-16), and median attendance through the preexisting service was 6 years (IQR: 3-9). After a median of 22 months follow-up (IQR: 16-25), 83% had clinical healing which was significantly higher than baseline rates at study inclusion (83 vs 48%, p&amp;lt;0.001). For patients in stage A at baseline, 68% achieved clinical healing with estimated clinical healing rates of 39% (95%CI: 24-60) and 85% (95%CI: 64-97) at 1 and 2 years, respectively. This paralleled a significant reduction in radiologic disease activity and increase in radiologic fibrosis, with radiologic remission observed in 51% and radiologic response in 47% overall (Table 1). Patients who achieved clinical healing had significantly less radiologic disease activity and greater fibrosis compared to patients with non-healing fistulas. Overall, 53% had biologic dose escalation and 10% switched to an alternative biologic agent with the new care model. Thirty-seven percent underwent a median of two perianal surgical interventions (IQR: 1-3), 15% had closure or ablative techniques performed, and 15% had seton removal only. Conclusion A novel coordinated multi-disciplinary care model optimising medical and surgical treatments resulted in high rates of clinical healing and improved radiologic disease activity and fibrosis of Crohn’s perianal fistulas. Controlled-matched studies evaluating treatment optimisation are needed.

P443 Transmural Remission Associates with a Lower Risk of Phenotype Progression in Crohn’s Disease

Abstract Background Patients with Crohn’s disease (CD) are at risk of progressing from inflammatory to stricturing and penetrating phenotypes. The influence of the type of remission on phenotype progression has not been adequately evaluated. Methods Retrospective cohort study including surgically naïve CD patients with inflammatory or stricturing phenotype evaluated concomitantly by magnetic resonance enterography and colonoscopy. The degree of remission was correlated with the risk of progressing to stricturing and penetrating phenotypes. Results 381 CD patients were included, 21.8% with transmural remission, 21.3% with isolated endoscopic remission, 10.5% with isolated radiologic remission, and 46.5% without remission. Patients with transmural remission presented the lowest rates of phenotype progression (1.2%), with a significant difference compared to isolated endoscopic remission (18.3%, P≤ 0.001), isolated radiologic remission (17.5%, P=0.002), and no remission (36.9%, P≤0.001). In multivariate regression analysis, transmural remission (OR 0.023 95%CI 0.003-0.171, P&amp;lt;0.001), isolated radiologic remission (OR 0.342 95%CI 0.141-0.826, P=0.017), and isolated endoscopic remission (OR 0.441 95%CI 0.220-0.881, P=0.020) resulted in lower rates of phenotype progression compared to no remission. Conclusion The degree of intestinal remission correlates with the risk of phenotype progression. Patients with transmural remission are at the lowest risk of progressing to stricturing and penetrating phenotypes. Figure 1 presents the Kaplan-Meier estimates of remaining free of penetrating complication (upper curve) and free of stricturing and/or penetrating complication (lower curve) after the baseline assessment in patients with no remission (A), isolated endoscopic remission (B), isolated radiologic remission (C), and transmural remission (D). B1, non-stricturing non-penetrating phenotype; B2, stricturing phenotype; B3, penetrating phenotype.

P490 Prevalence and clinical features of chronic nonbacterial osteomyelitis in a nationwide cohort of children with inflammatory bowel diseases

Abstract Background Among musculoskeletal extraintestinal manifestations (EIM), the association between IBD and a rare autoinflammatory condition, chronic nonbacterial osteomyelitis (CNO), has been reported. The primary objective of our study was to report the clinical characteristics and the disease course of a cohort of patient with concurrent diagnosis of CNO and IBD. The secondary outcome was to define the prevalence of CNO in a nationwide cohort of patients with IBD. Methods This is a retrospective, multicenter study based on the Italian Society of Gastroenterology, Hepatology, and Pediatric Nutrition (SIGENP) IBD National Registry. The diagnosis of CNO was defined as the presence of uni- or multifocal bone inflammatory lesions with suggestive radiological or histopathological characteristics, having excluded infectious, oncological, or other inflammatory conditions. All patients under 18 years of age with a combined diagnosis of IBD and CNO identified in the registry were included. Results 18 patients with a combined diagnosis of CNO and IBD out of 4229 patients with IBD were identified, with an overall prevalence of 0.4%. 15 (83.3%) patients were male. Median age at IBD diagnosis was 10.1 years (IQR: 6.16 years), whereas median age at CNO diagnosis was 11.7 years (IQR: 6.31 years). The most frequently reported IBD phenotype was CD (13 patients, 72.2%), followed by IBD-U (3 patients, 16.7%) and UC (2 patients, 11.1%). The diagnosis of concurrent CNO was more common in patients affected by CD than in those affected by either UC or IBD-U (13/1843, 0.7% vs 5/2886, 0.2%, p=0.01). Similarly, the occurrence of CNO was more frequent in male gender when compared to female one (15/2312, 0.6% vs 3/1917, 0.1%, p=0.01). All the patients had multifocal bone involvement; 2 (11.1%) developed subsequently dermatological manifestations consistent with SAPHO syndrome. In 8 patients (44.4%) IBD onset preceded CNO diagnosis, in 6 (33.3%) IBD onset followed CNO diagnosis, whereas in the remaining 4 patients (22.2%) the diagnosis of IBD and CNO was concomitant. Table 1. summarizes therapeutic approach to both conditions in each of the patient identified in our case series. At the end of follow-up, 14 (77.8%) patients had achieved IBD clinical and biochemical remission. Ten (55.6%) patients achieved clinical and radiological remission of bone lesions, 6 (32.3%) had achieved clinical remission but showed persistence of bone lesions at magnetic resonance imaging (MRI), 2 (11.1%) had persistence of both clinical and radiological activity. Conclusion Our findings support the hypothesis that CNO disease spectrum can be considered a rare extraintestinal manifestation of IBD, with a low but still non-negligible prevalence.