Introduction

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease, with a substantial impact on quality of life; longer disease duration increases the risk of fibrostenosis, which may reduce both clinical and histologic response to therapy. Dupilumab, a fully human monoclonal antibody that blocks key drivers of type 2 inflammation, is approved for the treatment of EoE in adults and adolescents aged ≥12 years weighing ≥40 kg in the EU, and for patients aged ≥1 year, weighing ≥15 kg in the US.

Aims & Methods

The objective of this post-hoc subgroup analysis of the LIBERTY EoE TREET study (NCT03633617) was to assess the long-term efficacy of dupilumab in patients with EoE stratified by baseline disease duration. In Part B, patients received 24 weeks of dupilumab 300 mg once weekly (qw), dupilumab 300 mg once every 2 weeks, or placebo qw. Eligible patients who completed Part B received dupilumab through 52 weeks (Part C). This analysis focuses on patients who were originally randomized to dupilumab 300 mg qw or placebo. Co-primary endpoints were the proportion achieving peak esophageal intraepithelial eosinophil count (PEC) ≤6 eosinophils per high-power field (eos/hpf) and absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) total score. Key secondary endpoints included proportion achieving PEC <15 eos/hpf, and mean change from baseline in Endoscopic Reference Score (EREFS) total score and Histologic Scoring System (HSS) grade/stage scores. Data were stratified by baseline disease duration defined as time since diagnosis (≤5 years, >5-10 years, >10 years), as reported by the investigator.

Results

At Part B baseline (Week 0) in the dupilumab and placebo groups, respectively, 43 and 48 patients had EoE for ≤5 years, 22 and 13 patients had EoE for >5-≤10 years, and 15 and 18 patients had EoE for ≥10 years. Each of the co-primary endpoints—PEC ≤6 eos/hpf and DSQ total score at Week 24—favored dupilumab over placebo, regardless of disease duration (Table). At Week 24, marked improvements with dupilumab vs placebo were also seen for EREFS and HSS grade/stage scores across all disease duration subgroups (Table). At Week 52, all patients who received continued dupilumab maintained improvement across all outcomes, including 88.6%, 73.7%, and 90.9% achieving ≤6 eos/hpf in the ≤5, >5-≤10, and ≥10 year subgroups, respectively. Regardless of subgroup, 100% of patients receiving continued dupilumab achieved PEC <15 eos/hpf at Week 52. Patients who switched from placebo to dupilumab at Week 24 showed improvement in all outcomes at Week 52, comparable to patients who received continued dupilumab.

Conclusion

Dupilumab 300 mg qw demonstrated notable histologic response and substantial symptomatic and endoscopic improvements in adults and adolescents with EoE through 52 weeks. These results show that dupilumab 300 mg qw is an effective long-term treatment for patients with EoE, regardless of disease duration at baseline.

Disclosure

NG: Allakos, AstraZeneca, BMS, Regeneron Pharmaceuticals Inc., Exact Sciences, Sanofi, Takeda – consulting fees. Regeneron Pharmaceuticals Inc., Sanofi, Takeda – speaker bureau fees.
CSc: Adare Pharmaceuticals Inc., AstraZeneca, Calypso, Dr. Falk Pharma, EsoCap GmbH, Regeneron Pharmaceuticals Inc. – consulting fees
CSa: AstraZeneca, Doctaforum Medical Marketing S.L., Farma de Colombia SAS, Isomed Pharma S.L., Laborie/MMS, Medtronic Covidien AG, Menarini Consumer Healthcare – consulting fees. Adare Pharmaceuticals Inc., AstraZeneca, Celldex Therapeutics, Dr. Falk Pharma GmbH, EsoCap Biotech, International Marketing & Communication, Regeneron Pharmaceuticals Inc., S.A. – research funding.
KP: AGA, Alladapt, Allakos, AstraZeneca, BMS, Ellodi, Invea, Lucid, Nexstone, Peerview, Regeneron, Takeda, WebMD – consulting fees. Adare, Allakos, AstraZeneca, Celldex, Ellodi, Regeneron Pharmaceuticals Inc.-Sanofi, Revolo – research fees. AGA, Allakos, PeerView, Regeneron Pharmaceuticals Inc., Takeda, WebMD – speaker fees. Allakos, Chobani – grant support. Nexeos Bio – stock and options.
CX, BR, AR: Regeneron Pharmaceuticals Inc. – employees and shareholders.
TP, JAJ-N: Sanofi – employees, may hold stock and/or stock options in the company.

Clinical Case Summary

Recently, the concept of neoadjuvant therapy for unresectable locally advanced pancreatic cancer (PC) has received much attention. However, in patients who respond well to neoadjuvant therapy, even if resection is achieved, micro-cancer cells may remain around the major vessels. This may lead to early recurrence. A novel therapeutic strategy is needed to improve prognosis and achieve long-term survival. Under the situations, high-intensity focused ultrasound (HIFU) of new noninvasive therapy is expected as neoadjuvant therapy. A 75-year-old male, who was diagnosed as pancreas body cancer (38mm) infiltrating celiac artery (CA), common hepatic artery (CHA), splenic artery (SPA), and portal vein (PV) by enhanced CT, MRCP and EUS-FNA. There was no indication for surgery, and then chemotherapy (Gem/nab-PTX; GnP) was enforced due to unresectable locally advanced PC (Stage III). The chemotherapy with GnP was administered at 100% dose and performed for 4 courses. The main tumor became smaller (20mm) after 4 months from the diagnosis. However, there was still residual tumor adjacent to the CA, CHA, SPA, and PV (cT4N1aM0: stage III). Therefore, we cauterized the main tumor and the around CA, CHA, SPA, and PV using HIFU system with the aim of obtaining a negative surgical margin for one week before the surgical resection. A total pancreatectomy which included resection of the portal vein, was performed after HIFU therapy. The pathological findings showed that the tumor infiltrated the portal vein that was resected, but no tumor invasion to artery was observed. The surgical margin was negative (R0 resection). In conclusion, the combination of chemo and HIFU therapy may be promising therapies for patients with unresectable locally advanced PC for achieving curative resection.

References

Sofuni A, Asai Y, Tsuchiya T, et al. Novel therapeutic method for unresectable pancreatic cancer the impact of the long term research in therapeutic effect of high intensity focused
ultrasound (HIFU) therapy. Curr Oncol. 2021;28:4845 61.

Disclosure

No COI to report.

Introduction

Surgery represents an important part of the therapeutic armamentarium for the treatment of IBD, and has been associated with variable effects on the psychological profile of patients with inflammatory bowel disease. However, surgical treatment is often distressingly perceived by these patients as the failure of their therapies, and can be a trigger for anguish, anxiety or depression.

Aims & Methods

The aim of this study is to describe the psychological impact of surgery on operated IBD patients.
This is a prospective descriptive monocentric study, conducted at the Department of Hepato-Gastro-Enterology and Proctology "Medicine B" CHU Ibn Sina Rabat, which collected all patients followed for IBD (Crohn's + UC) and who were operated between August 2021 and August 2023, the psychological impact and apprehension regarding surgery will be addressed in this study. Patients of both sexes who agreed to answer the questionnaire were included, and patients who refused to answer the questionnaire and complicated patients who stayed in intensive care were excluded.

Results

43 operated patients were included in our study, including 29 (67.4%) in the emergency setting and 14 (32.6%) scheduled. Mean age was 43 ± 16.17 years. The sex ratio was 1.26 (F/H=24/19). 35 patients (81.4%) were being followed for Crohn's disease and 8 patients (18.6%) for ulcerative colitis (UC), of whom 11 patients (25.5%) had a history of previous resection, and 1 patient (2.3%) was being followed for depression.
The surgical indications were GCA in 12 cases (27.9%), stenosis in 18 cases (41.8%), perforation in 1 case (2.3%), abscess in 8 cases (18.6%), and fistula in 4 cases (9.3%).
Our patients underwent ileo-caecal resection in 22 cases (51.2%), hemicolectomy in 6 patients (14%), coloproctectomy in 3 patients (7%), sub-total colectomy in 11 patients (25.6%), of whom 18 patients (41.9%) had an ostomy.
On the announcement of a possible surgical procedure, the thymic symptoms and feelings expressed by patients can be classified as follows: preoperative anxiety in 18 patients (41.9%), fear of death in 7 patients (16.3%), while 24 patients (55.8%) were indifferent.
The main anxiety-generating concern was postoperative pain in 7 patients (14%), potential complications in 7 patients (16.3%), failure of the procedure in 6 patients (14%), fear of dying in 7 patients (16.3%), and 25 patients (58.1%) expressed no anxiety.
The postoperative psychological experience was unremarkable in 37 patients (86%), 3 patients (7%) reported transient postoperative sadness and 3 patients (7%) developed postoperative depression, prompting consultation with a psychiatrist.

Conclusion

The impact of surgery in IBD patients not only concerns the body, but also has an effect on psychological well-being.
This study found that the pre-operative period induces a significant burden of anxiety in these patients, and depression in some.

Introduction

High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). The visual characterization of high-grade intraepithelial lesions (HSIL) is hampered by a limited interobserver agreement. Artificial intelligence (AI) algorithms have shown high levels of efficiency in detecting and differentiating HSIL from low-grade squamous intraepithelial lesions (LSIL) in HRA images. Nevertheless, these studies have been conducted using a digital videoproctoscope, whose use is not predicted in the standards of the International Anal Neoplasia Society (IANS). Our aim was to develop a deep learning system for automatic detection and differentiation of HSIL versus LSIL using HRA images from both conventional and digital proctoscopes.

Aims & Methods

A convolutional neural network (CNN) was developed based on 151 HRA exams from 137 patients undergoing HRA at two large volume centres (GH Paris Saint-Joseph, Paris, France and Emílio Ribas Infecciology Institute, São Paulo, Brazil), using conventional HRA (KLP 200 LED®, Kolplast) and digital HRA (THD Proctostation®, THD SpA). A total of 58,498 images were included, 29,212 images containing HSIL and 29,286 LSIL. Partial subanalyses were performed to evaluate the performance of the CNN in the subset of images with no staining (n=2,820), acetic acid (n=27,191), lugol (n=10,011), and after treatment of the anal canal (n=11,047). For these subanalyses, training, and testing datasets comprised 90% and 10% of each class's total number of images. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve (AUC) were calculated.

Results

The overall accuracy of the CNN in distinguishing HSIL from LSIL during the testing stage was 98.6%. The algorithm had an overall sensitivity and specificity of 97.3% and 99.1%, respectively. The overall AUC was 0.99. For staining with acetic acid, HSIL was differentiated from LSIL with an overall accuracy of 96.4%, while for lugol and after therapeutic manipulation these values were 96.6% and 99.3%, respectively. The AUC ranged between 0.98 and 1.00 in these particular subgroups.

Conclusion

The introduction of AI algorithms to HRA may enhance the early diagnosis of ASCC precursors, and this system showed to perform adequately across conventional and digital HRA interfaces. Improving the detection of ASCC precursors may improve the treatment outcomes and prognosis. The developed AI model is the first model capable of performing adequately in different clinical sub settings and in different systems available on the market.

References

1. Hillman, R.J.; Cuming, T.; Darragh, T.et al. 2016 IANS International Guidelines for Practice Standards in the Detection of Anal Cancer Precursors. J Low Genit Tract Dis 2016; 20: 283-291.
2. Mistrangelo, M.; Salzano, A. Progression of LSIL to HSIL or SCC: is anoscopy and biopsy good enough? Tech Coloproctol 2019; 23: 303-304.
3. Deshmukh, A.A.; Suk, R.; Shiels, M.S.et al. Recent Trends in Squamous Cell Carcinoma of the Anus Incidence and Mortality in the United States, 2001-2015. J Natl Cancer Inst 2020; 112: 829-838.
4. Palefsky, J.M.; Lee, J.Y.; Jay, N.et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. New England Journal of Medicine 2022; 386: 2273-2282.
5. Neukam, K.; Milanés Guisado, Y.; Fontillón, M.et al. High-resolution anoscopy in HIV-infected men: Assessment of the learning curve and factors that improve the performance. Papillomavirus Res 2019; 7: 62-66.
6. Saraiva, M.M.; Spindler, L.; Fathallah, N.et al. Artificial intelligence and high-resolution anoscopy: automatic identification of anal squamous cell carcinoma precursors using a convolutional neural network. Tech Coloproctol 2022; 26: 893-900.
7. Pathologists, C.o.A. Protocol for the Examination of Excision Specimens From Patients With Carcinoma of the Anus. 2021; 4.2.0.

Introduction

Effective timing of endoscopic interventions and follow-ups is crucial in the management of severe acute pancreatitis. Implementing a multidisciplinary team (MDT) approach not only enhances this timing but also ensures consistent clinical care, providing rapid responses to complications and timely adjustments in treatment plans. This coordinated approach optimises recovery and improves patient outcomes by integrating timely diagnostics and interventions. The MDT’s strategic involvement is vital for maintaining high standards of care and safety and ensuring consistent and effective treatment of severe acute pancreatitis.

Aims & Methods

This retrospective cohort study assessed the impact of a novel hub-and-spoke severe acute pancreatitis (SAP) multidisciplinary team (MDT) model at a tertiary hepato-pancreato-biliary (HPB) centre. The model, which included Gastroenterologists, Surgeons, Nurses, Dieticians, and Radiologists, focused on optimising clinical outcomes by enhancing the coordination of hospital transfers and precision in the timing of interventional endoscopies. The study compared patient outcomes before the MDT implementation (January 2022 to January 2023) and after (November 2023 to March 2024), to improve intervention scheduling and establish systematic follow-up protocols to ensure comprehensive care. The primary objective was to evaluate how the MDT model influenced the timing of interventions and follow-up procedures in severe acute pancreatitis management.

Results

This study evaluated clinical outcomes for acute pancreatitis across two cohorts, comprising 191 patients before the implementation of a multidisciplinary team (MDT) and 76 patients following the implementation. For the pre-MDT cohort, the aetiology of pancreatitis included gallstone-induced cases (n=50), alcohol-related (n=45), idiopathic (n=2), and unspecified (n=94), with 28.79% of the cohort having a history of gallstones. In the pre-MDT group, the scheduling of interventions lacked consistency. 10 patients required inpatient endoscopic procedures, with a median time from admission to intervention of 13.0 days and a mean time of 12.79 days.
Post MDT implementation, 7 patients required inpatient endoscopic procedures, with waiting times reduced to a median of 6.5 days and a mean of 6.3 days. All these inpatients (n=7/7) received their procedures within the first week. The median duration of hospital stays was reduced from 8 days (pre-MDT) to 5 days (post-MDT). Additionally, the proportion of inpatients discharged within the first week post-intervention increased from 30% (n=3/10) pre-MDT to 71.4% (n=5/7) post-MDT. The average clinic follow-up time decreased from 169 days pre-MDT to 43 days post-MDT. The median timing to outpatient endoscopy was reduced, with 68% of patients receiving it in a six-week window post-discharge.

Conclusion

The integration of a multidisciplinary team (MDT) has markedly improved the management of severe acute pancreatitis, enhancing the precision and efficiency of interventional endoscopies. This optimised coordination has reduced hospital stays and ensured timely interventions, significantly boosting patient outcomes. The MDT approach effectively addresses the complexities of the condition, transforming patient care with tailored and rapid treatment strategies.

Disclosure

No disclosures

Introduction

Colorectal cancer (CRC) patients commonly encounter anemia, with estimates indicating that up to 58% are affected and iron deficiency (ID) anemia being the most prevalent. This study aimed to compare the efficacy and safety of preoperative intravenous iron (IVI) with standard care (no iron or oral iron) in CRC patients with ID anemia.

Aims & Methods

We conducted a systematic search of the Cochrane Library, PubMed, Scopus, and Web of Science databases from inception to September 20, 2023, to identify studies comparing intravenous iron (IVI) versus standard care in colorectal cancer (CRC) patients with iron deficiency anemia. Pooled results were analyzed for changes in hemoglobin (Hb) levels from baseline, need for red blood cell (RBC) transfusions, mean number of RBC units transfused, overall survival (OS), disease-free survival (DFS), and complications.We evaluated randomized clinical trials using the Cochrane Risk of Bias 2 tool and observational studies using the Newcastle Ottawa Scale. Statistical analysis was performed using Revman software Version 5.4.1.

Results

We analyzed data from 11 studies, encompassing 2,024 patients, and found that IVI significantly increased Hb levels at various crucial time points: preoperative (MD=1.17, CI 95% [0.95, 1.40], P<0.01), postoperative day one (MD=1.32, CI 95% [0.89, 1.76], P<0.01), hospital discharge (MD=0.76, CI 95% [0.28, 1.24], P=0.002), and 30 days postoperative (MD=1.57, CI 95% [1.27, 1.87], P<0.01). The overall need for RBCT significantly decreased with IVI (RR=0.39, CI 95% [0.27, 0.56], P<0.01), particularly in the postoperative period (RR=0.69, CI 95% [0.52, 0.92], P=0.01). No significant differences were found between preoperative and intraoperative periods. IVI notably reduced transfused red blood cell units, total complications, and wound dehiscence. However, there were no significant differences in total death, hospital stay, OS and DFS.

Conclusion

Preoperative IVI significantly increased Hb levels at critical time points and markedly reduced the overall need for RBCT, complications, and wound dehiscence. To further validate these findings, more well-designed randomized controlled trials are warranted.

Introduction

Managing decompensated cirrhosis is a significant challenge due to high morbidity and mortality rates. The recently proposed Baveno VII criteria provide a standardized definition to assess recompensation. In this study, we validated the Baveno VII definition of recompensation and aimed to evaluate recompensation factors in patients with decompensated viral cirrhosis.

Aims & Methods

This is a retrospective descriptive study over a 10-year period between 2012 and 2022, enrolling 99 patients from the hepato-gastroenterology department of Mohamed Taher Maamouri Hospital in Nabeul who had been treated for decompensated viral cirrhosis B or C and achieved sustained virological response with a follow-up of at least 12 months.

Results

A total of 99 patients with decompensated viral cirrhosis (B or C), who had received treatment and achieved sustained virological response, were included in the study. The mean age was 62 ± 11 years, and 56 patients were female. The most common mode of decompensation was ascites, observed in 81.8% of the patients. The mean MELD score was 15 ± 4, and the majority (59.7%) were classified as Child-Pugh class B. Overall, 45.5% of the decompensated patients achieved recompensation during the study period. The recompensation rate was higher in patients with hepatitis B-related cirrhosis (51.1%) compared to those with hepatitis C-related cirrhosis (40.4%).
According to the results of logistic regression, four independent factors associated with recompensation were found: albumin ( OR = 2.033, IC95% [1,461-2,827], p<0.001 ), diabetes ( OR =0.003, IC95%[0.000-0.045], p<0.001 ), Child Pugh score ( OR=0.162, IC95% [0.057-0.459], p=0.001 ), INR ( OR =0.017, IC95%[0.000-0.939].

Conclusion

This study identified key factors associated with recompensation in patients with viral decompensated cirrhosis, including serum albumin levels, INR values, history of diabetes, and severity of liver disease. The knowledge of recompensated indicators may help support the development of different prevention strategies to reduce the incidence of acute decompensation.