Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.

We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.

Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers.

Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.

Perianal fistulising Crohn's disease (PFCD) is a debilitating phenotype of Crohn's disease, with a lifetime incidence of 20-30% in people living with the dieases. Symptoms include perianal pain, perianal discharge and faecal incontinence, with repercussions for a patient's physical and mental health, psychosocial wellbeing and productivity. PFCD is challenging to treat, with existing therapeutic options achieving modest fistula remission rates only. While research initiatives are under way to characterise PFCD pathogenesis and optimal treatment approaches, the focus should be on early diagnosis and prompt management. This can be achieved with patient education, effective co-ordination of care within the multidisciplinary team and an accessible inflammatory bowel disease (IBD) service. IBD specialist nurses may be the first health professionals to encounter a patient with a new diagnosis of PFCD or its complications. This review article summarises the existing evidence relating to clinical aspects of PFCD from a multiprofessional perspective and discusses the role of a dedicated IBD surgical link nurse in PFCD management in a tertiary centre setting.

Perianal fistulizing Crohn's disease (pfCD) represents a severe manifestation of Crohn's disease (CD) that often leads to significant morbidity. Clinical examination alone of perianal fistulae is unlikely to be sufficient in the context of complex pfCD, as patients are likely to have complex disease and are more likely to experience complications, treatment failure, and recurrent disease. Furthermore, the relapsing-remitting nature of Crohn's disease and our limited understanding of the pathogenesis of this potentially destructive disease necessitate regular examination and radiological assessment, often in the form of magnetic resonance imaging (MRI). Recent advancements in diagnostic techniques have enhanced the accuracy and timeliness of pfCD diagnosis, facilitating better patient outcomes. A growing appreciation of isolated perianal Crohn's disease has prompted a recent attempt to develop consensus recommendations on diagnosing and treating this group of patients who would previously not have been offered CD medications. This narrative review aims to summarize current practice and the latest developments in the diagnosis of pfCD, highlighting: 1. Clinical examination and assessment tools 2. Current imaging practices 3. Innovations in imaging and biomarkers 4. The diagnosis of isolated perianal Crohn's disease.

Perianal lesions of Crohn's disease (CD) are complex and disabling conditions. Mesenchymal stem cell (MSC)-based therapies have emerged as an innovative approach in managing refractory perianal fistulizing CD. We conducted a systematic review and meta-analysis to describe and compare combined remission and clinical outcomes of MSC-based therapies, and then whether one approach stands out from the rest.

We searched in MEDLINE, EMBASE and CENTRAL (up to December 31, 2023) all prospective studies assessing a local injection of MSC-based therapy in perianal fistulas of CD. The primary outcome was achievement of combined remission. MSC-based therapy strategies were compared.

Twenty-five studies were included in the meta-analysis, enrolling 596 patients with perianal fistulizing CD. The combined remission rate at 3, 6 and 12 months were 36.2% (95% confidence interval (CI), 24.5-49.7), 57.9% (95% CI 51.3-64.2) and 52% (95% CI 38.8-64.8), respectively. MSC-based therapies demonstrated a significant effect in achieving combined remission compared to placebo at 3 months (relative risk (RR) = 1.6; 95% CI 1.0-2.8) and at 6 months (RR = 1.5; 95% CI 1.1-1.9). At 6 months, the combined remission rate was 57.2% (95% CI 47.2-66.6) for adipose-derived stem cells (ASCs) and 55.7% (95% CI 26.4-81.5) for bone marrow-derived stem cells (BMSCs). In the network meta-analysis, allogeneic ASCs and BMSCs did not demonstrate superiority over each other (RR = 0.74; 95% CI 0.31-1.77).

MSC-based therapies are effective for achieving combined remission of refractory and/or complex perianal fistulizing CD. The optimal efficacy effect is reached after 6 months of treatment. No superiority has yet been demonstrated between ASCs and BMSCs therapies.

To present an overview to summarize the efficacy and safety of biologics for the treatment of Crohn's disease (CD).

We gathered systematic reviews or meta-analyses on the efficacy and safety of biologic therapy for CD from the beginning to September 30, 2023, by searching the databases of the Chinese National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database, Web of Science, the Cochrane Library, PubMed, and Embase. Analysing reviews and extracting data, two researchers worked independently. Any discrepancies in the two researchers' assessments of the review process were reevaluated, and the argument was settled by consulting to other researchers. The following details was taken out of the data: author, publication year, study type, number of included studies, country of study, sample size, risk bias tools, biologic therapy, and primary outcomes. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) and the AMSTAR-2, a critical appraisal tool for systematic reviews (2nd edition), were then utilized to assess the methodological quality and reporting quality of the evidence.

There were 19 reviews in all. One systematic review, 5 meta-analyses, and 13 systematic reviews and meta-analyses were among the reviews that were included. Nine studies met the high quality, 5 met the moderate quality, 3 met the poor quality, and 2 met the critically low quality requirements of the AMSTAR-2 criteria.

The analysis of the evidence finds biologic agents for CD are effective and safe. Overall, there was moderate to high quality biologic evidence for CD, but future head-to-head controlled studies are required to better inform the relative positioning of these drugs for the management of CD.

Perianal draining tunnels in hidradenitis suppurativa (HS) and perianal fistulizing inflammatory bowel disease (IBD) present diagnostic and management dilemmas.

We conducted a retrospective chart review of patients with perianal disease evaluated at Mayo Clinic from January 1, 1998, through July 31, 2021. Patients' demographic and clinical data were extracted, and 28 clinical features were collected. After experimenting with several machine learning techniques, random forests were used to select the 15 most important clinical features to construct the diagnostic prediction model to distinguish perianal HS from fistulizing perianal IBD.

A total of 263 patients were included (98 with HS, 100 with IBD, and 65 with both IBD and HS). Patients with HS had a higher mean body mass index, a higher smoking rate, and more commonly showed cutaneous manifestations of tunnels and comedones, while fistulas, abscesses, induration, anal tags, ulcers, and anal fissures were more common in patients with IBD. In addition to having lesions in the perianal area, patients with IBD often had lesions in the buttocks and perineum, while those with HS had additional lesions in the axillae and groin. Among the statistically significant features, the 15 most important were identified by random forest: fistula, tunnel, digestive symptom, knife-cut ulcer, perineum, body mass index, age, axilla, abscess, tags, smoking, groin, genital cutaneous edema, erythema, and bilateral/unilateral.

The results of this study may help differentiate perianal lesions, especially perineal HS and fistulizing perineal IBD, and provide promise for a better therapeutic outcome.

Perianal fistulizing Crohn's disease is one of the most disabling phenotypes of Crohn's disease, due to the severe impairment in quality of life including social and personal wellbeing. A multimodal approach with patient-tailored care is the key to optimal management of this condition. Medical therapy is needed to optimize the luminal disease, and surgical intervention is required to control any associated perianal sepsis and attempt palliative or definitive fistula repair. While several medical and surgical options are available, the majority of patients continue to have symptomatic disease. Fortunately, this continues to drive novel innovations which are revolutionizing the treatment and outcomes of perianal fistulizing Crohn's disease. However, there continues to be a need for randomized trials and consistent metrics utilized for classification and treatment outcomes in order to accurately describe optimal treatment outcomes.

Dual-energy computed tomography enterography (DECTE) has significantly improved gastrointestinal imaging quality. Double-balloon endoscopy (DBE) has enabled comprehensive visualization of the small intestinal mucosa. This study aimed to assess the diagnostic efficacy of small-intestine DECTE and DBE for small bowel Crohn's disease (CD).

This retrospective study was conducted between 1 July 2016 and 1 November 2023 at the First Affiliated Hospital of Soochow University. The study included 72 CD patients who underwent both DECTE and DBE, with 4 patients repeating both procedures within 3 months.

The diagnostic rate of small bowel CD using DBE was 80.3%, which was higher than that using DECTE (65.8%, P = 0.044). The combined small bowel CD diagnostic rate was 89.5%, which was higher than that of DECTE alone (P < 0.001). The detection rate of stenosis using DBE was 46.1%, which was higher than that using DECTE (13.2%; P < 0.001). The combined detection rate of stenosis was 52.6%, which was higher than that of DECTE alone (P < 0.001). For ulcers, DBE had a higher detection rate (73.7%) than DECTE (7.9%; P < 0.001). The combined ulcer detection rate was 76.3%, which was higher than that of DECTE alone (P < 0.001). The detection rate of long ulcers (≥ 2 cm) and non-ileocecal ulcers by DBE were both 17.9%. For patients with abdominal pain, DBE had a diagnostic rate of 79.4%, higher than 63.5% of DECTE (χ2 = 3.889, P = 0.049). The combined diagnostic rate was 87.3%, which was higher than that of DECTE alone (χ2 = 9.626, P = 0.002). For patients with diarrhoea, the DBE's diagnostic rates were 86.8% and 68.4% for DECTE (P = 0.097). The combined diagnostic rate was 94.7%, higher than DECTE alone (χ2 = 7.092, P = 0.008). For patients with other symptoms, such as abdominal distension or vomiting, the DBE diagnostic rate was 79.4% compared with 61.8% for DECTE (P = 0.183). The combined diagnostic rate was higher than DECTE alone (χ2 = 6.620, P = 0.010). Furthermore, notable differences in C-reactive protein, erythrocyte sedimentation rate, faecal calprotectin, haemoglobin, platelet count, albumin, haematocrit, Crohn's Disease Activity Index scores, and Simple Endoscopic Score for Crohn's Disease scores were observed between ulcer-positive and ulcer-negative patients detected by DBE (P < 0.05), whereas DECTE did not show significant differences (P > 0.05).

DBE or the combined use of DECTE and DBE provides superior diagnostic performance for small bowel CD, particularly in detecting stenosis and ulcers, compared with DECTE alone. DBE can be used to identify long ulcers and non-ileocecal ulcers. Moreover, DBE helps diagnose small bowel CD across different clinical manifestations and assess disease activity in various inflammatory states.

Perianal fistulizing Crohn's disease (pfCD) poses significant healing challenges, closely associated with neutrophil extracellular traps (NETs). This study aimed to investigate the microbe-host interactions influencing NETs in pfCD.

From January 2019 to July 2022, patients with pfCD were screened at Ren Ji Hospital. Patients in remission following comprehensive treatment were recruited. We documented clinical characteristics, medication regimens, healing outcomes, and infliximab levels in fistula tissues. NET positivity was confirmed by positive results in citrullinated histone H3 (CitH3) enzyme-linked immunosorbent assay (ELISA) and dual immunofluorescence staining for myeloperoxidase and CitH3. Microbial and transcriptomic profiles from fistula tissues, obtained during surgery, were analyzed using 16S rRNA gene sequencing and RNA sequencing. Differences in microbiome and transcriptomic profiles were evaluated, and their relationships were assessed using Mantel's and Spearman's coefficients.

Significant differences in microbial communities were found between groups (P = .007). Representatively differential microbes such as Prevotella bivia, Streptococcus gordonii, and Bacteroides dorei were enriched in NETs-positive fistulas (P < .05). Functional analysis of microbes revealed reduced ubiquinol biosynthesis and butanoate production in NETs-negative fistulas (P < .05). Transcriptomic analysis indicated increased neutrophil and monocyte infiltration in NETs-positive fistulas, associated with pathways involving bacterial response, neutrophil chemotaxis, secretory processes, and peptidase activity (P < .05). Species prevalent in NETs-positive fistulas correlated positively with immune responses and wound healing pathways, whereas bacteria in NETs-negative fistulas correlated negatively. NETs were negatively associated with tissue infliximab levels (P = .001) and healing outcomes (P = .025).

Our findings reveal unique microbial and transcriptomic signatures associated with NETs in pfCD, highlighting their profound influence on clinical outcomes.

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic conditions characterised by inflammation of the intestinal tract. Alterations in virtually all intestinal cell types, including immune, epithelial and stromal cells, have been described in these diseases. The study of IBD has historically relied on bulk transcriptomics, but this method averages signals across diverse cell types, limiting insights. Single-cell omic technologies overcome the intrinsic limitations of bulk analysis and reveal the complexity of multicellular tissues at a cell-by-cell resolution. Within healthy and inflamed intestinal tissues, single-cell omics, particularly single-cell RNA sequencing, have contributed to uncovering novel cell types and cell functions linked to disease activity or the development of complications. Collectively, these results help identify therapeutic targets in difficult-to-treat complications such as fibrostenosis, creeping fat accumulation, perianal fistulae or inflammation of the pouch. More recently, single-cell omics have gradually been adopted in studies to understand therapeutic responses, identify mechanisms of drug failure and potentially develop predictors with clinical utility. Although these are early days, such studies lay the groundwork for the implementation in clinical practice of new technologies in diagnostics, monitoring and prediction of disease prognosis. With this review, we aim to provide a comprehensive survey of the studies that have applied single-cell omics to the study of UC or CD, and offer our perspective on the main findings these studies contribute. Finally, we discuss the limitations and potential benefits that the integration of single-cell omics into clinical practice and drug development could offer.

Perianal fistulizing disease, commonly associated with Crohn's disease, poses significant diagnostic and therapeutic challenges due to its complex anatomy and high recurrence rates. Radiological imaging plays a pivotal role in the accurate diagnosis, classification, and management of this condition. This article reviews the current radiological modalities employed in the evaluation of perianal fistulizing disease, including magnetic resonance imaging (MRI), endoanal ultrasound, and computed tomography (CT). MRI, recognized as the gold standard, offers superior soft tissue contrast and multiplanar capabilities, facilitating detailed assessment of fistula tracts and associated abscesses. CT, although less detailed than MRI, remains valuable in acute settings for detecting abscesses and guiding drainage procedures. This article discusses the advantages and limitations of each modality, highlights the importance of standardized imaging protocols, and underscores the need for interdisciplinary collaboration in the management of perianal fistulizing disease. Future directions include advancements in imaging techniques and the integration of artificial intelligence to enhance diagnostic accuracy and treatment outcomes.

Faecal calprotectin (FC) is a noninvasive marker that reflects intestinal inflammation with good sensitivity. A prior study indicated that FC values above 150 μg/g could distinguish between anal fistulas (AF) of cryptoglandular or Crohn's disease (CD) origin. It is hypothesized as a useful triage test to rule out CD in newly referred AF patients, thus reducing the number of ileocolonoscopies performed and optimizing treatment regimens in AF while minimizing patient discomfort as well as healthcare costs. The aim of the study was to determine the accuracy of FC in distinguishing between anal fistulas of cryptoglandular and CD origin, as well as compare characteristics in fistulas.

Patients referred with anal fistula who had an FC measurement and either ileocolonoscopy or colonoscopy within 12 weeks were included. Demographic and clinical characteristics were registered. Area under the curve (AUC) was calculated as well as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy.

A total of 63 patients were included (CD n = 31, 49%). FC was significantly higher in CD compared to cryptoglandular fistulas, even when CD was medically treated or had no luminal activity on endoscopy. FC ≥110 μg/g was significantly associated with CD (OR 12.5; 95% CI: 3.77-41.4) p < 0.0001. This was found by plotting a receiver operating characteristic (ROC) curve, with AUC 80.8 (95% CI: 0.6952-0.9217). Sensitivity and specificity were 0.76 and 0.80, respectively (PPV 76%, NPV 80% and accuracy 78%).

FC discriminates CD from cryptoglandular fistulas, even in medically treated CD with normal endoscopic findings.

Anal fistula is a common disease with recurrent inflammation and accumulated exudate. Traditional treatments often fail to effectively eliminate inflammation and ensure adequate drainage, leading to prolonged healing time and a high recurrence rate. Herein, a new class of quaternized molecular brush-grafted injectable microgel (denoted as GAA@CNT-g-PVBTMA) is developed through thermal polymerization and mechanical fragmentation to promote the healing process of anal fistula. Benefiting from the fragmented morphology with a porous structure, the microgel can effectively fill the fistula and facilitate the drainage of exudate. Owing to the electrostatic interactions between the positively charged quaternized carbon nanotube molecular brush (CNT-g-PVBTMA) and the negatively charged inflammatory cytokines, GAA@CNT-g-PVBTMA microgel exhibits excellent anti-inflammatory properties with scavenging rates of 92.6% for tumor necrosis factor-α (TNF-α) and 92.5% for interleukin-1β (IL-1β). Rat inflammatory anal fistula model demonstrates that the microgel can effectively reduce inflammation and epithelialization of the fistula, thereby promoting the healing of the anal fistula. By integrating effective filling, adequate drainage, and excellent anti-inflammatory properties, GAA@CNT-g-PVBTMA microgel provides a promising new direction for the treatment of anal fistula.

Intestinal mucus, a viscoelastic medium with mucin2 (MUC2) as its main component, covers the surface of intestinal epithelial cells and protects the intestine from invasion, forming the first barrier of the intestinal tract. Unlike the small intestine, where the mucus layer is a single layer, the colonic mucus layer can be divided into a sterile inner layer and an outer layer with bacterial colonization. Many of the substances in the mucus layer have beneficial effects on the intestinal epithelium, but the mucus layer is often affected by a variety of factors, mainly microbiological, dietary, and immunological. Inflammatory bowel disease (IBD) is a disease of increasing morbidity worldwide, with a complex etiology and a high relapse rate. In recent years, the mucus barrier in IBD has received increasing attention and is considered a key factor in the pathogenesis of IBD. Loss of goblet cells (GCs) and changes in the composition and properties of the mucus layer material are commonly found in the colon of IBD patients. Damage to the mucus layer may make it easier for microorganisms to access the intestinal epithelium and cause inflammation. There are currently a number of herbs and other therapies that can be used to treat IBD and repair the damaged mucus barrier. This review highlights the important role of the mucus layer in IBD and the therapies that target the mucus layer in IBD.

Empirical reviews suggested that cryptoglandular anal fistulas require surgical resolution. However, some reports have indicated the possibility of nonsurgical and conservative treatment, which is discussed in this review.

This review explores the potential of nonsurgical approaches for curing anal fistulas through bacterial inhibition and immunomodulation. The longstanding cryptoglandular theory has been a subject of controversy, prompting the reevaluation of conventional surgical interventions for anal fistulas. The review was conducted through database searches, including Medline, EMBASE, PubMed, and the Cochrane Library.

Emerging evidence suggests that targeting the anaerobic environments present in anal fistulas and perianal abscesses and eradicating bacteria and their by-products may be critical for successful treatment. Immunomodulatory strategies show promise as a potential avenue for the nonsurgical management of anal fistulas.

Ongoing developments in pharmacological research offer opportunities for alternative treatment options, shedding light on the prospects of noninvasive anal fistula management.

Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking.

To examine the usability of darvadstrocel therapy in managing perianal CD.

We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression.

Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported.

Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.

Perianal fistulas have posed a medical and surgical problem since ancient times. The plethora of surgical operations described nowadays for anal fistula treatment is real proof that there is no ideal therapeutic procedure. The cornerstone of all approaches is the equilibrium between the definitive treatment of the fistula with the maintenance of the anal continence mechanism, i.e., anal sphincters. Especially complex anal fistulas (multiple tracts, high transphincteric fistulas, rectovaginal and Crohn disease-associated anal fistulas) are difficult to deal with to preserve this therapeutic balance. Contemporary experimental procedures include the use of autologous biological products such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs), either in their "raw" matrix (stromal vascular fraction, SVF) or after isolation and cultivation before delivered to the patient. Herein, we present a new experimental procedure that we implemented for four patients with perianal fistulas, which is safe and effective, easily reproduced, and cheap. It is a one-stage procedure that requires only simple means and could serve as a first-line approach in complex anal fistulas. In this article, we will present four indicative cases treated with this method, using different syringes for various patient conditions, while analyzing the corresponding clinical and imaging results.

Crohn's disease (CD) is a chronic, complex inflammatory disorder of the gastrointestinal tract that presents significant therapeutic challenges. Despite the availability of a wide range of treatments, many patients experience primary non-response, secondary loss of response, or adverse events, limiting the overall effectiveness of current therapies. Clinical trials often report response rates below 60%, partly due to stringent inclusion criteria. Emerging therapies that target novel pathways offer promise in overcoming these limitations. This review explores the latest investigational drugs in phases I, II, and III clinical trials for treating both luminal and perianal CD. We highlight promising therapies that target known mechanisms, including selective Janus kinase inhibitors, anti-adhesion molecules, tumor necrosis factor inhibitors, and IL-23 selective inhibitors. In addition, we delve into novel therapeutic strategies such as sphingosine-1-phosphate receptor modulators, miR-124 upregulators, anti-fractalkine (CX3CL1), anti-TL1A, peroxisome proliferator-activated receptor gamma agonists, TGFBRI/ALK5 inhibitors, anti-CCR9 agents, and other innovative small molecules, as well as combination therapies. These emerging approaches, by addressing new pathways and mechanisms of action, have the potential to surpass the limitations of existing treatments and significantly improve CD management. However, the path to developing new therapies for inflammatory bowel disease (IBD) is fraught with challenges, including complex trial designs, ethical concerns regarding placebo use, recruitment difficulties, and escalating costs. The landscape of IBD clinical trials is shifting toward greater inclusivity, improved patient diversity, and innovative trial designs, such as adaptive and Bayesian approaches, to address these challenges. By overcoming these obstacles, the drug development pipeline can advance more effective, accessible, and timely treatments for CD.

Inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), are complex chronic inflammatory intestinal conditions with a multifaceted pathology, influenced by immune dysregulation and genetic susceptibility. The challenges in understanding IBD mechanisms and implementing precision medicine include deciphering the contributions of individual immune and non-immune cell populations, pinpointing specific dysregulated genes and pathways, developing predictive models for treatment response, and advancing molecular technologies. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to address these challenges, offering comprehensive transcriptome profiles of various cell types at the individual cell level in IBD patients, overcoming limitations of bulk RNA sequencing. Additionally, single-cell proteomics analysis, T-cell receptor repertoire analysis, and epigenetic profiling provide a comprehensive view of IBD pathogenesis and personalized therapy. This review summarizes significant advancements in single-cell sequencing technologies for enhancing our understanding of IBD, covering pathogenesis, diagnosis, treatment, and prognosis. Furthermore, we discuss the challenges that persist in the context of IBD research, including the need for longitudinal studies, integration of multiple single-cell and spatial transcriptomics technologies, and the potential of microbial single-cell RNA-seq to shed light on the role of the gut microbiome in IBD.

Perianal fistulising Crohn's disease (pfCD) is a distinct and debilitating phenotype seen in around one-third of patients with CD. Clinical trials in pfCD are increasingly using magnetic resonance imaging (MRI) criteria as a primary endpoint, but there is heterogeneity in the radiological definition of a healed perianal fistula that currently limits our ability to perform meaningful meta-analyses of studies. Our aim is to standardise outcomes through the generation of an international consensus definition of a radiologically healed fistula.

This international Delphi consensus study employs a two-part strategy.The first is a systematic review to identify a longlist of variables used to define radiological healing in pfCD. MRI-based indices used to score fistula severity and healing will be assessed for their methodological quality using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN). The systematic review protocol will be conducted using COSMIN methodology and reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses.The second part will be an online Delphi consensus, guided by the results of the systematic review. Radiologists, gastroenterologists and colorectal surgeons with expertise in the management of pfCD will be invited to take part in two to three rounds of online surveys. Once an a priori threshold of >80% agreement is reached on individual radiological components used to define 'healing' and 'healed', a final meeting of key stakeholders will be organised to generate a consensus definition of a healed fistula.

The study has been deemed exempt from a formal Research Ethics Committee review as no patients will participate directly in the consensus process, given the technical nature of the research question. The study is registered with the local R&D department (Reference RD24/007). Publication of this study will help standardise radiological endpoint measurement in clinical trials of pfCD and improve the synthesis and meta-analysis of comparative studies.

CRD42024504334.

Stem cell therapy in dogs has increased considerably in recent years; however, there are few publications on the treatment of perianal fistulas (PF) in this species. The aim of this open-label clinical trial was to demonstrate the efficacy and safety of a new protocol for the in situ administration of low-dose adipose-derived allogeneic stem cells (ASCs) for the treatment of refractory spontaneous perianal fistula. The methodology consisted of applying one to three doses of 5 × 106 cryopreserved allogeneic ASCs to each fistula. The study was performed in 14 dogs regardless of sex, breed, or age, with a clinical diagnosis of refractory PF. Cells diluted in phosphate-buffered saline were applied to five sites of the PF in an amount of 1 × 106 per application site. Efficacy was determined by the complete closure of the fistula, which was observed in 100% of the cases studied one month after therapy, with a subsequent follow-up of 12 to 48 months after therapy. Furthermore, safety was demonstrated by the absence of local or systemic adverse effects. In conclusion, the protocol used in this work demonstrates the efficacy without adverse effects of the in situ application of low doses of allogeneic ASCs, providing a simple, non-invasive, long-lasting and low-cost therapeutic option.

Crohn disease perianal fistulas are associated with considerable morbidity and impaired quality of life. Nurses who specialize in inflammatory bowel disease (IBD) play a vital role in the management of Crohn disease perianal fistulas from diagnosis to long-term care; however, there is little evidence available to inform Crohn associated perianal fistula management strategies for nurses. This narrative review aims to provide IBD nurses with an up-to-date overview of Crohn perianal fistulas. It discusses the vital role IBD nurses play within the multidisciplinary team; the physical, social, and psychological impacts of Crohn perianal fistulas on patients; available treatment options; and how IBD nurses can support patients in their perianal fistula journey to enable optimum outcomes for patients. It also reviews diagnostic techniques and IBD nurses' involvement in Crohn perianal fistula diagnosis. While this article is aimed at IBD nurses, it is relevant to all nurses irrespective of their role (unit, clinic, community, and stoma) who interact with patients with Crohn perianal fistulas because awareness of the signs and symptoms of this condition will enable timely referrals and diagnosis.

In this editorial we comment on the article by Pacheco et al published in a recent issue of the World Journal of Gastroenterology. We focus specifically on the burden of illness associated with perianal fistulizing Crohn's disease (PFCD) and the diagnostic and therapeutic challenges in the management of this condition. Evolving evidence has shifted the diagnostic framework for PFCD from anatomical classification systems, to one that is more nuanced and patient-focused to drive ongoing decision making. This editorial aims to reflect on these aspects to help clinicians face the challenge of PFCD in day-to-day clinical practice.

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.

Due to the high prevalence of posterior horseshoe anal fistula and causing numerous complications, this study aimed to investigate the clinical effect of radial incision combined with tunnel floating line drainage (RCTD) and arc incision internal drainage in the treatment of the disease and the influence on perianal flora.

Ninety-six subjects treated with high posterior horseshoe anal fistula were stochastically assigned to a joint group (RCTD), and control group (arc incision internal drainage). The operation-related conditions, complication rate, anal function, and recurrence rate of 6 months after operation were compared, and perianal secretions were collected before operation and 1 day after operation to detect the changes of microbial flora.

After operation, it was corroborated notable difference between joint group and control group in operation time, intraoperative blood loss, wound healing time, visual analogue scale score 6 hours after operation and phase I cure rate. Chi square test analysis showed notable difference between control group (27.08%) and joint group (10.40%) in incidence of complications, in terms of number of pathogens detected around anus, significantly smaller of the incremental change for the joint subgroup versus the control subgroup 1 day after operation.

RCTD can be the best choice for patients with high posterior horseshoe anal fistula. This operation method has the advantages of short operation time, less trauma, fewer complications, fast recovery of anal function, and can also reduce perianal pathogenic bacteria infection.

Crohn's disease (CD) has a progressive nature and commonly perianal involvement. The aim of this study is to assess the prevalence, surgical treatment, and outcome of perianal fistulizing CD with associated risk factors in a large Chinese cohort.

Hospitalized patients diagnosed with CD in our center were consecutively enrolled between January 2000 and December 2018. Transition of disease behavior was classified according to the presence or absence of penetrating behavior (B3 in the Montreal classification) at diagnosis and at a median follow-up of 102 months.

A total of 504 patients were included, of whom 207 (41.1%) were classified as B3 and 348 (69.0%) as L2/3 at follow-up. Transition of behavior to B3 was observed in 86 patients (17.1%). The incidence of perianal fistulizing lesions was 10.9% at 10 years with a final prevalence of 27.0% (n = 136) at the end of follow-up. Multivariate Cox regression identified independent risks of perianal fistulizing lesions for persistent B3 (hazard ratio, 4.72; 95% confidence interval, 1.91-11.66) and behavior transition of progressed to B3 (hazard ratio, 9.90; 95% confidence interval, 4.60-21.33). Perianal surgical treatments were performed in 104 patients (20.6%). Thirty-six cases (7.1%) were refractory, and it is independently associated with behavior of persistent B3 (P= 0.011).

Perianal fistulizing lesions occurred frequently in Chinese CD patients. Its incidence and refractory outcome were closely associated with the penetrating CD behavior. An additional risk of perianal fistulizing lesions was indicated for CD patients with behavior of progressing to B3, suggesting further attention.

Precise prediction of the occurrence of complicated perianal abscesses (PAs) in monkeypox (mpox)-infected patients is important for therapeutic optimization. This study sought to identify risk factors of complicated PA.

A total of 48 patients with mpox infection (PA group, n = 10; non-PA (NPA) group, n = 38) were enrolled in our study, who were hospitalized in Hangzhou Xixi Hospital, China from 29 June to 3 September 2023. The data of demographic characteristics, and clinical symptoms, serum SAA, PCT, CRP, and IL-6 levels were collected by the Electronic Medical Record. The diagnostic values of these biomarkers were assessed using multivariate logistic regression and ROC curve analyses.

A decrease in serum IL-6, SAA, and CRP levels (all p-value < 0.05), but not PCT, was observed in all mpox-infected patients. A significant positive correlation was also noted between IL-6, SAA, CRP, and PCT levels (all p-value < 0.05). There was a significant increase in IL-6 and SAA levels and the SAA/CRP ratio in serum samples from patients in the PA group. Multivariate logistic regression and ROC curve analyses identified that the combined use of perianal symptoms and SAA was more sensitive than perianal symptoms or SAA alone as predictors of complicated PA. This combination had the highest predictive value for disease progression, with an AUC of 0.920 (p-value < 0.001).

The combination of perianal symptoms and SAA levels was strongly linked to the occurrence of complicated PA in mpox-infected patients. These findings may inform the early diagnosis of this patient population.

Perianal fistuliing Crohn's disease [PFCD] is an aggressive phenotype of Crohn's disease defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by the TOpCLASS consortium, which seeks to unify disease severity with patient-centred goals but has not yet been validated. We aimed to apply this to a real-world cohort and to identify factors that predict transition between classes over time.

We identified all patients with PFCD and at least one baseline and one follow-up pelvic MRI [pMRI]. TOpCLASS classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs.

We identified 100 patients with PFCD, of whom 96 were assigned TOpCLASS Classes 1-2c at baseline. Most patients [78.1%] started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex [72.0%, 46.6%, 40.0%, p = 0.03] and prior perianal surgery [52.0% vs 44.6% vs 40.0%, p = 0.02] were more frequently observed in those with improved class compared to unchanged and worsened class. Baseline pMRI indices were not associated with changes in classification; however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modelling identified only male sex [-0.31, 95% CI -0.60 to -0.02] with improvement in class.

The TOpCLASS classification highlights the dynamic nature of PFCD over time. However, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower TOpCLASS classification.

Penetrating Crohn's disease (CD) often necessitates surgical intervention, with the open approach traditionally favored. Robotic-assisted surgery offers potential benefits but remains understudied in this complex patient population. Additionally, the lack of standardized surgical complexity scoring in CD hinders research and comparisons.

We retrospectively analyzed adult patients with penetrating CD who underwent either robotic-assisted ileocolic resection (RICR) or open ileocolic resection (OICR) at our institution from January 2007 to December 2021. We assessed endpoints, including length of stay, complications, readmissions, reoperations, and other perioperative outcomes.

RICR demonstrated safety outcomes comparable to OICR. Importantly, RICR patients experienced significantly reduced estimated blood loss (p < 0.0001), shorter hospital stays (median 4.5 days versus 6.9 days; p = 0.01), lower surgical site infection rates (0% versus 15.4%; p = 0.01), and decreased 30-day readmission rates (0% versus 15.4%; p = 0.01). Linear regression analysis revealed the need for additional strictureplasties (coefficient: 84.8; p = 0.008), colonic resections (coefficient: 41.7; p = 0.008), and estimated blood loss (coefficient: 0.07; p = 0.002) independently correlated with longer operative times).

Robotic-assisted surgery appears to be a safe and potentially beneficial alternative for the surgical management of penetrating CD, offering advantages in perioperative outcomes reducing length of stay, blood loss, surgical site infection rates, and readmission rates. Further validation with larger cohorts is warranted.

The optimal treatment of perianal fistulizing Crohn's disease [PFCD] is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-tumour necrosis factor [anti-TNF] therapy [combined therapy] vs either therapy alone.

MEDLINE, EMBASE, and Cochrane databases were searched systematically up to end December 2023. Surgical intervention was defined as an exam under anaesthesia ± setons. We calculated weighted risk ratios [RRs] with 95% confidence intervals [CIs] for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively.

Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention, and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response [RR 1.10; 95% CI 0.93-1.30, p = 0.28] and healing [RR 1.06; 95% CI 0.86-1.31, p = 0.58] was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response [RR 1.25; 95% CI 1.10-1.41, p < 0.001] and healing [RR 1.17; 95% CI 1.00-1.36, p = 0.05] compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures.

Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings.

Complicated perianal disease (cPD) may be the sole presentation of Crohn's disease (CD). The role of small-bowel capsule endoscopy (SBCE) in the diagnostic algorithm of cPD is unclear. We aimed to evaluate the role of SBCE as a diagnostic tool, in patients with cPD, after a negative standard workup for CD.

A multicenter, retrospective, cross-sectional study, in patients with cPD, and negative standard workup for CD (ileocolonoscopy and cross-sectional imaging), who underwent SBCE for suspected CD. Demographics, biomarkers, and the Lewis Score (LS) were recorded and analyzed. An LS ≥ 135 was considered a positive SBCE for diagnosing CD.

Ninety-one patients were included: 65 (71.4%) males; median age: 37 (29-51) years; cPD duration: 25.1 (12.5-66.1) months. Positive SBCE: 24/91 (26.4%) patients. Fecal calprotectin (FC) positively correlated with LS (r = 0.81; p < 0.001). FC levels of 100 µg/g and 50 µg/g had a sensitivity of only 40% and 55% to rule out small-bowel CD, with a negative predictive value (NPV) of only 76% and 80%, respectively.

SBCE contributed to CD diagnosis in a quarter of patients with cPD after a negative standard workup. FC levels correlated with the degree of inflammation defined by the LS. However, the NPV of FC was low, suggesting that SBCE should be considered for patients with cPD even after a negative standard workup.

Defining histological variables that make it possible to establish the activity of Crohn's disease (CD) and predict the patients who may present a higher risk of clinical complications and surgical interventions could lead to timely adjustments in medical therapy and elective surgeries that represent a lower risk of complications. The purpose of the study is to determine the relation between the histopathological findings using the Naini and Cortina (N&C) score, the clinical severity, and the indication for surgery in a group of patients with CD.

Descriptive, retrospective, cross-sectional study of 44 patients diagnosed with CD, treated at the San Vicente Fundación University Hospital in Medellín, Colombia, between 2010 and 2022.

Of the 44 patients, 36 ileum samples and 34 colon samples were obtained. Of the patients with inflammatory behavior, 87.5% did not have surgical intervention (P=.022), a value that remained significant in the ileum subgroup (P=.0058). 91.3% of the patients with ileal involvement did not develop perianal disease (P=.01). Granulomas only occurred in two patients with a colon sample (5.8%). In the histological score of N&C both in the ileum and in the colon, no statistically significant differences were obtained in relation to the surgical outcome (P=.34 and P=.054, respectively).

The histological index of N&C was not a predictor in Crohn's disease (CD) related to the surgical outcome.