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1.
Stem Cell Res Ther ; 15(1): 140, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745184

RESUMO

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .


Assuntos
Doença de Crohn , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fístula Retal , Humanos , Doença de Crohn/complicações , Doença de Crohn/terapia , Masculino , Adulto , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Fístula Retal/terapia , Fístula Retal/etiologia , Células-Tronco Mesenquimais/citologia , Adulto Jovem , Transplante Homólogo/métodos , Adolescente , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Resultado do Tratamento , Qualidade de Vida
2.
Tunis Med ; 102(4): 181-188, 2024 Apr 05.
Artigo em Francês | MEDLINE | ID: mdl-38746955

RESUMO

INTRODUCTION: Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab. AIM: Update on the different therapeutic alternatives for anal fistula in Crohn's disease after failure of Infliximab. METHODS: A research in the medical literature on PubMed and Google Scholar was carried out. We included cohort studies, reviews and randomized double-blinded therapeutic trials. Case reports and fundamental research studies have been excluded. RESULTS: Anti-TNF therapy, notably Infliximab remain the therapeutic option of choice. Since Infliximab efficacy has been estimated at 60%, with a significant loss-of response rate, new therapeutic strategies have been evaluated and may offer new opportunities for the management of anal fistulas: for example, Ustekinumab could be effective after failure of anti-TNF therapy, although further studies are required. Recent guidelines suggest that injection of mesenchymal stem cells is an effective and safe treatment for complex fistulas. Other surgical options have been proposed, such as endorectal advancement flap, fibrin glue injection, anal fistula plug and ligation of the intersphincteric fistula tract, but all with limited and debatable efficacy. Given the failure rate of all these options, new strategies are currently being evaluated. CONCLUSION: Anal fistulas in Crohn's disease are a real therapeutic challenge. New medical and surgical therapies are currently being evaluated, with promising results.


Assuntos
Doença de Crohn , Fármacos Gastrointestinais , Infliximab , Fístula Retal , Falha de Tratamento , Humanos , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Fístula Retal/etiologia , Fístula Retal/tratamento farmacológico , Fístula Retal/terapia , Infliximab/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/administração & dosagem
3.
Nihon Yakurigaku Zasshi ; 159(3): 150-155, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38692877

RESUMO

Crohn's disease (CD) is a chronic and relapsing inflammatory bowel disease affecting the entire gastrointestinal tract. The prevalence of CD among Japanese people is increasing. One of the most frequent complications of CD is perianal fistulas. People living with CD may experience complex perianal fistulas, which can cause intense pain, bleeding, swelling, infection, and anal discharge. Despite medical and surgical advancements, complex perianal fistulas in CD remain challenging for clinicians to treat. CD patients living with perianal fistulas reported a negative impact on many aspects of their quality of life. Darvadstrocel is a cell therapy product containing a suspension of allogeneic expanded adipose-derived mesenchymal stem cells. It has been approved in Europe and Japan for the treatment of complex perianal fistulas that have shown an inadequate response to at least one conventional or biologic therapy in adult patients with non-active/mildly active luminal CD. By exhibiting immunomodulatory and local anti-inflammatory effects at the site of inflammation, it offers a new treatment option for complex perianal fistulas in CD patients. In this manuscript, the characteristic of darvadstrocel, the summary of results from the pivotal phase 3 studies in Europe and Japan, and the development strategy in Japan were introduced.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Mesenquimais , Fístula Retal , Doença de Crohn/terapia , Doença de Crohn/complicações , Humanos , Fístula Retal/terapia , Fístula Retal/etiologia , Japão , Células-Tronco Mesenquimais , Tecido Adiposo
4.
Surg Clin North Am ; 104(3): 491-501, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38677815

RESUMO

Anal suppurative processes are commonly encountered in surgical practice. While the initial therapeutic intervention is philosophically straightforward (incision and drainage), drainage of the appropriate space and treatment of the subsequent fistula in ano require a thorough understanding of perianal anatomy and nuanced decision making. Balancing the risk of fecal incontinence with simple fistulotomy versus the higher risk of fistula recurrence with all sphincter-sparing fistula treatments can be a challenge for surgeons and patients alike.


Assuntos
Canal Anal , Fístula Retal , Humanos , Fístula Retal/cirurgia , Fístula Retal/terapia , Canal Anal/cirurgia , Drenagem/métodos , Medicina Baseada em Evidências
5.
Indian J Gastroenterol ; 43(1): 48-63, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38308773

RESUMO

Crohn's disease (CD), a chronic inflammatory bowel disorder, manifests in various phenotypes, with fistulizing perianal CD (CD-PAF) being one of its most severe phenotypes. Characterized by fistula formation and abscesses, CD-PAF impacts 17% to 34% of all CD cases and with a significantly deleterious impact on patient's quality of life, while increasing the risk for anorectal cancers. The pathogenesis involves a complex interplay of genetic, immunological and environmental factors, with cytokines such as tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) playing pivotal roles. Diagnostic protocols require a multi-disciplinary approach including colonoscopy, examination under anesthesia and magnetic resonance imaging. In terms of treatment, biologics alone often prove inadequate, making surgical interventions such as setons and fistula surgeries essential. Emerging therapies such as mesenchymal stem cells are under study. The South Asian context adds layers of complexity, including diagnostic ambiguities related to high tuberculosis prevalence, healthcare access limitations and cultural stigma toward perianal Crohn's disease and ostomy surgery. Effective management necessitates an integrated, multi-disciplinary approach, especially in resource-constrained settings. Despite advances, there remain significant gaps in understanding the disease's pathophysiology and a dearth of standardized outcome measures, underscoring the urgent need for comprehensive research.


Assuntos
Doença de Crohn , Fístula Retal , Humanos , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Fístula Retal/terapia , Qualidade de Vida , Fator de Necrose Tumoral alfa , Citocinas , Resultado do Tratamento
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(1): 42-47, 2024 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-38269458

RESUMO

OBJECTIVES: To investigate the clinical characteristics, treatment, and prognosis of children with perianal fistulizing Crohn's disease (pfCD). METHODS: A retrospective analysis was conducted on the children, aged 6-17 years, who were diagnosed with Crohn's disease (CD) from April 2015 to April 2023. According to the presence or absence of perianal fistulizing lesions, they were divided into two groups: pfCD (n=60) and non-pfCD (n=82). The two groups were compared in terms of clinical characteristics, treatment, and prognosis. RESULTS: The incidence of pfCD was 42.3% (60/142). The proportion of males in the pfCD group was higher than that in the non-pfCD group. Compared with the non-pfCD group, the pfCD group had a significantly higher proportion of children with involvement of the colon and small intestine or those with upper gastrointestinal lesions (P<0.05). Compared with the non-pfCD group, the pfCD group had a significantly higher rate of use of infliximab during both induction and maintenance treatment (P<0.05). In the pfCD group, the children with complex anal fistula accounted for 62% (37/60), among whom the children receiving non-cutting suspended line drainage accounted for 62% (23/37), which was significantly higher than the proportion among the children with simple anal fistula patients (4%, 1/23) (P<0.05). There were no significant differences between the two groups in mucosal healing rate and clinical remission rate at week 54 of treatment (P>0.05). The pfCD group achieved a fistula healing rate of 57% (34/60) at week 54, and the children with simple anal fistula had a significantly higher rate than those with complex anal fistula (P<0.05). CONCLUSIONS: There is a high incidence rate of pfCD in children with CD, and among the children with pfCD, there is a high proportion of children with the use of biological agents. There is a high proportion of children receiving non-cutting suspended line drainage among the children with complex anal fistula. The occurrence of pfCD should be closely monitored during the follow-up in children with CD.


Assuntos
Doença de Crohn , Fístula Retal , Criança , Masculino , Humanos , Doença de Crohn/complicações , Estudos Retrospectivos , Prognóstico , Infliximab/uso terapêutico , Fístula Retal/etiologia , Fístula Retal/terapia
7.
Surgery ; 175(2): 242-249, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37661485

RESUMO

BACKGROUND: Crohn-related rectovaginal fistulas are notoriously difficult to treat. Studies of mesenchymal stem cells for the treatment of perianal Crohn fistulizing disease have largely excluded rectovaginal fistulas. The aim of this study was to determine the safety and efficacy of mesenchymal stem cells for refractory rectovaginal fistulizing Crohn disease. METHODS: A phase IB/IIA randomized control trial was performed in a 3:1, single-blinded study. Patients included were adult women with an anovaginal/rectovaginal fistula in the setting of Crohn disease. Seventy-five million mesenchymal stem cells were administered with a 22G needle after curettage and primary closure of the fistula tract at day 0 and month 3. Adverse and serious adverse events were recorded at post-procedure day 1, week 2, week 6, month 3, month 6, and month 12, along with clinical healing, magnetic resonance imaging, and patient-reported outcomes. RESULTS: A total of 19 patients were enrolled and treated-15 treatment and 4 control. There were no adverse or serious adverse events related to mesenchymal stem cell therapy. At 6 months, 50% of the treatment group and 0% of the control had complete clinical and radiographic healing; 91.7% of the treatment group had improvement at 6 months with only one patient having a lack of response, whereas only 50% of the control group had improvement at 6 months. CONCLUSION: Bone marrow-derived mesenchymal stem cells offer a safe alternative treatment approach for rectovaginal fistulas in the setting of Crohn disease. Complete healing was achieved in half of the patients.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Fístula Retal , Adulto , Humanos , Feminino , Doença de Crohn/complicações , Doença de Crohn/terapia , Fístula Retovaginal/etiologia , Fístula Retovaginal/cirurgia , Medula Óssea , Fístula Retal/etiologia , Fístula Retal/terapia , Resultado do Tratamento
9.
Acta Chir Belg ; 124(2): 143-146, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37668063

RESUMO

Crohn's disease patients frequently develop perianal fistulas during their life. They are also at higher risk to develop cancers. Rarely, those cancers appear within a prior chronic fistula. The main types are adenocarcinoma mostly mucinous and squamous cell carcinoma. They are generally discovered at an advanced stage with a poor prognosis because symptoms are generally the same as those of the fistula itself. Regular follow-up of chronic fistulas is then important for an early diagnosis as well as histological analysis of the fistula during surgery. There is no consensus on the ideal treatment but abdominoperineal resection is the corner stone with or without neo or adjuvant chemo-radiotherapy. This paper presents a rare case of mucinous adenocarcinoma in a chronic perianal fistula in a Crohn's disease female and provides a review of the literature.


Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma , Carcinoma de Células Escamosas , Doença de Crohn , Fístula Retal , Humanos , Feminino , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Fístula Retal/diagnóstico , Fístula Retal/etiologia , Fístula Retal/terapia , Adenocarcinoma/etiologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/cirurgia
11.
Surgery ; 175(4): 984-990, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38097485

RESUMO

BACKGROUND: Mesenchymal stem cells have been administered via direct injection to treat perianal Crohn's fistulizing disease. We herein sought to determine the safety and durability of treatment response to 12 months with 3 individual phase IB/IIA clinical trials of mesenchymal stem cells for refractory perianal, rectovaginal, and ileal pouch fistulas in the setting of Crohn disease. METHODS: Three phase IB/IIA randomized placebo-controlled single-blinded clinical trials were performed for (1) perianal fistulas, (2) rectovaginal fistula, and (3) ileal pouch in situ with anovaginal and/or perianal fistulas. Bone marrow-derived mesenchymal stem cells (75 million in 7.5 mL) were injected at the time of exam under anesthesia on day 0 and month 3. Outcome measures were adverse events and combined clinical and pelvic magnetic resonance imaging healing at month 6 and month 12. RESULTS: Across all 3 trials, 64 patients were enrolled; 49 were treatment and 15 were control. At 6 months, combined clinical and radiographic healing was achieved in 83.3%, 33.3%, and 30.8% of the perianal, rectovaginal, and pouch fistula treatment cohorts, respectively. At 12 months, the treatment response was durable, with 67.7% of perianal, 37.5% of rectovaginal, and 46.2% of peripouch fistulas maintaining complete clinical and radiographic healing. Two patients in the perianal fistula control cohort achieved combined clinical and radiographic healing at 12 months, whereas 0% of rectovaginal and pouch control patients healed. CONCLUSION: Bone marrow-derived mesenchymal stem cells offer a safe and effective alternative treatment approach for severe perianal, rectovaginal, and peripouch fistulizing Crohn's disease. Treatment results are durable at 12 months.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Fístula Retal , Feminino , Humanos , Doença de Crohn/complicações , Doença de Crohn/terapia , Medula Óssea , Resultado do Tratamento , Fístula Retal/etiologia , Fístula Retal/terapia
12.
EBioMedicine ; 98: 104879, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38042747

RESUMO

BACKGROUND: Local fistula injection of mesenchymal stromal/stem cells (MSC) is effective for complex perianal Crohn's fistulas but is also expensive and requires specialised facilities for cell revival before administration. Human amnion epithelial cells (hAEC) are non-MSC cells with therapeutic properties. The primary aim of this study was safety of hAEC therapy. Secondary aims included hAEC efficacy, feasibility of the protocol and impact on quality of life. METHODS: A phase I open label study of ten adults with active complex Crohn's perianal fistulas refractory to conventional treatment, including anti-tumour necrosis factor alpha therapy, was undertaken. A single dose of hAEC was injected into the fistula tract(s) after surgical closure of the internal opening(s). Study outcomes were assessed at week 24 with follow up for at least 52 weeks. FINDINGS: Local injection of hAEC was safe, well tolerated and the injection procedure was feasible. Complete response occurred in 4 patients, and a partial response in an additional 4 patients. There was a mean reduction in the Perianal Disease Activity Index of 6.5 points (95% CI -9.0 to -4.0, p = 0.0002, paired t-test), modified Van Assche MRI Index of 2.3 points (95% CI -3.9 to -0.6, p = 0.012, paired t-test) and a mean improvement of 15.8 points (95% CI 4.9 to 26.8, p = 0.010, paired t-test) in quality of life using the Short IBD-Questionnaire in complete responders. INTERPRETATION: Local injection of hAEC therapy for refractory complex perianal fistulising Crohn's disease appears safe, well-tolerated, feasible and demonstrated improvement. Quality of life is improved in those who achieve complete fistula healing. FUNDING: This study was funded by competitive research grant funding from the Gastroenterological Society of Australia Seed Grant 2018.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Fístula Retal , Adulto , Humanos , Âmnio , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Células Epiteliais , Seguimentos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Qualidade de Vida , Fístula Retal/terapia , Fístula Retal/tratamento farmacológico , Resultado do Tratamento
13.
Stem Cell Res Ther ; 14(1): 375, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110978

RESUMO

The meta-analysis by Wang et al. (Stem Cell Res Ther 14(1):103, 2023) aims to explore whether mesenchymal stem cells are effective for perianal fistulas. The authors indicated that the difference in cell types, cell sources and cell dosages did not influence mesenchymal stem cells' efficacy, which may not be accurate. I think that local treatment with higher dosages of mesenchymal stem cells seems to not result in a higher healing rate. And, future trials should focus on donor characteristics considering past medical history of further autoimmunity, timely and cost-effective treatment to lighten the optimized therapeutic goals. In the future, it will be interesting to assess the safety and feasibility of injection of fibrin glue combined with mesenchymal stem cells in perianal fistulas.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fístula Retal , Humanos , Fístula Retal/terapia , Doença de Crohn/terapia , Adesivo Tecidual de Fibrina/uso terapêutico , Resultado do Tratamento
14.
Arq Gastroenterol ; 60(4): 490-524, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38018554

RESUMO

BACKGROUND: Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome. OBJECTIVE: Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients. METHODS: This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. RESULTS: Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men. CONCLUSION: This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.


Assuntos
Doença de Crohn , Fístula Retal , Criança , Humanos , Masculino , Feminino , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Estudos Retrospectivos , Estudos Prospectivos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fístula Retal/etiologia , Fístula Retal/terapia , Resultado do Tratamento , Infliximab/uso terapêutico
15.
Expert Opin Biol Ther ; 23(12): 1197-1202, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37992074

RESUMO

INTRODUCTION: This study provides an overview of the development of the first drug authorized for use in cell therapy. AREAS COVERED: We analyze the case of darvadstrocel, an example of a successful cell-therapy drug used worldwide to treat Crohn's perianal fistula. A bibliographic-historical analysis of the first cellular treatment approved by the EMA, including relevant aspects concerning the authors, who were involved in the whole process. We would like to highlight the following messages: Development: The article describes the development process of the drug, from initial concept through the clinical trial phases. Learning from failure: In describing the development of darvadstrocel, the authors highlight the importance of learning from failures, which is crucial to achieving successful outcomes. Collaboration: The article underscores the need for collaboration between public and private institutions to facilitate the advancement of cell-therapy drugs and ensure efficiency while adhering to regulatory guidelines. EXPERT OPINION: Regulatory requirements play a crucial role in the design and development of advanced therapies such as cell-therapy drugs. The findings of this study underscore the significance of appropriate disease application, meticulous donor selection, robust manufacturing processes, and proper therapy administration. Only by adopting these measures can cell-therapy drugs successfully complete all phases of the clinical trial process.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fístula Retal , Humanos , Resultado do Tratamento , Fístula Retal/terapia , Doença de Crohn/terapia
16.
Colorectal Dis ; 25(11): 2170-2176, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37849054

RESUMO

AIM: The aim of this study was to evaluate the real-life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn's disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical-radiological response (deep remission). METHODS: After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow-up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response. RESULTS: A total of 43 patients were included (M/F: 22/21, median age 37 [26-45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow-up of 383 (359-505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn's disease <3 years was significantly associated with deep remission (OD 4.5 [1.0-19.1], p = 0.04). CONCLUSION: Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn's disease was associated with deep remission.


Assuntos
Doença de Crohn , Fístula Retal , Humanos , Adulto , Doença de Crohn/complicações , Doença de Crohn/terapia , Doença de Crohn/diagnóstico , Resultado do Tratamento , Terapia Combinada , Fístula Retal/etiologia , Fístula Retal/terapia , Células-Tronco , Imunossupressores/uso terapêutico
17.
Sci Rep ; 13(1): 18416, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891236

RESUMO

Natural course of perianal abscess (PA) in infancy remains obscure. This study aimed to investigate the natural course of infants with PA after conservative treatment. A retrospective cohort study was conducted in infants with PA who were treated conservatively (due to the parents' refusal of surgery), for more than 2 months between 2014 and 2020 at a single tertiary center. 153 patients (149 boys and 4 girls) were identified. The median follow-up was 5.3 years (range 3-8.2 years). Initially, 119 patients (77.8%) were completely cured by conservative treatment, and 34 (22.2%) failed. Among the 34 patients, 23 continued conservative treatment (20 cure, 3 fistula formation) and 11 underwent surgery. After conservative treatment, the rate of fistula formation, abscess recurrence, and new-onset abscess were 15.0%, 4.6%, and 6.5%, respectively. Overall, 139 patients (90.8%) were cured conservatively without surgery, and 11 (7.2%) underwent surgical management. In addition, 3 (2.0%) patients developed fistula-in-ano (under observation). PA in infants may be a time-limited and self-limited condition. Conservative management should be the first choice of treatment in most cases. Longer periods of conservative treatment may achieve better clinical outcomes in selected cases. There will be a percentage of patients (about 10%) that would require surgical treatment.


Assuntos
Doenças do Ânus , Fístula Retal , Masculino , Feminino , Humanos , Lactente , Estudos Retrospectivos , Abscesso/terapia , Resultado do Tratamento , Drenagem , Doenças do Ânus/terapia , Fístula Retal/terapia
18.
Stem Cell Res Ther ; 14(1): 311, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37904247

RESUMO

OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of allogeneic umbilical cord-derived mesenchymal stem cells (TH-SC01) for complex perianal fistula in patients with Crohn's disease (CD). METHODS: This was an open-label, single-arm clinical trial conducted at Jinling Hospital. Adult patients with complex treatment-refractory CD perianal fistulas (pfCD) were enrolled and received a single intralesional injection of 120 million TH-SC01 cells. Combined remission was defined as an absence of suppuration through an external orifice, complete re-epithelization, and absence of collections larger than 2 cm measured by magnetic resonance imaging (MRI) at 24 weeks after cell administration. RESULTS: A total of 10 patients were enrolled. Six patients (60.0%) achieved combined remission at 24 weeks. The number of draining fistulas decreased in 9 (90.0%) and 7 (70.0%) patients at weeks 12 and 24, respectively. Significant improvement in Perianal Crohn Disease Activity Index, Pelvic MRI-Based Score, Crohn Disease Activity Index, and quality of life score were observed at 24 weeks. No serious adverse events occurred. The probability of remaining recurrence-free was 70% at week 52. CONCLUSION: The study demonstrated that local injection of TH-SC01 cells might be an effective and safe treatment for complex treatment-refractory pfCD after conventional and/or biological treatments fail (ClinicalTrials.gov ID, NCT04939337). TRIAL REGISTRATION: The study was retrospectively registered on www. CLINICALTRIALS: gov (NCT04939337) on June 25, 2021.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Fístula Retal , Adulto , Humanos , Doença de Crohn/terapia , Projetos Piloto , Qualidade de Vida , Fístula Retal/terapia , Resultado do Tratamento
19.
Rev Prat ; 73(3): 289-295, 2023 Mar.
Artigo em Francês | MEDLINE | ID: mdl-37289118

RESUMO

MANAGEMENT OF SECONDARY LESIONS IN ANO-PERINEAL CROHN'S DISEASE. Anoperineal involvement in Crohn's disease is common and affects around 1/3 of patients during their disease. It constitutes a pejorative factor with an increased risk of permanent colostomy and proctectomy and is associated with a major deterioration in quality of life. Secondary anal lesions in Crohn's disease are fistulas and abscesses. They are difficult to treat and often recurrent. A multidisciplinary medico-surgical management in several stages is essential. The classic sequence is based on a first phase of drainage of fistulas and abscesses, a second phase of medical treatment based primarily on anti-TNF alpha and finally a third phase of surgical closure of the fistula tract(s). Conventional closure techniques such as biologic glue, plug, advancement flap and intersphincteric ligation of the fistula tract have limited effectiveness, are not always feasible, require technical skills and some have an impact on anal continence. In recent years, we have witnessed a real enthusiasm generated by the arrival of cell therapy. This has not spared proctology since adipose-derived allogeneic mesenchymal stem cells have had Marketing Authorisation and have been reimbursed in France since 2020 in the treatment of complex anal fistulas in Crohn's disease after failure of at least one biologic therapy. This new treatment offers an additional alternative in patients often in a situation of therapeutic impasse. Preliminary results in real life are satisfactory with a good safety profile. However, it will be necessary to confirm these results in the longer term and to work to determine the profile of the patients who could benefit the most from this expensive therapy.


PRISE EN CHARGE DES LÉSIONS SECONDAIRES DE LA MALADIE DE CROHN ANOPÉRINÉALE. L'atteinte anopérinéale de la maladie de Crohn est fréquente ; elle affecte environ un tiers des patients durant leur maladie. Elle constitue un facteur péjoratif responsable d'une majoration du risque de colostomie définitive et de proctectomie, et est associée à une altération majeure de la qualité de vie. Les lésions anales secondaires de la maladie de Crohn sont des fistules et des abcès. Elles sont difficiles à traiter et souvent récidivantes. Une prise en charge multidisciplinaire médico-chirurgicale en plusieurs étapes s'impose. La séquence classique se fonde sur une phase de drainage des fistules et des abcès, une phase de traitement médical fondé en priorité sur les anti-TNF alpha et enfin une phase de fermeture chirurgicale du (ou des) trajet(s) fistuleux. Les techniques de fermeture classiques comme la colle biologique, le plug, le lambeau d'avancement et la ligature intersphinctérienne du trajet fistuleux ont une efficacité limitée, ne sont pas toujours réalisables, nécessitent des compétences techniques et ont, pour certaines, un impact sur la continence anale. Ces dernières années, l'arrivée de la thérapie cellulaire suscite un véritable enthousiasme. Cet engouement n'a pas épargné la proctologie, puisque les cellules souches mésenchymateuses (CSM) allogéniques d'origine adipocytaires ont obtenu une autorisation de mise sur le marché (AMM), sont commercialisées et remboursées en France depuis 2020 dans le traitement des fistules anales complexes de la maladie de Crohn en échec d'au moins une biothérapie. Cette thérapie offre une alternative supplémentaire à des patients souvent en situation d'impasse thérapeutique. Les résultats préliminaires en vraie vie sont satisfaisants, avec un bon profil d'innocuité. Toutefois, il faudra confirmer ces résultats à plus long terme et travailler à identifier le profil des patients qui pourraient bénéficier au mieux de cette thérapie onéreuse.


Assuntos
Doença de Crohn , Fístula Retal , Humanos , Doença de Crohn/complicações , Doença de Crohn/terapia , Qualidade de Vida , Abscesso/terapia , Abscesso/complicações , Inibidores do Fator de Necrose Tumoral , Fístula Retal/etiologia , Fístula Retal/terapia , Resultado do Tratamento
20.
Inflamm Bowel Dis ; 29(12): 1912-1919, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37263018

RESUMO

BACKGROUND: Perianal fistulizing Crohn's disease is notoriously difficult to treat. Recent studies of mesenchymal stem cells have demonstrated safety and efficacy of this novel treatment approach. However, no studies to date have included pediatric patients. We sought to determine safety and efficacy of mesenchymal stem cells for pediatric perianal fistulizing Crohn's disease. METHODS: This was a phase I clinical trial to evaluate safety and feasibility of mesenchymal stem cells in pediatric perianal Crohn's patients 13 to 17 years of age. At the time of an exam under anesthesia, following curettage of the fistula tract and closure of the internal opening with absorbable suture, 75 million mesenchymal stem cells were administered with a 22-gauge needle. This was repeated at 3 months if complete clinical and radiographic healing were not achieved. Adverse and serious adverse events at were measured at postprocedure day 1, week 2, week 6, month 3, month 6, and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient-reported outcomes were measured at the same time points. RESULTS: Seven pediatric patients were enrolled and treated (6 male; median age of 16.7 years). There were no adverse or serious adverse events related to the investigational product or injection procedure. At 6 months, 83% had complete clinical and radiographic healing. The perianal Crohn's Disease Activity Index, Wexner incontinence score, and Van Assche score had all decreased at 6 months. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells offer a safe, and likely effective, treatment approach for pediatric perianal fistulizing Crohn's disease.


Assuntos
Doença de Crohn , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Fístula Retal , Humanos , Masculino , Criança , Adolescente , Doença de Crohn/complicações , Doença de Crohn/terapia , Medula Óssea , Fístula Retal/terapia , Fístula Retal/tratamento farmacológico , Resultado do Tratamento
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