BACKGROUND: 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. AIMS: To examine the usability of darvadstrocel therapy in managing perianal CD. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
- Klíčová slova
- Crohn's disease, darvadstrocel, mesenchymal stem cell treatment, perianal disease,
- MeSH
- Crohnova nemoc * terapie komplikace MeSH
- dospělí MeSH
- indukce remise MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- rektální píštěl * terapie etiologie MeSH
- retrospektivní studie MeSH
- spokojenost pacientů MeSH
- transplantace mezenchymálních kmenových buněk * metody škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Following approval of darvadstrocel, the INSPIRE registry is being conducted in order to evaluate long-term safety and effectiveness of the drug on a large, heterogenous population.An online expert meeting was held from March 20 to March 30, 2023, which provided relevant insights into the decision-making process regarding seton use and obtained feedback on the first experiences with darvadstrocel. The aim of this article is to present the perspectives from gastroenterologists and colorectal surgeons practicing in Czechia, Hungary, Israel, Lithuania, Serbia, and Slovenia in topics such as diagnosis and treatment options for patients with complex Crohn's perianal fistulas (CPF), specifically focusing on the use of setons and darvadstrocel.During this virtual session, unavailability of comprehensive data on safety and efficacy of available treatment procedures was emphasized as an important obstacle towards development of standardized recommendations and improvement of outcomes in treatment of (CPF). Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition.
- Klíčová slova
- Crohn's Disease, Darvadstrocel Therapy, Long-term Safety Evaluation, Multidisciplinary Management, Perianal Fistulas, Surgical Procedures, Treatment Challenges,
- Publikační typ
- časopisecké články MeSH
- MeSH
- Crohnova nemoc komplikace farmakoterapie chirurgie MeSH
- gastrointestinální trakt chirurgie MeSH
- konsensus MeSH
- lidé MeSH
- perforace střeva etiologie chirurgie MeSH
- perioperační péče normy MeSH
- střevní nádory etiologie chirurgie MeSH
- střevní píštěle etiologie chirurgie MeSH
- výběr pacientů * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
OBJECTIVE: Local application of adipose-derived mesenchymal stem cells (ADSC) represents a novel approach for the management of perianal fistula in patients with Crohn's disease. A randomised study on an animal model was performed to investigate the efficacy and to detect the distribution of implanted ADSCs by bioluminescence (BLI). MATERIALS AND METHODS: A caecostomy was used as a fistula model in 32 Lewis rats. The ADSCs were isolated from transgenic donor expressing firefly luciferase. Animals were randomly assigned to groups given injections of 4 × 106 cells (n = 16, group A) or placebo (n = 16, group B) in the perifistular tissue. Fistula drainage assessment was used to evaluate the fistula healing. After application of D-luciferin, cell viability and distribution was detected using an IVIS Lumina XR camera on days 0, 2, 7, 14 and 30. RESULTS: The fistula was identified as healed in 6 (38%) animals in group A vs. 1 case (6.3%) in group B (p = .033). The BLI was strongest immediately after administration of ADSCs 31.2 × 104 (6.09-111 × 104) p/s/cm2/sr. The fastest decrease was observed within the first 2 days when values fell by 50.2%. The BLI 30 days after injection was significantly higher in animals with healed fistulas - 8.23 × 104 (1.18-16.9 × 104) vs. 1.74 × 104 (0.156-6.88 × 104); p = .0393. CONCLUSIONS: Local application of ADSCs resulted in significantly higher fistula closure rate on an animal model. BLI monitoring was proved to be feasible and showed rapid reduction of the ADSC mass after application. More viable cells were detected in animals with healed fistula at the end of the follow-up.
- Klíčová slova
- Mesenchymal stem cell, bioluminescence, perianal fistula,
- MeSH
- Crohnova nemoc komplikace patologie MeSH
- hojení ran * MeSH
- krysa rodu Rattus MeSH
- luminiscenční měření MeSH
- mezenchymální kmenové buňky cytologie MeSH
- modely nemocí na zvířatech MeSH
- náhodné rozdělení MeSH
- potkani inbrední LEW MeSH
- prospektivní studie MeSH
- regenerativní lékařství metody MeSH
- rektální píštěl terapie MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- tuková tkáň cytologie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Novel, less invasive approaches such as single-incision laparoscopic cholecystectomy or natural orifice transluminal endoscopic surgery require preclinical evaluation and training. Therefore, there is a need for an experimental model closely mimicking the clinical situation. The aim of our study was to create an experimental model of calculous cholecystitis in a large laboratory animal and test its feasibility for the evaluation of different techniques of cholecystectomy. METHODS: In 11 laboratory pigs, gallstones were placed inside the gallbladder laparoscopically. Levels of inflammatory markers-leucocytes (WBC), C-reactive protein (CRP) and interleukin 6 (IL-6)-were monitored on the postoperative days (POD) 1, 2, 3, 7 and 30. Abdominal ultrasound was performed 2 and 4 weeks after the operation. Four weeks after the lithiasis induction, laparoscopic cholecystectomy was performed. The control group consisted of ten healthy animals in which a cholecystectomy was performed. The pigs were monitored for 30 days after surgery. All removed gallbladders were assessed histologically. RESULTS: The induction of lithiasis took 42 (35-52) min with no morbidity and mortality. The values of WBC, CRP and IL-6 increased significantly (vs. baseline) on POD 1, 2 and 3 (p < 0.05) and then normalised. Ultrasonography confirmed the presence of chronic calculous cholecystitis in all cases after 4 weeks. Laparoscopic cholecystectomy was significantly longer in animals with lithiasis, 63 (42-91) versus 46 (31-62) min (p = 0.018). Perioperative gallbladder wall perforation was significantly more frequent in the model group (8/11 vs. 1/10; p = 0.04). In contrast to healthy animals, all gallbladders with stones showed histological signs of chronic inflammation. CONCLUSIONS: A new animal model of calculous cholecystitis was created. Laparoscopic cholecystectomy was more technically difficult compared to operating on a healthy gallbladder. This model may be a suitable tool for effective preclinical training and also for the evaluation of different techniques of cholecystectomy.
- Klíčová slova
- Animal model, Cholecystolithiasis, Laparoscopic cholecystectomy, Learning curve, NOTES,
- MeSH
- cholecystektomie laparoskopická výchova metody MeSH
- cholecystolitiáza chirurgie MeSH
- endoskopické operace přirozenými otvory výchova metody MeSH
- miniinvazivní chirurgické výkony MeSH
- modely nemocí na zvířatech MeSH
- prasata MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Treatment of non-specific inflammatory bowel diseases was from the start accompanied by forced operations. In the 19th and early 20th century operations were burdened with high mortality, but most were more successful than the limited possibilities of conservative treatment. Gradually developed principles for the treatment of Crohns disease, a length of bowel sparing surgery are still valid today. Surgical treatment of ulcerative colitis passed the time of colonic irrigation, bypass surgery, limited resection to todays gold standard - proctocolectomy with ileo-pouch-anal anastomosis.
- MeSH
- Crohnova nemoc dějiny MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- idiopatické střevní záněty dějiny MeSH
- lidé MeSH
- ulcerózní kolitida dějiny MeSH
- Check Tag
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Studies have shown the value of using fast-track postoperative recovery. Standard procedures (non-fast-track strategies) remain in common use for perioperative care. Few prospective reports exist on the outcome of fast-tracking in Central Europe. The aim of our study was to assess the effect and safety of our own fast-track protocol with regard to the postoperative period after open bowel resection. PATIENTS AND METHODS: One hundred and five patients with ASA score I-II scheduled for open intestinal resection in the period April 2005-December 2007 were randomly selected for the fast-track group (FT) and non-fast-track group (non-FT). A designed protocol was used in the FT group with the emphasis on an interdisciplinary approach. The control group (non-FT) was treated by standard established procedures. Postoperative pain, rehabilitation, gastrointestinal functions, postoperative complications, and post-op length of stay were recorded. RESULTS: Of 105 patients, 103 were statistically analyzed. Patients in the FT group (n=51) and non-FT group (n=52) did not differ in age, surgical diagnosis, or procedure. The fast-track procedure led to significantly better control of postoperative pain and faster restoration of GI functions (bowel movement after 1.3 days vs. 3.1, p<0.001). Food tolerance was significantly better in the FT group and rehabilitation was also faster. Hospital stay was shorter in the FT group - median seven days (95% CI 7.0-7.7) versus ten days (95% CI 9.5-11.3) in non-FT (p<0.001). Postoperative complications within 30 postoperative days were also significantly lower in the FT group (21.6 vs. 48.1%, p=0.003). There were no deaths and no patients were readmitted within 30 days. CONCLUSIONS: Following the FT protocol helped to reduce frequency of postoperative complications and reduced hospital stay. We conclude that the FT strategy is safe and effective in improving postoperative outcomes.
- MeSH
- délka pobytu statistika a číselné údaje MeSH
- dospělí MeSH
- klid na lůžku statistika a číselné údaje MeSH
- klinické protokoly * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pacientem kontrolovaná analgezie statistika a číselné údaje MeSH
- perioperační péče metody MeSH
- pooperační komplikace epidemiologie MeSH
- prospektivní studie MeSH
- senioři MeSH
- střeva chirurgie MeSH
- trávicí systém - fyziologické jevy MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Česká republika MeSH
