Local application of adipose-derived mesenchymal stem cells supports the healing of fistula: prospective randomised study on rat model of fistulising Crohn's disease.

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.

A new experimental model of calculous cholecystitis suitable for the evaluation and training of minimally invasive approaches to cholecystectomy.

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.

[History of surgical treatment of non-specific inflammatory bowel diseases]. / Historie chirurgické lécby nespecifických zánetu strevních.

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.

Insights into treatment of complex Crohn's perianal fistulas.

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.

Fast-track in open intestinal surgery: prospective randomized study (Clinical Trials Gov Identifier no. NCT00123456).

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.

Clinical features and management of postoperative pouch bleeding after ileal pouch-anal anastomosis (IPAA).

AIM: The clinical features of postoperative bleeding from the ileal pouch-anal anastomosis(IPAA) vary and its management can be difficult. There is no published literature regarding pouch bleeding and its treatment. MATERIALS AND METHODS: Pouch bleeding was defined as the passage of blood or clots transanally or into the ileostomy bag with or without hypotension or a drop in hemoglobin within 30 days after surgery. Patients were identified from a prospectively maintained pouch database. RESULTS: Pouch bleeding developed in 47 (1.5%) patients out of 3,194 patients undergoing IPAA since 1983. Forty-two patients had inflammatory bowel disease, four had familial adenomatous polyposis, and one had colonic inertia. Sixty-six percent of bleeding occurred within 7 days postoperatively and 59.6% required transfusion; 72.3% patients developed transanal bleeding, nine from ileostomy and two from both. After initial fluid resuscitation, five patients were observed while 28 patients had pouch endoscopy and clot evacuation followed by cauterization or epinephrine(1:100,000) enemas, 27 of these had cessation within 24 h. Epinephrine enema was used as initial treatment in the remaining 12 patients. Overall success rate of epinephrine enema was 96%. CONCLUSION: Postoperative pouch bleeding after IPAA is uncommon, and it usually requires nonsurgical intervention. Epinephrine enema appears to be successful in managing this complication.