A Novel Method for Chronic Anal Fissure Treatment
Condition: Anal Fissure
MeSH terms: Fissure in Ano
Study type: Interventional

Summary: 
      Investigators performed a prospective pilot study to test the feasibility and safety of
      autologous adipose derived regenerative cell (ADRC) transplantation in treatment of anal
      fissures. The study included 6 patients with chronic anal fissures with symptoms that had an
      average duration of 24 months. All patients were candidates for surgical treatment as all
      previous conservative treatments were unsuccessful. The pain level was measured using the VAS
      scale and was recorded before the treatment and on every consultation following the
      treatment.

      The initial hypothesis is that application of ADRCs may be an alternative to lateral
      sphincterotomy and a reliable procedure to avoid fecal incontinence.
    

Detailed description: 
      This prospective pilot study includes 6 patients suffering from chronic anal fissure. All
      patients were previously treated with different local applications of glyceryl trinitrate or
      topical Xylocaine gel. Some patients took oral analgesics as a concomitant therapy for
      additional pain control. None of the patient received neither topical calcium channel
      blockers nor Botulinum toxin injection due to the unavailability.

      The primary outcome measured is "time to complete cessation of anal pain". The secondary
      outcome includes the healing of chronic anal fissure defined as "time to complete
      epithelization".

      The study was approved by the Ethics Committee of the First Surgical Clinic, Faculty of
      Medicine, and University of Belgrade. The study was performed in accordance with the
      Declaration of Helsinki and current Good Clinical Practices. All patients gave the written
      informed consent prior to the participation.

      Physical examination and the detail medical history has been taken by an experienced
      colorectal surgeon. Pain assessment is quantified using the visual analog scale (VAS) before
      the treatment and during each postoperative outpatient visit. Bowel continence has been also
      assessed using Wexner fecal incontinence score prior to the treatment and during each
      postoperative outpatient visit. The liposuction procedure has been performed performed under
      the combination of local anesthesia and moderate sedation/general anesthesia. The mixture of
      180 mL saline solution, 1mL Epinephrine (1:10,000) and 20 mL of 2% lidocaine is injected in
      the subcutaneous layer of the abdominal wall to allow the tumescence and to decrease the
      blood loss. The manual liposuction procedure has been carried out through two or three small
      incisions using Sforza harvester (Tulip® medical products, San Diego, USA). Approximately
      150-200 mL of raw lipoaspirate is obtained from each patient. The harvest site is then
      covered with a pressure dressing for 10 days to reduce swelling and hematoma. The closed
      system PureGraft® 250mL (PureGraft®, Solana Beach, California, USA) has been used used to
      collect the specimen. The specimen is transferred within 15 min to the BelPrime Clinic
      laboratory where the Celution® 800/CRS system (Cytori Therapeutics, Inc. San Diego,
      California, USA) is applied to process the lipoaspirate in order to obtain ADRCs. The
      Celution® 800/CRS system is a closed automated medical device that helps to separate blood
      and fat. The system will then digests fat using the proprietary enzyme reagent Celase 835/CRS
      (Cytori Therapeutics, Inc. San Diego, California, USA) to release the stromal vascular
      fraction (SVF). SVF is subsequently concentrated by a short centrifugation and then automated
      wash cycles to obtain the ADRC fraction. This 90 to 120-minute process provides approximately
      5mL of pellet. A few drops of the obtained pellet were immediately used for cell counting
      (ChemoMetec A/S DK-3450, Allerod, Denmark).

      The second procedure has been performed in lithotomy position. Intravenous prophylactic
      antibiotic (1gm Metronidazol) are administered. After the careful and gentle anal
      examination, anal fissure is first curetted using a small size curette. The pellet is divided
      into two parts. The first 2mL of the pellet is mixed with 8mL of the lipid part of the
      lipoaspirate purified by Puregraft® 50 system. This solution (10mL) is injected
      subcutaneously into the edge of the fissure using the criss-cross lattice technique by Tulip®
      1,2 mm injector. The rest of the pellet, (approximately 2-5mL), is infiltrated directly into
      the fissure base (internal anal sphincter) using a 20G needle. No laxatives or stool softener
      is prescribed. Patients have been discharged from the hospital a few hours after the
      procedure.

      Patients are followed up weekly by telephone interview during the first 2 months, then
      monthly up to 12 months after the procedure. The outpatient visits are scheduled monthly
      until 9 months to ensure the healing of anal fissure. Visual analogue scale (VAS) score and
      Wexner fecal incontinence score [31] are also recorded.
    

Intervention name(s): ADRCs therapy; Celution; Tulip cannulas; 20mL Lidocaine 2% and Epinephrine 1:100 000
Intervention type(s): Other; Device; Device; Other
Intervention description(s): Patients with chronic anal fissures will receive one treatment of local injections of fat enriched with adipose derived regenerative cells starting from December 2014.; Adipose derived regenerative cell isolation; Lipoaspiration; Infiltration prior to liposuction
Other intervention name(s): Xylocaine 2% and adrenaline 1:100 000
Intervention MeSH terms: Lidocaine; Epinephrine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ADRC; Celution