RU2841914C1 - Method of transvaginal fistuloplasty for vesicovaginal fistulas - Google Patents

Abstract

FIELD: medical science.

SUBSTANCE: invention refers to medicine, particularly to gynaecology and urology. Transvaginal fistuloplasty is performed. Stromal-vascular fraction (SVF) is obtained from the patient’s own subcutaneous fat. Defect of the bladder wall is closed by applying a first row of sutures in an oblique direction, after which the obtained SVF is introduced into 6 points, as shown in Fig. 2, by 0.5 ml into 1 point at depth of 2 mm, retreating from the wound-healthy tissue border 5 mm. Thereafter, the second line of sutures is applied on the bladder wall defect.

EFFECT: method enables stimulating the regeneration process, providing faster and more effective postoperative tissue healing, improving the therapeutic effect and reducing a risk of developing complications of fistuloplasty.

1 cl, 2 dwg, 1 ex

Description

The invention relates to medicine, in particular to urology, and can be used for complex surgical treatment of vesicovaginal fistulas (VVF).

PVS is an abnormal communication between the bladder and the vagina, resulting in urine leakage from the vagina, which in turn leads to a significant decrease in the quality of life of patients, loss of ability to work, and desocialization. Among all types of urogenital fistulas, PVS is the most common pathology. [Hillary, C.J.; Osman, N.I.; Hilton, P.; Chappie, C.R. The Aetiology, Treatment, and Outcome of Urogenital Fistulae Managed in Well- and Low-Resourced Countries: A Systematic Review. Eur. Urol. 2016, 70, 478-492, doi:10.1016/j.eururo.2016.02.015., Malik, M.A.; Sohail, M.; Malik, M.T.; Khalid, N.; Akram, A. Changing Trends in the Etiology and Management of Vesicovaginal Fistula. Int. J. Urol. 2018, 25, 25-29, doi:10.1111/iju.13419.]

The most common cause of PVS is obstetric and gynecological surgery, especially hysterectomy (up to 70%).

Conservative treatment of PVS, which consists of long-term catheterization of the bladder, has low treatment efficiency. According to studies, the frequency of spontaneous healing of PVS against the background of long-term catheterization does not exceed 10%, while in the group of patients who underwent radiation therapy, spontaneous healing of PVS is not observed at all [Matthew P. Rutman, Larissa V. Rodrigues, Shlomo Raz. Vesicovaginal fistula: vaginal approach. In: Raz S., Rodriguez L.V. [Edit.] Female Urology, 3rd ed. WB Saunders, Philadelphia, Pa., P. 794-801. [Hilton P. Urogenital fistula in the UK: a personal case series managed over 25 years // BJU Int. 2012. Vol. 110(1). P. 102-110.] The choice of surgical approach is determined according to the location and etiology of the fistula, the size of the fistula tract, and the experience of the surgical team. The most effective and frequently used surgical method of treatment is fistuloplasty. There are several methods of surgical treatment of PVS: transvaginal, transvesical, hybrid. Surgery can be performed both openly and using laparoscopic or robot-assisted techniques.

Transvaginal access has advantages over transabdominal access, which include reduced recurrence rates, early and late complications, rapid postoperative rehabilitation, and shorter duration of bladder catheterization. However, it requires high professionalism of the operating surgeon. Despite the high level of development of medicine, the use of more advanced techniques for surgical treatment of fistulas, and the use of modern suture materials, the effectiveness of fistuloplasty in PVS continues to be insufficiently high [Loran O.B., Sinyakova L.A., Seregin A.V., Tverdokhlebov N.E. Surgical treatment of patients with complex urinary fistulas // Urology. 2010. No. 5. P. 76-79]. The recurrence rate after fistuloplasty performed for the first time reaches slightly less than 12%. Probably, the frequency of relapses of the disease is associated with insufficient tissue regeneration capabilities in the area of the fistula tract [Budrevich A.E., Nechiporenko N.A. Vesicovaginal fistulas: problems of treatment and prevention. Journal GrSMU [Internet]. December 23, 2015].

In this regard, it is important to develop and improve the technique of surgical treatment of PVS, which ensures an increase in the regenerative capacity of tissues and a reduction in the frequency of disease relapses.

The closest analogue of the invention is the method of surgical treatment of PVS with local intra-tissue application of autologous plasma enriched with platelets (APOT). Injections were performed as part of preoperative preparation 6-7 weeks before the operation with an interval of 7 days. Parafistular infiltration injections of APOT were performed in the direction from healthy tissues to cicatricial ones. Each injection was 2-3 ml and was performed at 8-10 points. After each session of APOT therapy, antibacterial therapy was prescribed according to bacteriological urine culture, and in the absence of microflora growth, a single dose of a broad-spectrum antibiotic was prescribed to prevent infectious complications, as well as transvaginal instillations of an aqueous solution of chlorhexidine, vaginal iodopyrone-containing suppositories. In the presence of significant pain syndrome after the manipulation, analgesia was performed using non-steroidal anti-inflammatory drugs [Opolsky O.M. Surgical treatment of ureterovaginal fistulas with local intra-tissue application of platelet-rich autoplasma: dis. candidate of medical sciences: 14.01.23. - Rostov state medical university, Rostov-on-Don, 2021 - 62 p.].

The main advantage of this method is the ease of access to material for isolating the APOT fraction and the positive results of therapy: 50% of patients showed a decrease in the largest diameter of the PVS by at least 2 times.

The disadvantages of the method are: pain both during and after the manipulation, hemorrhagic post-puncture phenomena, which become more abundant and longer during the process of preoperative APOT injections for 6-7 weeks, it is difficult for patients to constantly undergo these manipulations due to the discomfort that occurs during the procedures, as well as the need for multiple visits to the institution and the implementation of painful procedures.

The objective of the invention is to develop a method for transvaginal fistuloplasty in vesicovaginal fistulas, ensuring improved long-term treatment results.

The technical result of using the invention is an increase in the therapeutic effect due to the initiation of regeneration processes in parafistula tissues, which contributes to the restoration of the structure of the affected tissues.

There is no information in the available scientific, medical and patent literature on the use of stromal-vascular fraction in the treatment of PVS.

The invention is illustrated by the following figures: Figure 1 shows suturing of a bladder wall defect with the first row of sutures; Figure 2 shows the introduction of a stromal-vascular fraction using the proposed method.

The proposed method of transvaginal fistuloplasty in PVS is as follows. On the evening before the surgery, the patient is given a cleansing enema. Antibiotic prophylaxis with a broad-spectrum drug is administered 60 minutes before the expected skin incision. If the bacteriological urine culture and uroantibioticogram are positive, antibacterial therapy is started on the eve of surgery. In the operating room, the patient is placed in the lithotomy position. The operating table is set in the Trendelenburg position. Before fistuloplasty, under endotracheal anesthesia and after three treatments of the surgical field with 10% povidone-iodine solution, adipose tissue is collected from the subcutaneous fat of the anterior abdominal wall through a 5 mm skin incision in the paraumbilical area using lipoaspiration in a volume of 100-150 ml to obtain autologous stromal vascular fraction (SVF).

Cystoscopy is performed. The main anatomical features of the vesicovaginal fistula are determined. For intraoperative navigation and to prevent trauma to the mouths and distal parts of the ureters, catheterization of the ureters is performed with ureteral catheters CH 6.

Vaginal speculums are installed. If the fistula tract has a diameter that allows the passage of a Foley CH 12 urethral catheter, then the latter is installed through the fistula tract, and the cuff balloon is inflated in the bladder cavity to 10 ml. Otherwise, a guidewire is passed through the fistula tract, one end of which is brought out through the urethra, the second through the vagina.

Perform traction on yourself using a Foley catheter or a guidewire. Using a scalpel with a #12 sickle blade, make a circular bordering parafistular incision of the anterior vaginal wall within healthy, well-perfused tissues. Identify the wall of the urinary bladder. Using scissors, perform a wide mobilization of the anterior vaginal wall and urinary bladder using blunt and sharp methods. Then excise the parafistular cicatricial tissues and fistula tract. Perform hemostasis control.

The bladder wall defect is sutured with atraumatic monofilament absorbable thread 3\0 - 4\0 sutures in an oblique direction (Figure 1). To improve regeneration and stimulate angiogenesis, which is important in the area of the primary suture, as well as to reduce the degree of scarring and maintain tissue functionality after the first row of sutures, SVF is administered in a total volume of 3 ml using a 3 ml syringe and a 22G needle, 40 mm long, at 6 points of 0.5 ml to a depth of 2 mm, retreating from the wound - healthy tissue boundary 5 mm (Figure 2). After that, the bladder wall is sutured with a second row of similar sutures.

In connection with the available data on the ability of multipotent mesenchymal stem cells from the SVF to secrete various biologically active molecules, including growth factors that promote healing and restoration of tissues in the injection zone, in order to ensure a sufficient zone of physiological action and better regeneration, the administration is carried out, retreating from the wound - healthy tissue border by 5 mm in 6 points. Considering the average thickness of the bladder walls of 2-4 mm and the anatomical features of the bladder membranes, performing injections of 0.5 ml to a depth of 2 mm ensures reliable introduction into the muscle membrane zone. After performing the injections, the bladder wall is sutured with an atraumatic monofilament absorbable thread with a second row of similar sutures. The second row of sutures reduces the risk of failure of the first row sutures, additionally provides tightness, and reduces the risk of infection.

The urinary bladder is drained using a Foley catheter CH 14. The tightness of the urinary bladder wall is checked through the installed urethral Foley catheter CH 14, filling the urinary bladder with saline solution up to 200 ml.

The anterior wall of the vagina is sutured with separate interrupted sutures of 3/0 monofilament absorbable thread. A tampon soaked in Levomekol ointment is inserted into the vagina. Drainage of the bladder with a urethral catheter is carried out for 10 days; urethrocystography is performed before removing the catheter.

The production of SVF is carried out in several stages.

The first stage is manual tumescent liposuction. A 5 mm skin incision is made paraumbilically. After that, the subcutaneous fat of the anterior abdominal wall is infiltrated from the center to the periphery with a solution of 0.5 ml of 1% adrenaline and 500 ml of 0.9% sodium chloride) using a 250 mm long, 3 mm diameter infiltration cannula and a 50 ml Luer-Lock syringe.

After infiltration, exposure is carried out for 7 minutes. Then, syringe lipoaspiration is carried out using an aspiration cannula with a diameter of 4 mm, a length of 300 mm, with one central hole and two side holes. The cannula is fixed to a syringe with a volume of 60 ml through a connector with an internal diameter of 2.4 mm. Reciprocating movements are used to collect adipose tissue in a volume of 100-150 ml. For subsequent isolation of SVF, the adipose tissue is transferred to specialized double Arthrex ACP® syringes with a volume of 15 ml.

After liposuction, 4 Arthrex ACP® syringes are placed in a Rotofix 32 A tabletop centrifuge with spider rotors and freely suspended cups. Centrifugation is performed at 2500 rpm for 4 minutes. After a single centrifugation, the remaining tumescent liquid is removed and the adipose tissue is transferred to a 20 ml Luer-Lock syringe. Next, using a 1.4 mm diameter connector and two 20 ml Luer-Lock syringes, the remaining adipose tissue is sequentially transferred from syringe to syringe through the connector 30 times for the purpose of mechanical processing. After which the processed tissue is transferred to an Arthrex ACP syringe for repeated centrifugation at 2500 rpm for 4 minutes. Based on the results of repeated centrifugation, the adipose tissue is separated into fractions. At the final stage, the SVF is transferred into a 3 ml Luer-Lock syringe. Thus, from 60 ml of adipose tissue it is possible to obtain 2-3 ml of SVF, which contains 50 million or more cells.

The cellular component of SVF is heterogeneous and varies depending on the site of liposuction, donor gender and age, and the presence of chronic diseases. The most significant cellular fraction with a therapeutic effect is multipotent mesenchymal stem cells (MMSCs), in addition to which SVF contains endothelial progenitor cells, progenitor cells, pericytes, monocytes/macrophages, regulatory T lymphocytes, and hematopoietic stem cells. [Ramakrishnan V.M., Boyd N.L. The Adipose Stromal Vascular Fraction as a Complex Cellular Source for Tissue Engineering Applications. Tissue Eng Part B Rev. 2018 Aug;24(4):289-299. doi: 10.1089/ten.TEB.2017.0061. Epub 2017 Apr 13.].

The main mechanism of action is based on the complex interaction of the heterogeneous SVF cell population with cells, leading to stimulation of cell differentiation, angiogenesis, immunomodulatory, antiapoptotic effects and, accordingly, restoration of damaged cells and tissues. [Bourin, P.; Bunnell, B.A.; Casteilla, L.; Dominici, M.; Katz, A.J.; March, K.L.; Redl, H.; Rubin, J.P.; Yoshimura, K.; Gimble, J.M. Stromal Cells from the Adipose Tissue-Derived Stromal Vascular Fraction and Culture Expanded Adipose Tissue-Derived Stromal/Stem Cells: A Joint Statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 2013, 15, 641-648, doi:10.1016/j.jcyt.2013.02.006.].

In this case, there is stimulation of the compensatory capabilities of the microcirculatory bed due to an increase in the capillary network, which is achieved by stimulating neoangiogenesis in the area of the plastic surgery and surrounding tissues, which in turn reduces the risk of relapse of the disease. The proposed method allows stimulating regenerative processes and ensures early healing in the area of the surgical access.

Macrophages present in the SVF, according to identified markers (CD163, CD209, CD200, CD1β and CD1c), belong to alternatively activated macrophages and may also play a role in reducing inflammation [Ala Lozinski, MD, FRCPC, DABD, Nasim S. Huq, MD, FRCSC, MSc, FACS, CAQHS, DABPS, DOI: https://doi.org/10.1016/j.cps.2013.07.006].

The essence of the invention is illustrated by the following clinical example.

Patient G., 40 years old, diagnosed with vesicovaginal fistula. Upon admission, she complained of involuntary and constant leakage of urine from the vagina, the need to use absorbent sanitary pads.

History: in 2022, a hysterectomy was performed for benign pathology, 6 days after surgery, she began to notice urine leakage from the vagina. Drainage of the bladder with a urethral catheter for 14 days did not give a positive effect, after removing the urethral catheter, urine leakage from the vagina was again noted. Per day, it was necessary to use 2 to 5 hygienic absorbent pads. Hospitalized in the Clinic of the Belarusian State Medical University on a planned basis for surgical treatment. According to urethrocystoscopy and colposcopy - in the area of the Lieto triangle, there is a vesicovaginal fistula with a diameter of 8-10 mm, the orifices of the ureters are somewhat pulled up to the fistula tract, there is no scarring or peripheral defect. The patient underwent fistuloplasty via transvaginal access and intraoperative injections of 0.5 ml of SVF each at 6 points to a depth of 2 mm, 5 mm from the wound-healthy tissue boundary. The patient was discharged on the 5th day after the surgery. On the 10th day, urethrocystography was performed with the introduction of 150 ml of contrast agent - no contrast agent leakage was detected, after which the urethral catheter was removed. During a follow-up examination of the patient 30 days after discharge from the hospital, no signs of recurrence of the vesicovaginal fistula were detected. When questioning the patient after 6 and 12 months, the patient had no complaints, uroflowmetric parameters corresponded to the reference parameters.

Eight patients with PVS were treated with the proposed method, with informed consent.

The advantages of this method are the simplicity of implementation, natural stimulation of regeneration processes, provision of faster and more effective tissue healing after surgery, improvement of the result and reduction of the risk of complications of fistuloplasty. The claimed method improves the remote results of transvaginal fistuloplasty in patients with vesicovaginal fistulas.

Claims (1)

A method for treating a vesicovaginal fistula, characterized by the fact that transvaginal fistuloplasty is performed, whereby stromal vascular fraction (SVF) is obtained from the patient's own subcutaneous fat, the bladder wall defect is sutured, applying the first row of sutures in an oblique direction, after which the obtained SVF is injected into 6 points, as shown in Fig. 2, 0.5 ml at 1 point to a depth of 2 mm, retreating 5 mm from the wound-healthy tissue boundary, after which a second row of sutures is applied to the bladder wall defect.