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Division of Gastrointestinal and Minimally Invasive Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North CarolinaDepartment of Surgery, Franciscus Gasthuis en Vlietland, Rotterdam, the Netherlands
Division of Gastrointestinal and Minimally Invasive Surgery, Department of Surgery, Carolinas Medical Center, Charlotte, North CarolinaDepartment of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
Fascial closure significantly reduces postoperative complications and hernia recurrence after abdominal wall reconstruction (AWR), but can be challenging in massive ventral hernias.
A prospective single-institution cohort study was performed to examine the effects of preoperative injection of botulinum toxin A (BTA) in patients undergoing AWR for midline or flank hernias.
A total of 108 patients underwent BTA injection with average 243 units, mean 32.5 days before AWR, without complications. Comorbidities included diabetes (31%), history of smoking (27%), and obesity (mean body mass index 30.5 ± 7.7). Hernias were recurrent in 57%, massive (mean defect width 15.3 ± 5.5 cm; hernia sac volume 2154 ± 3251 cm3) and had significant loss of domain (mean 46% visceral volume outside abdominal cavity). Contamination was present in 38% of patients. Fascial closure was achieved in 91%, with 57% requiring component separation techniques (CSTs). Subxiphoidal hernias needed a form of CST in 88% compared with 50% for hernia not extending subxiphoidal (P < 0.001). Mesh augmentation was used in 98%. Postoperative complications occurred in 40%: 19% surgical site occurrences, 12% surgical site infections, and 7% respiratory failure requiring intubation, 2% mesh infection and no fascial dehiscence. Recurrence was identified in seven patients after mean 14 months of follow-up. Patients undergoing AWR with CST had more surgical site occurrences (29 versus 7%, p0.003) and respiratory failures (18 versus 0%, P = 0.002) than patients who did not require CST.
In patients with massive ventral hernias, the use of preoperative BTA injections for AWR is safe and is associated with high fascial closure rates and excellent recurrence rates.
Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement versus primary suture only in midline laparotomies (PRIMA): 2-year follow-up of a multicentre, double-blind, randomised controlled trial.
In large hernia defects with LOD, closure of the fascia can be challenging. Failure to close the fascia significantly increases the risk of surgical site occurrences and recurrence, and a bridging repair should preferably be avoided in AWR.
however, these techniques require laceration of a myofascial layer of the abdominal wall and can distort the normal anatomy. Some of these techniques require large lipocutaneous flaps to be created, leading to an increased risk of wound complications, with potentially increased risk of infection of implanted prosthesis and hernia recurrence.
Other techniques have been used to expand abdominal domain in large ventral hernias, including progressive pneumoperitoneum and soft tissue expanders; however, these techniques are invasive and not without morbidity.
BTA is a neurotoxin produced by the bacterium Clostridium botulinum, which has an inhibitory effect on presynaptic cholinergic nerve terminals. Treatment of a muscle with BTA results in functional denervation within 2 d, with peak effect after approximately 2 to 4 wk, ultimately leading to flaccid paralysis that wears off after 3 to 6 mo.
The neurotoxin BTA results in a form of chemical component separation, causing a relaxation of the lateral muscles of the abdomen and increasing abdominal wall compliance by elongation and thinning of the musculature.
The objective of the present study was to examine the effects of preoperative BTA injections in AWR on fascial closure rates, the need for CSTs, postoperative complications, and recurrence rates.
After approval from the institutional review board, patients were selected from a prospectively collected database of patients undergoing AWR at a large tertiary hernia referral center (Carolinas Medical Center in Charlotte NC, USA). All patients signed an informed consent for data collection and analysis. All patients in the BTA cohort received preoperative BTA injection in preparation for AWR if there was a clinical suspicion that fascial closure would be unlikely, even with CSTs. The hernia center consists of four fellowship-trained surgeons with a collective experience of over 45 y and more than 9000 ventral hernia repairs. After careful review of each patient's computed tomography (CT) scan and operative notes, and physical examination, the decision to give preoperative BTA was made. A descriptive prospective cohort study of all patients receiving BTA was performed.
Preoperative CT scans of patients were used to measure hernia defect dimensions and calculate hernia sac volume (HV), intra-abdominal volume (IAV), and LOD. CT scans were analyzed using the TeraRecon software Aquarius, iNtuition Edition, version 4.4.13. The ratio of HV to IAV was calculated (HV:IAV) as a measurement of LOD. The detailed technique of this volumetric analysis is previously described by the authors’ group.
A ratio of 0.5 indicates that one-third of the total visceral volume is outside the abdominal cavity, whereas a ratio of 1 indicates that half of the total visceral volume is outside the abdominal cavity.
Baseline patient characteristics, hernia characteristics, intraoperative details, and details of the postoperative course were collected. Hernias were classified in two ways: in accordance with the European Hernia Society (EHS) Classification of primary and incisional abdominal wall hernias (Fig. 1)
and based on the degree of contamination in accordance with the surgical wound classification of the Centers for Disease Control and Prevention (CDC class). The primary outcome was fascial closure, defined as a complete suture closure of the hernia defect. Secondary outcomes included need for CST, specified as open external oblique release (EOR), which often included a posterior rectus sheath release, or transversus abdominis release.
or intraperitoneal. A delayed primary closure of the skin and subcutaneous tissues was performed in patients with active ongoing infection as seen at the time of the operation and included negative pressure wound vacuum therapy until primary skin closure approximately 5 d after the index operation.
Patients were scored on the following postoperative complications: death, fascial dehiscence, mesh infection, fistulas, surgical site infection (SSI), surgical site occurrence (SSO), anastomotic leakage, intra-abdominal abscess formation, small bowel obstruction, urinary tract infection, renal insufficiency or failure, cardiac complication (dysrhythmias, myocardial infarction), pulmonary complications (pneumonia, embolism, respiratory failure, reintubation), and deep venous thrombosis. The standardized definition of SSI by the CDC was used
Patients were followed up in our clinic after standard 2 wk, 3 mo, 6 mo, and 1 y and after that yearly by their family doctor. If doubt existed about a possible recurrence on physical examination, radiological imaging was performed. Available radiological imaging, performed for other indications, was reviewed for hernia recurrence.
Data were analyzed using the SAS program, version 9.4, (SAS, Cary, NC, USA) and standard statistical methods. Descriptive statistics included means and standard deviations for continuous variables or counts and percentages for categorical variables. For continuous variables, comparisons were made between groups using t-tests and Wilcoxon–Mann–Whitney tests. For categorical variables, chi square and Fisher's exact tests were used to compare between groups. Outcomes included achievement of fascial closure, need for CST, and postoperative outcomes and complications.
BTA injection technique
Our detailed BTA injection protocol is published previously.
The risks and benefits of the procedure were explained to the patient, and written informed consent was obtained for all patients undergoing BTA injections. Patients were either injected in all three abdominal wall muscle layers (external oblique [EO], internal oblique [IO], and transversus abdominis [TA]), or the outermost two layers (EO and IO). The decision whether to inject the TA was determined by muscle size and atrophy during the initial cases of this series, with only the EO and IO muscles routinely injected in the latter cases, especially after a published series showed no differences in outcome between a two- and three-layer technique.
Using the anterior axillary line as a landmark, six injection sites are marked on the skin (three on the right and three on the left), equidistantly spaced between the ribs and iliac crest, approximately 5 cm apart. When three-layer injection was used, 300 units of onabotulinum toxin A (Botox Allergan, Irvine, CA, USA) were diluted into 150 mL sterile saline (2:1 concentration). For injection of EO and IO only, 200 units were diluted into 100 mL sterile saline. For unilateral injection for flank hernias, half the amount was used. The patient's abdomen near the anterior axillary line was prepped and draped in a sterile manner. Using sterile technique, local anesthesia, and either low-dose CT fluoro or ultrasound (US) guidance, 25- or 22-gauge needles were placed into EO and IO, with or without the TA, and 8 cc (16 units) of the BTA mixture was injected into each muscle at each of the total six injection sites. Negative aspiration was performed before each injection to avoid intravascular injection. Patients were injected approximately 1 mo before planned AWR.
A total of 118 patients were injected with BTA before AWR between May 2013 and October 2019. Indications were massive ventral or flank hernias in 113 patients, massive inguinal hernias in three patients, and open abdomen in two patients. Four of these patients did not receive an operation: one did not stop smoking, one was found to have metastatic disease, one developed hepatitis, and one developed increasing pulmonary dysfunction. One patient was found to have a severe infection of prosthesis during surgery, and after resection of infected materials, he was planned for a staged AWR. Patients with an open abdomen, inguinal hernias, or those that did not undergo AWR were excluded. A total of 108 patients with ventral and flank hernias were included in the descriptive cohort. Over half of patients had a recurrent incisional hernia, with an average of 2.3 prior failed repairs (standard deviation (SD) 2.5, range: 1-11). Baseline characteristics of these patients are presented in Table 1.
Table 1Baseline characteristics of 108 patients treated with BTA before AWR.
Number or mean
History of smoking
History of MRSA infection
BMI = body mass index; COPD = chronic obstructive pulmonary disease; MRSA = methicillin-resistant staphylococcus aureus.
CT measurements showed large hernia defects with often severe LOD. Hernia defect size ranged from 37.4 to 721.0 cm2, with 63% of hernias over 200 cm2. HV was over 1000 cm3 in 56% and ranged up to 28,363 cm3. Most patients had severe LOD, with 18% of patients having an HV:IAV ratio between 0.5 and 1.0 (33%-50% LOD), and 16% having an HV:IAV ratio over 1.0 (>50% LOD). One patient had an extremely large hernia with almost all the abdominal organs in the hernia sac and an HV:IAV ratio of 30.6 (Fig. 2). Hernia characteristics and measurements are presented in Table 2. Using the EHS classification, midline hernias extended over more than one M-zone in 96% of patients and over four or five M-zones in 28% of patients.
BTA injection was three layered in 56 (52%) and two layered in 52 patients (48%), with 106 patients injected under CT guidance and two under US guidance. Three patients received unilateral injections: two flank hernias and one ventral hernia with severe muscle atrophy of the left side after earlier CST and abdominal wall resection. Patients received an average of 243 units of BTA, an average of 32.5 (SD 10.1) d before surgery. There were no complications of BTA injection. The surgical wound was classified as CDC class three or four in 41 patients (38%), with 15 enterocutaneous fistulas (13%) and 15 mesh infections (13%). In 19% of patients, an ostomy was involved in the surgery, and in 27%, the gastrointestinal tract was entered as part of the procedure. Operative details of all patients can be found in Table 3.
In all but ten patients (9%), fascial closure was achieved. Five patients had severe LOD with an HV:IAV>0.5, five patients had prior abdominal wall resections, three patients had extensive scarring and stiffening of the abdominal wall after previous hernia repairs and infection, and two patients had large hernias with multiple abdominal wall defects. CST was required in 62 patients (57%) to achieve fascial closure. There was no difference in fascial closure or the need for CST comparing two- versus three-layer BTA. Hernias that were predominantly in the upper midline zones, especially going onto the costal margin bilaterally, required significantly higher rates of CST to achieve fascial closure than lower abdominal hernias. Using the EHS classification,
88% subxiphoidal hernias (M1) needed a form of CST (compared with 50% for hernia not extending into M1, P < 0.001), with 48% of the M1-hernias requiring bilateral EOR. Overall complications (53 versus 22%, P < 0.001), occurrence of SSO (29 versus 7%, P = 0.003), and respiratory failure (18 versus 0%, P = 0.002) were significantly increased in those patients requiring CST compared with patients not requiring CST.
Mesh augmentation was performed in almost all patients, with 95% of the meshes placed preperitoneal and 5% intraperitoneal. Implanted meshes had a mean size of 1,085 cm2 (SD 596.7) and a mean mesh to hernia defect ratio of 5.16. Patients with CDC class three or four or immunosuppression received a non–cross-linked porcine biologic (Strattice, Allergan Inc., Irvine, CA, USA) or biosynthetic mesh (Gore Bio-A, WL Gore & Assoc, Flagstaff, AZ, USA).
Complications occurred in 40% of patients, with the most common complications being SSO in 19%, SSI in 12%, cardiac dysrhythmias in 10%, acute kidney injury in 9%, respiratory failure requiring reintubation in 7%, deep venous thrombosis in 6%, pneumonia in 5%, and pulmonary embolism in 5%. Two patients died in the postoperative course: one by aspiration pneumonia and one due to abdominal sepsis caused by a perforated duodenal ulcer after discharge but within 30 d of surgery. There was no fascial dehiscence, and two mesh infections (2%) occurred, both in a synthetic mesh (macroporous midweight polypropylene mesh). Mean length of stay was 9.2 d (SD 7.2).
Seven recurrences were found after mean 14 mo of follow-up. All patients underwent surgery for recurrent hernias, six were diabetics, in six, prior implanted mesh was excised, five hernias were abutting bony structures (costal margins, pelvis, or spine), three had severe LOD with an HV:IAV>0.5, and three had CDC class 4 wound at the time of surgery. In two CDC class four patients, the fascia could not be completely closed during AWR and a partially bridging non–cross-linked porcine biological mesh was implanted, which made a small recurrence inevitable.
In this study on patients with massive ventral hernias and LOD, preoperative BTA was associated with very high rates of fascial closure during AWR. The ability to close the fascia is an important factor in decreasing SSO and recurrence rates.
The recurrence rate in patients receiving preoperative BTA for AWR was 6% after 14 months of follow-up. This is an excellent recurrence rate considering the size of the hernia defects (mean width 15 cm) and severe LOD (mean 46% of the visceral volume in the hernia sac).
Because administering BTA preoperatively for AWR is a relatively new technique, studies with long-term follow-up will need to be performed in the coming years to determine the influence on long-term hernia recurrence rates.
Almost half of the patients receiving preoperative BTA did not need CST during AWR. Hernias in the upper midline needed significantly more CST to achieve fascial closure than lower midline hernias. Subxiphoid hernias needed a form of CST in 88% to achieve fascial closure. Mid and lower midline hernias seem to benefit the most from preoperative BTA injections in decreasing need for CST. It appears that when the rectus muscles retract well back at the level of the costal margin, a unilateral or bilateral EOR well up onto the costal margin is often required to complete the subxiphoid fascial closure. Any form of CST in large ventral hernia is associated with increased wound complications and recurrence rates.
Comparing BTA patients with and without CST, a significant reduction in postoperative complications, especially SSOs and respiratory failure requiring reintubation, was found. This could partly be due to the avoidance of large subcutaneous dissections and creation of skin flaps required for open EOR. Patients requiring any form of CST typically have more tension on the abdominal wall and fascial closure. In patients without CST, an overall reduction in tension on the abdominal wall and healing tissues might have improved tissue perfusion in general and improve wound healing.
Although BTA use for AWR is currently off-label, in the present study, it was found to be safe with no known complications. This is comparable with other studies that reported none or minor complications after BTA injection in the abdominal wall.
Patients with neuromuscular junction disorders, such as myasthenia gravis, Lambert-Eaton syndrome, and anterior horn disorders are particularly susceptible to adverse events of botulinum toxin and should not be injected with BTA.
At least the EO and IO muscle of the abdominal wall should be injected with BTA. In this initial period of this study, the TA was not injected if it was felt to be atrophic on CT or US images. After publication of a study comparing the two- versus three-layer BTA injections with no differences in outcomes,
only the EO and IO were routinely injected during the latter cases. In our study, there were no differences between fascial closure rates, CST, or postoperative complications when comparing injection techniques including all three muscle layers or the EO and IO only, but a reduction of costs was achieved. Paralysis of all three layers of the lateral abdominal wall could interfere with the stabilizing function of the core abdominal muscles, potentially causing back pain after BTA injections.
However, in large ventral hernias, the stabilizing function is likely already impaired because of disruption of the midline. The present study used 200U of onabotulinum toxin A (Botox) for 2-layered and 300U for 3-layered BTA injection in a 2U per mL concentration, which is comparable with other published dosage and techniques.
Timing of BTA injection of approximately a month before surgery seems the most beneficial for AWR.
There is currently no clear consensus on how to select patients that will benefit from preoperative BTA before AWR. When selecting patients, it is important not only to take into account the hernia defect size, location, and proximity to bony structures, but also the presence and severity of LOD. By using three-dimensional volume measurements on preoperative CT scans, distribution of adipose tissue and the LOD can be accurately determined and used for selecting patients.
The positive results of preoperative BTA on reducing CST and postoperative complications might expand the indication for use to moderate-sized abdominal wall hernias and make it quite cost-effective. We would propose that patients with hernia defects over 10 cm in width, LOD over 20%, and after previous hernia repair including CSTs would qualify for preoperative BTA injection. Patients who have retracted and bulky lateral abdominal muscle on CT, or increased abdominal girth without laxity on abdominal examination, will benefit from preoperative BTA injection.
The major limitations of this study are the observational character, lack of clearly defined criteria to select patients for BTA, and lack of a control group. However, this study shows the safety and effectiveness of BTA use in AWR. If BTA is approved for use in AWR, a randomized controlled trial is needed to confirm these results.
Improving outcomes of AWR in large hernias starts with optimization of modifiable patient factors, such as weight loss, smoking cessation, and diabetes regulation. To reduce complication and recurrence rates, during AWR, the goal should be to achieve primary fascial closure with mesh reinforcement, instead of bridging the hernia defect with mesh.
BTA is currently off-label in AWR. However, this study shows that preoperative BTA is safe and allows optimization of previously nonmodifiable hernia-specific characteristics and increases the ability to achieve fascial closure during hernia repair with excellent recurrence rates. Considering that most patients had a previous failed hernia repair, BTA may need to be used as first-line hernia therapy to minimize the need for deconstruction of the abdominal wall during ventral hernia repair. In selected patients, chemical component separation and preperitoneal mesh placement may provide a conservative and more effective option for repair of complex ventral hernias.
We would like to acknowledge the contributions of Mrs Tanushree Prasad, MA, by performing all statistical analysis for this study.
Authors' contributions: All authors made substantial contributions of (1) conception and design, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be published, and (4) agree to be accountable for all aspects of the work if questions arise related to its accuracy or integrity. R.J.R., R.L., V.A.A., K.W.K., and B.T.H. developed and implemented the specified botulinum-toxin injection protocol at our institution and designed this study. V.A.A., K.W.K., P.D.C., and B.T.H. performed all abdominal wall reconstructions and acquired patient data. E.B.D., S.A.E., and J.M.S. performed CT measurements, follow-up, data collection, and interpretation.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. B.T.H. has been awarded education grants and honoraria from W.L. Gore, Allergan, and Stryker. V.A.A. has received honoraria for speaking for Medtronic, Allergan, Intuitive, Acelity, and W.L. Gore. These involvements did not influence the interpretation of results or drafting of this manuscript. All other authors have no relevant financial or personal relationships to disclose that could influence this work or its conclusions.
Small bites versus large bites for closure of abdominal midline incisions (STITCH): a double-blind, multicentre, randomised controlled trial.
Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement versus primary suture only in midline laparotomies (PRIMA): 2-year follow-up of a multicentre, double-blind, randomised controlled trial.