Clinical Neurology and Neurosurgery 116 (2014) 20–23
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Autologous dural substitutes: A prospective study Giovanni Sabatino, Giuseppe Maria Della Pepa ∗ , Federico Bianchi, Gennaro Capone, Luigi Rigante, Alessio Albanese, Giulio Maira, Enrico Marchese Institute of Neurosurgery, Catholic University of Rome, Rome, Italy
a r t i c l e
i n f o
Article history: Received 27 July 2013 Received in revised form 16 October 2013 Accepted 9 November 2013 Available online 17 November 2013 Keywords: Duraplasty Dural substitutes Dural graft Pericranium Galea
a b s t r a c t Objective: Duraplasty can be performed both by means of autologous tissues (such as galea-pericranium, temporal muscle, fascia lata) or by commercially available dural patches. Nowadays many neurosurgeons consider galea-pericranium duraplasty time-consuming, technically demanding or not adequate, thus dural surrogates are increasingly popular. In this prospective research we compared duraplasty using autologous galea-pericranium vs. dural patches in terms of postoperative long term results, ease/time required and costs. Patients and methods: Research has been designed as prospective cohort study, that included 185 patients undergoing supratentorial elective neurosurgery with galea-pericranium or non-autologous duraplasty (minimum follow-up 12 months). Variables taken into account were: wound infection, CSF fistula, subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence (particularly after postoperative radiotherapy). Time for galea-pericranium collection, size of galeapericranium harvest and dural defects were recorded in each case. Costs for non-autologous duroplasty were calculated. Results: No statistically significant differences were evident in long term postoperative results between the two groups. Mean time of galea-pericranium collection is less than 2 min and enough galeapericranium can be harvested in supratentorial approach to cover almost any dural defect. The only difference between the two groups is costs: an average of 268.7D /patient spent just for duraplasty. This figure is surely substantial if considered for the entire amount of surgeries performed in a department. Conclusions: Considering that in our study long term results are equivalent, that galea-pericranium duraplasty is feasible and rapid, our indications are in favor of saving a considerable amount of money since an ideal autologous dural substitute is available and “free”. © 2013 Elsevier B.V. All rights reserved.
1. Introduction Neurosurgeons often deal with the problem of a complete and watertight dural closure after cerebral operative procedures [1]. When dura mater cannot be sutured directly a dural substitute is needed; despite 100 years of experimentation and investigation of a wide range of materials, the research for the ideal substitute still continues. In everyday neurosurgical practice, numerous autogenic, allogenic, xenogenic, absorbable, and nonabsorbable synthetic materials have been used with varying degrees of success in the search for the perfect dural graft [2–6]. Autologous grafts such as galea-pericranium or fascia lata represent an optimal dural graft substrate because they do not induce immunological or inflammatory reactions and they are nontoxic, rapidly integrated into native tissues, flexible, strong, easily
∗ Corresponding author at: Institute of Neurosurgery Catholic University of Rome, Largo A. Gemelli 8, 00168 Rome, Italy. Tel.: +39 0630154120; fax: +39 063051343. E-mail address: [email protected] (G.M. Della Pepa). 0303-8467/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2013.11.010
suturable, and inexpensive. Unfortunately, it is not always possible to perform autograft using these tissues [3,5,7,8]. Nowadays non-autogenous dural surrogates are increasingly popular and widely diffused in neurosurgical practice, as effective, feasible, easy to use and rapidly deployable, although some articles underline their association with potentially harmful complications [2,3,6,8,9]. Although the clear qualities of autologous grafts, there are few articles about their use and indications, while many authors emphasize the properties of numerous non-autologous dural substitutes. Although many authors advice to implant autologous tissue such as pericranium whenever possible, as a matter of fact, nowadays, many neurosurgeons are believe it is time demanging and that not enough galea-pericranium can be easily harvested to fill large dural defects [1]. We present a prospective study in which we aim to demonstrate that galea-pericranium duraplasty is as easy/rapid to use and as effective as non-autogenous dural surrogates: the only difference is cost.
G. Sabatino et al. / Clinical Neurology and Neurosurgery 116 (2014) 20–23
2. Materials and methods
Table 1 Overview of population characteristics.
2.1. Study design
Total number of patients
This prospective cohort study includes all patients who underwent duraplasty with galea-pericranium or non-autologous dural patch from November 2009 to November 2011 in our Neurosurgical Department. Study has been designed in a randomized fashion so that autologous or non-autologous graft material were used alternatively (if duraplasty with patch is used in a surgical procedure, in the following one, if duraplasty is required, galea-pericranium duraplasty would be used). Informed consent was obtained from any study participant in which it was clearly stated what kind of duraplasty was going to be performed if necessary and that data would have been included in a trial. Galea-pericranium graft was always performed by the same operator in order to standardize the procedure. Non-autologous dural patch used was Tutopatch (Tutogen Medical GmbH).
Total galea-pericranium patients
2.2. Inclusion criteria We considered for the study cases operated on elective surgery, for supratentorial neoplasms, meningiomas and cerebral aneurysms, in which duroplasty was necessary (native dura cannot be tight directly). Only first time surgery was considered. Emergency surgery, posterior cranial fossa, cerebello-pontine angle and skull base surgery were not included in order to standardize patient sample. 2.3. Data collection Time used for galea-pericranium collection was measured in all procedures in which it was adopted, by means of operating room timer. Size of galea-pericranium (measured as soon as collected) and dural defect was measured in all cases using sterile centimeter. For those cases in which non-autologous patch was applied, its size was recorded. It is worth to emphasize that in several cases the dural defect has an irregular shape or a size different from the standard measures of commercialized patches: for this reason a patch larger than the defect in order to perform duraplasty is sometimes needed. The follow-up period was in all cases of at least 12 months. Patients who survived less than 12 months were not included in the study. Variables taken into account for follow up were: the presence of wound infection, CSF fistula, subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence (particularly in patients undergoing postoperative radiotherapy). Data were collected for each patient on standardized forms including age, sex, neurological diagnosis, site of surgery, comorbidities. All patients underwent same prophylactic antibiotics medication (cephazoline 1 g initiated before skin incision). For all patients, protocols for infection surveillance were the same (check of temperature at least three times per day and examination of wound every 3 days). Costs for non-autologous duroplasty were calculated (data regarding costs of dural patches were provided by our Hospital Administration) and expressed as cost per patient, overall cost for the entire study sample and cost per cm2 of dural defect. 2.4. Galea-pericranium collection procedure and duraplasty Galea-pericranium is blunt dissected by means of Metzenbaum scissors and/or by fingers. During collection the surgical area is continuously irrigated with Ringer solution. At the dura closure
21
Total tutopatch patients Mean dural gap Mean galea-pericranium collection time Surgical approaches used in the galea-pericranium group
Surgical approaches in the tutopatch group
185 (61 M/124F, mean age 55 ± 15 years old) 93 (28 M/65F, mean age 53.5 ± 15 years old) 92 (33 M/59F, mean age 56.7 ± 15.9 years old) 12.7 ± 7.7 cm2 1.45 ± 0.38 min 23 Pterional, 10 fronto-temporal, 5 occipital, 17 fronto-parietal, 14 parietal, 3 occipito-parietal and 23 frontal 20 Pterional, 15 fronto-temporal, 2 occipital, 10 fronto-parietal, 5 parietal, 1 occipito-parietal and 37 frontal
the galea-pericranium is placed over the dural defect and firmed with 3 or 4 stitches; it is then sutured in by the use of running 3–0 monocryl suture. Fibrin glue (Tisseel Baxter) is then applied over the suture as a sealant. Similarly when non-autologous dural patch is used, it is directly sutured to native dura (first firmed with 3 or 4 stitches and then sutured with a running 3–0 monocryl suture). Fibrin glue (Tisseel Baxter) is applied over the suture. 2.5. Statistical analysis For data concerning size of dural gap and galea-pericranium collection time data were expressed as mean ± standard deviation. Significance of data concerning postoperative complications (wound infection, CSF fistula, subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence) was analyzed by two-sided Fisher Exact test; a probability of 0.05 or less was considered significant. Homogeneity between the groups in terms of sex and age (divided in the following sub-categories 0–20 years, 21–40 years, 41–60 years, 61–80 years, >81 years) has been also analyzed by means of 2 test (probability of 0.05 or less has been considered significant). 3. Results During the study period, in our Department 1637 craniotomies were performed. Only 192 cases satisfied inclusion criteria; among these, 7 patients died before reaching the minimum 12 months follow-up period. Thus, we have analyzed 185 patients, 61 males and 124 females, mean age of 55 years with a minimum of 16 years old and a maximum of 85 years old. Main results are reported in Table 1. They were divided in two groups: the galea-pericranium group formed by 93 patients (28 males and 65 females, mean age 53.5 ± 15 years old) and the Tutopatch (Tutogen Medical GmbH) group including 92 patients (33 males and 59 females, mean age 56.7 ± 15.9 years old). The co-morbidity rate was 33.5% (62 of 185 patients) with pathologies such as arterial hypertension, diabetes, atrial fibrillation, parkinsonism, leukemia, COPD, and hypercholesterolemia. Population of the two groups were statistically homogenous in terms of sex (p = 0.361 n.s.) and age (p = 0.9408 n.s.). In the galea-pericranium group there were 24 aneurysms, 6 cavernomas, 29 meningiomas, 34 tumors while in the Tutopatch group there were 20 aneurysm, 2 cavernomas, 22 meningiomas, 48 tumors. Surgical approaches used in the galea-pericranium group were 23 pterional, 10 fronto-temporal, 5 occipital, 17 fronto-parietal, 14 parietal, 3 occipito-parietal and 23 frontal; while in the tutopatch
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G. Sabatino et al. / Clinical Neurology and Neurosurgery 116 (2014) 20–23
Table 2 Postoperative complications.
Galea-pericranium Tutopatch p
Subcutaneous fluid collection
Wound infection
3 4 0.7175 (n.s.)
0 1 0.4973 (n.s.)
group were 20 pterional, 15 fronto-temporal, 2 occipital, 10 frontoparietal, 5 parietal, 1 occipito-parietal and 37 frontal. Mean time of dissection to harvest galea-pericranium graft was 1.45 ± 0.38 min with a minimum of 1 min and a maximum of 2.5 min; obviously for the Tutopatch group no collection time was needed. The 37.3% (29 of 93 patient of the galea-pericranium group and 40 of 92 patients of the tutopach group) of the patients was treated with postoperative radiotherapy. The mean entity of the dural gap in the whole group was 12.7 ± 7.7 cm2 ; for the galea-pericranium group it was 12.8 ± 7.8 cm2 while for the Tutopatch group it was 12.6 ± 7.6 cm2 . Wound infection rate in the galea-pericranium group was 0% (0 of 93 patients) and 1.08% in the Tutopatch group (1 of 92 patients) (two-sided Fisher exact test, p ≤ 0.4973 n.s.). Subcutaneous fluid collection rate in the galea-pericranium and Tutopatch groups were: 3.2% (3 of 93 patients) and 4.34% (4 of 92 patients) (two-sided Fisher exact test, p ≤ 0.7175 n.s), respectively. In both group there were no CSF fistula, brain abscess, empyema, wound dehiscence or radiotherapic sequelae. From the analysis of this data it is possible to see how there were no statistically significative differences between the two groups in the studied variables, as shown in Table 2. The total cost for the Tutopatch group was 24,721D with a cost per patient of 268.7D and a cost per cm2 of 21.2D . 4. Discussion
However also nonautogenous grafts have been associated with potentially harmful complications in a relatively small number of papers; these include hemorrhage, bacteria, virus and fatal Creutzfeldt-Jakob disease transmission, foreign body reaction, systemic immune response, excessive scarring, lower healing, premature graft dissolution, CSF fistula, aseptic meningitis, hydrocephalus, pseudomeningocele, cortical inflammation, adhesions, and wound dehiscence [1–3,6,8,9]. Although many authors advice to implant autologous tissue such as pericranium whenever possible, as a matter of fact, nowadays, many neurosurgeons are discouraged to do so because it requires time both to withdraw the galea-pericranium layer and to suture it. In addition, the issue of whether or not it is better to use a galea-pericranium graft or a non-autologous dural substitute for dural closure in neurosurgery has probably never been adequately studied.
4.2. Galea harvest – limited and time demanding? Galea-pericranium collection requires only attention during skin incision, avoiding any damage in dissecting it from subcutaneous tissue in order to obtain a layer large enough for dural closure. We showed that the time for dural closure with galeapericranium or any dural substitutes is short. From our results mean time of galea-pericranium collection is less than 2 min (namely an average of 1.45 ± 0.38 min). In addition, enough galea-pericranium can be harvested during any type of supratentorial approach both with linear and horseshoe skin incision shaped. With the introduction of neuronavigation systems, craniotomies are always smaller and so in our procedure dural defect are often around 12 cm2 (12.7 ± 7.7 cm2 ). This size is easily covered from galea-pericranium previously taken. In particular in our study we managed to fill with galea-pericranium defects up to 39 cm2 , and collected even larger galea-pericranium grafts.
4.1. Duraplasty – an historical glance 4.3. Galea vs. patch – complications Since 1890 when Beach suggested use of gold foil to prevent meningocerebral adhesions, many substances have been experimented and used clinically as dural substitutes [10]. However, the ideal solution still remains to be found [5]. Watertight dural closure is necessary to prevent postoperative cerebrospinal fluid (CSF) fistula, infections, hypertensive pneumocephalus, pseudomeningocele, neural tissue hernation and cortical scarings [5,11]. The large number of materials used as dural graft include both biologic tissues (autologous, homologous, and heterologous) and synthetic materials [2,5,8,12,13]. For many years lyophilized homologous dura mater sterilized by X-rays (Lyodura) has been widely used because of its easiness and its wide availability. Unfortunately, the present sterilization methods do not protect from the risk of latent virus infections, and some cases of probable Creutzfeldt-Jacob disease (CJD) have been reported [14,15]. However, these cases remain unclear because there are not other cases in patients treated with the same lot of dura. Moreover, the use of dural grafts obtained from cadaver has not been prohibited by World Health Organization [15]. Autografts, such as pericranium or temporal fascia, have several and clear advantages: they are easy to handle, nontoxic, inexpensive, and have a favorable biologic behavior. Unfortunately, it is not always possible to perform autograft with these tissues. Pericranium can be damaged and can be insufficient when the dural defect is large. The use of autologous fascia lata has never been popular because it requires an additional incision, with additional operating time, and it can be related with complications at the donor site [2,16].
In our study we analyzed a broad spectrum of possible complications related with duraplasty, as wound infection, CSF fistula, the presence of subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence, especially for those patients undergoing postoperative radiotherapy. Surgical procedures and preoperative risk factors for neurosurgical site infections were similar in the patch and galea-pericranium groups. The results of our investigation indicates that no significant differences between galea-pericranium and the other dural substitute, we employed, exist; from our results galea-pericranium vs. nonautologous patch display a similar rate of complications also in long term follow up and in those cases undergoing postoperative radio/chemio-therapy. Hoover et al. described an ossification of autologous pericranium used in duraplasty [7]. In our series, we have not recorded similar complications because our galea-pericranium has no vascolarization, as it is not peduncolated. In fact periosteum has traditionally been considered osteogenic because it contains quiescent osteoblasts that become active in special situations: this phenomenon occur only if it is vascularized. Stendel et al. described extensive meningocerebral adhesions to occur after use of autologous grafts [9]. We have not faced such a complication because we did not include reoperations. However in our study there was no clinical evidence of cerebral adhesion. Filippi et al. described their positive experiences with the use of solvent preserved gamma sterilized bovine pericardium (Tutopatch+, Tutogen Medical GmbH) [17]. Our data confirmed such a finding.
G. Sabatino et al. / Clinical Neurology and Neurosurgery 116 (2014) 20–23
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4.4. Galea vs. patch – pharmacoeconomics
Disclosure statement
At a time when physicians are attempting to curtail the rising cost of medicine, lowering medical costs is both an ethical and medical goal. In our prospective study we showed that galeapericranium duraplasty is comparable to other dural substitutes in terms of postoperative results. The macroscopic difference between the two groups is, however, costs. Form our analysis the total cost for the Tutopatch group was 24,721D with a cost per patient of 268.7D and a cost per cm2 of 21.2D . These figures represent certainly an even more relevant data if considered on a longer term analysis including the entire number of neurosurgical procedures. In fact in our study we have taken into account only a very restricted population sample (93 patients), with a 24,989D saved. If in our Department we would have regularly used galea-pericranium in all the procedures in which it could be potentially applied, the potential cost-retail would have been certainly relevant on the department budget.
The authors declare no interest to disclose, they have any personal or institutional financial interest in drugs, materials, or devices described in this submission and that they did not receive any specific funding. The paper and any of its contents have been presented previously.
5. Conclusions Considering that long term results are equivalent, that galeapericranium collection is an easy feasible procedure that requires no longer than 2 min before craniotomy. Thus it does not significantly prologues surgical time. Is it really worth to spend a considerable amount of money for duraplasty when it is available an ideal autologous dural surrogate that is simply “free”? So based on an ethical and pharmacoeconomic prospective we advice the use of galea-pericranium for all neurosurgical procedures, as it has no side effects, it is comparable to the available commercialized non-authologous patches, and it is costless. Even if in the present study we have taken into account only supratentorial surgery in order to standardize our sample, it should also considered relevant recent literature that has tested as effective the use of galea-pericranium also for other neurosurgical procedures, including posterior cranial fossa surgery [3,8]. The aim of the present study was not to demonstrate superiority of galea-pericranium duraplasty compared to other non-authologous patches. Indeed our results display that it is equivalent to duraplasty performed with other common nonauthologous dural patches in terms of postoperative results. The only massive difference is cost. Our study shows that galeapericranium duraplasty is feasible, collection is not time consuming and that even large dural defects can be repaired. The issue of unnecessary costs in medicine is nowadays imperative; we hope there will be more studies in the future about its economical impact, particularly in communities with limited resources.
References [1] Ostendorf AP, Connolly AM. Medical management of eosinophilic meningitis following bovine graft duraplasty for Chiari malformation Type I repair. J Neurosurg Pediatr 2013;12:357–9. [2] Sandoval-Sanchez JH, Ramos-Zuniga R, de Anda SL, Lopez-Dellamary F, Gonzalez-Castaneda R, Ramirez-Jaimes Jde L, et al. A new bilayer chitosan scaffolding as a dural substitute: experimental evaluation. World Neurosurg 2012;77:577–82. [3] Lam FC, Kasper E. Augmented autologous pericranium duraplasty in 100 posterior fossa surgeries-a retrospective case series. Neurosurgery 2012;71(Suppl. Operative):ons302–7. [4] Gazzeri R, Galarza M, Alfieri A, Neroni M, Roperto R. Simple intraoperative technique for minor dural gap repair using fibrin glue and oxidized cellulose. World Neurosurg 2011;76:173–5. [5] Malliti M, Page P, Gury C, Chomette E, Nataf F, Roux FX. Comparison of deep wound infection rates using a synthetic dural substitute (neuro-patch) or pericranium graft for dural closure: a clinical review of 1 year. Neurosurgery 2004;54:599–603 [discussion 603–594]. [6] Cappabianca P, Esposito F, Magro F, Cavallo LM, Solari D, Stella L, et al. Natura abhorret a vacuo – use of fibrin glue as a filler and sealant in neurosurgical dead spaces. Technical note. Acta Neurochir (Wien) 2010;152:897–904. [7] Hoover DA, Mahmood A. Ossification of autologous pericranium used in duraplasty. Case report. J Neurosurg 2001;95:350–2. [8] Stevens EA, Powers AK, Sweasey TA, Tatter SB, Ojemann RG. Simplified harvest of autologous pericranium for duraplasty in Chiari malformation Type I. Technical note. J Neurosurg Spine 2009;11:80–3. [9] Stendel R, Danne M, Fiss I, Klein I, Schilling A, Hammersen S, et al. Efficacy and safety of a collagen matrix for cranial and spinal dural reconstruction using different fixation techniques. J Neurosurg 2008;109:215–21. [10] Knopp U, Christmann F, Reusche E, Sepehrnia A. A new collagen biomatrix of equine origin versus a cadaveric dura graft for the repair of dural defects – a comparative animal experimental study. Acta Neurochir (Wien) 2005;147:877–87. [11] Della Pepa GM, Montano N, Lucantoni C, Alexandre AM, Papacci F, Meglio M. Craniotomy repair with the retrosigmoid approach: the impact on quality of life of meticulous reconstruction of anatomical layers. Acta Neurochir (Wien) 2011;153:2255–8. [12] Zaidi HA, Pendleton C, Cohen-Gadol AA, Quinones-Hinojosa A. Harvey Cushing’s repair of a dural defect after a traumatic brain injury: novel use of a fat graft. World Neurosurg 2011;75:696–9. [13] Rosen CL, Steinberg GK, DeMonte F, Delashaw Jr JB, Lewis SB, Shaffrey ME, et al. Results of the prospective, randomized, multicenter clinical trial evaluating a biosynthesized cellulose graft for repair of dural defects. Neurosurgery 2011;69:1093–103 [discussion 1103–1094]. [14] Tanaka S, Fukushima M. Size of Creutzfeldt-Jakob disease epidemic associated with cadaveric dura transplantation. Neuroepidemiology 2010;34:232–7. [15] Ishida C, Okino S, Kitamoto T, Yamada M. Involvement of the peripheral nervous system in human prion diseases including dural graft associated CreutzfeldtJakob disease. J Neurol Neurosurg Psychiatry 2005;76:325–9. [16] Lam FC, Penumaka A, Chen CC, Fischer EG, Kasper EM. Fibrin sealant augmentation with autologous pericranium for duraplasty after suboccipital decompression in Chiari 1 patients: A case series. Surg Neurol Int 2013;4:6. [17] Filippi R, Schwarz M, Voth D, Reisch R, Grunert P, Perneczky A. Bovine pericardium for duraplasty: clinical results in 32 patients. Neurosurg Rev 2001;24:103–7.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Autologous dural substitutes: A prospective study Giovanni Sabatino, Giuseppe Maria Della Pepa ∗ , Federico Bianchi, Gennaro Capone, Luigi Rigante, Alessio Albanese, Giulio Maira, Enrico Marchese Institute of Neurosurgery, Catholic University of Rome, Rome, Italy
a r t i c l e
i n f o
Article history: Received 27 July 2013 Received in revised form 16 October 2013 Accepted 9 November 2013 Available online 17 November 2013 Keywords: Duraplasty Dural substitutes Dural graft Pericranium Galea
a b s t r a c t Objective: Duraplasty can be performed both by means of autologous tissues (such as galea-pericranium, temporal muscle, fascia lata) or by commercially available dural patches. Nowadays many neurosurgeons consider galea-pericranium duraplasty time-consuming, technically demanding or not adequate, thus dural surrogates are increasingly popular. In this prospective research we compared duraplasty using autologous galea-pericranium vs. dural patches in terms of postoperative long term results, ease/time required and costs. Patients and methods: Research has been designed as prospective cohort study, that included 185 patients undergoing supratentorial elective neurosurgery with galea-pericranium or non-autologous duraplasty (minimum follow-up 12 months). Variables taken into account were: wound infection, CSF fistula, subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence (particularly after postoperative radiotherapy). Time for galea-pericranium collection, size of galeapericranium harvest and dural defects were recorded in each case. Costs for non-autologous duroplasty were calculated. Results: No statistically significant differences were evident in long term postoperative results between the two groups. Mean time of galea-pericranium collection is less than 2 min and enough galeapericranium can be harvested in supratentorial approach to cover almost any dural defect. The only difference between the two groups is costs: an average of 268.7D /patient spent just for duraplasty. This figure is surely substantial if considered for the entire amount of surgeries performed in a department. Conclusions: Considering that in our study long term results are equivalent, that galea-pericranium duraplasty is feasible and rapid, our indications are in favor of saving a considerable amount of money since an ideal autologous dural substitute is available and “free”. © 2013 Elsevier B.V. All rights reserved.
1. Introduction Neurosurgeons often deal with the problem of a complete and watertight dural closure after cerebral operative procedures [1]. When dura mater cannot be sutured directly a dural substitute is needed; despite 100 years of experimentation and investigation of a wide range of materials, the research for the ideal substitute still continues. In everyday neurosurgical practice, numerous autogenic, allogenic, xenogenic, absorbable, and nonabsorbable synthetic materials have been used with varying degrees of success in the search for the perfect dural graft [2–6]. Autologous grafts such as galea-pericranium or fascia lata represent an optimal dural graft substrate because they do not induce immunological or inflammatory reactions and they are nontoxic, rapidly integrated into native tissues, flexible, strong, easily
∗ Corresponding author at: Institute of Neurosurgery Catholic University of Rome, Largo A. Gemelli 8, 00168 Rome, Italy. Tel.: +39 0630154120; fax: +39 063051343. E-mail address: [email protected] (G.M. Della Pepa). 0303-8467/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2013.11.010
suturable, and inexpensive. Unfortunately, it is not always possible to perform autograft using these tissues [3,5,7,8]. Nowadays non-autogenous dural surrogates are increasingly popular and widely diffused in neurosurgical practice, as effective, feasible, easy to use and rapidly deployable, although some articles underline their association with potentially harmful complications [2,3,6,8,9]. Although the clear qualities of autologous grafts, there are few articles about their use and indications, while many authors emphasize the properties of numerous non-autologous dural substitutes. Although many authors advice to implant autologous tissue such as pericranium whenever possible, as a matter of fact, nowadays, many neurosurgeons are believe it is time demanging and that not enough galea-pericranium can be easily harvested to fill large dural defects [1]. We present a prospective study in which we aim to demonstrate that galea-pericranium duraplasty is as easy/rapid to use and as effective as non-autogenous dural surrogates: the only difference is cost.
G. Sabatino et al. / Clinical Neurology and Neurosurgery 116 (2014) 20–23
2. Materials and methods
Table 1 Overview of population characteristics.
2.1. Study design
Total number of patients
This prospective cohort study includes all patients who underwent duraplasty with galea-pericranium or non-autologous dural patch from November 2009 to November 2011 in our Neurosurgical Department. Study has been designed in a randomized fashion so that autologous or non-autologous graft material were used alternatively (if duraplasty with patch is used in a surgical procedure, in the following one, if duraplasty is required, galea-pericranium duraplasty would be used). Informed consent was obtained from any study participant in which it was clearly stated what kind of duraplasty was going to be performed if necessary and that data would have been included in a trial. Galea-pericranium graft was always performed by the same operator in order to standardize the procedure. Non-autologous dural patch used was Tutopatch (Tutogen Medical GmbH).
Total galea-pericranium patients
2.2. Inclusion criteria We considered for the study cases operated on elective surgery, for supratentorial neoplasms, meningiomas and cerebral aneurysms, in which duroplasty was necessary (native dura cannot be tight directly). Only first time surgery was considered. Emergency surgery, posterior cranial fossa, cerebello-pontine angle and skull base surgery were not included in order to standardize patient sample. 2.3. Data collection Time used for galea-pericranium collection was measured in all procedures in which it was adopted, by means of operating room timer. Size of galea-pericranium (measured as soon as collected) and dural defect was measured in all cases using sterile centimeter. For those cases in which non-autologous patch was applied, its size was recorded. It is worth to emphasize that in several cases the dural defect has an irregular shape or a size different from the standard measures of commercialized patches: for this reason a patch larger than the defect in order to perform duraplasty is sometimes needed. The follow-up period was in all cases of at least 12 months. Patients who survived less than 12 months were not included in the study. Variables taken into account for follow up were: the presence of wound infection, CSF fistula, subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence (particularly in patients undergoing postoperative radiotherapy). Data were collected for each patient on standardized forms including age, sex, neurological diagnosis, site of surgery, comorbidities. All patients underwent same prophylactic antibiotics medication (cephazoline 1 g initiated before skin incision). For all patients, protocols for infection surveillance were the same (check of temperature at least three times per day and examination of wound every 3 days). Costs for non-autologous duroplasty were calculated (data regarding costs of dural patches were provided by our Hospital Administration) and expressed as cost per patient, overall cost for the entire study sample and cost per cm2 of dural defect. 2.4. Galea-pericranium collection procedure and duraplasty Galea-pericranium is blunt dissected by means of Metzenbaum scissors and/or by fingers. During collection the surgical area is continuously irrigated with Ringer solution. At the dura closure
21
Total tutopatch patients Mean dural gap Mean galea-pericranium collection time Surgical approaches used in the galea-pericranium group
Surgical approaches in the tutopatch group
185 (61 M/124F, mean age 55 ± 15 years old) 93 (28 M/65F, mean age 53.5 ± 15 years old) 92 (33 M/59F, mean age 56.7 ± 15.9 years old) 12.7 ± 7.7 cm2 1.45 ± 0.38 min 23 Pterional, 10 fronto-temporal, 5 occipital, 17 fronto-parietal, 14 parietal, 3 occipito-parietal and 23 frontal 20 Pterional, 15 fronto-temporal, 2 occipital, 10 fronto-parietal, 5 parietal, 1 occipito-parietal and 37 frontal
the galea-pericranium is placed over the dural defect and firmed with 3 or 4 stitches; it is then sutured in by the use of running 3–0 monocryl suture. Fibrin glue (Tisseel Baxter) is then applied over the suture as a sealant. Similarly when non-autologous dural patch is used, it is directly sutured to native dura (first firmed with 3 or 4 stitches and then sutured with a running 3–0 monocryl suture). Fibrin glue (Tisseel Baxter) is applied over the suture. 2.5. Statistical analysis For data concerning size of dural gap and galea-pericranium collection time data were expressed as mean ± standard deviation. Significance of data concerning postoperative complications (wound infection, CSF fistula, subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence) was analyzed by two-sided Fisher Exact test; a probability of 0.05 or less was considered significant. Homogeneity between the groups in terms of sex and age (divided in the following sub-categories 0–20 years, 21–40 years, 41–60 years, 61–80 years, >81 years) has been also analyzed by means of 2 test (probability of 0.05 or less has been considered significant). 3. Results During the study period, in our Department 1637 craniotomies were performed. Only 192 cases satisfied inclusion criteria; among these, 7 patients died before reaching the minimum 12 months follow-up period. Thus, we have analyzed 185 patients, 61 males and 124 females, mean age of 55 years with a minimum of 16 years old and a maximum of 85 years old. Main results are reported in Table 1. They were divided in two groups: the galea-pericranium group formed by 93 patients (28 males and 65 females, mean age 53.5 ± 15 years old) and the Tutopatch (Tutogen Medical GmbH) group including 92 patients (33 males and 59 females, mean age 56.7 ± 15.9 years old). The co-morbidity rate was 33.5% (62 of 185 patients) with pathologies such as arterial hypertension, diabetes, atrial fibrillation, parkinsonism, leukemia, COPD, and hypercholesterolemia. Population of the two groups were statistically homogenous in terms of sex (p = 0.361 n.s.) and age (p = 0.9408 n.s.). In the galea-pericranium group there were 24 aneurysms, 6 cavernomas, 29 meningiomas, 34 tumors while in the Tutopatch group there were 20 aneurysm, 2 cavernomas, 22 meningiomas, 48 tumors. Surgical approaches used in the galea-pericranium group were 23 pterional, 10 fronto-temporal, 5 occipital, 17 fronto-parietal, 14 parietal, 3 occipito-parietal and 23 frontal; while in the tutopatch
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Table 2 Postoperative complications.
Galea-pericranium Tutopatch p
Subcutaneous fluid collection
Wound infection
3 4 0.7175 (n.s.)
0 1 0.4973 (n.s.)
group were 20 pterional, 15 fronto-temporal, 2 occipital, 10 frontoparietal, 5 parietal, 1 occipito-parietal and 37 frontal. Mean time of dissection to harvest galea-pericranium graft was 1.45 ± 0.38 min with a minimum of 1 min and a maximum of 2.5 min; obviously for the Tutopatch group no collection time was needed. The 37.3% (29 of 93 patient of the galea-pericranium group and 40 of 92 patients of the tutopach group) of the patients was treated with postoperative radiotherapy. The mean entity of the dural gap in the whole group was 12.7 ± 7.7 cm2 ; for the galea-pericranium group it was 12.8 ± 7.8 cm2 while for the Tutopatch group it was 12.6 ± 7.6 cm2 . Wound infection rate in the galea-pericranium group was 0% (0 of 93 patients) and 1.08% in the Tutopatch group (1 of 92 patients) (two-sided Fisher exact test, p ≤ 0.4973 n.s.). Subcutaneous fluid collection rate in the galea-pericranium and Tutopatch groups were: 3.2% (3 of 93 patients) and 4.34% (4 of 92 patients) (two-sided Fisher exact test, p ≤ 0.7175 n.s), respectively. In both group there were no CSF fistula, brain abscess, empyema, wound dehiscence or radiotherapic sequelae. From the analysis of this data it is possible to see how there were no statistically significative differences between the two groups in the studied variables, as shown in Table 2. The total cost for the Tutopatch group was 24,721D with a cost per patient of 268.7D and a cost per cm2 of 21.2D . 4. Discussion
However also nonautogenous grafts have been associated with potentially harmful complications in a relatively small number of papers; these include hemorrhage, bacteria, virus and fatal Creutzfeldt-Jakob disease transmission, foreign body reaction, systemic immune response, excessive scarring, lower healing, premature graft dissolution, CSF fistula, aseptic meningitis, hydrocephalus, pseudomeningocele, cortical inflammation, adhesions, and wound dehiscence [1–3,6,8,9]. Although many authors advice to implant autologous tissue such as pericranium whenever possible, as a matter of fact, nowadays, many neurosurgeons are discouraged to do so because it requires time both to withdraw the galea-pericranium layer and to suture it. In addition, the issue of whether or not it is better to use a galea-pericranium graft or a non-autologous dural substitute for dural closure in neurosurgery has probably never been adequately studied.
4.2. Galea harvest – limited and time demanding? Galea-pericranium collection requires only attention during skin incision, avoiding any damage in dissecting it from subcutaneous tissue in order to obtain a layer large enough for dural closure. We showed that the time for dural closure with galeapericranium or any dural substitutes is short. From our results mean time of galea-pericranium collection is less than 2 min (namely an average of 1.45 ± 0.38 min). In addition, enough galea-pericranium can be harvested during any type of supratentorial approach both with linear and horseshoe skin incision shaped. With the introduction of neuronavigation systems, craniotomies are always smaller and so in our procedure dural defect are often around 12 cm2 (12.7 ± 7.7 cm2 ). This size is easily covered from galea-pericranium previously taken. In particular in our study we managed to fill with galea-pericranium defects up to 39 cm2 , and collected even larger galea-pericranium grafts.
4.1. Duraplasty – an historical glance 4.3. Galea vs. patch – complications Since 1890 when Beach suggested use of gold foil to prevent meningocerebral adhesions, many substances have been experimented and used clinically as dural substitutes [10]. However, the ideal solution still remains to be found [5]. Watertight dural closure is necessary to prevent postoperative cerebrospinal fluid (CSF) fistula, infections, hypertensive pneumocephalus, pseudomeningocele, neural tissue hernation and cortical scarings [5,11]. The large number of materials used as dural graft include both biologic tissues (autologous, homologous, and heterologous) and synthetic materials [2,5,8,12,13]. For many years lyophilized homologous dura mater sterilized by X-rays (Lyodura) has been widely used because of its easiness and its wide availability. Unfortunately, the present sterilization methods do not protect from the risk of latent virus infections, and some cases of probable Creutzfeldt-Jacob disease (CJD) have been reported [14,15]. However, these cases remain unclear because there are not other cases in patients treated with the same lot of dura. Moreover, the use of dural grafts obtained from cadaver has not been prohibited by World Health Organization [15]. Autografts, such as pericranium or temporal fascia, have several and clear advantages: they are easy to handle, nontoxic, inexpensive, and have a favorable biologic behavior. Unfortunately, it is not always possible to perform autograft with these tissues. Pericranium can be damaged and can be insufficient when the dural defect is large. The use of autologous fascia lata has never been popular because it requires an additional incision, with additional operating time, and it can be related with complications at the donor site [2,16].
In our study we analyzed a broad spectrum of possible complications related with duraplasty, as wound infection, CSF fistula, the presence of subcutaneous CSF collection, bone flap osteitis, brain abscess, empyema and tardive wound dehiscence, especially for those patients undergoing postoperative radiotherapy. Surgical procedures and preoperative risk factors for neurosurgical site infections were similar in the patch and galea-pericranium groups. The results of our investigation indicates that no significant differences between galea-pericranium and the other dural substitute, we employed, exist; from our results galea-pericranium vs. nonautologous patch display a similar rate of complications also in long term follow up and in those cases undergoing postoperative radio/chemio-therapy. Hoover et al. described an ossification of autologous pericranium used in duraplasty [7]. In our series, we have not recorded similar complications because our galea-pericranium has no vascolarization, as it is not peduncolated. In fact periosteum has traditionally been considered osteogenic because it contains quiescent osteoblasts that become active in special situations: this phenomenon occur only if it is vascularized. Stendel et al. described extensive meningocerebral adhesions to occur after use of autologous grafts [9]. We have not faced such a complication because we did not include reoperations. However in our study there was no clinical evidence of cerebral adhesion. Filippi et al. described their positive experiences with the use of solvent preserved gamma sterilized bovine pericardium (Tutopatch+, Tutogen Medical GmbH) [17]. Our data confirmed such a finding.
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4.4. Galea vs. patch – pharmacoeconomics
Disclosure statement
At a time when physicians are attempting to curtail the rising cost of medicine, lowering medical costs is both an ethical and medical goal. In our prospective study we showed that galeapericranium duraplasty is comparable to other dural substitutes in terms of postoperative results. The macroscopic difference between the two groups is, however, costs. Form our analysis the total cost for the Tutopatch group was 24,721D with a cost per patient of 268.7D and a cost per cm2 of 21.2D . These figures represent certainly an even more relevant data if considered on a longer term analysis including the entire number of neurosurgical procedures. In fact in our study we have taken into account only a very restricted population sample (93 patients), with a 24,989D saved. If in our Department we would have regularly used galea-pericranium in all the procedures in which it could be potentially applied, the potential cost-retail would have been certainly relevant on the department budget.
The authors declare no interest to disclose, they have any personal or institutional financial interest in drugs, materials, or devices described in this submission and that they did not receive any specific funding. The paper and any of its contents have been presented previously.
5. Conclusions Considering that long term results are equivalent, that galeapericranium collection is an easy feasible procedure that requires no longer than 2 min before craniotomy. Thus it does not significantly prologues surgical time. Is it really worth to spend a considerable amount of money for duraplasty when it is available an ideal autologous dural surrogate that is simply “free”? So based on an ethical and pharmacoeconomic prospective we advice the use of galea-pericranium for all neurosurgical procedures, as it has no side effects, it is comparable to the available commercialized non-authologous patches, and it is costless. Even if in the present study we have taken into account only supratentorial surgery in order to standardize our sample, it should also considered relevant recent literature that has tested as effective the use of galea-pericranium also for other neurosurgical procedures, including posterior cranial fossa surgery [3,8]. The aim of the present study was not to demonstrate superiority of galea-pericranium duraplasty compared to other non-authologous patches. Indeed our results display that it is equivalent to duraplasty performed with other common nonauthologous dural patches in terms of postoperative results. The only massive difference is cost. Our study shows that galeapericranium duraplasty is feasible, collection is not time consuming and that even large dural defects can be repaired. The issue of unnecessary costs in medicine is nowadays imperative; we hope there will be more studies in the future about its economical impact, particularly in communities with limited resources.
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