Resection Of Skull Base Tumors Research Articles

Surgical approaches to resection of anterior skull base and paranasal sinuses tumors.

Malignant tumours of the sinonasal tract comprise approximately 3% of the malignancies that arise in the upper aerodigestive tract. Approximately 10% of tumours that arise in the sinonasal tract originate in the ethmoid and/or frontal sinuses, and are likely to involve the anterior cranial base. The route of spread of tumours originating in the anterior skull base and paranasal sinuses is determined by the complex anatomy of the craniomaxillofacial compartments. These tumours may invade laterally into the orbit and middle fossa, inferiorly into the maxillary antrum and palate, posteriorly into the nasopharynx and pterygopalatine fossa, and superiorly into the cavernous sinus and brain. Recent improvements in endoscopic technology now allow the resection of the majority of benign neoplasms and some early malignant tumours with minor dural involvement. For advanced-stage malignant tumours and benign tumours with frontal bone involvement, the classical open approaches remain viable surgical techniques. In this paper, we review the open surgical resection approaches used for resections in the craniomaxillofacial area.

Challenges and surgical nuances in reconstruction of large planum sphenoidale tuberculum sellae defects after endoscopic endonasal resection of parasellar skull base tumors

Endoscopic endonasal transplanum transtuberculum (EETT) resection of parasellar skull base (SB) tumors often results in large SB defects with intraoperative high-flow cerebrospinal fluid (CSF) leaks. Reconstruction of these defects can be challenging because of the large defects size, communication with the suprasellar cistern, and close proximity to the optic nerves and chiasm. Recent studies have postulated that transplanum defects may be associated with increased postoperative CSF leakage. We review our experience with reconstruction of transplanum defects after EETT resection of parasellar SB tumors. Challenges encountered during these repairs and our operative nuances for successful reconstruction are discussed. A retrospective analysis was performed between March 2010 and February 2012 on patients undergoing reconstruction of transplanum defects after EETT resection of parasellar SB tumors. Repair materials, defect sizes, postoperative CSF leakage, postoperative CSF diversion, and demographic data were collected. Nineteen patients who underwent 22 repairs with a pedicled nasoseptal flap (PNSF) were identified. The mean age was 47.6 years (range, 12-68 years). Average defect size was 5.6 cm(2) (range, 2.2-10.4 cm(2)). Three failed repairs necessitated a revision procedure. All three revisions were successfully reconstructed with the previously used PNSF. The mean follow-up period was 13.5 months (range, 1-26 months). The overall success rate was 86.4% for transplanum defects alone, as compared to 97.0% for our comprehensive PNSF experience in 99 repairs. Repair of large transplanum defects after EETT resection of parasellar SB tumors presents a unique challenge. Using a PNSF along with meticulous multilayer closure may help decrease postoperative CSF leaks.

Extracranial Radial Forearm Free Flap Closure of Refractory Cerebrospinal Fluid Leaks

Although rare, recalcitrant cerebrospinal fluid (CSF) leak after skull base tumor resection or major head trauma is a difficult therapeutic challenge, often complicated by lack of local vascularized tissue in a scarred, radiated field. Craniotomy with a free tissue transfer has been described for CSF leak repair from these complicated skull base defects. : We present our experience with a novel extracranial approach to manage refractory CSF leaks with a radial forearm free flap set in through a transantral and ethmoid sinus approach. Five patients with recalcitrant CSF leaks in the anterior skull base underwent radial forearm free tissue transfer via a hybrid transantral-endoscopic approach. There were 4 female patients and 1 male patient. Average age was 58 years (range, 30-72 years). Four patients had previous neurosurgical anterior skull base tumor resections, and 1 patient had significant head trauma leading to a recalcitrant CSF leak. All 5 patients had undergone multiple prior endoscopic and/or open repairs. All 5 patients had successful resolution of their leak after undergoing radial forearm free tissue transfer. Two of 5 patients required a second minor endoscopic procedure. No patients required a craniotomy. An extracranial transantral-endoscopic approach for the inset of radial forearm free flap is a safe treatment technique that precludes the need for a craniotomy and promotes effective repair of CSF leaks refractory to traditional endoscopic procedures. RFFF, radial forearm free flap.

Adaptive Hybrid Surgery: Feasibility of Planned Subtotal Resection of Benign Skull Base Tumors Followed by Radiosurgery to Minimize Morbidity Without Compromising Tumor Control

Adaptive Hybrid Surgery: Feasibility of Planned Subtotal Resection of Benign Skull Base Tumors Followed by Radiosurgery to Minimize Morbidity Without Compromising Tumor Control

Assessment of frontal lobe sagging after endoscopic endonasal transcribriform resection of anterior skull base tumors: Is rigid structural reconstruction of the cranial base defect necessary?

The endoscopic endonasal transcribriform approach (EETA) is a viable alternative option for resection of selected anterior skull base (ASB) tumors. However, this technique results in the creation of large cribriform defects. Some have reported the use of a rigid substitute for ASB reconstruction to prevent postoperative frontal lobe sagging. We evaluate the degree of frontal lobe sagging using our triple-layer technique [fascia lata, acellular dermal allograft, and pedicled nasoseptal flap (PNSF)] without the use of rigid structural reconstruction for large cribriform defects. Retrospective analysis. Nine patients underwent an EETA for resection of large ASB tumors from August 2010 to November 2011. The degree of frontal lobe displacement after EETA, defined as the ASB position, was calculated based on the most inferior position of the frontal lobe relative to the nasion-sellar line defined on preoperative and postoperative imaging. A positive value signified upward displacement, and a negative value represented inferior displacement of the frontal lobe. The average cribriform defect size was 9.3 cm(2) (range, 5.0-13.8 cm(2) ). The average distance of postoperative frontal lobe displacement was 0.2 mm (range, -3.9 to 2.9 mm) without any cases of significant brain sagging. The mean follow-up period was 10.1 months (range, 4-19 months). There were no postoperative CSF leaks. Rigid structural repair may not be necessary for ASB defect repair after endoscopic endonasal resection of the cribriform plate. Our technique for multilayer cranial base reconstruction appears to be satisfactory in preventing delayed frontal lobe sagging.

Triple‐layer reconstruction technique for large cribriform defects after endoscopic endonasal resection of anterior skull base tumors

Endoscopic endonasal transcribriform (EET) resection of anterior skull base (ASB) tumors results in large defects that may extend the entirety of the cribriform plate. Endoscopic repair of these cribriform defects can often be challenging. We describe our reconstruction technique for large ASB defects after EET resection of ASB tumors. This triple-layer technique is comprised of autologous fascia lata, acellular dermal allograft, and a vascularized pedicled nasoseptal flap (PNSF). The technique is described and postoperative cerebrospinal fluid (CSF) leak rate is evaluated. Retrospective review over a 2-year period identified 10 patients who underwent a purely EET approach for resection of ASB tumors. Patients who underwent combined cranionasal approaches and those treated for ASB encephaloceles were excluded from this study. After tumor resection, patients underwent triple-layer reconstruction using autologous fascia lata inlay, acellular dermal allograft inlay/overlay, followed by a PNSF to reconstruct the cribriform defect. No postoperative lumbar drainage was used. The average cribriform defect size was 9.1 (range, 5.0-13.8) cm(2) . All 10 patients underwent successful reconstruction with a postoperative CSF leak rate of 0% without the use of postoperative lumbar drainage. The mean follow-up period was 7.4 (range, 2-17) months. The mean age was 45.8 (range, 15-81) years with 30% of the patients being females. The triple-layer reconstruction technique is effective in reconstructing large ASB defects after endoscopic resection of the cribriform plate. We feel that the use of postoperative lumbar drainage is not necessary when using this repair technique.

Double flap technique for reconstruction of anterior skull base defects after craniofacial tumor resection: technical note

Successful reconstruction of large anterior skull base (ASB) defects after craniofacial resection of malignant skull base tumors is paramount for preventing cerebrospinal fluid (CSF) fistulas. The vascularized pedicled pericranial flap (PCF) has been the gold standard for repairing ASB defects after transbasal transcranial approaches. However, flap necrosis and delayed CSF leaks can occur after adjuvant radiation therapy. We describe a "double flap" reconstruction technique in which the PCF is augmented inferiorly by a secondary vascularized pedicled nasoseptal flap (NSF) that is harvested and rotated using an endoscopic endonasal approach. This technique is illustrated in 2 patients who underwent a combined cranionasal (transbasal and endoscopic endonasal) approach for large sinonasal malignancies with significant intracranial extension (1 esthesioneuroblastoma, 1 sinonasal teratocarcinosarcoma). After tumor removal via a combined cranionasal approach, primary repair of the ASB dural defect was performed with a free patch graft. The ASB defect was then repaired using the double flap technique with a vascularized PCF from above and augmented with a vascularized NSF from below. Postoperatively, there were no complications of CSF leakage, meningitis, or tension pneumocephalus in both patients. After subsequent radiation therapy, the double flap repair remained intact at 2 years postoperatively in both patients. The double flap skull base reconstruction technique provides an additional barrier of vascularized tissue to prevent CSF leakage, meningitis, tension pneumocephalus, and postradiation necrosis. This technique is a viable option if a combined transcranial and transnasal endoscopic tumor resection is performed and postoperative radiation is anticipated.

Versatility of the pedicled nasoseptal flap in the complicated basal skull fractures

With the advancement of transnasal endoscopic technique, endoscopic repair of basal skull fractures has considerably substituted former external approaches. The endoscopically feasible pedicled flap, named nasoseptal flap has been extending its range of application, since it was introduced for the reconstruction of the defect after resection of skull base tumors. We introduce two patients with complicated basal skull fractures at different sites who were successfully treated by the transnasal endoscopic approach using nasoseptal flap.

Submandibular High-Flow Bypass in the Treatment of Skull Base Lesions

Cerebral bypass surgery remains an integral part of the treatment of complex skull base tumors and unclippable aneurysms. The authors retrospectively analyzed a single-surgeon experience using a high-flow submandibular-infratemporal saphenous vein graft bypass technique after carotid artery sacrifice in the resection of complex skull base tumors and carotid isolation in unclippable aneurysms. Data on indications, surgical technique, bypass patency, complications, and outcome were collected for patients treated with adjunctive submandibular high-flow bypass for skull base lesions. Eleven patients (age range, 13-77 years) were treated for various skull base lesions: 4 patients were treated for skull base tumors with resection of the internal carotid artery (ICA), 6 were treated for aneurysms not amenable to clipping, and one was treated for invasive Mucor infection. With the use of a saphenous vein graft, a high-flow bypass was created from the high cervical ICA or external carotid artery to ICA or middle cerebral artery by means of a submandibular-infratemporal route. Postoperative angiography indicated bypass patency in 10 of 11 patients. There was no operative mortality. Follow-up of up to 12 years (mean, 56 months) was achieved. Direct high-flow submandibular-infratemporal interpositional saphenous vein bypass graft is an effective and durable technique for the treatment of complex skull base lesions where ICA revascularization is indicated.

Quality of Life Following Endoscopic Resection of Skull Base Tumors

The objective of the study is to evaluate patients' quality of life (QOL) after endoscopic resection of skull base tumors. We estimated the QOL of 41 patients who underwent surgery for removal of skull base tumors via the expanded endonasal approach (EEA). The Anterior Skull Base Surgery Questionnaire (ASBS-Q), a multidimensional, disease-specific instrument containing 36 items was used. The rate of meningitis and cerebrospinal fluid leak was 1.4 and 0%, respectively. There was one case of uniocular visual impairment. The internal consistency of the instrument had a correlation coefficient (α-Cronbach score) of 0.8 to 0.92. Of 41 patients, 30 (75%) reported improvement or no change in overall QOL. Improved scores were reported in the physical function domain and worse scores in the specific symptoms domain. The most significant predictor of poor QOL was female gender, which led to a significant decrease in scores of all domains. Site of surgery, histology, age and comorbidity were not significant predictors of outcome. This paper further validates the use of the ASBS-Q for patients undergoing endoscopic skull base resection. The overall QOL of patients following endoscopic extirpation of skull base tumors is good. Female patients experience a significant decline in QOL compared with males.

Vagus Nerve Monitoring During Skull Base Surgery: A Transnasal Nerve Monitoring Technique

Objective: The vagus nerve is at risk during open resection of skull base tumors involving the high parapharyngeal space and infratemporal fossa, particularly with less invasive approaches where the superior exposure may be limited. Nerve monitoring using an endotracheal nerve monitoring system is well established for thyroid surgery. However, an oral endotracheal tube limits operative exposure of some skull base tumors either by being in the surgical field or by preventing full mobilization of the mandible with transcervical approaches. We describe the novel use of a commercially available nerve-monitoring endotracheal tube, which is placed transnasally during open skull base surgery for infratemporal fossa or high parapharyngeal space tumors.

Comparison of Quality of Life After Transnasal Endoscopic vs Open Skull Base Tumor Resection

To evaluate the impact of the open and endoscopic skull base surgery performed by the same team on patients' quality of life. Retrospective survey. University-affiliated medical center. The study included 78 patients who underwent surgery for removal of skull base neoplasms through an expanded endoscopic (n=41) or a subcranial (n=37) approach. A multidimensional, disease-specific questionnaire with 36 items was used. Six relevant domains of QOL were assessed: role of performance, physical functioning, vitality, pain, specific symptoms, and impact on emotions. There were no significant clinical or demographic differences between the 2 study groups (P>.06). Univariate and multivariate analyses showed that patients who underwent endoscopic surgery reported significantly better scores in the physical function and impact on emotions domains than the patients who underwent subcranial surgery (P<.04). Analysis of the minimal clinically important difference revealed that these differences were clinically significant. In certain domains, quality of life after endoscopic skull base surgery appears to be better than that after open approaches.

The Clinical Importance of Quality-of-Life Scores in Patients with Skull Base Tumors: A Meta-Analysis and Review of the Literature

Health-related quality of life (QOL) outcomes are frequently used by clinicians, patients, and researchers for assessing the effectiveness of an intervention. Small differences in QOL may be statistically significant but their clinical relevance remains undefined. The smallest changes in QOL scores of the anterior skull base surgery questionnaire (ASBS-Q) which could be considered clinically significant have not been delineated. Here we present a meta analysis and review of the literature of 273 patients undergoing skull base tumor resection. The minimal clinically important difference (MCID), defined as "the smallest change in QOL which patients perceive as beneficial", was calculated using several statistical approaches. The MCID of the ASBS-Q was 0.4 (8%, score range 1-5). Various other instruments for QOL estimations revealed a larger range of MCID score (between 6.2%-17.5%) for the different QOL domains. The statistical analyses reveal that histology (benign vs malignant), time elapsed from surgery (< or ≥6months), and surgical approach (open vs endoscopic) have significant clinical impact on different QOL domains. This paper brings level 1b evidence which demonstrates the importance of MCID as an adjunct for estimation of QOL in patients undergoing skull base surgery.

Placement of NP Airways after Skull Base Tumor Resection

Objective: 1) Assess the efficacy of nasopharyngeal (NP) airways in lieu of tracheotomy to prevent tension pneumocephalus after open resection of anterior skull base (ASB) tumors. 2) Determine predictors of tension pneumocephalus in patients undergoing NP airway placement after open resection of ASB tumors. Method: A total of 121 ASB resections (mean age, 48.5 years; M:F 73:47) performed between 1994 to 2009 with documented NP airway placement were identified and charts retrospectively reviewed. Main outcome measures were presence of tension pneumocephalus, while controlling for other clinical parameters (presence of CSF leak, placement of lumbar drain, type of reconstruction). Results: All patients were extubated on the day of surgery and NP airways remained in place for 3 days; no complications from NP airways were seen (eg, nasal septal pressure necrosis, displacement of the tubes). A total of 3 (2.5%) cases of tension pneumocephalus occurred. There were 34 (28%) lumbar drains placed and 14 (12%) CSF leaks. Although only 3 events were recorded, there was a statistically significant difference in the rate of tension pneumocephalus stratified by lumbar drain placement ( P = .02), presence of CSF leak ( P = .04), and both together ( P = .004). Type of reconstruction did not affect rate of tension pneumocephalus ( P = 1.0). Conclusion: Resection of anterior skull base tumors does not necessitate prophylactic tracheotomy and use of a nasopharyngeal airway to divert airflow is well tolerated and highly successful. Lumbar drainage, the presence of a CSF leak, or both together may increase the risk of tension pneumocephalus.

Microvascular Free Flap Reconstruction of Skull Base Penetrating Tumors

This is a follow-up study of 31 consecutive patients who underwent skull base tumor resection and microvascular tissue reconstruction in anterior and middle cranial fossa. Parameters recorded included factors related to operation, hospital stay, and outcome. All patients had a minimum follow-up of 5 years. There were no flap losses and no reoperations due to anastomoses-related complications. Five of 30 patients had cerebrospinal fluid leak that resolved with spinal drain except in one case, where the flap was placed incorrectly and the patient died of meningitis. Two other patients died due to early complications of the surgery. Although the complication rate was quite high, we consider this type of surgery worth performing, and even palliative surgery is to be considered in selective cases. Rectus abdominis flap due to its pliability and long pedicle proved to be most suitable flap together with superficial temporal artery and vein as recipient vessels.

Feasibility of intraoperative motor-evoked potential monitoring for skull base tumors with a high risk of postoperative motor deterioration

To establish the validity and utility of motor-evoked potential (MEPs) monitoring for skull base tumor resection, we explored the relationship between MEP monitoring results and postoperative motor function. MEPs were successfully monitored during 76 operations in 68 patients with a high risk of motor morbidity. MEP monitoring data were correlated with perioperative clinical motor function. MEPs remained stable in 56 operations (73.7%), and no postoperative motor deterioration was observed. Transient or permanent deterioration of MEPs (<50% of the initial amplitude before surgery) occurred in 20 operations (26.3%). This deterioration was reversible after intervention in seven cases (9.2%). Irreversible deterioration in MEPs was seen in 13 cases (17.1%). In five cases, the final amplitude was greater than 10%. Two of these patients experienced transient loss of MEPs and moderate to severe hemiparesis. Both patients showed full recovery within 6months after the operation. The other three patients experienced no postoperative worsening of motor function. The final MEP amplitude was less than 10% in the other eight patients, including five with permanent MEP loss. All of these patients experienced severe postoperative motor dysfunction. Recovery of motor function was worse in most participants in this group compared with those in the other groups. Intraoperative MEP monitoring is a valid indicator of pyramidal tract pathway function for skull base tumor surgery.

Clinical outcome after Hypofractionated Stereotactic Radiotherapy (HSRT) for benign skull base tumors

Objective: Surgical resection of skull base tumors can be associated with significant morbidity. In cases where the risks outweigh the benefits, radiation therapy can offer an alternative means to effectively control tumor growth. However, the optimal dose regime for radiation therapy remains controversial. The objective of this study was to assess the neurological outcome, local control rate and morbidity associated with a 5-fraction regime of hypofractionated stereotactic radiotherapy (HSRT) for benign skull base tumors.Methods: Twenty-six patients presenting with two of the most prevalent benign skull base tumors were included in the study. The tumors comprised 16 meningiomas and 10 acoustic neuromas. All patients exhibited preserved cranial nerve function prior to treatment, and a detailed audiological assessment was performed pre- and post-treatment for those patients with acoustic neuroma. Stereotactic radiosurgery was administered with the frameless CyberKnife Robotic Radiosurgery System. In each case, a 5-fraction HSRT regime was used: a dose of 5 Gy × 5 = 25 Gy to 6 Gy × 5 = 30 Gy was prescribed for skull base meningiomas, and 5 Gy × 5 = 25 Gy was prescribed for acoustic neuromas.Results: The clinical and radiographic median follow-up was 22 months (range: 6-54 months). Radiological assessment showed local control in all 26 tumors (100%), and in 5/26 patients (20%) the tumor showed a decrease in size. Cranial nerve function was preserved in all cases thus far studied; however, 28% of patients had transient Grade II side effects, including fatigue, headaches, unsteadiness and transient subjective worsening of hearing. In two of these patients, the period of transient worsening of hearing was associated with a temporary increase in the size of the tumor on control T2 MR images, consistent with radiation-induced edema. One patient had transient decrease in visual acuity from treatment-related edema. At the last follow-up, 3/16 patients with meningiomas (19%) and 2/10 with acoustic neuromas (20%) showed a decrease in tumor volume and improvement in hearing.Conclusion: A 5-fraction stereotactic radiotherapy regime, as used in this study, seems to be effective for local control of benign skull base tumors in this early follow-up evaluation. Neurological function preservation is excellent with this short regime in the early post-treatment period, but long-term follow-up is crucial for validation.

Use of a side-cutting aspiration device for resection of tumors during endoscopic endonasal approaches

Accessing intra- and extradural tumors via an endonasal approach requires working safely in a relatively narrow area with unobstructed visibility. The authors describe their experience to highlight the utility of a side-cutting aspiration device for endoscopic endonasal resection of skull base tumors. The authors used this device in 13 nonconsecutive endoscopic endonasal procedures for different skull base tumors (8 pituitary macroadenomas, 2 craniopharyngiomas, 1 chordoma, 1 recurrent ependymoma, and 1 lymphoma). Illustrative cases and video are presented to demonstrate its use. The instrument was easy to use and effective in the removal of the lesions presented in this series. In 10 patients (77%), gross-total resection was possible; in the other 3 patients (23%), more than 80% of the tumor was resected. No collateral tissue damage or any other complication resulted from device-related debulking or aspiration. The side-cutting tissue resector is a safe, easy to use, and effective tool for internal debulking and extracapsular dissection of nonvascularized tumors that are too firm for bimanual suction or blunt ring curette dissection. It is particularly useful when working through a deep and narrow corridor such as is encountered in endoscopic endonasal skull base surgery.

Retrospective assessment of the dismasking flap procedure as a craniofacial approach

In 1997 the authors presented the case of a 3-year-old girl who underwent complete resection of a huge tumor via a new technique using a dismasking flap. Since that report, 14 patients have undergone surgery using this technique. There have been few reports on long-term follow-up after a craniofacial surgical approach and reconstruction of a huge tissue defect. The authors report details of this procedure based on these cases, including long-term follow-up in the original case. The dismasking flap is a cranioorbitofacial degloving method that uses a circumpalpebral approach with or without piriform margin incisions and presents a wide surgical field under direct vision. Fourteen patients have undergone surgery using the dismasking flap technique. These patients had multiple craniofacial bone fractures (3 cases) and malignant or premalignant craniofacial tumors (11 cases). Patients ranged in age from 3 to 62 years old. The longest follow-up period was 15 years. The results of these cases are reported regarding changes in the facial bones and soft tissues with growth, the various pathologies involved, and complications. Complications using this approach were lagophthalmos with ectropion of the lower eyelid, disturbance of the superior orbital nerve, disturbance of the inferior orbital nerve, maxillary hypoplasia, and blepharoptosis. In all affected patients these complications were almost always temporary. In 2 of the 14 cases, a repair operation for lagophthalmos was necessary, while others showed spontaneous improvement approximately 6 months to a year after the procedure. In the case with the longest follow-up duration, the patient's nose is asymmetrical, especially the alar portion, due to hypoplasia of the grafted bone and/or the fixation with titanium miniplates. This flap is very useful for en bloc resection of huge skull base tumors, multiple craniofacial bone fractures, and as a lateral approach to a deep portion of the middle cranial base. Careful attention is necessary, however, because one may encounter unexpected complications if one does not ensure adequate protection of the perioperative flap. Meticulous postoperative management is also essential.

Endoscopic Endonasal Approach for Nonvestibular Schwannomas

Nonvestibular schwannomas of the skull base often represent a challenge owing to their anatomic location. With improved techniques in endoscopic endonasal skull base surgery, resection of various ventral skull base tumors, including schwannomas, has become possible. To assess the outcomes of using endoscopic endonasal approach (EEA) for nonvestibular schwannomas of the skull base. Seventeen patients operated on for skull base schwannomas by EEA at the University of Pittsburgh Medical Center from 2003 to 2009 were reviewed. Three patients underwent combined approaches with retromastoid craniectomy (n = 2) and orbitopterional craniotomy (n = 1). Three patients underwent multistage EEA. The rest received a single EEA operation. Data on degree of resection were found for 15 patients. Gross total resection (n = 9) and near-total (>90%) resection (n = 3) were achieved in 12 patients (80%). There were no tumor recurrences or postoperative cerebrospinal fluid leaks. In 3 of 7 patients with preoperative sensory deficits of trigeminal nerve distribution, there were partial improvements. Patients with preoperative reduced vision (n = 1) and cranial nerve VI or III palsies (n = 3) also showed improvement. Five patients had new postoperative trigeminal nerve deficits: 2 had sensory deficits only, 1 had motor deficit only, and 2 had both motor and sensory deficits. Three of these patients had partial improvement, but 3 developed corneal neurotrophic keratopathy. An EEA provides adequate access for nonvestibular schwannomas invading the skull base, allowing a high degree of resection with a low rate of complications.