The authors previously described a graded approach to skull base repair following endonasal microscopic or endoscope-assisted tumor surgery. In this paper they review their experience with skull base ...reconstruction in the endoscopic era.
A retrospective review of a single-institution endonasal endoscopic patient database (April 2010–April 2017) was undertaken. Intraoperative CSF leaks were graded based on size (grade 0 no leak, 1, 2, or 3), and repair technique was documented across grades. The series was divided into 2 epochs based on implementation of a strict perioperative antibiotic protocol and more liberal use of permanent and/or temporary buttresses; repair failure rates and postoperative meningitis rates were assessed for the 2 epochs and compared.
In total, 551 operations were performed in 509 patients for parasellar pathology, including pituitary adenoma (66%), Rathke’s cleft cyst (7%), meningioma (6%), craniopharyngioma (4%), and other (17%). Extended approaches were used in 41% of cases. There were 9 postoperative CSF leaks (1.6%) and 6 cases of meningitis (1.1%). Postoperative leak rates for all 551 operations by grade 0, 1, 2, and 3 were 0%, 1.9%, 3.1%, and 4.8%, respectively. Fat grafts were used in 33%, 84%, 97%, and 100% of grade 0, 1, 2, and 3 leaks, respectively. Pedicled mucosal flaps (78 total) were used in 2.6% of grade 0–2 leaks (combined) and 79.5% of grade 3 leaks (60 nasoseptal and 6 middle turbinate flaps). Nasoseptal flap usage was highest for craniopharyngioma operations (80%) and lowest for pituitary adenoma operations (2%). Two (3%) nasoseptal flaps failed. Contributing factors for the 9 repair failures were BMI ≥ 30 (7/9), lack of buttress (4/9), grade 3 leak (4/9), and postoperative vomiting (4/9). Comparison of the epochs showed that grade 1–3 repair failures decreased from 6/143 (4.1%) to 3/141 (2.1%) and grade 1–3 meningitis rates decreased from 5 (3.5%) to 1 (0.7%) (p = 0.08). Prophylactic lumbar CSF drainage was used in only 4 cases (< 1%), was associated with a higher meningitis rate in grades 1–3 (25% vs 2%), and was discontinued in 2012. Comparison of the 2 epochs showed increase buttress use in the second, with use of a permanent buttress in grade 1 and 3 leaks increasing from 13% to 55% and 32% to 76%, respectively (p < 0.001), and use of autologous septal/keel bone as a permanent buttress in grade 1, 2, and 3 leaks increasing from 15% to 51% (p < 0.001).
A graded approach to skull base repair after endonasal surgery remains valid in the endoscopic era. However, the technique has evolved significantly, with further reduction of postoperative CSF leak rates. These data suggest that buttresses are beneficial for repair of most grade 1 and 2 leaks and all grade 3 leaks. Similarly, pedicled flaps appear advantageous for grade 3 leaks, while CSF diversion may be unnecessary and a risk factor for meningitis. High BMI should prompt an aggressive multilayered repair strategy. Achieving repair failure and meningitis rates lower than 1% is a reasonable goal in endoscopic skull base tumor surgery.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and ...arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-β transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reconstruction of the cranial base using vascularized tissue promotes rapid and complete healing, thus avoiding complications caused by persistent communication between the cranial cavity and the ...sinonasal tract. The Hadad-Bassagasteguy flap (HBF), a neurovascular pedicled flap of the nasal septum mucoperiosteum and mucoperichondrium based on the nasoseptal artery, seems to be advantageous for the reconstruction of the cranial base after endonasal cranial base surgery.
We performed a retrospective review of patients who underwent endonasal cranial base surgery at the University of Pittsburgh Medical Center from January 30, 2006 to January 30, 2007, identifying patients who experienced reconstruction with a vascularized septal mucosal flap (HBF). We analyzed the demographic data, pathological characteristics, site and extent of resection, use of cerebrospinal fluid (CSF) diversion techniques, and outcome.
Seventy-five patients who underwent endonasal cranial base endoscopic surgery received repair with the HBF. In this population, we encountered eight postoperative CSF leaks (10.66%), all in patients who required intra-arachnoidal dissection. When we correct the statistical analysis to include only patients with intra- arachnoidal lesions, the postoperative CSF leak rate is 14.5% (eight of 55 patients). It is notable that six CSF (33%) leaks occurred in our first 25 repairs, whereas we encountered only two postoperative leaks (4%) in the last 50 patients. The corrected CSF leak rate, considering only intra-arachnoidal lesions, was two (5.4%) of 37 patients. This improvement in the CSF leak rate reflects our growing experience and comfort with this reconstructive technique. All of our failures could be matched to a specific technical mistake. In addition, we modified the flap-harvesting technique to allow for staged procedures and the removal of caudal lesions. These special circumstances require storage of the flap in the antrum during the removal of caudal lesions, and suturing of the flap in its original position for staged procedures. One patient experienced a posterior nose bleed from the posterior nasal artery. This was controlled with bipolar electrocautery, thereby preserving the flap blood supply. We encountered no infectious or wound complications in this series of patients. The donor site accumulates crusting, which requires debridement until mucosalization is complete; this usually occurs 6 to 12 weeks after surgery.
The HBF is a versatile and reliable reconstructive technique for repairing defects of the anterior, middle, clival, and parasellar cranial base. Its use has resulted in a significant decrease in our incidence of CSF leaks after endonasal cranial base surgery. Attention to technical details is of paramount importance to achieve the best outcomes.
Background: In patients with large dural defects of the anterior and ventral skull base after endonasal skull base surgery, there is a significant risk of a postoperative cerebrospinal fluid leak ...after reconstruction. Reconstruction with vascularized tissue is desirable to facilitate rapid healing, especially in irradiated patients.
Methods: We developed a neurovascular pedicled flap of the nasal septum mucoperiosteum and mucoperichondrium based on the nasoseptal artery, a branch of the posterior septal artery (Hadad‐Bassagasteguy flap HBF). A retrospective review of patients undergoing endonasal skull base surgery at the University of Rosario, Argentina, and the University of Pittsburgh Medical Center was performed to identify patients who were reconstructed with a vascularized septal mucosal flap.
Results: Forty‐three patients undergoing endonasal cranial base surgery were repaired with the septal mucosal flap. Two patients with postoperative cerebrospinal fluid leaks (5%) were successfully treated with focal fat grafts. We encountered no infectious or wound complications in this series of patients. One patient experienced a posterior nose bleed from the posterior nasal artery. This was controlled with electrocautery and the flap blood supply was preserved.
Conclusion: The HBF is a versatile and reliable reconstructive technique for defects of the anterior, middle, clival, and parasellar skull base. Its use has resulted in a sharp decrease in the incidence of postoperative cerebrospinal fluid leaks after endonasal skull base surgery and is recommended for the reconstruction of large dural defects and when postoperative radiation therapy is anticipated.
ABSTRACT
OBJECTIVE
The endonasal route may be feasible for the resection of anterior cranial base tumors that abut the paranasal sinuses. There are several case reports and mixed case series ...discussing this approach. Other than pituitary adenomas, there is a lack of literature describing the outcomes of endonasal approaches for single-tumor types such as meningiomas.
METHODS
In this study, we describe our current endoscopic endonasal technique and demonstrate the feasibility of using it to access anterior cranial base meningiomas from the back wall of the frontal sinus to the sella and laterally to the region of the midorbit. After this discussion, which includes key technical considerations and nuances, we address safety and efficacy by reporting the outcomes of our early experience with endoscopic endonasal resection of 35 anterior cranial base meningiomas.
RESULTS
A total of 35 patients underwent endoscopic endonasal resection of anterior cranial base meningiomas from October 2002 to October 2005. Degree of resection by tumor location was as follows: 10 of the 12 (83%) patients with olfactory groove meningiomas planned for complete resection underwent gross total (seven of 12) or near-total (>95%) (three of 12) resection (67% of all 15 olfactory tumors); 12 of 13 patients (92%) with tuberculum meningiomas underwent gross (11 of 13) or near (>95%) (one of 13) total resection; five patients diagnosed with petroclival meningiomas had successful resection of the parasellar portion of their tumors with relief of visual symptoms (no patients underwent complete resection of their tumors via the endoscopic, endonasal approach); two giant petroclival meningiomas were debulked with 63 and 89% resection, respectively.
All patients experienced resolution or improvement of visual symptoms. No patient experienced permanent worsening of vision after surgery. Only one (3%) patient without preoperative endocrine dysfunction experienced a new, permanent pituitary deficit, diabetes insipidus. One (3%) patient experienced a new neurological deficit after experiencing a hemorrhage 3 weeks after surgery. The postoperative cerebrospinal fluid leak rate was 40% (14 of 35) and varied by tumor location. All leaks were resolved without craniotomy. There were no cases of bacterial meningitis. One patient developed a superinfection of a sterile granuloma from a sinusitis 2 years after surgery. There were two cases of deep venous thrombosis and one pulmonary embolus. There were no operative or perioperative deaths.
CONCLUSION
Cranial base meningiomas can be successfully managed via a purely endoscopic endonasal approach with acceptable morbidity and mortality rates. The extent of resection is guided by patient factors and symptoms, not by approach. This series had a high cerebrospinal fluid leak rate. With the evolution of new reconstruction techniques, these rates have been substantially reduced.
•The AJCC 8th ed. has much improved hazard discrimination and outcome prediction for HPV+ OPSCC.•In the 8th edition staging system, the vast majority patients now reclassified as pStage I.•Pathologic ...nodal staging alone does not show separate survival curves with the exception of pN2.•Presence of pathologic ENE confers a modest but significant decrease in overall survival.
The American Joint Commission on Cancer (AJCC) recently created new staging for human papillomavirus associated oropharyngeal cancer (HPV+ OPSCC) for its 8th edition. These proposals have not yet been validated in a national registry.
Review of National Cancer Database (NCDB) for surgically-treated HPV+ OPSCC for years 2010–2014 to validate the new staging system using the Kaplan Meier method to explore survival outcomes.
3745 cases were analyzed. Median follow-up was 31.3months. Most patients were Caucasian males with tonsillar cancer. Distribution of stage I disease increased from 3.7% to 80.2% in AJCC 8th. pN1 disease shifted from 17.3% to 75.9%. Treatment and distribution of T-stage varied by pathologic nodal (pN) staging. Extranodal extension (ENE) was positive in 41% cases. Four-year overall survival (OS) for AJCC 8th stages I (92%), II (81%), and stage III (62%) showed excellent hazard discrimination (all pairwise p<0.001). Only 4-year OS by pN staging showed significantly different curves when comparing pN2 (79%) with others (pN0 88%; pN1 91%, p=0.01 and <0.001 respectively). Presence of ENE confers a negative effect on overall survival (92% ENE− vs. 85% ENE+, p<0.001).
The NCDB shows improved hazard discrimination and outcome prediction in the AJCC 8th edition staging for HPV+ OPSCC. While overall staging had excellent hazard discrimination, this accounted for poorer discrimination between pN0 and pN1. The majority of patients are reclassified as overall stage I. Presence of extranodal extension demonstrated a statistically significant but modest negative effect on overall survival.
Using NCDB data for validation, the AJCC 8th ed. pathologic staging system offers much improved hazard discrimination and prognostication in HPV oropharyngeal cancer, with the majority of cases reclassified as pStage I. Of note, only pN2 offered hazard discrimination within nodal staging and presence of pathologic extranodal extension has a modest negative effect on survival.
Despite the increasing application of endoscopic transsphenoidal surgery for pituitary lesions, the prognostic factors that are associated with sinonasal quality of life (QOL) and nasal morbidity are ...not well understood. The authors examine the predictors of sinonasal QOL and nasal morbidity in patients undergoing fully endoscopic transsphenoidal surgery.
An exploratory post hoc analysis was conducted of patients who underwent endoscopic pituitary surgery and were enrolled in a prospective multicenter QOL study. End points of the study included patient-reported sinonasal QOL and objective nasal endoscopy findings. Multivariate models were developed to determine the patient and surgical factors that correlated with QOL at 2 weeks through 6 months after surgery.
This study is a retrospective review of a subgroup of patients studied in the clinical trial "Rhinological Outcomes in Endonasal Pituitary Surgery" (clinical trial no. NCT01504399, clinicaltrials.gov ). Data from 100 patients who underwent fully endoscopic transsphenoidal surgery were included. Predictors of a lower postoperative sinonasal QOL at 2 weeks were use of nasal splints (p = 0.039) and female sex at the trend level (p = 0.061); at 3 months, predictors of lower QOL were the presence of sinusitis (p = 0.025), advancing age (p = 0.044), and use of absorbable nasal packing (p = 0.014). Health status (multidimensional QOL) was also predictive at 2 weeks (p = 0.001) and 3 months (p < 0.001) and was the only significant predictor of sinonasal QOL at 6 months (p < 0.001). A Kaplan-Meier analysis was performed to study time to resolution of nasal crusting, mucopurulence, and synechia as observed during nasal endoscopy after surgery. The mean time (± SEM) to absence of nasal crusting was 16.3 ± 2.1 weeks, mucopurulence was 6.2 ± 1.1 weeks, and synechia was 4.4 ± 0.5 weeks. Use of absorbable nasal packing was associated with more severe mucopurulence.
Sinonasal QOL following endoscopic pituitary surgery reaches a nadir at 2 weeks and recovers by 3 months postoperatively. Use of absorbable packing and nasal splints, while used in a minority of patients, negatively correlates with early sinonasal QOL. Sinonasal QOL and overall health status are well correlated in the postoperative period, suggesting the important influence of sinonasal QOL on the patient experience.
Craniopharyngiomas are notoriously difficult to treat. Surgeons must weigh the risks of aggressive resection against the long-term challenges of recurrence. Because of their parasellar location, ...often extending well beyond the sella, these tumors challenge vision and pituitary and hypothalamic function. New techniques are needed to improve outcomes in patients with these tumors while decreasing treatment morbidity. An endoscopic expanded endonasal approach (EEA) is one such technique that warrants understanding and evaluation. The authors explain the techniques and approach used for the endoscopic endonasal resection of suprasellar craniopharyngiomas and introduce a tumor classification scheme.
The techniques and approach used for the endoscopic, endonasal resection of suprasellar craniopharyngiomas is explained, including the introduction of a tumor classification scheme. This scheme is helpful for understanding both the appropriate expanded approach as well as relevant involved anatomy.
The classification scheme divides tumors according to their suprasellar extension: Type I is preinfundibular; Type II is transinfundibular (extending into the stalk); Type III is retroinfundibular, extending behind the gland and stalk, and has 2 subdivisions (IIIa, extending into the third ventricle; and IIIb, extending into the interpeduncular cistern); and Type IV is isolated to the third ventricle and/or optic recess and is not accessible via an endonasal approach.
The endoscopic EEA requires a thorough understanding of both sinus and skull base anatomy. Moreover, in its application for craniopharyngiomas, an understanding of tumor growth and extension with respect to the optic chiasm and infundibulum is critical to safely approach the lesion via an endonasal route.
Objectives:
The introduction of the pedicled nasoseptal flap (NSF) has decreased postoperative cerebrospinal fluid (CSF) leak rates from >20% to <5% during expanded endoscopic skull base surgery. The ...NSF must be raised at the beginning of the operation to protect the posterior pedicle during the expanded sphenoidotomy. However, in most pituitary tumor cases, an intraoperative CSF leak is not expected but at times encountered. In these cases, a “rescue” flap approach can be used, which consists of partially harvesting the most superior and posterior aspect of the flap to protect its pedicle and provide access to the sphenoid face during the approach. The rescue flap can be fully harvested at the end of the case if the resultant defect is larger than expected, or if an unexpected CSF leak develops. This technique minimized septum donor site morbidity for those patients without intraoperative CSF leaks.
Results:
The rescue flap technique allows for binaural and bimanual access to the sella without compromise of the pedicle during the extended sphenoidotomies and tumor removal. If an intraoperative CSF leak is encountered, the rescue flap is then converted into a normal nasoseptal flap for skull base reconstruction. If no leak is obtained, then the patient does not suffer additional donor site morbidity from the full flap harvest.
Conclusions:
This new technique allows for sellar tumor removal prior to the nasoseptal harvest, thereby eliminating donor site morbidity for those pituitary tumor patients who do not have an intraoperative CSF leak.
Objectives
As the adoption of endoscopic endonasal approaches (EEA) continues to proliferate, increasing numbers of internal carotid artery (ICA) injuries are reported. The objective of this study ...was to develop a synthetic ICA injury‐training model that could mimic this clinical scenario and be portable, repeatable, reproducible, and without risk of biological contamination.
Methods
Based on computed tomography of a human head, we constructed a synthetic model using selective laser sintering with polyamide nylon and glass beads. Subsequently, the model was connected to a pulsatile pump using 6‐mm silicon tubing. The pump maintains a pulsatile flow of an artificial blood‐like fluid at a variable pressure to simulate heart beats. Volunteer surgeons with different levels of training and experience were provided simulation training sessions with the models. Pre‐ and posttraining questionnaires were completed by each of the participants.
Results
Pre‐ and posttraining questionnaires suggest that repeated simulation sessions improve the surgical skills and self‐confidence of trainees.
Conclusion
This ICA injury model is portable; reproducible; and avoids ethical, biohazard, religious, and legal problems associated with cadaveric models. A synthetic ICA injury model for EEA allows recurring training that may improve the surgeon's ability to maintain endoscopic visualization, control catastrophic bleeding, decrease psychomotor stress, and develop effective team strategies to achieve hemostasis.
Level of Evidence
NA Laryngoscope, 127:38–43, 2017