Graded repair of skull base defects following endoscopic pituitary adenoma surgery

Graded repair of skull base defects following endoscopic pituitary adenoma surgery | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 5 May 2025 V1 Latest version Share on Graded repair of skull base defects following endoscopic pituitary adenoma surgery Authors : Macarena Viñuela 0000-0002-4433-3718 , Claudia González , Francisco Guarda , Flavia Nilo , Pablo Villanueva , and Claudio Callejas 0000-0002-6993-4456 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174643060.05860838/v1 170 views 97 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objectives: To describe the evolution and outcomes of our graded skull base repair protocol in endoscopic pituitary surgery. Methods: Retrospective cohort study of 406 consecutive patients who underwent endoscopic pituitary surgery for adenoma at our institution. The repair protocol underwent two modifications across three study periods. From 2013 to 2016, protocol was based solely on the grade of intraoperative cerebrospinal fluid (CSF) leaks. Between 2017 and 2019, sellar diaphragm descent was incorporated. Since 2020, preoperative risk factors such as obesity, previous surgeries, and prior irradiation were included, influencing the materials used in skull base repair. Results: Postoperative CSF leak rate decreased across study periods; 12.5% (14/112), 6.2% (7/113) and 2.2% (4/181), respectively. This difference was statistically significant between the first and last period. Overall, CSF leak incidence was 6.2% (25/406), CNS infection 0.7% (3/406) and mortality rate 0.2% (1/406). Among study periods, intrasellar fat graft utilization increased from 44.6% (50/112), 77.9% (88/113) and 84.0% (152/181). Vascularized flaps were employed in 20.5% (23/112), 52.2% (59/113), and 47.5% (86/181). Nasoseptal flap was the predominant choice. Dural substitute use decreased progressively: 81.2% (82/112), 55.4% (51/113), and 7.2% (13/181). Conclusions: The learning curve and refinement of our graded skull base repair protocol resulted in a substantial reduction in postoperative CSF leak rate. The presence and magnitude of intraoperative CSF leaks, diaphragm descent, and preoperative risk factors for postoperative CSF leaks were essential for guiding skull base reconstruction following pituitary surgery. Abstract Objectives: To describe the evolution and outcomes of our graded skull base repair protocol in endoscopic pituitary surgery. Methods: Retrospective cohort study of 406 consecutive patients who underwent endoscopic pituitary surgery for adenoma at our institution. The repair protocol underwent two modifications across three study periods. From 2013 to 2016, protocol was based solely on the grade of intraoperative cerebrospinal fluid (CSF) leaks. Between 2017 and 2019, sellar diaphragm descent was incorporated. Since 2020, preoperative risk factors such as obesity, previous surgeries, and prior irradiation were included, influencing the materials used in skull base repair. Results: Postoperative CSF leak rate decreased across study periods; 12.5% (14/112), 6.2% (7/113) and 2.2% (4/181), respectively. This difference was statistically significant between the first and last period. Overall, CSF leak incidence was 6.2% (25/406), CNS infection 0.7% (3/406) and mortality rate 0.2% (1/406). Among study periods, intrasellar fat graft utilization increased from 44.6% (50/112), 77.9% (88/113) and 84.0% (152/181). Vascularized flaps were employed in 20.5% (23/112), 52.2% (59/113), and 47.5% (86/181). Nasoseptal flap was the predominant choice. Dural substitute use decreased progressively: 81.2% (82/112), 55.4% (51/113), and 7.2% (13/181). Conclusions: The learning curve and refinement of our graded skull base repair protocol resulted in a substantial reduction in postoperative CSF leak rate. The presence and magnitude of intraoperative CSF leaks, diaphragm descent, and preoperative risk factors for postoperative CSF leaks were essential for guiding skull base reconstruction following pituitary surgery. Key words: Pituitary adenoma, skull base, cerebrospinal fluid leak, transsphenoidal surgery. Key Points: 1. Reparative strategies in skull base defects following transsphenoidal surgery have undergone a notable evolution, favoring a graded repair based on the risk profile for postoperative cerebrospinal fluid (CSF) leaks 2. A specialized multidisciplinary pituitary tumor program was instituted at Pontificia Universidad Católica de Chile Hospital, which refined their skull base repair protocol over three distinct periods, aiming to reduce complication rates. 3. The current protocol considers severity of intraoperative CSF leaks, extent of sellar diaphragm descent, and preoperative risk factors such as obesity, prior sellar surgery, and previous radiotherapy. 4. Besides, our repair protocol shifted from the use of synthetic materials to autologous alternatives. 5. Modifications to our protocol led to significant reductions in postoperative CSF leaks, while maintaining central nervous system and mortality rates stable. These rates are consistent with international reports. Introduction Reparative strategies for skull base defects following transsphenoidal surgery for pituitary adenomas have evolved significantly, now favoring a graded repair approach based on the risk profile for postoperative cerebrospinal fluid (CSF) leaks[1,2]. One of the most significant risk factors for developing a postoperative CSF leak is the occurrence and severity of intraoperative CSF leak[1,2]. Esposito et al. classified intraoperative CSF leak as: Grade 0: absence of intraoperative fistula, Grade 1: small ”weeping” leak without evident diaphragm defect, Grade 2: moderate CSF leak with obvious diaphragmatic defect, and Grade 3: large defect resulting from tumor dissection extending into the suprasellar cistern, typically via a transtuberculum approach[1]. Another important risk factor is the integrity of the sellar diaphragm following tumour resection. A thin, weakened diaphragm—often associated with descent—increases the likelihood of leaks, even in the absence of intraoperative ones. Abdelmaksoud et al. classified diaphragm descent as: Grade 0 (no descent), Grade 1 (mild descent, <⅓ of sellar height), Grade 2 (moderate descent, <⅔ of sellar height), and Grade 3 (extensive descent, reaching the sellar floor)[3]. Other risk factors include obesity (body mass index prior radiotherapy[2,4-6]. In 2013, a specialized multidisciplinary pituitary tumor program was instituted at Pontificia Universidad Católica de Chile Hospital. Through periodic audits, our team refined their skull base repair protocol over three distinct periods, aiming to reduce complication rates. This study aims to describe the evolution of our skull base repair protocol and incidence of postoperative complications, including postoperative CSF leaks, central nervous system (CNS) infections, and mortality rates. Materials and Methods Study design Retrospective study of 406 consecutive patients with pituitary adenoma who underwent endoscopic endonasal resection at Pontificia Universidad Católica de Chile Hospital between December 2013 and October 2023. Data collection Demographic and clinical data, intraoperative findings and follow-up were extracted from patient records through comprehensive chart reviews. Skull base repair protocols and study periods: Regular audits prompted two key protocol changes in order to decrease postoperative CSF leak rates. These delineated three distinct study periods. First period: From December 2013 to December 2016, repair solely focused on intraoperative CSF leak grading by Esposito [1]. Postoperative leak risk was classified as: very low (Grade 0), low (Grade 1), moderate (Grade 2), and high (Grade 3). Multilayered repair strategies were tailored to risk category: very low-risk involved a dural substitute and fibrin glue; low-risk added intrasellar fat; moderate-risk included a vascularized flap; and high-risk required the same as moderate-risk, with the addition of non-resorbable packing as a buttress. Nasal packing was removed seven days postoperatively. Second Period: An audit of our outcomes revealed cases of postoperative CSF leak without intraoperative leaks. We attributed them to the tearing of a thinned, descended diaphragm post-resection, possibly triggered by postoperative Valsalva maneuvers. Consequently, between 2017 and 2019, we incorporated the extent of diaphragm descent -classified according to Abdelmaksoud [3]- as a variable in the reconstruction protocol. Consequently, postoperative CSF leak risk was classified as follows: very low (Grade 0 leak, Grade 0-1 descent), low (Grade 0-1 leak, Grade 2 descent), moderate (Grade 2 leak or Grade 3 descent), and high (Grade 3 leak or large skull base defects, e.g., transplanum/transtuberculum approach). Repair strategy was adjusted, with: (1) reduced overall use of dural substitutes and (2) increased repositioning of lateralized, preserved sphenoid sinus mucosa in very low- and low-risk patients. Third Period: Since 2020, a second audit of outcomes led to the incorporation of preoperative risk factors such as obesity, previous radiotherapy, and prior pituitary surgery. We estimated the risk of postoperative CSF leaks as in the second period (based on intraoperative CSF leak and diaphragm descent); however, the presence of one or more preoperative risk factors increased the likelihood of postoperative CSF leak by one level (e.g., from moderate to high). The repair strategy remained consistent with the second period with two main modifications: (1) reduced use of fibrin glue and (2) incorporation of free mucoperiosteal grafts as an alternative to sphenoid mucosa. Patients A total of 406 consecutive patients with pituitary adenomas who underwent endoscopic endonasal tumor resection were included in this cohort. Demographic data and tumor characteristics closely resemble what has been documented in the existing literature (Table 1)[1,7]. Statistical analysis Descriptive statistics were used to present demographic and clinical characteristics. ANOVA tests compared postoperative outcomes; CSF leaks, CNS infection, and mortality rate, defined as mortality within 30 days following surgery. Data was analyzed with Rstudio v1.3 and STATA 17. P value <0.05 was considered significant. Ethical approval The study received ethical approval from the Ethics Committee at Pontificia Universidad Católica de Chile (ID: 221215002). Postoperative complications Postoperative CSF Leak Rate: Postoperative CSF leak rate decreased significantly across the three study periods (Table II). In the first period, the rate was 12.5% (14/112), which dropped to 6.2% (7/113) in the second period, and further to 2.2% (4/181) in the third period (p<0.005). Overall, our CSF leak rate was 6.2% (25/406). Rates of intraoperative fistula and diaphragm descent were not statistically significant among study periods (p=0.104), see Table III. A total of 57.8% patients (233/403) had identifiable risk factors for postoperative CSF leak. Obesity was the most common, affecting (36.0%; 146/406), followed by previous surgery (21.9%; 89/406), and prior radiotherapy (2.0%; 8/406). These factors varied across the three study periods. Obesity prevalence increased progressively, from 25.9% (29/112) in the first period to 40.9% (74/181) in the third period. Prior surgery rates decreased slightly, and radiotherapy exposure remained relatively uncommon. Most postoperative CSF leaks were managed with lumbar drain placement (64%; 16/25). Only one case experienced treatment failure requiring surgical repair. Surgical repair was performed in 36% (9/25), and all were successfully treated after a single surgical attempt. CNS Infections: 0.7% (3/406) developed CNS postoperative infections. Two cases occurred during the first period (ventriculitis and meningitis) and one in the third period (meningitis). Perioperative Mortality Rate: The perioperative mortality rate was 0.2% (1/406), with a single case during the first period. Additionally, two late postoperative deaths (>6 months) were recorded during the same period due to complications unrelated to surgery (status epilepticus and urologic sepsis). Reconstruction components Materials used in reconstruction varied throughout the study periods. Intrasellar fat use increased progressively, rising from 44.6% (50/112) in the first period to 77.9% (88/113) in the second period, and reaching 84.0% (152/181) in the third period (p<0.001). Local vascularized flaps increased from 20.5% (23/112), 52.2% (59/113) and 47.5% (86/181) respectively (p<0.001). Nasoseptal flap was the predominant choice. Free mucoperiosteal grafts were introduced in the third period (8.8%; 16/181), and were harvested from nasal floor (37.5%; 7/16), inferior turbinate (31.3%; 5/16), middle turbinate (18.8%; 3/16), and septum (6.3%; 1/16). Repositioning of lateralized, preserved sphenoid sinus mucosa notably increased over time, rising from 2.7% (3/112), 5.3% (6/113), and 48.1% (87/181), respectively (p<0.001). Dural substitute use decreased progressively, from 81.2% (82/112) to 55.4% (51/113), and to 7.2% (13/181), (p<0.001). DuragenⓇ was the predominant dural substitute employed (93.8%; 146/170), and the sole dural substitute utilized during the third period. Fibrin glue (BeriplastⓇ) exhibited a statistically significant decrease (p<0.001), from 83.0% (93/112) and 83.2% (94/113) in the first periods, and dropping sharply to 2.2% (4/181) in the third period. Non-absorbable nasal packing was employed as a firm buttress (19.2%, 78/406). Polyvinyl alcohol nasal packing (Merocel® or Ivalon®) was the preferred material. Merocel® wrapped in a finger-glove was utilized in 38.5% of cases that required non-absorbable nasal packing. Rapid Rhino® was introduced in the third period (17.5%, 7/40). Posisep X® was used as a soft bolster to prevent synechia formation which began in the second study period at 10.6% (12/113), and increased to 72.3% (131/181) during the third study period. Discussion We describe our ten-year experience addressing skull base defects following endoscopic surgery for pituitary adenomas at Pontificia Universidad Católica de Chile Hospital. Systematic analysis of our results led to two major protocol modifications aimed at reducing postoperative CSF leak rates, incorporating variables such as severity of intraoperative CSF leaks, extent of diaphragm descent, and preoperative risk factors. This led to significant reductions in postoperative CSF leaks, from 12.5% (2013-2016) to 2.2% (2020 onwards). Overall incidence of postoperative CSF leaks was 6.2%, aligning with international rates ranging from 0.3-14%[1]. Our study contributes to the existing body of research on skull base reconstruction following endoscopic pituitary surgery by presenting a decade-long refinement of a graded skull base repair protocol. Unlike previous studies, it integrates multiple predictors of postoperative CSF leaks into a comprehensive, risk-based strategy. The progressive reduction of CSF leaks highlights the effectiveness of this approach. Additionally, the shift toward autologous materials supports cost-effective, low-complication techniques. By validating these protocols in a high-volume center outside North America and Europe, this study enhances their applicability across diverse healthcare systems, contributing to global research on skull base reconstruction. Among the identified risk factors, presence and severity of intraoperative fistula plays a key role in our protocol. Previous studies such as Esposito et al . demonstrated that higher-grade intraoperative leaks correlate significantly with increased postoperative leak rates[1], as they were significantly higher in Grade 3 (p=0.0003) and lower in Grade 0 fistulas (p=0.005)[1], suggesting a strong association between intraoperative and postoperative CSF leaks. In our cohort, overall incidence of intraoperative CSF leak did not differ significantly between study periods. When analyzing the proportion of intraoperative CSF leaks, incidence of Grade 1 leaks decreased after the first period; however, the difference in incidence of Grade 2 and 3 leaks was not statistically significant. An additional variable considered is the extent of diaphragm descent, described by Abdelmaksoud et al .[3]. Previous research has established a correlation between the degree of diaphragm descent and postoperative CSF leaks[3,10]. We believe that incorporating this parameter was essential in achieving a statistical significant reduction in complication rates. Obesity is a well-known risk factor for postoperative CSF leak. Dlouhy et al . concluded that patients had an odds ratio 1.61 higher of developing postoperative CSF leaks for every 5 kg/m² increase in BMI (p=0.016)[8]. Interestingly, despite a rising prevalence of obesity throughout study periods, our CSF leak rates declined. This finding suggests that our protocol effectively mitigated obesity-related risk. Prior pituitary surgery and radiotherapy have been correlated with an elevated risk of postoperative CSF leak[9]. Zhou et al . reported a postoperative CSF leak rate of 30% in reoperated patients, in contrast to 16.4% in patients undergoing primary surgery (p=0.033)[10]. Radiotherapy is a recognized risk factor for impaired tissue healing. Yong et al. found a trend of increased postoperative CSF leaks in patients with prior radiation therapy that was not statistically significant (OR 1.73, CI 95%:0.98-3.05)[11]. In our cohort, prevalence of prior surgery and previous radiotherapy remained relatively stable, but we believe that their consideration contributed to improvement of our outcomes. Different graded repair protocols have been published internationally. Esposito et al .[1] proposed a protocol based on intraoperative CSF leak, with an overall rate of postoperative CSF leak of 2.0%. Conger et al. published their protocol based on intraoperative CSF leaks using different materials for reconstruction, with a reported rate of postoperative fistula of 1.6%[7]. Baussart et al. proposed a closure strategy based on grade of intraoperative CSF leak and risk factors such as severe obesity (BMI>40 kg/m 2 ), sellar floor lysis, large skull base destruction, >2 prior surgeries and prior radiotherapy [9]. Our protocol offers an alternative approach that considers multiple risk factors and uniquely integrates them to determine the optimal closure strategy. Finally, the learning curve of the surgical team is another attributable factor of success previously described by other authors[9,12,13]. As skills and familiarity with the protocol increased, outcomes were improved even among patients with higher risk profiles. However, analyzing team experience as a singular variable is challenging. Our study reported a low incidence of CNS infections (0,7%) which closely aligns with international reports (0.45-2.6%)[14], despite higher postoperative leak rates in earlier periods. This observation holds relevance as failed intraoperative CSF leak repair significantly increases infection risk (OR: 5.6, Cl 95%:3-10.5)[5]. Overall mortality rate remained low at 0.2%, involving a single case -who developed ventriculitis and hydrocephalus- among 406 patients. This aligns with globally reported rates of less than 1%[15]. Our repair protocol evolved significantly, shifting from synthetic materials to autologous alternatives. Single-cohort studies have evaluated the efficacy of synthetic materials. Dusick et al. reported a 1.6% postoperative CSF leak rate in patients treated with dural substitutes[17]. Seda et al. found similar rates with fibrin glue and autologous materials[18]. However, the quality of evidence supporting synthetic materials is limited[19], and their use increases surgical costs[2] In contrast, adoption of autologous materials -including the repositioning of sphenoid sinus mucosa, sellar fat and local flaps- demonstrated a significant increase, as they are considered safe and highly effective[20,21]. Yoon et al . reported an overall incidence of postoperative CSF leak of 8.8%, with rates of 0% in patients with total mucosal coverage and 24% in those with partial or no mucosal coverage. Autologous sellar fat is a cost-effective, minimally invasive option. Nasoseptal flap is a reliable and versatile choice[2,22,23]. Zanation et al. reported a 94% success rate in reconstructing high-flow intraoperative CSF leaks with autologous materials[24,25]. Autologous materials are less expensive and are associated with fewer rates of postoperative CSF leak while maintaining CNS infection and mortality rates stable. A limitation inherent to this retrospective study is inconsistent data documentation, particularly regarding diaphragm descent and intraoperative CSF leak grades during earlier periods. However, there was no missing data related to main outcomes: postoperative CSF leaks, CNS infections, and mortality. Conclusion Our skull base repair protocol for skull base defects following endoscopic endonasal pituitary adenoma surgery was systematically analyzed and refined as our team gained experience. The current protocol considers severity of intraoperative CSF leaks, extent of sellar diaphragm descent, and preoperative risk factors such as obesity, prior sellar surgery, and previous radiotherapy. These modifications significantly reduced postoperative CSF leak rates while maintaining low CNS infection and mortality rates. References: 1. Esposito F, Dusick JR, Fatemi N, Kelly DF. Graded repair of cranial base defects and cerebrospinal fluid leaks in transsphenoidal surgery. Oper Neurosurg (Hagerstown) . 2007;60(4 Suppl 2):295-304. doi:10.1227/01.NEU.0000255354.64077.66 2. Wang EW, Zanation AM, Gardner PA, et al. ICAR: endoscopic skull-base surgery. Int Forum Allergy Rhinol . 2019;9(S3):S145-S365. doi:10.1002/alr.22326 3. Abdelmaksoud A, Fu P, Alwalid O, et al. Degrees of Diaphragma Sellae Descent during Transsphenoidal Pituitary Adenoma Resection: Predictive Factors and Effect on Outcome. Curr Med Sci . 2018;38(5):888-893. doi:10.1007/s11596-018-1958-2 4. Reyes C, Mason E, Solares CA. Panorama of reconstruction of skull base defects: from traditional open to endonasal endoscopic approaches, from free grafts to microvascular flaps. Int Arch Otorhinolaryngol . 2014;18(Suppl 2):S179-S186. doi:10.1055/s-0034-1395268 5. Shahangian A, Soler ZM, Baker A, et al. Successful repair of intraoperative cerebrospinal fluid leaks improves outcomes in endoscopic skull base surgery. Int Forum Allergy Rhinol . 2017;7(1):80-86. doi:10.1002/alr.21845 6. Fraser S, Gardner PA, Koutourousiou M, et al. Risk factors associated with postoperative cerebrospinal fluid leak after endoscopic endonasal skull base surgery. J Neurosurg . 2018;128(4):1066-1071. doi:10.3171/2016.12.JNS1694 7. Conger A, Zhao F, Wang X, et al. Evolution of the graded repair of CSF leaks and skull base defects in endonasal endoscopic tumor surgery: trends in repair failure and meningitis rates in 509 patients. J Neurosurg . 2019;130(3):861-875. doi:10.3171/2017.11.JNS172141 8. Dlouhy BJ, Madhavan K, Clinger JD, et al. Elevated body mass index and risk of postoperative CSF leak following transsphenoidal surgery. J Neurosurg . 2012;116(6):1311-1317. doi:10.3171/2012.2.JNS111837 9. Baussart B, Venier A, Jouinot A, Reuter G, Gaillard S. Closure strategy for endoscopic pituitary surgery: Experience from 3015 patients. Front Oncol . 2023;12:1067312. Published 2023 Jan 4. doi:10.3389/fonc.2022.1067312 10. Zhou Q, Yang Z, Wang X, et al. Risk Factors and Management of Intraoperative Cerebrospinal Fluid Leaks in Endoscopic Treatment of Pituitary Adenoma: Analysis of 492 Patients. World Neurosurg . 2017;101:390-395. doi:10.1016/j.wneu.2017.01.119 11. Yong M, Wu YQ, Su S, et al. The effect of prior radiation on the success of ventral skull base reconstruction: A systematic review and meta-analysis. Head Neck . 2021;43(9):2795-2806. doi:10.1002/hed.26709 12. Frara S, Rodriguez-Carnero G, Formenti AM, Martinez-Olmos MA, Giustina A, Casanueva FF. Pituitary Tumors Centers of Excellence. Endocrinol Metab Clin North Am . 2020;49(3):553-564. doi:10.1016/j.ecl.2020.05.010 13. Mortini P, Nocera G, Roncelli F, Losa M, Formenti AM, Giustina A. The optimal numerosity of the referral population of pituitary tumors centers of excellence (PTCOE): A surgical perspective. Rev Endocr Metab Disord . 2020;21(4):527-536. doi:10.1007/s11154-020-09564-7 14. Shah S, Durkin J, Byers KE, Snyderman CH, Gardner PA, Shields RK. Microbiologic and Clinical Description of Postoperative Central Nervous System Infection After Endoscopic Endonasal Surgery. World Neurosurg . 2023;175:e434-e438. doi:10.1016/j.wneu.2023.03.119 15. Tamasauskas A, Sinkūnas K, Draf W, et al. Management of cerebrospinal fluid leak after surgical removal of pituitary adenomas. Medicina (Kaunas) . 2008;44(4):302-307. 16. Burton BN, Hu JQ, Jafari A, et al. An updated assessment of morbidity and mortality following skull base surgical approaches. Clin Neurol Neurosurg . 2018;171:109-115. doi:10.1016/j.clineuro.2018.06.015 17. Dusick JR, Mattozo CA, Esposito F, Kelly DF. BioGlue for prevention of postoperative cerebrospinal fluid leaks in transsphenoidal surgery: A case series. Surg Neurol . 2006;66(4):371-376. doi:10.1016/j.surneu.2006.06.043 18. Seda L, Camara RB, Cukiert A, Burattini JA, Mariani PP. Sellar floor reconstruction after transsphenoidal surgery using fibrin glue without grafting or implants: technical note. Surg Neurol . 2006;66(1):46-49. doi:10.1016/j.surneu.2005.10.021 19. Pang JC, Bitner BF, Nottoli MM, et al. Tissue Sealant Impact on Skull Base Reconstruction Outcomes: A Systematic Review and Meta-Analysis. Laryngoscope . 2024;134(8):3425-3436. doi:10.1002/lary.31390 20. Kelly DF, Oskouian RJ, Fineman I. Collagen sponge repair of small cerebrospinal fluid leaks obviates tissue grafts and cerebrospinal fluid diversion after pituitary surgery. Neurosurgery . 2001;49(4):885-890. doi:10.1097/00006123-200110000-00020 21. Yoon TM, Lim SC, Jung S. Utility of sphenoid mucosal flaps in transnasal transsphenoidal surgery. Acta Otolaryngol . 2008;128(7):785-789. doi:10.1080/00016480701730752 22. Zhang C, Ding X, Lu Y, Hu L, Hu G. Cerebrospinal fluid rhinorrhoea following transsphenoidal surgery for pituitary adenoma: experience in a Chinese centre. Rinoliquorrea dopo chirurgia dell’adenoma ipofisario con approccio transfenoidale: esperienza in un centro cinese. Acta Otorhinolaryngol Ital . 2017;37(4):303-307. doi:10.14639/0392-100X-1086 23. Eloy JA, Kalyoussef E, Choudhry OJ, et al. Salvage endoscopic nasoseptal flap repair of persistent cerebrospinal fluid leak after open skull base surgery. Am J Otolaryngol . 2012;33(6):735-740. doi:10.1016/j.amjoto.2012.07.005 24. Zanation AM, Carrau RL, Snyderman CH, et al. 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Semin Plast Surg . 2017;31(4):189-196. doi:10.1055/s-0037-1607273 TABLE I: Demographic data and CSF leak risk factors 2013-2016 2017-2019 2020-2023 Total Sex (n° of patients) Female 55 52 113 220 Male 57 61 68 186 Average Age (years ± SD) Total 54.3 ± 12.6 50.0 ± 13.6 49.5 ± 14.4 51.0 ± 13.8 Female 54.6 ± 12.8 50.8 ± 13.9 48.2 ± 14.9 50.5 ± 14.3 Male 54.1 ± 12.4 49.3 ± 13.5 51.2 ± 13.5 51.4 ± 13.3 Type of adenoma Non-functional 73 77 109 259 Cushing 15 13 29 57 Acromegaly 22 18 27 67 Other: Prolactinoma 1 6 10 17 Gonadotroph 2 0 3 5 Thyrotroph 0 0 1 1 Gigantic macroadenoma Non-functional 10 9 14 33 Prolactinoma 0 1 1 2 Acromegaly 0 1 0 1 Microadenoma Acromegaly 1 3 5 9 Cushing 0 3 13 16 TABLE II: Postoperative CSF leak a 2013-2016 (112 cases) n (%) 2017-2019 (113 cases) n (%) 2020-2023 (181 cases) n (%) 2013-2016 vs 2017-2019 p-value 2017-2019 vs 2020-2023 p-value 2013-2016 vs 2020-2023 p-value Postoperative CSF leak 14 (12.5) 7 (6.2) 4 (2.2) 0.104 0.080 <0.005 a Contrasts were conducted with ANOVA test among the three study periods. Data from all 406 patients included in the study was available for analysis. TABLE III: Intraoperative CSF leak and descent of sellar diaphragm a 2013-2016 (112 cases) n (%) 2017-2019 (113 cases) n (%) 2020-2023 (181 cases) n (%) 2013-2016 vs 2017-2019 p-value 2017-2019 vs 2020-2023 p-value 2013-2016 vs 2020-2023 p-value Intraoperative Sellar Diaphragm Grade 1 41 (36.6) 42 (37.1) 50 (27.6) 0.931 0.086 0.11 Grade 2 16 (14.2) 9 (7.9) 42 (23.2) 0.131 <0.001 0.063 Grade 3 0 (0) 7 (6.1) 36 (19.8) 0.007 0.001 4.667 Total 57 (50.8) 58 (51.1) 128 (70.6) Intraoperative fistula Grade 0 71 (63.3) 78 (69.0) 133 (73.4) 0.372 0.409 0.068 Grade 1 17 (15.1) 6 (5.3) 13 (7.1) 0.015 0.525 0.028 Grade 2 10 (8.9) 9 (7.9) 26 (14.3) 0.795 0.099 0.168 Grade 3 2 (1.7) 3 (2.6) 6 (3.3) 0.658 0.749 0.435 Total 100 (89) 96 (84.8) 178 (98.1) a Contrasts were conducted with ANOVA test among the three study periods Percentages were calculated based on the total number of cases per period Supplementary Material File (tables pit co.docx) Download 19.95 KB Information & Authors Information Version history V1 Version 1 05 May 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Macarena Viñuela 0000-0002-4433-3718 Pontificia Universidad Catolica de Chile Facultad de Medicina View all articles by this author Claudia González Pontificia Universidad Catolica de Chile Facultad de Medicina View all articles by this author Francisco Guarda Pontificia Universidad Catolica de Chile Facultad de Medicina View all articles by this author Flavia Nilo Pontificia Universidad Catolica de Chile Facultad de Medicina View all articles by this author Pablo Villanueva Pontificia Universidad Catolica de Chile Facultad de Medicina View all articles by this author Claudio Callejas 0000-0002-6993-4456 [email protected] Pontificia Universidad Catolica de Chile Facultad de Medicina View all articles by this author Metrics & Citations Metrics Article Usage 170 views 97 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Macarena Viñuela, Claudia González, Francisco Guarda, et al. 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