Clinical and Histologic Studies of Olfactory Outcomes After Nasoseptal Flap Harvesting

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1 The Laryngoscope VC 2013 The American Laryngological, Rhinological and Otological Society, Inc. Clinical and Histologic Studies of Olfactory Outcomes After Nasoseptal Flap Harvesting Sang-Wook Kim, MD; Kyung Bum Park, MD; Roza Khalmuratova, MD; Hong-Kyoung Lee, MD; Sea-Yuong Jeon, MD; Dae Woo Kim, MD Objectives/Hypothesis: Since the introduction of an endonasal endoscopic approach in transsphenoidal pituitary surgery, reports of perioperative olfactory changes have presented conflicting results. We examined the incidence of olfactory loss in cases of endoscopic transsphenoidal pituitary surgery with skull base repair using the nasoseptal flap (NSF) and the effects of monopolar electrocautery commonly used in designing the NSF. Study Design: Case-control study. Methods: Fifteen patients who underwent endoscopic transsphenoidal pituitary surgery with skull base reconstruction using the NSF were divided into cold knife (n 5 8) and electrocautery (n 5 7) groups according to the device used in the superior incision of the NSF. Patients were followed regularly to monitor the need for dressing or adhesiolysis around the olfactory cleft. All subjects received olfactory tests before and 6 months after surgery. Septal mucosa specimens obtained during posterior septectomy were incised with different devices, and the degree of mucosal damage was evaluated. Results: One patient in the electrocautery group demonstrated olfactory dysfunction postoperatively, but the other 14 patients showed no decrease in olfaction. In histologic analyses, 55.8% and 76.9% of the mucosal surface showed total epithelial loss when the mucosa was cut with cutting- and coagulation-mode electrocautery, respectively. In contrast, only 20% of the mucosal surface exhibited total epithelial loss when the mucosa was cut with a cold knife (P <.01). Conclusions: Olfactory impairment is not common after use of the NSF. Use of the cold knife in making superior incision may reduce tissue damage with better olfactory outcomes. Key Words: Electrocoagulation, hypophysectomy, nasal surgical procedures, olfaction disorders, smell, surgical flaps. Level of Evidence: 3b Laryngoscope, 123: , 2013 INTRODUCTION Olfaction is closely related to our quality of life. It not only guides a person s attention to environmental hazards, such as smoke and poisonous fumes, but also influences our eating habits, nutritional intake, and interpersonal relationships. 1 Particularly in terms of safety, an impaired sense of smell can lead to the ingestion of spoiled food or a toxic substance and the inability to detect fires or gas leaks. 2 Some patients with a normal sense of smell experience smell loss following various endonasal surgeries, such as septoplasty, rhinoplasty, and transsphenoidal pituitary surgery. 3 5 Given the critical impact of smell loss on daily life, From the Department of Otorhinolaryngology (S.-W.K., R.K., H.-K.L., S.-Y.J.) and Neurosurgery (K.B.P.), Gyeongsang National University Hospital, Jinju, Institute of Health Sciences (S.-W.K., K.B.P., S.-Y.J.), Gyeongsang National University, Jinju; Department of Otorhinolaryngology (D.W.K.), Seoul National University College of Medicine, Boramae Medical Center, Seoul, Korea. Editor s Note: This Manuscript was accepted for publication February 25, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Dae Woo Kim, MD, PhD, Department of Otorhinolaryngology, Seoul National University College of Medicine, Boramae Medical Center, 425 Shindaebang 2-dong, Dongjak-gu, Seoul, Republic of Korea kicubi@daum.net DOI: /lary preservation of olfaction cannot be overemphasized in all types of endonasal surgery. The conventional approach to sellar lesions has been a transseptal microscopic approach. Because the primary goal of surgery was the complete removal of the tumor, less attention was paid to preservation of olfactory function. The incidence of olfactory loss has been variously reported, in the range of 10% to 30%. 4,6,7 After the introduction of endoscopic transsphenoidal pituitary surgery, however, this method was reported to have no significant effect on olfaction. Although patients experienced transient loss of smell in the first postoperative month, olfactory function was recovered by 3 months postoperatively. 8 Conversely, in another study, all patients who underwent endoscopic transsphenoidal pituitary surgery complained of smell loss when the nasoseptal flap (NSF) 9 was used for the reconstruction of skull defects. 10 In this study, we investigated the incidence and causes of olfactory dysfunction in cases in which the NSF was used for skull base reconstruction. MATERIALS AND METHODS Subjects and Surgical Techniques Fifteen patients (9 men, 6 women) with pituitary tumors underwent endoscopic transsphenoidal pituitary surgery with cerebrospinal fluid leak repair using an NSF. 9 Patients mean age was 53.4 years (range, 36 75). This study was approved by

2 the institutional review board of Gyeongsang National University Hospital. To avoid injury to the olfactory epithelium, the superior incision was made at least 1 cm below the most superior aspect of the septum. The inferior third of the right middle turbinate was removed to secure a wide surgical field. All subjects underwent nasal endoscopy and computed tomography (CT) of the paranasal sinuses, and those who showed abnormalities in the sinonasal space were excluded. Patients with a history of asthma or sinonasal diseases, such as allergic rhinitis and sinusitis, were excluded. Subjects with a history of medication use that could influence olfaction or who had previous sinonasal or pituitary surgeries or expanded endoscopic skull base surgeries beyond pituitary lesions were also excluded. Patients were categorized into the cold knife group (CK group, n 5 8) and electrocautery group (EC group, n 5 7) according to the device used in the superior incision of the NSF. They were allocated to each group by using a balanced block randomization. In the CK group, a cold knife was used to make the superior incision of NSF, and monopolar electrocautery (System 2450, 15 W power, cutting mode; Conmed Electrosurgery, Centennial, CO) was used to make the inferior and vertical incisions. In the EC group, all three incisions were made by monopolar electrocautery (15 W, cutting mode). Olfactory Function All subjects had a normal sense of smell before surgery, which was confirmed by the butanol threshold test (BTT) and the cross-cultural smell identification test (CCSIT). 11,12 Both olfactory tests were also carried out 6 months after surgery. All subjects received weekly nasal dressing during the first postoperative month and then monthly nasal dressings until synechia or crust formation ceased. If necessary, patients were advised to conduct daily nasal irrigation with saline. Before postoperative olfactory evaluation, Lund-Kennedy endoscopic scores (LKESs) were normal in all patients. 13 Changes of 2 in BTT or CCSIT scores were considered significant. Histologic Analysis To compare the distinct impacts of cold knife and monopolar electrocautery techniques on nasal mucosa, a large piece ( cm) of septal mucosa was obtained from each of five subjects during posterior septectomy, which was routinely performed during endoscopic transsphenoidal pituitary surgery. Each mucosal specimen was sliced into three long strips ( cm), and each strip was cut by different devices at a site 5 mm from its end. The specimens were assigned to the CK group (group A), cutting-mode monopolar electrocautery group (15 W power; group B), or coagulation-mode monopolar electrocautery group (15 W power; group C). Mucosal strips were then fixed in 2% paraformaldehyde, and the tissues were stained with hematoxylin and eosin. The degree and the proportion of mucosal injury were examined by an author (L.H.K.) who was blinded to group assignment. The degree of mucosal injury was evaluated using three grades: intact epithelium with cilia, partial epithelial loss, and total epithelial loss (Fig. 1). Partial epithelial loss indicated partial damage to multiple layers of epithelial cells combined with the loss of cilia (Fig. 1E). Total epithelial loss meant the absence of epithelial cells (Fig. 1F). Statistical Analyses Differences between pre- and postoperative olfactory tests were evaluated using the Wilcoxon signed-rank test. Differences in the incidence of olfactory disturbance between patient groups and proportion of total epithelial loss among groups in histologic study were compared with the Fisher exact test and Kruskal-Wallis test, respectively. All statistical analyses were conducted using the SPSS software (ver for Windows; SPSS Inc., Chicago, IL). P <.05 was considered to indicate statistical significance. RESULTS Changes in the Olfactory Function Mean pre- and postoperative BTT scores were 7.7 and 8.0 in the CK and EC groups, respectively. Similarly, mean pre- and postoperative CCSIT scores were 9.5 and 10.0, respectively. Neither score changed significantly after the operation (P 5.45 and P 5.24, respectively; Fig. 2A and 2B). Olfactory test scores did not decrease in any patient in the CK group, whereas one patient in the EC group showed a significant reduction in BTT score after surgery (P 5.059; Fig. 2C). Histologic Analysis Intact ciliated respiratory epithelium was often observed when the mucosa was incised with a cold knife. The area of partial or total epithelial loss increased markedly when the mucosa was cut using electrocautery. In particular, total epithelial loss was found more frequently with the use of coagulation mode in comparison with cutting mode (Fig. 1E and 1F). In group A, an average of 62% of the mucosal surface showed intact epithelia, and 18% and 20% exhibited partial and total epithelial loss, respectively. In group B, in contrast, no intact epithelia existed, whereas 44.2% and 55.8% of epithelia exhibited partial and total epithelial loss, respectively. Finally, in group C, 76.9% of mucosa demonstrated total epithelial loss, followed by partial epithelial loss (18.4%) and intact epithelium (4.8%) (Fig. 3). The proportion of total epithelial loss differed significantly among groups A, B, and C (P <.01). DISCUSSION In the past, variable olfactory outcomes were reported after transseptal transsphenoidal pituitary surgery. Because most studies evaluated patients symptoms alone without administering objective olfactory function tests, the exact incidence of postoperative olfactory dysfunction was unknown. For example, two of 20 (10%) patients who underwent endoscopically guided transseptal transsphenoidal surgery experienced smell loss. 14 In other studies of larger populations, 22% to 27% of patients experienced a decreased sense of smell after the use of the endonasal transsphenoidal approach for sellar lesions. 6,7 On the other hand, in a single study that used Toyota and Takagi olfactometry to evaluate patients smell, three of 25 (12%) patients were experiencing hyposmia at 1 year postoperatively. 4 Two of them showed bilateral opacification of olfactory clefts on coronal CT images. Thus, cautious manipulation of intranasal structures is recommended to avoid olfactory problems. More recently, there were two conflicting 1603

3 Fig. 1. Histologic analysis of nasal mucosal injury according to the incision technique. Intact respiratory epithelium with cilia (large arrow) was frequently seen when the incision was made using a cold knife (A, D). Overall partial (small arrow) or total (arrowheads) damage to the epithelium was observed when the mucosal strip was cut by electrocautery, particularly with the use of coagulation mode (C, F) compared with cutting mode (B, E). Stars mark the incision sites. (A C), original magnification 340; (D F), original magnification [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] reports on the olfactory outcomes after endoscopic transsphenoidal pituitary surgery. 8,10 The preceding study showed that olfactory function was recovered by 3 months postoperatively, although patients experienced transient loss of smell. It was concluded that endoscopic technique has no detrimental effects on olfaction compared with the conventional approach. However, the method for reconstructing the skull defects after tumor removal was not mentioned specifically. 8 In contrast, the other study focused on the effect of the use of NSF on olfaction. They claimed that when the NSF was used for reconstruction, all patients complained of their smell loss, being confirmed by an objective olfactory function test, the University of Pennsylvania Smell Identification Test. 10 Conversely, in the present study, only a single patient complained of smell loss at the 6-month postoperative visit, which was also ascertained by BTT and UPSIT. Furthermore, in cases where a cold knife was used for superior incision of the NSF, none experienced olfactory disturbance. As shown in Figure 1, mucosal damage by electrocautery reached nearly a full length of the mucosal strip obtained. Therefore, it can be assumed that a subtle difference in the amount of remaining 1604 superior septal mucosa could have caused big differences in olfactory outcomes, although the surgical technique was basically same. The human olfactory mucosa occupies 2 cm 2 of the superior portion of the nasal vault, overlying the superior nasal septum, the cribriform plate, and the superior aspect of the superior turbinate. 15 Given this anatomic location, preservation of mucosal integrity and patency of the adjacent space in the superior aspect of the nasal septum and superior turbinate is important to avoid olfactory mucosal injury during endonasal surgery. We made an effort to save as much of the superior aspect of septal mucosa as possible (1 1.5 cm). Four patients in the present study noted a decreased sense of smell during the postoperative followup period. They had profuse crust formation on the donor site of the NSF, significant mucosal swelling, or synechiae around the olfactory clefts, likely related to conductive olfactory dysfunction. To obviate these conductive component issues, rhinologists conducted intensive synechiolysis and regular nasal cleansing. Finally, on the day of postoperative olfactory evaluation, LKES scores were normal in all patients. Despite the use of

4 Fig. 2. Comparison between pre- and postoperative olfactory tests. Overall, no significant change was found in butanol threshold test (BTT) (A) or crosscultural smell identification test (CCSIT) (B) scores. Yellow and green blocks indicate improved and worsened (2) olfactory function scores, respectively (C). CK 5 cold knife; EC 5 monopolar electrocautery; L 5 left; Post 5 postoperative test; Pre 5 preoperative test; R 5 right. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] the same surgical technique and postoperative courses, one patient in the EC group suffered from partial olfactory loss. To ascertain whether thermal burns from monopolar electrocautery caused olfactory damage, the degree of mucosal injury was evaluated using septal mucosa obtained during the operation. Mucosal strips incised with a cold knife showed 20% total epithelial loss, probably occurring during the harvesting of the mucosa and the preparation of tissues for histologic examination. The degree of mucosal injury was aggravated when the mucosa was cut using monopolar electrocautery (Fig. 3). Differences in the degree of tissue damage and woundhealing status according to cutting device have been reported previously. In an experimental study using a porcine model, significantly lower wound-healing burst strength was observed in porcine skin cut with electroscalpels compared with that incised with a cold knife. 16 In addition, a considerable zone of coagulation necrosis was found in porcine skin cut with electroscalpels, whereas this zone was absent in skin cut with a cold knife. In another animal study using sheep, when compared with the use of a surgical device carrying radiofrequency energy, monopolar electrocautery showed marked replacement of respiratory epithelium with robust squamous epithelium and sizeable areas of complete mucosal loss. 17 Similar findings were identified in human skin obtained from patients who underwent abdominoplasties. Compared with the cold scalpel or a device using radiofrequency energy, monopolar electrocautery caused deeper acute thermal injury and wider scarring. 18 As mentioned, in the present study, cutting with monopolar electrocautery caused significantly wider epithelial injury compared with the use of the cold knife. Also, the use of coagulation mode induced more severe epithelial damage than the use of cutting mode. Some surgeons use coagulation mode in the elevation of the NSF to reduce the risk of bleeding at the edge of the elevated flap. Given our results, however, the use of cutting mode is recommended to reduce the Fig. 3. Degree of mucosal injury according to the mode of mucosal incision. The proportion of total epithelial loss differed significantly among groups (Kruskal-Wallis test, P <.01). Group A 5 cold knife; Group B 5 cutting-mode electrocautery; Group C 5 coagulationmode electrocautery. 1605

5 degree of tissue damage. In addition, the use of a cold knife to make the superior incision of the NSF is desirable to minimize the risk of olfactory disturbance. On the other hand, two patients exhibited improved olfaction, as revealed by BTT and CCSIT scores (Fig. 2C). Both patients showed nasal septal deviation on preoperative CT, but olfactory clefts were patent bilaterally. Because both patients had normal senses of smell preoperatively and showed no change in their perception of smell postoperatively, the clinical significance of this objective improvement in olfaction remains undetermined. CONCLUSION Olfactory impairment is not a common complication when the NSF is used for the reconstruction of skull base defects in endoscopic transsphenoidal pituitary surgery. Use of the cold knife in making a superior incision of the NSF may reduce mucosal damage with better outcomes in olfactory functions. BIBLIOGRAPHY 1. Hummel T, Nordin S. Olfactory disorders and their consequences for quality of life. Acta Otolaryngol 2005;125: Santos DV, Reiter ER, DiNardo LJ, Costanzo RM. Hazardous events associated with impaired olfactory function. Arch Otolaryngol Head Neck Surg 2004;130: Durr J, Lindemann J, Keck T. Sense of smell before and after functional esthetic rhinoplasty[in German]. HNO 2002;50: Ikeda K, Watanabe K, Suzuki H, et al. Nasal airway resistance and olfactory acuity following transsphenoidal pituitary surgery. Am J Rhinol 1999;13: Damm M, Eckel HE, Jungehulsing M, Hummel T. Olfactory changes at threshold and suprathreshold levels following septoplasty with partial inferior turbinectomy. Ann Otol Rhinol Laryngol 2003;112: Zada G, Kelly DF, Cohan P, Wang C, Swerdloff R. Endonasal transsphenoidal approach for pituitary adenomas and other sellar lesions: an assessment of efficacy, safety, and patient impressions. J Neurosurg 2003;98: Dusick JR, Esposito F, Mattozo CA, Chaloner C, McArthur DL, Kelly DF. Endonasal transsphenoidal surgery: the patient s perspective-survey results from 259 patients. Surg Neurol 2006;65: ; discussion, Hart CK, Theodosopoulos PV, Zimmer LA. Olfactory changes after endoscopic pituitary tumor resection. Otolaryngol Head Neck Surg 2010;142: Hadad G, Bassagasteguy L, Carrau RL, et al. A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap. Laryngoscope 2006;116: Rotenberg BW, Saunders S, Duggal N. Olfactory outcomes after endoscopic transsphenoidal pituitary surgery. Laryngoscope 2011;121: Smith DV. Assessment of patients with taste and smell disorders. Acta Otolaryngol Suppl 1988;458: Doty RL, Marcus A, Lee WW. Development of the 12-item Cross-Cultural Smell Identification Test (CC-SIT). Laryngoscope 1996;106: Lund VJ, Kennedy DW. Quantification for staging sinusitis. The Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl 1995;167: Koren I, Hadar T, Rappaport ZH, Yaniv E. Endoscopic transnasal transsphenoidal microsurgery versus the sublabial approach for the treatment of pituitary tumors: endonasal complications. Laryngoscope 1999;109: Escada PA, Lima C, da Silva JM. The human olfactory mucosa. Eur Arch Otorhinolaryngol 2009;266: Vore SJ, Wooden WA, Bradfield JF, et al. Comparative healing of surgical incisions created by a standard "bovie," The Utah Medical Epitome Electrode, and a Bard-Parker cold scalpel blade in a porcine model: a pilot study. Ann Plast Surg 2002;49: Kakarala K, Faquin WC, Cunningham MJ. Radiofrequency volumetric tissue reduction of the inferior turbinate in a sheep model. Laryngoscope 2012;122: Ruidiaz ME, Messmer D, Atmodjo DY, et al. Comparative healing of human cutaneous surgical incisions created by the PEAK plasmablade, conventional electrosurgery, and a standard scalpel. Plast Reconstr Surg 2011;128: