**5. Sinus wall thickness and blood eosinophilia as the indicators for revision surgeries**

The success of FESS for CRS is still variable, ranging from 76 to 98% [4]. Although the exact predictive factors are still controversial, several risk factors, such as nasal polyps, allergic rhinitis, aspirin intolerance, and bacterial resistance, can result in unfavorable treatment outcomes for CRS patients. In this study, we found that the presence of thickened maxillary sinus walls of more than 3.03 mm and increased peripheral blood eosinophil count are good predictors of unfavorable outcomes from FESS. In addition to the classical L-M scoring system, a twodimensional parameter, we suggest that these two factors may represent another three-dimensional parameter that may indicate the depth of inflammation in CRS in order to evaluate its severity.

The sinonasal organ is an expanding air-filled space that grows in a random pattern proven by using a simple computerized equation [14]. The sinus pneumatization process may be considered as using limited material ballooning to occupy the space among the eyeballs, brain, and mouth. This expanding process creates one frontal, maxillary, and sphenoid sinus cell on each side and, more importantly, the complexity of the ethmoid cell system. The bony sinus wall, which confines this sinonasal cavity, represents the boundary and most peripheral lining of this organ. If it is involved in the inflammatory process, it might be considered as one of the dimensions of the depth of disease extent, indicating a more severe form of sinonasal disease. One study showed that CRS patients had smaller maxillary sinuses than normal controls. These authors proposed that the increased bone thickness in the maxillary sinus itself might be related to the size of the sinus [15]. Accordingly, we demonstrated that maxillary sinus wall thickness is an indicator of poor surgical outcome.

#### *Rhinosinusitis*

The success rate of surgical outcomes for CRS patients across surgeons varies. The experience and technique of the surgeon are important factors related to the successfulness of treatment. Surgical studies contain congenital bias, that is, procedures or interventions are not executed in a uniform way; there is also a lack of patient-blinding to the surgical intervention and performance bias, which is also the case between different surgeons. Therefore, it is crucial to establish a standard surgical protocol in order to avoid the impact of the confounding effect of surgical techniques on patient outcomes. Therefore, over the past 10 years, we have made an effort to standardize surgical procedures in order to eliminate differences among surgeons. The standard eight-step FESS procedure is based on Stammberger and Kennedy's methods, which sequentially remove the obstruction of the drainage pathway anterior to posterior to reach the sphenoid sinus ostium; then, it is moved from posterior back to anterior along the identified skull base until the AEA is identified and the frontal sinus is opened. If the diseased sinuses are limited, the surgical procedure can be tailored so that the normal sinus mucosa and draining pathway are exposed and identified; this is also a way to educate beginners to understand FESS in an organized method.

In 1992, it was first suggested that chronic inflammation of the bony framework of paranasal sinuses plays a pivotal role in the pathophysiology of CRS; this hypothesis was further confirmed by subsequent animal studies [16]. Georgalas et al. proposed a global osteitis scoring scale as an indicator of revised sinus surgery [17]. Snidvongs et al. proposed that the osteitic sinus bone is a surrogate of tissue or serum eosinophilia in CRS patients [18]. Osteitis changes in the sinus bone are present in heterogeneous, irregular bone in areas of growth and destruction. Some studies have proposed that bone thickness can predict the severity of osteitis [19, 20]. Recently, sinus osteitis and subsequent bony remodeling were also suggested as a contributing factor to refractory CRS. At a microscopic level, osteitis is associated with eosinophilic inflammation and may represent a method to predict patients with P-glycoprotein overexpression by using an epithelial-tobackground staining ratio; increased osteitis burden is associated with increased P-glycoprotein membranous expression in CRS [21–23]. In our study, the sinus bony walls in Group A were significantly thicker than those in Groups C and D; in Group B, only the maxillary sinus wall was significantly thicker than that of the control group. These results reflect the importance of the role of a surgeon in evaluating surgical outcomes. Our data also suggest that a posterolateral maxillary sinus wall thickness of 3.03 mm should be the cutoff value in order to predict refractory CRS.

The existence of bacterial biofilms (BBF) has also been proposed to be associated with osteitis in CRS [10]. Biofilm formation might reflect the severity, chronicity, or both of sinus infection; therefore, the release of inflammatory mediators would stimulate osteoblast activity, inducing bony remodeling and osteitis. Osteitis may further spread the pathogen either via the Haversian canal system hematogenously or from direct local invasion [24]. Intraepithelial bacteria are also found in CRS patients [25]. Considering the histology of sinus mucosa, these factors represent the depth of involvement of inflammatory process and indicate a prolonged treatment course. Although it did not reach statistical significance, maxillary sinus wall thickness is also related to shortened time to recurrence (**Figures 3** and **4**); therefore, compared to L-M scores of sinus CT, sinus wall thickness may represent greater proximity for the chronicity of CRS. At present, the mainstay of sinus surgery still focuses on restoring ventilation, yet no specific surgical method has been proven to be effective in treating osteitis associated with CRS. Instead, long-term or topical antibiotic treatment is administrated in cases of sinus osteitis and refractory sinusitis [26].

**83**

interest.

*Refractory Rhinosinusitis*

selection in CRS patients.

**6. Conclusions**

**Acknowledgements**

**Conflict of interest**

probable systemic inflammatory disease.

*DOI: http://dx.doi.org/10.5772/intechopen.84714*

aggressive postoperative medical treatment are needed.

It has previously been reported that eosinophilic inflammation in the sinonasal

There are several limitations of this study. First, we had small case numbers. Second, there are individual differences in the tolerance of sinusitis, as revision surgery was used as the judgment for refractory sinusitis. Despite the limitations, the knowledge gained in our study provides crucial information to guide surgical

In summary, a variety of factors lead to refractory CRS. As a result, treatment for refractory CRS is a great challenge for ENT surgeons. Thickness of posterolateral maxillary sinus wall of more than 3.03 mm indicates possibility for revised surgery. For those CRS patients with thickened sinus wall in which we expect poor outcomes, further research is needed in order to justify the surgical procedure in such a

In this study of subjects of chronic rhinosinusitis (CRS) undergoing functional endoscopic sinus surgery (FESS), we determined which clinical features are associated with higher possibility for revised surgery. We have developed an eight-step standard procedure to perform FESS in order to eliminate the bias of surgical technique. Sinus wall thickness and blood eosinophilia are associated with the need for revision surgery. Thickness of posterolateral sinus wall of more than 3.03 mm in maxillary sinus indicates the higher possibility for revised surgery. Also, CRS

This study was supported by a grant (100-2314-B-002-044) from the Ministry

There are no financial or other relationships that could lead to a conflict of

patients with thickened sinus walls were found to have poorer outcomes.

of Science and Technology (MOST) of the Republic of China.

tissues is correlated with the advanced severity of CRS and the poor outcomes associated with FESS [12]. Recent evidence has shown that eosinophilic inflammation in Caucasians CRS patients with polyps does not affect Asian to the same extent. A study from Thailand indicated a time-shifting migration of neutrophilic inflammation to eosinophilic inflammation, and a study from Korea suggested that eosinophilic inflammation might not be related to surgical outcome in Korean CRS patients [27, 28]. In our study, increased peripheral eosinophil numbers had a limited impact on surgical outcomes, suggesting that the clinical implication of eosinophilic inflammation might be different in Asian patients. Nevertheless, our study strengthens the hypothesis that increased eosinophil numbers are a poor indicator of CRS outcomes. Blood eosinophilia is induced from proliferation of eosinophil progenitor from bone marrow (myeloproliferative) or clonal expansion of peripheral eosinophil in the blood stream [29, 30]. The proposal that refractory CRS represents a local manifestation of systemic inflammatory disease is supported by our results. Our study suggested that, for those patients with obvious sinus wall thickening, more detailed preoperative consultation and laboratory tests and more

#### *Refractory Rhinosinusitis DOI: http://dx.doi.org/10.5772/intechopen.84714*

*Rhinosinusitis*

understand FESS in an organized method.

The success rate of surgical outcomes for CRS patients across surgeons varies. The experience and technique of the surgeon are important factors related to the successfulness of treatment. Surgical studies contain congenital bias, that is, procedures or interventions are not executed in a uniform way; there is also a lack of patient-blinding to the surgical intervention and performance bias, which is also the case between different surgeons. Therefore, it is crucial to establish a standard surgical protocol in order to avoid the impact of the confounding effect of surgical techniques on patient outcomes. Therefore, over the past 10 years, we have made an effort to standardize surgical procedures in order to eliminate differences among surgeons. The standard eight-step FESS procedure is based on Stammberger and Kennedy's methods, which sequentially remove the obstruction of the drainage pathway anterior to posterior to reach the sphenoid sinus ostium; then, it is moved from posterior back to anterior along the identified skull base until the AEA is identified and the frontal sinus is opened. If the diseased sinuses are limited, the surgical procedure can be tailored so that the normal sinus mucosa and draining pathway are exposed and identified; this is also a way to educate beginners to

In 1992, it was first suggested that chronic inflammation of the bony framework of paranasal sinuses plays a pivotal role in the pathophysiology of CRS; this hypothesis was further confirmed by subsequent animal studies [16]. Georgalas et al. proposed a global osteitis scoring scale as an indicator of revised sinus surgery [17]. Snidvongs et al. proposed that the osteitic sinus bone is a surrogate of tissue or serum eosinophilia in CRS patients [18]. Osteitis changes in the sinus bone are present in heterogeneous, irregular bone in areas of growth and destruction. Some studies have proposed that bone thickness can predict the severity of osteitis [19, 20]. Recently, sinus osteitis and subsequent bony remodeling were also suggested as a contributing factor to refractory CRS. At a microscopic level, osteitis is associated with eosinophilic inflammation and may represent a method to predict patients with P-glycoprotein overexpression by using an epithelial-tobackground staining ratio; increased osteitis burden is associated with increased P-glycoprotein membranous expression in CRS [21–23]. In our study, the sinus bony walls in Group A were significantly thicker than those in Groups C and D; in Group B, only the maxillary sinus wall was significantly thicker than that of the control group. These results reflect the importance of the role of a surgeon in evaluating surgical outcomes. Our data also suggest that a posterolateral maxillary sinus wall thickness of 3.03 mm should be the cutoff value in order to predict

The existence of bacterial biofilms (BBF) has also been proposed to be associated with osteitis in CRS [10]. Biofilm formation might reflect the severity, chronicity, or both of sinus infection; therefore, the release of inflammatory mediators would stimulate osteoblast activity, inducing bony remodeling and osteitis. Osteitis may further spread the pathogen either via the Haversian canal system hematogenously or from direct local invasion [24]. Intraepithelial bacteria are also found in CRS patients [25]. Considering the histology of sinus mucosa, these factors represent the depth of involvement of inflammatory process and indicate a prolonged treatment course. Although it did not reach statistical significance, maxillary sinus wall thickness is also related to shortened time to recurrence (**Figures 3** and **4**); therefore, compared to L-M scores of sinus CT, sinus wall thickness may represent greater proximity for the chronicity of CRS. At present, the mainstay of sinus surgery still focuses on restoring ventilation, yet no specific surgical method has been proven to be effective in treating osteitis associated with CRS. Instead, long-term or topical antibiotic treatment is administrated in cases of sinus osteitis and refractory

**82**

sinusitis [26].

refractory CRS.

It has previously been reported that eosinophilic inflammation in the sinonasal tissues is correlated with the advanced severity of CRS and the poor outcomes associated with FESS [12]. Recent evidence has shown that eosinophilic inflammation in Caucasians CRS patients with polyps does not affect Asian to the same extent. A study from Thailand indicated a time-shifting migration of neutrophilic inflammation to eosinophilic inflammation, and a study from Korea suggested that eosinophilic inflammation might not be related to surgical outcome in Korean CRS patients [27, 28]. In our study, increased peripheral eosinophil numbers had a limited impact on surgical outcomes, suggesting that the clinical implication of eosinophilic inflammation might be different in Asian patients. Nevertheless, our study strengthens the hypothesis that increased eosinophil numbers are a poor indicator of CRS outcomes. Blood eosinophilia is induced from proliferation of eosinophil progenitor from bone marrow (myeloproliferative) or clonal expansion of peripheral eosinophil in the blood stream [29, 30]. The proposal that refractory CRS represents a local manifestation of systemic inflammatory disease is supported by our results. Our study suggested that, for those patients with obvious sinus wall thickening, more detailed preoperative consultation and laboratory tests and more aggressive postoperative medical treatment are needed.

There are several limitations of this study. First, we had small case numbers. Second, there are individual differences in the tolerance of sinusitis, as revision surgery was used as the judgment for refractory sinusitis. Despite the limitations, the knowledge gained in our study provides crucial information to guide surgical selection in CRS patients.

In summary, a variety of factors lead to refractory CRS. As a result, treatment for refractory CRS is a great challenge for ENT surgeons. Thickness of posterolateral maxillary sinus wall of more than 3.03 mm indicates possibility for revised surgery. For those CRS patients with thickened sinus wall in which we expect poor outcomes, further research is needed in order to justify the surgical procedure in such a probable systemic inflammatory disease.
