| PartⅠThe Clinical Research of nasal endoscopy Surgical Therapy and Therapeutic Effect of Sinonasal Inverted PapillomaBackgroundSinonasal inverted papilloma (SNIP) is a kind of benign sinonasal tumor which constitutes 0.4% to 4.7% of all nasal tumors and commonly seen in middle aged men. It has a marked tendency to recur after surgical treatment. The tumor is associated with recurrence and malignancy and during growth it can destroy surrounding tissue and correlated with squamous carcinoma. Surgical excision is regarded as the treatment of choice for it. Traditional surgery such as the lateral rhinotomy has served as the standard for surgical management for SNIP, however, the s approach has some questions which have more impaired, more hemorrhagic and more length of hospital stay. All SNIP, arise typically from the lateral nasal wall or within the maxillary sinus. Males are 4-5 times more frequently affected than females. SNIP is prevalent in the fifth and sixth decades of life. The four characteristic attributes of Inverted papilloma are its tendency to recur, its destructive capacity, the associated nasal polyps, and its propensity to be associated with malignancy. The main treatment is surgery. The best surgical approach and the extent of resection are somewhat controversial, as is discussed in the literature. The approaches include conservative intranasal piecemeal excision, Caldwell—Luc surgeries and a more aggressive wide excision by lateral rhinotomy. The above procedure has a high recurrence rate and facial scars. With the development of nasal endoscopy and imaging diagnostic technique, endoscopic surgery or associated with open approaches has been accepted by more and more scholar as the major therapy measure. Endoscopic sinus surgery for nasal inverted papilloma is characterized by a less trauma and the function of nasal cavity and paranasal sinuses were better retained. Endoscopic resection is a favorable treatment option for most cases of sinonasal inverted papilloma. The primary purpose of this research is to investigate the surgical methods and the therapeutic effect of SNIP undergoing endoscopic sinus surgery.ObjectiveThe objective of this study was to compare the endoscopic with tradition and associated with open approaches for surgical management of SNIPs. Operative parameters included the operated time(OT), estimated blood loss(EBL), length of hospital stay(HS)were al so compared.MethodsA retrospective analysis was performed of medical records for 91 cases treated with endoscopic resection of sinonasal inverted papilloma at the Department Otorhinolaryngology Head and Neck Surgery of the 3rd hospital affiliated Sun-Yet Sen University from August 1996 to February 2008. There were 62 males and 29 females in the study group. The patient ages ranged from 23 to 70 years, with an average age of 48.6 years. All patients were classified according to the staging systems separately reported Krouse specifically for SNIP. In 2000, Krouse developed a staging system based on the extent of tumor involvement depending on endoscopic, CT, and MRI examinations. The importance of this classification is because of the impact of the portion or portions of the antrum involved and/or extra sinonasal extensions on surgical plan:T1:tumor totally confined to the nasal cavity; the tumor Can be localized to one wall of the nasal cavity or can be extensive within the nasal cavity;T2:tumor limited to the medial and superior portions of the maxillary sinus. And/or involving the ethmoid sinus, with or without involvement of the nasal cavity; T3:tumor involving the lateral inferior; anterior; or posterior walls of the maxillary sinus, the sphenoid sinus, and/or the frontal sinus, with or without involvement of the ethmoid sinuses, or the nasal cavity;T4:tumor extending outside the confines of the nose and/or paranasal sinuses to involve adjacent, contiguous structures(e.g., the orbit, intracranial compartment, or the pterygomaxillary space) Nowadays, Krause's system is used to be the standard of the classification for SNIP. The staging was summarized as following:18 pts in gradeⅠ,45 pts in gradeⅡ,25 pts in gradeⅢ,3 pts in gradeⅣ. Simple endoscope approach group(A group):18 cases in gradeⅠ ,33 cases in gradeⅡand 13 cases in gradeⅢ. Endoscopic surgery combined with Caldwell-luc approach group (B group),12 cases in gradeⅡand 12 cases in gradeⅢ. Endoscopic surgery combined with external approach group(C group):3 cases in gradeⅣ. The classification system based on the origin of SNIP is helpful in planning surgery and evaluating results:①In gradeⅠandⅡ, we performed with conservative transnal endoscopic en bloc excision and according to the root of the tumor;②In gradeⅡand cases involved the media wall of maxillary sinus, we performed with extend local-excision;③In gradeⅢand cases involve the lateral, front, media and rear wall of maxillary, we performed with radical excision by endoscopic combined with improved Caldwell-luc procedure to remove the tumor in ethmoidal and maxillary sinus;④In gradeⅣand cases involved superior wall of orbit and rear wall of frontal sinus, we performed radical excision by endoscopic surgery combined with anterior wall fenestration of frontal sinus. Statistical analysis:All the data were analyzed by the software SPSS 11.0. Ratio comparison is done by chi-square and Fish's methods.ResultThe patients were following up for 18 to 90 months, average 37 months. The total recurrence rate is 15.4%(14/91). The recurrence rate for A group:gradeⅠis 5.6%(1/18),gradeⅡis 6.1%(2/33),theⅢgrade is 53.8%(7/13); The recurrence rate for B group:gradeⅡis 16.7%(2/12), theⅢgrade is 8.3%(1/12); The recurrence rate for C group:gradeⅣis 33.3%(1/3). The main complaint was unilateral nasal obstruction and epitasis. Lesions arising from the nasal septum or lateral nasal wall presenting the nasal cavity resulting in the nasal obstruction and early diagnosis while the lesion is relatively small and limited. Tumors originating from the maxillary sinus give vague symptoms and result in late diagnosis while the lesion is large and extensive. SNIP regardless of its size, location, and/or extent could be traced to its origin. In gradeⅠ, the origin of the lesion was localized in most of the cases and pedicled in about 60% cases. In gradeⅡ, the origins were wide and diffuse in all cases. All cases were unilateral with no secondary attachment and/or multicentricity. In gradeⅡ, medial wall was involved in all cases, inferior involved in some cases, anterior, lateral, posterior, superior wall. In most case, tumors were found in nose cavity. In gradeⅠ, maxillary sinus was involved in four cases that were origined from lateral nasal wall. Nasolacrimal duct was involved in more than half. The extension of tumor beyond the confines of the nasal cavity and paranasal sinuses(e.g., orbit, nasopharynx, dura, or soft tissue of nose or face) were not found in all cases. With recent advances in transnasal endoscopic sinus surgery and CT/MRI, in KrouseⅡ cases, the difference was not statistically significant in rate of recurrence between A and B group. However, the recurrence rate is higher in the group of A than that of group B in KrouseⅢcases. The cases of recurrence required additional surgery and there were no relapse for following-up 24 months.ConclusionWith nasal endoscopy and CT/MRI, we can trace the origin of NIE The classification system based on the origin of SNIP is helpful in planning surgery and evaluating results. Lesions arising from the nasal septum or lateral nasal wall present in the nasal cavity resulting in nasal obstruction and early diagnosis while the lesion is relatively small and limited. Tumors originating from the maxillary sinus give vague symptoms and result in late diagnosis while the lesion is large and extensive. It may get the better therapeutic effect in patients with Endoscopic nasal surgery, if the indications are appropriate. And the patient's quality of life may be improved significantly. Endoscopic sinus surgery is an excellent procedure for treating SNIP who have limited disease that involves the lateral nasal wall. the anterior and posterior ethmoid sinuses, and the medial maxillary wall(KrouseⅠ,Ⅱand parts ofⅢ). It can completely remove the tumor and the nasal function can be retained.1. The endoscopic surgery is the preferred method which has less bleeding, fewer complications and shorter hospitalization time and reduce the financial burden of patients.2. The recurrence of the inverted papilloma undergoing endoscopic surgery is in a reasonable range and better than the external approach.3. The endoscopic surgery is a safe, economical and effective method for the SNIPs cases in Krouse gradeⅠandⅡFor the KrouseⅢor/andⅣcases in recurrence or extensive disease, endoscopic surgery combined with external approach is a better choice which should be studied in clinical practice. 1) In gradeⅠ, we performed with conservative transnal endoscopic en bloc excision if the tumor located in the nasal cavity.8. We performed with conservative transnasal endoscopic excision and with performed conservative transnasal endoscopic excision, radical transnasal endoscopic medial maxillectomy, combined approach, Lateral rhinotomy.2) For gradeⅡ, we performed ethmoidectomy and enlarged the ostia of maxillary as impossible for promoting the postoperative follow-up. At the same time, the favorable operation effect requires not only making a clean sweep of tumor, but also maintaining the integrity of the normal mucosa.3) For gradeⅢ, the patients should be operated by the combination of endoscopic surgery and anterior wall fenestration of frontal sinus procedure, when the tumor involved the lateral wall of frontal sinus or the anterior wall of orbit.4) For gradeⅣ, the patients should be performed with endoscopic surgery and external approach, when the tumor involved the external nasal including orbit and the skull base.PartⅡExpression of Survivin and Capase-3 in Sinonasal inverted papilloma and their clinical significanceBackgroundSinonasal inverted Papilloma (SNIP) is a kind of benign tumor originated in nasal sinus mucosa, but characterized by aggressive nature and high recurrence rate and malignant transformation potential. Its incidence and recurrence and malignant transformation mechanism is not clear. Survivin is a new antiapoptosis gene, which is discovered recently. And survivin protein is a new member of inhibition of apoptosis protein (IAP) family. It can inhibit cell apoptosis, and play a significant role in cell mitosis and cytoplastic cleavage. Research shows that survivin is a tumor specific apoptosis gene, which is expressed in the process of embryonic development and human tumor tissue, but in the mature terminal differentiation organization in reducing loss or cannot be found. Survivin is an anti—apoptosis gene which is cloned by DC.Altirei. Survivin plays a pivotal role in not only cell survival but also cell cycle progression. Survivin is a potent inhibitor of apoptosis; being a member of inhibitors of apoptosis proteins (tAP) family which also includes XIAP, clAP1, clAP2, NIAP, ML-IAP and apollon. The lAP family members inhibit apoptosis via the baculovims IAP repeat domains which can directly or indirectly interact with caspases (pro-caspase-9, caspase-3 and caspase-7). In addition, Survivin may promote proliferation by facilitating accurate sister chromatid segregation and stabilization of microtubules in late mitosis where it forms a complex with the inner centromere protein, Aurora B kinase and Borealin. Survivin is normally expressed in abundance during embryonic development, coordinating cell divisions of normal growth and tissue differentiation. Survivin often becomes undetectable in terminally differentiated tissues. However, during carcinogenesis, survivin is often highly expressed. High expression of survivin is associated with poor prognosis and increased frequency of relapse in many common human cancers(e.g. colorectal cancer, acute myeloid leukemia and prostate cancer). In addition, targeting survivin by specific antisense oligonucleotides can effectively kill tumor cells. Overexpression of survivin has been suggested to cause resistance to various chemotherapeutic compounds in cancers. Therefore, survivin has been hailed by scientists as one of the most cancer-specific targets for cancer therapeutics. The capase-3 is a member of the cysteine-aspartic acid protease (caspase) family. The occurrence of apoptosis is a complicated protease cascade process that is guided by the caspase family group, Activation of effector caspases is a central and ultimate step in many apoptosis pathways. Caspase-3 is the key executioner caspase, it exists as an inactive zymogen that is activated by upstream signals. Several groups have considered using the human caspase-3 gene as a novel form of anticancer gene therapy. However, overexpression of the wild-type caspase-3 in mammalian cells does not induce apoptosis, which is due to their inability to undergo autocatalytic processing without upstream caspase for activation. Recently, constitutively active recombinant caspase-3(re-caspase-3)has been was generated by making its small subunit preceding its large subunit. Unlike its wild-type counterpart that is the large subunit preceding the small subunit, the re-caspase-3 is capable of autocatalytic processing and inducing apoptosis independent of the upstream initiator caspase molecules. In addition, it could resist the effect of some apoptosis restraining genes. As caspase-3 is the most downstream executioner of apoptosis, the re-caspase-3 could be used at very low concentrations to induce apoptosis in target cells. To determine the effect of inhibit apoptosis and proliferative activity in SNIP and the relations of each others, and to Provide a new way of the clinical monitoring and prognostic evaluation of SNIP, and also provide an objective basis for treatment on the SNIP.ObjectiveThis study focused on the pathological form of the SNIP, according to the relationship between the SNIP unique features and caspase-3 and survivin's biological characteristics of the tumor, to detect the expression of the caspase-3 and survivin in the SNIP using the immunohistochemical methods.MethodsThe experimental group was selected from SNIP patients in Otorhinolaryngology of the 3rd affiliated hospital of Sun-Yet Sen University during 2003-2008, surgical excision, clinical data and follow-up records are all integrity, reviewing the original HE dying pathological section confirmed cases can be evaluation 46 cases. Among these cases,33 cases was male,13 cases was female. Their age was between 39 to 70 years old, average 53.8 years. To detect the expressing of caspase-3 and survivin in tissue of 46 cases of SNIP using immunohistochemistry methods with mouse anti-human monoclonal antibody caspase-3 and Rabbit anti-human polyclonal antibody Survivin. At the same time, to detect the expression of Caspase-3 and Survivin in tissue samples of 10 cases of SCC (squamous cell carcinoma,SCC) and 10 patients with normal nasal mucous as the control group.(The SNIP group was subdivided into the new-onset group, the recurrence group and the malignant group).Statistical treatmentAll data processing used statistical software SPSS 13.0, and p<0.05 was significant for the difference. The comparison between constituent ratios was made with Chi-square test. We used Spearman rank correlation to analysis the correlation of Survivin and Caspase-3, significance level was set to a=0.05. To compare the expression of Survivin and Caspase-3 in the three group of SNIP and the SCC group, ordinal multi-categorical data and the two categorical data was described by Wilcoxon signed rank test.ResultSurvivin was expression in 69.6% cases of SNIP,90.0% cases of SCC and not expressed in 0% cases of normal inferior concha tissues. Caspase-3 was expressed in 20% cases of SCC, which is significantly lower than cases of normal nasal mucosa(P<0.01). Caspase-3 was expressed in 41.3% cases of SNIP, which is lower than that in normal tissues 100%(P<0.01), but there was no significant difference between them(P>0.05). Expression of Survivin and Caspase-3 was negatively related to expression of survivin in SNIP. The expression of Survivin in the normal mucosa group, SNIP and SCC group had significant differences. The expression of Survivin in the SNIP new-onset group, the recurrence group, the malignant group and SCC group were all gradually increased, and the expression among these groups were significant differences. Rank test showed that Survivin in the SNIP new-onset group and the recurrence group, the malignant group and SCC group were significant difference between each two groups, there was no significant difference in the other groups. The expression of caspase-3 in the normal mucosa group, SNIP and SCC group had significant differences. The expression of Caspase-3 in the SNIP new-onset group, the recrudescent group, malignant group and SCC group were all gradually decreased, and the expression among these groups were no significant differences.ConclusionThe results are significantly different between the expression Survivin and Caspase-3 in tissue samples of SNIP, SCC and normal mucosa, and the two results have closed relations. The results showed that the development process of SNIP involved the activation of apoptosis inhibitory factor Survivin and the altered function of Caspase-3.1. SNIP is a benign tumor, but with high recurrence and malignant transformation in the clinical characteristics, which should cause enough attention. Survivin may play an important role in the pathway of progressing of SNIP and SCC. It may be identified as a new therapeutic target.2. The expression of Survivin increased in the SNIP. The expression of Survivin in the SNIP new-onset group, the recrudescent SNIP, the malignant SNIP and SCC group gradually increase.3. From the new-onset SNIP, the recrudescent SNIP and the malignant SNIP to SCC organizations, Caspase-3 expression gradually decrease. Prompting that Caspase-3 may regulate the homeostasis of normal nasal mucosa and the apoptosis of transformed cells. The expression of Caspase-3 may play important role in the pathogenesis of sinonasal inverted papilloma and squamous cell carcinoma.4. There was negative significant correlations between the expression of Survivin protein and the expression of Caspase-3, thus the results had shown that survivin was a bifuntional protein capable both of suppressing apoptotic cell death and regulating cell proliferation, and it could promote the neoplastic progression by both inhibition of cell apoptosis and progress of cell proliferation.5. By the detection of Survivin and Caspase-3 there is an important reference value for the diagnosis and prognosis of SNIP. |
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