Study On Effects And Possible Mechanism Of Treating Nasal Inverted Papilloma With Traditional Chinese Medicine Xiaoliutang

Nasal inverted papilloma (IP) is a common benign tumor of the otorhinolaryngology accounting for 0.5% to 4% of all nasal tumors. Although benign in nature, this tumor has the propensity to local invasion, recurrence and association with transformation to squamous cell carcinoma. The treatment of nasal inverted papilloma is a challenge for rhinologist. The cause of IP remains unknown. With high recurrence rate and infectiosity, the clinical behaviour of IP closely resembles that of recurrent respiratory papillomatosis (RRP) and genital condylomas, which have been confirmed to be an infectious aetiology of human papillomavirus (HPV). So it suggests a possible effect of HPV infection on IP etiology. That is a new way for IP treatment if we confirm it. The prevalence rate of HPV in RRP and genital condylomas is almost 100%, whereas the detection rate of HPV DNA in IP is low and varies widely (0-80%), which hints the need for further study. With respect to the treatment of IP, an aggressive surgical therapy (i.e. lateral rhinotomy) was recommended. However, after a long period follow-up, the recurrence rate of conservative surgical management, such as endoscopic sinus surgery, showed no significant difference compared with aggressive en bloc resection, and the traditional Chinese medicine might play an important role in IP treatment. During the last ten years, we treated IP with endoscopic techniques, then the patients took traditional Chinese medicine (TCM), Xiaoliutang, which was made by ZHANG zanchen, a famous veteran doctor of TCM, after the surgery. We had found that Xiaoliutang had effects on reducing tumor recurrence, preventing canceration, inhibiting and eliminating tumor development. To date, there were no published reports available on treating IP by traditional Chinese medicine and no study on the mechanism. So it deserves to summarize the therapeutic effects and to study the mechanism.Purpose1. To study correlation between HPV infection and the etiology and prognosis of IP in order to provide a new way for IP precaution and treatment.2. To further study the clinical therapeutic effects and possible mechanism of taking traditional Chinese medicine, Xiaoliutang.Methods1. Sixty formalin-fixed, paraffin-embedded specimens of IP from the affiliated EENT hospital of Fudan University were definitely diagnosed by pathologists from 2003 to 2004. They were exmamined by the polymerase chain reaction (PCR) technique to amplify HPV DNA with HPV L1 consensus primer and HPV 57 type-specific primer. Ten specimens of chronic sinusitis were taken as control group.2. We selected sixty IP patients treated in the affiliated EENT hospital of Fudan University from September 2003 to August 2004. After resecting the tumor totally by endoscopic sinus surgery, all patients were divided into intervention group or control group randomly. Each group had 30 patients. The patients in the intervention group took traditional Chinese medicine Xiaoliutang after the surgery. They were all submitted to six courses of treatment persistently, with the duration of four weeks for each course. Meanwhile, patients in the control group did not take any medication after the surgery. After more than 8 months' follow-up, we observed the recurrence rate and canceration rate of two gropes. Then we used Chi square test to analyze the difference between intervention group and control group. By using logistic regression, we analyzed tumor recurrence and its correlated factors such as gender, age, tumor grade and intervention in order to compare the difference between two groups.3. In order to observe the effects of Xiaoliutang on regulating cellular immunity activity of IP patients, we drew 1 ml peripheral blood from patients before the operation and 6 months after the operation respectively, then detected T cell subsets (i.e. CD3+ total T lymphocyte, CD4+ helper/induced T cells, CD8+ cytotoxic/inhibitor T cell) and natural killer cell (i.e. CD3CD16+56* NK cell) cytoactive by flow cytometry. We used Paired-Sample T test to analyze the difference of cellular immunity changes between two groups. Meanwhile, we selected 30 healthy adultsfor medical examination, using the same technique in detecting T cell subsets and NK cells cytoactive to serve as normal control group. Results1. All of the sixty IP specimens showed negative after amplification by HPV L1 consensus primer MY09/11. There were forty-seven specimens(47/60, 78.3%) showed positive for HPV type 57 after amplification by HPV 57 type-specific primer. It possibly suggested an important effect of HPV infection on IP aetiology. After a follow-up period of 8 months to 18 months, 10 patients whose tumors were HPV 57 positive recurred, whereas 13 patients whose tumors were HPV 57 negative did not recur. It suggested that the presence of HPV type 57 may predict recurrence of inverted papilloma.2. After a mean follow-up period of 12.6 months (range from 8 to 18 months), no patients in the intervention group dropout. After a mean follow-up period of 12.4 months (range from 8 to 18 months), 2 cases in the control group dropout. The compliance rate met the requirements of clinical trials (compliance > 80%). Two cases among the 30 patients in the intervention group recurred, while 8 cases among the 28 patients in the control group recurred. There were no canceration cases in two groups, whereas 3 cases among the 8 recurrent patients in the control group showed mild to moderate atypical hyperplasia. Chi square test analysis showed no significant differences in gender, age and tumor grade distribution between two groups (p>0.05), while significant difference in recurrence rate was observed between two groups (p<0.05) . Logistic regression analysis indicated that after precluding the interaction effect of several factors such as gender, age, tumor grade and intervention, intervention was the only influential factor affecting the prognosis of IP patients. Patients taking Xiaoliutang after operation were less likely to recur than others.3. Before the operation, the cellular immunity of IP patients were lower than healthy adults. The T cell subsets were as following: CD3+T cell 57.27 ± 10.88%, CD4+ T cell 32.74+8.60%, CD8+ T cell 19.31 ±6.19% and natural killer cells cytoactive 14.46+6.77%. There were significant differences in CD3+ T cell, CD8+ T cell and NK cell between IP patients and healthy adultsanalyzed by t test (p<0.05) , whereas there was no significant...