| Part One:Epidemiology and clinical characterization of Esthesioneuroblastoma1 Esthesioneuroblastoma: A general review of the cases published since the discovery of the tumorObjective To establish the esthesioneuroblastoma data base and to analyse the clinical characterization .Methods A retrospective thorough literature review of patients with esthesioneuroblastoma was finished by searching for the key word"esthesioneuroblastoma" in CHKD and Pub Med between 1994-2004 and looking for its reference.ResuIt The first case was reported by Berger and Luc in 1924,total reported cases were 3455 between 1924 and 2004 in countries besides china .The first case in china was reported by Fan Zhong in 1964. ,total reported cases were 625 between 1964 and 2004 .There were 4080 cases reported since 1924.Sex distribution was male (889)and female(655) in 254 literatures.The ratio of male to female was 1.357. The age ranged from 6 months to 71 years. The first esthesioneuroblastoma of children was reported in China by Cao Jin Kang in 1964.,and reported by Portman in foreign country in 1929. The two frequent time stage of disease was 20 to 30 years and 51 to 60 years,respectively.Duration of disease ranged from 2 hours to 10 years,of which the most common time stage was 1 to 3 years .Kadish classfication was applied to 1218 cases revealing 154(12.6%) class A,414(34%)class B and 650 (53.4%)class C cases.Treatment could be classfied in 1426 cases. It consisted of surgery alone in 20.5%(293 cases),radiotherapy alone in 12.9%(184 cases),chemotherapy alone in 16.1 %(230 cases),combined surgery and radiotherapy in 44.1%(629 cases), combined radiotherapy and chemotherapy in 0.6%(8 cases),combined surgery, radiotherapy and chemotherapy in 0.7%(10 cases),bone marrow transplantation 4.8%(68 cases),followed in 4 cases(0.3%) by other therapy.According to the frequency,the main symptoms were nasal blockage , epistaxis, proptasis, headache ,the location of disease was mainly in ethmoid sinus, intranasal, maxillary sinus, orbital, anterior craninal base.Esthesioneuroblastoma was misdiagnosised as nasal polyp mostly.2 Epidemiology and clinical characterization of Esthesioneuroblastoma in chinaObjective To establish the Chinese esthesioneuroblastoma database and analyze their clinical characterization.Methods A retrospective thorough literature review of patients with esthesioneuroblastoma by searching for the key word"esthesioneuroblastoma" in CHKD between 1994-2004 and looking for its reference was retrieved and analyzed.Results The first case in China was reported by Fan Zhong in 1964.1n our search we found a total of 625 cases.Sex distribution was male (385)and female(199) in 584 cases and the ratio of male to female is 1.94.Kadish classfication was applied to 452 cases revealing A(45), B(173) and C(234),respectively.Treatment could be classfied in 350 cases. It consisted of surgery alone(59 cases),radiotherapy alone(82 cases),chemotherapy alone(7 cases),combined surgery and radiotherapy(180 cases), combined radiotherapy and chemotherapy in(8 cases),combined surgery > radiotherapy and chemotherapy(10 cases),followed by other therapy(4 cases). There were 213 patients who had clinical records,ranged in age from 6 months to 71 years,with a male-to-female distribution of 143 to 7O.The two frequent time stage were 20 to 30 years old and 51 to 60 years old,respectively.Duration of disease ranged from 2 hours to 10 years,of which the most common time stage was 1 to 3 years .Patients were grouped by tumor stage using Kadish system and included A (8.3%), B(45.0%) and C(46.7%),respectively.According to the frequency, nasal blockage and epistaxis were the main symptoms,the location of disease were mainly in ethmoid sinus and intranasal roof.Esthesioneuroblastoma was first misdiagnosised as nasal polyp,then as undifferentiated cancer..3 Esthesioneuroblastoma in childrenObjective To establish the esthesioneuroblastoma data base of children and analyze their clinical characterization .Methods The esthesioneuroblastoma in children treated in our hospital from 1993 to 2004 were retrospectively evaluated,and thorough literature review of patients with esthesioneuroblastoma was performed by searching for the key word "esthesioneuroblastoma" in CHKD and in Pub Med between 1994-2004 ,also looking for its reference. Results In our hospital,4 case were found .The first esthesioneuroblastoma of children in China was reported by Cao Jin Kang in 1964.The clinical characterization ofesthesioneuroblastoma in china(37 cases)were: Sex distribution of male to female is 1.85, the youngest patient was six month old and the most frequent age stage was 11 to 15 years. Duration of disease ranged from 3 days to 2 years, of which the most common time stage was 1 to 3 months. According to the frequency, nasal occlusion n proptosis^ epistaxis > headache were the main symptoms and the intranasak ethmoid sinus > orbitah anterior craninal fossa were the main location of disease. Treatment was mainly combined surgery and radiotherapy, then surgery alone. Follow-up was not enough and patients mainly died of primary tumour. In foreign country, the first esthesioneuroblastoma of children was reported by Portman in 1929. There had been 130 cases reported from 1929 to 2004. The clinical characterization of esthesioneuroblastoma in foreign country were: Sex distribution of male to female is 1.47(79 cases), the youngest patient was 2 years old ,and as in china, the most frequent age stage was 11 to 15 years old. Comparing with china, treatment was mainly surgery ,then was combined surgery and radiotherapy.Follow-up was better in foreign country than that in china and also most patients died of primary tumour.Conclusions Esthesioneuroblastoma is a rare tumor and most patients were at advanced stage when diagnosed.Esthesioneuroblastoma should be suspected with patients who had epistaxis^ nasal obstruction and intranasal , ethmoid sinus mass.Combined surgery and radiotherapy should be selected first.Part Two:Clinical analysis of esthesioneuroblastoma.Objective To illustrate the diagnosis .biological behavior and therapy modality of esthesioneuroblastoma.Methods All of the patients' records with esthesioneuroblastoma from Mar.1993 to Jun.2004 including age^ gender duration> Kadish stagings Hymas grading^ primary therapy modality > recurrence > salvage treatment outcome were analyzed.Results There were 24 cases,the age of patients ranged from 4 to 71 years,averaging 38.21 years old and with a male-to-female distribution of 1.4. Duration of disease ranged from 20 days to 6 years,averaging 9 months.Patients were grouped by tumor stage using Kadish (stages A,B and C )included 1,12 and 11 patients,respectively.According to theHymas 1-, 2^ 3 s 4 grading,there were 1-. 6> 9> 5 cases,respectively.The most common symptoms of adult were nasal obstruction and epistaxis ,and that of children were nasal obstruction and proptosis.According to the frequency,the location of disease were mainly in intranasal and ethmoid sinus.Esthesioneuroblastoma were misdiagnosised most as nasal polyp and sinusitis.On histopathological examination^ was misdiagnosised as embryonal rhabdomyosarcoma most and confused with other small cell malignant tumor and peripheral primitive neuroectodermal tumors.Imaging study was not in accord with exact primary site,with a ratio of 66.67 percent.Primary treatment modality were composed of 16 cases with combined therapy(surgery^ radiotherapy and chemotherapy in 5 cases,surgery and radiotherapy in 11 cases),7 cases with surgery alone and one patient without therapy. 10 cases relapsed,the time ranged from 6 days to 48 months ,averaging 7.52 months.The location of recurrence were 4 cases with primary site and 6 cases with neck lymph node metastases.After salvage treatment for 23 months and 36 months,2 cases relapsed again ,and the location were intracranial and ethmoid sinus,respectively. r -knife , combined surgery and radiotherapy were applied as second treatment modality to control disease,respectively.The technique of surgery in primary treatment included 7 cases with endoscopy,4 cases with lateral rhinotomy,4 cases with local endonasal resection,3 cases with lateral rhinotomy and maxillectomy,3 cases with transcranial and endoscopy, 2 cases with craniofacial resection.In salvage treatment,the approach included 3 cases with elective neck dissection,2 cases with lateral rhinotomy, 1 case with endoscopy and 1 case with craniofacial resection.Postoperative complication occured on three patients,one was cerebrospinal fluid leak,one was intracranial bleeding and the other was maxillary sinus fistula.Chemotherapy were applied on 5 cases in primary treatment,3 cases in salvage treatment.The main component of chemical drug contain etoposide and platin.After followed-up by letter or telephone for 6 months to 10 years,only 9 cases replied(4 cases were alive with tumor,4 cases were alive without tumor, 1 cases died from tumor), 15 cases were lost to follow-up.Conclusions There are no specific symptoms for esthesioneuroblastoma. Early diagnosis , differential diagnosis and combined treatment regimes areimportant to control the metastases of esthesioneuroblastoma and may lead to long-term disease-free survival.Part Three: A meta-analysis of esthesioneuroblastoma(1994-2004) Objective To evaluate predictors of survival ofesthesioneuroblastoma.Methods A retrospective thorough literature review of patients with esthesioneuroblastoma was finished by searching for the key word"esthesioneuroblastoma" in Pub Med between 1994-2004 and Only primary tumor series giving individual patient age,gender,Kadish stage,Hymas grade,primary treatment,recurrence,survival,and disease status were included in the analysis.Evaluation of survival rates using the Kaplan-Meier method.Analysis of prognostic factors was carried out with the log-rank test and the Cox proportional hazards mode.Result There were 162 articles entered into study between 1994-2004 year and only 6 articles and 81 cases provided adequate information.Sex distribution was male 42(51.85%)and female39(48,15%) .The ratio of male to female is 1.08.The age of patients ranged from 10 to 85 years old ,average 43 years old and the two frequent time stage was 31 to 40 years and 51 to 60 years,respectively.Kadish classfication revealing 6(7.4%) class A,34(41.98%)class B and 41(50.62%) class C cases.Hymas grdae revealing 13 (16.05%)grade 1,22 (27.16%)grade 2,18(22.22%) grade 3,14(17.28%) grade 4 and 14(17.28%) case without available information.Treatment was composed of surgery alone in 19.75%(16 cases),radiotherapy alone in 4.94%(4 cases),chemotherapy alone in 1.23%(1 cases),combined surgery and radiotherapy in 48.15%(39 cases), combined radiotherapy and chemotherapy in 33.33%(7 cases),combined surges radiotherapy and chemotherapy in 18.52%(15 cases). 33 cases relapsed and 16 cases were given salvage therapy.After follow up for 1 month to 21 year,40 cases survived,33 cases died of tumor and 9 cases died of other reason. According to Cox proportional hazards model,time of survival was related to Kadish stage (P: 0.0005) > primary treatment modality (P: 0.0099) > Hymas grade ( P: 0.0102) > recurrence ( P: 0.0308) > age(P:0.0427) , sex(P:0.0454).The 5-year, 10-year survival rate of male and female was 63%, 45% and 52%^40%,respectively(P=0.29).The 5-year, 10-year survival rate of over50 years old and younger was 55% n 34% and 63% > 35%,respectively(P=0.33).The 5-year> 10-year survival rate of Kadish stage A/B andCwas76%> 57%and38%^ 23%,respectively(P=0.001).The 5-year > 10-year survival rate of Hymas grade 1/2 and 3/4 was 72% -. 47% and 35%, 30%,respectively(P=0.018).The 5-year> 10-year survival rate of recurrence and nonrecurrence was 27% ^ 20% and 78% > 55%,respectively(P=0.OO03).The 5-year> 10-year survival rate of local relapse ^ regional metastases and distant metastases was 23% > 17%,50%. 0%and25%^ 0%,respectively.Conclusions Kadish stage > Hymas pathological grade -. recurrence were the main predictors of survival of esthesioneuroblastoma.Aggresive multimodality therapeutic strategies and salvage treatment can improve 5-yean 10-year survival rate. The 5-yean 10-year survival rate of male and younger patient is higher than that of female and older patient.Part Four:TGF-Bl/Smad4/ MMP-2 ^ MMP-9 signal transduction of esthesioneuroblastoma.Objective To examine the expression of TGF-Bl > Smad4, MMP-2, MMP-9 in esthesioneuroblastoma and discuss its relationship to clinical biological behaviour. Methods 24 specimens of human esthesioneuroblastoma were assessed by using immunohistochemical method(S-P method). Results The expression of TGF-Bl and Smad4 were significantly higher than that of MMP-2 and MMP-9 respectively., but TGF-Bl was no different from Smad4;The positive rates of TGF-Bl was significantly higher in the tissue of patients with neck lymph node transfer;The positive rates of Smad4 and MMP-2 were significantly higher in the tissue of Kadish C-D stage than those of Kadish A-B stage, The positive rates of MMP-9 was significantly higher in the tissue of Hymas grade 3-4 than those of Hymas grade 1-2;The positive rates of MMP-9 was significantly different between young and old patients;recurrence was in close relationship to MMP-9;and the expression of TGF-Bl, Smad4> MMP-2> MMP-9 were no different between male and female.Conclusions TGF—pi> Smad^ MMP—2> MMP—9 were involved in the formation of esthesioneuroblastoma, but the mechanism of TGF — pi controling MMP-2 and MMP-9 was not by TGF—(51/Smad4 signal transduction;TGF — pi can predict the neck lymph node transfer of patient with esthesioneuroblastoma;MMP-2 can indict the progression of esthesioneuroblastoma;MMP-9 can predict the malignant degree ofesthesioneuroblastoma;TGF — pi also can indict the different biological behavior between young and old patient with esthesioneuroblastoma indirectly.
|
PDF Full Text Request