| Backgrounds:Bladder cancer is a common malignant tumor.Worldwide,the incidence of bladder cancer among malignant tumors in male ninth,ranked sixth,ranked tenth in women after[1].In Europe,the incidence of bladder cancer in male malignant tumor after fourth,prostate cancer,lung cancer and colon cancer,also ranked in ten place after[2-3]in female malignant tumor.The 2002 World bladder cancer age standardized incidence rate of male was 10.1/10 million,2.5/10 million women,age standardized mortality rate of male was 4/10 million,1.1/10 million women.The United States male bladder cancer incidence rate of 24.1/10 million,6.4/10 million women[1].The American Cancer Association predicted that in 2010 the number of new cases of bladder cancer in the United States for 70530 cases(male 52760 cases,female 17770 cases),the number of deaths in 14680 cases(male 10410 cases,female 4270 cases)[4].In our country,the male bladder cancer rate ranked eighth place of all tumors and women ranked 12th[5].the incidence rate is much lower than that in western countries,2002 Chinese bladder cancer age standardized incidence rate in male and female 3.8/10 1.4/10 million[5].In recent years,our country city part of the tumor incidence report shows the incidence of bladder cancer has increased[6].Male bladder cancer incidence rate was 3-4 times higher than women.City residents and bladder cancer mortality was significantly higher than that in rural areas.In 2009 our country city residents bladder cancer age standardized mortality rate of male was 3.79/10 million,1.30/10 million women;rural male residents aged standard bladder cancer mortality rate was 2.42/10 million,0.81/10 million women[6].On the same stage of bladder cancer,the worse prognosis than men women[6].The incidence of bladder cancer in the male was higher than female does not fully account for the smoking habits and occupation factors,sex hormone[8-9]may be an important reason leading to this result.Bladder cancer can occur at any age,even in children.But the main age in middle age,and its incidence increases with age[10].2001-2005,the United States under the age of 65 male bladder cancer incidence rate of 9.5/10 million,2.9/10 million women;and over 65 years old male incidence rate was 229.4/10 million,54.3/10 million[12]women.Influence of race on bladder cancer had not yet determined.African American bladder cancer risk rate is half of the whites in the United States,but the overall survival rate is poor,and white American incidence was higher than that of blacks in the United States are limited to non muscle invasive tumors,and myoletriai invasion of bladder cancer incidence rate is similar[13].Bladder cancer is divided into non muscle invasive bladder cancer and muscle layer invasive bladder cancer,non muscle invasive bladder cancer(non muscle-invasive bladder cancer)or table of superficial bladder carcinoma accounted for superficial bladder cancer primary bladder tumor of 70%,of which TA accounted for 70%,accounted for 20%of T1,tis accounted for 10%[14].Ta and T1 both belong to non muscle invasive bladder cancer,but their biological characteristics are significantly different,because of the intrinsic layer of blood vessels and lymphatics is rich,so T1 to tumor spread[15].Some factors with the prognosis of non muscle invasive bladder cancer is closely related to the.The frequency of recurrence and recurrence is closely related to the factors which include tumor number,tumor,especially after 3 months with no recurrence,tumor size,tumor grade.With the progress of the most relevant factors including tumor pathological grade and tumor stage[16-20].The bladder neck tumor with poor prognosis[21].Currently for non muscle invasive bladder tumor treatment for surgical treatment,including:transurethral resection of the bladder tumor resection and transurethral laser surgery,photodynamic therapy,and so on.After TUR-BT surgery has 10%～67%patients will relapse within 12 months.24%～84%within 5 years after surgery in patients with relapsed,may with the new primary tumors,tumor cells to grow or primary tumor resection,related to incomplete[22.23].Non muscle invasive bladder cancer recurrence after TUR-BT had two peaks,respectively 100～200 postoperative day and after 600 days.The postoperative disseminated tumor cells with a recurrence of the first peak in the operation,and can greatly reduce the intravesical therapy due to tumor cell dissemination of postoperative recurrence.Although in theory,TUR-BT operation can complete resection of non muscle invasive bladder cancer,but there is still a very high probability of recurrence in clinical treatment,and in some cases for muscle invasive bladder cancer.With TUR-BT alone can not solve the high recurrence and progression of[24],suggested that all non muscle invasive bladder cancer patients after operation were adjuvant intravesical therapy.(1)TUR-BT surgery immediately after intravesical chemotherapy:within 24 hours after TUR-BT surgery completed soft table than star(e-adm),topiramate and soft than star(THP)or Mitomycin(VDM)and bladder perfusion chemotherapy can make tumor recurrence rate reduce 39%[25-26]therefore recommended all non muscle layer dip run of bladder cancer patients with NMIBC postoperative 24 hours in bladder perfusion chemotherapy,but operation have bladder perforation operation or after obvious hematuria should not be used[27].TUR-BT postoperative instillation of chemotherapy on single and multiple bladder cancer are effective.Low risk of non muscle invasive bladder cancer after operation immediately after reperfusion,the probability of tumor recurrence is very low,so immediately after reperfusion can not continue the intravesical treatment of[25].(2)postoperative early intravesical chemotherapy and maintain intravesical chemotherapy:for moderate-and high-risk non muscle invasive bladder cancer,within 24 hours after the operation immediately intravesical instillation after treatment,it is recommended to intravesical chemotherapy,1 times per week,a total of 8 weeks,followed by bladder maintain perfusion chemotherapy,1 times a month,a total of 6 to 12 months[28].Research shows that non muscle invasive bladder cancer to maintain perfusion in the treatment of more than 6 months can not continue to reduce the probability of recurrence of tumor,therefore recommended postoperative maintenance of intravesical therapy for 6 months[28].But it has also been found that the recurrence probability of[28]epirubicin maintain perfusion can reduce bladder cancer for 1 years.Severe bladder perfusion during stimulation symptoms,should delay or stop infusion therapy,to avoid secondary contracture of bladder.Intravesical therapy side effects and drug dosage and frequency of reperfusion.Intravesical therapy is mainly used to reduce recurrence rate of bladder cancer,there is no evidence that it can prevent tumor progression of[29].(3)intravesical chemotherapy drugs:Intravesical chemotherapeutic drugs including epirubicin star,mitomycin,imidacloprid soft than star,adriamycin,hydroxyl camptothecin.The concentration of urine pH value,chemotherapy and chemotherapy effect on bladder perfusion,and the drug concentration is more important than the dosage of[30].Chemotherapy drugs should be poured into the bladder through the catheter,and keep 0.5-2 hours(Note:Intravesical retention time according to drug instructions).Do not drink too much water before infusion,avoid urine drug dilution.Soft than the star used to dose for 50～80mg Mitomycin for 20～60mg,pirarubicin 30mg,hydroxyl Camptotheca acuminata alkali 10～20mg.Other chemotherapy drugs include geGcitabinen[31].The main side effects of intravesical chemotherapy is chemical cystitis,and the degree of perfusion dose and frequency,TUR-BT postoperative instillation should pay more attention to the side effects of drugs.Most side effects can be improved in the stop after reperfusion.2.Postoperative intravesical immunotherapy:(1)Bacillus Calmette Guerin(BCG):intravesical instillation of BCG indications:BCG in the exact mechanism of action is not clear,most studies that the immune response mediated.BCG is suitable for the treatment of high-risk non muscle invasive bladder cancer[32-35]can prevent the progress of bladder cancer.BCG cannot change the low risk of non muscle invasive bladder cancer progression,but due to the side effects of BCG perfusion has high incidence rate,low risk for non muscle invasive urothelial carcinoma of the bladder is not recommended for BCG perfusion therapy.For the risk in non muscular layer infiltration of urinary bladder epithelial cancer and the postoperative 5-year recurrence probability is 42%～65%,and progress of probability is 5%～8%[36,37]Therefore,crisis in non muscle infiltration of bladder urothelial carcinoma of bladder perfusion,the main purpose is to prevent tumor recurrence is generally recommended by intravesical instillation chemotherapy,some cases can also be treated with BCG perfusion.Because of postoperative bladder wound,so immediately after reperfusion therapy should be avoided by BCG,so as not to cause serious side effects.Intravesical instillation of BCG dose:BCG treated with 6 weeks of reperfusion induced immune response,plus 3 weeks of perfusion enhancement to maintain a good immune response.BCG perfusion for the treatment of high-risk non muscle invasive bladder urothelial carcinoma,the general use of routine dose(120～150mg);BCG for prevention of non muscle invasive bladder urothelial cancer recurrence,generally with low dose(60-75mg).The study found that non hazardous by 1/3 dose BCG infusion for the treatment of muscle invasive bladder cancer,the curative effect is the same with full dose effect,side effect was significantly lower[38-39].There is no difference between the efficacy of different BCG strains.BCG perfusion in general TUR-BT at 2 week after operation.BCG can maintain perfusion of bladder tumor progression reduces the probability of 37%[40-43].To maintain BCG perfusion 1～3(at least 1 years,so maintain perfusion)proposed in 3,6,12,18,24 and 36 months of repeated BCG perfusion,in order to maintain and strengthen the curative effect of[39].The main side effects of intravesical instillation of BCG bladder stimulation symptoms and systemic flu like symptoms,rare side effects include tuberculosis sepsis,prostatitis,epididymitis,hepatitis and other[45].Therefore,TUR-BT postoperative bladder open wounds or hematuria under such circumstances,can carry out BCG intravesical instillation.(2)immune modulators:some immunomodulators and chemotherapy drugs can prevent the recurrence of bladder tumor,including interferon,keyhole limpet hemocyanin(keyhole limpet hemocyanin,KLH).Reported in the literature,the invasion of bladder epithelium in defense of harmful factors play an important role,the physical barrier consisting of a layer of mucus like substance on the surface of the bladder epithelium and have to resist pathogens,microcrystals,protein,carcinogenic effects of adhesion factor[45].Has confirmed that this layer of mucus like material is mainly composed of mucin,one of the major components of acidic polysaccharides,called glycosaminoglycans(GAG),hyaluronic acid(HA)is a kind of classification.The foreign aid of SH leads to the defect of glycosaminoglycans(GAG)to restore the original state of[46].At present,sodium hyaluronate has been used for the treatment of interstitial cystitis,non bacterial cystitis,cystitis and Department of chemistry.See(Literature)and other research that bladder mucosa amino dextran had anti-tumor function,complete bladder mucosa is not conducive to tumor cell implantation,impaired bladder mucosa can improve the tumor formation rate of transplanted bladder perfusion,bladder mucosa intact lossless animal tumor incidence rate often less than 7010%[47]Nakamura found that the human bladder cancer cell(HT-1197)perfusion to the animal bladder cavity,tumor cells more easily attached to the damaged bladder mucosa and growth of[48].The commonly used electric cautery[49]to Damage animal bladder mucosa,some people with hydrochloride[50]or trypsin[51]animal perfusion of bladder and by chemical injury of bladder mucosa to improve tumor formation rate of bladder perfusion method.These studies also from the reverse proved bladder mucosa is extremely important significance.In the bladder tumors electric cutting process also undermines the bladder mucosa integrity,exfoliated cancer cells grow great possibility to transurethral incision,therefore increased the risk of bladder tumor recurrence;on the other hand,regardless of is transurethral resection of the bladder tumor resection,or postoperative chemotherapy,of patients with bladder mucosa have greater physical and chemical injury.To make water is painful,frequent micturition,make water urgent for the performance of chemical cystitis occurred at a higher rate,severe hematuria,affect the patient’s quality of life and to continue chemotherapy in confidence and serious need to suspend or discontinue chemotherapy.Seriously affect the quality of life of patients after surgery.Therefore,we have reason to believe that after bladder tumors were treated with transurethral resection of the bladder tumor resection and postoperative chemotherapy,by exogenous supplement sodium hyaluronate to repair bladder mucosa,can reduce the recurrence rate after resection of bladder tumor and reduce the complications caused by bladder perfusion chemotherapy,so as to greatly improve the life quality of the patients after operation.一、Effect of sodium hyaluronate on bladder tumor implantation success rate in ratsWe use hydrochloric acid injury of bladder mucosa of rats after using allograft model,selection of rat bladder transitional cell carcinoma cell line AY-27,a method for transurethral bladder perfusion.Were randomly divided into 2 groups,group A perfusion of tumor cell lines,B group first instillation of sodium hyaluronate,reperfusion tumor cell lines.Two animal groups were 45-50d after inoculation.Complete resection of bladder and bladder tumor weighing,open cavity shape,number and position.Observe whether the ureteral dilatation and hydronephrosis.To understand whether the adjacent organ invasion,pelvic lymph node metastasis.Finally,comparison of two groups of rat bladder cancer implant success rate.Objective:To investigate the effect of sodium hyaluronate on tumor of bladder mucosa injury rats success rate.Methods:to establish the 40 female nude rat model of bladder cancer,first with hydrochloric acid injury of bladder mucosa after by allograft model,selection of rat bladder transitional cell carcinoma cell line T739 perfusion,creating method of transurethral resection of bladder perfusion method.Were randomly divided into 2 groups,group A perfusion of tumor cell lines,B group first instillation of sodium hyaluronate,reperfusion tumor cell lines.2 animal groups were 45d after inoculation.Complete resection of bladder and weighing,shape,number and location of open bladder tumor cavity,and observe its pathological form,eventually A and B two groups of tumor formation rate and effects on tumor staging.Respectively,were compared to theResults:we found 1,a group of bladder cancer incidence rate was 100%,of which the superficial carcinoma in 18 cases,2 cases of tumor invasion of the muscularis;B group tumor incidence rate was 65%(13/20),superficial cancer 13 cases,no tumor invasion of the muscle layer,B group and a group of tumor occurrence rate,stage difference had statistical significance(P<0.05);2,the experimental group A,the B group,the bladder average quality(327.1 + 10.8(30.95 + 29.3 mg experiment a,B group tumor average quality(64.5 + 16.5),(46.1 + 19.2 mg),and the difference was significant(P<0.05),indicating that the hyaluronic acid sodium significantly inhibited the bladder tumor growth.Conclusion:1.Tumor cells more easily in the damaged bladder mucous membrane adhesion and value-added;2.By exogenously added hyaluronic acid sodium can repair the damaged bladder mucosa;3.Sodium hyaluronate can significantly reduce bladder mucosal injury after tumor cell planting success rate and effect of the tumor stage,sodium hyaluronate and significantly inhibited the tumor growth.二、Sodium hyaluronate and pirarubicin perfusion study on reducing the quality of life of the patients and improve the recurrence of bladder cancerUsed after July 2012 by surgery and pathology of non muscle invasive bladder cancer(T0/T1/TIS)in 80 cases of this disease.Were randomly divided into 2 groups,after a group of patients with bladder tumor after transurethral cutting complete excision of the mirror,after routine perfusion chemotherapy drugs(imidacloprid soft than star needle 30mg + water for injection 40ml);group B patients with bladder tumor after transurethral cutting complete excision of the mirror,postoperative routine perfusion chemotherapy drugs(imidacloprid soft than star needle 30mg +water for injection 40ml),after each infusion chemotherapy for 30min,emptying the bladder reperfusion transparent hyaluronic acid sodium 20ml.The two groups of patients to evaluate the quality of life of quality of life assessment scale FACT International;and followed up for 2 years.Bladder tumor recurrence rate of 2 groups were observed after operation;the international quality of life assessment scale FACT,compared two groups of patients with quality of life.Objective:To study the effect of sodium hyaluronate and pirarubicin combined with perfusion to decrease after resection of bladder cancer recurrence rate and improve the curative effect and safety of quality of life,Methods:the July 2012 after surgical resection and pathology of non muscle invasive bladder cancer in 180 cases.Were randomly divided into 2 groups,after a group of patients with bladder tumor after transurethral cutting complete excision of the mirror,after routine perfusion chemotherapy drugs(imidacloprid soft than star needle 30mg + water for injection 4ml);group B patients with bladder tumor after transurethral cutting complete excision of the mirror,postoperative routine perfusion chemotherapy drugs(imidacloprid soft than star needle 30mg + water for injection 40ml),after each infusion chemotherapy for 30min,emptying the bladder reperfusion transparent hyaluronic acid sodium 20ml.The bladder visual analog scale(VAS)score,International Prostate Symptom Score(IPSS)and daily voiding frequency to evaluate its efficacy and safety).And 2 years of follow-up,regular cystoscopy and bladder tumor recurrence rate of 2 groups were observed after.Results:Curative effect analysis:group a VAS score before treatment 0.8(judges 1.9),group B(0.5(judges 2.7),the difference between the two groups did not statistically significant(P = 0.82),after a month of intravesical therapy,we again compare VAS scores of the two groups found in group A,group B with respect to both pelvic pain pain or urinary tract irritation symptoms were improved obviously.The difference is statistically significant(Table 3,P = 0.04),until the end of our clinical follow-up,we found that in group A than in group B VAS score consistently good performance(P =0.02).Before treatment,2 groups of patients with IPSS score for 12.6(judges 3.4),13.5(judges 4.0),after treatment,a group of IPSS 14.3(judges 3.5)than in group B,the IPSS score(15.5 scholar 1.9)only a little lower,no statistical significance(P =0.1),but a group of IPSS score increase rate was obviously lower in group A is statistically significant(P = 0.02).A group frequency number from before treatment of(10.06 judg 4.09)reduced to(8.69 + 2.68 times),the number of frequent micturition of group B from(9.85 + 3.32)increased to(11 judg 4.4),the difference between the two groups have statistical significance(Table 4,P<0.01).We also found that the two groups patients with urgency and dysuria symptom improvement was not obvious,before and after the treatment in who hematuria assessment level changes in the difference had no statistical significance.In the 2 groups on chemotherapy perfusion times was no statistically significant differences,patients can carry out the intravesical instillation of pirarubicin in the study period.Conclusion:hyaluronic acid sodium combined with chemotherapy drugs perfusion can significantly improve the bladder perfusion chemotherapy in patients with VAS scores,rapid,sustained remission patients with bladder pain,and improve patients with urinary frequency and nocturia in shape and improve the quality of life of patients and VAS score in patients with a high improvement effect is more obvious.We further found that cystistat and chemotherapy drugs perfusion to prevent non muscle invasive bladder cancer recurrence after curative effect is satisfactory. |
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