Utilizing Instilling Negative Pressure Wound Therapy with Vashe Wound Solution for an Infected Sternal Dehiscence: A Case Report

Utilization of negative pressure wound therapy with instillation (NPWTi) for sternal dehiscence wounds secondary to sternal wound infection after surgery has become an accepted therapy. NPWTi accelerates wound healing through macrostrain, microstrain, and cyclic fluid instillation. Wounds benefit from additional superficial infection control with the removal of microorganisms, the release of proinflammatory mediators, stimulation of angiogenesis, as well as mechanical debridement. However, very few cases of utilizing NPWTi in the treatment of sternal wound infections have been reported in the literature. This case study describes the use of NPWTi with hypochlorous acid for the treatment of a sternal wound infection.

Swallowing Difficulties,Oral Symptoms,and Nutrition in Long-Term Care Elderly Residents-A Secondary Publication

Oral health is often impaired in people living in residential care.In older people,poor oral health is associated with functional deficits,multiple sclerosis,and memory disorders.Keeping one’s teeth healthy throughout life would promote both oral health and general health.Biting and swallowing problems in older people are also linked to oral health,limiting eating activities and requiring diet changes to softer foods that are easy to chew and swallow.This may limit dietary diversity and adequate nutrient intake.Although eating-related chewing and swallowing problems are common in institutionalized residents,they are often addressed too late,when the resident is already malnourished.Nutrition in nursing and retirement homes has been the subject of various studies since the 2000s.However,studies on swallowing and chewing difficulties are scarce and their link to adequate nutrient intake has received lesser attention[6,7].

Sudden sensorineural hearing loss-A contemporary review of management issues

Sudden sensorineural hearing loss(SSNHL)is an enigmatic entity,with obscure pathophysiology and debatable efficacy of the treatment agents used.An underlying cause is identified in only 10-15%of cases.The management of the remaining patients,classified as‘idiopathic’,is empirical,and is conventionally with systemic steroids,vasodilator therapy,rheological agents,and antioxidants,to list a few amongst the host of the agents employed for the treatment.The availability of conflicting outcomes and lack of conclusive evidence has resulted in the propagation of consensus-based treatment protocols.In the present review,we discuss the various controversial issues and newer developments in the management of idiopathic SSNHL.The current review aims to present a narrative outlook of the updated evidence base available from PUBMED,augmented with relevant designated publications.

Oxidative Damage to Lung Tissue and Peripheral Blood in Endotracheal PM_(2.5)-treated Rats

Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats. Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase （GSH-Px） and concentration of malondialdehyde （MDA） were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length （μm） and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length （μm） and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length （μm） and rate of tail are simple and valuable biomarkers of PM2 5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis

AIM: To assess the efficacy of topical Semaphorin 3A(SEMA3A) in the treatment of allergic conjunctivitis.METHODS: Experimental allergic conjunctivitis(EAC)mice model induced by short ragweed pollen(SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin(H&E) staining, immunofluor-escence and light microscope photographs. Early phase took the samples in 24 h after instillation and late phase took the samples between 4 to 14 d after the start of treatment. The study use of topical SEMA3A(10 U, 100 U,1000 U) eye drops and subconjunctival injection of SEMA3 A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics.· RESULTS: Clinical score of composite ocular symptoms of the mice treated with SEMA3 A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3 A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3 A 1000 U-treated group were significantly lower than low-concentration of SEMA3 A treated groups and non-treated group. SEMA3 A treatment also suppressed T-cell proliferation in vitro and decreased serum total Ig E levels in EAC mice. Moreover, treatment of SEMA3 A suppressed Th2-related cytokines(IL-5, IL-13 and IL-4)and pro-inflammatory cytokines(IFN-γ, IL-17 and TNF-α)release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC mice.CONCLUSION: SEMA3 A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3 A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.

Feasibility of drug delivery to the eye’s posterior segment by topical instillation of PLGA nanoparticles

We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles(NPs). Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan(CS) and glycol chitosan(GCS), which are mucoadhesive polymers, and polysorbate 80(P80) were used as surface modifiers, and have been reported to increase the association of NPs with cells.Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal,non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation.

The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device

Background: Middle East respiratory syndrome coronavirus(MERS-Co V), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health.Methods: To simulate the clinical aerosol transmission route, h DPP4 transgenic mice were infected with MERS-Co V by an animal nose-only exposure device and compared with instillation-inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues.Results: MERS-Co V aerosol-infected mice with an incubation period of 5-7 days showed weight loss on days 7-11, obvious lung lesions on day 7, high viral loads in the lungs on days 3-9 and in the brain on days 7-9, and 60% survival. MERS-Co V instillation-inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3-5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3-5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS-Co V aerosol-infected mice than in the MERS-Co V instillation-inoculated mice.Conclusion: h DPP4 transgenic mice were successfully infected with MERS-Co V aerosols via an animal nose-only exposure device, and aerosol-and instillation-infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS-Co V developed disease and lung pathology progressions that more closely resembled those observed in humans.

Intravesical Non-Alkalinized Lidocaine Instillation for Interstitial Cystitis/Bladder Pain Syndrome Patients

Purpose: The effectiveness of daily or weekly instillation of non-alkalinized lidocaine for patients suffering interstitial cystitis and/or bladder pain syndrome was evaluated retrospectively. Patients and methods: Five female patients (40 - 71 years old) diagnosed as interstitial cystitis by cystoscopic findings and a 68 year-old bladder pain syndrome patient were enrolled. All patients, having interstitial cystitis, had undergone hydrodistention therapy previously and had not improved their symptoms by empirical therapies. Daily or weekly (upon their severity of symptoms) intravesical instillation of 20 ml of 4% non-alkalinized (pH 6.0 - 7.0) lidocaine solution was performed for several times, and patients were asked to keep them in the bladder as long as two hours each time. Previous medications such as anti-cholinergic drugs and analgesics were continued according to patient's requirements and symptoms. The treatment effect was evaluated comparing O'Leary-Sant Symptom Index for interstitial cystitis patients and visual analog pain scale before and after the series of lidocaine therapies. Results: Instillation was made 6 to 16 times. Patients with interstitial cystitis improved their symptoms from O'Leary-Sant Symptom Index 17.5 to 10, Problem Index from 14.8 to 6 in an average. Crouching pain disappeared in all these patients after the instillation therapy. Severe interstitial cystitis findings on cystoscopy disappeared completely in one patient after the therapy. One patient having bladder pain syndrome reduced her analgesics use, and bladder-filling pain decreased from 7 to 3 as a visual analog scale score. One patient complained palpitation at 11th instillation and abandoned treatment thereafter, otherwise, none of these patients showed side effect concerning lidocaine toxicity. Conclusions: Intravesical non-alkalinized lidocaine instillation therapy for interstitial cystitis/bladder pain syndrome patients were an easy, safe and effective treatment.

Intravesical Instillation in Pure Line LEW Rats and Nude Mice

In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and an- gle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activi- ties of animals weren’t influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

A Five-year Follow-up Study on the Efficacy and Safety of Female Tubal Sterilization by Chemical Instillation

A multi center randomized clinical trial was adopted in the present study. 1705 eligible women with identical demographic and gynecological characteristics were divided into two groups: 871 using phenol atabrine paste (PAP) and 834 using phenol mucilage (PM). The five year follow up rates for the two groups were 97.5% and 98.1%, respectively. The multiple decrement life table analysis showed that there was a significant difference in the gross cumulative failure rates between the two groups. The 60th month gross cumulative failure rates for PAP group and PM group were 4.61% and 11.87%, respectively, thus indicating the efficacy of PAP to be significantly higher than that of PM. 97.7% users had cervical smear examinations, but no suspected cancer cells or cancer cells were found. Meanwhile, there was no known diseases related to the chemical reagent. This follow up study indicates that tubal sterilization by chemical instillation is a simple,safe and efficient female method. It suggested that this method would be introduced to a wider use on the basis of modification in the composition of chemical agents, standardized operational procedure, and improved administrative regulation in the use of this technology.

Effect of Ketamine Instillation on Acute and Chronic Post Mastectomy Pain, a Dose Finding Clinical Study

Background: Uncontrolled acute postoperative pain is considered a risk factor for the development of chronic pain afterward. Objectives: To explore the most effective dose of ketamine instillation (1 of 3 doses: 1, 2, or 3 mg/kg) for acute and chronic post mastectomy pain (PMP). Methods: Ninety female patients with cancer breast, aged (18 - 60 yrs), weighted (50 - 90 kg), scheduled for modified radical mastectomy, randomly allocated into 3 groups to receive ketamine instillation after surgical homeostasis before wound closure (1 of 3 doses;1, 2, or 3 mg/kg as A, B or C groups respectively) patients were followed up for 48 h for acute pain (total morphine consumption, the first request of analgesia and visual analog scale at rest and movement (VASR/M), chronic pain by Leeds assessment of neuropathic signs and symptoms (LANSS) for six-months, hemodynamics, and side effects. Results: Median total dose of morphine consumption was 8 mg (5 - 10) versus 6 mg (6 - 7) in A and B groups respectively in the first 48 h postoperatively. Lowest VASR/M was recorded in C then B and lastly A group (P = 0.037). No patients in the C group requested analgesia versus thirty (100%) and nine (30%) patients in the A and B groups respectively with the first request of analgesia was 12 h (5 - 36) in the A group versus 30 h (12 - 36) in the B group respectively (P Conclusion: Ketamine instillation effectively controlled acute post mastectomy pain (PMP) in a dose-dependent manner and reduced the incidence and severity of chronic pain in patients who undergoing a modified radical mastectomy.

Technical Evaluation of Eye Drops Instillation： A Systematic Review

Objective： Assess the profile of eye drops in patients with eye diseases. Methods： Studies available in the scientific literature were identified without any time limits using the databases Embase-Medline, Scielo, Scopus and Web of Knowledge. The selected studies were compared with the following inclusion criteria： （i） if the study evaluated the eye drop instillation, （ii） if the study involved participation of patients with eye diseases. Results： Twelve studies met the inclusion criteria. Of them, 83.33% evaluated the technique of eye drop instillation in patients with glaucoma, 8.33% in patients with eye diseases and 8.33% in patients with cataract after undergoing surgery to correct. 41.66% of studies have chosen to record a video of patients to analyze the technique of instilling eye drops and 41.66% did not describe the/esearch location. Regarding the type of study, 75% had the design as prospective cross-sectional, 8.33% prospective open label study, 8.33% intervention study and 8.33% study called masked trial. Although studies evaluate the technique of eye drop instillation, only 8.33% describe in the article the reference in the literature used to evaluate patients. 50% of articles acknowledged some sort of bias or limitation. Conclusion： The limitations inherent in these types of studies should guide future research.

The clinical use of interventional chemotherapy and intravesical instillation for preventing recurrence of superficial bladder cancer

Objective To study the therapeutic efficacy of combined interventional chemotherapy and intravesical instillation of mitomycin on preventing bladder cancers from recurring after local ablation. Methods 28 patients with superficial bladder cancers were randomized into combined interventional chemotherapy and intravesical instillation of mitomycin or intravesical instillation of mitomycin alone for preventing recurrence after local ablation. The result was assessed by x2 test. Results The patients have been followed up for 12-26 months (mean 21 months). 1 case has had tumor recurrence in the combined modality therapy group and 4 in the intravesical instillation alone group, the tumor recurrence rate being 7% (1/14) and 29% (4/14) respectively (P【0.05). Conclusion Combined use of interventional chemotherapy and intravesical instillation of mitomycin is effective in preventing superficial bladder cancer from recurring after local ablation with fewer adverse effects. The ragimen is not only reliable but

Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis

Ivermectin is a US Food and Drug Administration(FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties.Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries,its potential therapeutic effect on pulmonary fibrosis(PF)has not been investigated.This study aimed to explore the ability of ivermectin(0.6 mg/kg)to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model.This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF.The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury,as manifested by the reduced infiltration of inflammatory cells,as well as decreased the inflammation and fibrosis scores.Intriguingly,ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-β1(TGF-β1)and fibronectin protein expression,highlighting its anti-fibrotic activity.This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome,as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),with a subsequent decline in the interleukin-1β(IL-1β)level.In addition,ivermectin inhibited the expression of intracellular nuclear factor-κB(NF-κB)and hypoxia‑inducible factor‑1α(HIF-1α)proteins along with lowering the oxidative stress and apoptotic markers.Altogether,this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin.These beneficial effects were mediated,at least partly,via the downregulation of TGF-β1 and fibronectin,as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1αand NF-κB.

Pilot study of intravesical instillation of two new generation anthracycline antibiotics in prevention of superficial bladder cancer recurrence

Background Superficial bladder cancer accounts for 60%-70% of all bladder cancer cases in China, when treatment consists of only transurethral resection of the bladder tumor （TUR-BT）, recurrence and progresses in the bladder are observed in some patients. There are numerous reports of trials of intravesical instillation of anticancer agents with the objective of lowering this recurrence rate. The aim of this study was to compare the prophylactic efficacy and safety of epirubicin （EPI）, pirarubicin （THP） and hydroxycamptothecin （HCPT） in superficial bladder cancer.Methods This study enrolled a total of 189 patients who had been diagnosed with superficial bladder cancer during the period from 2004 through 2007 at Beijing Friendship Hospital. All patients were randomly allocated to one of three treatment groups. Patients in group A received 29 doses of EPI 30 mg/30 ml, patients in group B received 29 doses of THP 30 mg/30 ml, and patients in group C received 29 doses of HCPT 30 mg/30 ml, over a period of 24 months.Results The recurrence-free rate in the 2 anthracycline treatment groups （A and B） were significantly better than that of the HCPT treatment group. In the safety evaluation, the incidences of pollakiuria, pain on urination, dysuria, hematuria,and contracted bladder were not significantly different between groups A and B, but some were significantly higher in groups A and B than that in group C.Conclusion The efficacy of EPI and THP was significantly better than HCPT in the prevention of bladder cancer recurrence.

Efficacy of immediate instillation combined with regular instillations of pirarubicin for Ta and T1 transitional cell bladder cancer after transurethral resection： a prospective, randomized, multicenter study

Background Immediate intravesical instillation of chemotherapeutic agents after transurethral resection （TUR） of non- muscle invasive transitional cell bladder cancer has recently been suggested and has been proven to decrease the tumor recurrence rate significantly. This study is to evaluate the efficacy and safety of immediate intravesical instillation combined with regular instillations of Pirarubicin （THP~） as prophylaxis compared to regular instillations only after TUR operation. Methods This was a prospective, randomized, multi-center, clinical study. Patients diagnosed with non-muscle invasive bladder cancer （Ta and T1） pathologically and suitable for TUR were enrolled randomly into two groups. In the study group, the patients received intravesical instillation within 24-hour post TURBT, followed by regular intravesical therapy using 30 mg/50 ml of THP~ once a week for 8 weeks, and then once a month to 1 year postoperatively Among the patients. In the control group, patients received regular instillation only. Results A total of 403 patients were enrolled into this study from 26 institutions in China. Among the potients, 210 were enrolled into the study group and 193 were enrolled into the control group. At the median follow-up of 18 months, the recurrence rate was 7.8% in the study group, significantly lower than that in the control group （14.3%; P=0.042）. Subgroup analysis showed that the recurrence rate in low and intermediate-risk patients was significantly lower in the study group （6.8%） than in the control group （14.0%; P=0.047）, although no significant differences were found in high-risk patients. Conclusion One immediate dose of THP 30 mg after TURBT followed by regular intravesical therapy appears well tolerated and more effective than regular intravesical therapy for preventing tumor recurrence, especially in low and intermediate-risk patients.

Transrectal ultrasonography-guided transperineal bilateral seminal vesicle puncture and continuous irrigation for the treatment of intractable hematospermia

Hematospermia is a rare condition, but often causes frustration. The reason for this frustration is that theexact incidence of hematospermia remains unknown and its cause is difficult to determine.^1 Many reports in the past decades have focused on the etiology of hematospermia.^2 Hematospermia is treated initially by administration of antibiotics, coagulants, and sex steroid hormones. However, some cases may prove resistant to this therapy and the condition may continue. For some intractable and agnogenic cases, the therapeutic strategy mentioned above is not very effective. Recently, we treated 63 such nonresponsive patients by direct continuous antibiotic irrigation into the bilateral seminal vesicles through puncture under transrectal ultrasonography （TRUS） guidance.

Impact of surgery and epirubicin intravesical chemotherapy on peripheral blood dendritic cell subsets in patients with superficial urothelial carcinoma of the bladder

Background Superficial urothelial carcinoma （SUC） of the bladder is a common urinary tract tumor in China. There is a high recurrence rate of this tumor even after surgery and intravesical instillation. Previous reports have described a suppression of the immune system in cancer patients. Dendritic cells （DCs） play a pivotal role in the induction of an effective antitumor immune response. The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy （IC） on peripheral blood DCs in subsets of patients with bladder SUC. Methods A total of 66 SUC patients and 38 healthy controls were enrolled in this study. All the patients had undergone transurethral resection （TUR） of their cancer and adjunctive IC after tumor removal. The patients were divided into a non-recurrence group （n=40） and a recurrence group （n=26） based on the presence or absence of tumor recurrence. Blood samples were taken preoperatively （PreOP）, on postoperative days （POD） 1 and 7, and at postoperative month （POM） 3. Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets. Results The preoperative percentages of myeloid dendritic cells （mDCs） and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls （P 〈0.05）. The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7, remaining higher than the preoperative values in POM 3 （P 〈0.05）. The percentages of mDCs, and CD80 and CD86 in the non-recurrence group on PreOP, POD 7, and POM 3 were higher than those in recurrence group. Conclusions Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function. Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.

Folic Acid Modified Polymeric Micelles for Intravesical Instilled Chemotherapy

In this study, a targeting micellar drug delivery system was developed for intravesical instilled chemotherapy of bladder cancer. The amphiphilic diblock copolymer poly（？-caprolactone）-block-poly（ethylene glycol）（PCL-b-PEO） with functional amino group（NH2） at the end of PEO block was synthesized. Then the copolymer was conjugated with folic acid（FA） and fluorescein isothiocyannate（FITC） via the PEO-NH2 terminus, and then assembled into micelles with the target moiety and fluorescence labeling. In addition, drug loaded micelles were also fabricated with anticancer drug doxorubicin（DOX） encapsulated in the hydrophobic core. The micelles were characterized in terms of size, drug loaded efficiency and critical micellization concentration（CMC） by means of DLS, UV and fluorescence spectra. In vitro cellular uptake and cytotoxicity studies showed that FA modified PCL-b-PEO-FA micelles have a greater targeting efficiency to human bladder cancer cell（T-24 cell） compared to PCL-b-PEO-NH2 micelles due to the conjugation of FA on the surface, while no targeting effect to normal tissue originated human embryonic kidney 293（HEK-293） cells was observed, enabling the micelles a promising drug carrier for intravesical instilled chemotherapy of bladder cancer.

Reduced dose of Bacillus Calmette-Guérin versus full dose of Bacillus Calmette-Guérin for non-muscle-invasive bladder cancer after transurethral resection bladder tumor： a meta-analysis of randomized controlled trials

Background Bladder cancer is widely known as the most common malignant tumor in the urinary tract,with 75％-85％ of patients suffering from nonmuscle invasive bladder cancer （NMIBC）.However,the optimal dose of Bacillus Calmette-Guérin （BCG） remains controversial.The aim of this study was to compare the therapeutic efficacy of full dose （FD） with the reduced dose （RD） of BCG.Methods Randomized controlled trials （RCTs） were selected through the Cochrane Library,PubMed and Embase and were supplemented by hand searching of bibliographies.The end points include overall survival rate,recurrence rate,progression rate and side effects.Results Five RCTs that included a total of 1 473 patients （727 in the reduced dose group vs 746 in the full dose group）,with a median follow-up period from 33.5 month to 7.1 year.Disease in 80 of 687 （11.6％） patients assigned to the RD group progress to the muscular layer or distant metastasis,compared with 81 of 698 （11.6％） patients assigned to the FD group （RR=1.02; 95％ CI,0.77-1.36; P=0.89）.The incidence of recurrence at three year was reported in all five studies to be 41.1％ （299 of 727） and 36.1％ （269 of 746） in the RD and FD groups,respectively （RR=1.13; 95％ CI,1.00-1.29; P=0.05）.The 5-year survival rate was 75.9％ （502 of 662） in the RD group,and 75.8％ （510 of 673） in the FD group.In the RD group 41 of 655 （6.3％） patients and 56 of 663 （8.7％） patients in the FD group did not complete the treatment due to systemic or local side effects （RR=0.75; 95％ CI,0.51-1.10; P=0.14） Conclusions In general,the results of our study demonstrate a trend towards a reduction of the toxicity in reduced dose group without affecting the efficacy of treatment when compared with full dose.More trials with large sample size are still necessary to explore the prognosis of the patients with high risk of tumor in different dose group.