Objective:Bacillus Calmette-Gue´rin(BCG)instillation is the standard adjuvant treatment for intermediate-and high-risk non-muscle-invasive bladder cancer after transurethral resection.Nevertheless,its toxicity of...Objective:Bacillus Calmette-Gue´rin(BCG)instillation is the standard adjuvant treatment for intermediate-and high-risk non-muscle-invasive bladder cancer after transurethral resection.Nevertheless,its toxicity often causes bladder complications.On follow-up cystoscopy,post-BCG bladder lesions can be pathologically benign,urothelial carcinoma recurrence,or other types of bladder malignancy.Only a small number of case reports have been published on post-BCG bladder lesions.Their clinical features,natural course,and management remain unknown.Methods:We retrospectively studied cystoscopic videos and medical records of BCG-treated bladder cancer patients at our center.During a long-term follow-up,we took biopsies on tumor-like lesions and described their changes.In addition,we summarized previous studies on post-BCG bladder lesions by systematic literature searching and review.Results:We described a series of three cases with post-BCG bladder lesions mimicking tumor recurrence from a total of 38 cases with follow-up data for more than 5 years.Those lesions could last,grow,or disappear spontaneously,and remain pathological benign for years.In systematic review,we identified and analyzed a total of 15 cases with post-BCG bladder lesions with detailed clinical information.Eleven of the 15 were benign and have a good prognosis with nephrogenic adenoma being the most common pathological type.Conclusion:Based on previous studies and our experience,benign lesions after BCG instillation cannot distinguish with cancer recurrence by cystoscopy alone,even under narrow band imaging mode.Nonetheless,given most of them have a good prognosis,random biopsy or transurethral resection might be spared in the patients with long-term negative biopsy and urine cytology.展开更多
Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinica...Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.展开更多
COVID-19 has become one of the critical health issues globally,which surfaced first in latter part of the year 2019.It is the topmost concern for many nations’governments as the contagious virus started mushrooming o...COVID-19 has become one of the critical health issues globally,which surfaced first in latter part of the year 2019.It is the topmost concern for many nations’governments as the contagious virus started mushrooming over adjacent regions of infected areas.In 1980,a vaccine called Bacillus Calmette-Guérin(BCG)was introduced for preventing tuberculosis and lung cancer.Countries that have made the BCG vaccine mandatory have witnessed a lesser COVID-19 fatality rate than the countries that have not made it compulsory.This paper’s initial research shows that the countries with a longtermcompulsory BCGvaccination system are less affected by COVID-19 than those without a BCG vaccination system.This paper discusses analytical data patterns for medical applications regarding COVID-19 impact on countries with mandatory BCG status on fatality rates.The paper has tackled numerous analytical challenges to realize the full potential of heterogeneous data.An analogy is drawn to demonstrate how other factors can affect fatality and infection rates other than BCG vaccination only,such as age groups affected,other diseases,and stringency index.The data of Spain,Portugal,and Germany have been taken for a case study of BCG impact analysis.展开更多
Bacillus Calmette-Guerin(BCG) intravesical instillation has been adopted in the treatment of patients with superficial bladder cancer.BCG-induced disseminated infection,though rare,has been associated with the histolo...Bacillus Calmette-Guerin(BCG) intravesical instillation has been adopted in the treatment of patients with superficial bladder cancer.BCG-induced disseminated infection,though rare,has been associated with the histological finding of epithelioid granulomas in different organs,including the liver.We report the case of an adult patient with multi-organ failure,who developed sepsis,acute respiratory failure and acute hepatic failure with encephalopathy whose liver biopsy confirmed the presence of atypical,granulomatous-like lesions.Recovery was observed only after empirical therapy for Mycobacterium bovis with isoniazid,rifampicin,ethambutol and steroids was introduced.This case highlights the importance of a thorough patient assessment in order to exclude other more common causes of hepatic granulomas and to confirm diagnosis.Histological findings may be non-specific when the liver is involved in BCGinduced disseminated infection.展开更多
A novel prophylactic regimen is demanded for preventing bladder cancer recurrence, because of the high side-effect tolls of conventional adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy, in addition to its o...A novel prophylactic regimen is demanded for preventing bladder cancer recurrence, because of the high side-effect tolls of conventional adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy, in addition to its only moderate efficacy. In vitro and animal studies have demonstrated the anti-cancer properties of a medicinal mushroom called Ganoderma lucidum (GL). In this study, a pre-malignant human uroepithelial cells (HUC-PC) model was utilized to compare the effectiveness between ethanol extract of GL (GLe) and BCG on interleukin-6 (IL-6) secretion and lactate dehydrogenase (LDH) cytotoxicity. Additionally, parameters relevant to the BCG efficacy and safety, including free soluble fibronectin (FN) and cell-surface glycosaminoglycans (GAGs) levels were tested, following the exposure of GLe to the cells. GLe at 100 μg/ml and BCG at 4.8 × 107 CFU were shown to induce equivalent levels of IL-6, suggesting the potential synergism, while the tested concentrations of GLe were non-cytotoxic. During the initial four hours of GLe exposure, the free FN concentrations in harvested media were significantly reduced that might facilitate the binding of BCG for uroepithelial internalization to enhance BCG efficacy. Furthermore, the cell membrane-bound GAGs levels of HUC-PC cells were significant increased in response to GLe to suggest cellular protection from BCG infection. In summary, current findings suggest the potential additive synergism of GLe with the BCG efficacy, as well as its protective effects, and thus reducing the BCG toxicity.展开更多
Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery,radiotherapy,and chemotherapy,with some promising results.It aims to kill tumor cells by mobilizing or stimulating cyto...Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery,radiotherapy,and chemotherapy,with some promising results.It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells.However,the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity.Recently,nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens,activating targeted T cells,modulating the immunosuppressive tumor microenvironment,and improving the treatment efficacy.bacillus Calmette-Gué;rin(BCG)is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis,which was first reported to have antitumor activity in 1927.BCG therapy can activate the immune system by inducing various cytokines and chemokines,and its specific immune and inflammatory responses exert antitumor effects.BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer,which effectively improved immune antitumor activity and prevented tumor recurrence.More recently,nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses.In this study,we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.展开更多
Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries.Moreover,metabolic diseases increase the risk of having infectious diseases.The treat...Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries.Moreover,metabolic diseases increase the risk of having infectious diseases.The treatment of metabolic disease may require a long-term strategy of taking multiple medications,which can be costly and have side effects.Attempts to expand the therapeutic use of vaccination to prevent or treat metabolic diseases have attracted significant interest.A growing body of evidence indicates that Bacillus Calmette-Guerin(BCG)offers protection against non-infectious diseases.The non-specific effects of BCG occur likely due to the induction of trained immunity.In this regard,understanding how BCG influences the development of chronic metabolic health including liver diseases would be important.This review focuses on research on BCG,the constellation of disorders associated with metabolic health issues including liver diseases and diabetes as well as how BCG affects the gut microbiome,immunity,and metabolism.展开更多
基金the National Natural Science Foundation of China(No.82172871)the Innovation Cultivation Fund of the Seventh Medical Center of People’s Liberation Army General Hospital(QZX-2023-17)the Youth Innovation Fund of People’s Liberation Army General Hospital(22QNFC095).
文摘Objective:Bacillus Calmette-Gue´rin(BCG)instillation is the standard adjuvant treatment for intermediate-and high-risk non-muscle-invasive bladder cancer after transurethral resection.Nevertheless,its toxicity often causes bladder complications.On follow-up cystoscopy,post-BCG bladder lesions can be pathologically benign,urothelial carcinoma recurrence,or other types of bladder malignancy.Only a small number of case reports have been published on post-BCG bladder lesions.Their clinical features,natural course,and management remain unknown.Methods:We retrospectively studied cystoscopic videos and medical records of BCG-treated bladder cancer patients at our center.During a long-term follow-up,we took biopsies on tumor-like lesions and described their changes.In addition,we summarized previous studies on post-BCG bladder lesions by systematic literature searching and review.Results:We described a series of three cases with post-BCG bladder lesions mimicking tumor recurrence from a total of 38 cases with follow-up data for more than 5 years.Those lesions could last,grow,or disappear spontaneously,and remain pathological benign for years.In systematic review,we identified and analyzed a total of 15 cases with post-BCG bladder lesions with detailed clinical information.Eleven of the 15 were benign and have a good prognosis with nephrogenic adenoma being the most common pathological type.Conclusion:Based on previous studies and our experience,benign lesions after BCG instillation cannot distinguish with cancer recurrence by cystoscopy alone,even under narrow band imaging mode.Nonetheless,given most of them have a good prognosis,random biopsy or transurethral resection might be spared in the patients with long-term negative biopsy and urine cytology.
基金We thank Dr. Neha Sanwalka for the support with the statisticalanalysis and Dr. Meenal Hastak and Dr. Bijal Kulkarnifor their continued support and in discussion of pathologicalaspects of disease.
文摘Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.
文摘COVID-19 has become one of the critical health issues globally,which surfaced first in latter part of the year 2019.It is the topmost concern for many nations’governments as the contagious virus started mushrooming over adjacent regions of infected areas.In 1980,a vaccine called Bacillus Calmette-Guérin(BCG)was introduced for preventing tuberculosis and lung cancer.Countries that have made the BCG vaccine mandatory have witnessed a lesser COVID-19 fatality rate than the countries that have not made it compulsory.This paper’s initial research shows that the countries with a longtermcompulsory BCGvaccination system are less affected by COVID-19 than those without a BCG vaccination system.This paper discusses analytical data patterns for medical applications regarding COVID-19 impact on countries with mandatory BCG status on fatality rates.The paper has tackled numerous analytical challenges to realize the full potential of heterogeneous data.An analogy is drawn to demonstrate how other factors can affect fatality and infection rates other than BCG vaccination only,such as age groups affected,other diseases,and stringency index.The data of Spain,Portugal,and Germany have been taken for a case study of BCG impact analysis.
文摘Bacillus Calmette-Guerin(BCG) intravesical instillation has been adopted in the treatment of patients with superficial bladder cancer.BCG-induced disseminated infection,though rare,has been associated with the histological finding of epithelioid granulomas in different organs,including the liver.We report the case of an adult patient with multi-organ failure,who developed sepsis,acute respiratory failure and acute hepatic failure with encephalopathy whose liver biopsy confirmed the presence of atypical,granulomatous-like lesions.Recovery was observed only after empirical therapy for Mycobacterium bovis with isoniazid,rifampicin,ethambutol and steroids was introduced.This case highlights the importance of a thorough patient assessment in order to exclude other more common causes of hepatic granulomas and to confirm diagnosis.Histological findings may be non-specific when the liver is involved in BCGinduced disseminated infection.
文摘A novel prophylactic regimen is demanded for preventing bladder cancer recurrence, because of the high side-effect tolls of conventional adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy, in addition to its only moderate efficacy. In vitro and animal studies have demonstrated the anti-cancer properties of a medicinal mushroom called Ganoderma lucidum (GL). In this study, a pre-malignant human uroepithelial cells (HUC-PC) model was utilized to compare the effectiveness between ethanol extract of GL (GLe) and BCG on interleukin-6 (IL-6) secretion and lactate dehydrogenase (LDH) cytotoxicity. Additionally, parameters relevant to the BCG efficacy and safety, including free soluble fibronectin (FN) and cell-surface glycosaminoglycans (GAGs) levels were tested, following the exposure of GLe to the cells. GLe at 100 μg/ml and BCG at 4.8 × 107 CFU were shown to induce equivalent levels of IL-6, suggesting the potential synergism, while the tested concentrations of GLe were non-cytotoxic. During the initial four hours of GLe exposure, the free FN concentrations in harvested media were significantly reduced that might facilitate the binding of BCG for uroepithelial internalization to enhance BCG efficacy. Furthermore, the cell membrane-bound GAGs levels of HUC-PC cells were significant increased in response to GLe to suggest cellular protection from BCG infection. In summary, current findings suggest the potential additive synergism of GLe with the BCG efficacy, as well as its protective effects, and thus reducing the BCG toxicity.
基金supported by the Tianjin Natural Science Foundation(Nos.21JCYBJC00220 and 22JCQNJC01640)the Tianjin Health Science and Technology Project(No.ZC20162)the Tianjin Key Medical Discipline(Specialty)Construction Project,and the National Natural Science Foundation of China(No.82202323).
文摘Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery,radiotherapy,and chemotherapy,with some promising results.It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells.However,the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity.Recently,nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens,activating targeted T cells,modulating the immunosuppressive tumor microenvironment,and improving the treatment efficacy.bacillus Calmette-Gué;rin(BCG)is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis,which was first reported to have antitumor activity in 1927.BCG therapy can activate the immune system by inducing various cytokines and chemokines,and its specific immune and inflammatory responses exert antitumor effects.BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer,which effectively improved immune antitumor activity and prevented tumor recurrence.More recently,nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses.In this study,we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.
基金This study is supported by grants funded by the USA National Institutes of Health(R01CA222490).
文摘Metabolic diseases have overtaken infectious diseases as the most serious public health issue and economic burden in most countries.Moreover,metabolic diseases increase the risk of having infectious diseases.The treatment of metabolic disease may require a long-term strategy of taking multiple medications,which can be costly and have side effects.Attempts to expand the therapeutic use of vaccination to prevent or treat metabolic diseases have attracted significant interest.A growing body of evidence indicates that Bacillus Calmette-Guerin(BCG)offers protection against non-infectious diseases.The non-specific effects of BCG occur likely due to the induction of trained immunity.In this regard,understanding how BCG influences the development of chronic metabolic health including liver diseases would be important.This review focuses on research on BCG,the constellation of disorders associated with metabolic health issues including liver diseases and diabetes as well as how BCG affects the gut microbiome,immunity,and metabolism.