Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literatur...Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results.Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs. 46% to 100% vs. 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p=0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p<0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%.Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.展开更多
Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most commo...Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.展开更多
Objective:Placement of human placenta derived grafts during robotic-assisted radical prostatectomy(RARP)hastens the return of continence and potency.The long-term impact on the oncologic outcomes remains to be investi...Objective:Placement of human placenta derived grafts during robotic-assisted radical prostatectomy(RARP)hastens the return of continence and potency.The long-term impact on the oncologic outcomes remains to be investigated.Our objective was to determine the oncologic outcomes of patients with dehydrated human amnion chorion membrane(dHACM)at RARP compared to a matched cohort.Methods:In a referral centre,from August 2013 to October 2019,599 patients used dHACM in bilateral nerve-sparing RARP.We excluded patients with less than 12 months follow-up,simple prostatectomy,and unilateral nerve-sparing.Patients with dHACM(amnio group)were 529,and were propensity score matched 1:1 to 2465 patients without dHACM(non-amnio group)and a minimum follow-up of 36 months.At the time of RARP,dHACM was placed around the neurovascular bundle in the amnio group.Continuous and categorical variables in matched groups was tested by two-sample Kolmogorov-Smirnov test and Fisher's exact test respectively.Outcomes measured were biochemical recurrence(BCR),adjuvant and salvage therapy rates.Results:Propensity score matching resulted in two groups of 444 patients.Cumulative incidence functions for BCR did not show a difference between the groups(p=0.3).Patients in the non-amnio group required salvage therapy more frequently than the amnio group,particularly after partial nerve-sparing RARP(6.3%vs.2.3%,p=0.001).Limitations are the absence of prospective randomization.Conclusion:The data suggest that using dHACM does not have a negative impact on BCR in patients.Outcomes of cancer specific and overall survival will require follow-up study to increase our understanding of these grafts’impact on prostate cancer biology.展开更多
Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o ...Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.展开更多
Prostate cancer is the second most prevalent cancer in men.Robot-assisted radical prostatectomy(RARP)has altered the landscape of prostate cancer treatment.Despite the excellent oncological outcomes associated with RA...Prostate cancer is the second most prevalent cancer in men.Robot-assisted radical prostatectomy(RARP)has altered the landscape of prostate cancer treatment.Despite the excellent oncological outcomes associated with RARP,the rate of erectile dysfunction(ED)remains high.Primary repair of disrupted cavernous nerves with interpositional nerve grafts has been described;however,the outcomes have been inconsistent.We hypothesize that this is attributed to Schwann cell atrophy and axonal regeneration limitations caused by long nerve grafts.We proposed the use of nerve transfer to support axonal regrowth via an inter-positional graft with additional donor axons.A cadaveric study was performed to evaluate the anatomical feasibility of a vastus lateralis nerve(VLN)transfer to the distal recipient cavernous nerve stump.The VLN is long with multiple branching patterns that allow tension-free coaptation of the cavernous nerve.We postulate that a dual innervation method using VLN nerve transfer together with interpositional nerve graft repair of the transacted cavernous nerves may improve the outcomes of ED post-RARP.展开更多
Mountain streams act as conveyors of sediments within the river continuum,where the physical transport of sediments between river reaches through the catchment or between individual parts(e.g.,between hillslopes and c...Mountain streams act as conveyors of sediments within the river continuum,where the physical transport of sediments between river reaches through the catchment or between individual parts(e.g.,between hillslopes and channels)of the catchment is assumed.This study focused on sediment connectivity analysis in the SlavíčRiver catchment in the MoravskoslezskéBeskydy Mts in the eastern part of the Czech Republic.The connectivity index and connectivity index target modelling were combined with an analysis of anthropogenic interventions.Additionally,field mapping,grain size of bed sediments and stream power analysis were used to obtain information about connectivity in the catchment.Based on the analysis and obtained results,terrain topography is the current main driving factor affecting the connectivity of sediment movement in the SlavíčRiver catchment.However,the modelling provided valuable information about high sediment connectivity despite different recent land use conditions(highly forested area of the catchment)than those in historical times from the 16th to 19th centuries when the SlavíčRiver catchment was highly deforested and sediment connectivity was probably higher.The analysis of anthropogenic interventions,field mapping,grain size of bed sediments and stream power analysis revealed more deceleration of sediment movement through the catchment,decreased sediment connectivity with bed erosion,and gradual river channel process transformation in some reaches.Field mapping has identified various natural formations and human-induced changes impacting the longitudinal and lateral connectivity in the SlavíčRiver.For instance,embankments along 48%of the river's length,both on the right and left banks,significantly hinder lateral sediment supply to the channel.Stream power index analysis indicates increased energy levels in the flowing water in the river's upper reaches(up to 404.8 W m^(-2)).This high energy is also observed in certain downstream sections(up to 337.6 W m^(-2)),where it is influenced by human activities.These conditions lead to intensified erosion processes,playing a crucial role in sediment connectivity.Similar observations were described in recent studies that pointed out the long-term human interventions on many streams draining European mountains,where a decrease in sediment connectivity in these streams is linked with sediment deficits and the transformation of processes forming channels.展开更多
文摘Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results.Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs. 46% to 100% vs. 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p=0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p<0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%.Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.
文摘Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.
文摘Objective:Placement of human placenta derived grafts during robotic-assisted radical prostatectomy(RARP)hastens the return of continence and potency.The long-term impact on the oncologic outcomes remains to be investigated.Our objective was to determine the oncologic outcomes of patients with dehydrated human amnion chorion membrane(dHACM)at RARP compared to a matched cohort.Methods:In a referral centre,from August 2013 to October 2019,599 patients used dHACM in bilateral nerve-sparing RARP.We excluded patients with less than 12 months follow-up,simple prostatectomy,and unilateral nerve-sparing.Patients with dHACM(amnio group)were 529,and were propensity score matched 1:1 to 2465 patients without dHACM(non-amnio group)and a minimum follow-up of 36 months.At the time of RARP,dHACM was placed around the neurovascular bundle in the amnio group.Continuous and categorical variables in matched groups was tested by two-sample Kolmogorov-Smirnov test and Fisher's exact test respectively.Outcomes measured were biochemical recurrence(BCR),adjuvant and salvage therapy rates.Results:Propensity score matching resulted in two groups of 444 patients.Cumulative incidence functions for BCR did not show a difference between the groups(p=0.3).Patients in the non-amnio group required salvage therapy more frequently than the amnio group,particularly after partial nerve-sparing RARP(6.3%vs.2.3%,p=0.001).Limitations are the absence of prospective randomization.Conclusion:The data suggest that using dHACM does not have a negative impact on BCR in patients.Outcomes of cancer specific and overall survival will require follow-up study to increase our understanding of these grafts’impact on prostate cancer biology.
文摘Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.
基金The funding for this project was provided by SingHealth Duke-NUS Musculoskeletal Sciences Academic Clinical Program Pitch for Fund Research Support Grant 2019.
文摘Prostate cancer is the second most prevalent cancer in men.Robot-assisted radical prostatectomy(RARP)has altered the landscape of prostate cancer treatment.Despite the excellent oncological outcomes associated with RARP,the rate of erectile dysfunction(ED)remains high.Primary repair of disrupted cavernous nerves with interpositional nerve grafts has been described;however,the outcomes have been inconsistent.We hypothesize that this is attributed to Schwann cell atrophy and axonal regeneration limitations caused by long nerve grafts.We proposed the use of nerve transfer to support axonal regrowth via an inter-positional graft with additional donor axons.A cadaveric study was performed to evaluate the anatomical feasibility of a vastus lateralis nerve(VLN)transfer to the distal recipient cavernous nerve stump.The VLN is long with multiple branching patterns that allow tension-free coaptation of the cavernous nerve.We postulate that a dual innervation method using VLN nerve transfer together with interpositional nerve graft repair of the transacted cavernous nerves may improve the outcomes of ED post-RARP.
基金supported by an internal grant of the University of Ostrava[SGS10/PřF/2021-Specificity of fluvial landscape in the context of historical and future changes].
文摘Mountain streams act as conveyors of sediments within the river continuum,where the physical transport of sediments between river reaches through the catchment or between individual parts(e.g.,between hillslopes and channels)of the catchment is assumed.This study focused on sediment connectivity analysis in the SlavíčRiver catchment in the MoravskoslezskéBeskydy Mts in the eastern part of the Czech Republic.The connectivity index and connectivity index target modelling were combined with an analysis of anthropogenic interventions.Additionally,field mapping,grain size of bed sediments and stream power analysis were used to obtain information about connectivity in the catchment.Based on the analysis and obtained results,terrain topography is the current main driving factor affecting the connectivity of sediment movement in the SlavíčRiver catchment.However,the modelling provided valuable information about high sediment connectivity despite different recent land use conditions(highly forested area of the catchment)than those in historical times from the 16th to 19th centuries when the SlavíčRiver catchment was highly deforested and sediment connectivity was probably higher.The analysis of anthropogenic interventions,field mapping,grain size of bed sediments and stream power analysis revealed more deceleration of sediment movement through the catchment,decreased sediment connectivity with bed erosion,and gradual river channel process transformation in some reaches.Field mapping has identified various natural formations and human-induced changes impacting the longitudinal and lateral connectivity in the SlavíčRiver.For instance,embankments along 48%of the river's length,both on the right and left banks,significantly hinder lateral sediment supply to the channel.Stream power index analysis indicates increased energy levels in the flowing water in the river's upper reaches(up to 404.8 W m^(-2)).This high energy is also observed in certain downstream sections(up to 337.6 W m^(-2)),where it is influenced by human activities.These conditions lead to intensified erosion processes,playing a crucial role in sediment connectivity.Similar observations were described in recent studies that pointed out the long-term human interventions on many streams draining European mountains,where a decrease in sediment connectivity in these streams is linked with sediment deficits and the transformation of processes forming channels.