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1.
Immunity ; 52(3): 487-498.e6, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32155411

RESUMO

Vγ9Vδ2 T cells respond in a TCR-dependent fashion to both microbial and host-derived pyrophosphate compounds (phosphoantigens, or P-Ag). Butyrophilin-3A1 (BTN3A1), a protein structurally related to the B7 family of costimulatory molecules, is necessary but insufficient for this process. We performed radiation hybrid screens to uncover direct TCR ligands and cofactors that potentiate BTN3A1's P-Ag sensing function. These experiments identified butyrophilin-2A1 (BTN2A1) as essential to Vγ9Vδ2 T cell recognition. BTN2A1 synergised with BTN3A1 in sensitizing P-Ag-exposed cells for Vγ9Vδ2 TCR-mediated responses. Surface plasmon resonance experiments established Vγ9Vδ2 TCRs used germline-encoded Vγ9 regions to directly bind the BTN2A1 CFG-IgV domain surface. Notably, somatically recombined CDR3 loops implicated in P-Ag recognition were uninvolved. Immunoprecipitations demonstrated close cell-surface BTN2A1-BTN3A1 association independent of P-Ag stimulation. Thus, BTN2A1 is a BTN3A1-linked co-factor critical to Vγ9Vδ2 TCR recognition. Furthermore, these results suggest a composite-ligand model of P-Ag sensing wherein the Vγ9Vδ2 TCR directly interacts with both BTN2A1 and an additional ligand recognized in a CDR3-dependent manner.


Assuntos
Antígenos/imunologia , Butirofilinas/imunologia , Células Germinativas/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Animais , Antígenos/metabolismo , Antígenos CD/química , Antígenos CD/imunologia , Antígenos CD/metabolismo , Butirofilinas/química , Butirofilinas/metabolismo , Células CHO , Cricetinae , Cricetulus , Células Germinativas/metabolismo , Células HEK293 , Humanos , Fosforilação , Ligação Proteica , Multimerização Proteica , Receptores de Antígenos de Linfócitos T gama-delta/química , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-38915276

RESUMO

FATP4 was thought to mediate intestinal lipid absorption which was disputed by a study using keratinocyte-Fatp4-rescued Fatp4-/- mice. These knockouts when fed with a western diet showed elevated intestinal triglyceride (TG) and fatty-acid levels. To investigate a possible role of FATP4 on intestinal lipid processing, ent-Fatp4 (KO) mice were generated by Villin-Cre-specific inactivation of the Fatp4 gene. We aimed to measure circulating and intestinal lipids in control and KO mice after acute or chronic fat intake or during ageing. Remarkably, ent-Fatp4 mice displayed a ~30% decrease in ileal behenic, lignoceric, and nervonic acids, ceramides containing these FA, as well as, ileal sphingomyelin, phosphatidylcholine, and phosphatidylinositol levels. Such decreases were concomitant with an increase in jejunal cholesterol ester. After 2-week recovery from high lipid overload by tyloxapol and oral-lipid treatment, ent-Fatp4 mice showed an increase in plasma TG and chylomicrons. Upon overnight fasting followed by an oral fat meal, ent-Fatp4 mice showed an increase in plasma TG-rich lipoproteins and particle number of chylomicrons and very low-density lipoproteins. During ageing or after feeding with a high-fat high-cholesterol (HFHC) diet, ent-Fatp4 mice showed an increase in plasma TG, fatty acids, glycerol, and lipoproteins as well as intestinal lipids. HFHC-fed KO mice displayed an increase in body weights, the numbers of lipid droplets with larger sizes in the ileum concomitant with a decrease in ileal ceramides and phosphatidylcholine. Thus, enterocyte FATP4 deficiency led to a metabolic shift from polar to neutral lipids in distal intestine rendering an increase in plasma lipids and lipoproteins.

3.
World J Urol ; 42(1): 35, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217727

RESUMO

PURPOSE: Past decade has seen a renewed interest in minimally invasive surgical techniques (MISTs) for management of enlarged prostate. This narrative review aims to explore newer MIST for benign prostatic hyperplasia (BPH) which are not yet integrated into established societal guidelines. METHODS: We conducted a literature search across PubMed, Google Scholar, and FDA ClinicalTrials.gov databases on June 1st, 2023, to identify studies published within the past decade exploring various MISTs for BPH. Additionally, we gathered insights from abstracts presented in meetings of professional associations and corporate websites. We broadly classified these procedures into three distinct categories: energy-based, balloon dilation, and implant/stent treatments. We collected detail information about the device, procedure details, its inclusion and exclusion criteria, and outcome. RESULTS: Our review reveals that newer energy-based MISTs include Transperineal Laser Ablation, Transurethral Ultrasound Ablation, and High-Intensity Focused Ultrasound. In the sphere of balloon dilation, Transurethral Columnar Balloon Dilation and the Optilume BPH Catheter System were gaining momentum. The noteworthy implants/stents that are on horizon include Butterfly Prostatic Retraction Device, Urocross Expander System, Zenflow Spring System, and ProVee Urethral Expander System. CONCLUSION: The exploration of various MISTs reflects ongoing efforts to enhance patient care and address limitations of existing treatments. This review provides a bird-eye view and valuable insights for urologists and researchers seeking to navigate the dynamic landscape of MISTs in the quest for effective and minimally invasive solutions for enlarged prostates.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Hiperplasia Prostática/cirurgia , Próstata/cirurgia , Ressecção Transuretral da Próstata/métodos , Prostatectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Stents
4.
World J Urol ; 42(1): 299, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710824

RESUMO

PURPOSE: The primary aim of the study was to evaluate if en-bloc vs. non en-bloc made a difference to intra-, peri- and post-operative surgical outcomes of anatomical endoscopic enucleation (AEEP) in large (> 80 cc) and very large prostates (> 200 cc). The secondary aim was to determine the influence of energy and instruments used. METHODS: Data of patients with > 80 cc prostate who underwent surgery between 2019 and 2022 were obtained from 16 surgeons across 13 centres in 9 countries. Propensity score matching (PSM) was used to reduce confounding. Logistic regression was performed to evaluate factors associated with postoperative urinary incontinence (UI). RESULTS: 2512 patients were included with 991 patients undergoing en-bloc and 1521 patients undergoing non-en-bloc. PSM resulted in 481 patients in both groups. Total operation time was longer in the en-bloc group (p < 0.001), enucleation time was longer in the non en-bloc group (p < 0.001) but morcellation times were similar (p = 0.054). Overall, 30 day complication rate was higher in the non en-bloc group (16.4% vs. 11.4%; p = 0.032). Rate of late complications (> 30 days) was similar (2.3% vs. 2.5%; p > 0.99). There were no differences in rates of UI between the two groups. Multivariate analysis revealed that age, Qmax, pre-operative, post-void residual urine (PVRU) and total operative time were predictors of UI. CONCLUSIONS: In experienced hands, AEEP in large prostates by the en-bloc technique yields a lower rate of complication and a slightly shorter operative time compared to the non en-bloc approach. However, it does not have an effect on rates of post-operative UI.


Assuntos
Complicações Pós-Operatórias , Pontuação de Propensão , Prostatectomia , Hiperplasia Prostática , Humanos , Masculino , Idoso , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Pessoa de Meia-Idade , Resultado do Tratamento , Tamanho do Órgão , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Próstata/cirurgia , Próstata/patologia , Incontinência Urinária/epidemiologia
5.
World J Urol ; 42(1): 180, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507108

RESUMO

PURPOSE: To evaluate complications and urinary incontinence (UI) after endoscopic enucleation of the prostate (EEP) stratified by prostate volume (PV). METHODS: We retrospectively reviewed patients with benign prostatic hyperplasia who underwent EEP with different energy sources in 14 centers (January 2019-January 2023). INCLUSION CRITERIA: prostate volume ≥ 80 ml. EXCLUSION CRITERIA: prostate cancer, previous prostate/urethral surgery, pelvic radiotherapy. PRIMARY OUTCOME: complication rate. SECONDARY OUTCOMES: incidence of and factors affecting postoperative UI. Patients were divided into 3 groups. Group 1: PV = 80-100 ml; Group 2 PV = 101-200 ml; Group 3 PV > 200 ml. Multivariable logistic regression analysis was performed to evaluate independent predictors of overall incontinence. RESULTS: There were 486 patients in Group 1, 1830 in Group 2, and 196 in Group 3. The most commonly used energy was high-power Holmium laser followed by Thulium fiber laser in all groups. Enucleation, morcellation, and total surgical time were significantly longer in Group 2. There was no significant difference in overall 30-day complications and readmission rates. Incontinence incidence was similar (12.1% in Group 1 vs. 13.2% in Group 2 vs. 11.7% in Group 3, p = 0.72). The rate of stress and mixed incontinence was higher in Group 1. Multivariable regression analysis showed that age (OR 1.019 95% CI 1.003-1.035) was the only factor significantly associated with higher odds of incontinence. CONCLUSIONS: PV has no influence on complication and UI rates following EEP. Age is risk factor of postoperative UI.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Incontinência Urinária , Masculino , Humanos , Próstata/cirurgia , Estudos Retrospectivos , Incidência , Terapia a Laser/métodos , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Incontinência Urinária/cirurgia , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/complicações , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Lasers de Estado Sólido/efeitos adversos , Resultado do Tratamento
6.
World J Urol ; 42(1): 79, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353743

RESUMO

PURPOSE: To identify laser settings and limits applied by experts during laser vaporization (vapBT) and laser en-bloc resection of bladder tumors (ERBT) and to identify preventive measures to reduce complications. METHODS: After a focused literature search to identify relevant questions, we conducted a survey (57 questions) which was sent to laser experts. The expert selection was based on clinical experience and scientific contribution. Participants were asked for used laser types, typical laser settings during specific scenarios, and preventive measures applied during surgery. Settings for a maximum of 2 different lasers for each scenario were possible. Responses and settings were compared among the reported laser types. RESULTS: Twenty-three of 29 (79.3%) invited experts completed the survey. Thulium fiber laser (TFL) is the most common laser (57%), followed by Holmium:Yttrium-Aluminium-Garnet (Ho:YAG) (48%), continuous wave (cw) Thulium:Yttrium-Aluminium-Garnet (Tm:YAG) (26%), and pulsed Tm:YAG (13%). Experts prefer ERBT (91.3%) to vapBT (8.7%); however, relevant limitations such as tumor size, number, and anatomical tumor location exist. Laser settings were generally comparable; however, we could find significant differences between the laser sources for lateral wall ERBT (p = 0.028) and standard ERBT (p = 0.033), with cwTm:YAG and pulsed Tm:YAG being operated in higher power modes when compared to TFL and Ho:YAG. Experts prefer long pulse modes for Ho:YAG and short pulse modes for TFL lasers. CONCLUSION: TFL seems to have replaced Ho:YAG and Tm:YAG. Most laser settings do not differ significantly among laser sources. For experts, continuous flow irrigation is the most commonly applied measure to reduce complications.


Assuntos
Alumínio , Túlio , Neoplasias da Bexiga Urinária , Ítrio , Humanos , Túlio/uso terapêutico , Neoplasias da Bexiga Urinária/cirurgia , Lasers , Tecnologia
7.
World J Urol ; 42(1): 33, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217743

RESUMO

PURPOSE: To identify laser lithotripsy settings used by experts for specific clinical scenarios and to identify preventive measures to reduce complications. METHODS: After literature research to identify relevant questions, a survey was conducted and sent to laser experts. Participants were asked for preferred laser settings during specific clinical lithotripsy scenarios. Different settings were compared for the reported laser types, and common settings and preventive measures were identified. RESULTS: Twenty-six laser experts fully returned the survey. Holmium-yttrium-aluminum-garnet (Ho:YAG) was the primary laser used (88%), followed by thulium fiber laser (TFL) (42%) and pulsed thulium-yttrium-aluminum-garnet (Tm:YAG) (23%). For most scenarios, we could not identify relevant differences among laser settings. However, the laser power was significantly different for middle-ureteral (p = 0.027), pelvic (p = 0.047), and lower pole stone (p = 0.018) lithotripsy. Fragmentation or a combined fragmentation with dusting was more common for Ho:YAG and pulsed Tm:YAG lasers, whereas dusting or a combination of dusting and fragmentation was more common for TFL lasers. Experts prefer long pulse modes for Ho:YAG lasers to short pulse modes for TFL lasers. Thermal injury due to temperature development during lithotripsy is seriously considered by experts, with preventive measures applied routinely. CONCLUSIONS: Laser settings do not vary significantly between commonly used lasers for lithotripsy. Lithotripsy techniques and settings mainly depend on the generated laser pulse's and generator settings' physical characteristics. Preventive measures such as maximum power limits, intermittent laser activation, and ureteral access sheaths are commonly used by experts to decrease thermal injury-caused complications.


Assuntos
Alumínio , Lasers de Estado Sólido , Litotripsia a Laser , Urolitíase , Ítrio , Humanos , Túlio , Urolitíase/cirurgia , Litotripsia a Laser/métodos , Lasers de Estado Sólido/uso terapêutico , Tecnologia , Hólmio
8.
Curr Opin Urol ; 34(4): 286-293, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38595170

RESUMO

PURPOSE OF REVIEW: Surgical treatment of benign prostatic hyperplasia (BPH) carries a significant risk of ejaculation dysfunction. Preservation of antegrade ejaculation while providing effective, well tolerated, and durable treatment of BPH is a paramount component of physical and sexual well being for significant number of men. We reviewed available literature with an aim of providing status on antegrade ejaculation preserving BPH surgical therapies. RECENT FINDINGS: Minimally invasive surgical therapies for BPH have been developed over the last decade, with significant marketing emphasis on their potential for preservation of antegrade ejaculation. However, the question about durability of relief of bladder outlet obstruction remains. Parallel to this technological development, the understanding of anatomical structures involved in ejaculation have resulted in technical modifications of well established surgical treatments modalities like transurethral resection of prostate, endoscopic enucleation of prostate and simple prostatectomy, thereby providing safe and durable relief of bladder outlet obstruction secondary to BPH with a satisfactory preservation of antegrade ejaculation. SUMMARY: Preservation of antegrade ejaculation is an important goal for significant number of men needing BPH surgery. Novel minimally invasive surgical technologies have been developed for this purpose; but understanding of the anatomical structures essential for antegrade ejaculation have allowed technical modification of existing surgical techniques with excellent preservation of antegrade ejaculation.


Assuntos
Ejaculação , Prostatectomia , Hiperplasia Prostática , Humanos , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/complicações , Masculino , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Tratamentos com Preservação do Órgão/efeitos adversos , Resultado do Tratamento , Micção/fisiologia , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/prevenção & controle , Disfunções Sexuais Fisiológicas/fisiopatologia , Obstrução do Colo da Bexiga Urinária/cirurgia , Obstrução do Colo da Bexiga Urinária/etiologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Ressecção Transuretral da Próstata/métodos , Ressecção Transuretral da Próstata/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos
9.
Neurourol Urodyn ; 43(1): 126-143, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38010924

RESUMO

INTRODUCTION: Men with detrusor underactivity (DUA) and concomitant bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE) may present poorer functional outcomes after surgical desobstruction. This study aimed to evaluate the safety and efficacy of BPE surgery in men with DUA compared with those with normal detrusor contractility (NC). MATERIALS AND METHODS: This review was performed according to the 2020 PRISMA framework. A comprehensive literature search was performed until May 7, 2023, using MEDLINE, EMBASE, and Cochrane Database. No date limits were imposed. Only comparative studies were accepted. The primary endpoint was to assess if there was any difference in short- and long-term functional outcomes after BPE surgery in men with DUA and NC. The secondary endpoint was to evaluate the differences in perioperative outcomes and postoperative complications between the two groups. Meta-analysis was performed using Review Manager (RevMan) software. RESULTS: There were 5 prospective nonrandomized studies and 12 retrospective studies, including 1701 DUA and 1993 NC patients. Regarding surgical procedures, there were eight TURP (transurethral resection of the prostate) studies, four GreenLight PVP (photoselective vaporization of the prostate) studies, two HoLEP (Holmium laser enucleation of the prostate) studies, one GreenLight PVP/HoLEP study, one Holmium laser incision of the prostate study, and one study did not report the type of surgery. We did not find a statistically significant difference between the two groups in terms of perioperative outcomes, including postoperative catheterization time, hospitalization time, urinary retention, need to recatheterization, transfusion rate, or urinary tract infections. Also, we found no significant differences in long-term complications, such as bladder neck stenosis or urethral stenosis. Posttreatment bladder recatheterization and retreatment rate for BPE regrowth could not be evaluated properly, because only one study reported these findings. When we analyzed functional outcomes at 3 months, those with NC had lower International Prostatic Symptom Score (IPSS), lower quality-of-life (QoL) score, better maximum flow rate (Qmax), and lower post-voiding residual (PVR) of urine. These results were maintained at 6 months postoperatively, with exception of PVR that showed no difference. However, at 12 and more than 12 months the functional outcomes became similar regarding IPSS and QoL. There were few data about Qmax and PVR at longer follow-up. CONCLUSION: In this meta-analysis, data suggest that BOO surgical treatment in patients with concomitant BPE and DUA appears to be safe. Despite patients with DUA may present worse functional outcomes in the short postoperative term compared with the NC population, IPSS and QoL scores become comparable again after a longer follow-up period after surgery.


Assuntos
Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Obstrução do Colo da Bexiga Urinária , Bexiga Inativa , Masculino , Humanos , Ressecção Transuretral da Próstata/efeitos adversos , Bexiga Inativa/complicações , Bexiga Inativa/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Estudos Prospectivos , Resultado do Tratamento , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Obstrução do Colo da Bexiga Urinária/etiologia , Obstrução do Colo da Bexiga Urinária/cirurgia , Terapia a Laser/métodos
10.
Immunol Rev ; 298(1): 218-236, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32981055

RESUMO

Both, jawless and jawed vertebrates possess three lymphocyte lineages defined by highly diverse antigen receptors: Two T-cell- and one B-cell-like lineage. In both phylogenetic groups, the theoretically possible number of individual antigen receptor specificities can even outnumber that of lymphocytes of a whole organism. Despite fundamental differences in structure and genetics of these antigen receptors, convergent evolution led to functional similarities between the lineages. Jawed vertebrates possess αß and γδ T-cells defined by eponymous αß and γδ T-cell antigen receptors (TCRs). "Conventional" αß T-cells recognize complexes of Major Histocompatibility Complex (MHC) class I and II molecules and peptides. Non-conventional T-cells, which can be αß or γδ T-cells, recognize a large variety of ligands and differ strongly in phenotype and function between species and within an organism. This review describes similarities and differences of non-conventional T-cells of various species and discusses ligands and functions of their TCRs. A special focus is laid on Vγ9Vδ2 T-cells whose TCRs act as sensors for phosphorylated isoprenoid metabolites, so-called phosphoantigens (PAg), associated with microbial infections or altered host metabolism in cancer or after drug treatment. We discuss the role of butyrophilin (BTN)3A and BTN2A1 in PAg-sensing and how species comparison can help in a better understanding of this human Vγ9Vδ2 T-cell subset.


Assuntos
Receptores de Antígenos de Linfócitos T gama-delta , Subpopulações de Linfócitos T , Animais , Antígenos , Butirofilinas/genética , Humanos , Filogenia
11.
Am J Physiol Gastrointest Liver Physiol ; 324(5): G389-G403, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36881564

RESUMO

Newborns with FATP4 mutations exhibit ichthyosis prematurity syndrome (IPS), and adult patients show skin hyperkeratosis, allergies, and eosinophilia. We have previously shown that the polarization of macrophages is altered by FATP4 deficiency; however, the role of myeloid FATP4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) is not known. We herein phenotyped myeloid-specific Fatp4-deficient (Fatp4M-/-) mice under chow and high-fat, high-cholesterol (HFHC) diet. Bone-marrow-derived macrophages (BMDMs) from Fatp4M-/- mice showed significant reduction in cellular sphingolipids in males and females, and additionally phospholipids in females. BMDMs and Kupffer cells from Fatp4M-/- mice exhibited increased LPS-dependent activation of proinflammatory cytokines and transcription factors PPARγ, CEBPα, and p-FoxO1. Correspondingly, these mutants under chow diet displayed thrombocytopenia, splenomegaly, and elevated liver enzymes. After HFHC feeding, Fatp4M-/- mice showed increased MCP-1 expression in livers and subcutaneous fat. Plasma MCP-1, IL4, and IL13 levels were elevated in male and female mutants, and female mutants additionally showed elevation of IL5 and IL6. After HFHC feeding, male mutants showed an increase in hepatic steatosis and inflammation, whereas female mutants showed a greater severity in hepatic fibrosis associated with immune cell infiltration. Thus, myeloid-FATP4 deficiency led to steatotic and inflammatory NASH in males and females, respectively. Our work offers some implications for patients with FATP4 mutations and also highlights considerations in the design of sex-targeted therapies for NASH treatment.NEW & NOTEWORTHY FATP4 deficiency in BMDMs and Kupffer cells led to increased proinflammatory response. Fatp4M-/- mice displayed thrombocytopenia, splenomegaly, and elevated liver enzymes. In response to HFHC feeding, male mutants were prone to hepatic steatosis, whereas female mutants showed exaggerated fibrosis. Our study provides insights into a sex-dimorphic susceptibility to NASH by myeloid-FATP4 deficiency.


Assuntos
Proteínas de Transporte de Ácido Graxo , Hepatopatia Gordurosa não Alcoólica , Animais , Feminino , Masculino , Camundongos , Colesterol/metabolismo , Dieta Hiperlipídica , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Esplenomegalia/complicações , Esplenomegalia/metabolismo , Esplenomegalia/patologia
12.
Biochem Biophys Res Commun ; 687: 149161, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-37931418

RESUMO

Evidence from mice with global deletion of fatty-acid transport protein4 (FATP4) indicates its role on ß-oxidation and triglycerides (TG) metabolism. We reported that plasma glycerol and free fatty acids (FA) were increased in liver-specific Fatp4 deficient (L-FATP4-/-) mice under dietary stress. We hypothesized that FATP4 may mediate hepatocellular TG lipolysis. Here, we demonstrated that L-FATP4-/- mice showed an increase in these blood lipids, liver TG, and subcutaneous fat weights. We therefore studied TG metabolism in response to oleate treatment in two experimental models using FATP4-knockout HepG2 (HepKO) cells and L-FATP4-/- hepatocytes. Both FATP4-deificient liver cells showed a significant decrease in ß-oxidation products by ∼30-35% concomitant with marked upregulation of CD36, FATP2, and FATP5 as well as lipoprotein microsomal-triglyceride-transfer protein genes. By using 13C3D5-glycerol, HepKO cells displayed an increase in metabolically labelled TG species which were further increased with oleate treatment. This increase was concomitant with a step-wise elevation of TG in cells and supernatants as well as the secretion of cholesterol very low-density and high-density lipoproteins. Upon analyzing TG lipolytic enzymes, both mutant liver cells showed marked upregulated expression of hepatic lipase, while that of hormone-sensitive lipase and adipose-triglyceride lipase was downregulated. Lipolysis measured by extracellular glycerol and free FA was indeed increased in mutant cells, and this event was exacerbated by oleate treatment. Taken together, FATP4 deficiency in liver cells led to a metabolic shift from ß-oxidation towards lipolysis-directed TG and lipoprotein secretion, which is in line with an association of FATP4 polymorphisms with blood lipids.


Assuntos
Lipólise , Ácido Oleico , Camundongos , Animais , Lipólise/fisiologia , Triglicerídeos/metabolismo , Ácido Oleico/metabolismo , Glicerol/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Lipoproteínas/metabolismo
13.
World J Urol ; 41(10): 2577-2582, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37819587

RESUMO

En bloc resection of bladder tumors (ERBT) orginally described in 1980 and adopted by few centers in the late 1990s has regained attention in the 2010s as a renaissance of a technique with high potential. The advent of new lasers indirectly lead to a better understanding of anatomical dissection from the experience in anatomical dissection in endoscopic enucleation of the prostate. 12 years after the reintroduction of ERBT evidence mounts that it is not only equivalent but better in some regards. However, ERBT still falls short with regard to wide adoption despite the striking technique inherent and reproducible features of accurate staging and specimen quality as requested by pathologist, as well and despite the high intraoperative safety and fast adoption of this technique even in early phase of training. The editorial walks the reader through the timeline of the renaissance speculating why there is a blockage between cognitive understanding and dissonance in surgical practice. The special issues presents the meta-analysis of surgical and oncological data on one hand and the level of understanding and power of this surgical technique in fields offsite oncological results in training achieving results almost right from the start after adoptation. Unlike in earlier years reviewing the literature of ERBT in 2023, ERBT seems not only to be a viable alternative, but something one should turn towards no to underperform with regards to the endpoints achievable by ERBT in a critical disease like bladder cancer.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Masculino , Cistectomia , Dissecação , Lasers , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia
14.
World J Urol ; 41(4): 969-980, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36752853

RESUMO

PURPOSE: To investigate and assess outcomes, complications, and functional results amongst different modifications of endoscopic enucleation of the prostate (EEP). METHODS: We conducted a systematic review and meta-analysis according to the PRISMA checklist. We searched the Medline, Cochrane, and Embase databases. We included only randomised-controlled trials (RCT) comparing modifications of EEPs and assessed the risk of bias (RoB). RESULTS: Seven RCTs were included in the study. Overall, 1266 patients were treated with Holmium laser enucleation of the prostate (HoLEP) and 80 patients with thulium laser vapo-enucleation of the prostate (ThuVEP). The operative time during pulse shape-modified HoLEP was shorter when compared to standard pulse HoLEP (MD 18.08 min, 95% CI 8.11-28.05 min, p = 0.0004). The decrease in haemoglobin was significantly lower for two-lobe HoLEP when compared to three-lobe HoLEP (MD 0.16 g/dl, 95% CI 0.22-0.1 g/dl, p < 0.00001). Virtual Basket (VB) HoLEP showed a smaller haemoglobin decrease when compared to standard pulse HoLEP (1.12 ± 1.78 vs. 2.54 ± 1.23 g/dl, p = 0.03). When directly comparing one- vs. two- vs. three-lobe HoLEP, surgical time (p < 0.001) and enucleation efficiency (p = 0.006) were significantly different and favouring one- and two-lobe HoLEP in the study with the largest patient population included. No significant differences for complications were observed; however, Clavien-Dindo IVa events were reported for two patients. CONCLUSION: All variations of EEP improve symptoms and functional parameters with a low incidence of high-grade complications. One- and two-lobe approaches and pulse shape-modified HoLEP seem to be beneficial in terms of operative time and blood loss.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Próstata/cirurgia , Hiperplasia Prostática/terapia , Resultado do Tratamento , Lasers de Estado Sólido/uso terapêutico , Endoscopia/métodos , Ressecção Transuretral da Próstata/efeitos adversos , Terapia a Laser/métodos , Hólmio
15.
World J Urol ; 41(1): 1-12, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36515722

RESUMO

PURPOSE: We looked into the Thulium: yttrium-aluminum-garnet (TM:YAG), Thulium Fibre laser (TFL) and Holmium: yttrium-aluminum-garnet (Ho:YAG) thermal laser tissue effect during lithotripsy and tissue ablation. METHODS: We performed a PubMed, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) search. RESULTS: During lithotripsy, the Ho:YAG generated temperatures from 24 to 68.7 °C at powers < 20 W, the Tm:YAG from 43.7 °C at 30 W to 68 °C at powers < 20 W, and the TFL from 33 to 40.46 °C. During ablation, the Ho:YAG and continuous wave (cw) Tm:YAG tissue incision depths ranged from 0.08 to 2.26 mm, and from 0.28 to 3.22 mm. The Ho:YAG and Tm:YAG vaporization areas ranged from 0.044 to 0.078 mm2 and from 0.050 to 0.078 mm3 and their coagulation zones were 0.075 mm2 and 0.125 mm3 respectively. Ho:YAG and Tm:YAG laser damage zones ranged from 0.093 to 2.6 mm3 and from 0.207 to 0.98 mm3 respectively. The TFL incision depth ranged from 0.04 to 5.7 mm. The cw and SuperPulsed (SP) vaporization volumes ranged from 8 to 28.2 mm3/s and from 4 to 11 mm3/s. TFL coagulation depth and coagulation zone ranged from zero to 1.1 mm, 2.2 to 5.1 mm3 in SP mode and from 7.7 to 18.1 mm3 in cw mode. CONCLUSION: During lithotripsy all lasers caused similar temperature changes and had a safe temperature profile at < 40 W. During tissue ablation, Ho:YAG has a deeper incision depth, while cwTm:YAG and cwTFL have broader coagulation and total laser areas.


Assuntos
Lasers de Estado Sólido , Litotripsia a Laser , Litotripsia , Humanos , Túlio , Hólmio , Lasers de Estado Sólido/uso terapêutico
16.
World J Urol ; 41(10): 2607-2615, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37244879

RESUMO

BACKGROUND: The number of studies suggesting that en bloc resection of bladder tumor (ERBT) is superior to transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer (NMIBC) management is growing. The aim of this review is to discuss the features of these procedures and to determine the prospects of en bloc in NMIBC management. MATERIALS AND METHODS: We conducted a literature search using two databases (Medline and Scopus) and included any research which reported ERBT outcomes. RESULTS: The lasers with minimal tissue penetration depth are becoming the main tool for ERBT. Unfortunately, most of the systematic reviews continue to be characterized by high heterogeneity. However, recent studies indicate that ERBT may have the edge when it comes to the detrusor muscle rate and the quality of the histological specimen. ERBT may favor in terms of in-field relapse, but its rate in the studies varies greatly. As for out-field relapse-free survival, the data are still lacking. The strongest evidence supports that ERBT is superior to TURBT in complications rate (bladder perforation). ERBT is feasible irrespective to tumor size and location. CONCLUSIONS: ERBT has gained in momentum with the increasingly widespread use of this kind of laser surgery. The introduction of novel sources (TFL and Thulium:YAG pulsed laser) will definitely affect how the field develops and will result in further improvements in safety and precision. The latest trials make us more certain in our belief that ERBT will be beneficial in terms of histological specimen quality, relapse rate and complications rate.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Cistectomia , Procedimentos Cirúrgicos Urológicos/métodos , Lasers , Recidiva
17.
World J Urol ; 41(12): 3817-3827, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37906263

RESUMO

PURPOSE: Technological advancements in laser lithotripsy are expanding into numerous fields of urology, like ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), and benign and malignant soft-tissue treatments. Since the amount of research regarding lasers in urology has grown exponentially, we present a systematic review of the most recent and relevant advances encompassing all lasers used in urological endoscopic treatment. METHODS: We performed a literature search using PubMed (May 2023) to obtain information about lasers for urological purposes. We included only recent data from published articles between 2021 and 2023 or articles ahead of print. RESULTS: Lasers are widely used in lithotripsy for ureteric, renal, and bladder stones, benign prostate surgery, and bladder and upper tract tumor ablation. While the holmium (Ho:YAG) laser is still predominant, there seems to be more emphasis on pulse modulation and newer lasers such as thulium fiber laser (TFL) and pulsed Tm:YAG laser. CONCLUSION: The use of lasers and related technological innovations have shown increasing versatility, and over time have proven to be invaluable in the management of stone lithotripsy, treatment of benign and malignant prostate diseases, and urothelial tumors. Laser endoscopic treatment is heavily based on technological nuances, and it is essential to know at least the basics of these technologies. Ultimately the choice of laser used depends on its availability, cost, surgeon experience and expertise.


Assuntos
Lasers de Estado Sólido , Litotripsia a Laser , Litotripsia , Cálculos da Bexiga Urinária , Masculino , Humanos , Bexiga Urinária , Lasers de Estado Sólido/uso terapêutico , Túlio/uso terapêutico , Hólmio
18.
World J Urol ; 41(10): 2617-2625, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35567624

RESUMO

PURPOSE: We aimed to examine how different endoscopic bladder tumor resection techniques affect pathologists' clinical practice patterns. METHODS: An online survey including 28 questions clustered in four main sections was prepared by the ESUT ERBT Working Group and released to the pathologists working in the institutions of experts of the ESUT Board and the working groups and experts in the uropathology working group. A descriptive analysis was performed using the collected data. RESULTS: Sixty-eight pathologists from 23 countries responded to the survey. 37.3% of the participants stated that they always report the T1 sub-staging. Of those who gave sub-staging, 61.3% used T1a, b. 85.2% think that en bloc samples provide spatial orientation faster than piecemeal samples, and 60% think en bloc samples are timesaving during an inspection. 55.7% stated that whether the tissue sample is en bloc or piecemeal is essential. 57.4% think en bloc sample reduces turnaround time and is cost-effective for 44.1%. A large number of pathologists find that the pathology examination of piecemeal samples has a longer learning curve. CONCLUSION: The survey shows that pathologists think that they can diagnose faster, accurately, and cost-effectively with ERBT samples, but they do not often encounter them in practice. Moreover, en bloc samples may be a better choice in pathology resident training. Evidence from real-life observational pathology practice and clinical research can reveal the current situation more clearly and increase awareness on proper treatment in endoscopic management of bladder tumors.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Análise de Custo-Efetividade
19.
World J Urol ; 41(9): 2303-2309, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37421419

RESUMO

PURPOSE: Our objective was to establish a standardized technique for Anatomical Endoscopic Enucleation of Prostate (AEEP) utilizing a consensus statement to provide robust recommendations for urologists who are new to this procedure. METHODS: The participants were electronically sent a questionnaire in three consecutive rounds. In the second and third rounds, the anonymous aggregate results of the previous round were presented. Experts' feedback and comments were then incorporated to refine existing questions or to explore more controversial topics in greater depth. RESULTS: Forty-one urologists participated in the first round. In the second round, all Round 1 participants received a 22-question survey, resulting in a consensus on 21 items. In the third round, 76% (19/25) of the second-round respondents also participated, reaching a consensus on 22 additional items. The panelists consensually agreed on detaching the urethral sphincter at the beginning of the enucleation and not at the end of the enucleation. To prevent incontinence, it was recommended that the apical mucosa be preserved through various approaches between 11 and 1 o'clock while gently disrupting the lateral lobes in their apical part, avoiding an excess energy delivery approximation to the apical mucosa. CONCLUSION: To optimize laser AEEP procedures, urologists must follow expert guidelines on equipment and surgical technique, including early apical release, using the 3-lobe technique for enucleation, preserving apical mucosa with appropriate approaches, gently disrupting lateral lobes at their apical regions, and avoiding excessive energy delivery near the apical mucosa. Following these recommendations can lead to improved outcomes and patient satisfaction.


Assuntos
Lasers de Estado Sólido , Próstata , Masculino , Humanos , Próstata/cirurgia , Técnica Delphi , Endoscopia , Prostatectomia/métodos
20.
World J Urol ; 41(11): 2915-2923, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37515650

RESUMO

PURPOSE: To compare Holmium laser with MOSES technology (MoLEP) and Thulium fiber laser enucleation of the prostate (ThuFLEP) in terms of surgical and functional outcomes. METHODS: We performed a retrospective analysis of all patients who underwent either procedure in five centers (January 2020-January 2022). EXCLUSION CRITERIA: previous urethral/prostatic surgery, radiotherapy, concomitant surgery. Propensity score matching (PSM) analysis was performed to adjust for the bias inherent to the different characteristics at baseline. Differences between procedures were estimated using Firth Penalized Likelihood regression for International prostate symptom score (IPSS), quality of life (QL), maximum flow rate (Qmax). RESULTS: PSM retrieved 118 patients in each group. Baseline characteristics were similar except for PSA and number of men on indwelling catheter (higher in MoLEP group). Median surgical time was significantly longer in the MoLEP group despite the enucleation and morcellation times being similar. Median catheter dwelling time and postoperative length of stay were similar. Most of the early complications were Clavien ≤ 2 grade. There were only two Clavien grade 3 complications (one for each group), one grade 4 in MoLEP group. Rate and type of early and persistent incontinence (> 3 months) were similar. At 12-month, proportion of patients reaching a decrease (Δ) of IPSS ≥ 18 from baseline was significantly larger in MoLEP group, with no significant difference in ΔQmax > 12 ml/sec and ΔQL ≥ -3. CONCLUSION: MoLEP and ThuFLEP were safe and efficacious procedures with similar short-term operative and functional outcomes. At 1-year, MoLEP patients had a sustained reduction of IPPS score.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Masculino , Humanos , Próstata/cirurgia , Lasers de Estado Sólido/uso terapêutico , Túlio/uso terapêutico , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Pontuação de Propensão , Resultado do Tratamento , Terapia a Laser/métodos
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