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1.
Dig Endosc ; 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433315

RESUMO

OBJECTIVES: This consensus was developed by the Asian EUS Group (AEG), who aimed to formulate a set of practice guidelines addressing various aspects of endoscopic ultrasound-guided tissue acquisition (EUS-TA). METHODS: The AEG initiated the development of consensus statements and formed an expert panel comprising surgeons, gastroenterologists, and pathologists. Three online consensus meetings were conducted to consolidate the statements and votes. The statements were presented and discussed in the first two consensus meetings and revised according to comments. Final voting was conducted at a third consensus meeting. The Grading of Recommendations, Assessment, Development, and Evaluation system was adopted to define the strength of the recommendations and quality of evidence. RESULTS: A total of 20 clinical questions and statements regarding EUS-TA were formulated. The committee recommended that fine-needle biopsy (FNB) needles be preferred over conventional fine-needle aspiration (FNA) needles for EUS-TA of subepithelial lesions. For solid pancreatic masses, rapid on-site evaluation is not routinely recommended when FNB needles are used. For dedicated FNB needles, fork-tip and Franseen-tip needles have essentially equivalent performance. CONCLUSION: This consensus provides guidance for EUS-TA, thereby enhancing the quality of EUS-TA.

2.
Proc Natl Acad Sci U S A ; 117(34): 20741-20752, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32788346

RESUMO

Unresolved inflammation can lead to tissue fibrosis and impaired organ function. Macrophage-myofibroblast transition (MMT) is one newly identified mechanism by which ongoing chronic inflammation causes progressive fibrosis in different forms of kidney disease. However, the mechanisms underlying MMT are still largely unknown. Here, we discovered a brain-specific homeobox/POU domain protein Pou4f1 (Brn3a) as a specific regulator of MMT. Interestingly, we found that Pou4f1 is highly expressed by macrophages undergoing MMT in sites of fibrosis in human and experimental kidney disease, identified by coexpression of the myofibroblast marker, α-SMA. Unexpectedly, Pou4f1 expression peaked in the early stage in renal fibrogenesis in vivo and during MMT of bone marrow-derived macrophages (BMDMs) in vitro. Mechanistically, chromatin immunoprecipitation (ChIP) assay identified that Pou4f1 is a Smad3 target and the key downstream regulator of MMT, while microarray analysis defined a Pou4f1-dependent fibrogenic gene network for promoting TGF-ß1/Smad3-driven MMT in BMDMs at the transcriptional level. More importantly, using two mouse models of progressive renal interstitial fibrosis featuring the MMT process, we demonstrated that adoptive transfer of TGF-ß1-stimulated BMDMs restored both MMT and renal fibrosis in macrophage-depleted mice, which was prevented by silencing Pou4f1 in transferred BMDMs. These findings establish a role for Pou4f1 in MMT and renal fibrosis and suggest that Pou4f1 may be a therapeutic target for chronic kidney disease with progressive renal fibrosis.


Assuntos
Proteína Smad3/metabolismo , Fator de Transcrição Brn-3A/genética , Fator de Crescimento Transformador beta1/metabolismo , Animais , Feminino , Fibrose/fisiopatologia , Redes Reguladoras de Genes , Humanos , Inflamação/patologia , Rim/patologia , Nefropatias/genética , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/metabolismo , Transdução de Sinais/genética , Fator de Transcrição Brn-3A/metabolismo , Fator de Transcrição Brn-3A/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Sistema Urinário/metabolismo
3.
Br J Surg ; 109(11): 1140-1149, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36052580

RESUMO

BACKGROUND: Limited liver resections (LLRs) for tumours located in the posterosuperior segments of the liver are technically demanding procedures. This study compared outcomes of robotic (R) and laparoscopic (L) LLR for tumours located in the posterosuperior liver segments (IV, VII, and VIII). METHODS: This was an international multicentre retrospective analysis of patients who underwent R-LLR or L-LLR at 24 centres between 2010 and 2019. Patient demographics, perioperative parameters, and postoperative outcomes were analysed; 1 : 3 propensity score matching (PSM) and 1 : 1 coarsened exact matching (CEM) were performed. RESULTS: Of 1566 patients undergoing R-LLR and L-LLR, 983 met the study inclusion criteria. Before matching, 159 R-LLRs and 824 L-LLRs were included. After 1 : 3 PSM of 127 R-LLRs and 381 L-LLRs, comparison of perioperative outcomes showed that median blood loss (100 (i.q.r. 40-200) versus 200 (100-500) ml; P = 0.003), blood loss of at least 500 ml (9 (7.4 per cent) versus 94 (27.6 per cent); P < 0.001), intraoperative blood transfusion rate (4 (3.1 per cent) versus 38 (10.0 per cent); P = 0.025), rate of conversion to open surgery (1 (0.8 per cent) versus 30 (7.9 per cent); P = 0.022), median duration of Pringle manoeuvre when applied (30 (20-46) versus 40 (25-58) min; P = 0.012), and median duration of operation (175 (130-255) versus 224 (155-300); P < 0.001) were lower in the R-LLR group compared with the L-LLR group. After 1 : 1 CEM of 104 R-LLRs with 104 L-LLRs, R-LLR was similarly associated with significantly reduced blood loss and a lower rate of conversion to open surgery. CONCLUSION: Based on a matched analysis of well selected patients, both robotic and laparoscopic access could be undertaken safely with good outcomes for tumours in the posterosuperior liver segments.


Assuntos
Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Procedimentos Cirúrgicos Robóticos , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Humanos , Laparoscopia/métodos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de Propensão , Estudos Retrospectivos
4.
Surgeon ; 20(3): 129-136, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33726957

RESUMO

BACKGROUND: Robotic distal pancreatectomy has been accepted to be safe and effective for pancreatic tail lesion. Whether spleen preservation by preserving the splenic vessels with robot assistance is feasible and beneficial remains controversial. Here we would like to compare the operative outcomes of robotic distal pancreatectomy and splenectomy (DPS) with robotic spleen preserving distal pancreatectomy by means of splenic vessel preservation (SVP). METHODS: Between March 2011 and September 2019, 56 consecutive patients undergoing robotic distal pancreatectomy were identified, with 28 patients in each group. Patient demographics, histopathology findings and operative outcomes were prospectively collected and compared between the two groups. A subgroup analysis was made after excluding malignant and pancreatic lesions >6 cm in the DPS group. RESULTS: The two groups had similar conversion rate, blood loss, morbidity and pancreatic fistula rate. There was no operative mortality. The SVP group had shorter median operative time (245 vs 303.5 min, P = 0.019) and shorter median hospital stay (5 vs 6 days, P = 0.019) than the DPS group. However, all malignant lesions occurred in the DPS group and lesion size in DPS group was significantly larger. After matching, there were 28 SVP and 15 DPS. The histopathology findings and lesion size became comparable. The SVP group still had shorter operative time (245 vs 290 min, P = 0.022) and shorter hospital stay (5 vs 7 days, P = 0.014) than the DPS group. CONCLUSION: Apart from avoiding risk of overwhelming postsplenectomy sepsis, robotic SVP had additional advantage of shorter operative time and shorter hospital stay than robotic DPS.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Tempo de Internação , Duração da Cirurgia , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Baço/cirurgia , Resultado do Tratamento
5.
Endoscopy ; 53(6): 595-602, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32650341

RESUMO

BACKGROUND: Although endoscopic ultrasound (EUS) features and criteria have been described in chronic pancreatitis, challenges remain with interoperator variability and ease of adoption. The aim of this study was to define and validate the EUS features of chronic pancreatitis in a multicenter prospective study in Asia. METHOD: The study was divided into two parts: the first part was conducted to derive the EUS features of chronic pancreatitis with adequate interoperator agreement; the second was to prospectively evaluate these features in a multicenter cross-sectional study and determine the optimal combination of features for the diagnosis of chronic pancreatitis. Prospectively enrolled cases had standard internationally validated radiologic or histologic features of chronic pancreatitis, and controls were patients without chronic pancreatitis who underwent EUS examination. RESULTS: The top six EUS features that had good interobserver agreement (mean kappa 0.73, range 0.60 - 0.90) were selected to be further evaluated in part II of the study. These included: hyperechoic foci with shadowing, lobularity with honeycombing, cysts, dilated main pancreatic duct, dilated side branches, and calculi in the main pancreatic duct. A total of 284 subjects (132 cases, 152 controls) were enrolled from 12 centers in Asia. All six features had high accuracy ranging from 63.3 % to 89.1 %. Two or more of these six EUS features accurately defined chronic pancreatitis (sensitivity 94.7 %, specificity 98.0 %), with an area under the receiver operating curve of 0.986. CONCLUSION: This multicenter Asian study characterized and defined the EUS features of chronic pancreatitis. This provides a useful tool in clinical practice and further research in pancreatic cancer surveillance.


Assuntos
Pancreatite Crônica , Ásia , Povo Asiático , Estudos Transversais , Endossonografia , Humanos , Pancreatite Crônica/diagnóstico por imagem , Estudos Prospectivos , Sensibilidade e Especificidade
6.
Am J Gastroenterol ; 115(6): 867-875, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32149781

RESUMO

OBJECTIVES: Previous exposure to hepatitis B virus (HBV) may increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. We aim to study the impact of previous HBV infection on the severity and outcomes of patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This was a multicenter study of 489 patients with biopsy-proven NAFLD and 69 patients with NAFLD-related or cryptogenic HCC. Antihepatitis B core antibody (anti-HBc) was used to detect the previous HBV infection. RESULTS: In the biopsy cohort, positive anti-HBc was associated with lower steatosis grade but higher fibrosis stage. 18.8% and 7.5% of patients with positive and negative anti-HBc had cirrhosis, respectively (P < 0.001). The association between anti-HBc and cirrhosis remained significant after adjusting for age and metabolic factors (adjusted odds ratio 2.232; 95% confidence interval, 1.202-4.147). At a mean follow-up of 6.2 years, patients with positive anti-HBc had a higher incidence of HCC or cirrhotic complications (6.5% vs 2.2%; P = 0.039). Among patients with NAFLD-related or cryptogenic HCC, 73.9% had positive anti-HBc. None of the patients had positive serum HBV DNA. By contrast, antihepatitis B surface antibody did not correlate with histological severity. DISCUSSION: Positive anti-HBc is associated with cirrhosis and possibly HCC and cirrhotic complications in patients with NAFLD. Because a significant proportion of NAFLD-related HCC may develop in noncirrhotic patients, future studies should define the role of anti-HBc in selecting noncirrhotic patients with NAFLD for HCC surveillance.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Anticorpos Anti-Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Feminino , Hepatite B/imunologia , Hong Kong/epidemiologia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Fatores de Risco , Índice de Gravidade de Doença
7.
Surg Endosc ; 34(6): 2730-2741, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31722046

RESUMO

BACKGROUND: Endoscope is the eye of surgeon in minimally invasive surgery (MIS). Prevailing handheld endoscopes are manually steered, which can cause endoscope-instrument fencing. Robotic endoscopes can reduce the fatigue but could not reduce collisions. Handheld endoscopes with a flexible bending tip can reduce the shaft pivoting and collisions. However, its steering is challenging. In this paper, we present a robotic flexible endoscope with auto-tracking function and compare it with the conventional rigid endoscopes. METHODS: A robotic flexible endoscope (RFE) with shared autonomy is developed. The RFE could either track the instruments automatically or be controlled by a foot pedal. A mockup cholecystectomy was designed to evaluate the performance. Five surgeons were invited to perform the mockup cholecystectomy in an abdominal cavity phantom with a manual rigid endoscope (MRE), a robotic rigid endoscope (RRE), and the RFE. Space occupation, time consumption, and questionnaires based on the NASA task load index were adopted to evaluate the performances and compare the three endoscope systems. An ex vivo experiment was conducted to demonstrate the feasibility of using the RFE in a biological tissue environment. RESULTS: All surgeons completed the mockup cholecystectomy with the RFE independently. Failure occurred in the cases involving the RRE and the MRE. Inside the body cavity, the space occupied when using the RFE is 17.28% and 23.95% (p < 0.05) of that when using the MRE and the RRE, respectively. Outside the body cavity, the space occupied when using the RFE is 14.60% and 15.53% (p < 0.05) of that by using MRE and RRE. Time consumed in the operations with MRE, RRE, and RFE are 28.3 s, 93.2 s and 34.8 s, respectively. Questionnaires reveal that the performance of the RFE is the best among the three endoscope systems. CONCLUSIONS: The RFE provides a wider field of view (FOV) and occupies less space than rigid endoscopes.


Assuntos
Colecistectomia/instrumentação , Endoscópios , Procedimentos Cirúrgicos Robóticos/instrumentação , Colecistectomia/educação , Desenho de Equipamento , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/educação , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Modelos Anatômicos , Autonomia Profissional , Procedimentos Cirúrgicos Robóticos/educação , Treinamento por Simulação
8.
Dig Surg ; 37(1): 65-71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30917378

RESUMO

BACKGROUND: The advantages of radiofrequency ablation (RFA) over hepatectomy as a treatment for early-stage hepatocellular carcinoma (HCC) include reduced morbidity and more rapid recovery. Although minimally invasive surgery provides similar benefits, few studies have compared the long-term oncological outcomes of these techniques. This study aimed to compare the outcomes of minimally invasive hepatectomy (MIH) and RFA. METHODS: Patients who underwent MIH or RFA for HCC between January 2005 and January 2015 were included in a propensity score matching analysis. Only patients who underwent minimally invasive procedures for small HCC were included. Baseline clinical and laboratory parameters were retrieved from the hospital database and analyzed. RESULTS: Two hundred and twenty-five patients underwent MIH or RFA for HCC during the study period. Propensity score matching yielded 59 patient-pairs. The complication rates did not differ statistically between the 2 groups (p = 0.309). However, MIH provided significantly better overall (p = 0.005) and disease-free survival outcomes (p < 0.001) than RFA. CONCLUSIONS: Compared with RFA, MIH provided better long-term survival outcomes in patients with early-stage HCC, with no increase in the incidence of complications. When feasible, MIH should be considered a first-line treatment for this patient population.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Laparoscopia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos
9.
Surgeon ; 18(3): 178-186, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31601470

RESUMO

Prognosis of patients that have undergone liver resection can be predicted preoperatively. Albumin-Bilirubin (ALBI) is a useful score to evaluate liver function objectively. This score is simple to use, uses objective parameters, and can stratify patients into grades. In combination with other liver cancer scores, the prognosis and survival of patients can be evaluated with more accuracy. Current literatures supporting the use of the ALBI score relating to prognosis of post hepatectomy, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), radiotherapy and systemic therapy are available. Therefore, ALBI score is worthy of clinical application. The following is a review of the current literatures on the ALBI score.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Albumina Sérica/metabolismo , Carcinoma Hepatocelular/mortalidade , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Prognóstico , Taxa de Sobrevida
10.
Mod Pathol ; 32(11): 1646-1656, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31231126

RESUMO

Programmed death ligand 1 (PD-L1) protein expression by immunohistochemistry is a promising biomarker for PD-1/PD-L1 blockade in hepatocellular carcinoma. There are a number of commercially available PD-L1 assays. Our study aimed to compare the analytical performance of different PD-L1 assays and evaluate the reliability of pathologists in PD-L1 scoring. Consecutive sections from tumor samples from 55 patients with surgically resected primary hepatocellular carcinoma were stained with four standardized PD-L1 assays (22C3, 28-8, SP142, and SP263). We also correlated the PD-L1 protein level by immunohistochemistry with the mRNA level of those genes associated with tumor immune microenvironment by the NanoString platform. Five pathologists independently assessed PD-L1 expression on tumor cells [tumor proportion score] together with tumor-infiltrating immune cells (combined positive score). The 22C3, 28-8, and SP263 assays had comparable sensitivity in detecting PD-L1 expression, whereas the SP142 assay was the least sensitive assay. The inter-assay agreement measured by intraclass correlation coefficients for the tumor proportion score and combined positive score were 0.646 and 0.780, respectively. The inter-rater agreement was good to excellent (the overall intraclass correlation coefficient for the tumor proportion score and combined positive score was 0.946 and 0.809, respectively). Pathologists were less reliable in scoring combined positive score than tumor proportion score, particularly when using the SP142 assay. Up to 18% of samples were misclassified by individual pathologists in comparison to the consensus score at the cutoff of combined positive score ≥ 1. The combined positive score by the 22C3 assay demonstrated the strongest correlation with immune-related gene mRNA signatures, closely followed by combined positive scores by the 28-8 and SP263 assays. In conclusion, the 22C3, 28-8, and SP263 assays are highly concordant in PD-L1 scoring and suggest the interchangeability of these three assays. Further improvement of the accuracy in assessing PD-L1 expression at a low cutoff is still necessary.


Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/imunologia , Imuno-Histoquímica/métodos , Neoplasias Hepáticas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes
11.
Gut ; 67(5): 931-944, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28939663

RESUMO

OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) contribute to tumour immunosuppressive microenvironment and immune-checkpoint blockade resistance. Emerging evidence highlights the pivotal functions of cyclin-dependent kinases (CDKs) in tumour immunity. Here we elucidated the role of tumour-intrinsic CDK20, or cell cycle-related kinase (CCRK) on immunosuppression in hepatocellular carcinoma (HCC). DESIGN: Immunosuppression of MDSCs derived from patients with HCC and relationship with CCRK were determined by flow cytometry, expression analyses and co-culture systems. Mechanistic studies were also conducted in liver-specific CCRK-inducible transgenic (TG) mice and Hepa1-6 orthotopic HCC models using CRISPR/Cas9-mediated Ccrk depletion and liver-targeted nanoparticles for interleukin (IL) 6 trapping. Tumorigenicity and immunophenotype were assessed on single or combined antiprogrammed death-1-ligand 1 (PD-L1) therapy. RESULTS: Tumour-infiltrating CD11b+CD33+HLA-DR- MDSCs from patients with HCC potently inhibited autologous CD8+T cell proliferation. Concordant overexpression of CCRK and MDSC markers (CD11b/CD33) positively correlated with poorer survival rates. Hepatocellular CCRK stimulated immunosuppressive CD11b+CD33+HLA-DR- MDSC expansion from human peripheral blood mononuclear cells through upregulating IL-6. Mechanistically, CCRK activated nuclear factor-κB (NF-κB) via enhancer of zeste homolog 2 (EZH2) and facilitated NF-κB-EZH2 co-binding to IL-6 promoter. Hepatic CCRK induction in TG mice activated the EZH2/NF-κB/IL-6 cascade, leading to accumulation of polymorphonuclear (PMN) MDSCs with potent T cell suppressive activity. In contrast, inhibiting tumorous Ccrk or hepatic IL-6 increased interferon γ+tumour necrosis factor-α+CD8+ T cell infiltration and impaired tumorigenicity, which was rescued by restoring PMN-MDSCs. Notably, tumorous Ccrk depletion upregulated PD-L1 expression and increased intratumorous CD8+ T cells, thus enhancing PD-L1 blockade efficacy to eradicate HCC. CONCLUSION: Our results delineate an immunosuppressive mechanism of the hepatoma-intrinsic CCRK signalling and highlight an overexpressed kinase target whose inhibition might empower HCC immunotherapy.


Assuntos
Carcinoma Hepatocelular/imunologia , Quinases Ciclina-Dependentes/metabolismo , Neoplasias Hepáticas/imunologia , Células Supressoras Mieloides/imunologia , Animais , Western Blotting , Carcinoma Hepatocelular/metabolismo , Técnicas de Cultura de Células , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunoprecipitação , Terapia de Imunossupressão , Fígado/patologia , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Quinase Ativadora de Quinase Dependente de Ciclina
12.
Kidney Int ; 93(1): 173-187, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29042082

RESUMO

Src activation has been associated with fibrogenesis after kidney injury. Macrophage-myofibroblast transition is a newly identified process to generate collagen-producing myofibroblasts locally in the kidney undergoing fibrosis in a TGF-ß/Smad3-dependent manner. The potential role of the macrophage-myofibroblast transition in Src-mediated renal fibrosis is unknown. In studying this by RNA sequencing at single-cell resolution, we uncovered a unique Src-centric regulatory gene network as a key underlying mechanism of macrophage-myofibroblast transition. A total of 501 differentially expressed genes associated with macrophage-myofibroblast transition were identified. However, Smad3-knockout largely reduced the transcriptome diversity. More importantly, inhibition of Src largely suppresses ureteral obstruction-induced macrophage-myofibroblast transition in the injured kidney in vivo along with transforming growth factor-ß1-induced elongated fibroblast-like morphology, α-smooth muscle actin expression and collagen production in bone marrow derived macrophages in vitro. Unexpectedly, we further uncovered that Src serves as a direct Smad3 target gene and also specifically up-regulated in macrophages during macrophage-myofibroblast transition. Thus, macrophage-myofibroblast transition contributes to Src-mediated tissue fibrosis. Hence, targeting Src may represent as a precision therapeutic strategy for macrophage-myofibroblast transition-driven fibrotic diseases.


Assuntos
Transdiferenciação Celular , Cicatriz/enzimologia , Nefropatias/enzimologia , Rim/enzimologia , Macrófagos/enzimologia , Miofibroblastos/enzimologia , Quinases da Família src/metabolismo , Animais , Transdiferenciação Celular/efeitos dos fármacos , Transdiferenciação Celular/genética , Células Cultivadas , Cicatriz/genética , Cicatriz/patologia , Cicatriz/prevenção & controle , Modelos Animais de Doenças , Fibrose , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/genética , Nefropatias/patologia , Nefropatias/prevenção & controle , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/patologia , Inibidores de Proteínas Quinases/farmacologia , Análise de Sequência de RNA , Transdução de Sinais , Análise de Célula Única , Proteína Smad3/genética , Proteína Smad3/metabolismo , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/enzimologia , Obstrução Ureteral/genética , Quinases da Família src/genética
13.
Gastrointest Endosc ; 87(2): 476-485, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28750840

RESUMO

BACKGROUND AND AIMS: The role of electroacupuncture (EA) in reducing sedative and analgesic requirements during EUS is uncertain. The aim of this study was to investigate the efficacy of EA in reducing procedure-related pain and discomfort during EUS. METHODS: This was a double-blinded randomized controlled study conducted between March 2014 and July 2016. Consecutive patients who were scheduled for diagnostic EUS were recruited and randomized to receive EA or sham-electroacupuncture (SA). The primary outcome was the dosage of propofol used. Other outcome measurements included pain scores, anxiety scores, satisfaction scores, patients' willingness to repeat the procedure, total procedure time, and adverse events. RESULTS: A total of 128 patients were recruited to the study. The patients who received EA had significantly fewer requirements for patient-controlled sedation and analgesia (PCA). The median (interquartile range) number of demands for PCA (2 [1-5] vs 16.5 [8.5-33.8]; P < .001), the number of successful demands (2 [1-4] vs 9 [5.3-13]; P < .001), and the total dose of propofol (0.15 [0.08-0.34] vs 0.77 [0.38-1.09]; P < .001) and alfentanil (0.38 [0.20-0.86] vs 1.92 [0.94-2.72]; P < .001) were all significantly less. Patients who received EA also had significantly lower procedural pain scores and anxiety scores (P < .001), and higher satisfaction scores (P < .001), and they were more willing to repeat the procedure (P < .001). Being in the SA group and the procedure time were significant predictors of increased PCA demands (P < .001 and P = .009, respectively). CONCLUSIONS: In conclusion, the use of EA reduced sedative and analgesia demands, improved patient experience, and was associated with a low risk of adverse events during diagnostic EUS. (Clinical trial registration number: NCT02066194.).


Assuntos
Analgésicos Opioides/administração & dosagem , Eletroacupuntura , Endossonografia/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Dor/prevenção & controle , Idoso , Alfentanil/administração & dosagem , Analgesia Controlada pelo Paciente , Ansiedade/etiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Aceitação pelo Paciente de Cuidados de Saúde , Satisfação do Paciente , Propofol/administração & dosagem , Estudos Prospectivos , Fatores de Tempo
14.
Hepatobiliary Pancreat Dis Int ; 17(6): 524-530, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30413348

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma (HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor (GEP) and ATP-dependent binding cassette (ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. METHODS: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low (GEP-/ABCB5-), intermediate (either GEP+/ABCB5- or GEP-/ABCB5+) and high (GEP+/ABCB5+). Early recurrence (recurrence within 2 years after resection) and disease-free survival were analyzed. RESULTS: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone (P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. CONCLUSIONS: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group (either GEP+/ABCB5- or GEP-/ABCB5+). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/terapia , Progranulinas/análise , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/química , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/química , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/química , Prognóstico
15.
Surgeon ; 16(3): 163-170, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28807570

RESUMO

BACKGROUND AND PURPOSE: Whether liver resection or ablation should be the first-line treatment for very early/early hepatocellular carcinoma (HCC) in patients who are candidates for both remains controversial. The aim of this study was to determine if the newly-developed Albumin-Bilirubin (ALBI) grade might help in treatment selections and to evaluate the survival of patients treated with liver resection and radiofrequency ablation (RFA). METHODS: Patients with BCLC stage 0/A HCC who were treated with curative liver resection and RFA from 2003 to 2013 were included. Baseline clinical and laboratory parameters were retrieved and reviewed from the hospital database. Liver function and its impact on survival was assessed by the ALBI score. Overall and disease-free survivals were compared between the two groups. RESULTS: 488 patients underwent liver resection (n = 318) and RFA (n = 170) for BCLC stage 0/A HCC during the study period. Liver resection offered superior survival to RFA in patients with BCLC stage 0/A HCC in the whole cohort. After propensity score matching, liver resection offered superior overall survival and disease-free survival to RFA in patients with ALBI grade 1 (P = 0.0002 and P < 0.0001 respectively). In contrast, there were no significant differences in overall survival and disease-free survival between liver resection and RFA in patients with ALBI grade 2 (P = 0.7119 and 0.3266, respectively). CONCLUSIONS: Liver resection offered superior survival to RFA in patients with BCLC stage 0/A HCC. The ALBI grade could identify those patients with worse liver function who did not gain any survival advantage from curative liver resection.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Hepatectomia , Neoplasias Hepáticas/cirurgia , Albumina Sérica/análise , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos
16.
Endoscopy ; 49(2): 130-138, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27875855

RESUMO

Background and study aim There are no data comparing endoscopic ultrasound (EUS)-guided gallbladder drainage (EGBD) with percutaneous cholecystostomy as a treatment for patients with acute cholecystitis. Patients and methods This was a 1 : 1 matched cohort study of all patients who were unfit for cholecystectomy and underwent EGBD or percutaneous cholecystostomy instead for the treatment of acute cholecystitis. The outcomes were matched for age, sex, and American Society of Anesthesiologists grade. Outcome measures included the technical and clinical success rates, adverse events, hospital stay, the number of unplanned admissions, and mortality. Results Between November 2011 and August 2014, a total of 118 patients were included in the study (59 EGBD, 59 percutaneous cholecystostomy). Technical and clinical success rates were similar. In the EGBD group, significantly fewer patients suffered from overall adverse events (19 [32.2 %] vs. 44 [74.6 %]; P < 0.001) and serious adverse events (14 [23.7 %] vs. 44 [74.6 %]; P < 0.001) compared to the percutaneous cholecystostomy group. Patients in the EGBD group required fewer unplanned admissions (4 [6.8 %] vs. 42 [71.2 %]; P < 0.001), which were due to problems related to the cholecystostomy tube in 95.2 %. The 30-day adverse event rates were similar between the groups (17 [28.8 %] vs. 10 [16.9 %]; P = 0.13). For instance, recurrent acute cholecystitis occurred in 0 patients in the EGBD group and in 4 (6.8 %) patients in the percutaneous cholecystostomy group (P = 0.12). The 30-day mortality rates were non-significantly higher in the EGBD group (5 [8.5 %] vs. 1 [1.7 %]; P = 0.21). Conclusions EGBD and percutaneous cholecystostomy were both effective means of achieving gallbladder drainage. EGBD may be a promising alternative to percutaneous cholecystostomy for treatment of acute cholecystitis in patients who are unfit for surgery, provided that experienced endosonographers are available.


Assuntos
Colecistite Aguda/cirurgia , Colecistostomia , Drenagem , Endossonografia/métodos , Cirurgia Assistida por Computador , Idoso , Idoso de 80 Anos ou mais , China , Colecistectomia/métodos , Colecistostomia/efeitos adversos , Colecistostomia/métodos , Pesquisa Comparativa da Efetividade , Drenagem/efeitos adversos , Drenagem/métodos , Feminino , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/cirurgia , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/métodos
17.
J Gastroenterol Hepatol ; 32(2): 506-514, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27490702

RESUMO

BACKGROUND AND AIM: Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post-hepatectomy liver failure. METHODS: A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post-hepatectomy liver failure according to the International Study Group of Liver Surgery definition. RESULTS: A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post-hepatectomy liver failure. (P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high-grade post-hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor. CONCLUSIONS: Liver stiffness measurement using Fibroscan is good to predict high-grade post-hepatectomy liver failure especially in patients without right lobe tumor.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatectomia , Falência Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Estudos de Coortes , Técnicas de Imagem por Elasticidade/instrumentação , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Índice de Gravidade de Doença
18.
Ann Hepatobiliary Pancreat Surg ; 27(4): 437-442, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37599108

RESUMO

Emergency pancreaticoduodenectomy (EPD) is a rarely performed operation. It is important to know the indications and outcomes of EPD to have a better understanding of its application in clinical practice. A review of eight consecutive cases of EPD was done. Between January 2003 and December 2021, 8 out of 370 patients (2.2%) in a single center received pancreaticoduodenectomy as emergency. There were six males and two females with a median age of 45.5 years. The indications were trauma in three patients, bleeding tumors in two patients, and one patient each in obstructing duodenal tumor, postoperative complication and post-endoscopic retrograde cholangiopancreatography (ERCP) complication. The median operative time and blood loss were 427.5 minutes and 1,825 mL, respectively. There was no operative mortality. Seven patients (87.5%) had postoperative complications. Three patients (37.5%) developed postoperative grade B pancreatic fistula. The median postoperative hospital stay was 23.5 days. Five patients were still alive while three patients survived for 13, 31, and 42 months after the operation. The causes of death were recurrent tumors in two patients, and sepsis in one patient. According to this case series, EPD is associated with increased morbidity and pancreatic fistula, but is still deserved in life-threatening situations and long-term survival is possible after EPD.

19.
Surgeon ; 10(5): 260-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22959159

RESUMO

BACKGROUNDS AND PURPOSE: To determine the predictors for recurrence in patients receiving curative hepatectomy for hepatocellular carcinoma (HCC). METHODS: From January 2001 to July 2007, all patients having hepatectomy for first occurrence HCC with curative intent were identified from a prospectively collected database. Prognostic factors for recurrence and survival after resection were analyzed. RESULTS: A total of 235 patients were included. With a median follow-up of 50.2 (0.07-125.1) months, the recurrence rate was 57.0%. The 1-, 3-, and 5-year overall survival rates were 83.9%, 66.0%, and 58.1% respectively. Multivariate analysis demonstrated that multi-focal lesions (HR: 2.93, P < 0.001), alpha-fetoprotein (AFP) level greater than 100 ng/ml (HR: 1.74, P = 0.002) and history of tumor rupture (HR: 2.84, P = 0.003) were independent risk factors for recurrence of HCC after hepatectomy. CONCLUSIONS: Predictors for HCC recurrence can be identified before operation. These important parameters should be considered before and after contemplating curative resection for HCC patients and for risk stratification in future clinical trials for neoadjuvant or post-resection adjuvant therapy. The possible use of neoadjuvant or adjuvant treatment to improve survival should be addressed by further trials.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco
20.
Cardiovasc Intervent Radiol ; 45(3): 315-327, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34609579

RESUMO

PURPOSE: To compare the survival outcomes of patients treated with transarterial ethanol ablation (TEA) with those treated with liver resection (LR) for solitary HCC less than 5 cm in diameter, in patients stratified according to liver function using ALBI grade. MATERIALS AND METHODS: This retrospective study approved by the Institutional Committee included all treatment-naïve patients with solitary HCC (≤ 5 cm) and Child-Pugh score 5, and who had received TEA (33 patients) or LR (192 patients) between 2004 and 2012. Treatment outcomes were compared between patients treated with TEA and LR after a period of at least 7 years of follow-up. Comparison was repeated for those patients with ALBI grade 2 or 3. RESULTS: Both overall survival (OS, months) and recurrence-free survival (RFS months) were significantly longer in the LR group (OS: LR 129.7[119.5, 140], TEA 69.1[55.9, 82.3], P < 0.0001; RFS: LR 91.3[43.5, 139.1], TEA 13.8 [11, 16.5], P < 0.0001). In patients with ALBI grade 2 or 3, there was no significant difference between the groups in OS or RFS (OS: LR 43.1[0, 91.2], TEA 55.4 [43.7, 67.2], P = 0.65; RFS: LR 17.8 [11.4, 24.2], TEA 11.9 [6.7, 17.1], P = 0.132). Transient epigastric discomfort and low-grade fever without consequence occurred in 8 patients (8/33 or 24.2%) in the TEA group. CONCLUSION: The overall survival after LR for HCCs ≤ 5 cm was superior to that after TEA but similar when compared in patients with ALBI grade 2 or 3, the ALBI grade is useful for patient selection for TEA or LR for HCCs ≤ 5 cm.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Bilirrubina , Carcinoma Hepatocelular/terapia , Etanol/uso terapêutico , Humanos , Neoplasias Hepáticas/terapia , Estudos Retrospectivos , Albumina Sérica
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