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1.
Langenbecks Arch Surg ; 409(1): 152, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703240

RESUMO

PURPOSE: This study evaluated the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) calculator in predicting outcomes after hepatectomy for colorectal cancer (CRC) liver metastasis in a Southeast Asian population. METHODS: Predicted and actual outcomes were compared for 166 patients undergoing hepatectomy for CRC liver metastasis identified between 2017 and 2022, using receiver operating characteristic curves with area under the curve (AUC) and Brier score. RESULTS: The ACS-NSQIP calculator accurately predicted most postoperative complications (AUC > 0.70), except for surgical site infection (AUC = 0.678, Brier score = 0.045). It also exhibited satisfactory performance for readmission (AUC = 0.818, Brier score = 0.011), reoperation (AUC = 0.945, Brier score = 0.002), and length of stay (LOS, AUC = 0.909). The predicted LOS was close to the actual LOS (5.9 vs. 5.0 days, P = 0.985). CONCLUSION: The ACS-NSQIP calculator demonstrated generally accurate predictions for 30-day postoperative outcomes after hepatectomy for CRC liver metastasis in our patient population.


Assuntos
Neoplasias Colorretais , Hepatectomia , Neoplasias Hepáticas , Complicações Pós-Operatórias , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sudeste Asiático , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Medição de Risco , População do Sudeste Asiático
2.
Surgery ; 176(1): 11-23, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782702

RESUMO

BACKGROUND: This study evaluated the cost-effectiveness of open, laparoscopic, and robotic liver resection. METHODS: A comprehensive literature review and Bayesian network meta-analysis were conducted. Surface under cumulative ranking area values, mean difference, odds ratio, and 95% credible intervals were calculated for all outcomes. Cluster analysis was performed to determine the most cost-effective clustering approach. Costs-morbidity, costs-mortality, and costs-efficacy were the primary outcomes assessed, with postoperative overall morbidity, mortality, and length of stay associated with total costs for open, laparoscopic, and robotic liver resection. RESULTS: Laparoscopic liver resection incurred the lowest total costs (laparoscopic liver resection versus open liver resection: mean difference -2,529.84, 95% credible intervals -4,192.69 to -884.83; laparoscopic liver resection versus robotic liver resection: mean difference -3,363.37, 95% credible intervals -5,629.24 to -1,119.38). Open liver resection had the lowest procedural costs but incurred the highest hospitalization costs compared to laparoscopic liver resection and robotic liver resection. Conversely, robotic liver resection had the highest total and procedural costs but the lowest hospitalization costs. Robotic liver resection and laparoscopic liver resection had a significantly reduced length of stay than open liver resection and showed less postoperative morbidity. Laparoscopic liver resection resulted in the lowest readmission and liver-specific complication rates. Laparoscopic liver resection and robotic liver resection demonstrated advantages in costs-morbidity efficiency. While robotic liver resection offered notable benefits in mortality and length of stay, these were balanced against its highest total costs, presenting a nuanced trade-off in the costs-mortality and costs-efficacy analyses. CONCLUSION: Laparoscopic liver resection represents a more cost-effective option for hepatectomy with superior postoperative outcomes and shorter length of stay than open liver resection. Robotic liver resection, though costlier than laparoscopic liver resection, along with laparoscopic liver resection, consistently exceeds open liver resection in surgical performance.


Assuntos
Análise Custo-Benefício , Hepatectomia , Laparoscopia , Tempo de Internação , Procedimentos Cirúrgicos Robóticos , Humanos , Hepatectomia/economia , Hepatectomia/métodos , Hepatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Laparoscopia/economia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Metanálise em Rede , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
3.
J Minim Access Surg ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726970

RESUMO

INTRODUCTION: Minimally invasive surgery (MIS) for limited resections for pancreatic uncinate lesions is not widely performed but can adequately treat benign or low-grade malignant lesions. The aim of this study was to evaluate the short-term outcomes of MIS-limited pancreatic resections for patients with suspected pancreatic neuroendocrine tumours (PNETs). PATIENTS AND METHODS: This was a retrospective study of six consecutive patients who underwent MIS for PNET within a single institution between 2017 and 2022. RESULTS: Six patients underwent limited pancreas-preserving MIS of the uncinate process (uncinectomy or enucleation), of which two were performed through the robotic approach and four through laparoscopic approach. The median operation time was 212.5 (175-338.75) min, and the median blood loss was 50 (50-112.5) ml. The median post-operative hospital length of stay was 5.5 (3.75-11.5) days. Two patients (33.3%) had major post-operative morbidities (Clavien-Dindo ≥Grade 3). There were no open conversions or post-operative mortalities. Five patients had histologically proven Grade 1 neuroendocrine tumours. One was T2 and four were T1. CONCLUSIONS: This study suggests that limited MIS resections of pancreatic uncinate PNETs are a feasible procedure with good patient outcomes. It offers a safe alternative to radical surgical resections like pancreatoduodenectomies in selected patients with low-grade malignant or benign tumours.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38710538

RESUMO

This systematic review and meta-analysis aimed to evaluate the impact of prospective payment systems (PPSs) on cholecystectomy. A comprehensive literature review was conducted, examining studies published until December 2023. The review process focused on identifying research across major databases that reported critical outcomes such as length of stay (LOS), mortality, complications, admissions, readmissions, and costs following PPS for cholecystectomy. The studies were specifically selected for their relevance to the impact of PPS or the transition from fee-for-service (FFS) to PPS. The study analyzed six papers, with three eligible for meta-analysis, to assess the impact of the shift from FFS to PPS in laparoscopic and open cholecystectomy procedures. Our findings indicated no significant changes in LOS and mortality rates following the transition from FFS to PPS. Complication rates varied and were influenced by the diagnosis-related group categorization and surgeon cost profiles under episode-based payment. There was a slight increase in admissions and readmissions, and mixed effects on hospital costs and financial margins, suggesting varied responses to PPS for cholecystectomy procedures. The impact of PPS on cholecystectomy is nuanced and varies across different aspects of healthcare delivery. Our findings indicate a need for adaptable, patient-centered PPS models that balance economic efficiency with high-quality patient care. The study emphasizes the importance of considering specific surgical procedures and patient demographics in healthcare payment reforms.

5.
Surg Endosc ; 38(6): 3035-3051, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38777892

RESUMO

BACKGROUND: This study compared the cost-effectiveness of open (ODP), laparoscopic (LDP), and robotic (RDP) distal pancreatectomy (DP). METHODS: Studies reporting the costs of DP were included in a literature search until August 2023. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area (SUCRA) values, mean difference (MD), odds ratio (OR), and 95% credible intervals (CrIs) were calculated for outcomes of interest. Cluster analysis was performed to examine the similarity and classification of DP approaches into homogeneous clusters. A decision model-based cost-utility analysis was conducted for the cost-effectiveness analysis of DP strategies. RESULTS: Twenty-six studies with 29,164 patients were included in the analysis. Among the three groups, LDP had the lowest overall costs, while ODP had the highest overall costs (LDP vs. ODP: MD - 3521.36, 95% CrI - 6172.91 to - 1228.59). RDP had the highest procedural costs (ODP vs. RDP: MD - 4311.15, 95% CrI - 6005.40 to - 2599.16; LDP vs. RDP: MD - 3772.25, 95% CrI - 4989.50 to - 2535.16), but incurred the lowest hospitalization costs. Both LDP (MD - 3663.82, 95% CrI - 6906.52 to - 747.69) and RDP (MD - 6678.42, 95% CrI - 11,434.30 to - 2972.89) had significantly reduced hospitalization costs compared to ODP. LDP and RDP demonstrated a superior profile regarding costs-morbidity, costs-mortality, costs-efficacy, and costs-utility compared to ODP. Compared to ODP, LDP and RDP cost $3110 and $817 less per patient, resulting in 0.03 and 0.05 additional quality-adjusted life years (QALYs), respectively, with positive incremental net monetary benefit (NMB). RDP costs $2293 more than LDP with a negative incremental NMB but generates 0.02 additional QALYs with improved postoperative morbidity and spleen preservation. Probabilistic sensitivity analysis suggests that LDP and RDP are more cost-effective options compared to ODP at various willingness-to-pay thresholds. CONCLUSION: LDP and RDP are more cost-effective than ODP, with LDP exhibiting better cost savings and RDP demonstrating superior surgical outcomes and improved QALYs.


Assuntos
Análise Custo-Benefício , Laparoscopia , Metanálise em Rede , Pancreatectomia , Procedimentos Cirúrgicos Robóticos , Pancreatectomia/economia , Pancreatectomia/métodos , Humanos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/economia , Laparoscopia/métodos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos
6.
Surgery ; 175(2): 393-403, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38052675

RESUMO

BACKGROUND: This study aims to compare the outcomes of high-volume, medium-volume, and low-volume hospitals performing hepatic resections using a network meta-analysis. METHODS: A literature search until June 2023 was conducted across major databases to identify studies comparing outcomes in high-volume, medium-volume, and low-volume hospitals for liver resection. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area values, odds ratio, and mean difference with 95% credible intervals were reported for postoperative mortality, failure-to-rescue, morbidity, length of stay, and hospital costs. RESULTS: Twenty studies comprising 248,707 patients undergoing liver resection were included. For the primary mortality outcome, overall and subgroup analyses were performed: group I: high-volume = 5 to 20 resections/year; group II: high-volume = 21 to 49 resections/year; group III: high-volume ≥50 resections/year. Results demonstrated a significant association between hospital volume and mortality (overall-high-volume versus medium-volume: odds ratio 0.66, 95% credible interval 0.49-0.87; high-volume versus low-volume: odds ratio 0.52, 95% credible interval 0.41-0.65; group I-high-volume versus low-volume: odds ratio 0.34, 95% credible interval 0.22-0.50; medium-volume versus low-volume: odds ratio 0.56, 95% credible interval 0.33-0.92; group II-high-volume versus low-volume: odds ratio 0.67, 95% credible interval 0.45-0.91), as well as length of stay (high-volume versus low-volume: mean difference -1.24, 95% credible interval -2.07 to -0.41), favoring high-volume hospitals. No significant difference was observed in failure-to-rescue, morbidity, or hospital costs across the 3 groups. CONCLUSION: This study supports a positive relationship between hospital volume and surgical outcomes in liver resection. Patients from high-volume hospitals experience superior outcomes in terms of lower postoperative mortality and shorter lengths of stay than medium-volume and low-volume hospitals.


Assuntos
Hepatectomia , Hospitais com Alto Volume de Atendimentos , Humanos , Teorema de Bayes , Hepatectomia/métodos , Mortalidade Hospitalar , Hospitais , Fígado , Metanálise em Rede
7.
Gastroenterology ; 165(4): 1016-1024.e5, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37406887

RESUMO

BACKGROUND & AIMS: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance. METHODS: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer. RESULTS: Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5). CONCLUSIONS: The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm.


Assuntos
Carcinoma Ductal Pancreático , Cistos , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Neoplasias Intraductais Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Estudos Retrospectivos , Neoplasias Pancreáticas/patologia , Pâncreas/patologia , Cistos/patologia , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas
8.
Mol Oncol ; 17(11): 2275-2294, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36896891

RESUMO

Hepatocellular carcinoma (HCC) is the third deadliest and sixth most common cancer in the world. Histone-lysine N-methyltransferase EHMT2 (also known as G9a) is a histone methyltransferase frequently overexpressed in many cancer types, including HCC. We showed that Myc-driven liver tumours have a unique H3K9 methylation pattern with corresponding G9a overexpression. This phenomenon of increased G9a was further observed in our c-Myc-positive HCC patient-derived xenografts. More importantly, we showed that HCC patients with higher c-Myc and G9a expression levels portend a poorer survival with lower median survival months. We demonstrated that c-Myc interacts with G9a in HCC and cooperates to regulate c-Myc-dependent gene repression. In addition, G9a stabilises c-Myc to promote cancer development, contributing to the growth and invasive capacity in HCC. Furthermore, combination therapy between G9a and synthetic-lethal target of c-Myc, CDK9, demonstrates strong efficacy in patient-derived avatars of Myc-driven HCC. Our work suggests that targeting G9a could prove to be a potential therapeutic avenue for Myc-driven liver cancer. This will increase our understanding of the underlying epigenetic mechanisms of aggressive tumour initiation and lead to improved therapeutic and diagnostic options for Myc-driven hepatic tumours.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Epigênese Genética , Antígenos de Histocompatibilidade/genética , Antígenos de Histocompatibilidade/metabolismo , Antígenos de Histocompatibilidade/uso terapêutico , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Metilação
9.
Circ Res ; 132(7): 795-811, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-36852690

RESUMO

BACKGROUND: Smooth muscle cells (SMC), the major cell type in atherosclerotic plaques, are vital in coronary artery diseases (CADs). SMC phenotypic transition, which leads to the formation of various cell types in atherosclerotic plaques, is regulated by a network of genetic and epigenetic mechanisms and governs the risk of disease. The involvement of long noncoding RNAs (lncRNAs) has been increasingly identified in cardiovascular disease. However, SMC lncRNAs have not been comprehensively characterized, and their regulatory role in SMC state transition remains unknown. METHODS: A discovery pipeline was constructed and applied to deeply strand-specific RNA sequencing from perturbed human coronary artery SMC with different disease-related stimuli, to allow for the detection of novel lncRNAs. The functional relevance of a select few novel lncRNAs were verified in vitro. RESULTS: We identified 4579 known and 13 655 de novo lncRNAs in human coronary artery SMC. Consistent with previous long noncoding RNA studies, these lncRNAs overall have fewer exons, are shorter in length than protein-coding genes (pcGenes), and have relatively low expression level. Genomic location of these long noncoding RNA is disproportionately enriched near CAD-related TFs (transcription factors), genetic loci, and gene regulators of SMC identity, suggesting the importance of their function in disease. Two de novo lncRNAs, ZIPPOR (ZEB-interacting suppressor) and TNS1-AS2 (TNS1-antisense 2), were identified by our screen. Combining transcriptional data and in silico modeling along with in vitro validation, we identified CAD gene ZEB2 as a target through which these lncRNAs exert their function in SMC phenotypic transition. CONCLUSIONS: Expression of a large and diverse set of lncRNAs in human coronary artery SMC are highly dynamic in response to CAD-related stimuli. The dynamic changes in expression of these lncRNAs correspond to alterations in transcriptional programs that are relevant to CAD, suggesting a critical role for lncRNAs in SMC phenotypic transition and human atherosclerotic disease.


Assuntos
Placa Aterosclerótica , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/metabolismo , Placa Aterosclerótica/metabolismo , Fatores de Transcrição/metabolismo , Fenótipo , Miócitos de Músculo Liso/metabolismo
10.
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
11.
J Hepatocell Carcinoma ; 9: 839-851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35999856

RESUMO

Objective: We aimed to prognosticate survival after surgical resection of HCC stratified by stage with amalgamation of the modified Barcelona Clinic Liver Cancer (BCLC) staging system and location of tumour. Methods: This single-institutional retrospective cohort study included patients with HCC who underwent surgical resection between 1st January 2000 to 30th June 2016. Participants were divided into 6 different subgroups: A-u) Within MC with Unilobar lesions; A-b) Within MC + Bilobar lesions; B1-u) Out of MC + within Up-To-7 + Unilobar lesions; B1-b) Out of MC + within Up-to-7 + Bilobar lesions; B2-u) Out of MC + Out of Up-To-7 + Unilobar lesions; B2-b) Out of MC + Out of Up-To-7 + Bilobar lesions. A separate survival analysis was conducted for solitary HCC lesions according to three subgroups: A-S (Within MC); B1-S (Out of MC + within Up-To-7); B2-S (Out of MC + out of Up-To-7). Results: A total of 794 of 1043 patients with surgical resection for HCC were analysed. Groups A-u (64.6%), A-b (58.4%) and B1-u (56.2%) had 5-year cumulative overall survival (OS) rates above 50% after surgical resection and median OS exceeding 60 months (P = 0.0001). The 5-year cumulative recurrence-free survival rates (RFS) were 40.4% (group A-u), 38.2% (group A-b), 36.3% (group B1-u), 24.6% (group B2-u), and 7.3% (group B2-b)(P=0.0001). For solitary lesions, the 5-year OS for the subgroups were A-S (65.1%), B1-S (56.0%) and B2-S (47.1%) (P = 0.0003). Compared to A-S, there was also a significant trend towards relatively poorer OS as the lesion sizes increased in B1-S (HR 1.46, 95% CI 1.03-2.08) and B2-S (HR 1.65, 95% CI 1.25-2.18). Conclusion: We adopted a novel approach combining the modified BCLC B sub-classification and dispersion of tumour to show that surgical resection in intermediate stage HCC can be robustly prognosticated. We found that size prognosticates resection outcomes in solitary tumours.

12.
Circulation ; 145(6): 469-485, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-34990206

RESUMO

BACKGROUND: Smooth muscle cells (SMCs) transition into a number of different phenotypes during atherosclerosis, including those that resemble fibroblasts and chondrocytes, and make up the majority of cells in the atherosclerotic plaque. To better understand the epigenetic and transcriptional mechanisms that mediate these cell state changes, and how they relate to risk for coronary artery disease (CAD), we have investigated the causality and function of transcription factors at genome-wide associated loci. METHODS: We used CRISPR-Cas 9 genome and epigenome editing to identify the causal gene and cells for a complex CAD genome-wide association study signal at 2q22.3. Single-cell epigenetic and transcriptomic profiling in murine models and human coronary artery smooth muscle cells were used to understand the cellular and molecular mechanism by which this CAD risk gene exerts its function. RESULTS: CRISPR-Cas 9 genome and epigenome editing showed that the complex CAD genetic signals within a genomic region at 2q22.3 lie within smooth muscle long-distance enhancers for ZEB2, a transcription factor extensively studied in the context of epithelial mesenchymal transition in development of cancer. Zeb2 regulates SMC phenotypic transition through chromatin remodeling that obviates accessibility and disrupts both Notch and transforming growth factor ß signaling, thus altering the epigenetic trajectory of SMC transitions. SMC-specific loss of Zeb2 resulted in an inability of transitioning SMCs to turn off contractile programing and take on a fibroblast-like phenotype, but accelerated the formation of chondromyocytes, mirroring features of high-risk atherosclerotic plaques in human coronary arteries. CONCLUSIONS: These studies identify ZEB2 as a new CAD genome-wide association study gene that affects features of plaque vulnerability through direct effects on the epigenome, providing a new therapeutic approach to target vascular disease.


Assuntos
Aterosclerose/genética , Epigênese Genética/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Animais , Aterosclerose/patologia , Humanos , Camundongos , Análise de Célula Única
13.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wpr-969041

RESUMO

Background and Objectives@#The purpose of this study was to examine the benefits of ultrasonography performed by a surgeon rather than a radiologist.Subjects and Method This retrospective study enrolled 122 cases of ultrasonography performed by a head and neck surgeon and 116 cases of the same examination performed by a radiologist before surgery. The time intervals between the first visit and surgery were compared in both groups. @*Results@#The average waiting time for surgery after the first hospital visit was significantly reduced when a surgeon performed the ultrasound examination. Furthermore, there was no significant difference in sampling inadequacy rate on thyroid fine needle aspiration (FNA) between FNA performed by a head and neck surgeon and a radiologist. @*Conclusion@#Surgeons can utilize ultrasound as a diagnostic and therapeutic tool in an office-based setting. For patients, diagnosis and treatment provided by a single doctor will lead to more efficient outcomes.

14.
Liver Cancer ; 10(3): 224-239, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34239809

RESUMO

INTRODUCTION: Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS). METHOD: We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC). RESULTS: Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC. CONCLUSION: The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics.

15.
Cancer Rep (Hoboken) ; 4(5): e1393, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33939335

RESUMO

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is highly lethal. Surgery offers the only chance of cure, but 5-year overall survival (OS) after surgical resection and adjuvant therapy remains dismal. Adjuvant trials were mostly conducted in the West enrolling fit patients. Applicability to a general population, especially Asia has not been described adequately. AIM: We aimed to evaluate the clinical outcomes, prognostic factors of survival, pattern, and timing of recurrence after curative resection in an Asian institution. METHODS AND RESULTS: The clinicopathologic and survival outcomes of 165 PDAC patients who underwent curative resection between 1998 and 2013 were reviewed retrospectively. Median age at surgery was 62.0 years. 55.2% were male, and 73.3% had tumors involving the head of pancreas. The median OS of the entire cohort was 19.7 months. Median OS of patients who received adjuvant chemotherapy was 23.8 months. Negative predictors of survival include lymph node ratio (LNR) of >0.3 (HR = 3.36, P = .001), tumor site involving the body or tail of pancreas (HR = 1.59, P = .046), presence of perineural invasion (PNI) (HR = 2.36, P = .018) and poorly differentiated/undifferentiated tumor grade (HR = 1.86, P = .058). The median time to recurrence was 8.87 months, with 66.1% and 81.2% of patients developing recurrence at 12 months and 24 months respectively. The most common site of recurrence was the liver. CONCLUSION: The survival of Asian patients with resected PDAC who received adjuvant chemotherapy is comparable to reported randomized trials. Clinical characteristics seem similar to Western patients. Hence, geographical locations may not be a necessary stratification factor in RCTs. Conversely, lymph node ratio and status of PNI ought to be incorporated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Quimioterapia Adjuvante/mortalidade , Recidiva Local de Neoplasia/mortalidade , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Singapura , Taxa de Sobrevida
16.
Cancer Res Treat ; 53(4): 944-961, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33421974

RESUMO

PURPOSE: NUF2 has been implicated in multiple cancers recently, suggesting NUF2 may play a role in the common tumorigenesis process. In this study, we aim to perform comprehensive meta-analysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA). MATERIALS AND METHODS: RNA-sequencing data in 31 cancer types in the TCGA data and 11 independent datasets were used to examine NUF2 expression. Silencing NUF2 using targeting shRNAs in hepatocellular carcinoma (HCC) cell lines was used to evaluate NUF2's role in HCC in vitro and in vivo. RESULTS: NUF2 up-regulation is significantly observed in 23 out of the 31 cancer types in the TCGA datasets and validated in 13 major cancer types using 11 independent datasets. NUF2 overexpression was clinically important as high NUF2 was significantly associated with tumor stages in eight different cancers. High NUF2 was also associated with significantly poorer patient overall survival and disease-free survival in eight and six cancers, respectively. We proceeded to validate NUF2 overexpression and its negative association with overall survival at the protein level in an independent cohort of 40 HCC patients. Compared to the non-targeting controls, NUF2 knockdown cells showed significantly reduced ability to grow, migrate into a scratch wound and invade the 8 µm porous membrane in vitro. Moreover, NUF2 knockdown cells also formed significantly smaller tumors than control cells in mouse xenograft assays in vivo. CONCLUSION: NUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias/mortalidade , Animais , Apoptose , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Transplant Proc ; 53(1): 65-72, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32951861

RESUMO

Hepatic artery (HA) complications after liver transplant (LT) can lead to biliary complications, graft failure, and mortality. Although microsurgery has been established to improve anastomotic outcomes, it prolongs surgical time and has not reached widespread adoption at all transplant centers. We investigated the incidences of arterial, biliary complications and outcomes after using microsurgery to anastomose HA during LT. Retrospective cohort of consecutive LT performed from 2006 to 2018 was reviewed for operative details and postoperative outcomes. Cox-regression models were used to investigate the relationship between variables and outcomes. Eighty (62.5%) LTs (Group 1) were performed without and compared with 48 (Group 2) with microsurgical anastomosis of HA. Both groups were comparable in terms of arterial and biliary anastomoses performed. Incidence of early HA thrombosis was similar (6.2% vs 2.1%, P = .28). Group 2 had lower incidence of short- and long-term arterial complications, especially amongst living donor liver transplantations (LDLT) (5.3% vs 35.0%, P = .022). On multivariate analysis, microsurgery was associated with lower risk (hazard ratio [HR] 0.09, 95% confidence interval [CI] 0.01-0.71) of, and LDLT had higher risk (HR 4.23, 95% CI 1.46-12.27) of arterial complications. Biliary complications were associated with LDLT (HR 3.91, 95% CI 1.30-11.71) and dual biliary anastomoses (HR 5.26, 95% CI 1.15-24.08) but not with occurrence of HA complications. Worse patient survival was associated with the occurrence of any HA complication (HR 4.11, 95% CI 1.78-9.48). Hepatic arterial complications can be reduced using microsurgical techniques for the anastomosis, resulting in improved patient survival outcomes after liver transplantation.


Assuntos
Artéria Hepática/cirurgia , Transplante de Fígado/métodos , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Estudos de Coortes , Feminino , Humanos , Incidência , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-913816

RESUMO

Purpose@#NUF2 has been implicated in multiple cancers recently, suggesting NUF2 may play a role in the common tumorigenesis process. In this study, we aim to perform comprehensive meta-analysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA). @*Materials and Methods@#RNA-sequencing data in 31 cancer types in the TCGA data and 11 independent datasets were used to examine NUF2 expression. Silencing NUF2 using targeting shRNAs in hepatocellular carcinoma (HCC) cell lines was used to evaluate NUF2’s role in HCC in vitro and in vivo. @*Results@#NUF2 up-regulation is significantly observed in 23 out of the 31 cancer types in the TCGA datasets and validated in 13 major cancer types using 11 independent datasets. NUF2 overexpression was clinically important as high NUF2 was significantly associated with tumor stages in eight different cancers. High NUF2 was also associated with significantly poorer patient overall survival and disease-free survival in eight and six cancers, respectively. We proceeded to validate NUF2 overexpression and its negative association with overall survival at the protein level in an independent cohort of 40 HCC patients. Compared to the non-targeting controls, NUF2 knockdown cells showed significantly reduced ability to grow, migrate into a scratch wound and invade the 8 μm porous membrane in vitro. Moreover, NUF2 knockdown cells also formed significantly smaller tumors than control cells in mouse xenograft assays in vivo. @*Conclusion@#NUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies.

19.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wpr-920169

RESUMO

Background and Objectives@#Follicular thyroid carcinoma (FTC) is the second common thyroid cancer which comprises about 10% of differentiated thyroid carcinoma. Hurthle cell carcinoma (HCC) is a relatively rare disease that has been classified as a subtype of FTC. However, there have been insufficient reports about these two similar thyroid cancers in South Korea due to low incidences. This study aims to present clinical features and evaluate prognostic factors of FTC and HCC.Subjects and Method We reviewed data of 189 FTC and 12 HCC patients who underwent surgery in our center from January 2000 to December 2020. Variables such as clinical characteristics, surgical method, pathologic result, post-operative treatment, survival rate and prognostic factors were included in our study. @*Results@#As for age, 67.2% of patients in FTC group and 33.3% of patients in HCC group were older than 55 years-old (p=0.017). The average tumor sizes of FTC and HCC were 2.98 and 3.1 cm, respectively. The 10-year overall survival rates of FTC and HCC were 96.5% and 100%, respectively. The 10-year disease free survival rates of FTC and HCC were 89.1% and 91.7%, respectively. Subclassification (widely invasive: p=0.036) and initial distant metastasis (p<0.001) were significant prognostic factors in FTC. @*Conclusion@#This study will be helpful for diagnosis and treatment of FTC and HCC, which are relatively rare.

20.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wpr-920165

RESUMO

Cogan’s syndrome is a rare inflammatory disease characterized by non-syphilitic keratitis and vestibulo-auditory symptoms including hearing loss, tinnitus, and vertigo. Although its precise pathogenesis is not known, Cogan’s syndrome is generally considered an autoimmune disease. This hypothesis is supported by the frequently successful remission of hearing loss after steroid administration and the association with other autoimmune disorders such as rheumatoid arthritis. Medical treatment of Cogan’s syndrome depends on disease severity and on how extensive the disease is. The involvement of inner ear pathology requires systemic corticosteroid therapy. In cases of treatment failure or the need for a corticosteroid-sparing effect, other immunosuppressive drugs can be used. We experienced two patients with typical Cogan’s syndrome, presenting bilateral progressive sensorineural hearing loss and dizziness with ocular involvement, which we have successfully treated with systemic steroid administration and immunosuppressive therapy.

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