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1.
J Hepatol ; 81(4): 667-678, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38782118

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected hepatocellular carcinoma (HCC), reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of HCC. These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for personalized treatment strategies tailored to specific tumor evolutionary and transcriptomic profiles. The coexistence of multiple subtypes within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort).


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transcriptoma , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Variações do Número de Cópias de DNA , Evolução Molecular , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Mutação , Prognóstico , Estudos Prospectivos
2.
Hepatology ; 76(5): 1329-1344, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35184329

RESUMO

BACKGROUND AND AIMS: Hypoxia is one of the central players in shaping the immune context of the tumor microenvironment (TME). However, the complex interplay between immune cell infiltrates within the hypoxic TME of HCC remains to be elucidated. APPROACH AND RESULTS: We analyzed the immune landscapes of hypoxia-low and hypoxia-high tumor regions using cytometry by time of light, immunohistochemistry, and transcriptomic analyses. The mechanisms of immunosuppression in immune subsets of interest were further explored using in vitro hypoxia assays. Regulatory T cells (Tregs) and a number of immunosuppressive myeloid subsets, including M2 macrophages and human leukocyte antigen-DR isotype (HLA-DRlo ) type 2 conventional dendritic cell (cDC2), were found to be significantly enriched in hypoxia-high tumor regions. On the other hand, the abundance of active granzyme Bhi PD-1lo CD8+ T cells in hypoxia-low tumor regions implied a relatively active immune landscape compared with hypoxia-high regions. The up-regulation of cancer-associated genes in the tumor tissues and immunosuppressive genes in the tumor-infiltrating leukocytes supported a highly pro-tumorigenic network in hypoxic HCC. Chemokine genes such as CCL20 (C-C motif chemokine ligand 20) and CXCL5 (C-X-C motif chemokine ligand 5) were associated with recruitment of both Tregs and HLA-DRlo cDC2 to hypoxia-high microenvironments. The interaction between Tregs and cDC2 under a hypoxic TME resulted in a loss of antigen-presenting HLA-DR on cDC2. CONCLUSIONS: We uncovered the unique immunosuppressive landscapes and identified key immune subsets enriched in hypoxic HCC. In particular, we identified a potential Treg-mediated immunosuppression through interaction with a cDC2 subset in HCC that could be exploited for immunotherapies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Linfócitos T Reguladores , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Granzimas/metabolismo , Linfócitos T CD8-Positivos , Receptor de Morte Celular Programada 1/metabolismo , Ligantes , Microambiente Tumoral , Terapia de Imunossupressão , Hipóxia/metabolismo , Células Dendríticas/metabolismo , Antígenos HLA
3.
BMC Cancer ; 23(1): 118, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737737

RESUMO

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples. RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica
4.
Langenbecks Arch Surg ; 408(1): 317, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37587225

RESUMO

BACKGROUND: Reducing clinically relevant post-operative pancreatic fistula (CR-POPF) incidence after pancreatic resections has been a topic of great academic interest. Optimizing post-operative drain management is a potential strategy in reducing this major complication. METHODS: Studies involving pancreatic resections, including both pancreaticoduodenectomy (PD) and distal pancreatic resections (DP), with intra-operative drain placement were screened. Early drain removal was defined as removal before or on the 3rd post-operative day (POD) while late drain removal was defined as after the 3rd POD. The primary outcome was CR-POPF, International Study Group of Pancreatic Surgery (ISGPS) Grade B and above. Secondary outcomes were all complications, severe complications, post-operative haemorrhage, intra-abdominal infections, delayed gastric emptying, reoperation, length of stay, readmission, and mortality. RESULTS: Nine studies met the inclusion criteria and were included for analysis. The studies had a total of 8574 patients, comprising 1946 in the early removal group and 6628 in the late removal group. Early drain removal was associated with a significantly lower risk of CR-POPF (OR: 0.24, p < 0.01). Significant reduction in risk of post-operative haemorrhage (OR: 0.55, p < 0.01), intra-abdominal infection (OR: 0.35, p < 0.01), re-admission (OR: 0.63, p < 0.01), re-operation (OR: 0.70, p = 0.03), presence of any complications (OR: 0.46, p < 0.01), and reduced length of stay (SMD: -0.75, p < 0.01) in the early removal group was also observed. CONCLUSION: Early drain removal is associated with significant reductions in incidence of CR-POPF and other post-operative complications. Further prospective randomised trials in this area are recommended to validate these findings.


Assuntos
Infecções Intra-Abdominais , Pancreatectomia , Humanos , Pancreatectomia/efeitos adversos , Remoção de Dispositivo , Pâncreas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia
5.
Clin Transplant ; 36(2): e14520, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34687558

RESUMO

AIMS: This study seeks to evaluate the association between pre-transplant portal vein thrombosis (PVT) and overall survival, graft failure, waitlist mortality, and post-operative PVT after liver transplantation. METHODS: A conventional pairwise meta-analysis between patients with and without pre-transplant PVT was conducted using hazard ratios or odds ratios where appropriate. RESULTS: Prevalence of preoperative PVT was 11.6% (CI 9.70-13.7%). Pre-operative PVT was associated with increased overall mortality (HR 1.45, 95% CI 1.27-1.65) and graft loss (HR 1.58, 95% CI 1.34-1.85). In particular, grade 3 (HR 1.59, 95% CI 1.00-2.51) and 4 (HR 2.24, 95% CI 1.45-3.45) PVT significantly increased mortality, but not grade 1 or 2 PVT. Patients with PVT receiving living donor (HR 1.54, 95% CI 1.24-1.91) and deceased donor (HR 1.52, 95% CI 1.21-1.92) liver transplantation had increased mortality, with no significant difference between transplant types (P = .13). Furthermore, pre-transplant PVT was associated with higher occurrence of post-transplant PVT (OR 5.06, 95% CI 3.89-6.57). Waitlist mortality was not significantly increased in patients with pre-transplant PVT. CONCLUSION: Graft failure, mortality, and post-operative PVT are more common in pre-transplant PVT patients, especially in grade 3 or 4 PVT. Prophylactic anticoagulation can be considered to reduce re-thrombosis and improve survival.


Assuntos
Hepatopatias , Transplante de Fígado , Trombose Venosa , Humanos , Hepatopatias/complicações , Hepatopatias/mortalidade , Hepatopatias/terapia , Veia Porta , Prevalência , Trombose Venosa/complicações
6.
Pediatr Transplant ; 26(2): e14187, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34724594

RESUMO

PURPOSE OF THE SYSTEMATIC REVIEW: To determine the efficacy and safety of percutaneous trans-hepatic balloon and/or stent angioplasty (PTA) in the management of portal vein (PV) stenosis following paediatric liver transplantation. METHODS: Articles were included from a systematic search of Medline, Embase, Cochrane CENTRAL, ClinicalTrials.gov and International Clinical Trials Registry from inception to the 29th of August 2020. RESULTS: There were 213 paediatric liver recipients who underwent PTA for PV stenosis in 19 included studies published between 1991 and 2019. Balloon angioplasty was the initial treatment in the majority (n = 153). Primary stent placement (n = 34) was performed for elastic recoil, intimal tears and PV kinks and rescue stent placement (n = 14) for recurrent PV stenosis following primary balloon angioplasty. The technical success was 97.6%-100% overall, 97.6%-100% for balloon-angioplasty-only and 100% for primary stenting. The clinical success was 50%-100% overall, 50%-100% for balloon-angioplasty-only and 100% for primary stenting. Long-term PV patency was 50%-100% overall, 37.5%-100% for balloon-angioplasty-only and 100% for primary stenting. Primary balloon angioplasty was successful in 78% of the cases. Of the recurrent PV stenoses, 9% resolved with stent placement and one required a meso-Rex shunt. There was one re-transplantation without stenting. The complication rate was 2.6% for balloon-angioplasty-only (bleeding, liver abscess, 2 PV thromboses) and 5.9% for primary stenting (bleeding, stent-fracture). There was no procedure-related mortality. CONCLUSION: Percutaneous transhepatic balloon angioplasty may be the initial management of portal vein stenosis in paediatric liver recipients. Stent placement may be a primary option in selected cases and a reliable rescue option for recurrent portal vein stenosis following balloon-angioplasty-only.


Assuntos
Angioplastia com Balão/métodos , Veia Porta/patologia , Veia Porta/cirurgia , Stents , Criança , Constrição Patológica , Humanos
7.
World J Surg Oncol ; 20(1): 360, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368995

RESUMO

Pheochromocytomas (PCC) are rare and functional neuroendocrine tumors developing from adrenal chromaffin cells. Predicting malignant behavior especially in the absence of metastasis can be quite challenging even in the era of improved understanding of the molecular mechanisms involved in PCCs. Currently, two histopathological grading systems Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) score are used in clinical practice, but these are subject to significant interobserver variability. Some of the most useful clinical factors associated with malignancy are large size ([4-5 cm), and genetic features such as presence of SDHB germline mutations. Local invasion is uncommon in PCC and metastasis seen in 10 to 17% but higher in germline mutations and when this occurs management can be challenging. Here, we report on a case with challenges faced by the pathologist and clinicians alike in diagnosis and management of PCC recurrence.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Paraganglioma/diagnóstico , Paraganglioma/genética , Paraganglioma/patologia , Mutação em Linhagem Germinativa , Fígado/patologia
8.
HPB (Oxford) ; 24(4): 516-524, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34544630

RESUMO

BACKGROUND: Given the complexity of living donor hepatectomy, it is expected that high hospital volume will better outcomes. This study aims to evaluate post-operative outcomes for living donor hepatectomy in a medium volume liver transplant centre and compare to outcomes in high volume centres. Also, it serves as a validation tool for framework of structure-process-outcome model for safe living donor hepatectomy program. METHODS: 204 donors who underwent donor hepatectomy between June 1996 to September 2019 were reviewed retrospectively and compared to outcomes in high volume centres. RESULTS: At 6 months, overall donor morbidity rate was 20/204 (9.8%). Wound complications were most common at 5/204 (2.5%). Majority of complications were either Clavien grade 1 or 2 and only 3 donors had Clavien grade 3 complications. There was zero donor mortality. DISCUSSION: Our centre's donor morbidity rate of 9.8% is the one of the lowest reported in the published literature. With increased experience, stringent donor selection and enhanced perioperative care by a multi-disciplinary team, outcomes in a medium volume centre can match the outcomes reported in high volume centres. The framework for quality in terms of structure, process and outcomes is presented which can be adopted for developing programs.


Assuntos
Transplante de Fígado , Doadores Vivos , Hepatectomia/efeitos adversos , Humanos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Estudos Retrospectivos
9.
J Hepatol ; 73(4): 873-881, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32454041

RESUMO

BACKGROUND & AIMS: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multicenter study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the quadripartite equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium-sized liver transplant centers from 12 countries across 4 continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a "sickest-first" approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - recipient outcome, donor/graft safety, waiting list mortality and healthcare resources - for 7 countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of quadripartite equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems. LAY SUMMARY: There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources during the COVID-19 pandemic. We describe a four-dimensional model of quadripartite equipoise that models these ethical tensions and can guide the regulation of transplant activity in response to the increasing burden on healthcare systems.


Assuntos
Infecções por Coronavirus/epidemiologia , Doença Hepática Terminal , Recursos em Saúde/tendências , Transplante de Fígado , Pandemias , Pneumonia Viral/epidemiologia , Obtenção de Tecidos e Órgãos , Betacoronavirus , COVID-19 , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Humanos , Cooperação Internacional , Transplante de Fígado/ética , Transplante de Fígado/métodos , Inovação Organizacional , Pandemias/ética , Pandemias/prevenção & controle , Seleção de Pacientes/ética , SARS-CoV-2 , Inquéritos e Questionários , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/organização & administração , Obtenção de Tecidos e Órgãos/tendências , Listas de Espera/mortalidade
10.
Pancreatology ; 19(4): 507-518, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31088718

RESUMO

BACKGROUND: This study aims to review the clinical management of patients with acute pancreatitis in a tertiary institute in Singapore, and to identify areas qualiy improvement based on validation against the recommendations in the IAP/APA and the Japanese guidelines. METHODS: 391 patients from a prospective electronic database were included and reviewed for compliance to the International Association of Pancreatology (IAP)/American Pancreatic Association (APA) guidelines (2013) and the Japanase Guidelines (2015). RESULTS: The 90 day mortality was 8.4% for moderately severe and 11.9% for severe pancreatitis. The accuracy of SIRS in predicting severe acute pancreatitis on admission was 72.1% and at 48 h 80.8%. Only 61.1% patients had ultrasound scan during their admission of whom 32.9% had it within 24 h of admission. 18.3% patients with initial diagnosis of idiopathic pancreatitis had EUS. 50% received Ringer lactate for initial fluid resuscitation. 38.7% received antibiotics as prophylaxis. 21.4% with severe acute pancreatitis had early enteral nutrition. Only 21.4% patients with biliary pancreatitis had index admission cholecystectomy. CONCLUSION: The compliance to existing guidelines for management of acute pancreatitis is variable. Identifying gaps and implementing measures to address them allows for continued improvement in the management of patients with acute pancreatitis.


Assuntos
Gerenciamento Clínico , Pancreatite/terapia , Centros de Atenção Terciária , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Hidratação , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico por imagem , Pancreatite/mortalidade , Pancreatite Necrosante Aguda/diagnóstico por imagem , Pancreatite Necrosante Aguda/mortalidade , Pancreatite Necrosante Aguda/terapia , Estudos Prospectivos , Melhoria de Qualidade , Singapura , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
11.
HPB (Oxford) ; 21(2): 242-248, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30087053

RESUMO

BACKGROUND: To compare the presentations and outcomes of anti-HBc seropositive Hepatocellular Carcinoma (HBc-HCC) with anti-HBc seronegative (NHBc-HCC) patients in HBsAg negative Non-HBV Non-HCV (NBNC-HCC) HCC population. METHODS: 515 newly diagnosed HCC patients from January 2011 to September 2016 were retrospectively reviewed. 145 (66.5%) NHBc-HCC and 73 (33.5%) HBc-HCC patients were identified. Patient demographics, disease characteristics, details of treatments, recurrence and survival outcomes were analysed. RESULTS: A significantly lower proportion of HBc-HCC patients were diagnosed through surveillence (6.8% vs 26.2%, p = 0.001). HBc-HCC patients were less likely cirrhotic (p < 0.001), portal hypertensive (p < 0.001), ascitic (p = 0.008) and thrombocytopenic (p = 0.003). A higher proportion of HBc-HCC patients had treatment with curative intent (46.6% vs 30.3%, p = 0.018) and surgery (39.7% vs 16.6%, p < 0.001). Although HBc-HCC patients had larger median tumor size (74.0 mm vs 55.0 mm, p = 0.016) with a greater proportion of patients having tumors ≥5 cm, there was no difference in the overall median survival (19.0 months vs 22.0 months, p = 0.919) and recurrence rates (38.2% vs 40.9%). CONCLUSION: Isolated anti-HBc seropositivity in HbsAg negative patients tend to present incidentally with delayed diagnoses resulting in larger tumors, but their long-term survival remain comparable.


Assuntos
Carcinoma Hepatocelular/terapia , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Hepatite C/virologia , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Diagnóstico Tardio , Feminino , Hepatite C/sangue , Hepatite C/diagnóstico , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
12.
HPB (Oxford) ; 21(5): 547-556, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30292529

RESUMO

BACKGROUND: In adult right lobe living donor liver transplantation, the decision to include the middle hepatic vein (MHV) remains controversial. METHODS: A retrospective analysis of 50 R-LDLTs between January 2008 and June 2016 was performed. RESULTS: Twenty-one procedures were performed using a MHV+ graft (42.0%) and 29 procedures using a MHV- graft (58%). MHV- donors were taller (173 vs 166 cm, p = 0.004) with a larger standard liver volume (1351 vs 1245 mls, p = 0.014) compared to MHV+ donors. The duration of operation for donors was significantly longer in the MHV+ group (530 (313-975) mins) compared to the MHV- group (489 (336-708) mins) (p = 0.029). Similarly, the operative time for recipients was longer in the MHV+ group (660 (428-831) mins) compared to MHV- (579 (359-1214) mins) (p = 0.023). MHV- grafts were heavier compared to MHV+ grafts (918 vs 711 g, p = 0.017). Recipient mortality rates and Kaplan-Meier survival analysis were comparable (p = 0.411). All donors were well at last review. CONCLUSION: Both MHV+ and MHV- grafts are safe for the donor and recipient. The decision to take the MHV should be based on specific donor-recipient characteristics.


Assuntos
Veias Hepáticas/transplante , Transplante de Fígado , Doadores Vivos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
13.
HPB (Oxford) ; 20(4): 313-320, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29100711

RESUMO

BACKGROUND: Single-staged laparoscopic common bile duct exploration (LCBDE) offers clear benefits in terms of cost and shorter hospitalization stays. However, a failed LCBDE requiring conversion to open surgery is associated with increased morbidity. This study reviewed the factors determining success of LCBDE, and created a predictive nomogram to stratify patients for the procedure. METHODS: A retrospective analysis of 109 patients who underwent LCBDE was performed. A nomogram was developed from factors significantly associated with conversion to open surgery and validated. RESULTS: Sixty-two patients underwent a successful LCBDE, while 47 patients required a conversion to open CBDE. The presence of underlying cholangitis (crude OR 2.70, 95% CI: 1.12-6.56, p = 0.017), together with its subsequent interventions, seemed to adversely increase the rate of conversion to open surgery. The predictive factors included in the nomogram for a failed laparoscopic CBDE included prior antibiotic use (adjusted OR (AOR) 2.98, 95% CI: 1.17-7.57, p = 0.022), previous ERCP (AOR 4.99, 95% CI: 2.02-12.36, p = 0.001) and abnormal biliary anatomy (AOR 9.37, 95% CI: 2.18-40.20, p = 0.003). CONCLUSION: LCBDE is useful for the treatment of choledocholithiasis. However, patients who were predicted to have an elevated risk for open conversion might not be ideal candidates for the procedure.


Assuntos
Colecistectomia Laparoscópica , Coledocolitíase/cirurgia , Técnicas de Apoio para a Decisão , Nomogramas , Adulto , Idoso , Colecistectomia Laparoscópica/efeitos adversos , Coledocolitíase/diagnóstico por imagem , Tomada de Decisão Clínica , Ducto Colédoco/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
World J Surg ; 40(11): 2735-2744, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27255942

RESUMO

BACKGROUND: Acute cholecystitis (AC) is an important cause of emergency admissions among the elderly. The use of percutaneous cholecystostomy (PC) as bridging therapy among high-risk patients is widely accepted. However, the use of PC as definitive treatment is controversial. AIM: To determine the characteristics, clinical outcomes and predictors of recurrence of AC among patients who underwent PC. METHODS: A retrospective case series of 71 consecutive patients [73 (38-96) years, 43/71 males] treated with PC for AC at a tertiary hospital from 2007 to 2013, with data collected from case records. RESULTS: Patients were followed up for 37.0 (0.1-110.8) months after PC. Mortality rate was 8.5 % (6/71) during the index admission and 32.4 % (23/71) at the end of follow-up. Recurrence rate for AC was 11.9 % (7/59). Median time to recurrence was 62 (13-464) days. PC was definitive treatment in 33/59. Predictors of recurrence were higher serum alkaline phosphatase (ALP) at diagnosis (OR = 1.01, 95 % CI 1.00-1.02, p = 0.021) and acute myocardial infarction (AMI) during index admission (OR = 8.00, 95 % CI 1.19-54.0, p = 0.033). Fifteen patients (26.3 %, 15/71) had post-procedural complications including dislodgement (14 %, 10/71), tube obstruction (7.0 %, 5/71), bile leaks (2.8 %, 2/71), gallbladder perforation (1.4 %, 1/71), bowels perforation (1.4 %, 1/71) and severe post-procedural haemorrhage (1.4 %, 1/71). CONCLUSION: PC is effective and relatively safe in high-risk patients with AC. However, patients with higher ALP or AMI during index admission have higher risk of recurrence and might benefit from definitive cholecystectomy.


Assuntos
Colecistite Aguda/cirurgia , Colecistostomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Complicações Pós-Operatórias , Recidiva , Estudos Retrospectivos
16.
World J Surg ; 39(4): 897-904, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25446490

RESUMO

INTRODUCTION: An increasing body of evidence is being published about single-incision laparoscopic cholecystectomy (SILC), but there are no well-powered trials with an adequate evaluation of post-operative pain. This randomized trial compares SILC against four-port laparoscopic cholecystectomy (LC) with post-operative pain as the primary endpoint. METHODS: Hundred patients were randomized to either SILC (n = 50) or LC (n = 50). Exclusion criteria were (1) Acute cholecystitis; (2) ASA 3 or above; (3) Bleeding disorders; and (4) Previous open upper abdominal surgery. Patients and post-operative assessors were blinded to the procedure performed. The site and severity of pain were compared at 4 h, 24 h, 14 days and 6 months post-procedure using the visual analog scale; non-inferiority was assumed when the lower boundary of the 95% confidence interval of the difference was above -1 and superiority when p ≤ 0.05. RESULTS: The study arms were demographically similar. At 24 h post-procedure, SILC was associated with less pain at extra-umbilical sites (rest: p = 0.004; movement: p = 0.008). Pain data were inconclusive at 24 h at the umbilical site on movement; SILC was otherwise non-inferior for pain at all other points. Operating duration was longer in SILC (79.46 vs 58.88 min, p = 0.003). 8% of patients in each arm suffered complications (p = 1.000). Re-intervention rates, analgesic use, return to function, and patient satisfaction did not differ significantly. CONCLUSIONS: SILC has improved short-term pain outcomes compared to LC and is not inferior in both short-term and long-term pain outcomes. The operating time is longer, but remains feasible in routine surgical practice.


Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Dor Pós-Operatória/etiologia , Adulto , Idoso , Analgésicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Medição da Dor , Satisfação do Paciente , Reoperação , Estatísticas não Paramétricas , Fatores de Tempo , Umbigo
17.
HPB (Oxford) ; 17(8): 713-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26172138

RESUMO

BACKGROUND: With improvements in patient survival after a liver transplantation (LT), long-term sequelae such as metabolic syndrome (MS) have become increasingly common. This study aims to characterize the prevalence, associations and long-term outcomes of post-LTMS and its components in an Asian population. METHODS: A retrospective review of all adult patients who underwent LT at the National University Health System Singapore between December 1996 and May 2012 was performed. MS was defined using the Adult Treatment Panel (ATP) III criteria modified for an Asian population. RESULTS: The median age of this cohort of 90 patients was 50.0 (16.0-67.0) years, with a median follow-up duration of 60.0 (7.0-192.0) months. The prevalence of post-LTMS was 35.6%, diabetes mellitus (DM) 51.1%, hypertension 60.0%, obesity 26.7% and dyslipidaemia 46.7%. On univariate analysis, factors significantly associated with post-LT MS include female gender (P = 0.066), pre-LT respiratory comorbidities (P = 0.038), pre-LT obesity (P = 0.014), pre-LTDM (P < 0.001), pre-LT hypertension (P = 0.039), pre-LTMS (P < 0.001), prednisolone use ≥24 months (P = 0.005) and mycophenolate mofetil use ≥24 months (P = 0.035). On multivariate analysis, independent associations of post-LT MS were pre-LTDM (P = 0.011) and pre-LTMS (P = 0.024). There was no difference in long-term survival of patients with and without post-LTMS (P = 0.425). CONCLUSION: In conclusion, pre-LT components of the MS and the use of certain immunosuppressants are related to developing post-LTMS.


Assuntos
Povo Asiático/estatística & dados numéricos , Transplante de Fígado/estatística & dados numéricos , Síndrome Metabólica/etnologia , Adolescente , Adulto , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Estimativa de Kaplan-Meier , Transplante de Fígado/efeitos adversos , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/mortalidade , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Singapura/epidemiologia , Circunferência da Cintura
18.
Transplant Direct ; 10(7): e1642, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38911272

RESUMO

Background: The cause of liver disease is changing, but its impact on liver transplantation (LT) for hepatocellular carcinoma (HCC) in women and men is unclear. We performed a nationwide study to assess the prevalence and posttransplant survival outcomes of the various causes of liver disease in women and men with HCC. Methods: Data were obtained from the United Network for Organ Sharing database from 2000 to 2022. Data related to the listing, transplant, waitlist mortality, and posttransplant mortality for HCC were extracted. The proportion of HCC related to the various causes of liver disease among LT candidates and recipients and posttransplant survival were compared between women and men. Results: A total of 51 721 individuals (39 465 men, 12 256 women) with HCC were included. From 2000 to 2022, nonalcoholic steatohepatitis (NASH) was the fastest-growing cause of liver disease among female LT candidates with HCC (P < 0.01), followed by alcohol-associated liver disease. NASH overtook chronic hepatitis C as the leading cause of liver disease in 2020 and 2022 among waitlisted women and men with HCC, respectively. Female patients with HCC spent a significantly longer time on the LT waitlist compared with male patients (ß: 8.73; 95% confidence interval [CI], 2.91-14.54). Female patients with HCC from alcohol-associated liver disease also have a lower probability of receiving LT (subdistribution hazard ratio: 0.90; 95% CI, 0.82-0.99). Among transplant recipients with NASH HCC, female sex was associated with lower posttransplant mortality compared with male sex (hazard ratio: 0.79; 95% CI, 0.70-0.89; P < 0.01). Conclusions: Women have a significantly longer waitlist duration compared with men. NASH is now the leading cause of liver disease among both female and male LT candidates and recipients with HCC.

19.
Hepatol Commun ; 8(9)2024 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-39167427

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a deadly cancer with a high global mortality rate, and the downregulation of GATA binding protein 4 (GATA4) has been implicated in HCC progression. In this study, we investigated the role of GATA4 in shaping the immune landscape of HCC. METHODS: HCC tumor samples were classified into "low" or "normal/high" based on GATA4 RNA expression relative to adjacent non-tumor liver tissues. The immune landscapes of GATA4-low and GATA4-normal/high tumors were analyzed using cytometry by time-of-flight, bulk/spatial transcriptomic analyses and validated by multiplex immunofluorescence. RESULTS: GATA4-low tumors displayed enrichment in exhausted programmed cell death protein 1+ T cells, immunosuppressive regulatory T cells, myeloid-derived suppressor cells, and macrophages, highlighting the impact of GATA4 downregulation on immunosuppression. Spatial and bulk transcriptomic analyses revealed a negative correlation between GATA4 and C-C Motif Chemokine Ligand 20 (CCL20) expression in HCC. Overexpressing GATA4 confirmed CCL20 as a downstream target, contributing to an immunosuppressive tumor microenvironment, as evidenced by increased regulatory T cells and myeloid-derived suppressor cells in CCL20-high tumors. Lastly, the reduced expression of GATA4 and higher expression of CCL20 were associated with poorer overall survival in patients with HCC, implicating their roles in tumor progression. CONCLUSIONS: Our study reveals that GATA4 downregulation contributes to an immunosuppressive microenvironment, driven by CCL20-mediated enrichment of regulatory T cells and myeloid-derived suppressor cells in HCC. These findings underscore the critical role of GATA4 reduction in promoting immunosuppression and HCC progression.


Assuntos
Carcinoma Hepatocelular , Quimiocina CCL20 , Regulação para Baixo , Fator de Transcrição GATA4 , Neoplasias Hepáticas , Microambiente Tumoral , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Fator de Transcrição GATA4/genética , Quimiocina CCL20/genética , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica , Tolerância Imunológica , Células Supressoras Mieloides/imunologia , Masculino , Linfócitos T Reguladores/imunologia
20.
Hepatobiliary Surg Nutr ; 13(1): 89-104, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38322212

RESUMO

Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

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