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1.
PLoS One ; 19(7): e0304838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38950006

RESUMO

INTRODUCTION: The treatment of perihilar Cholangiocarcinoma (pCCA) poses specific challenges not only due to its high perioperative complication rates but also due its dismal long-term prognosis with only a few long-term survivors (LTS) among the patients. Therefore, in this analysis characteristics and predictors of LTS in pCCA patients are investigated. MATERIAL AND METHODS: In this single center analysis, patients undergoing curative-intent liver resection for pCCA between 2010 and 2022 were categorized into long-term and short-term survivors (STS) excluding perioperative mortality. Binary logistic regression was used to determine key differences between the groups and to develop a prognostic composite variable. This composite variable was subsequently tested in the whole cohort of surgically treated pCCA patients using Cox Regression analysis for cancer-specific survival (CSS). RESULTS: Within a cohort of 209 individuals, 27 patients were identified as LTS (median CSS = 125 months) and 55 patients as STS (median CSS = 16 months). Multivariable analysis identified preoperative portal vein infiltration (OR = 5.85, p = 0.018) and intraoperative packed red blood cell (PRBC) transfusions (OR = 10.29, p = 0.002) as key differences between the groups. A prognostic composite variable based on these two features was created and transferred into a Cox regression model of the whole cohort. Here, the composite variable (HR = 0.35, p<0.001), lymph node metastases (HR = 2.15, p = 0.001) and postoperative complications (HR = 3.06, p<0.001) were identified as independent predictors of CSS. CONCLUSION: Long-term survival after surgery for pCCA is possible and is strongly negatively associated with preoperative portal vein infiltration and intraoperative PRBC transfusion. As these variables are part of preoperative staging or can be modulated by intraoperative technique, the proposed prognostic composite variable can easily be transferred into clinical management to predict the oncological outcome of patients undergoing surgery for pCCA.


Assuntos
Neoplasias dos Ductos Biliares , Tumor de Klatskin , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tumor de Klatskin/cirurgia , Tumor de Klatskin/mortalidade , Tumor de Klatskin/patologia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Idoso , Prognóstico , Estudos Retrospectivos , Hepatectomia/mortalidade , Veia Porta/cirurgia , Veia Porta/patologia , Adulto
2.
World J Gastroenterol ; 30(23): 2981-2990, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38946870

RESUMO

BACKGROUND: Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis (AE). Currently, there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial. Radical hepatectomy combined with regional lymph node dissection is a better treatment. AIM: To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy. METHODS: A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed. Fifty-five patients with combined lymph node metastasis were analysed for their clinical data, diagnosis and treatment methods, follow-up efficacy, and characteristics of lymph node metastasis. Finally, we comparatively analysed the lymph node metastasis rates at different sites. Categorical variables are expressed as frequencies and percentages, and the analysis of difference was performed using the χ 2 test. The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables. RESULTS: A lymph node metastasis rate of 8.8% (55/623) was reported in patients with hepatic AE, with a female predilection (69.1%) and a statistically significant sex difference (χ 2 = 8.018, P = 0.005). Of the 55 patients with lymph node metastasis, 72.7% had a parasite lesion, neighbouring organ invasion, and metastasis stage of P3N1M0 and above, of which 67.3%, 78.2%, and 34.5% of hepatic AE lesions invaded the bile ducts, blood vessels, and distant metastases, respectively. Detection rates of lymph node metastasis of 16.4%, 21.7%, and 34.2% were reported for a preoperative abdominal ultrasound, magnetic resonance imaging, and computed tomography examinations. All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection. After surgery, a routine pathological examination was conducted on the resected lymph nodes. A total of 106 positive lymph nodes were detected in six groups at various sites, including 51 single-group metastasis cases and four multi-group metastasis cases. When the metastasis rates at different sites were statistically analysed, we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites (χ 2 = 128.089, P = 0.000 < 0.05). No statistical difference was observed in the metastasis rate between the five other groups. Clavien-Dindo grade IIIa complication occurred in 14 cases, which improved after administering symptomatic treatment. Additionally, lymph node dissection-related complications were not observed. Recurrence after 2 years was observed in one patient. CONCLUSION: Lymph node metastasis is a rare form of metastasis in hepatic AE, which is more frequent in women. Para-hepatoduodenal ligament lymph nodes are commonly observed. Radical hepatectomy combined with regional lymph node dissection is a safe, effective, and feasible treatment for liver AE combined with lymph node metastasis.


Assuntos
Equinococose Hepática , Hepatectomia , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Humanos , Masculino , Feminino , Estudos Retrospectivos , Equinococose Hepática/cirurgia , Equinococose Hepática/diagnóstico por imagem , Equinococose Hepática/patologia , Pessoa de Meia-Idade , Adulto , Hepatectomia/métodos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Adulto Jovem , Idoso , Resultado do Tratamento , China/epidemiologia , Adolescente
3.
World J Gastroenterol ; 30(22): 2881-2892, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38947296

RESUMO

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.


Assuntos
Anticoagulantes , Heparina , Hepatectomia , Falência Hepática , Neoplasias Hepáticas , Complicações Pós-Operatórias , Humanos , Hepatectomia/efeitos adversos , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Falência Hepática/prevenção & controle , Falência Hepática/mortalidade , Neoplasias Hepáticas/cirurgia , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Resultado do Tratamento , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Tempo de Internação/estatística & dados numéricos , Fatores de Risco , Unidades de Terapia Intensiva/estatística & dados numéricos , Pontuação de Propensão
5.
Cancer Med ; 13(13): e7342, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967142

RESUMO

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.


Assuntos
Neoplasias dos Ductos Biliares , Hepatectomia , Icterícia , Tumor de Klatskin , Falência Hepática , Humanos , Masculino , Hepatectomia/efeitos adversos , Feminino , Pessoa de Meia-Idade , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Estudos Retrospectivos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Falência Hepática/etiologia , Falência Hepática/prevenção & controle , China/epidemiologia , Icterícia/etiologia , Fígado/cirurgia , Fígado/patologia , Idoso , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Adulto , Tamanho do Órgão
6.
Medicine (Baltimore) ; 103(27): e38721, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968499

RESUMO

BACKGROUND: Raiomics is an emerging auxiliary diagnostic tool, but there are still differences in whether it can be applied to predict early recurrence of hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to systematically evaluate the predictive power of radiomics in the early recurrence (ER) of HCC. METHODS: Comprehensive studies on the application of radiomics to predict ER in HCC patients after hepatectomy or curative ablation were systematically screened in Embase, PubMed, and Web of Science. RESULTS: Ten studies which is involving a total of 1929 patients were reviewed. The overall estimates of radiomic models for sensitivity and specificity in predicting the ER of HCC were 0.79 (95% confidence interval [CI]: 0.68-0.87) and 0.83 (95% CI: 0.73-0.90), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.88 (95% CI: 0.85-0.91). CONCLUSIONS: The imaging method is a reliable method for diagnosing HCC. Radiomics, which is based on medical imaging, has excellent power in predicting the ER of HCC. With the help of radiomics, we can predict the recurrence of HCC after surgery more effectively and provide a useful reference for clinical practice.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Hepatectomia/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Radiômica
7.
Minerva Surg ; 79(4): 419-429, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38953755

RESUMO

BACKGROUND: The surgical management of perihilar carcinoma (pCCA) is still subject of ongoing debate. To provide more clarity, this study was conducted to evaluate outcomes related to the side and extent of heatectomy in patients with pCAA. METHODS: A total of 32 patients with curative resection for pCCA were identified from our prospective database. Short-and long-term clinical outcome data and histopathological results were compared between right-sided (R-H) and left-sided (L-H) hepatectomy. RESULTS: Nine patients (28.13%) underwent left-sided hepatectomy while a right-sided hepatectomy was accomplished in 23 patients (71.87%). In the R-H group hepatic conditioning of the future liver remnant (FLR) prior to extended resection was necessary in 13 cases (56.52%), and simultaneous pancreaticoduodenectomy was performed in 5 patients (21.74%). The arterial and portal venous reconstruction rates were 17.39% and 11.11% (P=1.00), and 60.87% and 33.33% (P=0.243) in the R-H and L-H groups, respectively. No statistically significant differences in short-term morbidity and mortality between both groups were observed. The rate of R0 resections was comparable (R-H: 78.26% versus L-H: 66.67%; P=0.654) resulting in similar long-term overall and disease-free survival rates after right-and left hepatectomy. CONCLUSIONS: In patients with pCCA, both right- and left-sided resections appear to be safe and feasible options with similar postoperative morbidity and oncologic outcomes. Consecutively, the ideal surgical approach should be patient-tailored based on anatomical considerations and the functional future liver capacity.


Assuntos
Neoplasias dos Ductos Biliares , Hepatectomia , Tumor de Klatskin , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/mortalidade , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Tumor de Klatskin/mortalidade , Resultado do Tratamento , Idoso , Fatores de Tempo , Adulto , Pancreaticoduodenectomia
8.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000266

RESUMO

Liver resection (LR) is the primary treatment for hepatic tumors, yet posthepatectomy liver failure (PHLF) remains a significant concern. While the precise etiology of PHLF remains elusive, dysregulated inflammatory processes are pivotal. Therefore, we explored the theragnostic potential of extracellular high-mobility-group-box protein 1 (HMGB1), a key damage-associated molecular pattern (DAMP) released by hepatocytes, in liver recovery post LR in patients and animal models. Plasma from 96 LR patients and liver tissues from a subset of 24 LR patients were analyzed for HMGB1 levels, and associations with PHLF and liver injury markers were assessed. In a murine LR model, the HMGB1 inhibitor glycyrrhizin, was administered to assess its impact on liver regeneration. Furthermore, plasma levels of keratin-18 (K18) and cleaved cytokeratin-18 (ccK18) were quantified to assess suitability as predictive biomarkers for PHLF. Patients experiencing PHLF exhibited elevated levels of intrahepatic and circulating HMGB1, correlating with markers of liver injury. In a murine LR model, inhibition of HMGB1 improved liver function, reduced steatosis, enhanced regeneration and decreased hepatic cell death. Elevated levels of hepatic cell death markers K18 and ccK18 were detected in patients with PHLF and correlations with levels of circulating HMGB1 was observed. Our study underscores the therapeutic and predictive potential of HMGB1 in PHLF mitigation. Elevated HMGB1, K18, and ccK18 levels correlate with patient outcomes, highlighting their predictive significance. Targeting HMGB1 enhances liver regeneration in murine LR models, emphasizing its role in potential intervention and prediction strategies for liver surgery.


Assuntos
Proteína HMGB1 , Hepatectomia , Falência Hepática , Proteína HMGB1/metabolismo , Proteína HMGB1/sangue , Animais , Humanos , Hepatectomia/efeitos adversos , Camundongos , Falência Hepática/etiologia , Falência Hepática/metabolismo , Falência Hepática/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Regeneração Hepática , Biomarcadores , Morte Celular , Queratina-18/metabolismo , Queratina-18/sangue , Idoso , Hepatócitos/metabolismo , Fígado/metabolismo , Fígado/patologia , Ácido Glicirrízico/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
9.
Int J Mol Sci ; 25(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39000295

RESUMO

Olprinone (OLP) is a selective inhibitor of phosphodiesterase III and is used clinically in patients with heart failure and those undergoing cardiac surgery; however, little is known about the effects of OLP on hepatoprotection. The purpose of this study aimed to determine whether OLP has protective effects in in vivo and in vitro rat models of endotoxin-induced liver injury after hepatectomy and to clarify the mechanisms of action of OLP. In the in vivo model, rats underwent 70% partial hepatectomy and lipopolysaccharide treatment (PH/LPS). OLP administration increased survival by 85.7% and decreased tumor necrosis factor-α, C-X-C motif chemokine ligand 1, and inducible nitric oxide synthase (iNOS) mRNA expression in the livers of rats treated with PH/LPS. OLP also suppressed nuclear translocation and/or DNA binding ability of nuclear factor kappa B (NF-κB). Pathological liver damage induced by PH/LPS was alleviated and neutrophil infiltration was reduced by OLP. Primary cultured rat hepatocytes treated with the pro-inflammatory cytokine interleukin-1ß (IL-1ß) were used as a model of in vitro liver injury. Co-treatment with OLP inhibited dose-dependently IL-1ß-stimulated iNOS induction and NF-κB activation. Our results demonstrate that OLP may partially inhibit the induction of several inflammatory mediators through the suppression of NF-κB and thus prevent liver injury induced by endotoxin after liver resection.


Assuntos
Modelos Animais de Doenças , Hepatectomia , Hepatócitos , Imidazóis , NF-kappa B , Óxido Nítrico Sintase Tipo II , Piridonas , Animais , Hepatectomia/efeitos adversos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Ratos , Masculino , Piridonas/farmacologia , Piridonas/uso terapêutico , NF-kappa B/metabolismo , Imidazóis/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Inibidores da Fosfodiesterase 3/farmacologia , Inibidores da Fosfodiesterase 3/uso terapêutico , Interleucina-1beta/metabolismo , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/toxicidade , Sepse/tratamento farmacológico , Ratos Sprague-Dawley , Células Cultivadas , Fator de Necrose Tumoral alfa/metabolismo , Quimiocina CXCL1/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo
10.
Int J Mol Sci ; 25(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-39000319

RESUMO

Liver regeneration induced by partial hepatectomy (PHx) has attracted intensive research interests due to the great significance for liver resection and transplantation. The zebrafish (Danio rerio) is an excellent model to study liver regeneration. In the fish subjected to PHx (the tip of the ventral lobe was resected), the lost liver mass could be fully regenerated in seven days. However, the regulatory mechanisms underlying the liver regeneration remain largely unknown. In this study, gene expression profiles during the regeneration of PHx-treated liver were explored by RNA sequencing (RNA-seq). The genes responsive to the injury of PHx treatment were identified and classified into different clusters based on the expression profiles. Representative gene ontology (GO) enrichments for the early responsive genes included hormone activity, ribosome biogenesis and rRNA processing, etc., while the late responsive genes were enriched in biological processes such as glutathione metabolic process, antioxidant activity and cellular detoxification. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were also identified for the differentially expressed genes (DEGs) between the time-series samples and the sham controls. The proteasome was overrepresented by the up-regulated genes at all of the sampling time points. Inhibiting proteasome activity by the application of MG132 to the fish enhanced the expression of Pcna (proliferating cell nuclear antigen), an indicator of hepatocyte proliferation after PHx. Our data provide novel insights into the molecular mechanisms underlying the regeneration of PHx-treated liver.


Assuntos
Hepatectomia , Regeneração Hepática , Transdução de Sinais , Transcriptoma , Peixe-Zebra , Animais , Peixe-Zebra/genética , Regeneração Hepática/genética , Fígado/metabolismo , Perfilação da Expressão Gênica , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Ontologia Genética
11.
BMJ Case Rep ; 17(7)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39038874

RESUMO

Adenoid cystic carcinoma (ACC) is a rare tumour of the salivary glands characterised by distant metastases, mainly to lungs and bone. Isolated metastasis to the liver is unusual. We present the case of a woman with an ACC of the submandibular gland (pT1N0) who underwent radical submandibular gland excision and selective neck dissection. Preoperative imaging identified a liver lesion with features suggestive of a haemangioma. Two-year postoperatively, a surveillance CT neck/trunk showed an increase in size of the left liver lobe lesion. Subsequent MR liver and US-guided biopsy confirmed the lesion to be metastatic ACC. The patient underwent a successful left lateral liver sectionectomy. She remains disease-free 2.5 years after her liver resection. A literature search revealed only four other similar cases. This report highlights that even early-stage ACCs of the salivary gland may present with synchronous solitary liver metastasis which can be effectively treated with curative surgery.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Hepáticas , Neoplasias da Glândula Submandibular , Humanos , Carcinoma Adenoide Cístico/secundário , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoide Cístico/diagnóstico por imagem , Feminino , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias da Glândula Submandibular/patologia , Neoplasias da Glândula Submandibular/secundário , Neoplasias da Glândula Submandibular/cirurgia , Tomografia Computadorizada por Raios X , Pessoa de Meia-Idade , Glândula Submandibular/patologia , Glândula Submandibular/cirurgia , Hepatectomia , Imageamento por Ressonância Magnética , Esvaziamento Cervical
12.
Trials ; 25(1): 490, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030637

RESUMO

BACKGROUND: The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. METHODS: This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. DISCUSSION: Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. TRIAL REGISTRATION: www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Terapia Neoadjuvante , Piridinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Masculino , Hepatectomia , Adulto , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como Assunto , Feminino , Resultado do Tratamento , China , Idoso
13.
Langenbecks Arch Surg ; 409(1): 211, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985363

RESUMO

PURPOSE: Whether hospital volume affects outcome of patients undergoing hepatobiliary surgery, and whether the centralization of such procedures is justified remains to be investigated. The aim of this study was to analyze the outcome of liver surgery in Italy in relationship of hospital volume. METHODS: This is a nationwide retrospective observational study conducted on data collected by the National Italian Registry "Piano Nazionale Esiti" (PNE) 2023 that included all liver procedures performed in 2022. Outcome measure were case volume and 30-day mortality. Hospitals were classified as very high-volume (H-Vol), intermediate-volume (I-Vol), low-volume (L-Vol) and very low-volume (VL-VoL). A review on centralization process and outcome measures was added. RESULTS: 6,126 liver resections for liver tumors were performed in 327 hospitals in 2022. The 30-day mortality was 2.2%. There were 14 H-Vol, 19 I-Vol, 31 L-Vol and 263 VL-Vol hospitals with 30-day mortality of 1.7%, 2.2%, 2.6% and 3.6% respectively (P < 0.001); 220 centers (83%) performed less than 10 resections, and 78 (29%) centers only 1 resection in 2022. By considering the geographical macro-areas, the median count of liver resection performed in northern Italy exceeded those in central and southern Italy (57% vs. 23% vs. 20%, respectively). CONCLUSIONS: High-volume has been confirmed to be associated to better outcome after hepatobiliary surgical procedures. Further studies are required to detail the factors associated with mortality. The centralization process should be redesigned and oversight.


Assuntos
Hepatectomia , Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Neoplasias Hepáticas , Humanos , Hepatectomia/mortalidade , Itália , Estudos Retrospectivos , Masculino , Feminino , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Idoso , Pessoa de Meia-Idade , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Sistema de Registros , Mortalidade Hospitalar , Resultado do Tratamento
14.
Sci Rep ; 14(1): 15827, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982109

RESUMO

The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin-eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.


Assuntos
Hepatectomia , Cirrose Hepática , Falência Hepática , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Cirrose Hepática/cirurgia , Cirrose Hepática/patologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Falência Hepática/etiologia , Falência Hepática/patologia , Hepatectomia/efeitos adversos , Idoso , Prognóstico , Complicações Pós-Operatórias/etiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Veia Porta/patologia , Veia Porta/cirurgia , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/mortalidade , Adulto , Regeneração Hepática , Fatores de Risco , Estudos Retrospectivos , Resultado do Tratamento , Ligadura
15.
Endocrinology ; 165(8)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38963813

RESUMO

Vitamin D signals through the vitamin D receptor (VDR) to induce its end-organ effects. Hepatic stellate cells control development of liver fibrosis in response to stressors and vitamin D signaling decreases fibrogenesis. VDR expression in hepatocytes is low in healthy liver, and the role of VDR in hepatocyte proliferation is unclear. Hepatocyte-VDR null mice (hVDR) were used to assess the role of VDR and vitamin D signaling in hepatic regeneration. hVDR mice have impaired liver regeneration and impaired hepatocyte proliferation associated with significant differential changes in bile salts. Notably, mice lacking hepatocyte VDR had significant increases in expression of conjugated bile acids after partial hepatectomy, consistent with failure to normalize hepatic function by the 14-day time point tested. Real-time PCR of hVDR and control livers showed significant changes in expression of cell-cycle genes including cyclins D1 and E1 and cyclin-dependent kinase 2. Gene expression profiling of hepatocytes treated with vitamin D or control showed regulation of groups of genes involved in liver proliferation, hepatitis, liver hyperplasia/hyperproliferation, and liver necrosis/cell death. Together, these studies demonstrate an important functional role for VDR in hepatocytes during liver regeneration. Combined with the known profibrotic effects of impaired VDR signaling in stellate cells, the studies provide a mechanism whereby vitamin D deficiency would both reduce hepatocyte proliferation and permit fibrosis, leading to significant liver compromise.


Assuntos
Ácidos e Sais Biliares , Proliferação de Células , Hepatectomia , Hepatócitos , Regeneração Hepática , Camundongos Knockout , Receptores de Calcitriol , Animais , Regeneração Hepática/efeitos dos fármacos , Regeneração Hepática/fisiologia , Receptores de Calcitriol/metabolismo , Receptores de Calcitriol/genética , Masculino , Camundongos , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácidos e Sais Biliares/metabolismo , Fígado/metabolismo , Ciclina D1/metabolismo , Ciclina D1/genética , Ciclina E/metabolismo , Ciclina E/genética , Quinase 2 Dependente de Ciclina/metabolismo , Quinase 2 Dependente de Ciclina/genética , Camundongos Endogâmicos C57BL , Vitamina D/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Oncogênicas
17.
World J Gastroenterol ; 30(25): 3166-3178, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-39006386

RESUMO

BACKGROUND: Integrating conventional ultrasound features with 2D shear wave elastography (2D-SWE) can potentially enhance preoperative hepatocellular carcinoma (HCC) predictions. AIM: To develop a 2D-SWE-based predictive model for preoperative identification of HCC. METHODS: A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital. The patients were divided into the modeling group (n = 720) and the control group (n = 164). The study included conventional ultrasound, 2D-SWE, and preoperative laboratory tests. Multiple logistic regression was used to identify independent predictive factors for malignant liver lesions, which were then depicted as nomograms. RESULTS: In the modeling group analysis, maximal elasticity (Emax) of tumors and their peripheries, platelet count, cirrhosis, and blood flow were independent risk indicators for malignancies. These factors yielded an area under the curve of 0.77 (95% confidence interval: 0.73-0.81) with 84% sensitivity and 61% specificity. The model demonstrated good calibration in both the construction and validation cohorts, as shown by the calibration graph and Hosmer-Lemeshow test (P = 0.683 and P = 0.658, respectively). Additionally, the mean elasticity (Emean) of the tumor periphery was identified as a risk factor for microvascular invasion (MVI) in malignant liver tumors (P = 0.003). Patients receiving antiviral treatment differed significantly in platelet count (P = 0.002), Emax of tumors (P = 0.033), Emean of tumors (P = 0.042), Emax at tumor periphery (P < 0.001), and Emean at tumor periphery (P = 0.003). CONCLUSION: 2D-SWE's hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions, correlating significantly with MVI and antiviral treatment efficacy.


Assuntos
Carcinoma Hepatocelular , Técnicas de Imagem por Elasticidade , Neoplasias Hepáticas , Fígado , Humanos , Técnicas de Imagem por Elasticidade/métodos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Valor Preditivo dos Testes , Hepatectomia , Nomogramas , Adulto , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Fatores de Risco , Sensibilidade e Especificidade
18.
Langenbecks Arch Surg ; 409(1): 223, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023651

RESUMO

OBJECTIVE: Our study aimed to assess the ability of high-sensitivity modified Glasgow prognostic Score (HS-mGPS) predicting survival in patients undergoing radical surgery for hepatocellular carcinoma (HCC) and to compare the impact with other Inflammation-Based prognostic scoring systems including Glasgow prognostic Score (GPS) and modified GPS (mGPS). METHODS: Our study evaluated 293 patients with HCC who had undergone hepatectomy at the Third Affiliated Hospital of Soochow University between 2010 and 2018. The HS-mGPS, mGPS, and GPS were calculated based on particular cut-off values of preoperative C-reactive protein and albumin, and the correlations between HS-mGPS and clinicopathological parameters were evaluated. Univariate and multivariate survival analyses were conducted by Kaplan-Meier method and Cox proportional hazards model. To evaluate the discrimination ability of each prognostic score, the receiver operating characteristic (ROC) curve were generated and the areas under the curve (AUC) were measured and compared. RESULT: The study results indicated a correlation between elevated HS-mGPS scores and adverse clinical factors, including higher BCLC stage, C-P grade, multiple tumors, and larger tumor diameter. Kaplan-Meier and univariate survival analyses revealed that higher scores of HS-mGPS, GPS, and mGPS were all associated with significantly reduced overall survival (OS) (all p < 0.001). In multivariate survival analysis, HS-mGPS emerged as an independent risk factor for poor OS in patients undergoing hepatectomy for HCC (p = 0.010), along with factors including maximal tumor diameter (p < 0.001), microvascular invasion (MVI) (p = 0.008), and BCLC stage (p = 0.001). The analysis of ROC curves and the AUC values indicated that HS-mGPS outperforms GPS and mGPS in predicting the long-term prognosis of patients with resectable HCC. CONCLUSION: Preoperative HS-mGPS proves superior in predicting adverse long-term outcomes in HCC patients undergoing radical surgery.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/sangue , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Retrospectivos , Adulto , Estimativa de Kaplan-Meier , Taxa de Sobrevida , Proteína C-Reativa/análise
19.
BMC Anesthesiol ; 24(1): 244, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026144

RESUMO

BACKGROUND: Conventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients' recovery. METHODS: In total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2-0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2-0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome. RESULTS: Blood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P < 0.05). Both the nitroglycerin group and milrinone group exerted similar CVP (P > 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P < 0.05) and also exhibited higher cardiac index and cardiac output during the surgery (P < 0.05). Significant differences were also found in terms of fluids administered during hepatectomy, urine volume during hepatectomy, total urine volume, and norepinephrine dosage used in the surgery between the two groups. The two groups showed a similar incidence of postoperative complications (P > 0.05). CONCLUSION: Our findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin. TRIAL REGISTRATION: ChiCTR2200056891,first registered on 22/02/2022.


Assuntos
Perda Sanguínea Cirúrgica , Pressão Venosa Central , Hepatectomia , Laparoscopia , Milrinona , Nitroglicerina , Vasodilatadores , Humanos , Milrinona/administração & dosagem , Nitroglicerina/administração & dosagem , Hepatectomia/métodos , Masculino , Feminino , Método Duplo-Cego , Laparoscopia/métodos , Pessoa de Meia-Idade , Pressão Venosa Central/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Idoso , Adulto , Complicações Pós-Operatórias/prevenção & controle
20.
J Cancer Res Clin Oncol ; 150(7): 354, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39031214

RESUMO

BACKGROUND: Patients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies. METHODS: Operated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality. RESULTS: From 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (-) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence. CONCLUSION: Our study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings.


Assuntos
Doenças Autoimunes , Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Masculino , Feminino , Hepatectomia/mortalidade , Doenças Autoimunes/complicações , Doenças Autoimunes/mortalidade , Doenças Autoimunes/cirurgia , Pessoa de Meia-Idade , Idoso , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de Risco , Adulto , Taxa de Sobrevida , Prognóstico
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