RESUMEN
OBJECTIVES: Donor hepatectomy is a major surgery with a relatively safeprofile anda reportedcomplication rate of ~20%. Most complications are non-life threatening and are resolved with conservative measures. However, rare complications may need invasive precautions, ranging from percutaneous interventions to surgeries. MATERIALS AND METHODS: We retrospectively analyzed all living donor hepatectomies at our center. Donors were divided into 2 groups: laparoscopic and open procedures. We collected preoperative, intraoperative and postoperative data of donors.Donor complications were recorded separately intraoperatively and postoperatively according to the Clavien-Dindo postoperative complication classification system. RESULTS: Between July 2018 and April 2023, 215 living donors had hepatectomies, including 48 laparoscopic and 167 open donor hepatectomies. Among donors, 91 were female donors (42.3%) and 124 were male donors (57.7%).The meanage of alldonorswas 33.5±8.1 years, and the mean body mass index (in kilogram divided by meters squared) was 24.6 ± 3.8. Among donors, 124 underwent right and 91 underwent left or left lateral hepatectomies. The mean operative time for all donors was 301 ± 83 minutes, the mean hospital stay was 5.8 ± 1.4 days, and the mean follow-up was 31.9 ± 15.8 months. Four patients (1.8%) had intraoperative complications, including 2 cases of bleeding, 1 diaphragm perforation, and 1 portal vein stenosis. Fourteen patients (7.4%) had major postoperative complications, with 5 patients requiring surgical intervention. CONCLUSIONS: Donor hepatectomy is a complicated surgery that requires extensive preoperative preparation and appropriate donor selection. Postoperative donor complications can be diagnosed early with close follow-up, and a multidisciplinary approach is essential for complication management.
Asunto(s)
Hepatectomía , Laparoscopía , Trasplante de Hígado , Donadores Vivos , Complicaciones Posoperatorias , Humanos , Femenino , Trasplante de Hígado/efectos adversos , Masculino , Hepatectomía/efectos adversos , Estudios Retrospectivos , Adulto , Laparoscopía/efectos adversos , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Factores de Tiempo , Adulto Joven , Persona de Mediana EdadRESUMEN
BACKGROUND: Postoperative recurrence is a vital reason for poor 5-year overall survival in hepatocellular carcinoma (HCC) patients. The ADV score is considered a parameter that can quantify HCC aggressiveness. This study aimed to identify HCC patients at high-risk of recurrence early using the ADV score. METHODS: The medical data of consecutive HCC patients undergoing hepatectomy from The First Affiliated Hospital of Nanjing Medical University (TFAHNJMU) and Nanjing Drum Tower Hospital (NJDTH) were retrospectively reviewed. Based on the status of microvascular invasion and the Edmondson-Steiner grade, HCC patients were divided into three groups: low-risk group (group 1: no risk factor exists), medium-risk group (group 2: one risk factor exists), and high-risk group (group 3: coexistence of two risk factors). In the training cohort (TFAHNJMU), the R package nnet was used to establish a multi-categorical unordered logistic regression model based on the ADV score to predict three risk groups. The Welch's T-test was used to compare differences in clinical variables in three predicted risk groups. NJDTH served as an external validation center. At last, the confusion matrix was developed using the R package caret to evaluate the diagnostic performance of the model. RESULTS: 350 and 405 patients from TFAHNJMU and NJDTH were included. HCC patients in different risk groups had significantly different liver function and inflammation levels. Density maps demonstrated that the ADV score could best differentiate between the three risk groups. The probability curve was plotted according to the predicted results of the multi-categorical unordered logistic regression model, and the best cut-off values of the ADV score were as follows: low-risk ≤ 3.4 log, 3.4 log < medium-risk ≤ 5.7 log, and high-risk > 5.7 log. The sensitivities of the ADV score predicting the high-risk group (group 3) were 70.2% (99/141) and 78.8% (63/80) in the training and external validation cohort, respectively. CONCLUSION: The ADV score might become a valuable marker for screening patients at high-risk of HCC recurrence with a cut-off value of 5.7 log, which might help surgeons, pathologists, and HCC patients make appropriate clinical decisions.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico , Estudios Retrospectivos , Femenino , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Detección Precoz del Cáncer/métodos , Invasividad Neoplásica , Tasa de Supervivencia , AncianoRESUMEN
BACKGROUND: This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR). METHODS: In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence. RESULTS: The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion. CONCLUSIONS: The predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels.
Asunto(s)
Neoplasias de los Conductos Biliares , Antígeno CA-19-9 , Colangiocarcinoma , Hepatectomía , Linfocitos , Recurrencia Local de Neoplasia , Neutrófilos , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/sangre , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Masculino , Femenino , Neutrófilos/patología , Persona de Mediana Edad , Pronóstico , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/mortalidad , Estudios Retrospectivos , Linfocitos/patología , Antígeno CA-19-9/sangre , Anciano , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Adulto , Periodo Preoperatorio , Recuento de Linfocitos , Factores de RiesgoRESUMEN
BACKGROUND: Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. METHODS: This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS: Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). CONCLUSIONS: These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Neoplasias Hepáticas , Puntaje de Propensión , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Masculino , Femenino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/etiología , Persona de Mediana Edad , Antígenos e de la Hepatitis B/sangre , Pronóstico , Antivirales/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Nucleósidos/uso terapéutico , Estudios Retrospectivos , Adulto , Anciano , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virologíaRESUMEN
Nucleostemin (NS) plays a role in liver regeneration, and aging reduces its expression in the baseline and regenerating livers following 70% partial hepatectomy (PHx). Here we interrogate the mechanism controlling NS expression during liver regeneration and aging. The NS promoter was analyzed by TRANSFAC. Functional studies were performed using cell-based luciferase assay, endogenous NS expression in Hep3B cells, mouse livers with a gain-of-function mutation of C/EBPα (S193D), and mouse livers with C/EBPα knockdown. We found a CAAT box with four C/EBPα binding sites (-1216 to -735) and a GC box with consensus binding sites for c-Myc, E2F1, and p300-associated protein complex (-633 to -1). Age-related changes in NS expression correlated positively with the expression of c-Myc, E2F1, and p300, and negatively with that of C/EBPα and C/EBPß. PHx upregulated NS expression at 1d, coinciding with an increase in E2F1 and a decrease in C/EBPα. C/EBPα bound to the consensus sequences found in the NS promoter in vitro and in vivo, inhibited its transactivational activity in a binding site-dependent manner, and decreased the expression of endogenous NS in Hep3B cells. In vivo activation of C/EBPα by the S193D mutation resulted in a 4th-day post-PHx reduction of NS, a feature shared by 16-m/o livers. Finally, C/EBPα knockdown increased its expression in aged (24-m/o) livers under both baseline and regeneration conditions. This study reports the C/EBPα suppression of NS expression in aged livers, providing a new perspective on the mechanistic orchestration of tissue homeostasis in aging.
Asunto(s)
Envejecimiento , Proteínas de Unión al GTP , Regeneración Hepática , Proteínas Nucleares , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-myc , Animales , Regeneración Hepática/genética , Regeneración Hepática/fisiología , Ratones , Envejecimiento/metabolismo , Envejecimiento/fisiología , Envejecimiento/genética , Humanos , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Proteína beta Potenciadora de Unión a CCAAT/genética , Factor de Transcripción E2F1/metabolismo , Factor de Transcripción E2F1/genética , Hepatectomía , Sitios de Unión , Hígado/metabolismo , Proteína p300 Asociada a E1A/metabolismo , Regulación de la Expresión Génica , Transcripción Genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Proteína alfa Potenciadora de Unión a CCAAT/genética , Masculino , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Ratones Endogámicos C57BL , Línea Celular Tumoral , Proteínas de Unión al ARNRESUMEN
OBJECTIVE: To evaluate the safety and advisability of repeated liver resection (RLR) for recurrent intrahepatic cholangiocarcinoma (ICC). MATERIAL AND METHODS: The results of RLR for ICC recurrence (n=10) were retrospectively analyzed between 1999 and 2023. The control group consisted of patients undergoing primary liver resection for ICC (n=195). RESULTS: Surgery time (p=0.001) and blood loss (p=0.038) were lower in the RLR group. There were no blood transfusions (0 vs. 31.8%, p=0.034) and 90-day mortality (0 vs. 3.2%, p=1.0) in the same group. The risk of complications (30.0% vs.45.6%, p=0.517) and adverse events grade ≥ III (20.0% vs. 17.9%, p=1.0) was similar in both groups. Multifocal intrahepatic nodes were more common in the RLR group (60% vs. 37.9%, p=0.193), while there were no negative factors such as lymph nodes involvement (0 vs. 34.4%, p=0.032) and invasion of surrounding structures (0 vs. 38.5%, p=0.015). Dimensions of the largest node were smaller in repeated resection (2 vs. 8 cm, p<0.0001). Incidence of R0 resections (80.0% vs. 82.1%, p=1.0) was comparable. Long-term results were similar: five-year overall survival 17.2% and 34.7% (p=0.912), three-year disease-free survival 20.0% and 26.5% (p=0.421). CONCLUSION: Similar results of repeated and primary liver resections confirm advisability of RLR for intrahepatic recurrence of ICC.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Hepatectomía , Recurrencia Local de Neoplasia , Humanos , Colangiocarcinoma/cirugía , Masculino , Femenino , Hepatectomía/métodos , Hepatectomía/efectos adversos , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Reoperación/estadística & datos numéricos , Reoperación/métodos , Anciano , Federación de Rusia/epidemiología , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Tempo Operativo , Evaluación de Procesos y Resultados en Atención de SaludRESUMEN
PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. METHODS: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. RESULTS: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03-0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce. CONCLUSION: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Trasplante de Hígado , Estadificación de Neoplasias , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Humanos , Selección de Paciente , Tasa de SupervivenciaRESUMEN
Background: To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection. Data and methods: A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation. Results: A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively. Conclusion: Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Nomogramas , Humanos , Masculino , Femenino , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Virus de la Hepatitis B , Estudios Retrospectivos , Hepatitis B/complicaciones , China/epidemiología , Anciano , PronósticoAsunto(s)
Carcinoma Hepatocelular , Hepatectomía , Arteria Hepática , Laparoscopía , Neoplasias Hepáticas , Vena Porta , Humanos , Neoplasias Hepáticas/cirugía , Carcinoma Hepatocelular/cirugía , Vena Porta/cirugía , Vena Porta/anomalías , Hepatectomía/métodos , Laparoscopía/métodos , Arteria Hepática/cirugía , Arteria Hepática/anomalías , MasculinoRESUMEN
PURPOSE: Augmented reality navigation in liver surgery still faces technical challenges like insufficient registration accuracy. This study compared registration accuracy between local and external virtual 3D liver models (vir3DLivers) generated with different rendering techniques and the use of the left vs right main portal vein branch (LPV vs RPV) for landmark setting. The study should further examine how registration accuracy behaves with increasing distance from the ROI. METHODS: Retrospective registration accuracy analysis of an optical intraoperative 3D navigation system, used in 13 liver tumor patients undergoing liver resection/thermal ablation. RESULTS: 109 measurements in 13 patients were performed. Registration accuracy with local and external vir3DLivers was comparable (8.76 ± 0.9 mm vs 7.85 ± 0.9 mm; 95% CI = -0.73 to 2.55 mm; p = 0.272). Registrations via the LPV demonstrated significantly higher accuracy than via the RPV (6.2 ± 0.85 mm vs 10.41 ± 0.99 mm, 95% CI = 2.39 to 6.03 mm, p < 0.001). There was a statistically significant positive but weak correlation between the accuracy (dFeature) and the distance from the ROI (dROI) (r = 0.298; p = 0.002). CONCLUSION: Despite basing on different rendering techniques both local and external vir3DLivers have comparable registration accuracy, while LPV-based registrations significantly outperform RPV-based ones in accuracy. Higher accuracy can be assumed within distances of up to a few centimeters around the ROI.
Asunto(s)
Realidad Aumentada , Hepatectomía , Imagenología Tridimensional , Neoplasias Hepáticas , Cirugía Asistida por Computador , Humanos , Hepatectomía/métodos , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Cirugía Asistida por Computador/métodos , Anciano , Vena Porta/cirugía , Vena Porta/diagnóstico por imagen , Puntos Anatómicos de Referencia , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND: One of the main limitations to achieving a complete tumor resection in patients with technically resectable liver tumors is the presence of a small future liver remnant (FLR). Portal vein embolization (PVE) allows hypertrophy of the non-embolized lobe, reducing the risk of postoperative liver failure. AIM: To describe the experience of portal embolization prior to hepatectomy and its effectiveness in converting advanced unresectable liver tumors into resectable tumors. METHODS: Non-concurrent cohort study. All patients who underwent PVE before hepatectomy between 2016 and 2020 in our center were included. Demographic and diagnostic variables, pre and post-PVE volumes, perioperative variables, and global and disease-free survival were analyzed. RESULTS: Nineteen patients were included. Median age 66 (54-72) years and 57.9% (n= 11) were women. Bilateral metastases were present in 78.9% (n= 15). Sixteen patients (84.2%) received neoadjuvant chemotherapy. One patient (5.3%) had a complication after PVE. The median time between embolization and volumetry was 5.3 weeks (4.7-7.1). Median FLR before and after PVE were 19.8% (16.2-27.7) and 30% (25.2-40.5), respectively. The median percentage of hypertrophy was 48% (40.4-76.5). Fifteen patients (78.9%) underwent hepatectomy. Significant complications occurred in 26.6% (n= 4); among them, three patients (20%) presented postoperative liver failure. CONCLUSIONS: PVE is safe and effective in promoting FLR hypertrophy in the presence of chemotherapy, allowing patients with advanced liver tumors to undergo surgery with curative intent.
Asunto(s)
Embolización Terapéutica , Hepatectomía , Neoplasias Hepáticas , Vena Porta , Humanos , Hepatectomía/métodos , Femenino , Embolización Terapéutica/métodos , Persona de Mediana Edad , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/terapia , Anciano , Chile , Resultado del Tratamiento , Estudios Retrospectivos , Supervivencia sin Enfermedad , Cuidados Preoperatorios/métodosRESUMEN
Platelets play a crucial role in tissue regeneration, and their involvement in liver regeneration is well-established. However, the specific contribution of platelet-derived Transforming Growth Factor Beta 1 (TGFß1) to liver regeneration remains unexplored. This study investigated the role of platelet-derived TGFß1 in initiating liver regeneration following 2/3 liver resection. Using platelet-specific TGFß1 knockout (Plt.TGFß1 KO) mice and wild-type littermates (Plt.TGFß1 WT) as controls, the study assessed circulating levels and hepatic gene expression of TGFß1, Platelet Factor 4 (PF4), and Thrombopoietin (TPO) at early time points post-hepatectomy (post-PHx). Hepatocyte proliferation was quantified through Ki67 staining and PCNA expression in total liver lysates at various intervals, and phosphohistone-H3 (PHH3) staining was employed to mark mitotic cells. Circulating levels of hepatic mitogens, Hepatocyte Growth Factor (HGF), and Interleukin-6 (IL6) were also assessed. Results revealed that platelet-TGFß1 deficiency significantly reduced total plasma TGFß1 levels at 5 h post-PHx in Plt.TGFß1 KO mice compared to controls. While circulating PF4 levels, liver platelet recruitment and activation appeared normal at early time points, Plt.TGFß1 KO mice showed more stable circulating platelet numbers with higher numbers at 48 h post-PHx. Notably, hepatocyte proliferation was significantly reduced in Plt.TGFß1 KO mice. The results show that a lack of TGFß1 in platelets leads to an unbalanced expression of IL6 in the liver and to strongly increased HGF levels 48 h after liver resection, and yet liver regeneration remains reduced. The study identifies platelet-TGFß1 as a regulator of hepatocyte proliferation and platelet homeostasis in the early stages of liver regeneration.
Asunto(s)
Plaquetas , Hepatectomía , Regeneración Hepática , Ratones Noqueados , Trombopoyetina , Factor de Crecimiento Transformador beta1 , Animales , Regeneración Hepática/fisiología , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Ratones , Plaquetas/metabolismo , Trombopoyetina/metabolismo , Interleucina-6/metabolismo , Interleucina-6/genética , Proliferación Celular , Factor de Crecimiento de Hepatocito/metabolismo , Factor de Crecimiento de Hepatocito/genética , Hígado/metabolismo , Hepatocitos/metabolismo , Masculino , Factor Plaquetario 4/metabolismo , Factor Plaquetario 4/genética , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab. METHODS: Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan-Meier method and Cox regression models. RESULTS: Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001-3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150-5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078-6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173-12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043). CONCLUSIONS: Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6-VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.
Asunto(s)
Bevacizumab , Inestabilidad Cromosómica , Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Humanos , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , Masculino , Femenino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Persona de Mediana Edad , Pronóstico , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Adulto , Interleucina-6/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Estudios RetrospectivosRESUMEN
Sarcomas are challenging and conventionally referred to sarcoma specialist centres. In select cases with required surgical expertise, collaboration with a quaternary sarcoma centre rather than an upfront transfer of care may reduce logistic challenges without compromising patient care.We present a case series of three rare tumours of hepatobiliary origin-two cases of undifferentiated embryonal liver sarcoma in adults and one case of follicular dendritic sarcoma of the cystic lymph node.All three patients underwent surgery in a non-sarcoma specialist centre by hepatobiliary specialist surgeons with concurrent remote referrals to a sarcoma specialist quaternary centre. Both centres belong to the same cluster. R0 resection and no significant postoperative morbidity were achieved. All three patients currently remain disease-free.The unique and integrated healthcare systems within Singapore render cross-institution management possible. This case series suggests that an established setup for cross-centre collaboration facilitates wholistic patient care with good outcomes.
Asunto(s)
Hospitales de Enseñanza , Neoplasias Hepáticas , Sarcoma , Humanos , Sarcoma/cirugía , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Masculino , Femenino , Adulto , Singapur , Persona de Mediana Edad , Hepatectomía/métodosRESUMEN
Objectives: Treatment of metastatic colorectal cancer (mCRC) includes resection of liver metastases (LM), however, no validated biomarker identifies patients most likely to benefit from this procedure. This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC (i.e., RAS, BRAF, SMAD4, PIK3CA) as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection. Methods: A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM, stratified according to RAS, BRAF, PIK3CA, and SMAD4 mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined. The search was conducted in numerous databases, including MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host), and WHO Global Index Medicus, through March 18th, 2022. Meta-analyses, editorials, letters to the editor, case reports, studies on other primary cancers, studies with primary metastatic sites other than the liver, studies lacking specific oncological outcome variables or genetic data, non-English language studies, and studies omitting residual disease data from liver metastasectomy were excluded. The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented. Results: RAS mutation status was negatively associated with overall survival (OS) (HR, 1.68; 95% CI, 1.54-1.84) and recurrence free survival (RFS) (HR, 1.46; 95% CI, 1.33-1.61). A negative association was also found for BRAF regarding OS (HR, 2.64; 95% CI, 2.15-3.24) and RFS (HR, 1.89; 95% CI, 1.32-2.73) and SMAD4 regarding OS (HR, 1.93; 95% CI, 1.56-2.38) and RFS (HR, 1.95; 95% CI, 1.31-2.91). For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted. Conclusion: RAS, BRAF, and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer. No conclusion can be drawn for PIK3CA due to the limited literature availability. These data support the integration of RAS, BRAF, and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis. Nevertheless, we have to consider several limitations, the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival (DFS) or RFS; the inclusion of patients with minimal residual disease and unconsidered potential confounding factors, such as variability in resectability definitions, chemotherapy use, and a potential interaction between biological markers and pre- and post-resection pharmacological treatments.
Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Mutación , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Biomarcadores de Tumor/genética , Pronóstico , Hepatectomía/métodos , Proteínas Proto-Oncogénicas B-raf/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Proteína Smad4/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugíaRESUMEN
INTRODUCTION: Robotic-assisted surgery has become increasingly popular because of its potential benefits. Anatomical liver resection (ALR) is a valuable strategy in hepatocellular carcinoma (HCC) management. ALR with indocyanine green (ICG) fluorescence navigation was reported as an effective solution for segment identification. We reported a simple and convenient "preoperative positive staining technique" for laparoscopic ALR to overcome some limitations. To our knowledge, this is the first report of robotic-assisted surgery in which ALR was performed using this technique. MATERIALS AND SURGICAL TECHNIQUE: A 69-year-old man presented with a 12-mm HCC in segment 8. Preoperative three-dimensional simulation images showed that the fourth-order branch of the portal vein was a tumor-bearing portal pedicle. After anesthesia induction, 1 mL of 0.025 mg/mL ICG was injected percutaneously into this branch under B-mode ultrasound guidance before pneumoperitoneum. A robotic laparoscope was inserted. The preoperative positive staining area was clearly stained on the liver surface with the Firefly mode on the da Vinci Xi system. Based on the demarcation line, the liver parenchymal resection was started. The ICG fluorescence staining area was checked frequently on the resected side of the liver transection plane. Subsequently, the fourth-order portal branch was identified with the ICG fluorescence technique and ligated. Finally, the specimen was resected. The operation took 352 min, with 10 mL of blood loss, and was completed without any operative problems. DISCUSSION: Although many cases are required, the proposed preoperative positive staining technique appears useful for accurate and precise surgery given the increasing application of robotic-assisted hepatectomy.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Verde de Indocianina , Neoplasias Hepáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Anciano , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Procedimientos Quirúrgicos Robotizados/métodos , Hepatectomía/métodos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Ultrasonografía Intervencional , Colorantes , Laparoscopía/métodos , Cuidados Preoperatorios/métodosRESUMEN
BACKGROUND: The prognostic implications of the RAS status in colorectal cancer liver metastasis (CRLM) remain unclear. This study investigated the prognostic significance of RAS status after curative hepatectomy, focusing on surgical controllability. METHODS: This retrospective study included liver-only CRLM patients who underwent the first hepatectomy between 2015 and 2022 at the National Cancer Center Hospital. Recurrence-free survival (RFS), surgically controllable period (SCP), and overall survival (OS) were compared between RAS wild-type (RAS-wt) and mutant (RAS-mt) patients. Multivariate analyses were conducted to identify independent prognostic factors for each outcome and independent risk factors for less than 1 year SCP. RESULTS: A total of 150 patients were evaluated, comprising 63 patients with RAS-mt status. There was no significant difference in RFS between RAS-mt and RAS-wt (7.00 vs. 8.03 months, p = 0.48). RAS-mt patients exhibited worse SCP (11.80 vs.21.13 months, p < 0.001) and OS (44.03 vs. 70.03 months, p < 0.001) compared to RAS-wt. Multivariate analysis identified RAS-mt as an independent prognostic factor for both OS (hazard ratio [HR]: 3.37, p < 0.001) and SCP (HR: 2.20, p < 0.001), and as an independent risk factor for less than 1 year of SCP (odds ratio, 2.31; p = 0.03). CONCLUSIONS: CRLM with RAS mutations should be considered for strict surgical indications with preoperative chemotherapy and thorough examination, considering the possibility of short SCP.
Asunto(s)
Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Mutación , Humanos , Estudios Retrospectivos , Masculino , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Femenino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Hepatectomía/métodos , Pronóstico , Tasa de Supervivencia , Anciano , Estudios de Seguimiento , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/epidemiología , Adulto , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: Evaluation of the influence of the age of the patients upon the outcomes of liver resection (LR) for hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent LR between 2010 and 2020 were analyzed. They were divided into 3 groups depending on the patient's age. Group I (patients less than 60 years), Group II (patients between 60 and 69 years), and Group III (patients equal to or more than 70 years). RESULTS: 364 patients were included. A significantly higher serum bilirubin and alpha feto-protein were noted in Group I and serum creatinine was noted in Group III. The study groups did not show any significant differences regarding HCC site, number, macrovascular invasion, the extent of LR, Pringle maneuver, and perioperative blood transfusions. Longer operation time was found in Groups II and III, while more blood loss was noted in Group (I) Group I patients had longer hospital stays. Higher postoperative morbidities were noted in both Group I and Group (II) Higher incidence of post-hepatectomy liver dysfunction was noted in Group I. More early mortalities were found in Group I, related to liver failure. We did not experience early mortality in Group (III) Late Mortalities occurred in 117 patients (32.1%). HCC recurrence occurred in 165 patients (45.3%). Regarding the overall- and tumor-free survival, we did not experience any significant differences among the 3 groups (Log Rank: p = 0.371 and 0.464 respectively). CONCLUSIONS: Curative LR can be safely performed in selected elderly patients with HCC. An advanced patient's age should not be considered as a contraindication for curative LR.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Hepatectomía/métodos , Anciano , Masculino , Femenino , Persona de Mediana Edad , Factores de Edad , Estudios Retrospectivos , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano de 80 o más Años , Adulto , Tempo Operativo , Tiempo de Internación/estadística & datos numéricosRESUMEN
Gallbladder cancer (GBC) is a rare disease with a poor prognosis. Simple cholecystectomy may be an adequate treatment only for very early disease (Tis, T1a), whereas reoperation is recommended for more advanced disease (T1b and T2). Radical cholecystectomy should have two fundamental objectives: To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes. However, recent studies have shown that compared with lymph node dissection alone, liver resection does not improve survival outcomes. The oncological roles of lymphadenectomy and liver resection is distinct. Therefore, for patients with incidental GBC without liver invasion, hepatic resection is not always mandatory.