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BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.
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Carcinome hépatocellulaire , Hépatectomie , Tumeurs du foie , Charge tumorale , Humains , Carcinome hépatocellulaire/chirurgie , Carcinome hépatocellulaire/anatomopathologie , Carcinome hépatocellulaire/mortalité , Carcinome hépatocellulaire/sang , Tumeurs du foie/chirurgie , Tumeurs du foie/anatomopathologie , Tumeurs du foie/mortalité , Tumeurs du foie/sang , Mâle , Femelle , Adulte d'âge moyen , Hépatectomie/méthodes , Sujet âgé , Études rétrospectives , Alphafoetoprotéines/métabolisme , Alphafoetoprotéines/analyse , Facteurs de risque , Récidive tumorale locale/épidémiologie , Survie sans rechute , Tumeurs primitives multiples/chirurgie , Tumeurs primitives multiples/anatomopathologie , Tumeurs primitives multiples/sang , Tumeurs primitives multiples/mortalité , AdulteRÉSUMÉ
Donor safety is crucial for living donor liver transplantation (LDLT), and sufficient liver regeneration significantly affects outcomes of living donors. This study aimed to investigate clinical factors associated with liver regeneration in living donors. The study retrospectively reviewed 380 living donors who underwent liver donation at Chang Gung Memorial Hospital in Linkou. The clinical characteristics and medical parameters of donors were analyzed and compared according to liver donation graft type. There were 355 donors (93.4%) with right hemi-liver donations and 25 donors (6.6%) with left hemi-liver donations. Left hemi-liver donors had a higher body mass index (BMI) and a larger ratio of remnant liver volume (RLV) to total liver volume (TLV). However, the 2 groups showed no significant difference in the liver regeneration ratio. The type of remnant liver (Pâ <â .001), RLV/body weight (Pâ =â .027), RLV/TLV (Pâ <â .001), serum albumin on postoperative day 7 and total bilirubin levels on postoperative day 30 were the most significant factors affecting liver regeneration in living donors. In conclusion, adequate liver regeneration is essential for donor outcome after liver donation. The remnant liver could eventually regenerate to an adequate volume similar to the initial TLV before liver donation. However, the remnant left hemi-liver had a faster growth rate than the remnant right hemi-liver in donors.
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Régénération hépatique , Transplantation hépatique , Humains , Donneur vivant , Hépatectomie , Études rétrospectives , Foie/chirurgie , HépatomégalieRÉSUMÉ
AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.
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BACKGROUND Taiwan has a high prevalence of hepatitis B virus (HBV) infection. HBV-related end-stage liver disease is the leading cause of liver transplantation (LT). Tenofovir alafenamide (TAF) is a recently approved agent for the treatment of chronic HBV infection that improves renal profiles compared with tenofovir disoproxil fumarate (TDF) in phase III trials. This study aimed to assess the outcomes of TAF treatment in LT recipients. MATERIAL AND METHODS This retrospective study analyzed 17 LT recipients who underwent treatment with TDF and TAF. Changes in baseline renal function were compared. RESULTS Seventeen LT recipients received TDF for ≥48 weeks and were switched to TAF. During TDF treatment, estimated glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease [MDRD] formula) decreased significantly at weeks 24 and 48. At week 48, only 2 patients (11.8%) displayed improved renal function, whereas the other patients showed decreased eGFR ranging from 5.48% to 62.84%. After switching to TAF, the median eGFR increased by 3.01% at week 24 and decreased by 0.31% at week 48. Seven patients (47%) showed improved renal function at week 48 after TAF treatment. CONCLUSIONS Switching from TDF to TAF was associated with fewer short-term renal impairment while maintaining the antiviral efficacy in LT recipients.
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Hépatite B chronique , Hépatite B , Transplantation hépatique , Humains , Ténofovir/usage thérapeutique , Études rétrospectives , Transplantation hépatique/effets indésirables , Alanine/usage thérapeutique , Adénine/usage thérapeutique , Hépatite B/traitement médicamenteux , Antiviraux/usage thérapeutique , Virus de l'hépatite BRÉSUMÉ
(1) Background: The prognosis of gastric cancer-associated peritoneal carcinomatosis (GCPC) is poor, with a median survival time of less than six months, and current systemic chemotherapy, including targeted therapy, is ineffective. Despite growing evidence that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for GCPC improves overall survival (OS), optimal patient selection remains unclear. We aimed to evaluate preoperative clinical factors and identify indicative factors for predicting postoperative OS in patients with GCPC undergoing CRS-HIPEC. (2) Methods: We retrospectively reviewed 44 consecutive patients with GCPC who underwent CRS-HIPEC between May 2015 and May 2021. Data on demographics and radiologic assessment were collected and analyzed. (3) Results: Elevated preoperative serum neutrophil-to-lymphocyte ratio > 4.4 (p = 0.003, HR = 3.70, 95% CI = 1.55-8.79) and number of computed tomography risks > 2 (p = 0.005, HR = 3.26, 95% CI = 1.33-7.98) were independently indicative of OS post-surgery. A strong correlation was observed between intraoperative peritoneal cancer index score and number of computed tomography risks (r = 0.534, p < 0.0001). Two patients after CRS-HIPEC ultimately achieved disease-free survival for more than 50 months. (4) Conclusions: Our experience optimizes GCPC patients' selection for CRS-HIPEC, may help to improve outcomes in the corresponding population, and prevent futile surgery in inappropriate patients.
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Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.
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COVID-19 , Transplantation hépatique , Humains , Immunosuppresseurs/usage thérapeutique , Vaccin ARNm-1273 contre la COVID-19 , Tacrolimus , Production d'anticorps , Donneur vivant , Vaccination , Évérolimus , Acide mycophénolique/usage thérapeutique , COVID-19/prévention et contrôle , ARN messager/génétique , Receveurs de transplantation , Anticorps antivirauxRÉSUMÉ
Background: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment. Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed. Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55-3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20-3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32-0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21-0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients. Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.
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Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver allograft recovery. How to define the damage of liver grafts is unclear. A total of 47 liver donors, 23 deceased and 24 living, were enrolled in this study. All deceased donors had suffered from severe brain damage, and six of them had experienced cardio-pulmonary-cerebral resuscitation (CPR). The exploration of liver graft metabolomics was conducted by liquid chromatography coupled with mass spectrometry. Compared with living donor grafts, the deceased liver grafts expressed higher levels of various diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, oleoylcarnitine and linoleylcarnitine; and lower levels of cardiolipin and phosphatidylcholine. The liver grafts from the donors with CPR had higher levels of cardiolipin, phosphatidic acid, phosphatidylcholine, phatidylethanolamine and amiodarone than the donors without CPR. When focusing on amino acids, the deceased livers had higher levels of histidine, taurine and tryptophan than the living donor livers. In conclusion, the deceased donors had suffered from cardio-circulation instability, and their lipid metabolites were increased. The elevation of lipid metabolites can be employed as an indicator of liver graft suffering.
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Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1−2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.
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BACKGROUND: No prognostic models specific to hepatocellular carcinoma patients receiving surgical resection have been considered strong and convincing enough for survival prediction thus far, and there are no models including only preoperative predictors. We derived a nomogram to predict disease-free survival in a previous study. AIM: To simplify our score and compare research outcomes among other scoring systems. METHODS: We retrospectively reviewed data from 1106 patients with hepatocellular carcinoma who underwent liver resection at the Linkou Chang Gung Memorial Hospital between April 2003 and December 2012. Multivariate analyses were conducted to identify the significant survival predictors. Homogeneity, Harrell's C-index, and Akaike information criterion were compared between our score, AJCC 8th edition, Tokyo score, and Taipei Integrated Scoring System (TTV-CTP-AFP model). RESULTS: Among the 1106 patients, 731 (66.1%) had tumor recurrence at a median follow-up of 83.9 mo. Five risk factors were identified: platelet count, albumin level, indocyanine green retention rate, multiplicity, and radiologic total tumor volume. Patients were divided into three risk groups, and the 5-year survival rates were 61.7%, 39%, and 25.7%, respectively. The C-index was 0.617, which was higher than the Tokyo score (0.613) and the Taipei Integrated Scoring System (0.562) and equal to the value of the AJCC 8th edition (0.617). CONCLUSION: The modified score provides an easier method to predict survival. Appropriate treatment can be planned preoperatively by dividing patients into risk groups.
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Background: The therapeutic efficacy of dendritic cell (DC)-immunotherapy for large hepatoma in mice is unsatisfactory. Materials & methods: DC-based immunotherapy was used to treat Hepa1-6 tumors measuring 6 ± 1 mm in diameter, enhanced by boosting tumor antigens. Results: CD4+ and CD8+ T-cells were contracted and transformed into memory phenotypic cells after DC-based vaccination. When T-cells were re-stimulated, T-cells obtained from mice boosted by tumor antigen injection showed highest proliferation capacity. When mice with large tumors were treated, DC-based vaccination boosted by tumor antigen and an additional DC-infusion yielded curative rates of 50% and 23.1%, respectively. Conclusion: DC vaccination induced effector memory cells. Antigen presentation recalled by DC or tumor antigens increased the curative rate in mice with large tumors.
Hepatocellular carcinoma is the most common liver malignancy and is often found at advanced stage. Immune checkpoint inhibitor combined with a molecular targeting agent is a new strategy for the treatment of advanced hepatocellular carcinoma and yields 30% of objective response rate. However, we still need another treatment for the patients who are not responsive to immune checkpoint inhibitor combined with a molecular targeting agent. Dendritic cell-based immunotherapy is one of the treatments for advanced hepatocellular carcinoma. In this animal study, dendritic cells can activate T-lymphocytes to kill cancer cells. Dendritic cells can also induce memory T-lymphocytes, which can be reactive by boost tumor antigens and increase therapeutic efficacy. This treatment strategy, dendritic cell infusion followed by tumor-antigen injection, can be translated into clinical practice in the future.
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Vaccins anticancéreux , Carcinome hépatocellulaire , Tumeurs du foie , Animaux , Antigènes néoplasiques , Lymphocytes T CD8+ , Vaccins anticancéreux/usage thérapeutique , Cellules dendritiques , Immunothérapie , Tumeurs du foie/thérapie , SourisRÉSUMÉ
Background: The extent of hepatic resection In HCC depends on the remnant liver reserve or the proximity of the tumor to major vessels. In this study, we evaluated the effects of very close resection margins on postoperative recurrence. Methods: Consecutive LR for HCC between 2003 and 2009 were studied. Patients were divided into groups with very narrow (≤1â mm) or wider (>1â mm) resection margins. Propensity score matching (PSM) was used to balance demographic, surgical, and pathological factors. Results: 983 patients were included in the study. After PSM, 173 patients were analyzed in each group. 5-year tumor recurrence and survival rates were comparable. Most recurrences were multiple intrahepatic. Section margin recurrences were similar in both groups. By multivariate analysis, tumor size >5â cm was associated with a very narrow resection margin, whereas low platelet count and tumor macrovascular invasion were significant factors related to tumor recurrence. Conclusions: Patients with very narrow surgical margins showed outcomes comparable to those with wider surgical margins. Most recurrences were multiple intrahepatic and associated with the degree of portal hypertension and adverse tumor biology. Although wide surgical margins should be aimed whenever possible, a narrow tumor-free margin resection still represents an effective therapeutic strategy.
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Staged hepatectomy is a promising strategy for curative resection of advanced colorectal liver metastasis (CRLM) to prevent inadequate future remnant liver (FRL). However, the selection criteria for conventional two-stage hepatectomy (cTSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) remain unclear. This study aimed to propose a selection criterion for determining the optimal staged hepatectomy for patients with advanced CRLM. A selection criterion based on the degree of metastatic tumors within the FRL was established to determine staged hepatectomy approaches. Generally, ALPPS is recommended for patients with ≤3 metastatic nodules and whose nodules do not measure >3 cm in the FRL. cTSH is performed for patients whose tumor burden in FRL beyond the selection criteria. Data of 37 patients who underwent staged hepatectomy and curative intent of CRLM were analyzed. The clinical characteristics and outcomes of the two approaches were compared. Overall, cTSH and ALPPS were performed for 27 (73.0%) and 10 (27.0%) patients, respectively. Of those, 20 patients in the cTSH group and all patients in the ALPPS group had completed staged hepatectomy. The 1-, 3-, and 5-year survival rates were 91.6%, 62.4%, and 45.4% for all patients, respectively. The outcomes of patients who had successfully completed the staged hepatectomy were significantly better than those of other patients who failed to achieve staged hepatectomy. However, no significant difference was observed in the overall survival of patients who underwent staged hepatectomy between the two groups, but those in the ALPPS group had 100% survival at the end of this study. The individualized selection criteria based on tumor burden in the FRL that could balance the operative risk and oncologic outcome appear to be a promising strategy for achieving complete staged hepatectomy in patients with advanced CRLM.
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Background: Patients with hepatocellular carcinoma (HCC) tend to be referred for liver transplantation (LT) at an early stage of cirrhosis, with lower pre-LT Model of End-Stage Liver Disease (MELD) scores. We investigated the impact of high MELD scores on post-LT outcomes in patients with HCC and validated the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR). Patients and Method: This retrospective single-center cohort study enrolled 230 patients with HCC who underwent LDLT from 2004−2019 in our institute. We defined a high MELD score as ≥20. Results: The MELD < 20 and MELD ≥ 20 groups comprised 205 and 25 cases, respectively. Although there was no significant difference in disease-free survival between the two groups (p = 0.629), the incidence of septic shock (p = 0.019) was significantly higher in the high MELD group. The one-, three-, and five-year overall survival rates were not significantly different between the two groups (p = 0.056). In univariate analysis, a high pre-LT NLR was associated with poorer survival in the high MELD group (p = 0.029, hazard ratio [HR]: 1.07, 90% confidence interval [CI]: 1.02−1.13). NLR cut-off values of ≥10.7 and <10.7 were predictive of mortality, with an AUC of 0.705 (90% CI: 0.532−0.879). The one-, three-, and five-year post-LT survival rates were significantly higher among the recipients with an NLR < 10.7 than those with an NLR ≥ 10.7 (p = 0.005). Conclusions: Pre-LT MELD score ≥ 20 was associated with a higher risk of developing post-LT septic shock and mortality. The pre-LT serum NLR is a useful predictive factor for clinical outcomes in patients with HCC with high MELD scores.
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Carcinome hépatocellulaire , Maladie du foie en phase terminale , Tumeurs du foie , Transplantation hépatique , Choc septique , Carcinome hépatocellulaire/chirurgie , Études de cohortes , Maladie du foie en phase terminale/étiologie , Maladie du foie en phase terminale/chirurgie , Humains , Tumeurs du foie/chirurgie , Transplantation hépatique/effets indésirables , Donneur vivant , Lymphocytes/anatomopathologie , Granulocytes neutrophiles/anatomopathologie , Études rétrospectives , Choc septique/étiologieRÉSUMÉ
BACKGROUND: Combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) to treat peritoneal surface malignancy (PSM) has gained a positive result compared with palliative chemotherapy alone in several cancer types. However, its postoperative care could be challenging. We aimed to develop a predicting model on early mortality. METHODS: We retrospectively reviewed 132 PSM patients who had received CRS-HIPEC. The optimal cut-off value of the neutrophil-to-lymphocyte ratio (NLR) was determined as 4.4 by using the receiver operating characteristic curve analysis with an area under the curve (AUC) of 0.75. The impact of NLR on survival was elucidated by comparing the pre-operative low (NLR≤ 4.4, n = 101) and high (NLR> 4.4, n = 31) groups using the Kaplan-Meier method. The significant variables selected in multivariate analysis on early mortality were used in prediction model development. RESULTS: Multivariate analysis showed that incomplete CRS, major postoperative complications, higher pre-operative NLR, and dynamic NLR changes were significant predictors of early mortality. Our perioperative prediction of prognosis (triple P) model contained four independent risks, and the AUC after classification was 0.860 (95% confidence interval [CI]: 0.773-0.947). External validation confirmed positive discrimination ability (AUC: 0.808, 95% CI: 0.666-0.950). CONCLUSION: In conclusion, our triple P model provides great determination in outcomes prediction and it is easily obtained, reliable, and applicable in routine practice.
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Hyperthermie provoquée , Tumeurs du péritoine , Humains , Interventions chirurgicales de cytoréduction/méthodes , Chimiothérapie hyperthermique intrapéritonéale , Granulocytes neutrophiles , Hyperthermie provoquée/méthodes , Études rétrospectives , Association thérapeutique , Tumeurs du péritoine/thérapie , Tumeurs du péritoine/anatomopathologie , Pronostic , Lymphocytes , Taux de survieRÉSUMÉ
BACKGROUND: GALNT14-rs9679162 "TT" genotype is associated with favorable clinical outcomes in hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We investigated whether patients with GALNT14-rs9679162 "non-TT" unfavorable genotype benefited from chemoembolization plus sorafenib combination therapy. METHODS: Intermediate stage HCC patients were recruited for GALNT14-rs9679162 genotyping before TACE. Patients with "TT" genotype received only TACE, labeled as TT (TACE) group. Patients with "non-TT" genotype ("GG" or "GT") were randomized to receive either TACE alone, labeled as Non-TT (TACE) group, or TACE plus sorafenib, labeled as Non-TT (TACE + Sora) group. The latter group received sorafenib 400 mg daily plus TACE. RESULTS: From October 2015 to April 2019, 103 HCC patients scheduled to receive chemoembolization were screened. Of them, 84 met inclusion criteria and were assigned to TT (TACE) (n = 25), Non-TT (TACE) (n = 30) and Non-TT (TACE + Sora) (n = 29) groups according to their GALNT14 genotypes. Repeated TACE sessions were performed on-demand and patients were followed until November 2020. It was found that TT (TACE) and Non-TT (TACE + Sora) patients had shorter time-to-complete response compared with that in Non-TT (TACE) patients (p < 0.001 and 0.009, respectively). These two groups also had longer time-to-TACE progression (p < 0.001 and 0.006, respectively) and longer progression-free survival (p = 0.001 and 0.021, respectively). However, TT (TACE) patients harbored longer overall survival compared with those in non-TT (TACE + Sora) and non-TT (TACE) patients (p = 0.028, < 0.001, respectively). CONCLUSION: Combination of sorafenib and TACE for "non-TT" patients partially overcame the genetic disadvantage on treatment outcomes in terms of time-to-complete response, time-to-TACE progression and progression-free survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT02504983.
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Antinéoplasiques , Carcinome hépatocellulaire , Chimioembolisation thérapeutique , Tumeurs du foie , Antinéoplasiques/usage thérapeutique , Carcinome hépatocellulaire/traitement médicamenteux , Association thérapeutique , Génotype , Humains , Tumeurs du foie/traitement médicamenteux , Nicotinamide/usage thérapeutique , Phénylurées/usage thérapeutique , Sorafénib/usage thérapeutique , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities. This study aimed to analyze patients who had undergone curative treatment for early HCC at LLS. METHODS: A retrospective analysis of 179 patients who underwent curative treatment for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The long-term outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed. RESULTS: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.1-60.9 months) and 17.6 (range: 2.4-94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-, 2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. The 1-, 2-, and 5-year recurrence free survival rates in the laparoscopic (n = 37) and conventional open (n = 82) LR groups were 94.1%, 82.0%, and 66.9% versus 86.1%, 74.6%, and 53.1%, respectively. (p = 0.506) Conclusion: Early HCC at LLS had satisfactory outcomes after curative treatment, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery.
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BACKGROUND Duct-to-duct biliary reconstruction has been increasingly used in living-donor liver transplantation. Information regarding dual duct-to-duct biliary anastomoses is limited. We present the largest case series to date on the use of the cystic and common hepatic ducts as dual-ductal anastomosis, along with long-term follow-up results. MATERIAL AND METHODS In this study, 740 patients underwent right-lobe living-donor liver transplantation; 56 of them were documented as dual-ductal anastomoses. We analyzed recipient and donor characteristics, surgical procedures, appearance of biliary complications, corresponding interventions, and long-term biliary outcomes. RESULTS Cystic and common hepatic ducts were utilized in 56 cases of dual-ductal biliary reconstruction, which we categorized into 2 types: A (78.6%), in which the right anterior intrahepatic duct was anastomosed to the common hepatic duct and the right posterior intrahepatic duct to the cystic duct; and B (21.4%), which was the reverse of A. After a median follow-up period of 46.4 months, 23 patients (41.1%) experienced complications, including biliary leakage and biliary stricture. However, after aggressive intervention (patent biliary anastomosis in most of them), 50 of 56 patients (89.3%) had patent biliary anastomosis and restored normal liver function at the end of follow-up. A small graft (graft-to-recipient weight ratio <0.9%) was the only predictor of biliary complications after multivariate analysis. CONCLUSIONS Dual-ductal biliary reconstruction in adult right-lobe living-donor liver transplantation is challenging but feasible. Our findings support the use of the cystic duct for reconstruction in selected patients. Good long-term results can be achieved with adequate management of patients with biliary complications.
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Transplantation hépatique , Adulte , Anastomose chirurgicale , Conduits biliaires/chirurgie , Conduit hépatique commun , Humains , Foie/chirurgie , Donneur vivantRÉSUMÉ
Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5 mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375 mg/m2 ) on post-operative day 1 to deplete B-cells. Eight patients received this quick preparation regimen to undergo ABO-I LDLT for acute liver failure from 2012 to 2019. They aged between 50 and 60 years. The median MELD score was 39 with a range from 35 to 48. It took 4.75 ± 1.58 days to prepare such an urgent ABO-I LDLT. All the patients had successful liver transplantations, but one patient died of antibody-mediated rejection at post-operative month 6. The 3-month, 6-month, and 1-year graft/patient survival were 100%, 87.5%, and 75%, respectively. In conclusion, this quick preparation regimen can reduce isoagglutinin titers quickly and make timely ABO-I LDLT feasible for acute liver failure.
Sujet(s)
Défaillance hépatique aigüe , Transplantation hépatique , Système ABO de groupes sanguins , Incompatibilité sanguine , Rejet du greffon/étiologie , Humains , Défaillance hépatique aigüe/chirurgie , Donneur vivant , Adulte d'âge moyen , Rituximab/usage thérapeutique , Résultat thérapeutiqueRÉSUMÉ
Human cytomegalovirus (CMV) infection has been reported to compromise liver transplantation (LT) outcomes. Recent studies have shown that CMV has a beneficial oncolytic ability. The aim of this study was to investigate the impact of CMV on tumor recurrence in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). This retrospective study enrolled 280 HCC patients with LT at our institute between January 2005 and January 2016. Their relevant demographic characteristics, pre- and post-LT conditions, and explant histology were collected. A CMV pp65 antigenemia assay was performed weekly following LT to identify CMV infection. A total of 121 patients (43.2%) were CMV antigenemia-positive and 159 patients (56.8%) were negative. A significantly superior five-year recurrence-free survival was observed among CMV antigenemia-positive patients compared with the CMV-negative group (89.2% vs. 79.9%, p = 0.049). There was no significant difference in overall survival between the positive and negative CMV antigenemia groups (70.2% vs. 75.3%, p = 0.255). The major cause of death was HCC recurrence in CMV antigenemia-negative patients (51.3%), whereas more CMV antigenemia-positive patients died due to other bacterial or fungal infections (58.3%). In the multivariate analysis, the independent risk factors for tumor recurrence included positive CMV antigenemia (p = 0.042; odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.20-0.97), microscopic vascular invasion (p = 0.001; OR = 3.86; 95% confidence interval (CI) = 1.78-8.36), and tumor status beyond the Milan criteria (p = 0.001; OR = 3.69; 95% CI = 1.77-7.71). In conclusion, in addition to the well-known Milan criteria, human CMV is associated with a lower HCC recurrence rate after LT. However, this tumor suppressive property does not lead to prolonged overall survival, especially in severely immunocompromised patients who are vulnerable to other infections.