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PURPOSE: Single large hepatocellular carcinoma >5cm (SLHCC) traditionally requires a major liver resection. Minor resections are often performed with the goal to reduce morbidity and mortality. Aim of the study was to establish if a major resection should be considered the best treatment for SLHCC or a more limited resection should be preferred. METHODS: A multicenter retrospective analysis of the HE.RC.O.LE.S. Group register was performed. All collected patients with surgically treated SLHCC were divided in 5 groups of treatment (major hepatectomy, sectorectomy, left lateral sectionectomy, segmentectomy, non-anatomical resection) and compared for baseline characteristics, short and long-term results. A propensity-score weighted analysis was performed. RESULTS: 535 patients were enrolled in the study. Major resection was associated with significantly increased major complications compared to left lateral sectionanectomy, segmentectomy and non-anatomical resection (all p<0.05) and borderline significant increased major complications compared to sectorectomy (p=0.08). Left lateral sectionectomy showed better overall survival compared to major resection (p=0.02), while other groups of treatment resulted similar to major hepatectomy group for the same item. Absence of oncological benefit after major resection and similar outcomes among the 5 groups of treatment was confirmed even in the sub-population excluding patients with macrovascular invasion. CONCLUSION: Major resection was associated to increased major post-operative morbidity without long-term survival benefit; when technically feasible and oncologically adequate, minor resections should be preferred for the surgical treatment of SLHCC.
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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Puntaje de Propensión , Humanos , Hepatectomía/métodos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Tasa de Supervivencia , AdultoRESUMEN
BACKGROUND: The aim of this national survey on liver hypertrophy techniques was to track the trends of their use and implementation in Italy and to detect analogies and heterogeneities among centers. METHODS: In December 2022, Italian centers with liver resection activity were specifically contacted and asked to fill an online questionnaire composed of 6 sections including a total of 51 questions. RESULTS: 46 Italian centers filled the questionnaire. The proportion of major/total number of liver resections was 27% and the use of hypertrophy techniques was required in 6,2% of cases. The most frequent reason of drop out was disease progression in 58.5% of cases. Most frequently used techniques were PVE and ALPPS with an increasing use of hepatic venous deprivation (HVD). Heterogeneous answers were provided regarding the cutoff values to indicate the need for hypertrophy techniques. Criteria to allocate a patient to different hypertrophy techniques are not standardized. CONCLUSIONS: The use of hypertrophy techniques is deep-rooted in Italy, documenting the established value of their role in improving resectability rate. While an evolution of techniques is detectable, still significant heterogeneity is perceived in terms of cutoff values, indications and managing protocols.
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Hepatocellular carcinoma typically metastasizes within the liver and may involve extrahepatic sites such as the lungs, adrenal glands, and bones at advanced stages. However, hepatocellular carcinoma metastasis to the thyroid is very uncommon and tumor-to-tumor metastasis from a hepatocellular cancer to a thyroid neoplasm is extremely rare. In this report, we present a case of a 70-year-old man with a hepatocellular carcinoma metastasizing to oncocytic thyroid carcinoma, emphasizing the importance of clinical history and of a multidisciplinary approach, as well as the usefulness of site-specific immunohistochemical markers, in diagnosing and managing cases of Rosai's metastasis, especially when donor and recipient neoplasms share similar histologic features.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias de la Tiroides , Humanos , Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/diagnóstico , Masculino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/secundario , Anciano , Biomarcadores de Tumor/análisis , Inmunohistoquímica , Adenoma Oxifílico/patología , Adenoma Oxifílico/secundarioRESUMEN
Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP's prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child-Pugh class B-C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child-Pugh class B-C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/sangre , alfa-Fetoproteínas/análisis , Neoplasias Hepáticas/sangre , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Anciano , Biomarcadores de Tumor/sangre , Adulto , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
BACKGROUND AND STUDY AIM: The development of a new cholangioscope, the SpyGlass™ Discover (Boston Scientific), has allowed the laparoscopic transcystic common bile duct exploration and stone clearance. The possibility of simultaneous treatment of choledocholithiasis during early laparoscopic cholecystectomy offers the opportunity to enormously reduce the time between acute cholecystitis diagnosis and the execution of cholecystectomy with better outcomes for patients. Furthermore, an altered anatomy of the gastrointestinal tract is not an obstacle to this technique. The aim of the study was to determine whether this new procedure is feasible, safe, and effective. PATIENTS AND METHODS: The investigation employs a retrospective case series study including all consecutive patients with a diagnosis of common bile duct stones undergoing cholecystectomy and intraoperative laparoscopic common bile duct clearance using SpyGlass™ Discover at IRCCS Policlinico San Matteo in Pavia (Italy). Eighteen patients were included from May 2022 to May 2023. RESULTS: A complete clearance of the common bile duct was obtained in 88.9% of patients. The mean postoperative length of stay was 3 days. No major complications occurred. After a median follow-up of 8 months, no recurrence of biliary events or readmissions occurred. CONCLUSION: This procedure has proven to be feasible, safe, and effective.
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Cálculos Biliares , Laparoscopía , Humanos , Estudios Retrospectivos , Colecistectomía , Cálculos Biliares/cirugía , Conducto Colédoco/cirugíaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Abdominal ultrasound (US) is by far the most widely used first-level exam for the diagnosis of HCC. We aimed to assess whether different ultrasound patterns were related to tumor prognosis. METHODS: We retrospectively reviewed all patients with a new diagnosis of HCC (single nodule) and undergoing radiofrequency thermal ablation (RFTA) at our clinic between January 2009 and December 2021. Patients were classified according to four HCC ultrasound patterns: 1A, single capsulated nodule; 1B, well capsulated intra-node nodule; 1C, cluster consisting of capsulated nodules; and 2, non-capsulated nodule. RESULTS: 149 patients were analysed; median follow-up time was 43 months. US patterns 1A (32.9%) and 1B (61.1%) were the most commonly seen. Median overall survival (OS) and recurrence-free survival (RFS) from RFTA were 54 months (95% CI, 42-66) and 22 months (95% CI, 12-32), respectively. Pattern 1A showed the best OS. Compared to pattern 1A, 1B was independently associated with worse OS (51 months (95% CI, 34-68) vs. 46 months (95% CI, 18-62)) and RFS (34 months (95% CI, 27-41) vs. 18 months (95% CI, 12-24)). Patterns 1C and 2 were associated with worse RFS compared to 1A, while no difference was seen for OS. Among baseline clinical variables, pattern 1B exhibited higher histological grade (p = 0.048) and tumor dimension (p = 0.034) compared to pattern 1A. CONCLUSIONS: Our findings demonstrate that different US patterns correlate with different survival outcomes and tumor behavior in patients with HCC. Prospective studies are needed to confirm these results.
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Key Clinical Message: Concurrent polycystic liver disease and echinococcus infection can hinder diagnosis. Surgery may be needed for accurate diagnosis and treatment. Multidisciplinary collaboration is crucial. Abstract: Cystic echinococcosis, caused by Echinococcus granulosus eggs, is a parasitic zoonosis that typically affects humans through accidental ingestion. Polycystic liver disease is a condition characterized by the presence of multiple liver cysts and is often associated with polycystic kidney disease. Here, we present a case of a man in his 70s with a pre-existing diagnosis of polycystic liver disease. Radiological findings of a suspicious cyst in the S4 segment initially lacked serological evidence of echinococcosis; however, intraoperative confirmation revealed the presence of an echinococcal cyst. This article aims to explore both clinical conditions and highlight the therapeutic considerations for their management. Moreover, we discuss the significance of this unique case, emphasizing the possibility of the coexistence of these two pathologies.
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International guidelines exclude from surgery patients with peritoneal carcinosis of colorectal origin and a peritoneal cancer index (PCI) ≥ 16. This study aims to analyze the outcomes of patients with colorectal peritoneal carcinosis and PCI greater or equal to 16 treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) (CRS + HIPEC). We retrospectively performed a multicenter observational study involving three Italian institutions, namely the IRCCS Policlinico San Matteo in Pavia, the M. Bufalini Hospital in Cesena, and the ASST Papa Giovanni XXIII Hospital in Bergamo. The study included all patients undergoing CRS + HIPEC for peritoneal carcinosis from colorectal origin from November 2011 to June 2022. The study included 71 patients: 56 with PCI < 16 and 15 with PCI ≥ 16. Patients with higher PCI had longer operative times and a statistically significant higher rate of not complete cytoreduction, with a Completeness of Cytoreduction score (CC) 1 (microscopical disease) of 30.8% (p = 0.004). The 2-year OS was 81% for PCI < 16 and 37% for PCI ≥ 16 (p < 0.001). The 2-years DFS was 29% for PCI < 16 and 0% for PCI ≥ 16 (p < 0.001). The 2-year peritoneal DFS for patients with PCI < 16 was 48%, and for patients with PCI ≥ 16 was 57% (p = 0.783). CRS and HIPEC provide reasonable local disease control for patients with carcinosis of colorectal origin and PCI ≥ 16. Such results form the basis for new studies to reassess the exclusion of these patients, as set out in the current guidelines, from CRS and HIPEC. This therapy, combined with new therapeutical strategies, i.e., pressurized intraperitoneal aerosol chemotherapy (PIPAC), could offer reasonable local control of the disease, preventing local complications. As a result, it increases the patient's chances of receiving chemotherapy to improve the systemic control of the disease.
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BACKGROUND: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group). METHODS: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups. RESULTS: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011). CONCLUSION: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Hepatectomía/efectos adversos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Terapia RecuperativaRESUMEN
Cholangiocarcinoma (CCA) is a rare cancer characterized by a global increasing incidence. Extracellular vesicles (EV) contribute to many of the hallmarks of cancer through transfer of their cargo molecules. The sphingolipid (SPL) profile of intrahepatic CCA (iCCA)-derived EVs was characterized by liquid chromatography-tandem mass spectrometry analysis. The effect of iCCA-derived EVs as mediators of inflammation was assessed on monocytes by flow cytometry. iCCA-derived EVs showed downregulation of all SPL species. Of note, poorly-differentiated iCCA-derived EVs showed a higher ceramide and dihydroceramide content compared with moderately-differentiated iCCA-derived EVs. Of note, higher dihydroceramide content was associated with vascular invasion. Cancer-derived EVs induced the release of pro-inflammatory cytokines in monocytes. Inhibition of synthesis of ceramide with Myriocin, a specific inhibitor of the serine palmitoyl transferase, reduced the pro-inflammatory activity of iCCA-derived EVs, demonstrating a role for ceramide as mediator of inflammation in iCCA. In conclusion, iCCA-derived EVs may promote iCCA progression by exporting the excess of pro-apoptotic and pro-inflammatory ceramides.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Vesículas Extracelulares , Humanos , Monocitos , Ceramidas/análisis , Inflamación , Colangiocarcinoma/patología , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Vesículas Extracelulares/químicaRESUMEN
BACKGROUND: Less invasive alternatives than early cholecystectomy (EC) for acute calculous cholecystitis (ACC) treatment have been spreading in recent years. We still lack a reliable tool to select high-risk patients who could benefit from these alternatives. Our study aimed to prospectively validate the Chole-risk score in predicting postoperative complications in patients undergoing EC for ACC compared with other preoperative risk prediction models. METHOD: The S.P.Ri.M.A.C.C. study is a World Society of Emergency Surgery prospective multicenter observational study. From 1st September 2021 to 1st September 2022, 1253 consecutive patients admitted in 79 centers were included. The inclusion criteria were a diagnosis of ACC and to be a candidate for EC. A Cochran-Armitage test of the trend was run to determine whether a linear correlation existed between the Chole-risk score and a complicated postoperative course. To assess the accuracy of the analyzed prediction models-POSSUM Physiological Score (PS), modified Frailty Index, Charlson Comorbidity Index, American Society of Anesthesiologist score (ASA), APACHE II score, and ACC severity grade-receiver operating characteristic (ROC) curves were generated. The area under the ROC curve (AUC) was used to compare the diagnostic abilities. RESULTS: A 30-day major morbidity of 6.6% and 30-day mortality of 1.1% were found. Chole-risk was validated, but POSSUM PS was the best risk prediction model for a complicated course after EC for ACC (in-hospital mortality: AUC 0.94, p < 0.001; 30-day mortality: AUC 0.94, p < 0.001; in-hospital major morbidity: AUC 0.73, p < 0.001; 30-day major morbidity: AUC 0.70, p < 0.001). POSSUM PS with a cutoff of 25 (defined in our study as a 'Chole-POSSUM' score) was then validated in a separate cohort of patients. It showed a 100% sensitivity and a 100% negative predictive value for mortality and a 96-97% negative predictive value for major complications. CONCLUSIONS: The Chole-risk score was externally validated, but the CHOLE-POSSUM stands as a more accurate prediction model. CHOLE-POSSUM is a reliable tool to stratify patients with ACC into a low-risk group that may represent a safe EC candidate, and a high-risk group, where new minimally invasive endoscopic techniques may find the most useful field of action. TRIAL REGISTRATION: ClinicalTrial.gov NCT04995380.
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Colecistectomía , Colecistitis , Humanos , Medición de Riesgo/métodos , Estudios Prospectivos , MorbilidadRESUMEN
Importance: Clear indications on how to select retreatments for recurrent hepatocellular carcinoma (HCC) are still lacking. Objective: To create a machine learning predictive model of survival after HCC recurrence to allocate patients to their best potential treatment. Design, Setting, and Participants: Real-life data were obtained from an Italian registry of hepatocellular carcinoma between January 2008 and December 2019 after a median (IQR) follow-up of 27 (12-51) months. External validation was made on data derived by another Italian cohort and a Japanese cohort. Patients who experienced a recurrent HCC after a first surgical approach were included. Patients were profiled, and factors predicting survival after recurrence under different treatments that acted also as treatment effect modifiers were assessed. The model was then fitted individually to identify the best potential treatment. Analysis took place between January and April 2021. Exposures: Patients were enrolled if treated by reoperative hepatectomy or thermoablation, chemoembolization, or sorafenib. Main Outcomes and Measures: Survival after recurrence was the end point. Results: A total of 701 patients with recurrent HCC were enrolled (mean [SD] age, 71 [9] years; 151 [21.5%] female). Of those, 293 patients (41.8%) received reoperative hepatectomy or thermoablation, 188 (26.8%) received sorafenib, and 220 (31.4%) received chemoembolization. Treatment, age, cirrhosis, number, size, and lobar localization of the recurrent nodules, extrahepatic spread, and time to recurrence were all treatment effect modifiers and survival after recurrence predictors. The area under the receiver operating characteristic curve of the predictive model was 78.5% (95% CI, 71.7%-85.3%) at 5 years after recurrence. According to the model, 611 patients (87.2%) would have benefited from reoperative hepatectomy or thermoablation, 37 (5.2%) from sorafenib, and 53 (7.6%) from chemoembolization in terms of potential survival after recurrence. Compared with patients for which the best potential treatment was reoperative hepatectomy or thermoablation, sorafenib and chemoembolization would be the best potential treatment for older patients (median [IQR] age, 78.5 [75.2-83.4] years, 77.02 [73.89-80.46] years, and 71.59 [64.76-76.06] years for sorafenib, chemoembolization, and reoperative hepatectomy or thermoablation, respectively), with a lower median (IQR) number of multiple recurrent nodules (1.00 [1.00-2.00] for sorafenib, 1.00 [1.00-2.00] for chemoembolization, and 2.00 [1.00-3.00] for reoperative hepatectomy or thermoablation). Extrahepatic recurrence was observed in 43.2% (n = 16) for sorafenib as the best potential treatment vs 14.6% (n = 89) for reoperative hepatectomy or thermoablation as the best potential treatment and 0% for chemoembolization as the best potential treatment. Those profiles were used to constitute a patient-tailored algorithm for the best potential treatment allocation. Conclusions and Relevance: The herein presented algorithm should help in allocating patients with recurrent HCC to the best potential treatment according to their specific characteristics in a treatment hierarchy fashion.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Femenino , Anciano , Masculino , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Sorafenib/uso terapéutico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , HepatectomíaRESUMEN
OBJECTIVE: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC). BACKGROUND: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program. METHODS: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival. RESULTS: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival. CONCLUSIONS: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence.
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Carcinoma Hepatocelular , Fallo Hepático , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/cirugía , Cirrosis Hepática/complicaciones , Fallo Hepático/complicaciones , Recurrencia Local de Neoplasia/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Natural killer (NK) cells play a key role in immune surveillance and response to tumors, their function regulated by NK cell receptors and their ligands. The DNAM-1 activating receptor recognizes the CD155 molecule expressed in several tumor cells, such as hepatocellular carcinoma (HCC). This study aims to investigate the role of the DNAM-1/CD155 axis in mediating the NK cell response in patients with HCC. METHODS: Soluble CD155 was measured by ELISA. CD155 expression was sought in HCC cells by immunohistochemistry, qPCR, and flow cytometry. DNAM-1 modulation in NK cells was evaluated in transwell experiments and by a siRNA-mediated knockdown. NK cell functions were examined by direct DNAM-1 triggering. RESULTS: sCD155 was increased in sera from HCC patients and correlated with the parameters of an advanced disease. The expression of CD155 in HCC showed a positive trend toward better overall survival. DNAM-1 downmodulation was induced by CD155-expressing HCC cells, in agreement with lower DNAM-1 expressions in tumor-infiltrating NK (NK-TIL) cells. DNAM-1-mediated cytotoxicity was defective both in circulating NK cells and in NK-TIL of HCC patients. CONCLUSIONS: We provide evidence of alterations in the DNAM-1/CD155 axis in HCC, suggesting a possible mechanism of tumor resistance to innate immune surveillance.
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Indocyanine green (ICG) is a safe dye widely used in the biomedical field. Its photodynamic effect (PDT), originating from laser irradiation at 803 nm, opens interesting perspectives in theranostic applications. To overcome its low water stability, ICG can be shielded with nanoparticles (NPs). In this work, previously developed NPs based on poly lactic-co-glycolic acid (PLGA) coated with chitosan oleate (CS-OA) and loaded with resveratrol as a hydrophobic model drug have been proposed as an ICG carrier. These systems have been selected for their observed immunostimulatory properties. The possible loading of the dye by adsorption onto NP surface by electrostatic interaction was studied here in comparison with the encapsulation into the PLGA core. The ICG-chitosan (CS) interaction has been characterized by spectrophotometry, spectroscopy and in-cell in vitro assays. Fluorescence quenching was observed due to the ionic interaction between ICG and CS and was studied considering the dye:polymer stoichiometry and the effect of the NP dilution in cell culture medium (DMEM). The NP systems have been compared in vitro, assessing their behaviour in Caco-2 cell lines. A reduction in cell viability was observed after irradiation of ICG associated with NPs, evident also for the samples loaded by adsorption. These findings open the opportunity to exploit the association of PDT's effect on ICG with the properties of CS-OA coated NPs, whose immunostimulatory effect can be associated with PDT mechanism in cancer therapy.
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BACKGROUND: Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined. METHODS: Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care (ABC) method was employed to identify the benchmarks. The outcomes assessed were the rate of complications, major comorbidities, post-operative ascites (POA), post-hepatectomy liver failure (PHLF), 90-day mortality. Benchmarking was stratified for surgical complexity (CP1, CP2 and CP3). RESULTS: A total of 978 of 2698 patients fulfilled the inclusion criteria. 431 (44.1%) patients were treated with CP1 procedures, 239 (24.4%) with CP2 and 308 (31.5%) with CP3 procedures. Patients submitted to CP1 had a worse underlying liver function, while the tumor burden was more severe in CP3 cases. The ABC for complications (13.1%, 19.2% and 28.1% for CP1, CP2 and CP3 respectively), major complications (7.6%, 11.1%, 12.5%) and 90-day mortality (0%, 3.3%, 3.6%) increased with the surgical difficulty, but not POA (4.4%, 3.3% and 2.6% respectively) and PHLF (0% for all groups). CONCLUSION: We propose benchmarks for open liver resections in HCC cirrhotic patients, stratified for surgical complexity. The difference between the benchmark values and the results obtained during everyday practice reflects the room for potential growth, with the aim to encourage constant improvement among liver surgeons.
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Carcinoma Hepatocelular , Fallo Hepático , Neoplasias Hepáticas , Benchmarking , Hepatectomía/efectos adversos , Hepatectomía/métodos , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Cirrosis Hepática/cirugía , Fallo Hepático/etiología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
The major histocompatibility complex-class I chain related proteins A and B (MICA/B) is upregulated because of cellular stress and MICA/B shedding by cancer cells causes escape from NKG2D recognition favoring the emergence of cancers. Cholangiocarcinoma (CCA) is a relatively rare, though increasingly prevalent, primary liver cancer characterized by a late clinical presentation and a dismal prognosis. We explored the NKG2D-MICA/B axis in NK cells from 41 patients with intrahepatic cholangiocarcinoma (iCCA). The MICA/B-specific 7C6 mAb was used for ex vivo antibody-dependent cytotoxicity (ADCC) experiments using circulating, non tumor liver- and tumor-infiltrating NK cells against the HuCCT-1 cell line and patient-derived primary iCCA cells as targets. MICA/B were more expressed in iCCA than in non-tumoral tissue, MICA transcription being higher in moderately-differentiated compared with poorly-differentiated cancer. Serum MICA was elevated in iCCA patients in line with higher expression of ADAM10 and ADAM17 that are responsible for proteolytic release of MICA/B from tumor. Addition of 7C6 significantly boosted peripheral, liver- and tumor-infiltrating-NK cell degranulation and IFNγ production toward MICA/B-expressing established cell lines and autologous iCCA patient target cells. Our data show that anti-MICA/B drives NK cell anti-tumor activity, and provide preclinical evidence in support of 7C6 as a potential immunotherapeutic tool for iCCA.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Antineoplásicos Inmunológicos , Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos/metabolismo , Colangiocarcinoma/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Inmunoterapia/métodos , Células Asesinas Naturales/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismoRESUMEN
BACKGROUND: We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments. METHODS: Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments). RESULTS: 2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS. CONCLUSION: SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Hepatectomía/efectos adversos , Humanos , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of the study was to compare SURG vs SOR regarding the OS and progression-free survival (PFS) in a real-world clinical scenario. BACKGROUND DATA: The treatment for advanced nonmetastatic HCC belonging to the Barcelona Clinic Liver Cancer stage C (BCLC C) is still controversial. METHODS: BCLC C patients without extrahepatic spread and tumoral invasion of the main portal trunk were considered. Surgical patients were obtained from the HE.RC.O.LE.S. Register, whereas sorafenib patients were obtained from the ITA.LI.CA register The inverse probability weighting (IPW) method was adopted to balance the confounders between the 2 groups. RESULTS: Between 2008 and 2019, 478 patients were enrolled: 303 in SURG and 175 in SOR group. Eastern Cooperative Oncological Group Performance Status (ECOG-PS), presence of cirrhosis, steatosis, Child-Pugh grade, hepatitis B virus and hepatitis C virus, alcohol intake, collateral veins, bilobar disease, localization of the tumor thrombus, number of nodules, alpha-fetoprotein, age, and Charlson Comorbidity index were weighted by IPW to create two balanced pseudo-populations: SURG = 374 and SOR = 263. After IPW, 1-3-5âyears OS was 83.6%, 68.1%, 55.9% for SURG, and 42.3%, 17.8%, 12.8% for SOR (P < 0.001). Similar trends were observed after subgrouping patients by ECOG-PS = 0 and ECOG-PS >0, and by the intrahepatic location of portal vein invasion. At Cox regression, sorafenib treatment (hazard ratio 4.436; 95% confidence interval 3.19-6.15; P < 0.001) and Charlson Index (hazard ratio 1.162; 95% confidence interval 1.06-1.27; P = 0.010) were the only independent predictors of mortality. PFS at 1-3-5âyears were 65.9%, 40.3%, 24.3% for SURG and 21.6%, 3.5%, 2.9% for SOR (P = 0.007). CONCLUSIONS: In BCLC C patients without extrahepatic spread but with intrahepatic portal invasion, liver resection, if feasible, was followed by better OS and PFS compared with sorafenib.
Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Estadificación de Neoplasias , Niacinamida/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Estudios Retrospectivos , Sorafenib/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: We investigated the clinical impact of the newly defined metabolic-associated fatty liver disease (MAFLD) in patients undergoing hepatectomy for HCC (MAFLD-HCC) comparing the characteristics and outcomes of patients with MAFLD-HCC to viral- and alcoholic-related HCC (HCV-HCC, HBV-HCC, A-HCC). METHODS: A retrospective analysis of patients included in the He.RC.O.Le.S. Group registry was performed. The characteristics, short- and long-term outcomes of 1315 patients included were compared according to the study group before and after an exact propensity score match (PSM). RESULTS: Among the whole study population, 264 (20.1%) had MAFLD-HCC, 205 (15.6%) had HBV-HCC, 671 (51.0%) had HCV-HCC and 175 (13.3%) had A-HCC. MAFLD-HCC patients had higher BMI (p < 0.001), Charlson Comorbidities Index (p < 0.001), size of tumour (p < 0.001), and presence of cirrhosis (p < 0.001). After PSM, the 90-day mortality and severe morbidity rates were 5.9% and 7.1% in MAFLD-HCC, 2.3% and 7.1% in HBV-HCC, 3.5% and 11.7% in HCV-HCC, and 1.2% and 8.2% in A-HCC (p = 0.061 and p = 0.447, respectively). The 5-year OS and RFS rates were 54.4% and 37.1% in MAFLD-HCC, 64.9% and 32.2% in HBV-HCC, 53.4% and 24.7% in HCV-HCC and 62.0% and 37.8% in A-HCC (p = 0.345 and p = 0.389, respectively). Cirrhosis, multiple tumours, size and satellitosis seems to be the independent predictors of OS. CONCLUSION: Hepatectomy for MAFLD-HCC seems to have a higher but acceptable operative risk. However, long-term outcomes seems to be related to clinical and pathological factors rather than aetiological risk factors.