Search Results (24)

Purpose: Surgical resection has been the gold standard for colorectal liver metastases (CRLM) for decades. In recent years, thermal ablation has emerged as a first-line treatment option for small-size CRLM, while for intermediate-size lesions (3–5 cm), it is reserved for patients with unresectable disease. In this setting, thermal ablation has proven safe and effective, achieving durable local control (LC) in the majority of patients. This retrospective study compares oncological outcomes of thermal ablation versus surgical resection of intermediate-size (3–5 cm) CRLM. Material and methods: Patients treated with thermal ablation or surgical resection for intermediate-size CRLM between 2000 and 2025 were included. Baseline per-patient and per-procedure characteristics were compared across three groups: thermal ablation, surgical resection, and combined treatment. Per tumor characteristics were compared between thermal ablation and surgical resection. Primary outcomes included local tumor progression-free survival (LTPFS) and complication rates. Secondary outcomes were OS, distant progression-free survival (DPFS), LC, and length of hospital stay. Survival outcomes were analyzed using the Kaplan–Meier method; additionally, LTPFS was assessed using Cox proportional hazards regression models, with multivariable analyses performed to adjust for potential confounders. Results: A total of 320 patients with 448 metastases were included: 135 patients underwent thermal ablation, 156 underwent surgical resection, and 29 received combined treatment. LTPFS per tumor was significantly higher in the surgical resection group (HR 1.86, 95% CI 1.24–2.81, p = 0.0025), however, LC per tumor did not significantly differ amongst groups (HR 1.48, 95% CI 0.70–3.11, p = 0.307). Complication rates were significantly higher after resection (p < 0.001). OS and DPFS did not differ significantly between the three groups (p = 0.08 and p = 0.084). OS comparing only thermal ablation and resection was significantly lower in the thermal ablation group. Median hospital stay was 3, 5, and 7 days for the ablation, resection, and combined groups, respectively (p < 0.001). Conclusions: Thermal ablation offers a safe alternative to surgical resection for selected patients with intermediate-size (3–5 cm) CRLM, with higher treatment-site recurrence rates. With the option of repeat ablation, comparable local tumor control can be achieved. Improvements in local control with both modalities over time support the need for a prospective clinical trial. Full article

Major hepatectomy (MH) has traditionally been associated with higher R0 rates in colorectal liver metastases (CRLM), but at the cost of increased morbidity. Parenchymal-sparing hepatectomy (PSH) has emerged as an alternative approach aimed at reducing perioperative complications while preserving functional liver parenchyma without compromising oncological outcomes. We retrospectively analyzed 248 consecutive patients undergoing liver resection for CRLM between 2016 and 2025, classified as PSH (n = 215, 86.7%) or MH (n = 33, 13.3%). MH was performed more frequently in patients with greater tumor burden, including larger lesions, more numerous metastases, and bilobar disease (all p < 0.001). PSH was associated with shorter hospital stay, fewer postoperative complications, and lower 30-day readmission rate. In multivariable Cox analyses, surgical strategy was not associated with recurrence-free survival or overall survival, which were primarily driven by tumor burden. Among patients who developed liver recurrence, repeat hepatectomy was more often feasible after PSH than MH (p = 0.026), emphasizing the long-term value of preserving functional parenchyma. Overall, PSH was associated with lower postoperative morbidity, enabling earlier recovery, while facilitating future liver resections when needed in this chronically evolving disease. Full article

Background: Glucocorticoids may grant a protective effect against postoperative complications. The evidence on their efficacy, however, has been inconclusive thus far. We investigated the effects of preoperatively administered glucocorticoids on the overall postoperative complication rate, and on liver function recovery in patients undergoing major liver surgery. Methods: We performed a systematic literature search on PubMed, Embase, and CENTRAL in October 2021, and repeated the search in April 2023. Pre-study protocol was registered on PROSPERO (ID: CRD42021284559). Studies investigating patients undergoing liver resections or transplantation who were administered glucocorticoids preoperatively and reported postoperative complications were eligible. Meta-analyses were performed using META and DMETAR packages in R with a random effects model. Risk of bias was assessed using RoB2. Results: The selection yielded 11 eligible randomized controlled trials (RCTs) with 964 patients. Data from nine RCTs (n = 837) revealed a tendency toward a lower overall complication rate with glucocorticoid administration (odds ratio: 0.71; 95% confidence interval: 0.38–1.31, p = 0.23), but it was not statistically significant. Data pooled from seven RCTs showed a significant reduction in wound infections with glucocorticoid administration [odds ratio: 0.64; 95% confidence interval: 0.45–0.92 p = 0.02]. Due to limited data availability, meta-analysis of liver function recovery parameters was not possible. Conclusions: The preoperative administration of glucocorticoids did not significantly reduce the overall postoperative complication rate. Future clinical trials should investigate homogenous patient populations with a specific focus on postoperative liver recovery. Full article

(1) Background: With the increasing demand for repeat hepatectomy, preventing perihepatic adhesion formation following initial hepatectomy is crucial. Adhesion-preventative barriers, like the new spray-type AdSpray^TM (Terumo Corporation, Tokyo, Japan), have been proposed to reduce adhesion risk. However, data on their safety in minimally invasive hepatectomy (MIH) remain scarce. This is the first prospective study to evaluate the safety and feasibility of AdSpray^TM in MIH. (2) Methods: A total of 124 patients who underwent MIH with AdSpray^TM and 20 controls were analyzed. Subgroup analysis according to the AdSpray™ application area was conducted. Major complications were assessed using the Clavien–Dindo classification. Moreover, intraperitoneal pressure during AdSpray™ application was monitored in 20 cases. (3) Results: Major complications occurred in 6.4% of the patients, which was comparable to that in open hepatectomy. Intraperitoneal pressure remained stable below 12 mmHg during AdSpray™ application without any complications. No significant difference in complication rates was observed among subgroups. However, a potential increase in intra-abdominal abscess formation was suspected with AdSpray™ application to the resected liver surfaces. (4) Conclusions: AdSpray™ can be safely used in MIH; however, further research is needed to confirm the appropriacy of using AdSpray™, particularly over resected liver surfaces. Overall, AdSpray™ is a promising tool for enhancing the safety of MIH. Full article

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the sixth most common malignant tumor in the world, with an incidence of 2–8% per year in patients with hepatic cirrhosis or chronic hepatitis. Despite surveillance schedules, it is sometimes diagnosed at an advanced stage, requiring complex therapeutic efforts with both locoregional and systemic treatments. Traditional radiological tools (computed tomography and magnetic resonance) are used for the post-treatment follow-up of HCC. The first follow-up imaging is performed at 4 weeks after resection or locoregional treatments, or after 3 months from the beginning of systemic therapies, and subsequently every 3 months for the first 2 years. For this reason, these radiological methods do not grant the possibility of an early distinction between good and poor therapeutic response. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced ultrasound (DCE-US) have gained the interest of several researchers for their potential role in the early assessment of response to locoregional treatments (chemoembolization) or antiangiogenic therapies in patients with advanced HCC. In fact, DCE-US, through a quantitative analysis performed by specific software, allows the construction of time–intensity curves, providing an evaluation of the parameters related to neoplastic tissue perfusion and its potential changes following therapies. It has the invaluable advantage of being easily repeatable, minimally invasive, and able to grant important evaluations regarding patients’ survival, essential for well-timed therapeutic changes in case of unsatisfying response, and eventual further treatment planning. Full article

Accurate minimally invasive anatomic liver (sub)segmentectomy (MIAS) is technically demanding and not yet standardized, and its surgical outcomes are undefined. To study the impact of the minimally invasive approach on perioperative outcomes of anatomic liver (sub)segmentectomy (AS), we retrospectively studied and compared perioperative outcomes of 99 open AS (OAS) and 112 MIAS (laparoscopic 77, robotic 35) cases using the extrahepatic Glissonean approach, based on the 1:1 propensity score matched analyses. After matching (71:71), MIAS was superior to OAS in terms of blood loss (p < 0.0001), maximum postoperative serum total bilirubin (p < 0.0001), C-reactive protein (p = 0.034) levels, R0 resection rate (p = 0.021), bile leak (p = 0.049), and length of hospital stay (p < 0.0001). The matched robotic and laparoscopic AS groups (30:30) had comparable outcomes in terms of operative time, blood loss, transfusion, open conversion, postoperative morbidity and mortality, R0 resection, and hospital stay, although the rate of Pringle maneuver application (p = 0.0002) and the postoperative aspartate aminotransferase level (p = 0.002) were higher in the robotic group. Comparing the matched posterosuperior (sub)segmentectomy cases or unmatched repeat hepatectomy cases between MIAS and OAS, we observed significantly less blood loss and shorter hospital stays in MIAS. Robotic AS yielded comparable outcomes with laparoscopic AS in the posterosuperior (sub)segmentectomy and repeat hepatectomy settings, despite the worse tumor and procedural backgrounds in robotic AS. In conclusion, various types of MIAS standardized by the extrahepatic Glissonean approach were feasible and safe with more favorable perioperative outcomes than those of OAS. Although robotic AS had almost comparable outcomes with laparoscopic AS, robotics may serve to decrease the surgical difficulty of MIAS in selected patients undergoing posterosuperior (sub)segmentectomy and repeat hepatectomy. Full article

Background: The aim of this study was to evaluate the clinical impact of a combination of systemic sequential therapy and locoregional therapy on the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). Methods: Sixty-four consecutive patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The clinical impact of the combined use of systemic sequential therapy and locoregional therapy was evaluated by determining overall survival (OS). The combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while only systemic sequential therapy and repeated locoregional-treatment was defined as a single treatment procedure (STP). Results: R0 resection, MCT, and STP resulted in significantly better OS compared with no additional treatment (median OS, not reached vs. 18.2 months and 12.6 vs. 8.1 months, respectively; p = 0.002). Multivariate analysis confirmed that the use of R0 resection and MCT were associated with better OS (hazard ratio [HR]; 0.053, p = 0.006 and 0.189, p < 0.001, respectively) compared with that for STP (HR; 0.279, p = 0.003). Conclusions: MCT is may effective in patients with BCLC stage C HCC and intrahepatic target nodules who have previously received systemic therapy-based treatment. Full article

Background: Hepatocellular carcinoma (HCC) leads to 600,000 people’s deaths every year. The protein ubiquitin carboxyl-terminal hydrolase 15 (USP15) is a ubiquitin-specific protease. The role of USP15 in HCC is still unclear. Method: We studied the function of USP15 in HCC from the viewpoint of systems biology and investigated possible implications using experimental methods, such as real-time polymerase chain reaction (qPCR), Western blotting, clustered regularly interspaced short palindromic repeats (CRISPR), and next-generation sequencing (NGS). We investigated tissues samples of 102 patients who underwent liver resection between January 2006 and December 2010 at the Sir Run Run Shaw Hospital (SRRSH). Tissue samples were immunochemically stained; a trained pathologist then scored the tissue by visual inspection, and we compared the survival data of two groups of patients by means of Kaplan–Meier curves. We applied assays for cell migration, cell growth, and wound healing. We studied tumor formation in a mouse model. Results: HCC patients (n = 26) with high expression of USP15 had a higher survival rate than patients (n = 76) with low expression. We confirmed a suppressive role of USP15 in HCC using in vitro and in vivo tests. Based on publicly available data, we constructed a PPI network in which 143 genes were related to USP15 (HCC genes). We combined the 143 HCC genes with results of an experimental investigation to identify 225 pathways that may be related simultaneously to USP15 and HCC (tumor pathways). We found the 225 pathways enriched in the functional groups of cell proliferation and cell migration. The 225 pathways determined six clusters of pathways in which terms such as signal transduction, cell cycle, gene expression, and DNA repair related the expression of USP15 to tumorigenesis. Conclusion: USP15 may suppress tumorigenesis of HCC by regulating pathway clusters of signal transduction for gene expression, cell cycle, and DNA repair. For the first time, the tumorigenesis of HCC is studied from the viewpoint of the pathway cluster. Full article

Laparoscopic liver resection (LLR) is widely accepted in the surgical treatment of hepatocellular carcinoma (HCC) through international consensus conferences and the development of difficulty classifications. LLR has been reported to result in earlier postoperative recovery and fewer postoperative complications than open liver resection (OLR) for HCC. However, the prevalence of liver cirrhosis, obesity, the elderly, HCC recurrence (repeat liver resection), and major resection must be considered for LLR for HCC. Some systematic reviews, meta-analysis studies, and large cohort studies indicated that LLR is technically feasible for selected patients with HCC with these factors that led to less intraoperative blood loss, fewer transfusions and postoperative complication incidences, and shorter hospital stays than OLR. Furthermore, some reported LLR prevents postoperative loss of independence. No difference was reported in long-term outcomes among patients with HCC who underwent LLR and OLR; however, some recent reports indicated better long-term outcomes with LLR. In recent years, robot-assisted liver resection (RALR) has gradually become popular, and its short- and long-term results for HCC are not different from those of LLR. Additionally, RALR is expected to become the mainstay of minimally invasive surgery in the future. Full article

Recurrence of liver cancers after liver resection (LR), such as recurrences of hepatocellular carcinoma and colorectal liver metastases, is often treated with repeat LR (RLR) as the only curative treatment. However, RLR is associated with an increased risk of complications. The indications for the currently emerging laparoscopic LR and its advantages and disadvantages for repeat treatment are still under discussion. Our multi-institutional propensity-score matched analyses of laparoscopic vs. open RLRs for hepatocellular carcinoma showed the feasibility of laparoscopic RLR with comparable short- and long-term outcomes. Small blood loss and low morbidity was observed in selected patients treated using laparoscopic RLR in which total adhesiolysis can be dodged, with speculations that laparoscopic minor repeated LR can minimize functional deterioration of the liver. However, there are several disadvantages, such as easily occurring disorientation and difficulty in repeated wide-range dissection of Glissonian pedicles. Recently emerging small anatomical resection, indocyanine green fluorescence-guided surgery, and robot-assisted surgery are promising tools for the further development of laparoscopic RLR. This review discusses how laparoscopic RLR, as a powerful unique local therapy causing less damage to the residual liver and surrounding structures, could contribute to the outcomes of repeated treatments for cancers and its future perspectives. Full article

Surgical resection is the optimal treatment for HCC, despite a high risk of recurrence. Few data are available on patient’s survival after resection. This is a retrospective study of tumor recurrence occurring after hepatectomy for HCC from 2000 to 2016. Univariate and multivariate analyses were performed to identify prognostic factors of survival after recurrence (SAR). Among 387 patients, 226 recurred (58.4%) with a median SAR of 26 months. Curative treatments (liver transplantation, repeat hepatectomy, thermal ablation) were performed for 44.7% of patients. Independent prognostic factors for SAR were micro-vascular invasion on the primary surgical specimen, size of the initial tumor >5 cm, preoperative AFP, albumin and platelet levels, male gender, number, size and localization of tumors at recurrence, time to recurrence, Child–Pugh score and treatment at recurrence. In subgroup analysis, early recurrence (46%) was associated with a decrease in SAR, by contrast with late recurrence. However, the overall survival (OS) of patients with early recurrence and curative treatment did not significantly differ from that of non-recurring patients. For late recurrence, OS did not significantly differ from that of non-recurring patients, regardless of the proposed treatment. Aggressive and repeat treatments are therefore key to improve prognosis of patients with HCC. Full article

Introduction: There is no standard treatment after resection of colorectal liver metastases and the role of systemic therapy remains controversial. To avoid over- or undertreatment, proper risk stratification with regard to postoperative treatment strategy is highly needed. We recently demonstrated the prognostic relevance of EMT-related (epithelial-mesenchymal transition) genes in stage II/III CRC. As EMT is a major step in CRC progression, we now aimed to analyse the prognostic relevance of EMT-related genes in stage IV CRC using the study cohort of the FIRE-3 trial, an open-label multi-centre randomised controlled phase III trial of patients with metastatic CRC. Methods: Overall and progression free survival were considered as endpoints (n = 350). To investigate the prognostic relevance of EMT-related genes on either endpoint, we compared predictive performance of different models using clinical data only to models using gene data in addition to clinical data, expecting better predictive performance if EMT-related genes have prognostic value. In addition to baseline models (Kaplan Meier (KM), (regularised) Cox), Random Survival Forest (RSF), and gradient boosted trees (GBT) were fit to the data. Repeated, nested five-fold cross-validation was used for hyperparameter optimisation and performance evaluation. Predictive performance was measured by the integrated Brier score (IBS). Results: The baseline KM model showed the best performance (OS: 0.250, PFS: 0.251). None of the other models were able to outperform the KM when using clinical data only according to the IBS scores (OS: 0.253 (Cox), 0.256 (RSF), 0.284 (GBT); PFS: 0.254 (Cox), 0.256 (RSF), 0.276 (GBT)). When adding gene data, performance of GBT improved slightly (OS: 0.262 vs. 0.284; PFS: 0.268 vs. 0.276), however, none of the models performed better than the KM baseline. Conclusion: Overall, the results suggest that the prognostic relevance of EMT-related genes may be stage-dependent and that EMT-related genes have no prognostic relevance in stage IV CRC. Full article

Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. According to Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) 2020, globally HCC is the sixth most common cancer and the third most common cause of cancer-related deaths. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. Liver transplantation is the treatment of choice in early stages, while surgical resection, radiofrequency ablation (RFA) and trans arterial chemoembolization (TACE) are Food and Drug Administration (FDA)-approved treatments for advanced HCC. Additional first line therapy for advanced HCC includes broad-spectrum tyrosine kinase inhibitors (TKIs), such as sorafenib and lenvatinib, as well as a combination of immunotherapy and anti-angiogenesis therapy, namely atezolizumab and bevacizumab. However, these strategies provide nominal extension in the survival curve, cause broad spectrum toxic side effects, and patients eventually develop therapy resistance. Some common mutations in HCC, such as in telomerase reverse transcriptase (TERT), catenin beta 1 (CTNNB1) and tumor protein p53 (TP53) genes, are still considered to be undruggable. In this context, identification of appropriate gene targets and specific gene delivery approaches create the potential of gene- and immune-based therapies for the safe and effective treatment of HCC. This review elaborates on the current status of HCC treatment by focusing on potential gene targets and advanced techniques, such as oncolytic viral vectors, nanoparticles, chimeric antigen receptor (CAR)-T cells, immunotherapy, and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), and describes future prospects in HCC treatment. Full article

Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group. Full article

Introduction: Intrahepatic cholangiocarcinoma (ICC) has devastating outcomes owing to its advanced stage at diagnosis and high recurrence after hepatectomy. There is no preferred treatment for recurrent ICC. We retrospectively reviewed our patients who underwent repeated operations for recurrent ICCs based on their different indications to appraise the outcomes. Methods: In all, 160 out of 216 patients with ICC (71.4%) experienced recurrence after curative resection from 1977 to 2014. The patterns of recurrence were categorized according to the locations and numbers of recurrent tumors. Results: Patients with merely intrahepatic recurrence (n = 38) had superior overall survival (OS) compared with those with beyond intrahepatic recurrence (p < 0.0001). Twenty-seven out of 160 patients (16.8%) underwent repeat hepatectomy or/with metastatectomy for recurrence and had superior OS when compared to the remaining 133 patients who received nonoperative treatment/palliation (85.6 months versus 20.9 months, p < 0.001). Furthermore, patients suitable for repeat hepatectomy in the intrahepatic recurrent group (n = 12) had superior post-recurrence overall survival (PROS) than the remaining 26 patients receiving nonoperative treatment (61.6 months versus 14.7 months, p < 0.05). Conclusion: Liver is the most commonly involved site of recurrent ICC. However, merely intrahepatic recurrence may have a favorable prognosis compared to recurrence involving other sites. Aggressive hepatectomy may provide a survival benefit in selected patients. Full article