To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM).
The t-CS relies on the following ...factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS.
Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients.
A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not.
Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.
HCC is a major global health concern, necessitating effective treatment strategies. This study conducts a meta-analysis of meta-analyses comparing liver resection (LR) and liver transplantation (LT) ...for HCC.
The systematic review included meta-analyses comparing liver resection vs. liver transplantation in HCC, following PRISMA guidelines. Primary outcomes included 5-year overall survival (OS) and disease-free survival (DFS). AMSTAR-2 assessed study quality. Citation matrix and hierarchical clustering validated the consistency of the included studies.
A search identified 10 meta-analyses for inclusion. The median Pearson correlation coefficient for citations was 0.59 (IQR 0.41-0.65). LT showed better 5-year survival and disease-free survival in all HCC (OR): 0.79; 95% CI: 0.67-0.93, I^2:57% and OR: 0.44; 95% CI: 0.25-0.75, I^2:96%). Five-year survival in early HCC and ITT was 0.63 (95% CI: 0.50-0.78, I^2:0%) and 0.60 (95% CI: 0.39-0.92, I^2:0%). Salvage LT vs. Primary LT did not differ between 5-year survival and disease-free survival (OR: 0.62; 95% CI: 0.33-1.15, I^2:0% and 0.93; 95% CI: 0.82-1.04, I^2:0%).
Overall, the study underscores the superior survival outcomes associated with LT over LR in HCC treatment, supported by comprehensive meta-analysis and clustering analysis. There was no difference in survival or recurrence rate between salvage LT and primary LT. Therefore, considering the organ shortage, HCC can be resected and transplanted in case of recurrence.
Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with limited therapeutic options and short overall survival. iCCA is characterized by a strong desmoplastic reaction in the ...surrounding ecosystem that likely affects tumoral progression. Overexpression of the Notch pathway is implicated in iCCA development and progression. Our aim was to investigate the effectiveness of Crenigacestat, a selective inhibitor of NOTCH1 signaling, against the cross-talk between cancer cells and the surrounding ecosystem in an in vivo HuCCT1-xenograft model. In the present study, a transcriptomic analysis approach, validated by Western blotting and qRT-PCR on iCCA tumor masses treated with Crenigacestat, was used to study the molecular pathways responsive to drug treatment. Our results indicate that Crenigacestat significantly inhibited NOTCH1 and HES1, whereas tumor progression was not affected. In addition, the drug triggered a strong immune response and blocked neovascularization in the tumor ecosystem of the HuCCT1-xenograft model without affecting the occurrence of fibrotic reactions. Therefore, although these data need further investigation, our observations confirm that Crenigacestat selectively targets NOTCH1 and that the desmoplastic response in iCCA likely plays a key role in both drug effectiveness and tumor progression.
Background We aimed to evaluate the feasibility and long-term results of 2-stage hepatectomy (TSH) in patients with bilobar colorectal liver metastases (CRLM). Study Design We performed a ...retrospective multicenter study including 4 Italian hepatobiliary surgery units. One hundred thirty patients were selected for TSH between 2002 and 2011. The primary endpoint was feasibility of TSH and analysis of factors associated with failure to complete the procedure. The secondary endpoint was the long-term survival analysis. Results Patients presented with synchronous CRLM in 80.8% of cases, with a mean number of 8.3 CRLM and with concomitant extrahepatic disease in 20.0% of cases. The rate of failure to complete TSH was 21.5% and tumor progression was the most frequent reason for failure (18.5% of cases). Primary tumor characteristics, type, number, and distribution of CRLM were not associated with significantly different risks of disease progression. Multivariable logistic regression analysis showed that tumor progression during prehepatectomy chemotherapy was the only independent risk factor for failure to complete TSH. The 5- and 10-year overall survival rates for patients who completed TSH were 32.1% and 24.1%, respectively, with a median survival of 43 months. Duration of prehepatectomy chemotherapy ≥6 cycles was found to be the only independent predictor of overall and disease-free survival. Conclusions This study showed that selection of patients by response to prehepatectomy chemotherapy may be extremely important before planning TSH because tumor progression while receiving prehepatectomy chemotherapy was associated with significantly higher risk of failure to complete the second stage. For patients who completed the TSH strategy, long-term outcomes can be achieved with results similar to those observed after single-stage hepatectomy.
In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally ...recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence.
KRAS mutation is reportedly associated with poor prognosis in patients with different cancer types. However, mutational data on hilar cholangiocarcinoma are few and controversial. The aim of this ...study was to evaluate the rate of KRAS mutations in a single-center homogeneous population resected for hilar cholangiocarcinoma and the subsequent impact on prognosis. KRAS mutation status was evaluated in 54 patients undergoing major hepatectomy combined with resection of the main biliary confluence and regional lymphadenectomy for hilar cholangiocarcinoma between 2001 and 2019. Among these 54 patients, 12 (22.2%) had a KRAS mutation. KRAS mutation was not related with pathologic characteristics of the tumor. Five-year overall survival (OS) in patients with KRAS mutation was significantly lower than that observed in patients with KRAS wild type (0 vs. 49.2%, respectively; p = 0.003). In the multivariable analysis; independent predictors of poor OS were KRAS mutation (HR = 5.384; p = 0.003) and lymph node metastases (HR = 2.805; p = 0.023). The results of our study suggested that KRAS mutation in hilar cholangiocarcinoma was not rarely observed. KRAS mutation was an independent strong predictor of poor OS. KRAS mutation analysis should be included in the routine pathologic evaluation of resected hilar cholangiocarcinoma in order to better stratify prognosis
Background Hepatectomy for colorectal liver metastases (CRLM) may offer good long-term survival. The impact of the tumor-free surgical margin on long-term results remains controversial, and we have ...assessed this component in 185 patients. Methods Between 1992 and 2005, 185 patients underwent primary hepatectomy with curative intent for CRLM (which originated from colon/rectum 133/52, synchronous/metachronous 66/119, and single/multiple 100/85). In this study, 105 major and 80 minor hepatectomies were evaluated; 133 hepatectomies had pedicle clamping. Results Operative mortality was 1.1%, morbidity was 25.7%, and blood transfusion requirement was 27.6%. Stratification of tumor-free margin in the patients with R0 liver resection was greater than or equal to 10 mm (63.0% of patients), 6–9 mm (11.4% of patients), 3–5 mm (16.5% of patients), and less than or equal to 2 mm (9.1% of patients), with infiltrated margin in the remainder (R1 liver resection 4.9% of the total number of patients). The 3-year, 5-year, and 10-year survival rates were 54.9%, 37.9%, and 22.9%, respectively. Global and surgical margin recurrence rates increased as the tumor-free margin decreased ( P = .01 and P < .001, respectively). At univariate analysis, the width of surgical margin ( P < .001), transfusion requirement, major hepatectomy, R1 resection, number of metastases, high preoperative CEA, and increasing tumor size ( P value from .001 to .03) were associated with lesser rates of long-term survival. A similar association was found with disease-free survival. At multivariate analysis, width of surgical margin was the only independent predictor of both overall ( P = .003) and disease-free ( P < .001) survival. Although smaller margins were associated with synchronicity, increasing number of, and with bilobar distribution of, metastases which contributed to explaine recurrences away from the margin), the width of surgical margin maintained the prominent impact on outcome. Conclusions In our patients, the width of the surgical margin was a powerful prognostic factor after hepatectomy for CRLM. A resection margin less than or equal to 5 mm was associated with a greater risk of recurrence on the surgical margin, with a lesser rate of overall and disease-free survival.
Background
Increased expertise with minimally invasive liver surgery (MILS) could cause an unjustified extension of indications to resect liver benign disease (BD). The aim of this study was to ...evaluate the operative risk of MILS for BD and if implementation and diffusion of MILS have widened indications for BD resection.
Methods
A prospective study including centers with > 6 MILS for BD, enrolled in the I Go MILS registry from January 2015 to October 2016. Cysts fenestrations were excluded.
Results
Eight hundred eighteen MILS were performed in 15 centers. One hundred seventy-three of these (21.1%) were for BD: conversion rate was 6.9%, postoperative mortality and morbidity rates were 0 and 13.9%. During the same period, 3713 liver resections (open + MILS) were performed and 407 (11.0%) were for BD. A time-trend analysis showed that the total number of MILS and the number of MILS for malignant disease significantly increased, but this increasing trend was not documented for the number of MILS for BD, which remained stable during the study period of time. This trend was confirmed for the overall rate of resected BD (open + MILS) that remained stable.
Discussion
BD represents a valid indication for MILS. For BD, 21.1% of MILS was performed, rate significantly lower than that previously reported in Italy. Although an evident growth of the use of MILS was observed during the time period analysis in Italy, this trend did not correspond to an increased number of MILS for BD, and the overall rate of resected BD was comparable to that reported in previous large open series.
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