Early Tumor Recurrence Research Articles

Surgical Strategies for Combined Hepatocellular-Cholangiocarcinoma (cHCC-CC).

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a tumor entity presenting features of hepatocellular and cholangiocellular epithelial differentiation. Due to the likeness between cHCC-CC, HCC and CC, accurate pretherapeutical diagnosis is challenging and advanced stages are prevalent. Radical oncological surgery is the only curative therapeutical option in patients with cHCC-CC. To reach this goal a profound understanding of this rare liver tumor is crucial. Factors such as clinicopathological characteristics, growth patterns and biological behavior are of central importance. To explore onco-surgical strategies and aspects for complete resection of cHCC-CC and to answer important key questions, an extensive review of the literature was conducted to answer the following questions: What are the best surgical options? Is there a significance for nonanatomical resections? Is there a prognostic value of concomitant lymphadenectomy? What about multimodal concepts in local advanced cHCC-CC? The role of minimally invasive liver surgery (MILS) including the role of robotic liver surgery for cHCC-CC will be discussed. While liver transplantation (LT) is standard for patients with unresectable HCC, the role of LT in cHCC-CC patients is still controversial. How can patients with high risk for early tumor recurrence be identified to avoid aggressive surgical treatment without clinical benefit? The comprehensive understanding of this challenging liver tumor will help to improve future treatment options for these patients.

Risk Group Stratification for Recurrence-Free Survival and Early Tumor Recurrence after Radiofrequency Ablation for Hepatocellular Carcinoma.

Although the prognosis after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) may vary according to different risk levels, there is no standardized follow-up protocol according to each patient's risk. This study aimed to stratify patients according to their risk of recurrence-free survival (RFS) and early (≤2 years) tumor recurrence (ETR) after RFA for HCC based on predictive models and nomograms and to compare the survival times of the risk groups derived from the models. Patients who underwent RFA for a single HCC (≤3 cm) between January 2012 and March 2014 (n = 152) were retrospectively reviewed. Patients were classified into low-, intermediate-, and high-risk groups based on the total nomogram points for RFS and ETR, respectively, and compared for each outcome. Restricted mean survival times (RMSTs) in the three risk groups were evaluated for both RFS and ETR to quantitatively evaluate the difference in survival times. Predictive models for RFS and ETR were constructed with c-indices of 0.704 and 0.730, respectively. The high- and intermediate-risk groups for RFS had an 8.5-fold and 2.9-fold higher risk of events than the low-risk group (both p < 0.001), respectively. The high- and intermediate-risk groups for ETR had a 17.7-fold and 7.0-fold higher risk than the low-risk group (both p < 0.001), respectively. The RMST in the high-risk group was significantly lower than that in the other two groups 9 months after RFA, and that in the intermediate-risk group became lower than that in the low-risk group after 21 months with RFS and 24 months with ETR. Our predictive models were able to stratify patients into three groups according to their risk of RFS and ETR after RFA for HCC. Differences in RMSTs may be used to establish different follow-up protocols for the three risk groups.

Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma.

KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations. 221 blood samples from 108 PDAC patients (65 curative, 43 palliative) were analyzed. Baseline peripheral and tumor-draining portal venous (PV), postoperative, and follow-up blood were analyzed and correlated with prognosis. Significantly higher KRAS mutant detection rates and copy numbers were observed in palliative compared to curative patients baseline blood (58.1% vs 24.6%; P = 0.002; and P < 0.001). Significantly higher KRAS mutant copies were found in PV blood compared to baseline (P < 0.05) samples. KRAS detection in pre- and postoperative and PV blood were significantly associated with shorter recurrence-free survival (all P < 0.015) and identified as independent prognostic markers. KRAS ctDNA status was also an independent unfavorable prognostic factor for shorter overall survival in both palliative and curative cohorts (hazard ratio [HR] 4.9, P = 0.011; HR 6.9, P = 0.008). KRAS ctDNA detection is an independent adverse prognostic marker in curative and palliative PDAC patients-at all sites of blood draw and a strong follow-up marker. The most substantial prognostic impact was seen for PV blood, which could be an effective novel tool for identifying prognostic borderline patients-guiding future decision-making on neoadjuvant treatment despite anatomical resectability. In addition, higher PV mutant copy numbers contribute to an improved technical feasibility.

Tumor ratio of unsaturated to saturated sulfatide species is associated with disease-free survival in intrahepatic cholangiocarcinoma

PurposeCholangiocarcinoma (CCA) is a malignancy arising from the bile duct epithelium and has a poor outcome. Sulfatides are lipid components of lipid rafts, and are implicated in several cancer types. In the liver, sulfatides are specifically present in the bile ducts. Here, sulfatide abundance and composition were analyzed using mass spectrometry imaging in intrahepatic CCA (iCCA) tumor tissue, and correlated with tumor biology and clinical outcomes.MethodsSulfatides were analyzed in iCCA (n = 17), hepatocellular carcinoma (HCC, n = 10) and colorectal liver metastasis (CRLM, n = 10) tumor samples, as well as tumor-distal samples (control, n = 16) using mass spectrometry imaging. Levels of sulfatides as well as the relative amount in structural classes were compared between groups, and were correlated with clinical outcomes for iCCA patients.ResultsSulfatide localization was limited to the respective tumor areas and the bile ducts. Sulfatide abundance was similar in iCCA and control tissue, while intensities were notably higher in CRLM in comparison with control (18-fold, P < 0.05) and HCC tissue (47-fold, P < 0.001). Considerable variation in sulfatide abundance was observed in iCCA tumors. A high ratio of unsaturated to saturated sulfatides was associated with reduced disease-free survival (10 vs. 20 months) in iCCA. The sulfatide pattern in HCC deviated from the other groups, with a higher relative abundance of odd- versus even-chain sulfatides.ConclusionSulfatides were found in tumor tissue of patients with iCCA, with sulfatide abundance per pixel being similar to bile ducts. In this explorative study, sulfatide abundance was not related to overall survival of iCCA patients. A high ratio of unsaturated to saturated sulfatides was associated with earlier tumor recurrence in patients with iCCA.

Pre-Operative Predicting Model of Early Tumor Recurrence outside the Milan Criteria for Hepatocellular Carcinoma

Purpose: Liver resection is a primary curative treatment for early stage hepatocellular carcinoma (HCC), but the outcomes are impeded by early tumor recurrence. This study aimed to establish a prediction model which could predict tumor recurrence outside the Milan criteria prior to liver resection.

Analysis of recurrence probability following radiotherapy in patients with CNS WHO grade 2 meningioma using integrated molecular-morphologic classification.

The current World Health Organization (WHO) classification of brain tumors distinguishes 3 malignancy grades in meningiomas, with increasing risk of recurrence from CNS WHO grades 1 to 3. Radiotherapy is recommended by current EANO guidelines for patients not safely amenable to surgery or after incomplete resection in higher grades. Despite adequately predicting recurrence probability for the majority of CNS WHO grade 2 meningioma patients, a considerable subset of patients demonstrates an unexpectedly early tumor recurrence following radiotherapy. A retrospective cohort of 44 patients with CNS WHO grade 2 meningiomas were stratified into 3 risk groups (low, intermediate, and high) using an integrated morphological, CNV- and methylation family-based classification. Local progression-free survival (lPFS) following radiotherapy (RT) was analyzed and total dose of radiation was correlated with survival outcome. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities were further assessed. Risk stratification of CNS WHO grade 2 meningioma into integrated risk groups demonstrated a significant difference in 3-year lPFS following radiotherapy between the molecular low- and high-risk groups. Recurrence pattern analysis revealed that 87.5 % of initial relapses occurred within the RT planning target volume or resection cavity. Integrated risk scoring can identify CNS WHO grade 2 meningioma patients at risk or relapse and dissemination following radiotherapy. Therapeutic management of CNS WHO grade 2 meningiomas and future clinical trials should be adjusted according to the molecular risk-groups, and not rely on conventional CNS WHO grading alone.

High Platelet Count is a Potential Prognostic Factor of the Early Recurrence of Hepatocellular Carcinoma in the Presence of Circulating Tumor Cells.

Recent studies indicated the vital role of platelet in enhancing the survival of circulating tumor cells (CTCs) in the blood, thereby stimulating the metastasis of tumors. CTCs have been considered an indicator of early tumor recurrence. Therefore, this study evaluated the prognostic potential of platelet count in predicting the early recurrence of hepatocellular carcinoma (HCC) in the presence of CTCs. 127 patients, whose preoperative CTCs were detected, were enrolled in this study. Univariate analysis was performed to identify the significant association of factors with the early recurrence of HCC, followed by multivariate analysis to determine the independent prognostic indicators. The prediction potential was evaluated using receiver operating characteristic (ROC) curves. A total of 81 (63.7%) patients showed early HCC recurrence. The platelet count ≥225×109/L (hazard ratio, HR: 1.679, P = 0.041), CTCs >5/5 mL (HR: 2.467, P = 0.001), and presence of microvascular invasion (MVI) (HR: 2.580, P = 0.002) were independent factors correlated with the early recurrence of HCC in multivariate analysis. The prognostic potential of the combined CTCs-platelet count (0.738) was better than that of CTCs (0.703) and platelet (0.604) alone. The subgroup analysis, excluding 23 patients with pathological cirrhosis and splenomegaly, showed that the platelet count ≥225×109/L and CTCs >5/5 mL were also independent factors of early HCC recurrence. The prediction potential of the combined CTCs-platelet count was 0.753, which was better than that of the whole cohort. Kaplan-Meier survival curve analysis indicated that the HCC patients with high platelet or CTCs had the worse recurrence-free survival (RFS). The high platelet count was an independent factor of early HCC recurrence in the presence of CTCs. The combination of preoperative CTCs and platelet count could effectively predict the early recurrence of HCC. The subgroup analysis also showed similar results.

Laparoscopic liver resection is associated with less significant muscle loss than the conventional open approach

BackgroundLaparoscopic liver resections (LLR) have been shown a treatment approach comparable to open liver resections (OLR) in hepatocellular carcinoma (HCC). However, the influence of procedural type on body composition has not been investigated. The aim of the current study was to compare the degree of skeletal muscle loss between LLR and OLR for HCC.MethodsBy using propensity score matching (PSM) analysis, 64 pairs of patients were enrolled. The change of psoas muscle index (PMI) after the operation was compared between the matched patients in the LLR and OLR. Risk factors for significant muscle loss (defined as change in PMI > mean change minus one standard deviation) were further investigated by multivariate analysis.ResultsAmong patients enrolled, there was no significant difference in baseline characteristics between the two groups. The PMI was significantly decreased in the OLR group (P = 0.003). There were also more patients in the OLR group who developed significant muscle loss after the operations (P = 0.008). Multivariate analysis revealed OLR (P = 0.023), type 2 diabetes mellitus, indocyanine green retention rate at 15 min (ICG-15) > 10%, and cancer stage ≧ 3 were independent risk factors for significant muscle loss. In addition, significant muscle loss was associated with early HCC recurrence (P = 0.006). Metabolomic analysis demonstrated that the urea cycle may be decreased in patients with significant muscle loss.ConclusionLLR for HCC was associated with less significant muscle loss than OLR. Since significant muscle loss was a predictive factor for early tumor recurrence and associated with impaired liver metabolism, LLR may subsequently result in a more favorable outcome.

PP183 MRI radiomics may predict early tumor recurrence in patients with paranasal sinus squamous cell carcinoma

PP183 MRI radiomics may predict early tumor recurrence in patients with paranasal sinus squamous cell carcinoma

Higher Risk of Tumor Recurrence in NASH-Related Hepatocellular Carcinoma Following Curative Resection.

The outcomes for patients with NASH-related HCC after curative resection have not been clarified. This study compared the overall survival (OS), time-to-tumor recurrence (TTR), and recurrence-free survival (RFS) associated with NASH-related HCC and virus-related HCC after resection. Methods: Patients with HCC who underwent curative resection were retrospectively enrolled. Baseline characteristics, including disease etiologies and clinical and tumor features, were reviewed. The primary outcomes were OS, TTR, and RFS. Results: Two hundred and six patients were enrolled (HBV: n = 121, HCV: n = 54, NASH: n = 31). Of those with virus-related HCC, 84.0% achieved viral suppression. In both the overall and propensity-score-matched cohorts, those with NASH-related HCC experienced recurrence significantly earlier than those with virus-related HCC (median TTR: 1108 days vs. non-reached; p = 0.03). Through multivariate analysis, NASH-related HCC (hazard ratio (HR), 2.27; 95% confidence interval (CI), 1.25-4.12) was independently associated with early recurrence. The unadjusted RFS rate of the NASH-related HCC group was lower than the virus-related HCC group. There was no difference in the OS between the two groups. Conclusions: NASH-related HCC was associated with earlier tumor recurrence following curative resection compared to virus-related HCC. Post-surgical surveillance is crucial for detecting early recurrence in patients with NASH-related HCC.

Use of radiomics containing an effective peritumoral area to predict early recurrence of solitary hepatocellular carcinoma ≤5 cm in diameter.

Hepatocellular carcinoma (HCC) is the sixth leading type of cancer worldwide. We aimed to develop a preoperative predictive model of the risk of early tumor recurrence after HCC treatment based on radiomic features of the peritumoral region and evaluate the performance of this model against postoperative pathology. Our model was developed using a retrospective analysis of imaging and clinicopathological data of 175 patients with an isolated HCC ≤5 cm in diameter; 117 patients were used for model training and 58 for model validation. The peritumoral area was delineated layer-by-layer for the arterial and portal vein phase on preoperative dynamic enhanced computed tomography images. The volume area of interest was expanded by 5 and 10mm and the radiomic features of these areas extracted. Lasso was used to select the most stable features. The radiomic features of the 5-mm area were sufficient for prediction of early tumor recurrence, with an area under the curve (AUC) value of 0.706 for the validation set and 0.837 for the training set using combined images. The AUC of the model using clinicopathological information alone was 0.753 compared with 0.786 for the preoperative radiomics model (P >0.05). Radiomic features of a 5-mm peritumoral region may provide a non-invasive biomarker for the preoperative prediction of the risk of early tumor recurrence for patients with a solitary HCC ≤5 cm in diameter. A fusion model that combines the radiomic features of the peritumoral region and postoperative pathology could contribute to individualized treatment of HCC.

Regional lymph node metastasis detected on preoperative CT and/or FDG-PET may predict early recurrence of pancreatic adenocarcinoma after curative resection

The objective of this study was to evaluate the role of regional lymph node (LN) metastasis detected on preoperative CT and/or 18F-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) scans in the prediction of early tumor recurrence after curative surgical resection of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 137 patients who underwent upfront surgery with R0 resection of PDAC between 2013 and 2016. Regional LN metastasis was identified using two criteria: positive findings for regional LN metastasis on either preoperative CT or FDG-PET scans (LNOR), or on both preoperative CT and FDG-PET scans (LNAND). A total of 55 patients had early tumor recurrence within 12 months after curative resection. Univariable and multivariable Cox proportional hazard regression analysis showed that preoperative carbohydrate antigen 19–9 (CA19-9) levels, preoperative locally advanced status, and regional LN metastasis (both LNOR and LNAND criteria) were significant risk factors for early recurrence. Positive LNOR and LNAND showed significantly poorer recurrence-free survival compared to negative regional LN metastasis groups (p = 0.048 and p = 0.020, respectively). Compared with the LNAND criteria, the LNOR criteria provided higher sensitivity (22.4% vs. 15.5%, p = 0.046) and a higher negative predictive value (61.9% vs. 59.8%, p = 0.046). The LNOR definition provided more sensitive and accurate performance in diagnosing preoperative regional LN metastasis.

Hepatic resection versus microwave ablation for the treatment of early hepatocellular carcinoma: a comparative analysis of treatment outcomes and survival predictors

IntroductionLiver resection and local ablation are the two primary curative treatments for early-stage hepatocellular carcinoma (HCC). Microwave ablation (MWA) shows promising performance in terms of early tumor response, recurrence, and survival. This study aims to determine whether MWA would be comparable to liver resection in treating early-stage HCC.MethodsThis study included patients with hepatitis C-related HCC attending the multidisciplinary HCC clinic, Kasr Al-Ainy Hospital (March 2018 to September 2020). We included adults with early-stage HCC (BCLC stages 0-A). We studied patients and tumor characteristics, HCC treatment response, recurrence, and overall survival.ResultsThirty-one patients were treated with liver resection and 41 patients were treated with MWA, including 4 patients who received intraoperative MWA. By the end of the study, 21 patients (28.77%) died. Patients who underwent MWA were younger compared to the hepatectomy group with lower baseline AFP (21 (6.7–54) versus 77 (31.3–136.0), respectively, (P value 0.024) and tumor size (2.78 (0.87) cm versus 3.77 (0.97) cm, respectively, (P value < 0.001). We found no differences between the studied groups in terms of treatment response, post-treatment decompensation, recurrence, or overall survival. One-year survival probability in the MWA and resection groups was 75.5% and 76.3% respectively. Post-procedure hepatic decompensation was the only independent predictor of lower survival by multivariate logistic regression analysis (OR 37.74, 95%CI 6.251–227.87, P value < 0.001) after adjusting for age, AFP, and tumor size.ConclusionLiver resection and MWA showed similar satisfactory results in the treatment of early-stage HCC, in terms of treatment response, recurrence, and overall survival.

Loss of RPTPγ primes breast tissue for acid extrusion, promotes malignant transformation and results in early tumour recurrence and shortened survival.

While cellular metabolism and acidic waste handling accelerate during breast carcinogenesis, temporal patterns of acid-base regulation and underlying molecular mechanisms responding to the tumour microenvironment remain unclear. We explore data from human cohorts and experimentally investigate transgenic mice to evaluate the putative extracellular HCO3--sensor Receptor Protein Tyrosine Phosphatase (RPTP)γ during breast carcinogenesis. RPTPγ expression declines during human breast carcinogenesis and particularly in high-malignancy grade breast cancer. Low RPTPγ expression associates with poor prognosis in women with Luminal A or Basal-like breast cancer. RPTPγ knockout in mice favours premalignant changes in macroscopically normal breast tissue, accelerates primary breast cancer development, promotes malignant breast cancer histopathologies, and shortens recurrence-free survival. In RPTPγ knockout mice, expression of Na+,HCO3--cotransporter NBCn1-a breast cancer susceptibility protein-is upregulated in normal breast tissue but, contrary to wild-type mice, shows no further increase during breast carcinogenesis. Associated augmentation of Na+,HCO3--cotransport in normal breast tissue from RPTPγ knockout mice elevates steady-state intracellular pH, which has known pro-proliferative effects. Loss of RPTPγ accelerates cellular net acid extrusion and elevates NBCn1 expression in breast tissue. As these effects precede neoplastic manifestations in histopathology, we propose that RPTPγ-dependent enhancement of Na+,HCO3--cotransport primes breast tissue for cancer development.

Timing of recurrence and overall survival in epithelial ovarian cancer: A 10-year retrospective review

Background: The timing of recurrence of epithelial ovarian cancer (EOC) after a standard primary treatment is an important indicator of the degree of response of the tumour to treatment. It, however, remains unclear if the timing of recurrence will predict survival outcomes. Aim: This study explored the impact of timing of recurrence after an initial response to standard primary treatment on the overall survival (OS) of patients with EOC. Methods: Data was extracted from the records of patients who underwent standard primary treatment and follow-up after EOC diagnosis between January 2011 and December 2020. The Kaplan-Meier survival estimates and Cox proportional hazards model adjusted for covariates were used for analyses. Results: The risks of recurrence of EOC increased steadily with increasing time from the start of primary treatment from 13.6% in 6-months to 71.0% after 12-months. In the final multivariate analyses, recurrence within 6 months of treatment was a significant independent predictor of poor OS in EOC patients (hazard ratio=7.23, 95%CI: 3.87–13.51, P&lt;0.01). Conclusion: Our study suggests that recurrence within 6-months is an important prognostic predictor of poor OS in EOC. Early tumour recurrence may be a useful surrogate of OS and thus this information should be considered in the design of future tailored randomized controlled trials. Future strategies to improve OS in EOC patients should focus on identifying effective measures to prevent early tumour recurrence.

Macrotrabecular-Massive Hepatocellular Carcinoma: Light and Shadow in Current Knowledge

The subject of this narrative review is macrotrabecular-massive hepatocellular carcinoma (MTM‐HCC). Despite their rarity, these tumours are of general interest because of their epidemiological and clinical features and for representing a distinct model of the interaction between the angiogenetic system and neoplastic cells. The MTM‐HCC subtype is associated with various adverse biological and pathological parameters (the Alfa-foetoprotein (AFP) serum level, tumour size, vascular invasion, and satellite nodules) and is a key determinant of patient prognosis, with a strong and independent predictive value for early and overall tumour recurrence. Gene expression profiling has demonstrated that angiogenesis activation is a hallmark feature of MTM-HCC, with overexpression of both angiopoietin 2 (ANGPT2) and vascular endothelial growth factor A (VEGFA).

Impact of pathological response after preoperative transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion and early tumor recurrence in hepatocellular carcinoma: a multicenter propensity score matching analysis.

To study the influence of pathological responses (PR) after transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion (MVI) and early recurrence in hepatocellular carcinoma (HCC) patients. Between 2013 to 2015, consecutive HCC patients who underwent liver resection with "curative" intent at three hospitals were enrolled in this study. Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI, early recurrence rates and patterns of recurrence before and after propensity score matching (PSM). Of 1,970 patients, 737 patients who received preoperative TACE were divided into three groups according to the areas of PR: ≥90% (n=226), 60-90% (n=447), and <60% (n=64). PR ≥90% was an independent protective factor of incidences of MVI [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.082-0.245, P<0.001) and early recurrence (HR, 0.742; 95% CI, 0.561-0.963, P=0.032); while PR<60% was an independent risk factor of incidences of MVI (OR, 6.076; 95% CI, 3.004-11.728, P<0.001) and early recurrence (HR, 1.428; 95% CI, 1.095-1.929; P=0.009). Furthermore, patients with PR <60% were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE. This study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence. Patients with PR <60% were at significantly higher risks of having more MVI, early and multiple tumor recurrences.

Guiding Value of Circulating Tumor Cells for Preoperative Transcatheter Arterial Embolization in Solitary Large Hepatocellular Carcinoma: A Single-Center Retrospective Clinical Study.

BackgroundLarge hepatocellular carcinoma (LHCC) is highly malignant and prone to recurrence, leading to a poor long-term prognosis for patients. There is an urgent need for measures to intervene in postoperative recurrence. Preoperative Transcatheter Arterial Embolization (TACE) is an effective treatment. However, there is a lack of reliable preoperative indicators to guide the application of preoperative TACE. We, therefore, investigated whether the preoperative status of circulating tumor cells (CTCs) could be used to guide preoperative TACE for HCC treatment.MethodsThis study recruited 361 HCC patients and compared recurrence-free survival (RFS) and overall survival (OS) in patients treated with TACE prior to surgery and those not treated with TACE. Patients were divided into CTC-positive group and CTC-negative group according to CTC status, and the effect of preoperative TACE on RFS and OS was compared in each subgroup.ResultsIn CTC-positive patients, preoperative TACE reduces early recurrence and improves long-term survival. However, HCC patients did not benefit from preoperative TACE for the overall population and CTC-negative patients.ConclusionsPreoperative CTC testing is a reliable indicator of whether HCC patients received TACE preoperatively. CTC positivity was associated with early tumor recurrence, and preoperative TACE could reduce early recurrence and long-term prognosis in CTC-positive patients.

MR elastography as a biomarker for prediction of early and late recurrence in HBV-related hepatocellular carcinoma patients before hepatectomy

PurposeTo investigate the diagnostic performance of preoperative MR elastography (MRE) in predicting early recurrence (ER) and late recurrence (LR) of HCC after hepatectomy. MethodIn total, 180 patients (median age, 52 years; interquartile range, 41–50 years; 161 men) who underwent conventional MRI and MRE before hepatectomy between December 2014 and April 2020 were retrospectively recruited. A preoperative clinic-radiologic model and a combined postoperative clinic-pathologic and radiologic model were built using quantitatively MRE-derived stiffnesses, and image features to predict tumor ER and LR after hepatectomy. The Cox proportional hazards model and ROC analyses were used to identify the value of parameters to predict ER and LR. ResultsSeventy-three (40.5%) and 16 (8.9%) developed ER and LR after hepatectomy, respectively. For prediction of ER, the preoperative model integrated higher tumor stiffness (TS) (hazard ratio [HR],1.142; p < 0.001) with AFP ≥ 400 ng/mL (HR,1.761; p = 0.022), multifocal tumors (HR,3.229; p < 0.001) and lower ADC (HR,0.998; p = 0.017) variables; and the postoperative model incorporated higher TS, microvascular invasion, multifocal tumors, Child-Pugh class and ADC predictors. The two models provided comparable predictive performance (pre- 0.812 vs. post- 0.834, p = 0.283). Moreover, TS alone had a high sensitivity (90.4%) for predicting ER. Liver stiffness (LS) (HR, 1.757; p < 0.001) was the only independent predictor for LR in multivariate analysis in both the pre- and postoperative models with high specificity (90.0%), and its AUC with an optimal cut-off of 3.62 kPa was 0.860. ConclusionsQuantitative MRE-based stiffness is a useful biomarker for preoperative prediction of ER and LR of HCC.

Acute-Phase Serum Amyloid A May Predict Microvascular Invasion and Early Tumor Recurrence in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma Undergoing Liver Resection

Objective To elucidate the impact of acute-phase protein serum amyloid A (aSAA) on microvascular invasion (MVI) and early recurrence in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods HBV-related HCC patients (n = 192) undergoing liver resection were included in the study. The protein levels of aSAA were analyzed by immunohistochemical staining in 172 tumor specimens, and further detected via western blotting in HCC and their corresponding portal vein tumor thrombus (PVTT) (n = 20). Cox and logit regression analysis was performed. Exploratory subgroup analysis was used to balance the potential confounders. Results HBV-related HCC patients with high aSAA levels tended to have high HBV-DNA loads. Logit and Cox regression analyses revealed high expression of aSAA is an independent risk factor not only for MVI (OR 5.384, 95% CI 2.286–13.301, P < 0.001) but also for early recurrence (HR 6.040, 95% CI 1.970–18.540, P = 0.002), overall recurrence (HR 3.720, 95% CI 2.140–6.450, P < 0.001), and overall survival (HR 4.15, 95% CI 2.380–7.230, P < 0.001). Subgroup analysis showed that the effects of aSAA were consistent across all subgroups examined. Additionally, the aSAA protein level was significantly higher in PVTT than that in its corresponding tumor specimen. A high HBV-DNA level and large tumor size were the independent risk factors for early HCC recurrence in patients with high levels of aSAA. Conclusions High expression of aSAA was an independent risk factor for MVI and early tumor recurrence in HBV-related HCC patients after liver resection. The aSAA protein level could thus be a promising biomarker for predicting MVI and early recurrence in these patients.