Molecular detection of lymph node metastasis in breast cancer patients treated with preoperative systemic chemotherapy: a prospective multicentre trial using the one-step nucleic acid amplification assay

Background:

For patients with breast cancer treated with preoperative chemotherapy, residual tumour burden in lymph nodes is the strongest prognostic factor. However, conventional pathological examination has limitations that hinder the accurate and reproducible measurement. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method for detecting nodal metastasis. In this prospective multicentre trial, we assessed the performance of the OSNA assay in detecting nodal metastasis after chemotherapy.

Methods:

In total, 302 lymph nodes from 80 breast cancer patients who underwent axillary dissection after chemotherapy were analysed. Each node was cut into two or four slices. One piece or alternate pieces were evaluated by pathology, and the other(s) were examined using the OSNA assay. The results of the two methods were compared. Stromal fibrosis, histiocytic aggregates, and degenerated cancer cells were regarded as chemotherapy-induced histological changes.

Results:

The overall accuracy, sensitivity, and specificity of the OSNA assay compared with the reference pathology were 91.1%, 88.3%, and 91.7%, respectively. Of the 302 lymph nodes, 66 (21.9%) exhibited chemotherapy-induced histology. For these nodes, the accuracy, sensitivity, and specificity were 90.9%, 88.9%, and 93.3%, respectively.

Conclusion:

The OSNA assay can detect the residual tumour burden as accurately as conventional pathology, although chemotherapy-induced histological changes are present.     

Incidence and possible pathogenesis of sentinel node micrometastases in ductal carcinoma in situ of the breast detected using molecular whole lymph node assay

Background:

The pathogenesis of lymph node metastases in preinvasive breast cancer – ductal carcinoma in situ (DCIS) – remains controversial. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can assess a whole node and detect clinically relevant metastases. In this retrospective cohort study, we determined the performance of the OSNA assay in DCIS and the pathogenesis of node-positive DCIS.

Methods:

The subjects consisted of 623 patients with DCIS who underwent sentinel lymph node (SN) biopsy. Of these, 2-mm-sectioned nodes were examined using frozen-section (FS) histology in 338 patients between 2007 and 2009, while 285 underwent OSNA whole node assays between 2009 and 2011. The SN-positivity rate was compared between cohorts, and the characteristics of OSNA-positive DCIS were investigated.

Results:

The OSNA detected more cases of SN metastases than FS histology (12 out of 285, 4.2% vs 1 out of 338, 0.3%). Most of the metastases were micrometastases. The characteristics of high-risk DCIS (i.e., mass formation, size, grade, and comedo) and preoperative breast biopsy (i.e., methods or time to surgery) were not valid for OSNA assay–positive DCIS.

Conclusion:

The OSNA detects more SN metastases in DCIS than FS histology. Further examination of the primary tumours and follow-up of node-positive DCIS are needed to elucidate the pathogenesis.     

Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer

Background:

The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases.

Methods:

Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or ⩾4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis.

Results:

In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and ++ was 19.3% and 53.4%, respectively, and that in patients with ⩾4 LN metastases who were OSNA+ and ++ was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (⩾5.0 × 10³; OSNA++) in the SLN was the most significant predictors of non-SLN metastases (P=0.003). The CK19 mRNA copy number (⩾1.0 × 10⁵) in the SLN was the only independent predictor of ⩾4 LN metastases (P=0.014).

Conclusion:

Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and ⩾4 LN metastases.     

Population-based comparison of prognostic factors in invasive micropapillary and invasive ductal carcinoma of the breast

Background:

Invasive micropapillary carcinoma (IMPC) is a variant of breast carcinoma with a higher propensity for lymph node metastases compared with invasive ductal carcinoma (IDC).

Methods:

Retrospective analysis of 636 IMPC and 297 735 IDC cases in the Surveillance, Epidemiology and End Results database comparing disease-specific survival (DSS) and overall survival (OS) between IMPC and IDC.

Results:

A higher percentage of IMPC cases (52.0%) had nodal metastases compared with IDC cases (34.6%). The 5-year DSS and OS for IMPC was 91.8% and 82.9%, respectively compared with 88.6% and 80.5% for IDC, respectively. For both IMPC and IDC, oestrogen-receptor positivity was associated with better survival, while having four or more positive lymph nodes or larger tumour size correlated with worse survival. Radiotherapy provided a survival benefit for both histological types.

Conclusions:

Despite IMPC''s higher propensity for lymph node metastasis, IMPC has DSS and OS that compare favourably with IDC.     

Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment

Background:

Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status.

Methods:

We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes.

Results:

In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1–6 nodes in cT1 and 6–8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively.

Conclusions:

Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.     

Clinical relevance of lymph node ratio in breast cancer patients with one to three positive lymph nodes

Background:

To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT).

Methods:

Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR).

Results:

Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17–0.89; P=0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT.

Conclusion:

This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.     

Contribution of pelvic and para-aortic lymphadenectomy with sentinel node biopsy in patients with IB2-IIB cervical cancer

Objective:

Detection of lymph node involvement in women with IB2–IIB cervical cancer could have a positive effect on survival. We set out to evaluate the incidence of pelvic and/or para-aortic lymph node involvement using the sentinel node (SN) biopsy and its impact on survival.

Methods:

From 2002 to 2010, 66 women with IB2–IIB cervical cancer underwent a pelvic and paraaortic lymphadenectomy with SN biopsy. Survival between groups according to lymph node status was evaluated.

Results:

Mean tumour size was 43.5 mm. At least one SN was detected in 69% of the 45 SN procedures performed. Sixteen of these patients had metastatic SN and the false negative rate was 20%. Metastatic pelvic SNs or non-SNs were detected in 33 patients (50%), including pelvic-positive nodes in 26 (40%), pelvic- and paraaortic-positive lymph nodes in seven (11%), and paraaortic skip metastases in two (6%). Positive paraaortic node was the sole determinant for disease-free survival (DFS) and overall survival (OS; P<0.001). Differences in DFS and OS between groups according to the nodal status were observed (P<0.001).

Conclusion:

SN procedure gave a higher rate of metastasis detection. Further studies are required to evaluate whether pre-therapeutic node staging, including paraaortic and pelvic lymphanedectomy, should be performed.     

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research

Background:

Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.

Methods:

The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.

Results:

The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND⩽0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.

Conclusion:

This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.     

Value of staging squamous cell carcinoma of the anal margin and canal using the sentinel lymph node procedure: an update of the series and a review of the literature

Background:

Inguinal metastases in patients affected by anal cancer are an independent prognostic factor for local failure and overall mortality. Since 2001, sentinel lymph node biopsy was applied in these patients. This original study reports an update of personal and previous published series, which were compared with Literature to value the incidence of inguinal metastases T-stage related and the overall incidence of false negative inguinal metastases at sentinel node.

Methods:

In all, 63 patients diagnosed with anal cancer submitted to inguinal sentinel node. Furthermore a research in the Pub Med database was performed to find papers regarding this technique.

Results:

In our series, detection rate was 98.4%. Inguinal metastases were evidentiated in 13 patients (20.6%). Our median follow-up was 35 months. In our series, no false negative nodes were observed.

Conclusion:

Sentinel node technique in the detection of inguinal metastases in patients affected by anal cancer should be considered as a standard of care. It is indicated for all T stages in order to select patients to be submitted to inguinal radiotherapy, avoiding related morbidity in negative ones. An overall 3.7% rate of false negative must be considered acceptable.     

The impact of positive peritoneal cytology on prognosis in patients with cervical cancer: a meta-analysis

Background:

The impact of positive peritoneal cytology on the prognosis of cervical cancer is controversial. Thus, we performed a meta-analysis to determine its impact on recurrence, and to investigate correlations between abnormal cytology and/or lymph node metastasis in cervical cancer.

Methods:

A systematic literature review was conducted through July 2014. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated by standard meta-analysis techniques with the fixed-effects models, if there was no significant statistical heterogeneity across studies by using I².

Results:

Of 303 studies retrieved, 6 were included in the meta-analysis. These six case–control observational studies included 1360 cervical cancer patients who showed negative peritoneal cytology and 64 who showed positive peritoneal cytology. Over the combined study period, 20 of 45 in the positive peritoneal cytology group experienced recurrence, whereas 88 of 539 controls did. The meta-analysis based on the fixed-effects model indicated a significant increase in the risk of recurrence in the positive peritoneal cytology group relative to the control group (OR: 4.47; 95% CI: 2.33–8.58, P<0.001, I²=0.0%). Moreover, the results of our meta-analysis suggested that the positive peritoneal cytology group displayed more lymph node metastasis than the negative peritoneal cytology group (OR: 3.73; 95% CI: 2.13–6.53, P<0.001, I²=0.0%).

Conclusions:

Although based mainly on retrospective observational studies, our meta-analysis indicates that abnormal peritoneal cytology may be strongly associated with poor prognosis in patients with cervical cancer. Future research should verify this relationship through prospective observational studies over a longer term.     

Identification of pathologically insignificant prostate cancer is not accurate in unscreened men

Background:

Identification of men harbouring insignificant prostate cancer (PC) is important in selecting patients for active surveillance. Tools have been developed in PSA-screened populations to identify such men based on clinical and biopsy parameters.

Methods:

Prospectively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre. Tumour volume was assessed by pathological examination. For each tool, receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared. Comparison of accuracy in screened and unscreened populations was performed.

Results:

Of 848 patients, 415 had Gleason 3+3 disease on biopsy. Of these, 32.0% had extra-prostatic extension and 50.2% were upgraded. One had positive lymph nodes. Two hundred and six (24% of cohort) were D''Amico low risk. Of these, 143 had more than two biopsy cores involved. None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden. Accuracy is low in PSA-screened and -unscreened populations.

Conclusions:

In our unscreened population, tools designed to identify insignificant PC are inaccurate. Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy.     

Outcomes after radical hysterectomy in patients with early-stage adenocarcinoma of uterine cervix

Background:

To determine the prognostic factors and treatment outcomes of patients with early-stage adenocarcinoma (AdCa) of uterine cervix who underwent radical hysterectomy (RH).

Methods:

Patients with early-stage squamous cell carcinoma (SCCa) of the uterine cervix who underwent RH were compared with patients with AdCa by multivariate analysis.

Results:

A total of 1218 patients were eligible, of which 996 (81.8%) had SCCa and 222 (18.2%) had AdCa. In multivariate analysis, parametrial involvement and lymph node metastasis were significant factors for both recurrence-free survival(RFS) and overall survival (OS) of patients with AdCa, whereas age, tumour size, parametrial involvement and lymph node metastasis were significant factors for both RFS and OS of patients with SCCa. After adjusting for significant prognostic factors, patients with AdCa had significantly poorer RFS (odds ratio (OR)=2.07, 95% confidence interval (CI)=1.37–3.12, P=0.001) and OS (OR=2.56, 95% CI=1.65–3.96, P<0.001) than patients with SCCa. Recurrence outside the pelvis was more frequent in AdCa than in those with SCCa (75 vs 57.8%, P=0.084).

Conclusion(s):

Although RH is still acceptable for treatment of patients with AdCa, a more effective systemic adjuvant therapy is required.     

Spindle cell morphology is related to poor prognosis in vulvar squamous cell carcinoma

Background:

Vulvar cancer is the fourth most common gynaecological malignancy, with an annual incidence of 2 out of 100 000 women. Although most cases of early stage vulvar cancer have a good prognosis, recurrence and rapid tumour progression can occur. We investigated the prevalence of spindle cell morphology in vulvar cancer and its association with survival.

Methods:

This retrospective cohort study included 108 patients with primary vulvar squamous cell carcinoma who were treated at the Leiden University Medical Center during 2000–2009. Paraffin-embedded tissue was examined for the presence of spindle cell morphology. Survival and histology data were compared between cases with spindle and without spindle cell morphology.

Results:

Twenty-two (20%) tumours showed spindle cells infiltrating the stromal tissue. All spindle cell tumours were human papillomavirus (HPV) negative. Spindle cell morphology was strongly associated with poor prognosis and with a high risk of lymph node involvement at the time of diagnosis (relative risk 2.26 (95% CI 1.47–3.47)). Five-year disease-specific survival was lower in patients with vs without spindle cell morphology (45.2% vs 79.7%, respectively; P=0.00057).

Conclusion:

Vulvar spindle cell morphology occurs frequently and seems to develop through the non-HPV pathway. It is associated with a worse prognosis than conventional vulvar squamous cell carcinoma.     

Lymph node tissue kallikrein-related peptidase 6 mRNA: a progression marker for colorectal cancer

Background:

A most important characteristic feature for poor prognosis in colorectal cancer (CRC) is the presence of lymph node metastasis. Determination of carcinoembryonic antigen (CEA) mRNA levels in lymph nodes has proven powerful for quantification of disseminated tumour cells. Here, we investigate the utility of human tissue kallikrein-related peptidase 6 (KLK6) mRNA as a progression biomarker to complement CEA mRNA, for improved selection of patients in need of adjuvant therapy and intensified follow-up after surgery.

Methods:

Lymph nodes of pTNM stage I-IV CRC- (166 patients/503 lymph nodes) and control (23/108) patients were collected at surgery and analysed by quantitative RT–PCR.

Results:

Lymph node KLK6 positivity was an indicator of poor outcome (hazard ratio 3.7). Risk of recurrence and cancer death increased with KLK6 lymph node levels. Patients with KLK6 lymph node levels above the 90th percentile had a hazard ratio of 6.5 and 76 months shorter average survival time compared to patients with KLK6 negative nodes. The KLK6 positivity in lymph nodes with few tumour cells, that is, low CEA mRNA levels, also indicated poor prognosis (hazard ratio 2.8).

Conclusion:

In CRC patients, lymph node KLK6 positivity indicated presence of aggressive tumour cells associated with poor prognosis and high risk of tumour recurrence.     

DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer

Background:

Preoperative risk stratification is essential in tailoring endometrial cancer treatment, and biomarkers predicting lymph node metastasis and aggressive disease are aspired in clinical practice. DNA ploidy assessment in hysterectomy specimens is a well-established prognostic marker. DNA ploidy assessment in preoperative curettage specimens is less studied, and in particular in relation to the occurrence of lymph node metastasis.

Methods:

Curettage image cytometry DNA ploidy in relation to established clinicopathological variables and outcome was investigated in 785 endometrial carcinoma patients prospectively included in the MoMaTEC multicentre trial.

Results:

Diploid curettage status was found in 72.0%, whereas 28.0% were non-diploid. Non-diploid status significantly correlated with traditional aggressive postoperative clinicopathological features, and was an independent predictor of lymph node metastasis among FIGO stage I–III patients in multivariate analysis (OR 1.94, P=0.033). Non-diploid status was related to shorter disease-specific survival (5-year DSS of 74.4% vs 88.8% for diploid curettage, P<0.001). When stratifying by FIGO stage and lymph node status, the prognostic effect remained. However, in multivariate regression analysis, preoperative histological risk classification was a stronger predictor of DSS than DNA ploidy.

Conclusions:

Non-diploid curettage is significantly associated with aggressive clinicopathological phenotype, lymph node metastasis, and poor survival in endometrial cancer. The prognostic effect was also observed among subgroups with (presumably) less aggressive traits, such as low FIGO stage and negative lymph node status. Our results indicate curettage DNA ploidy as a possible supplement to existing parameters used to tailor surgical treatment.     

Statin use is not associated with reduced risk of skin cancer: a meta-analysis

Background:

There is contradictory evidence about the association between statin and skin cancer.

Methods:

Literature search in PubMed and Web of Science was undertaken up to June 2013. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated.

Result:

A total of 21 articles with 29 studies were identified. No association was found between statin and skin cancer among neither melanoma (RR, 0.94; 95% CI, 0.85–1.04) nor non-melanoma skin cancer (RR, 1.03; 95% CI, 0.90–1.19).

Conclusion:

Our meta-analysis does not support a potential role of statin use in the prevention of skin cancer.     

The impact of lymph node density on survival of cervical cancer patients

Background:

To evaluate the prognostic value of lymph node density (LND) in patients with lymph node-positive cervical cancer.

Methods:

A total of 88 consecutive patients were included in our study. Patients were treated with cisplatin-based concomitant chemoradiotherapy after surgical staging was performed at the Medical University of Vienna. Lymph node density, that is, the ratio of positive lymph nodes to the total number of lymph nodes removed, was assessed pathologically. Patients were stratified into two groups according to LND: patients with LND ⩽10% and patients with LND >10%. Lymph node density was correlated with clinicopathological parameters by χ²-tests. Univariate log-rank tests and multivariate Cox regression models were used to evaluate the association between LND and survival.

Results:

A significant correlation between LND and FIGO stage (P=0.03), but not patients'' age (P=0.2), histological grade (P=0.8), and histological type (P=0.5), was observed. In a univariate survival analysis, LND (P=0.01; P=0.01), FIGO stage (P=0.01; P=0.008), and histological grade (P=0.03; P=0.04) were associated with disease-free and overall survival, respectively. Patients with LND >10% had impaired disease-free and overall survival rates compared with patients with LND ⩽10%. In a multivariate regression model, LND (P=0.01; P<0.05) and FIGO stage (P=0.002; P=0.002) were independent predictors of disease-free and overall survival, respectively.

Conclusions:

LND >10% is associated with an impaired disease-free and overall survival. Lymph node density may be used as an independent prognostic parameter in patients with lymph node-positive cervical cancer.     

Cost-effectiveness of sentinel lymph node biopsy vs inguinofemoral lymphadenectomy in women with vulval cancer

Background:

This study examines the cost-effectiveness of sentinel lymph node biopsy, a potentially less morbid procedure, compared with inguinofemoral lymphadenectomy (IFL) among women with stage I and stage II vulval squamous cell carcinoma.

Methods:

A model-based economic evaluation was undertaken based on clinical evidence from a systematic review of published sources. A decision tree model was developed with the structure being informed by clinical input, taking the perspective of the health-care provider.

Results:

For overall survival for 2 years, IFL was found to be the most cost-effective option and dominated all other strategies, being the least costly and most effective. For morbidity-free related outcomes for 2 years, sentinel lymph node (SLN) biopsy with 99mTc and blue dye and haematoxylin & eosin (H&E) histopathology, with ultrastaging and immunohistochemistry reserved for those that test negative following H&E is likely to be the most effective approach.

Conclusion:

SLN biopsy using 99mTc and blue dye with ultrastaging may be considered the most cost-effective strategy based on the outcome of survival free of morbidity for 2 years. The findings here also indicate that using blue dye and H&E for the identification of the SLN and the identification of metastasis, respectively, are not sensitive enough to be used on their own.     

HCC-ART score,a simple,highly sensitive and specific test for early diagnosis of hepatocellular carcinoma: a large-scale,multicentre study

Background:

A simple scoring system is needed to discriminate HCC from patients with chronic liver diseases (CLD). The simplest score would be one that requires only variables that can be documented simply from routine laboratory tests without the need for sophisticated tests.

Methods:

Data from the estimation group (1351 patients) and the validation group (2208 patients) were retrospectively analysed. Liver fibrosis-negative control and liver cirrhosis were compared with HCC. Area under ROC curve (AUC) were used to develop HCC-α-fetoprotein-routine test (HCC-ART).

Results:

Hepatocellular carcinoma-AFP-routine test showed diagnostic accuracy for liver cirrhosis vs HCC with ROC curves of 0.99%, sensitivity of 97%, and specificity of 96% in the estimation, and 0.95%, 90%, and 83%, respectively, in the validation. Sensitivity (97%) and specificity (100%) were obtained to discriminate HCC from liver fibrosis. Area under curve for AFP at 400 U l⁻¹ was 0.70, sensitivity was 41%, and specificity was 99% in the estimation, and 0.77%, 54%, and 99%, respectively, in the validation. The AUC for HCC-ART in HCC with single tumour, absent vascular invasion, size <2 cm and CLIP score (0–1) were 0.95, 0.93, 0.86, 0.87, respectively, compared with 0.72, 0.71, 0.71, 0.50, respectively, for AFP.

Conclusion:

Hepatocellular carcinoma-AFP-routine test could increase the accuracy of HCC screening and surveillances and could be used worldwide without extra efforts.