Presence Of Microvascular Invasion Research Articles

Validated preoperative computed tomography risk estimation for postoperative hepatocellular carcinoma recurrence.

AIMTo develop and validate a risk estimation of tumor recurrence following curative resection of operable hepatocellular carcinoma (HCC).METHODSData for 128 patients with operable HCC (according to Barcelona Clinic Liver Cancer imaging criteria) who underwent preoperative computed tomography (CT) evaluation at our hospital from May 1, 2013 through May 30, 2014 were included in this study. Follow-up data were obtained from hospital medical records. Follow-up data through May 30, 2016 were used to retrospectively analyze preoperative multiphasic CT findings, surgical histopathology results, and serum α-fetoprotein and thymidine kinase-1 levels. The χ2 test, independent t-test, and Mann-Whitney U test were used to analyze data. A P-value of < 0.05 was considered statistically significant.RESULTSDuring the follow-up period, 38 of 128 patients (29.7%) had a postoperative HCC recurrence. Microvascular invasion (MVI) was associated with HCC recurrence (χ2 = 13.253, P < 0.001). Despite postoperative antiviral therapy and chemotherapy, 22 of 44 patients with MVI experienced recurrence after surgical resection. The presence of MVI was 57.9% sensitive, 75.6% specific and 70.3% accurate in predicting postoperative recurrence. Of 84 tumors without MVI, univariate analysis confirmed that tumor margins, tumor margin grade, and tumor capsule detection on multiphasic CT were associated with HCC recurrence (P < 0.05). Univariate analyses showed no difference between groups with respect to hepatic capsular invasion, Ki-67 proliferation marker value, Edmondson-Steiner grade, largest tumor diameter, necrosis, arterial phase enhanced ratio, portovenous phase enhanced ratio, peritumoral enhancement, or serum α-fetoprotein level.CONCLUSIONNon-smooth tumor margins, incomplete tumor capsules and missing tumor capsules correlated with postoperative HCC recurrence. HCC recurrence following curative resection may be predicted using CT.

Utility of Serum Inflammatory Markers for Predicting Microvascular Invasion and Survival for Patients with Hepatocellular Carcinoma.

Preoperative serum inflammatory markers have been correlated with outcome after resection of hepatocellular carcinoma (HCC), but studies have had conflicting results. This study aimed to evaluate the association of six inflammatory markers with recurrence-free survival (RFS), overall survival (OS), and microvascular invasion (MVI), a well-known prognostic factor. This study investigated 370 patients who underwent resection of HCC from 1992 to 2016, retrospectively evaluating their inflammatory indices and individual components including their neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase-to-neutrophil ratio index (ANRI). Uni- and multivariate analyses were performed to evaluate these markers for RFS, OS, and MVI. The median RFS was 23months, and the median OS was 60months. Factors independently associated with worse RFS were higher PLR and alpha-fetoprotein level, male gender, and the presence of MVI as well as multiple nodules. Factors independently associated with worse OS were higher PLR and international normalized ratio, male gender, older age, presence of MVI and multiple nodules, larger tumor, presence of cirrhosis, and absence of steatosis. The study identified MVI in 47% of the patients. Lower level of albumin, higher level of alpha-fetoprotein, and larger tumor on preoperative imaging were independently associated with MVI. This largest Western series to evaluate the utility of preoperative inflammatory markers in patients with HCC found that only PLR was associated with RFS and OS and that albumin was associated with MVI.

Primary Living-donor Liver Transplantation Is Not the Optimal Treatment Choice in Patients With Early Hepatocellular Carcinoma With Poor Tumor Biology

ObjectiveLiver resection (LR) and living-donor liver transplantation (LDLT) are considered the two potentially curative treatments for hepatocellular carcinoma (HCC). The aim of this study was to investigate whether there is a difference in the oncologic outcomes between LR and LDLT according to tumor biology. MethodsPatients (137 LDLTs and 199 LRs) were stratified into four groups by tumor biology according to the number of risk factors for recurrence (preoperative alpha-fetoprotein >200 ng/mL, Edmonson grade 3 or 4, tumor size >3 cm, and presence of microvascular invasion). ResultsIn the favorable tumor biology patients (groups I and II), there was a significantly worse recurrence-free survival rate in those patients who underwent LR compared to those who underwent LDLT (group I, P = .002; group II, P = .001). The overall survival rates in the LR and LDLT groups were not different (group I, P = .798; group II, P = .981). In the poor tumor biology patients (groups III and IV), there was no significant difference between the two groups in terms of recurrence-free survival rate (group III, P = .342; group IV, P = .616). The LDLT group showed a significantly lower overall survival rate (group III, P = .001; group IV, P = .025). ConclusionsPrimary LDLT should not be recommended in early stage HCC patients with poor tumor biology because of lower survival rates and a high chance of HCC recurrence.

Usefulness of PIVKA-II After Living-donor Liver Transplantation for Hepatocellular Carcinoma

ObjectiveProthrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) is a useful tumor marker for hepatocellular carcinoma (HCC). However, the usefulness of post-transplantation surveillance with PIVKA-II is not clear. We evaluated the clinical value of PIVKA-II in monitoring HCC recurrence after living-donor liver transplantation (LDLT). MethodsOne hundred twenty patients who had undergone LDLT for HCC from February 1999 to December 2010 and whose serum alpha-fetoprotein (AFP) and PIVKA-II had been measured sequentially before and after LDLT were included in this study. Patients were classified into four groups according to the preoperative level of AFP and PIVKA-II (group I, normal AFP and PIVKA-II; group II, elevated AFP; group III, elevated PIVKA-II; and group IV, elevated both AFP and PIVKA-II). ResultsPreoperative PIVKA-II level tended to increase with increasing tumor size, number of nodules, presence of microvascular invasion, and poor differentiation. In 27 patients developing recurrent HCC after LDLT, the sensitivity of AFP and PIVKA-II was 59.2% and 88.8%, respectively. When the two markers were combined, the sensitivity increased to 92.5%. Especially, the sensitivity for PIVKA-II was high at groups I and III (100.0% for both, respectively). In patients in groups I, III, and IV, an elevated PIVKA-II level was the most common first sign of HCC recurrence after LDLT. An elevated PIVKA-II level was the most common first sign of recurrence, regardless of recurrence site. ConclusionsPIVKA-II might be a useful tumor marker in the monitoring of recurrence after LDLT, complementary to AFP.

Prognostic significance of combined albumin-bilirubin and tumor-node-metastasis staging system in patients who underwent hepatic resection for hepatocellular carcinoma.

In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin-bilirubin (ALBI) with tumor-node-metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan-Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival.

Hepatocellular carcinoma biology predicts survival outcome after liver transplantation in the USA.

The aim of this study is to evaluate the clinicopathologic prognostic factors of cancer-specific survival (CSS) in hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) stratified by tumor size. From the Surveillance, Epidemiology, and End Results (SEER) 18 registries (2004-2012), we retrieved data of 570 patients who underwent LT for a solitary primary HCC lesion ≤5cm. A two multivariable Cox models were constructed to identify prognostic factors of CSS in a two different tumor sizes (2cm cutoff). Out of 570 HCC patients (median age 57years), 16% had microvascular invasion (MVI) and 12% had a poorly differentiated tumor. Male sex (odds ratio [OR] 2.6), tumor size >2cm (OR 1.78), elevated AFP (OR 2.31), and poor tumor differentiation (OR 2.59) are significant predictors of MVI. With a median follow up of 41.5months (range 1-107months), the 5-year CSS rate was 90% in the absence of MVI compared to 75% in the presence of MVI (p<0.001). Multivariate models revealed that age ≥60years (hazard ratio [HR] 2.08), MVI (HR 2.26), and poor tumor differentiation (HR 2.42), were significant risk factors of a dismal CSS with HCC size >2cm, but not with HCC ≤2cm. Primary HCC tumor size ≤2cm had an excellent prognosis after LT and was not affect by the presence of MVI or poor tumor differentiation.

Combination of FDG-PET and UCSF Criteria for Predicting HCC Recurrence After Living Donor Liver Transplantation.

F-18 fluorodeoxyglucose (FDG) uptake in hepatocellular carcinoma (HCC) is related to tumor biology and has predictive value for tumor recurrence after liver transplantation. This retrospective study assessed whether the degree of FDG uptake in positron emission tomography (PET) can be used to predict HCC recurrence after living donor liver transplantation (LDLT). One hundred forty-seven patients with HCC underwent FDG-PET studies before LDLT. The semiquantification of FDG uptake in FDG-positive HCC was done with maximum standardized uptake value (SUVmax) and tumor to nontumor ratio (TNR). Recurrence-free survivals (RFS) were calculated using the Kaplan-Meier method. In univariable analysis, T stage, presence of microvascular invasion, being FDG-positive, SUVmax, and TNR were significant predictors for worse RFS. The optimal cutoff values of SUVmax and TNR were 4.8 and 2.0, respectively. The high FDG uptake HCC (TNR ≥ 2) was a strong predictor for worse RFS (hazard ratio, 13.52; 95% confidence interval, 4.77-38.29; P < 0.001). Using a combination of FDG-PET and University of California San Francisco (UCSF) criteria, the patients can be divided into low-risk (within UCSF criteria and FDG-negative), intermediate-risk (beyond UCSF criteria and FDG-negative; FDG-positive and TNR < 2), and high-risk (FDG-positive and TNR ≥ 2) groups. The estimated 5-year RFS in these groups were 85.5%, 83.9%, and 29.6% according to the combination of FDG-PET and clinical UCSF criteria, and 94.0%, 75.8%, and 29.6% according to the combination of FDG-PET and pathologic UCSF criteria, respectively. Combination of FDG-PET and UCSF criteria can be used to predict the risk of HCC recurrence after LDLT.

Impact of Histological Factors of Hepatocellular Carcinoma on the Outcome of Liver Transplantation.

The aim of this study was to identify predictors of overall survival (OS), disease-free survival (DFS), and recurrence in a cohort of 151 patients with hepatocellular carcinoma (HCC) and cirrhosis who were treated by liver transplantation (LT). A retrospective database of patients undergoing LT for radiologically diagnosed HCC at "12 de Octubre" Hospital, Madrid during 1986-2006 was analyzed. The median follow-up was 67.44 months (SD= 55.7 months). Overall 1-, 3-, 5-, and 10-year survival was 87.5%, 73.7%, 64.1% and 43.4%, respectively. The 5-year OS of patients beyond the Milan criteria was 47.14%, whereas that of patients within the Milan criteria was 70.13% (P= .011). The 5-year OS of patients beyond the Milan criteria and with microvascular invasion (MVI) was 27.27%, whereas that of patients beyond theMilan criteria and without MVI criteria was 57.89% (P= .003). Multivariate analysis of prognostic factors revealed MVI and G3 to be independent and statistically significant factors affecting OS (P< .0001 and P= .045, respectively), DFS (P< .0001 and P= .004, respectively), and recurrence (P= .0002 and P= .028, respectively). Multivariate analysis of prognostic factors also revealed preoperative fine-needle aspiration (FNA) to be an independent negative statistically significant factor affecting recurrence (P= .0022). Multivariate analysis of predictive MVI factors revealed preoperative α-fetoprotein (AFP) levels >200ng/mL to be an independent positive and statistically significant predictor of MVI (P= .0004). MVI and G3 are independent negative factors affecting OS, DFS, and recurrence. The presence of MVI or AFP levels >200ng/mL represent a contraindication for LT, as long as the patient is beyond the Milan criteria.

A Preoperative Measurement of Serum MicroRNA-125b May Predict the Presence of Microvascular Invasion in Hepatocellular Carcinomas Patients

The high recurrence rate remains a major problem that strongly influenced the prognosis of hepatocellular carcinoma (HCC) patients who received hepatectomy. The presence of microvascular invasion (MVI) is regarded as the most important risk factor that contributes to the postoperative recurrence. Our previous study has hinted that serum microRNA-125b (miR-125b) was associated with MVI. The aim of the present study was to identify whether serum miR-125b can serve as a biomarker to reliably predict microvascular invasion (MVI) preoperatively. MiR-125b was quantified in 108 HCC patients’ serum before they received surgery by quantitative real-time PCR (qRT-PCR). Our results revealed that MVI was associated with relapse free survival (RFS) of postoperative HCC patients; surgical margin width was associated with postoperative RFS in MVI present patients, but not in the patients without MVI. Multivariate analysis revealed that miR-125b, tumor size and AFP were the independent predictive factors associated with MVI in this cohort (P = .001, .001, .003, respectively). The probability of the predictive accuracy of miR-125b was 76.95% (51.32% specificity and 87.50% sensitivity), which was almost equal to the classifier established by combination of AFP and tumor size (78.82% probability, 65.63% specificity and 84.21% sensitivity). Furthermore, the combination of tumor size, AFP and miR-125b yielded a ROC curve area of 86.68% (72.37% specificity and 84.38% sensitivity). Our study indicated that serum miR-125b can be used to predict MVI of HCC patients before they received hepatic resection. Therefore, miR-125b can potentially guide individualized treatment, which helps HCC patients, with or without MVI, to benefit from different surgical approach.

Hepatic resection and prognosis for patients with single hepatocellular carcinoma larger than 5 cm

Purpose: This study aimed to determine the factors that affect on the prognosis of hepatic resection for HCC larger than 5 cm. Methods: A total of 421 patients underwent hepatic resection for the HCC at Keimyung University Dong-San Medical Center between January, 2001 and November, 2013, we analyzed 114 patients underwent resection with single HCC larger than 5 cm, retrospectively. Results: During median follow-up period was 26.4 months (range), 3- and 5- year disease-free survival rates of 42%, 30%. Iin univariate analysis, positive hepatitis B surface antigen, AFP of 2000 ng/mL or higher, PIVKA-II of 200 mIU/mL or higher, Edmonson grade III/IV, the presence of macrovascular invasion, the presence of microvascular invasion, and the presence of satellite nodule were all significant predictors of poor prognosis. However, tumor size larger than 10 cm and surgical margin status were not associated with a poor prognosis. In multivariate analysis, positive hepatitis B surface antigen, PIVKA-II 200 mIU/ml, macrovascular invasion, and microvascular invasion remained independent predictors of poor survival. Conclusion: After resection of the tumors larger than 5 cm in diameter, more restrict application of surveillance modalities, imaging studies and tumor markers, is recommended to detect earlier recurrence for the patients who have poor prognostic factors.

Prognostic Value of Lymph Node Ratio in Patients Receiving Combined Surgical Resection for Gastric Cancer Liver Metastasis: Results from Two National Centers in China.

The purpose of this study was to evaluate the prognostic value of lymph node ratio (LNR) in patients with gastric cancer liver metastasis (GCLM) who received combined surgical resection.A retrospective analysis of 46 patients from two hospitals was conducted. Patients were dichotomized into two groups (high LNR and low LNR) by the median value of LNR. The overall survival (OS) and recurrence-free survival (RFS) were analyzed by the Kaplan–Meier method with the log-rank test. The Cox proportional hazard model was used to carry out the subsequent multivariate analyses. And the relationship between LNR and clinicopathological characteristics was assessed.The cut-off value defining elevated LNR was 0.347. With a median follow-up of 67.5 months, the median OS and RFS of the patients were 17 and 9.5 months, respectively. Six patients survived for >5 years after surgery. Patients with higher LNR had significantly shorter OS and RFS than those with lower LNR. In the multivariate analyses, higher LNR and multiple liver metastatic tumors were identified as the independent prognostic factors for both OS and RFS. Elevated LNR was significantly associated with advanced pN stage (P <0.001), larger primary tumor size (P = 0.046), the presence of microvascular invasion (P = 0.008), and neoadjuvant chemotherapy (P = 0.004).LNR may be prognostic indicator for patients with GCLM treated by synchronous surgical resection. Patients with lower LNR and single liver metastasis may gain more survival benefits from the surgical resection. Further prospective studies with reasonable study design are warranted.

Nomogram for Preoperative Estimation of Microvascular Invasion Risk in Hepatitis B Virus-Related Hepatocellular Carcinoma Within the Milan Criteria.

The presence of microvascular invasion (MVI) decreases surgical outcomes of hepatocellular carcinoma (HCC). An accurate preoperative prediction of MVI can help surgeons to better choose surgical procedures, but accuracy is still difficult to achieve. To develop a nomogram to predict MVI presence before liver resection for hepatitis B virus (HBV)-related HCC within the Milan criteria (solitary nodule ≤5 cm; ≤3 nodules, none >3 cm; and no macrovascular invasion). Data on 1004 consecutive patients who underwent liver resection for HBV-related HCC within the Milan criteria at the Eastern Hepatobiliary Surgery Hospital between April 6, 2004, and February 22, 2011, were prospectively collected. Of these, patients who underwent surgery in an earlier period formed the training cohort (n = 707) for nomogram development, and those who underwent surgery thereafter formed the validation cohort (n = 297) to confirm the model's performance. Data analysis was conducted from August 1 to November 11, 2014. Liver resection for HCC. Overall survival and time to recurrence after liver resection were measured. Multivariate logistic regression was used to identify the independent risk factors associated with MVI that then were incorporated into the nomogram. Histopathologically identified MVI was found in 211 of 707 patients (29.8%) and 89 of 297 patients (30.0%) in the training and validation cohorts, respectively. In the training cohort, the 5-year recurrence and overall survival rates were 78.5% and 46.9%, respectively, in patients with MVI and 58.4%, and 70.9%, respectively, in patients without MVI (both P < .001). The preoperative factors associated with MVI were large tumor diameter, multiple nodules, incomplete capsule, α-fetoprotein level greater than 20 ng/mL, platelet count less than 100 × 103/µL, hepatitis B virus DNA load greater than 104 IU/mL, and a typical dynamic pattern of tumors on contrast-enhanced magnetic resonance imaging. Incorporating these 7 factors, the nomogram achieved good concordance indexes of 0.81 (95% CI, 0.78-0.85) and 0.80 (95% CI, 0.75-0.86) in predicting MVI in the training and validation cohorts, respectively, and had well-fitted calibration curves. The positive and negative predictive values (95% CIs) of the nomogram were calculated, resulting in positive predictive values of 57.2% (52.0%-64.9%) and 57.9% (49.2%-68.5%) and negative predictive values of 87.2% (83.2%-89.4%) and 83.2% (76.0%-87.7%) for the training and validation cohorts, respectively. Patients who had a nomogram score of less than 200 or 200 or greater were considered to have low or high risks of MVI presence, respectively. The nomogram achieved an optimal preoperative prediction of MVI in HBV-related HCC within the Milan criteria. Using the model, the risk for an individual patient to harbor MVI can be determined, which can lead to a rational therapeutic choice.

Molecular pathways associated with micro-vascular invasion HCC.

249 Background: Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) has a reported incidence of 15-57%. It is associated with decreased overall and recurrence free survival in post-surgical resection and transplant patients. Currently, the biology of MVI+ HCC remains unknown and the absence of effective adjuvant therapy limits management options to prevent recurrence. Aim: To correlate gene signatures observed at the transcriptomic level with the presence of MVI in HCC, analyze molecular pathways with gene expression tools and validate with TCGA database. Methods: Whole genome expression was studied in two groups of Asian resected HCC tumour specimens: (i) MVI present (MVI+) (n = 14) and (ii) MVI absent (MVI-) (n = 33) both without macrovascular invasion on radiological imaging. 2 distinct pathway analysis tools – gene set enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were performed to identify significantly enriched pathways potentially explaining the observed MVI+ HCC phenotype. Selected gene sets from the identified pathways were subjected to in-silico validation with TCGA data to confirm their enrichment within MVI+ HCC. Results: Within 14 MVI+ and 33 MVI- HCC studied, we have found a total of 1401 significantly differentially expressed genes between them; 766 genes were up-regulated and 635 genes were down-regulated in MVI+ HCC. At p &lt; 0.05 and FDR &lt; 0.25, GSEA and IPA analyses identified enrichment of PI3K/AKT/mTOR, HIF1α, AMPK signaling and actin-mediated cell kinetics pathways: actiny, Cdc42 signaling and actin pathways regulated by Rho. A 90 gene signature derived from these enriched pathways, created on the basis of biological function was used to compare between average expression within the MVI+ vs MVI- HCCs in the TCGA Asian cohort. Genes found differentially expressed at p &lt; 0.05 corresponded with the enriched pathways: actiny, AMPK signaling and PI3K/AKT/mTOR. Conclusions: These pathways underscore functions in regulation of cell metabolism, growth, proliferation, survival, protein synthesis and cytoskeleton organization in MVI+ HCC. Further studies in these pathways may assist in development of molecular targeted therapies for MVI+ HCC. We propose to carry out a prospective study to validate this.

Preoperative Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Prediction of Microvascular Invasion in Small Hepatocellular Carcinoma.

This study aimed to assess the value of preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) for predicting microvascular invasion (MVI) in small hepatocellular carcinoma (HCC). We retrospectively examined 60 patients who received F-FDG PET-CT prior to hepatic resection for small HCC (≤30 mm) with subsequent MVI confirmation by histopathology. The associations between PET-positive status and tumor factors were assessed. Furthermore, independent predictors for MVI and diagnostic utility of each MVI predictor were assessed. Multivariate analysis revealed the presence of MVI as an independent predictor of PET-positive status (P = 0.023). Maximum standardized uptake value (SUVmax) of 3.2 or greater (P = 0.017) and lens culinaris agglutinin a-reactive α-fetoprotein (AFP-L3) 19% or greater (P = 0.010) were independent predictors of MVI. Areas under the receiver operating characteristic curves for SUVmax of 3.2 or greater, AFP-L3 19% or greater, and both factors combined for predicting MVI were 0.712 (0.493-0.932), 0.755 (0.563-0.947), and 0.856 (0.721-0.991), respectively. The sensitivity and specificity for predicting MVI were 77.8% and 74.5% for SUVmax of 3.2 or greater, 66.7% and 84.3% for AFP-L3 19% or greater, and 88.9% and 82.4% for the combination. F-FDG PET-CT and AFP-L3 may be useful for predicting MVI in small HCC, and the combination of the 2 factors provided reliable assessment for selection of suitable hepatic resection and liver transplantation candidates.

Can Current Preoperative Imaging Be Used to Detect Microvascular Invasion of Hepatocellular Carcinoma?

To determine the accuracy of imaging features, such as tumor dimension, multinodularity, nonsmooth tumor margins, peritumoral enhancement, and radiogenomic algorithm based on the association between imaging features (internal arteries and hypoattenuating halos) and gene expression that the authors called two-trait predictor of venous invasion (TTPVI), in the prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This single-center retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. One hundred twenty-five patients (median age, 63 years; interquartile range, 53-71 years) with a diagnosis of HCC and indications for hepatic resection were included. Two observers independently reviewed radiologic images to evaluate the following features for MVI: maximum diameter, number of lesions, tumor margins, TTPVI, and peritumoral enhancement. Interobserver agreement was checked, and diagnostic accuracy of radiologic features was investigated. The total number of HCC nodules was 140. Large tumor size, nonsmooth tumor margins, TTPVI, and peritumoral enhancement were significantly related to the presence of MVI (P < .05 in all cases and for both observers). Multinodularity was not significantly related (P = .158). Moreover, the diagnostic accuracy of the three "worrisome" radiologic features (nonsmooth tumor margins, peritumoral enhancement, and TTPVI) was associated with tumor size: The negative predictive value of the absence of worrisome features decreased from 0.84 for observer 1 and 0.91 for observer 2 for tumors smaller than 2 cm to 0.56 and 0.71, respectively, for tumors larger than 5 cm, whereas the presence of all three worrisome features returned to a positive predictive value of 0.95 for observer 1 and 0.96 for observer 2 independent of tumor size, with no significant interobserver differences (P > .10). "Worrisome" imaging features, such as tumor dimension, nonsmooth tumor margins, peritumoral enhancement, and TTPVI, have high accuracy in the prediction of MVI in HCC.

Second Hepatectomy Improves Survival in Patients With Microvascular Invasive Hepatocellular Carcinoma Meeting the Milan Criteria.

Microvascular invasion (MVI) is a strong risk factor for patients with hepatocellular carcinoma (HCC) meeting the Milan criteria and who have received curative hepatectomy. The relevance of a second hepatectomy in patients with MVI-positive recurrent HCC remains controversial.We had 329 cases of HCC hepatectomy meeting the Milan criteria and compared data on patient demographics, liver function, and tumor pathology between MVI-positive and MVI-negative group. We analyzed potential risk factors of overall survival (OS) and disease-free survival (DFS). Furthermore, newly developed pathological features following the second hepatectomy were also analyzed.The median OS and DFS were significantly superior in the MVI-negative group than in the MVI-positive group, 61 (10–81) versus 49 (11–82) months (P < 0.01) and 41 (7–75) versus 13 (3–69) months (P < 0.01), respectively. The presence of MVI and a total tumor diameter >3 cm were independent risk factors associated with both OS and DFS. Overall survival was significantly improved by a second hepatectomy in the MVI-positive group compared with the original MVI-positive group, 60 (26–82) versus 49 (11–82) months, respectively. This was now comparable to the MVI-negative group, 60 (26–82) versus 61 (10–81) months (P = 0.72). A second hepatectomy was consistently associated with better survival in the MVI-negative group as compared to the MVI-positive group.A second hepatectomy improves survival in patients with MVI HCC meeting the Milan criteria. The biology of MVI may change following a second hepatectomy. The absence of MVI is a good prognostic sign for patients undergoing second hepatectomy.

The significance of microvascular invasion after complete resection of early-stage non-small-cell lung cancer.

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'in patients with non-small-cell lung cancer who have undergone complete resection, does the presence of microvascular invasion (MVI) significantly impact long-term survival or prognosis?' Altogether, more than 250 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. Outcome parameters that were used in the assessment include 5-year overall survival, event-free or recurrence-free survival (RFS) and incidence of metastatic relapse. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. The majority of the data collected were retrospective. Meta-analysis of data of over 16 000 patients showed that when considering RFS, MVI positivity was associated with a significantly reduced period of RFS; pooled hazard ratio estimates by univariate and multivariate analyses were 3.28 (95% CI 2.14-5.05; P < 0.0001) and 3.98 (95% CI 2.24-7.06; P < 0.0001), respectively. Eight of the studies showed a significantly worse 5-year survival in the presence of MVI, whereas a further study found a reduced median survival with MVI. One study showed no difference, but concurred with five other studies that MVI was associated with a significantly shorter event-free or RFS. Multivariate analyses have furthermore demonstrated that MVI positivity correlates with larger tumour size, an increased risk of distant metastases, visceral pleural involvement, lymphovascular invasion, higher tumour grade and nodal status. We conclude that the presence of microvascular invasion in resected early-stage non-small-cell lung cancer is a negative prognostic factor.

Follow-up Imaging After Liver Transplantation Should Take Into Consideration Primary Hepatocellular Carcinoma Characteristics.

Tumor recurrence occurs in almost 10% after liver transplantation (LT) for early stage hepatocellular carcinoma (HCC). Evidence-based recommendation regarding these techniques and their schedule remains unclear. The aim was to analyze the imaging characteristics of HCC recurrence after LT according to the initial primary tumor characteristics to provide relevant evidence regarding their role. Among 336 cirrhotic patients undergoing LT between 2000 and 2011, 25 (7.4%) experienced HCC recurrence. Their pre-LT characteristics, long-term outcome and imaging characteristics of recurrences were retrospectively analyzed. All patients were men and median age at the time of recurrence was 54 (41-64) years. Before LT, 13 (52%) patients had HCC outside the Milan criteria. Median time to HCC recurrence was 13.8 months (1-75) after LT and 8 patients (32%) experienced recurrence longer than 24 months after LT. The most frequently involved organs were the lungs (n = 13, 52%) and the bones (n = 9, 36%). Recurrent HCC involved more than 1 organ in 11 patients (44%). Recurrences were limited to the liver in 1 patient (4%), exclusively extrahepatic in 18 patients (72%), and were both intra and extrahepatic in 6 patients (24%). Delay of recurrence was shorter in the presence of microvascular invasion (17 vs 28 months), but this was not significant (P = 0.208). Poorly differentiated tumors showed a trend toward decreased recurrence-free survival (8 vs 28 months, P = 0.075). Both pattern and delay of HCC recurrence support performing regular whole-body imaging initially every 6 to 12 months and continuing beyond 2 years after LT for HCC, especially in patients with pejorative pathological features of the primary tumor that could influence HCC recurrence pattern.

Intrahepatic, peri-hilar and distal cholangiocarcinoma: Three different locations of the same tumor or three different tumors?

BackgroundFew papers deal with pathologic characteristics and outcome of the 3 different cholangiocarcinomas based on location (intrahepatic, peri-hilar, distal). There is little evidence regarding similarity and differences. Patients and MethodsFrom two tertiary referral Italian Centers (in Bologna and Verona), 479 patients with cholangiocarcinoma were evaluated between 1980 and 2011. Several pathologic characteristics and their impact on survival were analyzed among resected patients for cholangiocarcinomas depending on the site of origin. ResultsTumour location was intrahepatic in 172 cases (36%), peri-hilar in 243 (51) and distal in 64(13%). Curative resection was performed in 339 (70%) patients. Intrahepatic cholangiocarcinoma showed higher probability to achieve R0 resection (81%), but was more frequently associated with presence of microvascular invasion (71%). Distal cholangiocarcinoma presented less R0 resections (58%), higher lymphnode involvement (60%) and lower microvascular invasion (49%). Hilar cholangiocarcinoma had intermediate characteristics (R0: 65% of cases). Median follow up was 30.2 ± 38 months; the 5 years overall survival was 31% in the resected population. Overall survival curves were similar among the three groups. At univariate analysis surgical margins, lymphnode status, perineural invasion, T category, TNM stage, microvascular invasion, tumour grading had significant impact on survival. At multivariate analysis, only microvascular invasion was significantly related to long term results (HR = 1,7; 95% CI = 1,0–2,5)”. ConclusionMicro-vascular invasion has the strongest impact on survival in all three types of cholangiocarcinoma. In case of comparable pathologic characteristics and stage, the three tumors show similar outcome; depending on location, it shows a different tendency to invade bordering structures which affect the outcome.

Risk factors and management for early and late intrahepatic recurrence of solitary hepatocellular carcinoma after curative resection

BackgroundIntrahepatic recurrence is a significant problem for patients who have undergone a hepatic resection for hepatocellular carcinoma (HCC). The objective of the present study was to identify risk factors and evaluate the management of early and late recurrence of solitary HCC after curative resection. MethodsIncluded in this study were 816 patients with solitary HCC who underwent a curative partial hepatectomy. Intrahepatic recurrence in these patients was followed up retrospectively. Prognosis and therapy for the recurrence were investigated and analysed. ResultsEarly and late intrahepatic recurrence occurred in 423 patients and 199 patients, respectively. Multivariate analysis showed that a tumour diameter >5 cm, the absence of a tumour capsule and the presence of microvascular invasion were correlated with early recurrence, whereas cirrhosis and alphafetal protein >400 μg/l were independent risk factors contributing to late recurrence. The 5year survival of HCC patients with early recurrence was significantly lower than that of patients with late recurrence. Further curative treatment for intrahepatic recurrence offered a 5year overall survival of 56.0%, which was better than alternative management. ConclusionEarly and late recurrences of solitary HCC after curative resection are associated with different predictive factors. The time to recurrence and further curative treatment after recurrence were the best predictors of survival post recurrence.