Presence Of Microscopic Vascular Invasion Research Articles

Early and late recurrence of surgically resected hepatitis B virus-related hepatocellular carcinoma on nucleos(t)ide analogues therapy

Hepatocellular carcinoma (HCC) is a highly recurrent tumor. Antiviral therapy with nucleos(t)ide analogues (NUCs) may reduce the risk of recurrence in hepatitis B virus (HBV)-related HCC. The risk factors associated with recurrence in HCC patients after surgical resection and with NUCs treatment should be delineated. Consecutive 339 HBV-related HCC patients receiving surgical resection of HCC with NUCs therapy (including 256 entecavir, 36 tenofovir, and 18 lamivudine) after the surgery were retrospectively reviewed. Factors related to the recurrence-free survival (RFS) and overall survival (OS) were evaluated. After a median of 48.5 months of follow-up, 183 (54%) patients developed HCC recurrence, with the 5-year RFS of 42.8% and OS of 79%. Male gender (HR=1.736, p=0.037), baseline HBsAg level >200 IU/ml (HR=1.748, p=0.008), platelet count ≦100 (109/L) (HR=1.592, p=0.023), presence of microscopic vascular invasion (MVI) (HR=1.499, p=0.026), safety cut margin of ≦0.5cm (HR=1.507, p=0.013), and Ishak fibrosis score 5-6 (HR=1.579, p=0.009) were independent factors associated with RFS in multivariate analysis. While tumor burden, platelet count, MVI, and safety cut margin were factors associated with early recurrence; baseline HBsAg level, and platelet count were independent factors associated with late recurrence. Ishak fibrosis score 5-6, poor differentiation, MVI, diabetes mellitus were factors associated with OS in multivariate analysis. For HBV-HCC patients on NUCs treatment, tumor factors are associated with early recurrence, while HBsAg level and thrombocytopenia determines late recurrence. For patient with a high baseline HBsAg level, warning of higher risk of recurrence is required even under NUCs treatment.

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Renal cell carcinoma (RCC) accounts for 2%–3% of all adultmalignancies, representing the seventh most common cancer inmen and the ninth most common cancer in women [1].Worldwide, there are ∼209000 new cases and 102000 deathsper year. The incidence of all stages of RCC has increased overthe past several years, contributing to a steadily increasing mor-tality rate per unit population. Active and passive cigarettesmoking is an established risk factor for RCC as well as hyper-tension. However, anti-hypertensive medications such as diure-tics are not independently associated with RCC development.RCC also appears to be more common in patients with obesity,end-stage renal failure, acquired renal cystic disease and tuber-ous sclerosis.Approximately 2%–3% of RCC are hereditary and severalautosomal dominant syndromes are described, each with a dis-tinct genetic basis and phenotype, the most common one beingVon Hippel Lindau disease.In recent years, many new genes associated with RCC havebeen reported (such as PBRM1, SETD2, BAP1). Their roles inpathogenesis and as prognostic biomarkers are currently underinvestigation.

Accuracy of vascular invasion reporting in hepatocellular carcinoma before and after implementation of subspecialty surgical pathology sign-out.

Liver cancers (including hepatocellular carcinoma [HCC] and cholangiocarcinoma) are the fifth most common cause of cancer death. The most powerful independent histologic predictor of overall survival after transplantation for HCC is the presence of microscopic vascular invasion (VI). Given that VI is known to have somewhat high interobserver variability in both HCC and other tumors, we hypothesized that pathologists with special interest and training in liver pathology would be more likely to identify and report VI in HCC than would general surgical pathologists. We searched our departmental surgical pathology archives for transplant hepatectomies performed for HCC. We identified 143 such cases with available sign-out reports and hematoxylin and eosin-stained slides. Kappa results (level of agreement) were calculated. Before surgical pathology subspecialty sign-out (SSSO) implementation, 49 of 88 HCC cases were reported as negative for VI; on rereview, 20 of these had VI. After SSSO implementation, 39 of 55 cases were reported as negative for VI; on our review, 8 of these had VI. Kappa (agreement) between general SO and subspecialty rereview was 0.562 (95% confidence interval [CI] = 0.411-0.714) "weak agreement." Kappa (agreement) between SSSO and rereview by select liver pathologists was 0.693 (95% CI = 0.505-0.880) "moderate agreement." Our study is one of only a few so far that have suggested improved accuracy of certain parameters under SSSO.

The Frequency and Prognostic Impact of Pathological Microscopic Vascular Invasion According to Tumor Size in Non-Small Cell Lung Cancer.

Microscopic vascular invasion (MVI) in patients with non-small cell lung cancer (NSCLC) has been reported to be a strong predictor of poor outcomes but it has not been a descriptor of the TNM classification. The purposes of this study were to determine whether the presence of MVI is related to a predictor of poor outcomes and to explore the degree of MVI according to tumor size. A total of 1,884 patients with stage pT1-4N0-2 NSCLC who underwent complete resection comprised the study sample. Overall survival (OS) and recurrence-free proportion were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to assess independent predictors of poor outcomes. Of 1,884 patients, 1,097 (58.2%) had MVI. Multivariate analysis showed MVI was a significant independent predictor of unfavorable OS (hazard ratio, 1.666; P < .001) and recurrence (hazard ratio, 2.268; P < .001). The frequency of MVI varied according to tumor size, and in each cohort of tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm, there were significant differences in survival outcome by MVI status. The proportions of patients with a 5-year recurrence-free period with tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm between MVI (+) and MVI (-) were 93.0% and 72.5% (P < .001), 90.8% and 63.3% (P < .001), and 86.4% and 59.9% (P < .001), respectively. This study demonstrated that MVI was a strong predictor of poor outcomes and that the effect is more prominent in patients with tumor sizes ≤ 5 cm. Further analysis of survival and MVI should be collected for future revision of the TNM system.

Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection†.

Despite impressive results in diagnosis and treatment of non-small-cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within 5 years after surgical treatment. Identification of prognostic factors to select patients with a poor prognosis and development of tailored treatment strategies are then advisable. The aim of our study was to design a model able to define prognosis in patients with Stage I NSCLC, submitted to surgery with curative intent. A retrospective analysis of two surgical registries was performed. Predictors of survival were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: age, gender, smoking habit, morbidity, previous malignancy, Eastern Cooperative Oncology Group performance status, clinical N stage, maximum standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic lymphadenectomy, vascular invasion, pathological T stage, histology and histological grading. The final model included predictors with P < 0.20, after a backward selection. Missing data in evaluated predictors were multiple-imputed and combined estimates were obtained from 10 imputed data sets. Analysis was performed on 848 consecutive patients. The median follow-up was 48 months. Two hundred and nine patients died (25%), with a 5-year overall survival (OS) rate of 74%. The final Cox model demonstrated that mortality was significantly associated with age, male sex, presence of cardiac comorbidities, DLCO (%), SUV(max), systematic nodal dissection, presence of microscopic vascular invasion, pTNM stage and histological grading. The final model showed a fair discrimination ability (C-statistic = 0.69): the calibration of the model indicated a good agreement between observed and predicted survival. We designed an effective prognostic model based on clinical, pathological and surgical covariates. Our preliminary results need to be refined and validated in a larger patient population, in order to provide an easy-to-use prognostic tool for Stage I NSCLC patients.

P-169 * SIGNIFICANCE OF THE PRESENCE OF MICROSCOPIC VASCULAR INVASION AFTER COMPLETE RESECTION OF NON-SMALL-CELL LUNG CANCER

Objectives: The aim of this study was to assess the significance of microscopic vascular invasion (MVI) in a population of completely resected patients with non-small-cell lung cancer (NSCLC), along with an analysis of impact of the MVI and clinicopathological factors on recurrence and survival. Methods: From September 2002 to December 2010, 1230 patients with NSCLC received complete resection at our institution. MVI was ascertained using histopathological and immunohistochemical techniques. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method. We performed multivariate analyses to determine the independent prognostic factors. Results: MVI was observed in 448 patients (36.4%). Prevalence of MVI was lower in Stage I cases than in higher stage cases (P < 0.001). The presence of MVI was associated with DFS (P< 0.001, 3-year DFS: 87.1% in MVI-positive vs 64.3% in MVI-negative) and with OS (P< 0.001). Especially in Stage IB patients, who often receive oral anticancer agents as adjuvant chemotherapy in our institution, the presence of MVI was associated with DFS (P < 0.001, 3-year DFS: 85.4% in MVI-positive vs 69.3% in MVI-negative) and with OS (P = 0.039). In a multivariate survival analysis, The significant indicator of poor DFS was MVI (P< 0.001, CI 1.61-2.96), pulmonary metastases (P < 0.001, CI 1.49-2.98), pleural invasion (P = 0.007, CI 1.04-1.27), tumour size (P < 0.001, CI 1.01-1.02), and CEA level (P= 0.002, CI 1.00-1.01), although adjuvant chemotherapy has no significant relationship with DFS (P = 0.60). Conclusions: The finding of MVI in NSCLC is frequent. MVI correlates with tumour stages. The presence of MVI is an independent negative prognostic factor on both DFS and OS. Patients with these predictive factors of recurrence may be good candidates for intensive adjuvant chemotherapy. Disclosure: No significant relationships.

Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on “number of patients needed to transplant” as measure of transplant benefit

Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC) in terms of "Number of patients needed to transplant (NTT)." Child-Turcotte-Pugh (CTP) Classes B-C, very large (>10 cm) and multi-nodular (>2 nodules) tumours, macroscopic vascular invasion and extra-hepatic metastases. 1028 HCC cirrhotic patients from one Eastern (n=441) and two Western (n=587) surgical units. Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analysed in relationship with number of nodules (modelled as ordinal variable: single vs. oligonodular), size of largest nodule (modelled as a continuous variable), presence of microscopic vascular invasion (MVI), and time horizon from surgery (5-year vs. 10-year). 330 patients were beyond the Milan criteria (32%) and 597 (58%) had MVI. The prevalence of MVI was 52% in patients within Milan criteria and 71% in those beyond (p<0.0001). In the 5-year transplant benefit analysis, nodule size and HCC number were positive predictors of transplant benefit, while MVI had a strong negative impact on NTT. Transplantation performed as an effective therapy (NTT <5) only in oligonodular HCC with largest diameter >3cm (beyond conventional LT criteria) when MVI was absent. The 10-year scenario increased drastically the transplant benefit in all subgroups of resectable patients, and LT became an effective therapy (NTT <5) for all patients without MVI whenever tumor extension and for oligonodular HCC with MVI within conventional LT criteria. Based on NTT analysis, the adopted time horizon (5-year vs. 10-year scenario) is the main factor influencing the benefit of LT in patients with resectable HCC and Child A cirrhosis.

SIRT2 overexpression in hepatocellular carcinoma mediates epithelial to mesenchymal transition by protein kinase B/glycogen synthase kinase-3β/β-catenin signaling

Sirtuin 1 (SIRT1) has been implicated in telomere maintenance and the growth of hepatocellular carcinoma (HCC). Nevertheless, the role of other sirtuins in the pathogenesis of HCC remains elusive. We found that sirtuin 2 (SIRT2), another member of the sirtuin family, also contributes to cell motility and invasiveness of HCC. SIRT2 is up-regulated in HCC cell lines and in a subset of human HCC tissues (23/45). Up-regulations of SIRT2 in primary HCC tumors were significantly correlated with the presence of microscopic vascular invasion (P = 0.001), a more advanced tumor stage (P = 0.004), and shorter overall survival (P = 0.0499). Functional studies by short hairpin RNA-mediated suppression of SIRT2 expression in HCC cell lines revealed significant inhibition of motility and invasiveness. Depletion of SIRT2 also led to the regression of epithelial-mesenchymal transition (EMT) phenotypes, whereas the ectopic expression of SIRT2 in the immortalized hepatocyte cell line L02 promoted cell motility and invasiveness. Mechanistic studies revealed that SIRT2 regulates the deacetylation and activation of protein kinase B, which subsequently impinges on the glycogen synthase kinase-3β/β-catenin signaling pathway to regulate EMT. Our findings have uncovered a novel role for SIRT2 in HCC metastasis, and provide a rationale to explore the use of sirtuin inhibitors in HCC therapy. (HEPATOLOGY 2013;).

SIRT2 Overexpression in Hepatocellular Carcinoma Mediates Epithelial to Mesenchymal Transition via Akt/GSK‐3β/β‐catenin Signaling.

The yeast silent information regulator 2 (SIR2) is a histone deacetylase that utilizes NAD+ as a cofactor for its functions. In mammals, SIR2 is represented by seven homologues (SIRT1–7). We found that Sirtuin 2 (SIRT2) contributes to cell motility and invasiveness of HCC. SIRT2 is upregulated in HCC cell lines and in a subset of human HCC tissues (23/45). Up‐regulations of SIRT2 in primary HCC tumors were significantly correlated with the presence of microscopic vascular invasion (p=0.001), more advanced tumor stage (p=0.004) and shorter overall survival (p=0.0499). Functional studies by shRNA‐mediated suppression of SIRT2 expression in HCC cell lines revealed significant inhibition of motility and invasiveness. Depletion of SIRT2 also led to the regression of epithelial‐mesenchymal transition (EMT) phenotypes, whereas the ectopic expression of SIRT2 in the immortalized hepatocyte cell line L02 enhanced the expression of EMT markers, and promoted cell motility and invasiveness. Mechanistic studies revealed that SIRT2 regulates the deacetylation and activation of Akt, which subsequently impinges on GSK‐3β/β‐catenin signaling pathway to regulate EMT. Concordantly, we showed that there is a positive correlation between the level of SIRT2 and β‐catenin in human HCC. Our findings uncover a novel role of SIRT2 in HCC metastasis, and provide a rationale to explore the use of sirtuin inhibitors in HCC therapy.

Significance of the Presence of Microscopic Vascular Invasion After Complete Resection of Stage I–II pT1-T2N0 Non-small Cell Lung Cancer and Its Relation with T-Size Categories: Did the 2009 7th Edition of the TNM Staging System Miss Something?

The aim of this study was to assess the significance of microscopic vascular invasion (MVI) in a population of resected patients with early-stage non-small cell lung cancer (NSCLC), along with an analysis of the effect of the combination of MVI and tumor size for the T-size categories T1a-T2b according to the 2009 7th edition of the tumor, node, metastasis (TNM) classification. From January 1993 to August 2008, 746 patients with pT1-T2N0 NSCLC received resection at our institution. MVI was ascertained using histopathological and immunohistochemical techniques. MVI was observed in 257 patients (34%). Prevalence was higher in adenocarcinoma (ADK) than in squamous cell carcinoma (p = 0.002). A significant correlation was found between MVI and ADK (p = 0.03), increased tumor dimension (p = 0.05), and the presence of tumor-infiltrating lymphocytes (p = 0.02). The presence of MVI was associated with a reduced 5-year survival overall (p = 0.003) and in ADK (p = 0.0002). In a multivariate survival analysis, MVI was an indicator of poor survival overall (p = 0.003) and in ADK (p = 0.0005). In each T category (T1a-T2b) of the 2009 TNM staging system, survival of MVI+ patients was significantly lower than the corresponding MVI- patients; T1a and T1b MVI+ patients had a survival similar to MVI- T2 patients. The finding of MVI in pT1-T2N0 NSCLC is frequent. MVI correlates with adenocarcinoma histotype, increased tumor dimensions, and tumor-infiltrating lymphocytes. The presence of MVI is an independent negative prognostic factor. In our experience, MVI was a stronger prognostic indicator than T size in T1a-T2b categories according to the 2009 TNM staging system.

Preoperative prediction of hepatocellular carcinoma tumour grade and micro-vascular invasion by means of artificial neural network: A pilot study

Hepatocellular carcinoma (HCC) prognosis strongly depends upon nuclear grade and the presence of microscopic vascular invasion (MVI). The aim of this study was to develop an artificial neural network (ANN) that is able to predict tumour grade and MVI on the basis of non-invasive variables. Clinical, radiological, and histological data from 250 cirrhotic patients resected (n=200) or transplanted (n=50) for HCC were analyzed. ANN and logistic regression models were built on a training group of 175 randomly chosen patients and tested on the remaining testing group of 75. Receiver operating characteristics curve (ROC) and k-statistics were used to analyze model accuracy in the prediction of the final histological assessment of tumour grade (G1-G2 vs. G3-G4) and MVI (absent vs. present). Pathologic examination showed G3-G4 in 69.6% of cases and MVI in 74.4%. Preoperative serum alpha-fetoprotein (AFP), tumour number, size, and volume were related to tumour grade and MVI (p<0.05) and were used for ANN building, whereas, tumour number did not enter into the logistic models. In the training group, ANN area under ROC curves (AUC) for tumour grade and MVI prediction were 0.94 and 0.92, both higher (p<0.001) than those of logistic models (0.85 for both). In the testing group, ANN correctly identified 93.3% of tumour grades (k=0.81) and 91% of MVI (k=0.73). Logistic models correctly identified 81% of tumour grades (k=0.55) and 85% of MVI (k=0.57). ANN identifies HCC tumour grades and MVI on the basis of preoperative variables more accurately than the conventional linear model and should be used for tailoring clinical management.

Surgical Management of Early-Stage Hepatocellular Carcinoma: Resection or Transplantation?

BackgroundThe surgical management of hepatocellular carcinoma in patients with well-compensated cirrhosis is controversial. The purpose of the current study was to compare the outcome of patients with well-compensated cirrhosis and early stage hepatocellular carcinoma treated with initial hepatic resection versus transplantation. MethodsBetween 1985 and 2008, 245 patients underwent hepatic resection, and 134 patients underwent liver transplantation for early stage hepatocellular carcinoma. All patients had well-compensated cirrhosis. Prognostic factors were evaluated using univariate and multivariate analyses; survival was calculated using the Kaplan–Meier method. ResultsCompared with transplantation, patients undergoing resection had larger tumors and a higher incidence of microscopic vascular invasion. Transplantation was associated with better 5-year disease-free and overall survival compared with resection. Hepatitis status, presence of microscopic vascular invasion, and tumor size were predictors for recurrence, while the presence of microscopic vascular invasion and tumor size conferred an increased risk of death. The disease-free survival advantage with transplantation was more pronounced in hepatitis C patients compared with non-hepatitis and hepatitis B patients. The overall survival advantage with transplantation persisted in cases of solitary lesions ≤3 cm, but was attenuated in patients with a MELD score ≤ 8. ConclusionIn well-compensated cirrhotic patients with early stage hepatocellular carcinoma, transplantation was associated with longer disease-free and overall survival. Patients undergoing resection did, however, have tumors with more advanced pathologic features. Patients best suited for initial resection as the treatment of hepatocellular carcinoma were those with a MELD score ≤ 8 without evidence of hepatitis.

Locoregional treatment for hepatocellular carcinoma: From clinical exploration to robust clinical data, changing standards of care

Locoregional treatment for hepatocellular carcinoma: From clinical exploration to robust clinical data, changing standards of care

Preoperative Assessment of Hepatocellular Carcinoma Tumor Grade Using Needle Biopsy

To examine the diagnostic agreement of preoperative needle core biopsy (NCB) grading of hepatocellular carcinoma (HCC) compared with the final surgical pathologic tumor grade. Some centers have adopted protocols for selecting patients with HCC for transplantation based on tumor grade as determined by preoperative NCB. The validity of NCB to predict final tumor grade has not been previously assessed. A total of 211 patients who underwent hepatic resection, open radiofrequency, or transplantation for HCC between 1998 and 2004 were identified. Clinicopathologic, NCB, and surgical data were collected and analyzed using chi and kappa statistics. A total of 120 (67.4%) of the 178 who underwent resection or transplantation had an NCB. On preoperative NCB, the majority of HCC cases were classified as well-differentiated (n = 35; 37.6%) or moderately differentiated (n = 44; 47.3%), while 14 (15.1%) cases were categorized as poorly differentiated. In contrast, when tumor grading was based on the final surgical specimen, there was a significantly higher proportion of HCC cases graded as poorly differentiated (well-differentiated, n = 34; 36.6%; moderately differentiated, n = 33; 35.5%; poorly differentiated, n = 26; 27.9%) (P < 0.05). The overall percent agreement of NCB and surgical pathology to determine tumor grade was poor (kappa = 0.18, P < 0.0001). Whereas final pathologic tumor grade predicted the presence of microscopic vascular invasion (well, 15.7%; moderate; 31.9%, poor; 58.4%; P = 0.001), NCB grade did not (well, 23.7%; moderate, 28.0%; poor, 25.4%; P = 0.65). Selection of candidates for transplantation based on NCB tumor grade may be misleading, as NCB tumor grade often did not correlate with grade or presence of microscopic vascular invasion on final pathology. Clinicomorphologic criteria (tumor size, number) should remain the major determinants of eligibility for transplantation.

Risk factors for early death after liver resection in patients with solitary hepatocellular carcinoma

Although most patients who receive hepatectomy for a solitary hepatocellular carcinoma (HCC) have a relatively fair result, some have a poor prognosis. The aim of this study was to evaluate the risk factors for early death after hepatectomy in patients with a solitary HCC. Eligible patients (n=110) who had undergone hepatectomy for solitary HCC between 1990 and 2002 and were able to be followed up for more than 2 years after the hepatectomy were divided into two groups, those who died of cancer recurrence within 2 years (early-death group; n=18) and those who survived for more than 2 years after the surgery (survival group; n=92). Risk factors for early death after liver resection were evaluated by univariate and multivariate analyses. The gross tumor classification, tumor diameter, macroscopic portal vein invasion, microscopic growth pattern, microscopic vascular invasion (MVI), and the width of the surgical margin were significant (P<0.05) factors by univariate analysis. Multivariate analysis showed that the presence of MVI was an independent and significant risk factor for early death of recurrence. Among patients with solitary HCC, the presence of MVI indicates a poor prognosis. These patients need adjuvant chemotherapy in the early period after hepatectomy.

Prognostic value of the expression of Ki-67, CD44 and vascular endothelial growth factor, and microvessel invasion, in renal cell carcinoma.

To determine if use of cell proliferation, cell adhesion, level of angiogenesis-related factors and presence of microscopic vascular invasion (MVI) could better predict the biological behaviour of renal cell carcinoma (RCC), which has a widely variable clinical outcome despite the use of conventional prognostic factors (staging and grading). The expression of Ki-67, CD44H and vascular endothelial growth factor (VEGF) were assessed immunohistochemically in formalin-fixed, paraffin-embedded tissues from 48 RCCs, using a Ki-67 labelling index (LI), CD44 LI and level of VEGF expression, respectively. In addition all the pathological slides were reviewed retrospectively for the presence and absence of MVI. The prognostic value of all the variables assessed was then evaluated, and correlated with the usual prognostic variables and cancer-specific survival. Univariate analysis of cancer-specific survival showed that tumour stage (P < 0.001), tumour size (P = 0.005), metastasis, MVI, Ki-67 LI, CD44H LI and VEGF expression (all P < 0.001) were predictors of tumour-related death. There was a statistical correlation between CD44H LI and each of Ki-67 LI (r = 0.61), expression level of VEGF (r = 0.72) and presence of MVI (r = 0.71). Independent predictors of cancer-specific survival in a multivariate analysis were: in all patients with RCC, the MVI (P = 0.003) and VEGF expression (P = 0.01); in those with no metastases, MVI (P = 0.01); in patients with no MVI, VEGF (P = 0.04); and in patients with MVI, Ki-67 LI (P = 0.003). No independent predictor was identified in patient with metastases. This study suggests that cell proliferation, cell adhesion, the level of VEGF expression and the presence of MVI represent a complex tumour-host interaction that may favour the progression of RCC. Cell proliferation, CD44H and VEGF expression appear to be powerful markers for identifying patients with an adverse prognosis.

Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy

Background/Aims: We conducted a retrospective cohort study to investigate factors to early and late phase recurrence of hepatocellular carcinoma (HCC).Methods: The study population consisted of 249 patients including 157 with cirrhosis who underwent hepatectomy for HCC. The endpoint was time-to-recurrence. Using a Cox regression model, factors to early and late phase recurrences were investigated censoring recurrence-free patients at the 2-year time point and in patients without recurrence at 2 years.Results: Actuarial probability of overall recurrence at 1, 3, and 5 years were 0.301, 0.623, and 0.790, respectively, with a median follow-up of 624 days. Early recurrence was observed in 123 out of 249 patients; while late recurrence was found in 61 out of 113 patients. Factors to early recurrence were as follows: non-anatomical resection, presence of microscopic vascular invasion, and serum alpha-fetoprotein level ≥32ng/ml. Those contributing to late phase recurrence were higher grade of hepatitis activity, multiple tumors, and gross tumor classification.Conclusions: Variables associated with metastatic recurrence were factors to early phase recurrence; whereas those related with elevated carcinogenesis contributed to late phase recurrence, thus providing an epidemiological evidence that different mechanisms, i.e. metastasis and de novo, are involved in intrahepatic recurrence after hepatectomy for HCC.

Impact of Histological Grade of Hepatocellular Carcinoma on the Outcome of Liver Transplantation

Histological grade of hepatocellular carcinoma (HCC) is an important prognostic factor affecting patient survival after orthotopic liver transplantation (OLT). Retrospective analysis. University-based teaching hospital. Of 952 OLTs performed between June 1991 and January 1999, 56 OLT recipients had histologically proven HCC in the explant liver. Of those, 53 patients with complete clinicopathologic data were analyzed. A single pathologist blinded to the outcome of each patient reviewed all histological specimens. Median follow-up was 709 days. Overall survival for patients with tumors sized 5 cm or less at 1, 3, and 5 years was 87%, 78%, and 71%, respectively (Kaplan-Meier). Univariate analysis revealed the size, number, and distribution of tumors; the presence of microscopic vascular invasion and lymph node metastasis; histological differentiation; and pTNM stage to be statistically significant factors affecting survival. Multivariate analysis revealed histological differentiation and pTNM stage to be the independent and statistically significant factors affecting survival (P =.002 and.03, respectively). When pTNM stage was excluded from multivariate analysis, histological differentiation and size remained the significant independent factors (P =.02 and.03, respectively). Three-year survival for patients with small (</=5 cm) tumor with well- to moderately differentiated and poorly differentiated HCC was 82% and 67%, respectively. Three-year survival for patients with large (>5 cm) tumor with well- to moderately differentiated and poorly differentiated HCC was 62.5% and 0%, respectively. In our retrospective experience, histological differentiation had a statistically significant effect on the prognosis of HCC after OLT. However, before altering the current OLT selection criteria for patients with HCC, prospective studies are required to confirm the impact of histological grade on clinical outcome.