Presence Of Portal Vein Invasion Research Articles

The impact of radiation dose and tumour burden on outcomes in hepatocellular carcinoma: 11-year experience in a 413-patient cohort treated with yttrium-90 resin microsphere radioembolisation

Introduction Transarterial radioembolisation (RE) using yttrium-90 (Y-90) microspheres is a widely used locoregional therapy for a broad spectrum of HCC given its favourable safety profile. We evaluated the real-world outcomes of unresectable HCC treated with resin Y-90 RE and the relationship between tumour absorbed dose and subsequent curative therapy with survival. Methods Included were consecutive patients treated with Y-90 resin microspheres RE for unresectable HCC between January 2008 and May 2019 at the National Cancer Centre Singapore /Singapore General Hospital. The outcomes were stratified by tumour burden, distribution, presence of portal vein invasion (PVI) and liver function to improve prognostication. Results The median overall survival (OS) evaluated on 413 included patients was 20.9 months (95% CI 18.2 – 24.0). More than half of the patients (214/413, 51.8%) had HCC beyond up-to-seven criteria, and 37.3% had portal vein invasion (154/413, 37.3%). Majority (71.7%) had dosimetry calculated based on the partition model. Patients who received ≥150 Gy to tumour had significantly better outcomes (OS 32.2 months, 95% CI 18.3 – 46.4) than those who did not (OS 17.5 months, 95% CI 13.7 – 22.7, p < 0.001). Seventy patients (17%) received curative therapies after tumour was downstaged by Y-90 RE and had better OS of 79.7 months (95% CI 40.4 – NE) compared to those who did not receive curative therapies (OS 17.1 months; 95% CI 13.5 – 20.4, p < 0.001). Radioembolisation-induced liver injury was observed in 5.08% of the patients while 3.2% of the patients had possible radiation pneumonitis but none developed Grade 3-4 toxicity. For HCC without PVI, overall survival differed significantly with performance status, ALBI grade, tumour distribution, and radiation dose; for HCC with PVI, Child-Pugh class and AFP were significant predictors of survival. Conclusions Treatment outcomes for unresectable HCC using Y-90 RE were favourable. Incorporating tumour burden and distribution improved prognostication. Patients who received tumour absorbed dose above 150 Gy had better OS. Patients who subsequently received curative therapies after being downstaged by Y-90 RE had remarkable clinical outcomes.

Refining MRI-based criteria for portal vein invasion in hepatocellular carcinoma: improving sensitivity beyond portal vein tumor thrombosis.

To investigate the imaging features indicating portal vein invasion (PVI) of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI and to create more accurate diagnostic criteria than the presence of portal vein tumor thrombosis (PVTT) on MRI. This retrospective study included patients with surgically resected HCC larger than 5 cm, and the presence of PVI was investigated. On MRI, we evaluated the image findings of portal vein occlusion, the parenchymal signal change caused by hemodynamic alterations of the portal vein, and their combination showing the highest odds ratio (OR) to define the diagnostic criteria for radiological PVI detection (rPVI criteria). The diagnostic performance and recurrence-free survival were compared between the rPVI criteria and the presence of PVTT using McNemar's test and Kaplan-Meier method, respectively. Interobserver agreement was evaluated using Cohen's weighted ĸ statistics. Of 189 enrolled patients, 25 (13.2%) had PVI on histology. To diagnose PVI on MRI, either peripheral wedge-shaped arterial peritumoral hyperemia with an abrupt cut-off of a portal vein or the presence of PVTT had the highest OR (41.67, p<0.001). The sensitivity of PVI was significantly increased under this diagnostic criterion (64.0% to 88.0%; p=0.031) with comparable accuracy (95.2% vs. 94.7%; p>0.999). In terms of recurrence-free survival, the patient group with rPVI was significantly worse (p=0.017) compared with the patients without rPVI. Interobserver agreement of radiologic findings was substantial (ĸ=0.64). Diagnostic criteria for radiologically PVI detection increase the sensitivity more than the only presence of PVTT.

Retrospective Study of the Efficacy and Safety of Chemoembolization with Drug-Eluting Microspheres Combined with Intra-Arterial Infusion of Bevacizumab for Unresectable Hepatocellular Carcinoma.

PurposeTo evaluate the efficacy and safety of chemoembolization with drug-eluting microspheres (DEM-TACE) combined with intra-arterial infusion of bevacizumab in patients with unresectable hepatocellular carcinoma (uHCC) and to identify possible prognostic factors.Patients and MethodsBetween November 2014 and December 2020, 34 patients underwent DEM-TACE combined with intra-arterial infusion of bevacizumab for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) beyond the Up-to-seven criteria or BCLC stage C HCC. Patients with extrahepatic metastasis or inferior vena cava invasion were excluded. The primary endpoint was overall survival (OS). The secondary endpoints were safety (assessed using Common Terminology Criteria for Adverse Events v5.0), the response rate at 1 month, and the identification of prognostic factors. The median OS was calculated using the Kaplan–Meier method. The response rate was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Prognostic factors were investigated by univariate and multivariable analysis using the Cox proportional hazards model.ResultsThe median OS was 13 months. BCLC stage and presence of portal vein invasion were not significantly associated with OS. There were no grade ≥3 adverse events. The Child–Pugh class did not decline after treatment in 31 of 34 patients. The overall response rate was 14.2% and the disease control rate was 100%. Significant prognostic factors were alcoholic liver disease, Child–Pugh score of ≥8, and microsphere size of 50–100 μm.ConclusionDEM-TACE combined with intra-arterial infusion of bevacizumab is safe and effective, and it could be a treatment option for unresectable HCCs.

Prognostic factors on survival in hepatocellular carcinoma

Purpose: Hepatocellular carcinoma is a potentially recurrent tumor determining the predictive factors effective on recurrence and mortality. Methods: In Seoul National University Bundang Hospital, 478 patients were operated for hepatocellular carcinoma between 2004 and 2015.Among them, data of 216 patients was obtained from prospectively collected data repository for determining the oncological outcomes. The exclusion criteria were the patients with R1 resection, history of preoperative tumor rupture and causes of mortality unrelated with hepatocellular carcinoma. Results: Among 216 patients, 124 patients had recurrences and 54 patients died during follow-up period. The BMI (<24kg/m2), number of postoperative TACE, were also significant in OS; but the male gender and presence of portal vein invasion were only significant in DFS. Finally in multiple Cox regression analyses; independent factors were BMI (p:0.001, HR: 0.85, 95% CI: 0.77-0.93), presence of satellite lesions (p: 0.000, HR: 4.56, 95% CI: 2.43-8.56) and number of lesions (<2) (p:0.001, HR:2.9, 95% CI: 1.56-5.51) in OS and male gender (p:0.013, HR: 2.05, 95% CI: 1.16-3.63), presence of satellite lesions (p: 0.001, HR: 2.35, 95% CI: 1.39-3.96) and grosstype of tumor (p:0.008, HR:5.95, 95% CI: 1.58- 22.3) in DFS.1.-3.-5.y. survival rates were 93%-85.7%-79.2%; with the recurrence free rates of 78.1% - 54.9% - 41.6% respectively. Conclusion: In this study, tumor size, number of tumors and male gender was also a strong indicator for recurrence. Interestingly, low BMI was a strong indicator for worrisome survival outcomes.

Abstract No. 528 Bland embolization versus radioembolization for the treatment of HCC in cirrhotic patients: propensity score analysis of the impact on hepatic function

Both bland transarterial embolization (TAE) and radioembolization (Y90) for the treatment of HCC have shown similar tumor responses and survival (excluding the radiation segmentectomy approach). While tumor control is a vital outcome, the degree of resulting hepatic impairment is important in this population who often have cirrhosis. The purpose of this study was to analyze the impact of TAE and Y90 on hepatic function based on the MELD score, with propensity score matching to optimally control potential confounders. Analysis was performed on 256 patients undergoing treatment of HCC in a lobar or bilobar fashion with Y90 (n= 100) or TAE (n=156) over a 10-year period. The total bilirubin, creatinine, and INR levels were ascertained immediately pre-procedure and at 1, 6, and 12 months after treatment to calculate MELD scores. Differences in MELD scores were compared using the paired or unpaired t-test and multivariate linear regression. Because confounders may result from selection bias, propensity score matching was performed with the following variables: treatment type, gender, age, unilobar versus bilobar, ECOG, AFP, maximum tumor diameter, viral hepatitis, presence of portal vein invasion, and initial MELD score. The mean baseline pretreatment MELD scores for patients undergoing TAE versus Y90 were 10.7 and 8.9, respectively (p<0.001). After TAE, the MELD score change at 1, 6, and 12 months were 0.8, 1.8, and 2.5 (p=0.036, 0.029, and 0.004), respectively. After Y90, the MELD score change was 2.6, 5.1, and 6.6 (p<0.001 for each). Using the propensity matched cohort, Y90 was associated with a higher change in MELD score at 1, 6, and 12 months (p=0.009, <0.001, and 0.001, respectively). Portal vein invasion was also associated with a higher change in MELD score at 6 months (p=0.004) and 12 months (p=0.04). In a propensity matched cohort of patients treated with lobar or bilobar TAE or Y90, Y90 was associated with significantly higher MELD score changes compared to TAE, and were most pronounced at 12 months. These findings may be important for patient selection and treatment planning, as well as understanding potential impact on liver transplant list status.

Multivariate analysis of factors influencing hepatocellular carcinoma prognosis after hepatectomy

Objective To retrospectively study the relationship between several risk factors such as cirrhosis, Child-Pugh classification, tumor size, portal vein tumor thrombus, intraoperative transfusion, hepatic portal occlusion time and the prognosis of hepatic cellular cancer (HCC) patients after hepatic resection. Methods The clinical data of 123 patients who received hepatic resection for HCC at Tongji Hospital between 2007 and 2009 were retrospectively analyzed. Log-Rank test and Cox proportional hazard model were used in the univariate and multivariate analyses of risk factors. Results 1, 2, 3, 5 year recurrence and survival rates were 54.17%, 66.67%, 81.40%, 87.50% and 93.50%, 73.17%, 58.54%, 27.64%, respectively. The mean recurrence time and survival time were 19.5 months and 42.9 months. In univariate analysis, presence of cirrhosis (χ2=11.159, P=0.005), Child-Pugh classification (χ2=7.715, P=0.028), tumor size (≥5cm) (χ2=11.483, P=0.004), presence of portal vein invasion (χ2=22.271, P=0.001) were risk factors affecting HCC recurrence. In multivariate analysis, presence of cirrhosis (χ2=8.993, P=0.003), tumor size (≥5cm) (χ2=4.022, P=0.039), presence of portal vein invasion (χ2=5.023, P=0.027) were independent risk factors affecting HCC recurrence. In univariate analysis, presence of cirrhosis (χ2=7.339, P=0.025), AFP>400 ng/ml (χ2=5.431, P=0.042), Child-Pugh classification (χ2=13.389, P=0.002), tumor size(≥5cm) (χ2=11.342, P=0.003), presence of portal vein invasion (χ2=52.167, P<0.001), hepatic portal occlusion (χ2=5.801, P=0.037), intraoperative blood transfusion (χ2=14.959, P=0.001) were risk factors affecting a shorter overall survival. In multivariate analysis, presence of cirrhosis (χ2=9.133, P=0.003), Child-Pugh classification (χ2=4.799, P=0.028), tumor size (≥5 cm) (χ2=9.101, P=0.004), presence of portal vein invasion (χ2=11.126, P=0.001), hepatic portal occlusion (χ2=3.985, P=0.046) were independent prognostic factors affecting shorter overall survival. Conclusion Cirrhosis, Child-Pugh classification, tumor size (≥5 cm), presence of portal vein invasion, and hepatic portal occlusion were independent prognostic factors for HCC patients after hepatic resection. Key words: Liver neoplasms; Prognosis; Risk factors

Clinical significance of microRNA 138 and cyclin D3 in hepatocellular carcinoma

BackgroundMicroRNA 138 (miR-138) is recently shown to inhibit tumor growth and block cell cycle arrest of hepatocellular carcinoma (HCC) by targeting cyclin D3 (CCND3). The aim of this study was to investigate the clinical significance of miR-138 and CCND3 in human HCC, which remains unclear. MethodsQuantitative real-time polymerase chain reaction analysis was performed to detect the expression levels of miR-138 and CCND3 messenger RNA (mRNA) in 180 self-pairs of HCC and noncancerous liver tissues. ResultsCompared with noncancerous liver tissues, the expression levels of miR-138 in HCC tissues were significantly downregulated (P < 0.001), whereas the expression levels of CCND3 mRNA in HCC tissues were significantly upregulated (P < 0.001). There was a negative correlation between miR-138 and CCND3 mRNA expression in HCC tissues (r = -0.56, P = 0.02). Additionally, statistical analysis showed that the combined miR 138 downregulation and CCND3 upregulation (miR-138-low-CCND3-high) was significantly associated with the advanced tumor-node-metastasis stage (P = 0.008) and the presence of portal vein invasion (P = 0.008) and lymph node metastasis (P = 0.01). More importantly, a significant trend was identified between the combined expression of miR-138-low-CCND3-high in HCC and worsening clinical prognosis. Multivariate survival analysis further recognized miR-138-low-CCND3-high expression as an independent prognostic factor for patients with HCC. ConclusionsOur data suggest that the combined expression of miR-138 and its direct target CCND3 may be correlated with significant characteristics of HCC. MiR-138 downregulation and CCND3 upregulation maybe concurrently associated with prognosis in patients with HCC.

Magnitude of Change in Alpha-Fetoprotein in Response to Transarterial Chemoembolization Predicts Survival in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy. In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child-Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt. Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8-8.5 cm), which decreased with tace to 5.0 cm (range: 3.3-7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival. The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.

Factors influencing hepatocellular carcinoma prognosis after hepatectomy: a single-center experience

Background/AimsRecurrence after hepatic resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). We identified prognostic factors affecting overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatic resection.MethodsThis study was of a retrospective cohort design, and 126 patients who underwent hepatic resection for HCC at Gachon University Gil Medical Center between January 2005 and December 2010 were enrolled. Various clinical, laboratory, and pathological data were evaluated to determine the prognostic factors affecting OS and DFS.ResultsTwo- and 4-year OS and 2- and 4-year DFS were 78.1% and 65% and 51.1% and 26.6%, respectively. In a multivariate analysis, preoperative α-fetoprotein (> 400 ng/mL), tumor size (≥ 5 cm), multiple tumors (two or more nodules), presence of portal vein invasion, modified Union for International Cancer Control (UICC) stage III/IV, and Barcelona Clinic Liver Cancer (BCLC) stage B/C were independent prognostic factors affecting a shorter OS. In the multivariate analysis, presence of microvascular invasion, modified UICC stage III/IV, and BCLC stage B/C were independent prognostic factors for a shorter DFS.ConclusionsThe presence of vascular invasion was an independent poor prognostic factor for OS and DFS in patients with HCC after hepatic resection. Thus, close postoperative surveillance for early detection of recurrence and additional treatments are urgently needed in patients with vascular invasion after hepatic resection.

Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis

BackgroundHepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM). It is crucial to elucidate the prognostic clinicopathological factors.MethodsEighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis.ResultsThe overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra- and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictive factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrahepatic recurrence were noted. In the subgroup with synchronous CRCLM, the combination of surgery and adjuvant chemotherapy controlled intrahepatic recurrence and improved the prognosis significantly.ConclusionsOptimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.

Which treatment modality should we choose for advanced hepatocellular carcinoma?

Which treatment modality should we choose for advanced hepatocellular carcinoma?

The preoperative positivity for serum hepatitis B e antigen did not affect overall survival after curative resection of hepatitis B virus‐related hepatocellular carcinoma

Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified. A total of 190 Hepatitis B surface antigen-positive patients who received curative resection for HCC were reviewed. We investigated prognostic factors for disease-free and overall survival after resection, and further analyzed the relationship between significant prognostic factors and risk factors for early (<or=14 months) and late (>14 months) intrahepatic recurrence. The 5-year disease-free and overall survival rates were 43.9% and 71.5%, respectively. In multivariate analysis, adverse prognostic factors for disease-free survival were presence of serum HBeAg, perioperative transfusion, and the presence of portal vein invasion (PVI) and/or intrahepatic metastasis (IM). Multivariate analysis revealed that overall survival was associated with ICG R15, serum albumin, Edmondson-Steiner grade, and the presence of PVI and/or IM. Independent risk factors for early intrahepatic recurrence were perioperative transfusion and PVI and/or IM, whereas positivity for HBeAg was the only risk factor for late recurrence. In addition, post-recurrence survival in patients with late intrahepatic recurrence was completely comparable to that of patients who never experienced recurrence. The presence of serum HBeAg, the risk factor for late intrahepatic recurrence did not affect overall survival after resection because late recurrence was relatively well controlled by current available treatments. To further improve long-term surgical outcomes, effective treatment and preventive methods for early intrahepatic recurrence should be investigated.

核酸アナログ療法中のB型関連肝癌に対する肝癌再発予測マーカーとしてのHBコア関連抗原の有用性

The tumor recurrence rate of hepatocellular carcinoma (HCC) is still high even in patients who receive a curative therapy. We analyzed predictive value of HBV-related viral markers, including HBcrAg, HBV DNA, and HBeAg, for HCC recurrence in the patients who developed HCC during antiviral nucleot(s)ide analogues therapy. By univariate analysis, HBV DNA, HBcrAg, tumor number and presence of portal vein invasion were significant predictive factors. By multivariate analysis, HBcrAg and presence of portal vein invasion were independent and significant predictive factors of recurrence after curative therapy for HCC. We conclude that HBcrAg is useful as a predictor of post-treatment recurrence of HCC after curative therapy in patients who received antiviral therapy.

Prognostic value of tumor-infiltrating FOXP3 + regulatory T cells in patients with hepatocellular carcinoma

Aims CD4 + CD25 + forkhead box P3 (FOXP3) + T reg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (T reg), we conducted a retrospective study on 164 patients with hepatocellular carcinoma (HCC) who underwent curative hepatic resection. Methods We investigated the number of tumor-infiltrating FOXP3 + T reg in formalin-fixed HCC specimens. The number of FOXP3 + T reg for each case was calculated as the total number of positive cells per 10 high-power fields (HPF) on light microscopy. Long-term survival rate after resection according to the number of FOXP3 + T reg was accessed by univariate and multivariate analyses. Results The mean and median numbers of tumor-infiltrating T reg were 29.0 and 14 per 10 HPF for FOXP3 + T reg. The number of FOXP3 + T reg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high T reg counts (≥14, n = 84) than in those with low T reg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high T reg counts, presence of portal vein invasion, and elevation of preoperative aspartate aminotransferase level were independent predictive factors of tumor recurrence. Conclusions The high number of tumor-infiltrating T reg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.

Predictors of hepatic venous trunk invasion and prognostic factors in patients with hepatocellular carcinomas that had come into contact with the trunk of major hepatic veins

In this study, we tried to identify the preoperative predictors of hepatic venous trunk invasion and the prognostic factors in patients with hepatocellular carcinoma (HCC) that had come into contact with the trunk of a major hepatic vein over a distance of 1.0 cm or more. Forty patients who had such HCCs resected were entered into this study and predictors of hepatic venous trunk invasion and prognostic factors were evaluated by univariate and multivariate analyses. A combined resection of the HCC and the venous trunk was performed in 29 patients. Hepatic venous trunk invasion was observed in 12 patients, including 2 with inferior vena cava tumor thrombus. A stepwise logistic regression analysis indicated that tumors larger than or equal to 7 cm in diameter and tumors showing a poorly differentiated histological grade were independent predictors of hepatic venous trunk invasion. The survival of patients without venous trunk invasion was significantly better than that for patients with venous trunk invasion (P = 0.048). A univariate analysis revealed that Child-Pugh classification B (P = 0.002), a high des-gamma-carboxy prothrombin concentration (> or =400 mAU/ml, P = 0.023), a large HCC (> or =5.0 cm in diameter, P = 0.002), the presence of portal vein invasion (P < 0.001), the presence of venous trunk invasion (P = 0.048), the presence of intrahepatic metastasis (P < 0.001), and poorly differentiated HCC (P = 0.006) correlated with a worse overall survival after hepatic resection. In a multivariate analysis, however, only the presence of intrahepatic metastasis (P = 0.037, relative risk 8.25) was an independent predictor of poor overall survival. Large tumors (> or =7 cm in diameter) and poorly differentiated HCCs were more likely to be associated with hepatic venous trunk invasion and intrahepatic metastasis was an independent prognostic factor in patients with HCC that had come into contact with the trunk of a major hepatic vein.

Expressions of HSP70 and HSP27 in Hepatocellular Carcinoma

The heat shock proteins (HSPs) are ubiquitous molecules induced in cells exposed to various stress conditions, including carcinogenesis. The HSP70 and HSP27 among HSPs are of special relevance in human cancer inhibiting apoptosis. The aim of this study is to investigate the expressions of HSP70 and HSP27 in hepatocellular carcinoma (HCC) in association to tumor cell proliferation and apoptosis. We examined the expressions of HSP70 and HSP27 by immunohistochemical staining in 71 cases of HCC, and then related their expressions to clinicopathologic parameters and expressions of p53, Ki-67 and Apotag. HSP70 and HSP27 were frequently stained in the cytoplasm and nuclei of tumor cells, but not in the non-neoplastic hepatocytes. Immunoreactivities of HSP70 and HSP27 were observed in 56.3% and 61.9% of HCCs, respectively. HSP70 immunoreactivity correlated with high Ki-67 labeling indices (LIs) (p=0.0159), large tumor size (p=0.0129), presence of portal vein invasion (p=0.0231), and high tumor stage (p=0.0392). HSP27 immunoreactivity significantly related with the subgroup of HBV-associated HCCs (p=0.0003), but not with the others. Both HSP70 and HSP27 immunoreactivities showed no relation to Apotag LIs or p53 immunoreactivity. In conclusion, expressions of HSP70 and HSP27 may play an important role in hepatocarcinogenesis, and especially HSP70 showed a close relationship to the pathological parameters associated with tumor progression and high Ki-67 LIs. Our results could be additional evidence that HSP70 expressions can contribute to not only hepatocarcinogenesis but also tumor progression by promoting tumor cell proliferation.

Factors influencing survival of patients undergoing hepatectomy for colorectal metastases.

The extent of surgical margin is still a matter of controversy with regard to outcome after liver resection for metastatic disease. The aim of this study was to clarify the significant prognostic factors after hepatectomy for colorectal metastases, with special reference to the surgical margin. Ninety-six patients who underwent initial hepatic resection for liver metastases from colorectal cancer between 1992 and 1994 were studied. Overall 1-, 3- and 5-year survival rates were 94, 61 and 51 per cent respectively. All of the independent factors associated with poor prognosis after hepatic resection were tumour-related factors, such as the number of tumours (four or more), presence of portal vein invasion, hepatic vein invasion and absence of a fibrous pseudocapsule. A positive resection margin was not an independent prognostic factor, because of its strong relationship with the number of tumours resected. A generous surgical margin is not essential for curative hepatic resection, although positive surgical margins should be avoided. New potential risk factors which affect survival, such as the presence of portal vein or hepatic vein invasion and the absence of a pseudocapsule, may be helpful for defining the indications for postoperative adjuvant treatment.

Overexpression of Sialyl Lewis x Antigen Is Associated with Formation of Extratumoral Venous Invasion and Predicts Postoperative Development of Massive Hepatic Metastasis in Cases with Pancreatic Ductal Adenocarcinoma

The clinicopathological factors and expression of sialyl Lewis antigens which are the cell adhesion molecules to endothelial cells were compared in relation to the extent of the postoperative hepatic metastasis in 23 consecutive patients with pancreatic ductal adenocarcinoma whose clinical courses were carefully monitored and documented. The overall survival of cases with massive hepatic metastasis (MHM) was significantly poorer than that of those with local or no hepatic metastasis (p = 0.0453). Postoperative MHM was significantly correlated with the presence of duodenal invasion (p = 0.0418), the presence of portal vein invasion (p = 0.0435), the presence of extratumoral venous invasion (p = 0.0052) and high expression of sialyl Lewis x antigen (p = 0.0022). Multivariate analysis confined significant correlation between the high expression of sialyl Lewis x antigen and the development of MHM (p = 0.0402). Kaplan-Meier analysis revealed that the overall survival of patients with a high expression of sialyl Lewis x antigen was significantly poorer than that of patients with a low expression of the antigen (p = 0.0216). These results indicate that the overexpression of sialyl Lewis x antigen plays an important role in the development of MHM, and also predicts a poorer overall survival of these patients. Further studies with more cases are warranted to confirm these results.