Hepatic Venous Invasion Research Articles

Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors: Where do we stand?

Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) is limited by factors such as tumor size, number, portal venous or hepatic venous invasion and extrahepatic disease. Although previously established criteria, such as Milan or UCSF, have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes, there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation. Immune checkpoint inhibitors (ICI) such as atezolizumab, pembrolizumab, or nivolumab have given hope to this group of patients. We completed a comprehensive literature review using PubMed, Google Scholar, reference citation analysis, and CrossRef. The search utilized keywords such as 'liver transplant', 'HCC', 'hepatocellular carcinoma', 'immune checkpoint inhibitors', 'ICI', 'atezolizumab', and 'nivolumab'. Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT, with acceptable early outcomes comparable to other criteria. Adverse effects of ICI have also been reported during the perioperative period. In such cases, a 1.5-month interval between ICI therapy and LT has been suggested. Overall, the results of downstaging using combination immunotherapy were encouraging and promising. Early reports suggested a potential ray of hope for patients with CLD and advanced HCC, especially those with multifocal HCC or branch portal venous tumor thrombosis. However, prospective studies and further experience will reveal the optimal dosage, duration, and timing prior to LT and evaluate both short- and long-term outcomes in terms of rejection, infection, recurrence rates, and survival.

Prognoses, outcomes, and clinicopathological characteristics of very elderly patients with hepatocellular carcinoma who underwent hepatectomy

ObjectivesThe aim was to evaluate the prognostic factors, clinicopathological characteristics, and surgical outcomes after hepatectomy in very elderly patients with hepatocellular carcinoma (HCC).MethodsWe analyzed 796 patients with HCC from 2000 to 2017. Patients aged 80 years or older were classified into the very elderly group (group VE; n = 49); patients younger than 80 years old and aged 65 years or older were classified into the elderly group (group E; n = 363), and patients younger than 65 years old were classified into the young group (group Y; n = 384). We investigated the prognoses, clinicopathological characteristics, and surgical outcomes after hepatectomy.ResultsThe number of surgical procedures and outcomes, including morbidities, was not significantly different. Groups VE, E, and Y showed similar prognoses in terms of both survival and recurrence. In group VE, prothrombin activity (PA) < 80% and PIVKA-II ≥ 400 mAU/ml were unfavorable factors for survival, and PIVKA-II ≥ 400 mAU/ml and the presence of portal venous invasion (PVI), hepatic venous invasion, and fibrosis were unfavorable factors for recurrence. In group E, ChE < 180 IU/l, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and hepatic venous invasion (HVI) were unfavorable factors for survival, and ChE < 180 IU/l, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and HVI were unfavorable factors for recurrence. In group Y, AFP ≥ 20 ng/ml, the presence of multiple tumors, poor differentiation, PVI, HVI, and blood loss ≥ 400 ml were unfavorable factors for survival, and PA < 80%, albumin < 3.5 g/dl, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, poor differentiation, and PVI were unfavorable factors for recurrence.ConclusionsTumor factors might have limited influence on the prognosis of very elderly patients, and liver function reserve might be important for the long-term survival of very elderly patients. Hepatectomy can be performed safely, even in very elderly patients. Hepatectomy should not be avoided in very elderly patients with HCC if patients have a good general status because these patients have the same prognoses as nonelderly individuals.

Peri-tumoral hyperintensity on hepatobiliary phase of gadoxetic acid-enhanced MRI in hepatocellular carcinomas: correlation with peri-tumoral hyperplasia and its pathological features

Peri-tumoral hyperintensity (P-hyperintensity) is occasionally seen in hepatocellular carcinoma (HCC) on the hepatobiliary (HB) phase of gadoxetic acid-enhanced MRI (EOB-MRI). A recent study reported peri-tumoral hyperplasia (P-hyperplasia) associated with over-expression of glutamine synthetase (GS) in HCC or metastatic carcinoma. The aim of this study was to analyze the correlation between P-hyperintensity on the HB phase and GS expression indicating P-hyperplasia and reveal its pathological features. Seventy-seven surgically resected HCCs from 68 patients were analyzed. The grade of P-hyperintensity on HB phase was divided according to the degree of the peri-tumoral hyperintense signal: grade 0 (no P-hyperintensity), grade 1 (less than 50% of the tumor border), grade 2 (50%-80%), grade 3 (80%-100%). Immunohistochemical staining for GS and organic anion transporter polypeptides (OATP)1B3 was performed. The relationships among P-hyperplasia (peri-tumoral GS expression) and OATP1B3 expression, P-hyperintensity, and pathological features of the tumor were analyzed. Thirty-four HCCs were classified as P-hyperintensity grade 0, 29 HCCs as grade 1,10 nodules as grade 2, and 4 HCCs as grade 3. P-hyperplasia was observed in 3/34 (8.8%) P-hyperintensity grade 0, 16/29 (55.2%) grade 1, 9/10 (90%) grade 2, and 4/4 (100%) grade 3. The incidence of P-hyperplasia was significantly increased in P-hyperintensity grades 1-3 compared with grade 0 (p<0.0001). Hepatocytes in all P-hyperplasia sites demonstrated definite OATP1B3 expression. Microscopic hepatic venous invasion was significantly increased in P-hyperintensity-positive HCCs compared with negative HCCs (p=0.0017). P-hyperintensity on HB phase in HCC may indicate p-hyperplasia with GS and OATP1B3 expression and a higher incidence of microscopic hepatic venous invasion.

Patient and tumor characteristics predictive of an elevated hepatopulmonary shunt fraction before radioembolization of hepatic tumors.

To determine whether any patient or hepatic tumor characteristics are predictive of hepatopulmonary shunt fraction when performed before radioembolization. A retrospective review was performed on 190 patients who underwent preradioembolization hepatic arteriography with calculation of hepatopulmonary shunt fraction using technetium-99m-labeled macroaggregated albumin perfusion scintigraphy. Patient and tumor characteristics including imaging features were reviewed for correlation with absolute shunt fraction, shunt fraction greater than 10%, and shunt fraction greater than 20%. Most tumor types showed some cases of elevated shunt fraction greater than 10%. Six patients had a shunt fraction greater than 20%: four were hepatocellular carcinoma and two were neuroendocrine tumor metastases. Univariate analysis showed that dominant tumor diameter, hepatic tumor burden, vascular invasion, hepatic venous invasion, and hypervascularity on angiography were associated with a shunt fraction greater than 10%. Only dominant tumor diameter and vascular invasion were associated with a shunt fraction greater than 20%. On multivariate analysis, only tumor diameter (odds ratio 1.2) and hepatic venous invasion (odds ratio 23.0) were associated independently with an increased shunt fraction greater than 10%. Multiple patient and tumor-related characteristics were significantly correlated with the hepatopulmonary shunt fraction on univariate analysis. However, on multivariate analysis, only the dominant tumor diameter and presence of hepatic venous invasion were associated independently with a greater than 10% shunt fraction.

Portal Vein Embolization Followed by Right-Side Hemihepatectomy for Hepatocellular Carcinoma Patients: A Japanese Multi-Institutional Study

Portal vein embolization (PVE) is useful to expand the indications of major hepatectomy; however, its oncologic effects are not fully understood. This study aimed to confirm the efficacy of preoperative PVE for hepatocellular carcinoma patients. Between 2000 and 2012, five hundred and ten patients with hepatocellular carcinoma undergoing right-side hemihepatectomy were enrolled (PVE group, n= 162 and non-PVE group, n= 348). To equalize background factors, one-to-one propensity case-matched analysis and multivariate analysis were performed. Short- and long-term outcomes were evaluated. Propensity score-matched patients, 148 in each group, were selected. The percentage of resected liver volume on admission was significantly greater in the PVE group (60.5% vs 48.3%; p < 0.001), but decreased considerably after PVE, from 60.5% to 50.3% (p<0.001). The 5-year cumulative recurrence-free survival (36.4% vs 35.3%) and overall survival (58.6% vs 52.8%) rates were comparable. Extrahepatic recurrences were less common in the PVE group (18.1% vs 38.8%; p= 0.004). Independent prognostic factors for recurrence-free survival were morbidity (hazard ratio [HR]= 1.56), multiple tumors (HR= 1.97), red cell concentrate administration (HR= 1.57), older age (HR= 2.09), and massive portal invasion (HR= 2.33); and those for overall survival were morbidity (HR= 2.37), multiple tumors (HR= 1.71), and massive hepatic venous invasion (HR= 3.49). Even though hepatocellular carcinoma patients who underwent preoperative PVE and right-side hemihepatectomy had a significantly larger resected liver volume on admission, they have a comparable long-term prognosis as patients with up front hepatectomy. In addition, PVE might decrease extrahepatic recurrences.

Yttrium-90 resin microspheres as an adjunct to sorafenib in patients with unresectable hepatocellular carcinoma

PurposeThe safety and efficacy of the combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS) to treat advanced hepatocellular carcinoma (HCC) is not well established. We determined the incidence of adverse events with this combination therapy in patients with advanced HCC at our institution and analyzed the treatment and survival outcomes.Materials and methodsWe reviewed the records of 19 patients with Barcelona Clinic Liver Cancer class B or C HCC who underwent treatment with Y90 RMS (for 21 sessions) while receiving full or reduced doses of sorafenib between January 2008 and May 2010. Therapy response was evaluated using Response Evaluation Criteria in Solid Tumors. We evaluated median overall survival (OS) and progression-free survival (PFS) as well as hepatic and extrahepatic disease PFS and incidence of adverse events.ResultsThe median patient age was 67 years, and portal or hepatic venous invasion was present in eight patients (42%). Ten patients received reduced doses of sorafenib. The median Y90 radiation activity delivered was 41.2 mCi. The partial response of Response Evaluation Criteria in Solid Tumors was observed in four patients (19%). The median hepatic disease PFS was 7.82 months, extrahepatic disease PFS was 8.94 months, OS was 19.52 months, and PFS was 6.63 months. Ninety days after treatment with Y90 RMS, five patients (26%) had grade II adverse events and four patients (21%) had grade III adverse events.ConclusionOS and PFS outcomes were superior to those observed in prior studies evaluating sorafenib alone in patients with a similar disease status, warranting further study of this treatment combination.

Fbxw7 regulates hepatocellular carcinoma migration and invasion via Notch1 signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies and also the leading cause of cancer-related death in the world. The mechanisms underlying the progression and metastasis of HCC remain unclear. The E3 ubiquitin ligase F-box and WD repeat domain-containing 7 (Fbxw7) is broadly considered as a tumor suppressor gene. However, the role of Fbxw7 in HCC is not clear. To investigate the expression and biological functions of Fbxw7 in HCC, we examined Fbxw7 expression level using HCC tissue microarray and immunohistochemistry. Our data showed that Fbxw7 expression is significantly reduced in HCC compared with non-cancerous tissues (P<0.05). Fbxw7 levels were significantly associated with tumor differentiation (P=0.013), the incidence of portal or hepatic venous invasion (P=0.031), metastasis (P=0.027) and AJCC cancer stage (P=0.047). Then, we observed a strong correlation between low Fbxw7 expression and a worse 5-year survival of HCC patients (P<0.001). Furthermore, multivariate Cox regression analyses demonstrated that the Fbxw7 expression (P<0.001) was an independent factor for the prediction of the overall survival of HCC patients. We also found that both Fbxw7 mRNA and protein levels were significantly reduced in HCC cell lines compared with human liver non-tumor cell line. Moreover, our in vitro experiments showed a remarkable increase of cell migration and invasion in Fbxw7-knockdown cells and a decrease in Fbxw7-overexpress cells. In addition, the present study demonstrated that Fbxw7 is involved in the migration and invasion of HCC cells via regulating Notch1 and the downstream molecules of Notch1. Taken together, our findings indicate that Fbxw7 can be used as a prognostic marker; it has an important role in HCC progression and inhibits HCC cell migration and invasion through the Notch1 signaling pathway.

Impact of STAT4 expression on cellular immunity and prognosis in hepatocellular carcinoma.

307 Background: Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of IL-12, leading to the production of IFN-γ and cytotoxicity. However, the significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains unknown. Herein, we investigated the association of STAT4 expression with cellular immunity and clinicopathological factors in HCC. Methods: A total of 66 HCC patients who underwent hepatic resection were enrolled. RT-PCR was performed to determine STAT4 mRNA and IFN gamma mRNA expression. Immunohistochemistry was performed to examine CD8+ T cells. Results: STAT4 was differentially expressed in tumor and non-tumor tissues (p &lt; 0.01), and positively correlated with IFN gamma and CD8+ T-cell infiltration (p &lt; 0.01). Significant correlations were observed between STAT4 expression and tumor TNM stage, hepatic venous invasion, tumor size, and tumor differentiation. Patients with high STAT4 expression had significantly better disease-free survival (p &lt; 0.01). In addition, low STAT4 expression (p &lt; 0.03) were independent risk factors for tumor recurrence. Conclusions: Down-regulation of STAT4 in HCC indicated aggressive tumor behavior and predicted worse clinical outcome. STAT4 might be a useful biomarker to identify patients with high risk of tumor recurrence after hepatic resection.

High STAT4 expression is a better prognostic indicator in patients with hepatocellular carcinoma after hepatectomy.

Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of interleukin-12, leading to the production of interferon gamma (IFN-γ) and natural killer cells cytotoxicity. However, the clinical significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains virtually unknown. A total of 66 HCC patients who underwent hepatectomy were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to determine STAT4 and IFNG mRNA expression levels. Tissue microarray-based immunohistochemistry was performed to examine CD8(+) T cells, STAT4, and INF-γ proteins. STAT4 was differentially expressed in tumor and nontumor tissues (P = 0.001) and positively correlated with IFNG expression (R (2) = 0.506, P < 0.05) and CD8(+) T cell infiltration (R (2) = 0.53, P < 0.001). Significant correlations were observed between STAT4 expression and tumor TNM stage (P = 0.043), hepatic venous invasion (P = 0.003), des-gamma-carboxy prothrombin (P = 0.011), tumor size (P = 0.036), and tumor differentiation (P = 0.034). Patients with high STAT4 expression had significantly better recurrence-free survival (P = 0.009). Low STAT4 expression (P = 0.030) and presence of portal venous invasion or hepatic venous invasion (P = 0.006) were independent risk factors for HCC recurrence. Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.

Recurrent hepatocellular carcinoma with tumor thrombus in right atrium - report of a successful liver resection with tumor thrombectomy using total hepatic vascular exclusion without concomitant cardiopulmonary bypass.

For resection of advanced hepatocellular carcinoma (HCC) in which tumor thrombus (TT) extends into inferior vena cava (IVC) or right atrium (RA) surgery is challenging and requires skillful techniques. Here, we report a case of recurrent HCC with TT extending to the RA, who underwent successful resection with tumor thrombectomy without concomitant cardiopulmonary bypass. A 71-year-old man, who had been followed- up for hepatitis C by a local hospital, was diagnosed as having HCC in segment 6 for which he had undergone segmentectomy of segment 6 in May 2009. During follow-up, he developed severe leg edema and ascites with investigations revealing recurrent HCC in segment 7 with TT extending to the right atrium via IVC. After transarterial embolization the patient underwent extended resection of the segment 7 with tumor thrombectomy of the IVC and the right atrium and partial resection of the IVC wall using total hepatic vascular exclusion, without concomitant cardiopulmonary bypass. Total ischemic time was 23 minutes, operation time was 6 hours and blood loss was 2,474mL. The postoperative course was uneventful. Histopathology was recurrent hepatocellular carcinoma with hepatic venous invasion. We report the case of resected recurrent HCC with TT extending to right atrium without concomitant cardiopulmonary bypass.

Isolated hepatic metastasis with hepatic venous invasion and tumor thrombus in right atrium.

A 78-year-old man was transferred to our hospital for detailed examination and treatment of sudden-onset and rapidly increasing general edema. Routine blood counts and laboratory test results were normal. His medical history included chronic heart failure over a very long period under medical treatment and a sigmoidectomy for 4-cm sigmoid colon cancer carried out 3 years previously. At that time, an isolated small (about 2 cm) liver metastasis (segment 4) was also detected. Simultaneous segmentectomy and sigmoidectomy was initially considered, but the patient’s cardiac problem prevented it, and ultrasound (US)-guided radio-frequency ablation (RFA) was selected as the most appropriate treatment for the hepatic metastasis. During the following three years, the patient visited the outpatient clinic regularly, and several whole-body computed tomography (CT) studies at intervals of 6 months showed no abnormalities. They also showed the treated hepatic metastasis to be completely necrosed (Fig. 1). The patient was symptom-free for a long time, but very recently he suddenly became edematous. Abdominal US performed in our hospital using a Toshiba Aplio XG unit (Tokyo, Japan) revealed an approximately 6 9 5-cm irregular and ill-margined slightly hypoechoic tumor in S4, which extended posteriorly and directly invaded the left, middle, and right hepatic veins. The left and middle hepatic veins were completely occluded and were not recognized on B-mode US, and the right hepatic venous lumen was partially recognized. The tumor extended towards the right atrium, and a huge tumor thrombus was found there (Fig. 2). The intrahepatic and extrahepatic portal system was normal, but a large amount of ascites was also present throughout the whole abdominal cavity. Contrast-enhanced US using Sonazoid solution (GE Health Care), performed to observe blood flow in the liver, provided more detailed information about the hemodynamics of the lesion and the surrounding hepatic veins (mechanical index *0.25). Soon R. Satoyoshi (&) H. Kotanagi Department of Surgery, Akita Red Cross Hospital, 222-1 Kamikitade Saruta, Nawashirosawa, Akita 010-1495, Japan e-mail: rika-s@alto.ocn.ne.jp

Caveolin-1 is related to invasion, survival, and poor prognosis in hepatocellular cancer

Caveolin-1 is the principal components of caveolae membranes, implicated in oncogenesis and angiogenesis. Until now, its expression and functional significance in hepatocellular carcinoma (HCC) are still unclear. In the present study, we demonstrated that expression of caveolin-1 was markedly upregulated in HCC patients. In addition, increased caveolin-1 expression correlated positively with the histological differentiation, portal venous invasion, hepatic venous invasion, intrahepatic metastases, and recurrence, suggesting a role for caveolin-1 in the progression of HCC. HepG2 cell line was transfected with pcDNA3.1/caveolin-1 to observe the significance of the change in caveolin-1 expression. We showed that caveolin-1 overexpression could not only protect HepG2 cells from apoptosis but also enhance its migration and invasion by upregulating MMP-2, MMP-9, and VEGF expressions. Collectively, our clinical and in vitro data indicate that the status of caveolin-1 expression may be one of causative factors for the invasion and poor prognosis in HCC.

Radiological assessment of hepatic vein invasion by hepatocellular carcinoma using combined computed tomography hepatic arteriography and computed tomography arterial portography

The aim of this study was to elucidate computed tomography hepatic arteriography (CTHA) and CT arterial portography (CTAP) findings characteristic of hepatocellular carcinoma (HCC) with large hepatic venous invasion (HVI) and then to examine whether the presence of minute HVI can be diagnosed based on each finding. Combined CTHA and CTAP of 106 HCCs were examined. Two radiologists analyzed the radiological findings of five nodules with large HVI (group vv2). The remaining 101 nodules were classified into two groups: group vv1, positive minute HVI; group vv0, negative HVI. They examined whether each finding observed in group vv2 could be detected in groups vv1 and vv0. Analysis of group vv2 identified (a) tumor thrombus, (b) early inflow of the contrast into the hepatic vein proximal to the invaded site, and (c) partially decreased portal venous flow in the peripheral parenchyma subject to the involved hepatic vein. Findings (b) and (c) were observed in 16% of group vv1. A significant difference in frequency of finding (c) was obtained between groups vv1 and vv0. The positive and negative predictive values of finding (c) were 66.7% and 77.9%, respectively. Findings (b) and (c), especially the latter, may partly contribute to the radiological diagnosis of minute HVI.

Increased Expression of a Disintegrin and Metalloprotease-9 in Hepatocellular Carcinoma: Implications for Tumor Progression and Prognosis

A disintegrin and metalloprotease-9 has been involved in the carcinogenesis of various solid tumors. However, its role in hepatocellular carcinoma remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of a disintegrin and metalloprotease-9 by immunohistochemistry. The expression profile of a disintegrin and metalloprotease-9 in association with the clinicopathological factors was determined by immunohistochemical analysis in hepatocellular carcinoma patients, and its potential prognostic value was investigated by comparing the survival rate between a disintegrin and metalloprotease-9-positive and a disintegrin and metalloprotease-9-negative patients. Hepatocellular carcinoma tissues with positive a disintegrin and metalloprotease-9 expression were larger and less differentiated than those with negative expression (P = 0.02 and 0.008, respectively). Portal venous invasion, hepatic venous invasion, bile duct invasion and intrahepatic metastasis were detected significantly more frequently in a disintegrin and metalloprotease-9-positive group (P = 0.009, 0.01, 0.03 and 0.02, respectively). In addition, high alpha-fetoprotein levels were significantly associated with the expression of a disintegrin and metalloprotease-9 in hepatocellular carcinoma (P = 0.01). Moreover, a disintegrin and metalloprotease-9-positive group had significantly poorer outcomes than a disintegrin and metalloprotease-9-negative group (P = 0.01) and was an independent prognostic factor for overall survival. A disintegrin and metalloprotease-9 is over-expressed in hepatocellular carcinoma tissues, consistent with findings in other tumor entities, and is an independent prognostic marker of overall survival following hepatectomy. Further studies are needed to investigate the precise function of a disintegrin and metalloprotease-9 in the progression of hepatocellular carcinoma.

Clinicopathological Prognostic Factors After Hepatectomy for Patients with Mass-Forming Type Intrahepatic Cholangiocarcinoma: Relevance of the Lymphatic Invasion Index

The present study was conducted to clarify the pathological factors in patients who underwent surgery for mass-forming type intrahepatic cholangiocarcinoma (IHC). From 1982 to July 2004, a total of 60 liver resections for mass-forming type IHC were performed at Kyushu University and its affiliated institutions. Portal venous, lymphatic, hepatic venous, and serosal invasion was examined by univariate and multivariate analyses for their prognostic value. The portal venous (PV) invasion index was defined as follows: PV0, portal venous invasion (-) and intrahepatic metastasis (-); PV1, portal venous invasion (+) or intrahepatic metastasis (+); PV2, portal venous invasion (+) and intrahepatic metastasis (+). The lymphatic invasion (LI) index was defined as follows: LI0, lymphatic duct invasion (-) and lymph node metastasis (-); LI1, intrahepatic lymphatic duct invasion (+) or lymph node metastasis (+); LI2, intrahepatic lymphatic duct invasion (+) and lymph node metastasis (+). In univariate analysis, statistically significant prognostic factors for poor outcome were tumor size (>5 cm), serosal invasion (+), PV1 or PV2, LI1 or LI2, histological grade (moderate and poor), hepatic venous invasion (+) and noncurative resection. After multivariate analysis, the lymphatic invasion index and histological grade were statistically independent prognostic factors for overall survival and recurrence-free survival. In patients with mass-forming type IHC, lymphatic invasion is the most important invasion pathway, compared with serosal and portal and hepatic venous invasion. Stratification of the lymphatic invasion pathway by lymphatic invasion, including intrahepatic lymphatic duct invasion and lymph node metastasis, is a good predictor for prognosis in patients after hepatectomy for mass-forming type IHC.

Histological evaluation of intracapsular venous invasion for discrimination between portal and hepatic venous invasion in hepatocellular carcinoma

Histological criteria for intracapsular venous invasion (IVI) that would allow its discrimination between portal and hepatic venous invasion in hepatocellular carcinoma (HCC) have not been established. We evaluated IVI immunohistochemically to discriminate between portal and hepatic venous invasion in 89 resected specimens from patients with HCC. IVI was defined as the microscopic involvement of the vessels within the fibrous capsule of HCC. The hepatic venous system was subdivided into the central vein and the sublobular/hepatic vein. Immunohistochemical analysis with the D2-40 monoclonal antibody revealed lymphatic vessels. In non-neoplastic liver tissues, the portal veins (n = 4355) were accompanied by lymphatic vessels (99.7%), bile ductules (100%) and arteries (96%), whereas the central veins (n = 3932) and sublobular/hepatic veins (n = 662) were rarely accompanied by lymphatic vessels (0% and 17%, respectively) and bile ductules (12% and 33%, respectively). In total, 29 IVI foci were detected; three foci were clearly visible within vessels that contained a distinct layer of connective tissue fibers, signifying sublobular/hepatic venous invasion. As the remaining 26 foci were accompanied by lymphatic vessels (26/26 [100%]), bile ductules (21/26 [81%]) and arteries (10/26 [38%]), these foci were considered to reflect intracapsular portal venous invasion rather than venous invasion of the central vein. Intracapsular portal venous invasion was significantly associated with extratumoral portal venous invasion (P < 0.001). D2-40 immunoreactivity for the histological evaluation of IVI in HCC allows discrimination between portal and hepatic venous invasion for cases in which portal venous invasion predominates.

Radiological detectability of minute hepatic venous invasion in hepatocellular carcinoma

Radiological detectability of minute hepatic venous invasion in hepatocellular carcinoma

Extent of liver resection for hilar cholangiocarcinoma

The extent of liver resection for hilar cholangiocarcinoma (HC) remains controversial despite extensive studies. The aim of this study was to determine the safety and efficacy of minor and major hepatectomy, selected by predetermined criteria in patients with HC. From 2000 to 2007, 187 patients with HC were studied prospectively; 138 patients underwent resection with curative intent. Minor hepatectomy was performed in 93 patients with Bismuth-Corlette type I, II or III HC without hepatic arterial or portal venous invasion, and major hepatectomy in 45 patients with type III HC with hepatic arterial or portal venous invasion, or type IV HC. Overall mortality and morbidity rates were 0 and 29.7 per cent respectively, and the bile leak rate was 1.4 per cent. Actuarial 1-, 3- and 5-year survival rates were 87, 54 and 34 per cent respectively in the minor liver resection group, and 80, 42 and 27 per cent for major resection (P = 0.300). Minor liver resection for HC, selected by predetermined criteria, had good results. Major liver resection, which had a higher operative morbidity rate than minor resection, should be reserved for Bismuth-Corlette type III HC with vascular invasion, or type IV HC.

Hepatic venous outflow obstruction after hydatid cyst surgery: evaluation with contrast enhanced magnetic resonance angiography

The aim of this study is to present the contrast enhanced magnetic resonance angiography findings of hepatic venous outflow obstruction in patients in whom surgery had been performed for hepatic hydatidosis. No patient history of parasitic hepatic venous invasion or earlier hepatic venous outflow obstruction is present. Four men and three women with a history of hydatid cyst surgery underwent contrast enhanced magnetic resonance angiography between April 2001 and June 2006. The mean age was 37.7 years. The mean time duration between the last date of surgery and the date of magnetic resonance angiography imaging was 65.5 months. The site of the hydatid cyst was the right lobe in two patients, the medial segment of the left lobe in two patients, the liver dome in two patients, and the conjunction of the right lobe anterior-left lobe medial segments in one patient. One patient had undergone total and one patient had undergone partial lobectomy, and cystectomy was performed in five patients. On magnetic resonance angiograms, nonvisualization or stenosis of the hepatic veins was detected in all cases. In one patient thrombosis and in another patient severe stenosis of the inferior vena cava were associated. The portal hilum was displaced anterosuperiorly in five patients. Intrahepatic collaterals were present in six patients and extrahepatic collaterals were seen in three. Associated thrombosis in the left portal vein was found in two patients. We conclude that patients with complicated hydatid cysts and who have had postoperative complications should be checked not only for recurrence or abscess formation, but also for vascular changes. magnetic resonance angiography is a useful alternative imaging technique and can provide useful information at one session within several minutes in patients who had undergone surgery for hydatid cyst of the liver.

Radiological detectability of minute hepatic venous invasion in hepatocellular carcinoma

Objective To determine if minute hepatic venous invasion in hepatocellular carcinoma (HCC) can be diagnosed radiologically. Materials and methods CT hepatic arteriography (CTHA) and CT arterioportography (CTAP) of 95 cases with HCCs were examined. Histopathology after surgery has been the gold standard in all patients. Based on the presence of microscopic portal venous invasion (MPVI) and microscopic hepatic venous invasion (MHVI), the cases were classified into four groups as follows: Group vp0vv0, negative MPVI and MHVI; Group vp1vv0, positive MPVI and negative MHVI; Group vp0vv1, negative MPVI and positive MHVI; Group vp1vv1, positive MPVI and MHVI. An area showing low attenuation on CTAP and high attenuation on CTHA around the tumor was defined as an area of peritumoral hemodynamic change (APTHC). The shape and size of APTHC were compared between Groups vp0vv1 and vp0vv0 or between Groups vp1vv1 and vp1vv0. The ratio of APTHC volume to tumor volume (RAT) was employed as an indicator of APTHC size. Each comparison was also made independently when tumor diameter was limited to either less than 3 cm or 3 cm or more. Results Three types of APTHC were identified: wedge-shaped, belt-shaped or irregular, and linear. No significant difference in the frequency of each type of APTHC was observed between Groups vp0vv1 and vp0vv0 or between Groups vp1vv1 and vp1vv0. There was no significant difference in RAT between Groups vp0vv1 and vp0vv0 or between Groups vp1vv1 and vp1vv0, unrelated to tumor size. Conclusions The presence of minute hepatic venous invasion in HCC is difficult to determine even on combined CTHA and CTAP.