Objective To evaluate the prospective outcome and summarize experience in re-resection for recurrent liver cancer and extrahepatic metastases. Methods The clinical data of 267 patients with recurrent primary liver c...Objective To evaluate the prospective outcome and summarize experience in re-resection for recurrent liver cancer and extrahepatic metastases. Methods The clinical data of 267 patients with recurrent primary liver cancer (PLC) after re-resection from January 1960 to July 2000 were retrospectively analyzed. Re-hepatectomy was performed on 205 cases, resection of extrahepatic metastases on 51 cases and combined resection of recurrent liver cancer and extrahepatic metastases on 11 cases. The clinico-pathologic features, operation type and survival were compared. Results The types of liver re-resection included left lateral lobectomy in 11.2% of patients, hemihepatetomy and extended hemi-hepatectomy in 4.4%, local radical resection in 68.3%, other subsegmentectomy in 17.1%. The peak recurrence rate (64.4%) occurred at 1–2 years. The overall 1-, 3, 5- and 10-year survival rates after second resection were 81.0%, 40.3%, 19.4% and 9.0% respectively, while they were 77.5%, 29.8%, 13.2% and 6.61% respectively after the third resection. The median survival time was 44 months. The re-resection with extrahepatic metastases also provided the possibility of longer survival. Conclusion The results suggest that subsegmentectomy and local excision is appropriate for the hepatic repeat resection. The peak recurrence may be correlated with portal thrombus and operative factor. The re-resection can be indicated not only in intrahepatic recurrent metastases but also in extrahepatic metastases in selected patients. Re-resection has become the treatment of choice for recurrence of PLC, as neither chemotherapy nor other nonsurgical therapies can achieve such favorable results. Key words prospective outcome - re-resection - primary liver cancer - recurrence - extrahepatic metastases展开更多
Previous reports of a solitary metastatic hepatocellular carcinoma have been rare. Because this tumor has a different treatment modality and prognosis, an accurate differential diagnosis is essential. Here we report a...Previous reports of a solitary metastatic hepatocellular carcinoma have been rare. Because this tumor has a different treatment modality and prognosis, an accurate differential diagnosis is essential. Here we report a rare case of a solitary chest wall metastasis from unknown primary site of hepatocellular carcinoma. It involves a 51-year-old man who was admitted to our hospital because of a palpable left upper chest wall mass. The mass was resected and pathologic examination confirmed a diagnosis of metastatic hepatocellular carcinoma. Despite our investigation, no evidence was found that indicated the primary origin of the hepatocellular carcinoma. Four months later, the patient was admitted again because of spinal cord compression at the third and fourth thoracic vertebrae. Emergent decompressive laminectomy was performed and microscopic features revealed the same pathology as the initial chest wall mass resected 4 months earlier. After one year, a follow-up abdominal computed tomography (CT) still revealed no evidence of primary hepatocellular carcinoma.展开更多
AIM To investigate the precise role of membrane type 1-matrix metalloproteinase (NTI-NNP) in hepatocellular carcinoma (HCC) metastasis. METHODS- Human HCC cells Hep3B with overexpression of MTT-MMP were establishe...AIM To investigate the precise role of membrane type 1-matrix metalloproteinase (NTI-NNP) in hepatocellular carcinoma (HCC) metastasis. METHODS- Human HCC cells Hep3B with overexpression of MTT-MMP were established by stable transfection, and compared with control cells carrying the empty vector. Cells were examined in vivo for their differences in the metastatic ability of athymic nude mice, and analyzed in vito for their differences in invasion ability by invasion chamber coated with Matrigel, adhesion towards collagen I and migration through culture chamber. Cell proliferation and apoptosis in adherent and suspension status were evaluated by MTr and flow cytometry analysis. RESULTS We found that overexpression of MT1-MMP could increase intrahepatic metastasis in nude mice with orthotopic implantation of HCC cells (incidence of 100% [MT1-MMP transfectants] vs 40% [vector control transfectants], P〈0.05). NT1-MMP could also enhance cell invasion through Natrigel (107.7 vs 39.3 cells/field, P〈0.001), adhesion towards matrix (0.30 vs 0.12 absorbance unit at 540 nm, P〈0.001), cell migration (89.3 vs 39.0 cells/field, P〈0.001), and cell proliferation (24.3 vs 40.5 h/doubling, P〈0.001). We also observed that NTI-NNP supported cell survival (71.4% vs 23.9%, P〈0.001) with reduced apoptosis (43.7% vs51.0%, P〈0.05) in an attachment-free environment. CONCLUSION: MT1-MMP overexpression could enhance metastasis. In addition to its active role in matrix degradation during tumor invasion, MT1-MMP enhances tumor cell survival upon challenge of detachment, which is important during metastasis when cells enter the circulation.展开更多
AIM: To analyze the imaging findings of hepatic malignancy with right atrial (RA) embolus. METHODS: Forty-six patients with an embolus in the RA were diagnosed, including 44 patients with hepatocellular carcinoma (HCC...AIM: To analyze the imaging findings of hepatic malignancy with right atrial (RA) embolus. METHODS: Forty-six patients with an embolus in the RA were diagnosed, including 44 patients with hepatocellular carcinoma (HCC), 1 patient with cholangiocellular carcinoma and 1 patient with hepatic carcinoma metastasis. The diagnosis was confirmed by clinical examination, serum α-fetoprotein and imaging. Seventeen patients underwent transcatheter arterial chemoembolization (TACE). RESULTS: On enhancement computer tomography (CT) or magnetic resonance (MR) imaging, a nodular filling defect in the RA could be easily found, with a slight enhancement in the arterial phase. The coronal images of CT or MR showed the extent of lesion. Lipiodol entered the embolus after TACE, hence reducing the speed of embolus growth. There was a survival benefit for patients receiving anticancer treatment. CONCLUSION: Patients with HCC, showing a filling defect of the inferior vena cava (IVC), hepatic vein (HV) and RA on images, can be diagnosed with RA embolus. Encroachment of the RA is very rare in patients with hepatic malignancies. Furthermore, a prolongation of survival time is found in those patients who underwent TACE.展开更多
AIM: To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3β), CCL20 (MIP-3a) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (...AIM: To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3β), CCL20 (MIP-3a) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (HCC) versus colorectal liver metastases (CRLM) and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS: Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT- PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS: Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION: Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.展开更多
Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely ...Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an “overview” of how these cells function in health and in diseases such as展开更多
AIM: To examine whether antithrombin (AT) could prevent hepatic ischemia/reperfusion (I/R)-induced hepatic metastasis by inhibiting tumor necrosis factor (TNF)-α-induced expression of E-selectin in rats. METH...AIM: To examine whether antithrombin (AT) could prevent hepatic ischemia/reperfusion (I/R)-induced hepatic metastasis by inhibiting tumor necrosis factor (TNF)-α-induced expression of E-selectin in rats. METHODS: Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically. The number of metastatic nodules was counted on day 7 after I/R. TNF-α and E-selectin mRNA in hepatic tissue, serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2, were measured. RESULTS: AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-α and E-selectin in animals subjected to hepatic I/R. Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF1α were significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT. Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenital AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice. CONCLUSION: AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-α-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.展开更多
DNA methylation is the most intensively studied epigenetic phenomenon, disturbances of which result in changes ingene transcription, thus exerting drastic imparts onto biological behaviors of cancer. Both the global d...DNA methylation is the most intensively studied epigenetic phenomenon, disturbances of which result in changes ingene transcription, thus exerting drastic imparts onto biological behaviors of cancer. Both the global demethylation andthe local hypermethylation have been widely reported in all types of tumors, providing both challenges and opportunitiesfor a better understanding and eventually controlling of the malignance. However, we are still in the very early stage ofinformation accumulation concerning the tumor associated changes in DNA methylation pattern. A number of excellentrecent reviews have covered this issue in depth. Therefore, this review will summarize our recent data on DNA methy-lation profiling in cancers. Perspectives for the future direction in this dynamic and exciting field will also be given.展开更多
AIM: To investigate the association of cyclooxygenase-2 (COX-2) expression with angiogenesis and the number and type of inflammatory cells (macrophages/Kupffer cells; mast cells) within primary hepatocellular car...AIM: To investigate the association of cyclooxygenase-2 (COX-2) expression with angiogenesis and the number and type of inflammatory cells (macrophages/Kupffer cells; mast cells) within primary hepatocellular carcinoma (HCC) tissues and adjacent non-tumorous (NT) tissues. METHODS: Immunohistochemistry for COX-2, CD34, CD68 and mast cell tryptase (MCT) was performed on 14 well-characterized series of liver-cirrhosis-associated HCC patients. COX-2 expression and the number of inflammatory cells in tumor lesions and surrounding liver tissues of each specimen were compared. Moreover, COX-2, CD34 staining and the number of inflammatory cells in areas with different histological degrees within each tumor sample were comparatively analyzed. RESULTS: The percentage of COX-2 positive cells was significantly higher in NT tissues than in tumors. COX-2 expression was higher in well-differentiated HCC than in poorly-differentiated tissues. Few mast cells were observed within the tumor mass, whereas a higher number was observed in the surrounding tissue, especially in peri-portal spaces of NT tissues. Abundant macrophages/ Kupffer cells were observed in NT tissues, whereas the number of cells was significantly lower in the tumor mass. However, a higher cell number was observed in the welldifferentiated tumor and progressively decreased in relation to the differentiation grade. Within the tumor, a positive correlation was found between COX-2 expression and the number of macrophages/Kupffer cells and mastcells. Moreover, there was a positive correlation between CD34 and COX-2 expression in tumor tissues. Comparison between well- and poorly-differentiated HCC showed that the number of CD34-positive cells decreased with dedifferentiation. However, COX-2 was the only independent variable showing a positive correlation with CD34 in a multivariate analysis. CONCLUSION: The presence of inflammatory cells and COX-2 expression in liver tumor suggests a possible relationship with tumor angiogenesis. COX-2 expressing cells and the number of macrophages/Kupffer cells and mast cells decrease with progression of the disease.展开更多
AIM: To explore the relation between heparanase (HPA) and nm23-H1 in hepatocellular carcinoma (HCC), and whether they could be used as valuable markers in predicting post-operative metastasis and recurrence of HCC. ME...AIM: To explore the relation between heparanase (HPA) and nm23-H1 in hepatocellular carcinoma (HCC), and whether they could be used as valuable markers in predicting post-operative metastasis and recurrence of HCC. METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry (S-P method) were used to measure the expressions of HPA mRNA and nm23-H1 protein in primary tumor tissue and paracancerous tissue of 33 cases of HCC. Paracancerous tissues of 9 cases of benign liver tumor were used as normal controls. The results were analyzed in combination with the results of clinicopathological examination and follow-up. RESULTS: The positive expression of HPA gene was significantly higher in primary tumor tissues of HCC (48.5%, 16/33) as compared to the paracancerous tissues of HCC and normal controls (3.03%, 1/33) (P<0.01). HPA expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state and cirrhosis of liver. The positive rates of HPA mRNA in the group with high tendency to metastasis or recurrence and in the group with metastasis or recurrence during the follow-up were significantly higher than those in the group with low tendency to metastasis or recurrence (62.5% vs 37.5%, P<0.05) and in the group without metastasis or recurrence (78.6% vs 21.4%, P<0.01). The poorly differentiated tumor and tumor of TNM stages Ⅲ-Ⅳ had a higher positive rate of HPA gene expression than the well differentiated tumor and tumor of TNM stages Ⅰ-Ⅱ (66.7% vs 33.3%, P<0.05). The positive expression rate of nm23-H1 protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (45.5, 72.7, 88.9%, P<0.05). nm23-H1 expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state, cirrhosis of liver, Edmondson grade, and TNM stage (P>0.05). The positive rates of nm23-H1 in the group with high tendency to metastasis and recurrence and in patients with metastasis or recurrence during the follow-up were obviously higher than those in the group with low tendency to metastasis and recurrence (P= 0.018) and in the patients without metastasis and recurrence (P = 0.024); but no significant difference was found between HPA positive and negative groups (P = 0.082). According to the results of follow-up, the rate of accuracy in predicting metastasis of positive HPA, negative nm23-H1 and combination of positive HPA with negative nm23-H1 was 78.6% (11/14), 68.8% (11/16) and 88.9% (8/9), respectively. CONCLUSION: Expression of HPA and/or nm23-H1 is related with metastasis and recurrence of HCC. Detection of the expression rate of HPA and nm23-H1 may help increase the accuracy in predicting post-operative metastasis and recurrence of HCC.展开更多
AIM: To analyze the metastasis-related proteins in hepatocellular carcinoma (HCC) and discover the biomarker candidates for diagnosis and therapeutic intervention of HCC metastasis with bioinformatics tools. METHODS: ...AIM: To analyze the metastasis-related proteins in hepatocellular carcinoma (HCC) and discover the biomarker candidates for diagnosis and therapeutic intervention of HCC metastasis with bioinformatics tools. METHODS: Metastasis-related proteins were determined by stable isotope labeling and MS analysis and analyzed with bioinformatics resources, including Phobius, Kyoto encyclopedia of genes and genomes (KEGG), online mendelian inheritance in man (OMIM) and human protein reference database (HPRD). RESULTS: All the metastasis-related proteins were linked to 83 pathways in KEGG, including MAPK and p53 signal pathways. Protein-protein interaction network showed that all the metastasis-related proteins were categorized into 19 function groups, including cell cycle, apoptosis and signal transduction. OMIM analysis linked these proteins to 186 OMIM entries. CONCLUSION: Metastasis-related proteins provide HCC cells with biological advantages in cell proliferation,migration and angiogenesis, and facilitate metastasis of HCC cells. The bird's eye view can reveal a global characteristic of metastasis-related proteins and many differentially expressed proteins can be identified as candidates for diagnosis and treatment of HCC.展开更多
Hepatocellular carcinoma (HCC) is a so highly invasive tumor that metastasizes hematogenously and lymphogenously to distant site. Frequent sites are lung, regional lymph node, bone, and adrenal gland. But metastasis...Hepatocellular carcinoma (HCC) is a so highly invasive tumor that metastasizes hematogenously and lymphogenously to distant site. Frequent sites are lung, regional lymph node, bone, and adrenal gland. But metastasis to the gastrointestinal (GI) tract is rare, and most common site is stomach. Metastasis to the small intestine is extremely rare. Moreover, metastatic HCC of the small bowel causing intussusception has not been reported until now. Here, we report a case of metastasis of HCC to the small bowel manifested by intussusception.展开更多
AIM:To develop a model using easily obtainable, objective, verifiable preoperative parameters, to help evaluate post transplant survival probability for hepatocellular carcinoma (HCC) patients with hepatitis B. METHOD...AIM:To develop a model using easily obtainable, objective, verifiable preoperative parameters, to help evaluate post transplant survival probability for hepatocellular carcinoma (HCC) patients with hepatitis B. METHODS:We retrospectively examined a cohort of 150 consecutive primary cadaveric liver transplants with HCC in our center over 6 years. Thirteen preoperative biochemical parameters and six tumor-related factors were analyzed to identify their correlation with post transplant survival using the Cox proportional-hazards regression model. The predictive power of a new model and the model for end stage liver disease was compared by the receiver operating characteristic curve. RESULTS:In univariate analysis, the factors significantly associated with post transplant survival were serum concentrations of albumin, total bilirubin, alkaline phosphatase, alpha-fetoprotein, γ-glutamyltransferase, aspartate aminotransferase, sodium, tumor diameter and the number of tumor nodules. Multivariate analysis showed alpha-fetoprotein, serum sodium, alkaline phosphatase and the number of tumor nodules were significantly associated with the post transplant outcome. Based on the four variables, we established a new model with a c-statistic of 0.72 which was significantly greater than 0.50 (P = 0.001), and the c-statistic of MELD was 0.59 (P = 0.146).CONCLUSION:The new model based on four objective tumor-related parameters has the capacity to evaluate the risk of post transplant mortality for HCC patients with hepatitis B.展开更多
To review the preventive approaches for recurrence after curative resection of hepatic metastases from colorectal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) cov...To review the preventive approaches for recurrence after curative resection of hepatic metastases from colorectal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) covered in PubMed. The treatment approaches presented above include adjuvant intrahepatic arterial infusion chemotherapy, systemic chemotherapy, neoadjuvant chemotherapy, and immunotherapy. Although no standard treatment has been established, several approaches present promising results, which are both effective and tolerable in post-hepatectomy patients. Intrahepatic arterial infusion chemotherapy should be regarded as effective and tolerable and it increases overall survival (OS) and disease free survival (DFS) of patients, while 5-fluorouracil-based systemic chemotherapy has not shown any significant survival benefit. Fortunately chemotherapy combined with hepatic arterial infusion and intravenous infusion has shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have been conducted to evaluate its effect on prolonging survivals although many retrospective studies and case reports are published in which unresectable colorectal liver metastases are downstaged and made resectable with neoadjuvant chemotherapy. Liver resection supplemented with immunotherapy is associated with optimal results; however, it is also questioned by others. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence after hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric RCT is still needed for further evaluation on their efficacy and systemic or local toxicities. In addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with resectable hepatic metastases from CRC.展开更多
AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control ...AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also tested.RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297,respectively, P<0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs42.69±6.99 ng/L, P<0.05). No statistical difference in ALT and AFP was observed between groups.CONCLUSION: Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.展开更多
AIM: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis.METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high pote...AIM: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis.METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high potential of lymphatic metastatic Hca-F and its synogenetic cell line Hca-P with a low metastatic potential was constructed by suppression subtracted hybridization(SSH) method. The screened clones of the subtracted library were sequenced and GeneBank homology search was performed.RESULTS: Fourteen differentially expressed cDNA fragments of Hca-F were obtained with two novel genes.CONCLUSION: SSH is a useful technique to detect differentially expressioned genes and an effective method to clone novel genes.展开更多
Multiple liver tumors represent a challenging condition for abdominal surgeons both in the selection of technique and the rarity of diagnosis. There are no case reports on co-existence of liver metastases from both in...Multiple liver tumors represent a challenging condition for abdominal surgeons both in the selection of technique and the rarity of diagnosis. There are no case reports on co-existence of liver metastases from both intestinal leiomyosarcoma and adenocarcinoma. The patient described in this report successfully underwent resection of both primary lesions and liver metastases in combination with chemotherapy. As for the leiomyosarcoma, the primary cecal lesion was revealed more than three years after the patient's first visit. Peritoneal, lymph-node, and lung recurrences were observed afterward, and thus surgeries on those regions were performed. Pathologically, the peritoneal and lung recurrences comprised leiomyosarcoma and the lymphnode recurrence was diagnosed as adenocarcinoma. Despite newly discovered multiple lung recurrences and regional lymph-node metastases, the patient lived a normal life for 73 mo after the initial operation based on multidisciplinary therapy. He ultimately died of liver failure due to invasive lymph-node recurrence from the rectal adenocarcinoma, in addition to multiple lung recurrences from the leiomyosarcoma. Hepatic recurrence did not occur in this patient's case, which appears to be one reason for his long-term survival.展开更多
Von Meyenburg complexes are benign liver lesions consisting of adenomatous bile duct proliferates. We present two patients suffering from esophageal cancer accompanied by the occurrence of yon Meyenburg complexes. Pre...Von Meyenburg complexes are benign liver lesions consisting of adenomatous bile duct proliferates. We present two patients suffering from esophageal cancer accompanied by the occurrence of yon Meyenburg complexes. Preoperative computerized tomography (CT) of the liver had not shown these lesions. In one of the patients, diffuse nodular manifestation was found in both liver lobes, mimicking diffuse hepatic metastases. Intraoperative frozen section revealed the benign nature of the lesions in both cases. The patients underwent esophageal resection without complications. To the best of our knowledge, the coincidence of von Meyenburg complexes and esophageal cancer has never been reported before. This uncommon entity should be taken into consideration as a differential diagnosis of liver lesions in malignancies. It underlines the importance of intraoperative frozen section for liver lesions of unknown origin.展开更多
This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting a huge mass in the left external auditory canal (EAC). The patient was a 55-year-old man with hepatitis B virus-related HCC. He...This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting a huge mass in the left external auditory canal (EAC). The patient was a 55-year-old man with hepatitis B virus-related HCC. He presented to our department with a three-month history of increasing left otalgia,and hearing loss with recent fresh aural bleeding. Histopathologic examination indicated that the tumor was secondary to HCC. Although external irradiation was not effective,the tumor was treated with surgical debulking and high dose rate 192 Ir remote afterloading system (RALS) for postoperative intracavitary irradiation. A review of the literature revealed only five other cases of HCC metastasis to the temporal bone,all of which mainly metastasized in the internal acoustic meatus. The present case is the first report of HCC metastasis to the EAC.展开更多
文摘Objective To evaluate the prospective outcome and summarize experience in re-resection for recurrent liver cancer and extrahepatic metastases. Methods The clinical data of 267 patients with recurrent primary liver cancer (PLC) after re-resection from January 1960 to July 2000 were retrospectively analyzed. Re-hepatectomy was performed on 205 cases, resection of extrahepatic metastases on 51 cases and combined resection of recurrent liver cancer and extrahepatic metastases on 11 cases. The clinico-pathologic features, operation type and survival were compared. Results The types of liver re-resection included left lateral lobectomy in 11.2% of patients, hemihepatetomy and extended hemi-hepatectomy in 4.4%, local radical resection in 68.3%, other subsegmentectomy in 17.1%. The peak recurrence rate (64.4%) occurred at 1–2 years. The overall 1-, 3, 5- and 10-year survival rates after second resection were 81.0%, 40.3%, 19.4% and 9.0% respectively, while they were 77.5%, 29.8%, 13.2% and 6.61% respectively after the third resection. The median survival time was 44 months. The re-resection with extrahepatic metastases also provided the possibility of longer survival. Conclusion The results suggest that subsegmentectomy and local excision is appropriate for the hepatic repeat resection. The peak recurrence may be correlated with portal thrombus and operative factor. The re-resection can be indicated not only in intrahepatic recurrent metastases but also in extrahepatic metastases in selected patients. Re-resection has become the treatment of choice for recurrence of PLC, as neither chemotherapy nor other nonsurgical therapies can achieve such favorable results. Key words prospective outcome - re-resection - primary liver cancer - recurrence - extrahepatic metastases
文摘Previous reports of a solitary metastatic hepatocellular carcinoma have been rare. Because this tumor has a different treatment modality and prognosis, an accurate differential diagnosis is essential. Here we report a rare case of a solitary chest wall metastasis from unknown primary site of hepatocellular carcinoma. It involves a 51-year-old man who was admitted to our hospital because of a palpable left upper chest wall mass. The mass was resected and pathologic examination confirmed a diagnosis of metastatic hepatocellular carcinoma. Despite our investigation, no evidence was found that indicated the primary origin of the hepatocellular carcinoma. Four months later, the patient was admitted again because of spinal cord compression at the third and fourth thoracic vertebrae. Emergent decompressive laminectomy was performed and microscopic features revealed the same pathology as the initial chest wall mass resected 4 months earlier. After one year, a follow-up abdominal computed tomography (CT) still revealed no evidence of primary hepatocellular carcinoma.
基金Supported by the Seed Funding Program of the University of Hong Kong
文摘AIM To investigate the precise role of membrane type 1-matrix metalloproteinase (NTI-NNP) in hepatocellular carcinoma (HCC) metastasis. METHODS- Human HCC cells Hep3B with overexpression of MTT-MMP were established by stable transfection, and compared with control cells carrying the empty vector. Cells were examined in vivo for their differences in the metastatic ability of athymic nude mice, and analyzed in vito for their differences in invasion ability by invasion chamber coated with Matrigel, adhesion towards collagen I and migration through culture chamber. Cell proliferation and apoptosis in adherent and suspension status were evaluated by MTr and flow cytometry analysis. RESULTS We found that overexpression of MT1-MMP could increase intrahepatic metastasis in nude mice with orthotopic implantation of HCC cells (incidence of 100% [MT1-MMP transfectants] vs 40% [vector control transfectants], P〈0.05). NT1-MMP could also enhance cell invasion through Natrigel (107.7 vs 39.3 cells/field, P〈0.001), adhesion towards matrix (0.30 vs 0.12 absorbance unit at 540 nm, P〈0.001), cell migration (89.3 vs 39.0 cells/field, P〈0.001), and cell proliferation (24.3 vs 40.5 h/doubling, P〈0.001). We also observed that NTI-NNP supported cell survival (71.4% vs 23.9%, P〈0.001) with reduced apoptosis (43.7% vs51.0%, P〈0.05) in an attachment-free environment. CONCLUSION: MT1-MMP overexpression could enhance metastasis. In addition to its active role in matrix degradation during tumor invasion, MT1-MMP enhances tumor cell survival upon challenge of detachment, which is important during metastasis when cells enter the circulation.
文摘AIM: To analyze the imaging findings of hepatic malignancy with right atrial (RA) embolus. METHODS: Forty-six patients with an embolus in the RA were diagnosed, including 44 patients with hepatocellular carcinoma (HCC), 1 patient with cholangiocellular carcinoma and 1 patient with hepatic carcinoma metastasis. The diagnosis was confirmed by clinical examination, serum α-fetoprotein and imaging. Seventeen patients underwent transcatheter arterial chemoembolization (TACE). RESULTS: On enhancement computer tomography (CT) or magnetic resonance (MR) imaging, a nodular filling defect in the RA could be easily found, with a slight enhancement in the arterial phase. The coronal images of CT or MR showed the extent of lesion. Lipiodol entered the embolus after TACE, hence reducing the speed of embolus growth. There was a survival benefit for patients receiving anticancer treatment. CONCLUSION: Patients with HCC, showing a filling defect of the inferior vena cava (IVC), hepatic vein (HV) and RA on images, can be diagnosed with RA embolus. Encroachment of the RA is very rare in patients with hepatic malignancies. Furthermore, a prolongation of survival time is found in those patients who underwent TACE.
文摘AIM: To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3β), CCL20 (MIP-3a) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (HCC) versus colorectal liver metastases (CRLM) and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS: Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT- PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS: Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION: Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.
基金Supported by the Fund for Scientific Research-Flanders, No. 1.5.001.04N[F.B.]
文摘Nowadays, liver metastasis remains difficult to cure. When tumor cells escape and arrive in the liver sinusoids, they encounter the local defense mechanism specific to the liver. The sinusoidal cells have been widely described in physiologic conditions and in relation to metastasis during the past 30 years. This paper provides an “overview” of how these cells function in health and in diseases such as
文摘AIM: To examine whether antithrombin (AT) could prevent hepatic ischemia/reperfusion (I/R)-induced hepatic metastasis by inhibiting tumor necrosis factor (TNF)-α-induced expression of E-selectin in rats. METHODS: Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically. The number of metastatic nodules was counted on day 7 after I/R. TNF-α and E-selectin mRNA in hepatic tissue, serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2, were measured. RESULTS: AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-α and E-selectin in animals subjected to hepatic I/R. Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF1α were significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT. Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenital AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice. CONCLUSION: AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-α-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.
基金The research performed in this lab is supported by Shanghai Science Foundation(NO.04DZ14006)National Natural Science Foundation(NO.30450001)+1 种基金Major State Basic Research Development program of China(NO.2004CB51 8804)the National High Technology Re-search and Development Program of China(NO.2002AA2Z3352).
文摘DNA methylation is the most intensively studied epigenetic phenomenon, disturbances of which result in changes ingene transcription, thus exerting drastic imparts onto biological behaviors of cancer. Both the global demethylation andthe local hypermethylation have been widely reported in all types of tumors, providing both challenges and opportunitiesfor a better understanding and eventually controlling of the malignance. However, we are still in the very early stage ofinformation accumulation concerning the tumor associated changes in DNA methylation pattern. A number of excellentrecent reviews have covered this issue in depth. Therefore, this review will summarize our recent data on DNA methy-lation profiling in cancers. Perspectives for the future direction in this dynamic and exciting field will also be given.
基金Supported by the MIUR and Progetto Strategico Oncologia "Terapia Preclinica Moleculare Oncologia" MIUR-CNR
文摘AIM: To investigate the association of cyclooxygenase-2 (COX-2) expression with angiogenesis and the number and type of inflammatory cells (macrophages/Kupffer cells; mast cells) within primary hepatocellular carcinoma (HCC) tissues and adjacent non-tumorous (NT) tissues. METHODS: Immunohistochemistry for COX-2, CD34, CD68 and mast cell tryptase (MCT) was performed on 14 well-characterized series of liver-cirrhosis-associated HCC patients. COX-2 expression and the number of inflammatory cells in tumor lesions and surrounding liver tissues of each specimen were compared. Moreover, COX-2, CD34 staining and the number of inflammatory cells in areas with different histological degrees within each tumor sample were comparatively analyzed. RESULTS: The percentage of COX-2 positive cells was significantly higher in NT tissues than in tumors. COX-2 expression was higher in well-differentiated HCC than in poorly-differentiated tissues. Few mast cells were observed within the tumor mass, whereas a higher number was observed in the surrounding tissue, especially in peri-portal spaces of NT tissues. Abundant macrophages/ Kupffer cells were observed in NT tissues, whereas the number of cells was significantly lower in the tumor mass. However, a higher cell number was observed in the welldifferentiated tumor and progressively decreased in relation to the differentiation grade. Within the tumor, a positive correlation was found between COX-2 expression and the number of macrophages/Kupffer cells and mastcells. Moreover, there was a positive correlation between CD34 and COX-2 expression in tumor tissues. Comparison between well- and poorly-differentiated HCC showed that the number of CD34-positive cells decreased with dedifferentiation. However, COX-2 was the only independent variable showing a positive correlation with CD34 in a multivariate analysis. CONCLUSION: The presence of inflammatory cells and COX-2 expression in liver tumor suggests a possible relationship with tumor angiogenesis. COX-2 expressing cells and the number of macrophages/Kupffer cells and mast cells decrease with progression of the disease.
文摘AIM: To explore the relation between heparanase (HPA) and nm23-H1 in hepatocellular carcinoma (HCC), and whether they could be used as valuable markers in predicting post-operative metastasis and recurrence of HCC. METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry (S-P method) were used to measure the expressions of HPA mRNA and nm23-H1 protein in primary tumor tissue and paracancerous tissue of 33 cases of HCC. Paracancerous tissues of 9 cases of benign liver tumor were used as normal controls. The results were analyzed in combination with the results of clinicopathological examination and follow-up. RESULTS: The positive expression of HPA gene was significantly higher in primary tumor tissues of HCC (48.5%, 16/33) as compared to the paracancerous tissues of HCC and normal controls (3.03%, 1/33) (P<0.01). HPA expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state and cirrhosis of liver. The positive rates of HPA mRNA in the group with high tendency to metastasis or recurrence and in the group with metastasis or recurrence during the follow-up were significantly higher than those in the group with low tendency to metastasis or recurrence (62.5% vs 37.5%, P<0.05) and in the group without metastasis or recurrence (78.6% vs 21.4%, P<0.01). The poorly differentiated tumor and tumor of TNM stages Ⅲ-Ⅳ had a higher positive rate of HPA gene expression than the well differentiated tumor and tumor of TNM stages Ⅰ-Ⅱ (66.7% vs 33.3%, P<0.05). The positive expression rate of nm23-H1 protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (45.5, 72.7, 88.9%, P<0.05). nm23-H1 expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state, cirrhosis of liver, Edmondson grade, and TNM stage (P>0.05). The positive rates of nm23-H1 in the group with high tendency to metastasis and recurrence and in patients with metastasis or recurrence during the follow-up were obviously higher than those in the group with low tendency to metastasis and recurrence (P= 0.018) and in the patients without metastasis and recurrence (P = 0.024); but no significant difference was found between HPA positive and negative groups (P = 0.082). According to the results of follow-up, the rate of accuracy in predicting metastasis of positive HPA, negative nm23-H1 and combination of positive HPA with negative nm23-H1 was 78.6% (11/14), 68.8% (11/16) and 88.9% (8/9), respectively. CONCLUSION: Expression of HPA and/or nm23-H1 is related with metastasis and recurrence of HCC. Detection of the expression rate of HPA and nm23-H1 may help increase the accuracy in predicting post-operative metastasis and recurrence of HCC.
基金National Basic Research Priorities Program No. 2001CB510202National Science and Technology Key Project No. 2002BAC11A11 and 2004BA711A19+2 种基金National Natural Science Foundation of China No. 20328508National High Technology Research Developing Program No. 02BAC11A11Shanghai Science and Technology Development Program No. 03DZ14024
文摘AIM: To analyze the metastasis-related proteins in hepatocellular carcinoma (HCC) and discover the biomarker candidates for diagnosis and therapeutic intervention of HCC metastasis with bioinformatics tools. METHODS: Metastasis-related proteins were determined by stable isotope labeling and MS analysis and analyzed with bioinformatics resources, including Phobius, Kyoto encyclopedia of genes and genomes (KEGG), online mendelian inheritance in man (OMIM) and human protein reference database (HPRD). RESULTS: All the metastasis-related proteins were linked to 83 pathways in KEGG, including MAPK and p53 signal pathways. Protein-protein interaction network showed that all the metastasis-related proteins were categorized into 19 function groups, including cell cycle, apoptosis and signal transduction. OMIM analysis linked these proteins to 186 OMIM entries. CONCLUSION: Metastasis-related proteins provide HCC cells with biological advantages in cell proliferation,migration and angiogenesis, and facilitate metastasis of HCC cells. The bird's eye view can reveal a global characteristic of metastasis-related proteins and many differentially expressed proteins can be identified as candidates for diagnosis and treatment of HCC.
文摘Hepatocellular carcinoma (HCC) is a so highly invasive tumor that metastasizes hematogenously and lymphogenously to distant site. Frequent sites are lung, regional lymph node, bone, and adrenal gland. But metastasis to the gastrointestinal (GI) tract is rare, and most common site is stomach. Metastasis to the small intestine is extremely rare. Moreover, metastatic HCC of the small bowel causing intussusception has not been reported until now. Here, we report a case of metastasis of HCC to the small bowel manifested by intussusception.
基金The National Basic Research Program of China, 973 Program, No. 2003CB515504
文摘AIM:To develop a model using easily obtainable, objective, verifiable preoperative parameters, to help evaluate post transplant survival probability for hepatocellular carcinoma (HCC) patients with hepatitis B. METHODS:We retrospectively examined a cohort of 150 consecutive primary cadaveric liver transplants with HCC in our center over 6 years. Thirteen preoperative biochemical parameters and six tumor-related factors were analyzed to identify their correlation with post transplant survival using the Cox proportional-hazards regression model. The predictive power of a new model and the model for end stage liver disease was compared by the receiver operating characteristic curve. RESULTS:In univariate analysis, the factors significantly associated with post transplant survival were serum concentrations of albumin, total bilirubin, alkaline phosphatase, alpha-fetoprotein, γ-glutamyltransferase, aspartate aminotransferase, sodium, tumor diameter and the number of tumor nodules. Multivariate analysis showed alpha-fetoprotein, serum sodium, alkaline phosphatase and the number of tumor nodules were significantly associated with the post transplant outcome. Based on the four variables, we established a new model with a c-statistic of 0.72 which was significantly greater than 0.50 (P = 0.001), and the c-statistic of MELD was 0.59 (P = 0.146).CONCLUSION:The new model based on four objective tumor-related parameters has the capacity to evaluate the risk of post transplant mortality for HCC patients with hepatitis B.
文摘To review the preventive approaches for recurrence after curative resection of hepatic metastases from colorectal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) covered in PubMed. The treatment approaches presented above include adjuvant intrahepatic arterial infusion chemotherapy, systemic chemotherapy, neoadjuvant chemotherapy, and immunotherapy. Although no standard treatment has been established, several approaches present promising results, which are both effective and tolerable in post-hepatectomy patients. Intrahepatic arterial infusion chemotherapy should be regarded as effective and tolerable and it increases overall survival (OS) and disease free survival (DFS) of patients, while 5-fluorouracil-based systemic chemotherapy has not shown any significant survival benefit. Fortunately chemotherapy combined with hepatic arterial infusion and intravenous infusion has shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have been conducted to evaluate its effect on prolonging survivals although many retrospective studies and case reports are published in which unresectable colorectal liver metastases are downstaged and made resectable with neoadjuvant chemotherapy. Liver resection supplemented with immunotherapy is associated with optimal results; however, it is also questioned by others. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence after hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric RCT is still needed for further evaluation on their efficacy and systemic or local toxicities. In addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with resectable hepatic metastases from CRC.
文摘AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also tested.RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297,respectively, P<0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs42.69±6.99 ng/L, P<0.05). No statistical difference in ALT and AFP was observed between groups.CONCLUSION: Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.
基金Supported by National Natural Science Foundation of China, No.30371583
文摘AIM: To screen genes differentially expressed in mouse hepatocarcinoma ascites cell line with high potential of lymphatic metastasis.METHODS: A subtracted cDNA library of mouse hepatocarcinoma cell line with high potential of lymphatic metastatic Hca-F and its synogenetic cell line Hca-P with a low metastatic potential was constructed by suppression subtracted hybridization(SSH) method. The screened clones of the subtracted library were sequenced and GeneBank homology search was performed.RESULTS: Fourteen differentially expressed cDNA fragments of Hca-F were obtained with two novel genes.CONCLUSION: SSH is a useful technique to detect differentially expressioned genes and an effective method to clone novel genes.
文摘Multiple liver tumors represent a challenging condition for abdominal surgeons both in the selection of technique and the rarity of diagnosis. There are no case reports on co-existence of liver metastases from both intestinal leiomyosarcoma and adenocarcinoma. The patient described in this report successfully underwent resection of both primary lesions and liver metastases in combination with chemotherapy. As for the leiomyosarcoma, the primary cecal lesion was revealed more than three years after the patient's first visit. Peritoneal, lymph-node, and lung recurrences were observed afterward, and thus surgeries on those regions were performed. Pathologically, the peritoneal and lung recurrences comprised leiomyosarcoma and the lymphnode recurrence was diagnosed as adenocarcinoma. Despite newly discovered multiple lung recurrences and regional lymph-node metastases, the patient lived a normal life for 73 mo after the initial operation based on multidisciplinary therapy. He ultimately died of liver failure due to invasive lymph-node recurrence from the rectal adenocarcinoma, in addition to multiple lung recurrences from the leiomyosarcoma. Hepatic recurrence did not occur in this patient's case, which appears to be one reason for his long-term survival.
文摘Von Meyenburg complexes are benign liver lesions consisting of adenomatous bile duct proliferates. We present two patients suffering from esophageal cancer accompanied by the occurrence of yon Meyenburg complexes. Preoperative computerized tomography (CT) of the liver had not shown these lesions. In one of the patients, diffuse nodular manifestation was found in both liver lobes, mimicking diffuse hepatic metastases. Intraoperative frozen section revealed the benign nature of the lesions in both cases. The patients underwent esophageal resection without complications. To the best of our knowledge, the coincidence of von Meyenburg complexes and esophageal cancer has never been reported before. This uncommon entity should be taken into consideration as a differential diagnosis of liver lesions in malignancies. It underlines the importance of intraoperative frozen section for liver lesions of unknown origin.
文摘This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting a huge mass in the left external auditory canal (EAC). The patient was a 55-year-old man with hepatitis B virus-related HCC. He presented to our department with a three-month history of increasing left otalgia,and hearing loss with recent fresh aural bleeding. Histopathologic examination indicated that the tumor was secondary to HCC. Although external irradiation was not effective,the tumor was treated with surgical debulking and high dose rate 192 Ir remote afterloading system (RALS) for postoperative intracavitary irradiation. A review of the literature revealed only five other cases of HCC metastasis to the temporal bone,all of which mainly metastasized in the internal acoustic meatus. The present case is the first report of HCC metastasis to the EAC.