Metastatic Nodules In Liver Research Articles

Combined use of intraoperative ultrasound and indocyanine green fluorescence imaging to detect liver metastases from colorectal cancer

ObjectivesSurgical excision is the standard strategy for managing liver metastases from colorectal carcinoma. The achievement of negative (R0) margins is a major determinant of disease-free survival in these patients. Current imaging techniques are of limited value in achieving this goal. A new approach to the intraoperative detection of colorectal liver metastatic tissue based on the emission of indocyanine green (ICG) fluorescence was evaluated. MethodsA total of 25 consecutive patients with liver metastases from primary colorectal cancers who were eligible for liver resection received a bolus of ICG (0.5mg/kg body weight) 24h before surgery. During surgery, ICG fluorescence, which accumulates around lesions as a result of defective biliary clearance, was detected with a near-infrared camera system, the Photodynamic Eye (PDE). Numbers of lesions detected by, respectively, PDE + ICG, intraoperative ultrasound (IOUS) and preoperative computed tomography (CT) were recorded. ResultsThe near-infrared camera plus ICG revealed a total of 77 metastatic liver nodules. Preoperative CT demonstrated 45 (58.4%) and IOUS showed 55 (71.4%). Preoperative CT and IOUS alone were inferior to the combined use of PDE + ICG and IOUS in the detection of lesions of ≤3mm in size. ConclusionsThis experience suggests that PDE + ICG, combined with IOUS, may represent a safe and effective tool for ensuring the complete surgical eradication of liver metastases from colorectal cancer.

Hepatic arterial infusion combined with systemic chemotherapy induced complete response of metachronous liver metastases after resection of pancreatic insulinoma.

Insulinomas are the most common functioning pancreatic neuroendocrine tumors (PNETs). We herein present the case of a 5-year survivor with insulinoma after complete response of postoperative liver metastases to hepatic arterial infusion combined with systemic chemotherapy. A 58-year-old woman was admitted to our hospital following loss of consciousness. Examination revealed a pancreatic tumor, and she underwent distal pancreatectomy following diagnosis of insulinoma. Superparamagnetic iron oxide magnetic resonance imaging (SPIO-MRI) revealed multiple liver metastases 3months after surgery. Therefore, we performed hepatic arterial infusion of 5-fluorouracil (5-FU) combined with systemic gemcitabine infusion. We observed complete ablation of all metastatic liver nodules after 11 cycles of the chemotherapy using MRI. We continued this chemotherapy regimen for 20 cycles, and the patient remains alive without any recurrence 7years after surgery.

Fine‐Needle aspiration cytology of primary renal angiosarcoma with histopathologic and immunocytochemical correlation

Primary renal angiosarcoma is an extremely rare neoplasm, with fewer than 28 cases reported thus far in the English literature. We report for the first time the cytomorphology and immunocytochemistry of this tumor in liquid-based (ThinPrep) fine-needle aspiration (FNA) samples in correlation with the conventional cytologic and histopathologic findings. Conventional smears showed pleomorphic tumor cells focally arranged in structures suggesting anastomosing vascular channels, while ThinPrep smears were less cellular with fewer and smaller tumor cells arranged in clusters or rosette-like formations. Immunocytochemical staining demonstrated positive results for vimentin, CD31, and CD34 and negative staining for epithelial markers, thus supporting the diagnosis of a mesenchymal tumor of vascular origin. The diagnosis of primary renal angiosarcoma was established after histopathologic evaluation of a metastatic liver nodule. The cytological differential diagnosis of this neoplasm and the utility of the ThinPrep method as a diagnostic adjunct to conventional FNA cytology are further discussed.

B-flow imaging of vascular structure for the diagnosis of liver tumor.

B-flow is a non-Doppler-based technology for visualizing blood flow and has a high spatial resolution. The aim of this study is to evaluate the blood flow information of liver tumors using B-flow in comparison with color Doppler sonography (CDS). Seventy-nine patients with 82 hepatic nodules were studied using B-flow and CDS. The study group included 45 HCC nodules, 23 liver metastasis nodules, four intrahepatic cholangiocarcinomas (ICC), and 13 hemangiomas. The visualized vascularity and morphological findings of the hepatic tumor vessel were evaluated. B-flow showed multiple vessels in 48 nodules (58.5%) and a single vessel in 13 nodules (15.9%). CDS showed multiple vessels in 44 nodules (53.7%) and a single vessel in 23 nodules (28.0%). Multivariate analysis showed basket pattern was significant for HCC (OR 49.263; p=0.0002), and penetrating vessel was significant for liver metastasis or ICC (OR 14.545; p<0.0001). B-flow detects hepatic tumor blood flow with sensitivity as high as that of CDS. Vascular structure information obtained using B-flow could be potentially used to diagnose liver tumors.

Mode of administration affected the capability of soybean‐derived peptide lunasin to prevent metastasis of human colon cancer cells in a mouse model

The objective was to evaluate soybean‐derived peptide lunasin to inhibit KM12L4 human colon cancer cell metastasis in mouse model of colorectal cancer. Mouse was injected with 1 × 106 KM12L4 colon cancer cells in the spleen and randomization was made after 4 days. Mice that received 4 mg lunasin/kg body weight per day (i.p.) had a reduced number of liver metastatic tumors compared to group that received PBS (P = 0.047). Liver‐tumor tissue showed lunasin (4 mg/kg bw, per day, i.p.) reduced the expression of histone H3K18 (P = 0.002) and H4K8 (P &lt; 0.0001) with reduction in the expression of p300 enzyme (P = 0.039). Orally administered lunasin for 28 days reduced the number of liver metastatic nodules from 18 (PBS, n = 6) to 8 (8 mg/kg bw, n = 5, P = 0.293) to 1 (20 mg/kg bw, n = 3, P = 0.247); however, these values were not statistically significant. Gavage lunasin (8 mg/kg bw) did not significantly affect expression of proliferating cell nuclear antigen, pro‐apoptotic Bax, anti‐apoptotic Bcl‐2 and H3K18 and significantly increased the expression of H4K8 in liver‐tumor tissue. No liver‐tumor tissue was present for analysis after gavage lunasin (20 mg/kg bw). In conclusion, intraperitoneally‐administered lunasin (4 mg/kg bw) was effective in preventing colon cancer metastasis but not after oral administration of the bioactive peptide lunasin up to 20 mg/kg bw.Grant Funding Source: USDA

A Study of Gastric Cancer Cases with Liver Metastasis

The prognosis of gastric cancer patients with liver metastasis is very poor because many cases of gastric cancer with liver metastasis have multiple metastatic nodules in the liver and other non-curative factors, such as severe lymph node metastasis and/or peritoneal metastasis. The prognosis for gastric cancer patients with synchronous liver metastasis and the significance of hepatectomy including metachronous liver metastasis from gastric cancer in Kurume University Hospital are reported. Methods: A total of 77 gastric cancer patients with synchronous liver metastasis were admitted between 1995 and 2010 to Kurume University Hospital. There were 17 hepatectomy cases (synchronous metastasis 12 cases, metachronous metastasis 5 cases) from 1984 to 2010. Results: With respect to prognostic factors for gastric cancer cases with liver metastasis, significant differences were observed for peritoneal metastasis, histology, lymph node metastasis, gastrectomy, systemic chemotherapy, the number of stage IV factors, the number of metastatic nodules (within 3), and intra-hepatic arterial infusion (HAI). Multivariate analysis showed that histology, chemotherapy, and HAI were independent prognostic factors. The number of metastatic nodules in all 17 hepatectomy cases was within 3. Three of five cases with hepatectomy for metachronous metastasis were alive more than 5 years after hepatectomy. On the prognosis of hepatectomy cases, there were significant differences for synchronous or metachronous metastasis, lymph node metastasis, the number of stage IV factors, and the stromal volume of the primary site. Conclusions: Multimodal treatment including HAI is considered effective for gastric cancer cases with liver metastasis. If patients have no stage IV factors except for H factor, and the number of metastatic nodules is within 3, hepatectomy is recommended, especially for patients with metachronous liver metastasis, medullary stromal volume type, and low-grade lymph node metastasis.

Antisense oligonucleotide against clusterin regulates human hepatocellular carcinoma invasion through transcriptional regulation of matrix metalloproteinase-2 and E-cadherin.

Secreted clusterin (sCLU) has been shown to be overexpressed in metastatic hepatocellular carcinoma (HCC) tissue, and its overexpression in HCC cells increases cell migration and the formation of liver metastatic tumor nodules in vivo. In this study, we tested the hypothesis that sCLU plays a role in the invasiveness of human HCC and may be associated with its metastatic spread. HCCLM3, a human hepatocellular carcinoma cell line, was transiently transfected with an antisense oligonucleotide (ASO) against sCLU (OGX-011). HepG2 liver hepatocellular cells were transiently transfected with the pc.DNA3.1-sCLU plasmid to overexpress sCLU, and subsequently evaluated for effects on invasion and the expression of molecules involved in invasion. We observed that suppression of the sCLU gene significantly reduced the invasive capability of the highly invasive HCCLM3 cells, and vice versa in the low invasive HepG2 cell line. The results revealed that knockdown of sCLU by OGX-011 resulted in a significant increase in the expression of E-cadherin and a decrease in matrix metalloproteinase-2 (MMP-2) gene transcription. Overexpression of sCLU by transfection with pc.DNA3.1-sCLU significantly decreased the expression of E-cadherin and increased MMP-2 gene transcription. These data were further verified by reverse transcription-PCR and Western blot analysis. A significant reduction in MMP-2 expression and an increase in E-cadherin expression in sCLU-knockdown HCCLM3 cells were observed, as well as a significant increase in MMP-2 expression and a decrease in E-cadherin expression in HepG2 cells overexpressing sCLU. These data indicate a role for sCLU in augmenting MMP-2 transcription and decreasing E-cadherin expression. Our data show the involvement of sCLU in human HCC invasion, and demonstrate that silencing sCLU gene expression inhibits the invasion of human HCC cells by inhibiting MMP-2 expression and promoting E-cadherin expression. Thus, OGX-011 could be an effective therapeutic agent for HCC.

In vivo real-time imaging of chemotherapy response on the liver metastatic tumor microenvironment using multiphoton microscopy

Invivo real-time visualization of chemotherapy response at the cellular level provides us with direct evidence of what happens on the tumor microenvironment of metastatic organs. We imaged the response of metastatic tumor cells and host stromal cells to chemotherapeutics on liver metastatic xenografts in living mice using intravital two-photon laser scanning microscopy (TPLSM). Red fluorescent protein-expressing human colorectal cancer cells (HT29) was inoculated to the spleen of green fluorescent protein-expressing nude mice. 5-Fluorouracil or irinotecan was intraperitoneally administered after the formation of macroscopic liver metastases. Intravital TPLSM was performed at multiple time-points for time-series imaging of liver metastatic xenografts in the same mice. Under the 1st TPLSM, HT29 cells were visualized in hepatic sinusoids at the single cell level. Liver metastatic nodules consisting of viable cancer cells and surrounding stroma with tumor vessels were visualized under the 2nd TPLSM. After chemotherapy, tumor cell fragmentation, condensation, swelling and intracellular vacuoles were observed under the 3rd TPLSM. There was no obvious morphological difference in tumor response between these chemotherapeutics. Time-series intravital TPLSM imaging on the metastatic tumor xenografts may be useful for screening and evaluating new chemotherapeutics with less interindividual variability.

Polysaccharide-K (PSK) may suppress surgical stress-induced metastasis in rat colon cancer

We previously demonstrated that hepatic ischemia and reperfusion (I/R) injury increased liver metastasis and cancer growth of RCN-H4 cells. Using a rat model of hepatic I/R-induced liver metastasis, we investigated the metastasis-suppressing effect of polysaccharide-K (PSK), a biological response modifier composed of protein-bound polysaccharide. Fischer rats underwent 60 min of 70% partial hepatic ischemia. After 60 min of reperfusion, rat colon adenocarcinoma cells (RCN-H4) were inoculated intrasplenically. PSK was administered orally before I/R, after I/R, or before and after I/R. The weights of metastatic lesions of the liver or the numbers of liver metastatic nodules were determined on day 21. The effect of PSK on angiogenesis was studied by a rat cornea model using RCN-H4 cells or a vascular endothelial growth factor (VEGF)-containing pellet and an in vitro VEGF-induced endothelial cell migration assay. PSK administration significantly (p < 0.05) suppressed the I/R-induced increase in hepatic metastasis of RCN-H4 cells. The suppression of I/R-promoted metastasis was observed irrespective of the timing of administration. Furthermore, PSK significantly suppressed angiogenesis induced by RCN-H4 cells (p < 0.05) and the VEGF pellet (p < 0.01). PSK significantly suppressed the VEGF-induced migration of vascular endothelial cells (p < 0.05). PSK may suppress metastasis induced by hepatic I/R. The suppression of angiogenesis by PSK may be one of the mechanisms of the inhibition of hepatic metastasis.

Lunasin potentiates the effect of oxaliplatin preventing outgrowth of colon cancer metastasis, binds to α 5β 1 integrin and suppresses FAK/ERK/NF-κB signaling

The effect of lunasin on colon cancer metastasis was studied using three human colon cancer cell lines in vitro and a liver metastasis model of colon cancer in vivo. Lunasin bound with α 5β 1 integrin and internalized into the nucleus of KM12L4 human colon cancer cells. Lunasin (10 μM) inhibited the activation of focal adhesion kinase (FAK) by 28%, 39% and 60% in RKO, HCT-116 and KM12L4 human colon cancer cells, respectively. Lunasin caused an increase in the expression of the inhibitor of kappa B alpha (IκB-α), a decrease in nuclear p50 NF-κB and a reduction in the migration of cancer cells. Lunasin (4 mg/kg bw) inhibited metastasis and potentiated the effect of oxaliplatin by reducing the expression of proliferating cell nuclear antigen. Liver metastatic nodules were reduced from 28 (PBS) to 14 (lunasin, P = 0.047) while combination of lunasin and oxaliplatin to 5 ( P = 0.004). The tumor burden was reduced from 0.13 (PBS) to 0.10 (lunasin, P = 0.039) to 0.04 (lunasin + oxaliplatin, P < 0.0001). Moreover, lunasin potentiated the effect of oxaliplatin in modifying expression of proteins involved in apoptosis and metastasis including Bax, Bcl-2, IKK-α and p-p65. Lunasin inhibited metastasis of human colon cancer cells by direct binding with α 5β 1 integrin suppressing FAK/ERK/NF-κB signaling, and potentiated the effect of oxaliplatin in preventing the outgrowth of metastasis.

Toxocariasis Masquerading as Liver and Lung Metastatic Nodules in Patents with Gastrointestinal Cancer: Clinicopathologic Study of Five Cases

There are sporadic reports in the literature in which radiologic liver and lung lesions found incidentally during follow-up metastatic surveillance were shown to be caused by toxocariasis. The objective of the work discussed in this report was to identify common clinical and histopathological features of toxocariasis resembling metastatic nodules in five patients with gastrointestinal cancer. We retrospectively analyzed clinical features of five gastrointestinal cancer patients with liver or lung nodules mimicking metastasis. Serologic tests for parasitic infestations and pathologic examinations were performed. All five patients were males and three patients had gastric cancer and two had colorectal cancer. All the cases of toxocariasis were confirmed serologically. On follow-up imaging, the lesions improved or resolved, suggestive of the phenomenon of visceral larva migrans. In two patients, liver biopsy was performed and showed eosinophilic abscess. Serologic tests and liver or lung biopsy should be performed aggressively to exclude toxocariasis when patients with underlying gastrointestinal cancer present with hepatic or pulmonary nodules associated with eosinophilia, particularly if the patients have a clinical history of raw animal liver ingestion. Curative surgical intervention should not be excluded just because of multiple nodules in the liver or the lungs.

Suppression of SOCS3 in macrophages prevents cancer metastasis by modifying macrophage phase and MCP2/CCL8 induction

Inflammation has been demonstrated to play important roles in tumorigenesis, tumor progression, and metastasis. STAT3 has been shown to be frequently activated in a variety of human cancer cells and STAT3 signaling promotes the growth and survival of tumor cells. However, the role of STAT3 of myeloid cells associated with tumors is currently unknown. Suppressor of cytokine signaling-3 (SOCS3) has been shown to be a negative regulator of STAT3. In this study, we used macrophage specific SOCS3 conditional knockout (cKO) mice to investigate the effect of the hyperactivation of STAT3 in macrophages on tumor development and metastasis. In a subcutaneous transplantation model of B16F10 melanoma cells, although tumor sizes were not significantly different, SOCS3-cKO mice survived longer than wild-type (WT) mice did. SOCS3-cKO mice exhibited fewer lung and liver metastatic tumor nodules than WT mice when B16F10 was challenged intravenously. SOCS3 −/− macrophages stimulated with tumor lysates in vitro exhibited prolonged STAT3 phosphorylation and produced less amount of TNFα and IL-6, and higher amount of MCP2/CCL8 than WT macrophages. MCP/CCL8 was induced via STAT3 and exhibited anti-tumor metastatic effect in WT mice. These data suggest that hyperactivation of STAT3 in myeloid cells simultaneously exerted an anti-inflammatory as well as anti-tumor effects. Thus, the targeted inhibition of SOCS3 activity in macrophages may be therapeutic for the suppression of tumor metastasis.

Abstract 2120: Secreted protein acidic and rich in cysteine, like 1(SPARCL1), inhibits aggressiveness and relates to better prognosis in colorectal cancers

Abstract Secreted protein that's acidic and rich in cysteine, like 1(SPARCL1), an extracellular de-adhesion glycoprotein, was down-regulated in several solid cancers such as non-small cell lung cancer and pancreatic cancer. Our previous study revealed that expression of SPARCL1 was negatively related to liver metastasis of colorectal cancer (CRC). To clarify the function of SPARCL1 and its mechanism in CRC, the overexpression cell clone, RKO-SPARCL1, was created for illustrating biological behavior of SPARCL1 in vitro and in vivo. It was shown that SPARCL1 significantly reduced colony formation (p=0.027), invasion ability (p=0.001) and adhesion (p=0.04) of CRC cells in vitro. In comparison with vector control (RKO-pLXSN), RKO-SPARCL1 displayed significantly reduction in liver metastatic nodules in intrasplenic injection nude mice model (p=0.009). Meanwhile, tissue samples from 412 CRC patients were reassembled as tissue microarray for an outcome study. The antibody against SPARCL1 was developed for Immunohistochemistry (IHC) staining to assess the expression level of SPARCL1. Uni- and multivariate Logistic analysis demonstrated that SPARCL1 was negatively related with poorly tumor differentiation (p=0.001), lymph node metastasis (Odds ratio, OR=0.67, 95% 0.45-1.00) and distant metastasis (OR=0.39, 95% 0.18-0.82). The Kaplan-Meier analysis revealed that overexpression of SPARCL1 was significantly related to better overall survival in CRCs (p=0.004). Furthermore, the multivariate COX proportional hazard analysis demonstrated that SPARCL1 significantly reduced the risk of death from CRC (Hazard ratio, HR=0.57, 95% 0.39-0.84). Based on bioinformatics gene ontology analysis for gene expression microarray, overexpression of SPARCL1 significantly inhibited focal adhesion pathway and other tumor-associated oncogenes, such as S100A4 and ERBB3, in RKO cell line. Therefore, it is concluded that SPARCL1 may function as a tumor suppressor inhibiting the aggressiveness of cancer cells and reducing the risk of death from CRCs. It is suggested that SPARCL1 may serve as a prognostic biomarker for CRCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2120. doi:10.1158/1538-7445.AM2011-2120

Reversal of gastrointestinal carcinoma-induced immunosuppression and induction of antitumoural immunity by a combination of cyclophosphamide and gene transfer of IL-12

Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC.

Real-Time Elastography in Differentiating Metastatic From Nonmetastatic Liver Nodules

The study was designed to evaluate the role of real-time elastography in differentiating metastatic from nonmetastatic liver nodules, which include various benign lesions, hepatocellular carcinoma (HCC) nodules and lymphoma. Out of 1000 prospective patients who underwent abdominal ultrasound (US) examination, 48 patients had liver nodules. Nodule stiffness was determined by real-time elastography (ES) using color maps and shear wave velocity (SWV) and nodules having marked stiffness or SWV of more than 2.5 m/s were diagnosed as metastatic. The final diagnosis was made on fine needle aspiration cytology. No statistically significant differences were seen on elastomaps in the stiffness of metastatic and nonmetastatic nodules ( p = 0.16) while SWV showed statistically significant differences in the strain velocities of benign, metastatic and heptocellular carcinoma nodules p < 0.0001 and < 0.008, respectively. At a cutoff value of SWV 2.5 m/s, the sensitivity, specificity and false positive to detect metastatic nodules by ES were 88%, 83% and 16%, respectively. When the SWV cut off value was set at 2.0 m/s the sensitivity, specificity and false positive were 94%, 70% and 29%, respectively. The study showed that estimation of SWV by ES at a cut off value of 2.5 m/s was a better and a more useful tool in diagnosing both solid and necrotic metastatic liver nodules compared with the color stiffness maps alone. (E-mail: info@advanceddiagnostics.in)

Adenosquamous Carcinoma Arising in Congenital Choledochal Cyst

Adenosquamous carcinoma arising in congenital choledochal cyst is very rare and herein we report a case thereof. A 37-year-old woman was referred for further evaluation of pancreas head mass and a hepatic nodule on CT. She had been diagnosed with congenital choledochal cyst at 22-years-old and received Roux-en-Y choledochojejunostomy at that time. Endoscopic ultrasonography-guided biopsy proved the pancreas head mass as a squamous cell carcinoma and liver biopsy also proved the liver mass as a metastatic squamous cell carcinoma. We performed pancreaticoduodenectomy and tumorectomy of metastatic liver nodule. Grossly, the primary lesion was located at intrapancreatic portion of choledochal cyst. Histologically, the primary lesion and hepatic nodule was metastatic adenosquamous carcinoma. So far, there have been only three cases of adenosquamous carcinoma arising in congenital choledochal cyst reported in English-language literature. This is another case and the first case reported in Korea.

Enlarged solitary necrotic nodule of the liver misinterpreted as a metastatic liver cancer.

Solitary necrotic nodule of the liver is a rare nonmalignant lesion of unknown etiology. It is defined as a nodule with a completely necrotic core enclosed by a hyalinized fibrotic capsule containing elastic fiber. We report a 74-year-old woman with a solitary necrotic nodule of the liver that mimicked metastasis from a previous rectal adenocarcinoma. She was referred to us for an asymptomatic liver nodule in segment 8 that had increased in diameter from 5 to 15mm over the past 8months. Ultrasonography showed a well-defined, oval, hypoechoic mass, and computed tomography showed a hypodense area without contrast enhancement except for a ring-like enhancement during hepatic arteriography. Magnetic resonance imaging revealed a mass that was hypointense on T1-weighted imaging and slightly hyperintense on T2-weighted imaging. The patient underwent hepatectomy of segment 8. The resected specimen contained an oval nonencapsulated nodule with firm and gritty consistency and a well-defined margin. Histologic findings were compatible with those of solitary necrotic nodule. Clinicians should recognize the existence of this lesion as one of the differential diagnoses of metastatic liver nodule. Solitary necrotic nodules can change size, and when enlarged, differentiation from metastasis is extremely difficult.

Prevention of hepatic tumor growth and metastasis in rats with rapamycin

To test the effect of rapamycin (RAPA) on hepatic tumor growth and metastasis in Sprague-Dawley (SD) rat model and explore the possible mechanism. SD rat hepatocellular carcinoma (HCC) model with metastatic potential was induced by diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR). 120 SD rats were randomized into four groups 16 weeks after DEN and NMOR treatment, and received 4-week intraperitoneal injection of RAPA (1.5 or 4.5 mg x kg(-1) x d(-1)), CsA (25 mg x kg(-1) x d(-1)) or equal volume of 0.9% saline, respectively. Tumor growth and metastasis were checked after the 4-week treatment. Serum vascular endothelial growth factor (VEGF) was determined by enzyme-linked immunosorbent assay (ELISA). Antiangiogenetic effects were assessed by CD34 immunostaining. The levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and VEGF proteins and mRNAs were detected by immunohistochemistry, western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). The mean liver weight (5.58% +/- 0.42% and 5.69% +/- 0.74%), the metastatic liver nodules (5.12 +/- 0.68 and 5.67 +/-1.12), the metastasis lung nodules (0.43 +/- 0.11 and 0.45 +/- 0.83), and the lung metastasis rate (17.2% and 14.8%) were lower in rats treated with RAPA 1.5 mg x kg(-1) x d(-1) or 4.5 mg x kg(-1) x d(-1) than those in rats treated with saline, which were 10.42% +/- 1.86%, 12.36 +/- 3.45, 1.81 +/- 0.3 and 50.0% respectively (P < 0.01 or P < 0.05). The intratumoral microvessel density (MVD), serum VEGF, and the levels of HIF-1 alpha and VEGF were lower in RAPA-treated rats than those in control rats. However, CsA-treated rats showed an opposite trend compared with the RAPA-treated rats. RAPA can repress the expression of angiogenesis-promoting factors HIF-1 alpha and VEGF, and significantly inhibits the growth and metastasis of HCC.

Extracranial Metastases of Glioblastoma in a Child

Glioblastoma (GBM) is the most common adult malignant brain tumor but is notably less common in children. Primary brain tumors rarely metastasize outside the central nervous system and when metastases occur, it is often in patients with diversionary shunting of the cerebrospinal fluid. This report details the case of a 13(1/2)-year-old boy who was diagnosed with GBM. He survived 10 months after diagnosis. At autopsy, the tumor was found to extensively infiltrate the leptomeninges as well as the cranial skin and soft tissue. Further examination disclosed multiple liver and lung metastatic GBM nodules. This pattern of spread is very uncharacteristic of gliomas and emphasizes the importance of adequate metastatic evaluation.

Treatment for multiple bilobar liver metastases of colorectal cancer

Recent advances have extended indications for hepatectomy to include multiple bilobar colorectal liver metastases (CLM). Staging systems based on the biological malignancy of primary and metastatic tumors provide appropriate indications for hepatectomy in CLM. However, suitability for resection in patients with complex and extensive hepatic metastases is controversial. A medline search was performed to identify papers reporting the resection for CLM. Techniques, indication, and results were reviewed. If the anticipated remnant liver volume is small (25-40% of total), suggesting a high risk of postoperative liver failure, portal vein embolization (PVE) is recommended prior to hepatectomy. However, curative resections are not always possible. Specifically in synchronous multiple bilobar CLM, two-stage hepatectomy, comprising bilateral hepatectomy and primary resection with or without PVE, can prevent growth of ipsilateral metastatic nodules in the remnant liver and reduce surgical risk. Several local ablation techniques can complement surgery if hepatic resection alone increases the risk of postoperative liver failure or is not curative. Chemotherapy combined with targeted treatment can suppress recurrence and extend indications for hepatectomy by reducing the size and number of primary irresectable tumors. PVE or staged procedure combining with local ablation or neoadjuvant, downstaging or adjuvant therapies extends indications for hepatectomy to include multiple bilobar CLM. The 5-year survival rate for multiple bilobar CLM treated with alternating hepatectomy and chemotherapy is comparable to the values reported for single and hemilateral CLM.