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Background: Circular RNAs (circRNAs) play a critical role in colorectal cancer (CRC) progression, including metastasis. However, the detailed molecular mechanism is not fully understood., Methods: Differentially expressed circRNAs between primary KM12C and liver metastatic KM12L4 colon cancer cells were identified by microarray. The expression of circRNAs was measured by semi-quantitative (semi-qPCR) and real time-quantitative PCR (RT-qPCR). Metastatic potential including invasive and migratory abilities, and liver metastasis were examined by transwell assays and intrasplenic injection, respectively. CircPPFIA1-associated microRNA (miRNA) and RNA-binding protein (RBP) were screened by an antisense oligonucleotide (ASO) pulldown experiment. The effects of circPPFIA1 on target gene expression were evaluated by RT-qPCR and western blot analyses., Results: By analyzing circRNA microarray data, we identified two anti-metastatic circRNAs generated from PPFIA1 with different length, which named circPPFIA1-L (long) and -S (short). They were significantly downregulated in liver metastatic KM12L4 cells compared to primary KM12C cells. The knockdown of circPPFIA1s in KM12C enhanced metastatic potential and increased liver metastasis. Conversely, overexpression of circPPFIA1s weakened metastatic potential and inhibited liver metastasis. circPPFIA1s were found to function as sponges of oncogenic miR-155-5p and Hu antigen R (HuR) by an ASO pulldown experiment. circPPFIA1s upregulated tumor-suppressing CDX1 expression and conversely downregulated oncogenic RAB36 by decoying miR-155-5p and by sequestering HuR, respectively., Conclusion: Our findings demonstrate that circPPFIA1s inhibit the liver metastasis of CRC via the miR-155-5p/CDX1 and HuR/RAB36 pathways., (© 2022. The Author(s).)

Background: Laparoscopic liver resection for metastatic colorectal cancer (CRC) remains controversial. The objective of this study was to compare the short-term and mid-term outcomes of patients with CRC undergoing laparoscopic versus open colorectal resection with simultaneous resection for liver metastases., Methods: A total of 126 patients underwent combined laparoscopic resection of CRC and synchronous colorectal liver metastases between 2008 and 2016. A total of 318 patients were treated by an open approach during the above period. By propensity score matching, 109 patients who underwent laparoscopic resection and 109 patients who had an open approach were compared. Analyzed variables included patient characteristics, tumor features, and short-term and mid-term outcomes., Results: Demographic features and pathologic outcomes were similar in both groups after propensity score matching. Three (2.8%) patients undergoing laparoscopic liver resection experienced conversion to open procedure. There was no difference in hospital stay (p = 0.078), transfusion rate (p = 0.686), or time of bowel function return (p = 0.570) between the two groups. The laparoscopic group and the open approach group also showed similar 3-year overall survival rate (74.4% vs. 79.1%; p = 0.792) and 3-year disease-free survival rate (58.5% vs. 55.2%; p = 0.391). However, postoperative morbidity rate was significantly lower in the laparoscopic group (20.2% vs. 33.0%; p = 0.032)., Conclusions: Laparoscopic colorectal resection with simultaneous resection of liver metastases showed satisfactory oncologic outcomes with some short-term advantages compared to the open approach. Thus, laparoscopic approach could be a good alternative of open approach for simultaneous liver and colon resection in patients with CRC.

Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.

Metastasis is the primary cause of cancer mortality. The primary tumors of colorectal cancer (CRC) often metastasize to the liver. In this study, we have collected 122 samples from 45 CRC patients. Among them, 32 patients have primary tumors, adjacent normal tissues, and matched liver metastases. Thirteen patients have primary tumors without distant metastasis and matched normal tissues. Characterization of these samples was conducted by whole-exome and RNA sequencing and SNP6.0 analysis. Our results revealed no significant difference in genetic alterations including common oncogenic mutations, whole genome mutations and copy number variations between primary and metastatic tumors. We then assembled gene co-expression networks and identified metastasis-correlated gene networks of immune-suppression, epithelial-mesenchymal transition (EMT) and angiogenesis as the key events and potentially synergistic drivers associated with CRC metastasis. Further independent cohort validation using published datasets has verified that these specific gene networks are up regulated throughout the tumor progression. The gene networks of EMT, angiogenesis, immune-suppression and T cell exhaustion are closely correlated with the poor patient outcome and intrinsic anti-PD-1 resistance. These results offer insights of combinational strategy for the treatment of metastatic CRC.

Purpose: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer tumor samples to determine whether tumor heterogeneity can predict tumor metastasis. Experimental Design: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole-exome sequencing. Tumor clonality was estimated from single-nucleotide and copy-number variations. The correlation between clinical parameters of patients and clonal heterogeneity in liver metastasis was evaluated. Results: Tumor heterogeneity across colorectal cancer samples was highly variable; however, a high degree of tumor heterogeneity was associated with a worse disease-free survival. Highly heterogeneous primary colorectal cancer was correlated with a higher rate of liver metastasis. Recurrent somatic mutations in APC, TP53 , and KRAS were frequently detected in highly heterogeneous colorectal cancer. The variant allele frequency of these mutations was high, while somatic mutations in other genes such as PIK3CA and NOTCH1 were low. The number and distribution of primary colorectal cancer subclones were preserved in metastatic tumors. Conclusions: Heterogeneity of primary colorectal cancer tumors can predict the potential for liver metastasis and thus, clinical outcome of patients. Clin Cancer Res; 23(23); 7209-16. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Liver metastasis is a leading cause of death in patients with colorectal cancer. Investigating the mechanisms of liver metastasis and control of disease progression are important strategies for improving survival of these patients. Liver metastasis is a multi-step process and relevant models representing these steps are necessary to understand the mechanism of liver metastasis and establish appropriate treatments. Recently, the development of animal models for use in metastasis research has greatly increased; however, there is still a lack of models that sufficiently represent human cancer. Thus, in order to select an optimal model for of a given study, it is necessary to fully understand the characteristics of each animal model. In this review, we describe the mouse models currently used for colorectal cancer with liver metastasis, their characteristics, and their pros and cons. This may help us specify the mechanism of liver metastasis and provide evidence relevant to clinical applications., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: KRAS mutations are common in colorectal cancer (CRC). The role of KRAS mutation status as a prognostic factor remains controversial, and most large population-based cohorts usually consist of patients with non-metastatic CRC. We evaluated the impact of KRAS mutations on the time to recurrence (TTR) and overall survival (OS) in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy., Methods: Patients who underwent curative resection for primary and synchronous metastases were retrospectively collected in a single institution during a 6 year period between January 2008 and June 2014. Patients with positive surgical margins, those with known BRAF mutation, or those with an unknown KRAS mutation status were excluded, and a total of 82 cases were identified. The pathological and clinical features were evaluated. Patients' outcome with KRAS mutation status for TTR and OS were investigated by univariate and multivariate analysis., Results: KRAS mutations were identified in 37.8% of the patients and not associated with TTR or OS between KRAS wild type and KRAS mutation cohorts (log-rank p = 0.425 for TTR; log-rank p = 0.137 for OS). When patients were further subdivided into three groups according to mutation subtype (wild-type vs. KRAS codon 12 mutation vs. KRAS codon 13 mutation) or amino acid missense mutation type (G > A vs. G > T vs. G > C), there were no significant differences in TTR or OS. Mutational frequencies were significantly higher in patients with lung metastases compared with those with liver and ovary/bladder metastases (p = 0.039), however, KRAS mutation status was not associated with an increased risk of relapsed in the lung., Conclusions: KRAS mutation was not associated with TTR or OS in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy.

Despite numerous studies involving patient-derived xenograft (PDX) models, few studies have investigated the relationship between the ability of the tumor to engraft (tumorigenicity) and the clinical features of colorectal cancer (CRC). The aim of this study was to determine whether tumorigenicity correlates with clinical outcomes of CRC patients. We included 241 CRC patients who underwent radical surgery from 2010 to 2013. PDX models were established by implanting tumor fragments obtained from these patients into the subcutaneous layer of immunodeficient mice. Xenografts were successfully established from 62.2%. Successful engraftment was associated with advanced stage (p < 0.001) and moderate/poor differentiation (p = 0.029). Three-year disease-free survival (DFS) rates were lower for patients with tumorigenicity (p = 0.011). In stage III patients, tumorigenicity was an independent predictor of poor DFS (p = 0.034). In addition, mutation of TP53 was most frequently detected in stage III patients with tumorigenicity. Two models of stage IV disease without KRAS mutations showed high sensitivity to EGFR-targeted agents, while none of the models with KRAS mutations showed high sensitivity. In conclusion, PDX models may provide an effective preclinical tool for predicting cancer progression and could be used to further genomic and pharmacologic research on personalized treatments.

Aim: To compare outcomes from radiofrequency ablation (RFA) and hepatectomy for treatment of colorectal liver metastasis (CRLM)., Methods: From January 2000 to December 2009, 408 patients underwent curative intent treatment for CRLM. We excluded patients using the criteria: size of CRLM > 3 cm, number of CRLM ≥ 5, percutaneous RFA, follow-up period < 12 mo, double primary cancer, or treatment with both RFA and hepatectomy. We matched 51 patients who underwent RFA with 102 patients who underwent hepatectomy by propensity scores., Results: The median follow-up period was 45 mo (range, 12 mo to 158 mo). Hepatic recurrence was more frequent in the RFA than the hepatectomy group (P = 0.021) although extrahepatic recurrence curves were similar (P = 0.716). Survival curves of hepatectomy group were better than that of RFA for multiple, large (> 2 cm) CRLM (P = 0.034). However, survival curves were similar for single or small (≤ 2 cm) CRLM (P = 0.714, P = 0.740)., Conclusion: Hepatectomy is better than RFA for the treatment of CRLM. However, RFA might be suitable for selected patients with single, small (≤ 2 cm) CRLM.

Aim: To investigate the survival outcomes of secondary hepatectomy for recurrent colorectal liver metastases (CRLM)., Methods: From October 1994 to December 2009, patients with CRLM who underwent surgical treatment with curative intent were investigated. Patients were divided into two groups: patients who underwent primary hepatectomy (Group 1) and those who underwent secondary hepatectomy for recurrent CRLM (Group 2)., Results: Survival and prognostic factors were analyzed. A total of 461 patients were included: 406 patients in Group 1 and 55 patients in Group 2. After a median 39-mo (range, 3-195 mo) follow-up, there was a significant difference between Groups 1 and 2 in terms of disease-free survival (P=0.029) although there was no significant difference in overall survival (P=0.206). Secondary hepatectomy was less effective in patients with multiple recurrent CRLM than primary hepatectomy for initial CRLM (P=0.008). Multiple CRLM and radiofrequency ablation therapy were poor prognostic factors of secondary hepatectomy in multivariate Cox regression analysis (P=0.006, P=0.004, respectively)., Conclusion: Secondary hepatectomy for single recurrent CRLM is as effective as primary surgical treatment for single recurrent CRLM. However, secondary hepatectomy for multiple recurrent CRLM is less effective than that for single recurrent CRLM.

Background and Objectives: The purpose of this study was to determine the risk factors for requirement of surgical or endoscopic interventions for complications caused by the primary tumor during chemotherapy in patients with unresectable metastatic colorectal cancer., Methods: A total of 259 patients were diagnosed with uncomplicated colorectal cancer with unresectable metastatic disease and underwent chemotherapy as an initial treatment. Among them, 57 (22.0%) patients underwent palliative interventions because of complications caused by the primary tumor during chemotherapy, including bypass surgery or diverting enterostomy for 22 patients, insertion of colonic stent for 22, and resection of primary tumor for 13., Results: Multivariate analysis revealed that rectal lesion (RR, 2.132; 95% CI, 1.080-4.210; P = 0.029) and tumor size larger than 5 cm (RR = 3.644, 95% CI = 1.923-6.902; P < 0.001) were significant risk factors for requirement of palliative intervention. Patients who had none of the risk factors showed better overall survival than those who had one or more (P = 0.021)., Conclusions: Tumor location in rectum and tumor size larger than 5 cm were significant risk factors for the requirement of surgical or endoscopic interventions during chemotherapy for complications caused by the primary tumor in patients with unresectable metastatic colorectal cancer., (© 2014 Wiley Periodicals, Inc.)

Colorectal cancer (CRC) patients have poor prognosis after formation of distant metastasis. Understanding the molecular mechanisms by which genetic changes facilitate metastasis is critical for the development of targeted therapeutic strategies aimed at controlling disease progression while minimizing toxic side effects. A comprehensive portrait of somatic alterations in CRC and the changes between primary and metastatic tumors has yet to be developed. We performed whole genome sequencing of two primary CRC tumors and their matched liver metastases. By comparing to matched germline DNA, we catalogued somatic alterations at multiple scales, including single nucleotide variations, small insertions and deletions, copy number aberrations and structural variations in both the primary and matched metastasis. We found that the majority of these somatic alterations are present in both sites. Despite the overall similarity, several de novo alterations in the metastases were predicted to be deleterious, in genes including FBXW7, DCLK1 and FAT2, which might contribute to the initiation and progression of distant metastasis. Through careful examination of the mutation prevalence among tumor cells at each site, we also proposed distinct clonal evolution patterns between primary and metastatic tumors in the two cases. These results suggest that somatic alterations may play an important role in driving the development of colorectal cancer metastasis and present challenges and opportunities when considering the choice of treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Metastasis is one of the main reasons for colorectal cancer (CRC)-related deaths due to the lack of effective therapeutics mainly for liver metastasis. In the present study, we established an orthotopic colorectal cancer mouse model using different transplantation protocols to determine the optimal conditions for CRC liver metastasis., Materials and Methods: Luciferin-expressing HCT116 cells were used to induce liver metastasis models of colorectal cancer following both intra-splenic and cecal injections. Magnetic resonance imaging (MRI) and the In Vivo Imaging system were used to monitor internal growth of the primary tumor and metastasis., Results: The intra-splenic injection with high cell number (5×10(6) cells/50 μL)-group achieved rapid tumor formation, and the highest metastatic rate. However, survival rates were shorter than those of the other groups. The time to develop primary tumors and liver metastases was slightly different between the two transplantation protocols followed and should be considered depending on the specific aim of each experiment. MRI and optical images correlated well with the pathological findings at necropsy with respect to both tumor growth and location., Conclusion: The model described herein will be effective in studying new therapeutic strategies against metastatic disease when used in conjunction with small animal MRI and optical imaging., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The veins from the lower rectum drain into the systemic venous system, while those from other parts of the colon drain into the portal venous system. The aim of this study was to investigate recurrence pattern and survival according to the anatomical differences in patients with colorectal liver metastases (CRLM)., Methods: From October 1994 to December 2009, synchronous CRLM patients who underwent surgery were identified from our prospectively collected database. The patients were excluded if there had been extrahepatic metastases. The patients were divided into two groups according to the location of the primary colorectal cancer: lower rectal cancer (group 1) and upper rectal or colon cancer (group 2). The recurrence patterns and survival were investigated., Results: A total of 316 patients were included: 53 patients in group 1 and 263 patients in group 2. After a median follow-up of 37 months, the extrahepatic recurrence curve of group 1 was superior to that of group 2 (P < 0.001), although there was no difference between the hepatic recurrence curves (P = 0.93). The disease-free and overall survival curves of group 1 were inferior to those of group 2 (P = 0.004) (P < 0.001). Lower rectal cancer was a significant risk factor for extrahepatic recurrence in Cox proportional hazard model analysis (hazard ratio = 1.7, P = 0.04)., Conclusions: The extrahepatic recurrence rate is high in lower rectal cancer patients after surgical treatment for synchronous CRLM.

Background: Although laparoscopic colorectal resection and laparoscopic liver resection have been accepted as effective alternatives to conventional open procedures, there are only a few reports on the clinical availability of simultaneous performance of these two procedures. We report our collective experience of patients with colorectal cancers treated with totally laparoscopic colorectal and liver resection, in comparison with those treated with an open approach., Patients and Methods: This study is a retrospective, case-match review of prospectively collected data. Between May 2008 and December 2012, 24 patients with primary colorectal cancer and associated hepatic lesions underwent simultaneous laparoscopic colorectal and liver resection (laparoscopic group). They were matched with patients who underwent an open procedure (open group; n=24 out of 232) based on the types of surgery. Patient demographics, operative details, tumor-related parameters, and postoperative outcomes were analyzed., Results: Demographic features and pathologic outcomes were similar in both groups. The median duration of operation was significantly longer in the laparoscopic group than in the open group (290 versus 244 minutes; P=.008), and the median estimated blood loss was larger (325 versus 250 mL; difference not significant, P=.35). However, the time to starting a soft blended diet (3.0 versus 4.5 days; P<.001) and postoperative stay (8.0 versus 10.5 days; P=.001) in the laparoscopic group were both significantly shorter than in the open group. The postoperative complication rate was lower in the laparoscopic group (17% versus 42%; difference not significant, P=.06). The minor complication rate was significantly lower in the laparoscopic group (4% versus 33%; P=.02)., Conclusions: A totally laparoscopic approach might provide short-term benefits associated with enhanced postoperative recovery despite a longer procedure time and larger blood loss. It can be a reasonable option for simultaneous colorectal and hepatic resection.

In metastatic colorectal cancers, tumor cells are disseminated prior to surgical resection of the primary tumor but remain dormant until proper colonization mechanisms are activated. To identify the colonization mechanisms of the metastatic tumors, we conducted a pairwise comparison between primary colorectal cancers and metastatic tumors (n=12 pairs), including six hepatic pairs and six pulmonary pairs. The mRNA levels of 224 genes previously reported to be associated with metastasis, cytokines and angiogenesis were quantitatively determined by PCR arrays. Among them, 27 genes were duplicated or triplicated to show consistent expression. Unsupervised hierarchical clustering of the Ct values of metastasis-related genes revealed that liver metastases were indistinguishable from primary colorectal cancers (n=5/6), whereas lung metastases were highly diversified from one another and from the primary tumors (n=6/6). Cytokines and receptor gene expression array data also confirmed the divergence of pulmonary metastases from primary colorectal cancers (n=6/6). Heat map analyses of ΔCt values of the metastasis-related genes identified a 17-gene tropism signature that was sufficient not only to distinguish liver and the lung metastases, but also reconstituted the clustering of primary tumors with the hepatic metastases (n=17/18). In this pilot experiment, pulmonary metastases were significantly diverged from hepatic metastases that were indistinguishable from primary colorectal cancers. Further genomic and clinical studies are in progress to evaluate the potential of the tropism signature as a therapeutic target to inhibit the colonization of metastatic colorectal cancers.

The main cause of death for colorectal cancer (CRC) patients is the development of metastatic lesions at sites distant from the primary tumor. Therefore, it is important to find biomarkers that are related to the metastasis and to study the possible mechanisms. Recent data have shown that soluble attractant molecules called chemokines support the metastasis of certain cancers to certain organs. To identify molecular regulators that are differentially expressed in liver metastasis of CRC, PCR array analysis was performed and CC chemokine ligand 7 (CCL7) showed remarkable overexpression in liver metastatic tumor tissues. To validate the results of the PCR array, 30 patients with primary CRC and liver metastases were selected. Immunohistochemistry and real-time PCR analysis showed that CCL7 was expressed in normal colonic epithelium and the expression was higher in liver metastases compared to primary CRC (p<0.001). Real-time PCR showed that the expression of CCR1, CCR2 and CCR3 was also higher in liver metastases compared to primary CRC (p=0.001, p=0.033 and p<0.001, respectively). In conclusion, correlation of CCL7 overexpression and its receptor expression with colon cancer liver metastasis suggests that CCL7 as a novel target in liver metastasis of CRC may be of potential clinical value for the prevention of hepatic recurrences.

Background: Several surgical and non-surgical therapeutic modalities have been used for the treatment of hepatocellular carcinoma (HCC). There have been several studies comparing hepatic resection (HR) and percutaneous ethanol injection (PEI) for the treatment of HCC. However, there is still disagreement about the best treatment modality., Methods: From 130 patients undergoing HR, 116 patients were individually matched to 116 controls from 249 patients undergoing PEI using propensity score matching to overcome possible biases in non-randomized study. Survival analyses were undertaken to compare these propensity score-matched groups., Results: After matching by propensity score, the major clinical outcomes in the HR (n = 116) and the PEI (n = 116) groups were found to be similar. The 1-, 3- and 5-year overall survival rates were higher in the HR group (94.8%, 76.5% and 65.6%) compared to the PEI group (95.7%, 73.5% and 49.3%) (P = 0.059). The cumulative 1-, 3- and 5-year disease-free survival rates showed the same trend (HR: 76.1%, 50.6% and 40.6%; PEI: 62.6%, 25.5% and 19.1%) (P < 0.001). However, when stratified by Child-Pugh classification, it was no longer the case in the Child B patients. Single intrahepatic recurrence was the most common pattern of tumor recurrence after both treatments., Conclusions: Patients undergoing HR had a better survival profile than those undergoing PEI. However, when considering which technique to use for optimal HCC management, the individual patient's hepatic function must be considered.

Background/aims: Anatomical hepatectomy for small hepatocellular carcinomas (HCCs) is widely preferred but evidence concerning its benefits is inadequate. The aim of this study was to determine whether patient outcome is influenced by the method used to treat small single HCCs., Methodology: An analysis was performed on 168 patients who underwent curative hepatectomy for a single HCC smaller than 5cm between Jan 1998 and Dec 2001 at Seoul National University Hospital. Ninety-nine of these patients underwent anatomic resection and 69 patients non-anatomic resection. Overall survival rates, disease-free survival rates, and prognostic factors for survival and recurrence were analyzed., Results: The cumulative 1-, 3- and 5-year overall survival rates were 86.9%, 73.6% and 65.5% in the anatomic resection group, and 88.4%, 63.8% and 49.7%% in the non-anatomic resection group, respectively (P = 0.032). And, the cumulative 1-, 3- and 5-year disease-free survival rates were 77.8%, 58.6% and 54.4% in the anatomic resection group and 62.3%, 42.0% and 28.6% in the non-anatomic resection group, respectively (P = 0.003). Anatomic resection was confirmed to be an independent favorable factor of disease-free survival by multivariate analysis., Conclusions: Anatomic resection for single small HCCs is superior to non-anatomic resection.

Background: The development of living donor liver transplantation has stimulated discussion about the expansion of tumor burden limits for patients with hepatocellular carcinoma (HCC). Although serum alphafetoprotein (AFP) level is an important predictor of tumor recurrence, it is not included in the existing selection criteria for HCC in transplantation., Methods: We performed a retrospective study of 63 consecutive adults with HCC diagnosed preoperatively who received living donor liver transplantation from February 1999 to September 2005 and survived over 1 month. The authors devised new scoring criteria that included tumor size, tumor number, and pretransplant AFP level as prognostic factors. The score of each parameter was classified from 1 to 4 points (tumor size, < or =3, 3.1 to 5, 5.1 to 6.5, >6.5 cm; tumor number, 1, 2 or 3, 4 or 5, or > or =6 nodules; and AFP, < or =20, 20.1 to 200, 200.1 to 1000, >1000 ng/mL, respectively). We defined that 3 to 6 points and 7 to 12 points were "transplantable" and "nontransplantable," respectively. The usefulness of the devised criteria was then investigated as a method of selecting candidates with HCC for transplantation., Results: The candidates' overall 3-year survival rate and recurrence-free survival rate were 67% and 70% after transplantation, respectively. Based on pretransplant imaging, 37 (59%), 41 (65%), and 44 (70%) of the 63 patients met the Milan criteria, University of Californica, San Francisco (UCSF) criteria, and the new scoring criteria. Their 3-year survival rates were 80%, 78%, and 79%, respectively. Moreover, based on posttransplant data, the scoring criteria correlated with the risk of death and HCC recurrence (Milan criteria, P = .005 and .001; UCSF criteria, P = .013 and .001 for death and recurrence; scoring criteria, P < .001 for both)., Conclusions: The newly devised scoring criteria could expand usefully current selection criteria for transplantation without detrimentally affecting outcome in the living donor transplantation setting for HCC.

Background: The proper role of surgical resection, given the various treatment modalities available, needs to be further clarified in patients with a single large hepatocellular carcinoma (HCC). To evaluate the role of surgical resection in this group of patients, we studied the long-term outcomes of patients that received hepatic resection for a single large (> 5-10 cm in diameter) HCC., Methods: The clinicopathologic data and long-term outcomes of 61 patients with a single large HCC (> 5-10 cm in diameter; L group) were compared with those of 169 patients with a single small HCC (< or = 5 cm; S group). Prognostic factors were evaluated by univariate and multivariate analysis., Results: Operative mortality rates were low in both groups (0.6% in group S and 1.6% in group L), and the incidence of postoperative hepatic failure was rare even in group L (1.6%). The cumulative 5-year overall survival rate in group S was 59.0%, whereas in group L it was 52.9% (p = 0.385), and the corresponding cumulative 5-year disease-free survival rates were 44.1% and 31.7%, respectively (p = 0.063). Child class B was found to predict poor overall and disease-free survival by multivariate analysis versus Child class A in both groups. The presence of microvascular invasion was also identified as a significant prognostic factor, but it only affected disease-free survival in the two groups., Conclusions: Single large HCCs do not require a large extent of hepatic resection and the associated increased risk of postoperative liver failure. The long-term survival of patients with a single large HCC is as good as that of patients with a single small HCC. We conclude that hepatic resection is a safe and effective therapy for single large HCCs.

Positron emission tomography (PET) using F-18 fluoro-2-deoxy-d-glucose ((18)F-FDG) is now well established as a noninvasive diagnostic tool for the detection of a variety of malignant tumors. However, in the case of hepatocellular carcinoma (HCC), several investigators have reported controversial conclusions and an inadequate sensitivity for PET (50-55%). Nevertheless, a high positive rate of (18)F-FDG accumulation has been reported in patients with high-grade HCC and in those with markedly elevated alpha-fetoprotein (AFP) levels. Here, we retrospectively reviewed 38 HCC cases that received liver transplantation (LT) at our center between November 2000 and July 2004 and underwent whole-body PET imaging. (18)F-FDG uptake was assessed in the liver, and its prognostic significance was investigated. Of 38 patients enrolled, 13 patients had positive PET scans for a liver tumor. When we analyzed the association between tumor factors and PET+ (greater PET lesion uptake) in the liver, preoperative AFP level and vascular invasion were found to be significantly associated with PET+ (P = 0.003 and P < 0.001, respectively). However, the association between histological grade and PET+ findings did not reach statistical significant difference (P = 0.074). Moreover, the 2-year recurrence-free survival rate of PET- patients was significantly higher than that of PET+ patients (85.1% vs. 46.1%) (P = 0.0005). Of 6 PET+ patients who met the Milan criteria, 4 patients (66.7%) had recurrence, but all 20 PET- patients who met the Milan criteria were recurrence free. Thus, PET imaging could be a good preoperative tool for estimating the post-LT risk of tumor recurrence, because histological grade and vascular invasion cannot be determined preoperatively. Importantly, our results indicate that tumor recurrence can be highly anticipated for PET-imaging-positive HCC patients who satisfy the Milan criteria. We advise that PET+ HCC patients be selected cautiously for LT., ((c) 2006 AASLD)