• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1003-1007
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• 2013

Objective: This work aimed to investigate the correlations of tumor-associated macrophages (TAMs) and their subtypes M1 and M2 with liver metastasis of colorectal cancer, and provide useful references for seeking predictors of liver metastasis and studying mechanisms. Methods: 120 patients with colorectal cancer from 2000 to 2009 were divided into low, middle and high liver metastasis groups (group A, B and C, respectively). S-P immunohistochemical staining and microscopic observation were conducted to compare expression in CD68-positive cells (TAMs), CD80-positive cells (M1) and CD163-positive cells (M2) in three groups. Correlations of TAMs, M1, M2, and M2/M1 ratio with clinical and pathological parameters were analyzed. Results: With increase of liver metastatic ability, the number of TAMs decreased gradually, with no significant difference between any two of the three groups (P > 0.05), while the numbers of M1 and M2 were significantly decreased and increased, respectively, with significant difference between any two of three groups (P < 0.05 or P < 0.01). In addition, the M2/M1 ratio increased with increase of liver metastatic ability (P < 0.01). There was no statistical significance of correlation of TAMs with each clinical and pathological parameter. M1 was negatively related with lymphatic metastasis and liver metastatic ability. M2 was positively correlated with preoperative CEA level, lymphatic metastasis, tumor differentiation degree and liver metastatic ability. The same was the case for the M2/M1 ratio. Conclusions: Effects of TAMs on liver metastasis of colorectal cancer do not depend on the total number of TAMs, but on the number and proportion of functional subtypes M1 and M2. M2 number and M2/M1 ratio are more accurate predictors for liver metastasis of colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3967-3971
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• 2012

Aims: To explore the relationship between various molecular makers and liver metastasis of colorectal cancer (CRC). Method: Using immunohistochemistry, protein expression of CEA, nm23, c-met, MMP2, COX-2, VEGF, EGFR, and CD44 was assessed in 80 CRC cases. The Chi-square test and logistic regression were performed to analyze the relationship between these indicators and CRC liver metastasis. Results: There were significant differences in expression of CEA, MMP2, CD44, VEGF and EGFR between the liver metastasis and non metastasis groups (P < 0.05); no significant differences were noted for nm23, c-met, and COX-2 expression. Logistic regression analysis showed that only CEA, VEGF, and EGFR entered into the regression equation, and had significant correlations with CRC liver metastasis (${\alpha}$ inclusion= 0.10, ${\alpha}$ elimination = 0.15, R2 = 0.718). Conclusions: Combination detection of CEA, VEGF, and EGFR may be an effective means to predict CRC liver metastasis. Nm23, c-met, MMP2, COX-2, and CD44, in contrast, are not suitable as prognostic markers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4699-4701
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• 2012

Objective: To explore the effect of portal vein chemotherapy on liver metastasis after surgical resection of colorectal cancer. Methods: Patients fulfilling the eligibility criteria were assigned to receive either surgery plus 1-week continuous infusion of 5-FU (study group) or surgery alone (observational group). Patients in the study group received portal vein chemotherapy, whereby 5-FU (1000 mg/d) and heparin (5000 IU/d) infusion was initiated from the day of surgery and lasted for 7 consecutive days. Liver metastasis was monitored during five years follow-up postoperatively. Results: Sixty four patients were recruited and assigned to the study group (12 with colon and 20 with rectal cancer) or the control group (10 with colon and 22 with rectal cancer). Liver metastasis rate was 12.5% in study and 25.0% in observational group, the difference being significant (P<0.01). Conclusion: Portal vein chemotherapy could be an effective treatment in preventing liver metastasis after surgical resection of colorectal cancer.

• Korean Journal of Radiology
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• v.22 no.6
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• pp.912-921
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• 2021

Objective: To compare the performance of the deep learning-based lesion detection algorithm (DLLD) in detecting liver metastasis with that of radiologists. Materials and Methods: This clinical retrospective study used 4386-slice computed tomography (CT) images and labels from a training cohort (502 patients with colorectal cancer [CRC] from November 2005 to December 2010) to train the DLLD for detecting liver metastasis, and used CT images of a validation cohort (40 patients with 99 liver metastatic lesions and 45 patients without liver metastasis from January 2011 to December 2011) for comparing the performance of the DLLD with that of readers (three abdominal radiologists and three radiology residents). For per-lesion binary classification, the sensitivity and false positives per patient were measured. Results: A total of 85 patients with CRC were included in the validation cohort. In the comparison based on per-lesion binary classification, the sensitivity of DLLD (81.82%, [81/99]) was comparable to that of abdominal radiologists (80.81%, p = 0.80) and radiology residents (79.46%, p = 0.57). However, the false positives per patient with DLLD (1.330) was higher than that of abdominal radiologists (0.357, p < 0.001) and radiology residents (0.667, p < 0.001). Conclusion: DLLD showed a sensitivity comparable to that of radiologists when detecting liver metastasis in patients initially diagnosed with CRC. However, the false positives of DLLD were higher than those of radiologists. Therefore, DLLD could serve as an assistant tool for detecting liver metastasis instead of a standalone diagnostic tool.

• The Journal of Internal Korean Medicine
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• v.34 no.4
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• pp.466-477
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• 2013

Objectives : To report and demonstrate the effect of decreasing ascites volume by SB intraperitoneal injection to a refractory ascites patient with synchronous colorectal liver metastasis and metachronous peritoneal carcinomatosis. Methods : Two cycles of intraperitoneal and intravenous SB injection were conducted. Each injection cycle was made up of 4 days. Nine vials of SB were injected to the patient every day. To compare the volume of ascites between pret- and post-treatment, follow-up computed tomography was done on June 3, 2013. To observe other therapeutic effects of SB injection, laboratory tests were conducted periodically. Results : On the follow-up computed tomography images, the amount of ascites and pleural effusion had decreased compared to the April 30, 2013 computed tomography images. The levels of aspartate transaminase, alanine aminotransferase and lactate dehydrogenase decreased significantly from May 9, to May 30, 2013. The amount of oral intake increased constantly during hospitalization. The patient's symptoms such as abdominal distension, abdominal pain and dyspnea were improving until discharge. Conclusions : Even if thiese results cannot be applied to every synchronous colorectal cancer liver metastasis patient, we demonstrated that SB intraperitoneal injection has ascites-decreasing effect to refractory ascites patients with synchronous colorectal liver metastasis and metachronous peritoneal carcinomatosis.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.1
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• pp.14-24
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• 2024

This study aims to assess the quality and performance of predictive models for colorectal cancer liver metastasis (CRCLM). A systematic review was performed to identify relevant studies from various databases. Studies that described or validated predictive models for CRCLM were included. The methodological quality of the predictive models was assessed. Model performance was evaluated by the reported area under the receiver operating characteristic curve (AUC). Of the 117 articles screened, seven studies comprising 14 predictive models were included. The distribution of included predictive models was as follows: radiomics (n = 3), logistic regression (n = 3), Cox regression (n = 2), nomogram (n = 3), support vector machine (SVM, n = 2), random forest (n = 2), and convolutional neural network (CNN, n = 2). Age, sex, carcinoembryonic antigen, and tumor staging (T and N stage) were the most frequently used clinicopathological predictors for CRCLM. The mean AUCs ranged from 0.697 to 0.870, with 86% of the models demonstrating clear discriminative ability (AUC > 0.70). A hybrid approach combining clinical and radiomic features with SVM provided the best performance, achieving an AUC of 0.870. The overall risk of bias was identified as high in 71% of the included studies. This review highlights the potential of predictive modeling to accurately predict the occurrence of CRCLM. Integrating clinicopathological and radiomic features with machine learning algorithms demonstrates superior predictive capabilities.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.1
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• pp.40-48
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• 2023

Backgrounds/Aims: Timing of resection for synchronous colorectal liver metastasis (CRLM) has been debated for decades. The aim of the present study was to assess the feasibility of simultaneous resection of CRLM in terms of major complications and develop a prediction model for safe resections. Methods: A retrospective single-center study of synchronous, resectable CRLM, operated between 2013 and 2021 was conducted. Upper limit of 95% confidence interval (CI) of major complications (≥ grade IIIA) was set at 40% as the safety threshold. Logistic regression was used to determine predictors of morbidity. Prediction model was internally validated by bootstrap estimates, Harrell's C-index, and correlation of predicted and observed estimates. Results: Ninety-two patients were operated. Of them, 41.3% had rectal cancers. Major hepatectomy (≥ 4 segments) was performed for 25 patients (27.2%). Major complications occurred in 20 patients (21.7%, 95% CI: 13.8%-31.5%). Predictors of complications were the presence of comorbidities and major hepatectomy (area under the ROC curve: 0.692). Unacceptable level of morbidity (≥ 40%) was encountered in patients with comorbidities who underwent major hepatectomy. Conclusions: Simultaneous bowel and CRLM resection appear to be safe. However, caution should be exercised when combining major liver resections with bowel resection in patients with comorbid conditions.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.2
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• pp.125-132
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• 2022

Backgrounds/Aims: It is generally accepted that non-anatomical resection (NAR) in colorectal liver metastasis (CRLM) has comparable safety and efficacy compared to anatomical resection (AR); however, there are reports that AR may have better outcomes in KRAS mutated CRLM. This study aimed to determine the effects of KRAS mutations and surgical techniques on survival outcomes in CRLM patients. Methods: Two hundred fifty patients who underwent hepatic resection of CRLM with known KRAS mutational status between 2007 and 2018 were analyzed. A total of 94 KRAS mutated CRLM and 156 KRAS wild-type CRLM were subdivided by surgical approach and compared for short- and long-term outcomes. Results: In both KRAS wild-type and mutated type, there was no difference in estimated blood loss, postoperative complications, and 30-day mortality. There was no difference in disease-free survival (DFS) between AR and NAR in both groups (p = 0.326, p = 0.954, respectively). Finally, there was no difference in intrahepatic DFS between AR and NAR groups in both the KRAS groups (p = 0.165, p = 0.516, respectively). Conclusions: The presence of KRAS mutation may not be a significant factor when deciding the approach in simultaneous resection of CRLM.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4151-4155
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• 2013

Background: To compare response evaluation criteria in solid tumours (RECIST) and volumetric evaluation (VE) for colorectal cancer with liver-limited metastasis. Patients and Methods: VE of liver metastases was performed by manual contouring before and after chemotherapy on 45 pairs of computed tomography (CT) images in 36 patients who suffered from metastatic colorectal cancer (mCRC) with liver metastasis only. Cohen kappa was used to compare the agreement between VE and RECIST. Pearson correlation was performed for their comparison after cubic root transformation of the aggregate tumor volumes. Logistic regression was done to identify clinical and radiographic factors to account for the difference which may be predictive in overall response (OR). Results: There were 16 partial response (PR), 23 stable disease (SD) and 6 progressive disease (PD) cases with VE, and 14 PR, 23 SD and 8 PD with RECIST. VE demonstrated good agreement with RECIST (${\chi}$=0.779). Discordant objective responses were noted in 6 pairs of comparisons (13.3%). Pearson correlation also showed excellent correlation between VE and RECIST ($r^2$=0.966, p<0.001). Subgroup analysis showed that VE was in slightly better agreement with RECIST for enlarging lesions than for shrinking lesions ($r^2$=0.935 and $r^2$=0.780 respectively). No factor was found predictive of the difference in OR between VE and RECIST. Conclusions: VE exhibited good agreement with RECIST. It might be more useful than RECIST in evaluation shrinking lesions in cases of numerous and conglomerate liver metastases.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.