Metachronous Hepatic Metastases Research Articles

The Doppler Perfusion Index of the Liver and the Underlying Duplex Sonography of Visceral Vessels-A Systematic and Comprehensive Evaluation of Reproducibility.

Prior to the curative resection of colorectal carcinoma (CRC) or pancreatic ductal adenocarcinoma (PDAC), the exclusion of hepatic metastasis using cross-sectional imaging is mandatory. The Doppler perfusion index (DPI) of the liver is a promising method for detecting occult liver metastases, but the underlying visceral duplex sonography is critically viewed in terms of its reproducibility. The aim of this study was to investigate systematically the reproducibility of the measured variables, the calculated blood flow, and the DPI. Between February and September 2023, two examinations were performed on 80 subjects within a period of 0-30 days and at two previously defined quality levels, aligned to the German standards of the DEGUM. Correlation analyses were carried out using Pearson's correlation coefficient (PCC) and the intraclass correlation coefficient (ICC). The diameters, blood flow, and DPI showed a high degree of agreement (PCC of 0.9 and ICC of 0.9 for AHP). Provided that a precise standard of procedure is adhered to, the Doppler examination of AHC, AHP, and PV yields very reproducible blood flows and DPI, which is a prerequisite for a comprehensive investigation of its prognostic value for the prediction of metachronous hepatic metastasis in the context of curatively treated CRC or PDAC.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Impact of EGFR and EGFR ligand expression on treatment response in patients with metastatic colorectal cancer.

Up to 50% of patients with colorectal cancer (CRC) have either synchronous or metachronous hepatic metastases in the course of their disease. Patients with metastatic CRC (mCRC) whose tumors express wild-type KRAS benefit from treatment with monoclonal antibodies (such as cetuximab or panitumumab) that target the epidermal growth factor receptor (EGFR). However, the therapeutic response to these antibodies is variable, and further predictive models are required. The present study examined whether expression of different EGFRs or their ligands in tumors was associated with the response to cetuximab treatment. Tumor tissues, collected during liver resection in 28 patients with mCRC, were analyzed. The protein expression levels of EGFR/ErbB1, ErbB2, ErbB3 and the EGFR ligands heregulin and amphiregulin were determined using Luminex 200® and enzyme-linked immunosorbent assays. Computed tomography or magnetic resonance imaging was performed 4 weeks before and 6-8 weeks after treatment with cetuximab. Response to treatment was assessed using the response evaluation criteria for solid tumors (RECIST). The association between the protein expression levels of different EGFRs and their ligands with RECIST criteria was then analyzed to determine whether these protein levels could predict the treatment response to cetuximab. A total of 12 patients exhibited a partial response, 9 exhibited stable disease and 7 exhibited progressive disease after cetuximab therapy according to RECIST. The expression levels of EGFRs (EGFR/ErbB1, ErbB2 and ErbB3) and their ligands (heregulin and amphiregulin) were not significantly associated with the response to cetuximab therapy. Therefore, the present study indicated that EGFR or EGFR ligand expression did not predict treatment response in patients with CRC with liver metastases following cetuximab therapy.

Site of relapse of ductal adenocarcinoma of the pancreas affects survival after multimodal therapy

BackgroundDuctal adenocarcinoma of the pancreas (PDAC) remains one of the most lethal malignancies. To date, no guidelines exists for isolated resectable metachronous disease. It is still unknown, which patients may benefit from relapse surgery. The aim of our study was to compare disease free survival (DFS) and post relapse survival (PRS) in patients with isolated local recurrence, metachronous hepatic or pulmonary metastases.MethodsPatients with isolated resectable local recurrence, metachronous hepatic or pulmonary metastases were included for survival analyses. PRS of surgically treated patients (local (n = 11), hepatic (n = 6) and pulmonary metastases (n = 9)) was compared to conservatively treated patients (local (n = 17), hepatic (n = 37) and pulmonary metastases (n = 8)).ResultsResected PDAC patients suffering from isolated metachronous hepatic metastases initially had a higher T-stage and venous invasion (V1) compared to the other patients. DFS in the metachronous pulmonary metastases group was longer compared to DFS of the hepatic metastases and local recurrence groups. Surgical resection significantly improved PRS in patients with local recurrence and pulmonary metastases, when compared to patients receiving chemotherapy alone. Very-long term survivors (> 5 years) were detected following secondary resection of local recurrence and 45% of these patients were still alive at the end of our study period.ConclusionAlthough DFS in PDAC patients suffering from isolated local recurrence was dismal and comparable to that of patients with isolated hepatic metastases, very-long term survivors were present only in this group. These results indicate that a surgical approach for isolated local recurrence, if anatomically possible, should be considered.

Hepatectomy for Liver Metastasis of Gastric Cancer: A Meta-Analysis.

Background. Management of gastric cancer (GC) with liver metastases is debated. It is still controversial whether surgical resection provides a survival benefit or not. This systematic review was designed to evaluate the efficacy of hepatectomy for GC liver metastasis. Methods. We searched several electronic databases to identify eligible studies updated on September 2018. Studies assessing the efficacy and safety of hepatectomy versus no hepatectomy were included. Odds ratio (OR) along with 95% confidence interval (95% CI) were utilized for main outcome analysis. Results. In all, 10 studies were included. Patients who underwent hepatectomy had lower 1-year (OR = 0.15, 95% CI = 0.10-0.22, P < .00001), 3-year (OR = 0.16, 95% CI = 0.10-0.27, P < .00001), and 5-year mortality (OR = 0.13, 95% CI = 0.07-0.24, P < .00001) than those without hepatectomy. We also reported favorable survival outcome in patients with metachronous hepatic resection versus synchronous hepatic resection (OR = 2.09, 95% CI = 1.21-3.60, P = .008). However, there was no significant difference between solitary and multiple liver metastases (OR = 0.61, 95% CI = 0.35-1.07, P = .08). Conclusion. The present study demonstrates that hepatic resection in the management of liver metastases of GC can prolong the survival of patients and should be considered a promising treatment for such patients. Furthermore, there are more favorable outcomes in patients with metachronous metastases versus those with synchronous disease. Therefore, metachronous hepatic metastases from GC are not necessarily a contraindication for hepatectomy of the metastatic site.

Resection of the Dorsal Sector of the Liver: The Anterior Transhepatic Approach

As defined by Couinaud et al. and Takasaki et al., the dorsal sector (DS) or caudate area is the portion of liver parenchyma located between the retrohepatic inferior vena cava (IVC) and the main hepatic veins confluence.1,2 Its complete resection, usually approached by right- or left-sided liver parenchymotomy, remains technically challenging.3,4 Moreover, these approaches usually fail to properly expose the middle (paracaval portion) and most cranial portion (i.e. behind the hepatic vein confluence) of the DS.5 METHODS: We report the case of a 50-year-old woman presenting with a unique metachronous hepatic metastasis of a colorectal adenocarcinoma. The 40-mm lesion was located behind the confluence of the three main hepatic veins, in front of the IVC, and extended caudally behind the hepatic hilum, thereby occupying the paracaval portion of the DS. The tumor board decision was surgical resection. The procedure included complete anatomic resection of the DS using an anterior transhepatic approach by opening the liver midplane along the Cantlie line. A well-tolerated continuous pedicle and IVC clamping of 30min was used. The duration of the surgery was 120min, and the blood loss was 200mL. The patient was discharged on postoperative day 5. R0 resection was achieved and the patient was free of disease at 1year post-surgery. Anatomic resection of the DS using a transparenchymal anterior approach is a safe and feasible procedure especially suitable for voluminous tumors. It allows the control of all major vascular structures narrowing the lesion, and facilitates an R0 resection.

Gastric cancer with synchronous and metachronous hepatic metastasis predicted by enhancement pattern on multiphasic contrast-enhanced CT

ObjectiveThe purpose of this study was to examine the relationship between the CT features of the primary-site gastric cancer and the concurrent existence or postoperative recurrence of hepatic metastasis. Materials and methodsFrom January 2013 to July 2016, 125 patients with advanced gastric cancer who were evaluated by gastroscopy and contrast-enhanced CT at our institution were included. Eleven patients had hepatic metastasis at the time of diagnosis (synchronous hepatic metastasis). Five patients had hepatic recurrence after surgery (metachronous hepatic metastasis, median follow-up period of 313 days), and another 56 patients had no hepatic recurrence during follow-up period (negative hepatic metastasis, median follow-up period of 1102 days). Two radiologists independently reviewed the CT images and they determined the peak enhancement phase, and then measured the CT attenuation value of the gastric lesion for each phase. We compared the parameters of synchronous, metachronous and negative hepatic-metastasis. We calculated diagnostic performance of CT for diagnosing synchronous and metachronous hepatic metastasis. ResultsThe peak enhancement was significantly diff ;erent between the three groups for both readers (reader 1, p = 0.0001; reader 2, p = 0.0002). Most of the synchronous and metachronous hepatic metastasis had peak enhancement in the arterial or portal phase. The CT attenuation values of synchronous and metachronous hepatic metastasis were significantly higher than those of negative hepatic metastasis in the delayed phase according to both readers (reader 1, p = 0.0003; reader 2, p = 0.0002). In predicting synchronous hepatic metastasis using peak enhancement, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 72.7%, 89.3%, 57.1%, 94.3%, and 86.6% for reader 1, and 54.5%, 94.6%, 66.7%, 91.4%, and 88.1% for reader 2. In predicting metachronous hepatic metastasis, the sensitivity, specificity, PPV, NPV, and accuracy were 60.0%, 89.3%, 33.0%, 94.3%, and 86.9% for reader 1, and 40.0%, 94.6%, 40.0%, 94.6%, and 90.2% for reader 2. ConclusionOur study showed that gastric cancer with synchronous and metachronous hepatic metastasis tends to show early enhancement with a washout pattern on contrast-enhanced CT. This feature would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of gastric cancer.

METACHRONOUS COLORECTAL LIVER METASTASES HAS BETTER PROGNOSIS - IS IT TRUE?

Liver metastases from colorectal cancer are an important public health problem due to the increasing incidence of colorectal cancer worldwide. Synchronous colorectal liver metastasis has been associated with worse survival, but this prognosis is controversial. The objective of this study was to evaluate the recurrence-free survival and overall survival between groups of patients with metachronous and synchronous colorectal hepatic metastasis. This was a retrospective analysis of medical records of patients with colorectal liver metastases seen from 2013 to 2016, divided into a metachronous and a synchronous group. The Cox regression model and the Kaplan-Meier method with log-rank test were used to compare survival between groups. The mean recurrence-free survival was 9.75 months and 50% at 1 year in the metachronous group and 19.73 months and 63.3% at 1 year in the synchronous group. The mean overall survival was 20.00 months and 6.2% at 3 years in the metachronous group and 30.39 months and 31.6% at 3 years in the synchronous group. Patients with metachronous hepatic metastasis presented worse overall survival in multivariate analysis. The use of biological drugs combined with chemotherapy was related to the best overall survival prognosis. Metachronous colorectal hepatic metastasis was associated with a worse prognosis for overall survival. There was no difference in recurrence-free survival between metachronous and synchronous metastases.

Long-term efficacy and prognostic factors of surgical treatment for gastric carcinoma with liver metastases: a Meta analysis

Objective To evaluate systematically the long-term efficacy and prognostic of surgical treatment for gastric carcinoma with liver metastases(GCLM). Methods Database including Chinese Journal Full Text Database, Wan Fang Database, VIP database, Chinese Database of Literature on Biomedicine, Pubmed, EMBASE, Cochrane Library, Medline, Springerlink and Wiley Online Library were searched with 胃癌, 胃肿瘤, 肝转移, 手术治疗, 外科手术, 肝切除术, 生存率, 预后因素, gastric cancer, gastric carcinoma, hepatic, resection, hepatic resection, hepatectomy, liver metastases, hepatic metastases, surgery, surgical, survival, prognostic factors . The time for retrieving was from January 1995 to August 2015. Literatures on long-term efficacy and prognostic of radical resection of gastric carcinoma combined with hepatectomy for GCLM were retrieved, and data were analyzed and evaluated by 2 independent researchers. The count data were presented by the relative risk (RR) and 95% confidence interval (95%CI). The group rate was merged by the formula RR/(1+ RR), corresponding 95%CI upper limit values were transferred by the formula RR/(1+ upper limit value RR), and the lower limit values were transferred by the formula RR/(1+ lower limit value RR). The comparison of group rates was done by indirect comparison, Z=difference between group rate/. The heterogeneity was analyzed by I2. Results Eighteen literatures of cross-sectional studies were retrieved and the total sample size was 410 patients. The results of Meta analysis: (1) the summary RR of 3-year overall survival of surgical patients with GCLM was 0.47 (95%CI: 0.37-0.60) while the summary 3-year overall survival rate was 32.0% (95%CI: 0.27-0.38). (2)The summary RR of 5-year overall survival of surgical patients with GCLM was 0.35 (95%CI: 0.27-0.45), summary RR of 5-year overall survival rate was 25.9% (95%CI: 0.21-0.31). (3)The summary RR of overall recurrence of surgical patients with GCLM was 2.95 (95%CI: 2.23-3.88) while the summary overall recurrence rate was 74.7% (95%CI: 0.69-0.80). (4)The summary RR of remnant liver recurrence of surgical patients with GCLM was 1.39 (95%CI: 0.91-2.15) while the summary RR of remnant liver recurrence rate was 58.2%(95%CI: 0.48-0.68). (5)The summary 3-year survival rate of surgical patients with GCLM and primary carcinoma serosal invasion was 32.9%(95%CI: 0.23-0.44), and summary 5-year survival rate was 25.9%(95%CI: 0.16-0.40). The summary 3-year survival rate of surgical patients with GCLM and without primary carcinoma serosal invasion was 47.9%(95%CI: 0.38-0.58), and summary 5-year survival rate was 38.3%(95%CI: 0.29-0.49). The summary 3-year survival rate of surgical patients with synchronous hepatic metastases was 30.6%(95%CI: 0.24-0.38), and summary 5-year survival rate was 24.2%(95%CI: 0.18-0.32). The summary 3-year survival rate of surgical patients with metachronous hepatic metastases was 40.1%(95%CI: 0.32-0.48), and summary 5-year survival rate was 32.9%(95%CI: 0.25-0.41). The summary 3-year survival rate of surgical patients with solitary metastatic hepatic carcinoma was 47.6%(95%CI: 0.40-0.56), and summary 5-year survival rate was 37.1%(95%CI: 0.26-0.48). The summary 3-year survival rate of surgical patients with multiple metastatic hepatic carcinoma was 28.6%(95%CI: 0.18-0.42), and summary 5-year survival rate was 15.3%(95%CI: 0.07-0.30). The summary 3-year survival rate of surgical patients with GCLM and R0 resection was 28.6%(95%CI: 0.19-0.40), and summary 5-year survival rate was 20.0%(95%CI: 0.12-0.32). The summary 3-year survival rate of surgical patients with GCLM and without R0 resection was 0.0, and summary 5-year survival rate was 9.1%(95%CI: 0.03-0.25). The summary 3-year survival rate of surgical patients with GCLM and resection margin<10 mm was 13.0%(95%CI: 0.05-0.30), and summary 5-year survival rate was 8.3%(95%CI: 0.02-0.28). The summary 3-year survival rate of surgical patients with GCLM and resection margin≥10 mm was 34.6%(95%CI: 0.21-0.52), and summary 5-year survival rate was 34.6%(95%CI: 0.21-0.52). The summary 3-year survival rate of surgical patients with GCLM and chemotherapy was 45.9%(95%CI: 0.29-0.64), and summary 5-year survival rate was 29.1%(95%CI: 0.19-0.42). The summary 3-year survival rate of surgical patients with GCLM and without chemotherapy was 38.7%(95%CI: 0.26-0.53), and the summary 5-year survival rate was 25.4%(95%CI: 0.18-0.35). The 3-year survival rate of surgical patients without primary carcinoma serosal invasion and with metachronous hepatic metastases, solitary metastatic hepatic carcinoma, R0 resection and resection margin≥10 mm was statistically significantly higher than that of surgical patients with primary carcinoma serosal invasion, synchronous hepatic metastases, multiple metastatic hepatic carcinoma and resection margin<10 mm and without R0 resection (Z=2.118, 1.999, 3.018, 5.295, 2.183, P<0.05). The 5-year survival rate of surgical patients with solitary metastatic hepatic carcinoma and resection margin≥10 mm was statistically significantly higher than that of surgical patients with multiple metastatic hepatic carcinoma and resection margin<10 mm (Z=4.528, 2.819, P<0.05). Conclusion Overall long-term efficacy of surgical patients with GCLM is not good enough, and there is the better prognosis in the surgical patients without primary carcinoma serosal invasion and with metachronous hepatic metastases, solitary metastatic hepatic carcinoma, R0 resection and resection margin≥10 mm. Key words: Gastric neoplasms; Liver metastases; Surgical procedures, operative; Prognosis; Meta analysis

異時性肝転移を切除した多発性内分泌腫瘍症2A型甲状腺髄様癌の1例

症例は75歳，女性．53歳時に甲状腺髄様癌（medullary thyroid carcinoma:以下，MTC）および両側副腎褐色細胞腫を発症した多発性内分泌腫瘍症2A型と診断され，甲状腺全摘術と両側副腎亜全摘術を施行された．その後20年間再発兆候なく，当院内分泌内科に紹介となったが，初回手術後21年目の腹部超音波検査にて肝S3に腫瘤を指摘された．腹部CT検査では，肝S3に石灰化を伴う20mm大の多血性腫瘍を認めた．血中CEA・カルシトニンも上昇しており，MTCの肝転移再発と診断した．当科で肝外側区域切除術を施行し，切除標本内に2個の腫瘍が指摘された．病理組織学的にもMTCの転移と診断された．肝転移巣切除後34カ月が経過し，無再発生存中である．甲状腺髄様癌の異時性肝転移に対して根治切除しえた症例の報告は稀であり，文献的考察を加えて報告する．

若年性胃gastrointestinal stromal tumorの転移性肝再発に対してsunitinibが奏効した1例

若年性胃gastrointestinal stromal tumorの転移性肝再発に対してsunitinibが奏効した1例

Oestrogen receptor-beta as a potential target for treatment in advanced colorectal cancer: a pilot study.

Oestrogen receptor-beta (ER-β) is expressed in colorectal cancer. Theoretically, ER-β stimulation could slow down tumour proliferation, and this is supported by preclinical research data. While preparing a Phase II trial for advanced colorectal cancer patients we performed a pilot study with three questions: (i) in what percentage of patients do metastases display strong ER-β1 expression; (ii) is there any concordance in expression between primary tumours and metastases; and (iii) is the immunohistochemical (IHC) scoring procedure reproducible? Thirty patients were selected, 15 with locoregional lymph node metastases and 15 with either synchronous or metachronous hepatic metastases. All primary tumours and metastases were analysed for immunohistochemical ER-β1 expression according to a predefined scoring system. The scoring was performed independently by two pathologists in order to calculate the weighted kappa value. Strong ER-β1 expression was found in four of 15 hepatic metastases and four of 15 lymph node metastases. In 15 of 30 patients, the level of ER-β1 expression in the metastasis was concordant with that observed in the primary tumour. Weighted kappa values of IHC ER-β1 expression were satisfactory. In twenty-five per cent of patients there was strong ER-β1 expression in metastases, biopsy of which will be considered mandatory for trial inclusion.

The serum level of carcinoembryonic antigen in drainage venous blood is not a sensitive predictor of metachronous hepatic metastasis for patients with colorectal cancer

To establish whether the serum levels of carcinoembryonic antigen (CEA) in drainage venous blood (d-CEA) is a better predictor of prognosis or survival than the preoperative CEA level in peripheral venous blood (p-CEA), and how these two CEA levels compare as predictive factors for metachronous hepatic metastasis. We examined specimens of peripheral and drainage venous blood from 119 patients with colorectal cancer. There was a strong positive correlation between p-CEA and d-CEA levels. The 5-year survival rates were 81.5% and 80.2% for patients with normal p-CEA and d-CEA levels (< or =5 ng/ml), respectively, and 68.4% and 71.1% for those with abnormal p-CEA and d-CEA levels (>5 ng/ml). The p-CEA and d-CEA levels were both normal in seven of ten patients with metachronous hepatic metastasis. The CEA gradient between the d-CEA and p-CEA levels (d-p CEA gradient) was not a significant predictive factor for hepatic metastases. There was virtually no change between preoperative p-CEA and d-CEA levels. These findings suggest that the d-CEA level is not a predictor for metachronous hepatic metastasis and that measuring p-CEA levels is sufficient in the surveillance of colorectal cancer.

Prognostic analysis of surgical resection for patients with liver metastases from colorectal carcinoma

Objective To assess the indication and efficacy of surgical treatment for patients with hepatic metastases from colorectal carcinoma. Methods Clinical data of 75 patients with hepatic metastases from colorectal carcinoma undergoing surgery from January 2000 to December 2007 were analyzed retrospectively. Results Among 75 patients,62 patients were found to have synchronous hepatic metastasis and 13 patients were found to have metachronous hepatic metastases. 70 patients underwent resection of hepatic metastases and complications occurred in 10 patients. The 1,3 and 5-year survival rates were 74. 67%, 58.67% and 28.00%respatectomy. Univariate analysis revealed that solitary metastasis was a significant factor for favorable prognosis after surgery . The expression of preoperative CEA, Dukes stage, the number of hepatic metastases, status of lymph node metastasis and histological differentiation of the primary colorectal carcinoma were all significant factors for prognosis after surgery. Conclusion The hepatic metastases from colorectal cancer should be treated by a surgical approach. T earlier stage of clinical pathology, higher differentiation extent, metastases less than 2, and low-level expression of preoperative CEA predict a better survival. Key words: Colorectal carcinoma; Liver metastasis; Surgical treatment; Prognosis

Cyclooxygenase (COX)-1, Cyclooxygenase (COX)-2 and E-cadherin Expression in Colorectal Cancer Patients with Hepatic Metastasis

Purpose: Recent studies have shown that cyclooxygenase (COX)-2 may be involved in colorectal carcinogenesis. In this study, we evaluate the differences of COX-2 expression in patients with synchronous and metachronous hepatic metastasis of colorectal cancer. In addition, the expression of COX-1 and E-cadherin were also evaluated. Methods: Paraffin embedded blocks were obtained from 41 patients who underwent surgery for colorectal cancer with hepatic metastasis. Samples from primary colorectal cancer, synchronous and metachronous hepatic lesions were stained by immunohistochemistry for monoclonal antibody against COX-1, COX-2, and E-cadherin. Results: In colonic COX-1 expression, there was no significant difference in the degree of COX-1 expression between primary colorectal cancer with synchronous hepatic metastasis and that of metachronous hepatic metastasis (P=0.507). In colonic COX-2 and E-cadherin expression, the degree of COX-2 expression was not different between the two groups. But, the patient survival rate in the positive group of COX-1 and COX-2 expression was lower than in the negative group, respectively (P=0.023, P=0.006). Conclusion: The degree of colonic COX-1 and COX-2 expression has an impact on prognosis in synchronous and metachronous hepatic metastasis. Further large-scale study is necessary to determine the meaning of COX-2 expression in colorectal cancer.

Erythropoietin production caused by metastatic colon cancer

Dear Editor: Erythrocytosis is one of the rare paraneoplastic syndromes and can be brought on by ectopic erythropoietin (EPO) production in renal cell carcinomas, cerebral meningiomas, and hepatocellular carcinomas. This syndrome presents with increased hemoglobin levels, pulmonary or deep venous thrombosis, and sometimes requires phlebotomy. We recently treated a patient with metachronous hepatic metastasis from colon cancer, presenting with erythrocytosis, jaundice, and hyperserum EPO concentration. Resection of the tumor normalized the serum EPO concentration and relieved the erythrocytosis. This might be the first case of erythrocytosis secondary to EPO production caused by metastatic colon cancer. A 56-year-old man had previously undergone resection of a transverse colon cancer in another hospital. Pathological examination revealed adenocarcinoma with subserosal invasion and regional nodal metastases. Before surgery, slight erythrocytosis was found; the patient’s hemoglobin level was 17.5 g/dl (normal range, 13.8–16.6) and hematocrit was 54.5% (normal range, 40.2–49.4). One year after colectomy, the hemoglobin level had decreased to 13.5 g/dl. Adjuvant chemotherapy was performed using 5-fluorouracil and lleucovorin for 1 year. However, his carcinoembryonic antigen (CEA) level increased to 31.0 ng/ml and enhanced computed tomography scan showed a heterogeneous, lowdensity tumor, measuring 2.3 cm in diameter, in the right liver 1.5 year after colectomy. He was referred to our institute for the treatment of the hepatic metastasis. The hemoglobin level and hematocrit had increased to 19.0 g/dl and 56.0%, respectively. The patient did not smoke and had no chronic pulmonary or cardiac disease. Bone marrow stem cell culture studies were normal. The serum EPO level was 87.0 mIU/ml (normal range, 7.4–29.8), and we suspected secondary erythrocytosis caused by the hepatic metastasis because there was no other neoplasm on extensive imaging examinations. We performed partial resection of the liver, and the serum EPO level decreased 17.0 mIU/ml on day7. The hemoglobin and hematocrit levels returned to their normal range within 1 month. Histopathological findings revealed that the hepatic tumor had metastasized from the primary colon cancer. Immunohistochemical study of the metastatic cells was negative for EPO-antibody. The patient is currently doing well without any recurrence or erythrocytosis 2 years after hepatectomy. The mechanism of EPO production in cancer cells remains unknown. It is reported that EPO is produced in the fetal liver, but this production is replaced by the kidney soon after birth. Thus, it may be understandable that renal cell carcinoma or hepatocellular carcinoma ectopically produces EPO. On the other hand, production of EPO by adenocarcinoma has not been described in vitro or in vivo. It was obvious that the serum EPO level decreased after resection of the hepatic metastasis, in parallel with the serum CEA level. We suppose that the EPO-producing hepatic metastasis from colon cancer might be extremely rare, although immunohistochemical study of the metastatic cells was negative for EPO-antibody, as a false negative has been reported using monoclonal antibodies. D. Ban :Y. Sakamoto (*) :K. Shimada : T. Kosuge Division of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan e-mail: yosakamo@ncc.go.jp

Radiofrequency Ablation for Metachronous Hepatic Metastases From Gastric Cancer

The objective of this study was to evaluate the results of radiofrequency ablation (RFA) for the treatment of metachronous hepatic metastases from gastric adenocarcinoma. Between January 2000 and February 2008, we retrospectively reviewed 7 cases for which RFA was performed for treating metachronous hepatic metastases after resection of the primary gastric adenocarcinoma. The median period between curative gastrectomy and metachronous hepatic metastasis was 14 months (range: 6 to 48 mo). The median survival of the patients was 11.0 months (range: 5.5 to 39.2) after the first detection of hepatic metastases and 10.0 months (range: 5 to 38.2) after the first RFA. Hepatic metastases recurred 3 to 21 months after RFA in all patients. A second RFA was performed for a single recurrent hepatic metastasis in 1 patient and this patient survived more than 3 years without recurrence until the time of this study. In conclusion, the efficacy of RFA alone for metachronous hepatic metastases from gastric adenocarcinoma was disappointing due to multiple intrahepatic recurrences. Combination therapy such as systemic chemotherapy or hepatic arterial infusion chemotherapy adjuvant to RFA would more reasonable for treating hepatic metastases from gastric cancer.

Metachronous hepatic metastases from gastric carcinoma: A multicentric survey

Background The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. Objective To survey the clinical approach to the subset of patients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. Methods Retrospective multi-center chart review evaluating 73 patients, previously submitted to D ≥ 2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. Results Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T ( p = 0.019), N ( p = 0.05) and G ( p = 0.018) of the gastric primary and by the therapeutic approach to the metastases ( p < 0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy ( p = 0.08) and 80.8%, 30.3% and 20.2% after surgical resection ( p < 0.001). Conclusions Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible.

Clinicopathologic Features and Difference in Prognosis in Synchronous and Metachronous Hepatic Metastases of Gastric Cancer

Purpose: The aim of this study was to compare synchronous and metachronous hepatic metastases in patients with gastric cancer to determine clinicopathologic features and differences in prognosis as a function of the timing of the metastasis and the treatment modality rendered. Materials and Methods: Sixty-seven patients who were diagnosed with gastric cancer metastatic to the liver and treated at the Hanyang University Hospital between June 1992 and December 2006 were retrospectively analyzed to study the pertinent clinicopathologic features and effect of treatment methods. Results: There was a significant difference with respect to lymphatic (P=0.041) and vascular invasion (P=0.036) in comparing the clinicopathologic features between the patients with synchronous and metachronous hepatic metastases. The 1-year survival rate and median survival time of patients with gastric cancer and liver metastases were 38.9% and 9.2 months in the entire patient cohort, 30.9% and 9.2 months in the synchronous group, and 44.5% and 9.7 months in the metachronus group, respectively (P=0.436). The group of patients undergoing local treatment (such as surgery and radiologic intervention) followed by systemic chemotherapy, the group of patients receiving systemic chemotherapy only, and the untreated group of patients were compared, and there was no difference between the synchronous and metachronous groups. The synchronous and metachronous groups had high survival rates with local treatment. Conclusion: In patients with gastric cancer and liver metastases, there was no difference in prognosis based on the timing of the hepatic metastases. Independent of the timing of hepatic metastasis, aggressive treatment, such as surgery and radiologic intervention, may help improve the prognosis.

Diagnosis and Treatment of Metastatic Disease to the Liver

A number of cancers present with synchronous or metachronous hepatic metastases. Historically, many of these patients were considered unresectable and were treated with either systemic chemotherapy or supportive care. Today, a variety of options exist for the management of hepatic metastases. Newer agents for systemic therapy continue to be introduced and are providing improved progression-free and overall survival and increased resectability of liver metastases. However, complete surgical resection of isolated hepatic metastases remains the optimal management for these patients. Surgical interventions can be offered to patients with hepatic-only metastases. Hepatic artery chemotherapy represents an adjunct for those patients undergoing resection and can improve survival. This benefit may be even more pronounced when combined with systemic chemotherapy. Newer generation biologic agents can improve results. New therapeutic modalities to treat lesions that are unresectable include ablative techniques such as radiofrequency ablation (RFA) and cryoablation. This article will examine modalities of diagnosis of hepatic metastases and highlight the data regarding hepatic resection for metastases of several types of primary cancers, the rationale for, and efficacy of, hepatic arterial chemotherapy, in both the postoperative adjuvant setting and in unresectable liver disease, and review the current literature for ablative techniques in the treatment of liver metastases.