Repeat hepatectomy for recurrent colorectal liver metastases is associated with a high survival rate

BackgroundThe outcome after a repeat hepatectomy for recurrent colorectal liver metastases (CLM) is not well defined. The present study examined the morbidity, mortality and long-term survivals after a repeat hepatectomy for recurrent CLM.MethodsData on patients who underwent surgery for recurrent CLM between 1993 and 2009 were retrospectively evaluated. Patients who underwent radiofrequency ablation at the time of first treatment or at recurrence of CLM were excluded.ResultsForty-three patients underwent a repeat hepatectomy for recurrent CLM. At the time of recurrence, patients had a median of 1 (1–3) lesions and the median tumour size was 2 (0.5–8.7) cm. The post-operative morbidity and mortality rates were 12% and 0%, respectively. After a median follow-up of 33 months from a repeat hepatectomy, 5-year overall and progression-free survival rates were 73% and 22%, respectively. Using multivariate analysis, the largest initial CLM ≥5 cm and positive surgical margins at initial resection were independently associated with a worse survival after surgery for recurrent CLM. Positive surgical margins at repeat hepatectomy were a predictive factor for an increased risk of further recurrence.DiscussionA repeat hepatectomy for recurrent CLM was associated with excellent survival, low morbidity and no mortality. Surgeon-controlled variables, including margin-negative resection at first and repeat hepatectomy, contribute to good oncological outcome.     

Portal and systemic serum growth factor and acute-phase response after laparotomy or partial hepatectomy in patients with colorectal liver metastases: a prognostic role for C-reactive protein and hepatocyte growth factor

BACKGROUND: Growth factors play a role in wound healing and tumour growth. The aim of this study was to compare the effect of partial hepatectomy (PH) and laparotomy on serum levels of growth factors and acute-phase proteins in patients with colorectal liver metastases and to correlate these levels with prognosis after PH. METHODS: Epidermal growth factor (EGF), hepatocyte growth factor (HGF), insulin like growth factor-I (IGF-I), insulin, interleukin-6 (IL-6), C-reactive protein (CRP) and serum amyloid-A (SAA) were determined in portal and systemic serum in 24 PH patients and 9 laparotomy patients. RESULTS: No differences were found in the clinicopathological characteristics of PH and laparotomy patients with the exception of the number of metastases, blood loss and operation time. The response of SAA, CRP and IGF-I was lower in PH patients than in laparotomy patients (P < 0.02). PH was associated with a higher IL-6 (P = 0.02) and HGF (P = 0.055) response than laparotomy. A higher HGF and CRP response was associated with a poorer prognosis. Total IGF-I was negatively correlated with the resected liver volume (r = -0.48, P < 0.05). CONCLUSIONS: PH is associated with a lower acute-phase and total IGF-I response and a higher HGF and IL-6 response compared with laparotomy. HGF and CRP responses had an influence on the prognosis.     

结直肠癌肝转移的危险因素分析138例

目的:探讨影响结直肠癌肝转移的危险因素.方法:采用Kaplan-Meier和多因素回归分析方法,分析138例有完整随访资料的结直肠癌肝转移患者的生存情况及影响预后的相关因素.结果:138例患者的中位生存时间为18.3mo.单因素分析显示,患者年龄(P=0.460)、原发肿瘤部位(P=0.568)、原发肿瘤最大直径(P=0.250)、原发肿瘤组织学分级(P=0.589)与患者的总生存时间无关,而性别(P=0.048)、治疗前血清CEA水平(P=0.023)、肝转移灶数目(P=0.000)、肝转移灶最大直径(P=0.001)、区域淋巴结转移情况(P=0.001)、肝转移灶手术与否(P=0.002)与患者的预后有关.多因素回归分析显示,治疗前血清CEA水平(P=0.028)、肝转移灶数目(P=0.001)、肝转移灶最大直径(P=0.001)、区域淋巴结转移情况(P=0.049)、肝转移灶手术与否(P=0.003)是影响结直肠癌肝转移患者预后的主要因素.结论:治疗前血清CEA水平、肝转移灶数目、肝转移灶最大直径、区域淋巴结转移情况、肝转移灶手术与否是结直肠癌肝转移患者预后的影响因素;治疗前血清CEA水平越低、肝转移灶数目越少、肝转移灶最大直径越小、无区域淋巴结转移、肝转移灶通过手术治疗的患者预后越好.     

General principles of hepatectomy in colorectal liver metastases

Hepatic resection for colorectal liver metastases remains the only therapeutic option that improves long-term survival and offers potential cure. By conventional resectability criteria, only a limited number of patients with metastatic disease can be subjected to surgical intervention. In the past decade, better understanding of the natural history of the disease, the introduction of new chemotherapy agents and the advances in surgical techniques have led to more patients being eligible for surgery. Neoadjuvant chemotherapy can reduce the size of the metastases, allowing operation on patients who were previously considered inoperable. Major resections can nowadays be safely performed with the development of new less-invasive techniques and with the use of supplementary tools like ablation techniques. Using portal vein embolization to induce hypertrophy of future liver remnant and combining it with two-staged hepatectomy allow more patients with advanced disease to undergo potentially curative surgery. Careful selection of patients and aggressive surgery in experienced centers improve survival rates.     

General principles of hepatectomy in colorectal liver metastases

Hepatic resection for colorectal liver metastases remains the only therapeutic option that improves long-term survival and offers potential cure. By conventional resectability criteria, only a limited number of patients with metastatic disease can be subjected to surgical intervention. In the past decade, better understanding of the natural history of the disease, the introduction of new chemotherapy agents and the advances in surgical techniques have led to more patients being eligible for surgery. Neoadjuvant chemotherapy can reduce the size of the metastases, allowing operation on patients who were previously considered inoperable. Major resections can nowadays be safely performed with the development of new less-invasive techniques and with the use of supplementary tools like ablation techniques. Using portal vein embolization to induce hypertrophy of future liver remnant and combining it with two-staged hepatectomy allow more patients with advanced disease to undergo potentially curative surgery. Careful selection of patients and aggressive surgery in experienced centers improve survival rates.     

Surgical treatment of pulmonary recurrence after hepatectomy for colorectal liver metastases

BACKGROUND/AIMS: Although pulmonary recurrence is frequent among the extrahepatic recurrences after hepatectomy, the efficacy of surgical treatment for pulmonary recurrence after hepatectomy has not been confirmed. Surgical resection of pulmonary recurrence after hepatectomy for colorectal metastases was reviewed retrospectively to evaluate the survival benefit. METHODOLOGY: From 1990 to 1995, 10 of the 17 patients with pulmonary recurrence after hepatectomy for colorectal metastases underwent surgical treatment. Ten patients underwent resection of pulmonary recurrence. RESULTS: Operative mortality was 0%, and a postoperative complication was observed in 1 patient after pulmonary metastasectomy. The overall 5-year survival rate after pulmonary metastasectomy was 10.0%, and the median survival was 21.7 (range: 2.4-77.9) months. One patient underwent resection two times for remnant lung recurrence after first lung metastasectomy, and is alive with no evidence of recurrence 77.9 months after the first pulmonary resection, and 50.7 months after the third pulmonary resection. In 3 patients with well-differentiated adenocarcinoma, the median survival time was 6.2 months (range: 2.4-9.7). The other hands, 7 patients with moderately differentiated adenocarcinoma have a longer median survival time of 29.2 months (range: 16.0-77.9). CONCLUSIONS: Pulmonary metastasectomy after hepatectomy for metastases from colorectal cancer is a safe treatment, and might offer prolonged survival for highly selected patients.     

Combined hepatectomy and hepatic pedicle lymphadenectomy in colorectal liver metastases is justified

Background

The aim of this study was to describe the outcome of patients with colorectal liver metastases (CRLM) and radiological or clinical evidence of metastatic hepatic lymph node involvement who underwent combined hepatectomy and hepatic pedicle lymphadenectomy.

A systematic review of two-stage hepatectomy in patients with initially unresectable colorectal liver metastases

Objectives

Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable using the two-stage hepatectomy (TSH) approach. This review was conducted with the aim of collating and evaluating published evidence for TSH in patients with initially unresectable CLM.

Methods

Searches of the MEDLINE and EMBASE databases were undertaken to identify studies of TSH in patients with initially unresectable CLM. Studies were required to focus on the perioperative treatment regimen, operative strategy, morbidity, technical success and survival outcomes.

Results

Ten observational studies were reviewed. A total of 459 patients with initially unresectable CLM were selected for the first stage of TSH. Preoperative chemotherapy was used in 88% of patients and achieved partial and stable response rates of 59% and 39%, respectively. Postoperative morbidity and mortality after the first stage of TSH were 17% and 0.5%, respectively. Portal vein embolization (PVE) was used in 76% of patients. Ultimately, 352 of the initial 459 (77%) patients underwent the second stage of TSH. Major liver resection was undertaken in 84% of patients; the negative margin (R0) resection rate was 75%. Postoperative morbidity and mortality after the second stage of TSH were 40% and 3%, respectively. Median overall survival was 37 months (range: 24–44 months) in patients who completed both stages of TSH. In patients who did not complete both stages of TSH, median survival was 16 months (range: 10–29 months). The 3-year disease-free survival rate was 20% (range: 6–27%).

Conclusions

Two-stage hepatectomy is safe and effective in selected patients with initially unresectable CLM. Further studies are required to better define patient selection criteria for TSH and the exact roles of PVE and preoperative and interval chemotherapy.     

Fas/CD95 signaling rather than angiogenesis or proliferative activity is a useful prognostic factor in patients with resected liver metastases from colorectal cancer

Background The selection of resective therapy for colorectal hepatic metastases remains controversial. The aim of this study is to investigate the prognostic factors for patients with resected liver metastases from colorectal cancer by analyzing not only clinicopathological factors but also recent immunohistological markers.Methods Eighty-five patients underwent hepatic resection for metastatic colorectal cancer over the past 20 years. Fas/CD95 expression, microvessel density, and proliferating cell nuclear antigen (PCNA) proliferative activity were assessed with immunohistochemical methods in addition to the clinicopathological factors. Survival analysis was performed using the Kaplan–Meier method and Cox proportional hazards model, both univariately and multivariately.Results Univariate and multivariate analyses revealed that the number of metastases, Fas/CD95 expression, and postoperative carcinoembryonic antigen doubling time (CEADT) were significant prognostic indicators, whereas the mode of hepatic resection, chemotherapy, and other clinicopathological factors had no influence on survival. Fas/CD95 index correlated with postoperative CEADT (p=0.039), number of metastases (p=0.018), and survival (p=0.023).Conclusions Our study confirmed the number of metastases and CEADT as prominent prognostic factors after hepatic resection for metastatic colorectal cancer. These two factors reflect the degree of Fas/CD95 signaling rather than angiogenesis or cancer growth rate.This work was presented at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, June 23 to 25, 2003     

Improved survival after resection of colorectal liver metastases in patients with unresectable lung metastases

BackgroundModern systemic therapies considerably improve tumour control and thus open the possibility of new surgical approaches in metastatic colorectal cancer. In this retrospective clinical cohort with a comparison group, we investigated whether liver resection in a combined liver–lung-metastasised stage is justified if pulmonary disease is not resected.MethodsFrom 283 patients treated in our institution between 2000 and 2014 for combined colorectal liver- and lung metastases, 35 patients had their pulmonary metastases left in situ while they were eligible for both treatment options: resection versus non-resection of liver metastases. Effectively, 15 of these patients received whereas 20 did not receive a liver resection. In these patients, we compared overall survival and determined risk factors that are associated with poor survival, applying a Cox-Proportional Hazards model.ResultsPatients whose liver metastases were resected showed significantly longer median survival compared to patients who did not undergo hepatic surgery (median 2.6 vs 1.5 years, P = 0.0182). The Cox-Proportional Hazards model revealed hepatic metastasectomy to be the strongest determinant of patient survival (HR 5.27; CI: (1.89, 14.65)).ConclusionOur results suggest that surgical removal of liver metastases may be beneficial in selected patients even if concomitant lung metastases cannot be resected.     

Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma

AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with historically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using X2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables. RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P<0.05). Moreover, higher vWF plasma levels were associated with advanced tumor stage (P<0.05) and the presence of multiple metastases (P=0.014). Patients with lower vWF plasma levels (≤160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P= 0.0043). By multivariate analysis, plasma vWF levels (P<0.001), the extent of metastasis (P= 0.012), and the performance status (P=0.014) were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.     

Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single-photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurements with the volume of the resected liver mass. The correlation coefficient between these methods was 0.899 (P less than 0.01). Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days the liver had regenerated maximally to a volume of 75 +/- 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 +/- 10% for the caffeine clearance and to 100 +/- 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. Our study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy.     

Carcinoembryonic antigen as an independent prognostic factor of recurrence and survival in patients resected for colorectal liver metastases

PURPOSE: We attempted to answer the question of whether serum levels of carcinoembryonic antigen provide prognostic information, in terms of survival, in patients resected for colorectal liver metastases, independently of that provided by other commonly used radioclinical and pathologic factors. METHOD: We performed a systematic review, without meta-analysis, of the biomedical literature using the methodology recommended by the Committee on Evidence-Based Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine. RESULTS: Despite the absence of sufficient details about the methods used to measure serum carcinoembryonic antigen in the 14 studies reviewed, strong arguments exist to include preoperative carcinoembryonic antigen measurements in future trials on the subject. In particular, preoperative carcinoembryonic antigen was found to be significant in the two studies with the greatest number of patients having a preoperative carcinoembryonic antigen assay, in the four studies with the most recent series of patients, in the study in which preoperative carcinoembryonic antigen was used as a continuous variable, and in the study in which preoperative carcinoembryonic antigen was used in terms of doubling time. Postoperative carcinoembryonic antigen was found to have a prognostic significance in the only two studies that evaluated this variable. CONCLUSION: Taking into account the possible reasons for disagreements regarding carcinoembryonic antigen prognostic value between the 14 studies reviewed, we propose some recommendations to improve the reproducibility and the quality of future studies in this field. In particular, we stress the need for a higher degree of multidisciplinary collaboration in clinical trials.     

Preoperative administration of bevacizumab is safe for patients with colorectal liver metastases

AIM:To assess the impact of preoperative neoadjuvant bevacizumab(Bev)on the outcome of patients undergoing resection for colorectal liver metastases(CLM). METHODS:Eligible trials were identified from Medline, Embase,Ovid,and the Cochrane database.The data were analyzed with fixed-effects or random-effects models using Review Manager version 5.0. RESULTS:Thirteen nonrandomized studies with a total of 1431 participants were suitable for meta-analysis. There was no difference in overall morbidity and severe complications between the Bev+group and Bev-group (43.3%vs 36.8%,P=0.06;17.1%vs 11.4%,P=0.07,respectively).Bev-related complications including wound and thromboembolic/bleeding events were also similar in the Bev+and Bev-groups(14.4%vs 8.1%, P=0.21;4.1%vs 3.8%,P=0.98,respectively).The incidence and severity of sinusoidal dilation were lower in patients treated with Bev than in patients treated without Bev(43.3%vs 63.7%,P<0.001;16.8%vs 46.5%,P<0.00,respectively). CONCLUSION:Bev can be safely administered before hepatic resection in patients with CLM,and has a protective effect against hepatic injury in patients treated with oxaliplatin chemotherapy.     

Multivariate analysis of the prognostic factors of patients with unresectable synchronous liver metastases from colorectal cancer

PURPOSE: It frequently is observed that widely varying prognoses are given for patients with the same extent of liver metastases from colorectal cancer, even though the same treatment is performed on these patients. One of the reasons for this variance is that prognostic factors for these patients have not been defined. This study was designed to elucidate which clinicopathologic factors were the most important in the prognosis of 73 patients with unresectable synchronous liver metastasis from colorectal cancer. METHODS: Univariate and multivariate analysis of 11 clinicopathologic factors were performed using the Cox proportional hazard model. Survival curves were generated using the Kaplan-Meier method. RESULTS: Extent of liver metastases was the most significant variable in this survival analysis, although the extent of lymph node metastases of the primary lesion also was significant. However, the method of treatment was not a significant determinant in the survival for patients with unresectable liver metastases. Median survival of patients with H₁, H₂, and H₃ was 13, 12, and 6 months, respectively, and there was a significant difference between survival curves for patients with H₁ and patients with H₃. Median survival of patients with n₀, n₁ and n₂ was 13, 7, and 7 months respectively, and there was a significant difference between survival curves for patients with n₀ and patients with n₂. Median survival of 6 patients with H₁ and n₀ and of 17 patients with H₃ and n₂ was 28 and 4 months, respectively. There was a significant difference in survival curves between these two groups. CONCLUSION: Longevity of patients with unresectable synchronous liver metastases from colorectal cancer is affected adversely by the presence of nodal metastases and extent of liver metastases. This should be considered in the planning treatment.     

Evaluation of peri-operative chemotherapy using a prognostic nomogram for survival after resection of colorectal liver metastases

Introduction:

Nomograms are statistical tools designed to predict outcomes. This study evaluates the effects of peri-operative chemotherapy on the accuracy of a prognostic nomogram for disease-specific survival (DSS) after resection of colorectal liver metastases (CRLM) established at Memorial-Sloan Kettering Cancer Center (MSKCC).

Methods:

An external cohort of 203 patients who underwent resection of CRLM between 1996 and 2006 was used to assess the nomogram.

Results:

After median follow-up of 30.4 months (range 0.33–150), Kaplan–Meier (KM) estimates for 3-, 5- and 8-year post-resection DSS were 56%, 41%, and 32%, respectively; similar to nomogram-predicted probabilities for DSS. The concordance index for the nomogram was higher (0.602) than for the Fong colorectal risk score (CRS; 0.533). KM DSS was longer for patients (n= 50) treated with at least 6 months of peri-operative irinotecan or oxaliplatin compared with all other patients (median 66 vs. 40 months, P= 0.06). KM DSS was greater than nomogram predicted DSS for treated patients and less than nomogram predicted DSS for all other patients.

Conclusions:

The CRLM nomogram was validated by an external cohort and more accurately predicted post-resection survival than the commonly used CRS. Differences in observed and nomogram-predicted survival may reflect the effect of treatment factors, such as peri-operative chemotherapy.     

Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer

Purpose

Recently, microRNA-124 (miR-124) has been demonstrated as a potential tumor suppressor in several types of cancers. However, the role of miR-124 in colorectal cancer remains unclear. This study was aimed at investigating the clinicopathological significance of miR-124 expression in colorectal cancer.

Methods

Quantitative real-time PCR was used to analyze miR-124 expression in 96 colorectal cancers and individual-matched normal mucosa samples. The expression of miR-124 was assessed for associations with clinicopathological characteristics using chi-square test. The survival curves were calculated by the Kaplan–Meier method. The influence of each variable on survival was examined by the Cox multivariate regression analysis.

Results

The miR-124 expression was significantly downregulated in colorectal cancer compared to normal mucosa (P?=?0.001). In colorectal cancer, miR-124 decreased expression correlated significantly with the grade of differentiation (P?=?0.021). Univariate survival analysis showed that the downregulated miR-124 was significantly correlated with worse prognosis, both in terms of overall survival (P?=?0.017) and disease-free survival (DFS) (P?=?0.014). Further, the downregulated miR-124 was demonstrated as a prognostic factor for overall survival (hazard ratio, HR?=?4.634; 95 % confidence interval, CI, 1.731–12.404; P?=?0.002) and DFS (HR?=?4.533, 95 % CI 1.733–11.856, P?=?0.002), independently of gender, age, location, maximum tumor size, depth of invasion, differentiation, and TNM stage.

Conclusions

MiR-124 may play a certain role in the development of colorectal cancer. The downregulation expression of miR-124 is an independent prognostic factor in patients with colorectal cancer.