Improved survival after resection of colorectal liver metastases

Background: The goal of this study was to determine if staging with intraoperative ultrasound (IOUS), assessment of porta hepatis lymph nodes, and evaluation of resection margins can improve selection of patients likely to benefit from resection of colorectal liver metastases. Methods: A retrospective evaluation was performed on patients undergoing celiotomy with intent to resect colorectal liver metastases. Patients were considered unresectable if extrahepatic disease was identified by peritoneal exploration or if IOUS demonstated greater than four lesions or the inability to achieve negative margins. Tumor-negative margins were confirmed by pathologic evaluation. Actuarial 5-year survival was calculated using the method of Kaplan and Meier. Results: Median follow-up is 25 months. Of the 151 patients undergoing operative exploration, 107 (71.0%) underwent liver resection (all margins tumor negative). Three operative deaths occurred in this group (2.8%). The disease of 30 patients (19.8%) was considered unresectable due to extrahepatic involvement, and that of 14 patients (9.2%) was demonstrated by IOUS to be unresectable. Five-year actuarial survival was 44% for the resected group and 0% for the unresectable patients (p<0.0001). Conclusions: IOUS, portal node assessment, and pathologic margin evaluation improves the selection of patients likely to benefit from resection of colorectal liver metastases. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Predictors of extrahepatic recurrence after resection of colorectal liver metastases

BACKGROUND: It is important to identify patients at high risk of extrahepatic recurrence after surgery for liver metastases, in order to maximize the survival benefit obtained by prophylactic regional chemotherapy. METHODS: Data from 68 patients who underwent resection of colorectal liver metastases but who did not receive hepatic arterial chemotherapy or intravenous systemic chemotherapy were collected. Twenty-two variables were examined by univariate and multivariate analyses to determine which factors were relevant to extrahepatic recurrence. A scoring system was developed that included the most relevant factors. RESULTS: The extrahepatic recurrence rate at 3 years after hepatectomy was 57.8 per cent. Three variables were independently associated with extrahepatic recurrence including raised serum level of carcinoembryonic antigen after hepatectomy (relative risk (RR) 5.4, P < 0.001), venous invasion of the primary tumour (RR 4.0, P = 0.001) and high-grade budding of the primary tumour (RR 3.1, P = 0.006). Patients with none of these risk factors had a 3-year extrahepatic recurrence rate of 7.1 per cent, compared with 61.6 per cent for those with one risk factor and 100 per cent for those with two or three risk factors. CONCLUSION: It was possible to identify patients at high risk of disease relapse at extrahepatic sites. This system might be used on an individual basis to select patients with colorectal liver metastases for regional chemotherapy or systemic chemotherapy after surgical intervention.     

Surgical management of recurrence after resection of colorectal liver metastases

The optimal treatment for recurrent lesions after hepatectomy for colorectal liver metastases is controversial. We report the outcome of aggressive surgery for recurrent disease after the initial hepatectomy and the influence on quality of life of such treatment. Forty-five (70%) of the 64 surviving patients developed recurrence after the initial hepatectomy for liver metastases. The determinants of hepatic recurrence were the distribution and the number of liver metastases. Twenty-eight (62%) of patients with recurrence underwent resection. A second hepatectomy was performed in 20 patients, and a third hepatectomy was done in 5 patients. Ten patients with pulmonary metastasis underwent partial lung resection on 14 occasions, while resection of brain metastases was performed in 3 patients on 5 occasions. There were no operative deaths after resection of recurrent disease. The morbidity rate was 28% after repeat hepatectomy, 21% after pulmonary resection, and 0% after resection of brain metastasis. The Karnofsky performance status (PS) after the last surgery was not significantly different from that after the initial hepatectomy. The 3- and 5-year survival rates after the second hepatectomy were 54% and 14%, respectively. The 3-and 5-year survival rates of the patients undergoing resection of extrahepatic recurrence were both 17%. The survival rate after resection of recurrent disease (n=28) was significantly better than that of patients (n=17) with unresectable recurrence (P < 0.05). For the 66 patients with colorectal liver metastases, the 5-year survival rate after initial hepatectomy was 50%. The distribution and the number of liver metastases and the presence of extrahepatic disease, as single factors, significantly affected prognosis after the initial hepatectomy. Multivariate analysis revealed that only the presence of extrahepatic metastasis and a disease-free interval of less than 6 months were independent predictors of survival after the initial and second hepatectomy, respectively. It is concluded that aggressive surgery is an effective strategy for selected patients with recurrence after initial hepatectomy. Careful selection of candidates for repeat surgery will yield increased clinical benefit, including long-term survival.     

Factors influencing survival after resection of pulmonary metastases from colorectal cancer

BACKGROUND: Selection of patients for resection of lung metastases from colorectal cancer is problematic. The aim of this study was to evaluate clinically relevant prognostic factors and to define a subgroup of patients who would most benefit from such surgery. PATIENTS: Seventy-five patients (median age 58 (range 33-82) years) with pulmonary metastases from colorectal cancer underwent 104 R0 lung resections. Median follow-up was 33 (range 4-116) months. Patients who had no evidence of recurrent extrathoracic disease, no more than three metastases on either side, lobectomy as the maximal surgical procedure, and adequate cardiorespiratory function were eligible for surgery. Univariate and multivariate Cox regression, and classification and regression tree subgroup analyses were performed. RESULTS: Overall median survival was 33 months, with 3- and 5-year survival rates of 47 and 27 per cent respectively. Size of metastases (relative risk (RR) 2.6) and extent of resection (RR 0.4) were identified as independent prognostic factors. Primary tumour stage was significant in univariate analysis. Subgroup analysis defined two statistically relevant prognostic groups: patients with a maximum metastasis size of 3.75 cm or less with a disease-free interval of more than 10 months and patients with larger metastases and a shorter disease-free interval. Median survival and 5-year survival were 45 months and 39 per cent in the former group, and 24 months and less than 11 per cent in the latter. CONCLUSION: Subgroup analysis provided criteria for the selection of patients for R0 resection of lung metastases from colorectal cancer and differentiated between those at high or low risk of early tumour progression; the latter patients would benefit most from surgery.     

Perioperative complications influence recurrence and survival after resection of hepatic colorectal metastases

Background

Perioperative outcomes, such as blood loss, transfusions, and morbidity, have been linked to cancer-specific survival, but this is largely unsupported by prospective data.

Methods

Patients from a previous, randomized trial that evaluated acute normovolemic hemodilution during major hepatectomy (≥3 segments) were reevaluated and those with metastatic colorectal cancer (n = 90) were selected for analysis. Survival data were obtained from the medical record. Disease extent was measured using a clinical-risk score (CRS). Log-rank test and Cox proportional hazard model were used to evaluate recurrence-free survival (RFS) and overall survival (OS).

Results

Median follow-up was 71 months. The CRS was ≥3 in 45 % of patients; 59 % had extrahepatic procedures. Morbidity and mortality were 33 and 2 %, respectively. Postoperative chemotherapy was given to 87 % of patients (78/90) starting at a median of 6 weeks. RFS and OS were 29 and 60 months, respectively. Postoperative morbidity significantly reduced RFS (23 vs. 69 months; P < 0.001) and OS (28 vs. 74 months; P < 0.001) on uni- and multi-variate analysis; positive resection margins and high CRS also were significant factors. Delayed initiation of postoperative chemotherapy (≥8 weeks) was common in patients with complications (37 vs. 12 %; P = 0.01).

Conclusions

In this selected cohort of patients from a previous RCT, perioperative morbidity was strongly (and independently) associated with cancer-specific outcome. It also was associated with delayed initiation of postoperative chemotherapy, the impact of which on survival is unclear.     

Predictors and outcome of early recurrence after resection of hepatic metastases from colorectal cancer

Purpose  

This study aimed to investigate the risk factors for early recurrence in patients who had undergone curative resection of colorectal liver metastases (CRLM) and to evaluate the outcome after recurrence.     

Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases

BACKGROUND: The aim of this study was to examine the relationship between surgical margin status and site of recurrence after potentially curative liver resection for colorectal metastases using an ultrasonic dissection technique. METHODS: Between January 2000 and December 2003, 176 patients underwent liver resection with curative intent for colorectal metastases at a single institution. Demographics, operative data, pathological margin status, site of recurrence and long-term survival data were collected prospectively and analysed. RESULTS: On pathological analysis, resection margins were positive in 43 patients, negative by 1-9 mm in 110, and clear by more than 9 mm in 23 patients. At a median follow-up of 33 months, 133 of 176 patients had developed a recurrence, only five of whom had recurrence at the surgical margin. Recurrence at the surgical margin was not significantly related to the size of the margin. Overall, the median time to recurrence was 12.6 months, which was independent of surgical margin size, although there was a significantly higher proportion of patients with multiple metastases in the group with a positive margin (P = 0.008). Margin status did not correlate significantly with either recurrence-free or overall survival. CONCLUSION: The rate of recurrence at the surgical margin was low and a positive margin was not associated with an increased risk of recurrence either at the surgical margin or elsewhere.     

The incidence and outcome of brain metastases after liver resection for colorectal cancer metastases

Aim Brain metastases from colorectal cancer are rare, with an incidence of 0.6–4%. The risk and outcome of brain metastases after hepatic and pulmonary metastasectomy have not been previously described. This study aimed to determine the incidence, predictive factors, treatment and survival of patients developing colorectal brain metastases, who had previously undergone resection of hepatic metastases. Method A retrospective review was carried out of a prospectively maintained database of patients undergoing liver resection for colorectal metastases. Results Fifty‐two (4.0%) of 1304 patients were diagnosed with brain metastases. The annual incidence rate was 1.03% per person‐year. In the majority of cases brain metastases were found as part of multifocal disease. Median survival was 3.2 months (95% CI: 2.3–4.1), but was best for six patients treated with potentially curative resection [median survival = 13.2 (range, 4.9–32.1) months]. Multivariate analysis showed that a lymph node‐positive primary tumour [hazard ratio (HR) = 2.7, 95% CI: 1.8–6.19; P = 0.019], large liver metastases (> 6 cm) [HR = 2.23, 95% CI: 1.19–2.33; P = 0.012] and recurrent intrahepatic and extrahepatic disease [HR = 2.11, 95% CI: 1.2–4.62; P = 0.013] were independent predictors for the development of brain metastases. Conclusion The annual risk of developing brain metastases following liver resection for colorectal metastases is low, but highest for patients presenting with a Dukes’ C primary tumour, large liver metastases or who subsequently develop disseminated disease. The overall survival from colorectal brain metastases is poor, but resection with curative intent offers patients their best chance of medium‐term survival.     

结直肠癌肝转移根治性切除预后因素分析

目的 分析影响结直肠癌肝转移患者根治性手术切除预后的临床病理因素,探讨改善患者预后的方法.方法 收集2005年1月至201 1年12月江苏省苏北人民医院和复旦大学附属肿瘤医院收治的103例结直肠癌肝转移根治性切除患者的临床资料.采用Kaplan-Meier法计算生存率,用Log-rank法分析患者生存情况,对各种影响预后的因素分别进行单变量和多变量Cox回归分析.结果 103例患者均获随访,随访时间10～ 60个月,术后1、3、5年生存率分别为90％、49％、39％.单因素分析结果显示:肝转移灶数目、大小、分布、术前CEA水平、手术并发症、术后化疗是肝转移灶切除术后的影响因素(x2值分别为24.732、9.461、9.568、25.948、25.370、5.701,P＜0.05);多因素分析显示,肝转移灶数目、肝转移灶切除术前CEA水平、手术并发症是影响预后的独立因素(Wald=7.974、12.051、11.547,P＜0.05).结论 肝转移灶数目、肝转移灶切除术前CEA水平和手术并发症是影响结直肠癌肝转移患者预后的独立因素.适当扩大手术切除的适应证,加强对高危患者的随访和术后辅助化疗,可能改善肝转移患者的预后.     

Perioperative blood transfusions are associated with decreased time to recurrence and decreased survival after resection of colorectal liver metastases.

Data from fifty-five patients who had hepatic resections for colorectal liver metastases at the National Cancer Institute (NCI) were analyzed to determine the effect of perioperative blood transfusions on disease recurrence and overall survival. Besides blood transfusions, other factors included in the analysis were size, number, and distribution of metastases, margin status of resected metastases, length of disease-free interval, Duke's stage of the primary tumor, type of hepatic resection, and anesthesia time. Using the Cox proportional hazards model, the amount of blood transfused was found to be a significant prognostic factor. For each additional unit of blood transfused the risk of disease recurrence and death was increased by 5% (p = 0.0015) and 7% (p = 0.0013), respectively. The median disease-free survival for patients who received 3-5, 6-10, and greater than or equal to 11 transfused units was 26, 12.1, and 11.4 months, respectively. The median overall survival for patients who received 3-5, 6-10, and greater than or equal to 11 transfused units was greater than 44, 39.2, and 33.6 months, respectively. The number of resected nodules (1-2 vs. greater than or equal to 3), type of resection (anatomic lobectomy vs. wedge resection), and nodule size (less than or equal to 3.0 cm vs. greater than 3.0 cm) were additional factors that were further evaluated to determine the effect of blood transfusions. Analyses stratified for each of these factors revealed that patients who received greater than or equal to 11 units of blood had a significantly decreased disease-free and overall survival compared with patients who received 3-10 units of blood. It is concluded that the amount of perioperative blood transfused is an independent prognostic factor that adversely effects disease-free and overall survival.     

Preoperative probability model for predicting overall survival after resection of pulmonary metastases from colorectal cancer

BACKGROUND: The aim of this study was identify readily available factors most helpful in predicting survival and to develop a prognostic nomogram for patients with pulmonary metastases from colorectal cancer who are candidates for thoracotomy. METHODS: Pretreatment data on 313 patients with metastases who underwent thoracotomy were analysed. Fourteen preoperative clinical and pathological variables were used to develop a probability model, in which their association with 3-year survival was tested. A nomogram to predict median, 1- and 3-year survival was constructed and validated internally using the concordance index (c-index). The nomogram was then validated with an external data set. RESULTS: Five variables were identified as independent predictors of 3-year survival: prethoracotomy carcinoembryonic antigen level, number of pulmonary tumours, presence of hilar or mediastinal tumour-infiltrated lymph nodes, histology of the primary tumour and presence of extrathoracic disease. The nomogram was well calibrated for predicting 3-year overall survival. The internal validated c-index of the nomogram was 0.72. Applied to another data set, the external validated c-index was 0.66. CONCLUSION: This model has moderate predictive ability to discriminate between patients who are likely to survive after thoracotomy for pulmonary metastases from colorectal cancer.     

Genetic heterogeneity of colorectal cancer liver metastases

Introduction: Although liver metastases are a leading cause of colorectal cancer, the molecular genetic basis of the advanced disease stages remains poorly understood. Whether the metastatic lesions are genetically homogeneous or heterogeneous may determine the response to therapy. We investigated whether synchronously-occurring, multi-focal colon cancer liver metastases were of multi-clonal origin by using genome-scale microarray analysis. Methods: Five distinct colon cancer liver metastases were biopsied from a single patient harboring 15 or more lesions. All specimens were microdissected to ensure >90% tumor cells and total RNA was extracted and prepared for hybridization. Each specimen was analyzed using the Affymetrix U133 GeneChip™ containing approximately 22,000 gene elements. The gene expression profiles of the five specimens were then compared using two independent methods: unsupervised hierarchical clustering to determine the relatedness of the samples and the chi-square test of independence to assess whether the distribution of ranks was different across the samples. Results: No histological difference was observed among the microdissected samples. Each specimen appeared to have equivalent numbers of tumor cells versus stromal cells. However, unsupervised hierarchical clustering of all 22,000 genes by five samples yielded five distinct clusters. Moreover, χ² analysis identified 5 statistically significant (p < 0.001) groups. Conclusions: Genetic profiling of multiple liver metastases using genome scale profiling suggests that colon cancer metastases are muti-clonal in origin. These results have negative implications for the effective application of single agent systemic therapy.     

Impact of parenchymal preserving surgery on survival and recurrence after liver resection for colorectal liver metastasis

Background

This study aimed to investigate the impact of non‐anatomical liver resection (NAR) versus anatomical resection (AR) in patients with colorectal liver metastasis (CRLM), with regard to perioperative and long‐term outcomes.

Methods

Analysis of prospectively collected data for patients with CRLM who underwent either AR or NAR between January 1993 and August 2011 was performed. The impact of AR and NAR on morbidity, mortality, margin positivity, redo liver resections, overall survival (OS) and disease free survival (DFS) was analysed.

Results

A total of 1574 resections for CRLM were performed. A total of 249 were redo resections and 334 patients underwent combined AR and NAR, hence, 583 were excluded. In total, 582 AR and 409 NAR were performed. The median age was 66 years (range 23.8–91.8). Median follow up was 32.2 months (interquartile range 17.5–56.9). The need for postoperative transfusion (11.6% versus 2.2%, P = <0.0001), overall complications (25% versus 10.7%, P < 0.0001) and 90‐day mortality (4.9% versus 1.2%, P < 0.0001) was higher in the AR group. R0 and R1 resection rates (AR 26.2% NAR 25%, P = 0.69) and number of patients with intrahepatic recurrence was similar between the two groups (AR 17.5% NAR 22%, P = 0.08). However, the need for redo liver surgery was higher in NAR group 15.4% versus 8.7% (P < 0.001). The OS (NAR 34.1 months versus AR 31.4 months, P = 0.002) and DFS were longer in the NAR group (NAR 18.8 months versus AR 16.9 months, P = 0.031).

Conclusions

A parenchymal preserving surgery (NAR) is associated with lower complication rates and better OS and DFS when compared with AR without compromising margin status. However, NAR increases the need for repeat liver resections.     

Biopsy of resectable colorectal liver metastases causes tumour dissemination and adversely affects survival after liver resection

BACKGROUND: Liver resection is increasingly being performed for metastatic colorectal cancer. This study assessed the need for preoperative biopsy of suspected metastases and whether biopsy has any effect on long-term survival. METHODS: Prospectively collected data on patients who underwent liver resection for colorectal metastases between 1986 and 2003 were reviewed retrospectively. The endpoints of morbidity, operative mortality and long-term survival were compared between patients who had biopsy before referral (group 1) and those who did not (group 2). RESULTS: Patient demographics and disease distribution were similar for 90 patients in group 1 and 508 in group 2. Seventeen patients (19 per cent) who had undergone biopsy either at the time of colorectal resection or radiologically had evidence of needle-track deposits. Operative mortality and morbidity rates in the two groups were similar. The 4-year survival rate after liver resection was 32.5 (s.e. 5.5) per cent in group 1, compared with 46.7 (2.8) per cent in group 2 (P = 0.008). CONCLUSION: Needle-track deposits are common after biopsy of suspected colorectal liver metastases. Biopsy of metastases confers poorer long-term survival on patients after liver resection and cannot be justified in patients with potentially resectable disease.     

Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases

BACKGROUND: Despite indications for resection of colorectal liver metastases having expanded, debate continues about identifying patients that may benefit from surgery. METHODS: Clinicopathologic data from a total of 700 patients was gathered between January 1993 and January 2006 from a prospectively maintained dataset. Of these, 687 patients underwent resection for colorectal liver metastases. RESULTS: The median age of patient was 64 years and 36.8% of patients had synchronous disease. The overall 5-year survival was 45%. The presence of an inflammatory response to tumor (IRT), defined by an elevated C-reactive protein (>10 mg/L) or a neutrophil/lymphocyte ratio of >5:1, was noted in 24.5% of cases. Only the number of metastases and the presence or absence of an IRT influenced both overall and disease-free survival on multivariable analysis. A preoperative prognostic score was derived: 0 = less than 8 metastases and absence of IRT; 1 = 8 or more metastases or IRT, and 2 = 8 or more metastases and IRT-from the results of the multivariable analysis. The 5-year survival of those scoring 0 was 49% compared with 34% for those scoring 1. None of the patients that scored 2 were alive at 5 years. CONCLUSION: The preoperative prognostic score is a simple and effective system allowing preoperative stratification.