结直肠癌肝转移的术前化疗

结直肠癌是最常见的恶性肿瘤之一,结直肠癌的肝脏转移是造成结直肠癌患者死亡的最主要原因之一。超过50%的结直肠癌患者会发生肝脏转移,其治疗的疗效直接影响着结直肠癌患者的预后。对于结直肠癌肝转移的患者行最佳支持治疗,患者的中位生存时间大约为6个月;行甲酰四氢叶酸钙(CF)+5-FU化疗,患者的中位生存时间为8～12个月;应用奥沙利铂或伊立替康的联合化疗(FOLFOX或FOLFIRI),其中位生存时间可延长至20～24个月。     

Optimal Future Liver Remnant in Patients Treated with Extensive Preoperative Chemotherapy for Colorectal Liver Metastases

Background

Patients with colorectal liver metastases (CLM) are increasingly treated with preoperative chemotherapy. Chemotherapy associated liver injury is associated with postoperative hepatic insufficiency (PHI) and mortality. The adequate minimum future liver remnant (FLR) volume in patients treated with extensive chemotherapy remains unknown.

Methods

All patients with standardized FLR > 20 %, who underwent extended right hepatectomy for CLM from 1993-2011, were divided into three cohorts by chemotherapy duration: no chemotherapy (NC, n = 30), short duration (SD, ≤12 weeks, n = 78), long duration (LD, >12 weeks, n = 86). PHI and mortality were compared by using uni-/multivariate analyses. Optimal FLR for LD chemotherapy was determined using a minimum p-value approach.

Results

A total of 194 patients met inclusion criteria. LD chemotherapy was significantly associated with PHI (NC + SD 3.7 vs. LD 16.3%, p = 0.006). Ninety-day mortality rates were 0 % in NC, 1.3 % in SD, and 2.3% in LD patients, respectively (p = 0.95). In patients with FLR > 30 %, PHI occurred in only two patients (both LD, 2/20, 10 %), but all patients with FLR > 30 % survived. The best cutoff of FLR for preventing PHI after chemotherapy >12 weeks was estimated as >30 %. Both LD chemotherapy (odds ratio [OR] 5.4, p = 0.004) and FLR ≤ 30 % (OR 6.3, p = 0.019) were independent predictors of PHI.

Conclusions

Preoperative chemotherapy >12 weeks increases the risk of PHI after extended right hepatectomy. In patients treated with long-duration chemotherapy, FLR > 30 % reduces the rate of PHI and may provide enough functional reserve for clinical rescue if PHI develops.     

Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases

Annals of Surgical Oncology - Studies have suggested that neutrophil-to-lymphocyte ratio (NLR) has value as a predictor of long-term outcomes in various cancer types. Its prognostic potential in...     

Results of Preoperative Hepatic Arterial Infusion Chemotherapy in Patients Undergoing Liver Resection for Colorectal Liver Metastases

Background Although hepatic artery infusion chemotherapy (HAIC) of floxuridine (FUDR) for colorectal liver metastases (CLM) can produce high response rates, data concerning preoperative HAIC are scarce. The aim of this study was to assess the feasibility and results of liver resection after preoperative HAIC with FUDR. Methods Between 1995 and 2004, 239 patients with isolated CLM received HAIC in our institution. Fifty of these patients underwent subsequent curative liver resection (HAIC group). Short- and long-term results of the HAIC group were compared with the outcomes of 50 patients who underwent liver resection for CLM without preoperative chemotherapy. Results Postoperative morbidity rate were comparable between the two groups. Overall disease-free survival at 1 and 3 years after hepatectomy were 77.5% and 57.5% in the HAIC group and 62.9% and 37% in the control group (P = .036). Overall survival from diagnosis of CLM at 1, 3, and 5 years were 97%, 59%, and 49% in the HAIC group versus 94%, 48%, and 35% in the control group (P = .097). When patients were stratified according to clinical-risk scoring (CRS) system, patients with more advanced disease at the time of liver resection (CRS ≥3) had a median survival of 41 months in the HAIC group (n = 37) and 35 months in the control group (n = 34) (P = .031). Conclusions HAIC of FUDR does not negatively affect the outcome of subsequent liver resection. Preoperative HAIC of FUDR may reduce liver recurrence rate and improve long-term survival in patients with more advanced liver disease. Part of this article was presented at the International Hepato-Pancreato-Biliary Association, 7th World Congress in Edinburgh, Scotland, September 3–7, 2006.     

Detection and Management of Extrahepatic Colorectal Cancer in Patients with Resectable Liver Metastases

The presence of extrahepatic disease has a great effect on the management of patients with metastatic colorectal cancer in the liver. FDG-PET scanning is currently the most sensitive way of detecting extrahepatic metastases in such patients. This is supported by 10 studies, which show that FDG-PET scan will discover extrahepatic disease in about one in six patients who have completed standard imaging. Staging laparoscopy is another means of detecting extrahepatic disease. Its role remains undefined especially in patients who have had FDG-PET scans. It should probably be restricted to patients with high clinical risk scores. In terms of treatment, patients with recurrence at the primary colorectal site as well as resectable liver metastases appear to benefit from resection of both sites provided that R0 resections can be obtained. Resection of involved hepatic pedicle lymph nodes in patients with resectable liver metastases is associated with poor outcome. The situation regarding patients with peritoneal and liver metastases bears a strong resemblance to that of primary site recurrence and liver metastases. Very acceptable survival can be expected if the peritoneal disease can be eradicated. Information regarding treatment of lung and liver metastases is the most complete of any of these areas. Good results may be expected if all the disease can be cleared. Caution is required in interpreting claims of good survival when study numbers are small and confidence intervals of data are not provided.     

Usefulness of Contrast-Enhanced Intraoperative Ultrasonography (CE-IOUS) in Patients with Colorectal Liver Metastases after Preoperative Chemotherapy

Aims

The aim of this study was to evaluate the ability of contrast-enhanced intraoperative ultrasonography to detect colorectal liver metastases after preoperative chemotherapy compared with intraoperative ultrasound and preoperative imaging techniques.

Methods

From January 2010 to December 2011, 28 patients with colorectal liver metastases underwent intraoperative ultrasonography and contrast-enhanced intraoperative ultrasonography during hepatectomy following preoperative chemotherapy. The findings were compared to preoperative imaging using contrast-enhanced ultrasonography, computed tomography, magnetic resonance imaging, and/or fluorodeoxyglucose positron emission tomography.

Results

Preoperative imaging techniques detected 58 metastatic lesions in 28 patients. In 32 % of patients (n?=?9), intraoperative ultrasound detected 24 missed hepatic nodules. In 14 % of patients (n?=?4), contrast-enhanced intraoperative ultrasonography detected an additional six nodules and change in operative management occurred in 18 % of patients. Using univariate analysis, we found three factors significantly related to detection of additional metastases with contrast-enhanced intraoperative ultrasonography: three or more metastases before chemotherapy (p?=?0.047), resolution of at least one metastasis (p?=?0.011), and small liver metastases (largest lesion size ≤20 mm) after chemotherapy (p?=?0.007).

Conclusion

In patients undergoing surgery for colorectal liver metastases after chemotherapy, contrast-enhanced intraoperative ultrasonography improved both the sensitivity of intraoperative ultrasonography to detect liver metastases and the R0 hepatic resection rate.     

Preoperative Chemotherapy and the Outcome of Liver Resection for Colorectal Metastases

Background Neoadjuvant systemic chemotherapy is being increasingly used prior to liver resection for colorectal metastases. Oxaliplatin has been implicated in causing structural changes to the liver parenchyma, and such changes may increase the morbidity and mortality of surgery. Patients and Methods A retrospective study was undertaken of 101 consecutive patients who had undergone liver resection for colorectal metastases in two HPB centers. Preoperative demographic and premorbid data were gathered along with liver function tests and tumor markers. A subjective assessment of the surgical procedure was noted, and in-hospital morbidity and mortality were calculated. The effect of preoperative chemotherapy on short-term and long-term outcome was analyzed, and actuarial 1 and 3 year survival was determined. Results Patients who received neoadjuvant chemotherapy had a higher number of metastases (median 2, range 1–8 versus median 1, range 1–5; P = 0.019) and more had synchronous tumors (24 patients versus 8; P < 0.001). Overall morbidity was 37% and hospital mortality was 3.9%. Operative and in-hospital outcome was not influenced by chemotherapy. Long-term survival was worse in patients who had received preoperative chemotherapy (actuarial 3-year survival 62% versus 80%; P = 0.04). Conclusions This study shows no evidence that neoadjuvant chemotherapy, and in particular oxaliplatin, increases the risk associated with liver resection for colorectal metastases. Long-term outcome is reduced in patients receiving preoperative chemotherapy, although they have more advanced disease.     

Preoperative Imaging of Colorectal Liver Metastases After Neoadjuvant Chemotherapy: A Meta-Analysis

Background

Chemotherapy treatment induces parenchymal changes that potentially affect imaging of CRLM. The purpose of this meta-analysis was to provide values of diagnostic performance of magnetic resonance imaging (MRI), computed tomography (CT), fluorodeoxyglucose positron emission tomography (FDG-PET), and FDG-PET/CT for preoperative detection of colorectal liver metastases (CRLM) in patients treated with neoadjuvant chemotherapy.

Methods

A comprehensive search was performed for original articles published from inception to 2011 assessing diagnostic performance of MRI, CT, FDG-PET, or FDG-PET/CT for preoperative evaluation of CRLM following chemotherapy. Intraoperative findings and/or histology were used as reference standard. For each imaging modality we calculated pooled sensitivities for patients who received neoadjuvant chemotherapy as well as for chemonaive patients, defined as number of malignant lesions detected divided by number of malignant lesions as confirmed by the reference standard.

Results

A total of 11 papers, comprising 223 patients with 906 lesions, were included. Substantial variation in study design, patient characteristics, imaging features, and reference tests was observed. Pooled sensitivity estimates of MRI, CT, FDG-PET, and FDG-PET/CT were 85.7% (69.7?C94.0%), 69.9% (65.6?C73.9%), 54.5% (46.7?C62.1%), and 51.7% (37.8?C65.4%), respectively. In chemonaive patients, sensitivity rates were 80.5% (67.0?C89.4%) for CT, 81.3% (64.1?C91.4%) for FDG-PET, and 71.0% (64.3?C76.9%) for FDG-PET/CT. Specificity could not be calculated because of non-reporting of ??true negative lesions.??

Conclusion

In the neoadjuvant setting, MRI appears to be the most appropriate imaging modality for preoperative assessment of patients with CRLM. CT is the second-best diagnostic modality and should be used in the absence of MRI. Diagnostic accuracy of FDG-PET and PET-CT is strongly affected by chemotherapy.     

The Role of FDG-PET in the Selection of Patients with Colorectal Liver Metastases

Background Selection of patients for hepatic resection of colorectal liver metastases is still limited. After conventional work up by computed tomography (CT) scan, 60% of patients will develop recurrent disease in the early years after resection. The aim of the present study was to evaluate whether an additional fluorine-18-deoxyglucose positron emission tomography (FDG-PET) improves patient selection and therefore adds value to select patients for curative liver resection. Methods Data from 203 patients selected for surgical treatment of colorectal liver metastases between 1995 and 2003 were collected in a prospective database. Group A consisted of 100 consecutive patients selected for hepatic surgery by conventional diagnostic imaging (CT chest and abdomen) only. Group B consisted of 103 consecutive patients selected for hepatic surgery by conventional diagnostic methods plus an additional FDG-PET. Results The number of patients with futile surgery, in which further treatment was considered inappropriate at laparotomy, was 28.0% in group A and 19.4% in group B. The reason for unresectable disease differed between groups. In group A, 10/100 (10.0%) patients showed extrahepatic abdominal disease versus 2/103 patients (1.9%) in group B (P = .017). In all other cases, resection was not performed because liver disease proved too extensive at laparotomy. For patients ultimately undergoing surgical treatment of the metastases, survival was comparable between groups. Overall survival at 3 years was 57.1% in group A versus 60.1% in group B. Disease-free survival at 3 years was 23.0% in group A and 31.4% in group B. Conclusions In patients with colorectal liver metastases, FDG-PET may reduce the number of negative laparotomies. However, the effect size on the selection of these patients seems not sufficient enough to affect the overall and disease-free survival after treatment.     

Sequential Preoperative Ipsilateral Portal and Arterial Embolization in Patients with Colorectal Liver Metastases

Background Preoperative portal vein embolization (PVE) induces ipsilateral atrophy of the hepatic parenchyma to be resected, as well as contralateral compensatory hypertrophy of the residual liver. However, there are two potential problems with this technique: inadequate contralateral hypertrophy and tumor progression while waiting for the non-embolized liver to hypertrophy. We devised a strategy to deal with these two problems by performing an ipsilateral hepatic artery embolization 6 weeks after an unsatisfactory PVE in an effort to accelerate the hypertrophy of the remnant liver. Materials and Methods Two patients with colorectal liver metastases underwent to this sequential preoperative treatment in order to achieve resectability of their metastatic disease. Results Both patients successfully underwent major hepatic resection. Conclusions In our experience sequential ipsilateral portal vein and hepatic artery embolization extended the indications for liver resection for metastatic colorectal cancer.     

ASO Author Reflections: Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases

Annals of Surgical Oncology -     

ASO Visual Abstract: Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases

Annals of Surgical Oncology -     

Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific. Presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, March 11, Miami, Florida.     

Blood Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients with Colorectal Liver Metastases Treated with Systemic Chemotherapy

Background  Whether neutrophil-to-lymphocyte ratio (NLR) predicts survival of patients with colorectal liver metastases (CLM) treated with systemic chemotherapy remains unclear. Methods  Clinicopathologic data were reviewed for patients with CLM treated with chemotherapy and resection (n = 200) or chemotherapy only (n = 90). Univariate and multivariate analyses for prognostic factors were performed. In the resection group, whether chemotherapy normalizes high NLR and the effect of NLR normalization on survival were evaluated. Results   In the resection group, patients with preoperative NLR > 5 had a worse 5-year survival rate than patients with NLR ≤ 5 (19% vs. 43%; P = 0.009), and NLR > 5 was the only independent preoperative predictor of worse survival (P = 0.016; hazard ratio [HR] = 2.22; 95% confidence interval [95% CI], 1.16–4.25). In the nonresection group, patients with prechemotherapy NLR > 5 had a worse 3-year survival rate than patients with NLR ≤ 5 (0% vs. 23%; P = 0.0002), and NLR > 5 was the only independent predictor of worse survival (P = 0.001; HR = 2.91; 95% CI, 1.54–5.50). In the resection group, chemotherapy normalized high NLR in 17 of 25 patients, and these 17 patients had better survival than the 8 patients with high NLR both before chemotherapy and before surgery (P = 0.021). Conclusion   NLR independently predicts survival in patients with CLM treated with chemotherapy followed by resection or chemotherapy only. When chemotherapy normalizes high NLR, improved survival is expected.     

Circulating Tumor Cells and Prognosis of Patients with Resectable Colorectal Liver Metastases or Widespread Metastatic Colorectal Cancer: A Meta-Analysis

Background

We performed a systematic review and meta-analysis to investigate the prognostic value of tumor cells in blood (circulating tumor cells [CTCs]) or bone marrow (BM) (disseminated tumor cells) of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer (CRC).

Materials and Methods

The following databases were searched in May 2011: MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cochrane Library. Studies that investigated the association between tumor cells in blood or BM and long-term outcome in patients with metastatic CRC were included. We extracted hazard ratios (HRs) and confidence intervals (CIs) from the included studies and performed random-effects meta-analyses for survival outcomes.

Results

The literature search yielded 16 studies representing 1,491 patients. The results of 12 studies representing 1,329 patients were suitable for pooled analysis. The overall survival (HR, 2.47; 95 % CI 1.74–3.51) and progression-free survival (PFS) (HR, 2.07; 95 % CI 1.44–2.98) were worse in patients with CTCs. The subgroup of studies with more than 35 % CTC-positive patients was the only subgroup with a statistically significant worse PFS. All eight studies that performed multivariable analysis identified the detection of CTCs as an independent prognostic factor for survival.

Conclusion

The detection of CTCs in peripheral blood of patients with resectable colorectal liver metastases or widespread metastatic CRC is associated with disease progression and poor survival.     

The Role of Liver Resection for Patients with Liver and Unresectable Lung Colorectal Metastases (LUNA)

Annals of Surgical Oncology -     

Liver Resection of Colorectal Liver Metastases in Elderly Patients

Background  

The percentage of elderly patients with colorectal liver metastases (CLM) has increased. Liver resection remains the only curative therapy; data evaluating the outcome in this age group is limited. Aim of the present study was to determine if postoperative morbidity, mortality, and other independent predictors influence survival in patients ≥70 years undergoing liver resection for CLM.     

Selective Intra-arterial Chemotherapy with Floxuridine as Second- or Third-Line Approach in Patients with Unresectable Colorectal Liver Metastases

Background  

An outcome assessment was performed of patients with unresectable colorectal liver metastases (CRLM) treated in second or third line with floxuridine (FUDR)-based hepatic artery infusion (HAI).     

Chemotherapy,Liver Injury,and Postoperative Complications in Colorectal Liver Metastases

Background  

Systemic chemotherapy (CTx) is increasingly used before surgery for colorectal liver metastases (CRC-LM). However, CTx may cause liver injury like steatosis, steatohepatitis, and sinusoidal injury which may be associated with postoperative morbidity. Some recent data have even shown an increased mortality in patients with CTx-associated steatohepatitis. We, therefore, analyzed our recent experience with potential hepatic injury and its association with CTx and morbidity in patients undergoing surgery for CRC-LM.