保留肝实质的治疗方式在结直肠癌肝转移手术切除中的应用分析

  目的   探讨保留肝实质的治疗方式在结直肠癌肝转移（colorectal liver metastases, CRLM）手术切除中的意义。  方法   回顾性分析北京大学肿瘤医院2000年1月至2016年5月手术切除的CRLM患者377例, 根据手术方式分为保留肝实质（parenchymalsparing hepatectomy, PSH）组305例和大范围肝切除（major hepatectomy, MH）组72例。比较两组患者的临床特征、手术情况、术后并发症及预后。  结果  PSH组肝转移灶个数少于MH组, 差异比较具有统计学意义（P=0.000）。全组采用PSH治疗的患者占80.9%, 且随时间增长逐渐增多。PSH组手术时间比MH组短（177.5 minvs.220 min, P=0.000）, 手术出血比MH组少（150 mLvs. 300 mL, P=0.000）, 术后并发症发生率比MH组低（47.4%vs.64.8%, P=0.008）。PSH组与MH组患者的总生存（overall survival, OS）时间、肝内无复发生存（hepatic recurrence free survival, HFRS）时间差异无统计学意义。PSH组患者复发后接受局部治疗的比例明显增加（42.8%vs.25.6%, P=0.040）, 复发患者中接受局部治疗的患者生存期明显延长（58个月vs.24个月, P=0.000）。  结论  CRLM患者手术时采用PSH的治疗方式肝内复发率更低, 安全性更高, 复发后再次接受局部治疗的可能性明显增加, 是推荐的治疗模式。      

Repeat hepatectomy for recurrent colorectal liver metastases

PURPOSE: Liver resection represents the best and potentially curative treatment for metastatic colorectal cancer (MCC) to the liver. After resection, however, most patients develop recurrent disease, often isolated to the liver. The aim of this study was to determine the value of repeat liver resection for recurrent MCC and to analyze the factors that can predict survival. PATIENTS AND METHODS: From January 1992 to October 2002, 42 patients from a group of 168 patients resected for MCC were submitted to 55 repeat hepatectomies (42 second, 11 third, and 2 fourth hepatectomies). Records were retrospectively reviewed. The primary tumor was carcinoma of the colon in 26 patients and carcinoma of the rectum in 16 patients. Liver metastases were synchronous in 24 patients (57.1%). RESULTS: There were 25 men and 17 women with the mean age of 63.5 years (range: 34-80). There was no intraoperative or postoperative mortality. The morbidity rates were 9.5%, 14.3%, and 18.2% (P = 0.6) respectively after a first, second, or third hepatectomies. No patients needed reoperation. Operative duration was longer after a second or third hepatectomie than after a first hepatectomie without difference for operative bleeding. Overall 5-year survivals were 33%, 21%, and 36% respectively after a first, second, or third hepatectomies. Factors of prognostic value on univariate analysis included serum carcinoembryonic antigen levels (P = 0.01) during the first hepatectomy, the presence of extrahepatic disease (P = 0.05) and tumor size larger than 5 cm (P = 0.04) during the second hepatectomie. CONCLUSIONS: Repeat hepatectomies can provide long-term survival rates similar to those of first hepatectomies.     

The extent of resection influences outcome following hepatectomy for colorectal liver metastases.

BACKGROUND: The acceptable indications for liver resection in patients with colorectal metastases have increased significantly in the last decade. It is thus becoming more difficult to ascertain the limitations for selection as the boundaries have been greatly extended. This has resulted in not only more extensive resections, but more atypical and bilobar resections. The aim of this study was to compare the outcome of patients undergoing different extent of liver resection in a specialist unit. METHODS: All patients undergoing liver resection for colorectal metastases at the Royal Infirmary of Edinburgh between October 1988 and April 2001 were reviewed. Patients were allocated into one of three groups: standard group, extended group, and segmental group. Patient information was collected from a prospectively completed database. RESULTS: One hundred and thirty-seven patients had liver resections for colorectal metastases during the study period. There were 69 standard hepatectomies, 41 extended resections and 27 segmental resections. CEA level was significantly lower in the segmental group(p = 0.012). There was a significant difference between the groups in terms of median operating time (p < 0.0001, Kruskal-Wallis test), operative blood loss (p = 0.006, Kruskal-Wallis test) and post-operative stay ( p = 0.036, Kruskal-Wallis test). Major post-operative complications were similar between standard and extended resections but less following segmental resection (p = 0.050. Predicted median survival was 51 months following standard resection, 23 months following extended resection and 59 months after segmental resection ( p = 0.037, log rank test), however, there was no difference between the three groups for actual 5-year survival (p = 0.662, Pearson chi-square test). CONCLUSION: Morbidity and mortality rates were comparable with other previous studies as was overall survival, although survival in patients undergoing extended resections was reduced. There was an acceptable level of morbidity and mortality for all three groups. Patients undergoing segmental resection had fewer complications, shorter length of stay, and the longest median survival suggesting adequate oncological clearance. Segmental resection has a role for favourably placed tumour deposits if oncological clearance can be ensured. Extended liver resections have a role for selected patients with bilobar colorectal metastases or large solitary deposits close to the hepatic vein confluence.     

Sarcopenia and primary tumor location influence patients outcome after liver resection for colorectal liver metastases

IntroductionRight-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. The prevalence of sarcopenia is known to worsen the outcome after hepatic resection. We sought to investigate the prevalence of sarcopenia and its prognostic application according to the primary CRC tumor site.Methods355 patients (62% male) who underwent liver resection in our center were identified. Clinicopathologic characteristics and long-term outcomes were stratified by sarcopenia and primary tumor location (right-sided vs. left-sided). Tumors in the coecum, right sided and transverse colon were defined as right-sided, tumors in the left colon and rectum were defined as left-sided. Sarcopenia was assessed using the skeletal muscle index (SMI) with a measurement of the skeletal muscle area at the level L3.ResultsPatients who underwent right sided colectomy (n = 233, 65%) showed a higher prevalence of sarcopenia (35.2% vs. 23.9%, p = 0.03). These patients also had higher chances for postoperative complications with Clavien Dindo >3 (OR 1.21 CI95% 0.9–1.81, p = 0.05) and higher odds for mortality related to CRC (HR 1.2 CI95% 0.8–1.8, p = 0.03).On multivariable analysis prevalence of sarcopenia remained independently associated with worse overall survival and disease free survival (overall survival: HR 1.47 CI 95% 1.03–2.46, p = 0.03; HR 1.74 CI95% 1.09–3.4, p = 0.05 respectively).ConclusionSarcopenia is known to have a worse prognosis in patients with CRLM and CRC. Depending on the primary location sarcopenia has a variable effect on the outcome after liver resection.     

Hepatic steatosis,body mass index and long term outcome in patients undergoing hepatectomy for colorectal liver metastases

Background

Hepatic steatosis (HS) is as an independent risk factor for morbidity and mortality post-hepatectomy. Recent studies report significant correlation between chemotherapy (now frequently employed pre-hepatectomy for colorectal liver metastases (CRLM)), HS and steatohepatitis. Furthermore, raised body mass index (BMI) predisposes to HS. However, no previous study has analysed the effect of HS on long-term survival.

Method

A retrospective analysis of a prospective consecutive cohort of 102 patients undergoing hepatectomy with 60 months follow-up data was performed. Resection specimens were examined histologically and the degree of steatosis graded accordingly. The data was compared to BMIs and other clinical characteristics. Statistical analyses included log-rank, contingency, logistic regression and Fisher's exact tests.

Results

No detectable fatty change in 27 patients; 1 patient had cirrhosis; 57 had HS: 26 graded mild; 10 moderate, 21 severe and 17 not graded. 1 patient (BMI 29.5 kg/m²) had steatohepatitis but survived surgery. No significant difference in median survival between patients with and without HS (28.6 vs. 32.3 months, log-rank p > 0.05). Results were similar between patients with BMI < 25 and BMI ≥ 25 (32.3 vs. 36.8 months, log-rank p > 0.05). Analyses of BMI against steatosis grade showed that patients with a higher BMI were at an increased risk of having a more severe HS (logistic regression, p < 0.01; Fisher's exact, p < 0.01). Contingency analyses on the influence of diabetes, chemotherapy and increasing number of risk factors on the likelihood of obtaining HS were insignificant (Fisher's exact, all p > 0.05).

Conclusion

While patients with higher body mass index values are at increased risk of having more severe hepatic steatosis, neither BMI nor hepatic steatosis significantly influences long-term survival. We conclude therefore that neither obesity nor hepatic steatosis has significant prognostic relevance on long-term survival of CRLM patients undergoing hepatectomy.     

Remnant liver regeneration after two-stage hepatectomy for multiple bilobar colorectal metastases.

AIMS: Two-stage hepatectomy for multiple, bilobar liver metastases from colorectal cancer aimed to minimize liver failure risk by performing the second resection after regeneration, but impact of this strategy on volume of the future liver remnant (FLR) remained to be demonstrated. We compared two-stage hepatectomy with one stage following portal vein embolization (PVE) for multiple, bilobar liver metastases from colorectal cancer as to effects on volume of the FLR. METHODS: Forty-three patients undergoing major hepatectomy for multiple colorectal cancer metastases were divided retrospectively into patients undergoing hepatectomy following PVE (n=21) and those undergoing two-stage hepatectomy (n=22). Increases in FLR volume were compared. RESULTS: While the increase in the volume FLR averaged approximately 70 mL (302.6 mL before PVE vs. 370.9 mL after PVE) and the increase in the ratio of FLR to total liver volume averaged approximately 7.5% (30.2% to 37.5%) following PVE, first-stage hepatectomy increased FLR volume by approximately 100mL (from 259.4 to 361.4), and the ratio, by 15% (26.9% to 41.6%). The FLR hypertrophy ratio relative to pre-procedure volume estimates in the two-stage group (50.2%) was twice that in the PVE group (25.3%). CONCLUSIONS: Superiority of two-stage hepatectomy in hypertrophy of the FLR was confirmed.     

Cryotherapy of the resection edge after hepatectomy of colorectal liver metastases

Obtaining a one-centimeter negative margin is an important factor in preventing disease recurrence after surgery for hepatic tumors. Cryotherapy of the resected edge has been used to achieve optimal margin clearance in cases in which the alternative would be an extended high-risk liver resection. As a concrete method, cryotherapy was delivered with a liquid nitrogen based compact system (CRY-AC, Brymill Co., USA). The resection edge with involved or inadequate resection margins was ablated directly by using the flat probe for 3 minutes per 1 place. Between 2002 and present, a total of 14 patients with colorectal liver metastases underwent edge cryotherapy. Although there was no hemorrhage from the stump, postoperative leak of the bile and stump recurrence were recognized in each patient. Since cryotherapy has features that make the vascular difficult to be damaged, the complication was not recognized in the patient with exposed vascular in the resected edge. By extending the follow-up period, we want to examine whether the edge recurrence could be controlled or not.     

Sub-millimeter surgical margin is acceptable in patients with good tumor biology after liver resection for colorectal liver metastases

BackgroundThe definition of R1 resection in colorectal cancer liver metastases (CRLM) remains debatable. This retrospective study was conducted to clarify the impact of R1 margin on patient survival after liver resection for CRLM, taking into consideration tumor biology, including RAS status and chemotherapy response.MethodsWe retrospectively analysed the clinical and survival data of 214 CRLM patients with initially resectable liver metastases who underwent liver resection after receiving neoadjuvant chemotherapy between January 2006 and December 2016.ResultsR1 resection significantly impacted patients’ overall survival (OS) and disease-free survival (DFS) in the overall patient cohort (5-year OS: 53.2% for R0 vs 38.2% for R1, P = 0.001; 5-year DFS: 26.5% for R0 vs 10.5% for R1, P = 0.002). In the RAS wild-type subgroup and respond to chemotherapy (RC) subgroup, R1 reached a similar OS to those who underwent R0 resection (RAS wild-type, P = 0.223; RC, P = 0.088). For the RAS mutated subgroup and no response to chemotherapy (NRC) subgroup, OS was significantly worse underwent R1 resection (RAS mutant, P = 0.002; NRC, P = 0.022). When considering tumor biology combining RAS and chemotherapy response status, R1 resection was only acceptable in patients with both RAS wild-type and RC (5-year OS: 66.4% for R0 vs 65.2% for R1, p = 0.884), but was significantly worse in those with either RAS mutation or NRC.ConclusionsTumor biology plays an important role in deciding the appropriate resection margin in patients with CRLM undergoing radical surgery. R1 resection margin is only acceptable in RAS wild-type patients who respond to chemotherapy.     

The predictors and oncological outcomes of repeat surgery for recurrence after hepatectomy for colorectal liver metastases

Purpose

Although recurrence after hepatectomy for colorectal liver metastases (CRLM) is common, the optimal treatment strategy remains unclear. The aims of this study were to clarify the impact of repeat surgery and identify the predictive factors for repeat surgery.

Methods

Among the 170 patients who underwent potentially curative surgery for CRLM, 113 developed recurrence. The predictive factors for the performance of repeat surgery were identified and a predictive model was constructed.

Results

The patterns of recurrence were as follows; single site [n?=?100 (liver, n?=?61; lung, n?=?22; other, n?=?17)], multiple site (n?=?13). Repeat surgery was performed in 54 patients (47.8%) including re-hepatectomy (n?=?25), radiofrequency ablation (n?=?12), and resection of the extrahepatic recurrent disease (n?=?17), and their overall survival (OS) was significantly better than that of those who could not (5-year OS 60.7 vs 19.5%, P?<?0.0001). A multivariate analysis revealed that a primary N-negative status [relative risk (RR) 2.93, P?=?0.017], indocyanine retention rate at 15 min ≤ 10% before hepatectomy (RR 2.49, P?=?0.04), and carcinoembryonic antigen ≤ 5 ng/mL before hepatectomy (RR 2.96, P?=?0.017) independently predicted the performance of repeat surgery. For patients who did not present any factors, the probability of repeat surgery was 19.6%. The addition of each subsequent factor increased the probability to 41.9, 67.8, and 84.0% (for 1, 2, and 3 factors, respectively).

Conclusions

Repeat surgery for not only intrahepatic but also extrahepatic recurrence is crucial for prolonging the survival of CRLM patients. The proposed model may help to predict the possibility of repeat surgery and provide optimal individualized treatment.

     

FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer

Background:

In patients with colorectal liver metastases (CLM) R0 resection significantly improves overall survival (OS).

Methods:

In this report, we present the results of a phase II trial of FOLFOX6+bevacizumab in patients with non-optimally resectable CLM. Patients received six cycles of FOLFOX6+ five of bevacizumab. Patients not achieving resectability received six additional cycles of each. A PET-CT was performed at baseline and again within 1 month after initiating treatment.

Results:

From September 2005 to July 2009, 21 patients were enrolled (Male/Female: 15/6; median age: 65 years). An objective response (OR) was documented in 12 cases (57.1% complete responses (CRs): 3, partial response (PR): 9); one patient died from toxicity before surgery. Thirteen patients underwent radical surgery (61.9%). Three (23%) had a pathological CR (pCR). Six patients (46.1%) experienced minor postsurgical complications. After a median 38.8-month follow-up, the median OS was 22.5 months. Patients achieving at least 1 unit reduction in Standard uptake value (SUV)max on PET-CT had longer progression-free survival (PFS) (median PFS: 22 vs 14 months, P=0.001).

Conclusions:

FOLFOX6+bevacizumab does not increase postsurgical complications, yields high rates of resectability and pCR. Early changes in PET-CT seem to be predictive of longer PFS.     

Efficacy of follow-up after surgical treatment of colorectal liver metastases

Purpose

There is an increasing tendency for an aggressive approach to colorectal liver metastases (CLM), even as second stage procedures after initial hepatic resection. This study assesses the efficacy of intensive follow-up after resection of CLM.

Patients and methods

Hundred and three patients, operated on for CLM, were followed for disease recurrence. Outcome measures were time and imaging modality that revealed recurrence, performed treatment for recurrence, and overall survival.

Results

After hepatic resection, 1- and 3-year overall survival (OS) rates were 91% and 50%, the disease-free survival rates 63% and 45%. Seventy-four patients developed recurrent disease during follow-up. Resection of recurrence was performed in 25 patients. OS of this group was 51 months. Patients with recurrence treated by chemotherapy had an OS of 34 months. In case of recurrence, 70% was observed within 12 months, 92% within 24 months. CT appeared to be far a very useful surveillance modality, directing surgical treatment in 19 asymptomatic patients.

Discussion

Follow-up of patients after surgical treatment of CLM proves worthwhile, resulting in meaningful re-operations in a quarter of all patients that underwent hepatic resection for CLM.     

Patient selection and outcome of hepatectomy for noncolorectal non-neuroendocrine liver metastases

Improved patient selection, introduction of more effective systemic treatments including targeted biologic and combined therapies, and the low morbidity and mortality rates of hepatobiliary surgery in centers of excellence are likely to provide continued improvements in outcomes for patients with noncolorectal non-neuroendocrine liver metastases. Further advances in treatment may emerge from better understanding of the underlying tumor biology for each cancer type and application of individualized care to each patient.     

Postoperative liver regeneration does not elicit recurrence of colorectal cancer liver metastases after major hepatectomy

Background and objectivesRecurrence is a frequent concern in curatively resected CRC liver metastases. Translational research suggests that regeneration upon hepatectomy may also alleviate metastatic recurrence; however, the significance in patients is unclear. We therefore sought to study the effect of liver regeneration on tumor recurrence in patients.MethodsIn this retrospective cohort study, we included 58 out of 186 potentially eligible patients from our prospectively maintained database of CRC liver metastasis patients between 2001 and 2012 with a median follow-up of 42 months who underwent a formal right or left hemihepatectomy. Liver regeneration in CT volumetry was correlated with recurrence of CRC liver metastases and overall survival.ResultsLiver regeneration increased up to 14 months to 21.0% for left and 122.6% for right hemihepatectomy, respectively, with comparable final volumes. Regeneration was independent of initial tumor stage, number of metastases, and preoperative chemotherapy. Patients with lower liver regeneration showed earlier recurrence of CRC liver metastases (p = 0.006). Overall survival did not differ in patients with weak versus strong liver regeneration.ConclusionsThe extent of liver regeneration after major hepatectomy does not impede overall survival. Therefore, our data encourage aggressive therapeutical regimes for CRC liver metastases involving major hepatectomies as part of a curative approach.     

Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.

BACKGROUND: The purpose of the study was to characterize histological response to chemotherapy of hepatic colorectal metastases (HCRM), evaluate efficacy of different chemotherapies on histological response, and determine whether tumor regression grading (TRG) of HCRM predicts clinical outcome. PATIENTS AND METHODS: TRG was evaluated on 525 HCRM surgically resected from 181 patients, 112 pretreated with chemotherapy. Disease-free survival (DFS) and overall survival (OS) were correlated to TRG. RESULTS: Tumor regression was characterized by fibrosis overgrowing on tumor cells, decreased necrosis, and tumor glands (if present) at the periphery of HCRM. With irinotecan/5-fluorouracil (5-FU), major (MjHR), partial (PHR), and no (NHR) histological tumor regression were observed in 17%, 13%, and 70% of patients, respectively. With oxaliplatin/5-FU, MjHR, PHR, and NHR were observed in 37%, 45%, and 18% of patients, respectively. Five patients, treated with oxaliplatin, had complete response in all their metastases. MjHR was associated with an improved 3-year DFS compared with PHR or NHR. MjHR and PHR were associated with an improved 5-year OS compared with NHR. CONCLUSION: Histological tumor regression of HCRM to chemotherapy corresponds to fibrosis overgrowth and not to increase of necrosis. TRG should be considered when evaluating efficacy of chemotherapy for HCRM. Histological tumor regression was most common among oxaliplatin-treated patients and associated with better clinical outcome.