Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection： Comparison of our scoring system to the positive number of risk factors

INTRODUCTION It is well accepted that hepatic resection for colorectal liver metastases is beneficial; it has been reported survival rates improve to as high as almost 30% to 50% at 5 years after curative hepatic resection recently[1-10]. However, the fea…     

Prognostic factors of survival and a new scoring system for liver resection of colorectal liver metastasis

BACKGROUNDHepatic resection has become the preferred treatment of choice for colorectal liver metastasis (CLM) patients.AIMTo identify the prognostic factors and to formulate a new scoring system for management of CLM.METHODSClinicopathologic and long-term survival data were analyzed to identify the significant predictors of survival by univariate and multivariate analyses with the Cox model. A clinical score was constructed based on the analysis results.RESULTSThree factors of worse overall survival were identified in the multivariate analysis. They were number of liver metastases ≥ 5, size of the largest liver lesion ≥ 4 cm, and the presence of nodal metastasis from the primary tumor. These three factors were chosen as criteria for a clinical risk score for overall survival. The clinical score highly correlated with median overall survival and 5-year survival (P = 0.002).CONCLUSIONPriority over surgical resection should be given to the lowest score groups, and alternative oncological treatment should be considered in patients with the highest score.     

Clinicopathological analysis of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma: Are they just apples and oranges?

BACKGROUNDS/AIMS: Intrahepatic cholangiocarcinoma and colorectal cancer liver metastasis are the most primary and secondary adenocarcinoma of the liver, respectively. A large-scale long-term comparative study of these two cohort patient is lacking. METHODS: A total of 166 colorectal cancer liver metastasis patients and 206 intrahepatic cholangiocarcinoma patients who had undergone curative liver resection were retrospectively analysed. Among 206 intrahepatic cholangiocarcinoma, there were 47 intraductal growth type-intrahepatic cholangiocarcinoma and 159 non-intraductal growth type-intrahepatic cholangiocarcinoma. The demographics, clinicopathological data, immunohistochemical study and survival were analysed. RESULTS: The intrahepatic cholangiocarcinoma patients were more female-predominated, associated with hepatolithiasis, symptomatic, jaundiced, and with larger tumour size compared with those of colorectal cancer liver metastasis. Prognostic factors of intrahepatic cholangiocarcinoma were pathologic staging, histologic pattern and section margin; whereas prognostic factors of colorectal cancer liver metastasis were rectal origin, differentiation, section margin and bilobar distribution. CK7 and CK20 differentiated majority of intrahepatic cholangiocarcinoma from colorectal cancer liver metastasis, while CDX2 and MUC5AC helped to differentiate inconclusive cases. The 1-, 3-, 5- and 10-year survival rates of colorectal cancer liver metastasis were 77%, 31%, 20% and 14%, compared to 53%, 21%, 13% and 7% of intrahepatic cholangiocarcinoma (p=.0001). Furthermore, the survival of colorectal cancer liver metastasis was comparable to staged II intrahepatic cholangiocarcinoma (p=.8866) and intraductal growth type-intrahepatic cholangiocarcinoma (p=.1915). CONCLUSIONS: Demographics, precipitating factor, clinical manifestations, and prognostic factors of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma differed remarkably. High incidence of CDX2 and MUC2 expression in colorectal cancer liver metastasis and intraductal growth type-intrahepatic cholangiocarcinoma might explain their similar cytoarchitecture and survival.     

结直肠癌肝转移新辅助治疗研究进展

结直肠癌的发病率及死亡率在全世界范围内逐年上升,其主要的死亡原因是肝转移。现代医学技术快速发展推动了诊治理念不断更新。个体化治疗及多学科综合治疗协作组（MDT）诊治理念的提出,外科技术以及局部治疗的迅速发展,使患者的生存期得以明显延长。结直肠癌肝转移新辅助治疗的应用有助于降低肿瘤分期,提高手术切除率,进而转化为患者生存获益,这一点在其他实体瘤中也已得到证实。但新辅助治疗是否延长所有患者生存期以及患者能否从局部治疗中获益仍存在争议,本文就结直肠癌肝转移新辅助治疗研究进展进行综述。     

结直肠癌肝转移的可切除性判断

结直肠癌最好发的转移部位是肝脏,手术是治愈结直肠癌肝转移并获得长期生存的唯一可能方式。就目前多学科治疗背景下,高效能的化疗方案联合靶向药物以及多种手术方式,如传统二步肝切除联合门静脉栓塞术/门静脉结扎术（portal vein embolization,PVE/portal vein ligation,PVL）及联合肝脏劈离及门静脉结扎的二期肝切除（associating liver partition and portal vein ligation for staged hepatectomy,ALPPS）的出现,包括各种消融等局部治疗手段拓展了过去对于肝脏可切除性的定义,而依据新的可切除标准对于可切除性的判断仍存在较大差异,本文将就肝脏可切除性判断展开探讨。     

结直肠癌脑转移的临床进展

结直肠癌是全球常见的恶性肿瘤之一,肿瘤转移是导致治疗失败和癌症相关死亡的主要原因.结直肠癌脑转移虽然并不常见,可一旦发生,患者预后极差.目前,结直肠癌脑转移的发病机制仍有待探索,影响预后的因素也多种多样,针对脑转移的治疗也以综合治疗为主,患者发生脑转移后的生存时间也不尽相同,目前仍需要针对患者个体情况进行个体化治疗.     

结直肠癌肝转移的治疗进展

结直肠癌的发病率和死亡率逐年上升,肝转移是主要死因。本文阐述了目前临床上使用较多的治疗方式及进展。分为系统性治疗,包括了新辅助化疗、转化治疗和分子靶向治疗;及局部治疗,包括手术切除、放射治疗、射频消融及介入治疗等。各种治疗手段各有优缺点,多学科综合治疗团队模式的推广,将为结直肠癌肝转移患者制定出较适合的方案,实现个体化治疗。     

International colorectal carcinoma staging and grading

Pathologic (Dukes) and clinicopathologic staging systems (Australian and TNM) are all used for the staging of colorectal cancer. Many modifications of the systems, with different standards of evidence, are currently used for a variety of purposes. It is not yet possible to readily exchange data from one staging system to another because of the lack of uniform anatomic and pathologic subdivisions. It would also be an advantage if staging systems more confidently predicted potential for cure. It is proposed that the TNM based system be modified to satisfy these requirements. Modifications identify common ground between the various systems, use prognostic variables shown to be significant by multivariate analyses, and introduce an abbreviated form of tumor grading. Grading improves prediction of cure and allows standardization of the composition of stages and substages because distant metastatic potential is shown to be related to the presence of high grade. The modifications are considered necessary and appropriate for epidemiologic and clinical studies. Copies of the cancer specific survival analyses performed for the M.S. Thesis may also be obtained from the same address.     

Hepatectomy for liver metastasis of colorectal cancer

Objective  The objective of this study was to investigate whether hepatic resection (HR) can increase the survival of liver metastasis of colorectal cancer (CRC). Materials and methods  CRC patients (n = 669) with liver metastasis treated at the Zhongshan Hospital, Fudan University from 1/2000 to 7/2007 were included in the study to investigate the relationship between HR and cancer survival. Results  CRC patients (n = 669) with liver metastases who had primary tumor resection were grouped in synchronous liver metastasis (SLM; 56.7%, n = 379) and metachronous liver metastasis (MLM) groups (43.3%, n = 290). Hepatic resection rates were lower (32.5%, n = 123) in the SLM than the MLM group (44.8%, n = 130, P < 0.05). The 30-day mortality rate in the MLM (2.3%) was significantly lower than SLM (2.4%) groups. The 5-year survival rates (36.6%) was same compared to SLM group (33.1%, P > 0.05). One-, 2-, and 3-year survival of stages I and II operation cases were 92.5% vs 86.5%, 0.7% vs 58.0%, and 42.1% vs 44.9% (P > 0.05) in the SLM group, respectively. Recurrence after first hepatic resection associated with a 2.23-fold increased risk of death (P < 0.01). Incision margins larger than 1 cm and HR for recurrence associated with 34% and 27% (P < 0.05) decreased death risk. Conclusions  Hepatic resection could help the survival of liver metastasis of colorectal cancer, and stage I surgery is safe for this disease. Xu Jianmin, Wei Ye, and Zhong Yunshi contributed equally to this paper.     

Histopathologic characteristics of colorectal cancer with liver metastasis

PURPOSE: Although prognostic factors of colorectal cancer have been studied, factors associated with liver metastasis have not been fully investigated. The aim of this study was to clarify the histopathologic characteristics of colorectal cancer with liver metastasis. METHODS: We performed a retrospective histopathologic study on 335 patients who underwent resection of colorectal cancer during 15 years. Histopathologic parameters of tumors with liver metastasis were compared with those without liver metastasis. RESULTS: Forty-one patients (12 percent) had simultaneous liver metastasis. Tumors having liver metastasis, when compared with those not having liver metastasis, were characterized by high frequency of tumor size more than 6 cm (51vs. 28 percent;P<0.01), presence of serosal invasion (98vs. 66 percent;P<0.01), lymphatic invasion (34vs. 15 percent;P<0.01), venous invasion (24vs. 3 percent;P<0.01), and lymph node metastasis (85vs. 39 percent;P<0.01). Multivariate analysis showed that factors independently associated with liver metastasis were serosal invasion, venous invasion, and lymph node metastasis. Accuracy in the diagnosis of liver metastasis was highest for venous invasion (88 percent) and lowest for serosal invasion (41 percent). Among 98 patients with both serosal invasion and lymph node metastasis, tumors with and without liver metastasis were different in frequency of venous invasion (26vs. 6 percent;P<0.01) and extracolic lymph node metastasis (68vs. 47 percent;P<0.05). CONCLUSION: In colorectal cancer important factors associated with liver metastasis were serosal invasion, venous invasion, and lymph node metastasis. Significant determinants for liver metastasis from colorectal cancer were venous invasion and extracolic lymph node metastasis.Presented at the meeting of The Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan, July 4, 1997.     

Radiomics-clinical nomogram for response to chemotherapy in synchronous liver metastasis of colorectal cancer: Good,but not good enough

There remains a persistent unmet need to detect the disease nonresponse (nonDR) subgroup before adjuvant therapy in synchronous liver metastasis patients with colorectal cancer. Ma’s radiomics-clinical nomogram shows potential for the early detection of nonDR subgroups, but it is not good enough owing to at least three limitaions, which we address in this letter to the editor. First, the study did not explore RAS/BRAF mutations, HER2 amplifications, etc. to complement the current nomogram. Second, the nomogram was not validated in left- and right-sided tumors separately. Third, the most critical factor for determining the success of adjuvant therapy should be resectability rather than tumor size shrinkage, which was used in the study.     

脂肪性肝病与结直肠癌肝转移的关系

目的 研究脂肪性肝病对结直肠癌肝转移的影响.方法 回顾性研究1993年1月至2002年12月共890例临床资料完整的结直肠癌患者,其中127例伴脂肪肝.763例无脂肪肝.分别统计两组患者的一般情况、病理资料、肝转移及术后近期死亡情况等临床资料,同时随访患者术后生存期、术后异时性肝转移并进行统计分析.结果 脂肪肝组肝转移7例,明显少于非脂肪肝组(102例,P=0.012).脂肪肝组肿瘤平均直径[(4.15±1.80)cm]小于非脂肪肝组[(4.77±2.25)cm,P=0.0016].脂肪肝组主要为Dukes A期(41/121,33.9%)和B期(40/121,33.1%)患者,而非脂肪肝组以Dukes B期(247/732,33.7%)和C期(232/732,31.75%)患者为主,差异有统计学意义(P＜O.05).两组获得随访资料的患者术后7年内远期生存率比较差异无统计学意义(P=0.3024).结论 脂肪性肝病患者结直肠癌肝转移率低,脂肪性肝病可能通过某种机制抑制肝脏转移性肿瘤的生长.     

The liver-first approach for synchronous colorectal liver metastasis: a 5-year single-centre experience

BackgroundFor patients who present with synchronous colorectal carcinoma and colorectal liver metastasis (CRLM), a reversed treatment sequence in which the CRLM are resected before the primary carcinoma has been proposed (liver-first approach). The aim of the present study was to assess the feasibility and outcome of this approach for synchronous CRLM.MethodsBetween 2005 and 2010, 22 patients were planned to undergo the liver-first approach. Feasibility and outcomes were prospectively evaluated.ResultsOf the 22 patients planned to undergo the liver-first strategy, the approach was completed in 18 patients (81.8%). The main reason for treatment failure was disease progression. Patients who completed treatment and patients who deviated from the protocol had a similar location of the primary tumour, as well as comparable size, number and distribution of CRLM (all P > 0.05). Post-operative morbidity and mortality were 27.3% and 0% following liver resection and 44.4% and 5.6% after colorectal surgery, respectively. On an intention-to-treat-basis, overall 3-year survival was 41.1%. However, 37.5% of patients who completed the treatment had developed recurrent disease at the time of the last follow-up.ConclusionsThe liver-first approach is feasible in approximately four-fifths of patients and can be performed with peri-operative mortality and morbidity similar to the traditional treatment paradigm. Patients treated with this novel strategy derive a considerable overall-survival-benefit, although disease-recurrence-rates remain relatively high, necessitating a multidisciplinary approach.     

Successful treatment of conversion chemotherapy for initially unresectable synchronous colorectal liver metastasis

A 72-year-old woman with a sigmoid colon cancer and a synchronous colorectal liver metastasis(CRLM),which involved the right hepatic vein(RHV)and the inferior vena cava(IVC),was referred to our hospital.The metastatic lesion was diagnosed as initially unresectable because of its invasion into the confluence of the RHV and IVC.After she had undergone laparoscopic sigmoidectomy for the original tumor,she consequently had 3 courses of modified 5-fluorouracil,leucovorin,and oxaliplatin(m FOLFOX6)plus cetuximab.Computed tomography revealed a partial response,and the confluence of the RHV and IVC got free from cancer invasion.After 3 additional courses of m FOLFOX6 plus cetuximab,preoperative percutaneous transhepatic portal vein embolization(PTPE)was performed to secure the future remnant liver volume.Finally,a right hemihepatectomy was performed.The postoperative course was uneventful.The patient was discharged from the hospital on postoperative day 13.She had neither local recurrence nor distant metastasis 18 mo after the last surgical intervention.This multidisciplinary strategy,consisting of conversion chemotherapy using FOLFOX plus cetuximab and PTPE,could contribute in facilitating curative hepatic resection for initially unresectable CRLM.     

Perioperative chemotherapy with bevacizumab and liver resection for colorectal cancer liver metastasis

Background:

Surgery remains the only curative option for patients with colorectal cancer liver metastases (CRLM). Perioperative chemotherapeutic strategies have become increasingly popular in the treatment of CRLM. Although the role of bevacizumab (Bev) in this setting remains unclear, its widespread use has raised concerns about the use of Bev as part of perioperative chemotherapy.

Methods:

We retrospectively reviewed all patients who received Bev and underwent liver resection between July 2004 and July 2008 at the McGill University Health Center. Chemotherapy-related toxicity, response to chemotherapy, surgical morbidity and mortality, liver function and survival data were assessed.

Results:

A total of 35 patients were identified. Of these, 26 (74.3%) patients received oxaliplatin-based cytotoxic chemotherapy, six (17.1%) received irinotecan-based therapy and the remainder received both agents. A total of 17 patients (48.6%) underwent portal vein embolization prior to resection and 12 (34.3%) underwent staged resection for extensive bilobar disease. A median of six cycles of preoperative Bev were administered. Nine patients (25.7%) experienced grade 3 or higher chemotherapy-related toxicities. Four events were deemed to be related to Bev. The overall response rate was 65.7% (complete and partial response). One patient progressed on therapy, but this did not prevent R0 resection. The incidence of postoperative morbidity was 42.3%. A total of 21.7% of complications were Clavien grade 3 or higher. There were no perioperative mortalities. There were no cases of severe sinusoidal injury or steatohepatitis. The Kaplan–Meier estimate of 4-year survival was 52.5%.

Conclusions:

These data confirm the safety of chemotherapy regimens which include Bev in the perioperative setting and demonstrate that such perioperative chemotherapy in patients with CRLM does not adversely affect patient outcome. There was no increase in perioperative morbidity compared with published rates. The addition of Bev to standard chemotherapy may improve response rates, which may, in turn, impact favourably on patient survival.     

结直肠癌肝转移同期肝切除的原则剖析

结直肠癌(CRC)是常见的消化系统恶性肿瘤,其发病率及病死率逐年升高,肝脏是其最常见转移部位。手术治疗是目前治疗结直肠癌肝转移最有效的方法。对于结直肠癌肝转移同期肝切除的手术时机的选择一直是外科医生争论的话题。诸如围手术期化疗或者一些其他新的方法,都可以影响手术时机的选择。随着对结直肠癌肝转移研究的不断深入以及外科手术技巧的不断进步,目前对于同期肝切除的原则仍在很大程度上依赖于新辅助化疗、外科医生对于可切除性的判断以及病人的体质。笔者综述了近些年来对于结直肠癌肝转移同期肝切除的原则剖析,并加以分析。