The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a population‐based study of current practice and survival

Aim

There is uncertainty regarding the optimal sequence of surgery for patients with colorectal cancer (CRC) and synchronous liver metastases. This study was designed to describe temporal trends and inter‐hospital variation in surgical strategy, and to compare long‐term survival in a propensity score‐matched analysis.

Method

The National Bowel Cancer Audit dataset was used to identify patients diagnosed with primary CRC between 1 January 2010 and 31 December 2015 who underwent CRC resection in the English National Health Service. Hospital Episode Statistics data were used to identify those with synchronous liver‐limited metastases who underwent liver resection. Survival outcomes of propensity score‐matched groups were compared.

Results

Of 1830 patients, 270 (14.8%) underwent a liver‐first approach, 259 (14.2%) a simultaneous approach and 1301 (71.1%) a bowel‐first approach. The proportion of patients undergoing either a liver‐first or simultaneous approach increased over the study period from 26.8% in 2010 to 35.6% in 2015 (P < 0.001). There was wide variation in surgical approach according to hospital trust of diagnosis. There was no evidence of a difference in 4‐year survival between the propensity score‐matched cohorts according to surgical strategy: bowel first vs simultaneous [hazard ratio (HR) 0.92 (95% CI: 0.80–1.06)] or bowel first vs liver first [HR 0.99 (95% CI: 0.82–1.19)].

Conclusion

There is evidence of wide variation in surgical strategy in dealing with CRC and synchronous liver metastases. In selected patients, the simultaneous and liver‐first strategies have comparable long‐term survival to the bowel‐first approach.     

Impact of liver-directed therapy in colorectal cancer liver metastases

Background

There is a paucity of data on the current management and outcomes of liver-directed therapy (LDT) in older patients presenting with stage IV colorectal cancer (CRC). The aim of the study was to evaluate treatment patterns and outcomes in use of LDT in the setting of improved chemotherapy.

Methods

We used Cancer Registry and linked Medicare claims to identify patients aged ≥66 y undergoing surgical resection of the primary tumor and chemotherapy after presenting with stage IV CRC (2001–2007). LDT was defined as liver resection and/or ablation-embolization.

Results

We identified 5500 patients. LDT was used in 34.9% of patients; liver resection was performed in 1686 patients (30.7%), and ablation-embolization in 554 patients (10.1%), with 322 patients having both resection and ablation-embolization. Use of LDT was negatively associated with increasing year of diagnosis (odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.93–0.99), age >85 y (OR = 0.61, 95% CI 0.45–0.82), and poor tumor differentiation (OR = 0.73, 95% CI 0.64–0.83). LDT was associated with improved survival (median 28.4 versus 21.1 mo, P < 0.0001); however, survival improved for all patients over time. We found a significant interaction between LDT and period of diagnosis and noted a greater survival improvement with LDT for those diagnosed in the late (2005–2007) period.

Conclusions

Older patients with stage IV CRC are experiencing improved survival over time, independent of age, comorbidity, and use of LDT. However, many older patients deemed to be appropriate candidates for resection of the primary tumor and receipt of systemic chemotherapy did not receive LDT. Our data suggest that improved patient selection may be positively impacting outcomes. Early referral and optimal selection of patients for LDT has the potential to further improve survival in older patients presenting with advanced colorectal cancer.     

Synchronous resection of colorectal cancer and liver metastases: comparative views of colorectal and liver surgeons

Aim The optimal management of patients presenting with colorectal cancer and synchronous liver metastases is controversial. This survey was intended to summarize the opinions of UK colorectal and liver surgeons on the specific issues pertaining to synchronous resection. Method A validated electronic survey was sent to the consultant members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the Association of Upper Gastrointestinal Surgeons (AUGIS). The questions were structured to allow direct comparison between the two groups of the responses obtained. Results Four hundred and twenty‐four specialist colorectal surgeons and 52 specialist hepatobiliary surgeons were identified from the register of their respective associations. Responses were obtained from 133 (31%) colorectal and 22 (42%) liver surgeons. A majority of both groups of surgeons felt that synchronous resection was a valid therapeutic option. A majority of both groups believed that synchronous resection was justified despite the options of laparoscopic surgery and enhanced recovery programmes for each discipline. Agreed possible advantages of synchronous resections were: a decrease in the overall length of hospital stay, cost and patient anxiety. The major concern about synchronous resections was an excessive overall physiological insult. Specific scenarios indicated that synchronous resection was favoured for major/complex major colorectal resection with minor liver resection or most colorectal resections not involving an anastomosis with either a minor or major liver resection. Conclusion Although significant concerns relating to synchronous resection remain amongst colorectal and liver surgeons, a majority of them felt that synchronous resections could be offered to appropriately selected patients.     

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.     

Resection of liver metastases from colorectal cancer – how can we improve results?

Resection of liver metastases due to large bowel cancer has become an important part of treatment. In recent years, there have been advances in technique and the selection of patients has been extended. Surgery is the only modality which currently offers the possibility of long‐term survival. Resection combined with chemotherapy may offer improved survival, but more data are needed. Chemotherapy may cause regression of metastases to permit resection where initially they were considered unresectable. The data available from such studies are presented.     

Selective internal radiation therapy with 90yttrium microspheres for extensive colorectal liver metastases

Increasing attention has been given to treatments for colorectal liver metastases ever since hepatic resection was established as being worthwhile. Given the high proportion of patients who die of colorectal cancer with liver-only disease, it seems appropriate to be developing and investigating methods of local liver tumor ablation. Selective internal radiation therapy (SIRT) 1s a relatively new, not widely used, modality suitable for use even in patients with extensive liver involvement. Fifty patients with advanced, nonresectable, colorectal liver metastases were treated with SIRT between February 1997 and June 1999. Estimated liver involvement was less than 25% in 30 patients, 25% to 50% in 13, and greater than 50% in seven. A single dose of between 2.0 and 3.0 GBq of⁹⁰yttrium microspheres was injected into the hepatic artery via a subcutaneous port and followed at 4-week intervals by regional chemotherapy with 5-fluorouracil. SIRT was well tolerated with no treatment-related mortality, although some treatment-related morbidity did occur including a 12% incidence of duodenal ulceration. Responses to SIRT were assessed by serial carcinoembryonic antigen (CEA) measurements and CT scans. Median CEA values 1 and 2 months after SIRT (expressed as percentage of initial CEA) were 19 and 13, respectively. Patients were assigned to one of two groups based on whether or not extrahepatic disease (EHD) developed within 6 months of SIRT Median survival from SIRT for group 1 (EHD) (n = 26) was 6.9 months (range 1.3 to 18.8 months) and estimated survival ± standard error at 6, 12, and 18 months was 57.7 ±3.8%, 23.1 ±4.8%, and 0%, respectively. For group 2 (no EHD) (n = 24), median survival was 17.5 months (range 1.0 to 30.3 months) with estimated survival at 6, 12, 18, 24, and 30 months of 79.2 ±2.9%, 66.7 ±3.6%, 55.9 ±3.3%, 25.2 ±4.4%, and 16.8 ±5.O%, respectively. This difference is statistically significant by log-rank test (P <0.010). SIRT is a highly effective and well-tolerated regional treatment for extensive colorectal liver metastases. Tumor marker data suggest that substantial destruction of liver tumors can be achieved in more than 90% of patients by a single treatment. Survival times, particularly for those who do not develop extrahepatic metastases for some time, appear to be extended. SIRT warrants further use and investigation in patients with advanced colorectal liver metastases.     

Intraoperative ultrasonographic detection of occult liver metastases in colorectal cancer

Summary The efficacy of intraoperative ultrasonographic detection of colorectal cancer liver metastases was evaluated in 85 patients undergoing operation for primary colorectal tumors or liver secondaries. The results of intraoperative ultrasonography were compared with those of preoperative ultrasonography and computed tomography, as well as the intraoperative appearances of the liver. Additional information about the number of metastases was obtained in 12 cases (14.1%); 17 (24.3%) out of 70 metastases could only be detected by intraoperative ultrasonography. In 4 cases (4.7%) these lesions were solitary. As a result, the operative procedure of choice was changed in 15.3% of the patients. We conclude that intraoperative ultrasonography has a significantly higher ability to detect colorectal cancer liver metastases than preoperative methods or intraoperative inspection and palpation. Intraoperative ultrasonography should be performed in patients without preoperative evidence of liver metastases and in all patients with planned resection of metastases.     

Borderline resectable for colorectal liver metastases: Present status and future perspective

Surgical resection for colorectal liver metastases (CRLM) may offer the best opportunity to improve prognosis. However, only about 20% of CRLM cases are indicated for resection at the time of diagnosis (initially resectable), and the remaining cases are treated as unresectable (initially unresectable). Thanks to recent remarkable developments in chemotherapy, interventional radiology, and surgical techniques, the resectability of CRLM is expanding. However, some metastases are technically resectable but oncologically questionable for upfront surgery. In pancreatic cancer, such cases are categorized as “borderline resectable”, and their definition and treatment strategies are explicit. However, in CRLM, although various poor prognosis factors have been identified in previous reports, no clear definition or treatment strategy for borderline resectable has yet been established. Since the efficacy of hepatectomy for CRLM was reported in the 1970s, multidisciplinary treatment for unresectable cases has improved resectability and prognosis, and clarifying the definition and treatment strategy of borderline resectable CRLM should yield further improvement in prognosis. This review outlines the present status and the future perspective for borderline resectable CRLM, based on previous studies.     

结直肠癌肝转移生存分析

目的分析结直肠癌肝转移病人的生存状况和相关影响因素。方法回顾性分析2000-2010年复旦大学附属中山医院收治的结直肠癌肝转移病人的临床资料、病理、治疗策略等情况,进行生存状况分析,并采用单因素和Cox比例风险回归模型等分析影响结直肠癌肝转移生存的相关因素。结果结直肠癌肝转移病人总体中位生存期22.0个月,5年存活率为16%,其中同时性肝转移为21.2个月和16%,异时性肝转移为30.1个月和23%,同时性肝转移组的存活率明显低于异时性肝转移组(P<0.01)。按治疗方式分组,手术组病人的中位生存期为49.8个月,5年存活率为37%,显著优于化疗组(22.2个月和0)、介入组(19.0个月和11%)、化疗+介入组(22.8个月和10%)、局部治疗组(28.5个月和0)。同时性肝转移、肠癌原发灶分化Ⅲ~Ⅳ级、肝转移灶≥4个、最大肝转移灶≥5cm和肝转移灶非手术处理是影响病人预后的独立危险因素。结论同时性肝转移病人生存期低于异时性肝转移。积极手术治疗可以改善病人存活率。扩大肝转移灶切除的适应证对病人存活率无显著影响。独立危险因素的评分体系可以评估病人的预后。     

Radioimmunoguided surgery for patients with liver metastases secondary to colorectal cancer

Background: Hepatic resection for metastatic colorectal cancer offers a 5-year survival rate of 30%. Selection of patients who are most likely to benefit from excision is challenging. The judgment is made by radiographic techniques preoperatively and by sight and touch and the instinct of the surgeon intraoperatively. Confirmation that all tumor tissue has been excised relies on the appearance and texture of the tissue and is verified by routine histology. The authors' objective was to evaluate (1) the ability of radioimmunoguided surgery (RIGS) to improve the intraoperative detection of metastatic disease, and (2) any change in the operative plan originating from the information gained in patients with colorectal liver metastases. Methods: Charts and tumor registry data for patients who underwent planned liver resection for colorectal cancer using the RIGS method from January 1985 to December 1993 were reviewed. This group of patients was compared to a similar group that underwent traditional liver resection for metastatic colorectal cancer during the same period. Patients who had the RIGS procedure during the earlier part of the period (1985–1990), were injected with tumor-associated glycoprotein (TAG) antibody B72.3; those in the later period (1990–1993) were injected with the second-generation anti-TAG monoclonal antibody CC49. Both monoclonal antibodies were labeled with sodium iodide I 125. Both traditional and RIGS exploration were used to determine the extent of the malignant process and any change in operative plan. Results: Seventy-four cases of planned liver resection were performed with the RIGS method (group I), and 215 cases were performed with the traditional method (group II). Age and sex distribution were similar in both groups, as were morbidity and mortality, with an overall perioperative mortality of 1%. The distribution and number of metastatic lesions to the liver were the same, although group I included more cases with smaller metastatic lesions and more patients with anatomic resections. No extrahepatic tumor was found in 140 patients (65%) in group II, whereas there were only 21 patients (28%) in group I in whom no extrahepatic disease was detected (P<.001). RIGS exploration identified additional tumor in 12 (16%) of 74 cases: in the gastrohepatic ligament lymph nodes (LN) in five patients, in the celiac axis LN in one patient, and in the periaortic LN in six patients. These discoveries changed the operative plan for all of these patients, avoiding excision in the latter six patients and extending the resection in the other six. Conclusions: RIGS surgery provides an immediate and more accurate intraoperative staging system of patients with colorectal liver metastases than does traditional exploration by identifying additional metastatic disease, mainly to the lymph nodes, thus changing the plan of resection in a significant number of patients. More studies are needed to evaluate any significant survival advantage of patients who undergo removal of all RIGS-positive tissue.     

结直肠癌肝转移转化治疗的研究进展

结直肠癌患者在全病程中发生肝转移的概率达40%~50%,肝转移是影响结直肠癌患者长期预后的重要不利因素。手术切除肝转移灶是唯一可能达到近似根治效果的治疗选择。对于判断为不可切除的肝转移灶,经过综合治疗,使肿瘤缩小,进而将初始不可切除病灶转化为可切除病灶,称为转化治疗。转化治疗可分为以化疗±靶向为主的系统治疗及局部治疗。本文重点综述近年来结直肠癌肝转移转化治疗相关研究成果:(1)梳理肝转移癌手术可切除性评估标准;(2)探讨疗效评估、手术时机及肿瘤侧性对转化治疗方案选择的影响等临床问题;(3)总结转化治疗方案新进展,包括经典双药方案、三药联合的加强方案、分子靶向药物、免疫检查点抑制剂、多种局部疗法以及门静脉栓塞/两步肝切除、联合肝脏分割和门静脉结扎的分步肝切除术在转化治疗中的应用效果。本综述通过分析结直肠癌肝转移转化治疗现有问题,以期为结直肠癌肝转移的临床治疗发展提供参考。     

Hepatic resections for bilobar liver metastases from colorectal cancer

The present study was performed to assess survival benefits in patients who underwent a hepatic resection for isolated bilobar liver metastases from colorectal cancer. Thirty-eight patients underwent a curative hepatic resection for isolated colorectal liver metastasis. Among them, 11 patients had bilobar liver metastases and 19 had a solitary metastasis. The remaining 8 patients had unilobar multiple lesions. We investigated survival in two groups those with bilobar and those with solitary metastatic tumors. Survival and disease-free survival were 36% and 18% at 5 years, respectively, in the patients with bilobar liver metastases, while these survivals were 43% and 34% in the patients with solitary liver metastasis. In the 38 patients, repeated hepatic resections were performed in 15 patients with recurrent liver disease. The 5-year survival and disease-free survival rates for these patients were 38% and 27%, respectively, after the second hepatic resections. Of the 11 patients with bilobar liver metastases, 5 underwent a repeated hepatic resection, and they all survived for over 42 months. Based on our observations, a hepatic resection was thus found to be effective even in selected patients with either bilobar nodules or recurrence in the remnant liver. Received: February 7, 2000 / Accepted: April 26, 2000     

Magnetic resonance colonography vs computed tomography colonography for the diagnosis of colorectal cancer: an indirect comparison

OBJECTIVE: The primary aim of this study was to use meta-regression techniques to compare the diagnostic accuracy of computed tomography colonography (CTC) and magnetic resonance colonography (MRC), compared with conventional colonoscopy for patients presenting with colorectal cancer (CRC). METHOD: Quantitative meta-analysis was performed using prospective studies reporting comparative data between CTC and MRC individually to conventional colonoscopy. Study quality was assessed and sensitivities, specificities, diagnostic odds ratios (DOR) were calculated. Summary receiver operating characteristic (SROC) curves and sensitivity analysis were utilized. Meta-regression was used to indirectly compare the two modalities following adjustment for patient and study characteristics. RESULTS: Overall sensitivity and specificity for CTC (0.96, 95% CI 0.92-0.99; 1.00, 95% CI 0.99-1.00 respectively) and MRC (0.91, 95% CI 0.79-0.97; 0.98, 95% CI 0.96-0.99 respectively) for the detection of CRC was similar. Meta-regression analysis showed no significant difference in the diagnostic accuracy of both modalities (beta=-0.64, P=0.37 and 95% CI of 0.12-2.39). Both tests showed high area under the SROC curve (CTC=0.99; MRC=0.98), with high DORs (CTC=1461.90, 95% CI 544.89-3922.30; MRC=576.41, 95% CI 135.00-2448.56). Factors that enhanced the overall accuracy of MRC were the use intravenous contrast, faecal tagging and exclusion of low-quality studies. No factors improved diagnostic accuracy from CTC except studies with more than 100 patients (AUC=1.00, DOR=2938.35, 95%CI 701.84-12 302.91). CONCLUSION: This meta-analysis suggested that CTC and MRC have similar diagnostic accuracy for detecting CRC. Study quality, size and intravenous/intra-luminal contrast agents affect diagnostic accuracies. For an exact comparison to be made, studies evaluating CTC, MRC and colonoscopy in the same patient cohort would be necessary.     

Repeat hepatic resection as effective treatment for recurrent colorectal liver metastases

Background: Approximately 20–40% of patients who undergo liver resection for colorectal metastases develop recurrent disease confined to the liver. The goals of this study were to determine whether the survival benefit of repeat hepatic resection justified the potential morbidity and mortality. Methods: A retrospective review was performed on all patients who underwent liver resection for colorectal cancer metastases between 1983 and 1995 (N=202). Repeat liver resections were performed on 23 patients for recurrent metastases. Results: There were no operative deaths in the 23 patients, and the postoperative morbidity rate was 22%. The 5-year actuarial survival rate after repeat resection was 32%, with a median length of survival of 39.9 months. There were three patients who survived for >5 years after repeat resection. Sixteen patients (70%) developed recurrent disease at a median interval of 11 months after the second resection; 10 of these 16 patients (62%) had new hepatic metastases. No clinical or pathological factors were significant in predicting long-term survival. Conclusions: Repeat liver resection for recurrent colorectal metastases (a) can be performed safely with acceptable mortality and morbidity rates and (b) may result in long-term survival in some patients.Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

What factors influence survival in patients with unresected synchronous liver metastases after resection of colorectal cancer?

OBJECTIVE: The aim of this study was to determine whether the survival of patients with untreated synchronous liver metastases after resection of a colorectal cancer was associated with any features of the primary tumour. METHODS: Information for 398 consecutive patients with unresected liver metastases in the period 1971-2001 was examined by multivariate survival analysis. RESULTS: Of 19 clinical and pathological variables considered, survival was independently associated only with residual tumour in a line of resection (hazard ratio (HR) 1.95), venous invasion (HR 1.87), right colonic tumour (HR 1.68), lymph node metastasis (HR 1.54), and extra-hepatic metastasis (HR 1.16); 8.3% of patients had none of these adverse features. Their 2-year overall survival rate was 39.2%, compared with only 16.5% (P < 0.001) in those with one or more adverse features. CONCLUSIONS: These findings may assist in selecting patients most likely to benefit from treatment of hepatic metastases and in counselling patients and their relatives.     

Contrast-enhanced intraoperative ultrasonography during hepatectomies for colorectal cancer liver metastases

Preliminary reports showed that contrast-enhanced intraoperative ultrasonography (CEIOUS) provides information on primary or metastatic tumors of the liver that is not obtainable with conventional intraoperative ultrasonography (IOUS). This study validates the impact of CEIOUS, focusing on resective surgery for colorectal cancer (CRC) liver metastases. Twenty-four consecutive patients underwent liver resection using IOUS and CEIOUS for CRC liver metastases. CEIOUS was accomplished with intravenous injection of 4.8 mL of sulphur-hexafluoride microbubbles. CEIOUS found lesions missed at preoperative imaging and at IOUS in four patients and confirmed all of the new findings of IOUS in four patients. In addition, CEIOUS helped to define the tumor margins of the main lesion in 29% of patients with CRC liver metastases. No adverse effects were observed in relation with CEIOUS. In conclusion, CEIOUS improves IOUS accuracy with a significant impact on surgical strategy and radicality in patients who undergo surgery for CRC liver metastases. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

结直肠癌肝转移同期腹腔镜与开腹手术的疗效比较：倾向性评分匹配分析

目的 比较倾向性评分匹配后的结直肠癌肝转移患者同期腹腔镜手术与开腹手术的安全性及近期疗效。方法 回顾性分析2011年1月至2020年8月温州医科大学附属第一医院收治的79例行一期联合切除手术的结直肠癌肝转移（CRLM）患者的临床资料。采用倾向性评分匹配方法将开腹组患者与腔镜组进行匹配,每组纳入24例,比较两组围手术期的临床指标。结果 两组患者并发症发生率、围手术期病死率、二次手术率、术中输血率、开始流质饮食时间、腹腔引流管留置时间、术后住院时间和住院费用差异均无统计学意义（P＞0.05）。相比开腹组,腔镜组手术时间更长[（274±57）min vs（190±53）min,P＜0.001],术后肛门排气时间更短[（4（2～11）d vs 5（3～15）d,P=0.005],术后第1天白细胞计数更低 [（10.3±3.7）×109 /L vs （12.4±3.5）×109 /L,P=0.047]。结论 结直肠癌肝转移同期腹腔镜手术是安全、可行的,与开腹手术相比,具有一定的临床优势。