Resection of hepatic metastases from colorectal cancer

Summary Background: The aim of this paper is to analyze our experience with liver resection for metastatic colorectal cancer and to evaluate the prognostic significance of various parameters. Methods: 40 consecutive patients treated with potentially curative liver resection between 1984 and 1996 were included. The prognostic significance of various parameters was evaluated with respect to survival. Univariate and multivariate analyses were performed for following factors: age, gender, site and stage and grading of the primary tumor, size of metastases, number of metastases, lobar distribution of metastases, diagnostic interval, type of liver resection, resection margin, perioperative blood transfusion and preoperative carcinoembryonic antigen (CEA) level. Results: 3-year- and 5-year survival was 54% and 33%, median survival was 37 months. The 30 day mortality rate was 0%, postoperative complications occurred in 8 patients (20%). As single factors the following significantly affected the prognosis: number of metastases (p=0.0001), mesenteric lymphnode involvement of the primary tumor (p=0.002), lobar distribution (p=0.002) and intraoperative units of blood (p=0.05). Multivariate analysis revealed that age, gender, mesenteric lymphnode involvement, number of metastases and synchronous versus metachronous metastatic disease were independent predictors of survival. Conclusions: Liver resection is effective in selected patients with hepatic metastases from colorectal cancer. In resectable patients it is not possible to establish a clear prognosis based on the investigated factors. Therefore, patients with adverse prognostic factors should not be denied resection.      

Hepatic arterial infusion after curative resection of colorectal cancer metastases: A meta-analysis of prospective clinical trials

The use of hepatic arterial infusion (HAI) for the delivery of chemotherapeutic agents to treat residual microscopic disease after curative hepatic resection for colorectal cancer metastases remains controversial. In recent years, a number of studies examining adjuvant HAI have shown conflicting results. A meta-analysis of prospective clinical trials was performed to determine if adjuvant HAI confers a survival benefit in this setting. Tworeviewers independently performed a literature search ofMEDLINE, PubMed, EMBASE, the Cochrane library, and the Cochrane Clinical Trials Registry. Prospective clinical trials comparing hepatic arterial chemotherapy after curative hepatic resection for colorectal cancer metastases against a control arm were included. Non-English-language publications were excluded. The outcome measure was survival difference at 1 and 2 years after surgery. Seven studies met the inclusion criteria, and all except one were randomized trials. The survival difference in months (positive values favoring the treatment arm) was 1.8 at 1 year (95% confidence interval, -4.9, 8.5) and 9.6 at 2 years (95% confidence interval, -2.2, 21.4). Neither was statistically significant (at 2 years, P = 0.11). Based on these findings, routine adjuvant HAI after curative resection for colorectal cancer of the liver cannot be recommended. However, given the trend toward a survival benefit at 2 years, further study is recommended.     

The volume-time index (VTI) is prognostic in patients with colorectal cancer peritoneal metastases undergoing cytoreductive surgery and intraperitoneal chemotherapy

BackgroundPeritoneal cancer index (PCI) is an important prognostic factor in colorectal cancer peritoneal metastases (CRPM), however it fails to consider the time period over which disease burden develops. The volume-time index (VTI) is the ratio between PCI and time from primary tumour resection.MethodsA retrospective cohort study of 182 patients managed from 1996 to 2017 was performed.ResultsAs stratified by high vs low VTI groups, median overall survival (OS) was 23 months (95% 17–46) vs 44 months (95% 35–72) with a difference in 5-year OS of 20.3% (95%CI 10.2–40.4) vs 40.1% (95%CI 29.7–54.1), p = 0.002. No difference in 5-year recurrence free survival (RFS) exists. On multivariable analysis, an elevated VTI was independently associated with poorer OS (adjusted HR 3.20, 95%CI 1.64–6.23, p < 0.001) and RFS (adjusted HR 1.90, 95%CI 1.10–3.29, p = 0.02).ConclusionVTI is an independent prognostic factor for OS and RFs in patients with CRPM undergoing CRS/IPC, behaving as a surrogate of tumour aggressiveness.     

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.     

开普拓、5-氟尿嘧啶、亚叶酸钙时辰化疗治疗大肠癌肝转移的临床观察

目的观察开普拓、5-氟尿嘧啶、亚叶酸钙时辰化疗治疗大肠癌肝转移临床疗效及毒副作用。方法大肠癌手术后肝转移患者28例，随机分为A、B两组进行化疗，方案为：开普拓、5-氟尿嘧啶、亚叶酸钙，A组按时辰给药法治疗，B组按常规给药法治疗，按WHO标准观察两组患者的近期疗效及不良反应。结果衄有效率（CR＋PR）为78.5％，B组为35．7％，A组与B组相比较差异有显著性意义（P〈0．01），A组对化疗药物的毒副反应均较B组轻，A、B两组Ⅲ／Ⅳ度中性粒细胞减少、腹泻、脱发的发生率相比较差异均有显著性意义（P〈0．05）。结论开普拓、5-氟尿嘧啶、亚叶酸钙时辰化疗作为一种新的给药方式进行大肠癌肝转移化疗，具有较好的临床疗效及较低的毒副反应。     

完全肿瘤细胞减灭术是改善结直肠癌腹膜转移患者预后的关键——评述PROPHYLOCHIP和PRODIGE 7研究

腹膜转移是结直肠癌治疗领域的热点和难点,NCCN指南和PSOGI推荐肿瘤细胞减灭术（CRS）加腹腔热灌注化疗（HIPEC）治疗轻中度结直肠癌腹膜转移。在CRS+HIPEC治疗结直肠癌腹膜转移领域,腹膜转移高风险患者行二次探查+HIPEC是否有生存获益,以及HIPEC在该整合治疗体系中的价值,是两个争议已久的重要问题。针...     

Audit of definitive colorectal surgery in patients with early and advanced colorectal cancer

Background : The role of surgery in patients with advanced colorectal cancer may be questioned in the era of specialized intensive palliative care. Should patients with advanced disease be advised against surgery because of the risks of the surgery itself? In this study, the perioperative outcomes in patients undergoing definitive surgery for early (Dukes’ stages A, B and C) and advanced colorectal cancer (stage D) were examined. Methods : All patients undergoing definitive surgery for colorectal cancer during a 15‐year period were identified. Details of tumour site and stage, surgery performed, perioperative complications and postoperative mortality were compared. Results : A total of 374 patients underwent definitive surgery. There were 193 men, a male : female ratio of 1:0.9. Seventy‐one patients had advanced disease. There were no differences between the early and advanced groups in perioperative requirements for either blood or total parenteral nutrition. In the advanced group, more operations were performed as emergencies than in the early group (32.4 vs 17.5%; P < 0.01) and more patients presented with bowel obstruction in the advanced group (23.9 vs 10.2%; P < 0.01). There were no site differences between the early and advanced groups and no differences between the operations performed except that endo‐anal destruction was not performed in advanced patients. There were no differences in perioperative morbidity or mortality in the groups studied. Conclusion : Resection rates, operation type and postoperative morbidity and mortality were similar in patients with both early and advanced colorectal cancers. In terms of perioperative outcome, the presence of advanced cancer, per se, should not, therefore, be a justification to decline surgery.     

Feasibility of adjuvant hepatic arterial infusion of chemotherapy after radiofrequency ablation with or without resection in patients with hepatic metastases from colorectal cancer

Background: The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases.Methods: Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil. Surgical complications, treatment-related toxicities, and patient outcomes were recorded.Results: Fifty patients were treated with RFA and HAI with or without resection. A median of two lesions per patient, with a median greatest diameter of 2.0 cm, were treated with RFA. Postoperative complications, including 1 death, occurred in 11 of 50 patients. Toxicity from HAI was relatively mild. At 20 months median follow-up, 32% of patients remained disease free. Ten percent of patients had recurrences at the site of RFA, 30% developed new liver metastases, and 48% developed extrahepatic disease.Conclusions:RFA of CRC liver metastases followed by HAI is feasible and is associated with acceptable complication and toxicity rates. The high rate of disease recurrence in our patients indicates that novel combinations of regional and systemic therapies are needed to improve patient outcomes.     

Morbidity of adjuvant hepatic arterial infusion pump chemotherapy in the management of colorectal cancer metastatic to the liver

BACKGROUND: Surgical resection remains the treatment of choice for patients with colorectal cancer metastatic to the liver. Hepatic arterial infusion pump (HAIP) chemotherapy in combination with surgical resection has been demonstrated in a recent study to improve disease-free and overall survival for patients with colorectal cancer metastatic to the liver. Other reports, however, have indicated significant toxicity related to HAIP chemotherapy in the form of biliary sclerosis. Thus, the value of adjuvant HAIP chemotherapy following hepatic resection or ablation remains controversial. The aim of this study was to examine the survival and toxicity in a single institutional experience with adjuvant HAIP chemotherapy. METHODS: Review of a prospective hepatobiliary database was performed. HAIP were placed in the standard technique following resection and/or radiofrequency ablation (RFA) of all liver metastases. Patients received floxuridine (FUDR) via the HAIP at standard doses. Complications were graded according to a standard 5-point grading scale. Statistical analysis was performed by chi(2) test. RESULTS: Thirty-four of 86 patients underwent placement of HAIP at the time of hepatic resection or ablation between January 1999 and November 2002. The HAIP group demonstrated a significantly greater (P <0.05) number (median 5 vs. 2) and size (median 5 cm vs. 3 cm) of hepatic lesions compared to the group without HAIP. The HAIP group experienced a greater frequency of complications (53% vs. 33%), with 6 (18%) patients in the HAIP group demonstrating biliary sclerosis. There were no deaths within 30 days of surgery. Median survival was similar in both groups (HAIP 20 months, no HAIP 24 months). CONCLUSIONS: Patients in the HAIP group had significantly worse overall predictors of outcome in metastatic colorectal cancer, yet the median overall survival in both groups was similar. However, adjuvant HAIP chemotherapy was associated with significantly greater morbidity. Given the availability of newer active systemic agents and regimens, the value of adjuvant HAIP chemotherapy remains controversial.     

Long-term outcomes after hepatic resection combined with radiofrequency ablation for initially unresectable multiple and bilobar liver malignancies

Background

Hepatic resection (HRE) combined with radiofrequency ablation (RFA) offers a surgical option to a group of patients with multiple and bilobar liver malignancies who are traditionally unresectable for inadequate functional hepatic reserve. The aims of the present study were to assess the perioperative outcomes, recurrence, and long-term survival rates for patients treated with HRE plus RFA in the management of primary hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC).

Methods

Data from all consecutive patients with primary and secondary hepatic malignancies who were treated with HRE combined with RFA between 2007 and 2013 were prospectively collected and retrospectively reviewed.

Results

A total of 112 patients, with 368 hepatic tumors underwent HRE combined with ultrasound-guided RFA, were included in the present study. There were 40 cases of HCC with 117 tumors and 72 cases of MLC with 251 metastases. Most cases of liver metastases originated from the gastrointestinal tract (44, 61.1%). Other uncommon lesions included breast cancer (5, 6.9%), pancreatic cancer (3, 4.2%), lung cancer (4, 5.6%), cholangiocarcinoma (4, 5.6%), and so on. The ablation success rates were 93.3% for HCC and 96.7% for MLC. The 1-, 2-, 3-, 4-, and 5-y overall recurrence rates were 52.5%, 59.5%, 72.3%, 75%, and 80% for the HCC group and 44.4%, 52.7%, 56.1%, 69.4%, and 77.8% for the MLC group, respectively. The 1-, 2-, 3-, 4-, and 5-y overall survival rates for the HCC patients were 67.5%, 50%, 32.5%, 22.5%, and 12.5% and for the MLC patients were 66.5%, 55.5%, 50%, 30.5%, and 19.4%, respectively. The corresponding recurrence-free survival rates for the HCC patients were 52.5%, 35%, 22.5%, 15%, and 10% and for the MLC patients were 58.3%, 41.6%, 23.6%, 16.9%, and 12.5%, respectively.

Conclusions

HRE combined with RFA provides an effective treatment approach for patients with primary and secondary liver malignancies who are initially unsuitable for radical resection, with high local tumor control rates and promising survival data.     

Prognostic factors in survival of colorectal cancer patients after surgery

Objective  To determine the factors affecting survival, following resection of large bowel for colorectal carcinoma.
Method  From the cancer database of a single referral institution, a total of 1090 patients who had undergone colorectal resection between 1999 and 2002 were identified. Cases with recurrent colorectal cancer or previous history of neoadjuvant chemotherapy were excluded. Survival curves were plotted using the Kaplan–Meier method. Univariate analysis of factors thought to influence survival was then made using Logrank test. Criteria studied consisted of age, sex, TNM stage, T-status, nodal status, distant metastasis, histological grade, lymphatic and vascular invasion, tumour location, preoperative carcinoembryonic antigen (CEA) level and liver function tests. Multivariate analysis was conducted using Cox regression analysis.
Results  The mean survival time for all patients was 42.8 (SEM = 2.8) months. The overall 1-, 3- and 5-year survival rates were 72%, 54% and 47%, respectively. In univariate analysis, patients' age ( P  < 0.0001), TNM stage ( P  < 0.0001), T-status ( P  = 0.015), nodal status ( P  = 0.016), distant metastasis ( P  < 0.0001), grade ( P  = 0.005), lymphatic and vascular invasion ( P  < 0.0001) and presurgery CEA level > 5 ng/ml ( P  = 0.021) were found to be predictors that could affect survival. In Cox regression analysis, age ( P  < 0.0001), TNM stage ( P  = 0.001) and grade ( P  = 0.008) were determined as independent prognostic factors of survival.
Conclusion  Age, TNM stage, T-status, nodal status, distant metastasis, grade, lymphatic and vascular invasion and presurgery CEA level can predict the postsurgical survival rate in patients with colorectal cancer.     

Effects of systemic and regional chemotherapy after hepatic resection for colorectal metastases

Background: Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. Methods: One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. Results: Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P<.05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. Conclusions: Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 26–28, 1998.     

结直肠癌患者手术前后凝血功能的变化及临床意义

目的了解结直肠癌患者手术前后凝血功能指标的变化及临床意义。方法结直肠癌患者50例,于术前3天、术后第1、7、14、30天测定血小板(PLT)、血浆纤维蛋白原(FIB)、血浆纤维蛋白原降解产物(FDP)、凝血酶-抗凝血酶复合物(TAT)、血浆纤维蛋白肽(FPA)、纤溶酶-抗纤溶酶复合物(PAP)、D-二聚体(D-D)量;对照组30例,为同期良性结直肠疾病手术者。结果与对照组比较,结直肠癌患者手术前后各检测指标值偏高,差异有统计学意义(P0.05),术后30天上述指标与对照组比较,差异无统计学意义;结直肠癌患者术后15天与术前比较,各项指标均有不同程度的改善,差异有统计学意义(P0.05)。结论结直肠癌患者存在明显的凝血、抗凝及纤溶机制的异常,其变化与病情发展及预后有关。     

The routine use of intra-operative ultrasound in patients with colorectal cancer improves the detection of hepatic metastases

INTRODUCTION: Up to one fifth of patients with carcinoma of the colon have occult liver metastases at the time of presentation. Intra-operative hepatic ultrasonography might improve disease staging. We report the use of intra-operative ultrasonography (IOUS) in routine clinical practice over a five-year period. METHOD: Seventy-six patients with colorectal carcinoma (F 21, M 55) of median age 67 years (range 43-89 years) for whom full data were available had IOUS at the time of colonic resection. All patients had had a computerized tomography (CT), magnetic resonance imaging (MRI) or ultrasonography (USS). RESULTS: Of 76 patients, 10 had a Dukes A, 32 had a Dukes B and 34 a Dukes C carcinoma. In 20 patients IOUS detected lesions not seen on pre-operative scanning including 11 metastases (one suitable for resection), seven benign hepatic cysts and two were benign hepatic nodules. Forty-nine patients have remained free of disease and 25 have died with systemic disease (mean survival 10 months, range 2-24 months). In the seven patients diagnosed as having hepatic cysts at IOUS two have died of systemic disease. The remaining patients (n=12) who died with systemic disease had a negative IOUS. CONCLUSION: IOUS increases diagnostic yield but a significant proportion of patients with occult hepatic metastases are not detected. IOUS improves disease staging in some patients refining the indications for adjuvant therapy and enhancing the estimate of prognosis and improving decision-making.     

Percutaneous hepatic venous isolation and extracorporeal charcoal hemoperfusion for high-dose intraarterial chemotherapy in patients with colorectal hepatic metastases

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100–120 mg/m², using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5–15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia <2,000/mm³ in 3 (25%), and gastric ulcer in 1 (8%). These results indicate that this method is a safe and useful procedure for otherwise hazardous high-dose intraarterial chemotherapy in patients with unresectable hepatic tumors.     

Laparoscopic colorectal cancer surgery in obese patients

Aim The aim of this study was to assess the oncological and postoperative outcomes of laparoscopic colorectal cancer surgery in obese patients. Method All obese (BMI > 30) patients who underwent laparoscopic colorectal cancer surgery from January 2005 to January 2008 were compared with nonobese patients undergoing similar surgery. We recorded patient demographics, intra‐operative details and postoperative morbidity and mortality. Results Sixty‐two obese and 172 nonobese patients underwent laparoscopic colorectal cancer resection. Both groups were well matched for demographic parameters. Overall mean operating times were not significantly different. Conversion to open surgery was more likely in obese patients. In particular, for rectal cancers, the conversion rate was 44% in the obese group compared with 17% in the nonobese group (P < 0.05). Postoperative morbidity was also greater in obese patients (P < 0.05). The duration of hospital stay was similar for laparoscopically completed cases (6 days obese vs 7 days nonobese), but in the obese‐converted group it was 14 days (P < 0.05). The resected specimen with respect to length, resection margin and lymph node retrieval was equivalent between obese and nonobese patients. Disease‐free survival and overall survival at a median follow up of 2 years were also similar. Conclusions Laparoscopic colorectal cancer surgery in obese patients is technically feasible and oncologically safe. Despite greater postoperative morbidity, obese patients benefit from shorter length of stay. However, a higher conversion rate, particularly for rectal cancers, should be anticipated in obese male patients.     

Surgery for colorectal cancer in elderly patients —A comparison with younger adult patients—

Between 1972 and 1986, 668 patients without familial polyposis coli underwent surgery for colorectal cancer at the National Kyushu Cancer Center. Among these, there were 85 patients aged 75 years and older, and 39 patients aged 39 years and younger. The older patients tended to have a higher frequency of less advanced disease (stage I–III) and the progression of cancer in the older patients appeared to be relatively mild. The operative mortality rate of the older patients was as low as 1.2 per cent, which was almost identical to that of the younger adults (0 per cent), being 16.7 per cent for emergency operations, whereas it was 0 per cent for elective operations. The five-year survival curve of the older patients with curative resections was significantly better than that of those with noncurative resections. There was no significant difference in the cancer-related five-year survival curves between the older and younger patients with curative resections. Surgery for colorectal cancer in elderly patients should therefore not be restricted on the basis of chronological age alone.