Regeneration After Two-Stage Hepatectomy vs Repeat Resection for Colorectal Metastasis Recurrence

Background Two-stage hepatectomy aims to minimize liver failure risk by performing a second resection after regeneration, assuming that remnant liver hypertrophy after the second resection is similar to that seen in repeat hepatectomy, yet the impact of a two-stage strategy on liver volume and function remains to be demonstrated. Patients and Methods Twenty patients undergoing two-stage hepatectomy for multiple colorectal cancer metastases and 21 patients with more than two sections of liver parenchyma totally removed by repeat liver resections for recurrence were enrolled. Liver volumes after final hepatectomy and postoperative liver function were compared. Results Median total liver volumes before initial hepatectomy and after final hepatectomy of multiple resections were 942 and 863 ml in patients with repeat hepatectomy, whereas volumes at corresponding time points were 957 and 777 ml in patients with two-stage hepatectomy. The ratio of total liver volume after both hepatectomies to preoperative volume in the two-stage group (81.7%) was lower than that in the repeat resection group (92.0%, P = 0.027). Greater aspartate aminotransferase and prothrombin time and lower platelet count 1 month postoperatively and lower albumin at 6 months were evident after two-stage hepatectomy compared with repeat hepatectomy. Conclusions Two-stage hepatectomy is characterized by diminished hepatic regenerative capacity and postoperative liver function.     

Systematic Review on Safety and Efficacy of Repeat Hepatectomy for Recurrent Liver Metastases from Colorectal Carcinoma

Background We critically appraised the quantity and quality of current clinical evidence to demonstrate the efficacy and safety of repeat hepatectomy for recurrent colorectal liver metastases (CRLM). Methods Electronic searches for relevant studies published in peer-reviewed medical journals on repeat hepatectomy for recurrent CRLM before January 2007 were performed on six databases. The quality of each included study was independently assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. Results Seventeen studies with more than 20 patients were included for quality appraisal and data extraction. All 17 included articles were observational cases series. The overall perioperative morbidity rate ranged from 7% to 30% and mortality rate varied from 0% to 5%. The overall median survival since the repeat hepatectomy ranged from 23 to 56 months, with 3- and 5-year survival of 24% to 68% and 21% to 49%, respectively. The median disease-free survival ranged from 9 to 52 months, with 3- and 5-year disease-free survival of 16% to 68% and 16% to 48%, respectively. Conclusions The current literature suggests that repeat hepatectomy is associated with a prolonged survival for recurrent CRLM and is justified in selected patients because there is a lack of evidence for effective alternative treatments.     

Repeat Hepatectomy for Recurrent Colorectal Metastases

Purpose To determine the risks and benefits of repeat hepatectomy for hepatic metastases from colorectal cancer.Methods During a recent 10-year-period, 106 patients underwent hepatectomy for hepatic metastases from colorectal cancer, in our hospital. Recurrence developed in the liver in 57 of these patients, 27 of whom underwent repeat hepatectomy. We reviewed the outcomes of these 27 patients.Results There were three complications after the first hepatectomy and six complications after the second hepatectomy, but there was no perioperative mortality after the first or second hepatectomy. The median survival from the date of second hepatectomy was 41 months with an actuarial 5-year survival rate of 48.7%. Patients who underwent repeat hepatectomy had significantly higher survival rates from the time of first hepatectomy than those who did not. Univariate analysis showed that among the prognostic factors of repeat hepatectomy, only a disease-free interval (DFI) between the first and second hepatectomy of more than 1 year was significantly predictive of a better outcome (P = 0.047).Conclusion Repeat hepatectomy for recurrent colorectal metastases can be performed safely with acceptable mortality and morbidity rates, and can help to extend survival, if the DFI between the first and second hepatectomy is longer than 1 year.     

Perioperative Morbidity Affects Long-Term Survival in Patients Following Liver Resection for Colorectal Metastases

Background Hepatic resection is the treatment of choice in patients with colorectal liver metastases. Perioperative morbidity is associated with decreased long-term survival in several cancers. The aim of this study was to assess the impact of perioperative morbidity and other prognostic factors on the outcome of patients undergoing liver resection for colorectal metastases. Methods One hundred ninety seven patients undergoing liver resection with curative intent were investigated. The influence of prognostic factors, such as complications, tumor stage, margins, age, sex, number of lesions, transfusion, portal inflow obstruction, and era and type of resection, was assessed using univariate and multivariate analysis. Complications were graded using an objective surgical complication classification. Results The 5-year survival rate was 38%, with a median follow up of 4.5 years. The disease-free survival rate at 5 years was 23%. The perioperative morbidity and mortality rates were 30 and 2.5%, respectively. The median survival of patients with perioperative complications was 3.2 years, compared to 4.4 years in those patients without complications (p < 0.01). For patients with positive resection margins, the median survival was 2.1 years, compared 4.4 years in patients with a margin (p = 0.019). Conclusion Perioperative morbidity and a positive resection margin had a negative impact on long-term survival in patients following liver resection for colorectal metastases. This paper has been presented at the annual meeting of the Royal Australian College of Surgeons 2006 and was accepted for oral presentation at the IHPBA 2006 meeting in Edinburgh.     

Outcome After Hepatectomy for Multiple (Four or More) Colorectal Metastases in the Era of Effective Chemotherapy

Background Hepatic resection is generally accepted as the only potential for long-term survival in patients with colorectal metastases confined to the liver. Despite an unknown benefit, hepatic resection is playing an increasing role in patients with extensive disease. Methods A retrospective review of a prospectively maintained hepatobiliary surgical database was carried out. Outcome after hepatectomy for four or more colorectal hepatic metastases was reviewed. Results Between 1998 and 2002, out of a total of 584 patients, 98 (17%) with four or more colorectal hepatic metastases were resected. Actuarial 5-year survival was 33% for the entire group, with seven actual 5-year survivors. There were no perioperative deaths, and the perioperative morbidity was 28%. Positive margins and extrahepatic disease resection were independently associated with poor outcome. The median disease-free survival was 12 months, with no actuarial disease-free survivors at 5 years. Recurrence pattern, response to neoadjuvant chemotherapy, time to recurrence, and resection of recurrent disease were also associated with outcome. Conclusions Long-term survival can be achieved after resection of multiple colorectal metastases; however, because most patients will experience recurrence of disease, effective adjuvant therapy and close follow-up is necessary.     

Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure

Background We have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown. Methods Patients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m² 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen). Results Forty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1–5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0–25). Toxicity included grade 3–4 neutropenia (43%), grade 2–3 neuropathy (43%), and grade 3–4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40–69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively. Conclusions HAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.     

Intrahepatic Lymphatic Invasion Independently Predicts Poor Survival and recurrences after Hepatectomy in Patients with Colorectal Carcinoma Liver Metastases

BACKGROUND: D2-40 monoclonal antibody immunoreactivity is specific for lymphatic endothelium and therefore provides a marker of lymphatic invasion. We hypothesized that intrahepatic lymphatic invasion reflects the nodal status of colorectal carcinoma liver metastases and may function as an adverse prognostic factor. METHODS: A retrospective analysis of 105 consecutive patients who underwent resection for colorectal carcinoma liver metastases was conducted. Intrahepatic lymphatic invasion was declared when either single tumor cells or cell clusters were clearly visible within vessels that showed immunoreactivity for D2-40 monoclonal antibody. The median follow-up time was 124 months. RESULTS: Of 105 patients, 13 were classified as having intrahepatic lymphatic invasion. All tumor foci of intrahepatic lymphatic invasion were detected within the portal tracts. Intrahepatic lymphatic invasion was significantly associated with hepatic lymph node involvement (P = 0.039). Survival after resection was significantly worse in patients with intrahepatic lymphatic invasion (median survival time of 13 months; cumulative five-year survival rate of 0%) than in patients without (median survival time of 40 months; cumulative five-year survival rate of 41%; P < 0.0001). Patients with intrahepatic lymphatic invasion also showed decreased disease-free survival rates (P < 0.0001). Intrahepatic lymphatic invasion thus independently affected both survival (relative risk, 7.666; 95% confidence interval, 3.732-15.748; P < 0.001) and disease-free survival (relative risk, 4.112; 95% confidence interval, 2.185-7.738; P < 0.001). CONCLUSIONS: Intrahepatic lymphatic invasion is associated with hepatic lymph node involvement and is an adverse prognostic factor in patients with colorectal carcinoma liver metastases.     

Profile of Plasma Angiogenic Factors Before and After Hepatectomy for Colorectal Cancer Liver Metastases

Background Circulating angiogenic factors in patients with colorectal cancer liver metastases may promote tumor growth and contribute to liver regeneration after partial hepatectomy. Methods We analyzed blood samples from 26 patients with colorectal cancer liver metastases before and after liver resection and used samples from 20 healthy controls as a reference. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and hepatocyte growth factor (HGF) were measured, and levels were correlated with recurrence. Results The median preoperative levels of all four factors were significantly higher and more variable in colorectal cancer liver metastasis patients than in controls. HGF and bFGF levels increased significantly 3 days and 1 month after hepatectomy, respectively, and returned to near preoperative levels at 3 months. Postoperative VEGF and EGF levels remained relatively stably increased over 3 months. After a median follow-up of 19 months, 10 patients (42%) experienced recurrence. Higher preoperative VEGF and HGF levels correlated with subsequent recurrence (P = .018 and .021, respectively), and a preoperative adjusted total value of all four factors accurately identified patients at low, moderate, and high risk of recurrence (P = .034). Patients who experienced disease recurrence also had relatively higher bFGF levels 3 months after operation (P = .035). Conclusions Plasma angiogenic factors are increased in patients with colorectal cancer liver metastases and remain increased at least 3 months after partial hepatectomy. Measurement of certain factors before and after hepatic resection can predict recurrence. Targeted biological agents may counteract the tumor-promoting effects of these circulating factors on subclinical disease.     

Second Hepatectomy for Recurrent Colorectal Liver Metastasis: Analysis of Preoperative Prognostic Factors

Background Second hepatectomy is a potentially curative treatment for patients with hepatic recurrence of colorectal cancer. However, there is still no consensus about the patient selection criteria for second hepatectomy under these circumstances, and the factors affecting prognosis after second hepatectomy remain uncertain.Methods Clinicopathologic data for 111 consecutive patients with colorectal liver metastasis who underwent second hepatectomy at a single institution between 1985 and 2004, and for whom complete clinicopathologic reports were available, were subjected to univariate and multivariate analyses.Results The morbidity and mortality rates were 14% and 0%, respectively, and the overall 5-year survival rate was 41%. Multivariate analysis revealed that synchronous resection for the first liver metastasis (hazard ratio, 1.8), more than three tumors at the second hepatectomy (1.9), and histopathological involvement of the hepatic vein and/or portal vein by the first liver metastasis (1.7) were independently associated with poor survival. We used these three risk factors to devise a preoperative model for predicting survival. The 5-year survival rates of patients without any risk factors, and with one, two, or three risk factors, were 62%, 38%, 19%, and 0%, respectively.Conclusions Second hepatectomy is beneficial for patients without any risk factors. Before second hepatectomy, chemotherapy should be considered for patients with any of these risk factors, especially with two or three factors, in the adjuvant or neoadjuvant setting to prolong survival. These results need to be confirmed and validated in another data set or future prospective trial according to the scoring scheme we outline.     

Multiagent Chemotherapy for Isolated Colorectal Liver Metastases: A Single-centered Retrospective Study

Background  Few studies identifying variables associated with prognosis after resection of colorectal liver metastases (CLM) account for treatment with multiagent chemotherapy (fluoropyrmidines with irinotecan, oxaliplatin, bevacizumab, and/or cetuximab). The objective of this retrospective study was to determine the effect of multiagent chemotherapy on long-term survival after resection of CLM. Methods  Demographics, clinicopathologic tumor characteristics, treatments, and long-term outcomes were reviewed. Results  From 1996 to 2006, 230 patients underwent resection of CLM. Treatment strategies before and after resection included fluoropyrimidine monotherapy (n = 34 and n = 39), multiagent chemotherapy (n = 81 and n = 73), and observation (n = 115 and n = 118). Prehepatectomy treatment strategy was not associated with overall survival. Actuarial 4-year survival was 63%, 39%, and 40% for patients treated with multiagent chemotherapy, fluoropyrimidine monotherapy, and observation after hepatectomy, p = 0.06. Posthepatectomy multiagent chemotherapy (p = 0.04, HR 0.52 [0.27–1.03]), duration of posthepatectomy chemotherapy treatment of 2 months or longer (p = 0.05, HR 0.49 [0.25–0.99]), carcino-embryonic antigen level >10 ng/mL (p = 0.03, HR 2.09, 95% CI [1.32–3.32]), and node positive primary tumor (p = 0.002, HR 1.79 [1.06–3.02]) were associated with overall survival in multivariate analysis. Conclusions  The association of posthepatectomy multiagent chemotherapy with overall survival in this retrospective study indicates the need for prospective randomized trials comparing multiagent chemotherapy and fluoropyrimidine monotherapy for CLM.     

Resection of Hepatic Colorectal Metastases Involving the Caudate Lobe: Perioperative Outcome and Survival

Purpose: To examine clinical features and outcome of patients who underwent hepatic resection for colorectal liver metastases (LM) involving the caudate lobe. Patients and Methods: Consecutive patients who underwent hepatic resection for LM from May 1990 to September 2004 were analyzed from a multicenter database. Demographics, operative data, pathologic margin status, recurrence, and survival were analyzed. Results: Of 580 patients, 40 (7%) had LM involving the caudate. Six had isolated caudate LM and 34 had LM involving the caudate plus one or more other hepatic segments. Patients with caudate LM were more likely to have synchronous primary colorectal cancer (63% vs. 36%; P = 0.01), multiple LM (70% vs. 51%; P = 0.02) and required extended hepatic resection more often than patients with non-caudate LM (60% vs. 18%; P < 0.001). Only four patients with caudate LM underwent a vascular resection; three at first operation, one after recurrence of a resected caudate tumor. All had primary repair (vena cava, n = 3; portal vein, n = 1). Perioperative complications (43% vs. 28%) and 60-day operative mortality (0% vs. 1%) were similar (caudate vs. non-caudate LM, both P > 0.05). Pathological margins were positive in 15 (38%) patients with caudate LM and in 43 (8%) with non-caudate LM (P < 0.001). At a median follow-up of 40 months, 25 (64%) patients with caudate LM recurred compared with 219 (40%) patients with non-caudate LM (P = 0.01). Patients with caudate LM were more likely to have intrahepatic disease as a component of recurrence (caudate: 51% vs. non-caudate: 25%; P = 0.001). No patient recurred on the vena cava or portal vein. Patients with caudate LM had shorter 5-year disease-free and overall survival than patients with non-caudate LM (disease-free: 24% vs. 44%; P = 0.02; overall: 41% vs. 58%; P = 0.02). Conclusions: Patients who undergo hepatic resection for caudate LM often present with multiple hepatic tumors and tumors in proximity to the major hepatic veins. Extended hepatectomy is required in the majority, although vascular resection is not frequently necessary; when performed, primary repair is usually possible. Despite resection in this population of patients with multiple and bilateral tumors, and despite close-margin and positive-margin resection in a significant proportion, recurrence on the portal vein or vena cava was not observed, and long-term survival is accomplished (41% 5-year overall survival). These data were presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, Miami, Florida, March 12, 2006.     

Hepatectomy with Perioperative Chemotherapy for Multiple Colorectal Liver Metastases is the Available Option for Prolonged Survival

Annals of Surgical Oncology - Hepatic resection combined with perioperative chemotherapy is the standard of care for patients with multiple colorectal liver metastases (CLMs). However, the optimal...     

A Critical Appraisal of the Role of Neoadjuvant Chemotherapy for Colorectal Liver Metastases: A Case-Controlled Study

Background The aim of this study was to analyze the outcome of patients that received neoadjuvant chemotherapy prior to resection for colorectal liver metastases (CRLM) and compare them with a matched cohort of patients that underwent resection followed by adjuvant chemotherapy. Methods 687 patients have undergone curative resection between January 1993 and January 2006. In this period, 84 patients received neo-adjuvant chemotherapy and 71 of this group went on to resection. A control group was chosen, matched with these patients, made up of patients who underwent resection followed by adjuvant chemotherapy. Results There was no difference in clinico-pathological features between the neoadjuvant and the control group. However patients in the control group had more-extended resections and longer hospital stays than those in the neoadjuvant group (p = 0.015). Patients in the control group had an increased incidence of early recurrences (p < 0.001). Despite this, there was no significant difference in either the cancer-specific or the disease-free survival between the two groups of patients. Conclusion Neoadjuvant chemotherapy has a role in the management of patients with disease that is considered initially unresectable as a down-sizing technique. In patients with resectable disease, the test-of-time approach that neoadjuvant therapy offers is yet to be proven.     

Survival After Resection of Multiple Hepatic Colorectal Metastases

Background: Hepatic resection is potentially curative in selected patients with colorectal metastases. It is a widely held practice that multiple colorectal hepatic metastases are not resected, although outcome after removal of four or more metastases is not well defined.Methods: Patients with four or more colorectal hepatic metastases who submitted to resection were identified from a prospective database. Number of metastases was determined by serial sectioning of the gross specimen at the time of resection. Demographic data, tumor characteristics, complications, and survival were analyzed.Results: From August 1985 to September 1998, 155 patients with four or more metastatic tumors (range 4–20) underwent potentially curative resection by extended hepatectomy (39%), lobectomy (42%), or multiple segmental resections (19%). Operative morbidity and mortality were 26% and 1%, respectively. Actuarial 5-year survival was 23% for the entire group (median 5 32 months) and there were 12 actual 5-year survivors. On multivariate analysis, only number of hepatic tumors (P = .005) and the presence of a positive margin (P = .003) were independent predictors of poor survival.Conclusions: Hepatic resection in patients with four or more colorectal metastases can achieve long-term survival although the results are less favorable as the number of tumors increases. Number of hepatic metastases alone should not be used as a sole contraindication to resection, but it is clear that the majority of patients will not be cured after resection of multiple lesions.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans.     

Long-Term Results of Hepatectomy After Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatic Colorectal Metastases

Background  The prognosis of unresectable hepatic colorectal metastases is poor even if chemotherapy is administered. The purpose of this study was to evaluate the long-term efficacy of hepatic arterial infusion (HAI) chemotherapy and hepatectomy following HAI for such condition. Methods  Seventy-two patients with unresectable hepatic colorectal metastases received continuous HAI of 5-fluorouracil. Results  The overall response rate was 38%. The median survival of all patients was 18 months. The overall 3-year survival rate was 18%. Seven patients (10%) survived more than 58 months. Of the eight patients with a complete response, seven developed liver and/or lung metastases, and of these, one patient undergoing additional hepatectomy has been disease-free and the other six receiving chemotherapy died of disease. Another complete-response case died of liver abscess. Of the 19 patients with a partial response, six could undergo hepatectomy after HAI. The overall 5-year survival rate of seven patients undergoing hepatectomy was 71%, whereas for patients without hepatectomy, the rate was 0%. Conclusions  Most patients showing response after HAI for unresectable hepatic colorectal metastases had relapses. The long-term prognosis of patients undergoing hepatectomy after HAI was favorable. Therefore, when HAI makes liver metastases resectable, they should be resected.     

Recurrence and Survival Outcomes after Hepatic Resection with or without Cryotherapy for Liver Metastases from Colorectal Carcinoma

Background Some reports support resection combined with cryotherapy for patients with multiple bilobar colorectal liver metastases (CRLM) that would otherwise be ineligible for curative treatments. This series demonstrates long-term results of 415 patients with CRLM who underwent resection with or without cryotherapy. Methods Between April 1990 and January 2006, 291 patients were treated with resection only and 124 patients with combined resection and cryotherapy. Recurrence and survival outcomes were compared. Kaplan-Meier and Cox-regression analyses were used to identify significant prognostic indicators for survival. Results Median length of follow-up was 25 months (range 1–124 months). The 30-day perioperative mortality rate was 3.1%. Overall median survival was 32 months (range 1–124 months), with 1-, 3- and 5-year survival values of 85%, 45% and 29%, respectively. The overall recurrence rates were 66% and 78% for resection and resection/cryotherapy groups, respectively. For the resection group, the median survival was 34 months, with 1-, 3- and 5- year survival values of 88%, 47% and 32%, respectively. The median survival for the resection/cryotherapy group was 29 months, with 1-, 3- and 5-year survival values of 84%, 43% and 24%, respectively (P = 0.206). Five factors were independently associated with an improved survival: absence of extrahepatic disease at diagnosis, well- or moderately-differentiated colorectal cancer, largest lesion size being 4 cm or less, a postoperative CEA of 5 ng/ml or less and absence of liver recurrence. Conclusions Long-term survival results of resection combined with cryotherapy for multiple bilobar CRLM are comparable to that of resection alone in selected patients.     

Interval Period Tumor Progression: Does Delayed Hepatectomy Detect Occult Metastases in Synchronous Colorectal Liver Metastases?

Background  Rapid remnant liver recurrence in patients with synchronous colorectal liver metastases (CRLM) is occasionally experienced after simultaneous colorectal and liver resection. We evaluated the tumor progression during interval periods to determine whether delayed hepatic resection detects occult metastases. Methods  One hundred thirty-seven patients underwent hepatectomy for synchronous CRLM. Up to 2003, 116 patients underwent simultaneous colorectal and hepatic resection. From 2004 onward, we identified 21 patients undergoing delayed hepatectomy for synchronous CRLM. The tumor progression during interval was determined by a dynamic computed tomography scan. Results  Median/mean interval between the two evaluations prior to the first and second surgery was 2/2.4 months. The median/mean number of metastases detected at each evaluation was 2/3.3 and 3/4.6, respectively. Nine of the 21 (43%) patients had new detectable metastatic lesions after reevaluation. For 11 of the 21 patients, it was necessary to reconsider planned surgical procedure which was determined prior to colorectal surgery. Hepatic disease-free survival was significantly different between patients undergoing delayed and simultaneous hepatectomy. Multivariate analysis showed that the delayed hepatectomy was a significant independent prognostic factor in hepatic disease-free survival. Conclusion  Tumor progression was recognized and occult metastases were detected after the interval reevaluation. Delayed hepatectomy may be a useful approach to reduce rapid remnant liver recurrence in synchronous CRLM.     

Outcome of Posthepatectomy-Missing Colorectal Liver Metastases after Complete Response to Chemotherapy: Impact of Adjuvant Intra-arterial Hepatic Oxaliplatin

Background Dramatic responses to chemotherapy are occurring more and more frequently in patients with multiple colorectal liver metastases (LMs), leading to resection. In a few patients, some LMs vanish on imaging studies, remain undetected during hepatectomy, and are left in place, which defines the “missing LMs.” The aim of our study was to assess the long-term outcome of such “missing LMs.” Patients Between January 1999 and June 2004, among 228 patients treated for colorectal LMs, missing LMs were observed in 16 patients. All the patients were operated within 4 weeks of imaging. Hepatic arterial infusion (HAI) with oxaliplatin was administrated in 12 patients (75%): seven before hepatectomy and five after. Results Overall, 69 missing LMs were diagnosed and left in place. Among the persistent LMs resected, a complete pathological response was significantly more often observed in the group with preoperative HAI (6 of 7), than in the group without (2 of 9, P < .02). With a mean follow-up of 51 months (24–90), missing LMs did not reappear in 10 patients (62%). Adjuvant HAI was significantly correlated with the definitive eradication of missing LMs (P < .01), as it was not a complete pathological response. The overall 3-year survival rate of these highly selected 16 patients was 94%. Conclusion Colorectal LMs under chemotherapy that vanish on high-quality imaging studies, remain undetected during hepatectomy, and are left in place, are definitively cured in 62% of cases. This excellent result seems to be due to the administration of adjuvant hepatic arterial infusion of chemotherapy and should stimulate new investigations.     

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.