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.     

Liver Resection for Primarily Unresectable Colorectal Metastases Downsized by Chemotherapy

This study was performed prospectively to assess the effect of systemic chemotherapy (FOLFIRI protocol) in patients with initially unresectable colorectal liver metastases (CRLM) and, after performing liver resection in patients with downsized metastases, to compare the postoperative and long-term results with those of patients with primarily resectable CRLM. Records from a prospective database including all consecutive admissions for CRLM between June 2000 and June 2004 were reviewed. The analysis addressed all patients who underwent hepatectomy for primarily resectable CRLM (Group A), or underwent chemotherapy for primarily unresectable CRLM and among these, particularly the patients who were finally resected after downsizing of CRLM (Group B). There were 60 primarily resected patients (Group A). Forty-two other patients underwent chemotherapy; after an average of nine courses, 18 of them (42.8%) with significantly downsized lesions were explored and 15 (35.7%, Group B) were resected, whereas three had peritoneal metastases. Group B differed from Group A for a significantly higher rate of synchronous CRLM upon diagnosis of colorectal cancer, a larger size of CRLM upon evaluation in our center, and a lower rate of major hepatectomies (20.0% vs. 51.6 %) at surgery. No patient in Group B had positive margins of resection. Operative mortality was nil and morbidity was 20.0% in both groups. In Group B vs. Group A median survival after hepatectomy was 46 vs. 47 months (n.s), 3-year survival rate was 73% vs. 71% (n.s.), disease-free survival rate was 31% vs. 58% (p = 0.04) and, at a median follow-up of 34 months, tumor recurrence rate was 53.3% vs. 28.3% (n.s.). Four out of the eight Group B patients with recurrence underwent a re-resection, and were alive at 9 to 67 months after the first resection. These results show that in about one-third of the patients with primarily unresectable CRLM, downsizing of the lesions by chemotherapy (FOLFIRI protocol) permitted a subsequent curative resection. In these patients, operative risk and survival did not differ from the figures observed in primarily resectable patients and, in spite of a lower disease-free survival with more frequent recurrence, re-resection still represented a valid option to continue treatment. Presented at the 2005 Surgical Spring Week AHPBA Meeting (April 14–17, 2005, Fort Lauderdale, Florida).     

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.     

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.     

Simultaneous Resections of Colorectal Cancer and Synchronous Liver Metastases: A Multi-institutional Analysis

Background The safety of simultaneous resections of colorectal cancer and synchronous liver metastases (SCRLM) is not established. This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections. Methods Clinicopathologic data, treatments, and postoperative outcomes from patients who underwent simultaneous or staged colorectal and hepatic resections at three hepatobiliary centers from 1985–2006 were reviewed. Results 610 patients underwent simultaneous (n = 135) or staged (n = 475) resections of colorectal cancer and SCRLM. Seventy staged patients underwent colorectal and hepatic resections at the same institution. Simultaneous patients had fewer (median 1 versus 2) and smaller (median 2.5 versus 3.5 cm) metastases and less often underwent major (≥ three segments) hepatectomy (26.7% versus 61.3%, p < 0.05). Combined hospital stay was lower after simultaneous resections (median 8.5 versus 14 days, p < 0.0001). Mortality (1.0% versus 0.5%) and severe morbidity (14.1% versus 12.5%) were similar after simultaneous colorectal resection and minor hepatectomy compared with isolated minor hepatectomy (both p > 0.05). For major hepatectomy, simultaneous colorectal resection increased mortality (8.3% versus 1.4%, p < 0.05) and severe morbidity (36.1% versus 15.1%, p < 0.05). Combined severe morbidity after staged resections was lower compared to simultaneous resections (36.1% versus 17.6%, p = 0.05) for major hepatectomy but similar for minor hepatectomy (14.1% versus 10.5%, p > 0.05). Major hepatectomy independently predicted severe morbidity after simultaneous resections [hazard ratio (HR) = 3.4, p = 0.008]. Conclusions Simultaneous colorectal and minor hepatic resections are safe and should be performed for most patients with SCRLM. Due to increased risk of severe morbidity, caution should be exercised before performing simultaneous colorectal and major hepatic resections.     

The Significance of Hepatic Pedicle Lymph Nodes Metastases in Surgical Management of Colorectal Liver Metastases and of Other Liver Malignancies

Background: Surgical resection of colorectal liver metastases (CLM) is the only hope for cure, with a 5-year survival rate ranging from 20% to 54%. However, the resectability rate of CLM is reported to be <20%. This limitation is mainly due to insufficient remnant liver and to extrahepatic disease. Among extrahepatic locations, lymph node metastases are often considered indications of a very poor prognosis and a contra-indication to resection.Methods and Results: Our studies showed that the prevalence of hepatic pedicle lymph node metastases ranges from 10% to 20%. When located near the hilum and along the hepatic pedicle (area 1) they should not be considered an absolute contra-indication to resection of CLM, and an extended lymphadenectomy should be performed. However, when they reach the celiac trunk (area 2), there is no survival benefit after resection of CLM. For other cases of liver malignancies, lymph node dissection seems justified only in cases of fibrolamellar hepatocellular carcinoma and in case of hilar cholangiocarcinoma. However, few data are available, and they are controversial.Conclusions: There is a need for more evaluation of lymph node involvement, at least in patients with high risk of such an extension, i.e., patients with more than three metastases, located in segment 4 or 5. There is also a need for prospective trials in order to evaluate the survival benefit of liver resection in such circumstances and the impact of extensive lymphadenectomy.     

Improved Long-Term Outcome of Surgery for Advanced Colorectal Liver Metastases: Reasons and Implications for Management on the Basis of a Severity Score

Background The outcome of liver resection for colorectal liver metastases (CRLM) appears to be improving despite the fact that surgery is offered to patients with more-severe disease. To quantify this assumption and to understand its causes we analyzed a series of patients on the basis of a standardized severity score and changes in management occurring over the years. Methods Patients’ characteristics, operative data, chemotherapies and follow-up were recorded. CRLM severity was quantified according to Fong’s clinical risk score (CRS), modified to take into account the presence of bilateral liver metastases. Three periods were analyzed, in which different indications, surgical strategies and uses of chemotherapy were applied: 1984–1992, 1993–1998, and 1999–2005. Results Between January 1984 and December 2005, 210 liver resections were performed in 180 patients (1984–1992, 43 patients; 1993–1998, 42 patients; 1999–2005, 95 patients). CRLM severity increased throughout the time periods, as did the use of neoadjuvant chemotherapies, repeat resections, and multistep procedures. While the disease-free survival did not improve over time, the 1-, 3- and 5-year overall survival rate increased from 85%, 30%, and 23% in the first period, to 88%, 60%, and 34% in the second period, and to 94%, 69%, and 46% in the third period. Conclusions Analysis according to the CRS showed that despite the fact that patients had more severe disease, the overall survival improved over the years, mainly thanks to more aggressive treatment of recurrent disease. Management of advanced CRLM should, from the start, take into account the likelihood of secondary procedures.     

Timing of Resection of Liver Metastases Synchronous to Colorectal Tumor: Proposal of Prognosis-Based Decisional Model

Background Timing of hepatectomy for synchronous metastases of colorectal cancer is still debated. The aim of this retrospective study was to analyze prognostic factors after synchronous and delayed liver resections to define selection criteria for choosing timing of hepatectomy. Methods The study was performed on 127 patients with synchronous metastases undergoing radical hepatectomy. We divided patients according to the timing of hepatectomy: 70 synchronous (group A) and 57 delayed (group B). Results Overall survival was similar between the two groups (5-year survival 30.8% vs. 32.0% A vs. B, P = .406). The multivariate analysis evidenced four independent prognostic factors in group A: male sex (P = .04), T4 (P = .0035), more than three metastases (P = .0001), and metastatic infiltration of nearby structures (P < .0001). There were no statistically significant prognostic factors in group B. Patients with more than three metastases had a significantly worse survival in group A than in group B (3-year survival, 15.0% vs. 34.3%, P = .007); similarly, borderline significant difference was encountered in patients with T4 primary tumor (3-year survival, 16.7% vs. 60%, P = .064) Conclusions Patients with liver metastases synchronous with colorectal cancer with T4 primary tumor, metastasis infiltration of neighboring structures, and especially with more than three metastases should receive neoadjuvant chemotherapy before liver resection.     

Major Liver Resections Synchronous with Colorectal Surgery

Background Surgical strategy in liver metastases synchronous to colorectal cancer remains controversial. The aim of this study was to evaluate feasibility and short-term outcomes of major hepatectomies synchronous to colorectal surgery. Methods Between January 1985 and December 2004, 79 patients underwent major hepatectomy for metastases synchronous to colorectal cancer; 31 underwent synchronous hepatectomy and colorectal surgery, and 48 underwent delayed liver resection. Results The synchronous group had a higher rate of right colectomy (38.7% vs. 18.8%, P = .0499) and larger metastases (8 vs. 5.3 cm, P = .0032). Mortality (one patient in synchronous group), morbidity, and anastomotic leak rates were similar in the two groups. Colon-related morbidity did not cause adjunctive liver complications. Hospitalization in delayed hepatectomies was shorter (10.4 days vs. 13.9 days, P = .0021). Blood and plasma transfusions were higher in synchronous resections (41.9% vs. 16.7%, P = .0131 and 54.8% vs. 31.3%, P = .0370); no differences were found in the last 10 years. Considering both surgical procedures (colorectal + liver resection), in delayed hepatectomies, morbidity was higher (56.3% vs. 32.6%, P = .0369) and hospitalization was longer (20.5 vs. 13.9 days, P = .00001). Nine patients underwent major hepatectomy at the same time as anterior rectal resection with no mortality (morbidity 22.2%, mean hospitalization 12.4 days). Conclusions Major hepatectomies can be safely performed at the same time as colorectal surgery in selected patients with synchronous metastases with similar short-term results, even in the presence of rectal cancer.     

Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific. Presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, March 11, Miami, Florida.     

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.     

Systemic Chemotherapy and Two-Stage Hepatectomy for Extensive Bilateral Colorectal Liver Metastases: Perioperative Safety and Survival

Background Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases (CLM). The aim of this study was to compare the outcome of patients with CLM treated with preoperative chemotherapy followed by one- or two-stage hepatectomy. Methods From a prospective database, 214 consecutive patients who received preoperative systemic chemotherapy (fluoropyrimidine with irinotecan or oxaliplatin) followed by planned one- or two-stage hepatectomy were retrospectively analyzed (1998–2006). In patients undergoing two-stage procedures, minor hepatectomy (wedge or segmental resection[s]) was systematically performed before major (more than three segments), second-stage hepatectomy. Preoperative portal vein embolization (PVE) was performed if indicated. Results One- (group I) and two-stage(group II) hepatectomies were performed in 184 and 21 patients, respectively. Median number of metastases in groups I and II were two (range 1–20) and seven (range 2–20). All patients in group II had bilateral disease vs 39% in group I. Major hepatectomy was performed in all patients in group II and 79% in group I. PVE was performed in 18 group I and 12 group II patients without increase in morbidity. For group I, group II first stage, and group II second stage, respectively, morbidity (24%, 24%, 43%), median hospital stay (7 days, 6 days, 6.5 days) and 30 days postoperative mortality (2%, 0%, 0%) were not significantly different (P = NS). Median follow-up was 25 months; median survival has not been reached. One- and 3-year overall and disease-free survival rates from the time of hepatic resection were 95% and 75%, 63% and 39%, respectively in group I; 95% and 86%, 70% and 51%, respectively in group II (P = NS). Conclusions Two-stage hepatectomy with preoperative chemotherapy results in comparable morbidity and survival rates as one-stage hepatectomy. This approach enables selection and treatment of patients with multiple, bilateral CLM who will benefit from aggressive surgery with good outcomes. Presented at the Society for Surgery of the Alimentary Tract 48th Annual Meeting, May 2007, Washington, DC.     

Management of Hepatic Arterial Infusion Port Following Prophylactic Regional Chemotherapy in Patients who have Undergone Curative Resection of Colorectal Liver Metastases

Purpose. Although hepatic arterial infusion (HAI) is widely performed as a prophylactic chemotherapy for patients who have undergone a curative resection of a metastatic liver tumor from colorectal cancer, the optimal management of implantable ports and catheters after the cessation of such adjuvant therapy remains to be elucidated.Methods. The survival and recurrence rate of 30 patients who received adjuvant regional chemotherapy following a hepatectomy were examined. The outcomes of the 15 patients who were regularly administered heparin into the port to prevent its occlusion were also analyzed.Results. With a median follow-up period of 38.1 months, local recurrence in the residual liver was observed in only 5 patients (17%), and the 3-year hepatic disease-free survival was as high as 82%. Out of the 15 patients who received heparin injection, the ports were successfully maintained in only 6 patients (40%) at from 8.8 to 24.7 months (median, 10.8 months) postoperatively, and 69% of the implantable ports were maintained without occlusion for 12 months. Furthermore, a second course of regional chemotherapy was carried out in only one patient, while a repeat hepatectomy was performed instead of chemotherapy in the other patients with hepatic recurrence.Conclusions. Because HAI remarkably reduced the degree of relapse in the residual liver, there is no benefit in maintaining the port after discontinuing the chemotherapy. Heparin administration via the same port after a cessation of the prophylactic HAI chemotherapy is not justified, and it is desirable to remove the implanted catheter when possible.     

Chemotherapy With Bevacizumab Does Not Affect Liver Regeneration After Portal Vein Embolization in the Treatment of Colorectal Liver Metastases

Background  Blockage of vascular endothelial growth factor (VEGF) in murine models has been shown to impair liver regeneration after partial hepatectomy. The aim of this study was to evaluate the effects of chemotherapy with or without bevacizumab (monoclonal antibody anti-VEGF) on liver regeneration after portal vein embolization (PVE) in the treatment of colorectal liver metastases and its possible effect on postoperative outcome after major liver resection. Methods  Records of 65 consecutive patients treated with or without preoperative chemotherapy (with or without bevacizumab) and PVE for colorectal liver metastases from September 1995 to February 2007 were reviewed from a prospective database. Future liver remnant (FLR) volume, degree of FLR hypertrophy after PVE, morbidity, mortality, and survival were analyzed. Results  Preoperative PVE was performed after chemotherapy in 43 patients and without chemotherapy in 22 patients. Among the 43 patients treated with chemotherapy, 26 received concurrent bevacizumab. After a median of 4 weeks after PVE, there was no difference in FLR volume increase among patients treated with or without chemotherapy. Similarly, there was no statistically significant difference in degree of FLR hypertrophy among patients treated without (mean, 10.1%) or with chemotherapy, with or without bevacizumab (8.8% and 6.8%) (P = .11). Forty-eight (74%) of 65 patients underwent extended right or right hepatectomy after PVE. No differences in morbidity and mortality were observed among patients treated with or without preoperative chemotherapy (with or without bevacizumab). Conclusion  Preoperative chemotherapy with bevacizumab does not impair liver regeneration after PVE. Liver resection can be performed safely in patients treated with bevacizumab before PVE. Presented at The Society of Surgical Oncology, 61st Annual Cancer Symposium, Chicago, IL, March 13–16, 2008.     

Five-Year Survival Following Hepatic Resection After Neoadjuvant Therapy for Nonresectable Colorectal [Liver] Metastases

Background: Surgical resection is the most effective treatment for colorectal liver metastases but only a minority of patients are candidates for a potentially curative resection. Our experience with neoadjuvant chemotherapy followed by resection and five years survival analysis of the patients treated is presented.Methods: Between February of 1988 and September of 1996, 701 patients with unresectable colorectal liver metastases were treated with neoadjuvant chemotherapy. Four categories of nonresectable disease were defined: large size, ill location, multinodularity, and extrahepatic disease. Liver resection was performed in those patients whose disease became resectable. After resection, the patients were followed up every 3 months. A 5-year survival analysis by the different categories described was performed.Results: Ninety-five patients (13.5%) were found to be resectable on reevaluation and underwent a potentially curative resection. There was no perioperative mortality, and the complication rate was 23%. As of December of 1999, 87 patients have completed 5 years of follow-up. The overall 5-year survival is 35% from the time of resection and 39% from the onset of chemotherapy. Respective 5-year survival rates are 60% for large tumors, 49% for ill-located lesions, 34% for multinodular disease, and 18% for liver metastases with extrahepatic disease. In this latter category, however, a 35% 5-year survival was found when all the patients with extrahepatic disease were analyzed rather than only those for whom extrahepatic disease was the main cause of nonresectability.Conclusions: Neoadjuvant chemotherapy enables liver resection in some patients with initially unresectable colorectal metastases. Long-term survival is similar to that reported for a priori surgical candidates.     

Microsatellite Instability as a Prognostic Factor in Resected Colorectal Cancer Liver Metastases

Background: Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are currently recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Untreated CRC hepatic metastases are incurable and are associated with a median survival of 4 to 12 months. Conversely, surgical resection in selected patients results in a 20% to 50% cure rate. The aim of this study was to investigate the prognostic importance of MSI-H in patients undergoing resection of hepatic CRC metastases.Methods: DNA was extracted from paraffin-embedded, resected metastatic CRC liver lesions and corresponding normal liver parenchyma from 190 patients. MSI-H status was determined by polymerase chain reaction–based evaluation of the noncoding mononucleotide repeats BAT-25 and BAT-26.Results: MSI was detected in tumors from 5 (2.7%) of the 190 CRC patients. All MSI-H tumors were in patients with node-positive CRC primary tumors. The median survival after hepatic resection of MSI-H and non–MSI-H tumors was 67 and 61 months, respectively (P = .9).Conclusions: These data suggest that MSI-H is not a common feature in resected CRC liver metastases and do not suggest a role for MSI in stratifying good versus poor prognosis in these patients.the Annual Meeting of the Society of Surgical Oncology, Los Angeles, California, March 5–9, 2003.     

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.     

Liver resection for hepatic metastases: 15 years of experience

Background/Purpose: Liver metastases, especially those from primary colorectal cancers, are treatable and potentially curable. Imaging techniques such as computed tomography, magnetic resonance, and ultrasonography have advanced in recent years and led to increased sensitivity and specificity in the diagnosis of liver metastases. Liver surgery also has been revolutionized in the past two decades. Dissection along nonanatomical lines has permitted the resection of multiple lesions that previously might have been considered unresectable. Methods: From 1986 to 2000, 181 patients underwent liver resection for hepatic metastasis from colorectal cancer. Of these, 56 patients underwent systematic anatomical major hepatic resection and 125 underwent nonanatomical limited resection. Results: Operative morbidity and mortality rates were higher in patients in whom anatomical procedures were performed. The overall 5-year survival rate of the 181 patients was 39.8%. Conclusions: An aggressive surgical procedure in patients with hepatic colorectal metastases is safe, and may prolong overall survival, and therefore should be considered in all patients with metastases confined to the liver. Received: April 14, 2002 / Accepted: May 12, 2002 Offprint requests to: G. Belli Via Cimarosa 2/a, 80127 — Naples, Italy Accepted at fifth World Congress of the International Hepato-Pancreato-Biliary Association (IHPBA)     

Update of Carcinoembryonic Antigen Radioimmunotherapy with <Superscript>131</Superscript>I-Labetuzumab After Salvage Resection of Colorectal Liver Metastases: Comparison of Outcome to a Contemporaneous Control Group

Background We tested whether adjuvant radioimmunotherapy (RAIT) given after R0 resection of liver metastases (LM) of colorectal cancer is safe and can improve survival. Resection of LM from colorectal cancer is the standard of care in this setting, yet two thirds will eventually relapse, and adjuvant systemic chemotherapy has failed to improve survival. Methods Twenty-three patients who underwent R0 resection for LM of colorectal cancer received a dose of 40 to 60 mCi/m^{2 131}I-labetuzumab, a humanized monoclonal antibody against carcinoembryonic antigen. Safety (n = 23), disease-free survival, and overall survival (n = 19) were analyzed, and efficacy was then compared retrospectively with a similar contemporaneous group of control patients (n = 19) treated at the same institution during the same time period but without RAIT. Results At a median follow-up of 91 months (95% confidence interval [CI], 68.0 months to infinity), the median overall survival for RAIT patients was 58.0 months (95% CI, 55.0 months to infinity), versus 31.0 months (95% CI, 26.0 months to infinity) at a 51-month median follow-up for the controls (P = .032). The median disease-free survival for RAIT patients was 18.0 months (95% CI, 11.0–31.0 months), versus 12.0 months (95% CI, 6.5–27.0 months) for the controls (P = .565). Corresponding survival rates (Kaplan-Meier analyses) were estimated to be 94.7% at 1 year, 78.9% at 2 years, 68.4% at 3 years, and 42.1% at 5 years with RAIT and 94.7%, 68.4%, 36.8%, and 15.8%, respectively, for the controls. RAIT was beneficial independently of bilobar involvement, size and number of LM, or resection margins. Transient myelosuppression was the principal adverse effect. Conclusions This first evidence of a promising survival advantage of adjuvant RAIT after long-term follow-up of colorectal cancer patients given salvage resection of LM warrants confirmation in a prospective randomized trial.