Role of neoadjuvant chemotherapy in the treatment of multiple colorectal metastases to the liver

BACKGROUND: The role of neoadjuvant chemotherapy for patients with multiple (five or more) bilobar hepatic metastases irrespective of initial resectability is still under scrutiny. The purpose of this study was to compare the outcome of hepatectomy alone with that of hepatectomy after neoadjuvant chemotherapy for multiple bilobar hepatic metastases from colorectal cancer. METHODS: Retrospective data were collected from 71 patients after hepatectomy for five or more bilobar liver tumours. The outcome of 48 patients treated by neoadjuvant chemotherapy followed by hepatectomy was compared with that of 23 patients treated by hepatectomy alone. RESULTS: Patients who received neoadjuvant chemotherapy had better 3- and 5-year survival rates from the time of diagnosis than those who did not (67.0 and 38.9 versus 51.8 and 20.7 per cent respectively; P = 0.039), and required fewer extended hepatectomies (four segments or more) (39 of 48 versus 23 of 23; P = 0.027). Multivariate analysis showed neoadjuvant chemotherapy to be an independent predictor of survival. CONCLUSION: In patients with bilateral multiple colorectal liver metastases, neoadjuvant chemotherapy before hepatectomy was associated with improved survival and enabled complete resection with fewer extended hepatectomies.     

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.     

Influence of postoperative morbidity on long-term survival following liver resection for colorectal metastases

BACKGROUND: Survival after resection of colorectal liver metastases may be influenced by the patient, the primary tumour and the liver metastases. Postoperative morbidity is associated with poor survival in several cancers. The aim of this retrospective study was to evaluate prognostic factors of survival after resection of colorectal liver metastases, including postoperative morbidity. METHODS: From 1985 to 2000, 311 consecutive patients with liver metastases from colorectal cancer underwent resection with curative intent. Univariate and multivariate analyses were performed to assess the influence of age, sex, site and stage of the colorectal tumour, disease-free interval, number, size and distribution of metastases, type of hepatectomy, pedicular clamping, resection margin, blood transfusion, postoperative morbidity and adjuvant chemotherapy on overall and disease-free survival. RESULTS: The postoperative mortality and morbidity rates were 3 and 30 per cent respectively. The 3- and 5-year overall survival rates were 53 and 36 per cent respectively. Both overall and disease-free survival rates were independently associated with nodal status of the colorectal tumour, number of metastases and postoperative morbidity. Patients with postoperative morbidity had an overall and disease-free 5-year survival rate half that of patients with no morbidity: 21 versus 42 per cent for overall survival (P < 0.001) and 12 versus 28 per cent for disease-free survival (P = 0.001) respectively. CONCLUSION: Long-term survival can be altered by postoperative morbidity after resection of colorectal liver metastases by increasing the risk of tumour recurrence. This justifies optimizing the surgical treatment of colorectal liver metastases to decrease postoperative morbidity and the use of efficient adjuvant treatments in patients with postoperative morbidity.     

Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases

OBJECTIVE:: To assess the effects of preoperative systemic chemotherapy on remnant liver parenchyma, liver function, and morbidity after major liver resection for colorectal liver metastases. BACKGROUND:: Many patients operated upon for colorectal cancer liver metastases receive previous chemotherapy. Whether systemic chemotherapy alters liver parenchyma in such way that it increases the risks of liver resection remains unclear. PATIENTS AND METHODS:: Among 214 patients who received a liver resection for colorectal liver metastases between 1998 and 2002 in a single institution, 67 who underwent a major liver resection under total hepatic vascular exclusion form the basis of this report. Forty-five patients operated upon after systemic chemotherapy were compared with 22 who did not receive any chemotherapy in the 6 months prior to resection. Postoperative mortality, morbidity, liver function tests, and pathology of the resected liver in the two groups were compared. RESULTS:: There was no postoperative mortality. Values of liver function tests on days 1, 3, 5, and 10 were similar in both groups. Morbidity rate was higher in the chemotherapy group (38% versus 13.5%, P = 0.03). Postoperative morbidity was correlated with the number of cycles of chemotherapy administered before surgery but not to the type of chemotherapy. Preoperative chemotherapy was significantly associated with sinusoidal dilatation, atrophy of hepatocytes, and/or hepatocytic necrosis (49% versus 25%, P = 0.005). CONCLUSION:: Prolonged neoadjuvant systemic chemotherapy alters liver parenchyma and increases morbidity after major resection under total hepatic vascular exclusion, but it does not increase operative mortality. This should be taken into consideration before deciding a major liver resection in patients who have received preoperative chemotherapy.     

Surgical treatment of liver metastases from colorectal cancer

We analyze our experience over a 10-year period in the surgical treatment of liver metastases from colorectal cancer. Between 01.01.1995 and 08.31.2005 189 liver resections were performed in 171 patients with liver metastases from colorectal cancer (16 re-resections - 2 in the same patient and a "two-stage" liver resection in 2 patients). In our series there were 83 patients with synchronous liver metastases (69 simultaneous resections, 12 delayed resections and 2 "two-stage" liver resection were performed) and 88 metachronous liver metastases. Almost all types of liver resections have been performed. The morbidity and mortality rates were 17.4% and 4.7%, respectively. Median survival was 28.5 months and actuarial survival at 1-, 3- and 5-year was 78.7%, 40.4% and 32.7%, respectively. Between January 2002 and August 2005 hyperthermic ablation of colorectal cancer liver metastases has been performed in 6 patients; in other 5 patients with multiple bilobar liver metastases liver resection was associated with radiofrequency ablation and one patient underwent only radiofrequency ablation for recurrent liver metastasis. In conclusion, although the treatment of colorectal cancer liver metastases is multimodal (resection, ablation, chemotherapy and radiation therapy), liver resection is the only potential curative treatment. The quality and volume of remnant liver parenchyma is the only limitation of liver resection. The morbidity, mortality and survival rates after simultaneous liver and colorectal resection are similar with those achieved by delayed resection. Postoperative outcome of patients with major hepatic resection is correlated with the surgical team experience. The long-term survival was increased using the new multimodal treatment schemes.     

In-contiguity and non-anatomical extension of right hepatic trisectionectomy for liver metastases

BACKGROUND: In some patients undergoing right hepatic trisectionectomy for metastases, extension of the resection beyond the falciform ligament is necessary to achieve tumour clearance. The aim of the present study was to assess the early and long-term outcomes and hepatic function in patients who underwent extensive liver resection beyond right trisectionectomy. METHODS: Thirty-eight patients who had extension of a right trisectionectomy, either in contiguity (IC) or in a non-anatomical (NA) fashion, for liver metastases were included in the study. In-hospital mortality, hepatic function and other morbidity were recorded. Survival outcomes were analysed for the subgroup of patients with colorectal liver metastases. The clinical risk score described by the Memorial Sloan-Kettering Cancer Center was applied to all patients with colorectal liver metastases. RESULTS: Sixteen patients had IC resection, 15 NA resection, and seven had both IC and NA procedures. There was one in-hospital death. Hepatic dysfunction was seen in 25 patients and two developed liver failure. Disease-free actuarial 3-year survival was 42 per cent for patients with colorectal liver metastases. Survival was significantly better in patients with a clinical risk score of 3 or less. CONCLUSION: Extension of right trisectionectomy for liver metastases was associated with a low risk of death and hepatic failure.     

Debunking dogma: Surgery for four or more colorectal liver metastases is justified

Treatment of four or more colorectal liver metastases (CRLMs) is controversial and remains a relative contraindication to surgery at some institutions. We sought to assess the outcome of patients with four or more CRLMs treated with surgery. Patients (159) with four or more CRLMs were treated surgically at a single institution. The median number of treated lesions was 5 (range, 4–14). The majority of patients received neoadjuvant chemotherapy (89.9%). Forty-six (29.0%) patients underwent resection only, 12 (7.5%) underwent radiofrequency ablation (RFA) only, and 101 (63.5%) underwent resection plus RFA. The 5-year actuarial disease-free and overall survival rates were 21.5% and 50.9%, respectively. Patients who underwent RFA as part of their surgical procedure (hazard ratio [HR] =1.81, P =0.03) and those with a positive surgical resection margin (HR=1.52, P =0.01) were more likely to have a shorter time to recurrence. Patients who did not have a reduction in tumor size following neoadjuvant chemotherapy had a higher likelihood of death following surgical treatment (HR=2.53, P =0.01). Patients with four or more CRLMs should be considered for aggressive surgical treatment, including liver resection with or without RFA, in order to improve the chance of long-term survival. Certain clinicopathologic factors, including lack of response to neoadjuvant chemotherapy, were associated with a worse prognosis. Presented at the American Hepato-Pancreato-Biliary Association 2005 meeting, Hollywood, Florida, April 14–17, 2005.     

Resection rate and effect of postoperative chemotherapy on survival after surgery for colorectal liver metastases.

BACKGROUND: The purpose of this study was to investigate whether adjuvant therapy can improve survival after curative resection of colorectal liver metastases. METHODS: Some 235 patients had 256 liver resections for metastatic colorectal cancer. There were no predefined criteria for resectability with regard either to the number or size of the tumours or to locoregional invasion, except that resection had potentially to be complete and macroscopically curative. All patients who had curative hepatic resection were advised to start postoperative adjuvant chemotherapy. RESULTS: The resectability rate in screened patients was 91 per cent (235 of 259 patients); the postoperative mortality rate was 4 per cent. In 35 patients resection of the primary tumour was performed simultaneously with partial liver resection. Forty-four patients (19 per cent) developed intra-abdominal recurrence; 14 (6 per cent) underwent reoperation and the recurrent tumour was resected. Adjuvant chemotherapy was given to 99 patients (55 per cent), most treatments being based on 5-fluorouracil with folinic acid. The overall actuarial survival rates at 1, 3 and 5 years were 87, 60 and 36 per cent respectively. In a multivariate analysis, four or more metastases, preoperative carcinoembryonic antigen level higher than 5 ng/ml and a positive resection margin were independent predictors of poor outcome. Adjuvant chemotherapy improved the 5-year survival rate to 53 per cent. CONCLUSION: This study provides some evidence that postoperative chemotherapy is beneficial; however, prospective randomized studies are necessary to define its exact role.     

Repeat hepatic resection as effective treatment for recurrent colorectal liver metastases

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

The Role and Limitations of 18-Fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose Positron Emission Tomography (FDG-PET) Scan and Computerized Tomography (CT) in Restaging Patients with Hepatic Colorectal Metastases Following Neoadjuvant Chemotherapy: Comparison with Operative and Pathological Findings

Background Recent data confirmed the importance of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the selection of patients with colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before hepatic resection in selected cases may improve outcome. The influence of chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases is not known. Methods Patients were assigned to either neoadjuvant treatment or immediate hepatic resection according to resectability, risk of recurrence, extrahepatic disease, and patient preference. Two-thirds of them underwent FDG-PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and FDG-PET/CT. Those without extensive extrahepatic disease underwent open exploration and resection of all the metastases according to original imaging findings. Operative and pathological findings were compared to imaging results. Results Twenty-seven patients (33 lesions) underwent immediate hepatic resection (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET: 93.3 vs 49%, P < 0.0001; CT: 87.5 vs 65.3, P = 0.038). CT had a higher sensitivity than FDG-PET in detecting CR metastases following neoadjuvant therapy (65.3 vs 49%, P < 0.0001). Sensitivity of FDG-PET, but not of CT, was lower in group 2 patients whose chemotherapy included bevacizumab compared to patients who did not receive bevacizumab (39 vs 59%, P = 0.068). Conclusions FDG-PET/CT sensitivity is lowered by neoadjuvant chemotherapy. CT is more sensitive than FDG-PET in detecting CR metastases following neoadjuvant therapy. Surgical decision-making requires information from multiple imaging modalities and pretreatment findings. Baseline FDG-PET and CT before neoadjuvant therapy are mandatory. The abstract was presented before the 58th Cancer Symposium of the Society of Surgical Oncology, Atlanta, GA, USA, 2005, and before the 2005 Congress of the American Hepato-Pancreato-Biliary Association, Fort-Lauderdale, FL, USA.     

Biopsy of resectable colorectal liver metastases causes tumour dissemination and adversely affects survival after liver resection

BACKGROUND: Liver resection is increasingly being performed for metastatic colorectal cancer. This study assessed the need for preoperative biopsy of suspected metastases and whether biopsy has any effect on long-term survival. METHODS: Prospectively collected data on patients who underwent liver resection for colorectal metastases between 1986 and 2003 were reviewed retrospectively. The endpoints of morbidity, operative mortality and long-term survival were compared between patients who had biopsy before referral (group 1) and those who did not (group 2). RESULTS: Patient demographics and disease distribution were similar for 90 patients in group 1 and 508 in group 2. Seventeen patients (19 per cent) who had undergone biopsy either at the time of colorectal resection or radiologically had evidence of needle-track deposits. Operative mortality and morbidity rates in the two groups were similar. The 4-year survival rate after liver resection was 32.5 (s.e. 5.5) per cent in group 1, compared with 46.7 (2.8) per cent in group 2 (P = 0.008). CONCLUSION: Needle-track deposits are common after biopsy of suspected colorectal liver metastases. Biopsy of metastases confers poorer long-term survival on patients after liver resection and cannot be justified in patients with potentially resectable disease.     

Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases

The purpose of this study was to compare the treatment and outcome in patients referred for staged re section of synchronous colorectal liver metastases. The records of patients who had undergone colon or rectal resection and were then referred for evaluation of clinically resectable synchronous liver metastases between January 1995 and January 2000 were reviewed. Comparisons were made between patients who did not receive neoadjuvant chemotherapy and had exploratory operations after recovery from colon re section and patients who did receive chemotherapy before liver resection. A total of 106 patients were treated during the 5-year period. Neoadjuvant chemotherapy was given to 52 of the patients; in 29 of them the disease did not progress, but in 17 patients the disease progressed while they were receiving treatment. Median follow-up was 30 months. Patient- and tumor-related variables were similar between groups. Five-year survival was statistically similar between patients who did and those who did not receive neoadjuvant chemotherapy (43% vs. 35%, P = 0.49). Patients within the neoadjuvant group whose dis ease did not progress while they were receiving chemotherapy experienced significantly improved sur vival as compared to patients who did not receive chemotherapy (85% vs. 35%, P = 0.03). In the setting of synchronous colorectal liver metastases, the response to neoadjuvant chemotherapy may be a prognos tic indicator of survival and may assist in the selection of patients for conventional or experimental adju vant therapies. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

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.     

Liver resection after downstaging with neoadjuvant chemotherapy for "unresectable" colorectal metastases

Hepatic resection is the only treatment that offers a chance of long-term survival in patients with metastases from colorectal cancer. Nevertheless, a curative resection can be performed in only 10-20 per cent of patients: multiple bilobar metastases or "unresectable" disease are the greatest obstacles to surgical radicality. Techniques such as preoperative portal embolisation, preoperative portal ligation, two-stage hepatectomy, and neoadjuvant chemotherapy, have extended the possibility of liver surgery to patients with advanced metastatic colorectal cancer. The outcomes of two patients treated successfully with neoadjuvant chemotherapy (one case with FOL-F-OX, and one with FOL-F-IRI) followed by liver resection were analyzed. In both patients neoadjuvant chemotherapy enabled a curative liver resection to be performed without significant complications. In some patients, neoadjuvant chemotherapy permits the "downsizing" of metastatic disease to such an extent that a surgical approach proves feasible. This advance can dramatically improve the prognosis of patients with multiple or unresectable liver metastases from colorectal cancer.     

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.     

Formal hepatic resection of colorectal liver metastases. Ploidy and prognosis.

Fifty consecutive patients who underwent 52 formal hepatic resections (excluding isolated wedge resections) for metastatic colorectal cancer were analyzed to determine whether DNA content was of prognostic significance. The Dukes' stages of the colorectal primaries were: A (10%), B (20%), C (40%), D (28%), and unknown in 2%. Four patients whose liver metastases were discovered at the time of resection of the primary bowel cancer underwent concomitant liver resection, and the remaining patients underwent delayed resections. The hepatic resections performed were right lobectomy (50%), extended right lobectomy (19%), left lobectomy (13%), left lateral segmentectomy (6%), left lobectomy and right wedge (6%), extended left lobectomy (4%), and right lobectomy and left wedge (2%). The overall morbidity rate was 29%. The in-hospital mortality rate was 9%. As of November 1991, 36 patients have recurred. The 5-year actuarial survival was 28%. Flow cytometry could be performed on 37 archival specimens, 15 of which were found to be diploid whereas 22 were aneuploid. All metastases from Dukes A colorectal primaries demonstrated a diploid DNA content. In addition, there was no difference in actuarial survival between diploid and aneuploid tumors. These data suggest that in selected patients, formal hepatic resection of colorectal liver metastases can be performed with an acceptable morbidity rate, mortality rate, and survival, but ploidy of the resected tumor is not of prognostic significance.     

Peritoneal Surface Disease from Colorectal Cancer: Comparison with the Hepatic Metastases Surgical Paradigm in Optimally Resected Patients

Background  Surgical resection is the treatment of choice for colorectal hepatic metastases (HM). In contrast, metastatic disease to the peritoneum is treated with systemic therapy. We examined our experience with cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC) for peritoneal surface disease (PSD) compared with liver resection for HM. Methods  A review of prospective databases of colorectal cancer patients undergoing surgery for metastatic disease to the peritoneum or liver (1992–2005) was carried out. Results  One hundred and twenty-one patients underwent CS + IPHC and 101 patients underwent hepatic resection with median follow-up of 86 and 56 months, respectively. Fifty-five (45%) patients in the IPHC group had complete resection of all gross tumor. Ninety-five (94%) of the HM patients had negative surgical margins. Comparison of the R0/R1 PSD and margin-negative HM group demonstrated significant differences in age, performance status, and preoperative chemotherapy. The 1-, 3-, and 5-year overall survival for the R0/R1 PSD patients was 91, 48, and 26%; while it was 87, 59, and 34% for the HM patients (P = 0.32). Perioperative morbidity was 42% versus 34% (P = 0.38) and mortality was 5.5% versus 4.2% (P = 0.71) between the PSD and HM patients, respectively. Conclusion  R0/R1 resection during CS + IPHC compared with margin-negative hepatic resection demonstrated no significant difference in overall survival and for select patients should be considered a viable treatment option. Further studies to improve the resectability of PSD patients and define the role of neoadjuvant and adjuvant drug strategies are needed. Oral presentation at the Society of Surgical Oncology Annual Meeting, Chicago, IL, March 14, 2008.     

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.     

Treatment strategy for patients with colorectal cancer and synchronous irresectable liver metastases

BACKGROUND: The aim of this case-matched study was to determine the best treatment strategy for patients with asymptomatic colorectal cancer and irresectable synchronous liver metastases. METHODS: Between 1997 and 2002, 27 patients with asymptomatic colorectal cancer and irresectable synchronous liver metastases were treated by chemotherapy without initial primary resection (chemotherapy group). These 27 patients were compared with 32 patients matched for age, sex, performance status, primary tumour location, number of liver metastases, nature of irresectable disease and type of chemotherapy, but who were treated initially by resection of primary tumour (resection group). RESULTS: The 2-year actuarial survival rate was 41 per cent in the chemotherapy group and 44 per cent in the resection group (P = 0.753). In the latter group, the mortality and morbidity rates for primary resection were 0 and 19 per cent (six of 32 patients) respectively. In the chemotherapy group, intestinal obstruction related to the primary tumour occurred in four of 27 patients. The mean overall hospital stay was 11 days in the chemotherapy group and 22 days in the resection group (P = 0.003). CONCLUSION: Systemic chemotherapy without resection of the bowel cancer is the option of choice because, for most patients, it is associated with a shorter hospital stay and avoids surgery without a detrimental effect on survival.