Neoadjuvant chemotherapy as a treatment strategy for multiple bilobar liver metastases from colorectal carcinoma

Hepatic resection remains the only potentially curative therapy for patients with colorectal liver metastases. Because most have multiple bilobar liver metastases, surgical resection is possible in only 25-58% of patients with colorectal liver metastases. Currently, attention is focused on the potential for neoadjuvant chemotherapy to render formerly unresectable patients resectable. The availability of more efficacious chemotherapy agents and an inventive approach to delivery schedules have resulted in an increase in the number of candidates for hepatic resection after neoadjuvant chemotherapy. Although tumor response varies with regimen and/or route of chemotherapy for colorectal liver metastases, with 16-63% tumor response rates, hepatic resection for responders after neoadjuvant chemotherapy gives survival benefits, with 20-48% 5-year survival rates after surgery. Provided that neoadjuvant chemotherapy controls multiple bilobar liver metastases well, aggressive hepatic resection should be considered for patients with those lesions. As a treatment strategy for multiple bilobar liver metastases, neoadjuvant chemotherapy is a useful to increase resection rates and may contribute to the improvement of prognosis in patients with such lesions.     

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.     

Effectiveness of prehepatectomy intra-arterial chemotherapy for multiple bilobar colorectal cancer metastases to the liver: a clinicopathologic study of peritumoral vasculobiliary invasion

BACKGROUND: Consensus remains to be achieved concerning prehepatectomy neoadjuvant chemotherapy as a treatment strategy for multiple bilobar colorectal liver metastases, in part because the effect of prehepatectomy neoadjuvant chemotherapy has not been determined pathologically. We investigated the efficacy of prehepatectomy intra-arterial chemotherapy for multiple bilobar colorectal cancer metastases to the liver. METHODS: Clinicopathologic data for 37 consecutive patients with > or =5 bilobar liver metastases from colorectal cancer who underwent hepatectomy were analyzed retrospectively with respect to long-term outcome and histological findings in resected liver tumors. RESULTS: In the 15 patients receiving neodadjuvant chemotherapy (NEO+ group), liver metastases progressed in 2 patients, remained stable in 8 patients, responded more than 50% in 4 patients, and responded completely in 1 patient (combined response rate, 33.3%). Overall and hepatic recurrence-free survival tended to be higher in responders than in nonresponders ( P = .053). Microscopic invasion of the portal vein, hepatic vein, and bile ducts near liver tumors was less frequent according to use of neoadjuvant chemotherapy and responsiveness to the therapy (responders, 20.0%; patients not receiving neoadjuvant therapy [NEO-], 72.7%; P < .05). Such microscopic invasion independently predicted hepatic recurrence by multivariate analysis ( P = .011). CONCLUSIONS: A neoadjuvant chemotherapy-associated decrease in microscopic vasculobiliary invasion by metastatic liver tumors was related to clinical response and favorable outcome.     

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.     

Perioperative complications in patients undergoing major liver resection with or without neoadjuvant chemotherapy

Systemic chemotherapy is used increasingly prior to resection of hepatic colorectal metastases. Previous reports have indicated an increased risk of perioperative complications associated with the use of systemic chemotherapy prior to resection. The purpose of this study was to investigate perioperative complications in patients receiving neoadjuvant systemic chemotherapy consisting of 5-fluorouracil (5-FU) and leucovorin (LV) with or without CPT-11 within 6 months of major liver resection. A retrospective review of 108 patients undergoing major liver resection for colorectal metastases with curative intent from 1997 to 2002 was performed. Patient and tumor characteristics, perioperative parameters, and morbidity and mortality were measured. Forty-seven patients (44%) received no chemotherapy, 27 patients (25%) received systemic 5-FU/LV, and 34 (31%) received systemic 5-FU/LV/CPT-11. A significantly higher number of patients in the group treated with preoperative 5-FU/LV plus CPT-11 had multiple tumors. Patients in this group also tended to have smaller tumors, fewer complications, and a higher R0 margin resection rate, but these findings were not statistically significant. Median blood loss and length of hospital stay were also not significantly different. There were no perioperative deaths. We conclude that the use of fluoropyrimidine-based chemotherapy and CPT-11 prior to major liver resection is not associated with increased morbidity or mortality. It may therefore provide a better therapeutic option, particularly in patients with multiple colorectal metastases. Presented as an abstract at the Fourth Biennial Congress of the American Hepato-Pancreato-Biliary Association (AHPBA), Miami Beach, Florida, February 27–March 2, 2003.     

Diagnosis and treatment of colorectal liver metastases - workflow

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.     

Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for resectable hepatic colorectal metastases

OBJECTIVES: The objectives of this study are 1) to determine whether the future liver remnant will grow after portal vein embolization (PVE) in patients with colon cancer on concurrent chemotherapy and 2) to determine whether recovery after extended hepatectomy is improved after PVE. PURPOSE: Neoadjuvant chemotherapy followed by hepatic resection is an increasingly used therapeutic strategy for curative treatment for colorectal metastases. However, such chemotherapy may result in steatosis, liver damage, and compromised liver regeneration and recovery. This study aims to determine whether PVE can be used during neoadjuvant therapy to enhance growth of future residual liver and to improve postoperative recovery. METHODS: From September 1999 to September 2004, 100 patients with colorectal metastases to the liver were subjected to PVE as preparation for extended hepatic resection, 43 of whom were embolized during neoadjuvant chemotherapy. Liver growth was examined by computed tomography volumetric analysis. Clinical outcomes of the 71 patients subsequently resected were compared with 100 consecutive patients subjected to extended resection without PVE (controls). RESULTS: After a median wait of 30 +/- 2 days after PVE, patients on neoadjuvant chemotherapy experienced a median contralateral (nonembolized) liver growth of 22% +/- 3% compared with 26% +/- 3% for those without chemotherapy (P = NS). The number of patients with <5% growth was also similar: 4 of 43 versus 6 of 57 (P = NS). Comparison of patients resected after PVE to a simultaneous cohort of 100 consecutive patients subjected to extended resection without prior PVE demonstrated a lower fresh frozen plasma requirement (P = 0.01), a lower peak bilirubin (P = 0.002), and a shorter length of stay (P = 0.03). Mortality was similar (0% vs. 2%). CONCLUSIONS: Liver growth occurs after PVE even when cytotoxic chemotherapy is administered. No major complications occurred with PVE. Patients requiring major hepatic resection should be considered for PVE during neoadjuvant chemotherapy to improve subsequent recovery after resection.     

OncoSurge: a strategy for long‐term survival in metastatic colorectal cancer

OncoSurge is a combined modality strategy for the management of colorectal cancer with hepatic metastases. It has emerged as a result of new and expanded patient selection criteria for resectability of metastases, coupled with more effective neoadjuvant and postoperative chemotherapy. By bringing together these developments in surgery and medical oncology, the new approach promises to increase significantly the resectability rate and long‐term survival in colorectal cancer patients with liver metastases. Surgery for colorectal liver metastases should now be considered across a range of clinical circumstances that would historically have been contraindications to resection. These contraindications include multiple or bilobar metastases, large tumour size, a Dukes stage C or poorly differentiated primary tumour, synchronous detection of metastases with the primary tumour, disease in elderly patients, or a resection margin of less than 1 cm. None of these criteria should necessarily exclude a patient from resection, because although they may be associated with a less favourable prognosis they do not exclude the possibility of long‐term survival. Non‐resectable extrahepatic disease and portal lymph node involvement, however, remain contraindications to resection in most circumstances. Retrospective studies of neoadjuvant therapy have indicated that a regimen based on low dose oxaliplatin, 5‐fluorourucil (5‐FU) and leucovorin increased the overall resectability rate of patients presenting with hepatic colorectal metastases from 20% to 30%, with 13.6% of patients with unresectable metastases becoming eligible for curative resection. More recently, studies using more potent oxaliplatin‐based regimens have reported significantly higher resectability rates of at least 40%, with 5‐year survival of 50% reported in one large study among patients whose liver metastases were resected after initial neoadjuvant therapy for unresectable tumours. Following resection, postoperative therapy based on a combination of hepatic artery infusion (HAI) and systemic chemotherapy reduces hepatic recurrence and increases survival, but more potent systemic therapy is required to reduce the rate of extrahepatic recurrence. Studies are now in progress combining HAI with oxaliplatin‐based systemic therapy to address this issue. By combining a more inclusive approach to surgery with more effective neoadjuvant and postoperative chemotherapy, the OncoSurge treatment model is likely to increase significantly the number of patients with hepatic colorectal metastases who can be treated with curative intent, and thus has the potential to improve overall patient survival.     

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.     

Clinical significance of and future perspectives for hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer

The most common site of metastases in patients with colorectal cancer is the liver. Hepatic resection is considered to be the treatment of choice for liver metastasis from colorectal cancer; however, hepatic resection can be performed in only 20 or 25 % of all patients. Recurrence develops in the remnant liver or other organs after hepatic resection in over half of all patients with liver-only metastasis. Hepatic arterial infusion (HAI) chemotherapy can provide relatively high concentrations of drugs to microscopic or macroscopic metastases in the liver, with less toxicity than systemic administration. Meta-analyses have shown HAI chemotherapy to have a significantly higher response rate than systemic chemotherapy and its effect on extrahepatic metastases is negligible. HAI chemotherapy provides much better local control of liver metastases from colorectal cancer than systemic chemotherapy. However, well-controlled studies are needed to elucidate the optimal treatment strategies for neoadjuvant and postoperative adjuvant chemotherapy that optimally combine HAI chemotherapy, molecular targeted agents, and systemic chemotherapy such as FOLFOX or FOLFIRI.     

Trends in the Multimodality Treatment of Resectable Colorectal Liver Metastases: an Underutilized Strategy

Objective

Advances in multimodality therapy have led to increased survival for patients with metastatic colorectal cancer, but the impact on patients undergoing resection for colorectal liver metastases is unclear. The purpose of this study was to evaluate patterns of treatment for resectable colorectal liver metastases in the USA over the last two decades.

Methods

Using the Surveillance, Epidemiology, and End Results-Medicare database, 1,926 patients who underwent hepatic resection for colorectal liver metastasis between 1991 and 2007 were included and divided into two cohorts: period 1 (1991–2000) and period 2 (2001–2007). Demographic data, treatment patterns, and outcomes of the two periods were compared by univariate methods. Multivariable regression models were constructed to predict the use of perioperative chemotherapy, postoperative complications, and 90-day mortality following liver resection.

Results

The overall use of perioperative chemotherapy was 33 % and did not differ between periods, but shifted from postoperative to preoperative over time. By multivariable analysis, older age, black race, stage III primary cancer, and metachronous disease were predictive of lesser likelihood of chemotherapy use. The use of preoperative chemotherapy was not associated with any increase in perioperative morbidity or mortality.

Conclusions

Despite increased survival and widespread recommendations for the use of multimodality therapy, the overall resection rate and use of perioperative chemotherapy for resectable colorectal liver metastases remain underutilized and have not increased over time. Efforts to investigate barriers to the widespread use of multimodality therapy for these patients are warranted.     

Outcome after hepatic resection versus combined resection and microwave ablation for multiple bilobar colorectal metastases to the liver

BACKGROUND: We investigated the efficacy of microwave ablation plus hepatectomy for multiple bilobar colorectal metastases to the liver. No consensus exists concerning local ablation plus hepatic resection for treating multiple bilobar colorectal liver metastases, partly because of a lack of long-term comparative survival data. METHODS: Clinicopathologic data were analyzed retrospectively for 53 consecutive patients with 5 or more bilobar liver metastases from colorectal cancer who underwent hepatectomy with or without microwave ablation. Outcome measures were recurrence rate, recurrence pattern, and survival. RESULTS: Combined resection/ablation was performed more frequently in patients with more liver metastases (P = .03). No significant differences were found for overall, disease-free, or hepatic recurrence-free survival between 16 patients with resection/ablation and 37 patients with resection (P = .43, .54, and .86, respectively). Multivariate analysis selected prehepatectomy carcinoembryonic antigen concentration in serum as an independent prognosticator for survival (P = .02), but not resection/ablation versus resection. In patients with combined resection/ablation, recurrence occurred near the resection or ablation line in only 2 patient (22%), whereas multiple neoplasms (>/=4) was the most common liver recurrence pattern (78%). CONCLUSIONS: Microwave ablation plus hepatic resection expanded indications for operation to treat multiple bilobar liver metastases, with survival similar to that in less-involved hepatic resection patients.     

Treatment for multiple bilobar liver metastases of colorectal cancer

Background Recent advances have extended indications for hepatectomy to include multiple bilobar colorectal liver metastases (CLM). Staging systems based on the biological malignancy of primary and metastatic tumors provide appropriate indications for hepatectomy in CLM. However, suitability for resection in patients with complex and extensive hepatic metastases is controversial. Methods A medline search was performed to identify papers reporting the resection for CLM. Techniques, indication, and results were reviewed. Results If the anticipated remnant liver volume is small (25–40% of total), suggesting a high risk of postoperative liver failure, portal vein embolization (PVE) is recommended prior to hepatectomy. However, curative resections are not always possible. Specifically in synchronous multiple bilobar CLM, two-stage hepatectomy, comprising bilateral hepatectomy and primary resection with or without PVE, can prevent growth of ipsilateral metastatic nodules in the remnant liver and reduce surgical risk. Several local ablation techniques can complement surgery if hepatic resection alone increases the risk of postoperative liver failure or is not curative. Chemotherapy combined with targeted treatment can suppress recurrence and extend indications for hepatectomy by reducing the size and number of primary irresectable tumors. Conclusion PVE or staged procedure combining with local ablation or neoadjuvant, downstaging or adjuvant therapies extends indications for hepatectomy to include multiple bilobar CLM. The 5-year survival rate for multiple bilobar CLM treated with alternating hepatectomy and chemotherapy is comparable to the values reported for single and hemilateral CLM.     

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.     

Portal triad clamping (TC) or hepatic vascular exclusion (VE) for major liver resection after prolonged neoadjuvant chemotherapy? A case-matched study in 60 patients

BACKGROUND: Prolonged systemic preoperative chemotherapy induces pathologic changes in liver parenchyma. The consequences of vascular occlusion on liver submitted to prolonged preoperative systemic chemotherapy are not known. The aim of this case-matched study was to assess which method of vascular occlusion is most appropriate for major liver resection in patients who have undergone prolonged preoperative systemic chemotherapy. METHODS: Among 305 patients who had liver resection for colorectal metastases from 1998 to 2003, 28 underwent major liver resections under portal triad clamping after more than 6 cycles of preoperative chemotherapy (TC group). These 28 patients were compared with 32 patients matched for age, sex, ASA status, number of liver metastases, type of liver resection, and type of preoperative chemotherapy, but who had major liver resection under hepatic vascular exclusion after more than 6 cycles of preoperative chemotherapy (VE group). RESULTS: There was no postoperative mortality. The morbidity rate was 18% after TC and 43% after VE (P = 0.044). Pulmonary complication rate was greater after VE (31% vs 3%, P = 0.017). The transfusion rate was 50% in the TC group and 40% in the VE group (P = 0.482). Postoperative changes of liver function tests were comparable in the two groups except for the prothrombin time, which was more prolonged from day 1 (P = 0.003) to day 5 (P = 0.04) after VE. CONCLUSION: Vascular occlusion can be used with no mortality and acceptable morbidity for major liver resection after prolonged preoperative chemotherapy. TC should be preferred to VE, permitted by the location of the neoplasm.     

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尽管已经有一些随机对照研究,但结直肠癌肝转移的诊治还存在很多争议。并非所有可切除病人都能从新辅助化疗中获益,应该选择高危病人进行新辅助化疗;对不可切除病人,除了全身化疗,肝动脉灌注(HAI)有望成为重要的转化手段;对于无法达到根治性切除(R0切除)的病人,如果能行R1切除也是有意义的;合并不可切除肺转移灶不再是肝转移灶切除的绝对禁忌;联合肝脏分隔和门静脉结扎的二步肝切除(ALPPS)由于其高并发症发生率和高病死率,应该客观看待。     

Adjuvant regional chemotherapy after hepatic resection for colorectal metastases.

BACKGROUND: This study explored the possibility of achieving a better survival rate and reduced recurrence in the remaining liver in patients with colorectal hepatic metastases undergoing hepatic resection. Adjuvant postoperative regional chemotherapy was administered via the hepatic artery or the portal vein. METHODS: A retrospective study was performed on 174 patients after hepatic resection for colorectal metastases. These comprised 78 patients who had hepatic artery infusion (HAI) chemotherapy (HAI group), 30 who had portal vein infusion (PVI) chemotherapy (PVI group) and 66 who had no regional chemotherapy (resection alone group). The three groups were compared with one another in terms of complications, survival rate and patterns of recurrence. RESULTS: Severe complications did not occur at any point during adjuvant HAI or PVI chemotherapy. The 5-year disease-free survival rate of patients in the HAI, PVI and resection alone groups were 35, 13 and 9 per cent respectively, including six hospital deaths. Patients in the HAI group showed significantly improved recurrence rates in the remaining liver compared with the resection alone group (P = 0.03), and more prolonged disease-free and overall survival than those in the PVI (P = 0.01 and P = 0.02 respectively) and resection alone (P = 0.0001 and P = 0.0006 respectively) groups. CONCLUSION: This study suggests that adjuvant HAI chemotherapy after hepatic resection may have therapeutic potential for improved management of patients with colorectal metastases.     

Perioperative Complications After Neoadjuvant Chemotherapy With and Without Bevacizumab for Colorectal Liver Metastases

Purpose

Bevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM).

Methods

Retrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, n?=?134), or chemotherapy alone (group 2, n?=?57). We compared demographics, surgical characteristics, and perioperative course.

Results

Perioperative complications developed in 35 % of patients in group 1, and 47 % in group 2 (p?=?0.11). Of those complications, 15 (11.2 %) in group 1, and 5 (8.8 %) in group 2 were considered major (p?=?0.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10 %, compared with 0 in group 2, p?=?0.56.

Conclusion

Neoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.     

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 resections for bilobar liver metastases from colorectal cancer

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