Surgical resection versus systemic therapy for breast cancer liver metastases: Results of a European case matched comparison.

BACKGROUND: Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted but not offered as therapeutic option. New evidence of the additional value of surgery in these patients is scarce while prognoses without surgery remains poor. PATIENTS AND METHODS: For this case matched analysis, all nationally registered patients with BCLM confined to the liver in the Netherlands (systemic group; N = 523) were selected and compared with patients who received systemic treatment and underwent hepatectomy (resection group; N = 139) at a hepatobiliary centre in France. Matching was based on age, decade when diagnosed, interval to metastases, maximum metastases size, single or multiple tumours, chemotherapy, hormonal or targeted therapy after diagnosis. Based on published guidelines, palliative systemic treatment strategies are similar in both European countries. RESULTS: Between 1983 and 2013, 3894 patients were screened for inclusion. Overall median follow-up was 80 months (95% CI 70-90 months). The median, 3- and 5-year overall survival of the whole population was 19 months, 29% and 19%, respectively. The resection and systemic group had median survival of 73 vs. 13 months (P < 0.001), respectively. Three and 5-year survival was 18% and 10% for the systemic group and 75% and 54% for the resection group, respectively. After matching, the resection group had a median overall survival of 82 months with a 3- and 5-year overall survival of 81% and 69%, respectively, compared with a median overall survival of 31 months in the systemic group with a 3- and 5-year overall survival of 32% and 24%, respectively (HR 0.28, 95% CI 0.15-0.52; P < 0.001). CONCLUSIONS: For patients with BCLM, liver resection combined with systemic treatment results in improved overall survival compared to systemic treatment alone. Liver resection should be considered in selected cases.

Hepatic vascular inflow occlusion is associated with reduced disease free survival following resection of colorectal liver metastases.

BACKGROUND: Hepatic vascular inflow occlusion (VIO) can be applied during resection of colorectal liver metastases (CRLM) to control intra-operative blood loss, but has been linked to accelerated growth of micrometastases in experimental models. This study aimed to investigate the effects of hepatic VIO on disease-free and overall survival (DFS and OS) in patients following resection for CRLM. METHODS: All patients who underwent liver resection for CRLM between January 2006 and September 2015 at our center were analyzed. Hepatic VIO was performed if deemed indicated by the operating surgeon and severe ischemia was defined as ≥20 min continuous or ≥45 min cumulative intermittent VIO. Cox regression analysis was performed to identify predictive factors for DFS and OS. RESULTS: A total of 208 patients underwent liver resection for CRLM. VIO was performed in 64 procedures (31%), and fulfilled the definition of severe ischemia in 40 patients. Patients with severe ischemia had inferior DFS (5-year DFS 32% vs. 11%, P < 0.01), and inferior OS (5-year OS 37% vs. 64%, P < 0.01). At multivariate analysis, a high clinical risk score (Hazard ratio (HR) 1.60 (1.08-2.36)) and severe ischemia (HR 1.89 (1.21-2.97)) were independent predictors of worse DFS. Severe ischemia was not an independent predictor of OS. CONCLUSION: The present cohort study suggests that prolonged hepatic VIO during liver resection for CRLM was associated with reduced DFS. A patient-tailored approach seems advisable although larger studies should confirm these findings.

Ruptured hepatic artery aneurysm: an unusual presentation of polyarteritis nodosa.

A 52-year-old woman presented with severe acute right upper quadrant abdominal pain and signs of intra-abdominal haemorrhage. CT and selective angiography revealed a ruptured right hepatic artery aneurysm and diffuse aneurysmatic disease involving most intra-abdominal organs, suggestive of polyarteritis nodosa. Although treatment with high-dose steroids was initiated, the patient died of progressive bowel ischaemia.

Repeat hepatectomy for recurrent colorectal metastases.

BACKGROUND: The oncological benefit of repeat hepatectomy for patients with recurrent colorectal metastases is not yet proven. This study assessed the value of repeat hepatectomy for these patients within current multidisciplinary treatment. METHODS: Consecutive patients treated by repeat hepatectomy for colorectal metastases between January 1990 and January 2010 were included. Patients undergoing two-stage hepatectomy were excluded. Postoperative outcome was analysed and compared with that of patients who had only a single hepatectomy. RESULTS: A total of 1036 patients underwent 1454 hepatectomies for colorectal metastases. Of these, 288 patients had 362 repeat hepatectomies for recurrent metastases. Some 225 patients (78·1 per cent) had two hepatectomies, 52 (18·1 per cent) had three hepatectomies, and 11 patients (3·8 per cent) had a fourth hepatectomy. Postoperative morbidity following repeat hepatectomy was similar to that after initial liver resection (27·1 per cent after first, 34·4 per cent after second and 33·3 per cent after third hepatectomy) (P = 0·069). The postoperative mortality rate was 3·1 per cent after repeat hepatectomy versus 1·6 per cent after first hepatectomy. Three- and 5-year overall survival rates following first hepatectomy in patients who underwent repeat hepatectomy were 76 and 54 per cent respectively, compared with 58 and 45 per cent in patients who had only one hepatectomy (P = 0·003). In multivariable analysis, repeat hepatectomy performed between 2000 and 2010 was the sole independent factor associated with longer overall survival. CONCLUSION: Repeat hepatectomy for recurrent colorectal metastases offers long-term survival in selected patients.

Impact of bevacizumab on functional recovery and histology of the liver after resection of colorectal metastases.

BACKGROUND: The impact of bevacizumab on functional recovery and histology of the liver was evaluated in patients undergoing hepatic resection for colorectal liver metastases (CLM) following bevacizumab treatment. METHODS: Consecutive patients who had resection of CLM between July 2005 and July 2009 following preoperative chemotherapy were identified retrospectively from a prospectively collected database. Patients who had received bevacizumab before the last chemotherapy line were excluded. Postoperative liver function and histology were compared between patients with and without bevacizumab treatment. Recorded parameters included serum prothrombin time, total bilirubin concentration, and levels of aspartate and alanine aminotransferase and γ-glutamyltransferase. RESULTS: Of 208 patients identified, 67 had received last-line bevacizumab, 44 were excluded and 97 had not received bevacizumab. Most patients in the bevacizumab group (66 per cent) received a single line of chemotherapy. Bevacizumab was most often combined with 5-flurouracil/leucovorin and irinotecan (68 per cent). The median number of bevacizumab cycles was 8·6 (range 1-34). Bevacizumab administration was stopped a median of 8 (range 3-19) weeks before surgery. There were no deaths. Postoperative morbidity occurred in 43 and 36 per cent of patients in the bevacizumab and no-bevacizumab groups respectively (P = 0·353). The mean(s.d.) degree of tumour necrosis was significantly higher in the bevacizumab group (55(27) versus 32(29) per cent; P = 0·001). Complete pathological response rates were comparable (3 versus 8 per cent; P = 0·307). Postoperative changes in functional parameters and objective signs of hepatic toxicity were similar in both groups. CONCLUSION: Preoperative administration of bevacizumab does not seem to affect functional recovery of the liver after resection of CLM. Tumour necrosis is increased following bevacizumab treatment.

Comparison of simultaneous or delayed liver surgery for limited synchronous colorectal metastases.

BACKGROUND: The optimal surgical strategy for patients with synchronous colorectal liver metastases (CLMs) is still unclear. The aim of this study was to compare simultaneous colorectal and hepatic resection with a delayed strategy in patients who had a limited hepatectomy (fewer than three segments). METHODS: All patients with synchronous CLMs who underwent limited hepatectomy between 1990 and 2006 were included retrospectively. Short-term outcome, overall and progression-free survival were compared in patients having simultaneous colorectal and hepatic resection and those treated by delayed hepatectomy. RESULTS: Of 228 patients undergoing hepatectomy for synchronous CLMs, 55 (24.1 per cent) had a simultaneous colorectal resection and 173 (75.9 per cent) had delayed hepatectomy. The mortality rate following hepatectomy was similar in the two groups (0 versus 0.6 per cent respectively; P = 0.557), but cumulative morbidity was significantly lower in the simultaneous group (11 per cent versus 25.4 per cent in the delayed group; P = 0.015). Three-year overall and progression-free survival rates were 74 and 8 per cent respectively in the simultaneous group, compared with 70.3 and 26.1 per cent in the delayed group (overall survival: P = 0.871; progression-free survival: P = 0.005). Significantly more recurrences were observed in the simultaneous group at 3 years (85 versus 63.6 per cent; P = 0.002); a simultaneous strategy was an independent predictor of recurrence. CONCLUSION: Combining colorectal resection with a limited hepatectomy is safe in patients with synchronous CLMs and associated with less cumulative morbidity than a delayed procedure. However, the combined strategy has a negative impact on progression-free survival.

Liver resection of colorectal metastases in elderly patients.

BACKGROUND: This study evaluated the outcome of liver surgery for colorectal metastases (CLM) in patients over 70 years old in a large international multicentre cohort. METHODS: Among 7764 patients who had resection of CLM, 999 (12.9 per cent) were aged 70-75 years, 468 (6.0 per cent) were aged 75-80 years and 157 (2.0 per cent) were at least 80 years old. Elderly patients were compared with the younger population. RESULTS: Multinodular and bilateral metastases were less common in elderly than in younger patients (P < 0.001). Preoperative chemotherapy was used less frequently and more limited surgery was performed (P < 0.001). Sixty-day postoperative mortality and morbidity rates were 3.8 and 32.3 per cent respectively, compared with 1.6 and 28.7 per cent in younger patients (both P < 0.001). Three-year overall survival was 57.1 per cent in elderly and 60.2 per cent in younger patients (P < 0.001), and was similar among patients aged 70-75, 75-80 or at least 80 years (57.8, 55.3 and 54.1 per cent respectively; P = 0.160). Independent predictors of survival were more than three metastases, bilateral metastases, concomitant extrahepatic disease and no postoperative chemotherapy. CONCLUSION: Liver resection for CLM in elderly patients can achieve a reasonable 3-year survival rate, with an acceptable morbidity rate. There should be no upper age limit but risk factors may help predict potential benefit.

Impact of portal vein embolization on long-term survival of patients with primarily unresectable colorectal liver metastases.

BACKGROUND: : Portal vein embolization (PVE) increases the resectability of initially unresectable colorectal liver metastases (CLM). This study evaluated long-term survival in patients with CLM who underwent hepatectomy following PVE. METHODS: : In a retrospective analysis patients treated by PVE before major hepatectomy were compared with those who did not have PVE, and with those who had PVE without resection. RESULTS: : Of 364 patients who underwent hepatectomy, 67 had PVE beforehand and 297 did not. Those who had PVE more often had more than three liver metastases (68 versus 40.9 per cent; P < 0.001) that were more frequently bilobar (78 versus 55.2 per cent; P < 0.001), and a higher proportion underwent extended hepatectomy (63 versus 18.1 per cent; P < 0.001). Postoperative morbidity rates were 55 and 41.1 per cent respectively (P = 0.035), and overall 3-year survival rates were 44 and 61.0 per cent (P = 0.001). Thirty-two other patients who were treated by PVE but did not undergo resection all died within 3 years. CONCLUSION: : PVE increased the resectability rate of initially unresectable CLM. Among patients who had PVE, long-term survival was better in those who had resection than in those who did not. PVE is of importance in the multimodal treatment of advanced CLM.

Long-term outcome in patients with adrenal metastases following resection of colorectal liver metastases.

BACKGROUND: The prognostic significance of adrenal metastases (AMs) in patients with colorectal liver metastases (CLMs) remains unknown. The aim of this study was to determine the influence of AMs on long-term outcome and the role of adrenalectomy in patients with CLMs. METHODS: All patients resected for CLMs who developed AMs at a single institution between 1992 and 2006 were included in the study. Their long-term outcome was compared with that of all other patients resected for CLMs but without AMs. RESULTS: Hepatectomy was performed in 796 patients, of whom 14 (1.8 per cent) developed AMs, a median of 28 months after initial diagnosis of CLMs; the remaining 782 patients (98.2 per cent) had no AMs. All 14 patients had chemotherapy, and ten went on to adrenalectomy. Median survival after diagnosis of CLMs was 50 months in patients with AMs versus 68 months in those without (P = 0.020). After diagnosis of AMs, median survival was 23 months, whether or not adrenalectomy was performed. CONCLUSION: The development of AMs after liver resection for colorectal cancer deposits carries a poor prognosis, and adrenalectomy is probably not warranted.

Bringing unresectable liver disease to resection with curative intent.

The majority of patients with colorectal liver metastases presents with unresectable disease. Without resection, the prognosis for these patients is extremely poor. The technical inability to completely remove all metastases while leaving at least 30% of remnant normal functioning liver parenchyma is nowadays regarded as the only absolute contraindication to resection. Chemotherapy regimens containing combinations of 5-fluorouracil, leucovorin, oxaliplatin and/or irinotecan can provide significant downstaging of liver disease enabling curative rescue resection and resulting in improved long-term survival. The addition of cetuximab and bevacizumab may result in higher resectability rates that may offer curative surgery in a larger amount of patients. In addition, different surgical techniques like portal vein embolization, two-stage hepatectomy and local ablation are available to achieve a resectable situation. Due to vascular exclusion and reconstruction techniques, tumoral involvement of the hepatic veins and inferior vena cava no longer limits the indication of resection. Overall, surgery should be performed as soon as liver metastases become resectable. Collaboration between oncologists and surgeons is essential to optimize individual therapeutic strategies.

[Better treatment for patients with colorectal liver metastases]. / Betere behandelingsmogelijkheden voor patiënten met colorectale levermetastasen.

Three patients, 61, 58 and 63 years old, presented with non-resectable liver metastases from colorectal cancer. The first patient, a man, who had a solitary lesion in the liver and severe cardiovascular morbidity, was successfully treated with laser-induced interstitial thermotherapy. The second patient, a woman, had large multiple liver metastases and two concomitant isolated pulmonary metastases. Following chemotherapy with fluorouracil, leucovorin and oxaliplatin, all lesions were downsized and a hemihepatectomy and pulmonary wedge resections were able to be performed in two stages. At the last follow-up, both patients were disease-free after 12 and 24 months respectively. The third patient, a man, presenting with multiple synchronous liver metastases, showed a significant decrease of hepatic tumour involvement after six courses of capecitabine. At present he is in a good condition and his disease is stable. Surgical resection ofcolorectal liver metastases leads to a 5-year survival rate of up to 45% in selected patients. Unfortunately, only 10 to 20% of patients are amenable to surgical resection. In the remaining group, a combination of new treatment options using local tumour ablative therapies and novel chemotherapeutic regimens provide alternative strategies with the potential of long-term survival.