Bevacizumab improves survival in patients with synchronous colorectal liver metastases provided the primary tumor is resected first

Background: Multimodal strategy including chemotherapy and hepatectomy is advocated for the management of colorectal liver metastases (CRLM). The aim of this study was to evaluate the impact of neoadjuvant Bevacizumab-based chemotherapy on survival in patients with resected stage IVA colorectal cancer and liver metastases. Methods: Data from 120 consecutive patients who received neoadjuvant chemotherapy and underwent curative-intent hepatectomy for synchronous CRLM were retrospectively reviewed. Overall survival (OS) was stratified according to administration of Bevacizumab before liver resection and surgical strategy, i.e., classical strategy (primary tumor resection first) versus reverse strategy (liver metastases resection first). Results: Patients who received Bevacizumab (n = 37; 30%) had a higher number of CRLM (p = 0.003) and underwent more often reverse strategy (p = 0.005), as compared to those who did not (n = 83; 70%). Bevacizumab was associated with an improved OS compared with conventional chemotherapy (p = 0.04). After stratifying by the surgical strategy, Bevacizumab was associated with improved OS in patients who had classical strategy (p = 0.03). In contrast, Bevacizumab had no impact on OS among patients who had liver metastases resection first (p = 0.89). Conclusions: Neoadjuvant Bevacizumab-based chemotherapy was associated with improved OS in patients who underwent liver resection of synchronous CRLM, especially in those who underwent primary tumor resection first

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Bevacizumab improves survival in patients with synchronous colorectal liver metastases provided the primary tumor is resected first.

BACKGROUND: Multimodal strategy including chemotherapy and hepatectomy is advocated for the management of colorectal liver metastases (CRLM). The aim of this study was to evaluate the impact of neoadjuvant Bevacizumab-based chemotherapy on survival in patients with resected stage IVA colorectal cancer and liver metastases. METHODS: Data from 120 consecutive patients who received neoadjuvant chemotherapy and underwent curative-intent hepatectomy for synchronous CRLM were retrospectively reviewed. Overall survival (OS) was stratified according to administration of Bevacizumab before liver resection and surgical strategy, i.e., classical strategy (primary tumor resection first) versus reverse strategy (liver metastases resection first). RESULTS: Patients who received Bevacizumab (n = 37; 30%) had a higher number of CRLM (p = 0.003) and underwent more often reverse strategy (p = 0.005), as compared to those who did not (n = 83; 70%). Bevacizumab was associated with an improved OS compared with conventional chemotherapy (p = 0.04). After stratifying by the surgical strategy, Bevacizumab was associated with improved OS in patients who had classical strategy (p = 0.03). In contrast, Bevacizumab had no impact on OS among patients who had liver metastases resection first (p = 0.89). CONCLUSIONS: Neoadjuvant Bevacizumab-based chemotherapy was associated with improved OS in patients who underwent liver resection of synchronous CRLM, especially in those who underwent primary tumor resection first.

Robot-assisted laparoscopic liver resection: A review.

Surgery using a robotic platform is expanding rapidly today, with a notable surge since its authorization on the international medical market by the US Food and Drug Administration in 2000. The first hepatectomy by a robotic approach was reported in 2002, 10 years after the first laparoscopic hepatectomy. Yet, in hepatic surgery, series are scarce and the lack of relevant data in the literature is an obstacle to the development of robot-assisted laparoscopic hepatectomy (RALH). Based on a review of the literature, this update focuses on current indications, short-term and oncologic outcomes following RALH.

Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy?

The partial liver's ability to regenerate both as a graft and remnant justifies right lobe (RL) living donor liver transplantation. We studied (using biochemical and radiological parameters) the rate, extent of, and predictors of functional and volumetric recovery of the remnant left liver (RLL) during the first year in 91 consecutive RL donors. Recovery of normal liver function (prothrombin time [PT] ≥70% of normal and total bilirubin [TB] ≤20 µmol/L), liver volumetric recovery, and percentage RLL growth were analyzed. Normal liver function was regained by postoperative day's 7, 30, and 365 in 52%, 86%, and 96% donors, respectively. Similarly, mean liver volumetric recovery was 64%, 71%, and 85%; whereas the percentage liver growth was 85%, 105%, and 146%, respectively. Preoperative PT value (p = 0.01), RLL/total liver volume (TLV) ratio (p = 0.03), middle hepatic vein harvesting (p = 0.02), and postoperative peak TB (p < 0.01) were predictors of early functional recovery, whereas donor age (p = 0.03), RLL/TLV ratio (p = 0.004), and TLV/ body weight ratio (p = 0.02) predicted early volumetric recuperation. One-year post-RL donor hepatectomy, though functional recovery occurs in almost all (96%), donors had incomplete restoration (85%) of preoperative total liver volume. Modifiable predictors of regeneration could help in better and safer donor selection, while continuing to ensure successful recipient outcomes.

Prognostic value of sarcopenia in liver surgery.

Current knowledge indicates that malnutrition increases the rate of post-operative complications, particularly respiratory and infectious, after major surgery. Almost all liver surgery is performed in patients with cancer, a factor that increases the risk of malnutrition. The primary risk factors for post-operative complications are pre-operative hypo-albuminemia and a body mass index less than 20 kg/m(2). To improve the prediction of complications in these patients, some teams have suggested measurement of muscle thickness by computed tomography. Muscular mass can thus be quantified by measuring the total surface of the psoas muscle or the total surface of all muscles (i.e. external and internal oblique, transverse, psoas and paravertebral muscles) seen on an axial CT slice at L3. As well, data exist suggesting that sarcopenia is an independent predictive factor of post-operative morbidity and poor long-term survival after resection for cancer. Nonetheless, the literature on the subject is limited, there are no standardized definitions for sarcopenia, and the need of special software to calculate the surfaces limits its usefulness. Lastly, there are little if any data concerning the nutritional or pharmacologic means to treat sarcopenia. This update, based on a literature review, deals with the value and the prognostic impact of sarcopenia in surgery for liver tumors. The current definition of sarcopenia, validated internationally, the methods of measurement, and the consequences of sarcopenia on the outcome of liver resections are detailed in this review.

Accessory liver lobes: anatomical description and clinical implications.

Accessory liver lobes are a rare condition and appear to be due to excessive development of the liver. The presence of an accessory hepatic lobe is often diagnosed incidentally and sometimes revealed if it develops torsion, especially in pedunculated forms. In most cases, the accessory lobe is located below the liver, i.e., infrahepatic. Riedel's lobe is the best-known example of an accessory lobe, corresponding to hypertrophy of segments V and VI. While accessories lobes can simulate tumors, there have also been reports of hepatocellular tumor(s) that developed in these accessory lobes. Based on a review of the literature, this update focuses on accessory hepatic lobes.

Indocyanine green fluorescence imaging in the surgical management of liver cancers: current facts and future implications.

Imaging detection of liver cancers and identification of the bile ducts during surgery, based on the fluorescence properties of indocyanine green, has recently been developed in liver surgery. The principle of this imaging technique relies on the intravenous administration of indocyanine green before surgery and the illumination of the surface of the liver by an infrared camera that simultaneously induces and collects the fluorescence. Detection by fluorescence is based on the contrast between the (fluorescent) tumoral or peri-tumoral tissues and the healthy (non-fluorescent) liver. Results suggest that indocyanine green fluorescence imaging is capable of identification of new liver cancers and enables the characterization of known hepatic lesions in real time during liver resection. The purpose of this paper is to present the fundamental principles of fluorescence imaging detection, to describe successively the practical and technical aspects of its use and the appearance of hepatic lesions in fluorescence, and to expose the diagnostic and therapeutic perspectives of this innovative imaging technique in liver surgery.

Vascular reconstruction combined with liver resection for malignant tumours.

BACKGROUND: The resectability criteria for malignant liver tumours have expanded during the past two decades. The use of vascular reconstruction after hepatectomy has been integral in this process. However, the majority of reports are anecdotal. This is a retrospective analysis of the techniques, morbidity, mortality and risk factors of liver resections with vascular reconstruction based on a large series from a single centre. METHODS: Patients who underwent hepatic resection combined with vascular resection and reconstruction between 1997 and 2009 were included in this study. Indications for surgery, morbidity and 90-day mortality are reported along with factors predictive of operative mortality. RESULTS: Eighty-four patients had liver resection with 97 vascular resections and reconstruction. There were 44 men and 40 women with a mean(s.d.) age of 56·9(12·1) years. Mean(s.d.) follow-up was 37·3(34·1) months. All patients had primary or metastatic liver tumours. The perioperative morbidity rate was 62 per cent (52 patients) and the operative mortality rate 14 per cent (12). Predictors of operative mortality were: bilirubin level exceeding 34 µmol/ml (P = 0·023), indocyanine green retention rate at 15 min over 10 per cent (P = 0·031), duration of ischaemia (P = 0·011), amount of blood transfused (P = 0·025) and combined major extrahepatic procedure (P = 0·042). Actuarial 3- and 5-year survival rates were 44 and 26 per cent respectively. CONCLUSION: Liver resection with combined vascular resection and reconstruction can be performed in selected patients with acceptable morbidity and mortality. The lack of therapeutic alternatives and the poor outcome of non-operative management seem to justify this approach. The identification of risk factors should help improve patient selection and postoperative outcome as well as facilitate objective risk communication with surgical candidates.

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.

Short- and long-term donor morbidity in right lobe living donor liver transplantation: 91 consecutive cases in a European Center.

The lack of use of a common grading system in reporting morbidity impedes estimation of the true risk to a right lobe living donor (RLLD). We report outcomes in 91 consecutive RLLD's using the validated 5-tier Clavien grading and a quality of life (QOL) questionnaire. The median follow-up was 79 months. The donors were predominantly female (66%), 22 (24%) received autologous blood transfusions. Fifty-three complications occurred in 43 donors (47% morbidity), 19 (37%) were ≥ Grade III, biliary fistula (14%) was the most common. There was no donor mortality. Two intraoperative complications could not be graded and two disfiguring complications in female donors were graded as minor. Two subgroups (first 46 vs. later 45 donors) were compared to study the presence if any, of a learning curve. The later 45 donors had lesser autologous transfusions, lesser rehospitalization and no reoperation and a reduction in the proportion of ≥ Grade III (major) complications (24% vs. 50%; p = 0.06). In the long term, donors expressed an overall sense of well being, but some sequelae of surgery do restrain their current lifestyle. Our results warn against lackadaisical vigilance once RLLD hepatectomy becomes routine.

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.

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.

Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor.

Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, 'progression' of AFP was defined by >15 microg/L per month before LT. A total of 127 (83%) were transplanted under and 26 (16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP>15 microg/L per month and preoperative nodules>3 were associated with decreased OS. Progression group and age>60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor>30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP>15 microg/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness.

[Surgical margin status in hepatectomy for liver tumors]. / Marges d'exérèse des tumeurs hépatiques malignes primitives et secondaires.

It is admitted that only complete tumor clearance with negative surgical margins provides benefit for patients undergoing surgery for hepatobiliary malignancies. For hepatocellular carcinoma, since micrometastases disseminate via portal venous branches, anatomic resection is preferred over non-anatomic resection in liver resection carried out with curative intent. Thus, an anatomic liver resection with a wider resection margin theoretically gives a higher potential for cure. However, preserving non-tumorous liver parenchyma is an important consideration, especially in cirrhotic liver resection to decrease the incidence of postoperative liver failure. The optimal liver resection margin is still controversial. It seems that a resection margin of 2 cm is associated with a decreased postoperative recurrence rate and improved survival outcomes especially for hepatocellular carcinoma

Adult liver transplantation: the Paul Brousse experience.

During the past 3 decades, more than 2,250 liver transplants were performed at Paul Brousse Hospital. Overall patient survival was 82% at one year, 71% at 5 years and 64% at 10 years. Our group has developed a variety of approaches to liver transplantation, including: 1. Anti HBs immunoglobulin prophylaxis for the prevention of HBV recurrence. Combination prophylaxis with lamivudine and anti HBs immunoglobulins reduced the rate of HBV re-infection to 20%. 2. Transplantation of HIV-HCV and HIV-HBV infected patients. These transplants are feasible and we achieved 2- year survival rates of 70% and 90%, respectively. The main problem was HCV recurrence which was more severe in HIV co-infected patients. 3. Transplantation for hepatocellular carcinoma on a cirrhotic liver with a single tumor <5 cm or <3 tumors <3 cm. 4. Transplantation for familial amyloidotic polyneuropathy (FAP). The 5- and 10-year survival rates were 76% and 72%, respectively. More than 100 livers obtained after hepatectomy from FAP patients were transplanted as "domino" living donor livers to patients with unresectable liver cancers with a 5-year survival rate of 64%. In some domino recipients, symptoms of FAP disease occurred more rapidly than expected and this could be an indication for a second transplantation of a non FAP-liver. 5. Split-liver transplantation for pediatric patients. This has increased the number of transplantable livers for children by 28%. 6. Split-liver transplantation for 2 adults. The grafts were prepared by ex-vivo or in-situ splitting and the overall 5-year survival rate was 56%. 7. Adult -to-adult living-related liver transplantation. There has been no mortality nor late complications in donors and the overall 5-year survival rate among recipients was 73%. 8. Liver retransplantation with good results in the elective situation. Retransplantation should be used with discretion in the emergency setting.