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Background The aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases. Methods The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). Results The univariate analysis revealed a significant difference (p < 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA > 5 and > 200 ng/ml, diameter of the lesion > 5 cm, time from primary tumor to metastases > 12 months, MSKCC-CRS > 2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA > 5 ng/ml, and high MSKCC-CRS. Conclusions No single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3-G4 differentiation, preoperative CEA > 5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery.

Background Left lateral sectionectomy is one of the most commonly performed laparoscopic liver resections, but limited clinical data are actually available to support the advantage of laparoscopic versus open-liver surgery. The present study compared the short-term outcomes of laparoscopic versus open surgery in a case-matched analysis. Materials and Methods Surgical outcome of 20 patients who underwent left lateral sectionectomy by laparoscopic approach (LHR group) from September 2005 to January 2007 were compared in a case-control analysis with those of 20 patients who underwent open left lateral sectionectomy (OHR group). Both groups were similar for: tumor size, preoperative laboratory data, presence of cirrhosis, and histology of the lesion. Surgical procedures were performed in both groups combining the ultrasonic dissector and the ultrasonic coagulating cutter without portal clamping. Results Compared with OHR, the LHR group had a decreased blood loss (165 mL versus 214 mL, P=0.001), and earlier postoperative recovery (4.5 versus 5.8 days, P=0.003). There were no significant differences in terms of surgical margin and operative time. Morbidity was comparable between the two groups, but two cases of postoperative ascites were recorded in two cirrhotic patients in the OHR. Major complications were not observed in either groups. Conclusions Laparoscopic resection results in reduced operative blood loss and earlier recovery with oncologic clearance and operative time comparable with open surgery. Laparoscopic liver surgery may be considered the approach of choice for tumors located in the left hepatic lobe.

Background It would be desirable to predict which patients are most likely to benefit from preoperative autologous blood donation. This aim of this study was to develop a point scoring system for predicting the need for blood transfusion in liver surgery. Methods The medical records of 480 consecutive patients who underwent hepatic resection were analysed. The data set was split randomly into a derivation set of two-thirds and a validation set of one-third. Univariable analysis was carried out to determine the association between clinicopathological factors and blood transfusion. Significant variables were entered into a multiple logistic regression model, and a transfusion risk score (TRS) was developed. The accuracy of the system was validated by calculating the area under the receiver–operator characteristic (ROC) curve. Results Factors associated with blood transfusion in multivariable analysis included preoperative haemoglobin concentration below 12·5 g/dl, largest tumour more than 4 cm, need for exposure of the vena cava, need for an associated procedure, and cirrhosis. Each variable was assigned one point, and the total score was compared with the transfusion status of each patient in the validation set. The TRS accurately predicted the likelihood of blood transfusion. In the validation set the area under the ROC curve was 0·89. Conclusion Use of the TRS could lead to substantial saving by improving the cost-effectiveness of the autologous blood donation programme.

Several techniques have been described for safe dissection of the liver parenchyma. The aim of this study was to evaluate the feasibility and effectiveness of combining two different electronic devices, the ultrasonic dissector and the harmonic scalpel, during hepatic resection. One hundred consecutive patients who underwent liver resection between January and December 2004 were enclosed in the study. Patients requiring concomitant colic resection or biliary-enteric anastomosis were excluded from the study. Operative variables (type of procedure, operating time, Pringle time, blood losses, transfusions, and histological tumor exposure at the transection surface), hospital stay, and complications were recorded. The extent of hepatic resection was a minor resection in 31 and major in 69 cases. Median blood loss was 500 mL (range, 100–2000 mL) and the Pringle maneuver was used in 58 patients. Median operative time was 367 minutes (range, 150–660 minutes). Hepatic resection was performed in 32 cirrhotic livers. Surgical complications included one postoperative hemorrhage and two bile leaks. The overall morbidity and mortality rate was 14 and 1 per cent, respectively. In conclusion, the combined use of these electronic devices allows liver resection to be safely performed, even in cirrhotic patients, with the advantage of reducing surgical complications. A prospective randomized trial is needed to clarify the clinical benefits of liver resections performed combining these two devices.

Background Based on previous studies in experimental models, pro-inflammatory Th1 cytokines (i.e. TNF-α and IFN-γ) are thought to play a pathogenic role in hepatic ischemia/reperfusion injury, while anti-inflammatory Th2 cytokines (i.e. IL-4 and IL-10) have been associated with reduced liver disease severity. To test the relevance of these concepts in humans, cytokine expression profiles were characterized in liver biopsies from patients undergoing hepatic resection following intermittent portal clamping. Methods Twelve patients were analyzed for the intrahepatic expression of TNF-α, IFN-γ, IL-4 and IL-10 before and about 90 min after the last reperfusion. In addition, parameters of liver damage including sALT and serum levels of TNF-α were analyzed at 2, 24 and 48 h after surgery. Results When compared with pre-reperfusion liver specimens, all post-reperfusion biopsies showed significantly increased levels of TNF-α and IFN-γ mRNAs. Conversely IL-4 and IL-10 mRNA levels were significantly increased in only seven patients. A negative correlation was observed between Th2 cytokines (IL-4, IL-10) and ALT and serum levels of TNF-α. Furthermore, the presence of hepatic steatosis was significantly associated with lower intrahepatic contents of IL-4 and IL-10. Conclusions The results suggest that the local early expression of Th2 cytokines may contribute to attenuate liver injury following ischemia reperfusion in humans. The early imbalance between pro- and anti-inflammatory cytokines seen in steatotic liver subjected to I/R could explain, at least partially, the decreased tolerance of steatotic livers to I/R injury.

We evaluated the feasibility and effectiveness of combining two different electronic devices, the ultrasonic dissector (UD) and the harmonic scalpel (HS), during hepatic resection. One hundred consecutive patients underwent liver resection using UD plus HS between January and December 2 004 (UD + HS group). The ultrasonic dissector was used to fracture liver parenchyma and the uncovered vessel was sealed using the HS. Surgical outcomes were compared with 100 consecutive patients who underwent liver resection using the clamp crushing method. Operative variables, postoperative liver function, hospital stay, and type and number of complications were compared. The two groups were equivalent in term of demographic and pathologic variables. The UD + HS group had a decreased blood loss (500 ml versus 700 ml, P = 0.005), number of patients transfused (22 versus 39, P = 0.009), tumor exposure at the transection surface (4 versus 12, P = 00.012), and hospital stay (7 versus 8.5 days, P = 0.020). Postoperative major complications, in particular, fluid collection and biliary fistula, were significantly less frequent in the UD + HS group (2 versus 9, P = 0.030). A longer operative time was recorded in the UD + HS group (385 versus 330 minutes, P = 0.001). The combined use of UD with HS allows liver resection to be safely performed, with the advantage of reducing blood losses and surgery-related complications. The only major disadvantage may be a longer transection time.

Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response.

Background Previous comparative studies have demonstrated that laparoscopic liver resection is associated with more frequent use and longer duration of portal camping than open liver resection, a fact that may partially explain the improvement in operative blood loss reported by most series of laparoscopic liver resection. The aim of this prospective study was to evaluate the real need for portal clamping in laparoscopic liver surgery. Study design Surgical outcomes of 40 consecutive patients who underwent laparoscopic liver resection for benign and malignant lesions from September 2005 to August 2007 were evaluate. Portal clamping was not systematically used. Results No patient required blood transfusion and median blood loss was 160 ml (range 100-340 ml). Mean operating time was 267 min (range 220-370 min) and portal clamping was necessary in only one patient. Surgical complications included two grade I complication, three grade II, and one case of postoperative hemorrhage (grade III). Conclusions Laparoscopic liver surgery without clamping can be performed safely with low blood loss.

Background Wedge resection (WR) for colorectal liver metastases (CLM) has become more common in an attempt to preserve liver parenchyma. However, some investigator have reported that WR is associated with a higher incidence of positive margin and an inferior survival compared with anatomic resection (AR) 1. Objectives This study evaluated survival, margin status, and pattern of recurrence of patients with CLM treated with WR or AR. Methods We identified 208 consecutive patients, in a single institutional database from 1995 to 2004, who underwent either WR or AR. WR was defined as a nonanatomic resection and AR was defined as single resection of one or two liver segments. Patients with combined WR–AR and patients requiring resection of more than two segments or radiofrequency ablation were excluded from the analysis. Results One hundred six patients underwent WR and 102 patients had AR. There were no differences in the rate of positive surgical margin (P = 0.146), overall recurrence rates (P = 0.211), and patterns of recurrence between the two groups (P = 0.468). The median survival was 32 months for WR and 42 for AR, with 5-year survival rates of 29% and 27% respectively, with no significant difference (P = 0.308). Morbidity was similar between the two groups. Conclusions WR is a safe procedure and does not disadvantage the patients in terms of tumor recurrence and overall survival. J. Surg. Oncol. 2008;97:503–507. © 2008 Wiley-Liss, Inc.

Parenchymal liver transection represents a fundamental phase of liver surgery. Several devices have been described for safe and careful dissection of the liver parenchyma during laparoscopic liver surgery, but the ideal technique has not yet been defined. This report describes the combined use of ultrasonic dissector and the ultrasonic coagulating cutter for laparoscopic liver resection. The ultrasonic dissector is used to fracture the parenchyma along the line of proposed division, and the uncovered bridging structures are sealed using the ultrasonic coagulating cutter. The combined use of ultrasonic dissector and harmonic scalpel allows liver resection to be safely performed, with the advantage of minimal surgical complication and low blood losses. (C) 2008 Excerpta Medica Inc. All rights reserved.

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.

Introduction Intra-Arterial Hepatic Chemotherapy (IAHC) based on floxuridine (FUdR) infusion is an effective treatment for hepatic metastases from colorectal cancer. A percutaneously implanted intra-arterial device may overcome the surgical stress of the laparotomic placement allowing an increase in the number of patients treated by IAHC. The aim of the present study is the comparative analysis of surgical and percutaneous transaxillary approaches to implant the catheter into the hepatic artery (HA) for IAHC. Materials and Methods Between September 1993 and February 1999, 56 patients received an implantable infusion system [SynchroMed® (Medtronic, USA) or Port-a-cath® (Deltec, USA) connected to an external infusion pump (CADD®, Deltec, USA)] for IAHC. Twenty-eight patients (LPT group) underwent laparotomy to implant the catheter into the HA, the other 28 patients (PCT group) received a percutaneous catheter into the HA through a transaxillary percutaneous access. Indications for the laparotomic placement were: 1) synchronous metastases not suitable [technically unresectable or large (>40% of liver parenchyma) or multiple (> 3) metastases] for hepatic resection during colorectal surgery; 2) metachronous metastases treated by radical hepatic resection and subsequent adjuvant IAHC. Indications for percutaneous placement were: 1) metachronous metastases not suitable [see above] for hepatic resection; 2) metachronous metastases suitable for hepatic resection after neoadjuvant IAHC for tumor downstaging. All patients received IAHC based on continuous infusion of FUdR (dose escalation 0.15–0.30 mg/kg/day for 14 days every 28 days) plus dexamethasone 28 mg. For the purpose of the study, the LPT group and the PCT group were comparatively analyzed in terms of age, gender, primary diagnosis, vascular anatomy of HA, ligation/embolization of aberrant HA, previous intestinal or hepatic surgery, contextual systemic chemotherapy, concomitant diseases. Safety and efficacy of surgical and percutaneous transaxillary approaches were then comparatively analyzed in terms of number of IAHC cycles administered, device-related complications causing temporary or definitive suppression of IAHC, biological costs of the procedures (procedure-related complications, postoperative pain and hospitalization). LPT cases without concomitant surgical procedure other than catheter placement (Cath-LPT group - 10 cases) were also compared with the PCT group for the same end points of the study. Results LPT group and PCT group were comparable (p=n.s.) when evaluated for all the above listed variables. As for the end points of the study, mean postoperative hospitalization was 8.2±2.2 days in the LPT group and 1.8±0.7 days in the PCT group (pConclusions Surgically implanted indwelling catheters for IAHC present lower incidence of device-related complications than percutaneous transaxillary implanted catheters. In spite of its irreversibility and significant biological costs, surgical implant is still advised when laparotomy has to be performed for other contextual procedures, such as colorectal or hepatic resection, while percutaneous transaxillary catheter placement is indicated for palliative or neoadjuvant IAHC.

Hepatocellular carcinoma (HCC) tends to invade the intrahepatic vasculature, especially the portal vein.1 The presence of portal vein tumor thrombus (PVTT) in patients with HCC is one of the most significant factors for a poor prognosis.2 – 5 The presence of macroscopic PVTT in patients with HCC is also a significant factor for poor prognosis, with a median survival of

Alterations in hemostatic parameters are a common finding after major hepatic resection. There is growing evidence that inflammation has a significant role in inducing coagulation disarrangement that follows major surgery. To determine whether preoperative methylprednisolone administration has a protective effect against the development of coagulation disorders, we evaluated the effect of preoperative steroids administration on changes in hemostatic parameters and plasma levels of inflammatory cytokines in patients undergoing liver surgery. Seventy-three patients undergoing liver resection were randomized to a steroid group or to a control group. Patients in the steroid group received 500 mg of methylprednisolone preoperatively. Serum levels of coagulation parameters (prothrombin time, platelets, fibrinogen, plasma fibrin degradation products [D-dimer], antithrombin III) and inflammatory mediators (IL-6 and TNF-alpha) were measured before and immediately after the operation and on postoperative days 1, 2, and 5. Multivariate analysis was performed to identify factors related to the characteristics of the patients and surgery affecting coagulation parameters between the two groups. Decreases in antithrombin III, platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products were significantly suppressed by the administration of methylprednisolone. Cytokines production was also significantly suppressed by the administration of methylprednisolone, and there was significant correlation between plasma levels of cytokines and coagulation alterations. These findings suggest that preoperative methylprednisolone administration inhibits the development of coagulation disarrangements in patients undergoing liver resection, possibly through suppressing the production of inflammatory cytokines.

Objectives To assess the safety of hepatic resections in the very old patient by comparing the outcome in patients younger and older than 75 years. Methods Thirty-two resections in 31 patients ≥75 years (Over-75 Group) were compared with 164 resections in 162 patients

Depending on the stage of the primary colorectal cancer, liver metastases occur in 20% to 70% of patients and represent the major cause of death in this disease.1,2 Surgical resection remains the only treatment that can, to date, ensure long-term survival in 25% to 40% of patients.3–8 It should be considered whenever liver metastases can be totally resected with clear margins and when there is no nonresectable extrahepatic disease. However, using the current indications for surgery, only 15% to 20% of patients with colorectal liver metastases are suitable for surgical resection.1,2 When liver metastases are nonresectable, palliative chemotherapy increases survival and enhances quality of life.9 Progresses including more efficient chemotherapy drugs such as oxaliplatin or irinotecan10,11 have opened new perspectives in the treatment of resectable and nonresectable liver metastases. These drugs can render resectable previously unresectable liver metastases.12–16 When liver metastases are resectable, the benefit of neoadjuvant chemotherapy on reducing the risks of recurrence after surgery is not yet demonstrated. However, in case of synchronous metastases, chemotherapy is often prescribed between the resection of the colorectal primary and the liver surgery. The risks of liver resections have been reduced in recent years. Postoperative mortality is less than 5% in most reported series.5–7 Postoperative morbidity, including transient liver failure, hemorrhage, subphrenic abscesses, and biliary fistula, occur in 20% to 40% of patients.3–8 It is not clearly established whether systemic preoperative chemotherapy increases the risks of surgery due to injury of liver parenchyma. Recent data have suggested that prolonged systemic chemotherapy could induce steatosis and microvascular changes such as peliosis or sinusoidal congestion.17 Sclerosing cholangitis, dilatation, and fibrosis of the central veins and moderate hepatocellular necrosis or cholestasis in the centrilobular area have been reported with the intra-arterial use of fluorodeoxyuridine, a 5-fluorouracil (5-FU) metabolite.13,17 These pathologic changes can be responsible for an increased risk of bleeding during surgery as the parenchyma tends to be more congested and friable.13,15 Hepatic arterial chemotherapy prior to liver resection was associated with an increased postoperative morbidity in one series (57% versus 18%).13 The consequences of systemic chemotherapy on liver parenchyma and on postoperative course following resections have not been specifically analyzed in the reports that have studied resectability following preoperative chemotherapy. The populations studied were heterogeneous regarding the duration and the regimens of preoperative chemotherapy, the extent of liver resections performed and the clamping methods used.12,14,16,18–20 The pathologic changes induced by chemotherapy in these patients have not been reported. The present study was designed to analyze the effects of preoperative systemic chemotherapy on remnant liver parenchyma and to assess the consequences on postoperative mortality, morbidity, and liver function tests. Among patients having received liver resection for metastases from colorectal cancer, we selected a homogeneous subgroup of patients who received a major liver resection under total vascular exclusion. In theory, the removal of more than three hepatic segments with continuous occlusion of hepatic inflow and outflow is at higher risk of inducing postoperative mortality and morbidity; therefore, this subgroup offers the better chances of showing an influence of preoperative chemotherapy.

The aim of this retrospective study was to evaluate the influence of age on the outcome of liver resection. A total of 129 consecutive liver resections were divided into two groups: greater than or equal to 70 years old [old group (O-group)] and < 70 years old [young group (Y-group)]. The two groups were first compared for the variables potentially affecting the postoperative course, including diagnosis, concomitant diseases, previous abdominal surgery, type of operation (major or minor resection), associated procedures, presence and length of portal clamping, intraoperative blood losses and transfusions, and length of operation. The outcome of liver resections was evaluated in terms of postoperative mortality, morbidity, transfusions, and length of hospitalization. The Y-group included 97 resections in 95 patients, aged 55.9 +/- 10.5 years (mean +/- SD; range: 23-69 years), and the O-group included 32 resections in 32 patients, aged 73.7 +/- 3.2 years (mean +/- SD; range: 70-82 years. The O-group included more hepatocellular carcinomas (46.9% versus 20.6%, p = 0.002) and cardiovascular diseases (15.2% versus 1.0%,p = 0.004). The two groups were comparable (p > 0.05) when evaluated for all other listed variables. As regards the postoperative outcome, the length of hospitalization was similar (median, range: 9.5 days, 5-60 days in the Y-group and 9 days, 5-48 days in the O-group) and the need for postoperative transfusions were not statistically different. Mortality included one case among young patients, while no deaths were recorded among elderly patients. Postoperative morbidity was higher in Y-group than in O-group (21.6% versus 9.4%, p = 0.2). In conclusion, the age factor does not negatively affect the outcome of liver resections.

Inihibition of cytokine response by methylprednisolone attenuates antithrombin reduction following hepatic resection