Granulocyte Colony-Stimulating Factor Increases Hepatic Sinusoidal Perfusion During Liver Regeneration in Mice

Conditioning with granulocyte colony-stimulating factor (G-CSF) promotes liver regeneration in an experimental small-for-size liver remnant mouse model. The mechanisms involved in this extraordinary G-CSF effect are unknown. The aim of this study was to investigate the influence of G-CSF on the hepatic microvasculature in the regenerating liver. The hepatic sinusoidal microvasculature and microarchitecture of the regenerating liver were evaluated by intravital microscopy in mice. Three experimental groups were compared: (1) unoperated unconditioned animals (control; n = 5), (2) animals conditioned with G-CSF 48 h after 60% partial hepatectomy (G-CSF-PH; n = 6), and (3) animals sham conditioned 48 h after 60% PH (sham-PH; n = 6). PH led to hepatocyte hypertrophy and increased hepatic sinusoidal velocity in the sham-PH and G-CSF-PH groups. Increased sinusoidal diameter and increased hepatic blood flow were observed in the G-CSF-PH group compared to the sham-PH and control groups. Furthermore, there was a strong positive correlation between spleen weight and hepatic sinusoidal diameter in the G-CSF-PH group. The increased hepatic blood flow could explain the observed benefit of G-CSF conditioning during liver regeneration. These results elucidate an unexplored aspect of pharmacological modulation of liver regeneration and motivate further experiments.     

Granulocyte colony-stimulating factor increases hepatic sinusoidal perfusion during liver regeneration in mice.

Conditioning with granulocyte colony-stimulating factor (G-CSF) promotes liver regeneration in an experimental small-for-size liver remnant mouse model. The mechanisms involved in this extraordinary G-CSF effect are unknown. The aim of this study was to investigate the influence of G-CSF on the hepatic microvasculature in the regenerating liver. The hepatic sinusoidal microvasculature and microarchitecture of the regenerating liver were evaluated by intravital microscopy in mice. Three experimental groups were compared: (1) unoperated unconditioned animals (control; n = 5), (2) animals conditioned with G-CSF 48 h after 60% partial hepatectomy (G-CSF-PH; n = 6), and (3) animals sham conditioned 48 h after 60% PH (sham-PH; n = 6). PH led to hepatocyte hypertrophy and increased hepatic sinusoidal velocity in the sham-PH and G-CSF-PH groups. Increased sinusoidal diameter and increased hepatic blood flow were observed in the G-CSF-PH group compared to the sham-PH and control groups. Furthermore, there was a strong positive correlation between spleen weight and hepatic sinusoidal diameter in the G-CSF-PH group. The increased hepatic blood flow could explain the observed benefit of G-CSF conditioning during liver regeneration. These results elucidate an unexplored aspect of pharmacological modulation of liver regeneration and motivate further experiments.     

The impact of 3-D virtual hepatectomy simulation in living-donor liver transplantation

Background/Purpose In living-donor liver transplantation, accurate assessments of liver graft volume and anatomical variation are mandatory for the preoperative planning of safe donor hepatectomy and successful recipient implantation. The aim of this study was to assess the feasibility and accuracy of novel three-dimensional (3-D) virtual hepatectomy simulation software in living-donor liver transplantation. Methods We developed the hepatectomy simulation software, which was programmed to analyze detailed 3-D vascular structure and to predict liver graft volume, based on hepatic circulation. Results In 101 individuals, including 4 living donors, the predicted liver resection volumes revealed a significant correlation with the actual value (P < 0.0001), with a mean difference of 7.9 ml. The drainage area by the individual hepatic vein branch was quantified to achieve reconstruction of the corresponding venous branch. The application of multidetector computed technology scanning and virtual cholangioscopy facilitated more detailed visualization of the 3-D hilar anatomy in a left trisectoral graft transplantation. Conclusions This hepatectomy simulation software reliably predicted accurate liver graft volume and the drainage volume of hepatic vein branches. This software may contribute to the preoperative planning of safe donor hepatectomy and implantation with satisfactory graft viability.     

Regeneration After Two-Stage Hepatectomy vs Repeat Resection for Colorectal Metastasis Recurrence

Background Two-stage hepatectomy aims to minimize liver failure risk by performing a second resection after regeneration, assuming that remnant liver hypertrophy after the second resection is similar to that seen in repeat hepatectomy, yet the impact of a two-stage strategy on liver volume and function remains to be demonstrated. Patients and Methods Twenty patients undergoing two-stage hepatectomy for multiple colorectal cancer metastases and 21 patients with more than two sections of liver parenchyma totally removed by repeat liver resections for recurrence were enrolled. Liver volumes after final hepatectomy and postoperative liver function were compared. Results Median total liver volumes before initial hepatectomy and after final hepatectomy of multiple resections were 942 and 863 ml in patients with repeat hepatectomy, whereas volumes at corresponding time points were 957 and 777 ml in patients with two-stage hepatectomy. The ratio of total liver volume after both hepatectomies to preoperative volume in the two-stage group (81.7%) was lower than that in the repeat resection group (92.0%, P = 0.027). Greater aspartate aminotransferase and prothrombin time and lower platelet count 1 month postoperatively and lower albumin at 6 months were evident after two-stage hepatectomy compared with repeat hepatectomy. Conclusions Two-stage hepatectomy is characterized by diminished hepatic regenerative capacity and postoperative liver function.     

Percentage of Future Liver Remnant Volume Before Portal Vein Embolization Influences the Degree of Liver Regeneration After Hepatectomy

Background

Clinical determinants of liver regeneration induced by portal vein embolization (PVE) and hepatectomy remain unclear. The aims of this study were to investigate how liver regeneration occurs after PVE followed by hepatectomy and to determine which factors strongly promote liver regeneration.

Methods

Thirty-six patients who underwent both preoperative PVE and major hepatectomy were enrolled in this study. Percentage of future liver remnant volume before PVE (%FLR-pre) was compared with the remnant liver volume after PVE (%FLR-post-PVE) and on postoperative day 7 after hepatic resection (%FLR-post-HR). Clinical indicators contributing to liver regeneration induced by both PVE and hepatectomy were examined by logistic regression analysis.

Results

PVE and hepatectomy caused a two-step regeneration. FLR-pre, FLR-post-PVE, and FLR-post-HR were 448, 579, and 761 cm³, respectively. The %FLR-pre was significantly associated with liver regeneration induced by both PVE and hepatectomy (r?=?0.63, p?<?0.0001). Multiple regression analysis showed that only %FLR-pre was independently correlated with posthepatectomy liver regeneration (p?=?0.027, odds ratio?=?13.8).

Conclusion

After PVE and the subsequent hepatectomy, liver regeneration was accomplished in a two-step manner. Liver regeneration was strongly influenced by the %FLR-pre.     

Hyperperfusion syndrome in small-for-size livers

BACKGROUND: Portal hyperperfusion in small-for-size livers might seriously impair postoperative liver regeneration. Using an experimental model, we investigated splenectomy as a measure to reduce portal blood flow and its impact on postoperative recovery following extended liver resection. METHOD: Wistar rats underwent partial (90%) hepatectomy with or without splenectomy under temporary inflow occlusion (30 min). In addition to 10-day survival rate, laser Doppler flowmetry of hepatic blood flow and fluorescence microscopic analysis of hepatic microcirculation were performed to assess the effect of splenectomy on initial microvascular reperfusion of liver remnants. RESULTS: While postischemic perfusion failure was comparable between both groups, portal blood flow was significantly reduced after simultaneous splenectomy (3.5+/-0.4 vs. 5.4+/-0.4 ml/min). Moreover, red blood cell velocity and volumetric blood flow were reduced in splenectomized animals. These animals experienced lower AST levels (421+/-36 vs. 574+/-73 U/l) and a significantly increased survival rate, reaching 6.6+/-1.3 vs 2.6+/-0.8 days. CONCLUSION: Simultaneous splenectomy significantly reduced the risk for postoperative hyperperfusion syndrome in small-for-size livers. Shear-stress-induced liver injury was diminished due to a significant reduction of portal venous blood flow, which positively influenced postoperative regeneration resulting in significantly higher survival.     

Half clamping of the infrahepatic inferior vena cava reduces bleeding during a hepatectomy by decreasing the central venous pressure

Background and aims  Bleeding from the hepatic vein is closely related to central venous pressure (CVP). To evaluate the effect of low central venous pressure during a hepatectomy, the infrahepatic inferior vena cava (IVC) was half clamped. Patients and methods  Between 2006 and 2007, 20 patients undergoing major hepatectomy with the IVC half clamping (half-clamping group) were compared with 58 patients undergoing hepatectomy without IVC half clamping between 2003 and 2005 (control group). The types of liver resection, amount of blood loss during the hepatectomy, volume of blood transfusion, length of hospital stay, and complications were compared between the two groups. Results  In the half-clamping group, blood loss was decreased in comparison to the control group (p = 0.041) and the suprahepatic CVP was low (2.4 ± 1.8 mmHg; p = 0.0002). The diameter at the root of the right hepatic vein was reduced in comparison to before clamping (5.8 ± 1.6 mm; p < 0.001). There were no complications of half clamping on any hemodynamic and blood electrolytic parameters. Conclusion  Using the half clamping technique of the IVC, intra-operative CVP was maintained below 3 mmHg without any side effects, and the low CVP significantly reduced the bleeding from hepatic veins during a major hepatectomy.     

Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray

Background/Purpose: Excessive hepatectomy often causes fatal liver failure. We have reported that this is mainly mediated by apoptosis, characterized pathologically by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) assay-positive hepatocytes and a ladder pattern in DNA fragmentation assays. Methods: To investigate the mechanism, we used cDNA microarray analysis to compare clearly differentiated rat partial hepatectomy (PHx) models (90%PHx, and 95%PHx). All 90%PHx rats survived, but the 95%PHx animals died of hepatic failure within 96 h. Remnant liver was obtained at four time points (1, 3, 12, and 24 h after PHx). After RNA extraction, two samples were labeled with different fluorescent dyes and hybridized to the Institute of Physical and Chemical Research (RIKEN) set of 18 816 full-length enriched mouse cDNA arrays. Scanning for fluorescent dye signals was performed, and the mRNA expression ratio of the two models was examined. Results: Genes of the p21 cyclin-dependent kinase (CDK) inhibitor, Fas, interleukin (IL)-18, and many caspases were upregulated at 1 h after PHx in the 95%PHx group. On the other hand, genes of Bcl-2, heat shock proteins, and glutathione-S-transferase were downregulated. Conclusions: We concluded that fatal hepatic failure after excessive hepatectomy was characterized by increased apoptosis and diminished liver regeneration. Received: July 25, 2001 / Accepted: November 16, 2001     

Simultaneous Resections of Colorectal Cancer and Synchronous Liver Metastases: A Multi-institutional Analysis

Background The safety of simultaneous resections of colorectal cancer and synchronous liver metastases (SCRLM) is not established. This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections. Methods Clinicopathologic data, treatments, and postoperative outcomes from patients who underwent simultaneous or staged colorectal and hepatic resections at three hepatobiliary centers from 1985–2006 were reviewed. Results 610 patients underwent simultaneous (n = 135) or staged (n = 475) resections of colorectal cancer and SCRLM. Seventy staged patients underwent colorectal and hepatic resections at the same institution. Simultaneous patients had fewer (median 1 versus 2) and smaller (median 2.5 versus 3.5 cm) metastases and less often underwent major (≥ three segments) hepatectomy (26.7% versus 61.3%, p < 0.05). Combined hospital stay was lower after simultaneous resections (median 8.5 versus 14 days, p < 0.0001). Mortality (1.0% versus 0.5%) and severe morbidity (14.1% versus 12.5%) were similar after simultaneous colorectal resection and minor hepatectomy compared with isolated minor hepatectomy (both p > 0.05). For major hepatectomy, simultaneous colorectal resection increased mortality (8.3% versus 1.4%, p < 0.05) and severe morbidity (36.1% versus 15.1%, p < 0.05). Combined severe morbidity after staged resections was lower compared to simultaneous resections (36.1% versus 17.6%, p = 0.05) for major hepatectomy but similar for minor hepatectomy (14.1% versus 10.5%, p > 0.05). Major hepatectomy independently predicted severe morbidity after simultaneous resections [hazard ratio (HR) = 3.4, p = 0.008]. Conclusions Simultaneous colorectal and minor hepatic resections are safe and should be performed for most patients with SCRLM. Due to increased risk of severe morbidity, caution should be exercised before performing simultaneous colorectal and major hepatic resections.     

Biliopancreatic diversion in rats is associated with intestinal hypertrophy and with increased GLP-1, GLP-2 and PYY levels

Background Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. The aims of this study were to develop an animal model for biliopancreatic diversion (BPD) and to determine changes in gut hormones, malabsorption and small bowel histology postoperatively. Methods 2 groups of Wistar rats underwent sham and BPD surgery.Daily postoperative weights and food intake were measured. 24-hour fecal collections were performed at Day 6 and 21. Bomb calorimetry was performed to determine the fecal calorific values. At day 23, levels of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) were determined and small bowel biopsies were taken. Results Animals in the BPD group had significant reduction in weight (P < 0.001) and in food intake (P < 0.001) compared to the sham group. Serum levels of PYY, GLP-1 and GLP-2 in the BPD group were significantly higher (P < 0.005). Animals in the BPD group had significantly higher fecal energy content at Day 6 (P < 0.001) but not at Day 21 when compared to the sham group. Small bowel histology confirmed the presence of significantly increased mitosis (P = 0.03) and labelled cells (P = 0.002) in the BPD animals when compared to sham. Conclusions In our animal model, the higher levels of PYY, GLP-1 and GLP-2 after BPD may be due to gut adaptation and hypertrophy and could be important in inducing and maintaining weight loss after bariatric surgery. *CMB and CLR contributed equally to this paper Presented at the 10th World Congress of the International Federation for the Surgery of Obesity, September 2, 2005, Maastricht, The Netherlands.     

Systemic Chemotherapy and Two-Stage Hepatectomy for Extensive Bilateral Colorectal Liver Metastases: Perioperative Safety and Survival

Background Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases (CLM). The aim of this study was to compare the outcome of patients with CLM treated with preoperative chemotherapy followed by one- or two-stage hepatectomy. Methods From a prospective database, 214 consecutive patients who received preoperative systemic chemotherapy (fluoropyrimidine with irinotecan or oxaliplatin) followed by planned one- or two-stage hepatectomy were retrospectively analyzed (1998–2006). In patients undergoing two-stage procedures, minor hepatectomy (wedge or segmental resection[s]) was systematically performed before major (more than three segments), second-stage hepatectomy. Preoperative portal vein embolization (PVE) was performed if indicated. Results One- (group I) and two-stage(group II) hepatectomies were performed in 184 and 21 patients, respectively. Median number of metastases in groups I and II were two (range 1–20) and seven (range 2–20). All patients in group II had bilateral disease vs 39% in group I. Major hepatectomy was performed in all patients in group II and 79% in group I. PVE was performed in 18 group I and 12 group II patients without increase in morbidity. For group I, group II first stage, and group II second stage, respectively, morbidity (24%, 24%, 43%), median hospital stay (7 days, 6 days, 6.5 days) and 30 days postoperative mortality (2%, 0%, 0%) were not significantly different (P = NS). Median follow-up was 25 months; median survival has not been reached. One- and 3-year overall and disease-free survival rates from the time of hepatic resection were 95% and 75%, 63% and 39%, respectively in group I; 95% and 86%, 70% and 51%, respectively in group II (P = NS). Conclusions Two-stage hepatectomy with preoperative chemotherapy results in comparable morbidity and survival rates as one-stage hepatectomy. This approach enables selection and treatment of patients with multiple, bilateral CLM who will benefit from aggressive surgery with good outcomes. Presented at the Society for Surgery of the Alimentary Tract 48th Annual Meeting, May 2007, Washington, DC.     

Indocyanine Green Plasma Disappearance Rate During the Anhepatic Phase of Orthotopic Liver Transplantation

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI] = 0.8–2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account. Presented at the Forty-eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington DC, May 19–24, 2007 (poster presentation).     

Right Portal Vein Ligation is as Efficient as Portal Vein Embolization to Induce Hypertrophy of the Left Liver Remnant

Background Aim of this retrospective study was to compare induction of left liver hypertrophy after right portal vein ligation (PVL) and right portal vein embolization (PVE) before right hepatectomy for liver metastases. Materials and Methods Between 1998 and 2005, 18 patients underwent a PVE, whereas 17 patients underwent a PVL during a first stage laparotomy. Results There was no complication related to PVE or PVL. After a similar interval time (7 ± 3 vs 8 ± 3 weeks), the increase of the left liver volume was similar between the two groups (35 ± 38 vs 38 ± 26%). After PVE and PVL, right hepatectomy was performed in 12 and 14 patients, respectively. Technical difficulties during the right hepatectomy were similar according to duration of procedure (6.4 ± 1 vs 6.7 ± 1 h, p = 0.7) and transfusion rates (33 vs 28%, p = 0.7). Mortality was nil in both groups, and morbidity rates were respectively 58% for the PVE group and 36% for the PVL group (p = 0.6). Conclusion Right PVL and PVE result in a comparable hypertrophy of the left liver. During the first laparotomy of a two-step liver resection, PVL can be efficiently and safely performed.     

Impact of hepatic vein deprivation on liver regeneration and function after major hepatectomy

Background and aims In extended liver resections, the preservation of vascular and biliary structures of the entire remnant liver is of paramount importance. The impact of venous outflow impairment and its consequences for liver regeneration and function are still a matter of debate. Materials and methods Rats (n = 75) were subjected to a 90% partial hepatectomy (PH), to a 70% liver resection with narrowing of the hepatic outflow of an additional 20% parenchyma (70%+ PH) or to an anatomic 70% PH. Postoperatively hepatocyte proliferation (Ki-67), liver function and survival were assessed. Gene expression analysis for markers of regeneration was determined by in-house complementary (DNA) arrays and quantitative real-time polymerase chain reaction (RT-PCR). Results Ninety percent PH led to a greater regenerative response as shown Ki-67 compared to animals with a 70%+PH (p < 0.05). However, liver function was equally impaired in both groups. Rats with 70% PH showed a greater proliferation index with less hepatic injury and better liver function. While mortality was 0% in the group of 70% PH, rats with 90% PH and 70+PH had a reduced survival of 75% (p < 0.05) Conclusion Venous outflow obstruction leads to an impairment of liver regeneration and liver function. In cases with critically small liver remnants, restoration of an adequate venous outflow may be mandatory.     

Resection of Hepatic Colorectal Metastases Involving the Caudate Lobe: Perioperative Outcome and Survival

Purpose: To examine clinical features and outcome of patients who underwent hepatic resection for colorectal liver metastases (LM) involving the caudate lobe. Patients and Methods: Consecutive patients who underwent hepatic resection for LM from May 1990 to September 2004 were analyzed from a multicenter database. Demographics, operative data, pathologic margin status, recurrence, and survival were analyzed. Results: Of 580 patients, 40 (7%) had LM involving the caudate. Six had isolated caudate LM and 34 had LM involving the caudate plus one or more other hepatic segments. Patients with caudate LM were more likely to have synchronous primary colorectal cancer (63% vs. 36%; P = 0.01), multiple LM (70% vs. 51%; P = 0.02) and required extended hepatic resection more often than patients with non-caudate LM (60% vs. 18%; P < 0.001). Only four patients with caudate LM underwent a vascular resection; three at first operation, one after recurrence of a resected caudate tumor. All had primary repair (vena cava, n = 3; portal vein, n = 1). Perioperative complications (43% vs. 28%) and 60-day operative mortality (0% vs. 1%) were similar (caudate vs. non-caudate LM, both P > 0.05). Pathological margins were positive in 15 (38%) patients with caudate LM and in 43 (8%) with non-caudate LM (P < 0.001). At a median follow-up of 40 months, 25 (64%) patients with caudate LM recurred compared with 219 (40%) patients with non-caudate LM (P = 0.01). Patients with caudate LM were more likely to have intrahepatic disease as a component of recurrence (caudate: 51% vs. non-caudate: 25%; P = 0.001). No patient recurred on the vena cava or portal vein. Patients with caudate LM had shorter 5-year disease-free and overall survival than patients with non-caudate LM (disease-free: 24% vs. 44%; P = 0.02; overall: 41% vs. 58%; P = 0.02). Conclusions: Patients who undergo hepatic resection for caudate LM often present with multiple hepatic tumors and tumors in proximity to the major hepatic veins. Extended hepatectomy is required in the majority, although vascular resection is not frequently necessary; when performed, primary repair is usually possible. Despite resection in this population of patients with multiple and bilateral tumors, and despite close-margin and positive-margin resection in a significant proportion, recurrence on the portal vein or vena cava was not observed, and long-term survival is accomplished (41% 5-year overall survival). These data were presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, Miami, Florida, March 12, 2006.     

Increased Expression and Activity of Hepatic Lipase in the Liver of Morbidly Obese Adult Patients in Relation to Lipid Content

Background  The types and sources of lipid deposition in the liver of most patients with morbid obesity, as well as the effects of bariatric surgery, are discussed. Methods  In 26 patients with morbid obesity who underwent bariatric surgery, we analyzed different kinds of lipids and hepatic lipase (HL) from both plasma and liver biopsies performed 12–18 months after surgery. Results  The HL activity and HL-mRNA in morbidly obese (MO) livers were high (258 ± 17 mU/g, and 4.5-fold, respectively); after surgery, the activity decreased (137 ± 15 mU/g, p < 0.001) but not the levels of HL-mRNA (4.3-fold). Plasma HL activity was also high (4.31 ± 0.94 mU/mL plasma), and it decreased during weight loss (2.01 ± 0.29 mU/mL, p < 0.01); moreover, it correlated (r = 0.3694, p < 0.05) with decreased liver HL activity. Adrenocorticotropic hormone in MO was higher (27 ± 3 pg/mL) than after surgery (13 ± 1 pg/mL, p < 0.001). All hepatic and plasma lipids were significantly increased in MO patients, but, after bariatric surgery, most of those parameters recovered or normalized. Liver HL activity correlated with total and esterified cholesterol (r = 0.4399, p < 0.001 and r = 0.4395, p < 0.01, respectively). Conclusion  High HL in MO patients could allow for liver intake of cholesterol that could be re-exported to steroidogenic organs to synthesize steroidal hormones. A decrease of plasma HL during weight loss could be a good index for improvement of liver disease.     

Effect of Ischemic Preconditioning and Postconditioning on Liver Regeneration in Prepubertal Rats

Background

Liver regeneration has great importance for transplantation, especially in children; however, it has not been studied sufficiently in development animals. Ischemia-reperfusion injury is a problem, and strategies such as ischemic preconditioning and postconditioning are not well defined regarding regeneration.

Objective

This study sought to evaluate liver regeneration with modulation by ischemic preconditioning and postconditioning in prepubertal rats subjected to total ischemia and reperfusion.

Methods

Thirty-five 5-week-old female Wistar rats were divided into groups of 7 animals each: control group (SHAM), 70% hepatectomy (HEP), total ischemia 30 minutes before hepatectomy (IR), ischemic preconditioning 10/10 minutes before ischemia (PRE), and two 30/30-second ischemic postconditioning cycles after ischemia and hepatectomy (POS). All animals were subjected to 24-hour reperfusion. Aspartate aminotransferase and alanine aminotransferase activity were measured to evaluate liver damage, and histological analysis, proliferating cell nuclear antigen (PCNA) and regenerated mass liver were used to evaluate liver regeneration. Statistical analyses were performed using ANOVA and Kruskal-Wallis test.

Results

Alanine aminotransferase and aspartate aminotransferase levels were significantly lower in conditioned groups than in the IR group. Regarding mitotic index, IR > control group and HEP (P < .05), PRE and POS were not significantly different from IR, and POS > HEP (P < .05). PCNA analysis showed that IR > HEP (P < .01), PRE < IR (P < .01), and no significant differences were observed between POS and IR groups. No significant differences in regenerated mass liver were observed between conditioned groups and HEP.

Conclusions

Ischemic postconditioning prevented ischemic injury, promoted greater liver regeneration, and should be further investigated as an alternative better than ischemic preconditioning.     

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

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

Long-term Outcomes and Prognostic Factors of Elderly Patients with Hepatocellular Carcinoma Undergoing Hepatectomy

Objective  The present study aimed to evaluate the long-term outcomes and prognostic factors of elderly patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. Material and Methods  From January 1983 to December 2006, 2,283 patients with HCC received hepatectomy in Sun Yat-sen University Cancer Center. The clinicopathological data and treatment outcomes of 67 elderly HCC patients (elderly group, ≥70 years of age) and 268 patients (control group, <70 years of age) who were selected randomly from the 2216 younger patients were compared retrospectively. Results  The elderly HCC patients had lower hepatitis B surface antigen-positive rate (P < 0.001), lower rate of marked α-fetoprotein elevation (P = 0.004), higher infection rate of hepatitis C virus (P = 0.010), more preoperative comorbidities (P < 0.001), higher rate of tumor encapsulation (P = 0.040), and better overall survival rate (P = 0.017); whereas there were no significant differences between these two groups in other factors, including gender ratio, liver function, accompanying cirrhosis, pathological tumor–node–metastasis (pTNM) staging, satellite nodules, vascular invasion, tumor rupture, resection margin, intraoperative blood loss, incidence of postoperative complications, hospital mortality, and disease-free survival rate. Multivariate analysis showed that pTNM staging was an independent prognostic factor of long-term survival in elderly patients with HCC. Conclusion  HCC in the elderly was less HBV-associated, less advanced, and less aggressive. Hepatectomy for selected elderly patients with HCC possibly have a better curative effect compared with younger patients. For the elderly patients without preoperative comorbidities or with controlled comorbidities, hepatectomy is a safe and effective treatment. pTNM staging is the only independent predictor of postoperative overall survival in elderly HCC patients.     

Effect of Portocaval Shunt on Residual Extreme Small Liver after Extended Hepatectomy in Porcine

Background When residual liver volume is extremely small after extended hepatectomy, postoperative hepatic failure may ensue. The cause of the hepatic failure is likely associated with the portal hypertension after hepatectomy. We investigated the effects of portocaval shunt on portal hypertension in producing sinusoidal microcirculatory injury after extended hepatectomy in pigs. Methods Fourteen pigs were divided into two groups: a group without a shunt, in which extended hepatectomy was carried out (i.e., residual volume was 17% of the whole liver), and a group with a shunt, in which extended hepatectomy was carried out and a portocaval shunt was inserted. The portocaval shunt was placed by side-to-side anastomosis between the portal vein and the inferior vena cava. Results In the group without a shunt, all pigs died of hepatic failure within postoperative day 3. In the group with a shunt, all pigs were alive for more than 4 days, and 4 pigs survived longer than 7 days. Portal vein pressure after hepatectomy was 15.9 ± 3.8 mmHg in the group without a shunt and 10.5 ± 0.6 mmHg in the group with a shunt (P < 0.01). The portal vein flow after 83% hepatectomy in the group without a shunt increased significantly more than at laparotomy and in the group with a shunt (P < 0.01). In the group without a shunt, remarkable destruction of the sinusoidal lining and edema of the portal triad and hydropic change of hepatocytes were observed 1 hour after hepatectomy, but these findings were not observed in the group with a shunt. Conclusions These results indicate that, after extended hepatectomy, overload of portal flow is one of the most significant risk factors of hepatic failure by sinusoidal microcirculatory injury. This study was presented at the Fourth International Meeting on Hepatocellular Carcinoma: Eastern and Western Experiences, Hong Kong, China, December 14–16, 2004