Parenchyma-preserving hepatectomy based on portal ramification and perfusion of the right anterior section: preserving the ventral or dorsal area.

BACKGROUND: Anatomical hepatectomy aims to eliminate the spread of malignant tumor cells via portal vein systemically. An anatomical concept of the right anterior section (RAS) and preservation of the liver parenchyma within the RAS has been proposed. METHODS: We focused on the anatomical concept of the RAS based on portal perfusion and described surgical procedures to preserve the ventral or dorsal RAS using preoperative simulation. RESULTS: In 370 patients undergoing a preoperative simulation, the ramification of the tertiary portal branches of the RAS could be divided into three types including the cranio-caudal type; Couinaud's classification in 50% of patients, ventro-dorsal type in 26% of patients, and multiple type in 24% of patients. Then in 32 patients of the ventro-dorsal type, curative parenchyma-sparing hepatectomy of the RAS was performed, preserving the ventral and dorsal RAS in 14 and 18 patients, respectively. There were no differences in the postoperative complications and long-term survival compared with the results obtained after segment 5 or 8 resection (n = 33). CONCLUSION: Three-dimensional simulation revealed three types of portal vein ramification of the RAS. Parenchyma-preserving hepatectomy based on the precise portal ramification may contribute to safe and curative hepatectomy in selected cases with liver neoplasm involving the RAS.

Anatomic liver resection of right paramedian sector: ventral and dorsal resection.

The purpose of anatomic resection of the liver is to systemically eliminate malignant tumors that spread via the portal vein. Moreover, it results in reducing bleeding and bile leakage from the cut surface of the liver because Glisson's pedicle resection leads to parenchyma transection. Anatomical resection includes hemi-hepatectomy, sectionectomy, and segmentectomy. Recently, it has been noticed that this concept is not always appropriate for the liver resection including the right paramedian sector. It can be divided vertically into the ventral and the dorsal area according to the ramification of the third order of the portal veins. In the present study, we focused on the right paramedian sector and described techniques of surgical procedures of hepatectomy including resection of the ventral or dorsal areas.

Granulocyte-colony stimulating factor-producing gallbladder carcinoma.

Abstract A 78-year-old man was admitted to our hospital with right upper abdominal pain and fever. His general condition was poor. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the gallbladder. (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, a granulocyte-colony stimulating factor (G-CSF)-producing tumor was diagnosed (G-CSF 120 pg/mL). We performed cholecystectomy with central bisegmentectomy of the liver, lymph node dissection and right hemicolectomy. Histologically, the tumor was an adenosquamous cell carcinoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for G-CSF. Postoperatively, the general condition of the patient was improved. The fever subsided, the leukocyte count and serum G-CSF level normalized, and FDG-PET showed no uptake in the spine postoperatively. The patient showed no signs of recurrence at 27 months after undergoing surgery. FDG-PET is a useful method for diagnosing G-CSF-producing gallbladder carcinoma. Aggressive curative resection for G-CSF-producing gallbladder carcinoma may improve patients' general condition and prognosis.

Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma.

BACKGROUND/AIMS: Complete operative resection is the only approach to cure for intrahepatic cholangiocellular carcinoma (ICC), but the disease's prognosis is notably poor. A novel therapeutic approach is urgently required. CXC chemokine receptor 2 (CXCR2) has been associated with tumorigenesis and metastasis in human cancers. In this study, we investigated the suppressive effect of ICC growth by blocking CXCR2. MATERIAL AND METHODS: The role of CXCR2 was estimated using the human ICC cell lines, RBE and SSP25. CXCR2 small interfering RNA (siRNA) and an antagonist (SB225002) were used to block CXCR2. Proliferation assays, migration assays, and invasion assays were performed to confirm the suppressive effect of blocking CXCR2. Subcutaneous SSP25 tumors were established in athymic nude mice, and the mice were given SB225002. The expression of CXCR2 in ICC was determined by immunohistochemical staining of 34 ICC specimens. We investigated the relationship between CXCR2 expression and prognosis in ICC. RESULTS: The prognosis of patients who had higher CXCR2 expression in ICC was significantly poor (P = .004). CXCR2 siRNA treatment significantly suppressed CXCR2 expression in both RBE and SSP25. Cell proliferation, migration, and invasion were significantly suppressed by both CXCR2 siRNA and SB225002 compared with the control group. SB225002 also suppressed the growth of transplanted subcutaneous tumors (P = .02) CONCLUSION: Our results demonstrated that blocking CXCR2 clearly suppressed the development of ICC. Blocking CXCR2 may be a promising therapeutic approach for ICC.

Analysis of unique liver volume restoration after laparoscopic fenestration of liver cysts.

INTRODUCTION: Laparoscopic fenestration is a standard procedure for the treatment of non-parasitic liver cysts. After fenestration, the remnant liver often restores its volume. However, no systematic analysis of the phenomenon exists. In the present study, the pattern of liver volume restoration after laparoscopic fenestration of liver cysts was analyzed, and the mechanism for the unique restoration was investigated. METHODS: Seven patients with giant non-parasitic liver cysts underwent laparoscopic fenestration. Liver volume restoration in each section and changes in the diameter of the portal branch were analyzed after fenestration with CT or MRI. In two patients, regional liver volume restoration was assessed in detail using region-growing software, and change in portal flow distribution was estimated using computational fluid dynamics. Then, the regional liver volume restoration rate was compared with the portal hemodynamic changes. RESULTS: Liver volume restoration after fenestration was dependent on the size and position of the cysts; it not uniform throughout the remnant liver. The liver volume restoration in sections that had been compressed by giant cysts was significantly greater than in other areas after fenestration. This volume restoration was accompanied by an increase in the diameters of the portal branches in these sections. In addition, a strong correlation between the regional liver volume restoration rate and the changes in portal flow distribution existed in the computationally analyzed cases. CONCLUSION: Liver volume restoration after the fenestration of giant liver cysts non-uniformly occurs in the remnant liver. Improved portal vein circulation in the hepatic area adjacent to the excised giant liver cysts most likely regulates the greater regional volume restoration rate in the area.

Regional hepatic regeneration after liver resection correlates well with preceding changes in the regional portal circulation in humans.

BACKGROUND AND AIMS: While portal hemodynamics largely affects the liver regeneration after partial hepatectomy, whether the remnant liver homogeneously regenerates is unclear, especially in humans. We hypothesized that change in flow distribution varies in each remnant portal branch after liver resection in humans and the liver consequently regenerates heterogeneously. METHODS: Twenty-two patients who underwent anatomical hepatic resection preserving intact drainage veins were analyzed. Based on perioperative contrast-enhanced computed tomography, the regional hepatic regeneration in each segment was analyzed using a region growing software. The perioperative change in the distribution of blood flow in each portal branch was assessed using the computational flow dynamics technique. The correlation between the change in the portal flow distribution and the later regional hepatic regeneration was investigated. RESULTS: The distribution of portal blood flow in each remnant branch largely changed at 2 weeks (71-389 %). Each remnant segment also heterogeneously regenerated at 3 months (85-204 %). Meanwhile, a good correlation between the regional regeneration rate at 3 months and the relative change in the flow distribution in each circulating portal branch at 2 weeks was detected in each patient (r = 0.74-0.99). CONCLUSIONS: After partial hepatectomy, the change in blood flow varies in each remnant portal branch and the liver heterogeneously regenerates in humans. The good correlation between the earlier change in the portal flow distribution and the later regional hepatic regeneration strongly suggests that the portal venous flow most likely regulates the non-uniform liver regeneration after hepatic resection in humans.

Angiogenesis is crucial for liver regeneration after partial hepatectomy.

BACKGROUND: Recent studies of hepatic regeneration have mainly focused on the growth of parenchymal cells. However, remodeling of liver vessels seems to be crucial during hepatic regeneration. In this study, we investigated the influence of antiangiogenesis on hepatic regeneration using sFlt-1, a soluble receptor for vascular endothelial growth factor that acts as a dominant negative receptor, and the hepatocyte growth factor antagonist NK4. METHODS: A sFlt-1-expressing adenoviral vector, an NK4-expressing adenoviral vector, or both combined were infected into C57BL6 mice via the tail vein. A 70% partial hepatectomy was performed on all of the mice 48 hours after infection. The remnants of the liver were removed after the partial hepatectomy, and hepatic regeneration was assessed by measuring the remnant liver weight and hepatocyte mitosis, bromodeoxyuridine staining, immunohistochemical staining with anti-platelet endothelial cell adhesion molecule-1 antibodies, and real-time polymerase chain reaction studies for angiogenic factors. RESULTS: The immunohistochemical staining for CD31 showed suppression of sinusoidal endothelial cells growth in sFlt-1-expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice. Increases in the remnant hepatic weight were significantly lower in the sFlt-1-expressing adenoviral vector-infected mice. The bromodeoxyuridine index and mitotic cell results revealed a significant decrease in hepatic regeneration in the sFlt-1-expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice. The suppressive effects on hepatic regeneration were significantly enhanced by combined sFlt-1-expressing adenoviral vector and NK4-expressing adenoviral vector infection. Real-time polymerase chain reaction results revealed the significant suppression of angiogenic growth factor receptors Tie-1 and Tie-2. CONCLUSION: The angiogenesis inhibitor significantly suppressed hepatic regeneration. These results suggest that hepatic regeneration after hepatectomy closely correlates with angiogenesis.

Sectionectomy of the liver.

Anatomic resection of the liver, which refers to the systemic elimination of the main tumor with micrometastases, preserves liver function and is highly recommended. Tumors located centrally or in the vicinity of major portal pedicles or hepatic veins, however, tend to require extensive hepatectomy. Anatomic sectionectomy of the liver might represent an alternative to such extensive resection. Preoperative simulation, external landmarks, selective devascularization, and intraoperative ultrasound are useful to achieve anatomic sectionectomy. Anatomic resection requires division of the relevant portal vein, hepatic artery, and bile duct. This may be achieved by individual isolation of the three elements or by mass isolation of all three in their surrounding fibrous sheath (Glisson's capsule). Both approaches are equally effective for extensive resections. When sectionectomy is performed, however, the isolation of individual vasculobiliary elements is sometimes difficult and dangerous compared with the isolation of the sectional portal pedicles. By identifying the portal pedicles to individual anatomic sections, it is possible to control the inflow to the section that is intended for resection. Anatomic sectionectomy is a safe alternative to extensive liver resection in selected patients, avoiding unnecessary sacrifice of functional liver parenchyma and increasing the opportunity to perform repeat resections in cases of recurrence.

Preoperative estimation of asialoglycoprotein receptor expression in the remnant liver from CT/99mTc-GSA SPECT fusion images correlates well with postoperative liver function parameters.

BACKGROUND: Accurate preoperative estimation of remnant liver function is critically important for hepatic surgery, and the expression of asialoglycoprotein receptors (ASGPR) is associated with hepatic function. METHODS: Thirty-two patients with hepatocellular carcinoma who underwent surgical resection were studied. To estimate the expression of ASGPR in the remnant liver, simulated surgery was performed on fusion images that combined data from (99m)technetium-galactosyl human serum albumin ((99m)Tc-GSA)/single photon emission computed tomography (SPECT) and computed tomography (CT) scanning. The liver uptake ratio (LUR) of (99m)Tc-GSA and the functional liver volume (FLV) in the remnant liver were predicted and were compared with postoperative liver function parameters. RESULTS: The LUR of (99m)Tc-GSA was strongly correlated with the extent of hepatic ASGPR expression (r = 0.944, p = 5.01 x 10(-16)), being confirmed to be a reliable parameter for the evaluation of liver function. The estimated remnant LUR, but not the estimated remnant FLV, was significantly correlated with postoperative liver function parameters, such as serum total bilirubin (r = -0.430, p < 0.05), prothrombin activity (r = 0.515, p < 0.01), and serum cholinesterase activity (r = 0.546, p < 0.01) at 1 week. CONCLUSION: Preoperative estimation of the extent of ASGPR expression in the remnant liver on CT/GSA-SPECT fusion images correlated well with postoperative liver function parameters, suggesting its usefulness for surgical decisions.

Minimally invasive laparoscopic liver resection: 3D MDCT simulation for preoperative planning.

BACKGROUND/PURPOSE: Laparoscopic liver resection has not gained wide acceptance compared with other laparoscopic procedures. We evaluated the impact of simulated surgery using data from multidetector CT scanning on planning for laparoscopic hepatectomy. METHODS: The hepatectomy simulation system was programmed to perform three-dimensional reconstruction of the vasculature and to calculate the liver resection volume and surgical margin. In 35 patients undergoing laparoscopic hepatectomy or laparoscopy-assisted hepatectomy, the liver resection volume and margin were estimated by simulation preoperatively. Then, the estimated values were compared with the actual resected liver weight and margin. RESULTS: Three-dimensional reconstruction allowed stereoscopic identification of the tumor-bearing portal vein and draining vein. The predicted liver resection volume and margin both showed a significant correlation with the actual values: the mean difference was 21 mL (P < 0.0001) and 1.3 mm (P < 0.01), respectively. Preoperative planning based on simulated resection facilitated laparoscopic mobilization of the liver and mini-laparotomy resection of a large tumor located in the upper right lobe. CONCLUSIONS: Three-dimensional simulation of hepatectomy facilitated intraoperative identification of the vascular anatomy, and accurately predicted the resected liver volume and surgical margin. This simulation method should contribute to preoperative planning for safe and curative laparoscopic hepatectomy.

Impact of preoperative planning using virtual segmental volumetry on liver resection for hepatocellular carcinoma.

BACKGROUND: Accurate assessment of resection volume and vascular anatomy is mandatory in preoperative planning for safe and curative hepatectomy to treat cancer. Accordingly, we examined feasibility and accuracy of a preoperative three-dimensional (3D) computed tomography (CT) scan based simulation in patients with impaired liver function undergoing hepatectomy for hepatocellular carcinoma (HCC). METHODS: Hepatectomy simulation software was programmed to reconstruct detailed 3D vascular structure and calculate liver volume based on hepatic circulation. In 113 patients with HCC, liver resection volume was estimated preoperatively by both simulation and conventional planimetry. For validation, predicted resection volumes were compared with actual resected specimen weights. The resection margin as estimated by the simulation was compared with the margin in the specimen. RESULTS: Simulation showed higher correlation and smaller discrepancy (r = 0.96; 9.3 ml) between predicted and actual liver resection volume than conventional planimetry (r = 0.74; 174 ml). Simulation showed correlation (p < 0.01) between estimated and actual segmental volume, which was not measurable by planimetry. Simulation showed a correlation (r = 0.84) between predicted and actual margin, with a difference of 1.6 mm. CONCLUSIONS: Hepatectomy simulation in 3D predicted segmental liver volume and the resection margin accurately. This virtual method should contribute to preoperative planning to achieve safe, curative resection in HCC patients, whose hepatic function is compromised.

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.

Impact of donor age on the growth of young recipient rats after liver transplantation.

PURPOSE: We studied the age-related changes in graft livers, and their impact on post-transplantation liver function and the growth of young recipient rats. METHODS: Rats aged 11-68 weeks old were studied as controls to assess liver histology, liver function, and body weight. We performed orthotopic liver transplantation using Kamada's cuff technique without arterial reconstruction. Young rats aged 11 weeks were randomized to receive livers from either 11-week-old donors (YD group) or 52-week-old donors (OD group). Recipient rats were killed 0, 8, or 16 weeks after surgery and we assessed the same variables as in the controls. RESULTS: We confirmed an age-related increase in the average size of hepatocytes and their nuclei. These age-related changes persisted and progressed in the graft liver after transplantation. There were no significant differences in the levels of serum transaminases or total bilirubin between the YD and OD groups, but the serum albumin level was significantly lower in the OD group. The YD group grew normally, whereas the OD group recipients lagged significantly in gaining body weight. CONCLUSION: We found that 52-week-old grafts transplanted into 11-week-old recipients resulted in deficient growth and a decline in serum albumin, suggesting that grafted old livers fail to produce enough protein to meet the demands of growth adequately.

Hepatic effects of influxed endothelin-1 from portal vein: in situ portal vein infusion model using dogs.

BACKGROUND/PURPOSE: Endothelin-1 is a potent vasoconstrictor formed by vascular endothelium. This study was designed to investigate the hepatic effect of endothelin-1 produced by portal vascular endothelium. METHODS: Portal venous pressure, portal venous flow, hepatic arterial flow, tissue blood flow, and tissue oxygen pressure were measured during portal vein endothelin-1 infusion in dogs at rates of 1.0 to 5.0 ng/kg per minute. Sinusoidal width during maximal infusion was determined morphometrically. Serum concentrations of mitochondrial glutamic oxaloacetic transaminase and endothelin-1 in portal and hepatic venous blood were also measured. RESULTS: Intraportal endothelin-1 infusion dose-dependently increased portal venous pressure and reduced portal venous and hepatic arterial blood flow. Tissue blood flow and oxygen pressure also decreased. Endothelin-1 also significantly increased serum mitochondrial glutamic oxaloacetic transaminase and constricted hepatic sinusoids. These changes reversed after completion of infusion. CONCLUSIONS: Intraportal endothelin-1 caused circulatory and histological changes in hepatic sinusoids that may suggest the role of endothelin-1 formed by portal venous bed epithelium.

Long-term safety of autotransfusion during hepatectomy for hepatocellular carcinoma.

PURPOSE: To evaluate the long-term safety of autotransfusion (AT) in hepatectomy for hepatocellular carcinoma (HCC). METHODS: Between 1988 and 1989, 46 patients with HCC underwent hepatectomy with AT (group 1). For a comparison, we matched 50 patients with HCC who underwent hepatectomy, and received homologous but not autologous blood (group 2). The 10-year cumulative survival curves and cancer-free curves of the two groups were examined, and the pattern of recurrence was compared. RESULTS: Group 1 had a significantly higher cumulative 10-year survival rate than group 2, at 20% vs 8%, respectively (P < 0.05). Among the patients who underwent curative resection, those in group 1 had significantly better cumulative survival and cancer-free survival rates than those in group 2, at 27% vs 11% (P < 0.05) and 13% vs 0% (P < 0.05), respectively. Among the patients with stage I-II HCC, those in group 1 had significantly better cumulative survival and cancer-free survival rates than those in group 2, at 30% vs 5% (P < 0.01) and 20% vs 5% (P < 0.05), respectively. However, the rates were similar among patients with stage III-IV disease in both groups. The pattern of recurrence in the two groups was similar. CONCLUSION: Autotransfusion promoted survival in patients undergoing hepatectomy for stage I or II HCC.

A novel 3D hepatectomy simulation based on liver circulation: application to liver resection and transplantation.

Hepatectomy is a complicated operative procedure because of its anatomical complexity, vascular variability, and impaired hepatic function due to associated hepatitis or cirrhosis. Thus preoperative detailed topography and precise liver resection volume measurements should be obtained for a curative hepatectomy. The aim of this study was to assess the feasibility and accuracy of a novel three-dimensional (3D) virtual hepatectomy simulation software in patients who underwent liver resection or living donor liver transplantation. We developed the hepatectomy simulation software, which was programmed to analyze detailed 3D vascular structure and to predict liver resection volume and margins. In 72 patients receiving hepatectomy, the predicted liver resection volumes and margins revealed a significant correlation with the actual value with a mean difference of 9.3 mL (P < .0001) and 1.6 mm (P < .01), respectively. The drainage area by hepatic veins was quantified to achieve reconstruction of the corresponding venous branch. In conclusion, this hepatectomy simulation software reliably predicted an accurate liver resection volume, the cancer-free margin, and the drainage volume of hepatic vein branches. This software may promote curative hepatectomy and may be used for other interventional therapies in the treatment of liver disease.

Successful liver resection for biliary atresia with intrahepatic biliary cysts after Kasai procedure.

A 29-year-old woman with congenital biliary atresia underwent liver resection for intrahepatic biliary cyst and recurrent cholangitis long after Kasai procedure. The patient is alive with normal liver function and no episode of cholangitis after 12 months of follow-up.

Hepatic venoplasty to overcome outflow block in living related liver transplantation.

A 14-year-old boy with congenital biliary atresia underwent living related liver transplantation. Because of anatomic variation in donor hepatic vein, there were small and double orifices of hepatic veins in the harvested left hemiliver graft. To minimize the risk of outflow block after reperfusion, the recipient's native hepatic vein was used as an autologous patch for hepatic vein reconstruction. After 3 years of follow-up, the patient is alive and well with normal liver function. Follow-up duplex ultrasound scan showed adequate hepatic vein outflow without signs of late obstruction. The new technique of the autologous vascular patch grafting for successful hepatic vein reconstruction is described.