Yueh-Wei Liu

Serum Levels of Hepatocyte Growth Factor in Patients with Breast Cancer

Objective: Hepatocyte growth factor (HGF) has been reported the cause of many biological events, including cell proliferation, movement, invasiveness, morphogenesis, and angiogenesis. Elevated hepatocyte growth factor content in tumor tissue was reported to predict a more aggressive biology in non–small cell lung cancer patients. However, there is still limited knowledge about the role of HGF in breast cancer. This study was designed with the aim to elucidate the possible relationship between the preoperative circulating soluble HGF and breast cancer. Materials and Methods: One hundred twenty-four consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation and stored at −70°C until assayed. The control group consisted of 35 patients with benign breast tumor (20 with fibrocystic disease and 15 with fibroadenoma). Serum concentrations of soluble HGF were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor staging, age, estrogen receptor status, lymph node status, distant metastases status, histologic grading, and tumor-node-metastasis (TNM) staging were reviewed and recorded. Results: The mean value of serum soluble HGF in patients with invasive breast cancer was 529.05 ± 123.33 pg/mL and that of control group was 343.00± 31.03 pg/mL and the difference was significant (P < 0.001). Furthermore, there were significantly higher serum levels of soluble HGF in patients with negative estrogen receptor (P = 0.035), in patients with poorer differentiated tumor (P < 0.001), in patients with more advanced primary tumor staging (P < 0.001), in patients with more advanced lymph node status (P < 0.001), in patients with distant metastases (P < 0.001), and in patients with more advanced TNM staging (P < 0.001). In multivariate analysis by the multiple linear regression method, TNM staging (P < 0.001) seemed an independent factor regarding the significant higher serum levels of soluble HGF. Conclusion: Patients with more advanced TNM staging were shown to have higher serum soluble HGF. Thus, preoperative serum soluble HGF levels might reflect the severity of invasive breast cancer and deserve further evaluation.

Living donor liver transplantation for hepatocellular carcinoma: a single-center experience in Taiwan.

Background. Living donor liver transplantation (LDLT) demonstrates certain survival benefits over deceased donor liver transplantation for hepatocellular carcinoma (HCC) but there is no consensus on criteria for the use of LDLT for HCC for hepatocellular carcinoma (HCC) taking into account strategies to improve survival. Methods. Thirty-five patients (89% men) underwent LDLT for HCC. The mean age was 51 years (range, 22–61). The median disease severity scores were B, 11–20, and 2B for Child-Turcotte-Pugh, Model for End-stage Liver Disease, and United Network for Organ Sharing, respectively. The transplant records were retrospectively analyzed. Results. All were within Milan criteria at time of transplantation. A novel approach to downstaging tumors initially beyond the Milan criteria was evaluated using transarterial embolization or percutaneous ethanol injection. Our initial results were encouraging as recipients whose tumors had been downstaged had not had recurrence to date. Seven (20%) patients underwent hepatectomy for HCC before undergoing transplant. The overall mean posttransplant follow-up in this series was 40.3 months (range, 23–75). The overall posttransplant complication rate requiring intervention was 11%. There was only one malignancy recurrence for an overall recurrence rate of 3%. Vascular invasion and small- for-size transplants did not seem to influence tumor recurrence. The nonestimated recipient 1-year, 3-year, and 5-year survivals were 98%, 96%, and 90%, respectively. Conclusion. This review emphasizes the need for early disease recognition and prompt intervention when Milan criteria are met to improve survival from HCC after LDLT.

Routine microsurgical biliary reconstruction decreases early anastomotic complications in living donor liver transplantation

Biliary reconstruction using a microsurgical technique in living donor liver transplantation was routinely performed on 88 grafts primarily transplanted into 85 patients. All procedures were performed under a microscope by a single microsurgeon. Except for biliary atresia and Alagille syndrome, duct‐to‐duct reconstruction was performed. Stents were not used. The outcomes with microsurgical biliary reconstruction (MB) were compared with the outcomes of a cohort of 86 grafts in 85 patients that underwent conventional biliary reconstruction (CB). The identification of complications included only up to 12 months of follow‐up for each recipient in both groups. The average graft duct sizes were 2.8 mm for MB and 3.4 mm for CB. Most complications occurred in the first 15 cases with MB, and these cases were considered to constitute the learning curve phase. The MB complication rate was 46.7% in the first 15 cases, 20.0% in the next 15 cases, and 5.4% in the last 55 cases. When the learning curve phase was excluded, the overall complication rate over time with MB (8.9%) was significantly lower than that with CB (21.9%). CB increased the risk of biliary complications by 2.5 times (relative risk: 2.5; attributable risk: 128; odds ratio: 2.9). In conclusion, routine MB is a technical innovation that leads to decreased early anastomotic complications in living donor liver transplantation. Liver Transpl 15:1766–1775, 2009.

Intimal dissection of the hepatic artery following transarterial embolization for hepatocellular carcinoma: An intraoperative problem in adult living donor liver transplantation

The objective of this study was to describe the relationship between intimal dissection (ID) in the recipient hepatic artery (HA) and transarterial embolization (TAE) and highlight the reconstructive methods for the different types of ID encountered in living donor liver transplantation (LDLT). Fifty‐four patients with hepatocellular carcinoma underwent LDLT. ID was classified as mild, moderate, or severe, and this classification was based on the extent of intimal injury. Mild, moderate, or severe ID were defined as ID that was less than one‐quarter of the circumference of the HA, had reached one‐half of the circumference of the HA, or was more than one‐half of the circumference of the HA or involved the entire vessel wall, respectively. The reconstructive methods were based on the severity of ID encountered. Forty patients underwent TAE before LDLT, and 23 of these patients (57.5%) had ID. Nine patients had mild ID, 6 had moderate ID, and 8 had severe ID. In the 14 patients who did not undergo TAE, 4 had ID (28.6%; 3 mild and 1 severe). The other 10 patients (71.4%) had normal HA. In mild and moderate ID, the native HA was used after trimming of the HA until a healthy segment was encountered. In severe ID, the HA was reconstructed with alternative vessels. Two HA thromboses occurred postoperatively. TAE increased the risk of developing ID 2‐fold. There was no graft loss or mortality in this series due to HA complications. In conclusion, ID of the HA is associated with pretransplant TAE among hepatocellular carcinoma patients undergoing LDLT. Intraoperative recognition of this complication and trimming until good vessel quality is encountered or using alternative vessels are important. Liver Transpl 15:1553–1556, 2009.

Improving hepatic and portal venous flows using tissue expander and Foley catheter in liver transplantation

Abstract:  Background and objective:  Vascular reconstruction is important in liver transplantation because its obstruction causes graft failure and eventual loss. Vascular outflow obstruction may be due to graft malposition. We describe our experience with liver allograft repositioning using tissue expander and Foley catheter to improve hepatic and portal venous outflows.

Section 14. Combination of entecavir plus low-dose on-demand hepatitis B immunoglobulin is effective with very low hepatitis B recurrence after liver transplantation.

Background and Aims Antiviral prophylaxis with hepatitis B immunoglobulin (HBIg) plus lamivudine reduces the risk of hepatitis B virus (HBV) recurrence after HBV-related liver transplant (LT). However, HBIg is expensive, and lamivudine therapy is limited by drug resistance. This study assessed a pilot study of entecavir plus low-dose, on-demand HBIg in preventing HBV recurrence after LT. Methods Between 2006 and May 2011, approximately 145 patients undergoing HBV-related LT and receiving entecavir plus low-dose, on-demand HBIg were enrolled and followed for a median of 36 months. A historical control group of 171 patients undergoing HBV-related LT between 1998 and 2010 and receiving lamivudine plus HBIg were followed for a median of 77 months. The primary end point was the proportion of patients with recurrent HBsAg-positivity. Results In the entecavir cohort, 2 (1.37%) of 145 patients experienced HBV recurrence, none of which had evidence of viral resistance. In the lamivudine cohort, 11 (6.4%) of 171 cases of HBV recurrence were observed, 5 of which were associated with lamivudine resistance. The cumulative probabilities of HBV recurrence were significantly different between both cohorts (P=0.055). HBsAg recurrence was associated with lower overall survival (P<0.001), even in patients with undetectable HBV DNA. Using pooled data from both cohorts, predictors of HBV recurrence were nucleoside selection, pre-LT hepatocellular carcinoma, post-LT low anti-HBs, male sex, and HBsAg-positivity in the explant liver tissue. Conclusions Entecavir plus low-dose, on-demand HBIg resulted in a low rate of HBV recurrence without evidence of resistance development and provided an effective and cost-saving strategy for patients having HBV-related LT.

Living donor liver transplantation: the Asian perspective.

Preoperative evaluation of donors for living-donor liver transplantation aims to select a suitable donor with optimal graft quality and to ensure donor safety. Hepatic steatosis, a common finding in living liver donors, not only influences the outcome of liver transplantation for the recipient but also affects the recovery of the living donor after partial hepatectomy. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but it is invasive, and results are vulnerable to sampling error. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. This article describes potential clinical applications for liver fat quantification of imaging methods for fat detection and quantification, with an emphasis on the advantages and limitations of ultrasonography, computed tomography, and magnetic resonance imaging for quantifying liver fat.

Dual grafts in adult-to-adult living donor liver transplantation: A single center experience in Taiwan

Volume mismatch is encountered when a single live donor cannot provide adequate graft volume to the recipient with a remnant liver volume which is safe for donation. Our objective is to present our experience in living donor liver transplantation using dual grafts. Record review of 4 dual graft recipients was done. The results were compared with 122 consecutive patients who received a single right lobe. All dual graft recipients were surviving with satisfactory liver function at a median follow-up of 21 months. Two recipients received 1 right and 1 left lobe graft, while the other 2 recipients received 2 left lobe grafts. One donor developed biloma and was managed by percutaneous drainage. The first recipient required re-laparotomy for postoperative bleeding. The second recipient underwent re-laparotomy for bile leak. The third recipient developed grade II decubitus ulcers due to a prolonged sedentary position. When compared with recipients who received a single right lobe, the operative time was prolonged in the dual graft group. There was no apparent increase in the rate of vascular and biliary complications or the incidence of acute cellular rejection. Actuarial patient survivals were comparable in both groups. Dual graft transplantation provides sufficient volume in the recipient without jeopardizing donor safety.

Bispectral Index Monitoring in Healthy, Cirrhotic, and End-Stage Liver Disease Patients Undergoing Hepatic Operation

The purpose of this study was to assess factors influencing the end-tidal concentrations of isoflurane within a bispectral index (BIS) range of 45-55 among healthy live liver donors (n = 11), chronic hepatitis B patients undergoing hepatectomy hepatocellular carcinoma (n = 10), and end-stage liver disease patients undergoing liver transplantation (n = 7). Patients data collected prospectively were compared among the groups using one-way analysis of variance as well as univariate and multivariate techniques. The results showed that end-stage liver disease patients required the least end-tidal isoflurane concentration. Patients with hepatocellular carcinoma with cirrhosis required intermediate end-tidal isoflurane concentrations; healthy live liver donors required the highest end-tidal isoflurane concentrations to provide sufficient anesthetic depth, as monitored by a target BIS (range, 45-55). Upon multivariate analysis, liver function was the only significant factor influencing the likelihood of lowering the end-tidal isoflurane concentration by 4 hours after anesthesia induction (P = .026). In conclusion, we recommend a preset target BIS within the range of 45-55 to monitor the depth of anesthesia during partial hepatectomy and liver transplantation because end-tidal isoflurane concentration requirements are different for patients with various liver status. This strategy may protect the patients from intraoperative recall or anesthesia over-depth as a consequence of insufficient or overdose of anesthesia, respectively.

Intra-operative management of low portal vein flow in pediatric living donor liver transplantation

For pediatric living donor liver transplantation, portal vein complications cause significant morbidity and graft failure. Routine intra‐operative Doppler ultrasound is performed after graft reperfusion to evaluate the flow of portal vein. This retrospective study reviewed 65 children who had undergone living donor liver transplantation. Seven patients were detected with suboptimal portal vein flow velocity following vascular reconstruction and abdominal closure. They underwent immediate on‐table interventions to improve the portal vein flow. Both surgical and endovascular modalities were employed, namely, graft re‐positioning, collateral shunt ligation, thrombectomy, revision of anastomosis, inferior mesenteric vein cannulation, and endovascular stenting. The ultrasonographic follow‐up assessment for all seven patients demonstrated patent portal vein and satisfactory flow. We reviewed our experience on the different modalities and proposed an approach for our future intra‐operative management to improve portal vein flow at the time of liver transplantation.