Chih-Hsien Cheng

Surgical resection of centrally located large hepatocellular carcinoma.

BACKGROUND Centrally located large hepatocellular carcinoma (HCC) is a difficult issue in surgery. These HCCs can be treated by hemi-/extended or central hepatectomies. The aim of this study was to analyze the results of hemi-/extended and central hepatectomies. METHODS One hundred and four patients with centrally-located large tumors were retrospectively reviewed. Patients were divided into group 1 (n = 41) with hemi-/extended hepatectomies, and group 2 (n = 63) with central hepatectomies. Characteristics were analyzed between groups and survival rates were calculated. RESULTS Parenchyma resection was limited in group 2. The resection margin in 92.6% of group 2 patients was < 1 cm, compared with 78.9% of group 1 patients (p = 0.056). The 1- and 5-year disease-free survival rates were 50% and 38.9% for group 1, and 50% and 15% for group 2 (p = 0.279). The 1-, 5-year overall survival rates were 89.5% and 66.2% for group 1 and 87.5% and 53.1% for group 2 (p = 0.786). Cirrhosis, the preoperative aspartate aminotransferase (AST) level and lower resected liver weight were independent factors impairing survival. CONCLUSION Hemi-/extended and central hepatectomies have comparable complication rates and long-term survival rates for patients with centrally located large HCC. Cirrhosis, the AST level and resected liver weight were independent factors determining long-term survival.

Prognostic significance of the number of tumors and aggressive surgical approach in colorectal cancer hepatic metastasis

BackgroundAlthough liver resection (LR) for colorectal cancer (CRC) hepatic metastasis is the best strategy to improve patient outcomes, there are considerable concerns regarding the recurrence of CRC after LR. In this study, we investigated the prognostic indicators associated with CRC recurrence after LR for hepatic metastasis.MethodsThis is a retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and December 2012. The clinicopathological features and outcome parameters affecting prognosis were analyzed.ResultsA total of 332 LRs with curative intent were performed in 278 patients, of whom 168 (60.4%) experienced CRC recurrence after the first LR, and 206 of the 332 LRs (62.0%) developed CRC recurrence. A preoperative serum carcinoembryonic antigen level greater than 100 ng/mL and four or more metastatic tumor nodules were independent prognostic factors for CRC recurrence after LR. The disease-free survival rate after LR was significantly associated with the number of metastatic nodules. The patients who underwent surgical resection for recurrent CRC had favorable outcomes, with a five-year overall survival rate of 65.2%.ConclusionThe number of metastatic tumors significantly affects the outcomes of patients who undergo LR for CRC hepatic metastasis, indicating that a novel therapeutic strategy for patients at high risk may be required. However, favorable long-term outcomes are achievable through aggressive treatment with surgical resection of the recurrent CRC.

Risk Factors and Clinical Outcomes of Ventilator-Associated Pneumonia in Patients on the Liver Transplant Waiting List

BACKGROUND Prolonged intubation results in ventilator-associated pneumonia (VAP), which contributes to significant mortality among patients on the waiting list. The aim of this study was to determine the risk factors for and clinical outcomes of VAP among patients into the intensive care unit (ICU). METHODS We enrolled 50 consecutive critically ill patients with end-stage liver disease admitted to the ICU from January 2005 through December 2010. All patients were intubated for more than 4 days; no definite infection was found initially. We evaluated potential risks factors for VAP and clinical outcomes. RESULTS Smoking, underlying liver disease, and lobar focal consolidations were significant factors for patients with versus without VAP. Fourteen-day mortality rates were 61.5% for VAP versus 40.5% for patients without VAP. Twenty-eight-day mortality rates for both groups were 92.3% and 86.5%, respectively. Multivariate analysis failed to identify independent predictors of early 14-day mortality. CONCLUSIONS Underlying liver disease and lobar focal consolidations were risks factors for VAP in patients with prolonged intubation. Patients with prolonged intubation have a dismal prognosis even without VAP. The clinical outcomes of patients with versus without VAP were similar. However, early liver transplantation (<14 days of intubation) improves the chance to rescue patients before development of VAP.

Ligation of the proximal splenic vein to overcome the effects of a large splenorenal shunt during living donor liver transplantation

Patients with severe cirrhosis with portal hypertension may develop a splenorenal shunt (SRS) spontaneously to divert portal flow. After transplantation, the SRS may be occluded spontaneously. However, a large SRS may persist. This persistent SRS can steal portal flow and cause portal vein thrombus, hepatic encephalopathy, and graft dysfunction. The methods to manage a large SRS in deceased donor liver transplantation include splenectomy, ligation of the SRS, ligation of the left renal vein, and percutaneous transfemoral embolization. In living donor liver transplantation, management of a large SRS becomes more complicated because closure of an SRS to increase portal flow may increase portal pressure and shear stress and result in small-for-size syndrome (SFSS). Therefore, the management of a large SRS during living donor liver transplantation has become a dilemma. Here we introduce ligation of the proximal splenic vein (SV) to resolve this dilemma. This study was approved by local ethic committee of ChangGung Memorial Hospital (IBR No. 101-2410B). A 51-year-old male patient had hepatitis C–related cirrhosis and hepatocellular carcinoma. Liver transplantation was performed because of tumor recurrence after radiofrequency ablation and transarterial chemoembolization. His body height was 168 cm, and his body weight was 81 kg. The liver cirrhosis status was Child-Pugh B, and the Model for End-Stage Liver Disease score was 13. Pretransplant computed tomography (CT) showed the diameter of the portal vein to be very small, and the portal flow was shunted into the renal vein via a large spontaneous SRS (Fig. 1). The living donor was the patient’s 45-year-old sister, whose body height was 162 cm and whose body weight was 56.4 kg. The liver volume calculated by CT volumetry was 1272.9 cm. The right lobe of the liver was 51.8% as calculated by Lee’s formula with the diameters of right and left portal veins, and the estimated graft weight was 659 g. During the donor operation, the right lobe of the liver without the middle hepatic vein was procured and weighed 650 g. The graft-to-recipient weight ratio was 0.80%. During the recipient’s operation, we found that the caliber of the portal vein was small, and the portal flow was 200 mL/minute as measured by a flowmeter (Transonic Systems, Ithaca, NY). Therefore, the infrapancreas superior mesenteric vein (SMV) was identified and exposed. The tunnel between the pancreatic neck and the SMV was made. The junction between the SMV and SV was hooked upward and snared with a 1-0 silk thread (Fig. 2). Subsequently, the native liver was removed, and the liver graft was implanted. The portal vein was reconstructed via the grafting of the recipient’s native portal vein to the graft portal vein. The portal flow was 500 mL/minute as measured by the flowmeter immediately the graft was reperfused. When the proximal SV was ligated, the portal flow was increased to 800 mL/minute. The hepatic artery was reconstructed by a microscopic technique, and the flow was 220 mL/minute. Posttransplant Doppler liver echo revealed a patent portal vein with a flow between 698 and 1051 mL/minute on early postoperative days. The patient was discharged uneventfully in week 4 after transplantation. A CT scan in postoperative month 4 showed a patent portal vein with a flow directly from the SMV, and the SRS was separated from the portal flow completely (Fig. 3). The diameter of the SV proximal and distal to the SRS was 10 and 14.7 mm, respectively (13.4 and 14.5 mm before transplantation). This meant that the splenic venous flow was totally decompressed into the left renal vein via the SRS. The liver volume was estimated to be 1190 cm by CT volumetry. Ligation of the proximal SV is a novel method to keep the portal vein flow adequate and separated from the large SRS completely. In living donor liver transplantation, the graft is smaller than a deceased donor liver graft. Closure of the large SRS to increase portal flow may increase portal pressure and shear stress and cause SFSS. Ligation of the proximal SV near the

Effects of Converting Tacrolimus Formulation from Twice-Daily to Once-Daily in Liver Transplantation Recipients

Typically, tacrolimus is administrated twice daily. Prolonged-release tacrolimus is the once-daily formulation and may be more convenient for patients. Experience with the administration of the once-daily formulation is still limited. This study enrolled 210 liver transplant recipients who had stable liver function and converted tacrolimus from a twice-daily to once-daily formulation on a 1 mg to 1 mg basis. Among 210 patients, seven patients (3.3%) were withdrawn from the once-daily formulation due to allergy and fatigue. For the other patients, the trough concentration after converting to the once-daily formulation was lower than that of the twice-daily formulation. Liver enzymes were mildly elevated in 3 months after formulation conversion and serum creatinine and uric acid were mildly decreased. Seven patients (3.4%) had clinical suspicion of acute rejection after the formulation conversion and three of them were caused by nonadherence. 155 patients (76.4%) experienced a more convenient life with an increase of social activity. Forty-seven patients (23.2%) experienced the convenience of once-daily formulation during overseas trips. In conclusion, tacrolimus can be safely converted from the twice-daily to the once-daily formulation for most stable liver recipients. Acute rejection may occur in a minority of patients during formulation conversion and should be carefully monitored.

Viral activity and outcome of hepatitis B surface antigen-positive grafts in deceased liver transplantation

Indications of liver transplantation are extensive, but deceased donation does not meet the demand. Hepatitis B surface antigen (HBsAg)‐positive grafts used to be discarded in the past. The aim of this study was to examine viral activity and outcome of HBsAg‐positive deceased grafts transplanted to HBsAg‐positive recipients. Eleven HBsAg‐positive deceased grafts were transplanted to HBsAg‐positive patients with acute liver failure (3 patients), hepatocellular carcinoma (6 patients) and repeatedly bleeding varices (2 patients). Postoperatively, hepatitis B virus (HBV) infection was treated by a combination of antiviral nucleoside and nucleotide analogues. HBV DNA and HBsAg were measured periodically. The median (interquartile) model of end‐stage liver disease score for the recipients was 19 (16‐32) with a range from 11 to 40. HBV DNA was detected in 6 patients with a range from 61 to 1083 IU/mL before transplantation. After transplantation, HBV DNA was detected in 4 patients in the first month and 2 patients in the 6th month and became undetectable for all patients at end of the first year. The quantitative HBsAg ranged from 0.86 to 241.1 IU/mL at 6 months and 0.34 to 238.5 IU/mL at 24 months (P = .135). Three of the patients died in the early phase, and the other patients were followed up for 40.0 ± 19.2 months with normal liver function. In conclusion, HBsAg‐positive deceased liver grafts function well with minimal viral activity under treatment of combined antiviral nucleoside and nucleotide analogues. Use of HBsAg‐positive deceased grafts is feasible and increases the donor pool to rescue dying patients.

De Novo Endotoxin-Induced Production of Antibodies against the Bile Salt Export Pump Associated with Bacterial Infection following Major Hepatectomy

Background Clinically severe infection-related inflammation after major liver resection may cause hyperbilirubinemia. This study aims to clarify the impact of bacterial infection and endotoxins on the hepatobiliary transporter system and to explore possible mechanisms of endotoxin-related postoperative hyperbilirubinemia. Method Mice that underwent major hepatectomy with removal of at least 70% of liver volume were exposed to lipopolysaccharide (LPS) at different dosages. Subsequently, hepatobiliary transporter compounds related to bile salt excretion were further investigated. Results The expression of genes related to hepatobiliary transporter compounds was not significantly different in the liver tissue of mice after major hepatectomy and LPS exposure. However, bile salt export pump (BSEP) protein expression within the liver tissue of mice treated with LPS after major hepatectomy was relatively weaker and was even further reduced in the high-dose LPS group. The formation of antibodies against the BSEP in response to endotoxin exposure was also detected. Conclusion This study illustrates a possible mechanism whereby the dysfunction of hepatobiliary transporter systems caused by endotoxin-induced autoantibodies may be involved in the development of postoperative jaundice associated with bacterial infection after major hepatectomy.

Difficult Situation of Pancreas Transplantation in the Setting of Scarce Organ Donation

BACKGROUND Currently, pancreas transplantation has been a promising strategy to restore long-term normoglycemia as well as to improve life quality for patients with insulin-dependent diabetes mellitus (DM). However, the discrepancy between the number of organs needed and the number donated for transplantation is always enormous. Under a setting of scarce organ donations, we examined our limited experience of pancreas transplantation. METHODS A retrospective review of pancreas transplantations was performed with the use of data from the Taiwan Organ Registry and Sharing Center and the Ministry of Health and Welfare. Pancreas transplantations in the Organ Transplantation Institute of Chang Gung Memorial Hospital also were reviewed. RESULTS At present, there are 5 medical centers approved for pancreas transplantation in Taiwan. Overall, a total of 156 pancreas transplantations were performed from 2005 to the end of 2016; only 9 of them were performed in the Organ Transplantation Institute of Chang Gung Memorial Hospital. Although the number of organ donations is rising, pancreas transplantation numbers remain low. More than 20 pancreas transplantations were performed in 2016, yet there remained a total of 111 patients registered on the wait list for pancreas transplantation at the end of this study. Thus the gap between organ donation and transplantation is still vast. CONCLUSIONS With continuing improvements in Taiwanese health policies and public education regarding organ transplantation, organ donation rates have risen steadily in recent years. Moreover, quality control and continuing evolution in organ transplantation is crucial to ameliorate the difficult situation of pancreas transplantation and other solid organ transplantation in the context of low levels of donation.

Impact of neutrophil to lymphocyte ratio on survival for hepatocellular carcinoma after curative resection

Neutrophil‐lymphocyte ratio (NLR) represents a pro‐tumor inflammatory environment and host immunity. The aim of this study was to examine the effect of subsequent NLR for hepatocellular carcinoma (HCC) after liver resection.

Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease

Chronic renal failure is a frequent complication in liver transplantation. Telbivudine, anti-hepatitis B virus (HBV) nucleoside, can improve renal function. It is interesting if using telbivudine for prophylaxis of HBV recurrence has additional value on renal function improvement. 120 liver transplant recipients with lamivudine prophylaxis for HBV recurrence were 1 : 1 randomized into lamivudine-continuous (n = 60) and telbivudine-replacement (n = 60) groups. Fifty-eight patients in lamivudine-continuous group and 54 in telbivudine-replacement group completed the study. In telbivudine-replacement group, the estimated glomerular filtration rate (eGRF) was improved from 63.0 ± 16.3 ml/min to 72.8 ± 21.1 ml/min at 12 months after telbivudine administration (p = 0.003). Stratifying the patients according to renal function staging, the eGRF was improved from 74.7 ± 6.9 ml/min to 84.2 ± 16.6 ml/min (p = 0.002) in 32 stage II patients and from 48.2 ± 7.3 ml/min to 59.7 ± 11.8 ml/min in 20 stage III patients after 12 months of telbivudine administration (p < 0.001). Eleven (18.3%) patients with telbivudine developed polyneuritis during the trial and post hoc following-up. In conclusion, renal function was improved by telbivudine in liver transplant recipients with long-term chronic kidney disease. However, the high incidence of polyneuritis induced by telbivudine has to be closely monitored. This trial is registered with ClinicalTrials NCT02447705.