Liver transplantation for advanced hepatocellular carcinoma

There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future.

A multicenter experience with generic mycophenolate mofetil conversion in stable liver transplant recipients

PURPOSE: Generic substitution of brand-name medications can lead to significant cost savings and is an accepted medical practice. This study evaluated clinical and safety outcomes among liver transplant recipients whose mycophenolate mofetil (MMF) was converted from the brand-name formulation (Cellcept) to a generic formulation (My-rept). METHODS: Clinical data from multiple centers were prospectively collected for determination of complications, safety, and quality of life after in 154 clinically stable, adult liver transplant recipients whose MMF was converted to a generic formulation between April 2010 and September 2012. This protocol was approved by Institutional Review Boards of all involved sites. RESULTS: In eight patients (5.19%), nine instances of drug-related complications occurred after medication conversion. Half of these complications were gastrointestinal disorders (n = 4), and most (7 of 9) were mild. No significant differences were noted in mean pre- and postconversion gastrointestinal symptoms via a rating system (8.9 vs. 10.4) or gastrointestinal quality-of-life index scores (125.6 vs. 123.1). More than 90% of patients reported a status of "about the same" when questioned about the brand-name and generic formulation using the Patient Overall Treatment Effect and Investigator Overall Treatment Effect measures. The incidence of serious adverse events was 5.8%. Acute rejection occurred in two patients, with no graft loss or death. CONCLUSION: Clinical experience as well as research data showed that generic MMF was comparable in efficacy to the brand-name drug. Given the lack of adverse events and the safety findings, conversion from brand-name MMF to generic MMF should be encouraged.

Paralysis of the right hemidiaphragm after liver transplantation: diagnosis and management / 中华肝胆外科杂志

Objective To review our experience in the diagnosis and management of paralysis of the right hemidiaphragm after liver transplantation. Methods 60 adult patients received liver transplantation from February 2001 to March 2007 in Sun Yat-sen Memorial Hospital were retrospectively analyzed. The pathophysiologic changes, clinical progress, and management of serious respiratory complications caused by post-transplant paralysis of the right hemidiaphragm were studied. Results Among 60 patients, 40 developed postoperative respiratory complications, and 5 were due to paralysis of the right hemidiaphragm. The 5 patients presented with paradoxical respiration and the ventilator supporting times were 14, 16, 34, 45, and 60 days, respectively. Tracheostomy was performed in 4. These patients developed pneumonia in 5, atelectasis in 4, acute respiratory distress syndrome (ARDS) in 4, hepatopulmonary syndrome in 4, and pulmonay interstitial edema in 3. Among the 5 patients, 4 patients survived and 1 patient died of ARDS and multiple organs failure 31 days after the transplantation. Conclusions After liver transplantation, strict monitoring of the respiratory function and timely use of a respirator for patients with the paralysis of the hemidiaphragm is very important. For patients with suspicious hemidiaphragm paralysis, tracheostomy should be decisively performed.

Síndrome hepatorrenal: Revisión de la literatura y análisis crítico de los criterios diagnósticos / Hepatorenal Syndrome: Review of the literature and critical analysis of diagnostic criteria

El síndrome hepatorrenal es una falla renal funcional que ocurre en pacientes con enfermedad hepática avanzada e hipertensión portal. Su fisiopatología es hoy en día materia de numerosos estudios. Se propone en esta revisión unos nuevos criterios diagnósticos y se revisa la fisiopatología y numerosas modalidades de tratamiento.

Hepatorenal syndrome a review of literature and critique analysis of diagnostic criteria. The hepatorenal syndrome is a functional renal failure that occurs in patients with severe liver disease and portal hypertension. Its pathophysiology is not clear and theme of several studies. New diagnostic criteria, pathophysiolgy and treatments are reviewed in this article.

Evaluation of Serum Magnesium Concentration Changes in Orthotopic Liver Transplant Patients / 대한마취과학회지

BACKGROUND: During orthotopic liver transplantation, magnesium monitoring has been done frequently because of its important role in the cardiovascular system. Generally hypomagnesemia may occur frequently during an operation, but some investigators reported serum magnesium levels returned to normal after reperfusion which is different from our result. Therefore, this study was done to confirm the changes of serum magnesium in the postanhepatic stage and also to confirm the need for prophylactic magnesium administration. METHODS: Thirteen patients plasma magnesium concentrations were measured 8 times during the operation on each patient. We also checked the total transfusion amount and required CaCl2 amount in every patient. The significance of all data were evaluated with a paired t-test and correlation method. RESULTS: Serum magnesium levels were significantly decreased after the beginning of the postanhepatic stage during an operation (P < 0.05). Correlation between transfused blood amounts and CaCl2 requirements showed significant correlation (r: 0.709), but no correlation between magnesium concentrations and transfused blood amounts was found. CONCLUSIONS: We concluded that serum magnesium concentrations were significantly decreased especially in the postanhepatic stage and an appropriate amount of a magnesium supply may be needed.

Anesthesia for Liver Transplantation in Patients with Hepatopulmonary Syndrome / 대한마취과학회지

Hepatopulmonary syndrome is essentially the triad of liver disease, pulmonary vascular dilations and abnormal arterial oxygenation, which can result in severe hypoxia. We managed two cases of 9 and 49-year-old males for liver transplantation with hepatopulmonary syndrome. Preoperative evaluation showed decreased diffusion capacity of carbon monooxide and severe hypoxemia, while breathing room air (PaO2 < 60 mmHg) but they responded to oxygen therapy. The pulmonary vascular resistance was low, consistent with an intrapulmonary vascular shunt but the pulmonary artery pressure was normal, reflecting a high cardiac output. Intraoperative oxygenation was satisfactory (PaO2 of 100 - 200 mmHg) in spite of a high shunt fraction (Qs/Qt 18.5 +/- 9.2%). This means that the impairment in gas exchange is not the result of a true shunt, suggesting the presence of a functional shunt, which is characterized by diffusion-perfusion impairment. The intraoperative course was uneventful in the two patients and they are in a successful postoperative course. In case 1, the hypoxemia was resolved promptly, but in case 2, it was persistent for sixteen months after transplantation. The hypoxemia itself in hepatopulmonary syndrome is not regarded as a contraindication to liver transplantation. (Korean J Anesthesiol 2001; 40: 677 ~ 683)

Application of continuous renal replacement therapy to the patients with acute renal failure after liver transplantation / 解放军医学杂志

Objective To study the curative effect of continuous renal replacement therapy (CRRT) to the patients with acute renal failure after liver transplantation. Methods From Mar. 2004 to Jan. 2005, the continuous renal replacement therapy was applied to 7 patients with acute renal failure after liver transplantation. The average time of CRRT was 36.1h. The volume of fluid displacer during CRRT was 2-4L/h and the volume of blood flow was 150～250ml/min. Normal heparin was used as anticoagulant. Results For the 7 patients, 4 improved, 2 died. The contents of blood urea nitrogen (BUN) and blood Cr of all the 7 patients have obviously declined(P0.05). The haemodynamic variables were stabilized during CRRT and no obvious side-effect related to CRRT was found. Conclusions CRRT improved the prognosis to the patients with acute renal failure after liver transplantation, showed a favorable tolerance, and may be applied as a emergency measure to the patients with acute renal failure.

The Effect of Lipo-PGE1 on Ischemia-Reperfusion Injury and Endothelin-1 Concentrations After Canine Partial Liver Transplantation / 대한간학회지

BACKGROUND/AIM: The lipo-PGE1, known for being more stable during pulmonary circulation and having more targeting effect, has been reported to inhibit ET-1 induced stellate cell contraction. We assessed the effect of lipo-PGE1 on the change of ET-1 concentration and the relationship between ET-1 concentration and the liver damage. METHODS: Mongrel dogs weighing about 25 kg were divided into a control (n=6) and a lipo-PGE1 (n=6) group. Partial liver allotransplantation was performed. In the lipo-PGE1 group, lipo-PGE1 was slowly infused through splenic venous cannulation during the donor liver harvesting procedure (50 microgram) and continuously infused (60 microgram/day) for 48 hours after reperfusion. The AST, ALP, LDH and ET-1 concentrations were monitored RESULTS: The AST and ALP levels of the lipo-PGE1 group were significantly lower than those of the control group both at 1 hour and 48 hours after reperfusion. The LDH level in the lipo-PGE1 group was lower at 1 hour and 48 hours after reperfusion. But there was no statistical difference between the two groups. The baseline ET-1 concentration of the lipo-PGE1 group was eight times higher than that of the control group. The ET-1 concentration was elevated gradually in the control group. There was no significant difference between the two groups at 48 hours. There was no correlation between ET-1 concentrations and AST, ALP, LDH levels. CONCLUSION: This study demonstrated the hepatoprotective effect of the lipo-PGE1 against ischemia-reperfusion injury in canine partial liver allotransplantation. However, the baseline ET-1 level was eight times higher in the lipo-PGE1 group than that of the control group in spite of the hepatoprotective effects of the lipo-PGE1.

Clinical Evaluation of Serum Magnesium Concentration and Its Related Effects after Prophylactic MgSO4 Administration during Orthotopic Liver Transplantation / 대한마취과학회지

BACKGROUND: Mg++ is an important control factor for transport of K+, Na+, Ca++ and also has been known for having an antiarrhythmic and inotropic action on the heart. Orthotopic liver transplantation is a complex surgical procedure with significant physiologic alterations resulting in electrolyte imbalances. Therefore, the goal of this study was to evaluate the effects of prophylactic MgSO4 administration on intraoperative serum magnesium concentration and its related clinical outcomes. METHODS: 19 patients receiving liver transplants were divided into two groups. Both groups received normal saline (300 ml/3 hr) right after anesthetic induction. MgSO4 (35 mg/kg) was mixed with saline in the experimental group but not in the control group. Serum magnesium concentration was measured four times during surgery. We also checked the total transfused units of packed cells and CaCl2 requirement, the severity of postreperfusion syndrome and base deficit. RESULTS: Serum magnesium concentration significantly decreased in the control group at the postanhepatic stage. The experimental group showed less prominent symptoms of postreperfusion syndrome and less need for potassium supply, but both groups did not reveal any differences in the amount of transfusion and CaCl2 requirement. CONCLUSIONS: We confirmed that our prophylactic administration of MgSO4 (35 mg/kg) may be considered a safe dose showing not only prevention of hypomagnesemia but also a decrease in the potassium requirement and in the severity of postreperfusion syndrome. However, routine administration of MgSO4 might cause disadvantageous effects, so more appropriate indications can be prepared after further clinical research.

Acid-Base Status without Sodium Bicarbonate Administration during Orthotopic Liver Transplantation / 대한마취과학회지

BACKGROUND: Marked derangements in acid-base status are frequently seen during orthotopic liver transplantaton. To prevent the progression of metabolic acidosis, treatment with sodium bicarbonate has been recommended. However, sodium bicarbonate may exacerbate intracellular acidosis, increase plasma lactate, contribute to hypernatremia. The value of giving bicarbonate has been questioned. Accordingly, we reviewed the intraoperative the acid-base status of patients who underwent orthotopic liver transplatation. METHODS: We reviewed ten patients showed severe metabolic acidosis (7.2 or = 10). Despite of BD > or = 10, sodium bicarbonate was not given to all. Intraoperative pH and BD were analyzed retrospectively. RESULTS: At the anhepatic and immediate post-reperfusion periods, the pH was decreased (P < 0.05) and BD was increased (P < 0.05), but both were normalized at the end of surgery. The mean blood pressure transiently decreased at the immediate post-reperfusion periods (P < 0.05), but that was acceptable. CONCLUSIONS: This study showed that a severe metabolic acidosis is tolerated by the patients undergoing orthotopic liver transplantation without administration of sodium bicarbonate.

Acid-Base Status without Sodium Bicarbonate Administration during Orthotopic Liver Transplantation / 대한마취과학회지

BACKGROUND: Marked derangements in acid-base status are frequently seen during orthotopic liver transplantaton. To prevent the progression of metabolic acidosis, treatment with sodium bicarbonate has been recommended. However, sodium bicarbonate may exacerbate intracellular acidosis, increase plasma lactate, contribute to hypernatremia. The value of giving bicarbonate has been questioned. Accordingly, we reviewed the intraoperative the acid-base status of patients who underwent orthotopic liver transplatation. METHODS: We reviewed ten patients showed severe metabolic acidosis (7.2 or = 10). Despite of BD > or = 10, sodium bicarbonate was not given to all. Intraoperative pH and BD were analyzed retrospectively. RESULTS: At the anhepatic and immediate post-reperfusion periods, the pH was decreased (P < 0.05) and BD was increased (P < 0.05), but both were normalized at the end of surgery. The mean blood pressure transiently decreased at the immediate post-reperfusion periods (P < 0.05), but that was acceptable. CONCLUSIONS: This study showed that a severe metabolic acidosis is tolerated by the patients undergoing orthotopic liver transplantation without administration of sodium bicarbonate.

A Total Intravenous Anesthetic Experience of Pediatric Living Related Liver Transplantation with Propofol: A case report / 대한마취과학회지

We have experienced one case of anesthesia for living related liver transplantation with propofol. The recipient was 18-month-old girl and 10.5 kg. She was suffered from congenital liver disease (biliary atresia). We decided propofol as an anesthetic agent of the recipient with permission of the recipient's parents. Total anesthetic time was about 13 hours and anhepatic phase was 110 min. Careful attention was paid to prevent infection, hypothermia, hepatic artery thrombosis and to keep proper lung function. Hemodynamic changes were relatively stable throughout the operation and postoperative mechanical ventilatory support was required for about 2 days.

A Total Intravenous Anesthetic Experience of Pediatric Living Related Liver Transplantation with Propofol: A case report / 대한마취과학회지

We have experienced one case of anesthesia for living related liver transplantation with propofol. The recipient was 18-month-old girl and 10.5 kg. She was suffered from congenital liver disease (biliary atresia). We decided propofol as an anesthetic agent of the recipient with permission of the recipient's parents. Total anesthetic time was about 13 hours and anhepatic phase was 110 min. Careful attention was paid to prevent infection, hypothermia, hepatic artery thrombosis and to keep proper lung function. Hemodynamic changes were relatively stable throughout the operation and postoperative mechanical ventilatory support was required for about 2 days.

Clinical Evaluation of Unplanned Extubation in Liver Transplant Patients / 대한마취과학회지

BACKGROUND: Unplanned extubation is a common occurrence in mechanically ventilated patients even in spite of careful attention. It is important to decide on reintubation or the retention of the extubated state especially in the critically ill patients. We tried to formulate general guideline for evaluation and safe management in unplanned extubated liver transplant patients with high risk of multiple organ failure and high mortality rate. METHODS: We reviewed all medical records of 5 unplanned extubated cases from 27 liver transplantation cases. We checked delayed extubation criteria which included United Network Organ Sharing (UNOS) class 1 or 2, preoperative Na (below 130 mEq) and albumin (below 3.0) level, transfusion amount in operating room, severity of postreperfusion syndrome (PRS) and need of vasopressor agents in the 5 unplanned extubated cases. We also checked direct intubation determining factors such as PaO2/FiO2 ratio, respiration rate and pattern, mental state and mode of ventilation. Finally, we reviewed additional factors influencing reintubation. RESULTS: We found a rate of 18 percent of unplanned extubation (5 of 27 events), and 80 percent of reintubation incidence (4 of 5 events). CONCLUSIONS: It is rational to reintubate immediately in unplanned extubated cases which meet 3 or more delayed extubation criteria. The direct reintubation determining factors are PaO2/FiO2 ratio (below 300) and the presence of paradoxical respiration with a high respiration rate (over 28/minute).

Evaluation of Clinical Factors Associated with Early Tracheal Extubation after Liver Transplantation / 대한마취과학회지

BACKGROUND: The timing of tracheal extubation in patients undergoing major intraoperative procedures is controversial. Immediate postoperative tracheal extubation after liver transplantation was not popularized. But in these days, early tracheal extubation has been safely performed in certain cases and routine use of mechanical ventilation is being questioned. We performed preliminary study of our 25 liver transplantation cases to evaluate factors affecting duration and indications of postoperative mechanical ventilation. METHODS: Our 25 cases were divided into two groups by periodic difference - early 13 cases (group 1) and late 12 cases (group 2). We evaluated preoperative UNOS (united network for organ sharing) scale, intraoperative transfusion and vasopressor requirement, postoperative multiple organ complications which would have influence upon tracheal extubation. RESULTS: We found great difference between two groups in duration of mechanical ventilation (Group 1: 94.4+/-7.12 hrs, Group 2: 36.1+/-28.3 hrs) and ICU stay (Group 1: 22.8+/-8.3 days, Group 2: 11.8+/-5.5 days). CONCLUSIONS: We concluded that early tracheal extubation in selected liver transplantation cases was safe and effective because it could shorten duration of ICU stay and reduce postoperative mortality. But more experience and knowledge may be needed to get more ideal guidelines for postoperative mechanical ventilation.

Risk Factors of Blood Requirements during Liver Transplantation / 대한마취과학회지

BACKGROUND: The large volume of blood products are required during orthotopic liver transplantation. Any preoperative and intraoperative factors may influence the intraoperative blood products usage. METHODS: We retrospectively reviewed the demographic information, coagulation screens, thrombelastographic variables, and intraoperative blood requirements in 952 adult patients, who underwent orthotopic liver transplantation at the University of Pittsburgh Medical Center between January 1992 and December 1995. A preoperative coagulation abnormality score (CAS) was calculated by assigning one point of each abnormal result of the coagulation tests (PT, aPTT, platelet count) and thrombelastographic variables (reaction time, alpha angle, maximal amplitude, clot lysis index). Intraoperatively, blood products and pharmacologic coagulation therapy were administered based on thrombelastographic and hemodynamic data. RESULTS: Underlying liver disease, retransplantation one month after the first transplantation, poor preoperative coagulation profiles were predictive of intraoperative blood usage. Age, preoperative PT >15 sec, and CAS were not predictive of intraoperative blood usage. The severe fibrinolysis during operation occurred. More blood products were required in patients with severe fibrinolysis. CONCLUSIONS: The understanding of preoperative and intraoperative factors affecting blood product requirements can help the management of blood component therapy during liver transplantation.