The Impact of Posthepatectomy Liver Failure on the Recurrence of Hepatocellular Carcinoma

Background

Patients with hepatocellular carcinoma (HCC) who underwent hepatectomy often developed an intrahepatic recurrence, even though it was a curative one. The relationship between surgery-induced liver damage and the recurrence of HCC has not been described. This study evaluated whether posthepatectomy liver failure, as defined by the International Study Group of Liver Surgery, affected the recurrence of HCC.

Methods

We performed a retrospective cohort study of 488 patients with HCC who underwent hepatectomy between 2004 and 2012 at Kyoto University Hospital. Early posthepatectomy liver failure (EPLF) was defined as liver failure occurring between postoperative days 5 and 10. The patients were divided into an EPLF group and a non-EPLF group. Disease-free survival (DFS) was compared between these groups. The influences of host-related, surgery-related, and tumor-related factors on patient outcomes were evaluated using multivariate analyses.

Results

The EPLF group and the non-EPLF group contained 153 and 335 patients, respectively. The probability of DFS was significantly increased in the non-EPLF group (median: 574 days) compared to the EPLF group (median: 348 days) (hazard ratio, HR [95 % confidence interval, CI] 1.61 [1.29–2.00]). The multivariate analysis revealed that EPLF was an independent factor for DFS (HR [95 % CI] 1.43 [1.13–1.81]), besides the factors previously described, including fibrosis (1.32 [1.05–1.67]), stage (1.85 [1.34–2.51]), tumor differentiation (1.46 [1.11–1.89]), and des-γ-carboxyprothrombin (1.39 [1.10–1.74]).

Conclusions

EPLF was associated with postoperative HCC recurrence. The prevention of EPLF might improve the prognosis of patients with HCC.     

活体肝移植供体的评估和随访

目的:探讨活体肝移植中供体的评估及随访策略。方法:对30例活体供肝者的临床资料进行回顾分析。结果:供体的总剔除率为28.6%(12/42),病毒性肝炎是最重要的剔除原因(6/12)。供肝重量与受体体重之比(graft鄄recipientweightratio,GRWR)均数为(1.39±0.45)%。所有供体均顺利康复。供体肝功能一般在5～7d内均恢复正常。供体随访时间为1个月～8年,随访时间超过6个月者23例,康复时间为(6±1.5)个月。供肝者残留肝恢复正常体积的时间为6～14个月。术后(8±1.0)个月,86.7%(26/30)的供体恢复术前工作或劳动;30%(9/30)的供体出现过一过性症状,如腹部不适、疼痛等,其中22.2%(2/9)的供体主诉疼痛较严重,需要就医。随访显示,供体均因献肝而赢得社会、朋友的尊重。结论:活体肝移植不仅安全可行,且献肝可能对供、受体的感情、心理、家庭及社交产生良好的、积极的影响。     

The Determination of Bile Leakage in Complex Hepatectomy Based on the Guidelines of the International Study Group of Liver Surgery

Background

The International Study Group of Liver Surgery (ISGLS) has defined bile leakage as a drain fluid-to-serum total bilirubin concentration (TBC) ratio (the bilirubin ratio) ≥3.0. The aim of the present study was to determine the clinical significance of this definition, and to outline characteristics of bile leakage in complex hepatectomy.

Methods

The TBCs of the serum and drain fluid were measured on postoperative days (POD) 1, 3, and 7 in 241 patients who had undergone hepatobiliary resection. The validation of the bilirubin ratio and predictors of bile leakage were retrospectively assessed.

Results

Grade A, B, or C bile leakage was found in 23 (9.5 %), 66 (27.4 %), and 0 patients, respectively. The median duration of drainage was 27 days in grade B bile leakage. The sensitivity and specificity of the bilirubin ratio for detecting grade B bile leakage were 59 and 87 %, respectively. The area under the receiver operating characteristics curve of the drain fluid TBC on POD 3 had the highest predictive value: 68 % sensitivity and 76 % specificity for a drain fluid TBC of 3.7 mg/dL. The multivariate analysis demonstrated that operative time, left trisectionectomy, bilirubin ratio, and TBC of the drain fluid on POD 3 were independent predictors of grade B bile leakage.

Conclusions

In complex hepatectomy, bile leakage develops most frequently after left trisectionectomy and often results in a refractory clinical course. The ISGLS biochemical definition is valid, and a combination of bilirubin ratio and drain fluid TBC may enhance risk prediction for grade B bile leakage.     

Hepatobiliary Scintigraphy in the Preoperative Evaluation of Potential Living Liver Donors

Background

Graft selection strategy in living donor liver transplantation (LDLT) is usually multifactorial, but special attention is paid to the determination of donor liver volumes to minimize any risk of posthepatectomy liver failure (PHLF). Hepatobiliary scintigraphy (HBS) with single-photon-emission computed tomography allows for the measurement of total and future liver remnant function (FLR-F) and has been shown to predict the risk of PHLF more accurately than liver volumetry.

Preoperative Evaluation of Liver Parenchyma of Potential Donors in Living Donor Liver Transplantation

BackgroundHepatic steatosis carries a risk of postoperative liver dysfunction in donors and graft nonfunction in recipients. This article discusses the evaluation of fatty infiltration in donor liver parenchyma on multidetector computed tomography.Materials and methodsThe methods of hepatic fat estimation include measurement of hepatic attenuation in HU and calculation of the liver attenuation index (LAI). Liver attenuation values reflect the degree of steatosis. Average attenuation of liver parenchyma is calculated by placing the circular region of interest of at least 1 cm² area at multiple places in the liver on noncontrast CT images. Splenic attenuation is measured by placing the circular region of interest at its upper, middle, and lower poles. The LAI is the difference between mean hepatic attenuation and mean splenic attenuation.ResultsA total of 52 donors were evaluated as potential recipients (34 men, 18 women; mean age, 33.2 years; range, 23-55 years). In 34 donors liver attenuation index (LAI) values were from 2 HU to 22 HU. An LAI > 5 HU correctly predicted the absence of significant macrovesicular steatosis. These donors were acceptable for a liver transplant. The LAI values of −10 to 5 HU were suggestive of mild to moderate steatosis (6%-30%); 18 (34.6%) volunteers did not proceed to donation because of negative LAI < −5 HU. In 2 cases with LAI of −7 and LAI of −8 liver biopsy was performed, and 30% steatosis was confirmed in the pathohistologic examination. Unacceptable liver biopsy result was considered as contraindication for donation. The LAI values of < −10 HU were suggestive of moderate to severe hepatic steatosis of 30% or greater. In these cases liver biopsy is not needed, as such donors are not acceptable for liver transplant.ConclusionComputed tomography imaging provides a detailed evaluation of fatty infiltration in donor liver parenchyma.     

Histopathological Evaluation of Gallbladder Specimens Obtained From Living Liver Donors

BackgroundCholecystectomy is routinely performed during living donor hepatectomy both to see the structure of the biliary tract and to determine the demarcation line based on the biliary tract junction. This study aims to present the general histopathological features of the gallbladder specimen obtained from living liver donors (LLD).MethodsData from 2577 LLDs who underwent living donor hepatectomy (n = 2511) or aborted living donor hepatectomy (n = 66) in our Liver Transplantation Institute between September 2005 and June 2021 were analyzed retrospectively. Age, gender, macroscopic (length, diameter, and wall thickness), and microscopic (histopathological) features of the gallbladder of the LLDs were recorded for use in this study.ResultsA total of 2493 LLDs (men: 1486, women: 1007) with a median age of 29 years (interquartile range [IQR]: 13) met the inclusion criteria in this study. The median length, width and wall thickness of the gallbladder specimens were measured as 70 mm (IQR: 20), 50 mm (IQR: 20), and 2 mm (IQR: 1), respectively. The most common histopathological findings are normal structure (2026; 81.3%), chronic cholecystitis (n = 446; 17.9%), adenomyomatosis (n = 9), and papillary hyperplasia (n = 6), respectively. The most common pathologic findings in the gallbladder lumen are cholesterolosis (n = 207; 0.4%), cholelithiasis (n = 53), cholesterol polyp (n = 31), and noncholesterol polyp (n = 19), respectively. Significant differences were detected between the male and female genders in terms of age (P < .001), height (P < .001), weight (P < .001), body mass index (P < .001), gallbladder width (P = .001), gallbladder length (P < .001), histopathological finding (content) (P < .001), and lymph node around the gallbladder (P = .015).ConclusionsThe results we obtained in this study are true gallbladder pathologies that can be detected in healthy people. In this study, it was shown that the diameter and size of the gallbladder were larger in men, whereas the incidence of cholesterolosis and cholelithiasis was higher in women.     

Estimation of Standard Liver Volume in Chinese Adult Living Donors

Aim

To determine a formula predicting the standard liver volume based on body surface area (BSA) or body weight in Chinese adults.

Materials and Methods

A total of 115 consecutive right-lobe living donors not including the middle hepatic vein underwent right hemi-hepatectomy. No organs were used from prisoners, and no subjects were prisoners. Donor anthropometric data including age, gender, body weight, and body height were recorded prospectively. The weights and volumes of the right lobe liver grafts were measured at the back table. Liver weights and volumes were calculated from the right lobe graft weight and volume obtained at the back table, divided by the proportion of the right lobe on computed tomography. By simple linear regression analysis and stepwise multiple linear regression analysis, we correlated calculated liver volume and body height, body weight, or body surface area.

Results

The subjects had a mean age of 35.97 ± 9.6 years, and a female-to-male ratio of 60:55. The mean volume of the right lobe was 727.47 ± 136.17 mL, occupying 55.59% ± 6.70% of the whole liver by computed tomography. The volume of the right lobe was 581.73 ± 96.137 mL, and the estimated liver volume was 1053.08 ± 167.56 mL. Females of the same body weight showed a slightly lower liver weight. By simple linear regression analysis and stepwise multiple linear regression analysis, a formula was derived based on body weight. All formulae except the Hong Kong formula overestimated liver volume compared to this formula.

Conclusions

The formula of standard liver volume, SLV (mL) = 11.508 × body weight (kg) + 334.024, may be applied to estimate liver volumes in Chinese adults.     

Effect of Graft Type on Postoperative Liver Function Recovery in Living Liver Donors

Background

Donor safety is the primary focus in living-donor liver transplantation. Although, the procedure carries a significant risk of morbidity and even death, the use of marginal living donors is a current issue of discussion.

Patients and Methods

Between September 2001 and October 2008, we performed 203 liver transplantation procedures using organs from living donors. Of 203 donors, 115 were men and 88 were women, with a mean (SD; range) age of 34.5 (9; 19-66) years. One hundred fifty donors were first-degree relatives of the recipients, 36 were second-degree relatives, and 17 were spouses. We did not accept grafts with remnant volume less than 40% or from donors with impaired liver function. We performed 96 right-lobe 38 left-lobe, and 69 left-lateral segmentectomies. For the right-lobe grafts, the median hepatic vein was always left in the remnant liver. The mean ratios of remnant to total donor liver volume were 42.0%, 66.8%, and 74.6% for the right-, left-, and left lateral segmentectomies, respectively. Mean hospitalization time was 7.0, 6.2, and 9.7 days, respectively. Mean operative time was 330, 324, and 324 minutes, respectively. Only 15 donors (7.8%) received autologous blood transfusions during surgery. Liver function tests including alanine aminotransferase, aspartate aminotransferase and bilirubin concentrations and prothrombin time were assessed postoperative days 1, 3, and 5 at outpatient follow-up, usually at week 3.

Results

There were no deaths; however, 26 complications occurred in 20 of 203 donors (5.2%), most of which were treated with radiologic interventions.

Conclusion

Larger grafts produce impaired function in the early postoperative period; however, they do not have a negative effect in the long term. The remnant volume should be measured fastidiously, and surgeons must avoid taking large volumes of liver, especially in right-lobe donors.     

Reversal of Experimental Posthepatectomy Liver Failure in Pigs: A New Application of Hepatocyte Bioreactors

Postoperative liver failure remains a major cause of morbidity and mortality after extensive hepatectomies. This study aims to evaluate the effectiveness of a hepatocyte bioreactor in the treatment of experimental post‐hepatectomy liver failure. Our experimental model included a combination of a side‐to‐side portacaval shunt, occlusion of the hepatoduodenal ligament for 150 min, 70% hepatectomy, and reperfusion. Following the development of liver failure, 12 pigs were randomized into a control group (n = 6) and a treatment group (n = 6). Both groups underwent extracorporeal perfusion through a plasma separation device, a membrane oxygenator, and two parallel bioreactors. In the latter group, the bioreactors were loaded with 10 billion fresh hepatocytes, isolated from a donor pig. Following hepatocyte treatment, all animals were maintained for 24 h under mechanical ventilation, with intravenous fluid and glucose supplementation. Hemodynamic parameters, intracranial pressure, and biochemical parameters were measured. Liver biopsies were obtained during the 24‐h autopsy. The extracorporeal circuit was well‐tolerated hemodynamically. Treated animals had lower intracranial pressure compared with controls (at 24 h, 15 ± 3.1 vs. 22 ± 3.5 mm Hg, P = 0.006). Plasma ammonia in treated animals was lower compared with controls at 12 h (100 ± 29 vs. 244 ± 131 µmol, P = 0.026). Liver histological study showed decreased necrosis and increased regeneration activity in treated animals compared with controls. Treatment through an extracorporeal hepatocyte bioreactor attenuates brain edema and improves histological and functional parameters of the liver remnant of pigs with posthepatectomy liver failure.     

Long-term Results of Living Donors in Simultaneous Kidney and Liver Transplantations

Introduction

Because of the shortage of organs available for transplantation, living related sequential transplantation with the use of liver and a kidney from the same donor has emerged as a reasonable therapeutic alternative. However, there is insufficient literature about the complications that living donors experience after simultaneous kidney and liver transplantations.

Early Predictor of Mortality due to Irreversible Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background

Although mortality after liver resection has declined, posthepatectomy liver failure (PHLF) remains a major cause of operative mortality. To date there is not consensus on a definition for PHLF. However, there have been many efforts to define PHLF causing operative mortality. In the present study we sought to identify early predictors of death from irreversible PHLF.

Materials and methods

We retrospectively analyzed the medical records of 359 patients with hepatocellular carcinoma who underwent liver resection between March 2000 and December 2010. Various biochemical parameters from postoperative days (POD) 1, 3, 5, and 7 were analyzed and compared with the “50–50” criterion.

Results

Operative mortality was 4.7 %. Prothrombin time (PT) <65 % and bilirubin ≥38 μmol/L on POD 5 showed the only significant difference as compared with “50–50” criterion. The new combination of bilirubin level and the international normalized ratio showed higher sensitivity, area under the curve, as well as similar accuracy (sensitivity 78.6 vs. 28.6 %; p = 0.002; area under the curve 0.8402 vs. 0.6396; p = 0.00176; accuracy 88.6 vs. 93.4 %; p = 0.090). Multivariate analysis revealed the combination of PT <65 % and bilirubin ≥38 μmol/L on POD 5 to be the only independent predictive factor of mortality (odds ratio, 82.29; 95 % confidence interval 8.69–779.64; p < 0.001).

Conclusions

In patients with chronic liver disease who will undergo liver resection the combination of PT <65 % and bilirubin ≥38 μmol/L on POD 5 may be a more sensitive predictor than the “50–50” criterion of mortality from PHLF. Although it needs to validated by prospective study, this measure may be applied to select patients receiving artificial liver supports or liver transplantation.     

Peptic Ulcer Disease in Living Liver Donors: A Longitudinal Population‐Based Study

The objective of this nationwide cohort study was to investigate the risk of peptic ulcer disease (PUD) in living liver donors (LDs). A total of 1333 LDs and 5332 matched nondonors were identified during 2003–2011. Hospitalized patients identified as LDs were assigned to the LD cohort, and the non‐LD comparison cohort comprised age‐ and sex‐matched nondonors. Cumulative incidences and hazard ratios (HRs) were calculated. The overall incidence of PUD was 1.74‐fold higher in the LD cohort than in the non‐LD cohort (2.14 vs. 1.48 per 1000 person‐years). After adjustment for age, sex, monthly income and comorbidities, we determined that the LD cohort exhibited a higher risk of PUD than did the non‐LD cohort (adjusted HR 1.74, 95% confidence interval [CI] 1.45–2.09). The incidence of PUD increased with age; the risk of PUD was 2.53‐fold higher in patients aged ≥35 years (95% CI 2.14–2.99) than in those aged ≤34 years. LDs with comorbidities of osteopathies, chondropathies and acquired musculoskeletal deformities exhibited a higher risk of PUD (adjusted HR 3.93, 95% CI 2.64–5.86) compared with those without these comorbidities. LDs are associated with an increased risk of PUD after hepatectomy.     

Enhanced Recovery after Implementation of Surgery Protocol in Living Kidney Donors: The ISMETT Experience

IntroductionLaparoscopic living donor nephrectomy (LLDN) has become the standard procedure for living kidney transplantation. Enhanced recovery after surgery (ERAS) is a multimodal perioperative management aimed at facilitating rapid patient recovery after major surgery by modifying the response to stress induced by exposure to surgery. This association can further reduce hospital stay, surgical stress, and perioperative morbidity of living kidney donors.Material and methodsIn this retrospective analysis conducted at our institute, we compared the first 21 patients who underwent LLDN enrolled with the ERAS protocol with 55 patients who underwent LLDN with the fast-track protocol in the 5 years prior to ERAS protocol implementation.ResultsWe evaluated 76 consecutive patients. After ERAS protocol implementation, elderly living donors had a shorter hospital stay and a faster return to normal life compared with the same age group of patients in the previous period. There were no major differences in median postoperative hospital stay and no meaningful differences in the percentage of complications after surgery and hospital readmissions.ConclusionsThe introduction of the ERAS protocol for patients undergoing LLDN compared with the traditional protocol led to a reduction in postoperative hospitalization in elder donors, without determining a raise in the number of hospital complications and readmissions.     

Disclosing Recipient Information to Potential Living Donors: Preferences of Donors and Recipients,Before and After Surgery

Consensus guidelines, while recommending that potential living donors should be given information that could impact their donation decision, are nonspecific about the types of information that should be disclosed. We surveyed potential (n = 36) and past (n = 45) living donors and transplant candidates (n = 45) and recipients (n = 45) about their preferences for sharing or knowing specific information about the recipient, how this information would impact decision‐making, and who should be responsible for disclosing information. Potential donors were less likely than all others to feel that recipient information should be disclosed to potential donors. Donors and recipients felt most strongly about disclosing if the recipient lost a previously transplanted kidney due to medication nonadherence as well as the likelihood of 1‐ and 5‐year graft survival. Most donors would be less likely to pursue donation if the recipient lost a previously transplanted kidney due to medication nonadherence or generally had problems with taking medications as prescribed. Transplant programs should consider how to best balance the potential donor's right to receive information that could reasonably be expected to affect their decision‐making process with the recipient's right to privacy and confidentiality.     

Adult Living Liver Donors have Excellent Long‐Term Medical Outcomes: The University of Toronto Liver Transplant Experience

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end‐stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow‐up of 12 months (range 12–96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 ± 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long‐term follow‐up may contribute to favorable donor outcomes.