[Clinical efficacy and prognostic risk factors of salvage liver transplantation, rehepatectomy, and local ablation in the treatment of postoperative recurrence of hepatocellular carcinoma].

Objective: To investigate and analyze the clinical efficacy of salvage liver transplantation (SLT), rehepatectomy (RH), local ablation (LA), and prognostic risk factors in patients with postoperative recurrence of hepatocellular carcinoma. Methods: Clinical data of 145 patients with recurrent liver cancer in the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2005 to June 2018 were retrospectively collected. SLT group, RH group, and LA group included 25, 44, and 76 cases, respectively. Follow-up and statistics were recorded on the overall survival rate, relapse-free survival rate, and complications of the three groups of patients at 1, 2, and 3 years after surgery. Univariate and multivariate COX analyses were used to analyze the prognostic risk factors in patients with recurrent HCC. Results: The overall survival rates of 1, 2, and 3 years following surgery in the SLT, RH, and LA groups were 100.0%, 84.0%, 72.0%, 95.5%, 77.3%, 65.9%, 90.8%, 76.3%, and 63.2%, respectively, when the recurrence of liver cancer met the Milan criteria. The overall survival rate did not differ statistically between SLT and RH (P = 0.303) or between RH and LA (P = 0.152). There were statistically significant differences in recurrence-free survival between SLT and RH or RH and LA (P = 0.046). There was no statistically significant difference in the incidence of complications between SLT and RH or RH and LA (P > 0.017). Age > 65 years was an independent risk factor affecting the overall survival rate in patients with recurrent HCC. Age > 65 years and recurrence time < 24 months were independent risk factors affecting the recurrence-free survival rate in patients with recurrent HCC. Conclusion: SLT is the best treatment option when the recurrence of HCC meets Milan's criteria. RH and LA are the appropriate treatment plans for recurrent HCC when the liver source is limited.

Effectiveness of Perioperative Immunologic Markers Monitoring for Predicting Early Acute Cellular Rejection After Living Donor Liver Transplantation.

BACKGROUND: The objective of this study was to determine whether perioperative immunologic markers monitoring could predict early acute cellular rejection (ACR) after living donor liver transplantation (LDLT). MATERIALS AND METHODS: From September 2010 to June 2013, a total of 172 patients underwent LDLT at our transplant center. Of them, 26 patients were excluded because of infection. We retrospectively reviewed the remaining 146 patients. CD4 lymphocyte activity, T cell subsets test, and serum cytokine panel were checked on the day before transplantation and at 20 days after transplantation. These patients were divided into 3 groups: 1. normal liver function test (LFT) group; 2. increased LFT without rejection group; and 3. early ACR group. We excluded the increased LFT without rejection group in order to rule out multiple factors influencing immunologic factors. RESULTS: CD4 lymphocyte activity (P = .004) was significantly increased while CD4+/CD25+/FOXP3+ cells (P < .001) and interleukin (IL)-17 (P = .002) levels were significantly decreased during the perioperative period. Pretransplant IL-6 (P = .014) and IL-17 (P = .029) levels in the early ACR group were significantly lower than those in the normal LFT group. The proportion of patients with increased IL-6 during perioperative period in the early ACR group was higher than that in the normal LFT group, although the difference was not statistically significant (P = .065). CONCLUSION: Our results suggest that IL-6 and IL-17 levels are associated with early ACR in LDLT patients. However, whether monitoring perioperative immunologic markers could predict early ACR remains unclear. Further prospective studies are needed to reach a definite conclusion.

Postoperative Doppler Ultrasonography in Liver Transplantation.

BACKGROUND: Doppler ultrasonography plays an important role in the postoperative management of liver transplantation. We present our initial experiences evaluating liver transplants with the use of postoperative Doppler sonography. METHODS: In our hospital, we performed 20 liver transplantations from July 2014 to October 2016. Among 20 patients, we performed 15 deceased-donor liver transplantations (DDLTs) and 5 living-donor liver transplantations (LDLTs). For deceased donors, inferior vena cava anastomoses were performed with the use of the piggyback technique, and for living donors, modified right grafts were used with middle hepatic vein reconstruction by Dacron graft. In the intensive care unit, we performed Doppler ultrasound at least once a day and at every clinical need. We checked hepatic blood flow by means of Doppler ultrasound. RESULTS: Eighteen patients underwent Doppler ultrasonography once a day up to postoperative day 6. Of the patients who received LDLT, 2 patients underwent Doppler ultrasonography twice a day because the operator was concerned about the hepatic artery anastomosis. Findings on Doppler ultrasound showed no abnormal wave form in hepatic artery, portal vein and hepatic veins. No patient had abnormal findings on angiographic computerized tomography. There was 1 graft failure in 20 recipients. The graft failure was primary nonfunction, and retransplantation was done. During the hospitalizations, there were no vascular complications. CONCLUSIONS: Doppler ultrasonography can be used to evaluate postoperative vascular complications in liver transplant patients. When the operator checks postoperative Doppler ultrasonography, it is possible to differentiate between patients, and it may help to detect the vascular complications earlier.

Carbapenem-resistant Acinetobacter baumannii Bacteremia in Liver Transplant Recipients.

BACKGROUND: Acinetobacter baumannii has become an increasingly important nosocomial pathogen. Carbapenem is the preferred drug of choice for treatment of multidrug-resistant gram-negative bacilli, but carbapenem-resistant A baumannii (CRAB) has now emerged. The aim of this study was to determine the incidence, outcomes, and risk factors for CRAB bacteremia in liver transplant recipients. METHODS: The medical records of 393 subjects who underwent living donor liver transplant at Seoul St. Mary's Hospital from January 2008 to April 2015 were reviewed. RESULTS: A total of 92 (23.4%) bacteremic patients, comprising 156 episodes, were identified. Fourteen patients, totaling 18 episodes, had CRAB bacteremia. The median time of emergence of CRAB bacteremia was 55.5 (range, 2-829) days after transplantation, and 72.2% of episodes (n = 13) occurred within 6 months of transplant. The presumed sources of infection were intra-abdominal (n = 11, 61.1%), biliary tract (n = 3, 16.7%), lung (n = 2, 11.1%), catheter (n = 1, 5.6%), and wound (n = 1, 5.6%). By multivariate analysis, length of post-transplant intensive care unit (ICU) stay (odds ratio [OR], 1.1, 95% confidence interval [CI], 1.11-1.15; P = .04) was associated with CRAB bacteremia. Overall mortality in 14 recipients with CRAB bacteremia was 50% (n = 7), but only 10% (30 of 301) in non-bacteremic patients and 20.5% (16 of 78) in other bacteremic patients excluding CRAB (P < .001). CONCLUSION: In our study, patients with CRAB bacteremia after liver transplant showed an unfavorable outcome and, recently, CRAB has become an increasingly major pathogen at our center. Reducing the length of ICU stay could be a solution for preventing CRAB bacteremia.

Impact of Pretransplant Infections on Clinical Course in Liver Transplant Recipients.

BACKGROUND: Uncontrolled infections are known to be an absolute contraindication for liver transplantation; however, the posttransplant prognosis of recipients treated for pretransplant infection is unclear. The aim of this study was to analyze pretransplant infections among liver transplant recipients and to determine their impact on posttransplant clinical outcomes. METHODS: This study retrospectively analyzed 357 subjects who had undergone living-donor liver transplantation between January 2008 and May 2014. RESULTS: Among 357 recipients, 71 patients (19.8%) had 74 episodes of infectious complications before liver transplantation. These complications consisted of pneumonia (n = 13), spontaneous bacterial peritonitis (n = 12), catheter-related infection (n = 10), urinary tract infection (n = 12), biliary tract infection (n = 6), and skin and soft-tissue infection (n = 3). Twenty-six patients experienced 29 episodes of bacteremia, and the most common pathogens were coagulase-negative staphylococci (n = 8), followed by Klebsiella pneumoniae (n = 7), Staphylococcus aureus (n = 4), and Streptococcus species (n = 3). Twenty-one bacteremic episodes (70%) occurred within 1 month before transplantation (n = 4). Recipients with pretransplant infections had significantly more frequent posttransplant infections (71.8% [51 of 71] vs 47.2% [35 of 286]; P = .0001), posttransplant bacteremia (33.8% [24 of 71] vs 20.3% [58 of 286]; P = .015), and longer posttransplant intensive care unit stays (11.2 ± 10.7 days vs 7.3 ± 4.2 days; P = .0004) than those without pretransplant infections. However, episodes of rejection (P = .36), length of hospitalization (P = .10), 28-day mortality (P = .31), and 1-year mortality (P = .61) after transplantation were not significantly different between the 2 groups. CONCLUSIONS: Pretransplant infection had an impact on posttransplant morbidity, although not on rejection and mortality. Alertness for posttransplant infection and proper management (including effective antimicrobial coverage) would improve patient morbidity.

Effect of donor-recipient age matching in living donor liver transplantation.

BACKGROUND: The use of a marginal donor, such as an elderly donor, in liver transplantation has been increasing in response to organ disparity; however, major risk factors for graft and patient survivals have been reported. METHODS: We retrospectively reviewed the medical records of 559 patients who underwent living-donor liver transplantation (LDLT) at our hospital from May 2003 to June 2013. Elderly donors were defined as those >50 years old, and elderly recipients were defined as those >60 years old. We evaluated the differences in survival according to donor and recipient ages. Furthermore, we compared post-transplantation outcomes according to donor-recipient age matching. RESULTS: The overall 5-year survival rate of the recipients was significantly lower in the elderly donor group than in the younger donor group (84.6% vs 58.2%; P < .001). However, no significant difference in survival rate was observed according to recipient age (P = .908). The survival rate of elderly recipients who received a graft from an elderly donor was significantly lower than those of the other groups (P < .001-.037). The mortality rate was significantly different among the groups (P < .001), and among the causes of death, surgical complications were most frequent cause in the elderly donor group (P < .001). CONCLUSIONS: LDLT with the use of elderly donors >50 years of age could result in higher mortality rates than using younger donors. As such, elderly donor livers ideally should be matched with young recipients and attention concentrated on the surgical complications.

Clinical significance of surveillance culture in liver transplant recipients.

BACKGROUND: Routine microbiologic surveillance is a method of infection control, but its clinical significance in transplant recipients is not known. We analyzed microbiologic data to evaluate the influence of cultured microorganisms between the point of surveillance and infectious episodes in liver transplant recipients. METHODS: We performed surveillance culture for sputum and peritoneal fluid in liver transplant recipients from January 2009 to December 2011, at the time of transplantation (T1), 5 days (T2), and 10 days (T3) postoperatively. RESULTS: Of the 179 recipients, 32.9% had a positive sputum culture result and 37.4% had a positive peritoneal culture result during surveillance. In the culture surveillance of sputum, 37 organisms were isolated from 35 recipients at T1, and the most common organism was Staphylococcus aureus (n = 13). At T2, 45 organisms were isolated from 39 recipients, including Klebsiella pneumoniae (n = 10), S aureus (n = 8), and Acinetobacter baumannii (n = 6). At T3, 18 organisms were isolated from 15 patients, including Stenotrophomonas maltophilia (n = 5) and K pneumonia (n = 4). In the peritoneal fluid, 11 organisms were isolated from 10 recipients at T1, including Pseudomonas aeruginosa (n = 2) and Enterococcus species (n = 2). At T2, 39 organisms were isolated from 36 recipients, including coagulase-negative Staphylococcus species (CNS; n = 8) and Enterococcus species (n = 7). At T3, 54 organisms were isolated from 51 recipients, including CNS (n = 17) and Candida species (n = 8). Among the 59 patients with positive culture results for sputum surveillance, 16.9% developed pneumonia caused by the same organisms. Among the 67 patients with positive peritoneal fluid culture, 16.4% developed an intra-abdominal infection caused by the same organisms cultured. The recipients with positive surveillance culture had a higher risk of pneumonia (20.3% [12/59] vs 1.6% [2/120]; P < .001) and intra-abdominal infection (31.3% [21/67] vs 18.7% [21/112]; P = .05). CONCLUSIONS: Periodic microbiologic surveillance may be useful in the prediction of post-transplantation pneumonia and intra-abdominal infection and could offer a potential target for empirical antimicrobial therapy in cases of infection.

Strategies to reduce infectious complication using epidemiologic data analysis in liver transplant recipients.

BACKGROUND: Infectious complications are major factors for morbidity and mortality in liver transplant recipients. To establish a proper strategy to reduce infectious complications, we analyzed epidemiologic and risk factors for post-transplant infections. METHODS: We analyzed the medical records of 231 consecutive liver transplant recipients from December 2007 to November 2011, including at least 1-year follow up, for comparison with those from 1996 to 2005. RESULTS: Among 231 patients, 126 (54.5%) experienced 244 infectious episodes, a rate of 1.05 per patient. Among overall mortality of 9.9% (23/231), infections were more prevalent (P = .04). Predominant infections were postoperative intra-abdominal problems (36.1%), peritonitis (15.2%), pneumonia (13.5%), bacteremia (4.1%), wound complications (1.6%), viral etiologies (18.0%), and other causes (11.5%). Causative organisms were bacterial (68.9%), viral (14.7%), fungal (7.0%), and unproven ones (9.4%). Multivariate analysis of risks for infection showed significant impacts of Model for End-stage Liver Disease score [P = .027; odds ratio (OR), 1.04], post-transplant biliary complications (P < .001; OR, 3.50), and rejection episodes (P = .023; OR, 3.39). Mortality was related to retransplantation (P = .003), post-transplant dialysis (P = .006), and infection (P = .056) upon univariate analysis, none of which were significant in multivariate analysis. Compared with data from the previous period, overall and infection-related mortality decreased from 24.5% to 9.9% and 52.9% to 26.1%, respectively. There were no significant changes in the types of infection or rate of drug-resistant bacteria, but candidal infections and cytomegalovirus reactivations were more prevalent. CONCLUSION: Our data showed current perioperative antimicrobial regimens need not be changed: however, new strategies are needed to reduce infectious complications after liver transplantation, to reduce biliary complications and to properly manage rejection episodes.

Antiviral prophylaxis versus preemptive therapy to prevent cytomegalovirus infection and related death in liver transplantation: a retrospective study with propensity score matching.

BACKGROUND: Cytomegalovirus (CMV), the most significant viral infection in liver transplant recipients, is addressed by 2 methods: Preemptive therapy (PT) or universal prophylaxis (UP). METHODS: We analyzed medical records including at least 1 year follow-up of patients who underwent liver transplantation from 2006 to 2009 in 3 tertiary hospitals. PT was used in 2 hospitals (PT group), whereas UP with valganciclovir for 3 months was adopted in the other hospital (UP group). The 2 groups were matched using propensity scoring by perioperative variables. We performed a 1:1 comparison of the efficacy of UP and PT. RESULTS: We analyzed 634 liver transplant patients, including 562 matched subjects. Baseline characteristics and underlying liver status were comparable. CMV immunoglobulin G of recipients was positive in 98.9% of the PT group and 99.3% of the UP group. CMV viremia episodes that required administration of an antiviral agent occurred in 26 (9.3%) PT and 37 (13.2%) UP subjects (P = .18). CMV-related mortalities were similar (0.7% vs 1.8%; P = .45), but all-cause mortality was higher in the PT group (18.5% vs 13.2%; P = .08). CONCLUSION: The efficacy of PT was similar to UP to prevent CMV disease and related mortality among a group at moderate risk for CMV infection.

Single-port laparoscopy-assisted donor right hepatectomy in living donor liver transplantation: sensible approach or unnecessary hindrance?

BACKGROUND: Single-port laparoscopic (SPL) surgery has rapidly gained attention worldwide. Since May 2008, we have propagated the use of SPL surgery, mainly for cholecystectomy and appendectomy. Recently, we have used this modality of minimally invasive surgery for various liver surgeries. We hereby discuss our outcomes of SPL-assisted donor right hepatectomies. METHODS: The preoperative workup is the same as for a standard donor hepatectomy. We retrospectively reviewed the data of 150 patients who underwent donor right hepatectomy from October 2008 to May 2011. We divided them into 3 groups depending on the type of surgical procedure. RESULTS: Among 150 patients, 20 underwent laparoscopy-assisted donor right hepatectomy (LADRH); 40 underwent single-port laparoscopy-assisted donor right hepatectomy (SPLADRH); and 90 underwent open donor right hepatectomy (ODRH). The donor demographics were comparable among the groups. Postoperative complication and reoperation rates revealed no significant differences. The SPLADRH group showed the lowest level of postoperative pain, thereby leading to a better quality of life postoperatively. CONCLUSIONS: SPLADRH seems to be a simple, feasible approach.

Extended criteria for living donor liver transplantation in patients with advanced hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to evaluate the possibility of expanding the selection criteria in living donor liver transplantation (LDLT) to treat hepatocellular carcinoma (HCC). METHODS: From October 2000 to December 2010, we retrospectively analyzed 71 patients who had undergone LDLT beyond the Milan criteria (MC), among the entire cohort of 199 HCC patients. We evaluated the tumor biology as well as overall and disease-free survival (DFS), seeking to identify risk factors for recurrence. The median follow-up was 37 months (range 5-124). RESULTS: Among the 71 patients beyond the MC were 18 recurrences and 30 deaths. Their 5-year overall and DFS rates were 52.3% and 67.7%, respectively. On multivariate analysis, tumor diameter, tumor number, and E-S grade significantly influenced overall and DFS. According to our new criteria (size≤7 cm, number≤7), 86% of our patients would be included compared with 64% using MC. Five-year DFS and overall survival rates according to our criteria were comparable with the MC: 86.8% and 72.3% versus 86.8% and 73.4%, respectively. CONCLUSION: Our criteria appear to achieve useful cut-off values beyond the MC.

High mortality associated with Acinetobacter species infection in liver transplant patients.

BACKGROUND: Acinetobacter species have become increasingly important nosocomial pathogens worldwide and can result in a wide range of infections, including bacteremia, pneumonia, urinary tract infection, peritonitis, among others. The aim of this study was to investigate clinical characteristics, mortality, and outcomes among liver transplant recipients with Acinetobacter species infections. METHODS: We retrospectively analyzed 451 subjects who had undergone living donor liver transplantations between January 2001 and May 2010. Pandrug-resistant (PDR) Acinetobacter species were defined as resistant to all commercially available antibiotics except colistin. RESULTS: Infectious complications due to Acinetobacter species appeared in 26 patients (5.8%) with a total of 37 episodes. Of the species identified, 34 were Acinetobacter baumannii and 3 Acinetobacter Iwoffiii. The presumed sources of infection were the biliary tract (n = 21, 56.8%), lung (n = 7, 18.9%), intra-abdomen (n = 6, 16.2%), catheter (n = 2, 5.4%), and urinary tract (n = 1, 3.6%). Among the 37 Acinetobacter species, 75.7% (28/37) were PDR species. Age, duration of intensive care unit stay, Child-Pugh score, and Model for End-stage Liver Disease score were not significant risk factors for Acinetobacter species infection. However, the overall mortality among patients with Acinetobacter species infections was 50% (13/26), which was significantly higher than that among those free of infection (50% vs 11.5%, P < .05). Multivariate analysis using a Cox regression model showed that inappropriate antimicrobial treatment was a significant independent risk factor for mortality among patients with Acinetobacter species infections (hazard Ratio = 4.19, 95% confidence interval 1.1-18.7; P = .06). CONCLUSION: Patients with Acinetobacter species infections after liver transplantation show a significantly worse prognosis. PDR Acinetobacter species have been a major problem in our center.

Performance of posttransplant Model for End-Stage Liver Disease (MELD) and delta-MELD scores on short-term outcome after living donor liver transplantation.

The performance of the Model for End-stage Liver Disease (MELD) and delta-MELD scores in predicting posttransplant survival has been variable and the results are conflicting, suggesting that posttransplantational factors are more important than pre- or peritransplantational factors in outcomes following liver transplantation (OLT). We assessed the value of posttransplant MELD and delta-MELD scores to predict short-term (90-day) posttransplant survival. We evaluated 279 consecutive patients undergoing living donor OLTs. The MELD scores were calculated serially from pretransplantation as well as 3, 7, and 14 days after transplantation. Twenty-seven (9.7%) among 279 patients died within 90 days after transplantation. Pretransplant MELD score was not associated with short-term posttransplant mortality. The area under the receiver operating characteristic (AUROC) curve in predicting 90-day mortality was 0.637 for posttransplant 3-day MELD, 0.746 for posttransplant 7-day MELD, and 0.859 for posttransplant 14-day MELD score (P = .047, <.001, and <.001, respectively); AUROC was 0.582, 0.646, and 0.784 for 3-day, 7-day, and 14-day delta-MELD scores (P = .235, .034, <.001, respectively). Upon multivariate analysis, posttransplant 14-day MELD (> or =20 vs <20), and 14-day delta-MELD scores (> or =-3 vs <-3) were independent short-term prognostic factors with risk ratios of 18.875 (95% confidential interval [CI]: 4.625-77.028, P < .001) and 13.577 (95% CI: 2.641-69.791, P = .002), respectively. In conclusion, determination of posttransplant 14-day MELD and 14-day delta-MELD scores may afford suitable short-term prognostic predictors for patients following living donor OLT.

Gene-gene and gene-environmental interactions of p53, p21, and IRF-1 polymorphisms in Korean women with cervix cancer.

BACKGROUND: The aim of this study was to identify gene-gene and gene-environmental factors affecting cervix carcinogenesis in Korean women. METHODS: We evaluated 530 subjects composed of 185 female cervix cancer patients and 345 normal healthy women. The single nucleotide polymorphisms (SNPs) of p53 codon 72, p21 codon 31, and interferon regulatory factor-1 (IRF-1) intron 6 were evaluated from extracted DNA of peripheral blood with an automatic DNA sequencer. The differences of each SNP, gene-gene and gene-environmental interactions between normal controls and patients were evaluated in the adjusted environmental background. RESULTS: In the environmental aspect, the rate of cervix cancer increased in the women with a lower level of education, a younger age at first sexual intercourse and more childbearing. The women who had p53 (Arg/Arg), IRF-1 (T/T), and <6 years of education showed a 14.7-fold increased risk of cervix cancer compared to the women who had p53 ( approximately Pro), IRF-1 ( approximately C), and >15 years of education. The women who had p53 (Arg/Arg), p21 (Ser/Ser), and >3 children showed a 6.4-fold increased risk of cervix cancer compared to the women who had p53 ( approximately Pro), p21 ( approximately Arg), and no children. The women who had p53 (Arg/Arg), IRF-1 (T/T), and first sexual intercourse before 22 years old showed a 5.5-fold increased risk of cervix cancer compared to the women who had p53 ( approximately Pro), IRF-1 ( approximately C), and first sexual intercourse after 26 years old. CONCLUSIONS: We found that the level of education, the age at first intercourse, and the number of children were independent risk factors in cervix carcinogenesis. The specific combinations of p53, p21, and IRF-1 gene-gene and gene-environmental interactions were significantly noted in the cervix carcinogenesis of Korean women.

A case of Behçet's disease combined with pulmonary artery aneurysm in a Korean female patient.

Behçet's disease (BD) is a systemic disorder of unknown process resulting from systemic vasculitis. The pulmonary involvements in BD are uncommon. Furthermore, in the female, involvement of the pulmonary artery is quite rare. There were a few cases of female patients with BD with pulmonary artery aneurysm confirmed by pulmonary artery angiogram. In this article, we report a case of BD, combined with pulmonary artery aneurysm, confirmed by pulmonary angiogram and treated by surgery in a Korean female patient.