Hepatectomy for hepatocellular carcinoma after perioperative management of portal hypertension.

BACKGROUND: Indications for hepatectomy in patients with hepatocellular carcinoma (HCC) who have portal hypertension (PH) have been controversial. Some studies have concluded that PH is a contraindication to hepatectomy, whereas others have suggested that perioperative prophylactic management (PPM) can help overcome complications after hepatectomy associated with PH. The objective of this retrospective study was to assess the short- and long-term outcomes after hepatectomy for HCC in patients with PH, with or without PPM. METHODS: Records were reviewed of consecutive patients who underwent hepatectomy for HCC, with or without PPM of PH, in a single institution from 1994 to 2015. Patients were divided into three groups: those who received PPM for PH (PPM group), patients who had PH but did not receive PPM (no-PPM group) and those without PH (no-PH group). RESULTS: A total of 1259 patients were enrolled, including 123 in the PPM group, 181 in the no-PPM group and 955 in the no-PH group. Three- and 5-year overall survival rates were 74·3 and 53·1 per cent respectively in the PPM group, 69·2 and 54·9 per cent in the no-PPM group, and 78·1 and 64·2 per cent in the no-PH group (P = 0·520 for PPM versus no PPM, P = 0·027 for PPM versus no PH, and P < 0·001 for no PPM versus no PH). Postoperative morbidity and mortality rates were 26·0 and 0·8 per cent respectively in the PPM group, 29·8 and 1·1 per cent in the no-PPM group, and 20·3 and 0 per cent in the no-PH group. CONCLUSION: The present study has demonstrated acceptable outcomes among patients with HCC who received appropriate management for PH in an Asian population. Enhancement of the safety of hepatic resection through use of PPM may provide a rationale for expansion of indications for hepatectomy in patients with PH.

Use of a Right Lateral Sector Graft in Living Donor Liver Transplantation Is Feasible, but Special Caution Is Needed With Respect to Liver Anatomy.

Right lateral sector (RLS) grafting has been introduced to enlarge the potential donor pool for living donor liver transplantation (LDLT); however, evidence of its feasibility is limited. Data from 437 LDLTs carried out between 2000 and 2013 were analyzed retrospectively. LDLTs using a right liver graft (n = 251) were compared with those using a RLS graft (RLSG; n = 28). No donor mortality occurred, and the major complication rates were similar between the two groups. Postoperative liver function preservation was better in the RLSG donors. Concerning the recipients, the mortality and overall survival rates were similar between the two groups. The complication rate for the recipients was higher when more than two arterial or biliary anastomoses were necessary. A systematic literature search identified four reports on LDLT using RLSGs. Among 66 LDLTs, including the present series, there were no cases of donor death, and the rates of major and minor complications in the donors were 6% and 29%, respectively. The major complication and overall mortality rates in the recipients were 29% and 6%, respectively. LDLT using an RLSG is feasible, with an acceptable survival rate among the recipients.

Surgical resection of peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma.

BACKGROUND: Peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma (HCC) occur occasionally after biopsy, percutaneous therapy or resection, and spontaneously, with no effective treatment available. The objective of this study was to clarify the indications for, and benefits of, surgical resection of such HCC implants. METHODS: This was a retrospective analysis of patients who underwent resection for peritoneal or chest wall implants from HCC over 14 years (1997-2011). Indications for surgery for implanted HCC were: limited number of implanted lesions including those found incidentally during surgery; intrahepatic lesion absent or predicted to be locally controllable; and absence of ascites with sufficient hepatic functional reserve. Prognostic factors affecting survival after resection were determined by univariable and multivariable analysis. RESULTS: A total of 32 patients underwent 36 resections. Cumulative 1-, 3- and 5-year overall survival rates were 71, 44 and 39 per cent respectively, with a median survival time of 34.5 months. Univariable and multivariable analysis revealed that poor perioperative intrahepatic disease control was associated with poor survival. CONCLUSION: Surgical resection of implanted HCC may improve long-term survival in selected patients as long as intrahepatic disease is absent or well controlled.

Resection of segment VIII for hepatocellular carcinoma.

BACKGROUND: Anatomical resection of segment VIII (SVIII) is technically demanding. Only two small studies have published short-term outcomes. The aim of the present study was to evaluate short- and long-term outcomes after anatomical resection involving SVIII for hepatocellular carcinoma (HCC), and to compare long-term outcomes with those after non-anatomical resection of SVIII. METHODS: Outcomes after anatomical resection of SVIII or its subsegments for HCC were compared with those in patients who underwent primary non-anatomical resection of SVIII during the same period. RESULTS: A total of 154 patients underwent anatomical resection involving SVIII and 122 had non-anatomical resection. In patients undergoing anatomical resection, the preoperative indocyanine green retention rate at 15 min ranged from 2·9 to 32·2 (median 13·6) per cent, and was 10 per cent or more in 109 patients (70·8 per cent). Median duration of operation and blood loss were 378 min and 705 ml respectively. There were no postoperative deaths, but major adverse events occurred in ten patients (6·5 per cent). The cumulative 5-year recurrence-free and overall survival rates were 28·5 and 79·6 per cent, which were significantly better than rates of 19·4 and 64·8 per cent respectively after non-anatomical resection (P = 0·036 and P < 0·001). CONCLUSION: Complete resection of SVIII or its subsegments can be performed safely and the long-term outcomes seem acceptable. This can be a curative procedure for HCC, especially in patients with limited liver function reserve, in whom right hepatectomy or right paramedian sectorectomy might otherwise be needed.

Recurrence-free survival more than 10 years after liver resection for hepatocellular carcinoma.

BACKGROUND: High recurrence rates after liver resection with curative intent for hepatocellular carcinoma (HCC) remain a problem. The characterization of long-term survivors without recurrence after liver resection may help improve the therapeutic strategy for HCC. METHODS: A nationwide Japanese database was used to analyse 20 811 patients with HCC who underwent liver resection with curative intent. RESULTS: The 10-year recurrence-free survival rate after liver resection for HCC with curative intent was 22.4 per cent. Some 281 patients were recurrence-free after more than 10 years. The HCCs measured less than 5 cm in 83.2 per cent, a single lesion was present in 91.7 per cent, and a simple nodular macroscopic appearance was found in 73.3 per cent of these patients; histologically, most HCCs showed no vascular invasion or intrahepatic metastases. Multivariable analysis revealed tumour differentiation as the strongest predictor of death from recurrent HCC within 5 years. CONCLUSION: Long-term recurrence-free survival is possible after liver resection for HCC, particularly in patients with a single lesion measuring less than 5 cm with a simple nodular appearance and low tumour marker levels.

Venous reconstruction based on virtual liver resection to avoid congestion in the liver remnant.

BACKGROUND: Hepatic vein (HV) reconstruction may prevent venous congestion following resection of liver tumours that encroach on major HVs. This study aimed to identify criteria for venous reconstruction based on preoperative evaluation of venous congestion. METHODS: A volumetric analysis using image-processing software was performed in selected patients with liver tumours suspected on preoperative imaging of major HV invasion. The size of the non-congested liver remnant (NCLR) was calculated by subtracting the congested area from the liver remnant. Venous reconstruction was scheduled in patients who met the following criteria: normal liver function (indocyanine green retention rate at 15 min (ICGR(15) ) of less than 10 per cent) with a NCLR smaller than 40 per cent of total liver volume (TLV), or liver dysfunction (ICGR(15) 10-20 per cent) with a NCLR smaller than 50 per cent of TLV. Surgical outcomes and liver regeneration were investigated. RESULTS: A total of 55 patients with suspected HV invasion were enrolled. Sacrifice of one or more HVs was deemed possible in 37 patients. Venous reconstruction was scheduled in 18 patients. At operation, there was seen to be no venous involvement in 11 patients. The HV was sacrificed in 29 patients, and preserved or reconstructed in 24. Volume restoration ratios at 3 months were similar in the sacrifice (88 per cent) and preserve (87 per cent) groups. Operating time was shorter (465 min) and blood loss was lower (580 ml) in the sacrifice than in the preserve group (523 min and 815 ml respectively). CONCLUSION: The HV can be sacrificed safely according to the proposed criteria, reducing surgical invasiveness without influencing the postoperative course.

Pseudomonas aeruginosa infection after living-donor liver transplantation in adults.

OBJECTIVES: Pseudomonas aeruginosa infection is a major cause of bacterial infection after deceased-donor liver transplantation. The incidence and risk factors of P. aeruginosa infection after living-donor liver transplantation (LDLT), however, are not known. METHODS: We retrospectively reviewed the data from 170 adult patients who underwent LDLT at the University of Tokyo Hospital. The microbiologic and medical records of the patients from admission to 3 months after LDLT were reviewed. Uni- and multivariate analyses were performed to identify the independent risk factors for postoperative P. aeruginosa infection. RESULT: Preoperative P. aeruginosa carriage was identified in 15 (9%) patients. Only 2 of the 15 patients later presented with postoperative P. aeruginosa infection. Postoperative P. aeruginosa infection occurred in 27 (16%) of 170 patients by median postoperative day 38. Among those 27 patients, surgical site infections were recorded in 8 (30%) and intra-abdominal infections in 14 (52%). In 5 of the 27 (19%) patients, P. aeruginosa isolates were multiple antimicrobial resistant. Postoperative bile leakage independently predicted postoperative P. aeruginosa infection. CONCLUSION: P. aeruginosa infections were frequently detected after LDLT, including those by multiple antimicrobial-resistant isolates. Postoperative bile leakage predisposed patients to P. aeruginosa infection. Surveillance culture should be checked periodically after LDLT to ensure that appropriate antimicrobials can be administered for postoperative infection.

Methicillin-resistant Staphylococcus aureus infection after living-donor liver transplantation in adults.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection frequently complicates the postoperative course in deceased-donor liver transplantation. The incidence and risk factors of MRSA infection after Living-donor Liver transplantation (LDLT), however, are unclear. METHODS: We retrospectively reviewed the data from 242 adult patients who underwent LDLT at the University of Tokyo Hospital. The microbiologic and medical records of the patients from admission to 3 months after LDLT were reviewed. Uni- and multivariate analyses were performed to identify the independent risk factors for postoperative MRSA infection. RESULTS: Postoperative MRSA infection occurred in 25 of 242 patients by median postoperative day 23. Preoperative MRSA colonization, preoperative use of antimicrobials, operation time (> or =16 h), and postoperative apheresis independently predicted postoperative MRSA infection. CONCLUSION: Surveillance culture should be checked periodically after admission to identify patients at high risk for MRSA infection and to administer appropriate antimicrobials for perioperative infection. Postoperative apheresis, suggesting postoperative liver dysfunction, predisposed patients to MRSA infection.

Heparin-induced thrombocytopenia after liver transplantation.

BACKGROUND: Unfractionated heparin sodium (UFH) or low-molecular weight heparin (LMWH) is used in anticoagulant protocols at several institutions to prevent thrombosis after liver transplantation. Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated reaction to heparin, resulting in platelet count decreases of more than 50%. The frequencies of HIT after liver transplantation and platelet factor 4/heparin-reactive antibody (HIT antibody) positivity in liver transplantation patients, however, are unknown. PATIENTS AND METHODS: The 32 men and 20 women underwent living donor liver transplantation. We started LMWH (25 IU/kg/h) on postoperative day (POD) 1, switching to UFH (5000 U/d) on POD 2 or 3. The dose of UFH was changed according to the activated clotting time level. HIT antibody levels were measured the day before surgery and on POD 7 and 14. Platelet count was measured daily for 3 weeks. RESULTS: The average platelet counts preoperatively, and on POD 7, 14, and 21 were 65, 88, 149, and 169 x 10(9)/L, respectively. Two patients developed hepatic artery thrombosis on POD 11 and 19, respectively, although they were HIT antibody-negative and their platelet counts were stable. In 2 other patients, the platelet count decreased suddenly from 107 x 10(9)/L on POD 4 to 65 x 10(9)/L on POD 6 and from 76 x 10(9)/L on POD 7 to 33 x 10(9)/L on POD 9, respectively. The heparin-induced platelet aggregation test was negative in these patients. The percentage of HIT antibody-positive patients was 0.5% preoperatively, 5.6% on POD 7, and 5.6% on POD 14. None of the subjects/patients developed UFH-related HIT. CONCLUSIONS: In our series, the occurrence of HIT after liver transplantation was uncommon.

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays.

Genomic amplification of oncogenes and inactivation of suppressor genes are critical in the pathogenesis of human cancer. To identify chromosomal alterations associated with hepatocarcinogenesis, we performed allelic gene dosage analysis on 36 hepatocellular carcinomas (HCCs). Data from high-density single-nucleotide polymorphism arrays were analysed using the Genome Imbalance Map (GIM) algorithm, which simultaneously detects DNA copy number alterations and loss of heterozygosity (LOH) events. Genome Imbalance Map analysis identified allelic imbalance regions, including uniparental disomy, and predicted the coexistence of a heterozygous population of cancer cells. We observed that gains of 1q, 5p, 5q, 6p, 7q, 8q, 17q and 20q, and LOH of 1p, 4q, 6q, 8p, 10q, 13q, 16p, 16q and 17p were significantly associated with HCC. On 6q24-25, which contains imprinting gene clusters, we observed reduced levels of PLAGL1 expression owing to loss of the unmethylated allele. Finally, we integrated the copy number data with gene expression intensity, and found that genome dosage is correlated with alteration in gene expression. These observations indicated that high-resolution GIM analysis can accurately determine the localizations of genomic regions with allelic imbalance, and when integrated with epigenetic information, a mechanistic basis for inactivation of a tumor suppressor gene in HCC was elucidated.

Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) is generally a highly vascular tumor, but the mechanisms of neovascularization that permit rapid growth have not been defined. Angiopoietins (Ang) recently have been identified as ligands for vascular endothelial-specific Tie2 receptor tyrosine kinase and may be important growth factors in the generation of new blood vessels. We investigated Ang expression in 23 samples of HCC and paired adjacent uninvolved liver samples to determine if these genes have a potential role in the growth and spread of this disease. The full coding sequence of a variant angiopoietin-2 (Ang2) cDNA was obtained from HCC specimens, and the biologic consequences of overexpression on tumor formation and hemorrhage were determined in an animal model system. Angiopoietin-1 (Ang1) was equally expressed in HCC and adjacent noncarcinomatous liver tissue. Surprisingly, Ang2 was found to be highly expressed only in tumor tissue. In addition, Ang2 was expressed in 10 of 12 hypervascular HCC, but only in 2 of 11 hypovascular HCC. Ectopic expression of Ang2 in nonexpressing HCC cells promotes the rapid development of human hepatomas and produces hemorrhage within tumors in nude mice. These results suggest a role for Ang2 in the neovascularization of HCC. This enhanced gene expression may contribute to the clinical hypervascular phenotype, as well as tumor formation and progression.

Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.

Insulin resistance is often associated with atherosclerotic diseases in subjects with obesity and impaired glucose tolerance. This study examined the effects of insulin resistance on coronary risk factors in IRS-1 deficient mice, a nonobese animal model of insulin resistance. Blood pressure and plasma triglyceride levels were significantly higher in IRS-1 deficient mice than in normal mice. Impaired endothelium-dependent vascular relaxation was also observed in IRS-1 deficient mice. Furthermore, lipoprotein lipase activity was lower than in normal mice, suggesting impaired lipolysis to be involved in the increase in plasma triglyceride levels under insulin-resistant conditions. Thus, insulin resistance plays an important role in the clustering of coronary risk factors which may accelerate the progression of atherosclerosis in subjects with insulin resistance.

Blood eosinophilia after living donor liver transplantation for hepatitis C virus-related cirrhosis.

BACKGROUND: Differentiating between acute cellular rejection (ACR) and recurrent hepatitis C virus after liver transplantation in hepatitis C virus-positive patients is difficult, but vital for preventing graft loss. METHODS: The blood eosinophil counts 3 days before or on the day of biopsy were retrospectively reviewed to evaluate their value for predicting ACR in 91 biopsy samples from 45 patients. RESULTS: Eosinophil counts on the day of biopsy were significantly higher in the ACR group (n = 20) than in the non-ACR (n = 71) group, although the difference was negligible 3 days before the biopsy. A relative eosinophil count of 2% or an absolute eosinophil count of 200 cells/mm(3) predicted ACR with a specificity of 94% or 96%, respectively. CONCLUSIONS: Blood eosinophil count on the day of biopsy can be helpful in the diagnosis of ACR in patients who underwent living donor liver transplantation for hepatitis C virus-related cirrhosis.

Three-dimensional computed tomography for planning donor hepatectomy.

BACKGROUND: An accurate estimation of preoperative volumetric measurements of the donor liver is essential in living donor liver transplantation. METHODS: Three-dimensional (3-D) computed tomography (CT) was applied to 56 living donors. 3-D images of the liver were constructed using the region-growing method and the volume of each sector was measured. RESULTS: The median volume ratios of the left liver, caudate lobe, right paramedian, and lateral sectors were 34%, 4%, 38%, and 25% of the total liver volume, respectively. The shape of the congestive area in the right paramedian sector was properly demonstrated by 3-D CT. The volume of the region corresponded to 32% of the right liver. The actual volume of the graft correlated well with the estimated graft volume (n = .86). CONCLUSIONS: The region-growing method was useful for graft selection and for determining the indication of middle hepatic vein reconstruction in right liver grafts.

Impact of live donor age (>or=50) on liver transplantation.

BACKGROUND: The question of whether donor age negatively impacts recipient outcome in adult-to-adult living donor liver transplantation (LDLT) is rarely discussed. The aim of this study was to evaluate the impact of older donor age (50 years or older) on recipient outcomes in adult-to-adult LDLT. METHODS: LDLT data were retrospectively evaluated from our 299 LDLT cases in 297 recipients, which were divided into 2 groups: a younger group (group Y, donor age<50, n=237) and an older group (Group O, donor age>or=50, n=62). Clinical parameters of both recipients and donors were comparable between groups. RESULTS: There was no difference between the groups in patient survival or postoperative complications of either donors or recipients. In recipients, graft regeneration was significantly impaired in Group O. Graft function, including protein synthesis and cholestasis, was comparable between the 2 groups. CONCLUSION: Although the regeneration capacity of aged grafts was impaired, the function of grafts from older donors was comparable to that of those from younger donors. There was no difference in the clinical outcomes between the groups.

Impact of new methicillin-resistant Staphylococcus aureus carriage postoperatively after living donor liver transplantation.

BACKGROUND: Preoperative carriage of methicillin-resistant Staphylococcus aureus (MRSA) is associated with an increased risk of MRSA infection after liver transplantation. It is not known, however, whether new MRSA carriage postoperatively also increases the risk of MRSA infection after liver transplantation. METHODS: We retrospectively reviewed the data from 242 adult patients who underwent living donor liver transplantation (LDLT) including microbiological and medical records from admission to 3 months after LDLT. Uni and multivariate analyses were performed to identify independent risk factors for postoperative MRSA infection among preoperative noncarriers of MRSA. RESULTS: Postoperative MRSA infection occurred in 18 of 219 preoperative noncarriers of MRSA by median postoperative day 26. Operation time of at least 16 hours and postoperative colonization with MRSA independently predicted postoperative MRSA infection. CONCLUSION: Postoperative surveillance cultures should be performed periodically after liver transplantation to identify high-risk candidates for postoperative MRSA infection, even among preoperative noncarriers of MRSA.

Ultrasonographic evaluation of an unusual peri-anal induration: a possible case of deep tissue injury.

High-resolution ultrasound produces good quality echo images of skin and subcutaneous lesions. Here, it was used to characterise an atypical induration, which the authors speculate might have been a deep tissue injury.

Impact of celiac axis stenosis on living donor hepatectomy.

BACKGROUND: Celiac axis stenosis was once cited as a reason for exclusion from living donor liver transplantation. Donor hepatectomy, however, leaves the pancreaticoduodenal artery arcade untouched, and theoretically, celiac axis stenosis has no impact on otherwise possible donors. METHODS: Among 350 consecutive adult living donors of liver transplantation at Tokyo University Hospital, we experienced 11 (3%) donors with celiac axis stenosis or occlusion due to the median arcuate ligament. RESULTS: Harvesting of the right liver was the most common procedure (n = 8), followed by harvesting of segments II and III (n = 2), and left liver (n = 1). The postoperative course was uneventful in all of the donors. CONCLUSIONS: Our results indicate that donor hepatectomy can be safely performed in the presence of significant celiac artery stenosis.

New-onset diabetes mellitus after living donor liver transplantation: possible association with hepatitis C.

BACKGROUND: The relationship between hepatitis C virus (HCV) infection and new-onset diabetes mellitus (NODM) after liver transplantation is a controversial issue. METHODS: A total of 223 adult living donor liver transplantation (LDLT) recipients followed for more than 6 months were analyzed for the prevalence of NODM. The prevalence was compared between 62 HCV-positive and 161 HCV-negative patients. All the HCV-positive patients underwent preemptive antiviral treatment with interferon alpha2b and ribavirin. RESULTS: Preoperative diabetes mellitus was more frequently observed in HCV-positive patients (18% vs 4%, P = .001). NODM occurred more frequently in HCV-positive patients (41% vs 22%, P = .003). Multivariate analysis, however, revealed that HCV was not a predictor for NODM. A comparison of 14 HCV-positive patients with persistent NODM and 48 patients without persistent NODM indicated that there was no significant difference in the frequency of the viral response to antiviral therapy nor in HCV-RNA levels. Impaired glucose tolerance did not impact postoperative survival after LDLT. CONCLUSIONS: HCV was not associated with the prevalence of NODM after LDLT. NODM did not influence patient survival.