Duct-to-duct Biliary Reconstruction in Living-donor Liver Transplantation for Primary Sclerosing Cholangitis: Report of a Case.

Although Roux-en Y hepaticojejunostomy was previously recommended for the biliary reconstruction in liver transplantation for primary sclerosing cholangitis (PSC), some recent reports showed no difference in the graft survival between Roux-en Y and duct-to-duct anastomosis in deceased-donor liver transplantation. On the other hand, considering the risk of recurrence and the short length of the bile duct of the graft, duct-to-duct biliary anastomosis has never been reported in a patient undergoing living-donor liver transplantation (LDLT) for PSC. A 45 year-old male underwent LDLT using a left-lobe graft donated from his brother. Cholangiography showed no lesion in his common bile duct and duct-to-duct anastomosis was chosen for him. Fifteen months later, he suffered cholangitis due to PSC recurrence and endoscopic retrograde cholangiography was performed. The stents were inserted into his B2 and B3, and he remains well. Because of the ability to easily manage biliary complication, duct-to-duct biliary reconstruction may become the first choice in LDLT for PSC without common bile duct lesions.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome after hematopoietic cell transplantation for lymphoma.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.

In Situ Procurement of a Recipient's Portal Vein for a Right Lobe Liver Graft With Multiple Venous Orifices: A Case Report.

Reconstruction of multiple venous orifices of a right lobe graft is a time-consuming and troublesome procedure in right lobe living-donor liver transplantation. In the current study, we present a new venous reconstruction technique for a right lobe graft with multiple and complex hepatic vein (HV) orifices, in which procurement of the recipient's left portal vein was performed in situ to keep the anhepatic period to a minimum. All of the HV orifices were reconstructed together at the back table, while maintaining patency of the recipient's systemic and splanchnic circulation. A homologous vein graft and veno-venous bypass were not necessary. All HVs were patent during the follow-up and the patient was free from complications. In conclusion, the present technique is readily available for reconstruction of complex and multiple HV tributaries, while avoiding a long anhepatic time and the use of veno-venous bypass.

Salvage Splenic Artery Embolization for Saving Falling Living Donor Graft due to Portal Overflow: A Case Report.

Portal decompression is an approach for reducing portal overflow caused by small-for-size syndrome. We report the case of a patient who recovered from rapidly progressing hyperbilirubinemia caused by a small graft by decompressing portal overflow with splenic artery embolization following a living donor liver transplantation (LDLT). The patient was a 54-year-old man with end-stage liver disease secondary to alcoholic liver cirrhosis; the donor was his 54-year-old wife. The graft volume of the left lobe was 444 mL, which was 34.8% of the standard liver volume (SLV) and insufficient for the recipient; thus, the plan was to use the right lobe for the graft. The patient underwent LDLT with a right lobe graft; the volume to SLV ratio was 39.1%, and the graft-to-recipient-weight ratio was 0.72%. Although portal pressure was low during the operation, the patient eventually developed small-for-size syndrome after LDLT. It was conceivable that because the patient had splenomegaly, portal decompression would be effective. Splenic arterial embolization was performed successfully on postoperative day (POD) 7. The patient's total bilirubin level was increased to 40 mg/dL on POD16. Decreased portal flow, which was shown by ultrasound screening to be "to-and-flo," increased again on POD23 to one-third of that on POD1. He was discharged without any infectious complications. Additional splenic artery embolization after LDLT may be a convenient option for reducing portal overflow for patients with splenomegaly if the portal decompression was not performed for some reason at the surgery.

Functional assessment of the liver with gadolinium-ethoxybenzyl-diethylenetriamine penta-acetate-enhanced MRI in living-donor liver transplantation.

BACKGROUND: A precise estimation of the capacity of the remnant liver following partial liver resection is important. In this study, the regional function of the liver in patients undergoing living-donor liver transplantation was evaluated by gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (EOB)-enhanced MRI, with special reference to the congested region. METHODS: EOB-MRI analysis was performed before hepatectomy in donors, and 7 days after surgery in the donor and recipient. In the hepatocyte phase, from images obtained 15 min after Primovist® injection, the signal intensity in each liver segment was measured and divided by the signal intensity of the erector spinae muscle (liver to muscle ratio, LMR) for standardization. Inter-regional differences in LMRs were analysed in donors and recipients. RESULTS: Thirty-two living donors and 31 recipients undergoing living-donor liver transplantation were enrolled. In donors, the LMRs of the remnant left lobe were almost equivalent among the liver segments. In the remnant right lobe without the middle hepatic vein, the mean(s.d.) LMR for congested segments (S5 and S8) was significantly lower than that for non-congested segments (S6 and S7): 2·60(0·52) versus 3·64(0·56) respectively (P < 0·001). After surgery, values in the non-congested region were almost identical to those in the preoperative donor liver. LMR values in the left and right lobe graft were significantly lower than those in the corresponding segment before donor surgery (P < 0·001). CONCLUSION: The function of the congested region secondary to outflow obstruction in the remnant donor liver was approximately 70 per cent of that in the non-congested region. EOB-MRI is a promising tool to assess regional liver function, with good spatial resolution.

Impact of platelets and serotonin on liver regeneration after living donor hepatectomy.

BACKGROUND: Several animal models have revealed that platelet-derived serotonin initiates liver regeneration after hepatectomy. However, there are few reports regarding the effects of serotonin in the clinical setting. The aim of this study was to explore the impact of serotonin and platelets in the early phase after healthy living donor hepatectomy. STUDY DESIGN: Stored samples from 34 living donors who received left lobectomy with caudate lobectomy (LL+C) or right lobectomy (RL) were available in the study. Serum serotonin levels and platelet counts associated with liver regeneration such as whole liver volume and hepatic graft weight (GW) were retrospectively collected from the database and analyzed. RESULTS: The remnant liver volume rate of RL grafts was smaller than that of LL+C grafts (45.4% vs 64.7%; P < .001). The regeneration rate at 7 days after surgery did not differ between the 2 groups (123% vs 122%). The serotonin levels and platelet counts decreased after surgery until postoperative day 3, then increased thereafter. The platelet counts and serotonin levels of LL+C donors were significantly higher than those of RL donors. CONCLUSIONS: Our findings suggest that platelets and serotonin play a pivotal role in initiating liver regeneration in the remnant liver.

Prognostic impact of des-γ-carboxyl prothrombin in living-donor liver transplantation for recurrent hepatocellular carcinoma.

BACKGROUND: Although the Milan criteria are widely accepted for liver transplantation (LT) in patients for hepatocellular carcinoma (HCC), they have not been fully evaluated for salvage LT in patients with recurrent HCC. We have previously reported outcomes of living-donor LT (LDLT) for HCC and identified 2 risk factors affecting recurrence-free survival (RFS): tumor size >5 cm and des-γ-carboxyl prothrombin (DCP) concentration >300 mAU/mL (Kyushu University criteria). This study was designed to clarify risk factors for tumor recurrence after LDLT in patients with recurrent HCC. METHODS: Outcomes in 114 patients who underwent LDLT for recurrent HCC were analyzed retrospectively. RFS rates after LDLT were calculated, and risk factors for tumor recurrence were identified. RESULTS: The 1-, 3-, and 5-year RFS rates after LDLT were 90.6%, 80.4%, and 78.8%, respectively. Univariate analysis showed that tumor recurrence was associated with alpha-fetoprotein concentration ≥ 300 ng/mL, DCP concentration ≥ 300 mAU/mL, tumor number ≥ 4, tumor size ≥ 5 cm, transarterial chemotherapy before LDLT, duration of last treatment of HCC to LDLT <3 months, bilobar distribution, exceeding Milan criteria, exceeding Kyushu University criteria, poor differentiation, and histologic vascular invasion. Multivariate analysis showed that DCP ≥ 300 mAU/mL (P = .03) and duration from last treatment to LDLT <3 months (P = .01) were independent predictors of RFS. CONCLUSIONS: DCP concentration and time between last treatment and LDLT are prognostic of RFS in patients undergoing LDLT for HCC.

Chronic immune-mediated reaction syndrome as the cause of late graft mortality in living-donor liver transplantation for primary biliary cirrhosis.

INTRODUCTION: Few studies to date have investigated the causes of late graft mortality after living-donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC). PATIENTS AND METHODS: Fifty-five LDLTs for PBC were retrospectively reviewed. Factors prognostic of graft survival after LDLT were investigated, and histologic findings in patients with late graft loss were assessed. RESULTS: The 1-, 5-, and 10-year cumulative graft survival rates were 85.1%, 82.5%, and 66.9%, respectively. Multivariate Cox regression analysis found that male donor and ≥ 4 HLA mismatches were independently associated with poor graft survival. Among the 13 grafts lost, 5 were lost >1 year after LDLT, including 1 each due to chronic rejection, veno-occlusive disease, and obliterative portal venopathy, and 2 to other causes. Pathologic reviews of the serial biopsy specimens and explanted grafts from these 5 patients, with graft rejections from "chronic immune-mediated reaction syndrome," showed reciprocal changes over time. No patient died of recurrent PBC. CONCLUSIONS: Male donor and ≥ 4 HLA mismatches were independent factors associated with poor graft survival. Late graft mortality after LDLT for PBC in some patients was due to chronic immune-mediated reaction syndrome, including chronic rejection, veno-occlusive disease, and obliterative portal venopathy, but not to recurrent PBC.

Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis.

BACKGROUND: Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT). METHODS: Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed. RESULTS: Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively. CONCLUSIONS: Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis.

Two-step selection criteria for living donor liver transplantation in patients with hepatocellular carcinoma.

We have proposed risk factors for tumor recurrence, such as tumor nodule ≥ 5 cm and des-gamma-carboxy prothrombin ≥ 300 mAU/mL after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors for HCC recurrence and mortality within our criteria. We enrolled 152 adult recipients who had undergone LDLT for end-stage liver disease with HCC who met our criteria. The recurrence-free survival rates after LDLT were calculated. Risk factors for tumor recurrence were identified. On univariate analysis, factors affecting recurrence-free survival were pretransplant treatment for HCC, neutrophil-to-lumphocyte ratio (NLR) >4, alpha-fetoprotein ≥ 400 ng/mL, ≥ 5 nodules, and bilobar tumor distribution. Multivariate analysis identified that NLR >4 and ≥ 5 nodules were independent risk factors for tumor recurrence after LDLT (P = .003 and P = .002, respectively). Two-step selection criteria enable selection of patients who have high-risk of tumor recurrence.

Esophageal replacement by colon interposition with microvascular surgery for patients with thoracic esophageal cancer: the utility of superdrainage.

Replacing the thoracic esophagus with the colon is one mode of reconstruction after esophagectomy for esophageal cancer. There is, however, a high incidence of postoperative necrosis of the transposed colon. This study evaluated the outcomes of colon interposition with the routine use of superdrainage by microvascular surgery. Twenty-one patients underwent colon interposition from 2004 to 2009. The strategy for colon interposition was to: (i) use the right hemicolon; (ii) reconstruct via the subcutaneous route; (iii) perform a microvascular venous anastomosis for all patients; and (iv) perform a microvascular arterial anastomosis when the arterial blood flow was insufficient. The clinicopathologic features, surgical findings, and outcomes were investigated. The colon was used because of a previous gastrectomy in 18 patients (85.7%) and synchronous gastric cancer in three patients (14.3%). Eight patients (38.1%) underwent preoperative chemoradiotherapy including three (14.3%) treated with definitive chemoradiotherapy. Seven patients (33.3%) underwent microvascular arterial anastomosis to supplement the right colon blood supply. Pneumonia occurred in four patients (19.0%). Anastomotic leakage was observed in five patients (23.8%); however, no colon necrosis was observed. The 3-year and 5-year overall survival rates were both 50.6%. Colon interposition with superdrainage results in successful treatment outcomes. This technique is one option for colon interposition employing the right hemicolon.

Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia.

The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issues were included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PT-INR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality.

The impact of IL28B genetic variants on recurrent hepatitis C in liver transplantation: significant lessons from a dual graft case.

IL28B genetic polymorphism is related to interferon-sensitivity in chronic hepatitis C, but the significance of grafts carrying different genotypes from recipients is still unclear in liver transplantation. A 51-year-old Japanese male carrying a minor genotype underwent dual liver transplantation for liver cirrhosis due to hepatitis C virus (HCV). The left lobe graft carried a major genotype, and the right a minor genotype. He achieved virological response during the course of pegylated-interferon and ribavirin therapy against recurrent hepatitis C for 2 years, but HCV relapsed immediately at the end of the therapy. Two years after antiviral therapy, liver biopsy was performed from each graft. The specimens showed A1F0 in the left lobe graft and A2F2 in the right. Moreover, quantitative polymerase chain reaction was performed using RNA extracted from each specimen to see there was no HCV RNA in the left lobe whereas there was in the right. This case provides clear evidence that IL28B genetic variants determine interferon sensitivity in recurrent hepatitis C following liver transplantation, which could result in new strategies for donor selection or for posttransplant antiviral therapy to HCV positive recipients.

End-stage liver cirrhosis with severe autoimmune hemolytic anemia, treated by blood type-incompatible living donor liver transplantation: a case report.

We present a case of successful living donor liver transplantation (LDLT) for liver cirrhosis caused by hepatitis B virus with severe autoimmune hemolytic anemia (AIHA) using an ABO-incompatible (ABOi) graft. The patient was a 47-year-old woman who had a history of ruptured esophageal varices, accumulation of intractable ascites, frequent hepatic encephalopathy and severe anemia, with a hemoglobin value of approximately 3 g/dL due to AIHA. We treated the patient by LDLT using an ABOi liver graft. The treatment strategy included anti-CD20 antibody, plasma exchange and transfusion before LDLT. The patient's anemia improved after surgery; she required only 2 units of irradiated red blood cell concentrates-leukocytes reduced. The patient was discharged from the hospital on postoperative day 35. Two years after surgery, the patient still shows normal hepatic and hematological findings. The immunomodulation protocol for ABOi LDLT was effective not only to avoid humoral reactions associated with ABOi LDLT, but also those associated with AIHA.

Prognostic importance of the gross classification of hepatocellular carcinoma in living donor-related liver transplantation.

BACKGROUND: The gross classification of hepatocellular carcinoma (HCC) has been reported to be a significant prognostic factor for patients with HCC undergoing partial hepatectomy. The present study investigated whether the gross classification of HCC is also a prognostic factor in living donor-related liver transplantation (LDLT). METHODS: Some 119 patients undergoing LDLT for HCC were identified retrospectively from a prospective institutional database containing information on all LDLTs carried out between 1996 and 2009. Patients were divided into three groups according to the gross classification of the largest tumour in the explanted liver: type 1 HCC, single nodular type (81 patients); type 2, single nodular type with extranodular growth (21); and type 3, contiguous multinodular type (17). Clinicopathological factors and recurrence-free survival rates were compared. RESULTS: Recurrence-free survival rates for the whole group were 87·7 per cent at 1 year, 83·5 per cent at 3 years and 81·0 per cent at 5 years after LDLT. Type 3 HCC was associated with large tumour size, poor histological grade, a high incidence of microvascular invasion and multiple tumours. Independent predictors of poor recurrence-free survival were preoperative serum level of des-γ-carboxy prothrombin exceeding 300 mAU/ml, microvascular invasion and type 3 HCC. CONCLUSION: The gross classification of HCC was an independent predictor for recurrence of HCC in patients undergoing LDLT.

Crescentic glomerulonephritis associated with totally implantable central venous catheter-related Staphylococcus epidermidis infection.

A 59-year-old woman was admitted to our hospital for treatment of acute renal insufficiency. She had been under home intravenous hyperalimentation therapy through a totally implantable central venous catheter for 2 years because of post-radiation enteritis. Clinical examination on admission revealed severe renal insufficiency complicated with hypocomplementemia, marked proteinuria and hematuria. Chest roentgenography demonstrated moderate pulmonary congestion. Hemodialysis was initiated and her pulmonary congestion improved. On the 14th and 21st hospital day, blood culture revealed Staphylococcus epidermidis colonization. Cefazolin was administered and C-reactive protein decreased, however, renal insufficiency and hypocomplementemia did not improve. To investigate the genesis of renal insufficiency, renal biopsy was performed. Light microscopic findings of the kidney revealed severe crescentic glomerulonephritis complicated with moderate tubulointerstitial damage. Immunofluorescence-microscopic findings of the kidney revealed positive IgG, IgM, C3 deposition along the capillary lumen. From these laboratory findings and the clinical course, we diagnosed her renal disease as crescentic glomerulonephritis induced by catheter-related bloodstream infection, and the central venous catheter was removed. After removal, urinary output and hypocomplementemia remarkably improved, however, unfortunately, her renal dysfunction did not improve and maintenance hemodialysis needed to be continued. Although her renal disease was not caused by ventriculo-atrial shunt but by central venous catheter-related bloodstream infection, we supposed that the pathogenesis was a closely similar entity to shunt nephritis.

Effects of several surfactants and high-molecular-weight organic compounds on decomposition of trichloroethylene with zerovalent iron powder.

We investigated the effects of coexisting surfactants and high-molecular-weight organic compounds on the reductive dechlorination of trichloroethylene by zerovalent iron powder to determine whether these additives had utility as washing reagents for remediation of soil and groundwater pollution. During the dechlorination reaction, the amount of trichloroethylene decreased, and the formation of cis-1,2-dichloroethylene was observed. The decomposition of trichloroethylene was found to be first-order with respect to the trichloroethylene and zerovalent iron concentrations when the solution contained no additives. The rates of decomposition of trichloroethylene in the presence of the additives were lower than the rate in the absence of the additives: the rate constant was reduced by a factor of 0.7 for the cationic surfactant cetyltrimethylammonium bromide; by a factor of 0.5 for the anionic surfactants sodium n-dodecylbenzenesulfonate, sodium n-dodecylsulfate, and sodium n-dodecanesulfonate and for the high-molecular-weight organic compounds soluble starch, beta-cyclodextrin, and polyethyleneglycol 6000; and by a factor of 0.2 for sodium laurate and the nonionic surfactants Triton X-100, Tween 20, Tween 60, Brij 35, and Brij 58. Comparison of the concentrations of the nonionic surfactants with their critical micellar concentrations indicated that the rate-reducing effect of these additives was due to solubilization of trichloroethylene into the micellar phase. The adsorption of trichloroethylene onto the zerovalent iron surface was also affected by the presence of the additives. Thus, our results indicated that the changes in the decomposition rate of trichloroethylene were determined by several factors.

Mandibular gingival arteriovenous malformation in pregnancy.

Arteriovenous malformations (AVM) are rare in the oral and maxillofacial regions. We report a case of a mandibular gingival AVM in a pregnant woman, who presented at 35 weeks' gestation with massive pulsatile bleeding from a mass in the mandibular gingival margin, which could be managed by local compression and cauterisation. After delivery, the mass gradually regressed. She developed a similar swelling during a second pregnancy. It was thought that increased cardiac output as a result of her pregnancy caused her AVM to progress.

Living donor liver transplantation using dual grafts from two donors: a feasible option to overcome small-for-size graft problems?

Living donor liver transplantation (LDLT) between adults inevitably implies two potential risks associated with a small-for-size graft for the recipient and small remnant liver for the donor. To overcome these problems, LDLT using dual grafts from two independent donors can be a solution, in which sufficient graft volume can be obtained while preserving donor safety. We present a case of LDLT that was managed successfully by using right and left lobe dual grafts from two donors. The recipient was a large-size male with hepatitis C cirrhosis complicated by multiple hepatocellular carcinomas (HCCs). The first donor donated a right lobe graft and the second donor donated a left lobe plus caudate lobe graft with the middle hepatic vein. Graft function was excellent throughout the course without evidence of small-for-size syndrome. In conclusion, LDLT using dual grafts can be justified in a selected case to avoid small-for-size graft problems without increasing independent donor risks.