Transition of Spleen Volume Long After Pediatric Living Donor Liver Transplantation for Biliary Atresia.

PURPOSE: After undergoing the Kasai procedure for biliary atresia (BA), most patients develop severe splenomegaly that tends to be improved by liver transplantation. However, fluctuations in splenic volume long after transplantation remain to be elucidated. PATIENTS AND METHODS: Seventy-one consecutive patients who had undergone pediatric living donor liver transplantation (LDLT) for BA were followed up in our outpatient clinic for 5 years. They were classified into 3 groups according to their clinical outcomes: a good course group (GC, n = 41) who were maintained on only 1 or without an immunosuppressant, a liver dysfunction group (LD, n = 18) who were maintained on 2 or 3 types of immunosuppressants, and a vascular complication group (VC, n = 11). Splenic and hepatic volumes were calculated by computed tomography in 464 examinations and the values compared before and after the treatment, especially in the VC group. RESULTS: Splenic volume decreased exponentially in the GC group, with splenic volume to standard spleen volume ratio (SD) being 1.59 (0.33) 5 years after liver transplantation. Splenic volume to standard spleen volume ratios were greater in the VC and LD groups than in the GC group. Patients in the VC group with portal vein stenosis developed liver atrophy and splenomegaly, whereas those with hepatic vein stenosis developed hepatomegaly and splenomegaly. Interventional radiation therapy tended to improve the associated symptoms. CONCLUSIONS: Fluctuations in splenic volume long after pediatric LDLT for BA may reflect various clinical conditions. Evaluation of both splenic and hepatic volumes can facilitate understanding clinical conditions following pediatric LDLT.

Evaluation of postoperative changes in vascularized iliac bone grafts used for mandibular reconstruction.

Vascularized iliac bone grafts are used for mandibular reconstruction, but the factors affecting graft maintenance are unknown. This study explored the postsurgical changes in vascularized iliac bone grafts in patients who had undergone mandibular reconstruction after segmental resection. The study involved 24 patients (16 men and eight women) with oral tumours or osteoradionecrosis. Thirteen patients required bare bone grafting (BBG) and 11 patients required reconstruction with soft tissue coverage (six with a skin paddle and five with direct closure). The bone graft maintenance rate (with regard to the height of the centre of the graft) was calculated immediately after surgery and at 3, 6, 12, 24, and 36months after surgery. The maintenance rate was significantly lower in the BBG group than in the soft tissue coverage group at 3, 6, 12, 24, and 36months, and in those who were fitted with dentures compared to those who were not at 6, 12, 24, and 36months. Local infection also influenced the maintenance rate, but not significantly so. These findings indicate that the reconstruction technique and denture use can affect the bone graft maintenance rate after mandibular reconstruction with vascularized iliac bone grafts.

Antibody Drug Treatment for Steroid-Resistant Rejection After Pediatric Living Donor Liver Transplantation: A Single-Center Experience.

BACKGROUND: Antibody drugs have been used to treat steroid-resistant rejection (SRR) after liver transplantation. Although anti-thymocyte globulin has been used for SRR after liver transplantation in place of muromonab-CD3 since 2011 in Japan, the effectiveness of anti-thymocyte globulin after pediatric living-donor liver transplantation (LDLT) has not yet been reported. The aim of this study was to evaluate the effectiveness of antibody drug treatment for SRR after pediatric LDLT in our single center. METHODS: Between May 2001 and December 2013, 220 pediatric LDLTs were performed. Initial immunosuppression after LDLT included tacrolimus and methylprednisolone therapy. Acute rejection was diagnosed by use of a liver biopsy and the administration of steroid pulse treatment, and SRR was defined as acute rejection refractory to the steroid pulse treatment. RESULTS: Acute rejection and SRR occurred in 74 (33.6%) and 16 patients (7.3%), respectively. The graft survival rates of non-SRR and SRR were 92.4% and 87.5%, respectively (P = .464). The median concentration of alanine aminotransferase before and after the administration of antibody drug was 193.5 mU/mL (range, 8-508) and 78 mU/mL (range, 9-655), respectively (P = .012). The median rejection activity index before and after the administration of antibody drugs was 5 (range, 2-9) and 1 (range, 0-9), respectively (P = .004). After antibody drug treatment, 12 patients had cytomegalovirus infections, 2 patients had Epstein-Barr virus infections, 3 patients had respiratory infections, and 1 patient had encephalitis. The cause of death in 1 patient with SRR was recurrence of infant fulminant hepatic failure. CONCLUSIONS: Antibody drug treatment for SRR after pediatric LDLT is safe and effective.

A distinct function of the retinoblastoma protein in the control of lipid composition identified by lipidomic profiling.

Here, by combining lipidomics with transcriptome analysis, we demonstrate that Rb depletion in mouse embryonic fibroblastss induces significant alterations in their lipid composition. We discovered that Rb depletion induced increase in lysophosphatidylserine, diacylglycerol (DAG), fatty acid (FA), acylcarnitine, phosphatidylcholine (PC), arachidonoyl ethanolamine, and decrease in phosphatidylglycerol, monoacylglycerol, without change in total lipid per protein levels. Analysis of the acyl chain composition of DAG, PC and phosphatidylserine revealed increase of saturated and mono-unsaturated acyl chains with specific carbon chain length. Consistently, we observed that Rb depletion increased the levels of fatty acids with the corresponding carbon chain length and number of carbon-carbon double bondssuch as myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0) and all forms of FA 18:1. Microarray analysis revealed that Rb depletion induced significant upregulation of enzymes involved in elongation and desaturation of fatty acids. Among these, we found that elongation of long chain fatty acid family member 6 (Elovl6) and stearoyl-CoA desaturase 1 (Scd1) are the most robustly controlled by Rb possibly through E2F and sterol regulatory element-binding protein transcription factors. Depletion of Elovl6 or Scd1 significantly suppressed colony formation, sphere formation and xenograft tumor growth of Rb-deficient tumor cells. Suppression of self-renewal by the SCD1 inhibitor was rescued upon supplementation of the mono-unsaturated fatty acids generated by this enzyme. This study suggests a novel role for Rb in suppressing the malignant progression of tumors by controlling the lipid composition.

Thermogenesis induced by amino acid administration prevents intraoperative hypothermia and reduces postoperative infectious complications after thoracoscopic esophagectomy.

Minimally invasive thoracoscopic esophagectomy has potential advantages in minimizing the impairment of respiratory function and reducing surgical stress. However, thoracoscopic esophagectomy occasionally results in anesthesia-induced hypothermia, particularly in cases involving artificial pneumothorax with CO2. Thermogenesis induced by amino acid administration has been reported during anesthesia. Here, we tested the efficacy of amino acid treatment for the prevention of hypothermia, and we investigated the potential of this treatment to reduce postoperative infectious complications after thoracoscopic esophagectomy. We conducted a randomized trial in patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position in two groups and analyzed the incidences of hypothermia and surgical complications. One-hundred and thirty patients were randomized. Administration of amino acids resulted in a significant increase in core body temperature. In the saline (n = 60) and amino acid (n = 70) administration groups, 30% and 14.2% of patients, respectively, experienced infectious surgical complications (P = 0.029), and 21.6% and 22.8% of patients, respectively, experienced noninfectious surgical complications (P = 0.86). Univariate analysis revealed that blood loss and amino acid administration were significant factors for infectious surgical complications. Multivariate analysis revealed that amino acid administration was an independent factor reducing infectious surgical complications (P = 0.025, 95% confidence interval: 0.105-0.864). Administration of amino acids prevents hypothermia and reduces postoperative infectious complications after thoracoscopic esophagectomy.

Complementary Indicators for Diagnosis of Hepatic Vein Stenosis After Pediatric Living-donor Liver Transplantation.

INTRODUCTION: Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia. OBJECTIVES: Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study. METHODS: We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes. RESULTS: The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment. CONCLUSIONS: Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy.

Living-Donor Liver Transplantation Using Segment 2 Monosegment Graft: A Single-Center Experience.

BACKGROUND: In small infants, left lateral segment grafts are sometimes too large to overcome the problems of large-for-size grafts in the abdominal compartment. To address this problem, we have developed a safe living donor graftectomy for neonates, a so-called "S2 monosegment graft" to minimize graft thickness. We reviewed our single-center experience to evaluate the feasibility of this technique for reducing graft size. METHODS: Eleven living-donor liver transplants using S2 monosegment grafts were performed between October 2008 and September 2014 at our institution. Medical records of both donors and recipients were reviewed and data collected retrospectively. RESULTS: The mean age of recipients at the time of transplantation was 125.3 days, including 3 neonates. The average S2 monosegment graft weight was 127.4 g, and the graft-to-recipient body weight ratio was successfully reduced to 3.5%. The graft livers were reduced to 4.1 cm in thickness. Two recipients with grafts larger than 5 cm could not undergo primary abdominal closure. Portal vein stenosis and biliary stenosis was observed in 1 recipient, and hepatic artery complications were seen in 2 recipients; the clinical course for all donors were uneventful. Liver regeneration was seen in every patient. The graft and patient 1-year survival rate was 100%. CONCLUSIONS: Living-donor liver transplantation using S2 monosegment grafts offers a safe and useful option for treating smaller infants. Here, we introduce our method of S2 monosegment graft emphasizing the donor harvest and graft thickness.

PARVB overexpression increases cell migration capability and defines high risk for endophytic growth and metastasis in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is highly diverse, even in its early stages. This cancer is classified into three subtypes (superficial, exophytic, and endophytic) based on macroscopic appearance. Of these subtypes, the endophytic tumours have the worst prognosis because of their invasiveness and higher frequency of metastasis. METHODS: To understand the molecular mechanism underlying the endophytic subtype and to identify biomarkers, we performed a comprehensive gene expression microarray analysis of clinical biopsy samples and also confirmed the clinical relevance of differential gene expression. RESULTS: Expression of the parvin-beta (PARVB) gene and its encoded protein was significantly upregulated in endophytic-type TSCC. PARVB is known to play a critical role in actin reorganization and focal adhesions. Knockdown of PARVB expression in vitro caused apparent decreases in cell migration and wound healing, implying that PARVB has a crucial role in cell motility. Moreover, metastasis-free survival was significantly lower in patients with higher tumour expression of PARVB. CONCLUSIONS: These findings suggest that PARVB overexpression is a candidate biomarker for endophytic tumours and metastasis. This protein may be a clinically useful target for adjuvant TSCC therapy.

Integrated genomic and functional analyses reveal glyoxalase I as a novel metabolic oncogene in human gastric cancer.

Chromosomal abnormalities are good guideposts when hunting for cancer-related genes. We analyzed copy number alterations of 163 primary gastric cancers using array-based comparative genomic hybridization and simultaneously performed a genome-wide integrated analysis of copy number and gene expression using microarray data for 58 tumors. We showed that chromosome 6p21 amplification frequently occurred secondary to ERBB2 amplification, was associated with poorer prognosis and caused overexpression of half of the genes mapped. A comprehensive small interfering RNA knockdown of 58 genes overexpressed in tumors identified 32 genes that reduced gastric cancer cell growth. Enforced expression of 16 of these genes promoted cell growth in vitro, and six genes showing more than two-fold activity conferred tumor-forming ability in vivo. Among these six candidates, GLO1, encoding a detoxifying enzyme glyoxalase I (GLO1), exhibited the strongest tumor-forming activity. Coexpression of other genes with GLO1 enhanced growth-stimulating activity. A GLO1 inhibitor, S-p-bromobenzyl glutathione cyclopentyl diester, inhibited the growth of two-thirds of 24 gastric cancer cell lines examined. The efficacy was found to be associated with the mRNA expression ratio of GLO1 to GLO2, encoding glyoxalase II (GLO2), another constituent of the glyoxalase system. GLO1 downregulation affected cell growth through inactivating central carbon metabolism and reduced the transcriptional activities of nuclear factor kappa B and activator protein-1. Our study demonstrates that GLO1 is a novel metabolic oncogene of the 6p21 amplicon, which promotes tumor growth and aberrant transcriptional signals via regulating cellular metabolic activities for energy production and could be a potential therapeutic target in gastric cancer.

Effect of articulatory rehabilitation after oral cancer surgery on higher brain activation.

The present study aimed to verify the importance of postoperative articulatory rehabilitation in patients with oral cancer and to clarify the neurological changes underlying articulatory functional recovery. A longitudinal assessment of oral function and accompanying brain activity was performed using non-invasive functional magnetic resonance imaging (fMRI). We assessed 13 patients with cancers of the tongue and oral floor before and after ablative surgery. Articulatory function was assessed preoperatively and postoperatively using a conversation intelligibility test and the Assessment of Motor Speech for Dysarthria test. Patients also performed a verbal task during fMRI scans. The assessments were then repeated after the patients had undergone 4-6 months of articulatory rehabilitation therapy. Compared to pretreatment levels, articulatory rehabilitation resulted in a significant increase in activation in the supplementary motor cortex, thalamus, and cingulate cortex. The present study offers a quantitative assessment of the effects of speech rehabilitation by investigating changes in brain activation sites.

Iron overload after pediatric liver transplantation: a case report.

Iron is an essential nutrient for living cells; however, an excessive accumulation of iron leads to organ damage and directly affects systemic immunity. Iron overload is clinically classified as hereditary or secondary. Most of secondary iron overload is caused by frequent blood transfusions because there is no active mechanism to excrete iron from the body. As recommended in various guidelines, chelation therapy is effective for reducing iron burden and improving organ function. There have been few reports on iron overload through blood transfusion during the perioperative period of liver transplantation. This report presents a case of iron overload due to repeated transfusions after pediatric liver transplantation managed by chelation therapy. The patient, an 11-month-old female with biliary atresia, underwent living donor liver transplantation. She revealed refractory anemia and required frequent blood transfusion. Both serum ferritin and transferrin saturation tended to increase after repeated transfusions, leading to secondary iron overload. Iron chelation therapy was started to prevent progression to organ failure and infection due to iron overload, and yielded a favorable outcome. It is crucial to consider the possibility of secondary iron overload and to achieve early detection and treatment to avoid progression to irreversible organ damage.

Should isolated peritoneal carcinomatosis from colorectal cancer be sub-classified into stage IVB in era of modern chemotherapy?

BACKGROUND: According to the 7th edition of the TNM staging system, stage IV metastatic colorectal cancer (CRC) at the time of initial diagnosis is sub-classified into stage IVA or IVB disease. Peritoneal carcinomatosis (PC), considered to have a dismal prognosis, is exclusively sub-classified into stage IVB, even though other metastases to a sole organ are sub-classified into stage IVA, which is considered to be associated with better survival. This retrospective study was undertaken to investigate the overall survival in metastatic CRC patients, focusing on PC patients. METHODS: We reviewed data on patients with metastatic CRC at initial diagnosis surgically treated between January 2006 and June 2011. A survival analysis was performed paying special attention to PC and sub-classifying patients with PC into three categories according to metastatic sites. RESULTS: There were 69 stage IVA patients (IVA group) and 83 stage IVB. Among stage IVB patients, 20 had isolated PC (PC-I group), 28 had PC with one or more other sites of metastasis (PC-II group), and 35 had at least 2 metastatic without peritoneal involvement (NPC group). Of 152 stage IV patients, 132 (87 %) underwent resection of the primary tumor and 19 (12 %) underwent radical resection of metastatic disease with microscopic free margins (R0 resection) including 5/20 (25 %) patients in the PC1 group. A total of 139 patients received oxaliplatin-based chemotherapy in a palliative (n = 125), neoadjuvant (n = 3), or adjuvant setting after R0 resection (n = 11). Compared with 36.6 months in the PC-I group, median survival was 32.5 months (P = 0.48) in the IVA group, 14.7 months (P = 0.07) in the PC-II group, and 12.9 months (P < 0.01) in the NPC group. CONCLUSIONS: The sub-classification of isolated PC into stage IVA instead of IVB might be more appropriate in the era of modern chemotherapy. Further investigation is warranted.

A comparison of open surgery and endovascular intervention for hepatic artery complications after pediatric liver transplantation.

There are currently 2 major therapeutic options for the treatment of hepatic artery complications: endovascular intervention and open surgery. We herein report a retrospective analysis of 14 pediatric patients with hepatic artery complications after pediatric living donor liver transplantation (LDLT) at our institution. We divided them into an open surgery group and an endovascular intervention group based on their primary treatment, and compared the results and outcomes. We then evaluated which procedure is more effective and less invasive. In the open surgery group, recurrent stenosis or spasm of the hepatic artery occurred in 3 of the 8 patients (37.5%). In the endovascular intervention group, 5 of the 6 patients were technically successfully treated by only endovascular treatment. Of the 5 successfully treated patients, 3 developed recurrent stenosis (60%). There were significant differences in the mean length of the operation for the first treatment of hepatic artery complications (open surgery, 428 minutes vs endovascular intervention, 160 minutes; P = .01) and in the mean value of the posttreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (open surgery > endovascular intervention; P = .04/.05). Although endovascular intervention needs to be examined in further studies to reduce the rate of relapse, it is a less invasive method for the patient and graft than open surgery.

Tumor vessel-injuring ability improves antitumor effect of cytotoxic T lymphocytes in adoptive immunotherapy.

Angiogenesis is required for normal physiologic processes, but it is also involved in tumor growth, progression and metastasis. Here, we report the development of an immune-based antiangiogenic strategy based on the generation of T lymphocytes that possess killing specificity for cells expressing vascular endothelial growth factor receptor 2 (VEGFR2). To target VEGFR2-expressing cells, we engineered cytotoxic T lymphocyte (CTL) expressing chimeric T-cell receptors (cTCR-CTL) comprised of a single-chain variable fragment (scFv) against VEGFR2 linked to an intracellular signaling sequence derived from the CD3ζ chain of the TCR and CD28 by retroviral gene transduction methods. The cTCR-CTL exhibited efficient killing specificity against VEGFR2 and a tumor-targeting function in vitro and in vivo. Reflecting such abilities, we confirmed that the cTCR-CTL strongly inhibited the growth of a variety of syngeneic tumors after adoptive transfer into tumor-bearing mice without consequent damage to normal tissue. In addition, CTL expressing both cTCR and tumor-specific TCR induced complete tumor regression due to enhanced tumor infiltration by the CTL and long-term antigen-specific function. These findings provide evidence that the tumor vessel-injuring ability improved the antitumor effect of CTLs in adoptive immunotherapy for a broad range of cancers by inducing immune-mediated destruction of the tumor neovasculature.

Impact of hepatic lymph node metastasis on survival of patients with synchronous resectable or unresectable liver metastases of colorectal cancer.

BACKGROUND: The goals of this retrospective study were to comprehensively evaluate the impact of hepatic lymph node (HLN) involvement on survival in patients with synchronous resectable or unresectable liver metastases from colorectal cancer and to highlight how to deal with such cases in the light of recent advances in chemotherapy. METHODS: The impact of HLN involvement on survival, along with various clinical, pathological, and therapeutic factors, was retrospectively evaluated in 61 patients with synchronous liver metastases from colorectal cancer (resectable, 26; unresectable, 35), undergoing resection of the primary tumor and histopathological evaluation between July 2000 and April 2008. RESULTS: The proportion with HLN metastasis was 11.5 % in resectable cases and 28.6 % in unresectable cases. On multivariate analysis using the Cox proportional hazards model, HLN metastasis (P < 0.001), along with non-resection of hepatic lesions (P < 0.001), larger metastatic tumor volume (P < 0.001), non-use of oxaliplatin-based chemotherapy (P < 0.001), involvement of 4 or more regional lymph nodes (P < 0.001), and excessive lymphatic invasion (P = 0.02), was identified as an independent risk factor for shorter survival. CONCLUSIONS: To establish a new therapeutic strategy for synchronous liver metastasis of colorectal cancer, the HLNs should be examined histologically in patients undergoing resection of their primary colon and rectal cancer.

Living donor liver transplantation from an asymptomatic mother who was a carrier for ornithine transcarbamylase deficiency.

Liver transplantation (LT) has been adopted as a radical treatment for ornithine transcarbamylase deficiency (OTCD), yielding favorable outcomes. Despite the fact that it is an inheritable disease, a blood relative who is heterozygous for the disorder must sometimes be used as a liver donor for living donor LT. There is ongoing discussion regarding the use of heterozygous donors, however, to our knowledge, no cases where donation was determined based on the Ornithine transcarbamylase (OTC) activity before LT have been reported. Between May 2001 and April 2011, 17 patients were indicated for living donor LT because of OTCD at our facility. There were three cases with heterozygous donor candidate (17.6%). All heterozygous candidates underwent a liver biopsy to measure their OTC activity before LT and made efforts to secure the safety of the both donor and recipient. Two of 3 candidates had headaches sometimes, and their activity was less than 40%, and thus they were not employed as the donor. One candidate with 104.4% activity was employed, yielding favorable outcomes. Our current experience supported the effectiveness of our donation criteria, however it is necessary to collect sufficient data on a large number of patients to confirm the safety of the procedure.

A clinicoradiological study of odontogenic carcinomas and their impact on clinical diagnosis.

OBJECTIVES: To investigate the clinical and radiological characteristics of odontogenic carcinomas (OCs) and evaluate their impact on early clinical diagnosis. METHODS: The clinical and radiological features of all patients with OCs in our pathology record from January 1988 to December 2009 were retrospectively reviewed. The impact on a tentative diagnosis before final histological examination of clinical, panoramic and CT features was investigated. RESULTS: Of 474 cases with malignant jaw tumours, 417 (88%) were gingival squamous cell carcinomas (SCCs) and 27 (6%) were OCs. The average age of the patients with OCs was significantly lower than that of those with gingival SCCs. 20 OCs were in the mandible and 7 were in the maxilla. 22 OC patients (81%) had pain and/or swelling as an initial symptom of the disease. Although the majority of OCs showed irregularly contoured radiolucency, one-third of the cases showed cyst-like radiolucency totally or partially surrounded by a sclerotic rim on panoramic radiography. Permeative or gross cortical bone destruction and mass extension outside the jaw bone were found on CT and a diagnosis of malignant tumour was more common. Mass extension outside the cortex had a significant influence on malignant diagnosis. However, 22% of the patients were still clinically diagnosed as having osteomyelitis after CT. CONCLUSIONS: Although CT was useful to obtain a diagnosis of malignant tumour in OC patients, 22% of patients were clinically diagnosed as having osteomyelitis even after CT. When an osteomyelitis case is resistant to conventional therapy and gross bone destruction and/or mass extension is found on CT, a histopathological examination should be done.

Veno-occlusive disease/sinusoidal obstruction syndrome associated with potential antibody-mediated rejection after pediatric living donor liver transplantation: a case report.

A 9-month-old girl with biliary atresia underwent successful living donor liver transplantation from her 42-year-old ABO blood-type incompatible mother. The postoperative course was uneventful until postoperative day (POD) 13 when the recipient displayed an increased volume of drained ascites and decreased her platelet count showing low-velocity portal venous inflow without hepatic venous outflow obstruction. We suspected potential veno-occlusive disease/sinusoidal obstruction syndrome (vod/sos) due to an acute cellular rejection (ACR) episode and performed a liver biopsy (LB). We diagnosed severe episode (Rejection Activity Index Score; P3V3B1 = 7) and started steroid pulse therapy. We performed a second LB on POD 27 because the patient showed weight gain and tender hepatomegaly, diagnosing moderate ACR (P1V3B1 = 5). We started a second course of steroid pulse therapy, but the patient's clinical findings did not improve. On POD 43, her third LB finding showed P1V1B1 with improved processes from ACR, but still displaying severe congestion and fibrotic obliteration of small hepatic veins. We suspected that her immunologic responses were associated with antibody-mediated rejection (AMR) because her anti-HLA class I and class II antibodies were positive by flow panel-reactive antibody method and donor-specific antigen class II and C4d staining were also positive. We added mycophenolate mofetil and administered high-dose intravenous immunoglobulin to control the AMR, and anticoagulant therapy for the VOD/SOS. Her clinical findings and graft venous abnormalities finally improved; she was eventually discharged without sequelae on POD 72.

Living donor liver transplantation in children with cholestatic liver disease: a single-center experience.

OBJECTIVES: Cholestatic liver disease (CLD) is the main indication for liver transplantation in children. This retrospective study evaluated the outcomes of living donor liver transplantation (LDLT) in children with CLD. METHODS: One hundred fifty-nine children with CLD who underwent 164 LDLT between May 2001 and May 2011 were evaluated. Their original diseases were biliary atresia (n=145, 91%), Alagille syndrome (n=8, 5%), primary sclerosing cholangitis (n=2), and the others (n=4). The mean age and body weight of the recipients at LDLT was 42±53 months and 14.0±11.0 kg, respectively. RESULTS: Parents were living donors in 98%. The left lateral segment was the most common type of graft (77%). There were no reoperations and no mortality in any living donor. Recipients' postoperative surgical complications consisted mainly of hepatic arterial problems (7%), hepatic vein stenosis (5%), portal vein stenosis (13%), biliary stricture (18%), intestinal perforation (3%). The overall rejection rate was 31%. Cytomegalovirus infection and Epstein-Barr virus disease were observed in 26% and 5%, respectively. Retransplantation was performed five times in four patients; the main cause was hepatic vein stenosis (n=3). Four patients died; the main cause was gastrointestinal perforation (n=2). The body height of Alagille syndrome patients less than 2 years old significantly improved compared with older patients after LDLT. The 1-, 5-, and 10-year patient survival rates were 98%, 97%, and 97%, respectively. CONCLUSIONS: LDLT for CLD is an effective treatment with excellent long-term outcomes.

USPIO-enhanced MRI of highly invasive and highly metastasizing transplanted human squamous cell carcinoma: an experimental study.

OBJECTIVE: The aim of this study was to investigate the signal intensity characteristics of highly invasive and highly metastasizing transplanted human squamous cell carcinoma using ultra-small super-paramagnetic iron oxide (USPIO)-enhanced MRI and to correlate them with USPIO distribution to tumour components revealed by histological examination. METHODS: 13 nude mice with transplanted human squamous cell carcinoma in the oral cavity were imaged before and 24 hours after intravenous administration of USPIO. The difference in signal intensity between pre-contrast and post-contrast MR images was visually evaluated. For quantitative analysis, signal intensity within a region of interest was measured. Histological findings were correlated with MR findings. The approximate USPIO concentration was evaluated using USPIO phantoms. RESULTS: Seven tumours had an area showing signal intensity increase on post-contrast T1 weighted images. Histopathologically, six of those tumours contained a small amount of iron particles in the stroma. The USPIO concentration was presumed low. Two tumours had an area showing signal intensity decrease on post-contrast T1 and T2 weighted images. The areas had a large amount of iron particles in the stroma and the USPIO concentration was presumed high. There was a minimal amount of iron particles in tumour parenchymal cells. CONCLUSIONS: The amount of USPIO accumulation into tumour stroma was considered to affect MR signal intensity. A small amount increases T1 weighted signal intensity, whereas a large amount decreases T1 and T2 weighted intensity. The USPIO accumulation into the tumour parenchyma was not thought to affect MR signal intensity.