Analysis of clinical characteristics, prognosis and antibody pathogenicity of pemphigus patients positive for anti-desmoglein IgG autoantibodies in remission: a retrospective cohort study.

BACKGROUND: The detection of serum anti-desmoglein (Dsg) IgG autoantibodies has been reported to be useful for assessment of disease activity in pemphigus. However, previous studies have reported that anti-Dsg autoantibodies remain detectable in some patients without active pemphigus lesions. OBJECTIVES: To investigate the clinical characteristics and antibody pathogenicity of pemphigus patients positive for anti-Dsg IgG autoantibodies in remission. METHODS: We retrospectively investigated pemphigus patients with a history of clinical remission who visited the Department of Dermatology of Keio University during 2019 and 2020. The antibody pathogenicity was assessed by bead aggregation assay. RESULTS: When patients were recognized as having entered remission (PDAI = 0 and PSL ≦ 10 mg/day for 2 months), serum autoantibodies against Dsg were detected in 72 of 132 patients (54.5%, positive group; PG), but were not detected in 60 patients (45.5%, negative group; NG). Anti-Dsg antibody titres in remission declined from the active phase in 33 patients in the PG for whom data were available. There were no differences in the chance of reducing PSL to 5 mg/day (P = 0.885) and rate of relapse (P = 0.279) between PG and NG, but fewer patients in PG discontinued corticosteroids (P = 0.004). The ability of patients' sera to block aggregation of Dsg/desmocollin beads was significantly reduced in remission compared to the active phase. However, our results revealed that whole sera in remission still had pathogenic activity in seven of nine patients, and the approximately equal amounts of anti-Dsg antibodies in active phase and remission showed similar pathogenicity. CONCLUSIONS: This study will provide guidance in cases where autoantibodies are found to be positive in pemphigus patients during remission or steroid reduction.

Effect of renin-angiotensin system inhibitors on pemetrexed plus platinum-induced hematological toxicities: a multicenter retrospective study using three propensity score analyses.

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. We retrospectively analyzed data from 305 consecutive patients with non-small cell lung cancer or malignant pleural mesothelioma who received their first cycle of a pemetrexed plus platinum regimen and were treated with or without RASIs. The primary endpoint was the incidence of severe myelosuppression after the first cycle. Propensity score (PS)-matched, PS-adjusted, and inverse probability of treatment weighting (IPTW) analyses were used. The number of patients with grade ≥3 hematological toxicities was 27 (8.9%). PS-matched analyses revealed that the concomitant use of RASIs was slightly associated with a lower risk of grade ≥3 hematological toxicities (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.20-2.32; p = 0.536). Additionally, sensitivity analyses using PS-adjusted and IPTW methods demonstrated similar results (OR, 0.63; 95% CI, 0.19-2.15; p = 0.463 and OR, 0.37; 95% CI, 0.11-1.29; p = 0.117, respectively). These findings suggest that RASIs might prevent pemetrexed plus platinum-induced hematological toxicities.

A patient with elderly-onset atypical hydroa vacciniforme with an indolent clinical course.

Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children and manifests as vesiculopapular eruptions in sun-exposed areas without systemic symptoms. HV-like lymphoma (HVLL) is one of the Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is based on monoclonal T-cell proliferation; however, its degree of malignancy is controversial owing to its variable prognosis. Elderly-onset cases of these diseases are extremely rare, and the clinical features remain unknown. It has been shown that late onset is closely associated with a severe phenotype in EBV-associated LPD including atypical HV. Here we describe a case of elderly-onset atypical HV accompanied by T-cell monoclonality, but with a very indolent clinical course. Our patient indicates a possible case with elderly-onset atypical HV manifesting a favourable course, and that T-cell monoclonality and age of onset cannot always predict the disease severity, and highlights the difficulty of prognosis prediction in elderly-onset atypical HV.

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.

Prediction of acute cellular rejection by peripheral blood eosinophilia in pediatric living donor liver transplantation.

BACKGROUND: Acute cellular rejection (ACR) is a common cause of morbidity following liver transplantation. Several reports have evaluated the predictive value of peripheral blood eosinophilia as a simple noninvasive diagnostic marker for ACR. This study examined whether the relative eosinophil counts (REC) predicted ACR in pediatric living donor liver transplantation (LDLT). METHODS: One hundred three patients underwent LDLT between May 2001 and December 2007. ACR were diagnosed based on the pathological findings. RESULTS: The incidence of ACR was 46.6% (48/103); ACR was diagnosed an average of 13.5 days after LDLT. The average REC at 4 and 2 days before the onset ACR (n = 39) within 30 postoperative day (POD) was 4.3% and 7.3%, respectively, and 9.0% at the onset. Patients with ACR showed significantly higher levels of REC compared with those free of ACR (P = .039). REC thresholds of 10% at POD 7 displayed a sensitivity and specificity of ACR detection of 80% and 75%, respectively. Moreover, the accumulated morbidity ratio of ACR within 30 POD was significantly higher with REC >10% at POD 7 (P = .007). CONCLUSION: ACR within POD 30 should be considered when REC is >10% at POD 7 after LDLT.

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.

Varicella zoster virus disease after pediatric living donor liver transplantation: is it serious?

OBJECTIVES: The aim of this study was to evaluate patients who developed varicella zoster virus (VZV) disease after pediatric living donor liver transplantation (PLDLT). METHODS: Two hundred fifty-five patients who underwent PLDLT between 1995 and 2010 were included in this study. Pretransplantation vaccination of VZV was performed for all recipients except emergency PLDLTs. Posttransplantation VZV vaccination was administered to the patients with a low VZV antibody titer 2 years or more after transplantation. The clinical course and outcomes of VZV disease in cases were reviewed with the transplant database and hospital medical records. RESULTS: Sixty-three patients developed VZV disease (chicken pox in 61, herpes zoster in 2) at a median onset of 36 months after PLDLT and at a median age of 4 years old, with a cumulative incidence of 25%. All chicken pox occurred in VZV antibody-negative patients. The onset of herpes zoster in the two patients occurred within 3 months after PLDLT; in addition, these patients were VZV antibody-positive patients. The clinical presentations of most patients were not serious and there were no disseminated infections. Although only 3 patients (5%) were hospitalized, the other 60 patients (95%) all showed a good response to oral antiviral therapy. CONCLUSIONS: Although VZV disease is an infectious disease with a high morbidity rate after PLDLT, it can normally be successfully managed on an outpatient basis at home. Pre- and posttransplantation vaccinations are effective for delaying the onset of chicken pox after PLDLT and to prevent it from developing into a serious illness.

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.

Interventional radiology for hepatic artery complications soon after living donor liver transplantation in a neonate.

Early hepatic artery complications after liver transplantation in children, having undergone LDLT, can directly affect graft and recipient outcomes, making early diagnosis and treatment essential. In the past, laparotomy (thrombectomy or reanastomosis) was generally employed to treat early hepatic artery complications. Recently, favorable outcomes of IR have been reported. In children, however, the number of such reports is small. To the best of our knowledge, there is no published report on IR applied to neonates with early hepatic artery complications. We recently succeeded in safely using IR for a neonate with early hepatic artery complications after LDLT and obtained a favorable outcome. This case is presented herein.

Hepatic artery reconstruction with the jejunal artery of the Roux-en-Y limb in pediatric living donor liver re-transplantation.

When re-anastomosis and re-transplantation becomes necessary after LDLT, arterial reconstruction can be extremely difficult because of severe inflammation and lack of an adequate artery for reconstruction. Frequently, the recipient's HA is not in good condition, necessitating an alternative to the HA. In such cases, the recipient's splenic artery, right gastroepiploic artery or another vessel can be safely used for arterial reconstruction. There have, however, been few reports on using the jejunal artery. Herein, we report our experience with arterial reconstruction using the jejunal artery of the Roux-en-Y limb as an alternative to the HA. A three-yr-old girl who had developed graft failure due to early HA thrombosis after LDLT required re-transplantation. At re-transplantation, an adequate artery for reconstruction was lacking. We reconstructed the artery by using the jejunal artery of the Roux-en-Y limb, as we judged it to be the most appropriate alternative. After surgery, stent was deployed because hepatic blood flow had reduced due to kinking of the anastomosed site, and a favorable outcome was obtained. In conclusion, when an alternative to the HA is required, using the jejunal artery is a feasible alternative.

Hepatic arterial buffer response after pediatric living donor liver transplantation: report of a case.

BACKGROUND: Excessive portal pressure at an early stage after living-donor liver transplantation (LDLT) can damage sinusoidal endothelial cells and hepatocytes through shear stress leading to graft failure, or hepatic arterial complications due to low hepatic artery flow from a hepatic arterial buffer response. We encountered a case in which excessive portal vein flow was observed from an early stage after pediatric LDLT. The hepatic artery flow decreased due to a hepatic arterial buffer response. CASE REPORT: A 6-month-old boy with biliary atresia showed excessive portal vein flow early after LDLT with a decreasing hepatic artery flow without anastomotic stenosis from postoperative day 3. The PV flow gradually exhibited a decrease at approximately postoperative day 8 and, similtaneously, hepatic artery flow exhibited improvement. CONCLUSION: Because excessive portal pressure after LDLT is reversible, it has been suggested that it may be possible to prevent the progress of hepatic arterial complications if temporary portal pressure modulation can be performed for cases among the high-risk group for hepatic arterial complications.

Living donor liver transplantation for ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency, the most common urea cycle disorder, causes hyperammonemic encephalopathy and has a poor prognosis. Recently, LT was introduced as a radical OTCD treatment, yielding favorable outcomes. We retrospectively analyzed LT results for OTCD at our facility. Twelve children with OTCD (six boys and six girls) accounted for 7.1% of the 170 children who underwent LDLT at our department between May 2001 and April 2010. Ages at LT ranged from nine months to 11 yr seven months. Post-operative follow-up period was 3-97 months. The post-operative survival rate was 91.7%. One patient died. Two patients who had neurological impairment preoperatively showed no alleviation after LT. All patients other than those who died or failed to show recovery from impairment achieved satisfactory quality-of-life improvement after LT. The outcomes of LDLT as a radical OTCD treatment have been satisfactory. However, neurological impairment associated with hyperammonemia is unlikely to subside even after LT. It is desirable henceforth that more objective and concrete guidelines for OTCD management be established to facilitate LDLT with optimal timing while avoiding the risk of hyperammonemic episodes.

Living-donor liver transplantation in 126 patients with biliary atresia: single-center experience.

OBJECTIVES: To describe our experience with 126 consecutive living-donor liver transplantation (LDLT) procedures performed because of biliary atresia and to evaluate the optimal timing of the operation. PATIENTS AND METHODS: Between May 2001 and January 2010,126 patients with biliary atresia underwent 130 LDLT procedures. Mean (SD) patient age was 3.3 (4.2) years, and body weight was 13.8 (10.7) kg. Donors included 64 fathers, 63 mothers, and 3 other individuals. The left lateral segment was the most commonly used graft (75%). Patients were divided into 3 groups according to body weight: group 1, less than 8 kg (n = 40); group 2,8 to 20 kg (n = 63); and group 3, more than 20 kg (n = 23). Medical records were reviewed retrospectively. Follow up was 4.5 (2.7) years. RESULTS: All group 3 donors underwent left lobectomy, and all group 1 donors underwent left lateral segmentectomy. No donors required a second operation or died. Comparison of the 3 groups demonstrated that recipient Pediatric End-Stage Liver Disease score in group 1 was highest, operative blood loss in group 2 was lowest (78 mL/kg), and operative time in group 3 was longest (1201 minutes). Hepatic artery complications occurred more frequently in group 1 (17.9%), and biliary stenosis (43.5%) and gastrointestinal perforation (8.7%) occurred more frequently in group 3. The overall patient survival rates at 1, 5, and 9 years was 98%, 97%, and 97%, respectively. Five-year patient survival rate in groups 1,2, and 3 were 92.5%, 100%, and 95.7%, respectively. Gastrointestinal perforation (n = 2) was the primary cause of death. CONCLUSIONS: Living-donor liver transplantation is an effective treatment of biliary atresia, with good long-term outcome. It seems that the most suitable time to perform LDLT to treat biliary atresia is when the patient weighs 8 to 20 kg.

Management of intra-abdominal drain after living donor liver transplantation.

BACKGROUND: There have been few reports on the management of intra-abdominal drains after living donor liver transplantation (LDLT). We retrospectively investigated changes in ascitic data related to management of an intra-abdominal drain. PATIENTS AND METHODS: Between March 2008 and June 2009, we performed 28 LDLT. On the first and the fifth postoperative day (POD) after LDLT, we examined the number of ascites cells and cell fractions as well as performed biochemical examination and cultures. RESULTS: The day of removal of the drain for massive ascites (10 mL/kg/d or more) was 14.2 ± 5.4 POD; for less than 10 mL/kg/d it was 8.7 ± 1.9 POD (P < .001). Nine patients were ascites culture positive; long-term placement of the drain caused an infection in two patients. CONCLUSIONS: When the amount of ascitic fluid on the fifth POD after LDLT was small, it was important to assess the properties of the ascitic fluid because of the possibility of a drain infection or of poor drainage. If the ascitic neutrophil count is less than 250/mm(3) or the examined ascites is normal, intra-abdominal drains should be removed.

Living donor liver transplantation for neonates using segment 2 monosubsegment graft.

The prognosis of liver transplantation for neonates with fulminant hepatic failure (FHF) continues to be extremely poor, especially in patients whose body weight is less than 3 kg. To address this problem, we have developed a safe living donor liver transplantation (LDLT) modality for neonates. We performed LDLTs with segment 2 monosubsegment (S2) grafts for three neonatal FHF. The recipient age and body weight at LDLT were 13-27 days, 2.59-2.84 kg, respectively. S2 or reduced S2 grafts (93-98 g) obtained from their fathers were implanted using temporary portacaval shunt. The recipient portal vein was reconstructed at a more distal site, such as the umbilical portion, to have the graft liver move freely during hepatic artery (HA) reconstruction. The recipient operation time and bleeding were 11 h 58 min-15 h 27 min and 200-395 mL, respectively. The graft-to-recipient weight ratio was 3.3-3.8% and primary abdominal wall closure was possible in all cases. Although hepatic artery thrombosis occurred in one case, all cases survived with normal growth. Emergency LDLT with S2 grafts weighing less than 100 g can save neonates with FHF whose body weight is less than 3 kg. This LDLT modality using S2 grafts could become a new option for neonates and very small infants requiring LT.

Living donor liver transplantation for congenital absence of the portal vein.

The congenital absence of the portal vein (CAPV) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. Liver transplantation (OLT) may be indicated for patients with symptomatic CAPV refractory to medical treatment, especially due to hyperammonemia, portosystemic encephalopathy, hepatopulmonary syndrome, or hepatic tumors. Because portal hypertension and collateral circulation do not occur with CAPV, significant splanchnic congestion may occur when the portocaval shunt is totally clamped during portal vein (PV) reconstruction in OLT. This phenomenon results in severe bowel edema and hemodynamic instability, which negatively impact the patient's condition and postoperative recovery. We have successfully reconstructed the PV in living donor liver transplantation (LDLT) using a venous interposition graft, which was anastomosed end-to-side to the portocaval shunt by a partial side-clamp, using a patent round ligament of the liver, which was anastomosed end-to-end to the graft PV with preservation of both the portal and caval blood flows. Owing to the differences in anatomy among patients, at LDLT for CAPV liver transplant surgeons should seek to preserve both portal and caval blood flows.

Effects of tomato juice consumption on plasma and lipoprotein carotenoid concentrations and the susceptibility of low density lipoprotein to oxidative modification.

Effects of tomato juice supplementation on the carotenoid concentration in lipoprotein fractions and the oxidative susceptibility of LDL were investigated in 31 healthy Japanese female students. These subjects were randomized to one of three treatment groups; Control, Low and High. The Control, Low and High groups consumed 480 g of a control drink, 160 g of tomato juice plus 320 g of the control drink, and 480 g of tomato juice, providing 0, 15 and 45 mg of lycopene, respectively, for one menstrual cycle. The ingestion of tomato juice, rich in lycopene but having little beta-carotene, increased both lycopene and beta-carotene. Sixty-nine percent of lycopene in plasma was distributed in the LDL fraction and 24% in the HDL fraction. In the Low group, the lycopene concentration increased 160% each in the VLDL+IDL, LDL and HDL fractions (p<0.01). In the High group, the lycopene concentration increased 270% each in the VLDL+IDL and LDL fractions, and 330% in the HDL fraction (p<0.01). Beta-carotene also increased 120% and 180% in LDL fractions of the Low and the High groups, respectively. Despite these carotenoid increases in LDL, the lag time before oxidation was not prolonged as compared with that of the Control group. The propagation rate decreased significantly after consumption in the High group. Multiple regression analysis showed a positive correlation between lag time changes and changes in the alpha-tocopherol concentration per triglyceride in LDL, and a negative correlation between propagation rate changes and changes in the lycopene concentration per phospholipid in LDL. These data suggest that alpha-tocopherol is a major determinant in protecting LDL from oxidation, while lycopene from tomato juice supplementaion may contribute to protect phospholipid in LDI, from oxidation. Thus, oral intake of lycopene might be beneficial for ameliorating atherosclerosis.