Toshiro Honna

Current role of liver transplantation for methylmalonic acidemia: A review of the literature

Abstract:  To evaluate the current role of liver transplantation (LT) for methylmalonic acidemia (MMA), we reviewed the literature on outcomes of this treatment, and describe three of our own cases of living‐donor liver transplantation (LDLT). The total number of LT cases identified was 18. Transplantation mode was deceased donor LT in 12, including five combined liver‐kidney transplantations (CLKT) from deceased donors, and LDLT in six. Three hospital mortalities were noted, because of metabolic decompensation, sepsis and aspergillosis. Although mean postoperative serum MMA level decreased to 13.8% ± 9.2% (range 1.25–26.1%) of preoperative levels, four patients (22.2%) had renal insufficiency after isolated LT and three (16.7%) had postoperative neurological disability. Continuing metabolic damage to the kidney and brain may occur even after successful LT. Further evaluation is required to determine the long‐term suitability of this treatment modality.

Idiopathic gastric volvulus in infancy and childhood.

Gastric volvulus is a rare condition in childhood. Most of the reported cases have been acute and secondary in type with predisposing factors. Between 1965 and 1988, 49 patients were treated at this institution for chronic idiopathic gastric volvulus. Patients were divided further into two groups according to age at admission. The main symptom was vomiting in the neonatal and infantile group, whereas it was abdominal distension, vomiting, weight loss, or constipation in the older age group. This clinical feature was different from that of acute gastric volvulus in which the symptoms resulted from gastric obstruction. Plain film of the abdomen showed no characteristic findings. Contrast study of upper gastrointestinal series showed findings similar to those of the acute volvulus, but the extent or degree was less significant. Conservative treatment was successfully undertaken for the patients in the neonatal and infantile group just by keeping them in prone position. The rationale for this method was demonstrated by the clinical and radiological improvement. Fundic gastropexy was performed in all of 18 patients of the older age group and in one of 31 patients of the neonatal and infantile group. The operative results were satisfactory except for one patient with mental retardation. In Japan, neonates or infants are customarily nursed in the supine position. This is presumed to be a reason why the chronic idiopathic gastric volvulus is frequently noticed.

Living donor liver transplantation with hyperreduced left lateral segments.

Liver transplantation is now an established technique to treat children with end-stage liver disease. Implantation of left lateral segment grafts (Couidauds segments II and III) can be a problem in small infants because of a large-for-size graft. Reduced left lateral segmental liver transplantation has been recently introduced for small infants to mitigate the problem of large-for-size graft. Further reduction of the left lateral segment graft increases the possibility of supplying an adequate hyperreduced left lateral segment graft as an alternative surgical technique. We report 3 cases of our experience of transplantation using hyperreduced left lateral segment grafts from living donors.

Double termination of the alimentary tract in females: A report of 12 cases and a literature review

Twelve female infants with double termination of the alimentary tract were reported. One patient had a high rectovaginal fistula, but in the other 11 cases the tract opened into the bowel uniformly at the level of the levator ani (anorectal-vestibular fistula). In these patients, diagnosis of the anatomical level of the fistula was made definitely with our radiological technique. Excision of not only the fistulous tract but also the anterior half of the rectum below the fistula is essential to achieve a cure without recurrence. The pathogenesis of this condition is discussed and the pertinent literature reviewed.

Resolution of hepatopulmonary syndrome after ligation of a portosystemic shunt in a pediatric patient with an Abernethy malformation

This report describes a case of Abernethy malformation associated with hepatopulmonary syndrome, which was resolved after shunt ligation. The clinical course indicated that hepatopulmonary syndrome can develop in Abernethy malformation in which liver function and portal pressure is normal, and liver transplantation is not the exclusive therapy for hepatopulmonary syndrome. The levels of endotoxin and endothelin 1 in the shunt blood were high, whereas those of tumor necrosis factor alpha and interleukin-1beta were within reference range. Although pathogenesis of hepatopulmonary syndrome remains unknown, the findings in this case suggest that bacterial translocation as well as elevated endothelin 1 may play a causal role in development of hepatopulmonary syndrome.

Serial determination of serum neuron-specific enolase in patients with neuroblastoma and other pediatric tumors*

The importance of determination of serum neuron-specific enolase (NSE) in patients with neuroblastoma has been emphasized by several authors. However, the specificity and sensitivity of NSE have not yet been well studied in tumors of infancy and childhood, nor is the role of serial determination of NSE in monitoring these patients fully understood. Concentrations of serum NSE were determined by a newly developed radioimmunoassay technique in 241 samples from 111 patients. NSE was also assayed in sera of nude mice bearing human pediatric tumors (16 samples), as well as in 30 tumor specimens. Eighty-two serum samples from 19 patients with neuroblastoma all showed NSE values (mean 120.2 ng/mL, range 16.2 to 722.0 ng/mL) elevated beyond the upper border of the normal range (14.6 ng/mL), even though four of the 19 patients had normal urinary excretion of 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA). Twelve of these patients were monitored with serial NSE determinations, and their serum NSE were found to correlate well with the tumor burden, but were transiently modified by chemotherapeutically induced cell death. All 68 samples from nine patients, free of neuroblastoma at assessment, showed NSE values within the normal range. Thirteen of 25 patients with tumors other than neuroblastoma, however, showed serum NSE values mildly elevated beyond the upper border of the normal range (mean of the 25 patients 36.7 ng/mL, range 5.0 to 234.0 ng/mL). Results from our nude mouse study and from NSE analysis of the tumor extracts paralleled the clinical results.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of Cyclin-dependent Kinase Inhibitor p27/Kipl and AP-1 Coactivator p38/Jabl Correlates with Differentiation of Embryonal Rhabdomyosarcoma

Cyclin‐dependent kinase (CDK) inhibitor p27/Kip1 (p27) is a diagnostic and prognostic marker of various malignancies. Low expression of p27 reflects poor differentiation and poor prognosis, and an inverse correlation between the expression of p27 and degree of tumor malignancy has been reported. Because p27 mutation is extremely rare in human tumors, it is important to study the expression of p27 and its inactivator, p38/Jab1 (JAB1). Here we analyzed the expression of p27 and JAB1 by immunohistochemistry in embryonal rhabdomyosarcoma (E‐RMS). We first confirmed the expression of p27 and JAB1 in normal human tonsillar epithelium, and observed a coordinated expression pattern depending on cell differentiation. Subsequently, specimens of eight poorlyand three well‐differentiated E‐RMS were examined for the expression of p27 and JAB1. The analyses revealed that four out of eight poorly‐differentiated E‐RMS were negative for p27, with positivity for nuclear JAB (NJAB) (‐ /± for p27/NJAB) in three and negativity for any JAB‐1 expression (‐ / ‐) in one. The remaining four poorly‐differentiated E‐RMS expressed p27 in the nuclei, together with predominant NJAB (±/±). In three well‐differentiated E‐RMS, only one expressed nuclear p27 and all of these three expressed no NJAB (±/ ‐ for p27/NJAB), but expressed predominant cytoplasmic JAB1 (CJAB). These findings suggest that JAB1 may play an important role in determining the differentiation stage of rhabdomyosarcoma cells by modulating the activity of CDK inhibitor p27.

Evaluating mortality and disease severity in congenital diaphragmatic hernia using the McGoon and pulmonary artery indices.

PURPOSE Lung hypoplasia is associated with mortality in congenital diaphragmatic hernia (CDH). However, the association between lung hypoplasia and disease severity is unclear. Early prediction of disease severity would provide parents with more precise information about the anticipated course of treatment, minimize treatment disruption, and maximize the efficient management of patients with CDH. We aimed at identifying the relationship between McGoon index (MGI) and pulmonary artery index (PAI) scores and disease severity among infants with CDH. METHODS We retrospectively reviewed the medical records of 19 high-risk patients with CDH born between January 2006 and December 2007. McGoon index and PAI scores were determined on admission. We evaluated statistically the relationship between these scores and variables representing severity as follows: number of vasodilators, use of inhaled nitric oxide (iNO), closed method of diaphragm, duration of intubation, duration of hospitalization, and use of home oxygen therapy. Statistical significance was P < .05. RESULTS Overall median MGI and PAI scores were 1.40 and 108, respectively; scores for nonsurvivors were significantly (P < .05 and P < .01, respectively) lower than those for survivors. Among survivors, PAI scores were significantly (P < .05) lower in infants requiring iNO than in infants not requiring iNO and patch repair. The PAI scores were significantly correlated with the number of vasodilators (r = -0.789; P < .01) and duration of intubation (r = -0.610; P < .05). CONCLUSIONS McGoon index (cutoff value, 1.31) and PAI (cutoff value, 90) are reliable indices for predicting mortality in CDH. Pulmonary artery index appears to be more useful than MGI for predicting disease severity among survivors.

The ratio of fucosylation of alpha-fetoprotein in hepatoblastoma

Hepatoblastoma differs from the adult type of hepatoma in clinical and pathologic features. The ratio of fucosylation of serum alpha‐fetoprotein (AFP) was determined in seven patients with hepatoblastoma and in 21 infants and children with otherwise elevated serum AFP, using the improved technique of lentil agglutinin‐affinity immunoelectrophoresis. The clinical data for the seven patients with hepatoblastoma were also reviewed. The ratio of fucosylation of AFP was significantly higher in all seven patients with hepatoblastoma, whereas it was minimal in all other cases of benign hepatic conditions such as neonatal hepatitis or biliary atresia, as well as in normal newborns. The ratio of fucosylation in hepatoblastoma, however, definitely decreased with the age of the patient at presentation. This finding suggests a correlation between fucosylation and a rapid rate of tumor growth, because all hepatoblastomas are believed to originate early in fetal life.

Repeat STEP procedure to establish enteral nutrition in an infant with short bowel syndrome.

The serial transverse enteroplasty (STEP) procedure is a safe and successful way to lengthen the small bowel in patients with short bowel syndrome. However, postoperative dilatation of the intestine may occur, which induces bacterial overgrowth and malabsorption leading to liver failure. We describe the case of an infant boy with short bowel syndrome caused by jejunal atresia requiring the STEP procedure twice. The first STEP improved the liver function, and the second STEP allowed 80% of the total calorie intake to be tolerated enterally. One should not hesitate to perform a second STEP if after the initial bowel lengthening procedure the patient develops small bowel dilatation that interferes with enteral nutrition.