Morihiro Saeki

Analysis of 1,992 patients with anorectal malformations over the past two decades in Japan

BACKGROUND/PURPOSE This report describes the results of a group study of the Japanese Study Group of Anorectal Anomolies (JSGA) to determine the relative incidence of specific types of anorectal anomaly in Japan, and includes discussion of rectourethral fistula regarding the relationship between the levels of the fistula and blind end of the rectum, low type deformity, rare types, and associated anomalies. METHODS A total of 1,992 patients (1,183 boys and 809 girls) registered from 1976 to 1995 were analyzed. RESULTS High-type deformities accounted for 26.0% of cases, intermediate 10.7%, low 57.2%, miscellaneous 4.5% and unclassified 1.8%. The most frequent deformity was male anocutaneous fistula (n = 364), followed by male rectourethral fistula (n = 333), and female anovestibular fistula (n = 241). There were 42 rectovesical fistulas in boys and 93 rectocloacal fistulas in girls. Covered anus complete occurred at the same frequency (10.1% of low deformities) as covered anal stenosis. In rectourethral fistula, the blind end of the rectum lay at or above the level of the P-C line in 40.3% of cases, at or above the M line in 39.6% and at the vicinity of the I line in 20.2%, respectively. There was no parallel relationship between the site of the fistula opening and the level of the rectal pouch. The overall incidence of patients having one or more associated anomalies was 45.2%: 70.6% in high deformity, 60.7% in intermediate, and 31.3% in low. The rate of association of Downs syndrome with deformities without fistula (40.3%) was significantly higher than with deformities with fistula (0.3%). CONCLUSIONS Rectovesical fistula and covered anus complete were not infrequent deformities in this series. We consider that at least 20% of rectourethral fistula should be categorized as intermediate or low deformity from the viewpoint of the position of the rectal pouch. A significant preponderance of Downs syndrome in the deformities without fistula suggests that further investigation of associated anomalies in comparision with other congenital diseases may provide insights into the pathogenesis of anorectal malformation in the field of molecular genetics.

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.

Long-term results of jejunal replacement of the esophagus

Since 1969, jejunal interpositions have been carried out in 19 patients for esophageal replacement. A segment of the upper jejunum was used to bridge the gap in the right thoracic cavity. The distal esophagus and its sphincteric mechanism was preserved in all but four patients, who had peptic strictures. Early postoperative complications such as total necrosis of the graft, perforation of the graft, and anastomotic leak developed in three patients (16%). There were no operative deaths but there were two later deaths (11%). We were able to follow 12 patients over a long term. Among these 12 patients there were two anastomotic strictures, one of which was dilated successfully by bouginage, and one marked redundancy of the jejunum which necessitated surgical correction. Both height and weight were lower than -2 SD on a Japanese standard growth curve in two patients who had anastomotic strictures. Transient stagnation of swallowed barium at the lower esophagus was the common finding; it was observed in seven cases (58%). Only three patients (25%) complained of occasional feelings of delay in swallowing. Stagnation with a mildly redundant jejunum was the common radiologic finding in these three patients. Reflux of the gastric content into the esophagus did not occur. All the patients, except one who still has dysphagia due to anastomotic stricture, can eat anything they wish at almost normal speed. These long-term results indicate that jejunal interposition with preservation of the lower esophagus is a recommendable procedure for esophageal replacement.

Longitudinal follow-up of pulmonary function after lobectomy in childhood - Factors affecting lung growth

Abstract We examined the changes in pulmonary function values in 27 patients who underwent a lobectomy due to cystic lung disease and compared the results regarding such factors as disease type, age at operation, and preoperative infections. Percent vital capacity (%VC) decreased immediately after lobectomy, but recovered to normal values within 2 postoperative years and remained within or above the normal range. The ratio of residual volume to total lung capacity (RV/TLC) rose temporally with the increase in %VC, but then remained normal after 2 postoperative years. There was no difference in %VC and RV/TLC between diseases, while bronchial atresia showed a significantly lower correlation with percent of forced expiratory volume at 1 s. The older group operated upon at over 4␣years of age and the group that had infections before operation showed relatively low %VC and high RV/TLC. Some patients demonstrated extremely low %VC along with funnel chest deformities. Our study suggests that overinflation of the remaining lung compensates VC in the early period after lobectomy while subsequently alveolar multiplication occurs. Factors affecting compensatory lung growth were considered to be operation later than 4 years of age, preoperative infection, and a thoracic deformity.

Congenital absence of the portal vein in a boy.

Abstract Congenital absence of the portal vein (CAPV) is a malformation that is generally thought to be limited to females. We encountered an 11-year-old boy with this malformation. In 17 previously reported cases of CAPV, 2 were male. Three male patients, including our case, were Abernethy type Ib malformation. They had no associated liver tumour and two had no additional congenital abnormality. Conversely, 13 of the 15 female patients had congenital abnormalities and 6 had liver mass lesions.

Clinical application of minimal residual neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction

The highly sensitive method to detect neuroblastoma (NB) cells using reverse transcriptase polymerase chain reaction (RT-PCR) was applied in the practical clinics, and its efficacy was assessed in the present study. Human tyrosine hydroxylase (TH), a rate-limiting enzyme in the catecholamine biosynthesis, was used as the marker for NB cells, and the expression of THmRNA was examined in 13 samples (four peripheral blood and nine bone marrow) harvested from seven patients (four with stage IV, one with stage III, two with stage II) using RT-PCR with our original primers. The positive signals for NB cells were detected in four samples (one peripheral blood and three bone marrow) by the PCR method, but were undetectable by the conventional histological examinations. In the present series, a case that showed a positive signal for NB cells in the peripheral blood showed a remarkably unfavorable clinical course, indicating that the circulating NB cells detected by the PCR method can be a sign of the progressively advanced NB, and may define a new prognostic factor suggesting higher risk. In another case, the PCR detection for the residual NB cells in the bone marrow provided important supporting evidence to determine the necessity of the additional chemotherapy and the suitable timing for bone marrow transplantation. This detection also guaranteed the safety of the bone marrow for transplantation. The PCR method was considered to be very beneficial in the selected cases. However, some problems such as the false-negative results in the negative urinary vanillylmandelic acid secretor were also highlighted in the present study.

Effectiveness of an intussusceptive antireflux valve to prevent ascending cholangitis after hepatic portojejunostomy in biliary atresia

An intussusceptive antireflux valve was created in the Roux-en-Y loop at the same time as the hepatic portojejunostomy (Kasai procedure) for the purpose of preventing ascending cholangitis in 14 new cases of biliary atresia and in 6 long-term survivors of the Kasai operation after episodes of ascending cholangitis. Ascending cholangitis did not develop in any of the 13 new patients who showed bile outflow following a modified Kasai procedure with antireflux valve nor in 5 of 6 patients who had secondary valve implementation. Postmortem examination of a patient with a valve who died 2 years 3 months after surgery showed that the structure of the valve was intact and that the valve still was quite effective as an antireflux mechanism.

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.

Prognostic significance of circulating tumor cells and bone marrow micrometastasis in advanced neuroblastoma

PURPOSE The aim of this study was to study the prognostic significance of circulating tumor cells (CTC) and the appropriate indications for aggressive surgery in advanced neuroblastoma. MATERIALS AND METHODS Micrometastasis was sequentially explored using our reverse transcriptase-polymerase chain reaction method in 29 neuroblastoma patients (International Neuroblastoma Staging System stage 4, n = 24; stage 3, n = 5) who treated at our department with the united chemotherapeutic regimen since 1991. Their medical records and detection of CTC and/or the bone marrow micrometastasis were retrospectively reviewed then analyzed statistically. RESULTS The overall survival rate was 58.6% (17/29). Circulating tumor cells were detected in 55.6% of the stage 4 patients, and all deaths were related to systemic metastases in the CTC-positive patients. The detection of CTC scarcely associated with MYCN amplification. In the patients showing MYCN amplification but no CTC, all deaths were related to local relapse or chemotherapy-associated complications. The survival rate was not significantly different between the patients with and without MYCN amplification (56.8% vs 52.7%). However, it was significantly lower in the patients with CTC and/or persistent bone marrow micrometastasis compared to those without detectable micrometastasis (33.8% vs 87.5%; P < .05). CONCLUSIONS The presence of CTC and/or persistent micrometastasis may indicate a significantly high risk, regardless of MYCN amplification. Patients with MYCN amplification but no micrometastasis would be most benefited by highly intensive surgery.