Toshio Nakajo

Treatment of advanced neuroblastoma with emphasis on intensive induction chemotherapy. A report from the study group of Japan

One hundred nine newly treated patients with advanced neuroblastoma were entered in this study between January 1985 and May 1989. The eligible patients included infants younger than 12 months of age with Stage IVA disease (bone cortex, distant lymph node, and/or remote organ metastases) and patients aged 12 months or older with Stage III or IV disease (IVA plus IVB with tumor crossing the mid‐line and with metastases confined to bone marrow, liver, and skin). The patients first received six cyclic course of intensive chemotherapy (regimen A1), consisting of cyclophosphamide (1200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (pyrarubicin; 40 mg/m2), and cisplatin (90 mg/m2). Original tumors and the regional lymph node metastases were removed some time during these first six cycles of chemotherapy. The patients were further divided into three groups. Patients in course 1 received alternating treatment by regimen B (cyclophosphamide and ACNU) and intensified regimen A1, and those in course 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in course 3 were treated with bone marrow transplantation (BMT) preceded by high‐dose preconditioning chemotherapy. Survival rates were 77% in Stage III and 54% in Stage IV at 2 years, and 70% in Stage III and 45% in Stage IV at 3 years. The major toxicities encountered were bone marrow suppression with leukocyte counts down to 100/mm3, mild cystitis, and hearing impairment. The 2‐year survival rate was 78% in 21 patients who underwent BMT when complete remission was achieved. We concluded that our intensive induction chemotherapy is of significant value in increasing the rate of complete response, and in widening the indications for and achieving improved results of treatment with BMT.

Evaluation of effects of nutrition intervention on healing of pressure ulcers and nutritional states (randomized controlled trial)

The objective of this study was to evaluate the effects of nutrition intervention on nutritional states and healing of pressure ulcers by standardizing or unified factors including nursing, care and treatment in a multicenter open randomized trial. Tube‐fed patients with Stage III–IV pressure ulcers were selected. The control group (30 patients) received the same nutrition management as before participating in this trial, whereas the intervention group (30 patients) was given calories in the range of Basal Energy Expenditure (BEE) × 1.1 × 1.3 to 1.5. The intervention period was 12 weeks. The efficacy and safety were evaluated based on the nutritional states and the sizes of ulcers (length × width), and on the incidence of adverse events related to the study, respectively. The calories administered to the control and intervention groups were 29.1±4.9 and 37.9±6.5 kcal/kg/day, respectively. Significant interactions between the presence or absence of the intervention and the intervention period were noted for nutritional states (p<0.001 for body weight, p<0.05 for prealbumin). Similarly, the size of ulcers differed significantly between subjects in the intervention group and in the control group (p<0.001). The results suggest that nutrition intervention could directly enhance the healing process in pressure ulcer patients.

Intussusception-type antireflux valve in the Roux-en-Y loop to prevent ascending cholangitis after hepatic portojejunostomy

An intussusception-type antireflux valve was created in the Roux-en-Y loop in 23 infants with biliary atresia (17 new cases, and six others after episodes of ascending cholangitis) and 10 patients with congenital bile duct dilatation, in order to prevent ascending cholangitis after hepatic portojejunostomy. Mesenteric blood vessels were divided in a 4 cm length of the Roux-en-Y loop, and the distal 1.5 cm of this portion was further denuded of the seromuscular layer; an antireflux valve was thus established by invaginating the proximal portion into the denuded jejunum. No case, in which this technique was used, was associated with any surgical complications, and ascending cholangitis never developed in any of the 17 new cases with biliary atresia, during an average follow-up of 32 months.

Advantages and pitfalls of amnion inversion repair for the treatment of large unruptured omphalocele: Results of 22 cases☆

This is a report of our experience with 22 cases of large unruptured omphaloceles treated by amnion inversion during the period 1973 through 1990. The method is characterized by three stages: (1) a silastic sheet is sutured directly to the skin around the amniotic membrane, under local anaesthesia, without dissection between the skin and the amnion; (2) the reduction of herniated viscera into the abdominal cavity is achieved by squeezing the sheeting using a specially modified stapler; and (3) the amniotic membrane is preserved intact, and inverted into the abdominal cavity at the time of abdominal wall closure. Of the 22 infants, 19 survived with satisfactory results. Two patients died of multiple associated anomalies, and the remaining patient died of sepsis arising at the time of the final abdominal closure. This procedure has proved to be effective and safe for high-risk patients with congenital heart diseases, anal atresia, tracheoesophageal fistula, or bronchial stenosis and prematurity. The practical aspects of the procedure, as well as its advantages and pitfalls, are illustrated.

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)

Anorectal malformations associated with a presacral tumor and sacral defect

The triad of anorectal malformation, presacral mass, and sacral bony defect is quite rare. During the past 18 years, five patients with this triad were treated in our institutions. Four had covered anal or anorectal stenosis, while one infant had anorectal agenesis. There was a central defect of the sacral bone in three and sacral hemivertebrae in two patients. An additional case that had an intact sacrum but was otherwise associated with the same anomalies is also reported. In the literature, we could find 51 cases (including 5 cases of our own) that fall under this symptom complex. All patients had a presacral tumor, the commonest being teratomas and meningoceles (20 cases each). Anal or anorectal stenoses were most frequently encountered (46 cases), while malformations such as anorectal agenesis (3) or anorectal stenosis plus rectovaginal fistula (2) were seen less frequently. We therefore contend that the spectrum of this symptom complex is broader than was previously considered. Among these patients, constipation was the most common presenting symptom. Barium enema and computer tomographic studies were helpful in identifying the presence, extent, and nature of the mass. The embryogenesis is discussed, reviewing the clinical and pathological characteristics of these patients.

Clinical efficacy of basic fibroblast growth factor on pressure ulcers: case-control pairing study using a new evaluation method.

A basic fibroblast growth factor (bFGF) case and a control case whose total scores of Pressure Ulcer Healing Process‐Ohura (PUHP‐Ohura) and risk factors for pressure ulcers, and level of care for pressure ulcers were equivalent were paired. Twenty‐three such eligible pairs were enrolled in this study. Both cases in each pair were treated under conditions in which extrinsic factors such as the use of a pressure‐relief mattress and the frequency of postural change were equivalent. The efficacy of bFGF was assessed by analyzing the data obtained over time as the scores of PUHP‐Ohura for nine observation items using the SAS MIXED procedure. Treatment of pressure ulcers with bFGF accelerated wound healing over time more significantly than the control in six observation items (exudate volume, ulcer depth, granulation formation, wound edge, epithelialization, total score of the PUHP‐Ohura). These data suggest that it may be possible to evaluate drugs for the treatment of pressure ulcers using the PUHP‐Ohura wound‐assessment tool.

Comprehensive planning of operative strategy for separation of ischiopagus tripus twins with particular reference to quality of life

A 27-year-old mother was diagnosed by prenatal ultrasonography as having triplets at gestational age 32 weeks. Following cesarean section at 37 weeks, a pair of female babies were noted for the first time to be joined by a common pelvis with three lower limbs. They had separate upper gastrointestinal tracts, which joined in the distal ileum, leading to a common colon, rectum, and a single anus. Each twin had a functioning kidney, with a single ureter leading to a common bladder. A common urethra originating from the bladder neck ran into the urogenital sinus of one baby. Prior to the surgical separation, placement of four tissue expanders and 20 pneumoperitoneums were performed, in order to stretch the parietes for easier approximation of the wound edges. At 13 months of age, separation was performed, requiring 17 hours. The skin and musculature from the conjoined third leg was used as a fillet for abdominal wall closure in each patient. One infant was given the distal half of the colon and an entire anus with a temporary jejunostomy, and the right half of the bladder with the urethra. The other infant was given the proximal half of the colon with a permanent colostomy, and the left half of the bladder with permanent cystostomy using appendiceal pedicle graft (Mitrofanoffs procedure). This is the 10th case of surgical separation in ischiopagus tripus twins reported in the literature, and the seventh successful separation with both patients alive.

Mid‐Cervical Malignant Pleomorphic Adenoma Prsenting With Upper Airway Obstruction.

The case of a 1 year and 6 months old girl with pleomorphic adenoma arising from the upper middle part of the neck is reported. Although the tumor invaded the hyoid bone, it was removed completely and symptoms of upper airway obstruction disappeared. We suspect it may have originated from thyroglossal duct structures.

DNA Studies in 109 Malignant Tumors in Children

It has been shown that some cellular oncogenes are involved in the genesis of human malignant diseases through their activation by mutation, translocation or amplification [ 1-31. As to neuroblastoma, amplification of the oncogene N-myc has been observed in about 50% of the cases that are in either the 3rd or 4th stages [ 3. 41 . N-myc is also amplified in some cases of retinoblastoma and small-cell carcinoma long with neuroendocrine properties [ 5, 61. Amplification of c-myc has been repeatedly described in various tumors [ 1 ] . Amplification of a few other oncogenes, such as c-erb B2 and Ha-ras, has been described in a small number of cases with a few different kinds of tumors including small-