Ikuo Okabe

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.

Clinical and histologic studies of neuronal intestinal dysplasia

Over a period of 10 years we have treated 10 patients with neuronal intestinal dysplasia (NID), including 3 in whom the entire intestinal tract was affected by NID, and one in whom small intestinal NID coexisted with total colonic aganglionosis. Three of these 4 patients have died and the one survivor requires parenteral feeding. The six patients with less extensive NID have all been treated successfully; three have required surgery (Duhamel procedure in 2 and colostomy in 1), but 3 responded to conservative measures. We have made detailed histologic studies, including acetylcholinesterase activity in all cases, silver impregnation studies in 4, and immunohistochemical investigation of the peptidergic innervation of the bowel in one case. Follow-up rectal biopsies have not shown any significant morphological changes with time, but functional improvement does occur and we suggest that the myenteric ganglia in NID may have the capacity for functional maturation.

Therapeutic significance of surgery in advanced neuroblastoma: A report from the study group of Japan

The role of surgery was evaluated in 19 stage III and 102 stage IV neuroblastoma patients, all of whom were treated with intensive induction chemotherapy by the Study Group of Japan between January 1985 and March 1990. For stage III neuroblastoma, surgical intervention at the primary site was performed in 18 of the 19 patients, 9 during and 9 after the first three cycles of A1 regimen, consisting of high-dose cyclophosphamide, vincristine, THP-adriamycin, and cis-platinum. Gross complete resection of primary tumor and regional lymph nodes was feasible in 17 of the 19 patients (89%), and the survival rate for the 17 patients were 79%, 70%, and 70% at 2 years, 3 years, and 4 years, respectively. For stage IV, surgical intervention at the primary site was performed in 92 of the 102 patients (90%): 30 cases during the first 3 cycles of A1 chemotherapy and 62 cases after that, with gross complete resection accomplished in 81 of the 102 patients (79%). The 81 patients with gross complete resection achieved had a better prognosis than those 11 patients with partial resection (P less than .05). Overall survival rate was 62% at 2 years for 27 patients who underwent complete resection after 3 cycles of A1 when resolution of all metastases was obtained, whereas the survival was 52% at 2 years for 31 patients who similarly underwent complete resection but when evidence of persistent metastases was present. Patients in whom the ipsilateral kidney was preserved at surgery had an outcome superior to that of those with associated nephrectomy (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological characteristics of neuroblastoma with spontaneous tumor reduction: a case report.

The authors examined the biological characteristics of a neuroblastoma with spontaneous tumor reduction. A 6-month-old boy with a pelvic neuroblastoma underwent surgical extirpation of the tumor 1 month after diagnosis. The size of the tumor reduced spontaneously while he was awaiting operation. The low proliferative activity of the tumor cells and the presence of apoptosis in the tumor tissue were shown by an immunohistochemical method using anti-PCNA antibody and a DNA fragmentation analysis, respectively. These results suggest that the spontaneous tumor reduction seen in this patient may well be caused by the overwhelming apoptosis of tumor cells.

Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant

Encouraging results are reported with high‐dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem.

Cell-mediated immune reactions to clinical neuroblastoma

Immunotherapy may be an effective treatment for neuroblastoma. It is of importance to delineate changes in various parameters of tumor immunity over an extended period, before and during the course of treatment, in any given case. In our patients with neuroblastoma, tumor-associated cell-mediated immune-reaction showed a good responsiveness before treatment. However, delayed cutaneous hypersensitivity reactions were shown to be negative in many cases, particularly in those with advanced tumor, and Tγ cells were enormously increased in some cases. During the course of therapy, the tumor-associated cellular immune responsiveness showed a tendency to become negative when the patient was tumor free or was in remission, but showed a tendency to become positive on regrowth, recurrence or metastasis of tumor. The Tγ cells showed much the same fluctuations as did the tumor-associated cellular immune responsiveness.

Unique presentation of heterotopic pancreatic tissue arising from small-bowel mesentery

Heterotopic pancreatic tissue in the small-bowel mesentery is an extremely rare anomaly: no such case has been reported in the English literature. We report a 5-year-old boy in whom the aberrant tissue formed a retroperitoneal cyst. The condition was further complicated by a ventral pancreatic duct defect. The unique clinical manifestations and difficulty in making the diagnosis are discussed.

Assessment of the percentages of maximum static pressure in the anal canal for postoperative continence in patients with imperforate anus

The maximum static pressure in the anal canal was measured using an open-tip manometric method with a continuous infusion system. The values obtained from 49 postoperative patients with imperforate anus were expressed as a percentage of those values obtained from 108 aged-matched controls. The value was observed to be 50 per cent or more in those patients with translevator type, showing normal defecation, 30–50 per cent in those with supralevator type, showing normal defecation or constipation, and 30 per cent or less in those with supralevator type, showing incontinence, and 30 per cent or less in those who had undergone surgery on the anal area at another hospital and required re-operation at our department, showing normal continence or incontinence.

In vitro growth and chemosensitivity studies of childhood cancers using clonogenic assay

We evaluated the usefulness of the recently developed Human Tumor Clonogenic Assay (HTCA) for chemosensitivity studies in childhood cancers. A total of 20 childhood cancer specimens containing 8 neuroblastomas, 4 malignant lymphomas, three hepatoblastomas, two rhabdomyosarcomas, two germinomas and one adrenal carcinoma were assayed. Overall, 65 per cent (13/20) of tumor cell specimens showed adequate colony forming ability to yield the sensitivity of anticancer drugs. The pattern ofin vitro sensitivity of a particular tumor to most anticancer drugs tested was not dissimilar to the clinical experiences of these agents. The overallin vitro response rate of childhood cancers to anticancer agents was 51 per cent. A retrospective analysis of this assay revealed a true positive rate of 57 per cent and a true negative rate of 100 per cent.