Shuhei Ogita

OK-432 therapy for lymphangioma in children: why and how does it work?

Intralesional injection of OK-432 (lyophilized incubation mixture of group A Streptococcus pyogenes of human origin) is safe and effective therapy for lymphangioma. The authors evaluated the mechanism of this therapy in 6 patients who had cystic lymphangioma. The intracystic fluid of the cystic lymphangioma was aspirated before and after (on days 1 and 4) the OK-432 therapy. Changes in cell populations and cytokine productions in each aspirated fluid were analyzed. White blood cells in the intracystic fluid increased markedly in number. Before OK-432 therapy, 96% of the intracystic white blood cells were lymphocytes, and the remaining were neutrophils and macrophages. On day 1, the percentages of neutrophils and macrophages increased to 72% and 21%, respectively. On day 4, the percentage of lymphocytes increased to 72%. Flow cytometry analysis using monoclonal antibodies showed that the number of natural killer cells (CD56+) and T cells (CD3+) had increased. The activity of cytotoxic tumor necrosis factor (TNF) and interleukin-6 increased immediately after OK-432 injection and remained high in titer until day 4. These findings suggest that the white blood cells induced and activated by OK-432, and the cytokines (including TNF) produced by these cells increased the endothelial permeability, and thus the accelerated lymph drainage and increased lymph flow let to shrinkage of the cystic spaces.

OK-432 therapy for unresectable lymphangiomas in children

To avoid surgery-related complications, intralesional OK-432 therapy was used in 23 patients with unresectable lymphangiomas (1986 through 1989). Total or near total shrinkage of the lesions, without serious complication, was noted in 10, marked shrinkage in 8, slight shrinkage in 3, and no response was noted in the remaining 2. Recurrence of the lesions has not been observed during follow-up (4 to 35 months). The side effects of OK-432 therapy were a fever for 2 to 3 days and a local inflammatory reaction lasting 3 to 5 days. The local inflammation did not cause any damage to the overlying skin and did not lead to scar formation. The results suggest that intralesional OK-432 therapy is effective for most unresectable lymphangiomas.

A clinical and manometric correlation for assessment of postoperative continence in imperforate anus

Functional results after surgical correction of anorectal malformations were assessed on a clinical basis following Kelly score and by manometric study. Forty-six patients, aged 2--17, were personally interviewed and 25 of these 46 had manometric studies to evaluate postoperative continence. The manometric study was also performed on 35 normal children as a control group. Continent patients characteristically had marked high pressure zones as did the normal subjects. On the other hand, in the patients with fair or poor results, the anorectal pressure profile had no marked high pressure zone in the anal canal. The presence of normal anal pressure at rest as well as adequate ano-rectal pressure difference was found to correlate well with continence. In patients with perineoplasty, the ano-rectal reflex correlated well with continence but not in patients treated by abdominoperineal rectoplasty.

Intraarterial chemotherapy with lipid contrast medium for hepatic malignancies in infants

Antitumor drugs dispersed in a lipid lymphographic medium (Lipiodol, Laboratorie Guerbert, Rue Jean‐Chaptal, France) were intraarterially administered in two infants with unresectable hepatoblastoma. The Lipiodol and antitumor drug complex was found to selectively accumulate in the tumor and was associated with a marked reduction in the tumor size and a 50% decrease in the alpha‐fetoprotein (AFP) level after 4 days in one patient and 16 days in the other. The tumor was successfully resected by right trisegmentectomy in one patient, but surgery was not performed on the other because of evidence of pulmonary metastasis. The patients had moderate fever for 2 to 3 days after the intraarterial chemotherapy. It is believed that intraarterial chemotherapy with Lipiodol may be a useful preoperative chemotherapy for initially unresectable hepatoblastoma.

Congenital cervical neuroblastoma associated with Horner syndrome

A rare case of congenital neuroblastoma of the neck associated with complete Horner syndrome and respiratory distress is described. The case was successfully treated by total excision secondary to chemotherapy. Horner syndrome was of value for early diagnosis of this lesion.

Ongoing osteolysis in patients with lymphangioma

Severe osteolysis is a rare complication of lymphangioma. It can progress despite treatment and may be fatal. Four patients presented with massive osteolysis and serious related complications. Of these, two responded well to OK-432 therapy with arrest of the osteolysis. Complete recovery from life-threatening pleural effusion has been noted in one. Of the two nonresponders, one died of progressive osteolysis of the cervical and occipital bones, the other, despite therapy, still shows progressive osteolysis of the left leg from the femur to the phalanges. A boneless leg may be the outcome.

Renal artery spasm: A cause of acute renal failure following abdominal surgery for neuroblastoma

Interruption of arterial blood supply to the kidney results in acute renal failure (ARF). We describe a case of ARF caused by renal artery spasm following resection of a large abdominal neuroblastoma, combined with paraaortic lymph node dissection and ipsilateral nephrectomy. The blood flow was reestablished by administration of local anesthetics (lidocaine) into the obliterated renal artery through the angiographic catheter. An urgent angiography was of value for the early diagnosis and treatment of this lesion.

Transabdominal closure of tracheoesophageal fistula: A new procedure for the management of poor-risk esophageal atresia with tracheoesophageal fistula

Nissen fundoplication results in closure of the tracheoesophageal fistula (TEF) without the necessity for a thoracic operation by preventing both the reflux of gastric contents into the lungs through the distal TEF, and leakage of air into the stomach of less than 30 cm H2O intrapulmonary pressure. This procedure can safely be used even for a poor-risk patient and adequate nutritional support (full-strength milk) can be provided immediately after the fundoplication by a gastrostomy tube because the gastric contents cannot reflux into the lungs. This procedure was performed on two patients with esophageal atresia and distal TEF in Waterston Group C and gave successful results.

Intraarterial injection of anti-tumor drugs dispersed in lipid contrast medium: A choice for initially unresectable hepatoblastoma in infants

Intraarterial injection of anti-tumor drugs (THP-ADR, CDDP, 5-FU) dispersed in lipid contrast medium (Lipiodol, Laboratorie Guerbert, France) was used in an infant with initially unresectable hepatoblastoma. Lipiodol complex selectively accumulated in the tumor tissue and may keep the chemotherapeutic agents in the tumor tissue for a longer period of time, and a significant reduction of the tumor with a four-day half-life of alpha-fetoprotein (AFP) was followed immediately after the institution of chemotherapy. Successful resection of decreased tumor by extended right hepatectomy under more favorable conditions was performed 2 months after diagnosis. Intraarterial chemotherapy with Lipiodol was particularly useful in potentiating the cytoreduction of anti-tumor drugs and was also useful in reducing the toxicities of anti-tumor drugs to the host.

A case of mosaic Down's syndrome concomitant with ganglioneuroma

We present the case of a 6-year-old boy with concomitant mosaic Downs syndrome and ganglioneuroma. To our knowledge, this is the first case report illustrating this association.