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.

Biliary tract complications in patients with hypoganglionosis and chronic idiopathic intestinal pseudoobstruction syndrome.

The biliary tract system was studied in two patients with hypoganglionosis and chronic idiopathic intestinal pseudoobstruction syndrome (CIIPS) to evaluate manifestations of these diseases, especially as for underlying motility disorder. In a 3-year-old boy with hypoganglionosis, cholelithiasis was diagnosed and the gallbladder specimen showed a markedly hypoplastic neural plexus on histopathology as was found in his total alimentary tract. In a 2-year-old girl with CIIPS, echo-guided gallbladder wall motility testing demonstrated an impaired response to a ceruletide diethylamine stimulation. These clinical experiences in two patients suggest that these pathological entities may be frequently associated with biliary tract complications not only due to a consequence of total parenteral nutrition, but also due to a possible intrinsic involvement of biliary tract dysmotility.

Reliability of anorectal manometry in the diagnosis of Hirschsprung's disease.

Anorectal manometry was performed in 79 patients, aged 2 days to 19 years, who were referred to us because of constipation or symptoms of intestinal obstruction. A definitive diagnosis was obtained in 75 of the 79 patients (95%). Thus, anorectal manometry is a reliable tool in the diagnosis of Hirschsprung's disease. In the neonatal period, however, a definite diagnosis was possible in only 17 of the 21 neonates (81%). The age at the time of the first examination was 14 +/- 2 days in those with a definite diagnosis and 5 +/- 1 days in those with an indefinite diagnosis (p less than 0.001). If intestinal obstruction can be managed by conservative therapy, examination should be repeated after two weeks of age if the diagnosis before one week of age is not definite. These results indicate that anorectal manometry is non-invasive and reliable in the diagnosis of Hirschprung's disease. However, further examinations such as barium enema or rectal biopsy should be done, even in the neonatal period.

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.

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.