Patients with lymphatic malformations who receive the immunostimulant OK-432 experience excellent long-term outcomes.

AIM: Sclerotherapy is the primary treatment for lymphatic malformations. The aim of this study was to evaluate the long-term outcome in patients with lymphatic malformations treated with the immunostimulant OK-432 as a sclerosant. METHODS: Between 1998 and 2013, we enrolled 131 of 138 eligible patients treated with OK-432 for lymphatic malformations in a retrospective study. The malformations were categorised according to the International Society for the Study of Vascular Anomalies. The outcome was assessed with a clinical examination and a questionnaire. RESULTS: The lymphatic malformations were localised to the head/neck (60%), the trunk (20%) and the extremities (6%) or involved with more than one region (14%). Patients with microcystic (10%), macrocystic (21%) and mixed lymphatic malformations (69%) underwent a median number of three, two and two injection treatments, respectively. The median age at the first injection was 3.4 years. Good or excellent clinical outcomes were seen in 70% of the patients. The number of injections, previous treatment and lesion localisation, but not time to follow-up and cyst size, predicted the clinical outcome. CONCLUSION: OK-432 treatment resulted in a successful outcome in 70% of patients with lymphatic malformations. The long-term outcome was comparable to the short-term outcome.

[A revolutionary Japanese method for treatment of lymphangioma]. / Japansk metod revolutionerar behandlingen av lymfangiom.

Large cystic lymphangiomas of the neck (hygroma colli) have traditionally been treated surgically or by local injection of various sclerosing agents. Owing to the infiltrative growth of these cysts, radical surgery has often been difficult due to the risk of damage to nerves and adjacent organs; and the use of available sclerosing agents has often resulted in disfigurement due to extensive scarring, thus rendering secondary surgery even more difficult. However, OK-432, a new agent for local injection, has been tested with good results, especially in Japan. In five consecutive paediatric cases of lymphangioma, we found ultrasound-guided injection of the cysts with OK-432 to yield good response without complications. In three cases, the lymphangioma disappeared leaving the child's appearance quite normal, and there has been no recurrence. In one case, the lymphangioma disappeared but apparently recurred within half a year (during which time we had lost contact with the family). This was the only case of small cysts (cavernous lymphangioma), which are putatively more resistant to OK-432. The only child to be operated also had thoracic lymphangioma which was not injected, though the cervical part which was injected was reduced by 50 per cent pre-operatively, the final outcome being excellent with no visible cysts in any region. Thus, hitherto our results suggest the therapeutic effect of OK-432 to be good, and further clinical investigation is planned.

Pharmacokinetics of imipenem/cilastatin sodium in children with peritonitis.

Fifteen children (3-12 years) with peritonitis were given imipenem/cilastatin intravenously (15 or 25 mg/kg) every six hours for 3-14 days. One day during treatment days 2-8, multiple blood and urine samples were collected from each individual over a six hour dosing interval. Twelve children completed the study. The urinary recovery of imipenem and cilastatin averaged 50-70% of the administered dose. The plasma t1/2 for imipenem averaged 55 min. while that for cilastatin was even more rapid (approximately 38 min.). Little or no accumulation of either imipenem or cilastatin was observed for this regimen in this age group of paediatric patients. Steady state conditions prevailed within 2 days of initiation of therapy. The pharmacokinetics of imipenem and cilastatin in paediatric patients 3-12 years of age appear similar to those observed for adults.

Experimental obstructive hydronephrosis in newborn rats. XI. A one-year follow-up study of renal function and morphology.

Partial obstruction of the left ureter was created in two-day-old rats and its effects on kidney function were studied with 99mTc-DMSA and 99mTc-DTPA after one, two, three and six weeks, and after one year. Kidneys from animals sacrificed at the age of six weeks or one year were also examined histologically. The obstructed renal pelvis was enlarged by about 35 times and there was a delayed excretion of 99mTc-DTPA during forced diuresis, indicating significant, chronic obstruction. The renal DMSA-uptake ratio (left kidney/(left and right kidney] was reduced to about 40% from the first week of obstruction. The parenchymal weight ratio (expressed as above) was reduced to about 45% after both six weeks and one year. The glomerular filtration rate, examined during forced diuresis and calculated on the basis of uptake capacity, was lowered to 42% after six weeks but was not significantly reduced after one year of obstruction. The incidence figures for medullary hemorrhage or accumulation of iron pigment, and chronic inflammatory changes in the cortex were somewhat higher after one year of obstruction than after 6 weeks, but the lesions were patchy in both groups. We conclude that partial unilateral ureteric obstruction, created in the neonatal period, leads to a slight but permanent functional disturbance and parenchymal weight reduction without prominent structural parenchymal damage.

Renal recovery after release of experimental neonatal ureteric obstruction.

Partial obstruction of the left ureter was created in 2-day-old rats and released 2 days later. The effects were studied after 1, 2, 3 or 6 weeks. The obstruction resulted in prominent hydronephrosis, but the pelvic volume returned to normal already within 1 week after the release operation. In most of the previously obstructed kidneys there were small regions with moderately widened convoluted tubules and collecting ducts and minor areas with mild chronic pyelonephritis; these lesions were similar after 1 week as after 2-6 weeks, indicating that they were permanent. Judging from the parenchymal weight difference between the right and left kidney, there was slight reduction on the previously obstructed side at the 3rd week, balanced by hypertrophy on the contralateral side. At the 6th week the parenchymal weight reduction was no longer apparent but there was still evidence of contralateral hypertrophy. Thus, early release of the partial ureteric obstruction prevented persistent ipsilateral parenchymal weight reduction, without ensuring healing of the tissue lesions. The catch-up of parenchymal weight is probably due to the fact that the release was performed before the end of the period of postnatal nephron differentiation. Interference with this period seems to be the main cause of parenchymal weight reduction in permanent neonatal partial ureteric obstruction.

Experimental partial ureteric obstruction in newborn rats. VII. Are the long term effects on renal morphology avoided by release of the obstruction?

Partial obstruction of the left ureter was created in newborn rats. The obstruction was either permanent or was released after two or seven days. The effects were studied at the age of six weeks. The permanently obstructed kidneys characteristically exhibited considerable enlargement (X 18) of pelvic volume and prominent deformation of the papilla, frequently associated with moderate widening of collecting ducts and convoluted tubuli, and focal inflammatory and degenerative lesions. The weight difference between the hydronephrotic and the contralateral, intact kidney was significantly higher than in a sham operated group, although the combined kidney weight was unchanged, indicating a reduction on the obstructed side and a compensatory contralateral hypertrophy. In the group released after seven days, the pelvic volume had returned to normal; nevertheless the parenchymal weight pattern and the histological lesions were similar to those found in animals obstructed for six weeks. In the group released after two days, the pelvic volume had normalized, and the histological changes were less prominent than in animals obstructed for seven days or six weeks. Yet there was a significant difference in parenchymal weight between the hydronephrotic and the contralateral kidney, almost entirely caused by hypertrophy on the nonobstructed side. Thus, the ureteric obstruction must be released very early to avoid parenchymal weight reduction and curb the tissue lesions. On the other hand, the resulting parenchymal damage is moderate and does not seem to progress with time.

Experimental partial ureteric obstruction in newborn rats. IV. Do the morphological effects progress continuously?

Partial obstruction of the ureter was created in newborn rats, and its effects were studied after 1, 2, 3, 6 and 9 weeks--that is, until adult age. Within 1 week, a considerable hydronephrosis had appeared. Within 2 weeks, parenchymal weight was found slightly reduced (8 per cent) on the obstructed side, and, within 3 weeks, equivalently increased on the contralateral, intact side. After these points in time, there was no further deterioration. Histological examination revealed marked deformation of the papilla and minor foci of degeneration and inflammation within 1 to 2 weeks which tended to become chronic in type after 3 to 9 weeks. Arterial hypertension was not noted. Thus, the effects of partial ureteric obstruction on the renal parenchyma are 1) discrete, 2) not in proportion to the degree of hydronephrosis, 3) fully compensated by contralateral hypertrophy and 4), after reaching an early maximum, not increasing with time.

Experimental obstructive hydronephrosis in newborn rats. I. Surgical technique and long-term morphologic effects.

Partial obstruction of one ureter was created in newborn rats and its effects were studied in the adult rat. The obstructed renal pelvis was found to be enlarged 10x. The parenchymal weight of this kidney was reduced by 8 per cent, primarily because of destruction of the papilla, and was completely compensated for by hypertrophy of the contralateral kidney. A high correlation was found between true volumes and areas on urography. The turnover time for urine in the hydronephrotic pelvis ranged from 47 to 473 min. The implications of this measurement for clearance values are discussed.

Roentgen stereophotogrammetry for evaluation of liver volume and shape.

Model experiments and tests on 2 patients were performed to probe the feasibility of roentgen stereophotogrammetry for evaluating variations in shape and volume of the liver. The surface of the object was marked with indicators, and the three-dimensional marker coordinates were determined. The model experiments demonstrate a good correlation between true volume and the volumes defined by the indicators, and also demonstrate the possibility of localizing an expansivity. The variability of the volume of a polyhedron defined by 15 liver indicators with stage of breathing is discussed.