Occult abdominal involvement with apparently isolated testicular relapse in children with acute lymphocytic leukemia.
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Biomedical subjects
Publications and source records attributed to R Heyn.
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In the period 1968--78, 3161 children were enrolled in six studies of acute lymphoblastic leukaemia by participating institutions of the Childrens Cancer Study Group. In the first two studies, which did not include central-nervous-system (CNS) prophylaxis in the treatment programme, the outcome for male and female patients was very similar. In the following four studies, which included radiation prophylaxis to the CNS, a difference in outcome favouring females appeared consistently. This difference began about 6--12 months after initial remission and was further accentuated by withdrawal of therapy. Some of these studies also included a randomised trial of duration of therapy, studying 3 versus 5 years of maintenance treatment. Analysis of these studies suggests that sex group has implications both for duration of treatment and for optimum central-nervous-system prophylaxis.
We have treated a patient with refractory T-cell acute lymphoblastic leukemia with 2'-deoxycoformycin, a potent inhibitor of the enzyme adenosine deaminase. Inhibition of adenosine deaminase activity resulted in (1) an abrupt rise in plasma deoxyadenosine, but not adenosine, concentrations; (2) accumulation of deoxyadenosine triphosphate by lymphoblasts; (3) inhibition of the enzyme S-adenoylhomocysteine hydrolase; and (4) rapid lysis of the leukemic cells. The patient died suddenly 3 days after therapy was discontinued, and postmortem examination revealed a complete absence of leukemic cells in all organs. Pharmacologic inhibition of adenosine deaminase activity can result in the lysis of T lymphoblasts in vivo, and this effect appears to be mediated by deoxyadenosine.
From May, 1970 through December, 1972, Children's Cancer Study Group entered 112 patients on an amended treatment program for rhabdomyosarcoma and undifferentiated sarcoma in children. These patients had Group II disease with residual tumor remaining after surgery, or metastatic disease at onset. Another group consisted of patients who previously had treatment with surgery and radiotherapy and had recurrent disease. Cyclophosphamide was added to a previously used drug regimen which consisted of actinomycin D and vincristine. The drugs were given sequentially in repeated cycles for 18 months. Of 97 evaluable patients, there were 24 with microscopic residual disease, 37 with gross residual disease, 22 with metastatic disease at onset, and 14 patients who were treated with chemotherapy for the first time with recurrent or metastatic disease. All patients have been followed for 3 or more years. Survival in each group was 70.8%, 43.2%, 27.2%, and 28.2%, respectively. Although the number of complete remissions was greater than with two-drug therapy, survival with three-drug therapy was not significantly different than that seen in the earlier study.
With the biopsy needle of Franzén, 403 needle biopsies were carried out in 263 patients with gynaecological malignant tumors. In 152 cases the results of the aspiration cytology were compared with microscopic examinations or with the clinical course for at least 6 months. In 88 cases with probable recurrence the needle biospy showed a positive or suspicious result in 73 cases. A positive needle biopsy result was confirmation of recurrent tumor whereas a negative result did not rule out a recurrence. Aspiration cytology is a valuable ancillary method in the diagnosis of the recurrence of gynaecological tumors.
With the progressive improvement in the survival of children with acute lymphocytic leukemia, the question of late effects of therapy on normal tissue becomes a more significant problem. In a review of a large number of children who have received long-term treatment with chemotherapy, especially methotrexate, a significant increase in the serious effects on hepatic, pulmonary, and skeletal tissue was noted. A review of the methotrexate-induced acute and chronic changes seen in these tissues is the basis for this report.
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Although an uncommon occurrence in childhood, hypertrophic osteoarthropathy secondary to tumors- most commonly to osteogenic sarcoma with pulmonary metastasis-may cause severe join pain and swelling. The syndrome should be considered in the differential diagnosis of acute arthritis in childhood
Testes from adult cats were studied by means of parallel transmission and scanning electron microscopy (SEM) after NaOH digestion technique, which selectively removed connective tissues or cells. The testis is covered by a dense fibroconnective tunica albuginea that partially divides the organ in lobules by sending septa into the parenchyma. The lamina propria of the seminiferous tubules consisted of one or two rows of cells. The interstitium was made up of randomly arranged collagen bundles. The most significant feature was the numerous Leydig cells rich in lipid droplets and displaying epithelioid features. Following alkali digestion and SEM these cells showed a cord-like arrangement. The cords were formed by one or two closely apposed cells, in between which some labyrinthine or canalicular-like spaces were left that in some areas opened in wide perivascular spaces. This particular arrangement of Leydig cells and the labyrinthine intercellular spaces is very likely designed to improve cell secretion of hormones, facilitating their transport into the blood, as well as the traffic of fluids and metabolites. The present techniques allowed the visualization of a real three-dimensional testicular microarchitecture and microtopography, not detectable with other methods. Such a study may help to better highlight the testicular morphophysiology.
Testes from adult cats were studied by means of scanning electron microscopy (SEM) after 2N-NaOH maceration method which selectively digests cells and tissue compounds. As seen by this technique, the testis appears covered by a dense fibroconnective tunica albuginea that divides partially the organ by sending septa into the parenchyma. The interstitium is made up by a rich connective tissue composed by randomly-arranged fine collagen bundles that clearly outline the spaces occupied by the seminiferous tubules. The basement membrane of the seminiferous tubules consists in two rough layers of collagen fibers that in some places leave small fenestrations. The three-dimensional arrangement of collagen fibers in the interstitium outlines a system of cavities likely to be lacunar spaces for Leydig cells and vascular imprints. Especially, the above chemical technique followed by deep observations under the SEM allowed a clear and complete view of the real three-dimensional microarchitecture of the connective tissue of the testis. Therefore, the collagen component was revealed to actually form a unique and complex skeleton for the whole organ. This three-dimensional figure closely follows indeed the classical histological compartmentalization of the testis with a better insight of its spatial microtopographical features. Moreover, this structural pattern is also likely to give rise to very fine morphofunctional subcompartmentalization, especially regarding the basement membrane of the seminiferous tubules and the lacunar spaces for Leydig cells including satellite vessels.
The ultrastructural organization of mouse submandibular gland from 15 days gestation to 180 days of age was studied by field emission scanning electron microscopy. At 15 days of gestation several groups of acini, intercalated and striated ducts were present. They consisted of numerous pyramidal and/or polyhedral cells with spherical or elongated nuclei and short microvilli. At 3 days after birth different shapes of acinar structures covered by a network of fine collagen bundles were observed. The acinar portions corresponded to the terminal tubules and showed the acinar cells containing immature secretory granules. Fractured specimens of ducts revealed a flat surface with large central nuclei. At 14 days after birth acinar terminal portions possessed a round shape; branches of either intercalated and striated ducts were also observed. Gap junctions and interdigitations were numerous at the base of acinar cells. At 30 days after birth the acinar terminal portions and striated ducts revealed a large number of secretory granules. Acinar cells showed a pyramidal shape and basal nuclei. Freeze-cracked surfaces of the striated ductal cells evidenced also a pyramidal shape. Secretory granules ranged from 0.3 to 1.2 microns in size and were clearly observed by infoldings of the basement membranes. At 90 days after birth the ultrastructural features were more differentiated when compared with the previous ages. The freeze-cracked specimens showed very numerous secretory granules in all acinar and striated ductal cells. The granules occupied almost all the apical region of the cells. The outer surface of the basement membrane of acinar and myoepithelial cells was constituted by a spongy-like material covered by fine collagen fibrils. At 180 days after birth numerous secretory granules were seen either in acinar and ductal cells. A morphofunctional polarization of the cell was finally clearly observed in that the cytoplasmic organelles were concentrated in the basal portion whereas the secretory granules were located in the apical region of the cells.