Peter Gutjahr

Secondary thyroid carcinoma after treatment for childhood cancer.

BACKGROUND Second malignant neoplasms (SMNs) have become a primary concern in evaluating long-term effects of treatment in pediatric oncology. Thyroid carcinoma has proven to be a common SMN. METHODS In a multicenter study involving 58 hospitals in Germany, Austria and Switzerland, 18 of 239 (7.5%) SMNs documented following first malignant neoplasm (FMN) in childhood were thyroid carcinoma. RESULTS The age at diagnosis of FMN ranged from 1 to 15 years. Eleven patients were female. Six children had survived Hodgkin disease, seven acute leukemia, two Ewing sarcoma and three various other tumors. Fifteen of the 18 patients had been treated with radiotherapy to the head and neck region. The time interval between treatment and diagnosis of thyroid carcinoma ranged from 4 to 19 years (median 8 years). The carcinoma was papillary in 17 cases and follicular in one. Eleven patients had metastases in the regional lymph nodes at presentation. DISCUSSION Radiotherapy appears to be an important risk factor in secondary thyroid carcinoma, but it does not explain all cases. The current data are remarkable for the large proportion of patients who received only prophylactic cranial irradiation for ALL and for the three patients who received no irradiation to the head and neck region. Genetic determinants and chemotherapy must also be considered. CONCLUSIONS Regular thyroid examination should be included in the long-term follow-up of survivors of childhood malignancy.

Evoked otoacoustic emissions and pure tone threshold audiometry in patients receiving cisplatinum therapy

Eight children and young adults with cancer were evaluated serially using pure tone audiometry as well as registration of click-evoked otoacoustic emissions (EOAE) 1 day prior to therapy as well as after various numbers of doses of cisplatinum. A reduction of EOAE-amplitudes following cisplatinum therapy was observed in all patients. This reduction tended to recover after the end of cisplatinum administration. Since EOAE are believed to result from cochlear bio-mechanical processes, the reduced emissions are interpreted as signs of cochlear dysfunction. We conclude, that EOAE testing may be a simple, non-invasive method that may detect early, transient functional impairment of hearing due to ototoxic agents such as cisplatinum, even in children. Further controlled trials are needed.

Cerebral haemorrhage in long-term survivors of childhood acute lymphoblastic leukaemia

Abstract Modern treatment of childhood acute lymphoblastic leukaemia (ALL) has dramatically improved the prognosis for children with this disease. Therapeutic approaches consist of multimodal chemotherapy and radiotherapy with significant long-term side-effects. We report on 4 children out of a group of 120 newly diagnosed patients with ALL, who survived the disease for more than 2 years and developed a cerebral haemorrhage after chemotherapy and fractionated cranial irradiation. Following a period of 2–12 years the four children presented with acute neurological signs and symptoms, i.e. seizures, ataxia and hemiparesis. CT and MRI revealed intracerebral mass lesions, interpreted as haemorrhage. After neurosurgery the patients neurological state improved. Histological examination confirmed the suspected diagnosis of bleeding cavernous haemangioma or capillary telangiectases. There are two possibilities to explain these rare alterations: they may be pre-existent to the disease and therapy or they may be caused by irradiation. Conclusion Acute neurological symptoms in patients treated for ALL may be caused by spontaneous cerebral haemorrhaging of cavernous haemangiomas or capillary telangiectases induced by chemotherapy and/or radiotherapy.

Physical performance in long-term survivors of acute leukaemia in childhood

Abstract The aim of this study was to assess the physical performance in long-term survivors of acute leukaemia in childhood and to evaluate the effects of anthracycline therapy. Electrocardiography, echocardiography and spiroergometry were carried out on 56 patients aged 9–28 years, of whom 44 patients had been treated with 15–483 mg/m2 doxorubicin (or equivalent). Acute leukaemia had been diagnosed 1.5–16 years earlier. Of the patients 75% reached normal maximal oxygen uptake, 69% normal oxygen uptake at the anaerobic threshold and 95% normal maximal work rate. Of the patients 75% achieved adequate values for maximal heart rate and 78% normal blood lactate concentration. No difference was seen between patients treated with and without anthracyclines. Conclusion The results of this study provide little evidence for cardiopulmonary impairment in long-term survivors of ALL. Both the cardiac function, as evaluated by ECG and echocardiography, and the physical performance in spiroergometry are normal in a large number of these patients. Anthracycline treatment does not appear to have a negative effect on these parameters.

Survivors of childhood cancer for more than twenty years.

Present health status, complications, and development of long-term survivors of childhood cancer followed for more than 20 years in a single institution were reviewed. The departmental database was searched to identify patients diagnosed with childhood cancer and consequently treated between 1965 and 1978. A total of 124 (77%) long-term survivors participated on a voluntary basis in the study. A semi-standardized interview consisted of measures evaluating the present health condition, sequelae of treatment, second malignancies, intellectual development and presence of offspring of the former patients. The majority of patients were treated with chemotherapy (82%), 67% received radiotherapy and 67% underwent surgery. A relapse of the primary tumor was diagnosed in four patients as well as a second malignancy in four other patients. In 33% of the long-term survivors one or more serious therapy-related health problems were noted. Adequate mental and intellectual development was achieved in 65%. Children treated in the early years of pediatric oncology seem to have a satisfactory outcome as viewed over the long term. Consequent ongoing follow-up is still necessary to detect health problems and enhance quality of life for subsequent generations of children with cancer.Present health status, complications, and development of long-term survivors of childhood cancer followed for more than 20 years in a single institution were reviewed. The departmental database was searched to identify patients diagnosed with childhood cancer and consequently treated between 1965 and 1978. A total of 124 (77%) long-term survivors participated on a voluntary basis in the study. A semi-standardized interview consisted of measures evaluating the present health condition, sequelae of treatment, second malignancies, intellectual development and presence of offspring of the former patients. The majority of patients were treated with chemotherapy (82%). 67% received radiotherapy and 67% underwent surgery. A relapse of the primary tumor was diagnosed in four patients as well as a second malignancy in four other patients. In 33% of the long-term survivors one or more serious therapy-related health problems were noted. Adequate mental and intellectual development was achieved in 65%. Children treated in the early years of pediatric oncology seem to have a satisfactory outcome as viewed over the long term. Consequent ongoing follow-up is still necessary to detect health problems and enhance quality of life for subsequent generations of children with cancer.

Early diffuse leptomeningeal primitive neuroectodermal tumors can escape detection by magnetic resonance imaging.

Abstract Primitive neuroectodermal tumors are easily detected by neuroradiologic imaging, as a rule. We report on two patients with early diffuse leptomeningeal primitive neuroectodermal tumors which escaped detection by contrast-enhanced magnetic resonance imaging.

Therapy of rhabdomyosarcoma of the larynx

A case of subglottic rhabdomyosarcoma in a 13-year-old boy is reported. Following partial conservative resection of the larynx with supplementary chemotherapy and without irradiation, the patient has had no functional impairment of the larynx and has shown no evidence of recurrence for more than 3 years.

Clinical aspects and prognosis of ependymoma in infants and children. A single institution experience.

Abstract Thirty-two patients (22 boys and 10 girls) with a histologically confirmed diagnosis of ependymoma were treated between 1972 and 1999. A total macroscopic resection was achieved in 16 of these patients, whereas 15 resections were classified by the surgeon as subtotal. In 1 patient a ventriculostomy was created as part of a palliative strategy. All children over 3 years old were treated with postoperative radiotherapy. Chemotherapy consisted of procarbazine, ifosfamide, etoposide, methotrexate, cisplatin and cytosine arabinoside. There was 1 perioperative death. Twenty children developed a relapse of disease within 2 months to 13 years and 1 month after the initial therapy. A maximal number of five recurrences were seen in 1 patient. The value of adjuvant chemotherapy on the prognosis of children with ependymoma seems to be limited. With regard to the poor outcome, the advisability of further treatment after multiple recurrences is debatable.

Immunological investigations in two brothers with ataxia telangiectasia Louis-Bar

Two of three brothers with the classical signs of ataxia telangiectasia were investigated for their immunological disorders at the ages of 13 and 16 years, respectively. The elder brother also suffers from autoimmune hemolytic anemia, a complication which has not yet been described in the course of ataxia telangiectasia.Immunological investigations made in both brothers showed a reduction in the number and function of T lymphocytes. The number of B lymphocytes was normal, among which there were cells staining for IgA, although serum IgA was absent. It seems possible that this phenomenon is caused by a disturbance in the process of maturation of lymphoid cells with a lack of differentiation into IgA-synthesizing plasma cells.ZusammenfassungZwei von drei Brüdern (13 und 16 Jahre alt) zeigten das klinische Vollbild der Ataxia teleangiectatica Louis-Bar. Der ältere der Knaben leidet zusätzlich an einer autoimmun-hämolytischen Anämie, die im Zusammenhang mit anderen Immunmangel-syndromen, nicht aber bei Ataxia teleangiectatica bislang bekannt ist.Eingehende immunologische Untersuchungen bei den Brüdern zeigten eine Einschränkung von Zahl und Funktion der T-Zellen. Die Zahl der B-Lymphocyten war normal, darunter fanden sich auch IgA-positive Zellen, obwohl Serum-IgA fehlte. Es erscheint möglich, daß dieses Phänomen durch eine Reifungsstörung mit fehlender Differenzierung in IgA-synthetisierende Plasmazellen zustande kommt.

Dermatoglyphische Untersuchungen bei Kindern mit embryonalen Tumoren

Dermatoglyphics were analyzed in 60 children with embryonic tumors. In comparison with normal children, several differences were found. Thus, the embryonal origin of the different tumors is underlined and the hypothesis of embryonic tumors as malformations is sustained. These tumors seem to be the clinically most important manifestation of a much more comprehensive malformation syndrome, which is not yet known in all its details.Zusammenfassung60 Kinder mit embryonalen Tumoren wurden auf Veränderungen des Hautleistensystems hin untersucht. Es stellten sich verschiedene Unterschiede gegenüber der Normalpopulation heraus. Dies unterstreicht die embryonale Genese der verschiedenen Tumoren und stützt den Begriff des Mißbildungstumors. Embryonale Tumoren müssen als klinisch wichtigste Manifestation eines umfassenderen, in seinem ganzen Umfang aber sicherlich noch nicht vollständig erfaßten Fehlbildungssyndroms verstanden werden.