Metastatic primitive neuroectodermal tumour of the ovary

Primitive neuroectodermal tumours (PNET) of the ovary are rare, aggressive tumours which are associated with high morbidity and mortality. Previously reported cases have shown limited response to therapy in patients presenting with metastatic disease and survival rates have been discouragingly low. We report the case of a 13-year-old girl who presented with a primary ovarian PNET and extensive metastatic disease. Pathologic studies confirmed the neural origin of the tumour and its morphologic appearance of neuroblastoma. Incomplete surgical resection was followed by treatment with aggressive multi-agent chemotherapy including cis-platinum, etoposide, cyclophosphamide, anddoxorubicin as per a neuroblastoma treatment protocol. Complete clinical remission ensued and she received consolidative therapy with myeloablative doses of thiotepa, melphalan, and carboplatin followed by autologous peripheral blood progenitor cell rescue. All therapy was well tolerated and the patient remains in complete remission with no evidence of disease 18 months from presentation. Mega-dose chemotherapy followed by progenitor cell rescue may provide optimal therapy for patients presenting with metastatic ovarian PNET. Med. Pediatr. Oncol. 29:308–312, 1997. © 1997 Wiley-Liss, Inc.     

Effects of pediatric cancer therapy on the musculoskeletal system

This review discusses the effects of treatment of pediatric malignancies on the musculoskeletal system with an emphasis on plain radiographic and MR imaging findings following radiation therapy, chemotherapy, bone marrow transplantation and hematopoietic growth factor administration. Received: 10 February 1997 Accepted: 17 March 1997     

Anti-thymocyte globulin, cyclosporin A and granulocyte colony-stimulating factor for severe aplastic anaemia complicating paediatric liver transplantation

We describe a sustained trilineage haematopoietic response to intensified immunosuppressive therapy with anti-thymocyte globulin, cyclosporin A and recombinant human granulocyte colony-stimulating factor in a 4-year-old girl, who developed severe aplastic anaemia after orthotopic liver transplantation for fulminant liver failure induced by non A-E hepatitis. The outcome was successful and allows the following. Conclusion Intense immunosuppression in combination with haemopoetic growth factors and antimicrobial prophylaxis should be considered as first line therapy in severe aplastic anaemia after orthotopic liver trans plantation. Received: 19 April 1997 / Accepted: 31 May 1997     

Hypercalcemia associated with dysgerminoma: case report and imaging findings

Hypercalcemia associated with malignancy is rare in children. We report a case of hypercalcemia associated with ovarian dysgerminoma in a 13-year-old girl with renal medullary calcinosis and vascular calcifications. To our knowledge this is the first report of the imaging findings in this condition and only the fourth case report of hypercalcemia associated with dysgerminoma. Received: 24 June 1997 Accepted: 25 August 1997     

Percutaneous drainage as the treatment of choice for neonatal ovarian cysts

Background Involution of neonatal ovarian cysts occurs usually by 12 months. Persisting cysts larger than 4 cm are prone to torsion. Two modes of therapy are advocated: surgery and percutaneous US-guided cyst aspiration.Objective To compare ovarian preservation following the use of US-guided aspiration or conventional surgery for the treatment of large asymptomatic neonatal ovarian cysts, and to suggest alternative treatment when intrauterine ovarian torsion occurs.Materials and methods The study population comprised 25 baby girls with an ovarian cyst, 5 with a simple cyst and 20 with a complex cyst. Of these 25 infants, 8 had surgery and 17 had US-guided cyst aspiration.Results In the surgical group of 8, 6 underwent oophorectomy, and in 2 the ovary was saved. In the aspirated group of 17, the ovary was saved in 10, and was lost in 5. At the time of this report one patient was still in the follow-up period, and one was lost to follow-up.Conclusion US-guided aspiration of large neonatal cysts preserves ovarian tissue in a higher percentage of patients than surgery. It is safe, effective, and repeatable. We recommend US-guided aspiration of asymptomatic large ovarian cysts for salvage or for decompression if intrauterine ovarian torsion occurs. Surgery should be reserved for patients with acute torsion, intestinal obstruction and intestinal volvulus.     

Reconversion of bone marrow in Gaucher disease treated with enzyme therapy documented by MR

Background. Skeletal complications are responsible for significant morbidity in Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow infiltration and activity. A way to assess bone marrow improvement is needed during enzyme therapy. Objective. The purpose of this paper is to assess the usefulness of MR in following improvement of abnormal bone marrow in Gaucher patients on enzyme therapy. Materials and methods. Three patients aged 2, 7, and 24 years underwent serial MR scans of the lower extremities before and during treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1-weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two patients were imaged after 16 months of therapy, and one patient was imaged after 6 months of therapy. Results. All patients had improvement in marrow signal consistent with partial reconversion to fatty marrow during treatment. The findings were more marked after prolonged therapy. T1-weighted images demonstrated findings most clearly. Conclusion. MR consistently showed improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller doses of enzyme therapy are the trend, MR can be utilized to determine if therapy is effecting a change in the bone marrow. Received: 20 June 1997 Accepted: 7 November 1997     

Long-term endocrine sequelae of childhood cancer

PURPOSE OF REVIEW: To update knowledge related to the long-term endocrine sequelae of childhood cancer. RECENT FINDINGS: Endocrine deficiencies are common after cranial irradiation, chemotherapy and specific tumors. These deficiencies include growth hormone, thyrotropin, adrenocorticotropin and gonadotropin deficiencies, primary hypothyroidism, gonadal failure and obesity. Recent studies highlight the impact of radiation on the development of endocrine sequelae. Risks for obesity after childhood tumors include hypothalamic injury, with inactivity and daytime sleepiness. About 6% of adult female survivors of childhood cancer develop persistent ovarian failure. Risks for ovarian damage include ovarian irradiation and alkylating agents. Appropriate fertility-preservation options should be offered. Offspring of women who had uterine irradiation as children are more likely to be born preterm or have low birth weight. Secondary neoplasia or relapse should be considered when treating endocrine deficiencies in cancer survivors. Risk of secondary neoplasia is increased following radiation exposure and certain malignancies. Treatment with growth hormone does not increase cancer recurrence, but survivors may have a 2-fold risk of developing a secondary solid tumor, most commonly a meningioma. SUMMARY: Standardized, multidisciplinary long-term surveillance is important in childhood cancer survivors to identify and treat endocrine and other late effects of cancer and its therapy.     

Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel

During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. Conclusion In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account. Received: 21 October 1997 and in revised form: 30 April 1998 /Accepted: 5 May 1998     

Pre-operative differentiation of pediatric ovarian tumors: morphological scoring system and tumor markers

OBJECTIVE: To investigate the importance of morphological scoring systems in differentiation of ovarian tumors in childhood. METHODS: Morphological assessment using DePriest's index was performed for all patients with histopathological confirmation of ovarian tumor, with evaluation of tumor markers, from January 1997. RESULTS: Fifty-three girls (age range 13 months to 19 years) were surgically treated for 59 ovarian tumors, including six bilateral. All lesions with cystic appearance on ultrasonography were benign, 23 of 35 semisolid, and four of ten solid tumors were also benign. Stage of malignant disease was as follows: stage I, ten; stage II, two; stage III, six. Sensitivity, positive predictive value and accuracy by DePriest's and Ueland's indexes for benign tumors (score <7) were: 0.88, 0.79; 0.89; and 0.94, 0.84; 0.93; respectively. Elevated levels of tumor markers were observed in 17 patients, including four patients with endocrine manifestations. In 24 patients ovaries were successfully preserved, including two patients with foci of immature teratoma in a dermoid cyst. CONCLUSION: Ultrasonographic assessment with morphological analysis recommended by DePriest and Ueland is a very useful procedure for differentiating benign from malignant ovarian tumors in children. Tumor markers and endocrinological investigation are also useful for preoperative evaluation.     

Neonatale Ovarialzysten

The detection rate of neonatal ovarian cysts has markedly increased with the widespread use of ultrasonography during pregnancy. Up to now the decision for an invasive therapy has depended primarily on the size of the cyst. Recent insights into the spontaneous postnatal course of ovarian cysts within the 1st year of life have made it possible to prefer a less invasive procedure or at least to postpone any invasive treatment beyond the neonatal period. Having studied the literature published to date, we recommend the following approach: (1) When ovarian cysts are so large that they distend the fetal abdomen to the extent of dystocia of labor primary cesarian section or prenatal aspiration in utero shortly before the time of birth should be performed. (2) All ovarian cysts that are symptomatic in the neonatal period require immediate surgical intervention, preferably by laparoscopy. (3) In the case of ovarian cysts that are asymptomatic in the neonatal period the approach needs to be more tailored to the individual case. (a) Asymptomatic simple cysts with a diameter of more than 5 cm and with no tendency to regress spontaneously should be operated on within the neonatal period, preferably by laparoscopy. (b) In the case of any other asymptomatic neonatal ovarian cyst a wait-and-see policy with ultrasound monitoring can be adopted and continued at least until the end of the neonatal period.     

Fertility preservation in children and adolescents with cancer

With excellent survival rates for individuals diagnosed with cancer during childhood or adolescence an awareness of quality of life, including fertility preservation is essential. Chemotherapeutic regimens that include alkylating agents and radiation treatments directed at the gonads or pituitary, including total body irradiation are particularly gonadotoxic. Assessment of potential for gonadotoxicity and appropriateness of fertility preservation techniques prior to the start of cancer directed therapies in every individual pediatric patient is crucial for limiting this late effect of therapy. Sperm banking for postpubertal males prior to the initiation of gonadotoxic therapy should be considered standard of care. Postpubertal females receiving highly gonadotoxic therapy that places them at risk of acute ovarian failure should consider embryo or oocyte cryopreservation prior to the initiation of therapy. Oocyte cryopreservation, as well as cryopreservation of gonadal tissue, whether ovarian or testicular, remain experimental and as such should be offered as part of a research protocol. Females who receive treatment that deplete their ovarian reserve should be evaluated for the development of premature menopause following their treatment. Embryo or oocyte cryopreservation post therapy may offer females at risk of premature menopause the opportunity to preserve their reproductive window. Further research clarifying gonadotoxicity of contemporary treatment regimens and improving interventions to preserve fertility are necessary to prevent infertility as a long term adverse effect of cancer treatment. The establishment of programs that streamline access to current fertility preservation techniques will assist in ensuring that all eligible patients can avail themselves of current options.     

Preserving female fertility following cancer treatment: Current options and future possibilities

Children and women of reproductive age are increasingly surviving cancer diagnoses, and therefore long‐term quality‐of‐life issues are of greater importance at the time of diagnosis. Cancer therapies including radiation and chemotherapy can be detrimental to fertility, and therefore many patients are motivated to preserve fertility prior to cancer treatment. The only highly successful method in preserving fertility to date is embryo cryopreservation, which may not be appropriate for some patients due to age, delay in treatment, cancer type and stage, as well as availability of an acceptable sperm donor. Alternative methods including oocyte cryopreservation and ovarian tissue banking may also preserve fertility while providing additional flexibility to patients. In vitro ovarian follicle maturation following tissue banking is one potential approach that would not require a delay in cancer therapy for ovarian stimulation, would not require an immediate sperm donor, and does not carry the risk of reintroducing malignant cells following tissue transplantation. In vitro follicle culture systems have resulted in successful live births in the mouse. However, many challenges must be addressed in translating the system to the human. This review summarizes current approaches to fertility preservation and discusses recent developments and future challenges in developing a human in vitro follicle culture system. Pediatr Blood Cancer 2009;53:289–295. © 2009 Wiley‐Liss, Inc.     

Premature Ovarian Failure in a Woman with 47,XXX Karyotype following Gonadotrophin Treatment

ABSTRACT A woman resulted in premature ovarian failure following gonadotrophin treatment for secondary sterility is described. The state of ovarian failure was confirmed by increased serum gonadotrophin titers, decreased serum estrogen levels, and lack of ovarian follicles on histological examination. The cause of premature ovarian failure was investigated and 47,XXX karyotype was found in chromosomal analysis. The role of sex chromosome abnormalities in the pathogenesis of this entity is discussed. Key words: premature ovarian failure, 47,XXX, gonadotrophin treatment     

Torsion of an ovarian cyst mimicking enteric duplication cyst on transabdominal ultrasound: two cases

We describe two girls with abdominal cysts which demonstrated the “double wall” or “muscular rim” sign. On the basis of this, the diagnosis of duplication cyst was made in each case. At surgery, both were found to have ovarian cysts, and histology revealed prominent haemorrhage within the cyst wall. To our knowledge, there has been no previous report of a false-positive “double wall sign”. Received: 24 March 1997 Accepted: 11 August 1997     

Ruby laser therapy for labial lentigines in Peutz-Jeghers syndrome

Some patients with Peutz-Jeghers syndrome may be disturbed by the appearance of lentigines. Such patients require management of their lentigines as well as their gastro-intestinal polyps. We describe ruby laser therapy of labial lentigines in two children with Peutz-Jeghers syndrome. The response to treatment was excellent and no sequelae or recurrence of the lesions was noted. Conclusion Our experience suggests that ruby laser therapy is safe and a suitable approach for the treatment of labial lentigines in children with Peutz-Jeghers syndrome. Received: 5 August 1997 and revised form: 7 October 1997 / Accepted: 21 October 1997     

Restoration of ovarian function after chemotherapy for osteosarcoma

Aim: To evaluate ovarian function after modern intensive multi-agent chemotherapy for osteosarcoma given during childhood or adolescence. Methods: After discontinuation of treatment, 10 female osteosarcoma survivors were followed up for 1.5–14 (median 4.6) years. Their age at diagnosis was a median of 12.9 (range 6–15) years and at the last follow up 18.6 (range 16–22). The main follow up included recording of their pubertal and menstrual status and of sex hormone determinations. Results: Prior to diagnosis, 5/10 had had their menarche, and one had it while on therapy. At discontinuation of chemotherapy, ovarian function had severely deteriorated; none of the girls experienced regular menstrual cycles. However, during follow up, significant restoration of ovarian function was evident. At the last follow up, 9/10 patients were menstruating spontaneously. During follow up, four patients, three of whom had received high doses of alkylating agents, presented with clear hypergonadotrophism with high FSH levels (14.4–132 IU/l). Three of these four patients initiated menstruation after their gonadotrophin levels normalised. Conclusions: The modern multi-agent chemotherapy applied for osteosarcoma impairs ovarian function. Normalisation of ovarian function is common, even in cases with severe hypergonadotrophic hypogonadism, but may only occur after several years off chemotherapy. Regular assessment of ovarian function and cautious use of hormone replacement therapy are important in patients with chemotherapy induced gonadal damage.     

Restoration of ovarian function after chemotherapy for osteosarcoma.

AIM: To evaluate ovarian function after modern intensive multi-agent chemotherapy for osteosarcoma given during childhood or adolescence. METHODS: After discontinuation of treatment, 10 female osteosarcoma survivors were followed up for 1.5-14 (median 4.6) years. Their age at diagnosis was a median of 12.9 (range 6-15) years and at the last follow up 18.6 (range 16-22). The main follow up included recording of their pubertal and menstrual status and of sex hormone determinations. RESULTS: Prior to diagnosis, 5/10 had had their menarche, and one had it while on therapy. At discontinuation of chemotherapy, ovarian function had severely deteriorated; none of the girls experienced regular menstrual cycles. However, during follow up, significant restoration of ovarian function was evident. At the last follow up, 9/10 patients were menstruating spontaneously. During follow up, four patients, three of whom had received high doses of alkylating agents, presented with clear hypergonadotrophism with high FSH levels (14.4-132 IU/l). Three of these four patients initiated menstruation after their gonadotrophin levels normalised. CONCLUSIONS: The modern multi-agent chemotherapy applied for osteosarcoma impairs ovarian function. Normalisation of ovarian function is common, even in cases with severe hypergonadotrophic hypogonadism, but may only occur after several years off chemotherapy. Regular assessment of ovarian function and cautious use of hormone replacement therapy are important in patients with chemotherapy induced gonadal damage.     

Van Wyk and Grumbach syndrome revisited: imaging and clinical findings in pre- and postpubertal girls

Background In 1960 Van Wyk and Grumbach described a syndrome of juvenile hypothyroidism, precocious puberty and ovarian enlargement. These findings undergo complete regression with thyroid hormone replacement therapy. This diagnosis can be made on the basis of imaging findings and thyroid function analysis, avoiding surgery. Objective To relate the distinctive clinical and imaging features and putative pathophysiological mechanism of a series of patients with Van Wyk and Grumbach syndrome (VWGS). Materials and methods Patients with VWGS diagnosed at two large children’s hospitals over a 6-year period beginning in 1999 were retrospectively reviewed. A literature review was also conducted. Results Five female patients were diagnosed with cystic ovarian enlargement and hypothyroidism at ages ranging from 9 to 17 years. Isosexual precocious puberty was found in prepubescent patients. Associated findings included delayed bone age, ascites, and pleural and pericardial effusions. Ovarian cyst involution occurred following treatment of the hypothyroidism. Conclusion The association of primary hypothyroidism with cystic ovarian enlargement and precocious puberty is important to recognize. In the absence of suspected ovarian torsion, surgery is unnecessary, as cyst regression occurs after appropriate thyroid hormone replacement. Noncompliance with hormone replacement therapy should be considered when cystic ovarian enlargement is noted in patients with a history of hypothyroidism.     

A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan

BACKGROUND: This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan. METHODS: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. RESULTS: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1,500 g and 39 infants weighed more than 2,500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. CONCLUSIONS: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN.     

Pulmonary embolism developing in patients with sickle cell disease on hypertransfusion and IV deferoxamine chelation therapy

Pulmonary disease, including thromboembolic problems, accounts for a large portion of the morbidity of sickle cell disease. Chronic transfusion therapy is now a part of long-term treatment of sickle cell patients with stroke and chest syndrome. The resultant iron overload must be treated with chelation therapy using deferoxamine. Poor compliance with subcutaneous chelation therapy has necessitated intravenous deferoxamine treatment. We describe two patients with sickle cell disease on such a regimen, who became hypoxic as a result of pulmonary thromboembolism, secondary to venous thrombophlebitis. The thrombophlebitis and subsequent pulmonary embolism probably reflect the hypercoagulable state seen in sickle cell and are not due to the deferoxamine therapy. Received: 6 June 1997 Accepted: 17 July 1997