HHT can be used as salvage treatment for CML patients who acquire the T315I BCR-ABL mutation.7 Chemotherapy consist- ing of daunorubicin, HHT and cytosine arabinoside induced CR in this patient, we added imatinib mesylate afterwards. This com- bination of drugs maintained complete hematological and cyto- genetic remission for 31 months; and no severe side effects was observed in this case.
In further studies, the effects of combination use of imatinib mesylate and HHT should be investigated to improve treatment results of Ph(+) AML. Our patient achieved molecular remission shortly after imatinib mesylate plus HHT-based antitumor che- motherapy and has long-term remission on maintenance therapy with imatinib, sustained for at least 31 months. To the best of our knowledge this is the longest reported survival of a child with de novo BCR-ABL-positive AML. Our results suggest that imatinib mesylate combined with HHT-based chemotherapy is very useful for treating childhood Ph(+) AML.
Acknowledgments
This study was supported in part by Tian Jin science and tech- nology support program (NO.09ZCZDSF03800). The authors thank Dr Hui Wei for editorial assistance.
References
1 Shah N, Leaker MT, Teshima I et al. Late-appearing Philadelphia chromosome in childhood acute myeloid leukemia. Pediatr. Blood Cancer 2008; 50 (5): 1052-3.
2 Mi Y, Xue Y, Yu W et al. Therapeutic experience of adult acute myeloid leukemia in a single institution of China and its relationship with chromosome karyotype. Leuk. Lymphoma. 2008; 49 (3): 524- 30.
3 Westbrook CA, Hooberman AL, Spino C et al. Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: A Cancer and Leukemia Group B Study (8762). Blood 1992; 80 (12): 2983-90.
4 Nishii K, Usui E, Sakakura M et al. Additional t(11;17)(q23;q21) in a patient with Philadelphia-positive mixed lineage antigen-
expressing leukemia. Cancer Genet. Cytogenet. 2001; 126 (1): 8-12.
5 Viniou NA, Vassilakopoulos TP, Giakoumi X et al. Ida-FLAG plus imatinib mesylate-induced molecular remission in a patient with chemoresistant Ph1+ acute myeloid leukemia. Eur. J. Haematol. 2004; 72 (1): 58-60.
6 Ito K, Tominaga K, Suzuki T et al. Successful treatment with ima- tinib mesylate in a case of minor BCR-ABL-positive acute myelog- enous leukemia. Int. J. Hematol. 2005; 81 (3): 242-5.
7 de Lavallade H, Khorashad JS, Davis HP et al. Interferon-alpha or homoharringtonine as salvage treatment for chronic myeloid leuke- mia patients who acquire the T315I BCR-ABL mutation. Blood 2007; 110 (7): 2779-80.
Supporting information
Additional Supporting Information may be found in the online version of this article:
Fig. S1 Acute myeloid leukemia-M5. Bone marrow smear shows several immature monocytoid cells with multiple prominent nucleoli and moderately abundant pale cytoplasm (Wright’s stain).
Fig. S2 Acute myeloid leukemia-M5. Bone marrow smear. Peri- odic acid-Schiff reaction. The cytoplasm of the monoblasts shows diffuse PAS staining.
Fig. S3 Acute myeloid leukemia with t (9;22) (q34;q11). R banded karyotype showing 46 chromosomes, including t (9;22) (q34;q11).
Fig. S4 Acute myeloid leukemia with t (9;22) (q34;q11). Metaphase fluorescence in situ hybridization using dual color probes BCR and ABL shows the presence of a BCR-ABL fusion.
Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.
Contralateral pleural recurrence of adrenocortical carcinoma after surgical resection
Eisuke Inage,1 Masahiro Saito,1 Yohei Saito,1 Oto Takata,1 Junya Fujimura,1 Atsuyuki Yamataka2 and Toshiaki Shimizu1
1Department of Pediatrics, and 2Pediatric Surgery, Juntendo University School of Medicine, Tokyo, Japan
Key words adrenocortical carcinoma, familial cancer, functional tumor, mitotane, pleural recurrence.
Correspondence: Eisuke Inage, MD, Department of Pediatrics, Jun- tendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Email: arigo_echigojin@hotmail.com
Received 8 June 2010; revised 16 August 2010; accepted 22 September 2010.
doi: 10.1111/j.1442-200X.2010.03263.x
Adrenocortical carcinoma (ACC) in children is rare and consti- tutes about 0.2% of childhood cancers. There is a strong relation- ship between ACC and some hereditary cancers, especially Li-Fraumeni syndrome. Most cases of ACC are endocrinologi- cally active tumors, and include hormonal symptoms such as
@ 2011 The Authors
precocious puberty and virilization. The prognosis of child- hood ACC is generally better than that of its adult counterpart, although the prognosis of recurrent or metastatic disease remains dismal.
This report describes a child with ACC and a family history of cancer who later showed contralateral pleural recurrence. We report the details of this case and discuss the manage- ment of stage II ACC and the therapeutic options for inoperable ACC.
Case report
An 8-year-old girl was referred with a 3-week history of a pain- less abdominal mass in the left upper quadrant. There was a family history of cancer, the patient’s mother had breast cancer at the age of 40 years and her brother died from a primitive neuro- ectodermal tumor of the brain at 8 years of age.
On physical examination facial acne was prominent. A bulky mass was palpable in the upper abdomen and its border was approximately 1-2 cm below the left costal margin. Breast enlargement (Tanner stage 2), pubic hair (Tanner stage 4), and enlargement of the clitoris with mild pigmentation were present.
Blood examination revealed anemia (hemoglobin, 10.6 g/dL), elevated lactate dehydrogenase (683 IU/L) and C-reactive protein (2.3 mg/dL) levels. The patient’s plasma testosterone level was extremely high (2.98 ng/mL).
Abdominal computed tomography (CT) showed a heteroge- neous mass 18 cm in diameter in the left retroperitoneal space (Fig. 1). The mass extended across the midline and there was a tumor thrombosis in the left renal vein. A bone and gallium scintigram showed no lymph node or distant metastasis.
A provisional diagnosis of left functional ACC (stage II) was made and the adrenal mass was resected en bloc with left nephre- ctomy. The surgical margin was negative. Histopathological analysis confirmed the diagnosis of ACC, based on the presence of abundant mitotic figures (Fig. 2).
As a result of surgical resection, precocious puberty and vir- ilization due to excess androgen production was alleviated and the patient’s blood testosterone level normalized (0.05 ng/ml). The patient received no postoperative therapy. Li-Fraumeni syn- drome was suspected given the family history. However, poly- merase chain reaction analysis of the p53 and CHK2 genes detected no germ line mutations.
Seven months postoperatively, the patient developed gradu- ally worsening dyspnea at rest. She was admitted to the emer- gency department of another hospital and transferred to our hospital the next day for further evaluation.
On admission, the breath sounds in the right lung were decreased and there was prominent distension of the jugular veins bilaterally. Chest CT revealed a mass lesion, multiple nodules and prominent pleural effusion with a mediastinal shift (Fig. 3a). Fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased glucose use corresponding to the mass lesion.
A thoracoscopic biopsy was performed. Thoracoscopy showed multiple nodules in the right thoracic cavity (Fig. 3b).
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Histopathological analysis revealed intrathoracic dissemination of ACC.
The patient was treated with cisplatin, etoposide, and doxo- rubicin, based on the protocol reported by Berruti et al.1 After the first course of chemotherapy, oral mitotane was started (1 g/m2, increased gradually to 3 g/m2). A reduction in the tumor mass and improvement of the mediastinal shift were obtained after two courses of chemotherapy. The dyspnea improved markedly.
After five courses of chemotherapy (five months after the recurrence), the patient was symptom-free, except for mild dyspnea on exertion. The tumor was about half the size it had been on second admission. However, sensitivity to the
a
R
b
chemotherapy gradually decreased. Finally, the patient died due to tumor dissemination and respiratory failure 14 months after the initial diagnosis (seven months after recurrence).
Discussion
The clinical stage of the disease determines the initial therapy for ACC. Several staging systems have been proposed, of which the modified Sandrini staging system is the most popular.2-4 Michalk- iewitz et al. reported on the overall prognosis of childhood ACC based on an international registry and showed that the prognosis of this disease is related to tumor stage.4 They reported a 5-year event-free survival rate of 72.8% for stage I/II ACC, whereas patients with stage III/IV disease had a 5-year event-free survival rate of approximately 20%. Recent reports confirm the unfavor- able prognosis of stage III/IV disease.5
In operable cases (i.e. stages I and II), several reports indicate that recurrence is related to the tumor volume, particularly when the tumor is over 200 g.4,6 Postoperative chemotherapy is a thera- peutic option for patients with giant tumors. However, a prospec- tive study on postoperative chemotherapy is absent and its effect remains controversial. In our case, the tumor mass exceeded
200 g. As the patient had a familial history of cancer, there was a trade-off between the risk of secondary cancer and therapeutic effect. As a result, no adjuvant chemotherapy was given before the recurrence.
Tumor recurrence occurs mainly within one year of the initial operation,4,7 and early recognition of recurrence is essential to therapeutic progress. Although there are no published recommen- dations for pediatric ACC, Fareau et al. recommend abdominal imaging every three months for the first year after resection in adults.8 In this case, we performed monthly blood examinations, including testosterone levels, and abdominal magnetic resonance imaging (MRI) every three months. Nevertheless, when detected, the intrathoracic dissemination was severe.
We found no reports on contralateral intrathoracic recurrence of ACC in a literature survey. In this case, the route of the recurrence may have been via the blood. Tumor thrombosis in the left renal vein may contribute to the hematogenous dissemination and metastasis. Radiological surveillance of the entire body after resection is appropriate. MRI is useful to prevent radiation expo- sure, especially in patients belonging to cancer-prone families. Some authors suggest the usefulness of FDG-PET in adult cases.6 Our case also shows the potential benefits of FDG-PET.
There is no standard therapy for inoperable ACC. Some authors report the usefulness of chemotherapeutic agents, such as cisplatin and other drugs.1,9,10 However, the response rate is only 20-40%, and no regimen clearly improves overall survival. Another therapeutic option is oral mitotane, an insecticide deriva- tive that has an adrenolytic anti-tumor effect. Mitotane can induce complete remission of ACC in some cases.11,12 However, the response rate of mitotane monotherapy remains at only 20-30%. Mitotane does not increase overall survival and its availability is restricted because of its toxicity.
Berruti et al. reported a 53% regression of ACC in response to combination therapy with multi-agent chemotherapy and mito- tane in adults.1 In our case, aggressive tumor growth with a mediastinal shift was a life-threatening oncological emergency. Urgent reduction of the tumor mass was required. Therefore, combined chemotherapy with mitotane was chosen, and resulted in marked tumor regression.
The effectiveness of the adult regimen in pediatric cases is not clear. However, multi-agent chemotherapy with mitotane is a therapeutic option for inoperable ACC.
References
1 Berruti A, Terzolo M, Pia A et al. Mitotane associated with etopo- side,doxorubicin,and cisplatin in the treatment of adrenocortical carcinoma. Italian Group for the Study of Adrenal Cancer. Cancer 1998; 83: 2194-200.
2 Sandrini R, Ribeiro RC, DeLacerda L. Childhood Adrenocortical tumors. J. Clin. Endocrinol. Metab. 1997; 82: 2027-31.
3 Sandrini R, De Lacerda L, Sampaio G et al. Adrenocartical tumors in children: Relationship between disease stage and outcome. Pediatr. Res. 1993; 33 (Suppl. 5): S22.
4 Michalkiewitz E, Sandrini R, Figueredo B et al. Clinical outcome characteristics of children with adrenocortical tumors: A report forom the international pediatric adrenocortical tumor registry. J. Clin. Oncol. 2004; 22: 838-45.
@ 2011 The Authors
5 Ribeiro R, Sandrini R, Schell M et al. Adrenocortical carcinoma in children: Astudy of 40 cases. J. Clin. Oncol. 1990; 8: 67-74.
6 Leboulleux S, Dromain C, Bonniaud G et al. Diagnositic and prog- nostic value of 18-fluorodeoxiglucose positron emission tomogra- phy in adrenocortical carcinoma: A prospective comparison with computed tomography. J. Clin. Endocrinol. Metab. 2006; 91: 920-5.
7 Hanna A, Pham T, Askegard-Giesmann J et al. Outcome of adrenocortical tumors in children. J. Pediatr. Surg. 2008; 4: 843-9.
8 Fareau G, Vassilopoulou-Sellin R. Diagnostic challenges in adrenocortical carcinoma: Recommendations for surveillance after surgical resection of selected adrenal nodules. Endcr. Pract. 2007; 13: 636-41.
9 Van Slooten H, Van Oosterom ACAP. cyclophosphamide,doxoru- bicin and cisplatinum)regimen in adrenal cortical carcinoma. Cancer Treat. Rep. 1983; 76: 377-9.
10 Schlumberger M, Brugieres L, Gicquel C et al. Fluorouracil,doxo- rubicin and cisplatin as treatment for adrenal cortical carcinoma. Cancer 1991; 67: 2997-3000.
11 Coelho Netto A, Wajchenberg B, Ravaglia C et al. Treatment of adrenocortical cancer with o,p’-DDD. Ann. Intern. Med. 1963; 59: 74-8.
12 Fisher D, Panos T, Melby J. Therapy of adrenocortical cancer with o,p’-DDD in two children. J. Clin. Endocrinol. Metab. 1963; 23: 218-21.
Mid-aortic syndrome in a preterm infant
Ming-Chou Chiang,1,3 Mei-Ching Yu,1 Chao-Jan Wang,2 Chi-Hui Cheng,1,3 Hung-Tao Chung1 and Reyin Lien1
1Department of Pediatrics, Chang Gung Children’s Hospital, 2Department of Radiology, Chang Gung Memorial Hospital, Chang Gung University, and 3Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan
Key words angioplasty, mid-aortic syndrome, neonate, preterm infant.
Introduction
Mid-aortic syndrome (MAS) is a rare condition presenting with severe hypertension. It manifests with variable narrowing of the abdominal aorta and its visceral branches. Stenosis of the renal arteries is common (90%), less common is the involvement of the celiac and superior mesenteric arteries (20%-40%). Involvement of the inferior mesenteric arteries is rare.1,2
The etiology of MAS can be classified as both congenital and acquired. Acquired etiologies of MAS include neurofibromatosis, fibromuscular dysplasia, retroperitoneal fibrosis, mucopolysac- charidosis, Williams syndrome, and giant cell arteritis, including Takayasu disease and temporal (cranial) arteritis.3 Therapies for MAS include medical treatment, surgery, and endovascular treat- ment.3 Treatment of MAS should be individualized and depends on patient age, size, degree of renal artery stenosis, and concomi- tant medical problems.1
Previous studies have reported MAS as a disease of late child- hood or early adulthood,45 but more recently, a lower age at diagnosis has been reported (mean age, 4.5 years).6 Very few, however, cases have been reported to be diagnosed in early neo- natal life or in very low birth weight infants.1,6 Herein, we describe our experience managing a 26-week preterm infant with
Correspondence: Hung-Tao Chung, MD, Department of Pediatrics, Chang Gung Children’s Hospital, 12th Fl., Building L, 5-7, Fu-Shin Street, Gueishan Township, Taoyuan County, 33305 Taiwan. Email: hungtao@adm.cgmh.org.tw
Received 26 June 2010; revised 4 October 2010; accepted 2 November 2010.
doi: 10.1111/j.1442-200X.2010.03305.x
MAS who presented with neonatal hypertension. We then discuss the morbidity after balloon angioplasty.
Case report
A corrected age 1-month-old female infant was born to a G2P1 mother through vaginal delivery at 26 weeks of gestation with a birth weight of 1060 gm and Apgar scores of 6 and 8 at 1 and 5 min, respectively. Antenatal examination was done regularly, and amnioreduction was performed once for polyhydramnios, which was noted along with fetal ascites, one week before the baby was born. The chromosome study revealed a normal karyotype.
At birth, there was no subcutaneous edema or any malfor- mation at physical examination. Chest X-ray disclosed respira- tory distress syndrome but no pleural effusion. Abdominal ultrasonography revealed mild pelviectasis of the left kidney and no evidence of ascites or hepatomegaly. Echocardiography revealed mildly dilated cardiomyopathy, with a left ventricular ejection fraction of 44%. Serological tests for TORCH and par- vovirus B19 were all negative. There was no evidence of tha- lathemia or anemia and the level of cardiac enzyme was normal. We attempted to insert an umbilical arterial catheter but were unsuccessful.
The infant developed hypertension (72/36 mmHg) at 5 days of age. Urinary analysis showed microscopic hematuria and renal ultrasonography revealed a globular-shaped left kidney. Furo- semide, followed by hydralazine and spironolactone were given for controlling blood pressure. Despite the medical treatment, hypertension persisted. Echocardiography and renal ultrasonog- raphy were arranged again. The data showed that there was no