Pancreatoblastoma: response to chemotherapy.

Two cases of pancreatoblastoma in children are reported here. Only biopsies were made at laparotomy as surgical resection by duodeno-pancreatectomy was not possible. In both children a dramatic response was observed with chemotherapy: doxorubicin plus cisplatin for one, cyclophosphamide, actinomycin D, bleomycin, vinblastine sulfate, and cisplatin for the other. After completion of the chemotherapy the first patient had a local resection; then he had radiotherapy. He is alive in first remission 40 months after the end of the treatment. In the second patient, regional recurrence occurred 8 months after chemotherapy was ended. A transient second remission was obtained with ifosfamide plus etoposide alternating with epirubicin plus vincristine. The patient died 36 months after the diagnosis. Therefore, these two cases suggest that chemotherapy may be proposed before any attempt at surgical excision. Nevertheless, early consolidation by radical resection or irradiation must be considered.     

Pancreatoblastoma: Response to chemotherapy

Two cases of pancreatoblastoma in children are reported here. Only biopsies were made at laparotomy as surgical resection by duodeno-pancreatectomy was not possible. In both children a dramatic response was observed with chemotherapy: doxorubicin plus cisplatin for one, cyclophosphamide, actinomycin D, bleomycin, vinblastin sulfate, and cisplatin for the other. After completion of the chemotherapy the first patient had a local resection; then he had radiotherapy. He is alive in first remission 40 months after the end of the treatment. In the second patient, regional recurrence occurred 8 months after chemotherapy was ended. A transient second remission was obtained with ifosfamide plus etoposide alternating with epirubicin plus vincristine. The patient died 36 months after the diagnosis. Therefore, these two cases suggest that chemo therapy may be proposed before any attempt at surgical excision. Nevertheless, early consolidation by radical resection or irradiation must be considered.     

High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma

Kosola S, Lauronen J, Sairanen H, Heikinheimo M, Jalanko H, Pakarinen M. High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma.
Pediatr Transplantation 2010: 14:646–650. © 2010 John Wiley & Sons A/S. Abstract: Unresectable malignant liver tumors may be treated by LTx. We evaluated the results of LTx for HB and HCC. All patients transplanted for HB or HCC between 1990 and 2007 were included. Effects of histologic tumor type, primary tumor resection, disease staging, and serum AFP levels at diagnosis and at transplantation on disease recurrence and survival were evaluated. Twelve patients with median age of five (range, 2–16) were transplanted and followed for a median of 11 (2–18) yr. Six patients had HB and six had HCC. At diagnosis, eight patients were staged as PRETEXT III and four patients as PRETEXT IV. Two patients had pulmonary metastases. All patients received neoadjuvant chemotherapy. Median time from diagnosis to LTx was seven (2–133) months. At LTx, none of the patients had radiological evidence of extrahepatic disease, and the median AFP level was 85 (6–15 180) μg/L. No routine chemotherapy after LTx was used.The overall one‐, five‐, and 10‐yr cumulative survival rates were 100%, 80%, and 67%, respectively. Survival was comparable between the two tumor types (4/6 for both). Two deaths occurred secondary to tumor recurrence, one of each tumor type. Both of these patients had an AFP response of <99%. Six of eight patients with primary LTx survived, when compared to two of four transplanted after primary resection. PRETEXT tumor staging had no effect on survival. LTx even without post‐transplantation chemotherapy is an effective treatment option for unresectable HB and HCC with comparable survival. Incomplete AFP response to chemotherapy and primary tumor resection were associated with decreased survival.     

Pleuropulmonary blastoma: a single-institution experience

Pleuropulmonary blastoma (PPB) is a rare primary intrathoracic mesenchymal malignancy that occurs exclusively in early childhood. Twelve patients were diagnosed with PPB (1 type I, 5 type II, and 6 type III) between 1979 and 2009 at our institution. Upfront complete tumor resection was successful in 5 of 6 patients. Six patients had biopsy followed by neoadjuvant chemotherapy, 2 had complete tumor resection, and 2 had microscopic residual disease after surgery. All patients received vincristine, dactinomycin, and cyclophosphamide chemotherapy. Eight received additional chemotherapy with doxorubicin, cisplatin, etoposide, or ifosfamide. Three patients received local irradiation. The 5-year event-free and overall survivals were 33% ± 14% and 42% ± 14%, respectively. Median time to progression was 8 months. Five of 9 patients with gross total resection survived, whereas all 3 with gross residual disease died. Three of 5 survivors did not receive radiation. A high index of suspicion for PPB must be maintained in all patients diagnosed with intrathoracic sarcoma in early childhood. Gross total resection is necessary for cure, and selected patients do not require radiation therapy.     

Liver transplant for metastatic pancreatoblastoma: 7‐year event‐free survival after chemotherapy,pancreatectomy, complete hepatectomy,and liver transplant

Pancreatoblastoma is a rare malignant tumor in children. Surgical resection of the tumor is necessary for cure; however, due to its aggressive nature, it is often unresectable at presentation due to tumor size, local invasion, and/or metastasis. Because it is a rare tumor, there is currently no standard treatment regimen. We report a case of a 4‐year‐old boy who presented with metastatic pancreatoblastoma with multiple large metastases involving all four sectors of the liver. We began treatment with chemotherapy (cisplatin, 5FU, vincristine, and doxorubicin), which significantly reduced the tumor burden in both the pancreas and liver. We then performed a staged subtotal pancreatectomy, complete hepatectomy, and living donor left lateral segment liver transplant. This was followed by postoperative adjuvant chemotherapy. Our patient is alive and healthy and has now been tumor‐free for 7 years with no tumor relapse.     

Management of pancreatoblastoma in children and young adults

Pancreatoblastoma is a very rare childhood tumor originating from the epithelial exocrine cells of the pancreas. It is the most common malignant pancreatic tumor in young children and has a mean age of diagnosis of 5 years. It is slow growing and its presentation is varied and often non-specific. Tumors tend to be quite large and appropriate cross sectional imaging is very important to assess for extent, metastatic disease, and resectability. Biopsy for tissue diagnosis is essential. Complete surgical resection is the goal of therapy although many patients are unresectable at initial diagnosis and require neoadjuvant chemotherapy. Adjuvant chemotherapy is also recommended and chemotherapeutic regimens involve cisplatin and doxorubicin. Even with curative resections, these lesions have a high recurrence rate and patients must be followed closely. Knowledge of this rare tumor is important for the clinician confronted with a large retroperitoneal mass in a young child.     

Prolonged survival of a patient with sickle cell trait and metastatic renal medullary carcinoma

PURPOSE: The treatment and outcome of a patient with sickle cell trait and metastatic renal medullary carcinoma is described. PATIENT AND METHODS: A 12-year-old boy with sickle cell trait had metastatic renal medullary carcinoma. After surgical resection of the primary tumor, he received chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. The carcinoma progressed after a 6-month period of stable disease. At that time, he received chemotherapy including ifosfamide, etoposide, carboplatin, and topotecan. RESULTS: The patient died of progressive disease 15 months from diagnosis. The patient's tumor in this report showed no progression while he was receiving methotrexate, vinblastine, doxorubicin, and cisplatin, but eventually became refractory to these and other cytotoxic agents. CONCLUSION: Renal medullary carcinoma is a highly chemotherapy-resistant tumor. Average survival after diagnosis is 15 weeks; the longest survival reported in the literature is 12 months from diagnosis. The patient in this report survived longer than the previously described patients before dying from progressive disease.     

Long-term survival of pancreatoblastoma in children

Pancreatoblastoma is an extremely rare pancreatic tumor of childhood. We report our experience in 2 patients with pancreatoblastoma who had long-term survival and review the literature with a focus on chemotherapy in pancreatoblastoma with vascular invasion. The cases were 7-year-old and 4-year-old girls who complained of an abdominal mass without jaundice. Laboratory findings including serum alpha-fetoprotein were within normal limits. Radiologic investigations revealed a mass in the pancreas with vascular invasion. After surgical resection, postoperative chemotherapy included cisplatin, doxorubicin, ifosfamide, and etoposide. They have now been well for 7 years without recurrence.     

Neoadjuvant chemotherapy before surgery of hepatoblastoma

Though surgical resection is the main stay of treatment for childhood hepatoblastoma (HB), many are unsuitable for radical surgery at diagnosis due to extensive intrahepatic and/or extra hepatic disease. We report experience in five patients of HB from a single institution (2001–2005) with preoperative Neoadjuvant chemotherapy (NACT) followed by surgery. Three patients received cisplatin, doxorubicin; and two cisplatin/vincristine/5-fluorouracil. All showed more than 50% reduction in tumor size confirmed by CT scan. Hepatic resection R0 was performed in all. There was no chemotherapy related toxicity nor post surgical morbidity or mortality. All are disease free at median follow up of 4 years. NACT produces adequate down staging of the HB with acceptable toxicity. Though cisplatin with doxorubicin produced good results, new protocol with cisplatin, vincristine and 5FU is promising without cardiotoxicity.     

Preliminary experience with arterial chemoembolization for hepatoblastoma and hepatocellular carcinoma in children

The objective of this work was to test feasibility and efficacy of hepatic artery chemoembolization (HACE) in unresectable malignant liver tumors. Five patients aged from 1-12 years were treated in the Medical University of Gdansk from 1999 to 2002. All had locally advanced tumors, which did not respond to systemic chemotherapy: four, hepatoblastoma (HB) and one, hepatocellular carcinoma (HCC). Arteriography was performed and chemoembolization suspension (cisplatin + doxorubicin + mitomycin mixed with lipiodol) was injected, followed by gelatin foam particles. The procedure was performed one to three times in each patient. In four patients (three, HB, one, fibrolamellar HCC), tumor response was observed, with decrease in the diameter of the mass of 25-33% and fall in the AFP level of 83-99%. One child with HB was non-evaluable due to early death caused by systemic myelotoxicity. Two patients (2 HB) underwent macroscopically complete tumor resection, 1 is alive and well, and 1 died at the end of surgery for an unknown reason (possibly related to cardiotoxicity of earlier systemic chemotherapy). One HB patient was successfully transplanted after two HACE courses. The only HCC patient died because of pulmonary oil embolism immediately after the third HACE course. HACE can lead to tumor regression in most cases and may be considered an alternative for patients with unresectable liver tumors who do not respond to primary systemic chemotherapy and are not candidates for liver transplantation for various reasons.     

Hepatic angiosarcoma in a child: Successful therapy with surgery and adjuvant chemotherapy

We report a 3-year and 11-month-old Caucasian female, who initially presented with an unresectable hepatic angiosarcoma. After three courses of chemotherapy with adriamycin/cisplatin, the tumor decreased in size considerably, allowing complete surgical resection. She also received postoperative chemotherapy with alternating cycles of ifosfamide/etoposide, cisplatinum/adriamycin, and vincristine/actinomycin D/cyclophosphamide for 18 months. She remains disease-free for greater than 44 months from the initial diagnosis. Our experience suggests that total excision of the tumor, together with an aggressive chemotherapy regimen, can improve the disease-free survival for children with this highly malignant vascular tumor of the liver. Med. Pediatr. Oncol. 28:139–143 © 1997 Wiley-Liss, Inc.     

Pancreatoblastoma: Case report and review of treatment in the literature

A case of pancreatoblastoma arising from the body-to-tail of the pancreas in a 5-year-old boy is presented. The patient underwent exploratory laparotomy and, 11 days later, resection of the tumor (partial pancreatectomy, pyloroplasty, and splenectomy). Before resection, cyclophosphamide and vincristine were administered. Because of tumor spillage during resection, a combination of chemotherapy (administration of cyclophosphamide and adriamycin on that day) and postoperative radiotherapy was given. Nine months after resection, partial hepatectomy was performed for liver metastasis and consolidated by a more intensive chemotherapy regimen using cisplatin, adriamycin, vincristine, and cyclophosphamide. After completion of the chemotherapy, the patient had a 14-month uneventful course, and a locally recurrent tumor was treated by the fourth surgery (extirpation of the recurrent tumor, partial hepatectomy, partial colectomy, and partial gastrectomy) and intraoperative radiation. Thereafter, the boy has shown no evidence of disease at 3 years 8 months. The literature of pancreatoblastoma is reviewed from the therapeutic viewpoint. © 1996 Wiley-Liss, Inc.     

Autologous peripheral blood stem cell transplantation in a patient with relapsed pleuropulmonary blastoma

Pleuropulmonary blastoma (PPB) is a rare and aggressive primary intrathoracic neoplasma of children. The prognosis is extremely poor with frequent metastasis to the brain and bone. We present a 4-year-old girl with a tumor mass in the right hemithorax initially diagnosed as pneumoniae. Tumor resection was performed and the histologic report indicated the diagnosis of PPB. The patient received chemotherapy comprising vincristine, actinomycin D, doxorubicin, cisplatin, and cyclophosphamide. Irradiation was performed with total 45 Gy at the right lower pulmonary lobe. She relapsed 29 months later at the pleura between the right middle and lower pulmonary lobe. Tumor resection and total 45 Gy of irradiation were performed again. High-dose chemotherapy comprising cisplatin, adriamycin, and cyclophosphamide was performed followed by autologous peripheral blood stem cell transplantation (PBSCT). The patient achieved complete hematologic recovery. Thirty-one months after PBSCT, no signs of relapse have been observed. Although it might be that the patient could have been cured with second surgery alone or by the surgery and subsequent chemotherapy, high-dose chemotherapy and PBSCT should be considered for the treatment of relapsed PPB.     

Midterm results with hepatectomy after preoperative chemotherapy in hepatoblastoma

We evaluated the results of surgical treatment for hepatoblastoma in infants and children after intensive preoperative chemotherapy, with special reference to histology and extent of liver involvement. The clinical features of 10 children with hepatoblastoma were reviewed regarding response to neoadjuvant chemotherapy, histological subtypes, extent of hepatectomy, operative complications, and prognosis. Response to chemotherapy was measured by volumetric assessment of tumour size by computed tomography scan. Cisplatin and Adriamycin (PLADO regime) up to three cycles markedly reduced the tumour volume on computed tomography (mean regression rate 65.9%); alpha-foetoprotein (AFP) levels also decreased from an initial mean of 16,116.4 ng/ml to 2,050.9 ng/ml. Five patients underwent right hepatectomy, two had right trisegmentectomy, two had left hepatectomy, and one had left trisegmentectomy. Histopathology of resected specimens revealed foetal histology in four patients, poorly differentiated (anaplastic) subtype in three, and mixed histology with mesenchymal components and osteoid formation in three. There was 100% resectability including six unresectable tumours (prechemotherapy). Moreover, hepatic resection tended to be less invasive in patients whose tumours had been much reduced after preoperative chemotherapy. Preoperative administration of cisplatin and Adriamycin reduces the tumour size significantly so that a safe radical hepatectomy can be performed. It also allows early administration of postoperative chemotherapy. Although overall good results were obtained with the current protocol, we also document our experience of unfavourable outcomes in patients with bilobar tumours (despite trisegmentectomy), patients with tumours showing poor response to neoadjuvant chemotherapy, and patients with anaplastic histology. Overall, at a 60-month follow-up we report an 80% survival rate by a combined approach.     

Successful treatment of doxorubicin and cisplatin resistant hepatoblastoma in a child with Beckwith-Wiedemann syndrome with high dose acetaminophen and N-acetylcysteine rescue

High dose acetaminophen (HDAC) with N-acetylcysteine (NAC) has been effective in adults with advanced malignancies. We report HDAC with NAC in a child with progressive hepatoblastoma, confirmed at biopsy of an unresectable hepatic mass. Alpha-fetoprotein (AFP) increased despite four courses of doxorubicin and one course of cisplatin, 5-flurouracil, and vincristine. Following HDAC with NAC, AFP markedly decreased. A continued response without toxicity was observed during four subsequent courses of HDAC with NAC and cisplatin. The residual necrotic tumor was resected. The child is now over 8 years disease free. HDAC and NAC are effective and well tolerated for progressive hepatoblastoma.     

小儿性腺外内胚窦瘤3例诊断与治疗分析

目的总结小儿原发性腺外内胚窦瘤的诊断与治疗经验。方法回顾性分析我院2003年10月-2011年9月收治的3例性腺外内胚窦瘤患儿的病历资料。结果术前均行PEB或JEB方案新辅助化疗,根治性手术切除,术后病理均为完全缓解,术后继续化疗。随访3个月～8年,2例无病存活,1例原位复发,经术前化疗、再次手术切除及术后化疗后,现随访25个月,无病存活。结论甲胎蛋白水平对小儿性腺外内胚窦瘤诊断及术后复发监测灵敏度较高,化疗与手术结合治疗效果良好。     

Lack of efficacy of postoperative chemotherapy and delayed radiation in very young children with pineoblastoma

Eleven infants with pineoblastomas were treated with prolonged postoperative chemotherapy in an attempt to delay radiation and reduce neurotoxicity. These infants were part of the Pediatric Oncology Group infant brain tumor study but the outcome of infants with pineoblastomas was not previously reported. Ages ranged from 1 month to 35 months, with eight of 11 ≦ 12 months at diagnosis. Four had + cytology and three had + myelograms at diagnosis. The majority had partial surgical resection (25–75% reduction in tumor) and 10 had shunts. Chemotherapy consisted of two 28-day cycles of cyclophosphamide plus vincristine, followed by one 28-day cycle of cisplatin plus etoposide. Craniospinal radiation was planned following completion of either 2 years of chemotherapy (children less than 24 months at diagnosis) or following one year (children 24–36 months at diagnosis). Neuroimaging results following two cycles of cyclophosphamide and vincristine were one partial response, five stable disease, and five progressive disease. There were no responders in the leptomeninges. All children ultimately failed chemotherapy (2 months–11 months). Nine failed in the primary site. Of those eight children in whom a metastatic workup was performed at time of progression, all had evidence of leptomeningeal disease. Six received radiation following failure on chemotherapy. All failed either in the primary site, leptomeninges or extraneurally (peritoneal cavity). All children died. Survival following diagnosis ranged from 4 months to 13 months. This chemotherapy regimen was neither effective in controlling tumor in the primary site nor in treating or preventing leptomeningeal spread. © 1995 Wiley-Liss, Inc.     

Use of intrahepatic chemotherapy to treat advanced pediatric hepatic malignancies

BACKGROUND: To evaluate the effect of intrahepatic arterial chemotherapy (IAC) on children with primary hepatic malignancies. METHOD: A nonrandomized inception cohort of 11 pediatric patients was referred for treatment of advanced primary hepatic malignancies at Children's Hospital of Pittsburgh. None of the patients was a candidate for resection before the initiation of IAC. Tumor response to treatment was observed by determining serum alpha-fetoprotein (AFP) levels and by abdominal computed tomographic scan. The patients received hepatic artery infusions of cisplatin and/or doxorubicin. The last five also received gelfoam embolization. RESULTS: Eight of 11 patients had multiple IAC treatments. Eight patients had AFP-producing tumors, and five of the eight had dramatic reductions in serum levels after IAC treatment. Five of the 11 patients underwent successful orthotopic liver transplantation after receiving IAC therapy, and the five explanted specimens showed varying degrees of tumor necrosis. One-year survival in patients in the authors' center is 67% for those with hepatoblastoma and 40% for those with hepatocellular carcinoma. Three-year survival is 60% and 30% for patients with hepatoblastoma and hepatocellular carcinoma, respectively. CONCLUSION: Intrahepatic arterial chemotherapy therapy can halt the progression and possibly down-stage advanced pediatric hepatic malignancies. This therapy can also be used as a successful adjunct in altering a patient's chance for successful liver transplantation.     

Chemotherapeutic approaches for newly diagnosed hepatoblastoma: Past, present, and future strategies

Surgical resection is the foundation of therapy in hepatoblastoma (HB), yet most patients have unresectable tumors at diagnosis 1 . Patients with resectable tumors have event‐free survival (EFS) of 80–90% and can be cured with cisplatin, 5‐fluorouracil, and vincristine. Patients whose tumors are unresectable but without overt metastases at diagnosis have EFS of 60–70%, and many can be rendered resectable without doxorubicin. Children with metastatic disease have fared poorly with 20–50% EFS 1 - 3 , and new approaches for these patients remain desperately needed. Dose intensification of cisplatin and doxorubicin appears beneficial in high‐risk patients. Future treatment strategies, which may be useful, include increasing intensity and/or duration of therapy, developing a maintenance regimen (oral irinotecan), using liver transplantation more often for patients to undergo complete resection, and identifying and incorporating novel agents. A better understanding of the biologic and pathologic factors is critical for predicting tumor behavior and developing more logical risk‐based treatments. Pediatr Blood Cancer 2012; 59: 809–812. © 2012 Wiley Periodicals, Inc.     

Intrahepatic arterial injections of cisplatin-phosphatidylcholine-Lipiodol suspension in two unresectable hepatoblastoma cases

Two cases with unresectable hepatoblastoma were treated by intrahepatic arterial injections of cisplatin-phosphatidylcholine-Lipiodol suspension (CPLS), combined with systemic chemotherapy. Unfortunately, the first patient who was given three injections of CPLS in association with systemic chemotherapy died of progressive disease 18 months after the commencement of the therapy. However, the second patient who received about 1 year of systemic chemotherapy followed by three injections of CPLS prior to subtotal tumor resection, plus four injections after surgery, is now alive and healthy 22 months after the commencement of treatment, with no detectable serum alpha-fetoprotein (AFP), although the AFP level on admission was 695,000 ng/ml. In the surgical specimens of case 2, there were areas with Lipiodol deposits rich in platinum and replaced by marked fibrosis around necrotic tumor nodules. Intrahepatic arterial injection of CPLS in combination with systemic chemotherapy and surgery should be considered as an effective method for unresectable cases.