Hepatoblastoma in a mosaic trisomy 18 patient

We report a case of hepatoblastoma in a 10-year-old girl with mosaic-type trisomy 18. A comprehensive literature review reveals only 2 cases involving mosaic trisomy 18 patients. Our patient underwent an abbreviated chemotherapy course before complete surgical resection. Her hepatoblastoma did not contain cells with trisomy 18. The conservative management approach resulted in a successful outcome; she remains disease free >2 years after surgery. Along with presenting a literature review, this report demonstrates a favorable outcome in a mosaic trisomy 18 child with hepatoblastoma where tumor cells lacked a trisomy 18 karyotype.     

Surgical and anesthetic management for hepatectomy in two pediatric patients with trisomy 18, pulmonary hypertension,and hepatoblastoma

Children with trisomy 18 are surviving longer and undergoing more aggressive life‐sustaining therapy. This report describes two patients with trisomy 18 and hepatoblastoma (HB) successfully resected in the setting of significant pulmonary hypertension. Forty‐four previously published cases of the association between HB and trisomy 18 are reviewed. With careful multidisciplinary preoperative planning, successful resection of HB in children with trisomy 18 who have significant pulmonary hypertension is feasible. Because HB and trisomy 18 are increasing in prevalence, the need for timely liver tumor resection in the setting of pulmonary hypertension will be more common.     

Analysis of treatment outcome for children with recurrent or metastatic hepatoblastoma

For better total survival rate of children with hepatoblastoma, the therapeutic strategy for recurrent or metastatic hepatoblastoma should be improved. From 1991 to 1999, 134 cases of hepatoblastoma were treated by surgery and combination chemotherapy of cisplatin (CDDP) and THP-Adriamycin (THP-ADR) based on the JPLT-1 protocol. In 114 non-metastatic cases, 90 primary liver tumors were resected completely by partial hepatectomy, but 12 recurrences were observed in the liver (4 cases) and the lungs (8 cases). Distant metastases on the diagnosis were observed in 20 cases. The treatment outcome of these 12 recurrent and 20 metastatic tumors was analyzed. In four recurrent liver tumors, surgical resection was performed in all four cases, and all the patients were alive and well. In eight recurrent lung tumors, surgical resection was performed completely in six cases with unilateral lung disease, and five of the six patients were alive and well. In stage IV tumors, the survival rate of the patients having primary tumors within two hepatic sections was significantly higher than that of the patients having primary tumors over three hepatic sections. Active surgical intervention to lung metastases and a more intensive chemotherapy to facilitate complete resection of primary hepatic tumor could improve survival rate of children with refractory hepatoblastoma.     

The current management of hepatoblastoma: a combination of chemotherapy, conventional resection, and liver transplantation

OBJECTIVE: To review our experience in the management of children who present with hepatoblastoma. STUDY DESIGN: Thirty patients treated for hepatoblastoma at a single institution were reviewed. RESULTS: Ten patients presented with stage I to stage II disease and underwent resection. Seventeen presented with stage III disease; two underwent initial resection of which one required rescue transplantation. The remaining 15 underwent biopsies, which were followed by chemotherapy. Nine patients had a reduction in tumor size and underwent conventional resection. One required rescue transplantation for residual disease. Five patients underwent primary transplantation for unresectable disease. One patient expired during chemotherapy. Three patients presented with stage IV disease and underwent biopsies, which were followed by chemotherapy. One patient responded but required "rescue" transplantation after conventional resection. Seven patients underwent aggressive conventional resection (trisegmentectomy or central liver resection); three had positive surgical margins and underwent transplantation. One developed recurrent disease. Five-year survival was 82.5% +/- 7.1%. There was no operative mortality during surgical therapy. All transplant recipients were tumor free, but one died from lymphoma 7 years post-transplant. CONCLUSION: Chemotherapy may reduce tumor size, allowing for conventional resection. If aggressive resection is necessary or bi-lobar disease persists, primary transplantation is recommended.     

Chemoresistant hepatoblastoma in a patient with mosaic trisomy 18 treated with orthotopic liver transplantation

We present a 9-month-old male with mosaic trisomy 18 with a right hepatic lobe mass. The tumor was completely resected and identified as pure fetal histology hepatoblastoma but contained increased mitotic activity. Adjuvant chemotherapy consisted of cisplatin, vincristine, and 5-fluorouracil. After the first and fourth cycles of chemotherapy, recurrent tumor developed. The patient underwent rescue orthotopic liver transplantation, and is currently alive without evidence of hepatoblastoma 28 months after transplantation. This report demonstrates the use of orthotopic liver transplantation in a child with mosaic trisomy 18 and hepatoblastoma.     

Experience with aggressive therapy in three children with unresectable malignant liver tumors

BACKGROUND: Children with malignant liver tumors often present with unresectable disease but need not be considered incurable. The advent of effective chemotherapy makes aggressive management feasible, as our experience with three such patients demonstrates. Procedure and Results One child with an unresectable undifferentiated sarcoma of the liver and two others with unresectable primary hepatoblastoma and lung metastases were treated with initial chemotherapy, followed by aggressive surgical management. Treatment with chemotherapy followed by hepatectomy and liver transplantation (cadaveric or live donor) in two children has resulted in disease-free survivals of 79 and 38 months. The third patient is alive and well 24 months following chemotherapy and aggressive resection of the primary and 12 metastatic lesions. CONCLUSIONS: Initial chemotherapy for unresectable liver tumors with or without metastases is supported by the review of the literature. Consideration of orthotopic liver transplantation (OLT) from cadaveric or living related donor is warranted when the malignancy is demonstrably chemosensitive, independent of initial staging. Aggressive resection of primary and metastatic disease may be called for in selected cases.     

Successful use of transarterial radioembolization with yttrium‐90 (TARE‐Y90) in two children with hepatoblastoma

Primary malignant liver tumors are rare but all require surgical resection as part of therapy with curative intent. A minority of patients have resectable tumors at diagnosis. Chemotherapy has a therapeutic role in hepatoblastoma but only one‐third of patients have resectable disease at diagnosis. Two children with hepatoblastoma and suboptimal responses to initial chemotherapy received therapy with transarterial radioembolization utilizing yttrium‐90 (TARE‐Y90) and had significant response leading to resection and remission. The role of TARE‐Y90 needs to be studied further to define its use in primary pediatric liver neoplasms.     

Management of liver tumors in childhood

Primary neoplasms of the liver occur rarely during childhood and constitute only 0.3-2% of all pediatric tumors. However, they comprise a variety of entities including benign and malignant epithelial, as well as mesenchymal tumors, the most common of these being hepatoblastoma and hepatocellular carcinoma. Clinical presentation, especially in young children is relatively uniform with abdominal enlargement and a painless tumor, and often specific symptoms develop late. Prerequisites for clinical diagnosis are a comprehensive laboratory workup and good quality imaging mainly with ultrasound, as well as CT and/or MRI scans. Histological diagnosis is essential for differential diagnosis and may only be omitted in some hepatoblastoma patients of the typical age (6 months to 3 years) with an excessively elevated serum-alpha-fetoprotein. Surgery is the mainstay of treatment for all benign and malignant liver tumors. Hepatoblastomas mostly respond well to chemotherapy. Therefore, this modality should always be combined with surgical resection in these patients and in many cases can reduce the size of a large tumor to resectability. Prognosis nowadays usually is good in all benign tumors and hepatoblastoma, as well as in some other rare malignancies, but dismal in hepatocellular carcinoma and other chemotherapy non-sensitive malignant tumors.     

Treatment of infantile fibrosarcoma with chemotherapy and surgery: results from the Dana-Farber Cancer Institute and Children's Hospital,Boston

PURPOSE: To retrospectively evaluate the treatment and outcome of patients diagnosed with infantile fibrosarcoma at the Dana-Farber Cancer Institute and Children's Hospital, Boston. PATIENTS AND METHODS: Between 1982 and 1998, a total of 11 infants were diagnosed pathologically with infantile fibrosarcoma. A retrospective chart review was conducted to determine the extent of surgical therapy and chemotherapy required for a favorable clinical outcome. Cytogenetic findings were reviewed and archived tumor specimens were analyzed, when available, for the presence of the TEL/TRKC fusion gene. RESULTS: Three patients had primary surgical resection with negative pathologic margins and have been lost to follow-up. Two patients received chemotherapy only after limited biopsy or subtotal resection and are alive with no evidence of disease 8 and 18 years from diagnosis. Four patients had limited biopsies followed by chemotherapy with delayed resection. One of these four patients had negative margins and received no further chemotherapy. The other three of these patients had positive microscopic margins; two of them received postoperative chemotherapy while the third did not. All four are currently alive with no evidence of disease. Two patients had progressive disease within 7 and 10 months of diagnosis while on chemotherapy after subtotal resections. One of these two patients is dead of disease; the other is alive after palliative radiotherapy. Seven patients had archived or frozen tissue available for molecular analysis. All seven had evidence of TEL gene rearrangement; six exhibited the TEL/TRKC fusion. Six patients had characteristic trisomies previously reported to be associated with infantile fibrosarcoma. CONCLUSIONS: Previously reported series of treatment outcomes in infantile fibrosarcoma have been limited to very few patients due to the rare occurrence of this tumor. In our experience, initial chemotherapy combined with surgery has been successful for most cases. When disease progression occurred, it was within one year of diagnosis. There was no development of distant metastases in the patients with progressive disease. The role of additional chemotherapy for microscopic margins after local control is not clear. We found a high incidence of the TEL/TRKC fusion gene, confirming its utility in diagnosis. We propose a uniform approach to treatment to gather clinical and biologic information about this rare and curable disease.     

Hepatoblastoma: a single institutional experience of 18 cases

Hepatoblastomas are the most common liver tumours in children. However, they are rare as compared to other solid malignancies. Thus, there is a need to integrate data from surgical centers around the world to provide a clearer view on the outcomes of multidisciplinary management of these tumours. We set out to retrospectively review our experience of patients with surgically resected hepatoblastomas looking at primary and secondary outcomes. Children diagnosed with hepatoblastoma and managed surgically (along with chemotherapy) at a single institution between 1 January 2000 and 31 May 2007, were analyzed. Out of the 18 patients, there were 12 male and 6 female patients. The median age was 18 months (range 8-72). A palpable mass in abdomen was the presenting symptom in 88% patients. Sixteen patients (88.8%) underwent major liver resection. Sixteen patients (88.8%) received preoperative chemotherapy. Complete gross resection (stage I and II) was achieved in all 18 patients (100%). The mortality and morbidity rates were 0 and 11.2%, respectively. The 80-month disease-free survival was 67%. This series, the largest from India in terms of surgical resections for hepatoblastoma, reaffirms that major liver resection can be performed with minimal perioperative mortality and morbidity and that the use of chemotherapy has definitely helped in down staging tumours for liver resection.     

Hepatoblastoma in a 2-year-old girl with trisomy 18.

A very rare case of mosaic type trisomy 18 associated with hepatoblastoma is described. The patient underwent an extended right hepatic lobectomy at 2 years of age, and the resected tumor was diagnosed as a fetal type dominant hepatoblastoma. The results of chromosome analysis demonstrated that in the peripheral blood and skin, the trisomy 18 cells were 80% and 67%, respectively. On the other hand, although virtually 100% of the cells in the normal liver tissue were 46, XX, about one third of the cells were trisomy 18 in the tumor tissue. At 2 years and 9 months after the operation, the patient was generally healthy and had no evidence of recurrence.     

The influence of preoperative chemotherapy and surgical technique in the treatment of hepatoblastoma--a report from the German Cooperative Liver Tumour Studies HB 89 and HB 94.

Despite the success of chemotherapy in the treatment of hepatoblastoma (HB), the complete surgical resection of the primary liver tumour and metastases is the most important factor for survival. METHODS: From 1989 to 1998, 141 children with HB were treated in the German Cooperative Paediatric Liver Tumour Study HB 89 and HB 94. The study determines the results of surgical strategy, which adapts the procedure at the initial operation to the tumour extension in the liver and the occurrence of metastases. RESULTS: The median follow-up of the survivors was 72 months (range 24 - 132 months). 98/141 (78 %) patients were alive and 31/141 (22 %) died. 12/141 (8.5 %) children had no surgical treatment. A complete resection of the primary tumour was achieved in 107/129 (83 %) cases. Forty-eight children were primary resected and eighty-one children were operated on after initial chemotherapy. In 36 cases, an atypical tumour resection, in 90 cases an anatomical liver resection, was performed. Three children were transplanted. There was no perioperative death. 14/48 (30 %) children with primary tumour resection had microscopical or macroscopical residual tumour in the liver. Despite the larger number of advanced HB in the primary chemotherapy group, an incomplete tumour resection was performed in only 15/78 (19 %) cases after liver resection (p < 0.044). 14/36 (38 %) cases with atypical tumour resection and only 16/90 (18 %) cases with anatomical liver resection had residual tumours in the liver (p < 0.019). These results underline the necessity for preoperative chemotherapy in all HB, which was accepted in the following study HB 99. Atypical tumour resection should be avoided because of the higher rate of incomplete tumour resections and local relapse compared to the group with anatomical tumour resection.     

术前化疗治疗肝母细胞瘤的应用价值

目的 通过总结22例经病理组织学确诊的肝母细胞瘤病例术前化疗的治疗效果,评价术前化疗对治疗肝母细胞瘤的应用价值.方法 回顾本院2000年3月至2006年12月期间收治的22例肝母细胞瘤的治疗经过,包括化疗前确诊方法、化疗方式、方案,手术时机的选择,治疗效果.结果本组化疗前采用B超引导下细针穿刺活检18例,明确诊断为肝母细胞瘤15例,疑似者3例.本组未经术前化疗I期手术切除肿瘤3例.经术前化疗并完成疗程延期手术14例,其中介入治疗2例,全身化疗12例,肿瘤体积在化疗后较化疗前平均缩小55.7%,完整切除肿瘤13例,肿瘤仍不能切除仅活检1例,化疗后肿瘤完整切除率为92.9%.化疗1～2个疗程后放弃继续治疗3例,化疗期间死亡1例.外院初次手术后肿瘤复发行肝移植1例,术后死于腹腔内出血.本组术后超过2年者10例,因肿瘤复发、转移死亡2例,术后不足2年者6例,存活5例,1例术后8个月时因肿瘤复发死亡.化疗后仅行活检者术后6个月死亡.结论化疗前必须经病理学确诊,采用B超引导下细针穿刺活检具有损伤小,确诊率高的特点.对不能工期切除的肿瘤,无论采用介入治疗或全身化疗均可使肿瘤明显缩小,对提高肝母细胞瘤的肿瘤完整切除率有很大的帮助.     

The contribution of transplantation to the treatment of liver tumors in children

Major progress has been achieved during the last decades in the treatment of malignant liver tumors in children, both in chemotherapy and surgical management. Chemosensitivity varies between tumor types, and radical resection remains essential to effect a cure. In tumors extensively involving a normal liver, in a diffuse or multifocal manner, radical resection cannot be accomplished with a partial hepatectomy. This has been the case for some instances of advanced hepatoblastoma and epithelioid hemangioendothelioma. In hepatoblastoma, current experience shows that results of primary liver transplantation with neoadjuvant chemotherapy are excellent with around an 80% 5-to-10-year disease-free survival rate. Epithelioid hemangioendothelioma is very rarely seen in children and may have a more malignant behavior than in adult patients, and liver transplantation may not be the best management option. In nonresectable hepatocellular carcinoma (HCC) developed on an otherwise normal liver, the results of liver transplantation are similarly poor to those obtained in adult patients, except in a few highly selected series fulfilling the Milano criteria. The experience with HCC is still very scarce in children. Incidental HCC associated with chronic liver disease does not seem to impact posttransplant survival. When they are symptomatic, however, indications for transplantation should be very selective regarding tumor size, multi-focality, vascular invasion and distant metastases.     

14例儿童肝母细胞瘤综合治疗的疗效观察

目的：肝母细胞瘤是儿童时期最为常见的原发性肝脏恶性肿瘤。新辅助化疗﹢手术﹢术后化疗已成为肝母细胞瘤治疗的基本原则。该文旨在总结肝母细胞瘤综合治疗的疗效,进而探讨合理治疗的策略。方法：回顾性分析14例儿童肝母细胞瘤患者的临床资料,并追踪随访其治疗后的生存状况。结果：12例肝母细胞瘤患儿接受全程治疗,中位随访时间为18个月（1.5~74月）。9例无瘤存活,1例死亡,1例肿瘤转移,1例未发现肿瘤残留但术后甲胎蛋白持续不降。结论：手术及规范化疗能有效提高儿童肝母细胞瘤患者的生存率。［中国当代儿科杂志,2009,11（6）：456-459］     

Primary follicular lymphoma of the testis: excellent outcome following surgical resection without adjuvant chemotherapy

The authors report a case of follicular lymphoma of the testis in a 3-year-old boy. Follicular lymphoma of childhood is rare, accounting for less than 5% of all non-Hodgkin lymphomas in the pediatric population. Children with follicular NHL have typically been described as presenting with localized disease, with a preponderance of male patients. The authors conducted a comprehensive review of the literature and found that this patient is the only child reported to have localized follicular lymphoma of the testis successfully treated without systemic chemotherapy. In all previously reported cases, a favorable outcome was seen following surgical resection and chemotherapy. This patient has remained disease-free for more than 2 years after surgical resection alone. The successful outcome in this case following surgical resection, without postoperative adjuvant chemotherapy, suggests that localized follicular non-Hodgkin lymphoma in children may not be associated with occult systemic disease and that subsequent chemotherapy may not be necessary for cure.     

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.     

Liver transplantation for hepatoblastoma: indications and contraindications in the modern era

In the past 20 yr, a dramatic improvement has been achieved in the outcome of children with hepatoblastoma by combining cisplatin based chemotherapy and surgery. Treatment of patients in the USA is an exception to the rule that all patients should receive neoadjuvant chemotherapy. It is paramount that surgical resection be complete, both macro- and microscopically. Complete tumor resection can be achieved after chemotherapy with a partial hepatectomy when the intrahepatic extent is limited to 1-3 sectors. In multifocal (and solitary) hepatoblastomas invading all four liver sectors, and in centrally located tumors with close proximity to the major veins, the SIOPEL-1 study and an extensive review of the world experience have shown that primary transplantation provides high, long term, disease-free survival rate in the range of 80%. In contrast, the results of rescue transplants for incomplete tumor resection or disease recurrence after partial hepatectomy are disappointing (in the range of 30%). Hazardous attempts at partial hepatectomy in children with extensive hepatoblastoma should be discouraged. Guidelines are provided for early referral of children with extended hepatoblastoma to a transplant surgeon. There is a trend for a better patient survival after living related liver transplantation. Patients who will become candidates to liver transplantation should be treated with chemotherapy following the same protocols as for children undergoing a partial hepatectomy. There is a concern about cumulative nephrotoxicity of calcineurin inhibitors and chemotherapeutic drugs. Recent data suggest that these patients tolerate lower Tacrolimus trough blood levels than those transplanted for non-malignant conditions, without increasing the risk of acute rejection. Due to the rarity of the disease, these children should be treated in specialized centers.     

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.     

Surgical treatment of childhood hepatoblastoma in the Netherlands (1990–2013)

Background

Achievement of complete surgical resection plays a key role in the successful treatment of children with hepatoblastoma. The aim of this study is to assess the surgical outcomes after partial liver resections for hepatoblastoma, focusing on postoperative complications, resection margins, 30-day mortality, and long-term survival.

Method

Chart reviews were carried out on all patients treated for hepatoblastoma in the Netherlands between 1990 and 2013.

Results

A total of 103 patients were included, of whom 94 underwent surgery. Partial hepatectomy was performed in 76 patients and 18 patients received a liver transplant as a primary procedure. In 42 of 73 (58 %) patients, one or more complications were reported. In 3 patients, information regarding complications was not available. Hemorrhage necessitating blood transfusion occurred in 33 (45 %) patients and 9 (12 %) patients developed biliary complications, of whom 8 needed one or more additional surgical interventions. Overall, 5-year disease-specific survival was 82, 92 % in the group of patients who underwent partial hepatectomy, and 77 % in the group of patients who underwent liver transplantation.

Conclusions

Partial hepatectomy after chemotherapy in children with hepatoblastoma offers good chances of survival. This type of major surgery is associated with a high rate of surgical complications (58 %), which is not detrimental to survival.