Little girl who conquered the ALPPS’’

An insufficient future liver remnant(FLR)is associated with post-hepatectomy liver failure.Associating liver partition and portal vein ligation for stage hepatectomy(ALPPS)has been shown to be effective for the induction of rapid FLR hypertrophy so as to improve the resectability in patients with insufficient FLR.We hereby report our experience of this novel approach for a 6-year-old patient with hepatoblastoma.Computed tomography showed a hepatoblastoma measuring12.5 cm×9.9 cm×11.7 cm in the right liver(Couinaud segmentⅣ,ⅤandⅧ).Volumetric assessment of the FLR i.e.,left lateral section was 112.6 mL i.e.,21.2%of the estimated total liver volume.In view of the small-for-size FLR,ALPPS was contemplated.An anterior approach was adopted for the in-situ parenchymal split without mobilisation of the right liver.FLR volumetry on the seventh postoperative day was 160.7 mL,which represented a 46.1%gain in volume,and a FLR/ESLV ratio of 30.2%.A right trisectionectomy was performed on the eighth postoperative day.Postoperative recovery was uneventful.Patient was discharged on day 16 after the first operation.To our knowledge,this was the first report that showed the applicability of ALPPS to a paediatric patient.     

Treatment of unresectable hepatoblastoma with cisplatin,vincristin and 5-fluorouracil

We here describe a 2.5 year old boy with a virilizing unresectable hepatoblastoma. Administration of cisplatin in combination with vincristine and 5-fluorouracil every third week was shown to be very effective and rendered the tumour resectable.Abbreviations AFP alpha-fetoprotein - hCG human chorion gonadotropin - 5-FU 5-fluorouracil     

Signaling pathway of insulin-like growth factor-Ⅱ as a target of molecular therapy for hepatoblastoma

AIM: To address the possibility that insulin-like growth factor (IGF)-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma.METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-Ⅱ was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-Ⅰ receptor (IGF-IR). Inhibitors of IGF-IR (piclopodophyllin, PPP),phosphatidyl-inositol (PI) 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF-Ⅱ. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation.RESULTS: IGF-Ⅱ stimulated cells proliferated to 2.7(269% ± 76%) (mean ± SD) (Huh-6) and 2.1 (211%± 85%) times (HepG2). IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44% ±11% (Huh-6) and 39% ± 5% (HepG2). LY294002 and Wortmannin suppressed the cell number to 30% ± 5%(Huh-6), 44% ± 0.4% (HepG2), 49% ± 1.0% (Huh-6)and 46% ± 1.1% (HepG2), respectively. PD98059 suppressed the cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited,many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis.CONCLUSION:IGF- Ⅱ was shown to be a growth factor of hepatoblastoma via IGF-I receptor and PI3 kinase which were good candidates for target of molecular therapy.     

小儿肝母细胞瘤术前化疗的组织学改变

目的观察肝母细胞瘤术前化疗后的组织学变化。方法采用软X线拍片、瘤组织浸泡银染方法，比较5例肝母细胞瘤化疗前后的组织学变化。结果化疗后瘤组织发生明显的坏死、纤维化，面积达80％以上。栓塞剂在瘤组织中的分布与瘤组织坏死纤维化的分布及程度无关。结论进展期肝母细胞瘤术前化疗有效。较短时间的肝动脉栓塞化疗可以达到与静脉化疗相近的组织学上的抗肿瘤效果。     

Alpha feta (alpha FP) monitoring of response to adriamycin in hepatoblastoma

While emphasizing the potential of chemotherapy (particularly adriamycin) in the treatment of hepatoblastoma, Andrassy et al., omit mention of the importance of serial serum alpha FP measurements in determining response and in early detection of recurrence. Serum alpha FP was elevated (range 5,000-1,800,000 micrograms/l) in 10 of 11 children with hepatoblastoma seen at our hospital between 1970 and 1980 and is, as others have emphasized, a potentially useful "marker" for this tumor. We report here the details of one patient in whom alpha FP monitoring was crucial to early detection of pulmonary metastases; complete response to adriamycin was subsequently documented.     

Hepatoblastoma in a 4-year-old girl with Fanconi anaemia

CASE REPORT: Hepatoblastoma was diagnosed in a 4-year-old girl receiving growth hormone substitution therapy for short stature. Owing to multiple congenital malformations, VACTERL-H (vertebral, anal, cardiac, tracheal, renal and limb anomalies with hydrocephalus) association had been suggested. Elevated chromosomal breakage rates and G2 phase arrest induced by DNA-crosslinking agents in cellular assays confirmed the diagnosis of Fanconi anaemia (FA), a tumour susceptibility syndrome known to be associated with hepatocellular carcinoma following androgen therapy. Subsequent genotyping revealed biallelic mutations in the FANCD1/BRCA2 gene. CONCLUSION: We describe the first case of hepatoblastoma in a patient with FA to raise awareness of this tumour type in the close clinical observation of early cancer-prone forms of this condition, particularly in the presence of FANCD1/BRCA2 mutations. The present case also underscores the importance of FA testing in patients with VACTERL(-H).     

TREATMENT OF ALPHA-FETOPROTEIN SECRETING HEPATOBLASTOMA BY RESPONSE OF SERUM ALPHA-FETOPROTEIN LEVELS: A New Concept

Hepatoblastoma, thecommonest primary malignant livertumorin infants and children, is usually associated with elevated serum alpha-fetoprotein (AFP) levels. The authors sought to determine if AFP levels can be used to modify treatment, thereby avoiding the wait for formal imaging studies and prolonged suboptimal treatment and limiting the use of effective but toxic chemotherapy. From April 1984 to December 1997, 8 children were diagnosed with AFP-secreting hepatoblastoma. Serum AFP levels were measured weekly. If AFP levels failed to improve, or increased on at least 2 successive examinations, the chemotherapy protocol was changed. When an excellent response was achieved, less toxic chemotherapy was substituted. Six patients (75%) were disease-free for at least 2 years, some with high-risk or metastatic disease. Two patients died. Six of the 7 nonmetastatic patients (86%) remain disease-free (only one had a resectable tumor). Chemotherapy changes resulted in reduced AFP levels in 7 patients. This study supports the use of AFP monitoring to modify treatment in hepatoblastoma responding to therapy with less toxic drugs and the use of nonstandard therapy when suboptimal responses are obtained.     

肝母细胞瘤患儿应用吡柔比星治疗前后实验室指标变化

目的 探讨肝母细胞瘤(hepatoblastoma,HB)患儿应用吡柔比星(pirarubicin,THP)化疗前后心脏毒性的实验室指标变化特点.方法 收集2012年1月至2015年6月我院收治的76例HB术后并给予含THP方案化疗后患儿的临床资料,应用统计学方法分析THP治疗前后血清实验室指标N端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)及肌酸激酶同工酶(creatine kinase isoenzymes,CK-MB)的变化特点.结果 76例患儿均未发生明确的心脏毒性.THP化疗前后血清NT-proBNP的水平分别为(80.93±74.13)ng/L和(211.85±211.42)ng/L,差异有统计学意义(P=0.00,P<0.05).THP累积剂量>200mg/m2治疗组化疗后血清NT-proBNP水平为(225.67±237.63)ng/L,高于THP累积剂量≤200mg/m2治疗组化疗后血清NT-proBNP水平(182.39±140.43)ng/L,但两组差异无统计学意义(P=0.338,P>0.05).THP化疗前后血清CKMB水平分别为(23.08±13.52)U/L和(30.90±13.92)U/L,变化有统计学差异(P=0.00,P<0.05).结论 儿童HB术后在应用THP化疗后血清NT-proBNP显著升高,对于早期监测心脏毒性有一定的临床意义.     

Chirurgische therapie von hepatoblastomen im kindesalter

Zusammenfassung Das hochmaligne Hepatoblastom ist ein seltener Lebertumor uberwiegend von Säuglingen und Kleinkindern. Fur eine Bewertung der chirurgischen Therapie bei diesen Patienten konnten Daten von 71 Kindern usgewertet werden, die von 1988-1993 nach dem Protokoll der multizentrischen Lebertumorstudie HB89 der Gesellschaft für Pädiatrische Onkologie und Hämatologie behandelt wurden. Initial komplett reseziert wurden 20 kleine Hepatoblastome (Stadium I), bei 6 wurde ein mikroskopischer Tumorrest zurückgelassen (Stadium II). 38 Kinder mit Tumoren, die beide Leberlappen betrafen (Stadium III), und 7 mit Fernmetastasen (Stadium IV) erhielten zunächst eine tumorreduktive Chemotherapie mit Ifosfamid, Cisplatin und Adriamycin (IPA). 38 der Stadium-III/IV-Tumoren konnten danach reseziert werden, 1 Leber wurde transplantiert. Das entspricht einer Resektionsquote von insgesamt 92% (65 von 71 Tumoren). Alle Patienten erhielten postoperativ eine adjuvante Chemotherapie. Derzeit sind 53 (75%) aller Patienten tumorfrei, 18 (25%) gestorben. Dabei beträgt die rezidivfreie Über-lebensrate für Stadium 1 100%, Stadium II 50%, Stadium III 7 1% und Stadium IV 29% (p=0,0009). Die chirurgische Radikalität bei der initialen oder sekundären Resektion korrelierte hochsignifikant mit dem rezidivfreien Überleben der Patienten (p < 0,0001). Die Anzahl der kompletten Resektionen war bei Lobektomien (24 von 28) und Trisegmentresektionen (19 von 23) höher als bei atypischen Leberresektionen (8 von 15). Die rezidivfreie Überlebensrate war bei letzteren geringfügig schlechter (p=0,079). Bei 3 Kindern mit Lungenmetastasen konnte durch z.T. mehrfache Thorakotomien nach vorheriger Chemotherapie eine anhaltende Remission erreicht werden. Bei 3 von 38 (8%) offenen Tumorbiopsien, 4 von 27 (15%) primären und 8 von 37 (22%) sekundaren Resektionen kam es zu perioperativen Komplikationen. Ein chirurgischer Todesfall trat nicht auf. Die Auswertung zeigt, daß mit der abgestuften chirurgischen Strategie der Studie HB89 bei Kindern mit Hepatoblastomen eine hohe Resektionsquote und eine tolerable Komplikatiosrate erreichbar sind. Primäre inkomplette Resektionen und nicht anatomische, atypische Resektionsverfahren führen häu-fig zu Tumorrezidiven und müssen vermieden werden. In Zukunft muß versucht werden, durch Anwendung hochentwickelter technischer Resektionsverfahren, durch Lebertransplantationen sowie durch vermehrte Operationen von Lungenmetastasen die Überlebenschance auch von Kindern mit fortgeschrittenen und metastasierenden Hepatoblastomen zu verbessern.

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Surgical therapy of childhood hepatoblastoma

Hepatoblastoma is a rare but highly malignant liver tumour, predominantly occurring during early childhood. Clinical data of 71 children treated from 1988 to 1993 according to the protocol of the multicentre liver tumour study (HB89) of the German Society for Paediatric Oncology and Haematology were evaluated to assess the effects of surgical therapy in these patients. The protocol prescribed an initial laparotomy for all children with a liver tumour, except for infants with distant metastases and a high serum- -fetoprotein; for small hepatoblastomas confined to one liver lobe primary resection by a lobectomy; and for those extending into both lobes and metastasizing tumours tumour reductive chemotherapy including ifosfamide, cisplatiin and adriamycin (IPA), preparatory to resection at second-look surgery. All patients received adjuvant IPA chemotherapy after tumour resection. In 20 of the 71 cases, the hepatoblastomas were completely resected at initial laparotomy (stage 1), while in 6 cases microscopic residues were left (stage 11). In 38 of 45 children with extended hepatoblastomas (stage 111, 38 patients) or distant metastases (stage IV, 7 patients) the tumour was resected during later surgery, and 1 patient received a liver transplant. Thus, the overall resection rate was 92% (65 of 71 hepatoblastomas). After a median follow-up of 3.8 years (range 1.0–5.9 years), 53 (75%) of the patients were tumor-free and 18 (25%) had died. Recurrence-free survival was 100% for stage I, 50% for stage 11, 71% for stage III and 29% for stage IV patients (P=0.0009). Statistically, there was a close relationship between the completeness of tumour resection at primary or delayed surgery and the patients' prognosis (P < 0.0001). Complete removal of the tumour was achieved more often by a lobectomy (24/28) or a trisegmentectomy (19/23) than by an atypical liver resection (8/15), although the rate of recurrence-free survival was only insignificantly worse in patients with the latter operation (P=0.079). Three children with lung metastases are now in permanent remission after chemotherapy and repeated thoracotomies. Perioperative complications occurred in 3 of 38 (8%) open tumour biopsies, 4 of 27 (15%) primary and 8 of 37 (22%) secondary tumour resections. All 9 thoracotomies were performed without any complications, and there was no case of surgical death. This study shows that the surgical strategy of the HB89 study entails a high resection rate in combination with tolerable perioperative complications, although most patients of this series were treated in institutions where the surgeons had not specialized in liver surgery. Non-anatomical atypical liver resections are more often associated with incomplete removal of the tumour than standard resection techniques and should therefore be avoided. Primary incomplete resections often lead to early tumour relapse. In future the chance of cure must be improved for children with advanced and metastatic hepatoblastomas, by the application of refined liver resection techniques and transplantations and also by aggressive surgical treatment of lung metastases.

     

Bone metastases in hepatoblastoma,an unusual presentation. Case report and review of the literature

Primary liver tumors are rare in childhood. Hepatoblastoma is the most prevalent and has a variable clinical presentation. The initial approach requires clinical suspicion, histopathological confirmation, and measurement of AFP levels, in addition to PRETEXT staging by abdominal computed tomography. PET-CT is useful in metastatic disease for diagnosis and evaluation of therapeutic response. Pulmonary metastases at the time of diagnosis are frequent, while bone metastases are rare. We present the case of an infant with a history of metastatic hepatoblastoma, multiple relapses, and poor response to multimodal management. The patient had bone metastases demonstrated by PET-CT imaging.