Background and Aims

Locally advanced hepatoblastomas pose unique clinical challenges. Despite chemotherapy, surgical resection remains the mainstay of cure. These tumors can be managed either by radical liver resections (RLR) or liver transplantation. Despite prior experiences with Indocyanine-green (ICG) in liver tumors, its potentials in children remains unclear. The aim of this study is to report the role of ICG in RLR.

Methods

Review of demographics, surgical technique, complications and survival of 3 patients with Hepatoblastomas, resected under ICG-guidance.

Results

Case-1, female, 12 months-old, presented with abdominal mass, Alpha-fetoprotein (AFP) 273,000. Images reported a multifocal PreTEXT-III, P+V-. Histology: epithelial/fetal Hepatoblastoma. Good response after 3 cycles of intermediate risk (IR) chemotherapy. ICG was administered 72 hours before surgery. A non-anatomical left-extended hepatectomy was performed (segments 2, 3, 4 and 5). Intraoperative margins were extended guided by ICG.

Case-2, male with prenatal liver mass. Imaging confirmed a mass, originated in the caudate lobe, PreTEXT-III, P+V+C+. AFP 380,000. Histology: embryonal/epithelial hepatoblastoma. After 3 cycles of IR chemotherapy, there was a good response. ICG was administered 72 hours before surgery. Resection of the caudate lobe was performed.

Case-3, male, presented with liver mass and precocious puberty. AFP 199,000, b-HCG: 567. Images reported a multifocal PreTEXT-IV, P+ V-. Histology: epithelial/mesenchymal Hepatoblastoma. After 6 cycles of IR chemotherapy, there was a good response. ICG was administered 70 hours before surgery, a right-extended hepatectomy plus wedge-resection of a segment 2 ICG-avid lesion, was performed.

Non intra-or-postoperative complications were reported. We achieved negative microscopic margins in all patients. No recurrence at 7, 4 and 2-months follow-up.

Conclusions

ICG-fluorescein guidance was safe and feasible for tumor demarcation, enhancing the accuracy of resection, allowing negative margins in tumors adjacent to vascular mayor vessels, also providing surgical visualization of multifocal disease after treatment, increasing the indications of radical resections over liver transplantation. Long-term follow up is needed.

Background and Aims

Driver mutations in CTNNB1 are a hallmark of hepatoblastoma and offer a common biomarker for a liquid biopsy approach that is based on the presence of CTNNB1 circulating tumour DNA (ctDNA).

Objectives: (A) To investigate the utility of a universal next-generation sequencing (NGS) assay to detect CTNNB1 ctDNA in patients with hepatoblastoma. (B) To compare the levels of: (1) NGS ctDNA, (2) ddPCR ctDNA, (3) serum Alpha-fetoprotein (AFP, current hepatoblastoma biomarker), and verify if they correlate with tumour burden and treatment response.

Methods

We developed and tested a custom digital NGS assay covering exons 2 to 4 of CTNNB1 for detection of somatic mutations in plasma. Our cohort included 19 patients, 16 with Sanger sequencing confirmed CTNNB1 somatic mutations in the matched tumours.

Results

NGS limit of detection was evaluated at 2% variant allele frequency (VAF) and accurately detected mutations in 11/16 (69%) of the Sanger confirmed cases in samples: taken at initial diagnosis in 8/9 (89%, including 2 patients with no diagnostic biopsy), following neoadjuvant chemotherapy in 4/9 (44%), post-operatively for fully resected localized disease in 0/4 (0%), and metastatic recurrence in 1/5 (20%), suggesting a positive correlation between CTNNB1 variants and tumour burden.

Available matched ddPCR data (7 patients, 21 samples) showed similar ctDNA levels for VAF>2%. ddPCR demonstrated higher sensitivity and was able to detect ctDNA in additional 7 NGS-negative samples, with VAF detected as low as 0.085%.

NGS ctDNA levels did not corelate with AFP levels in treatment naïve samples taken at initial diagnosis. Nevertheless, longitudinal samples (5 cases, 12 samples) showed similar dynamics of both ctDNA and AFP, reflecting response to treatment.

Conclusions

ctDNA is a good surrogate marker of tumour burden and shows correlation with treatment response. CTNNB1 NGS poses an opportunity for a universal somatic genotyping at disease presentation of hepatoblastoma.

Background and Aims

In unresectable, Post-TEXT III and IV hepatic neoplasms, liver transplantation (LT) is the only curative option. The presence of tumoral thrombus (TT) add a challenge. There is scarce literature for suprahepatic inferior vena cava TT (SHVC-TT). The aim of this study is to report a surgical alternative technique.

Methods

Review of demographics, surgical technique, postoperative complications and survival, of 2 cases of Hepatoblastoma with SHVC-TT, treated with LT, cava vein resection and suprahepatic-atrial shunt (SSHA).

Results

Case-1, female, 20 months-old, presented with abdominal mass, alpha-fetoprotein (AFP) 146,000. Images showed a multi focal, Pre-TEXT-IV tumor, pulmonary metastases (PM) and SHVC-TT. Histology reports fetal epithelial Hepatoblastoma. Post high-risk (HR) chemotherapy, there was resolution of PM and partial regression of TT. The patient was listed for deceased-LT. A left-lateral segment from an adult was implanted. An In-block hepatectomy with retro and SHVC resection was performed. An iliac vein graft was used to perform the SSHA without IVC replacement.

Case-2, female, 24 months-old, presented with abdominal mass, AFP >600,000. Images reported a multifocal PreTEXT-III, PM+, P+ and SHVC-TT. Histology: Predominantly fetal pattern Hepatoblastoma. Treated as per HR protocol. Post-TEXT-III, total PM and partial TT response. Living-donor (LD) transplantation was performed, with SHVC ligation without replacement of IVC and a SSHA using the left internal jugular vein from the same LD.

Intra and post-operative results: Warm ischemia time: 43 and 46 minutes, An-hepatic phase: 58 and 65 minutes. Histology showed negative margins. Hospital stay 60 and 47 days. Both patients are disease-free without complications related to their SSHA at 11 and 8 months follow-up.

Conclusions

We present a novel surgical technique, allowing a successful LT. Since these patients had total long-term thrombus of the IVC, and developed collateral drainage veins, we thought, replacement was not necessary. Longer follow-up is needed to determine long-term surgical complications and event-free survival.

Background and Aims

Mesenchymal hamartoma (MH) is a benign liver tumor with good long term outcome after surgical management. The aim was to evaluate the presentation, diagnosis, and outcome of surgical management of MH at a tertiary care center, over 15 years.

Methods

Retrospective analysis of children with a diagnosis and treated for MH managed at our center from January 2007 to January 2021

Results

Sixteen patients with a diagnosis of mesenchymal hamartoma of liver were included in the study. There were 9 (56%) males and 7 (44%) females. Mean age was 21 months (range 15 days to 96 months). While 2/16 (12.5%) were antenatally diagnosed, 2/16 (12.5%) were diagnosed incidentally, remaining 12/16 (75%) were diagnosed on investigations for abdominal distention. Ultrasonography and computed tomography were suggestive of a multiloculated, multiseptated thick walled solid lesion with cystic component in all children. 3/16 (19%) had preoperative severe respiratory distress and underwent preoperative ultrasound guided drainage of the largest cystic space. Right lobe was involved in 93% children. All underwent surgical resection: Non-anatomical in 5/16 (31%) and anatomical resection in 11/16 (69%; right hepatectomy in 9/11 and extended right hepatectomy in 2/11). Post-operative complications were observed in 2/16 (12.5%; bile leak and bleeding in one each). Two children had gross residual lesion after non anatomical resection and one of them had a recurrence 1 year after surgery which needed a re-resection. Histopathology was confirmatory of mesenchymal hamartoma in all patients with feature of chronic cholecystitis in 31%.

Conclusions

Most children with MH present with abdominal distention and liver resection was curative in majority of patients, with recurrence noted only in one (6%). The long term outcome is good, with 100% survival.