Deploying Indocyanine Green Fluorescence-Guided Navigation System in Precise Laparoscopic Resection of Pediatric Hepatoblastoma.

Background: Hepatoblastoma (HB) is the most common form of liver cancer in children. To date, complete tumor resection is still the gold standard for treating HB. Indocyanine green (ICG) has been identified as a sensitive adjunct that is highly effective in the identification and surgical management of local and metastatic HB. It has thus becomes an increasingly popular choice among surgeons in HB resection surgeries that are fluorescence-guided. However, laparotomy remains the preferred choice in most cases since the applications and limitations of fluorescence-guided laparoscopic surgery in treating HB remain unclear. In this study, the characteristics and outcomes of laparoscopic HB resections that were guided by intraoperative ICG fluorescent imaging were investigated. Methods: Seven HB patients underwent ICG-guided laparoscopic HB resection surgery from August 2019 to December 2021. ICG was intravenously administered to the patients at a dosage of 0.5 mg/kg 48 h prior to the scheduled operation. During operation, tumor localization and resection boundary were guided by fluorescence visualization. The data on surgical and clinical features were collected retrospectively. Results: The resection area and tumor boundary could be clearly viewed in real-time under the ICG fluorescence imaging navigation system during operation, except for one patient who had received interventional chemoembolization before surgery. The image produced by laparoscopic fluorescence navigation was clear since it was not affected by ambient light. All tumors were completely resected as confirmed by negative margins for HB during postoperative pathological examination. No residual or recurrence were also found through computed tomography during follow-up visits from 9 to 37 months. Conclusions: ICG fluorescence-guided laparoscopic surgery is safe and effective in treating HB due to its ability to provide clear information on tumor localization and delineate tumor margins in real-time.

Identification of hub genes and construction of prognostic nomogram for patients with Wilms tumors.

Background: In children, Wilms' tumors are the most common urological cancer with unsatisfactory prognosis, but few molecular prognostic markers have been discovered for it. With the rapid development of high-throughput quantitative proteomic and transcriptomic approaches, the molecular mechanisms of various cancers have been comprehensively explored. This study aimed to uncover the molecular mechanisms underlying Wilms tumor and build predictive models by use of microarray and RNA-seq data. Methods: Gene expression datasets were downloaded from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. Bioinformatics methods wereutilized to identified hub genes, and these hub genes were validated by experiment. Nomogram predicting OS was developed using genetic risk score model and clinicopathological variables. Results: CDC20, BUB1 and CCNB2 were highly expressed in tumor tissues and able to affect cell proliferation and the cell cycle of SK-NEP-1 cells. This may reveal molecular biology features and a new therapeutic target of Wilms tumour.7 genes were selected as prognostic genes after univariate, Lasso, and multivariate Cox regression analyses and had good accuracy, a prognostic nomogram combined gene model with clinical factors was completed with high accuracy. Conclusions: The current study discovered CDC20,BUB1 and CCNB2 as hub-genes associated with Wilms tumor, providing references to understand the pathogenesis and be considered a novel candidate to target therapy and construct novel nomogram, incorporating both clinical risk factors and gene model, could be appropriately applied in preoperative individualized prediction of malignancy in patients with Wilms tumor.

Two-stage laparoscopic resection of giant hepatoblastoma in infants combined with liver partial partition and artery ligation.

PURPOSE: Laparoscopic resection of giant hepatoblastoma (HB) in children has long been a subject of controversy. Here, a new procedure of two-stage laparoscopic resection of giant HB in infants was firstly reported and the feasibility was discussed. METHODS: The clinical data of three infants with HB were retrospectively reviewed, all of which received 3-5 cycles of neoadjuvant chemotherapy. Stage 1 laparoscopic selective hepatic artery ligation and liver partial partition were performed. Stage 2 laparoscopic hepatectomy was performed 2 weeks later. RESULTS: The results demonstrated that (1) the tumors shrank considerably in size and had relatively clear boundaries after neoadjuvant chemotherapy; (2) after stage 1 surgery, the tumor volume further reduced, while the intratumoral necrosis expanded; (3) 2 weeks later, stage 2 laparoscopic hepatectomy was performed successfully; (4) none of the cases had intraoperative complications such as tumor rupture, air embolism, hemorrhage, biliary fistula, or liver failure, and there was no recurrence or metastasis during follow-up. CONCLUSIONS: Two-stage laparoscopic hepatectomy associating selective hepatic artery ligation and liver partial partition for HB in infants has the benefits of small invasiveness, fast recovery, improved safety, and high feasibility. However, more cases and longer follow-up are needed to assess its long-term efficacy.

CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression.

Hepatoblastoma (HB) is a malignant embryonal tumor of the liver that consists of heterogenous populations of stem/progenitor cells. Although circular RNAs (circRNAs) play an essential role in tumor development, the effects of circRNA on the proliferation of HB cells, especially cancer stem cells (CSCs), remain unclear. We found that the circRNA, CDR1as, was highly expressed in CSC-enriched populations of HB cell lines. Results from flow cytometric and sphere-forming assays revealed that CDR1as knockdown in HB cell lines decreased the proportion of stem cells. The Cell Counting Kit-8 (CCK-8) assay, colony formation experiments, and EdU assay revealed that CDR1as knockdown in HB cell lines decreased cell growth and the colony-forming abilities. Biotin-coupled probe pull-down assays and biotin-coupled microRNA capture were conducted to evaluate the interaction between CDR1as and miR-7-5p. Dual-luciferase reporter assays demonstrated that Kruppel-like factor 4 (KLF4), expression of which is highly correlated with cancer stemness, was a target of miR-7-5p. Overall, the knockdown of CDR1as significantly inhibited the proliferation and stemness of HB cells by reducing the sponge activity on miR-7-5p and subsequently suppressing the interaction between miR-7-5p and KLF4. Results from this study suggest that CDR1as is an oncogene that effects the proliferation and stemness of HBs.

Effective surgical treatment of life-threatening huge vascular anomalies associated with thrombocytopenia and coagulopathy in infants unresponsive to drug therapy.

BACKGROUND: Systemic drug therapy is generally recommended for infant huge vascular anomalies associated with thrombocytopenia and coagulopathy, but some patients are not suitable due to drug unresponsiveness or life threatening conditions before the drug works, who will need to receive surgical treatment. This study retrospectively analyzed the clinical features, imaging features, and surgical outcomes of these patients. METHODS: The clinical data of 4 infants with huge vascular anomalies (2 vein malformations (VMs) and 2 kaposiform hemangioendothelioma (KHE)) associated with thrombocytopenia and coagulopathy treated from June 2016 to December 2017 were retrospectively analyzed. All patients received glucocorticoids, propranolol, vincristine or sirolimus treatment before admission, but the treatment was ineffective. Skin petechia, thrombocytopenia and coagulopathy were present at the time of admission. CT scanning was performed before operation. The patient's general clinical data, hematological examination results, operation time, surgical bleeding volume, blood transfusion volume and surgical complications were collected for analysis. The patients were followed up for 10-26 months. RESULTS: CT scanning results of 2 patients showed special CT features without detectable enhancement within the lesion after CT enhanced scanning and multiple phleboliths formation. Four patients underwent surgical treatment successfully. Two patients underwent complete resection of the lesion, and 2 underwent cytoreductive surgery. Preoperative clinical symptoms such as skin petechia, thrombocytopenia and coagulopathy were normal at 1 week after surgery. Postoperative pathological results showed 2 cases of KHE and 2 cases of VMs. All patients were discharged from hospital without physical dysfunction, recurrence, or death. CONCLUSIONS: Timely and appropriate surgical intervention can achieve satisfactory results for infants with huge VMs and KHE who were unresponsive to drug therapy or suffering from life-threatening occasion before the drug become effective.

Cobalt(II)-Catalyzed Oxidative C-H Arylation of Indoles and Boronic Acids.

Co(II)-catalyzed C-H C2 selective arylation of indoles with boronic acids through monodentate chelation assistance has been achieved for the first time. The unique features of this methodology include mild reaction conditions, highly C2 regioselectivity, and employment of a Grignard reagent-free catalytic system. A wide range of substrates, including unreactive arenes, are well tolerated, which enables the construction of the coupling products efficiently. This new strategy provides an alternative and versatile approach to construct biaryls using inexpensive cobalt catalyst.

Cobalt(II)-Catalyzed C-H Amination of Arenes with Simple Alkylamines.

A new method of cobalt-catalyzed amination of arylamides with simple alkylamines is reported through C(sp(2))-H bond functionalization. For the first time, inexpensive cobalt is exploited as the catalyst in the amination of C(sp(2))-H bond using simple alkylamines.