Systematic Lymphatic Repair for Reduction of Postoperative Lymphatic Leak Following Neuroblastoma Resection.

BACKGROUND: Gross total resection of neuroblastoma is associated with lymphatic leaks that can delay postoperative resumption of treatment. To prevent postoperative lymphatic leak, we introduced systematic lymphatic repair (SLR), which involved oversewing the entire edge of the disrupted lymphatic plane after neuroblastoma resection. We sought to study the impact of SLR on postoperative lymphatic leak and time to return to treatment. METHODS: We reviewed 60 neuroblastoma patients who underwent gross total resection at KK Women's and Children's Hospital. Patient, disease, and operative factors were correlated with surgical drainage, treatment delay and length of stay (LOS). Among patients with sufficient records, the interaction between variables associated with drainage, delay and LOS outcomes were compared in 14 patients who had SLR versus 35 historical controls who had targeted lymphatic repair (TLR). RESULTS: Postoperative drain duration and volume were significantly higher in tumors with ≥2 image-derived risk factors (IDRFs, P = 0.005 and P = 0.013, respectively) or vessel encasement (P = 0.031 and P = 0.024, respectively). Longer LOS was significantly associated with ≥2 IDRFs (P = 0.006). All forms of suture repair of lymphatics and use of Tachosil™ were associated with significantly longer postoperative drain duration (P < 0.05); the former was also associated with significantly higher total drain volume (P < 0.05) - indicating appropriate use of these adjuncts in patients at risk of chyle leak. In patients who had suture repair of lymphatics, SLR was significantly associated with reduced postoperative interval to chemotherapy resumption (P = 0.014, two-way ANOVA). CONCLUSION: A systematic approach to repair of lymphatic channels following neuroblastoma resection can significantly reduce time to postoperative resumption of treatment. TYPE OF STUDY: Clinical Research. LEVEL OF EVIDENCE: III.

Exosomal mRNA Cargo are biomarkers of tumor and immune cell populations in pediatric osteosarcoma.

Osteosarcoma is the commonest malignant bone tumor of children and adolescents and is characterized by a high risk of recurrence despite multimodal therapy, especially in metastatic disease. This suggests the presence of clinically undetected cancer cells that persist, leading to cancer recurrence. We sought to evaluate the utility of peripheral blood exosomes as a more sensitive yet minimally invasive blood test that could aid in evaluating treatment response and surveillance for potential disease recurrence. We extracted exosomes from the blood of pediatric osteosarcoma patients at diagnosis (n=7) and after neoadjuvant chemotherapy (n=5 subset), as well as from age-matched cancer-free controls (n=3). We also obtained matched tumor biopsy samples (n=7) from the cases. Exosome isolation was verified by CD9 immunoblot and characterized on electron microscopy. Profiles of 780 cancer-related transcripts were analysed in mRNA from exosomes of osteosarcoma patients at diagnosis and control patients, matched post-chemotherapy samples, and matched primary tumor samples. Peripheral blood exosomes of osteosarcoma patients at diagnosis were significantly smaller than those of controls and overexpressed extracellular matrix protein gene THBS1 and B cell markers MS4A1 and TCL1A. Immunohistochemical staining of corresponding tumor samples verified the expression of THBS1 on tumor cells and osteoid matrix, and its persistence in a treatment-refractory patient, as well as the B cell origin of the latter. These hold potential as liquid biopsy biomarkers of disease burden and host immune response in osteosarcoma. Our findings suggest that exosomes may provide novel and clinically-important insights into the pathophysiology of cancers such as osteosarcoma.

Clinicopathological and treatment response characteristics of updated rhabdomyosarcoma histomolecular subtypes: An Asian population-based study.

AIM: New histomolecular subtypes of rhabdomyosarcoma have recently been defined but their corresponding clinical characteristics are not well described. Also, these clinical phenotypes vary greatly by age and ethnicity but have not been profiled in Asian populations. Thus, we sought to determine the landscape of rhabdomyosarcoma subtypes in a national Asian cohort and compare clinical characteristics among age groups and molecular subtypes. METHODS: We performed a retrospective population-based study of all rhabdomyosarcoma patients in Singapore public hospitals from 2004 to 2014 (n = 67), and assigned histomolecular subtypes according to the updated 2020 WHO classification of soft tissue tumors following central pathology review and molecular profiling. RESULTS: Age-specific prevalence followed a tri-modal peak. There were significantly more embryonal and alveolar (p = 0.032) and genitourinary (non-bladder/prostate) tumors (p = 0.033) among children. Older age was associated with complete resection among spindle cell/sclerosing tumors (p = 0.027), with the omission of chemotherapy among embryonal tumors (p = 0.001), and with poorer survival among embryonal and alveolar tumors (p = 0.026, p = 0.022, respectively). Overall survival differed with stage, group, and surgical resection, adjusted for age group (p = 0.004, p = 0.001, p = 0.004, respectively). Spindle-cell/sclerosing tumors showed an indolent phenotype with a significantly lower incidence of nodal metastasis (p = 0.002), but two of 15 patients with MYOD1 mutations had a contrastingly aggressive disease. CONCLUSION: Disease and treatment response profiles of rhabdomyosarcoma subtypes vary significantly between adults and children, especially surgical resectability. In our Asian population, poorer outcomes were observed in adults with embryonal and alveolar tumors, while activating mutations influence the behavior of otherwise favorable spindle cell/sclerosing tumors.