Laparoscopic resection of congenital choledochal cyst and choledochojejunostomy in children is feasible. We feel that there is a considerable learning curve with the technique. Future studies will have to prove the feasibility of laparoscopic Roux-en-Y bowel anastomosis without the need for bowel exteriorization.
Rectal suction biopsy is the diagnostic procedure of choice in aganglionosis even if only mucosal tissue is obtained. In neuronal intestinal dysplasia it is essential to include parts of the submucous layer. Therefore some biopsies are unsuitable because they lack submucous tissue. In a retrospective analysis (1991-1993) this occurred in 34.9% of our biopsies. These samples were taken without attention to the level of suction. Prospectively we compared suction biopsies taken by a standard suction level (250-300 cm water column) with excision biopsies taken by scissors under speculum exposure in ten consecutive patients. Submucosa was missed in only one biopsy each, but two excision biopsies were made useless by mechanical traumatization. We conclude a correctly practised rectal suction biopsy still remains the procedure of choice for diagnostic screening in malformations of the enteric nervous system.
Numerous investigators have shown that video-assisted thoracoscopic surgery (VATS) can be safely used for specific conditions of newborns, infants, and children. The technique has been postulated to be associated with a lower morbidity, shorter hospital stay, lower costs, and clinical results similar to those achieved by open surgery. The present article reviews the state of the art of VATS for thoracic conditions in children. Most authors focus on the feasibility of single procedures, and only a small number of reports deals with the feasibility in series with multiple types of procedures and larger numbers of patients. Therefore, systematic research on the advantages and limits of VATS in children remains mandatory.
Aims
Cardiotoxicity leading to heart failure (HF) is a growing problem in many cancer survivors. As specific treatment strategies are not available, RNA discovery pipelines were employed and a new and powerful circular RNA (circRNA)-based therapy was developed for the treatment of doxorubicin-induced HF.
Methods and results
The circRNA sequencing was applied and the highly species-conserved circRNA insulin receptor (Circ-INSR) was identified, which participates in HF processes, including those provoked by cardiotoxic anti-cancer treatments. Chemotherapy-provoked cardiotoxicity leads to the down-regulation of Circ-INSR in rodents and patients, which mechanistically contributes to cardiomyocyte cell death, cardiac dysfunction, and mitochondrial damage. In contrast, Circ-INSR overexpression prevented doxorubicin-mediated cardiotoxicity in both rodent and human cardiomyocytes in vitro and in a mouse model of chronic doxorubicin cardiotoxicity. Breast cancer type 1 susceptibility protein (Brca1) was identified as a regulator of Circ-INSR expression. Detailed transcriptomic and proteomic analyses revealed that Circ-INSR regulates apoptotic and metabolic pathways in cardiomyocytes. Circ-INSR physically interacts with the single-stranded DNA-binding protein (SSBP1) mediating its cardioprotective effects under doxorubicin stress. Importantly, in vitro transcribed and circularized Circ-INSR mimics also protected against doxorubicin-induced cardiotoxicity.
Conclusion
Circ-INSR is a highly conserved non-coding RNA which is down-regulated during cardiotoxicity and cardiac remodelling. Adeno-associated virus and circRNA mimics-based Circ-INSR overexpression prevent and reverse doxorubicin-mediated cardiomyocyte death and improve cardiac function. The results of this study highlight a novel and translationally important Circ-INSR-based therapeutic approach for doxorubicin-induced cardiac dysfunction.
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