Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside.

Background: Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignancy, characterized by high clinicalopathological and molecular heterogeneity. Preclinical in vivo models are essential for advancing our understanding of RMS oncobiology and developing novel treatment strategies. However, the diversity of scholarly data on preclinical RMS studies may challenge scientists and clinicians. Hence, we performed a systematic literature survey of contemporary RMS mouse models to characterize their phenotypes and assess their translational relevance. Methods: We identified papers published between 01/07/2018 and 01/07/2023 by searching PubMed and Web of Science databases. Results: Out of 713 records screened, 118 studies (26.9%) were included in the qualitative synthesis. Cell line-derived xenografts (CDX) were the most commonly utilized (n = 75, 63.6%), followed by patient-derived xenografts (PDX) and syngeneic models, each accounting for 11.9% (n = 14), and genetically engineered mouse models (GEMM) (n = 7, 5.9%). Combinations of different model categories were reported in 5.9% (n = 7) of studies. One study employed a virus-induced RMS model. Overall, 40.0% (n = 30) of the studies utilizing CDX models established alveolar RMS (aRMS), while 38.7% (n = 29) were embryonal phenotypes (eRMS). There were 20.0% (n = 15) of studies that involved a combination of both aRMS and eRMS subtypes. In one study (1.3%), the RMS phenotype was spindle cell/sclerosing. Subcutaneous xenografts (n = 66, 55.9%) were more frequently used compared to orthotopic models (n = 29, 24.6%). Notably, none of the employed cell lines were derived from primary untreated tumors. Only a minority of studies investigated disseminated RMS phenotypes (n = 16, 13.6%). The utilization areas of RMS models included testing drugs (n = 64, 54.2%), studying tumorigenesis (n = 56, 47.5%), tumor modeling (n = 19, 16.1%), imaging (n = 9, 7.6%), radiotherapy (n = 6, 5.1%), long-term effects related to radiotherapy (n = 3, 2.5%), and investigating biomarkers (n = 1, 0.8%). Notably, no preclinical studies focused on surgery. Conclusions: This up-to-date review highlights the need for mouse models with dissemination phenotypes and cell lines from primary untreated tumors. Furthermore, efforts should be directed towards underexplored areas such as surgery, radiotherapy, and biomarkers.

An experimental study in six fresh human cadavers using a novel approach to avoid abdominal wall incisions in total colectomy: totally transanal laparoendoscopic single-site pull-through colectomy with J-pouch creation.

BACKGROUND: The use of transanal laparoscopic access to completely avoid abdominal wall incisions represents the most current evolution in minimally invasive surgery. The combination of single-site surgery and natural orifice transluminal endoscopic surgery (NOTES™) can be used for totally transanal laparoendoscopic pull-through colectomy with J-pouch creation (TLPC-J). The aim of the present study was to provide evidence for the feasibility of TLPC-J in adult human cadavers. METHODS: TLPC-J was performed in six fresh adult human cadavers. The procedure involved endorectal submucosal dissection from 1 cm above the dentate line to a point above the peritoneal reflection, where the rectal muscle was divided circumferentially. The edge of the mucosal cuff was closed distally in order to prevent fecal contamination and the endorectal tube was placed back into the abdomen. A Triport+™ or QuadPort+™ system was introduced transanally, and it served as a multiport device (MD). Resection of the entire colon, mobilization of the distal ileal segment, and extracorporeal suture of the ileal J-loop were performed via the transanal approach. The J-pouch was created using Endo GIA™. After removal of the MD, the J-pouch was sutured to the rectal wall. RESULTS: TLPC-J was performed in all cadavers, with a mean operation duration of 236 ± 22 min. Conversion to either transabdominal laparoscopy or laparotomy was not required in any of the cadavers. No bowel perforation or damage to other organs was observed. The use of a curved endoscope greatly facilitated visualization during transanal laparoscopic dissection for partial and total colectomy, making the procedure feasible. All specimens were retrieved through the anus, eliminating the need for additional transabdominal incisions. CONCLUSIONS: TLPC-J was technically feasible in adult human cadavers, and abdominal wall incisions were not required. However, clinical studies are needed to determine its feasibility in living adults.

Transumbilical cord access (TUCA) for laparoscopy in infants and children: simple, safe and fast.

PURPOSE: We herein report a case series evaluating the safety and complication rate of transumbilical cord access (TUCA) for pediatric laparoscopic surgery. METHODS: Data were collected for 556 infants and children. Access into the abdominal cavity was gained via a transverse infraumbilical stab incision passing the fibrotic umbilical cord remnant. Ninety-two infants underwent laparoscopic pyloromyotomy (LPM), 159 female infants underwent herniorrhaphy (LHR) and 309 infants underwent appendectomy (LAP). Of the total operations, 70 % were performed by board-certified surgeons and 30 % were performed by non-board-certified surgeons. The median time of follow-up was 24 months. RESULTS: No cases of acute severe bleeding or organ laceration were noted. TUCA-related complications were observed in nine patients (1.6 %). Omphalitis and persistent wound secretion were detected in eight children and foreign bodies consisting of cyanoacrylate were removed from three of these patients. Meanwhile, umbilical pain leading to surgical revision was observed in one child, and eight umbilical hernias were repaired during the TUCA procedures. No signs of postoperative incisional hernia were recorded. CONCLUSIONS: TUCA is a safe and comfortable access method for pediatric laparoscopic surgery in various age groups. This method is easy to learn and can be quickly and safely performed in the vast majority of children.

Can a simplified algorithm prevent incomplete laparoscopic pyloromyotomy?

PURPOSE: The purpose of this study is to analyze an algorithm intended to prevent incomplete pyloromyotomy in 3-port laparoscopic (3TP) and laparoendoscopic single-site (LESS-P) procedures in a teaching hospital. METHODS: We defined the pyloroduodenal and pyloroantral junctions as anatomical margins prior pyloromyotomy by palpating and coagulating the serosa with the hook cautery instrument. Incomplete pyloromyotomies, mucosa perforations, serosa lacerations, and wound infections were recorded for pediatric surgical trainees (PST) and board-certified pediatric surgeons (BC). RESULTS: We reviewed the medical files of 233 infants, who underwent LESS-P (n=21), 3TP (n=71), and open pyloromyotomy (OP, n=141). No incomplete pyloromyotomies occurred. In contrast to OP, mucosa perforations did not occur in the laparoscopic procedures during the study period (6.38% vs. 0%, P=.013). OP had insignificantly more serosal lacerations (3.5% vs. 1.4%, P=.407). There was no difference in the rate of wound infections between OP and laparoscopic procedures (2.8% vs. 4.3%, P=.715). In the latter, all wound infections were associated with the use of skin adhesive. CONCLUSIONS: This algorithm helps avoiding incomplete laparoscopic pyloromyotomy during the learning curve and in a teaching setting. It is not risky to assist 3TP and LESS-P to PST as this led to a decreased rate of mucosa perforations without experiencing incomplete pyloromyotomies.

Noncommunicating tubular duplication of the upper pouch in esophageal atresia without fistula.

We report a unique combination of an esophageal atresia without fistula associated with a tubular noncommunicating esophageal duplication. The diagnosis was made at delayed repair and led to a successful outcome.