Background: Children with hepatoblastoma (HB) are at risk of sarcopenia due to immobility, chemotherapy, and malnutrition. We hypothesized that children with HB have a low preoperative total psoas muscle area (tPMA), reflecting sarcopenia, which negatively impacts outcome.Procedure: Retrospective study of children (1‐10 years) with hepatoblastoma treated at a large university children's hospital from 2009 to 2018. tPMA was measured as the sum of the right and left psoas muscle area (PMA) at intervertebral disc levels L3‐4 and L4‐5. z‐Scores were calculated using age‐ and gender‐specific reference values and were compared to anthropometric measurements, clinical variables, and outcomes. Sarcopenia was defined as a tPMA z‐score below −2.Results: Thirty‐three children were included. Mean tPMA z‐score was −2.18 ± 1.08, and 52% were sarcopenic. A poor correlation between tPMA and weight was seen (r = 0.35; confidence interval [CI] 0.01, 0.62; P = .045), and most children had weights within the normal range (mean z‐score −0.55 ± 1.39). All children categorized as high risk with relapse (n = 5/12) were sarcopenic before surgery. Relapse was significantly higher in the high‐risk sarcopenic group compared to the nonsarcopenic group (P = .008). The change in tPMA z‐score 1‐4 months after surgery did not improve in patients with relapse, but did improve in 75% of children without relapse.Conclusions: The majority of children with HB were sarcopenic prior to surgery. Especially in children with high‐risk hepatoblastoma, sarcopenia is an additional risk factor for relapse. Large multicenter studies are needed to confirm these preliminary results.

The SP/NK1R-complex plays an important role in tumor proliferation. Targeting of the neurokinin-1 receptor in previous studies with its antagonist aprepitant (AP) resulted in anti-tumoral effects in colorectal cancer and hepatoblastoma. However, there is still a lack of knowledge regarding its effects on pancreatic cancer. Therefore, we treated human pancreatic ductal adenocarcinoma (PDAC) cell lines (Capan-1, DanG, HuP-T3, Panc-1, and MIA PaCa-2) and their cancer stem cell-like cells (CSCs) with AP and analyzed functional effects by MTT-, colony, and sphere formation assays, respectively; moreover, we monitored downstream mechanisms by flow cytometry. NK1R inhibition resulted in dose-dependent growth reduction in both CSCs and non-CSCs without induction of apoptosis in most PDAC cell lines. More importantly, we identified striking AP dependent cell cycle arrest in all parental cells. Furthermore, gene expression and the importance of key genes in PDAC tumorigenesis were analyzed combining RT-qPCR in eight PDAC cell lines with publicly available datasets (TCGA, GEO, CCLE). Surprisingly, we found a better overall survival in patients with high NK1R levels, while at the same time, NK1R was significantly decreased in PDAC tissue compared to normal tissue. Interestingly, there is currently no differentiation between the isoforms of NK1R (truncated and full; NK1R-tr and -fl) in any of the indicated public transcriptomic records, although many publications already emphasize on important regulatory differences between the two isoforms of NK1R in many cancer entities. In conclusion, analysis of splice variants might potentially lead to a stratification of PDAC patients for NK1R-directed therapies. Furthermore, we presume PDAC patients with high expressions of NK1R-tr might benefit from treatment with AP to improve chemoresistance. Therefore, analysis of splice variants might potentially lead to a stratification of PDAC patients for NK1R-directed therapies.

Rhabdoid tumors (RT) are among the most aggressive tumors in early childhood. Overall survival remains poor, and treatment only effectively occurs at the cost of high toxicity and late adverse effects. It has been reported that the neurokinin-1 receptor/ substance P complex plays an important role in cancer and proved to be a promising target. However, its role in RT has not yet been described. This study aims to determine whether the neurokinin-1 receptor is expressed in RT and whether neurokinin-1 receptor (NK1R) antagonists can serve as a novel therapeutic approach in treating RTs. By in silico analysis using the cBio Cancer Genomics Portal we found that RTs highly express neurokinin-1 receptor. We confirmed these results by RT-PCR in both tumor cell lines and in human tissue samples of various affected organs. We demonstrated a growth inhibitory and apoptotic effect of aprepitant in viability assays and flow cytometry. Furthermore, this effect proved to remain when used in combination with the cytostatic cisplatin. Western blot analysis showed an upregulation of apoptotic signaling pathways in rhabdoid tumors when treated with aprepitant. Overall, our findings suggest that NK1R may be a promising target for the treatment of RT in combination with other anti-cancer therapies and can be targeted with the NK1R antagonist aprepitant.

Background: Prophylactic abdominal drains for perforated appendicitis in children have generally been regarded as obsolete because several studies showed inferior results for drain placement in the past. Despite these results, prophylactic abdominal drains for perforated appendicitis remain omnipresent in pediatric surgery especially when gross spillage is observed at the time of appendectomy. Here, we hypothesize that even if accounting for gross intra-abdominal spillage, prophylactic drain placement for perforated appendicitis in children is not beneficial. Patients and Methods: The charts of all children (<18 years) who underwent an appendectomy at our institution from July 2013 to March 2020 were analyzed. The data from 65 patients who presented with perforated appendicitis were included. Patients were grouped according to the amount of intraoperative spillage. Demographics, laboratory data, operative findings, and postoperative outcomes were analyzed. Results: Of all patients, 34 were male, and 31 were female, with a mean age of 10.5 ± 3.7 years. There were no statistically significant differences between the groups for age and sex (p = 0.6985 and p = 0.6222, respectively). Prophylactic drains were placed according to the surgeon's preference in 32 children. There were no statistically significant differences between the groups in the rate of intra-abdominal abscess formation, wound infection, and bowel obstruction, regardless of the amount of spillage encountered during an appendectomy. However, independently of the amount of spillage, the length of hospital stay was longer in the children in which a drain had been placed (p = 0.0041). Conclusion: In our cohort, we could not find a benefit from drain placement even in case of gross spillage at the time of appendectomy. Rather, drain placement was associated with an increase in length of hospital stay.