Joerg Fuchs

University of Tuebingen | EKU Tübingen · Department of Paediatric Surgery and Pediatric Urology

Background This study aimed to assess the impact that the quality of primary and subsequent surgeries has on the survival of patients with para-testicular rhabdomyosarcoma (PTRMS). Methods Patients with localized (IRS I–III) and metastatic (IRS IV) PTRMS were enrolled in the two Cooperative Weichteilsarkom Studiengruppe (CWS) trials (CWS-96, CWS-2...

Centromeric nucleosomes are determined by the replacement of the canonical histone H3 with the centromere-specific histone H3 (CENH3) variant. Little is known about the centromere organization in allopolyploid species where different subgenome-specific CENH3s and subgenome-specific centromeric sequences coexist. Here, we analyzed the transcription...

Objective This study aimed to identify parameters that allow the estimation of tumor-infiltrated lymph nodes (LN) after pretreatment for unilateral Wilms tumor (WT). Summary Background Data Complete tumor resection with removal of regional LN is always necessary. Positive LNs require local irradiation influencing benefits in case of NSS in long-te...

Background Treatment of unstable forearm fractures in the metaphyseal-diaphyseal junction (MDJ) zone is still a matter of debate. Major drawbacks of all types of fixations include either invasiveness, technical impracticality, or lack of acceptance by patients. This study reports results after antegrade ESIN (a-ESIN) compared to transepiphyseal int...

The presence of incompatibility alleles in primary amphidiploids constitutes a reproductive barrier in newly synthesized wheat-rye hybrids. To overcome this barrier, the genome stabilization process includes large-scale chromosome rearrangements. In incompatible crosses resulting in fertile amphidiploids, the elimination of one of the incompatible...

Holocentric species are characterized by the presence of centromeres throughout the length of the chromosomes. We confirmed the holocentricity of the dioecious, small chromosome-size species Myristica fragrans based on the chromosome-wide distribution of the centromere-specific protein KNL1, α-tubulin fibers, and the cell cycle-dependent histone H3...

Background Treatment of unstable forearm fractures in the metaphyseal-diaphyseal junction (MDJ) zone is still a matter of debate. Major drawbacks of all types of fixations include either invasiveness, technical impracticality, or lack of acceptance by patients. This study reports results after antegrade ESIN (a-ESIN) compared to transepiphyseal int...

Objectives Paediatric patients with intestinal failure (IF) are at risk for both gastrointestinal (GI) and systemic complications, thus depending on a functioning network of multidisciplinary care. Data on the clinical impact of coronavirus disease 2019 (COVID‐19) or the pandemic‐related restrictions are limited. We aimed to analyse the clinical co...

Centromeric nucleosomes are determined by the replacement of the canonical histone H3 with the centromere-specific histone H3 (CENH3) variant. Little is known about the centromere organization in allopolyploid species where different subgenome-specific CENH3s and subgenome-specific centromeric sequences coexist. Here, we analyzed the transcription...

Non‐invasive differentiation of paediatric kidney tumours is particularly important in the SIOP‐RTSG protocols, which recommend pre‐operative chemotherapy without histological confirmation. The identification of clinical and tumour‐related parameters may enhance diagnostic accuracy. Age, metastases, and tumour volume (TV) were retrospectively analy...

Wild plants can contribute valuable genes to their domesticated relatives. Fertility barriers and a lack of genomic resources have hindered the effective use of crop-wild introgressions. Decades of research into barley’s closest wild relative, Hordeum bulbosum , a grass native to the Mediterranean basin and Western Asia, have yet to manifest themse...

Simple Summary Solid thoracic tumors in children are rare, with neuroblastoma being the most commonly diagnosed tumor entity. A safe and complete tumor resection is often not possible with a unilateral cervical approach, sternotomy, thoracotomy, or bilateral thoracotomy (single or staged) in certain localizations of the thorax, such as the cervicot...

(1) Background: The study aimed to investigate the influence of MRI-defined residual disease on local tumor control after resection of neuroblastic tumors in patients without routine adjuvant radiotherapy. (2) Methods: Patients, who underwent tumor resection between 2009 and 2019 and received a pre- and postoperative MRI, were included in this retr...

Introduction Cerebral oxygen desaturation during pediatric surgery has been associated with adverse perioperative outcomes. The aim of this pilot study was to analyze the frequency and severity of intraoperative cerebral oxygen desaturations and their impact on postoperative cerebral oxygen metabolism in neonates and infants undergoing pediatric su...

Background Outcome of primary metastatic rhabdomyosarcoma (RMS) is poor. Certain risk factors as fusion status, Oberlin score, and local treatment of primary tumor are known to influence prognosis. Procedure Patients with metastatic RMS were treated according to Cooperative Weichteilsarkom Studiengruppe (CWS) guidance with chemotherapy (CHT), radi...

Wilms tumors (WTs) are histologically diverse childhood cancers with variable contributions of blastema, stroma, and epithelia. A variety of cancer genes operate in WTs, including the tripartite‐motif‐containing‐28 gene ( TRIM28 ). Case reports and small case series suggest that TRIM28 mutations are associated with epithelial morphology and WT pred...

Solid pseudopapillary neoplasms (SPNs) are the most common entity among pediatric pancreatic tumors. Still, these are rare tumors with an annual incidence of 0.1–0.2/1,000,000, and little is known about their optimal treatment. This analysis aimed to increase knowledge about the occurrence and treatment strategies of SPN in childhood. Data regardin...

PURPOSE To analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS). METHODS One thousand four hundred seventy patients with localized RMS 21 years and younger entered on CWS-96, CWS-2002P, and SoTiSaR were eligible for the analysis....

In many species, the transmission of B chromosomes (Bs) does not follow the Mendelian laws of equal segregation and independent assortment. This deviation results in transmission rates of Bs higher than 0.5, a process known as “chromosome drive”. Here, we studied the behavior of the 103 Mbp-large B chromosome of Festuca pratensis during all meiotic...

Background The pretreatment International Neuroblastoma Risk Group Staging System (INRGSS) discriminates localized tumors L1/L2 depending on the absence/presence of image‐defined risk factors (IDRFs) at diagnosis. Referring to this new staging system, we assessed initial imaging of localized thoracic neuroblastoma (NB) and ganglioneuroma (GN) and t...

Purpose Treatment of neuroblastoma metastases usually consists of chemotherapy and irradiation. However, in selected cases, surgical treatment is also indicated. In this study, we present three cases of patients with neuroblastoma metastases at rare sites that underwent surgery. Materials and methods We retrospectively analyzed data of patients wh...

Simple Summary The combination treatment of organ-preserving tumor resection and brachytherapy in children with bladder/prostate and perianal rhabdomyosarcoma can reduce therapy-associated side effects while maintaining excellent oncological outcome. This highly individualized hybrid treatment concept poses specific challenges for all clinicians in...

Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas cove...

The centromere is the chromosome region where microtubules attach during cell division. In contrast to monocentric chromosomes with one centromere, holocentric species usually distribute hundreds of centromere units along the entire chromatid. We assembled the chromosome-scale reference genome and analyzed the holocentromere and (epi)genome organiz...

Purpose Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexi...

Background: Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance. Methods: Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carbopl...

Both congenital diaphragmatic hernias (CDHs) and omphaloceles show relevant overall mortality rates as individual findings. The combination of the two has been described only sparsely in the literature and almost always with a fatal course. Here, we describe a term neonate with a rare high-risk constellation of left-sided CDH and a large omphalocel...

Resection of lung metastases in children with solid tumors is regularly hampered by limited intraoperative detectability and relevant operative trauma of the open surgical access. The aim of this study was to analyze thoracoscopic resection of lung metastases in children following CT-guided labeling with coil wires. We retrospectively analyzed data...

Background/aim: Epigallocatechin gallate (EGCG), a major polyphenol of green tea, has been shown to inhibit cancer cell proliferation. In this study the effect of EGCG on cell metabolism and the human hedgehog signalling pathway (HH) in human rhabdomyosarcoma (RMS) cells was investigated. Materials and methods: Two human RMS cell lines (RD and R...

Purpose: Patients with relapsed high-risk neuroblastoma (rHR-NB) have a poor prognosis. We hypothesized that graft-versus-neuroblastoma effects could be elicited by transplantation of haploidentical stem cells (haplo-SCT) exploiting cytotoxic functions of natural killer cells and their activation by the anti-GD2 antibody dinutuximab beta (DB). Thi...

PURPOSE Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexi...

The genus Agave presents a bimodal karyotype with x = 30 (5L, large, +25S, small chromosomes). Bimodality within this genus is generally attributed to allopolyploidy in the ancestral form of Agavoideae. However, alternative mechanisms, such as the preferential accumulation of repetitive elements at the macrochromosomes, could also be important. Aim...

Introduction Inducing general anesthesia (GA) in children can considerably affect blood pressure, and the rate of severe critical events owing to this remains high. Cerebrovascular autoregulation (CAR) protects the brain against blood-flow-related injury. Impaired CAR may contribute to the risk of cerebral hypoxic–ischemic or hyperemic injury. Howe...

Introduction Inguinal procedures in children are frequent and typically performed in an outpatient setting. We aimed to analyze whether there is a difference in postoperative pain scores and setup time (start of anesthesia management to incision time) when comparing caudal block (CB) with local wound infiltration. Materials and Methods We enrolled...

Simple Summary Although survival after rhabdosarcoma treatment has improved over the years, one third of patients still develop locoregional relapse. This review aims to highlight developments pertaining to staging and local treatment of specific RMS tumor sites, including head and neck, chest/trunk, bladder-prostate, female genito-urinary, periana...

Double haploid production is the most effective way of creating true-breeding lines in a single generation. In Arabidopsis, haploid induction via mutation of the centromere-specific histone H3 (cenH3) has been shown when outcrossed to wild-type, whereas the wild-type genome remains in the haploid progeny. However, factors that affect haploid induct...

The centromere is the chromosome region where the microtubules attach during cell division. In contrast to monocentric chromosomes with one centromere location, holocentric species usually distribute hundreds of centromere units along the entire chromatid. We assembled the chromosome-scale reference genome and analyzed the holocentromere and (epi)g...

Background Cross-sectional imaging-based morphological characteristics of pediatric rhabdomyosarcoma have failed to predict outcomes. Objective To evaluate the feasibility and possible value of generating tumor sub-volumes using voxel-wise analysis of metabolic and functional data from positron emission tomography/magnetic resonance imaging (PET/M...

BACKGROUND Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs are linked with a higher potential morbidity at operation and lessen the chance of complete tumor resection. The IDRFs do not all carry the same weight in predicting tumor...

Background The survival of patients with localized embryonal rhabdomyosarcoma (RMS) completely resected at diagnosis is greater than 90%. Most patients have paratesticular, uterine, or vaginal RMS, limiting specific analyses of RMS localized in other anatomic regions. This international study was conducted to define the outcome for completely resec...

Usually, chromosome sets (karyotypes) and genome sizes are rather stable for distinct species and therefore of diagnostic value for taxonomy. In combination with (cyto)genomics, both features provide essential cues for genome evolution and phylogenetic relationship studies within and between taxa above the species level. We present for the first ti...

The great efforts spent in the maintenance of past diversity in genebanks are rationalized by the potential role of plant genetic resources (PGR) in future crop improvement—a concept whose practical implementation has fallen short of expectations. Here, we implement a genomics-informed prebreeding strategy for wheat improvement that does not discri...

Purpose Success of pediatric solid tumor surgery is regularly hampered by infiltration of essential neurovascular structures. A surgical dilemma arises when imaging data suggest a conflict between complete resection and preservation of neurological function. The aim of the study was to analyze data of children harboring tumors with involvement of n...

The generation of haploid plants accelerates the crop breeding process. One of the haploidization strategies is based on the genetic manipulation of endogenous CENH3. To extend the haploidization toolbox, we tested whether targeted in vivo degradation of CENH3 protein can be harnessed to generate haploids in Arabidopsis thaliana. We show that a rec...

Objective: This study aims to identify factors associated with the occurrence of local relapse (LR) after treatment for unilateral nephroblastoma. Summary of background data: Despite the fact that LR is rare (~5%) its adverse impact on the need for relapse treatment and outcome (40-80% OS) cannot be neglected. Identifying the causative factors m...

(1) Background: Vena cava thrombus (VCT) is rare in Wilms tumor (WT) (4–10%). The aim of this study is to identify factors for an outcome to improve treatment for better survival. (2) Methods: 148/3015 patients with WT (aged < 18 years) and VCT, prospectively enrolled over a period of 32 years (1989–2020) by the German Society for Pediatric Oncolog...

Purpose Natural products are generally regarded as safe and have been shown to mediate anticancer activities against a variety of cell types. Zerumbone is a natural cyclic sesquiterpene derived from the rhizome of Zingiber zerumbet, which has attracted extensive attention in the recent decade for anticancer activities. The present study investigate...

Introduction Pediatric radial neck and head fractures are rare, accounting for only 1% of all fractures in children. The aim of this study is to describe the management and results of the respective fracture types and different injury characteristics. Materials and methods This study performs a retrospective data analysis of 100 consecutive patien...

The centromere represents a single region in most eukaryotic chromosomes. However, several plant and animal lineages assemble holocentromeres along the entire chromosome length. Here, we compare genome organization and evolution as a function of centromere type by assembling chromosome-scale holocentric genomes with repeat-based holocentromeres fro...

Biomarkers allowing characterization of pediatric rhabdomyosarcoma (RMS) are lacking. Epitope detection in monocytes (EDIM) is a novel method focused on detection of the biomarkers TKTL1 (transketolase-like protein 1) and Apo10 (epitope of DNaseX) in activated monocytes (CD14+/CD16+) from patient’s blood. We investigated the expression of these bio...

Purpose In pediatric bladder/prostate-rhabdomyosarcoma, the rate of bladder preservation after neoadjuvant chemotherapy is high, with an excellent oncological outcome. Information about functional urological long-term outcomes is rare. Methods Data of all patients who had undergone bladder-preserving surgery with or without brachytherapy at our in...

Background Neuroblastoma (NB) is the most common paediatric extracranial solid malignancy. We analysed the role of the epitope detection in monocytes (EDIM) technique for liquid biopsy in NB patients. Methods Tumour epitopes transketolase-like 1 (TKTL1), Apo10 (DNaseX) and GD2 were assessed: expression levels in seven NB tumour samples and five NB...

Background Overexpression of phosphodiesterase type 5 (PDE5) has been detected in many types of malignant tumors. Sildenafil, a potent and selective inhibitor of a cGMP-specific PDE5, has been found to enhance the cytotoxic activity of different chemotherapeutic agents including doxorubicin. The combined therapy of doxorubicin with Sildenafil might...

Background: The ideal timing of genital surgery in differences/disorders of sex development (DSD) is controversial and differs according to the underlying type of DSD. Increasing numbers of persisting sinus as a result of delayed feminizing genitoplasty in DSD patients require interdisciplinary collaboration of pediatric surgeons/urologists and gyn...

Purpose: In pediatric bladder/prostate-rhabdomyosarcoma, the rate of bladder preservation after neoadjuvant chemotherapy is high, with an excellent oncological outcome. Information about functional urological long-term outcomes is rare. Methods: Data of all patients who had undergone bladder-preserving surgery with or without brachytherapy at our i...

The genomic landscape of recombination plays an essential role in evolution. Patterns of recombination are highly variable along chromosomes, between sexes, individuals, populations, and species. In many eukaryotes, recombination rates are elevated in sub-telomeric regions and drastically reduced near centromeres, resulting in large low-recombining...

Purpose Optimization of local therapies in synovial sarcoma (SS) considered unresectable at diagnosis is needed. We evaluated the effects of neoadjuvant versus adjuvant radiation versus surgery only on long-term outcomes. Methods Patients with macroscopic SS tumors before chemotherapy (IRS-group-III) in the trials CWS-81, CWS-86, CWS-91, CWS-96, C...

KINETOCHORE NULL2 (KNL2) plays key role in the recognition of centromeres and new CENH3 deposition. To gain insight into the origin and diversification of the KNL2 gene, we reconstructed its evolutionary history in the plant kingdom. Our results indicate that the KNL2 gene in plants underwent three independent ancient duplications in ferns, grasses...

Purpose In advanced tumor stages, pediatric rhabdomyosarcoma (RMS) shows an intrinsic resistance to standard chemotherapy, which is associated with a dismal prognosis. Alternative therapeutic approaches and optimization of already existent treatment protocols are urgently needed in these conditions. The µ-opioid receptor (OPRM1) agonist, D,L-methad...

Purpose Nonsurgical management has been identified as the treatment of choice for femoral shaft fractures in children below four years of age. For various reasons, the surgical approach has become increasingly popular in recent years. The aim of this study is to report results after vertical skin traction and analyze the benefits of this technique...

Purpose Surgery of complex neuroblastic tumors often requires additional procedures, especially in the situation of tumor extension within thorax and impossibility of securing the aorta above the tumor. These situations prompt the opening of the thoracic cavity. The concern regarding increased operative trauma and morbidity associated with this app...

Background Loss of available central vein access sites for parenteral nutrition delivery represents one of the main indications for intestinal transplantation in children with intestinal failure. Placement of central venous catheters can be challenging in advanced loss of patent venous pathways. We recently described the hybrid technique (intervent...

The freshwater plant water lettuce (Pistia stratiotes L.) grows in warm climatic zones and is used for phytoremediation and biomass production. P. stratiotes belongs to the Araceae, an ecologically and structurally diverse early monocot family, but the phylogenetic relationships among Araceae members are poorly understood. Ribosomal DNAs (rDNAs), i...

Background: Gastric transposition (GT) is a possible option for esophageal replacement in long-gap esophageal atresia (LGEA). The present study aims to report and compare indications and outcome of laparoscopic-assisted GT (LAGT) versus open (OGT) GT for LGEA repair. Methods: Retrospective single-center analysis of all LGEA patients undergoing G...

Some eukaryotes exhibit dramatic genome size differences between cells of different organs, resulting from the programmed elimination of chromosomes. Aegilops speltoides is an annual diploid species from the Poaceae family, with a maximum number of eight B chromosomes (Bs) in addition to its inherent seven pairs of standard A chromosomes (As). The...

Purpose: Treating refractory or relapsed neuroblastoma remains challenging. Monitoring body fluids for tumor-derived molecular information indicating minimal residual disease supports more frequent diagnostic surveillance and may have the power to detect resistant subclones before they give rise to relapses. If actionable targets are identified fr...

Most children with tumors will require one or more surgical interventions as part of the care and treatment, including making a diagnosis, obtaining adequate venous access, performing a surgical resection for solid tumors (with staging and reconstruction), performing procedures for cancer prevention and its late effects, and managing complications...

Simple Summary The major challenge in pediatric oncology is the optimal adaptation of therapy burden to risk profile, aiming to achieve the best outcome with minimum toxicities. The CWS-2002P study in patients ≤ 21 years with localized rhabdomyosarcoma was developed with this goal by reducing or intensifying the chemotherapy depending on the risk g...

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used an European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed g...

Simple Summary Rhabdomyosarcoma is the most common soft tissue tumor in children. Its two major subtypes show epigenetic alterations that are associated with poor prognosis. Therefore, targeting these epigenetic alterations by pharmacological intervention could be a therapeutic approach. We investigated two different types of substances that interf...

Background The benefit of adjuvant therapy in synovial sarcoma (SS) treatment is under debate. Long-term follow-up data are missing. Methods SS patients treated in the consecutive trials CWS-81, CWS-86, CWS-91, CWS-96, CWS-2002-P, and the SoTiSaR-registry till 2013 were analyzed. Results Median age of 185 patients was 13.9 years (0.1–56)—with med...

Purpose Glutamine plays an important role in cell viability and growth of various tumors. For the fetal subtype of hepatoblastoma, growth inhibition through glutamine depletion was shown. We studied glutamine depletion in embryonal cell lines of hepatoblastoma carrying different mutations. Since asparagine synthetase was identified as a prognostic...

Background: Solitary dysontogenetic liver cysts are rare in young children. However, large cysts can cause symptoms and require therapy. Cyst excision is the therapeutic method least associated with cyst recurrence. Only limited data are available on cyst excision performed laparoscopically in this age group. We present our experience using this su...