Reply to Peña, A. Comment on "Küppers et al. Percutaneous Anorectoplasty (PARP)-An Adaptable, Minimal-Invasive Technique for Anorectal Malformation Repair. Children 2022, 9, 587".

Thank you so much for your thoughtful comments [...].

Percutaneous Anorectoplasty (PARP)-An Adaptable, Minimal-Invasive Technique for Anorectal Malformation Repair.

BACKGROUND: Anorectal malformations comprise a broad spectrum of disease. We developed a percutaneous anorectoplasty (PARP) technique as a minimal-invasive option for repair of amenable types of lesions. METHODS: Patients who underwent PARP at five institutions from 2008 through 2021 were retrospectively analyzed. Demographic information, details of the operative procedure, and perioperative complications and outcomes were collected. RESULTS: A total of 10 patients underwent the PARP procedure during the study interval. Patients either had low perineal malformations or no appreciable fistula. Most procedures were guided by ultrasound, fluoroscopy, or endoscopy. Median age at PARP was 3 days (range 1 to 311) days; eight patients were male. Only one intraoperative complication occurred, prompting conversion to posterior sagittal anorectoplasty. Functional outcomes in most children were highly satisfactory in terms of continence and functionality. CONCLUSIONS: The PARP technique is an excellent minimal-invasive alternative for boys born with perineal fistulae, as well as patients of both sexes without fistulae. The optimal type of guidance (ultrasound, fluoroscopy, or endoscopy) depends on the anatomy of the lesion and the presence of a colostomy at the time of repair.

Pilonidal sinus disease on the rise: a one-third incidence increase in inpatients in 13 years with substantial regional variation in Germany.

PURPOSE: Collective evidence from single-centre studies suggests an increasing incidence of pilonidal sinus disease in the last decades, but population-based data is scarce. METHODS: We analysed administrative case-based principal diagnoses of pilonidal sinus disease and its surgical therapy between 2005 and 2017 in inpatients. Changes were addressed via linear regression. RESULTS: The mean rate of inpatient episodes of pilonidal sinus disease per 100,000 men increased from 43 in 2005 to 56 in 2017. In females, the mean rate of inpatient episodes per 100,000 women rose from 14 in 2005 to 18 in 2017. In the whole population, for every case per 100,000 females, there were 3.1 cases per 100,000 males, but the numbers were highly variable between the age groups. There was considerable regional variation within Germany. Rates of inpatient episodes of pilonidal sinus disease were increasing in almost all age groups and both sexes by almost a third. Surgery was dominated by excision of pilonidal sinus without reconstructive procedures, such as flaps, whose share was around 13% of all procedures, despite recommendations of the national guidelines to prefer flap procedures. CONCLUSION: Rates of inpatient episodes of pilonidal sinus disease in Germany rose across almost all age groups and both sexes with relevant regional variation. The underlying causative factors are unknown. Thus, patient-centred research is necessary to explore them. This should also take cases into account that are solely treated office-based in order to obtain a full-spectrum view of pilonidal sinus disease incidence rates.

Circumcision and its alternatives in Germany: an analysis of nationwide hospital routine data.

BACKGROUND/PURPOSE: Circumcisions are among the most frequent operations in children. Health service data on circumcision in the United States has documented an increase in neonatal circumcisions since 2012. We investigated whether a similar effect could be found in Germany, which does not endorse neonatal circumcision. METHODS: We analysed German routine administrative data for operations conducted on the preputium in order to analyse the frequency, age distribution, and time-trends in hospital-based procedures on a nationwide basis. RESULTS: There were 9418 [95% confidence interval (CI) 8860-10,029] procedures per year, of which 4977 (95% CI 4676-5337) were circumcisions. Age distributions were highly different between both circumcisions (van der Waerden's χ² = 58.744, df = 4, P < 0.0001) and preputium-preserving operations (van der Waerden's χ² = 58.481, df = 4, P < 0.0001). Circumcisions were more frequent in the first 5 years of life and above 15 years of age, whereas preputium-preserving procedures were preferred in the age groups between 5 and 14 years of age. The number of circumcisions and preputium-preserving operations decreased in absolute and relative numbers. CONCLUSIONS: The increasing trend towards neonatal circumcision observed in the United States is absent in Germany. The majority of patients were operated after the first year of life and absolute and relative numbers of hospital-based procedures were decreasing. Other factors such as increasing use of steroids for the preferred non-operative treatment of phimosis may play a role. As operations in outpatients and office-based procedures were not covered, additional research is necessary to obtain a detailed picture of circumcision and its surgical alternatives in Germany. LEVEL OF EVIDENCE: III.

[Thoracoscopic Sympathectomy for Palmar and Axillary Hyperhidrosis]. / Thorakoskopische Sympathektomie bei palmarer und axillärer Hyperhidrosis.

OBJECTIVE: This video is a step-by-step description of thoracoscopic sympathectomy. INDICATION: Sweating is essential for thermoregulation. Hyperhidrosis is a condition of excess sweating from the eccrine glands and is associated with severe suffering for patients of all ages. It often worsens during adolescence. A generalised and focal type of hyperhidrosis which affects mainly the face, armpits, hands and feet can be distinguished from the focal variant. Thoracic sympathectomy has become the standard treatment for palmar and axillary hyperhidrosis worldwide. METHODS: The procedure is performed in the supine position with the upper body elevated about 30° in an adolescent patient. Both arms are abducted at 90° and single tube endotracheal ventilation is employed. A 3 mm trocar is placed in the anterior axillary line for a 3 mm 30° optic. A 5 mm trocar placed on the anterior axillary line (or breast fold in female patients) of the 4th or 5th intercostal space is used for the bipolar forceps. The sympathetic trunk and ganglia T 2 - 4 are identified and coagulated over the heads of ribs. CONCLUSION: The thoracoscopic approach to focal palmar and axillary hyperhidrosis allows clear identification of the sympathetic structures on each side. Under direct vision, selective ablation of the ganglia and sympathetic trunk provides long-term benefit for patients.

[Artificial intelligence in pediatric surgery : Present and future]. / Künstliche Intelligenz in der Kinderchirurgie : Gegenwart und Zukunft.

BACKGROUND: Artificial intelligence, automatization and digital transformation increasingly dominate the business models of almost all enterprises. Even in medicine and medical technology, companies also no longer close their minds to this development as the advantages provided by the new ideas and processes in medicine and particularly in compact disciplines, such as pediatric surgery have occasionally been recognized. OBJECTIVE: This article gives a status quo analysis of artificial intelligence in international pediatric surgery with a discussion of future perspectives and suggestions from the authors' perspective. MATERIAL AND METHODS: Appraisal and discussion of international publications, external expert opinions and personal experiences of the authors. RESULTS: A wide spectrum of applications using artificial intelligence in surgery is internationally available. Many of these developments can also be further adapted for use in pediatric surgery. The experience using artificial intelligence for special pediatric surgical indications is currently limited to isolated cases. CONCLUSION: Disciplines such as pediatric surgery cannot disregard the trend towards the application of artificial intelligence in daily practice. In addition to the establishment of current developments, the requirements of pediatric surgery should also be taken into account. These were some of the impulses that led to the founding of the working group on digitalization of the German Association for Pediatric Surgery in September 2019.

Central Venous Access Devices (CVAD) in Pediatric Oncology Patients-A Single-Center Retrospective Study Over More Than 9 Years.

Background: Central venous access devices (CVAD) provide important benefits in the management of oncological pediatric patients. However, these catheters are responsible for severe complications. Methods: In this context, we aimed to analyze all patients receiving a CVAD in the Department of Pediatric Hematology and Oncology of the University hospital of Mainz over a period of 9 years, focused on CVAD related complications. Data on demographics, as well as intraoperative and postoperative complications were extracted. Results: A total of 296 patients with a mean age 93.2 ± 62.4 months were analyzed. The majority suffered from leukemia (n = 91, 30.7%), lymphomas (n = 50, 16.9%), and brain tumors (n = 48, 16.2%). In 63 (21.3) patients, complications were observed. No death caused by complications of CVADs was found in our series. Catheter-related blood stream infections (BSI) (7.4%) were most prevalent, followed by dislodgements (5.4%), occlusions (2.7%), thrombosis (2.4%), and catheter leakage (2.4%). Insertion site infections were observed in three patients (1.0%). Fifty-nine percent of all patients with catheter-related BSI suffered from Leukemia. In patients with Catheter-related BSIs we detected the condition leukemia as the underlying disease as a risk factor compared to solid tumors as the underlying disease. Overall, totally implanted devices (ports) have a lower complication rate than tunneled catheter. Conclusion: Implantation of CVADs seems to be safe and reliable in this large pediatric patient cohort. Even if complications occur in the long-term management of CVADs, they can be treated successfully and long-term catheter survival rates are excellent.

Multiphoton microscopy: A novel diagnostic method for solid tumors in a prospective pediatric oncologic cohort, an experimental study.

BACKGROUND: The prognosis of solid pediatric tumors strongly correlates with accurate staging and complete local control. Currently, surgeons rely on macroscopic cues and intraoperative cryosection to determine resection borders. Multiphoton Microscopy (MPM) is a real time technique that allows imaging of tissue without time-consuming tissue processing. PURPOSE: This pilot study evaluates the diagnostic potential of MPM in pediatric solid tumors compared to routine histopathology. METHODS: Slides of pediatric tumor samples (nephroblastoma and neuroblastoma [n = 2]; ganglioneuroma, pleuropulmonary blastoma, hepatocellular carcinoma [n = 1]) were prepared to allow direct comparison of MPM with conventional light microscopy. Additionally, we applied MPM to native tumor tissue blocks to evaluate direct visualization of malignant cells through the tumor capsule. Images were interpreted by an attending surgical pathologist. Detectability of tumor-specific features was compared between MPM and conventional histology. RESULTS: A total of 7 tumors from 7 recruited patients were analyzed. All MPM images were accurate in diagnosing typical criteria of each particular neoplasm. In addition, MPM clearly visualized tumors through the capsule without sectioning or labeling procedures. The quality of MPM was sufficient to make the diagnosis and visualize typical entity-specific architectural changes. CONCLUSION: MPM is comparable to conventional histopathology in the diagnosis of pediatric solid tumors without the need for fixation or staining. It therefore has tremendous potential for future real-time intraoperative diagnostics and as an alternative to conventional frozen section histopathology. LEVEL OF EVIDENCE: III.

[Laparoscopic Resection of Urachal Cysts]. / Die laparoskopische Resektion einer Urachuszyste.

Objective This video is a step-by-step description of the laparoscopic technique for the resection of urachal cysts. Indication The urachus is an embryonic extraperitoneal structure between the urinary bladder and the umbilicus. Failure of the allantois to obliterate in utero leads to urachal anomalies such as fistulas or cysts. Because of the risk of infection and malignant degeneration later in life, urachal fistulas or cysts are usually removed by surgical excision. Method The procedure is performed in supine position with 3 mm trocars in the epigastric angle, the left upper abdomen and the left middle abdomen. During the operation, the trocar in the epigastric angle will be upsized to 5 mm in order to introduce a 5 mm polymer clip applier. We use a 5 mm 30° optic and a 3 mm monopolar hook for dissection. Conclusion This laparoscopic approach to removing urachal remnants allows for the involved structures to be clearly identified and accurately dissected. A complete resection of urachal remnants is facilitated by direct visualization of the entire anomaly down to the bladder dome.

[Laparoscopic-assisted mobilisation and resection of a sacrococcygeal teratoma Altman type III]. / Die laparoskopisch assistierte Mobilisation und Resektion eines Steißbeinteratoms Altman Typ III.

Objective This video is a step-by-step illustration of the laparoscopic-assisted mobilisation and resection of a sacrococcygeal teratoma Altman type III. Indication Laparoscopic supralevatory tumour mobilisation is an established method in selected centres and can be the initial step in approaching sacrococcygeal teratomas with an intrapelvic portion, facilitating a complete (R0) resection. Method Laparoscopic surgery is performed in supine position with a 5 mm umbilical trocar, a 5 mm trocar in the right upper abdomen, and two 3 mm trocars in the left middle and lower abdomen. We use a 5 mm 45° optic and 3 mm laparoscopic grasping forceps as well as Overholt clamps. For coagulation, a laparoscopic 5 mm diathermy Sealer (LigaSure™, Covidien, Neustadt) is used. Conclusion In selected tumours, laparoscopic assisted tumour mobilisation enables surgeons to clearly identify and ligate the primary tumour-supplying vascular structures at the beginning of the operation, thereby avoiding the risk of major bleeding throughout the subsequent tumour mobilisation. The laparoscopic approach also allows an accurate dissection and mobilisation of the supralevatory tumour parts under direct vision. After repositioning the patient into the prone position, infralevatory preparation can be carried out safely and fast in the conventional sacral approach without any major risk of bleeding.

A case report of laparoscopic duodenal atresia repair in a neonate using a novel miniature stapling device.

INTRODUCTION: Laparoscopic duodenal atresia repair is an advanced procedure performed in select pediatric surgical centers. Recently, sub-6mm endosurgical staplers have been introduced, facilitating and accelerating the creation of intracorporeal intestinal anastomoses. PRESENTATION OF CASE: We performed a laparoscopic duodenojejunostomy in a one-day-old child with duodenal atresia due to annular pancreas using a novel 5.8mm articulating endostapler with excellent outcome. The technical details are reported. DISCUSSION: Laparoscopic duodenojejunostomy is a technically demanding procedure due to difficulty in hand-sewn anastomosis in a small and restricted space. With this novel 5.8mm articulating endostapler, we were able to perform a quicker and easier anastomosis. CONCLUSION: We report a case of laparoscopic duodenal atresia repair in a neonate using a novel miniature stapling device. This new technique is a safe, quick and easier way to perform laparoscopic duodenal atresia repair.

Low expression of N-myc downstream-regulated gene 2 (NDRG2) correlates with poor prognosis in hepatoblastoma.

BACKGROUND/PURPOSE OF THE STUDY: Despite tremendous progress in therapy, about 30% of patients with hepatoblastoma still succumb to the disease. Thus, the development of improved therapies as well as the identification of prognostic factors are urgently needed. METHODS: In the present study, expression and promoter methylation of the N-myc downstream-regulated gene (NDRG2), a tumor suppressor gene contributing to the regulation of the Wnt signalling pathway, was analysed in 38 hepatoblastoma samples by real-time reverse transcription-PCR and pyrosequencing, respectively. RESULTS: The NDRG2 gene was highly expressed in normal pediatric liver tissue, but was significantly downregulated in heptoblastoma primary tumors. Detailed methylation analysis of CpG sites in the NDRG2 promoter region revealed a general high degree of DNA methylation in hepatoblastoma, which correlated with the suppression of NDRG2. By analyzing clinicopathological features we could demonstrate a strong association between low NDRG2 expression and tumor metastasis. Importantly, the overall survival analysis by Kaplan-Meier revealed that high NDRG2 expression was correlated with a higher survival rate in hepatoblastoma patients. CONCLUSION: Our data show that downregulation of NDRG2 may play an important role in advanced hepatoblastomas.

Epigallocatechin-3-gallate inhibits hepatoblastoma growth by reactivating the Wnt inhibitor SFRP1.

Activation of Wnt signaling plays a central role in the formation of hepatoblastoma (HB), the most common pediatric liver cancer. Blocking this pathway with specific inhibitors is currently the target of various research endeavours. This study provides evidence that the naturally occurring flavonoid epigallocatechin-3-gallate (EGCG) is highly effective against HB growth through inhibition of Wnt signaling. We demonstrate that EGCG has a strong cytotoxic effect on HB cells in a time- and dose-dependent manner by impinging on cell viability, while leaving normal fibroblasts unaffected. Apoptotic features, including morphological changes, caspase 3 activity, and proteolytic cleavage of poly(ADP-ribose) polymerase, were frequently found in EGCG-treated HB cells, thereby suggesting involvement of the mitochondrial intrinsic apoptotic pathway. We furthermore show that EGCG effectively inhibits Wnt signaling, as evidenced by down-regulation of Wnt-responsive reporter gene activity and expression of the Wnt target genes MYC and CCND1. Interestingly, EGCG induced reexpression of the tumor suppressor gene SFRP1, which is transcriptionally silenced in HB cells and known to down-regulate Wnt signaling. Considering the lack of toxic effects on normal cells, EGCG should be preclinically validated as an adjuvant therapy in vivo with the ultimate goal of determining its efficacy in human trials.

Rapamycin blocks hepatoblastoma growth in vitro and in vivo implicating new treatment options in high-risk patients.

Activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway plays a central role in the formation of hepatoblastoma (HB), the most common liver cancer in childhood. Blocking this pathway with specific mTOR inhibitors such as the immunosuppressant rapamycin is being currently tested for a variety of cancers. Here, we report that rapamycin treatment induced a significant dose-dependent inhibition of cell viability and promoted apoptosis in HB cells in vitro. Moreover, rapamycin inhibited AKT/mTOR signalling by dephosphorylation of the downstream target p70S6 kinase (p70S6K). Most importantly, treating subcutaneous HUH6 xenograft tumour bearing mice orally with 5mg/kg/day rapamycin for three weeks resulted in a striking reduction of tumour growth, as evidenced by reduced volume and weight, and moderately lowered tumour-specific alpha-fetoprotein (AFP) serum levels. The anti-tumourigenic effect was primarily ascribed to a significantly reduced proliferation rate upon p70S6K dephosphorylation, as microvascular density of rapamycin-treated compared to vehicle-treated tumours stayed grossly unchanged. Of uttermost clinical importance, we found no evidence for a feedback-loop activation of AKT in vivo. In conclusion, we demonstrate that rapamycin effectively inhibits HB growth both in vitro and in vivo by blocking AKT/mTOR signalling at the level of p70S6K and that rapamycin should be considered to treat HB patients especially those to be indicated for liver transplantation to benefit from its anti-tumourigenic and immunosuppressive properties.

Delayed healing of forearm shaft fractures in children after intramedullary nailing.

BACKGROUND: In displaced and unstable forearm shaft fractures, elastic stable intramedullary nailing represents the current treatment of choice. Delayed healing has been observed in single cases, but the incidence of healing disturbances remains unclear. METHODS: Retrospective analysis of all patients with forearm shaft fractures and open epiphyseal plates, treated with elastic stable intramedullary nailing between 2000 and 2004 in 5 pediatric trauma units, was conducted. Evaluation of cases with insufficient consolidation 90 days after osteosynthesis was performed. RESULTS: Ten (1.9%) of 532 cases showed delayed healing. Mean age (12.3 years), part of open fractures (30%), and part of open reductions (60%) were clearly higher than in a nonselected collective; the ulna was concerned in 70%. One refracture, 1 local soft tissue infection, and 1 small sequestration were found. In 5 children, nails were extracted with (2x) or without (3x) local surgical intervention. In the other 5 children, the nails were left in place. All fractures healed within 13 months posttrauma without relevant functional restrictions. CONCLUSIONS: Delayed healing is possible especially in open fractures or open reduced fractures of the ulna in older children, but healing takes place up to 13 months. Therefore, no change of treatment principles is necessary. Protection of ulna periost has to remain in the center of surgical focus. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.