Transumbilical laparoscopic-assisted appendectomy in children and adolescents: what have we learnt in more than 1200 cases?

PURPOSE: TULAA combines the laparoscopic and open technique and is considered to be a safe, fast and cost-effective procedure. On the other hand, preparation is limited due to the single instrument, especially in complicated appendicitis. In this study we analyze the outcome of our TULAA patients, focusing on conversion and complication rates. METHODS: We performed a retrospective study including all patients treated with TULAA in our department between 2006 and 2016. We analyzed patient data, operative data, costs, complications, and conversion rate to standard laparoscopic or open appendectomy. RESULTS: 1275 children and adolescents were enrolled. Mean age was 10.2 years. TULAA was completed in 88% of cases. The overall mean operative time was 33 min. The overall complication rate was 5.7%. The most common complications were wound infection (2.7%), seroma (1.7%) and wound abscess (1.4%). Both the conversion rate and the complication rate were significantly higher in complicated appendicitis. Furthermore, the conversion rate is higher in overweight or obese patients. CONCLUSION: TULAA is a safe, quick and cost-effective treatment option for acute appendicitis in children and adolescents. The complication rate and conversion rate are significantly correlated with the degree of appendiceal inflammation and comparable other surgical procedures.

Cadaveric analysis of surgical techniques and working space for retroperitoneal tumors as model for improving resection of neuroblastoma.

PURPOSE: Neuroblastoma, the most common extracranial solid tumor in children under 5 years, often surrounds visceral arteries. This study aimed to analyze the working space provided by standardized surgical techniques at key arterial landmarks in adult cadavers. METHODS: We assessed in eight adult cadavers the mobilization of the left colon, spleen and pancreas, right colon, duodenum and mesenteric root, access to the bursa omentalis. The average working space score (AWSS) was evaluated at the left and right renal artery, left and right side of the coeliac trunk, superior mesenteric and common hepatic artery. The score was defined as: (0) vessel not visible, (1) working space at the vessel ≤ 1x diameter of the aorta, (2) < 3x the diameter of the aorta, (3) ≥ 3x diameter of the aorta. RESULTS: The maximum AWSS of 3 was achieved at key vascular landmarks through specific mobilization techniques. CONCLUSION: Additional mobilization of spleen, pancreas and mesenteric root and access to the bursa omentalis increase surgical working space at major visceral arteries. The results of our investigation provide surgeons with a useful guide to prepare for abdominal neuroblastoma resection.

Increasing the efficiency of hyperthermic intraperitoneal chemotherapy (HIPEC) by combination with a photosensitive drug in pediatric rhabdomyosarcoma in an animal model.

BACKGROUND: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. An enhancement of HIPEC using photodynamic therapy (PDT) might be beneficial. Therefore, a combination of the photosensitizer hypericin (HYP) with HIPEC was evaluated in an animal model. PROCEDURE: An established HIPEC animal model for rhabdomyosarcoma (NOD/LtSz-scid IL2Rγnullmice, n = 80) was used. All groups received HYP (100 µg/200 µl) intraperitoneally with and without cisplatin-based (30 or 60 mg/m2 ) HIPEC (37°C or 42°C, for 60 minutes) (five groups, each n = 16). Peritoneal cancer index (PCI) was documented visually and by HYP-based photodynamic diagnosis (PDD). HYP-based PDT of the tumor was performed. Tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (TUNEL). RESULTS: HYP uptake was detected even in smallest tumor nodes (<1 mm) with improved tumor detection during PDD (PCI with PDD vs. PCI without PDD: 8.5 vs. 7, p < .001***). Apoptotic effects after PDT without HIPEC were limited to the tumor surface, whereas PDT after HIPEC (60 mg/m2 , 42°C) showed additional reduction of tumor proliferation in the top nine to 11 cell layers (50 µm). CONCLUSION: HYP as fluorescent photosensitizer offers an intraoperative diagnostic advantage detecting intraperitoneal tumor dissemination. The combination of HYP and cisplatin-based HIPEC was feasible in vivo, showing enhanced effects on tumor proliferation and apoptosis induction across the tumor surface. Further studies combining HYP and HIPEC will follow to establish a clinical application.

Establishment of a new valid animal model for the evaluation of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric rhabdomyosarcoma.

BACKGROUND: Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy has been established as a novel treatment approach for peritoneal sarcomatosis. Despite promising clinical reports, there is still a lack of knowledge regarding optimal drug usage and local effects. Therefore, we intended to establish a murine animal model for further evaluation. PROCEDURE: Alveolar rhabdomyosarcoma cells were xenotransplanted into NOD/LtSz-scid IL2Rγnullmice (n = 100). The mice received a continuous intraperitoneal lavage with isotonic saline solution as control or with cisplatin (30 or 60 mg/m2 ) as treatment group for 60 minutes at 37°C or 42°C (6 subgroups, each n = 16). Tumor spread was documented by an adapted peritoneal cancer index and MRI (n = 4). Tumor and tissue samples, harvested at the end of the perfusion, were evaluated regarding morphology, proliferation, and apoptosis (H&E-, Ki-67-, cleaved caspase 3-staining, TUNEL assay). RESULTS: Extensive peritoneal sarcomatosis in over 91% of the cases was observed. HIPEC was feasible without acute side effects. Ki-67 staining revealed concentration- or temperature-dependent effects of cisplatin-based HIPEC on the tumors. Although cleaved caspase-3 showed only sporadic apoptotic effects. TUNEL assay detected concentration- or temperature-dependent apoptotic effects at the outer tumor surface. MRI scans confirmed the observed tumor dissemination. CONCLUSION: This is the first animal model for evaluation of HIPEC in pediatric RMS in mice. Cisplatin-based HIPEC had early effects on the proliferation whereas circumscribed apoptotic effects could be detected at the tumor surface. This model allows further insights on the possible efficiency of HIPEC in RMS. Further studies using other drug combinations and treatment will follow.

Prenatal Diagnosis of Fetus in Fetu pregnancy.

Fetus in fetus (FIF) represents an abnormal embryogenesis in monozygotic diamniotic twin gestation. It has been described in less than 200 cases worldwide. Differential diagnosis predominantly includes teratomas. The case presented here meets the accepted criteria of FIF and is one of the few prenatally diagnosed cases with FIF.

Hypericin and its radio iodinated derivatives - A novel combined approach for the treatment of pediatric alveolar rhabdomyosarcoma cells in vitro.

BACKGROUND: Alveolar rhabdomyosarcoma (RMA) is a highly malignant soft tissue tumor in children with poor prognosis and failure of established therapies in advanced stages. Therefore, novel treatment options are required. Photodynamic therapy (PDT) has been found useful for the treatment of different tumor entities and might represent such a novel treatment option. A major limitation of PDT remains the restriction to superficial tumor cell layers as illumination with light is essential for the generation of reactive oxygen species. Current research focusses on the development of modified Hypericin (HYP)-based photosensitizers, as well as combining PDT and targeted internal radiotherapy with 131I, to generate an additive anti-tumor effect. METHODS: A standardized protocol for in vitro Hypericin-PDT was established in RMA cells. The anti-tumor properties of this photosensitizer were analyzed on molecular and metabolic levels. Changes in cell morphology were visualized using bright field-, fluorescence- and scanning-electron microscopy. Iodinated Hypericin derivatives with both radioactive and non-radioactive isotopes 131I/127I were employed to establish a targeted radionuclide therapy and investigate the potential of a combined treatment with PDT. RESULTS: In vitro photodynamic treatment with Hypericin showed a strong anti-tumor efficiency with favorable cellular uptake and compromised cancer cells on metabolic and molecular levels. Iodination of the photosensitizer did not impair the photosensitizer´s properties. Targeted radiotherapy with 131I-HYP led to distinct reductions of tumor viability. A simultaneously performed PDT leads to a reduction of cell viability that begins earlier in time. However, an additive enhancement of the cell viability was not observed in the selected dose range. CONCLUSION: In this in vitro study, we got a first insight of a possible potential of Hypericin for the treatment of pediatric soft tissue sarcoma. By coupling with radioiodine, we developed a novel approach for a combined anti-tumor treatment. The in vitro experiments lay the foundation for further in vivo experiments, which are needed to study the effects of a sequential administration of 131I-HYP and HYP.

The Cologne pouch procedure for continent anal urinary diversion in children with bladder exstrophy-epispadias complex.

INTRODUCTION: In children who remain incontinent after reconstruction of bladder exstrophy-epispadias complex (BEEC), continent anal urinary diversion (CAD) is one option to achieve continence. Known problems after CAD are an increased stool frequency and ureterointestinal stenosis. We devised a new surgical technique of CAD that we named the "Cologne pouch procedure" (CPP) that renders the possibility of separate evacuation of urine and feces. Furthermore, we connect the bladder plate to the rectosigmoid pouch instead of performing a ureterosigmoidostomy to reduce the rate of ureterointestinal stenosis. In this study, we want to introduce the CCP and critically evaluate our results. STUDY DESIGN: In CPP a detubularized sigmoid-bladder pouch is created, which is naturally connected to the rectum. A retrospective study was performed including all patients with BEEC and CPP treated in our hospital between January 1, 2007, and December 31, 2016. Epidemiological and surgical key data, complications, and the need for alkaline supplementation were assessed. At follow-up examinations, we evaluated continence, ability of independent urine and feces evacuation, need for bicarbonate supplementation, status of the upper urinary tract, and complications such as urinary tract infections or urolithiasis. RESULTS: In total, 29 patients with BEEC and CPP were included. The mean age at surgery was 4.2 ± 3.3 years (range 0.1-12.7 years). Overall, 14 short-term complications occurred in nine patients. Postoperatively, all patients were continent for urine and feces during daytime and only one child occasionally lost small portions of urine at night. An independent evacuation of urine and feces was accomplished in 22 patients (81.5%). Continued bicarbonate supplementation was necessary in 15 patients (55.6%). During the follow-up period six patients (22.2%) had a single urinary tract infection and four patients (14.8%) calculi of the urinary tract. No urinary tract abnormalities-especially no vesicoureteral reflux (VUR) or stenosis-were detected during follow-up ultrasound examination. In two children, a preoperatively known hydronephrosis decreased after CPP. CONCLUSION: CPP is a novel technique that yields excellent results concerning continence. In contrast to other forms of rectosigmoid urinary diversion, functional separation of defecation and urination can be achieved in most patients.