Publications by authors named "Martin Metzelder"

50 Publications

Diagnosis and management of acute appendicitis in 21 pediatric hematology and oncology patients at a tertiary care cancer center.

Sci Rep 2021 Jun 9;11(1):12170. Epub 2021 Jun 9.

Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Kinderspitalgasse 6, 1090, Vienna, Austria.

Acute appendicitis is a rare gastrointestinal complication of anti-cancer chemotherapy and hematopoietic stem cell transplantation. Among a cohort of 2341 hemato-oncologic patients at a pediatric tertiary care cancer center, we identified 21 patients (0.9%) with 23 episodes of acute appendicitis, based on pathological imaging of the appendix and clinical findings. Median age at diagnosis was 10.21 years. Types of underlying disease included acute leukemias (n = 15), solid tumors (n = 4), and aplastic anemia (n = 2). Clinical symptoms seen in > 1 case were recorded for all 23 episodes as follows: abdominal pain, n = 22; abdominal tenderness, n = 4; fever, n = 7; nausea, n = 2; emesis; n = 2; diarrhea, n = 5; and constipation, n = 2. Median leukocyte count at diagnosis was 0.5 × 10/L, with a median of 0.1 × 10/L for the absolute neutrophil count (ANC). All patients received broad-spectrum antibiotics and 18/23 (78%) patients underwent uneventful appendectomy after a median of 5 days and with a median ANC of 0.7 × 10/L. Median duration until continuation of chemotherapy was 17 days for the 20 cases of appendicitis occurring during the patients' disease course. Overall, 5/21 (19%) patients died including one related to the appendicitis itself which progressed to a typhlitis and was due to a fungal infection. The other fatalities were transplant- (n = 2) and leukemia-related (n = 2). Acute appendicitis is a rare and usually not life-threatening event in pediatric hemato-oncologic patients, which, if managed by prompt administration of broad-spectrum antibiotics (and antimycotics), can be safely followed by an elective (delayed) appendectomy, even before complete recovery of the neutrophils is achieved.
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http://dx.doi.org/10.1038/s41598-021-90206-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190273PMC
June 2021

Characterization of the Hyperintense Bronchus Sign as a Fetal MRI Marker of Airway Obstruction.

Radiology 2021 Aug 25;300(2):423-430. Epub 2021 May 25.

From the Department of Biomedical Imaging and Image-guided Therapy (F.P., A.H., M.W., H.P., D.P., G.K.), Center for Anatomy and Cell Biology (P.C.B.), Department of Pathology (A.S.), Division of Paediatric Surgery, Department of Surgery (M.M.), and Department of Obstetrics and Gynaecology (J.B.), Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; E. B. Singleton Department of Radiology, Texas Children's Hospital, Houston, Tex (A.R.M.R., C.C.C.); and Division of Anatomy and Developmental Biology, Karl Landsteiner University of Health Sciences, Krems, Austria (G.M.G.).

Background Fetal MRI-based differential diagnosis of congenital lung malformations is difficult because of the paucity of well-described imaging markers. Purpose To characterize the hyperintense bronchus sign (HBS) in in vivo fetal MRI of congenital lung malformation cases. Materials and Methods In this retrospective two-center study, fetal MRI scans obtained in fetuses with congenital lung malformations at US (January 2002 to September 2018) were reviewed for the HBS, a tubular or branching hyperintense structure within a lung lesion on T2-weighted images. The frequency of the HBS and respective gestational ages in weeks and days were analyzed. Areas under the curve (AUCs), 95% CIs, and values of the HBS regarding airway obstruction, as found in histopathologic and postnatal CT findings as the reference standards, were calculated for different gestational ages. Results A total of 177 fetuses with congenital lung malformations (95 male fetuses) and 248 fetal MRI scans obtained at a median gestational age of 25.6 weeks (interquartile range, 8.9 weeks) were included. The HBS was found in 79% (53 of 67) of fetuses with bronchial atresia, 71% (39 of 55) with bronchopulmonary sequestration (BPS), 43% (three of seven) with hybrid lesion, 15% (six of 40) with congenital cystic adenomatoid malformation, and 13% (one of eight) with bronchogenic cyst at a median gestational age of 24.9 weeks (interquartile range, 9.7 weeks). HBS on MRI scans at any gestational age had an AUC of 0.76 (95% CI: 0.70, 0.83; = .04) for the presence of isolated or BPS-associated airway obstruction at histopathologic analysis and postnatal CT. The AUC of HBS on fetal MRI scans obtained until gestational age of 26 weeks (AUC, 0.83; 95% CI: 0.75, 0.91; < .001) was significantly higher ( = .045) than that for fetal MRI scans obtained after gestational age 26 weeks (AUC, 0.69; 95% CI: 0.57, 0.80; = .004). Conclusion The hyperintense bronchus sign is a frequently detectable feature at fetal MRI and is associated with airway obstruction particularly before gestational age 26 weeks. © RSNA, 2021 See also the editorial by Dubinsky in this issue.
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http://dx.doi.org/10.1148/radiol.2021204565DOI Listing
August 2021

Is fetal magnetic resonance imaging volumetry of eventrated organs in gastroschisis predictive for surgical treatment?

Pediatr Radiol 2021 May 5. Epub 2021 May 5.

Department of Surgery, Division of Pediatric Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Background: Fetal MRI is increasingly used in congenital abdominal wall defects. In gastroschisis, the role of fetal MRI in surgical therapy is poorly understood. Currently, the type of repair is determined primarily by clinical presentation and institutional preference.

Objective: To evaluate the feasibility of fetal MRI volumetry in gastroschisis treatment.

Materials And Methods: We included 22 cases of gastroschisis in this retrospective single-center study. Routine fetal MRI scans were acquired between Jan. 1, 2006, and July 1, 2018, at gestational ages of 19-34 postmenstrual weeks. Fetal-MRI-based manual segmentation and volumetry were performed utilizing steady-state free precision and T2-weighted sequences. Acquired parameters included intraabdominal volume, eventrated organ volume and total fetal body volume, and we calculated a volume ratio between eventrated organ volume and intraabdominal volume (E/I ratio).

Results: Primary closure was conducted in 13 cases and silo bag treatment with delayed closure in 9 cases. Prenatal MRI volumetry showed a significantly higher E/I ratio in patients with silo bag treatment with delayed closure (mean [M]=0.34; 95% confidence interval [CI] 0.30, 0.40) than in primary closure (M=0.23, 95% CI 0.19, 0.27; P=0.004). We propose a volume ratio cutoff value of 0.27 for predicting silo bag treatment.

Conclusion: Fetal MRI predicted silo bag treatment in patients with gastroschisis in 90% of the cases in our cohort and might facilitate prenatal counseling and treatment planning.
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http://dx.doi.org/10.1007/s00247-021-05066-zDOI Listing
May 2021

Cysto-Vaginoscopy of a 3D-Printed Cloaca Model: A Step toward Personalized Noninvasive Preoperative Assessment in Patients with Complex Anorectal Malformations.

Eur J Pediatr Surg 2021 Mar 23. Epub 2021 Mar 23.

Department of Pediatric Surgery, Medical University of Vienna, Vienna, Wien, Austria.

Introduction:  For the classification of the complexity of cloacal malformations and the decision on the operative approach, an exact anatomical assessment is mandatory. To benefit from using three-dimensional (3D)-printed models in preoperative planning and training, the practicability of these models should be guaranteed. The aim of this study was to evaluate the quality and feasibility of a real-size 3D-printed cloaca model for the purpose of cysto-vaginoscopic evaluation.

Materials And Methods:  We performed a 3D reconstruction and printed a real-size, rubber-like 3D model of an infant pelvis with a cloacal malformation and asked invited pediatric surgeons and pediatric urologists to perform a cysto-vaginoscopy on the model and to complete a brief questionnaire to rate the quality and feasibility of the model and to indicate whether they would recommend the model for preoperative planning and training.

Results:  Overall, 41 participants rated the model quality as good to very good (M = 3.28, standard deviation [SD] = 0.50, on a scale from 1 to 4). The model was rated as feasible for preoperative training (M = 4.10, SD = 0.75, on a scale from 1 to 5) and most participants (85.4%) would recommend the model for preoperative training. The cysto-vaginoscopy of the model was considered as a valid training tool for real-life cases and improved the confidence on the anatomy of a cloaca.

Conclusion:  The results of our study indicate that patient-specific 3D-printed models might be a useful tool in the preoperative evaluation of complex anorectal malformations by simulation of cysto-vaginoscopy with an excellent view on anatomical structures to assess the whole spectrum of the individual cloacal malformation. Our model might be a valuable add-on tool for specialty training in pediatric colorectal surgery.
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http://dx.doi.org/10.1055/s-0041-1726424DOI Listing
March 2021

Assessment of sacral ratio in patients with anorectal malformations - Can magnetic resonance imaging replace conventional radiographs?-Sacral-ratio from MRI.

J Pediatr Surg 2021 Jan 16. Epub 2021 Jan 16.

Department of Surgery, Clinical Department of Pediatric Surgery, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.

Introduction: In patients with anorectal malformations (ARM), the sacral ratio (SR) serves as an established predictive marker for functional prognosis and is derived from conventional radiographs. More recently, magnetic resonance imaging (MRI) has emerged as a diagnostic alternative for preoperative/baseline assessment of patients with ARM. With this study we aimed to evaluate if the SR could be reliable be measured from MRI images and if it correlated to SR measurements obtained from radiographs.

Methods: Two raters analyzed MRI data and conventional radiographs from thirty-one subjects (n = 17 with ARM; n = 14 controls). We calculated intra-class correlation coefficients (ICCs) to test inter-rater reliability and applied paired t-tests to examine if SR parameters from MRI were comparable with those from pelvic radiograph. We further computed Pearson's correlation coefficients to test the linear relationship between SR calculated from MRI and conventional radiographs.

Results: The ARM and control groups did not statistically differ in their age and weight on the day of the MRI scan. Reliability analysis revealed an excellent inter-rater agreement for SR from radiograph parameters with an intraclass correlation coefficient (ICC) of 0.94, respectively of 0.86 for MRI (frontal plane), and of 0.84 for MRI (sagittal plane). The correlation coefficient between SR calculated from the sagittal MRI and SR calculated from radiograph images was significant and high (r = 0.80, P < 0.001). The SRs from MRI images did not significantly differ from SRs from radiographs, but were also not statistically equivalent.

Conclusion: Our results demonstrate that the SR can be derived from MRI images with good inter-rater reliability. The SR value is marginal higher when calculated on MRI, presumably due to inclusion of cartilaginous yet unossified structures.
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http://dx.doi.org/10.1016/j.jpedsurg.2021.01.013DOI Listing
January 2021

Epidural versus general anesthesia for open pyloromyotomy in infants: A retrospective observational study.

Paediatr Anaesth 2021 Apr 29;31(4):452-460. Epub 2021 Jan 29.

Department of Anesthesia, General Intensive Care Medicine and Pain Therapy, Medical University of Vienna, Vienna, Austria.

Background: Thoracic epidural anesthesia for open infantile hypertrophic pyloric stenosis surgery is a controversial issue in the presence of little comparative data.

Aims: To compare this approach to general anesthesia for desaturation events (≤90% oxygen saturation) and absolute values of minimal oxygen saturation, minimal heart frequency, operating-room occupancy time, and durations of surgery in a retrospective study design.

Methods: Data were retrieved for patients with infantile hypertrophic pyloric stenosis managed by thoracic epidurals under sedation or general anesthesia with rapid sequence induction between 01/2007 and 12/2017. Oxygen saturation and heart rate were analyzed over eight 5-minutes intervals relative to the start of anesthesia / sedation (four-time intervals) and before discharge of the patient from the operating room (four-time intervals). Fisher's exact tests and mixed model two-way analysis of variance for repeated measures were employed for intergroup comparisons.

Results: The epidural and general anesthesia groups included 69 and 32 evaluable infants, respectively. Patients managed under epidural anesthesia had cumulatively higher minimimal mean (SD) oxygen saturation values (98.2 [2.6] % versus 96.6 [5.2] %, p < 0.001) and lower minimal mean (SD) heart rate values (127.9 [15.0] beats per minute versus 140.7 [17.2] beats per minute, p < 0.001) over time. Similarly, the frequency of desaturation events (defined as ≤90% oxygen saturation) was significantly lower for these patients during the period of 5 minutes after induction of sedation or general anesthesia (odds ratio 7.4 [2.1-25.9]; p = 0.001) and during the subsequent period of five minutes (odds ratio 6.2 [1.1-33.9]; p = 0.031). One case of prolonged respiratory weaning was observed in the general anesthesia group. The mean (SD) operating-room occupancy was 61.9 (16.6) minutes for the epidural anesthesia group versus 73.3 (22.2) minutes for the general anesthesia group (p = 0.005) as a result of shorter emergence from sedation.

Conclusions: In our series, maintaining spontaneous breathing with minimal airway manipulation in patients undergoing open repair of hypertrophic pyloric stenosis under single-shot epidural anesthesia resulted in fewer desaturation events ≤90% than general anesthesia. In addition, this approach seems to result in shorter turnover times in the operating room.
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http://dx.doi.org/10.1111/pan.14114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048494PMC
April 2021

Influence of Surgical Excision on the Survival of Patients With Stage 4 High-Risk Neuroblastoma: A Report From the HR-NBL1/SIOPEN Study.

J Clin Oncol 2020 09 8;38(25):2902-2915. Epub 2020 Jul 8.

Paediatric Haematology/Oncology, Our Lady's Children's Hospital, Crumlin, Dublin, Republic of Ireland.

Purpose: To evaluate the impact of surgeon-assessed extent of primary tumor resection on local progression and survival in patients in the International Society of Pediatric Oncology Europe Neuroblastoma Group High-Risk Neuroblastoma 1 trial.

Patients And Methods: Patients recruited between 2002 and 2015 with stage 4 disease > 1 year or stage 4/4S with amplification < 1 year who had completed induction without progression, achieved response criteria for high-dose therapy (HDT), and had no resection before induction were included. Data were collected on the extent of primary tumor excision, severe operative complications, and outcome.

Results: A total of 1,531 patients were included (median observation time, 6.1 years). Surgeon-assessed extent of resection included complete macroscopic excision (CME) in 1,172 patients (77%) and incomplete macroscopic resection (IME) in 359 (23%). Surgical mortality was 7 (0.46%) of 1,531. Severe operative complications occurred in 142 patients (9.7%), and nephrectomy was performed in 124 (8.8%). Five-year event-free survival (EFS) ± SE (0.40 ± 0.01) and overall survival (OS; 0.45 ± 0.02) were significantly higher with CME compared with IME (5-year EFS, 0.33 ± 0.03; 5-year OS, 0.37 ± 0.03; < .001 and = .004). The cumulative incidence of local progression (CILP) was significantly lower after CME (0.17 ± 0.01) compared with IME (0.30 ± 0.02; < .001). With immunotherapy, outcomes were still superior with CME versus IME (5-year EFS, 0.47 ± 0.02 0.39 ± 0.04; = .038); CILP was 0.14 ± 0.01 after CME and 0.27 ± 0.03 after IME ( < .002). A hazard ratio of 1.3 for EFS associated with IME compared with CME was observed before and after the introduction of immunotherapy ( = .030 and = .038).

Conclusion: In patients with stage 4 high-risk neuroblastoma who have responded to induction therapy, CME of the primary tumor is associated with improved survival and local control after HDT, local radiotherapy (21 Gy), and immunotherapy.
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http://dx.doi.org/10.1200/JCO.19.03117DOI Listing
September 2020

Joint Attention in a Laparoscopic Simulation-Based Training: A Pilot Study on Camera Work, Gaze Behavior, and Surgical Performance in Laparoscopic Surgery.

J Laparoendosc Adv Surg Tech A 2020 May 24;30(5):564-568. Epub 2020 Mar 24.

Division of Surgery, Clinical Department of Pediatric Surgery, Medical University of Vienna, Vienna, Austria.

Training in laparoscopic surgery seems to be an important aspect in gaining and maintaining professional competency. In experimental settings, camera navigation skills improved after simulation-based training, but the effect of camera work on the surgeon's performance is not well studied. The aim of this study was to investigate whether a fixed camera or an operated camera, as well as the experience of the camera operator has an effect on the performance of the surgeon. The study was performed on the LapSim laparoscopic training system. The task was to tie an intracorporal knot in a static surgical environment with three different camera conditions: fixed camera, camera operated by an inexperienced person (inexpert camera), and camera operated by an experienced surgeon (expert camera). The camera conditions were counterbalanced across trials. Performance variables were completion time in seconds and the extend of movements in path length and angular pathway. Gaze behavior was measured with eye-tracking glasses worn by the surgeon as well as the camera operator and was evaluated for performance-harming effects. Completion time varied across conditions, with participants performing significantly longer in the fixed camera condition than in the expert or the inexpert condition. The expert and inexpert conditions did not differ. The performance-harming effect of non-focusing on the tissue was especially visible in the fixed camera condition but disappeared in the expert camera condition. Neither the camera operators' gaze behavior nor the surgeon-camera operator fixation agreement predicted task performance. A camera operator can potentially eliminate performance-harming effects of maladaptive gaze behavior and promote optimal visual behavior of a surgeon. In our experimental task, there was no significant difference in whether the camera operator had previous training in laparoscopic surgery or not.
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http://dx.doi.org/10.1089/lap.2019.0736DOI Listing
May 2020

The Effect of Pediatric Colorectal Short-Term Medical Service Trips on Self-Reported Confidence in Patient Care in Volunteers in the Home Country.

Ann Glob Health 2020 03 12;86(1):28. Epub 2020 Mar 12.

Division of Surgery, Clinical Department of Pediatric Surgery, Medical University of Vienna, Vienna, AT.

Introduction: Short-term international medical service trips (MST) are established means to access specialized medical aid in resource-limited areas. The field of pediatric colorectal surgery is a subspecialty in pediatric surgery that mainly treats anorectal malformations (ARM) and Hirschsprung disease (HD). This study aimed to investigate the impact of MST on the donors' perception of competency concomitantly to the impact on patients in the donors' home country. We also wanted to investigate whether the donors' pre-existing experience in the field of ARM and HD affects the experience they gain during the MST, and the subjective perception in treating patients in their base country.

Methods: We created a questionnaire for the international medical staff participating in MSTs on the unique topic of pediatric colorectal diseases. The questionnaire was split into three parts: essential experience (1) in the field of colorectal surgery of the participant, the experience and impact on patient care in the home country during and after the MST in ARM (2), and in HD (3).

Results: We collected data from 20 participants (6 female, 14 male). The majority of them had prior experience with the MST program (75%) and came from institutions specialized in the treatment of pediatric colorectal disorders (80%). Participants felt that MST improved patient care in both the host country (p < 0.001) and their home country (p < 0.001). Experienced and less experienced participants did not differ in the overall MST evaluation (ps > 0.08). They reported that their competencies to treat ARM and HD improved significantly in response to the MST (ps < 0.001). Improvements in ARM and HD treatment were associated with the number of supervised HD surgeries during MST, while the other forms of participation were unrelated to the improvements.

Conclusion: The results of our questionnaire indicate that participation in MST in the specialized field of pediatric colorectal surgery helps to improve confidence in the care and treatment of affected patients in both the host and donor countries, independent of previous surgical experience.
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http://dx.doi.org/10.5334/aogh.2744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068847PMC
March 2020

Age-Dependent Presentation and Clinical Course of 1465 Patients Aged 0 to Less than 18 Years with Ovarian or Testicular Germ Cell Tumors; Data of the MAKEI 96 Protocol Revisited in the Light of Prenatal Germ Cell Biology.

Cancers (Basel) 2020 Mar 6;12(3). Epub 2020 Mar 6.

ESPED Surveillance Unit, University Düsseldorf, Coordination Center for Clinical Studies, 40225 Düsseldorf, Germany.

Objective: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT).

Methods: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival.

Results: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery.

Conclusions: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.
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http://dx.doi.org/10.3390/cancers12030611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139559PMC
March 2020

Midline Incision of a Graft in Staged Hypospadias Repair-Feasible and Durable?

Front Pediatr 2019 11;7:60. Epub 2019 Mar 11.

Department of Pediatric Surgery, Medical University Vienna, Vienna, Austria.

In severe hypospadias staged repair is commonly used and it is regarded as feasible, safe, and durable. In this article we want to describe the results of a modification of the staged repair: a midline incision of the graft during the second stage. This is a consecutive single team (2 surgeons) retrospective series. Between 2014 and 2017, 250 patients underwent hypospadias repair, among them 35 patients that had primary staged hypospadias surgery with completed first and second stage repair. 24 (68.6%) cases received a preputial skin graft and 11 (31.4%) buccal mucosa graft. Median age at first stage was 1.5 (0.5-22.1) years, mean time between first and second stage operation was 0.72 (0.4-1.76) years. Follow up rate was 100%, mean follow up period was 1.50 (0.4-3.8) years. The total complication rate was 22.9%. In buccal mucosa repair the complication rate was 36.4% and in preputial graft repair the complication rate was 16.7%, respectively. In 23 patients (65.7%) during second stage urethroplasty a midline incision was performed (8 glandular graft, 15 penile graft, 6 at level of urethral opening). Complication rate in non-incised urethroplasty was 8.3%, in incision at glandular level 37.5%, in incision at penile level 13.3% and in incision at urethral opening 16.7%, respectively. Two stage repair is the method of choice in the correction of severe hypospadias. In selected cases a midline incision of the graft is feasible and can be applied if needed. Randomized studies will be needed to evaluate the true benefit of incising the graft.
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http://dx.doi.org/10.3389/fped.2019.00060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423900PMC
March 2019

Impact of Capnoperitoneum on Renal Perfusion and Urine Production in Infant and Adolescent Pigs: Crystalloid versus Colloid Fluid Resuscitation.

Eur J Pediatr Surg 2019 Dec 16;29(6):539-544. Epub 2019 Jan 16.

Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.

Background:  Infants are likely to develop anuria during laparoscopy which is uncommon in older patients. The reason for this susceptibility remains unknown. We compared the impact of CO pneumoperitoneum on renal perfusion and urine production in piglets compared with adolescent pigs. We furthermore investigated the effects of different resuscitation strategies.

Materials And Methods:  Male piglets ( = 21) were divided into four groups: (a) infant controls ( = 5), (b) infants with crystalloid restitution ( = 6), (c) infants with colloidal restitution ( = 5), and (d) adolescents with crystalloid restitution ( = 5). Animals were ventilated, the central vessels and ureters were cannulated, and the animals were subjected to a 3-hour, 10 mm Hg CO pneumoperitoneum followed by 2-hour resuscitation. Renal perfusion was assessed by fluorescent microspheres and the rate of urine flow was measured.

Results:  Urine production significantly decreased after insufflation only in the infant crystalloid and adolescent group, but not in controls or infants treated with colloids. In the infant crystalloid group, urine production remained at levels below 20% of baseline throughout the experiment. In this group, the renal perfusion dropped significantly after the beginning of the capnoperitoneum and remained significantly reduced throughout the experiment.

Conclusion:  Our data indicates that capnoperitoneum impairs renal perfusion and urine production in infants. In moderate-pressure capnoperitoneum, this effect cannot be compensated by application of crystalloids but with colloids.
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http://dx.doi.org/10.1055/s-0038-1677486DOI Listing
December 2019

Late Presentation of a Duodenal Obstruction in a Child with Failure to Thrive and Abdominal Pain.

Klin Padiatr 2019 Jan 20;231(1):41-42. Epub 2018 Sep 20.

Department of Pediatric Surgery, Medical University Vienna, Vienna, Austria.

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http://dx.doi.org/10.1055/a-0642-1882DOI Listing
January 2019

Interleukin-6 serum levels predict surgical intervention in infants with necrotizing enterocolitis.

J Pediatr Surg 2019 Mar 23;54(3):449-454. Epub 2018 Aug 23.

Department of Pediatric Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Symptoms at suspicion of necrotizing enterocolitis (NEC) are often nonspecific and several biomarkers have been evaluated for their discriminative power to both diagnose and predict the course from NEC suspicion to complicated disease requiring surgical intervention. Thus, we aimed to assess the utility of interleukin-6 (IL-6) to predict surgical intervention in infants suffering from NEC and, furthermore, to discriminate infants with starting NEC or late-onset sepsis (LOS).

Methods: IL-6 serum levels at disease onset were retrospectively analyzed in 24 infants suffering from NEC as well as 16 neonates with LOS.

Results: IL-6 serum levels at disease onset were significantly higher in infants suffering from NEC necessitating surgical intervention in the disease course compared to infants with medical NEC (5000 [785-5000] vs. 370 [78-4716] pg/ml, p = 0.0008) as well as gram-positive LOS (5000 [785-5000] vs. 84 [12-269] pg/ml, p = 0.0001). Infants suffering from gram-negative LOS exhibited elevated IL-6 serum levels at disease onset comparable to infants with surgical NEC (5000 [1919-5000] vs. 5000 [785-5000] pg/ml, p = 1.00).

Conclusion: The proinflammatory cytokine IL-6 appears to be a promising marker to distinguish surgical NEC from medical NEC at the onset of disease but cannot discriminate between surgical NEC and gram-negative LOS.

Level Of Evidence: II.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.08.003DOI Listing
March 2019

Bladder augmentation in children: current problems and experimental strategies for reconstruction.

Wien Med Wochenschr 2019 Mar 6;169(3-4):61-70. Epub 2018 Aug 6.

General Hospital Vienna, Clinical Department of Paediatric Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Bladder augmentation is a demanding surgical procedure and exclusively offered for selected children and has only a small spectrum of indications. Paediatric bladder voiding dysfunction occurs either on a basis of neurological dysfunction caused by congenital neural tube defects or on a basis of rare congenital anatomic malformations. Neurogenic bladder dysfunction often responds well to a combination of specific drugs and/or intermittent self-catheterization. However, selected patients with spinal dysraphism and children with congenital malformations like bladder exstrophy and resulting small bladder capacity might require bladder augmentation. Ileocystoplasty is the preferred method of bladder augmentation to date. Because of the substantial long-and short-term morbidity of augmentation cystoplasty, recent studies have tried to incorporate new techniques and technologies, such as the use of biomaterials to overcome or reduce the adverse effects. In this regard, homografts and allografts have been implemented in bladder augmentation with varying results, but recent studies have shown promising data in terms of proliferation of urothelium and muscle cells by using biological silk grafts.
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http://dx.doi.org/10.1007/s10354-018-0645-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394595PMC
March 2019

EBV-positive B-cell lymphoma manifestation of the liver in an infant with RAG1 severe combined immunodeficiency disease.

Pediatr Blood Cancer 2018 Sep 1;65(9):e27258. Epub 2018 Jun 1.

Department of Pediatric Surgery, Medical University of Vienna, Vienna, Austria.

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http://dx.doi.org/10.1002/pbc.27258DOI Listing
September 2018

Using pediatric liver grafts (≤ 6 yr) for adult recipients: A considerable option?

Pediatr Transplant 2015 Dec 8;19(8):875-9. Epub 2015 Sep 8.

Department of General-Visceral and Transplant Surgery, University Hospital, University Duisburg-Essen, Essen, Germany.

In LT, the common policy is to allocate pediatric liver grafts to pediatric recipients. Pediatric organs are also offered to adults if there is no pediatric recipient. However, they are rarely accepted for adult recipients. So far, there is no information available reporting outcome of LT in adult recipients using pediatric livers from donors ≤ 6 yr. In this study, we included nine adult recipients (seven females and two males) who received grafts from children ≤ 6 yr from January 2008 to December 2013. We evaluated the graft quality, the GBWR and analyzed the recipients' perioperative course. Laboratory samples and graft perfusion were analyzed. Nine adults with a median age of 49 yr (range: 25-65) and a median weight of 60 kg (range: 48-64) underwent LT with a pediatric donor graft. Median donor age was five yr (range: 3-6). Median GBWR was 1.02 (range: 0.86-1.45). After a median follow-up of 3.9 yr (range: 11 months-6.6 yr), patient survival was 100%; graft survival was 89%. One patient needed re-transplantation on the second postoperative day due to PNF. Eight recipients were discharged from the ICU after 2-9 days with a regular graft function. Doppler scans revealed regular flow patterns at any time. Only if denied for pediatric recipients, the use of pediatric livers from donors ≤ 6 yr for adult recipients is a considerable option.
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http://dx.doi.org/10.1111/petr.12589DOI Listing
December 2015

Development of Port-Site Metastases Following Thoracoscopic Resection of a Neuroblastoma.

Pediatr Blood Cancer 2016 Jan 23;63(1):149-51. Epub 2015 Jul 23.

Department of Pediatric Hematology and Oncology, Kinderklinik III, Universitätsklinikum-Essen and the University of Duisburg-Essen, Essen, Germany.

We report a 26-month-old female who developed port-site metastases of a neuroblastoma following minimally invasive thoracoscopic interventions. After diagnosis of an intrathoracic low-risk neuroblastoma and 6 months of observation, she developed respiratory problems. She subsequently underwent total resection of a locally progressive tumor via thoracoscopy. Six months later, she developed local relapse and subcutaneous metastases within the thoracic wall. These port-site metastases were most likely iatrogenic. After excision of metastases, the residual tumor responded well to salvage chemotherapy. The patient has remained in remission for over 4 years.
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http://dx.doi.org/10.1002/pbc.25677DOI Listing
January 2016

First case studies of successful ABO-incompatible living-related liver transplantation in infants in Germany.

Eur J Pediatr Surg 2015 Feb 2;25(1):77-81. Epub 2015 Jan 2.

Department of Pediatrics, University Hospital Duisburg, Germany.

Aim: A series study mainly from Asia suggests that ABO-incompatible (ABOi) living-related liver transplantation (LRLT) for pediatric recipients is associated with excellent short- and long-term graft and patient survival. Until now, ABOi LRLT has been rarely performed in Europe. The aim of this study was to analyze the safety and early results of an ABOi LRLT in a German high-volume pediatric liver transplant center.

Methods: Six consecutive pediatric patients (four males and two females) were included in this prospective study from January, 2010 to January, 2013 with a median age of 13 months (range, 6-30 months) receiving ABOi LRLT and were matched with six patients receiving ABO-compatible LRLT in the same period. In the ABOi group, titers of IgG and IgM isoagglutinins against the donor's blood group were determined at day 14 before the transplantation and from day 1 to 14 after the transplantation, and then twice a week for another 8 weeks. The titer results were determined as the reciprocal number of the highest serum dilution that caused macroscopical reaction.

Results: The patients receiving ABOi and those receiving ABO-compatible LRLT were comparable regarding the recipient's preoperative pediatric end-stage liver disease (PELD), age, gender, and technical aspects of transplantation. The median follow-up was 2.6 years (range, 1-4.5 years). At the time of operation, the mean body weight was 7.7 kg (range, 5.7-16 kg) in ABO-compatible LRLT recipients and 8.8 kg (range, 5.5-18 kg) in ABOi LRLT recipients. In each group, the median PELD score was 28 (range, 28-35), respectively. All recipients received tacrolimus plus mycophenolate mofetil-based standard immunosuppression and four ABOi transplanted patients received intravenous immunoglobulins at days 1, 3, and 5 after liver transplantation. Patient and graft survival in this group was 83%. One female patient died within 24 hours due to fulminant gram-negative sepsis. Another patient developed acute cellular rejection at the 8th postoperative day, which responded to steroid treatment. No further complications occurred. In the ABO-compatible group, patient survival was 100% and graft survival was 83%; one patient in this group received retransplantation after 4 days. During follow-up, two patients of the ABOi group had maximum alloantibody titers of four against the donor's blood group; all other patients had titers below four.

Conclusion: ABOi LRLT seems to be safe without an escalation of immunosuppression and should be considered as an additional option to timely facilitate the transplantation.
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http://dx.doi.org/10.1055/s-0034-1387936DOI Listing
February 2015

Awake caudals and epidurals should be used more frequently in neonates and infants.

Paediatr Anaesth 2015 Jan 30;25(1):93-9. Epub 2014 Sep 30.

Department of Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria.

The current literature provides fundamental insights regarding the neurotoxic potency of various general anesthetic drugs in neonates and small infants. Therefore, considerations to minimize the use of general anesthetic drugs in this age group are required. The use of caudal and epidural anesthesia under sedation is one possibility to minimize the use of general anesthetic drugs. A large number of surgical procedures can be managed with this anesthetic concept. Training, practical hand skills, good infrastructure, a well-defined indication, and a team approach including the entire operation room staff are the major prerequisites to implement these techniques in the daily clinical practice. This review article discusses all present aspects and possible future evolutions of caudal and epidural anesthesia under sedation.
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http://dx.doi.org/10.1111/pan.12543DOI Listing
January 2015

Spectrum of pathogens in native liver, bile, and blood during pediatric liver transplantation.

Pediatr Transplant 2014 May 5;18(3):266-71. Epub 2014 Mar 5.

Division of Paediatric Surgery, Department of General-Visceral and Transplant Surgery, University Hospital, University Duisburg-Essen, Essen, Germany.

During LTX, there may be a risk that pathogens of the native liver are released into the systemic circulation. No investigations on incidence/spectrum of pathogens in native livers have been published. We hypothesized that pathogens are found in the native liver of a large proportion of pediatric patients during LTX and investigated the microbiology of native livers. These data may help optimize antibiotic therapy. Twenty-two consecutive pediatric patients (median age 14 months, range, 5 months-15 yr) receiving LTX in our department from October 2010 to October 2011 were included in this prospective study. Tissue and bile were collected from the explanted liver and were cultivated on different media. All liver tissues were investigated using a broad-range PCR (SepsiTest(®)). In 16 patients, blood cultures were collected post-transplantation. Eleven patients (50%) had at least one pathogen detected; nine of these patients had an underlying diagnosis of biliary atresia. SepsiTest(®) was positive in seven patients. In four patients it was the only test detecting any pathogen. In detail, the positivity rate for liver tissue in all patients was 41% (n = 9); for bile 25% (n = 3); and for blood 25% (n = 4). Thirteen different pathogens (69% bacterial, 31% fungal) were isolated. A highly-sensitive broad-range PCR appears to be an effective method to detect pathogens in native livers of patients undergoing LTX. A high number and variety of microbes, including a high proportion of fungal pathogens, were detected.
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http://dx.doi.org/10.1111/petr.12237DOI Listing
May 2014

Laparoscopic button cholecystostomy for progressive familial intrahepatic cholestasis in two children.

Eur J Pediatr Surg 2014 Oct 10;24(5):433-6. Epub 2013 Dec 10.

Division of Pediatric Surgery, Department of General, Visceral and Transplant Surgery, University Hospital, University Duisburg-Essen, Essen, Germany.

Background: Untreated, progressive familial intrahepatic cholestasis (PFIC) results in fibrosis, cirrhosis, and liver failure. It has been shown that partial external biliary diversion (PEBD) may prevent from liver transplantation in patients without cirrhosis. The aim of this study is to present a new laparoscopic technique using a button instead of a bowel conduit for PEBD.

Patients And Methods: Two boys with PFIC (patient 1, 17 months; patient 2, 12 years) underwent laparoscopic button cholecystostomy using a 3-trocar technique by insertion of a 14 French MIC KEY button (Kimberly-Clark Worldwide, Inc, Draper, Utah, United States) at the gallbladder fundus secured with two absorbable purse-string sutures. Beside the suitability of the procedure, end points included course of serum bile acids, total bilirubin, liver enzymes, and pruritus at a follow-up of 6 months.

Results: No complications related to the operation occurred. Relieve of pruritus was achieved in both the children, due to adequate bile drainage during a follow-up period of 6 months. In patient 2, a 10-mm gallstone was removed simultaneously. In patient 1, serum bile acids decreased from 12.3 to 6.6 µmol/L and in patient 2, serum bile acids decreased from 106.3 to 2.9 µmol/L. Total bilirubin, aspartate amino transferase, alanine amino transferase, and gamma-glutamyltransferase are kept in normal ranges during follow-up. Patient's and parent's acceptance with the button was excellent.

Conclusion: Laparoscopic button cholecystostomy is a simple, safe, and sufficient technique for PEBD in patients with PFIC. It achieves an adequate bile flow with consecutive relief of pruritus and avoids an enteric anastomosis.
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http://dx.doi.org/10.1055/s-0033-1360457DOI Listing
October 2014

Implementation of fast-track pediatric surgery in a German nonacademic institution without previous fast-track experience.

Eur J Pediatr Surg 2014 Oct 5;24(5):419-25. Epub 2013 Sep 5.

Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.

Fast-track concepts in pediatric surgery were established in a university hospital in consecutive studies within several years. They significantly reduced the length of hospitalization compared with German institutions without fast-track protocols. The aim of this study was to assess the implementation process of fast-track in a German nonacademic department of pediatric surgery without previous fast-track experience. All patients undergoing four types of operations (appendectomy, hypospadias repair, pyloromyotomy, and fundoplication) from February 2011 to January 2012 were included in this prospective study. Fast-track included detailed clinical pathways and specific pain treatment protocols using validated pain scales according to age. Mobilization and oral nutrition were started 2 hours postoperatively and documented with established scores. The length of hospital stay was compared with data from other hospitals with conventional treatment using information from the German reimbursement system (German diagnosis-related groups [G-DRG]) and with the hospital stay of patients from the corresponding university hospital undergoing fast-track treatment for the same procedures during the same study period. Two weeks after discharge, a questionnaire was completed by the patients/parents. A total of 143 patients with a mean age of 7.9 ± 5.0 years underwent fast-track treatment. The mean pain intensity during the immediate postoperative period was 1.7 ± 2.1 in patients < 4 years and 2.3 ± 2.1 in patients ≥ 4 years on a 10-point scale. Full mobilization was reached after a mean duration of 2.3 ± 2.0 days while full oral nutrition was completed after a mean duration of 1.8 ± 1.4 days. There were no complications associated with fast-track. The mean hospital stay was 5.8 ± 3.4 days which was not significantly different compared with G-DRG data from other hospitals without fast-track. This was in contrast to the mean hospital stay of patients from the corresponding university hospital (5.6 ± 3.0 days vs. G-DRG 6.9 ± 3.2 days, p < 0.05). After 2 weeks, patients/parents were highly satisfied with fast-track (mean score of 8.6 ± 1.4 on a 1-10-point scale) and 95.2% claimed that they would choose it again. Fast-track concepts can be applied in a nonacademic department of pediatric surgery without previous fast-track experience and with excellent patient/parent satisfaction. However, the G-DRG system interferes with concepts of early discharge of patients. Modifications of the reimbursement modalities within the German health care system seem to be mandatory.
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http://dx.doi.org/10.1055/s-0033-1352528DOI Listing
October 2014

Current status of laparoscopic appendectomy in children: a nation wide survey in Germany.

Eur J Pediatr Surg 2013 Jun 26;23(3):226-33. Epub 2013 Feb 26.

German Society for Pediatric Surgery, DGKCH, Task-force Minimally-Invasive Surgery, MIC-AG, Berlin, Germany.

Introduction: Management of appendicitis in children has changed remarkably over the last decade. The proven benefits of laparoscopic appendectomy (LA) over the open operation have made LA increasingly popular for pediatric patients. To date, no national clinical practice guideline is available for pediatric LA in Germany and the operation is not standardized. Thus, the aim of our study was to evaluate the current status of pediatric LA in Germany.

Materials And Methods: An internet-based survey was conducted on pediatric LA among all 98 registered pediatric surgical units in Germany, comprising 22 questions with regard to utilization and subjective appraisal of LA, technical standards, perioperative treatment, and training aspects.

Results: The survey was completed by 71 of the 98 units (72%). Technical infrastructure for LA was provided in all units, but only in 79% of the units was LA, the standard approach for appendectomy. Overall quality of LA was rated better compared with open appendectomy by 52% units, equivalent by 38% and worse by 3%. The three-port technique was used by 90% of the units; 10% used a single-port approach. Dissection of the mesoappendix was done with bipolar coagulation in 55%, monopolar coagulation in 24%, harmonic knife in 6%, and endostaplers in 11% of the units. Closure of the appendiceal stump was performed using endoloops in 57%, ligations in 3%, endostaplers in 39%, and harmonic knife in 1%. Removal of the appendix was done through the port by 79%, using a retrieval bag by 18%, whereas in 3% it was removed directly through laparotomy. In case of appendiceal perforation, an intra-abdominal drain was placed in 65%. Perioperative antibiotic treatment for nonperforated appendicitis was given as a single shot in 33% of the units, for 24 hours in 17%, for 3 days in 39%, and for 5 to 7 days in 11%. LA was performed by a trainee under supervision in 87%, by a board approved pediatric surgeon in 2%, by an attending pediatric surgeon in 7%, and by the surgeon-in-chief in 4% of the units. For 93% of the sample, LA was an essential part of pediatric surgical training.

Conclusion: LA is the favored surgical method for pediatric appendectomy in Germany. However, technical details, perioperative therapy and implementation into training programs remain inconsistent. An effort has to be made to establish national clinical practice guidelines to achieve standardization of LA.
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http://dx.doi.org/10.1055/s-0032-1333121DOI Listing
June 2013

General practitioners assessment highlights excellent patient satisfaction following bar removal after Nuss procedure in children and adolescents.

Eur J Pediatr Surg 2012 Jun 8;22(3):222-7. Epub 2012 May 8.

Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.

Background: We recently demonstrated that minimally invasive repair of pectus excavatum (MIRPE) achieves a lasting patient satisfaction after bar removal. This correlated with parent ratings. It has been postulated that patient ratings may be biased by high preoperative patient expectations. The aim of this study was to compare patient self-assessment with general practitioners (GPs) assessment.

Methods: Of the 39 patients who underwent bar removal after MIRPE between 2002 and 2006, 39 GPs were asked to answer a modified version of a former single-step questionnaire to evaluate their opinion on psychosocial and physical well-being of their patients. The subjective patient ratings were compared with the GP ratings.

Results: Of the 39 GPs, 22 (56%) completed a questionnaire and assessed the outcome of the Nuss procedure. There was a highly significant correlation between GP and patient ratings (p<0.001; correlation coefficient=0.437). Mean total scores obtained from GPs were similar to patient scores (63.4±2.6 SEM vs. 67.5±2.4 SEM; not significant [NS]). Detailed analysis revealed that GPs scored several items differently to their patients: GPs scored social activity (p<0.05) and preoperative self-esteem (p<0.05) significantly lower, but pain episodes (p<0.05) and impairment of daily activities (p<0.05) during the period with the implanted bar significantly higher than their patients. Comparison of the 17 nonassessed cases, with the self-assessment of 22 patients with GP assessment, revealed no significant difference, making an analytical bias unlikely (67.5±2.4 SEM vs. 67.3±2.8 SEM; NS).

Conclusion: GPs found a higher impairment of patient well-being during the period with an implanted bar, which might be related to the high patient motivation to cope with bar impairment. However, the all over GP and patient satisfaction was similar and excellent.
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http://dx.doi.org/10.1055/s-0032-1308703DOI Listing
June 2012

Normalization of serum bile acids after partial external biliary diversion indicates an excellent long-term outcome in children with progressive familial intrahepatic cholestasis.

J Pediatr Surg 2012 Mar;47(3):501-5

Department of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany.

Background/purpose: The surgical treatment for patients with progressive familial intrahepatic cholestasis (PFIC) is either liver transplantation (LTX) or partial external biliary diversion (PEBD). Both procedures achieve a good short-term outcome. However, the treatment strategy for these children remains controversial because the long-term outcome after PEBD is unknown. The aim of our study was to assess the long-term outcome and complications after PEBD in our institution.

Methods: We retrospectively analyzed the characteristics of all patients with PFIC undergoing PEBD in our department from 1994 to 2008. The course of serum bile acids, pruritus, and liver enzymes was assessed in a regular follow-up.

Results: Twenty-four patients underwent PEBD. Thirteen patients (54%) improved significantly, with a normalization of serum bile acids (P < .001 vs postoperatively) and lessened pruritus (P < .05 vs preoperatively) at 12 months after PEBD. None of these patients showed progression of cholestasis during a median follow-up of 9.8 years (range, 1.6-14.3 years). Partial external biliary diversion failed to normalize bile acids in 11 patients, of whom 9 required secondary LTX at a 1-year follow-up, with a median interval of 1.9 years (range, 0.5-3.8 years). All 7 patients (100%) with liver cirrhosis at the time of PEBD and 2 of 17 patients without cirrhosis (12%) required secondary LTX (P < .001).

Conclusions: Clinical improvement with normalization of serum bile acids within 1 year was associated with an excellent long-term outcome in patients with PEBD. The presence of liver cirrhosis at the time of PEBD indicated an unfavorable outcome. Thus, we recommend primary LTX only in PFIC patients with liver cirrhosis.
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http://dx.doi.org/10.1016/j.jpedsurg.2011.08.010DOI Listing
March 2012

Thoracoscopic resection of congenital pulmonary malformations in infants: is the feasibility related to the size of the lesion?

World J Pediatr 2012 Aug 27;8(3):272-4. Epub 2011 Aug 27.

Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.

Background: The size of congenital pulmonary malformation (CPM) in infants might interfere with the feasibility of thoracoscopic resection. This study was undertaken to evaluate the impact of the size of CPM on the applicability of video-assisted thoracic surgery (VATS) in infants.

Methods: Twenty-two infants were operated on for CPM from November 2000 to June 2009. The intra- and postoperative course was analyzed retrospectively from patient charts. Preoperative scans were evaluated blindly by a radiologist to calculate the relation between the maximum size of the lesion and the thoracic diameter in VATS and open procedures.

Results: VATS was performed in 14 (64%) of the 22 patients and thoracotomy in 8. VATS was successfully performed in 11 (79%) of the 14 patients, whereas VATS was converted to thoracotomy due to lack of overview in 3 (21%). The mean relative size of CPM at preoperative imaging was 0.34 ± 0.05 (range: 0.3-0.4) in patients who received successful VATS, 0.57 ± 0.06 (range: 0.5-0.6) in converted cases, and 0.68 ± 0.10 (range: 0.5-0.8) in infants who underwent thoracotomy. The relative CPM size was significantly lower in successful VATS than in cases of conversion (P<0.01) and thoracotomy (P<0.01).

Conclusions: The relative size of CPM at preoperative imaging might be useful information for a decision-making on the use of VATS in infants. A relative CPM size below 0.5, which is less than half of the thoracic diameter, indicates a good feasibility for thoracoscopic resection of CPM. A larger size may indicate that VATS might be technically difficult.
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http://dx.doi.org/10.1007/s12519-011-0283-7DOI Listing
August 2012

The role of laparoscopic techniques in children with suspected post-transplantation lymphoproliferative disorders.

J Laparoendosc Adv Surg Tech A 2011 Oct 2;21(8):767-70. Epub 2011 Feb 2.

Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.

Aim: To assess the role of minimally invasive surgery (MIS) to diagnose post-transplantation lymphoproliferative disorder (PTLD) in pediatric patients.

Methods: Thirty-four patients (20 male, 14 female) underwent organ transplantation (14 liver, 14 kidney, 3 heart, 2 lung, 1 heart-lung) from May 1992 to November 2008 (mean age at transplantation, 66 months; range, 5-277), in whom a biopsy was performed for suspected PTLD from May 1993 to September 2009. The time point of onset, type of PTLD, rate of intraabdominal manifestations with need of MIS, and its accuracy were assessed.

Results: Twenty-four of 34 patients (70%) had biopsies of superficial lymph nodes (9), oropharyngeal biopsy (5), gastrointestinal endoscopy or bronchoscopy (5), ultrasound-guided biopsies (3), biopsy of the bone marrow (1), or of the orbita (1). Data of the technique used were unavailable in 3 (9%). Due to lack of superficially located lesions, 6 of 34 patients (18%) had laparoscopic biopsy, of which 4 had abdominal organ graft. Laparoscopic biopsy was successful in 5 of 6 cases (83%). Abscess formation at area of transplanted kidney led to conversion in 1. Tumor extension to the abdominal wall led to a primary biopsy via a mini-laparotomy in another case. One patient with abdominal Burkitt's lymphoma developed a trocar metastasis, successfully treated by systemic chemotherapy. No other complications were observed after MIS. Accuracy of MIS biopsies was 100%. The onset of PTLD was significantly later diagnosed in cases of explicit intraabdominal PTLD (81 ± 6.3 versus 28 ± 5.3 months; P < .001). Morbidity and mortality were not influenced by biopsy technique or time point of PTLD onset.

Conclusions: In 20% of pediatric PTLD cases an intraabdominal biopsy is required due to explicit intraabdominal manifestation. As laparoscopic surgery was even feasible in patients after prior abdominal organ transplantation, we suggest laparoscopic biopsy as a safe tool for diagnosing PTLD.
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http://dx.doi.org/10.1089/lap.2010.0175DOI Listing
October 2011

Pain reduction in children during port-à-cath catheter puncture using local anaesthesia with EMLA™.

Eur J Pediatr 2010 Dec 10;169(12):1465-9. Epub 2010 Jul 10.

Department of Paediatric Haematology and Oncology, Medical University, Hannover, Germany.

Introduction: Alleviating pain is of high importance for children undergoing chemotherapy. Eutectic mixture of lidocain-prilocain cream (EMLA) is assumed to require 60 min application time.

Materials And Methods: We prospectively compared the pain during port-à-cath punctures after 40 min compared to 60 min of application time. A prospective, unblinded, cross-over study was performed. The children received two punctures during their chemotherapy protocol. Patients in group 1 had the first puncture after 40 min EMLA application time. Their second puncture (approximately a week later) was done after 60 min. Patients in group 2 started after 40 min. Pain was scored using the visual analogue scale (VAS) and the Bieri scale. Patients, parents and a nurse scaled the pain after the intervention. Eighty-seven children between 2 and 18 years with different malignant diseases were included.

Results And Discussion: On the VAS pain scale, the mean pain was 2.3 (minimum 0, maximum 9.2) after 40 min and 1.9 (minimum 0, maximum 9.4) after 60 min according to the observations of the nurse and very similarly according to the parents' observations. The children expressed more pain after 40 min of EMLA application time (mean pain, 3.5) and a significant pain reduction after 60 min application time (mean pain 1.7).

Conclusion: In this study children experienced less pain after 60 min application time, but pain reduction was already seen after 40 min. The child's perception of pain differed from observers' point of view and should therefore always be included in pain management.
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http://dx.doi.org/10.1007/s00431-010-1244-1DOI Listing
December 2010

Carbon dioxide modifies the morphology and function of mesothelial cells and facilitates transepithelial neuroblastoma cell migration.

Pediatr Surg Int 2010 Jan;26(1):29-36

Department of Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany.

Background: The response of mesothelial cells to surgical trauma and bacterial contamination is poorly defined. We have recently shown that CO(2) pneumoperitoneum increases systemic metastasis of neuroblastoma cells in a murine model. Thus, we hypothesized that CO(2) alters the morphology and function of mesothelial cells and facilitates transmesothelial tumor cell migration.

Materials And Methods: Murine mesothelial cells were exposed to 100% CO(2) and 5% CO(2) as control. Scanning electron microscopy (SEM) investigations, as well as LPS-induced granulocyte-colony stimulating factor (G-CSF) production and mitochondrial activity (MTT assay) were measured. Transmesothelial migration of neuroblastoma cells (Neuro2a) was determined using a transwell chamber system.

Results: CO(2) incubation was associated with a significant destruction of the microvillar formation in SEM. Migration studies showed that the barrier function of the mesothelial monolayer decreased. A significantly increased migration of neuroblastoma cells was identified after 100% CO(2) exposure (P < 0.05). Although the conversion of MTT as an indicator of mitochondrial activity was only slightly and not significantly reduced after CO(2) incubation, the release of G-CSF induced by LPS was completely blocked during the incubation with 100% CO(2) (P < 0.05). The capacity of G-CSF release recovered after the incubation.

Conclusion: We observed that peritoneal mesothelial cells lose their typical cell morphology by CO(2) incubation, which is accompanied by facilitated migration of neuroblastoma cells. Moreover, the synthesis of immunological factors is blocked, but this effect is not long lasting. These mechanisms may explain an increased metastasis rate of neuroblastoma cells after CO(2) pneumoperitoneum, which was recently observed in a murine model.
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http://dx.doi.org/10.1007/s00383-009-2503-yDOI Listing
January 2010
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