Steven W. Warmann

Interventional treatment of infantile hepatic hemangioendothelioma

BACKGROUND/PURPOSE Hemangioendothelioma is the most frequent liver tumor in infancy. Untreated symptomatic patients with heart failure have a high mortality rate. Symptomatic forms may request nonoperative treatment, because surgery is burdened with high risks in patients with heart failure. The authors report their experience with interventional coil occlusion of infantile hepatic hemangioendothelioma (IHE). METHODS Four patients (age range, 2 to 146 days; mean, 53 days) suffering from IHE associated with heart failure were treated by endovascular coil occlusion of arterial feeders. Catheter intervention was performed via an arterial (n = 2) or venous (n = 2) approach. RESULTS Signs of heart failure resolved within 2 to 8 days after occlusion in 3 patients. Tumor regression could be observed sonographically within 4 weeks postinterventionally. In 3 children, tumor size was reduced from a mean of 544 mL (65 to 1,350) to a mean of 4 mL (2 to 6); Mean systolic peak velocity in the hepatic artery was decreased from 170 cm/s (140 to 200) before occlusion to 45 cm/s (36 to 70) during follow-up. In the fourth patient, endovascular intervention could not control a rapidly progressing hemangioendotheliomatosis, and finally a liver transplantation had to be performed. CONCLUSIONS Interventional occlusion of feeding arteries in symptomatic IHE is a safe and effective alternative to early open surgery. The efficacy of endovascular intervention in multifocal tumors seems questionable.

Pancreatoblastoma: A report from the European cooperative study group for paediatric rare tumours (EXPeRT)

BACKGROUND Pancreatoblastoma is a very rare malignant tumour typically occurring in the early years of life. Due to its rarity, standardised diagnostic and therapeutic guidelines are not available for pancreatoblastoma. METHODS The newborn cooperative group denominated EXPeRT - European cooperative study group for paediatric rare tumours - combined in a joint analysis of all cases registered between 2000 and 2009 by the national groups of Italy, France, United Kingdom, Poland and Germany. RESULTS Twenty patients <18years old (median age 4years) were analysed: nine had distant metastases at diagnosis. Seventeen patients had tumour resection, at initial or delayed surgery. Eighteen received chemotherapy (response rate 73%), seven received radiotherapy. For the whole series, 5-year event-free survival and overall survival were 58.8% and 79.4%, respectively. Outcome did not correlate with tumour site and size, but was strongly influenced by the feasibility of tumour complete resection. CONCLUSIONS This international study confirms the rarity of the disease, the critical role of surgical resection both as therapy and as a prognostic variable, and the potential efficacy of chemotherapy. The adoption of an intensive multidisciplinary approach is required, as well as the referral to highly experienced centres. Further international cooperation is needed to collect larger series and stimulate biological studies to improve our understanding of the biology and the natural history of PBL.

Laparoscopic Surgery on Upper Urinary Tract in Children Younger Than 1 Year: Technical Aspects and Functional Outcome

PURPOSE Minimally invasive procedures are increasingly important in pediatric urology. However, experience is still limited with minimally invasive operations on the upper urinary tract in infants. We analyzed 3 minimally invasive procedures (pyeloplasty, heminephroureterectomy and nephrectomy) in children younger than 1 year. MATERIALS AND METHODS We analyzed 67 children (mean +/- SD age 5.1 +/- 2.9 months) undergoing minimally invasive pyeloplasty in 26 patients (group 1), heminephroureterectomy in 18 (group 2) or nephrectomy in 23 (group 3) with regard to technical aspects, surgical outcome and complications. Preoperative and postoperative ultrasound and mercaptoacetyltriglycine renal scan were statistically evaluated in groups 1 and 2. RESULTS Mean +/- SD patient weight was 6.4 +/- 1.8 kg and mean +/- SD operative time was 113.2 +/- 41.6 minutes. Conversion to open surgery was necessary in 1 pyeloplasty. One complication (missed intraoperative bowel perforation) occurred. No blood transfusion was required in any child. After pyeloplasty there were improved tracer clearances (mercaptoacetyltriglycine scan) and improved morphologies of the pyelon (ultrasound) in all patients. In groups 1 and 2 there was no statistical difference between preoperative and postoperative partial function of the affected kidney. Mean +/- SD followup was 32.5 +/- 19.8 months. CONCLUSIONS Minimally invasive procedures on the upper urinary tract in children younger than 1 year are technically challenging, and require expertise of the surgeon and the entire team. Given these assumptions, such procedures can be safely performed with excellent functional outcomes.

Transperineal Sonography for Determination of the Type of Imperforate Anus

OBJECTIVE The purpose of this study was to assess whether transperineal sonography is valid and accurate for discriminating the low (translevator) type of imperforate anus from the intermediate and high (supralevator) types. The distinction is critical in determination of the surgical approach. MATERIALS AND METHODS Fifty-six consecutively enrolled infants (0-90 days old) with imperforate anus underwent transperineal gray-scale sonography with a 12-MHz linear array transducer. The distance between the distal rectal pouch and the perineum was measured, and a cutoff distance for differentiating types of imperforate anus was identified. The sonographic findings were compared with the final diagnosis reached with radiographic and surgical findings. RESULTS Transperineal sonography was feasible in all children without specific preparation. The mean distance between the distal rectal pouch and the perineum in the 22 infants with low imperforate anus was 10 +/- 4 (SD) mm compared with a mean of 24 +/- 6 mm in the 34 infants with intermediate or high anomalies (p < 0.001). The sensitivity of transperineal sonography was 100%; all 34 cases of intermediate or high imperforate anus were identified with a cutoff distance between the distal rectal pouch and the perineum of 15 mm. The specificity of sonography was 86% and the accuracy, 95%. CONCLUSION Transperineal sonography is a valid and accurate noninvasive imaging technique for differentiating low and intermediate or high imperforate anus.

Surgical aspects in the treatment of patients with unilateral wilms tumor: a report from the SIOP 93-01/German Society of Pediatric Oncology and Hematology.

Objective:To assess surgical aspects in the treatment of children with unilateral Wilms tumor based on data from the Cooperative Tumor Study SIOP 93-01 of the German Society of Pediatric Hematology and Oncology. Summary Background Data:Although multiple international study trials exist for the treatment of nephroblastoma, the impact of surgical details and the outcome of the patients have not yet been described comparing different approaches of the trials. Methods:Treatment results of SIOP 93-01 of the German Society of Pediatric Hematology and Oncology were analyzed regarding frequencies of operations by surgeons and hospitals, surgical approaches, and operating subspecialties. Special attention was given to surgical complications, postoperative tumor stages and event-free survival. Results:Data sets from 757 of 1020 registered patients were received for evaluation. A unilateral Wilms tumor was observed in 512 of 757 children. Median follow-up was 4.8 years (1.2–10.7). Event-free survival rates were comparable for frequencies of operation by surgeons and hospitals, surgical approaches, and surgical specialties. Intraoperative tumor rupture rates were 12% in primarily operated patients (protocol violations) versus 3.2% in patients after preoperative chemotherapy. There were 7% intraoperative ruptures for hospitals and surgeons performing 1 operation per year, and 3% when more than 4 operations per year were carried out. Sampling of hilar lymph nodes was often incomplete for all surgical subspecialties. Conclusion:While the event-free survival for all groups is equal, there may be some long-term complications as a result of the more intensified therapy required for patients who suffer intraoperative ruptures. This will be defined only with longer term studies of late effects of the more intensified therapy. There is, however an increased rate of complications and ruptures associated with the use of midline laparotomy rather than a transverse or thoracoabdominal incision.

Inhibition of Bcl-2 and Bcl-X enhances chemotherapy sensitivity in hepatoblastoma cells†

An increased expression of anti‐apoptotic proteins is regularly found in malignant cells, contributing to their clonal expansion by conferring an improved survival ability. In Hepatoblastoma (HB) apoptosis regulation contributes to resistance and therapy failure, therefore we modulated apoptosis sensitivity of HB cells for an improved cytotoxic activity of commonly used drugs.

Minimally invasive nephrectomy for Wilms tumors in children - data from SIOP 2001.

PURPOSE To analyse the surgical and oncological outcome of minimally invasive surgery (MIS) for tumor nephrectomy in Wilms tumor (WT) patients. METHODS WT patients from the SIOP 2001 trial, undergoing MIS for tumor nephrectomy were analyzed with regard to demographic characterization, surgical specifications, complications, and outcome. RESULTS There were 24 children matching the inclusion criteria. Median age at operation was 40.35 months (14.3-65.4). All patients received preoperative chemotherapy. Median tumor volume was 177.5 ml at diagnosis (46.5-958) and 73.0 ml at surgery (3.8-776). There was one surgical complication (splenic injury), no intraoperative tumor rupture occurred. Abdominal stage was I in 14, II in 7, and III in 3 patients. Adequate lymph node sampling was performed in only 2 patients. One local relapse occurred. Event-free survival was 23/24, overall survival was 24/24, median follow up was 47 months (2-114). CONCLUSIONS We present the largest series so far of minimally invasive nephrectomies for nephroblastoma based on a multinational trial. Treatment results were comparable to those of open surgery; however, experience of operating surgeons was generally high. Discipline of lymph node sampling was inadequate. Based on this analysis a prospective study on MIS in nephroblastoma is planned by the SIOP Renal Tumor Study Group.

The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture

Chemoresistance and advanced tumour stage at time of diagnosis are the major reasons for poor treatment results in hepatoblastoma (HB) and paediatric hepatocellular carcinoma (HCC). Positive results with transplantation of liver and bone marrow revealed the impact of the immune system on the treatment of liver malignancies.

Nephron Sparing Surgery for Synchronous Bilateral Nephroblastoma Involving the Renal Hilus

PURPOSE Bilateral nephroblastoma involving the renal hilus represents a significant surgical challenge. Different operative strategies have been proposed for this condition. We analyzed the outcome of simultaneous bilateral partial nephrectomy for complex stage V nephroblastoma. MATERIALS AND METHODS We retrospectively analyzed patients with bilateral nephroblastoma involving the renal hilus operated on at our institution between 2002 and 2008. We assessed patient data and surgical and oncologic outcomes. RESULTS We analyzed data from 5 patients with a median age of 27 months at surgery (range 13 to 58). Two children had additional pulmonary metastases. Patients were treated according to the International Society of Pediatric Oncology 2001/German Society of Pediatric Oncology and Hematology protocol. All children underwent synchronous bilateral nephron sparing surgery (longitudinal partial nephrectomy or enucleation) of the central tumors. Median operating time was 182 minutes (range 129 to 291), with vascular exclusion performed in 4 patients (7 to 25 minutes). Complications consisted of urinary leakage in 2 cases. Postoperative renal function was unimpaired in 4 patients and 1 patient had Wilms tumor/aniridia/genitourinary malformations/retardation syndrome with glomerulopathy. One patient with pulmonary metastases and blastemal histology had multiple pulmonary relapses and died due to pulmonary progressive disease. Four patients are alive without evidence of disease at a median followup of 45 months (range 44 to 73). CONCLUSIONS Surgery for central stage V nephroblastoma is possible with good functional and oncologic outcomes. The single stage approach is safe, provided that operating and treating physicians have sufficient expertise with such conditions. The ultimate goal is to avoid tumor nephrectomy.

Analysis of sternotomy as treatment option for the resection of bilateral pulmonary metastases in pediatric solid tumors

BACKGROUND Radical surgical resection of metastases is an important prognostic factor for survival of patients suffering from solid pediatric tumors. The aim of this study is to evaluate the efficacy of median sternotomy as treatment option for the resection of multiple bilateral lung metastases in children with different tumor entities. Furthermore, the sensitivity of preoperative imaging (CT) was assessed by intraoperative findings. PATIENTS AND METHODS Between 2002 and 2007, 13 children (4 with sarcoma, 4 with nephroblastoma, 5 with hepatoblastoma) underwent median sternotomy for resection of bilateral lung metastases after R0-resection of the primary tumor. In 6/13 cases, the sternotomy was combined with the primary tumor resection. RESULTS Median patient age at the first operation was 5 years (range: 11 months to 17 years). The median total number of resected metastases per operation was 9 and ranged from 0 to 65. In 13/16 operations, the intraoperative number of metastases did not agree with the preoperative radiological work-up. Median hospital stay was 14 days (range from 9 to 36 days). Ten out of 13 children are alive after a median follow-up of 13 months (range from 6 to 66 months). CONCLUSION Median sternotomy is an adequate treatment modality for the resection of bilateral pulmonary metastases as a one-stage procedure. The combination of primary tumor resection with sternotomy should be considered as a treatment option. Complete resection of metastases of solid pediatric tumors should be aimed for in order to increase the survival of these patients.