High Dose Chemotherapy with Autologous Stem Cell Transplantation in Hepatoblastoma does not Improve Outcome. Results of the GPOH Study HB99.

INTRODUCTION: The purpose of the German HB99 trial (1999-2008) for hepatoblastoma (HB), was primarily to analyse the effect of high dose (HD) chemotherapy with carboplatin/etoposide (CE) in high risk (HR) patients with extended tumors, vessel involvement, extrahepatic tumor or distant metastases. In standard risk (SR) patients the effect of treatment reduction was analysed. METHODS: HR patients received 2 cycles CE at conventional dose, followed by 2 at HD with subsequent autologous stem cell transplantation before delayed surgery. SR patients received 3-4 cycles of ifosfamide, cisplatin and doxorubicin (IPA) and delayed surgery. Analysis was on an intention to treat basis including resection rate, AFP decline, event free survival (EFS) and overall survival (OS). The patients with HD therapy were additionally analysed on an "as treated" basis. The results were compared to historical/published data. RESULTS: Of the 142 patients, the 5-y OS was 58% for the 57 HR patients and 94% for the 85 SR patients. The AFP decline after 2 cycles CE was ≥ 50% in > 90% of the patients. 12/18 (67%) patients treated with HD therapy showed an AFP decline after the first cycle (as treated). Tumor resection was possible in 89% of the patients. The median FU was 7.4 years. Late deaths occurred in 4 patients. CONCLUSION: Use of HD chemotherapy for HB did not improve patient outcomes, compared to contemporaneous and more recent trials (SIOPEL 4 trial). Reduction of therapy in SR patients was possible without worsening of results compared to previous trials. The tumor response to CE was good. CE can therefore be considered for relapse patients.

Nephron sparing surgery (NSS) for unilateral wilms tumor (UWT): the SIOP 2001 experience.

BACKGROUND: Total nephrectomy (TN) remains the standard treatment of unilateral Wilms tumors (uWT). The SIOP WT-2001 protocol allowed Nephron Sparing Surgery (NSS) for polar or peripherally non-infiltrating tumors. AIM: Inventory of the current SIOP NSS-experience. PROCEDURES: 2,800 patients with a unilateral, localized or metastatic and an unequivocal surgical technique recorded were included. All had neo-adjuvant chemotherapy and delayed surgery. In 91 (3%) NSS was performed and in 2709 TN. Data was retrieved from the SIOP WT 2001 database. RESULTS: NSS group contained 65% stage I tumours and the TN group 48%. Tumor volume (at diagnosis and surgery) was significantly smaller in the NSS group. Within stage III, after NSS, 7/12 (58%) had positive margins (M +), 5 with tumor negative lymph nodes (LN-). After TN, 355/712 (55%) had M + , 182 were LN-. Treatment of M+ in the NSS group resulted in two conversions to TN (one combined with radiotherapy), three patients had radiotherapy only and in two patients local therapy, if given, was not recorded. After NSS, four recurrences occurred. For localized disease the 5-year overall (OS) and event free survival (EFS) in NSS group was 100 and 94.8 (95% CI:89.9-99.9), respectively, while OS and EFS in the TN group were 94.4 (95% CI: 93.2-95.5, log-rank test P = 0.06) and 86.5 (95% CI:85.0-88.1, log-rank test P = 0.06), respectively. CONCLUSIONS: NSS was only performed in 3% of patients with uWT. Despite excellent survival with few relapses, the gain of nephrons needs to be weighed against the risk to induce stage III with intensified therapy.

Self-administered procedural analgesia using nitrous oxide/oxygen (50:50) in the pediatric surgery emergency room: effectiveness and limitations.

INTRODUCTION: Minor surgical interventions in children are often at times challenging due to the lack of cooperation by the child. Procedural sedation and analgesia is often appropriate, but unpleasant or painful applications of medication add additional discomfort to the child. A mixture of nitrous oxide (N2O)/oxygen (O2) in a ratio of 50:50, functioning as an inhalational sedative analgesic, may be a viable alternative, in particular in an emergency care setting because such mixtures require no fasting period and are self-administered. Therefore, in this study we investigated the feasibility and the effectiveness of N2O/O2 (50:50) as a sedative analgesic when performing minor surgical procedures. PATIENTS AND METHODS: Procedural sedation and analgesia with an N2O/O2 (50:50) mixture applied during minor surgical procedures were prospectively evaluated over 2.5 years in a major pediatric hospital in Germany. Indications for sedation were either minor painful interventions, the injection of a local anesthetic, or a digital block in an emergency care setting. Diagnosis, type of surgery, inhalation time, complications, side effects, pain scores, and the child's behavioral reaction were assessed. RESULTS: A N2O/O2 (50:50) mixture was administered in 210 children, ages 2.7 to 16.5 years (mean 9.0 years). Three treatments were terminated because of lack of compliance, nausea, or dizziness. No other side effects were encountered. During the intervention, 80.5% of all patients were pain free, and 81.9% were relaxed and calm. A higher rate of insufficient pain control was observed when the indication was an injection of a digital block or a reposition of fractures and dislocations. CONCLUSIONS: The use of self-administered N2O/O2 (50:50) mixture for minor painful procedures in children is safe and adequate pain control can be achieved in most cases. The benefits of this approach for the child and its parents are its good acceptance and adequate pain control. The benefit for the health care provider is the lack of a fasting period before administration, good anxiolysis at minimum sedation, and a cooperative patient. Limitations are unsatisfying analgesia in some cases. Though not found in our study, potentially serious adverse events are a possibility and standard safety guidelines for minimal sedation should always be applied.

Treatment of hepatoblastoma in the German cooperative pediatric liver tumor studies.

Treatment with neoadjuvant and adjuvant chemotherapy together with tumor resection changed treatment strategies in hepatoblastoma and led to prospective cooperative studies. The treatment strategies and results of three German liver tumor studies HB89, HB94 and HB99 are reviewed. Here we provide an overview of the treatment of this tumor in the years 1989 to 2008 in Germany. The treatment protocols, aim of studies and results are outlined. The overall-survival (OS), response to chemotherapy and toxicity are followed over this period of different treatment. The overall-survival improved over the last years with 75 % in HB89, 77 % in HB94 and 89 % HB99. Patients with potentially resectable tumors have a good prognosis although the treatment was reduced over the last years. Patients with non resectable tumors or lung metastases have also a better but still bad prognosis. The intensified treatment for these patients in Germany in the last years showed comparable results to international studies but no advantage.