Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy.

The induction of apoptosis is a direct way to eliminate tumor cells and improve cancer therapy. Apoptosis is tightly controlled by the balance of pro- and antiapoptotic Bcl-2 proteins. BH3 mimetics neutralize the antiapoptotic function of Bcl-2 proteins and are highly promising compounds inducing apoptosis in several cancer entities including pediatric malignancies. However, the clinical application of BH3 mimetics in solid tumors is impeded by the frequent resistance to single BH3 mimetics and the anticipated toxicity of high concentrations or combination treatments. One potential avenue to increase the potency of BH3 mimetics is the development of immune cell-based therapies to counteract the intrinsic apoptosis resistance of tumor cells and sensitize them to immune attack. Here, we describe spheroid cultures of pediatric cancer cells that can serve as models for drug testing. In these 3D models, we were able to demonstrate that activated allogeneic Natural Killer (NK) cells migrated into tumor spheroids and displayed cytotoxicity against a wide range of pediatric cancer spheroids, highlighting their potential as anti-tumor effector cells. Next, we investigated whether treatment of tumor spheroids with subtoxic concentrations of BH3 mimetics can increase the cytotoxicity of NK cells. Notably, the cytotoxic effects of NK cells were enhanced by the addition of BH3 mimetics. Treatment with either the Bcl-XL inhibitor A1331852 or the Mcl-1 inhibitor S63845 increased the cytotoxicity of NK cells and reduced spheroid size, while the Bcl-2 inhibitor ABT-199 had no effect on NK cell-mediated killing. Taken together, this is the first study to describe the combination of BH3 mimetics targeting Bcl-XL or Mcl-1 with NK cell-based immunotherapy, highlighting the potential of BH3 mimetics in immunotherapy.

Experience with retroperitoneoscopy in pediatric surgical oncology.

BACKGROUND: Retroperitoneoscopy (RS) has been successfully introduced in adult oncology for diagnostic procedures, staging, and surgical treatment. Its value for children has rarely been reported. This report describes the authors' experience using RS in the diagnosis and staging of cancer for children and adolescents. METHODS: All RS procedures performed at the authors' institution between 2004 and 2010 were reviewed. The authors' operative technique entails a 10- to 12-mm flank incision followed by finger and balloon dissection of the retroperitoneal areolar tissue, with carbon dioxide (CO(2)) insufflation used to push the peritoneal lining medially. One to two additional working ports are placed above the iliac rim and below the costal margin. In cases of peritoneal tear with leakage of CO(2) and progressive retroperitoneal impingement, a Veress needle is placed in the umbilicus for pressure release. RESULTS: This review included 16 patients with a median age of 16.4 years (range, 4.4-29.8 years) who underwent RS for lymph node sampling (9 cases), diagnostic biopsy (6 cases), or resection of a metastatic nodule (1 case). Four complications were encountered (3 conversions to open surgery and 1 self-limited gross hematuria). The mean operative time was 123.3 ± 33.5 min. The patients required 1.1 ± 0.8 days of intravenous analgesia on the average. The mean hospital stay was 1.7 ± 0.6 days. CONCLUSIONS: The authors believe that RS is a safe surgical technique for access to the retroperitoneum in pediatric patients. In cases of a peritoneal tear, placement of a Veress needle in the umbilicus effectively prevents conversion to open surgery. Retroperitoneoscopy should be considered for children who need biopsies, lymph node dissections, or resections of primary tumors in the retroperitoneum.

Intramedullary nailing for metacarpal 2-5 fractures.

Twenty-eight patients with 31 closed fractures (27 acute fractures and four with malalignment after conservative treatment) of the metacarpal bones 2-5 were treated with only one elastic stable intramedullary nail and followed prospectively. Treatment protocol was without immobilization or physiotherapy. These patients were reviewed at a mean follow-up time of 15 months for ultrasound results as well as functional outcome concerning complications, pain, range of motion, and grip strength measured with a Vernier-Dynamometer. Satisfaction of the patients was investigated by Clients Satisfaction Questionnaire. Radiographs before nail removal, ultrasound, and clinical examination always showed complete union of the fracture without deviation of axis. All patients gained full range of motion without any limits in daily activity and sports. There was no loss of grip strength compared with the other hand. Patients' satisfaction was very high, especially because of almost no postoperative pain and lack of immobilization. This method can be offered as an effective and safe alternative in the treatment of closed displaced fractures of the 2-5 metacarpus without significant complications.