Clinical experience with radiation enhancement by hyperbaric oxygen in children with recurrent neuroblastoma stage IV.

The high risk group of patients with neuroblastoma are children over 1 year with stage IV disease. Most series report a maximum of 20% survival at 5 years. For recurrent neuroblastoma stage IV, cure rates are not reported in the literature, but they are nil. Any treatment for recurrent neuroblastoma stage IV remains a therapeutic dilemma. The outcome of radiation therapy is variable. A very important factor in tumour treatment remains tumour hypoxia, and others, such as metabolic factors, also play a role. Combined application of radiation modifiers may influence the final survival rate. In an attempt to improve the survival of recurrent neuroblastoma stage IV, hyperbaric oxygen and radioionated meta-Iodobenzylguanidine (MIBG) was used in a clinical setting. Although survival may not be used as a determinant of the usefulness of a treatment for stage IV neuroblastoma disease, a better one is not available. In this study, at 28 months, a cumulative probability of survival of 32% was recorded for patients treated with [131I]MIBG and hyperbaric oxygen compared to 12% for [131I]MIBG treatment alone. These preliminary results are promising but further studies are needed to reveal substantial therapeutic gain.

Tumor hypoxia--a confounding or exploitable factor in interstitial brachytherapy? Effects of tissue trauma in an experimental rat tumor model.

PURPOSE: To evaluate the potential effects of tumor hypoxia induced by afterloading catheter implantation on the effectiveness of brachytherapy in a rat tumor model. METHODS AND MATERIALS: Afterloading catheters (4) were implanted in subcutaneously growing R1M rhabdomyosarcoma in female Wag/Rij rats. A MicroSelectron (Nucletron) was used for interstitial high-dose-rate irradiation ((192)Ir). Tumor oxygenation, perfusion, and cell survival were assessed by pO(2) histography (Eppendorf), Tc-99m injection, and excision assay, respectively. RESULTS: Tumor perfusion was markedly reduced at 1 h after catheter implantation (33.9 +/- 6.0% (SEM, n = 9) of control) and partly recovered after 5 h (61.5 +/- 12.2%). At 24 h, the perfusion level reached control values (100.6 +/- 25.7%), but was highly variable with some of the tumors showing hardly any recovery at all. Tumor oxygenation showed a similar pattern, but with less recovery. Median pO(2) readings were 13.5, 1.2, and 5.3 mm Hg before and at 1 and 24 h after implantation, respectively (7 tumors). The percentages of pO(2) readings

Effects of hyperbaric oxygen and normobaric carbogen on the radiation response of the rat rhabdomyosarcoma R1H.

PURPOSE: Hypoxic tumor cells are an important factor of radioresistance. Hyperbaric oxygen (HBO) and normobaric carbogen (95% oxygen, 5% carbon dioxide) increase the oxygen delivery to tumors. This study was performed to explore changes of tumor oxygenation during a course of fractionated irradiation and to determine the effectiveness of normobaric carbogen and HBO during the final phase of the radiation treatment. METHODS AND MATERIALS: Experiments were performed on the rhabdomyosarcoma R1H growing on WAG/Rij rats. After 20 X-ray fractions of 2 Gy within 4 weeks, oxygen partial pressure (pO2) was measured using the Eppendorf oxygen electrode under ambient conditions, with normobaric carbogen or HBO at a pressure of 240 kPa. Following the 4-week radiation course, a top-up dose of 10-50 Gy was applied in 2-10 fractions of 5 Gy with or without hyperoxygenation. RESULTS: HBO but not carbogen significantly increased the median pO2 in irradiated tumors. The radiation doses to control 50% of tumors were 38.0 Gy, 29.5 Gy, and 25.0 Gy for air, carbogen, and HBO, respectively. Both high oxygen content gas inspirations led to significantly improved tumor responses with oxygen enhancement ratios (OERs) of 1.3 for normobaric carbogen and 1.5 for HBO (air vs. carbogen: p = 0.044; air vs. HBO: p = 0.02; carbogen vs. HBO: p = 0.048). CONCLUSION: Both normobaric carbogen and HBO significantly improved the radiation response of R1H tumors. HBO appeared to be more effective than normobaric carbogen, both with regard to tumor oxygenation and response to irradiation.

Early detection of hemorrhagic hypovolemia by muscle oxygen pressure assessment: preliminary report.

Skeletal muscle PO2 was studied during graded hemorrhagic shock in Labrador dogs by means of a polarographic needle PO2 electrode. Compared to hemodynamic, blood gas, biochemical, and hematologic variables, a shift to the left of the cumulative histogram of skeletal muscle PO2 was the earliest and most sensitive indicator of impaired skeletal muscle oxygenation. The mean arterial blood pressure and the mean of the medians of the skeletal muscle PO2, respectively, were as follows: during the control period 125 and 38.1 mm Hg, during the imminent shock period 143 and 24.5 mm Hg, and during the shock period 89 and 5.1 mm Hg. This electrode is suitable for clinical use.

HBO and the uptake and retention of [125I] MIBG in human platelets and two neuroendocrine cell lines.

In this paper we report the effects of Hyperbaric Oxygen (HBO) exposure on the uptake and retention of meta-Iodobenzylguanidine (MIBG) in human platelets and two neuroendocrine cell lines. The combination of [131I] MIBG and HBO is used for therapy of neuroblastoma. Exposure to HBO can cause oxidative stress, which is potentially capable of affecting uptake and storage of MIBG in both neuroendocrine cells and platelets. Oxidative stress generated by menadione decreased both the uptake and retention of MIBG in the platelets and the cell lines. HBO did not affect these processes, indicating that the HBO induced oxidative stress is not high enough to affect the MIBG uptake and storage pathways in these cells. This suggests that the positive effects observed by the treatment of neuroblastoma patients with the combination of HBO and [131I] MIBG are most likely not due to improved uptake or retention of MIBG in the neuroblastoma. Neither can reduced cytotoxicity (trombocytopenia) be expected due to decreased uptake/retention of [131I] MIBG in platelets or their precursor cells.

Red blood cell velocity in nailfold capillaries during hyperbaric oxygenation.

Microcirculatory hemodynamics of the skin during hyperbaric oxygenation were assessed by determination of nailfold capillary red blood cell velocity (Vrbc). Under hyperbaric conditions a continuous increase in Vrbc was found. Control values, 0.43 +/- 0.12 mm. sec-1 (mean +/- sem), were significantly (P < 0.05) lower compared with Vrbc at the end of hyperbaric oxygenation (0.62 +/- 0.16 mm.sec-1).

Continuous tissue oxygenation assessment during bloodflow alterations in an isolated hindlimb model of the pig.

A continuous intramuscular oxygen tension sensor was compared, with transcutaneous oximetry and laser Doppler flowmetry, during periods of arterial flow alterations in an isolated hindlimb model in the pig. The intramuscular oxygen tension sensor correlated well with bloodflow and was superior to the other two methods.

Skeletal muscle PO2 in anaerobic soft tissue infections during hyperbaric oxygen therapy.

In the present study skeletal muscle PO2 measurements were performed in patients with gas gangrene and anaerobic soft tissue infections before, during and after hyperbaric oxygen therapy. Polarographic PO2 needle electrodes appeared to be suitable for application during different ambient pressures. We found that patients with gas gangrene revealed higher skeletal muscle PO2 values than patients with an anaerobic soft tissue infection. This may be explained by a higher metabolic rate within the anaerobically infected soft tissues. The higher PO2 values in gas gangrene may be caused by alpha toxins, affecting cellular and intracellular membranes thus destroying PO2 diffusion barriers.