Ozone therapy versus surgery for lumbar disc herniation: A randomized double-blind controlled trial.

OBJECTIVES: Surgery is the treatment of choice for symptomatic disc herniation after conservative management. Several studies have suggested the potential utility of intradiscal ozone infiltration in this pathology. The aim of this trial was to compare intradiscal ozone infiltration vs. oxygen infiltration vs. surgery. DESIGN AND INTERVENTIONS: This was a randomized, double-blinded, and controlled trial in patients on a waiting list for herniated disc surgery. There were three treatment groups: surgery; intradiscal ozone infiltration (plus foraminal infiltration of ozone, steroids, and anesthetic); intradiscal oxygen infiltration (plus foraminal infiltration of oxygen, steroids, and anesthetic). MAIN OUTCOME MEASURES: The requirements for surgery. RESULTS: Five years after the treatment of the last recruited patient (median follow-up: 78 months), the requirement for further surgery was 20 % for patients in the ozone group and 60 % for patients in the oxygen group. 11 % of patients initially treated with surgery also required a second surgery. Compared to the surgery group, the ozone group showed: 1) significantly lower number of inpatient days: median 3 days (interquartile range: 3-3.5 days) vs. 0 days (interquartile range: 0-1.5 days), p = 0.012; 2) significantly lower costs: median EUR 3702 (interquartile range: EUR 3283-7630) vs. EUR 364 (interquartile range: EUR 364-2536), p = 0.029. CONCLUSIONS: Our truncated trial showed that intradiscal ozone infiltrations decreased the requirements for conventional surgery, resulting in decreased hospitalization durations and associated costs. These findings and their magnitude are of interest to patients and health services providers. Further validation is ongoing.

Spinal cord stimulation as adjuvant during chemotherapy and reirradiation treatment of recurrent high-grade gliomas.

AIMS: Relapsed high-grade gliomas (HGGs) have poor prognoses and there is no standard treatment. HGGs have ischemia/hypoxia associated and, as such, drugs and oxygen have low access, with increased resistance to chemotherapy and radiotherapy. Tumor hypoxia modification can improve outcomes and overall survival in some patients with these tumors. In previous works, we have described that cervical spinal cord stimulation can modify tumor microenvironment in HGG by increasing tumor blood flow, oxygenation, and metabolism. The aim of this current, preliminary, nonrandomized, study was to assess the clinical effect of spinal cord stimulation during brain reirradiation and chemotherapy deployed for the treatment of recurrent HGG; the hypothesis being that an improvement in oxygenated blood supply would facilitate enhanced delivery of the scheduled therapy. MATERIALS AND METHODS: Seven patients had spinal cord stimulation applied during the scheduled reirradiation and chemotherapy for the treatment of recurrent HGG (6 anaplastic gliomas and 1 glioblastoma). Median dose of previous irradiation was 60 Gy (range = 56-72 Gy) and median dose of reirradiation was 46 Gy (range = 40-46 Gy). Primary end point of the study was overall survival (OS) following confirmation of HGG relapse. RESULTS: From the time of diagnosis of last tumor relapse before reirradiation, median OS was 39 months (95% CI = 0-93) for the overall study group: 39 months (95% CI = 9-69) for those with anaplastic gliomas and 16 months for the patient with glioblastoma. Posttreatment, doses of corticosteroids was significantly decreased (P = .026) and performance status significantly improved (P = .046). CONCLUSIONS: Spinal cord stimulation during reirradiation and chemotherapy is feasible and well tolerated. In our study, spinal cord stimulation was associated with clinical improvement and longer survival than previously reported in recurrent anaplastic gliomas. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation in relapsed HGGs merits further research.

Long-term improvement in refractory headache following ozone therapy.

BACKGROUND: Headache afflicts approximately 10%-15% of the general population. Mixed results are obtained from various therapies, usually drugs, but also oxygen inhalation, behavioral psychology, physical therapy, and peripheral or central neurostimulation. When refractory to treatment, it has severe impact on quality of life. OBJECTIVES/SUBJECTS: Five (5) patients are presented who had suffered from severe/persistent headache refractory to standard management (including 5-HT1 agonist triptan drugs) and were treated with ozone therapy. INTERVENTIONS: Ozone administration was by major autohemotherapy. The procedure involved venous blood drawn into a sterile single-use glass bottle containing anticoagulant, gently mixed with an equal volume of O3/O2 gas mixture (prefiltered through a sterile 0.20-µm filter) and slowly reinfused back into the donor patient via the antecubital vein. OUTCOME MEASURES: The analyzed parameters were analgesia requirements, days of sick leave due to headache, number of headache events, and pain intensity according to the visual analogue scale (VAS); these recorded at three time points: pre-ozone therapy, post-ozone therapy, and before the last follow-up (mean: 64.6±36.8 months). RESULTS: The number of headache episodes pretreatment (n=80; range 5-200) was significantly decreased during the first 6 months post-treatment (n=0, range 0-1; p=0.042) and over the 6 months before the last follow-up visit (n=1, range 0-2; p=0.043). The corresponding VAS scores were 8.7±0.8 pretreatment versus 1.1±2.5 the 6 months post-treatment (p=0.003) and versus 3.1±3.3 the 6 months before last follow-up visit (p=0.036). CONCLUSIONS: Ozone therapy decreased headache episodes and pain severity over a protracted period. This novel approach is effective and merits further research.

Brain ischemia and hypometabolism treated by ozone therapy.

BACKGROUND: Radiation-induced brain injury (RBI) and low-perfusion brain syndromes are mediated by ischemia and hypometabolism and have limited treatment options. Ozone therapy as treatment in vascular diseases has been described, but the effects on brain tissue have not been well documented. CASE REPORT: We describe a 75-year-old patient with vascular risk factors and meningioma who was treated with stereotactic radiosurgery. 14 months later the patient presented with progressive clinical impairment despite the use of acetylsalicylic acid and corticosteroids. Clinical and imaging evaluations before/after ozone therapy were done by magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT), and positron emission tomography (PET); performance status assessment was done using Barthel Index and World Health Organization/Eastern Cooperative Oncology Group Scale (WHO/ECOG Scale). Ozone therapy was performed by autohemotransfusion. RESULTS: Basal images showed brain areas with ischemia and hypometabolism compatible with ischemic processes and/or RBI. There were no changes in MRI or CT scan images following ozone therapy. However, improvements in brain perfusion and metabolism were demonstrable with SPECT and PET; they correlated with clinical development and performance status scales. CONCLUSION: This report supports our previous works about the effect of ozone therapy in cerebral blood flow, and it suggests the use of ozone therapy in ischemic and hypometabolic brain syndromes such as stroke or RBI.

Modification of glucose metabolism in radiation-induced brain injury areas using cervical spinal cord stimulation.

PURPOSE: Radiation-induced brain injury (RBI) is an insidious side-effect of radiotherapy mediated by vascular alterations, inflammation and ischaemia. In previous studies we had shown potential increases in loco-regional blood flow and glucose metabolism in brain tumours by using electrical cervical spinal cord stimulation (SCS). In this preliminary report we demonstrate the effect of cervical SCS on RBI-tissue metabolism, as assessed using [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: SCS devices were inserted in eight patients with diagnosis of potential RBI in previously irradiated areas. While the SCS device was deactivated, each patient underwent an initial FDG-PET study to evaluate the clinical status. A second FDG-PET study was performed later the same day while the SCS device was activated in order to evaluate the effect of cervical SCS on glucose metabolism. RESULTS: Basal glucose metabolism in RBI areas was 31% lower than peri-RBI areas (p = 0.009) and 32% lower than healthy contra-lateral areas (p = 0.020). There was a significant increase in glucose uptake during SCS in both the RBI (p = 0.005) and the peri-RBI (p = 0.004) areas, with measured increases of 38 and 42%, respectively. The estimated potential maximal residual activity of the first FDG dose's contribution to the activity on the second scan was

Effect of cervical spinal cord stimulation on cerebral glucose metabolism.

OBJECTIVE: Syndromes resulting from decreased cerebral blood flow and metabolic activity have significant clinical and social repercussion. However, treatment options are limited. Cervical spinal cord stimulation has shown clinical benefit in the management of several ischemic syndromes. The aim of this report was to assess the effect of cervical spinal cord stimulation on cerebral glucose metabolism. MATERIALS AND METHODS: Between April 2000 and December 2005, 16 patients with brain tumors were assessed. Before and during spinal cord stimulation, they had cerebral glucose metabolism evaluated using 18fluoro-2-deoxyglucose positron emission tomography (18FDG-PET) in the healthy cerebral hemisphere contralateral to the lesion area. RESULTS: Following cervical spinal cord stimulation, there was a significant (p<0.001) increase in glucose metabolism in healthy cerebral hemisphere. The measured increase was 37.7%, with an estimated potential maximal contribution of the first 18fluoro-2-deoxyglucose injection to the quantification of the second positron emission tomography study (carry-over effect)

Modification of glucose metabolism in brain tumors by using cervical spinal cord stimulation.

OBJECT: In previous studies the authors have shown potential increases in locoregional blood flow and oxygenation in tumors by using electrical cervical spinal cord stimulation (SCS). In the present report they demonstrate the effect of cervical SCS on brain tumor metabolism, as assessed using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: Cervical devices were inserted in 11 patients who had high-grade gliomas, six of which had recurred. While the SCS device was deactivated, each patient underwent an initial FDG-PET study to clarify the clinical status. A second FDG-PET study was performed later the same day while the stimulation device was activated to determine the effect of cervical SCS on glucose metabolism. All 11 patients were invaluable for this PET study. Basal glucose metabolism was higher in the tumor than in the peritumoral areas (p = 0.048). There was a significant increase in glucose uptake during cervical SCS in both the tumor (p = 0.035) and the peritumoral (p = 0.001) areas, with measured increases of 43 and 38%, respectively. The estimated potential maximal residual activity of the first FDG dose's contribution to the activity on the second scan was 18.5 +/- 1% or less. CONCLUSIONS: This PET study is the first in which is described the effect of cervical SCS on glucose metabolism in brain tumors and supports previous study data indicating a modification of locoregional blood flow and oxygenation by cervical SCS. These results open up new approaches to modifying the effect of radiochemotherapy in the treatment of malignant brain tumors.

Intravesical ozone therapy for progressive radiation-induced hematuria.

BACKGROUND: Progressive radiation-induced cystitis can become a serious clinical problem the therapeutic solution of which is limited and almost invariably aggressive. Ozone therapy is a nonconventional therapy that has been reported to offer benefits in late-onset wound healing and ischemic disorders. This report describes a patient with progressive radiation-induced hematuria from standard conservative treatment that was further treated with ozone therapy. METHOD: Ozone therapy was achieved by intravesical instillation of ozonized bi-distilled water over a period of 30 minutes, three sessions per week during the first weeks. Later, ozone therapy sessions were decreased and involved ozonized water or direct intravesicular instillation of ozone at 20-25 microg/mL. RESULTS: Hematuria was successfully controlled by intravesical application of ozone therapy. CONCLUSIONS: The successes achieved with this technique suggest that intravesicular instillation of ozonized bi-distilled water or ozone merits further investigation with a view to its application to counter this radiation-induced side-effect.

Ozone Therapy for Tumor Oxygenation: a Pilot Study.

Tumor hypoxia is an adverse factor for chemotherapy and radiotherapy. Ozone therapy is a non-conventional form of medicine that has been used successfully in the treatment of ischemic disorders. This prospective study was designed to assess the effect of ozone therapy on tumor oxygenation. Eighteen subjects were recruited for the study. Systemic ozone therapy was administered by autohemotransfusion on three alternate days over one week. Tumor oxygenation levels were measured using polarographic needle probes before and after the first and the third ozone therapy session. Overall, no statistically significant change was observed in the tumor oxygenation in the 18 patients. However, a significant decrease was observed in hypoxic values

Blood flow increase by cervical spinal cord stimulation in middle cerebral and common carotid arteries.

The effect of spinal cord stimulation (SCS) on cerebral blood flow (CBF) has, in the past, been evaluated by semiquantitative techniques, but has not been used to treat CBF diseases. The aim of this study was to assess the effect of cervical SCS on regional blood flow by both semiquantitative and quantitative methods. Thirty-five patients with cervical SCS-implanted devices were enrolled. The following parameters were measured before and after cervical SCS: systolic and diastolic velocity (cm/s) in the middle cerebral artery (MCA) by transcranial Doppler (TCD) and volume blood flow quantification (ml/min) in the common carotid artery (CCA) by color Doppler. During cervical SCS there was a significant and bilateral increase in systolic (21%) and diastolic (26%) velocity in the MCA and in CCA blood flow (50%). We conclude that cervical SCS increases blood flow in the middle cerebral artery and common carotid artery. The consistent increase supports the potential usefulness of cervical SCS as an adjuvant treatment for cerebral blood flow diseases.

Ozone Therapy on Cerebral Blood Flow: A Preliminary Report.

Ozone therapy is currently being used in the treatment of ischemic disorders, but the underlying mechanisms that result in successful treatment are not well known. This study assesses the effect of ozone therapy on the blood flow in the middle cerebral and common carotid arteries. Seven subjects were recruited for the therapy that was performed by transfusing ozone-enriched autologous blood on 3 alternate days over 1 week. Blood flow quantification in the common carotid artery (n = 14) was performed using color Doppler. Systolic and diastolic velocities in the middle cerebral artery (n = 14) were estimated using transcranial Doppler. Ultrasound assessments were conducted at the following three time points: 1) basal (before ozone therapy), 2) after session #3 and 3) 1 week after session #3. The common carotid blood flow had increased by 75% in relation to the baseline after session #3 (P < 0.001) and by 29% 1 week later (P = 0.039). In the middle cerebral artery, the systolic velocity had increased by 22% after session #3 (P = 0.001) and by 15% 1 week later (P = 0.035), whereas the diastolic velocity had increased by 33% after session #3 (P < 0.001) and by 18% 1 week later (P = 0.023). This preliminary Doppler study supports the clinical experience of achieving improvement by using ozone therapy in peripheral ischemic syndromes. Its potential use as a complementary treatment in cerebral low perfusion syndromes merits further clinical evaluation.

Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study.

Advanced head and neck (H&N) tumors have a poor prognosis, and this is worsened by the occurrence of hypoxia and ischemia in the tumors. Ozonetherapy has proved useful in the treatment of ischemic syndromes, and several studies have described a potential increase of oxygenation in tissues and tumors. The aim of this prospective study was to evaluate the clinical effect of ozonetherapy in patients with advanced H&N cancer in the course of their scheduled radiotherapy. Over a period of 3 years, 19 patients with advanced H&N tumors who were undergoing treatment in our department with non-standard fractionated radiotherapy plus oral tegafur. A group of 12 patients was additionally treated with intravenous chemotherapy before and/or during radiotherapy. In the other group of seven patients, systemic ozonetherapy was administered twice weekly during radiotherapy. The ozonetherapy group was older (64 versus 54 years old, P = 0.006), with a higher percentage of lymph node involvement (71% versus 8%, P = 0.019) and with a trend to more unfavorable tumor stage (57% versus 8% IVb + IVc stages, P = 0.073). However, there was no significant difference in overall survival between the chemotherapy (median 6 months) and ozonetherapy (8 months) groups. Although these results have to be viewed with caution because of the limited number of patients, they suggest that ozonetherapy could have had some positive effect during the treatment of our patients with advanced H&N tumors. The adjuvant administration of ozonetherapy during the chemo-radiotherapy for these tumors merits further research.

Increased locoregional blood flow in brain tumors after cervical spinal cord stimulation.

OBJECT: Patients with high-grade gliomas have poor prognoses following standard treatment. Generally, malignant brain tumors have a decreased blood flow that results in increased resistance to radiation and reduced delivery of chemotherapeutic agents and oxygen. The aim of the present study was to assess the effect of spinal cord stimulation (SCS) on locoregional blood flow in high-grade tumors in the brain. METHODS: Fifteen patients (11 with Grade III and four with Grade IV brain tumors) had SCS devices inserted prior to scheduled radiotherapy. Both before and after SCS, the patients underwent the following procedures: 1) single-photon emission computerized tomography (SPECT) scanning; 2) middle cerebral artery (MCA) blood flow velocity measurements (centimeters/second) with the aid of transcranial Doppler (TCD) ultrasonography; and 3) common carotid artery (CCA) blood flow volume quantification (milliliters/minute) based on time-domain processing by using color Doppler ultrasonography. The indices demonstrated on SPECT scanning before SCS were significantly lower (p < 0.001) in tumor sites compared with those in peritumoral sites (32%) and healthy contralateral areas (41%). Poststimulation results revealed the following: 1) a mean increase of 15% in tumor blood flow in 75% of patients (p = 0.033), as demonstrated on SPECT scanning: 2) a mean increase of greater than 18% in systolic and diastolic blood flow velocities in both tumorous and healthy MCAs in all but one patient (p < 0.002), as exhibited on TCD ultrasonography; and 3) a mean increase of greater than 60% in blood flow volume in tumorous and healthy CCAs in all patients (p < 0.013), as revealed on color Doppler ultrasonography studies. CONCLUSIONS: Preliminary data show that SCS can modify locoregional blood flow in high-grade malignant tumors in the brain, thus indicating that SCS could be used to improve blood flow, oxygenation, and drug delivery to such tumors and could be a useful adjuvant in chemoradiotherapy.

Effect of ozone therapy on muscle oxygenation.

BACKGROUND AND OBJECTIVE: Ozone therapy is being used to treat ischemic disorders. However, the underlying mechanisms for the success are unknown and the therapy has not been accepted fully within conventional medicine. This study sought to assess the effect of ozone therapy on resting muscle oxygenation. PATIENTS AND DESIGN: Twenty-three (23) patients and 3 volunteers were recruited for this prospective study. Systemic ozone therapy was administered by autohemotransfusion on three alternate days over 1 week. Tissue oxygenation (mmHg) was directly measured in the tibialis anterior muscle using polarographic needle electrodes before and after the first and the third ozone therapy session. RESULTS: Globally, the differences in oxygenation were not statistically significant but there was a significant decrease in the percentage of low-oxygenated values (pO(2) < 5 mmHg) following ozone sessions (p < 0.02). The change in muscle oxygenation following ozone therapy was inversely correlated with age (r = -0.398; p = 0.044) and with the initial (baseline pretherapy) muscle oxygenation values (r = -0.644; p < 0.001), indicating that the more poorly oxygenated muscles benefited most from the therapy. A significant (p = 0.031) higher oxygenation in these tissues was observed 48 hours after the second session. CONCLUSIONS: Ozone therapy can modify oxygenation in resting muscles, particularly of those that are most hypoxic. Our results suggest that ozone therapy could be used effectively as a complementary treatment of hypoxic and ischemic syndromes and that the therapy warrants further investigation for possible application in other clinical conditions.

Influence of haemoglobin concentration and peripheral muscle pO2 on tumour oxygenation in advanced head and neck tumours.

Haemoglobin concentrations and tumour-pO(2) were evaluated pre-therapy in 30 patients with head and neck cancers. Anterior tibialis muscle-pO(2) was additionally measured in 16 of these patients. Tumour-pO(2) was lower in the most anaemic patients (P=0.032) and correlated with muscle-pO(2) (r=0.809, P<0.001). These results suggest that haemoglobin concentration influences tumour-oxygenation.

Increase of brain tumor oxygenation during cervical spinal cord stimulation. Report of three cases.

Malignant brain tumors have been shown to decrease O2 and blood flow resulting in hypoxia and low perfusion that in turn reduce radiation sensitivity and access by chemotherapeutic agents. Spinal cord stimulation (SCS) is a procedure that has been used quite successfully in the treatment of pain and ischemic syndromes. In the present study the authors applied the method and, with polarographic probes inserted in the tumor sites, measured the changes in tissue oxygenation and hypoxia in two separate tumor areas in three patients with high-grade astrocytomas. The results of the SCS indicated that overall tumor oxygenation increased by 90% (from 13.2+/-9.4 mm Hg to 25.1+/-9.6 mm Hg; p = 0.013); the percentage of moderately hypoxic values (< 10 mm Hg) decreased by 55% (from 48.6+/-20.1% to 22+/-13.3%; p = 0.026); and the percentage of considerably hypoxic values (< 5 mm Hg) decreased by 45% (from 28+/-20.3% to 15.5+/-15%; p = 0.018). In this report the authors describe a potential novel application of SCS, and the preliminary results suggest that tumor tissue oxygenation and hypoxia are significantly improved as a result. If these findings are confirmed, the method may be applicable as an adjuvant to radiotherapy and chemotherapy regimens.