Effects of ozone therapy on anxiety and depression in patients with refractory symptoms of severe diseases: a pilot study.

Background: Patients with refractory symptoms of severe diseases frequently experience anxiety, depression, and an altered health-related quality of life (HRQOL). Some publications have described the beneficial effect of ozone therapy on several symptoms of this kind of patient. The aim of this study was to preliminarily evaluate, in patients treated because of refractory symptoms of cancer treatment and advanced nononcologic diseases, if ozone therapy has an additional impact on self-reported anxiety and depression. Methods: Before and after ozone treatment, we assessed (i) anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS); (ii) the HRQOL (according to the EQ-5D-5L questionnaire), which includes a dimension on anxiety and depression and a visual analog scale (VAS) measuring self-perceived general health. Results: Before ozone therapy, 56% of patients were on anxiolytic and/or antidepressant treatment. Before and after ozone therapy, the anxiety and depression HADS subscales (i) significantly correlated with the anxiety/depression dimension of the EQ-5D-5L questionnaire and (ii) inversely correlated with the health status as measured by the VAS. After ozone therapy, we found a significant improvement in anxiety and depression measured by both the (i) HADS subscales and (ii) EQ-5D-5L questionnaire. Conclusion: The addition of ozone therapy for patients with refractory symptoms of cancer treatment and advanced chronic nononcologic diseases can decrease anxiety and depression severity levels. Additional, more focused studies are ongoing to provide the needed explanatory information for this finding.

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.

Ozone Therapy in Refractory Pelvic Pain Syndromes Secondary to Cancer Treatment: A New Approach Warranting Exploration.

Background: Chronic pain secondary to treatment in cancer survivors without tumor evidence is not unusual. Its management often requires specific approaches that are different from those applied for cancer patients with advanced disease and short life expectancy. Some studies have described clinical benefit with ozone therapy (O3T) in the management of pain and side effects secondary to cancer treatment. Objective: We present our preliminary experience with O3T in the management of refractory pelvic pain syndromes secondary to cancer treatment. Design: Case series. Subjects and Methods: Six cancer patients (without tumor evidence) who had been treated previously with radiotherapy, chemotherapy, or endoscopic procedures and were suffering persistent or severe pelvic pain (median 14 months) received O3T using ozone-oxygen gas mixture insufflation as a complementary therapy in addition to their scheduled conventional treatment. Results: All cases, except one, showed clinically relevant pain improvement. Visual analog scale score with the standard treatment was 7.8 ± 2.1 before O3T, 4.3 ± 3.4 (p = 0.049) after one month, 3.3 ± 3.7 (p = 0.024) after two months, and 2.8 ± 3.8 (p = 0.020) after three months of O3T. The median value of "pain symptom" according to the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v. 5.0 showed a decrease from 3 (range: 2-3) to 1 (range: 0-3) (p = 0.046). Conclusions: Following unsuccessful conventional treatments, O3T provided significant benefit in our patients with refractory pelvic pain secondary to cancer treatment. These results merit further evaluation in blinded, randomized clinical trials.

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.

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.

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.

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.

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.