Abstract

BACKGROUND:

Cognitive performance often is impaired permanently in long-term brain tumor survivors after neurosurgery and radiotherapy. Hyperbaric oxygen treatment (HBOT) stimulates neovascularization of hypoperfused tissue and may result in improved functionality of damaged tissue. In this pilot study, clinical neurophysiologic tests were used to assess the effect of HBOT on brain performance.

METHODS:

Ten long-term brain tumor survivors received HBOT for severe cognitive deficits after neurosurgery and radiosurgery. Patients were tested before HBOT and at 6 weeks and 4 months after HBOT. The tests comprised a quantitative electroencephalographic (EEG) examination, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for memory performance, and 2 cognitive tests, the number connection test (NCT) and the continuous reaction time test (CRTT). Late event-related components (LERCs) of averaged evoked EEG responses to a visual odd-ball stimulus were analyzed from whole-head activity maps. For comparison, a control group of healthy individuals (no HBOT) also were investigated.

RESULTS:

After HBOT, the amplitude of the LERC with the longest latency, P3b (involved in object interpretation) was improved significantly (P = .02). The amplitudes of the N200 (occipital, negative) and the intermediate P3a (centroparietal, positive), LERCs with shorter latencies, and of a small, positive, occipital visual component did not change. Neither latencies nor reaction times changed after HBOT. However, P3a and P3b (parietal, positive) latencies were longer in survivors than in healthy individuals. The NCT produced inconclusive results, but the IQCODE revealed an improvement. When outcomes of the NCT, CRTT, IQCODE, and P3b amplitudes were evaluated in common tests, HBOT appeared to provide substantial improvement (P<.006).

CONCLUSIONS:

On the basis of the current results, the authors concluded tentatively that HBOT improves neurophysiologic performance in long-term brain tumor survivors.

Abstract

One unique feature of tumors is the presence of hypoxic regions, which occur predominantly at the tumor center. Hypoxia has a major impact on various aspects of tumor cell function and proliferation. Hypoxic tumor cells are relatively insensitive to conventional therapy owing to cellular adaptations effected by the hypoxic microenvironment. Recent efforts have aimed to alter the hypoxic state and to reverse these adaptations to improve treatment outcome. One way to increase tumor oxygen tensions is by hyperbaric oxygen (HBO) therapy. HBO therapy can influence the tumor microenvironment at several levels. It can alter tumor hypoxia, a potent stimulus that drives angiogenesis. Hyperoxia as a result of HBO also produces reactive oxygen species, which can damage tumors by inducing excessive oxidative stress. This review outlines the importance of oxygen to tumors and the mechanisms by which tumors survive under hypoxic conditions. It also presents data from both experimental and clinical studies for the effect of HBO on malignancy.

Abstract

BACKGROUND AND AIMS:

Hyperbaric oxygen (HBO) therapy involves the administration of 100% oxygen at high pressure. It has been used to treat a variety of conditions including non-healing wounds, carbon monoxide poisoning, and as an adjuvant to radiotherapy or chemotherapy. The effect of HBO alone on the growth of malignancy remains controversial. This study investigates the impact of HBO on tumour growth, kinetics and microcirculation of colorectal cancer liver metastases in an experimental model.

METHODS:

Male CBA mice were induced with colorectal liver metastases via an intrasplenic injection of a murine derived colorectal cell line. Tumours were examined using quantitative stereological analysis, histology and scanning electron microscopy of microvascular resin casts. The effect of HBO on tumour proliferation and apoptosis was quantified using immunohistochemistry.

RESULTS:

Daily exposure to HBO at 2.4 atm for 90 min had no effect on the volume of liver metastases. At day 13, HBO caused a significant reduction in tumour necrosis and proliferation compared to the non-HBO group (p=0.002 and p=0.008, respectively). By day 25 however, no differences were observed (p>0.05). No differences in apoptosis or microvascular architecture were observed.

CONCLUSION:

HBO did not have a tumour stimulatory effect on colorectal liver metastases and may potentially be used safely in conjunction with other therapeutic treatment modalities.

Abstract

Hypoxia, which is commonly observed in many solid tumors, is a major impediment to chemo- or radiation therapy. Hypoxia is also known to overexpress/activate signal transducer and activator of transcription 3 (STAT3) leading to tumor progression as well as drug resistance. We hypothesized that increased oxygenation of the hypoxic tumor may have an inhibitory effect on STAT3 activation and hence tumor-growth inhibition. Mice containing human ovarian cancer xenograft tumor were exposed to hyperbaric oxygen (HBO; 100% oxygen; 2 atm; 90-min duration) daily, for up to 21 days. Mice exposed to HBO showed a significant reduction in tumor volume, with no effect on body weight. STAT3 (Tyr 705) activation and cyclin-D1 protein/mRNA levels were significantly decreased up on HBO exposure. Interestingly, HBO exposure, in combination with weekly administration of cisplatin, also significantly reduced the tumor volume; however, this group of mice had drastically reduced body weight when compared to other groups. While conventional wisdom might suggest that increased oxygenation of tumors would promote tumor growth, the results of the present study indicated otherwise. Hyperoxia appears to inhibit STAT3 activation, which is a key step in the ovarian tumor progression. The study may have important implications for the treatment of ovarian cancer in the clinic.

Abstract

Tetrahydropyranyladriamycin (THP or pirarubicin) destroys tumors via several mechanisms; one of which involves the production of ROS that requires molecular oxygen for its generation. SMA forms stable self-assembled associated micelles with pirarubicin (SMA-pirarubicin), and confers macromolecular characteristics to pirarubicin. This micellar macromolecular drug is selectively delivered to solid tumors via the EPR effect and its preferential tumor accumulation suppresses the systemic toxicity whilst its prolonged high concentration at the site of tumor enhances its efficacy much higher compared to free pirarubicin. Administration of SMA-pirarubicin micelle under HBO can further enhance the delivery of molecular oxygen that facilitates tumor selective generation of ROS, thus augmenting its antitumor potency. In this study, we evaluated the efficacy of SMA-pirarubicin micelles either as single drug or in combination with HBO in a mouse metastatic colorectal cancer model. At or below the maximum tolerated dose, SMA-pirarubicin remarkably reduced metastatic tumor nodules and it was far more effective than free pirarubicin. The data also suggests a potential benefit of combined therapy of HBO with micellar anthracyclins.

Abstract

Background: The importance of tumour hypoxia for the outcome of radiotherapy has been under investigation for decades. Numerous clinical trials modifying the hypoxic radioresistance in squamous cell carcinoma of the head and neck (HNSCC) have been conducted, but most have been inconclusive, partly due to a small number of patients in the individual trial. The present meta-analysis was, therefore, performed utilising the results from all clinical trials addressing the specific question of hypoxic modification in HNSCC undergoing curative intended primary radiotherapy alone. Methods: A systematic review of published and unpublished data identified 4805 patients with HNSCC treated in 32 randomized clinical trials, applying, normobaric oxygen or carbogen breathing (5 trials); hyperbaric oxygen (HBO) (9 trials); hypoxic radiosensitizers (17 trials) and HBO and radiosensitizer (1 trial). The trials were analysed with regard to the following endpoints: loco-regional control (32 trials), disease specific survival (30 trials), overall survival (29 trials), distant metastases (12 trials) and complications to radiotherapy (23 trials). Results: Overall hypoxic modification of radiotherapy in head and neck cancer did result in a significant improved therapeutic benefit. This was most dominantly observed when using the direct endpoint of loco-regional control with an odds ratio (OR) of 0.71, 95% cf.l. 0.63-0.80; p<0.001), but this was almost mirrored in the disease specific survival (OR: 0.73, 95% cf.l. 0.64-0.82; p<0.001), and to a lesser extent in the overall survival (OR: 0.87, 95% cf.l. 0.77-0.98; p=0.03). The risk of distant metastases was not significantly influenced although it appears to be less in the tumours treated with hypoxic modification (OR: 0.87, 95% cf.l. 0.69-1.09; p=0.22), whereas the radiation related late complications were not influenced by the overall use of hypoxic modifications (OR: 1.00, 95% cf.l. 0.82-1.23; p=0.96). The improvement in loco-regional control was found to be independent of the type of hypoxic modification. The trials have used different fractionation schedules, including large doses per fraction, which may result in relatively more hypoxia and greater benefit. However, analysis of HNSCC trials using conventional fractionation only, showed that the significant effect of hypoxic modification was maintained. Conclusion: The meta-analysis thus demonstrates that there is level 1a evidence in favour of adding hypoxic modification to radiotherapy of squamous cell carcinomas of the head and neck.

Abstract

OBJECTIVE:

The goal of this study was to determine the effect of hyperbaric oxygen therapy on the clinical outcome of patients after resection of meningiomas with conspicuous peritumoral brain edema (PTBE).

PATIENTS AND METHODS:

232 patients with intracranial meningiomas and conspicuous PTBE were allocated to the HBO2 Group or the Control Group (116 in each group). The Karnofsky Performance Score (KPS), the focal brain edema and the encephalomalacia in the operative region, as well as the number of patients with neurological deficits were compared statistically between the two groups at different times after the operation.

RESULTS:

On the third day after operation, the KPS and focal brain edema in the operative region between the HBO2 Group and the Control Group were not significantly different (p > 0.05), but 15 days after surgery, compared with the Control Group, the KPS of the HBO2 Group appeared obviously higher (p < 0.05), and the focal brain edema in the operative region was definitely smaller (p < 0.05). Six months after surgery, the volume of encephalomalacia in operative region and the number of patients with neurological deficits in the HBO2 Group were significantly less than those in the Control Group (p < 0.05).

CONCLUSION:

HBO2 therapy is effective in reducing edema formation and neurological deficits after resection of meningiomas with conspicuous PTBE.

Abstract

PURPOSE:

Soft tissue necrosis is reported in up to 26% of patients undergoing radiotherapy for penile cancer. Management options include local irrigation, wound debridement, antibiotics, anti-inflammatory medication, and analgesics. Refractory lesions may be treated with partial penectomy. Hyperbaric oxygen therapy (HBO) has a well-defined role in the treatment of late radiation toxicities. We present experience with HBO for medically refractory soft tissue necrosis after penile brachytherapy.

METHODS AND MATERIALS:

From November 2001 to January 2009, 7 men of 43 treated with penile brachytherapy for squamous carcinoma developed refractory soft tissue necrosis and were treated with HBO. All had received a prescribed dose of 60Gy through interstitial brachytherapy using Paris system guidelines. All had failed conservative medical therapies for soft tissue necrosis.

RESULTS:

Median age was 55 years (range, 35-72 years). Comorbidities potentially effecting wound healing included hypertension (2), current smokers (5), former smoker (1) but no diabetes mellitus, or peripheral vascular disease. Median time between completion of brachytherapy and appearance of soft tissue necrosis was 13 months (range, 9-24 months) and the median interval before starting HBO was 7.5 months (range, 3-13 months). The median number of "dives" per HBO course was 40 (30-53). All 7 experienced an excellent response with healing of the necrosis and resolution of symptoms, although 3 required an additional course, 2 for consolidation of healing, and 1 for a relapse 4 months later. No patient was submitted to penectomy.

CONCLUSIONS:

HBO should be considered as a treatment option in patients with refractory soft tissue necrosis of the penis after brachytherapy.

Abstract

INTRODUCTION AND OBJECTIVES:

hemorrhagic cystitis (HC) after pelvic radiotherapy occurs in 2-8% of patients. A variety of treatments have been described, most of them with uncertain results. We assessed the efficacy of hyperbaric oxygen therapy (HBOT) in HC cases.

PATIENTS AND METHODS:

retrospective analysis of patients with HC after pelvic radiotherapy receiving HBOT at our center between January 2002 and January 2010. Our protocol included 40 sessions of HBOT in a multiplace hyperbaric chamber with 90minutes of 100% oxygen breathing at 2.2 atm. Success was evaluated in terms of total or partial stop of bladder bleeding. Telephone follow-up was updated at the time of submission in all cases.

RESULTS:

twenty-five patients were treated (21 male, 4 female); the mean age was 66.7 years. Twenty men were irradiated for prostate cancer and one for bladder cancer. Three women had cervix cancer and one endometrial cancer. In all cases previous conservative treatment had failed and HBOT was considered only after other measures failed. All the patients responded to HBOT and none recurred after end of treatment at a mean follow-up of 21.2 months. There were no serious complications.

CONCLUSION:

HBOT is a highly effective and safe, non-invasive therapy for HC secondary to pelvic radiation; it should be considered as first line alternative in these difficult cases.

Abstract

BACKGROUND:

The purpose of this study was to determine the incidence and symptoms of postoperative ischemic bronchitis (POIB) after systematic lymph node dissection (LND) and evaluate the effect of hyperbaric oxygen therapy in patients with primary lung cancer.

METHODS:

From January 2004 to December 2009, 1,071 patients underwent a standard resection for non-small cell lung cancer and radical systematic lymph node dissection. Fiberoptic bronchoscopy was performed systematically between days 7 and 12. We analyzed the clinical and biologic signs of POIB. Once the diagnosis established a treatment by hyperbaric oxygen, therapy was undertaken.

RESULTS:

A POIB was observed in 34 patients (3.21%) (2 women and 32 men). Mean age was 59 ± 10 years (range, 25 to 79 years). A POIB occurred within 8 ± 3 days; after right pulmonary resection (n = 21; 62%) and after left resection (n = 13; 38%). A POIB appeared asymptomatically for 27 patients (80%), whereas only 7 patients (20%) presented with fever and hyperleukocytosis. Their localization were bronchial stumps (n = 21; 62%), homolateral bronchial tree (n = 11; 32%), or extension toward the contralateral bronchial tree (n = 2; 6%). The mean number of hyperbaric oxygen therapy sessions was 14 (1 to 48). A POIB worsening was observed in 6 patients (18%), requiring a surgical rescue therapy.

CONCLUSIONS:

The clinical presentation of POIB is poor and systematic fiberoptic bronchoscopy should be performed, especially in patients with a high risk of bronchopleural fistula. Hyperbaric oxygen therapy in the management of ischemic bronchitis may be a promising adjunctive treatment.

Abstract

BACKGROUND:

Artemisinin selectively kills cancer cells which have more intracellular free iron than do normal cells. Hyperbaric oxygen (HBO(2)) may be beneficial in the treatment of cancer. The hypothesis of this study was that HBO(2) enhances anticancer activity of artemisinin.

MATERIALS AND METHODS:

After pretreatment with 12 μM holotransferrin, Molt-4 human leukemia cells were cultured in 10 μM artemisinin and exposed for 90 min to one of three different conditions: control, room air control, and HBO(2). Cell growth was determined for 48 h after exposure.

RESULTS:

Differences in growth were noted after 6 h of incubation. After 48 h of incubation, growth of cells treated with artemisinin alone or HBO(2) alone was 85% of that of cells grown under artemisinin-free control conditions. Combined artemisinin and HBO(2) treatment resulted in an additional 22% decrease in growth.

CONCLUSION:

Combined HBO(2) and artemisinin exposure may be an effective anticancer chemotherapeutic strategy.

Abstract

OBJECTIVE:

We investigated the effects of hyperbaric oxygen (HBO2) and/or 5-fluorouracil (5-FU) on the proliferation and metastasis of human nasopharyngeal carcinoma (NPC) cell line CNE2Z and the underlying mechanisms involved.

METHODS:

Nasopharyngeal carcinoma (NPC) CNE2Z cells were randomly divided into four groups: Group A: control group; Group B: 5-FU group; Group C: HBO2 group; Group D: 5-FU plus HBO2 group. The inhibitory effects on CNE2Z cells proliferation in the four groups after 24, 48 and 72 hours of treatment were measured by MTT-colorimetric method. Transwell chamber assay was performed to determine the effects of HBO2 and/or 5-FU on the metastasis of CNE2Z cells; Expressions of MMP-9 and VEGF in CNE2Z cells were detected by immunocytochemical staining.

RESULT:

A significant difference was observed in the inhibitory effects on CNE2Z cell proliferation (OD values) between the 5-FU group (Group B) and the control group (Group A) after 24, 48, and 72 hours of treatment (p<0.01); between the HBO2 group (group C) and the control group (Group A) after 48 and 72 hours of treatment (p<0.01); and between the HBO2 plus 5-FU group (Group D) and the control group (Group A) as well as the HBO2 plus 5-FU group (Group D) and the HBO2 group (Group C) after 24, 48, and 72 hours of treatment (p<0.01). But a significant difference between the HBO2 plus 5-FU group (Group D) and the 5-FU group (Group B) was observed only after 48 hours of treatment (p=0.030). As for metastasis, as well as MMP-9 and VEGF expression OD values, significant difference was observed between the 5-FU group (Group B) and the control group (Group A) with p<0.05, but not between the HBO2 group (Group C) and the control group (Group A). Although effects on metastasis as well as MMP-9 and VEGF expression OD values were significantly different between the 5-FU plus HBO group (group D) and group A (p<0.01), no difference was observed between Group D and Group B as well as Group D and Group C.

CONCLUSIONS:

Simple HBO2 treatment after 48 and 72 hours could inhibit the proliferation of nasopharyngeal carcinoma CNE2Z cells. The combination of HBO2 with 5-FU exhibited significant synergism in the suppression of NE2Z cell proliferation only after 48 hours of treatment compared to 5-FU. Simple HBO2 treatment could not reduce the high expressions of MMP-9 and VEGF and inhibit the metastasis of human NPC CNE2Z cells, and no synergistic effect was observed for the combination of HBO2 with 5-FU compared to 5-FU alone.

Abstract

Although hyperbaric oxygen has been shown to enhance the efficacy of radiotherapy and chemotherapy for the treatment of several malignant tumors, the impact of hyperbaric oxygen on osteosarcoma has not yet been demonstrated. In this study, we investigated the efficacy of hyperbaric oxygen alone and in combination with an anti-cancer drug as an adjuvant to chemotherapy. In vitro, highly metastatic murine osteosarcoma cell lines were exposed to hyperbaric oxygen and cell viability was examined. Hyperbaric oxygen alone significantly suppressed cell proliferation, and hyperbaric oxygen plus carboplatin exhibited significant synergism in suppression of cell proliferation. In vivo, C3H mice were subcutaneously inoculated with osteosarcoma cells and divided into four groups: control, hyperbaric oxygen, carboplatin, and carboplatin plus hyperbaric oxygen. After 5 weeks, increase in both tumor volume and number of lung metastases was significantly suppressed in the hyperbaric oxygen group. Concomitant hyperbaric oxygen clearly enhanced the chemotherapeutic effects of carboplatin on both tumor growth and lung metastasis in osteosarcoma-bearing mice. Moreover, mortality in the carboplatin plus hyperbaric oxygen group was significantly lower than in the other three groups. These findings suggest that hyperbaric oxygen plus carboplatin combination therapy could be an appropriate therapeutic regimen for the treatment of patients with osteosarcoma.

Abstract

PURPOSE:

Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT).

METHODS AND MATERIALS:

From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up.

RESULTS:

On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC H&N35 Dry Mouth (p = 0.009), EORTC H&N35, Sticky Saliva (p = 0.01), PSS Eating in Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001).

CONCLUSIONS:

Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth.