Pathogenetic mechanisms in radiation fibrosis.

Background
Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery.

Objectives
To assess the benefits and harms of HBOT for treating or preventing LRTI.

Search methods
We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11), MEDLINE, EMBASE, DORCTIHM and reference lists of articles in December 2015. We also searched for ongoing trials at clinicaltrials.gov.

Selection criteria
Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing.

Data collection and analysis
Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials.

Main results
Fourteen trials contributed to this review (753 participants). There was some moderate quality evidence that HBOT was more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P value = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5; 246 participants, 3 studies). There was also moderate quality evidence of a significantly improved chance of wound breakdown without HBOT following operative treatment for ORN (RR 4.2; 95% CI 1.1 to 16.8, P value = 0.04, NNTB 4; 264 participants, 2 studies). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P value = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P value = 0.0002, NNTB 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P value = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P value = 0.009, NNTB 4).

There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no randomised data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse events.

Authors' conclusions
These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.

/pdf/hyperbaric-oxygen-therapy-for-late-radiation-tissue-injury-4bf3uk0upd.pdf

Hyperbaric oxygen therapy for late radiation tissue injury

Radiation enteropathy remains an important obstacle to uncomplicated cancer cures after radiation therapy of pelvic and abdominal malignancies. Moreover, the prevalence of radiation enteropathy in the population exceeds that of IBD. This Review introduces the clinical problem of radiation enteropathy, discusses contemporary concepts in pathogenesis, current therapeutic options and strategies for development of new radioprotective agents.

Radiation enteropathy--pathogenesis, treatment and prevention.

The goal of this review is to outline advances addressing the role that reactive species of oxygen and nitrogen play in therapeutic mechanisms of hyperbaric oxygen. The review will be organized around major categories of problems or processes where controlled clinical trials have demonstrated clinical efficacy for hyperbaric oxygen therapy. Reactive species are now recognized to play a major role in cell signal transduction cascades, and the discussion will focus on how hyperbaric oxygen acts through these pathways to mediate wound healing and ameliorate postischemic and inflammatory injuries.

https://www.physiology.org/doi/pdf/10.1152/japplphysiol.91004.2008

Oxidative stress is fundamental to hyperbaric oxygen therapy.

Backgound The number of patients with chronic gastrointestinal (GI) symptoms after cancer therapies which have a moderate or severe impact on quality of life is similar to the number diagnosed with inflammatory bowel disease annually. However, in contrast to patients with inflammatory bowel disease, most of these patients are not referred for gastroenterological assessment. Clinicians who do see these patients are often unaware of the benefits of targeted investigation (which differ from those required to exclude recurrent cancer), the range of available treatments and how the pathological processes underlying side effects of cancer treatment differ from those in benign GI disorders. This paper aims to help clinicians become aware of the problem and suggests ways in which the panoply of syndromes can be managed. Methods A multidisciplinary literature review was performed to develop guidance to facilitate clinical management of GI side effects of cancer treatments. Results Different pathological processes within the GI tract may produce identical symptoms. Optimal management requires appropriate investigations and coordinated multidisciplinary working. Lactose intolerance, small bowel bacterial overgrowth and bile acid malabsorption frequently develop during or after chemotherapy. Toxin-negative Clostridium difficile and cytomegalovirus infection may be fulminant in immunosuppressed patients and require rapid diagnosis and treatment. Hepatic side effects include reactivation of viral hepatitis, sinusoidal obstruction syndrome, steatosis and steatohepatitis. Anticancer biological agents have multiple interactions with conventional drugs. Colonoscopy is contraindicated in neutropenic enterocolitis but endoscopy may be life-saving in other patients with GI bleeding. After cancer treatment, simple questions can identify patients who need referral for specialist management of GI symptoms. Other troublesome pelvic problems (eg, urinary, sexual, nutritional) are frequent and may also require specialist input. The largest group of patients affected by chronic GI symptoms are those who have been treated with pelvic radiotherapy. Their complex symptoms, often caused by more than one diagnosis, need systematic investigation by gastroenterologists when empirical

https://gut.bmj.com/content/gutjnl/early/2011/11/04/gutjnl-2011-300563.full.pdf

Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer

BACKGROUND
In the critical care environment, individuals who undergo tracheostomy are highly susceptible to tracheostomy-related pressure injuries.


OBJECTIVE
To evaluate the effectiveness of interventions to reduce tracheostomy-related pressure injury in the critical care setting.


METHODS
MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for studies of pediatric or adult patients in intensive care units conducted to evaluate interventions to reduce tracheostomy-related pressure injury. Reviewers independently extracted data on study and patient characteristics, incidence of tracheostomy-related pressure injury, characteristics of the interventions, and outcomes. Study quality was assessed using the Cochrane Collaboration's risk-of-bias criteria.


RESULTS
Ten studies (2 randomized clinical trials, 5 quasi-experimental, 3 observational) involving 2023 critically ill adult and pediatric patients met eligibility criteria. The incidence of tracheostomy-related pressure injury was 17.0% before intervention and 3.5% after intervention, a 79% decrease. Pressure injury most commonly involved skin in the peristomal area and under tracheostomy ties and flanges. Interventions to mitigate risk of tracheostomy-related pressure injury included modifications to tracheostomy flange securement with foam collars, hydrophilic dressings, and extended-length tracheostomy tubes. Interventions were often investigated as part of care bundles, and there was limited standardization of interventions between studies. Meta-analysis supported the benefit of hydrophilic dressings under tracheostomy flanges for decreasing tracheostomy-related pressure injury.


CONCLUSIONS
Use of hydrophilic dressings and foam collars decreases the incidence of tracheostomy-related pressure injury in critically ill patients. Evidence regarding individual interventions is limited by lack of sensitive measurement tools and by use of bundled interventions. Further research is necessary to delineate optimal interventions for preventing tracheostomy-related pressure injury.

Prevention of Tracheostomy-Related Pressure Injury: A Systematic Review and Meta-analysis.

BACKGROUND
Hospital-acquired pressure injuries, including those related to airway devices, are a significant source of morbidity in critically ill patients.


OBJECTIVE
To determine the incidence of endotracheal tube-related pressure injuries in critically ill patients and to evaluate the effectiveness of interventions designed to prevent injury.


METHODS
MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for studies of pediatric or adult patients in intensive care units that evaluated interventions to reduce endotracheal tube-related pressure injury. Reviewers extracted data on study and patient characteristics, incidence of pressure injury, type and duration of intervention, and outcomes. Risk of bias assessment followed the Cochrane Collaboration's criteria.


RESULTS
Twelve studies (5 randomized clinical trials, 3 quasi-experimental, 4 observational) representing 9611 adult and 152 pediatric patients met eligibility criteria. The incidence of pressure injury was 4.2% for orotracheal tubes and 21.1% for nasotracheal tubes. Interventions included anchor devices, serial endotracheal tube assessment or repositioning, and barrier dressings for nasotracheal tubes. Meta-analysis revealed that endotracheal tube stabilization was the most effective individual intervention for preventing pressure injury. Nasal alar barrier dressings decreased the incidence of skin or mucosal injury in patients undergoing nasotracheal intubation, and data on effectiveness of serial assessment and repositioning were inconclusive.


CONCLUSIONS
Airway device-related pressure injuries are common in critically ill patients, and patients with nasotracheal tubes are particularly susceptible to iatrogenic harm. Fastening devices and barrier dressings decrease the incidence of injury. Evidence regarding interventions is limited by lack of standardized assessments.

Prevention of Endotracheal Tube-Related Pressure Injury: A Systematic Review and Meta-analysis.

Purpose Cancer patients who undergo radiotherapy remain at life-long risk of radiation-induced injury to normal tissues. We conducted a randomized, controlled, double-blind crossover trial with long-term follow-up to evaluate the effectiveness of hyperbaric oxygen for refractory radiation proctitis. Methods and Materials Patients with refractory radiation proctitis were randomized to hyperbaric oxygen at 2.0 atmospheres absolute (Group 1) or air at 1.1 atmospheres absolute (Group 2). The sham patients were subsequently crossed to Group 1. All patients were re-evaluated by an investigator who was unaware of the treatment allocation at 3 and 6 months and Years 1–5. The primary outcome measures were the late effects normal tissue-subjective, objective, management, analytic (SOMA-LENT) score and standardized clinical assessment. The secondary outcome was the change in quality of life. Results Of 226 patients assessed, 150 were entered in the study and 120 were evaluable. After the initial allocation, the mean SOMA-LENT score improved in both groups. For Group 1, the mean was lower ( p = 0.0150) and the amount of improvement nearly twice as great (5.00 vs. 2.61, p = 0.0019). Similarly, Group 1 had a greater portion of responders per clinical assessment than did Group 2 (88.9% vs. 62.5%, respectively; p = 0.0009). Significance improved when the data were analyzed from an intention to treat perspective ( p = 0.0006). Group 1 had a better result in the quality of life bowel bother subscale. These differences were abolished after the crossover. Conclusion Hyperbaric oxygen therapy significantly improved the healing responses in patients with refractory radiation proctitis, generating an absolute risk reduction of 32% (number needed to treat of 3) between the groups after the initial allocation. Other medical management requirements were discontinued, and advanced interventions were largely avoided. Enhanced bowel-specific quality of life resulted.

http://hyperbaricinformation.com/HBO-Articles/HBO-Radiation/Int-J-Radiation-Oncol-Biol-Phys-2008-72(1)-134-143-Clarke-HO.pdf

Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up.

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Prevention of Tracheostomy-Related Pressure Injury: A Systematic Review and Meta-analysis.

Prevention of Endotracheal Tube-Related Pressure Injury: A Systematic Review and Meta-analysis.

Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up.