A phase III randomized double-blind placebo-controlled clinical trial to determine the efficacy of low level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic cell transplantation. Low-level infrared laser therapy in chemotherapy-induced oral mucositis: a randomized placebo-controlled trial in children. Effect of low level helium-neon (He-Ne) laser therapy in the prevention & treatment of radiation induced mucositis in head & neck cancer patients. Patient-controlled analgesia vs. conventional intramuscular analgesia following colon surgery. Patient-controlled analgesic administration. A comparison of steady-state morphine infusions with bolus doses. Comparison of a patient-controlled analgesia system with continuous infusion for administration of diamorphine for mucositis. Adolescents use patient-controlled analgesia effectively for relief from prolonged oropharyngeal mucositis pain. Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy. Effect of the intensity of transcutaneous acupoint electrical stimulation on the postoperative analgesic requirement.
Oral mucositis (OM) is a significant early complication of hematopoietic cell transplantation (HCT). This phase III randomized double-blind placebo-controlled study was designed to compare the ability of 2 different low level GaAlAs diode lasers (650 nm and 780 nm) to prevent oral mucositis in HCT patients conditioned with chemotherapy or chemoradiotherapy.
                Seventy patients were enrolled and randomized into 1 of 3 treatment groups: 650 nm laser, 780 nm laser or placebo. All active laser treatment patients received daily direct laser treatment to the lower labial mucosa, right and left buccal mucosa, lateral and ventral surfaces of the tongue, and floor of mouth with energy densities of 2 J/cm2. Study treatment began on the first day of conditioning and continued through day +2 post HCT. Mucositis and oral pain was measured on days 0, 4, 7, 11, 14, 18, and 21 post HCT.
                The 650 nm wavelength reduced the severity of oral mucositis and pain scores. Low level laser therapy was well-tolerated and no adverse events were noted.
                While these results are encouraging, further study is needed to truly establish the efficacy of this mucositis prevention strategy. Future research needs to determine the effects of modification of laser parameters (e.g., wavelength, fluence, repetition rate of energy delivery, etc.) on the effectiveness of LLE laser to prevent OM. Oral mucositis (OM) is one of the most frequent complications of chemotherapy for which there is no standard therapy; treatment is mostly conservative. This study was conducted to determine whether low-intensity laser therapy (LLLT) can reduce the duration of chemotherapy-induced OM.
                A placebo-controlled randomized trial was carried out using LLLT or placebo (sham treatment). Children and adolescents with cancer receiving chemotherapy or hematopoietic stem-cell transplantation between October 2005 and May 2006 were eligible as soon as they developed OM. Patients received intervention for 5 days. The LLLT group was treated with laser GaAlAs, wavelength (lambda): 830 nm (infrared), power: 100 mW, dose: 4 J/cm, and placebo group underwent sham treatment. The grade of OM was clinically assessed by the National Cancer Institute, Common Toxicity Criteria scale.
                Twenty-one patients developed OM and were evaluable for analysis; 18 (86%) patients had a diagnosis of leukemia or lymphoma and 3(14%) had solid tumors. The mean age was 8.2 (+/-3.1) years. Nine patients were randomized in the laser group and 12 in the placebo-control group. Once OM was diagnosed, the patients had daily OM grading assessments before laser or sham application and thereafter until complete healing of the lesions. On day 7 after OM diagnosis, 1/9 of patients remained with lesions in laser group and 9/12 of patients in the placebo-control group (P=0.029). In the laser group, the mean of OM duration was 5.8+/-2 days and in the placebo group was 8.9+/-2.4 days (P=0.004).
                Our study has shown evidence that laser therapy in addition to oral care can decrease the duration of chemotherapy-induced OM. Our results confirm the promising results observed in adult cancer patients and should encourage pediatric oncologists to use laser therapy as first-line option in children with chemotherapy-induced OM. Oral mucositis is a common debilitating complication of radiotherapy occurring in about 60 per cent of cancer patients. Considerable buccal toxicity of radiotherapy or chemotherapy in cancer patients to become discouraged and can affect their quality of life. In addition, such toxicity can alter the treatment plan. At present, there is no clinically appropriate prophylaxis efficacious antidote for mucositis. The low level laser (LEL) appears to be a simple, non-traumatic technique for the prevention and treatment of radiation induced mucositis. Therefore the present study was carried out to find out the effect of low-level helium-neon (He-Ne) laser in the prevention and treatment of radiation induced mucositis in head and neck cancer patients.
                The patients with carcinoma of oral cavity with stages II-IV a being uniformly treated with curative total tumour dose of 66 Gy in 33 fractions over 6 wk were selected for the study. The patients were divided based on computer generated randamosization into laser (study group) and control groups with 25 patients in each group. Both study and control groups were comparable in terms of site of the lesion, stage of the cancer and histology. The study group patients were treated with He-Ne laser (wavelength 632.8 nm and output of 10mW) and control group patients were given oral analgesics, local application of anaesthetics, 0.9 per cent saline and povidine wash during the course of radiotherapy.
                All patients tolerated the laser treatment without any adverse effect or reactions. The result showed a significant difference in pain and mucositis (P<0.001) between the two groups. At the end of radiotherapy (after 6 wk) mean pain sure and mucositis grade were significantly lower (P<0.001) in the study group compared to control.
                The low-level He-Ne laser therapy during the radiotherapy treatment was found to be effective in preventing and treating the mucositis in head and neck cancer patients. Further studies need to be done on a larger sample to find the mechanism. Though patient-controlled analgesia (PCA) has been in use for over a decade, it has been popularized only recently. Conventional techniques of intermittent intramuscular (IM) administration of analgesia have fallen short of meeting the needs of patients following major abdominal surgery. This has prompted a search for methods to improve postoperative pain management. Though PCA has been accepted in many hospitals, few studies comparing conventional IM administration of morphine with PCA have been performed. A prospective randomized study comparing IM- and PCA-administered morphine in 62 patients undergoing colon surgery was performed. A comparison of the efficacy of analgesia and extent of sedation using these approaches shows that PCA allows for analgesia with less sedation and less drug requirement than that of IM administration. No differences were noted in postoperative duration of ileus, duration of hospitalization, and total hospital costs. This study confirms the safety and efficacy of PCA, and should be considered the current optimal method of controlling pain following major colonic surgery. The authors have shown previously that bone marrow transplant (BMT) patients who self-administered bolus doses of morphine gained equal oral mucositis pain relief while using less drug compared with similar patients receiving morphine by staff-controlled continuous infusion. In a follow-up study they compared the efficacy and side effects of morphine in two groups of marrow transplant patients who controlled their own analgesic administration either by conventional bolus-dose, patient-controlled analgesia (PCA) or by adjusting the rate of continuous morphine infusion to increase or decrease their plasma morphine concentration. Patients controlling their morphine infusion rates (pharmacokinetically based patient-controlled analgesia [PKPCA] group) obtained more relief from oral mucositis pain than did patients using conventional PCA. Patients in the PKPCA group used more morphine than PCA patients and achieved superior pain relief without significant increases in side effects (e.g., nausea, mood changes, sedation). The authors conclude that PKPCA improves the management of prolonged, severe pain in marrow transplant patients and that this approach to patient-controlled analgesia may be useful in other types of persistent pain. Mucositis remains an important problem following BMT and may delay discharge from hospital. Patient-controlled analgesia (PCA) systems have been reported to be of benefit in controlling BMT-associated mucositis. The present study comprised 65 patients (age range 16-68 years; 19 allografts, 29 peripheral blood stem cell autografts and 17 autologous bone marrow). Subjects were prospectively randomised to receive intravenous diamorphine for pain relief either by conventional continuous infusion (CI) or by PCA, using a Medex Walkman 440 delivery system. Each patient assessed his/her pain control and nausea daily by a visual analogue scale. Twenty-two patients did not require any diamorphine. Four patients required diamorphine for pain other than mucositis, and four patients failed PCA control. Of 35 assessable cases, no difference in pain control was noted between CI and PCA. However, PCA-controlled patients required significantly less diamorphine than CI controlled patients (mean, 131 +/- 23 mg for PCA vs 296 +/- 40 mg for CI; P = 0.001), and PCA required fewer days of diamorphine than CI (mean, 7.17 +/- 0.66 days for PCA, 9.00 +/- 0.65 days for CI; P = 0.03). Side-effects were minimal and equivalent in the two arms. The findings suggest that PCA and CI offer equivalent control of the pain of BMT-associated mucositis, but PCA requires less total consumption and duration of diamorphine therapy. We compared patient-controlled analgesia (PCA) and continuous infusion (CI) morphine delivery in a randomized controlled trial in adolescents during oropharyngeal mucositis pain after bone marrow transplantation. Results from 20 patients who completed 7 or more days on study (10 PCA, 10 CI) were evaluated. The group means for age, weight and height were comparable. Daily measures were morphine intake, self-report of pain intensity and side effect scores. Over 10 study days, the mean cumulative morphine dose to subjects in each group was 4.94 mg/kg (PCA) vs. 12.17 mg/kg (CI); the difference is significant (P less than 0.01). No significant differences were found between the groups for patient ratings of pain intensity or side effect scores despite the large difference in mean morphine intake, but the PCA group tended to report less intense sedation and less difficulty concentrating. Adolescents can use PCA effectively and safely for 1-3 weeks. Morphine intake of adolescent patients using PCA morphine intake is significantly lower than that of similar patients receiving staff-controlled CI. This study assessed the use of low-energy laser in the prevention or reduction of the severity of oral mucositis.
                A randomized clinical trial was carried out. Patients from 3 to 18 years of age treated with chemotherapy or hematopoietic stem-cell transplantation between May, 2003 and February, 2005 were eligible. The intervention group received laser application for 5 days following the start of chemotherapy. The grade of oral mucositis was assessed by the WHO per NCI-CTC common toxicity criteria and the assessments were made on days 1, 8 and 15 by a trained examiner blind to the intervention.
                Sixty patients were evaluable for analysis; thirty-nine (65%) were males, 35 (58%) patients had a diagnosis of leukemia or lymphoma, and 25 (42%) had solid tumors. The mean age was 8.7 +/- 4.3 years. Twenty-nine patients were randomized in the laser group and 31 in the control group. On day 1, no patients presented with mucositis. On day 8, of 20 patients (36%) who developed mucositis, 13 of them were from the laser group and 7 from the control group. On day 15, of 24 patients (41%) who developed mucositis, 13 of them were from the laser group and 11 from the control group. There was no significant difference between groups concerning the grades of mucositis on day 8 (P = 0.234) or on day 15 (P = 0.208).
                This study showed no evidence of benefit from the prophylactic use of low-energy laser in children and adolescents with cancer treated with chemotherapy when optimal dental and oral care was provided. Given the inherent side effects associated with both opioid and nonopioid analgesic drugs, a nonpharmacologic therapy that could decrease the need for analgesic medication would be valuable. We designed a sham-controlled study to assess the effect of the intensity of transcutaneous acupoint electrical stimulation (TAES) on postoperative patient-controlled analgesia (PCA) requirement for hydromorphone (HM), the incidence of opioid-related side effects, and the recovery profile after lower abdominal surgery. One hundred one healthy consenting women undergoing lower abdominal procedures with a standardized general anesthetic technique were randomly assigned to one of four postoperative analgesic treatment regimens: Group I (n = 26) PCA only; Group II (n = 25), PCA + sham-TAES (no electrical stimulation); Group III (n = 25), PCA + low-TAES (4-5 mA of electrical stimulation); Group IV (n = 25), PCA + high-TAES (9-12 mA of electrical stimulation). The PCA device was programmed to deliver HM, 0.2-0.4 mg intravenously boluses "on demand," with a minimum lockout interval of 10 min. The TAES skin electrodes were placed at the Hegu acupoint on the nondominant hand and on both sides of the surgical incision. The TAES frequency was set in the dense-and-disperse mode, alternating at 2 Hz and 100 Hz every 3 s, with stimulation of the hand and incision alternated every 6 s. The patients in Groups II-IV were instructed to use TAES every 2 h for 30 min while awake. After discontinuation of PCA, oral pain medications were administered on demand. The postoperative PCA-HM requirement, pain scores, opioid-related side effects, and requirements for antiemetic and antipruritic medication were recorded. High-TAES decreased the HM requirement by 65% and reduced the duration of PCA therapy, as well as the incidence of nausea, dizziness, and pruritus. Low-TAES produced a 34% decrease in the HM requirement compared with only 23% in the "sham" TAES group. We conclude that high-TAES produced a significant decrease in the PCA opioid requirement and opioid-related side effects after low intraabdominal surgery.
There is limited evidence from two small trials that low level laser treatment reduces the severity of the mucositis. Less opiate is used for PCA versus continuous infusion. Further, well designed, placebo or no treatment controlled trials assessing the effectiveness of interventions investigated in this review and new interventions for treating mucositis are needed.