Neurological Outcomes of Chemotherapy-Induced Peripheral Neuropathy in Patients With Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to determine whether chemotherapy-induced peripheral neuropathy (CIPN) affects the risk of falls and physical function in patients with cancer. METHODS: A literature search was conducted in the CINAHL, Scopus, and PubMed databases for articles published from January 1950 to April 2022. Seven review authors retrieved studies using predetermined eligibility criteria, extracted the data, and evaluated the quality. RESULTS: Nine studies were included in the analysis. Patients with CIPN had a significantly higher risk of falls than those without CIPN (risk ratio = 1.38, 95% confidence interval [CI] =1.18-1.62). Patients with CIPN had lower grip strength (standardized mean difference [SMD] =-0.42, 95% CIs = -0.70 to -0.14, P = .003), longer chair stand time (SMD = 0.56, 95% CIs = -0.01 to 1.17, P = .05), worse timed up and go test time (SMD = 0.79, 95% CIs = 0.41 to 1.17, P < .0001), and lower mean Fullerton Advanced Balance scale score (SMD = -0.81, 95% CIs = -1.27 to -0.36, P = .005) than patients without CIPN. There were no significant differences in gait speed (P = .38) or Activities-specific Balance Confidence Scale score (P = .09) between patients with and without CIPN. CONCLUSIONS: This systematic review and meta-analysis demonstrated that patients with CIPN are prone to falls and impaired balance function and muscle strength.

Effects of aerobic, resistance, and mixed exercises on quality of life in patients with cancer: A systematic review and meta-analysis.

BACKGROUND: Quality of life has multiple aspects, but little is known about the effects of exercise on each domain of it. This systematic review aimed to determine the effects of aerobic, resistance, and mixed exercise on multiple aspects of quality of life in patients with cancer through a meta-analysis. METHODS: Randomized controlled trials with quality of life were collected, and 20 studies were analyzed. Subgroup analyses were performed according to exercise types. RESULTS: Exercise improved global, physical, role, and emotional quality of life, but not cognitive and social quality of life. Aerobic, resistance, and mixed exercises improved global, physical, role, emotional, and social quality of life; global, physical and role quality of life; and only physical quality of life, respectively. CONCLUSION: According to exercise type, aerobic and resistance exercises improved global, physical, and role quality of life, whereas aerobic exercise only improved emotional quality of life.

Effect of Exercise on Mortality and Recurrence in Patients With Cancer: A Systematic Review and Meta-Analysis.

Purpose: Exercise could lower the risk of cancer recurrence and improve mortality, exercise capacity, physical and cardiovascular function, strength, and quality of life in patients with cancer. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to determine the effects of exercise on mortality and recurrence in patients with cancer. Methods: We searched for articles published before May 2019 in MEDLINE, CINAHL, the Cochrane Library, Scopus, ProQuest, and PEDro. We included RCTs of exercise interventions, such as resistance exercise and aerobic exercise, in patients with cancer that evaluated the risk of mortality and recurrence. The standardized mean difference with 95% confidence intervals (CIs) was calculated for quantitative indices. The random-effect model was used as the pooling method. Results: Of 2868 retrieved articles, 8 RCTs were included in the meta-analysis, with a mean PEDro score of 4.50 (SD = 1.25). Exercise significantly reduced the risk of mortality in patients with cancer and in cancer survivors (risk ratio [RR] = 0.76, 95% CI = 0.40-0.93, I2 = 0%, P = .009). Exercise significantly reduced the risk of recurrence in cancer survivors (RR = 0.52, 95% CI = 0.29-0.92, I2 = 25%, P = .030). Conclusion: This study found that exercise has a favorable effect on mortality and recurrence in patients with cancer. However, the effect could not be fully determined due to data insufficiency.

Effects of transcutaneous electrical nerve stimulation on physical symptoms in advanced cancer patients receiving palliative care.

Transcutaneous electrical nerve stimulation (TENS) is primarily used for pain, but might be useful for various other physical symptoms, including nausea, fatigue, dyspnea, and constipation. However, few studies have used TENS for treating the physical symptoms of patients with advanced cancer. In this crossover trial, we assess the effects of TENS on pain and other physical symptoms in 20 in-patients with advanced cancer receiving palliative care. For 5-day phases between wash out periods of 5 days, patients received TENS or non-TENS. TENS was delivered at four points: the center of the back for mainly nausea and dyspnea, on the back at the same dermatomal level as the origin of the pain (100 Hz), and on both ankle joints for constipation (10 Hz). The intensity of pain and the total opioid dose used during phases were recorded. Physical symptoms were evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL). Hematological and biochemical data were recorded before and after the TENS phase. The average pain and total number of opioid rescue doses were significantly reduced by TENS. TENS tended to improve nausea and appetite loss, but not constipation. There were no effects on hematological and biochemical parameters. Use of TENS could safely improve pain, nausea, and appetite loss in patients with advanced cancer. Although it cannot be used as a substitute for opioids and other pharmaceutical treatment, it may be useful to support palliative care.

Influence of Hemoglobin Level on Muscle and Physical Functions, Activities of Daily Living, and Quality of Life in Patients With Hematological Malignancies.

PURPOSE: Patients with hematological malignancies often present with reduced muscle and physical functions, which are caused by the disease or related treatment. Moreover, patients with hematological malignancies rapidly develop low hemoglobin levels, and this may affect muscle and physical functions. This study aimed to identify the influence of hemoglobin levels on muscle and physical functions in patients with hematological malignancies. METHODS: Using a cross-sectional study design, this study included 60 patients with hematological malignancies (mean age = 68.0 ± 10.2 years, women 56.7%) who were hospitalized for chemotherapy- and radiotherapy-related side effects and underwent examination for skeletal muscle mass (SMM), muscle strength, physical function, activities of daily living (ADLs), psychological status, and quality-of-life (QOL), including physical symptoms. Participants were divided into 3 groups according to tertiles of hemoglobin levels: low (n = 19), middle (n = 20), and high (n = 21). Evaluation items were compared among the 3 groups. RESULTS: There was no significant difference among the 3 groups in terms of SMM. The low hemoglobin group showed significantly higher values of fatigue and dyspnea and lower values of muscle strength, ADLs, and QOL than the high hemoglobin group. CONCLUSIONS: Hemoglobin levels did not affect SMM; however, muscle weakness, decrease in physical function, physical symptoms such as fatigue and dyspnea, and decline in ADLs and QOL were observed in patients with low hemoglobin levels.

Effects of Twitch Contraction Induced by Magnetic Stimulation on Expression of Skeletal Muscle Fibrosis Related Genes and Limited Range of Motion in Rats.

OBJECTIVE: We examined the effects of twitch contraction induced by lumbar spinal root magnetic stimulation on immobilization-induced limited range of motion and skeletal muscle fibrosis in rat soleus muscle. DESIGN: The groups included male Wistar rats (controls), rats with both bilateral ankle joints immobilized with plaster casts for 4 wks (immobilization [IM]), and rats in which twitch contraction of the soleus muscle was induced by lumbar magnetic stimulation for 4 wks of immobilization (twitch contraction [TC]). Group differences in ankle dorsiflexion range of motion, collagen content as determined by hydroxyproline assay, and the expression of fibrosis-related genes as determined by reverse transcription-polymerase chain reaction (hypoxia inducible factor 1α, α-smooth muscle actin, and types I and III collagen) in the soleus muscle were examined after the 4-wk-long experiment. RESULTS: Range of motion in the TC group was significantly greater than that in the IM group. The hydroxyproline content and the expressions of fibrosis-related genes decreased significantly in the TC group compared with those in the IM group. No significant differences were seen in the expression of transforming growth factor ß mRNA. CONCLUSIONS: These results suggest that twitch contraction induced by lumbar spinal root magnetic stimulation may reduce immobilization-induced limited range of motion and skeletal muscle fibrosis.

Effects of Physical-Agent Pain Relief Modalities for Fibromyalgia Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Purpose: We conducted a systematic review and meta-analysis to investigate the effects of the following physical-agent modalities for pain relief in fibromyalgia (FM) patients. Methods: We identified randomized controlled studies of adults with FM in the MEDLINE, CINAHL, and PEDro databases. The primary outcome measure was pain relief measured by a visual analogue scale (VAS), and the secondary outcome measures of interest were subjective improvements in the number of tender points, Fibromyalgia Impact Questionnaire (FIQ), and quality of life (QOL) scores. Results: Eleven studies were included in our review. The studies' physical-agent modalities were low-level laser therapy (LLLT), thermal therapy, electromagnetic field therapy, and transcutaneous electrical nerve stimulation (TENS). LLLT did not reduce VAS scores, but it significantly reduced both the number of tender points and FIQ score. Thermal therapy was associated with significantly reduced VAS scores, tender points, and FIQ scores. Electromagnetic field therapy was associated with significantly reduced VAS score and FIQ score. TENS significantly reduced VAS scores. Conclusion: Our analyses revealed that thermal therapy and LLLT had a partial effect on pain relief in FM patients, and this beneficial effect may have a positive influence on FM patients' health status.

Effects of Aerobic and Resistance Exercises on Physical Symptoms in Cancer Patients: A Meta-analysis.

OBJECTIVE: This study aimed to conduct a meta-analysis to establish the effect of exercise interventions on physical symptoms, including fatigue, nausea/vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, and diarrhea in cancer patients and survivors. METHODS: We searched articles published before April 2017 using the following databases: Cochrane Library, PubMed/MEDLINE, CINAHL, Scopus, PEDro, Health & Medical Collection, and Psychology Database. Randomized controlled trials (RCTs) of exercise intervention in cancer patients, which evaluated cancer-related physical symptoms using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, were included. Symptom scale data were extracted for meta-analysis. Subgroup analyses were performed for exercise types (aerobic, resistance, and mixed exercise programs). RESULTS: Of the 659 articles, 10 RCTs were included in the meta-analysis, of which the mean PEDro score was 5.43 (SD = 1.28). Fatigue, pain, dyspnea, and insomnia were significantly lower in the intervention group than in the control group at postintervention in cancer patients. However, exercise intervention did not promote or suppress nausea/vomiting, loss of appetite, constipation, and diarrhea in cancer patients. The effect of exercise type on each symptom was not different. CONCLUSION: Exercise intervention was confirmed to improve fatigue, pain, and insomnia and might have reduced dyspnea in cancer patients. However, the benefits of exercise on nausea/vomiting, loss of appetite, constipation, and diarrhea were not shown in any exercise type. Further research is warranted to examine the effects of exercise interventions on physical symptoms in cancer patients.

Cyclic muscle twitch contraction inhibits immobilization-induced muscle contracture and fibrosis in rats.

We investigated the effects of cyclic muscle twitch contraction caused by neuromuscular electrical stimulation (NMES) on immobilization-induced muscle contracture and fibrosis in rats. Twenty-nine rats were divided into control, immobilization, and immobilization with muscle contraction groups. The ankle joints of the immobilization and muscle contraction rats were fixed in full plantar flexion with a plaster cast for 4 weeks. In the muscle contraction group, cyclic muscle twitch contraction of the soleus muscle was induced using a commercial device (1 Hz, 4 ± 2 mA, 60 min/day, 5 times/week) with the ankle joint immobilized. The dorsiflexion range of ankle joint motion in the muscle contraction group was significantly greater than that in the immobilization group. The expressions of fibrosis-related genes (i.e., hypoxia inducible factor-1α, transforming growth factor-ß1, α-smooth muscle actin, and types I and III collagen) were significantly decreased in the muscle contraction group compared to the immobilization group. The fluorescence intensities of type I and type III collagen in the perimysium and endomysium in the muscle contraction group were significantly decreased compared to the immobilization group. These results suggest that cyclic muscle twitch contraction induced by NMES might alleviate skeletal muscle fibrosis, reducing immobilization-induced muscle contracture.

Hyperalgesia in an immobilized rat hindlimb: effect of treadmill exercise using non-immobilized limbs.

Cast immobilization of limbs causes hyperalgesia, which is a decline of the threshold of mechanical and thermal mechanical stimuli. The immobilization-induced hyperalgesia (IIH) can disturb rehabilitation and activities of daily living in patients with orthopedic disorders. However, it is unclear what therapeutic and preventive approaches can be used to alleviate IIH. Exercise that activates the descending pain modulatory system may be effective for IIH. The purpose of this study was to investigate the effects of treadmill exercise during the immobilization period, using the non-immobilized limbs, on IIH. Thirty-six 8-week-old Wistar rats were randomly divided into (1) control, (2) immobilization (Im), and (3) immobilization and treadmill exercise (Im+Ex) groups. In the Im and Im+Ex groups, the right ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for an 8-week period. In the Im+Ex group, treadmill exercise (15 m/min, 30 min/day, 5 days/week) was administered during the immobilization period while the right hindlimb was kept immobilized. Mechanical hyperalgesia was measured using von Frey filaments every week. To investigate possible activation of the descending pain modulatory system, beta-endorphin expression levels in hypothalamus and midbrain periaqueductal gray were analyzed. Although IIH clearly occurred in the Im group, the hyperalgesia was partially but significantly reduced in the Im+Ex group. Beta-endorphin, which is one of the endogenous opioids, was selectively increased in the hypothalamus and midbrain periaqueductal gray of the Im+Ex group. Our data suggest that treadmill running using the non-immobilized limbs reduces the amount of hyperalgesia induced in the immobilized limb even if it is not freed. This ameliorating effect might be due to the descending pain modulatory system being activated by upregulation of beta-endorphin in the brain.

The non-thermal effects of pulsed ultrasound irradiation on the development of disuse muscle atrophy in rat gastrocnemius muscle.

This study examined the effects of therapeutic pulsed ultrasound (US) on the development of disuse muscle atrophy in rat gastrocnemius muscle. Male Wistar rats were randomly distributed into control, immobilization (Im), sham US, and US groups. In the Im, sham US and US groups, the bilateral ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for a 4-wk period. The pulsed US (frequency, 1 MHz; intensity, 1.0 W/cm(2); pulsed mode 1:4; 15 min) was irradiated to the gastrocnemius muscle in the US group over a 4-wk immobilization period. The pulsed US irradiation delivered only non-thermal effects to the muscle. In conjunction with US irradiation, 5-bromo-2'-deoxyuridine (BrdU) was injected subcutaneously to label the nuclei of proliferating satellite cells 1 h before each pulsed US irradiation. Immobilization resulted in significant decreases in the mean diameters of type I, IIA and IIB muscle fibers of the gastrocnemius muscle in the Im, sham US and US groups compared with the control group. However, the degrees of muscle fiber atrophy for all types were significantly lower in the US group compared with the Im and sham US groups. Although the number of capillaries and the concentrations of insulin-like growth factor and basic fibroblast growth factor did not change in the muscle, the number of BrdU-positive nuclei in the muscle was significantly increased by pulsed US irradiation in the US group. The results of this study suggest that pulsed US irradiation inhibits the development of disuse muscle atrophy partly via activation of satellite cells.

[Differences in the bone mineral density in patients with Kanemi Yusho treated before and after the age of 18 years].

This study examined patients with Kanemi Yusho. The patients' height, weight, and bone mineral density were measured. The density of the distal end of the radius was measured using dual energy X-ray absorptiometry and the calcaneum was measured with ultrasound. We also measured urine levels of cross-linked N-telopeptides of type I collagen, serum tartrate-resistant acid phosphatase 5b, serum bone-specific alkaline phosphatase, serum Ca, serum P and blood PCB level. The patient group that took PCBs when they were 0 to 18 years old (such patients were 42 to 60 years old at the time of the study) showed no correlation between the bone density of the radius and calcaneum in spite of treatment received when they were over 18 years of age (> 60 years of age at the time of the study). The bone mineral density in Kanemi Yusho was not different from the control group. The levels of only serum bone-specific alkaline phosphatase were correlated with the bone mineral density of the radius and calcaneum in patients treated when they were over 18 years of age (currently over 60 years old). PCBs might have had an effect on bone density and bone metabolism.

Low-level laser irradiation promotes the recovery of atrophied gastrocnemius skeletal muscle in rats.

Low-level laser (LLL) irradiation promotes proliferation of muscle satellite cells, angiogenesis and expression of growth factors. Satellite cells, angiogenesis and growth factors play important roles in the regeneration of muscle. The objective of this study was to examine the effect of LLL irradiation on rat gastrocnemius muscle recovering from disuse muscle atrophy. Eight-week-old rats were subjected to hindlimb suspension for 2 weeks, after which they were released and recovered. During the recovery period, rats underwent daily LLL irradiation (Ga-Al-As laser; 830 nm; 60 mW; total, 180 s) to the right gastrocnemius muscle through the skin. The untreated left gastrocnemius muscle served as the control. In conjunction with LLL irradiation, 5-bromo-2-deoxyuridine (BrdU) was injected subcutaneously to label the nuclei of proliferating cells. After 2 weeks, myofibre diameters of irradiated muscle increased in comparison with those of untreated muscle, but did not recover back to normal levels. Additionally, in the superficial region of the irradiated muscle, the number of capillaries and fibroblast growth factor levels exhibited significant elevation relative to those of untreated muscle. In the deep region of irradiated muscle, BrdU-positive nuclei of satellite cells and/or myofibres increased significantly relative to those of the untreated muscle. The results of this study suggest that LLL irradiation can promote recovery from disuse muscle atrophy in association with proliferation of satellite cells and angiogenesis.

[Decreased serum aldolase levels in Yusho].

We measured serum aldolase levels in Yusho sufferers annually between the years 2000 and 2005. We observed a decrease in serum aldolase levels in 47.7% of the patients studied. We researched the relations among serum aldolase, serum creatine kinase, blood polychlorinated biphenyls, blood polychlorinated quaterphenyls, blood polychlorinated dibenzofurans and toxic equivalent quantity statistically. We conclude that a high concentration of blood polychlorinated biphenyls might play a role in the decrease of serum aldolase levels in Yusho sufferers.

[Elevation of serum creatine kinase and low serum aldolase in the patients with KANEMI YUSHOU].

We studied the rates of the patient with the elevation of serum creatine kinase using the routine medical checkup data from KANEMI YUSHOU patients between 1995 and 2001. We also studied the serum aldolase level and light microscopic observation of muscle tissue in rats during strenuous exercise given the polychlolinated biphenyls. Fifteen percent of the patients showed the elevation of serum creatine kinase. The patients with the elevation of serum creatine kinase also showed a higher concentration of polychlolinated biphenyls in their blood. 47.7% of the patients show low aldolase. There is no interrelation between the aldolase levels and PCBs or PCQs. There is also no interrelation between the serum levels of aldolase and creatine kinase. The rats given polycholorinated biphenyls showed a slight increase of necrotic fibers during strenuous exercise. Polycholorinated biphenyls may play some role for muscle necrosis. We could not clarify the significance of low serum aldolase in KANEMI YUSHOU.